Neurochemistry

Dopamine receptor activation mitigates mitochondrial dysfunction and oxidative stress to enhance dopaminergic neurogenesis in 6-OHDA lesioned rats: A role of Wnt signalling Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Akanksha Mishra, Sonu Singh, Virendra Tiwari, Swati Chaturvedi, M. Wahajuddin, Shubha Shukla Abstract Nigral dopaminergic (DAergic) cell degeneration and depletion of dopamine neurotransmitter in the midbrain are cardinal features of Parkinson's disease (PD). Dopamine system regulates different aspects of behavioural phenotypes such as motor control, reward, anxiety and depression via acting on dopamine receptors (D1-D5). Recent studies have shown the potential effects of dopamine on modulation of neurogenesis, a process of newborn neuron formation from neural stem cells (NSCs). Reduced proliferative capacity of NSCs and net neurogenesis has been reported in subventricular zone, olfactory bulb and hippocampus of patients with PD. However, the molecular and cellular mechanism of dopamine mediated modulation of DAergic neurogenesis is not defined. In this study, we attempted to investigate the molecular mechanism of dopamine receptors mediated control of DAergic neurogenesis and whether it affects mitochondrial biogenesis in 6-hydroxydopamine (6-OHDA) induced rat model of PD-like phenotypes. Unilateral administration of 6-OHDA into medial forebrain bundle potentially reduced tyrosine hydroxylase immunoreactivity, dopamine content in substantia nigra pars compacta (SNpc) and striatum region and impaired motor functions in adult rats. We found decreased D1 receptor expression, mitochondrial biogenesis, mitochondrial functions and DAergic differentiation associated with down-regulation of Wnt/β-catenin signalling in SNpc of 6-OHDA lesioned rats. Pharmacological stimulation of D1 receptor enhanced mitochondrial biogenesis, mitochondrial functions and DAergic neurogenesis that lead to improved motor functions in 6-OHDA lesioned rats. D1 agonist induced effects were attenuated following administration of D1 antagonist, whereas shRNA mediated knockdown of Axin-2, a negative regulator of Wnt signalling significantly abolished D1 antagonist induced impairment in mitochondrial biogenesis and DAergic neurogenesis in 6-OHDA lesioned rats. Our results suggest that dopamine receptor regulates DAergic neurogenesis and mitochondrial functions by activation of Wnt/β-catenin signaling in rat model of PD-like phenotypes.

Chrysin ameliorates cerebral ischemia/reperfusion (I/R) injury in rats by regulating the PI3K/Akt/mTOR pathway Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Teng-Fei Li, Ji Ma, Xin-Wei Han, Yong-Xu Jia, Hui-Fei Yuan, Shao-Feng Shui, Dong Guo, Lei Yan Abstract In this study, the effects of chrysin on cerebral ischemia by establishing middle cerebral artery occlusion (MCAO) in rat were investigated. In vivo experiments, the rats were orally administrated with clopidogrel or chrysin once daily for 7 days before the experimental of ischemia and the rats were divided into 5 groups: the sham group, the I/R group, I/R + clopidogrel group, I/R + chrysin (10 mg/kg), I/R + chrysin (20 mg/kg) group. Chrysin significantly ameliorated the I/R rats, evaluated by TTC staining, determination of brain wet to dry weight ratio and neurological deficits. Moreover, in serum and brain tissues of the I/R rats, chrysin also could effectively suppress the release of inflammatory cytokines, including levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, chrysin could improve the SOD activity in the I/R rats. Mechanically, chrysin could activate the PI3K/Akt/mTOR pathway, inhibited inflammation and apoptosis. In oxygen-glucose deprivation and recovery (OGD/R)-induced SH-SY5Y cells in vitro. Chrysin markedly decreased the levels of TNF-α, IL-6 and IL-1β in supernatant of OGD/R-induced SH-SY5Y cells via activating PI3K/Akt/mTOR pathway. In conclusion, our study demonstrated that chrysin might be a potential therapeutic agent for cerebral ischemia.

Dexmedetomidine protects neurons from kainic acid-induced excitotoxicity by activating BDNF signaling Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Kuan-Ming Chiu, Tzu-Yu Lin, Ming-Yi Lee, Cheng-Wei Lu, Ming-Jiuh Wang, Su-Jane Wang Abstract Glutamatergic excitotoxicity is crucial in the pathogenesis of epileptic seizures. Dexmedetomidine, a potent and highly selective α2 adrenoceptor agonist, inhibits glutamate release from nerve terminals in rat cerebrocortical nerve terminals. However, the ability of dexmedetomidine to affect glutamate-induced brain injury is still unknown. Therefore, the present study evaluated the protective effect of dexmedetomidine against brain damage by using a kainic acid (KA) rat model, a frequently used model for temporal lobe epilepsy. Rats were treated with dexmedetomidine (1 or 5 μg/kg, intraperitoneally) 30 min before the KA (15 mg/kg) intraperitoneal injection. KA-induced seizure score and elevations of glutamate release in rat hippocampi were inhibited by pretreatment with dexmedetomidine. Histopathological and TUNEL staining analyzes showed that dexmedetomidine attenuated KA-induced neuronal death in the hippocampus. Dexmedetomidine ameliorated KA-induced apoptosis, and this neuroprotective effect was accompanied by inhibited the KA-induced caspase-3 expression as well as MAPKs phosphorylation, and reversed Bcl-2 down-expression, coupled with increased Nrf2, BDNF and TrkB expression in KA-treated rats. The results suggest that dexmedetomidine protected rat brains from KA-induced excitotoxic damage by reducing glutamate levels, suppressing caspase-3 activation and MAPKs phosphorylation, and enhancing Bcl-2, Nrf2, BDNF and TrkB expression in the hippocampus. Therefore, dexmedetomidine may be beneficial for preventing or treating brain disorders associated with excitotoxic neuronal damage. In conclusion, these data suggest that dexmedetomidine has the therapeutic potential for treating epilepsy.

Involvement of anxiety-like behaviors and brain oxidative stress in the chronic effects of alarm reaction in zebrafish populations Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Vanessa A. Quadros, Luiz V. Rosa, Fabiano V. Costa, Talise E. Müller, Flavia V. Stefanello, Vania L. Loro, Denis B. Rosemberg Abstract Aversive conditions elicit anxiety responses that prepare the organism to an eventual threat. Nonetheless, prolonged anxiety is a pathological condition associated with various neuropsychiatric disorders. Here, we evaluated whether the conspecific alarm substance (CAS), a chemical cue that elicits aversion, influences anxiety-like behaviors and modulates brain oxidative stress-related parameters in wild-type (WT) and leopard (leo) zebrafish following a repeated exposure protocol. CAS exposure was performed for 5 min, once daily for 7 consecutive days. In the 8th day, animals were tested in the light/dark and novel tank tests and their brains were further dissected for biochemical analyses. CAS chronically induced anxiogenic-like states in WT and leo populations when their behaviors were analyzed in the light/dark and novel tank tests. CAS also increased catalase (CAT) and glutathione S-transferase (GST) activities, as well as non-protein thiol (NPSH) content in WT and leo, but only leo had increased thiobarbituric reactive substance (TBARS) levels in the brain. At baseline conditions, leo was more 'anxious' when compared to WT, displaying lower CAT activity and carbonylated protein (CP) levels. Overall, CAS chronically triggers anxiety-like behavior in zebrafish populations, which may be associated with changes in oxidative stress-related parameters. Furthermore, the use of different zebrafish populations may serve as an interesting tool in future research aiming to investigate the neurobehavioral bases of neuropsychiatric disorders in vertebrates. Graphical abstract

Phospho-mTOR expression in human glioblastoma microglia-macrophage cells Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Lucia Lisi, Gabriella Maria Pia Ciotti, Marta Chiavari, Michela Pizzoferrato, Annunziato Mangiola, Sergey Kalinin, Douglas L. Feinstein, Pierluigi Navarra Abstract The glioblastoma (GBM) immune microenvironment is highly heterogeneous, and microglia may represent 30–70% of the entire tumor. However, the role of microglia and other specific immune populations is poorly characterized. Activation of mTOR signaling occurs in numerous human cancers and has roles in microglia-glioma cell interactions. We now show in human tumor specimens (42 patients), that 39% of tumor-associated microglial (TAM) cells express mTOR phosphorylated at Ser-2448; and similar mTOR activation is observed using a human microglia-glioma interaction paradigm. In addition, we confirm previous studies that microglia express urea and ARG1 (taken as M2 marker) in the presence of glioma cells, and this phenotype is down-regulated in the presence of a mTOR inhibitor. These results suggest that mTOR suppression in GBM patients might induce a reduction of the M2 phenotype expression in up to 40% of all TAMs. Since the M2 profile of microglial activation is believed to be associated with tumor progression, reductions in that phenotype may represent an additional anti-tumor mechanism of action of mTOR inhibitors, along with direct anti-proliferative activities.

Repeated exposure to methiopropamine increases dendritic spine density in the rat nucleus accumbens core Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Wen Ting Cai, Hyung Shin Yoon, Sooyeun Lee, Jeong-Hoon Kim Abstract Repeated exposure to classical psychomotor stimulants, like amphetamine (AMPH), produces locomotor sensitization and accompanied structural plasticity of dendritic spines in the nucleus accumbens (NAcc). Following our previous report that repeated administration of methiopropamine (MPA), a structural analog to meth-AMPH, produces locomotor sensitization, it was examined in the present study whether this behavioral change also accompanies with structural plasticity in the NAcc in a similar way to AMPH. A week after adeno-associated viral vectors containing enhanced green fluorescent protein (eGFP) were microinjected into the NAcc core, rats were repeatedly injected with saline, AMPH (1 mg/kg, IP), or MPA (5 mg/kg, IP) once every 2–3 days for a total of 4 times. Two weeks after last injection, all rats were perfused and their brains were processed for immunohistochemical staining. The image stacks for dendrite segments of medium spiny neuronal cells in the NAcc core were obtained and dendritic spines were quantitatively analyzed. Interestingly, it was found that the number of total spine density, with thin spine as a major contributor, was significantly increased in MPA compared to saline pre-exposed group, in a similar way to AMPH. These results indicate that MPA, a novel psychoactive substance, has similar characteristics with AMPH in that they both produce structural as well as behavioral changes, further supporting MPA's dependence and abuse potential.

Effect of phosphodiesterase (1B, 2A, 9A and 10A) inhibitors on central nervous system cyclic nucleotide levels in rats and mice Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Jie Chen, Douglas Zook, Lindsay Crickard, Ali Tabatabaei Abstract Phosphodiesterase (PDE) inhibition has been broadly investigated as a target for a wide variety of indications including central nervous system (CNS) disorders. Cyclic nucleotide (cNT) changes within associated tissues may serve as a biomarker of PDE inhibition. We recently developed robust sample harvesting and bioanalytical methods to quantify cNT levels in rodent brain and cerebrospinal fluid (CSF). Herein, we report on the application of those methods to study rodent species-specific and rodent brain region-specific cNT changes following individual or concomitant PDE inhibitor administration. Male Sprague Dawley (Crl:CD® [SD]) rats were dosed subcutaneously (sc) with a PDE1B inhibitor (DNS-0056), a PDE2A inhibitor (PF-05180999), a PDE9A inhibitor (PF-4447943), and a PDE10A inhibitor (MP10), each at a single dose of 10 or 30 mg/kg, or concomitantly with all 4 inhibitors at 10 mg/kg each. Male Carworth Farms (Crl:CF1 ®[CF-1]) mice were dosed intraperitoneally (ip) with the four individual inhibitors at a single dose of 10 mg/kg or concomitantly with all 4 inhibitors at 10 mg/kg each. The doses studied are generally adequate for affecting measurable cNT levels in the tissues of interest and were thereby chosen for this investigation. Measured 3′,5′-cyclic adenosine monophosphate (cAMP) changes were generally statistically insignificant in the brain, striatum and CSF after administration of the aforementioned PDE inhibitors. However, the levels of 3′,5′-cyclic guanosine monophosphate (cGMP) increased in both rat and mouse striatum (2.2-, 2.1- and 1.7-fold and 6.4-, 2.8- and 1.7-fold, respectively) after PDE2A, 9A, and 10A inhibitor dosing. In all cases, the cNT changes followed the same trend in the brain, striatum and CSF after PDE inhibitor dosing and dose response was observed in rats. Concomitant treatment with PDE1B, PDE2A, PDE9A and PDE10A inhibitors resulted in a 4.4- and 36.7-fold increase of cGMP in rat and mouse striatum. The drug exposures after concomitant treatment were also higher than in the individual inhibitor-treated animals. cGMP enhancement observed could be due to synergistic effects, though an additive effect of the combined inhibitor concentrations may also contribute.

Effects of exercise-induced fatigue on the morphology of asymmetric synapse and synaptic protein levels in rat striatum Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Zhifeng Wang, Lijuan Hou, Dongmei Wang Abstract Corticostriatal synaptic plasticity is considered to be a cellular basis for somatic motor regulation and motor skill learning. Changes in synaptic transmission efficiency underlie functional plasticity, while structural plasticity involves changes in the ultrastructure of the synapse and the levels of synaptic proteins. Exercise-induced fatigue may impair corticostriatal synaptic plasticity, and this impairment may be an important mechanism for exercise-induced fatigue. However, prior research focused mainly on functional plasticity such that the structural plasticity was not well understood. Because corticostriatal synapses are typical asymmetric synapses, here we have used transmission electron microscopy to examine the changes of asymmetry synaptic ultrastructure in rat striatum before and after repetitive exercise-induced fatigue; we have also used western blotting to detect the levels of synaptic active region protein Munc 13, RIM1 and synaptic vesicle protein Rab3A and postsynaptic density PSD-95 protein in rat striatum before and after exercise-induced fatigue. The results showed that the ultrastructure of asymmetry corticostriatal synapses and synaptic protein levels in the striatum of rats were abnormally changed after repetitive exercise-induced fatigue. These abnormal changes in synaptic ultrastructure and related protein levels may be the structural basis for the corticostriatal plasticity impairment after exercise-induced fatigue.

Glutamate receptor metabotropic 7 (GRM7) gene polymorphisms in mood disorders and attention deficit hyperactive disorder Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Rezvan Noroozi, Mohammad Taheri, Mir Davood Omrani, Soudeh Ghafouri-Fard Abstract L-glutamate is the chief excitatory neurotransmitter in the central nervous system (CNS) which activates metabotropic receptors including the metabotropic glutamate receptor GRM7. Single nucleotide polymorphisms (SNPs) within GRM7 gene have been associated with several psychiatric conditions. In the present study, we assessed association between two GRM7 SNPs (rs6782011 and rs779867) and two neuropsychiatric disorders including attention deficit hyperactive disorder (ADHD) and mood disorders. There were no significant differences in genotype, allele and haplotypes frequencies of the rs6782011 and rs779867 between bipolar disorder 1 (BPD1) patients and controls. The CC genotype of the rs6782011 was significantly associated with BPD2 in recessive model (OR (95% CI) = 1.78 (1.09–2.91), adjusted P value = 0.04) and with ADHD in dominant and co-dominant models (OR (95% CI) = 1.98 (1.11–3.53), adjusted P value = 0.04; OR (95% CI) = 2.27 (1.23–4.17), adjusted P value = 0.04 respectively). The C G haplotype (rs6782011 and rs779867 respectively) was more prevalent among both BPD2 patients (OR (95%CI) = 2.03 (1.36–3.01), adjusted P value = 0.002) and MDD patients (OR (95%CI) = 2.08 (1.37–3.16), adjusted P value = 0.002) compared with controls. The current study provides further evidences for participation of GRM7 variants in conferring risk of neuropsychiatric disorders.

Ammonium induced dysfunction of 5-HT2B receptor in astrocytes Publication date: October 2019 Source: Neurochemistry International, Volume 129 Author(s): Tingting Yue, Baoman Li, Li Gu, Jingyang Huang, Alexei Verkhratsky, Liang Peng Abstract Previously we reported that gene expression of astrocytic 5-HT2B receptors was decreased in brains of depressed animals exposed to chronic mild stress (CMS) (Li et al., 2012) and of Parkinson's disease (Song et al., 2018). Depression is also one of the psychiatric symptoms in hyperammonemia, and astrocyte is a primary target of ammonium in brain in vivo. In the present study, we have used preparations of the brains of urease-treated mice and ammonium-treated astrocytes in culture to study gene expression and function of 5-HT2B receptors. The urease-treated mice showed depressive behaviour. Both mRNA and protein of 5-HT2B receptors were increased in the brains of urease-treated mice and in ammonium-treated cultured astrocytes. Further study revealed that mRNA and protein expression of adenosine deaminase acting on RNA 2 (ADAR2), an enzyme catalyze RNA deamination of adenosine to inosine was increased in the brains of urease-treated mice and in ammonium-treated cultured astrocytes. This increase in ADAR2 induced RNA editing of 5-HT2B receptors. Cultured astrocytes treated with ammonium lost 5-HT induced Ca2+ signalling and ERK1/2 phosphorylation, indicating dysfunction of 5-HT2B receptors. This is in agreement with our previous observation that edited 5-HT2Breceptors no longer respond to 5-HT (Hertz et al., 2014). Ammonium effects are inhibited by ADAR2 siRNA in cultured astrocytes, suggesting that increased gene expression and editing and loss of function of 5-HT2Breceptors are results of increased activity of ADAR2. In summary, we have demonstrated that functional malfunction of astrocytic 5-HT2B receptors occurs in animal models of major depression, Parkinson depression and hepatic encephalopathy albeit via different mechanisms. Understanding the role of astrocytic 5-HT2B receptors in different pathological contexts may instigate development of novel therapeutic strategies for treating disease-specific depressive behaviour.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

The Recommendation and Use of Extracorporeal Membrane Oxygenation (ECMO) in Cases Reported to the...

The Recommendation and Use of Extracorporeal Membrane Oxygenation (ECMO) in Cases Reported to the California Poison Control SystemAbstractIntroductionAntidotes are available to treat some specific poisonings; however, the mainstay of treatment for the poisoned patient remains supportive care. Extracorporeal membrane oxygenation (ECMO) is one of the most aggressive supportive measures available to manage poisoned patients.ObjectiveTo characterize the recommendation and use of ECMO in cases reported...

Αλέξανδρος Γ. Σφακιανάκης

now

Adverse Effects of Physostigmine AbstractIntroduction Physostigmine is a tertiary amine carbamate acetylcholinesterase...

Adverse Effects of PhysostigmineAbstractIntroductionPhysostigmine is a tertiary amine carbamate acetylcholinesterase inhibitor. Its ability to cross the blood-brain barrier makes it an effective antidote to reverse anticholinergic delirium. Physostigmine is underutilized following the publication of patients with sudden cardiac arrest after physostigmine administration in patients with tricyclic antidepressant (TCA) overdoses. We completed a narrative literature review to identify reported adverse...

Αλέξανδρος Γ. Σφακιανάκης

2m

Does Lidocaine Cause False Positive Results on Cocaine Urine Drug Screen? AbstractBackground Individuals...

Does Lidocaine Cause False Positive Results on Cocaine Urine Drug Screen?AbstractBackgroundIndividuals who have tested positive for cocaine have claimed that lidocaine, or its primary metabolite, norlidocaine (monoethylglycinexylidide (MEGX)), have caused false positive results for the cocaine metabolite benzoylecgonine (BE) on urinary immunoassay testing.ObjectiveThe goal of the study was to determine if lidocaine exposure from routine medical procedures can result in false positives on a commercially...

Αλέξανδρος Γ. Σφακιανάκης

2m

Gadolinium Aspiration Following Inadvertent Endotracheal Tube Cuff Injection in a Pediatric Patient...

Gadolinium Aspiration Following Inadvertent Endotracheal Tube Cuff Injection in a Pediatric PatientAbstractIntroductionGadolinium-based contrast agents (GBCA) are frequently used for MRI contrast studies. We report a case of pulmonary aspiration secondary to inadvertent GBCA injection.Case ReportA 12-year-old female with a past medical history significant for mitochondrial disorder, bronchial asthma, autism, recurrent urinary tract infection, epilepsy, developmental delay, dysautonomia, and thrombocytopenia...

Αλέξανδρος Γ. Σφακιανάκης

2m

Medical Toxicology

In Response to "Impact of Targeted Temperature Management on ED Patients with Drug Overdose–Related Cardiac Arrest"

Self-Analysis: Do I Comprehend Case Series and Cohort Studies? A Fellow's Perspective

Gadolinium Aspiration Following Inadvertent Endotracheal Tube Cuff Injection in a Pediatric Patient Abstract Introduction Gadolinium-based contrast agents (GBCA) are frequently used for MRI contrast studies. We report a case of pulmonary aspiration secondary to inadvertent GBCA injection. Case Report A 12-year-old female with a past medical history significant for mitochondrial disorder, bronchial asthma, autism, recurrent urinary tract infection, epilepsy, developmental delay, dysautonomia, and thrombocytopenia was scheduled for a contrast-enhanced MRI study using gadoterate meglumine for urinary incontinence. The patient was sedated and intubated in preparation for the study, during which 10 mL of gadoterate meglumine was inadvertently injected into the endotracheal tube cuff pilot line instead of intravenously. The patient remained intubated and was admitted to the intensive care unit with continuous monitoring for signs of pulmonary injury or gadolinium toxicity. She was successfully extubated approximately 24 hours later without complication. Discussion A variety of adverse effects attributable to parenteral GBCA exposure have been reported ranging from mild irritation to life-threatening anaphylaxis. Gadolinium deposition and storage have been implicated in a number of those adverse effects and multiple treatments modalities have been suggested, but no scientifically guided management exists. Conclusion This case of pulmonary aspiration secondary to inadvertent GBCA injection in a pediatric patient demonstrated no acute  side effects or complications within the first 24 hours. With the wide range of adverse effects attributed to gadolinium use in the medical literature, it is difficult to predict potential future adverse effects.

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In Reply: "Impact of Targeted Temperature Management on ED Patients with Drug Overdose–Related Cardiac Arrest"

ACMT Position Statement: Buprenorphine Administration in the Emergency Department

ACMT Position Statement: Addressing Pediatric Cannabis Exposure

Does Lidocaine Cause False Positive Results on Cocaine Urine Drug Screen? Abstract Background Individuals who have tested positive for cocaine have claimed that lidocaine, or its primary metabolite, norlidocaine (monoethylglycinexylidide (MEGX)), have caused false positive results for the cocaine metabolite benzoylecgonine (BE) on urinary immunoassay testing. Objective The goal of the study was to determine if lidocaine exposure from routine medical procedures can result in false positives on a commercially available cocaine immunoassay urine drug screen (UDS). Methods We performed a cross-sectional observational study of patients receiving lidocaine as part of their regular care. Standard immunoassay drug screens and confirmatory liquid chromatography-mass spectrometry (LC-MS) were performed on all urine samples to assess for MEGX and BE. Results In total, 168 subjects were enrolled; 121 samples positive for lidocaine were ultimately included for analysis. One hundred fourteen of the 121 were also positive for MEGX. None of the 121 were positive for cocaine/BE on the UDS (95% CI), 0–3.7% for the full sample and 0–3.9% for the 114 who tested positive for MEGX. Conclusion The present study found no evidence that lidocaine or norlidocaine are capable of producing false positive results on standard cocaine urine immunoassays.

Adverse Effects of Physostigmine Abstract Introduction Physostigmine is a tertiary amine carbamate acetylcholinesterase inhibitor. Its ability to cross the blood-brain barrier makes it an effective antidote to reverse anticholinergic delirium. Physostigmine is underutilized following the publication of patients with sudden cardiac arrest after physostigmine administration in patients with tricyclic antidepressant (TCA) overdoses. We completed a narrative literature review to identify reported adverse effects associated with physostigmine administration. Discussion One hundred sixty-one articles and a total of 2299 patients were included. Adverse effects occurred in 415 (18.1%) patients. Hypersalivation (206; 9.0%) and nausea and vomiting (96; 4.2%) were the most common adverse effects. Fifteen (0.61%) patients had seizures, all of which were self-limited or treated successfully without complication. Symptomatic bradycardia occurred in 8 (0.35%) patients including 3 patients with bradyasystolic arrests. Ventricular fibrillation occurred in one (0.04%) patient with underlying coronary artery disease. Of the 394 patients with TCA overdose, adverse effects were described in 14 (3.6%). Adverse effects occurred in 7.7% of patients treated with an overdose of an anticholinergic agent compared with 20.6% of patients with non-anticholinergic agents. Five (0.22%) fatalities were identified. Conclusions In conclusion, significant adverse effects associated with the use of physostigmine were infrequently reported. Seizures were self-limited or resolved with benzodiazepines, and all patients recovered neurologically intact. Physostigmine should be avoided in patients with QRS prolongation on EKG, and caution should be used in patients with a history of coronary artery disease and overdoses with QRS prolonging medications. Based upon our review, physostigmine is a safe antidote to treat anticholinergic overdose.

The Recommendation and Use of Extracorporeal Membrane Oxygenation (ECMO) in Cases Reported to the California Poison Control System Abstract Introduction Antidotes are available to treat some specific poisonings; however, the mainstay of treatment for the poisoned patient remains supportive care. Extracorporeal membrane oxygenation (ECMO) is one of the most aggressive supportive measures available to manage poisoned patients. Objective To characterize the recommendation and use of ECMO in cases reported to the California Poison Control System (CPCS). Methods This retrospective chart review queried the CPCS database from 1997 to 2016 for cases containing the American Association of Poison Control Centers (AAPCC) code for ECMO, and "ECMO" and "ECLS" free-text searches. The collected data included year, age, gender, substances involved, route of exposure, clinical effects, treatments, and medical outcome. Results A total of 94 cases discussed ECMO as a supportive option with 16 cases utilizing ECMO. Cases where ECMO was discussed rose from one case in 1997 to 13 cases in 2016. Of the 94 cases where ECMO was discussed, 38 cases (40%) involved toxicity from a cardiovascular agent(s) and 33 cases (35%) involved exposure to hydrocarbons. Of the 16 cases where ECMO was performed, 13 (81%) involved males. The median age was 17 years (range 1 month–54 years). Ten cases (63%) involve patients under the age of 18. In this series, 13 of 16 ECMO-supported patients survived (81%). Conclusions ECMO is being recommended more often for treatment of acute poisoning cases by the CPCS. All caregivers involved in the treatment of poisoning should gain a working knowledge of the potentially lifesaving technology of ECMO, its indications for use, adverse effects, and drug or poison interactions.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Remote Sensing

Assessment of the Temporal and Spatial Variations of Urban Development Using RS and GIS: A Case Study—Yasuj, Iran Abstract The temporal-spatial change of cities is one of the main challenges of managers and decision makers in urban development. In the present study, a parameter related to the evaluation of the capability of Yasuj City was selected, classed, and weighed to determine a desired location for urban development. Accordingly, in order to determine fuzzy maps, all factors and sub-factors were weighed using the AHP and hierarchical technique. Then, the maps of each sub-factor were standardized in IDRIS environment and the considered layers were combined in GIS environment to determine the land suitability for urban development. Next, in order to evaluate the trend of temporal-spatial variation of land use around Yasuj City, the prepared images of the Landsat satellite as well as TM, ETM+ and OLI sensors in Envin 5.1 software related to 1986, 2001, and 2016, respectively, were employed. Finally, based on the changes in land use of Yasuj City, the residential or urban sections widely changed. The changes included different uses such as forests, grasslands, agriculture, and water corpuses. In 1986–2016, the results of changes in land use around the Yasuj City indicated 5% increase in the residential section and 3, 2 and 1% decrease in rangelands, agricultural lands, and water bodies, respectively. Forests, which are located in the outer and inner sections of Yasuj City, have a lot of ecological functions. With the high speed of city development, the ecological functions of forests are decreasing, both quantitatively and qualitatively, and therefore, should be taken into consideration. The results of this study, and the similar studies, indicated that spatial data, especially data related to human settlements (since they are highly changeable), are a good foundation for detailed planning. Such kind of data is also used since they are suitable tools for research purposes.

Understanding Spatio-temporal Pattern of Grassland Phenology in the western Indian Himalayan State Abstract The present study has analysed grassland phenology: start of greening (SOG), end of greening (EOG) and length of greening (LOG), and their rate of change in the western Himalaya in India (Himachal Pradesh) using MODIS NDVI time series data (2001–2015). These metrics were inspected at different stratification levels: state, elevation, climatic zones and bio-geographic provinces. Delayed SOG was observed over 44.87% (P < 0.1), and delayed EOG over 63.3% (P < 0.1) of grassland grids. LOG was shortened in 24.37% (P < 0.1) and extended in 58.04% (P < 0.1) of the grids. At the state level, when statistically significant pixels (SSP) and all the pixels (AP) are used (given as SSP:AP), SOG is delayed by 20.27:6.28 days year−15, while EOG is delayed by 38.02:14.97 days year−15 and LOG is extended by 35.07:8.70 year−15 days. Extended LOG is observed over the temperate and cold arid regions, and shortened LOG is observed over sub-alpine and alpine regions. Variations in SOG and EOG are not uniform across different climatic and bio-geographic regions. However, in the sub-alpine and alpine zones, SOG and EOG followed elevation gradients, i.e. late SOG with early EOG over higher elevations, and early SOG with late EOG over lower elevations. Our study has revealed an interesting pattern of translational phenology (i.e. late SOG and late EOG) of grasslands which hints towards shifting winter period. Overall, it is observed that variations in timing of snowfall and snow cover extent are the reasons for inter-annual variations in the grassland phenology.

Short-Term Variability of Physico-Chemical Properties and pCO 2 fluxes off Dhamra estuary from north-eastern India Abstract Short-term variability in physico-chemical properties of Dhamra estuarine system located in north-eastern India was investigated to understand the inter-seasonal variability. The oxygen data show 89–92% saturation in winter months compared to 60–70% during summer. Overall, the nitrate ranged between < 1.0 and 22.0 µmol l−1; however, phosphate concentrations never exceeded 1 µmol l−1 during the whole study period. In general, the lowest nutrient values were recorded during March and December irrespective of the year sampled. Pearson correlation matrix shows poor relationships between inorganic nitrate and phosphate suggesting decoupling in the Dhamra estuary. However, relationship between surface chlorophyll and nitrate was significant highlighting modest control on phytoplankton population. Interestingly, pCO2(air) exhibited considerable monthly variability during the sampling period, thereby accentuating the sea–air CO2 gradient. The pCO2(air) varied between 370 and 421 µatm, whereas pCO2(water) ranged between 146 and 751 µatm. The ΔpCO2 therefore showed monthly fluctuation and acted as a weak to moderate source to the immediate atmosphere. Our observation from Dhamra estuary suggests large inter-annual variability which therefore necessitates the need for near real-time measurements which is now a possibility with emerging coastal biogeochemical buoys.

Estimation of Leaf Chlorophyll Concentration in Turmeric ( Curcuma longa ) Using High-Resolution Unmanned Aerial Vehicle Imagery Based on Kernel Ridge Regression Abstract High-resolution information is needed for precision agriculture to achieve precise management of inputs. High spatial and temporal resolution is requisite to get the actionable information for the timely response. The objective of the present study is to estimate the leaf chlorophyll Concentration using high-resolution (2 cm) images captured from UAV-mounted multispectral sensors for crop health monitoring. In this study, a hexacopter was flown at an elevation of 25 m to capture the images in green, red, red edge and NIR bands of turmeric plots grown at ICAR Research Complex, Northeast Hilly Region, India. A handheld SVC spectroradiometer having spectral range from 350 to 2500 nm was also used to collect the spectra of sample plants to support the UAV study. We evaluated an advanced machine learning algorithm kernel ridge regression combined with spectral information and ground-truth chlorophyll data to model the chlorophyll estimation. The multivariate analysis was also applied on spectroradiometer and UAV data, which recommended red band for chlorophyll prediction with R2 value greater than 0.6. We also found that kernel ridge regression is a robust method for developing chlorophyll estimation model with lesser training time. The results indicate that kernel ridge regression with a radial basis kernel function with four multispectral input bands can be utilized to evaluate the leaf chlorophyll concentration with an root mean squared error RMSE = 0.10 mg/g and regression coefficient R2 = 0.7452. However, this study is site specific and needs to be practiced in different crop sites in order to generalize this method for precision agriculture.

Detection of Urban Land Use Land Cover Dynamics Using GIS and Remote Sensing: A Case Study of Axum Town, Northern Ethiopia Abstract The present study was conducted in the Northern Ethiopia, the most ancient town, Axum to detect urban expansion of for the last 3 decades and predict the trend of urban expansion for the year of 2025. To do so, multi-temporal satellite images of 1985, 2000 and 2015 with other datasets were considered and analyzed to scrutinize level of urban expansion. Maximum likelihood algorithm of supervised classification was applied for each Landsat satellite images to generate land use and land cover map of the study area using ERDAS Imagine software. The levels of accuracy of these classifications were evaluated using confusion matrix to derive the overall accuracy. The finding of this study indicated that in the base year (1985), the largest LULC was occupied by agriculture covered, 60% of the entire area in 1985, 48% in 2000 and 38% in 2015, while the urban area increased by 10%, 19% and 39% in 1985, 2000 and 2015, respectively. The decline of the agricultural area was the fast conversion of the agricultural land into the urban areas. The vegetated area was 19% in 1985, 16% in 2000 and 20% in 2015, and also barren lands were possessed 11% in 1985, 17% in 2000 and 3% in 2015 of the entire study area. Even though many changes have observed among the LULC in the year between 1985 and 2015, the highest rate of changes was observed in urban land which increased by 9.9% in every year and vegetated areas by 0.1% per year. Besides, agricultural and barren lands are also decreased in size by 1.18% and 2.38%, respectively, in 2015 when compared with 1985. Therefore, the built-up area was under fast growing currently and some of the causative factors include population growth of the town and rural to urban migration. Finally, the forecast urban expansion of Axum Town for the year, 2025 was found 1497.9 ha Therefore, urban planning authorities and urban planners should think about the future impact of horizontal urban expansion and population growth of the town in line with possible infrastructures development.

Mapping of Soil Salinity Using the Landsat 8 Image and Direct Field Measurements: A Case Study of the Tadla Plain, Morocco Abstract Soil salinization from arid to semiarid climate is a serious environmental problem. In some countries, salinization is considered a real threat to food security and food quality because it lowers crop yields and can irretrievably damage land. In the irrigated area of the plain of Tadla (Central Morocco), the intensive use of groundwater and saline surfaces lead to the degradation of soil quality. Experimental methods of monitoring soil salinity by direct real-time measurements are in high demand, but also very limited in terms of spatial coverage. The objective of this paper is to map soil salinity in the arid and semiarid zone of the Tadla plain in Morocco, based on optical remote sensing data and field measurements of sodium absorption ratio. The first results of work were devoted to the evaluation and validation of salinity models in the study area. Observations on the site, correlation, verification and validation of the model enabled us to map the salinity. All these use the soil salinity map based on non-saline soil content, light saline soil, moderate saline soil and highly saline soil. The map obtained from our model allowed us to identify the distribution of salinity in the study area. The values of the electrical conductivity in the study area range from less than 2 ds/m (non-saline soil) to more than 8 ds/m (highly saline soil) with a significant variation between the different levels of soil salinity in the study area.

Using GIS to Develop a Model for Forest Fire Risk Mapping Abstract Forests are the most beautiful natural resources around the world and play a pivotal role in preserving environmental balance. An important measure taken for managing and protecting forest areas as well as for decreasing the potential damages caused by the fire is the detection of regions susceptible to forest fire through forest fire risk mapping with different models and methods. In recent years, a geographic information system (GIS)-based multi-criteria decision analyses (MCDA) have been successfully applied in the production of forest fire risk maps. In this study, GIS-based analytical network process as MCDA method was employed in order to provide the fire risk map of Noshahr Forests (North Iran) using slope, slope aspect, altitude, land cover, normalized difference vegetation index, annual rainfall, annual temperature, distance to settlements, and distance to road as input data. Furthermore, to prepare the map of the distribution of occurred fires, MODIS fire product and wide-field observations were used. Thereafter, each of these subcriteria of the utilized factors was standardized according to their significance in a forest fire and then with the extracted coefficients in the analytical network process model merged in ArcGIS software. Finally, the fire risk map was generated. Evaluation of the results obtained using receiver operating characteristic curve indicated that the designed model has good accuracy with a value of under curve area of 0.783. According to the map prepared, 57.45% of the study area (1034.41 km2) is located in the high and very high-risk classes.

Pol-InSAR for Forest Biomass Estimation with the Transformation of the Polarization Basis Abstract An improved method that uses polarimetric and Pol-InSAR information at the L-band and P-band was proposed in this study for estimating forest biomass. In the first phase, various polarimetric and polarimetric interferometry indicators were extracted via transformation of the polarization basis. In the second phase, the particle swarm optimization method is applied to identify optimal parameter values for biomass estimation. According to the results, the correlations between the polarimetric indicators and the biomass were stronger at the P-band compared to the L-band. Polarimetric indicators that involve HV and HH–VV show the maximum correlation with biomass prior to optimization. It is demonstrated that changing the polarization basis can significantly improve the correlations of estimators with the biomass, especially at the P-band. The globally optimal estimators involve the same scattering mechanisms (volume and double-bounce scattering), and the optimal polarization bases differ slightly among most of the cases, due to the adaptation to the forest natural geometry and/or the acquisition configuration. Regarding Pol-InSAR, several tree height retrieval estimators that are based on various assumptions have been analyzed under multiple polarization basis rotations. According to the results, the RVoG phase method, which represents the forest as a low-extinction structured volume, yielded the best accuracy, with R = 0.73 and RMSE = 4.30 m. The identification of the optimum polarization indicators via binary PSO could improve the biomass estimation accuracy by 2% and 6% at the P-band and L-band, respectively. It is demonstrated that such an approach can be employed to accurately estimate biomass via extrapolation of in situ measurements over an entire region.

Identification of Groundwater Prospect in Bara Region of Allahabad District Based on Hydro-Geomorphological Analysis Using Satellite Imagery Abstract Water scarcity is a major problem for villagers' survival as it determines the population density and affects the migration pattern in Bara region. In the present study, groundwater resource endowment is studied and correlated with the distributional pattern of population, settlements and economic activity for analysing regional development in the study area. The study has been carried out using geospatial platforms, i.e. Erdas Imagine 2014 and ArcGis 10.2.2 software. Sentinel-2 satellite imagery and Cartosat-1 DEM data were the major data sources for extracting factor layers. Geomorphology and lineament maps of NRSC, District Resource Map of GSI, topographic maps and Google Earth images along with field surveys were ancillary database. Saaty's 9-point rating scale of analytical hierarchy process was used to extract the GWPI by integrating factor layers of geomorphology, lineament density, slope, geology, rainfall, drainage density and land use land cover according to their relative influence. Final map shows different zones of groundwater prospects in the study region, which is validated from aquifer thickness data. Result shows that 39.19% (291.41 km2) of the total area (743.64 km2) is classified as high-to-excellent GWP, whereas 27.96% (207.89 km2) of the area is under very poor-to-poor GWP. Areas having poor-to-poorest groundwater storage impact on population distribution, as 14% of the total population is lying over these zones. The descriptive statistical analysis showed that CGWPI and built-up area are significantly correlated (F = 18.024 > 4.41*, t = − 4.245 > 2.101, R2 = 50.03%). CGWPI is also correlated significantly with population density (F = 18.855 > 4.41*, t = -4.342 > 2.101, R2 = 50.16%). However, the relationship is not very high on linear regression model as expected since only 50% variations in population distribution can be attributed to CGWPI, for example, the Shankargarh town having the highest population density and the second highest built-up percentage in the whole study area in spite of being endowed with the lowest groundwater potential.

Estimation of Canal Water Deficit Using Satellite Remote Sensing and GIS: A Case Study in Lower Chenab Canal System Abstract The timely precise information of land use land cover (LULC) in the canal command area can help in managing irrigation water according to the crop water requirement. A study was conducted to map the LULC of irrigated command area of three distributaries in the lower Chenab canal system, Pakistan, namely Mungi, Killianwala and Khurrianwala for the estimation of canal water deficit (CWD). Multispectral images of LANDSAT-7 were used for Rabi season of 2009–2010 and 2010–2011. Normalized difference vegetation index-based unsupervised classification was performed for the formation of LULC of the commands area. During the initial classification, totally nine clusters were created with maximum likelihood. These clusters were then merged into final four classes on the basis of field knowledge. Accuracy assessment was performed using error matrix; producer and user accuracies were estimated for each class with overall accuracy of 84% and 86% for the Rabi season 2009–2010 and 2010–2011, respectively. For the assessment of the irrigation water demand, potential evapotranspiration was estimated using the Penman–Monteith equation. Crop water requirement was estimated based on the 10-day Kc value of the mapped crop from the LULC. Irrigation water demand for cropped area was estimated from the LULC and crop evapotranspiration. Canal water deficit was estimated from the available canal water supply and irrigation water requirement in the Rabi season. During the Rabi seasons, average CWD was 64%, 72% and 32% (2009–2010) and 33%, 46% and 36% (2010–2011) for Khurrianwala, Killianwala and Mungi distributary, respectively.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Frailty & Aging

Relating the MNA Mobility Single Item to Usual Walking Speed in Hospitalized and Community-Dwelling Geriatric Patients Abstract Usual walking speed (WS) is a relatively easy and reproducible tool for detecting mobility impairment. For some reasons, however, geriatric patients might not be able to perform walking tests. Therefore, a subjective assessment could be an alternative method to screen for mobility impairment. In the present paper, we explore the use of the mobility item from the Mini Nutritional Assessment-short form (MNA-sf) to assess mobility and its congruence with walking speed in hospitalized and ambulatory patients. We analyzed retrospective data from 357 patients and found a highly significant correlation between WS and the MNA-sf mobility item. After dichotomization of the MNA-sf mobility score (mobility impairment ≤1 and no impairment >1), AUC for ROC curves showed that the mobility item derived from the MNA-sf reflects fairly well the mobility of geriatric hospitalized patients (AUC = 0.773), while it performs better in ambulatory patients (AUC = 0.838).

Adherence to a Mediterranean Diet is Not Associated with Risk of Sarcopenic Symptomology: A Cross-Sectional Analysis of Overweight and Obese Older Adults in Australia Abstract Adherence to a Mediterranean Diet (MedDiet) is inversely associated with sarcopenia. The aim of this study was to examine the association between adherence to a MedDiet and sarcopenic symptomology in obese older adults. For confirmation of sarcopenia, low appendicular skeletal muscle (ASM: males, ≤7.25kg/m2; females, ≤5.5kg/m2) accompanied low handgrip strength (males, ≤30kg; females, ≤20kg) or low physical performance (Short Physical Performance Battery [SPPB]: ≤8; or gait speed: ≤0.8m/sec). Adherence to a MedDiet was determined using the Mediterranean Diet Adherence Screener (MEDAS). Sixty-five older adults were included. Adherence to a MedDiet was not associated with a decreased risk of sarcopenic symptomology (SPPB: OR = 0.20; 95% CI: 0.01-3.1; P = 0.234; Muscle strength: OR = 1.81; 95% CI: 0.32-10.15; P = 0.499; Gait speed: OR = 0.58; 95% CI: 0.13-2.50; P = 0.468). Future research should investigate whether a Mediterranean-style intervention can prevent or improve sarcopenic symptomology, including in non-Mediterranean populations.

Proceedings of the Canadian Frailty Network Workshop: Identifying Biomarkers of Frailty to Support Frailty Risk Assessment, Diagnosis and Prognosis. Toronto, January 15, 2018 Abstract The Canadian Frailty Network (CFN), a pan-Canadian not-for-profit organization funded by the Government of Canada through the Networks of Centres of Excellence Program, is dedicated to improving the care of older Canadians living with frailty. The CFN has partnered with the Canadian Longitudinal Study on Aging (CLSA) to measure potential frailty biomarkers in biological samples (whole blood, plasma, urine) collected in over 30,000 CLSA participants. CFN hosted a workshop in Toronto on January 15 2018, bringing together experts in the field of biomarkers, aging and frailty. The overall objectives of the workshop were to start building a consensus on potential frailty biomarker domains and identify specific frailty biomarkers to be measured in the CLSA biological samples. The workshop was structured with presentations in the morning to frame the discussions for the afternoon session, which was organized as a free-flowing discussion to benefit from the expertise of the participants. Participants and speakers were from Canada, Italy, Spain, United Kingdom and the United States. Herein we provide pertinent background information, a summary of all the presentations with key figures and tables, and the distillation of the discussions. In addition, moving forward, the principles CFN will use to approach frailty biomarker research and development are outlined. Findings from the workshop are helping CFN and CLSA plan and conduct the analysis of biomarkers in the CLSA samples and which will inform a follow-up data access competition.

Serum Vitamin D and Age-Related Muscle Loss in Afro-Caribbean Men: The Importance of Age and Diabetic Status Abstract Background Prospective studies examining the potential association of vitamin D with age-related muscle loss have shown inconsistent results. Objective To examine the association between baseline serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and prospective change in lean mass with aging in African ancestry population. We also determined if associations were modulated by age and diabetes mellitus (DM). Design: Prospective observational cohort study. Setting Data were collected from a random sub-sample of 574 men, participants of the Tobago Bone Health Study (TBHS). Participants 574 Afro-Caribbean men, aged 43+ years (mean age: 59.1 ± 10.5), who were randomly selected as the participants in both the baseline and the follow-up visits. Measurements Baseline fasting serum 25(OH)D was measured using liquid chromatography mass spectrometry (LC-MS/MS), and and 1,25(OH)2D was measured using radioimmunosassay (RIA). Changes in dual-energy X-ray absorptiometry (DXA)-measured appendicular lean mass (ALM), and total body lean mass (TBLM) were measured over an average of 6.0 ± 0.5 years. The associations of 25(OH) D and 1,25(OH)2D with ALM and TBLM were assessed by multiple linear regression model after adjusting for potential confounders. Results When stratifying all men into two groups by age, greater baseline 25(OH) D and 1,25(OH)2D levels were associated with smaller losses of ALM and TBLM in older (age 60+ years) but not in younger (age 43–59 years) men. When stratifying by DM status, the associations of 25(OH)D and 1,25(OH)2D with declines in ALM and TBLM were statistically significant only in prediabetic, but not among normal glycemic or diabetic men. Conclusion Higher endogenous vitamin D concentrations are associated with less lean mass loss with aging among older and prediabetic Afro-Caribbean men independent of potential confounders. Our findings raise a possibility that maintaining high serum vitamin D level might be important for musculoskeletal health in elderly and prediabetic African ancestry men.

Development of Pharmacotherapies for the Treatment of Sarcopenia Abstract Sarcopenia, the associated loss of skeletal muscle mass and strength and impaired physical function seen with aging, is a growing, global public health challenge in need of accepted, proven treatments that address the needs of a broad range of older adults. While exercise, primarily resistance training, and increased dietary protein have been shown to delay and even reverse losses in muscle mass, strength and physical function seen with aging, proven treatments that are accessible globally, cost effective and sustainable by patients are needed. While no drug has yet demonstrated the substantial safety and clinical value needed to be the first pharmacological therapy registered for muscle wasting or sarcopenia, the field is active. Several approaches to treating the muscle loss and subsequent functional decline are being studied in a variety of patient populations across every continent. We provide a review of the leading programs and approaches and available findings from recent studies. In addition, we briefly discuss several related issues needed to facilitate the development of a safe and efficacious pharmacotherapeutic that could be used as part of a treatment plan for older men and women with sarcopenia.

Highlights from the 2019 International Congress on Frailty and Sarcopenia Research

Relationship between Grip Strength and Nonalcoholic Fatty Liver Disease in Men Living with HIV Referred to a Metabolic Clinic Abstract This study aimed to assess the relationship between grip strength (GS) and nonalcoholic fatty liver (NAFLD) in treated HIV-infected men. We included 169 HIV-infected men. GS was assessed using a hand-grip dynamometer. NALFD was defined by liver-spleen attenuation ratio <1.1 on computed tomography. Mean (SD) age was 57 (6) years and BMI 24.5 (2.9) kg/m2. NAFLD was diagnosed in 33% of men; sarcopenia was present in 28%. Mean (SD) hand grip strength in the dominant hand was 37.5 (7.6) kg. In multivariate logistic regression, intermediate and low GS were associated with higher risk of NAFLD (OR 3.05; CI 1.27-7.61, p=0.01; OR 2.47; CI 1.01-6.19, p=0.05, respectively). GS has an inverse association with NAFLD prevalence in HIV-infected men. Specific mechanisms through which muscle weakness and NAFLD are related require further exploration but are not accounted for merely by the burden of comorbid illness, HIV disease stage, or ART exposure.

The Growth Hormone Releasing Hormone Analogue, Tesamorelin, Decreases Muscle Fat and Increases Muscle Area in Adults with HIV Abstract Background Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue in people living with HIV, however, the effects on skeletal muscle fat and area are unknown. Objectives The goals of this exploratory secondary analysis were to determine the effects of tesamorelin on muscle quality (density) and quantity (area). Design Secondary, exploratory analysis of two previously completed randomized (2:1), clinical trials. Setting U.S. and Canadian sites. Participants People living with HIV and with abdominal obesity. Tesamorelin participants were restricted to responders (visceral adipose tissue decrease ≥8%). Intervention Tesamorelin or placebo. Measurements Computed tomography scans (at L4-L5) were used to quantify total and lean density (Hounsfield Units, HU) and area (centimeters2) of four trunk muscle groups using a semi-automatic segmentation image analysis program. Differences between muscle area and density before and after 26 weeks of tesamorelin or placebo treatment were compared and linear regression models were adjusted for baseline and treatment arm. Results Tesamorelin responders (n=193) and placebo (n=148) participants with available images were similar at baseline; most were Caucasian (83%) and male (87%). In models adjusted for baseline differences and treatment arm, tesamorelin was associated with significantly greater increases in density of four truncal muscle groups (coefficient 1.56-4.86 Hounsfield units; all p<0.005), and the lean anterolateral/abdominal and rectus muscles (1.39 and 1.78 Hounsfield units; both p<0.005) compared to placebo. Significant increases were also seen in total area of the rectus and psoas muscles (0.44 and 0.46 centimeters2; p<0.005), and in the lean muscle area of all four truncal muscle groups (0.64-1.08 centimeters2; p<0.005). Conclusions Among those with clinically significant decrease in visceral adipose tissue on treatment, tesamorelin was effective in increasing skeletal muscle area and density. Long term effectiveness of tesamorelin among people with and without HIV, and the impact of these changes in daily life should be further studied.

Decreased Handgrip Strength is Associated With Impairments in Each Autonomous Living Task for Aging Adults in the United States Abstract Objectives The primary purpose of this study was to determine the time-varying associations between decreased handgrip strength (HGS) and individual instrumental activities of daily living (IADL) impairments for a nationally-representative sample of aging adults in the United States. Design Longitudinal-Panel. Setting Detailed interviews were completed in person and core interviews were typically completed over the telephone. Participants A total of 15,336 participants aged at least 50 years who participated in the 2006 wave of the Health and Retirement Study were followed biennially for 8-years. Measurements A hand-held dynamometer assessed HGS and performance in IADLs were self-reported. Results Every 5-kilogram decrease in HGS was associated with an increased odds ratio for the following IADL impairments: 1.11 (95% confidence interval (CI): 1.09, 1.13) for using a map, 1.10 (CI: 1.07, 1.12) for grocery shopping, 1.09 (CI: 1.05, 1.14) for taking medications, 1.07 (CI: 1.05, 1.09) for preparing hot meals, 1.06 (CI: 1.04, 1.08) for managing money, and 1.05 (CI: 1.02, 1.09) for using a telephone. Conclusions Decreased HGS was associated with each IADL impairment, and slightly different associations were observed in individual IADL tasks for aging adults in the United States. Our findings suggest that decreased HGS, which is reflective of reduced function of the neuromuscular system, is associated with diminished performance in autonomous living tasks during aging. Losses in HGS may lead to the development of an IADL impairment. Therefore, health-care providers working with aging adults should utilize measures of HGS as a screening tool for identifying future deficits in neuromuscular functioning. Interventions designed to preserve IADLs in aging adults should also include measures of HGS for detecting early changes in IADL capacity, and intervening at the onset of HGS declines may help aging adults retain their ability to live autonomously.

Relationship of Physical Frailty to Phosphocreatine Recovery in Muscle After Mild Exercise Stress in the Oldest-Old Women Abstract Background Physical frailty is a clinical syndrome associated with aging and manifesting as slowness, weakness, reduced physical activity, weight loss, and/or exhaustion. Frail older adults often report that their major problem is "low energy", and there is indirect evidence to support the hypothesis that frailty is a syndrome of dysregulated energetics. We hypothesized that altered cellular energy production underlies compromised response to stressors in the frail. Methods We conducted a pilot study to assess muscle energetics in response to a mild isometric exercise challenge in women (n=30) ages 84–93 years. The frailty status was assessed by a validated physical frailty instrument. Localized phosphorus (P31) magnetic resonance spectroscopy with a 1.5T magnet was used to assess the kinetics of Phosphocreatine recovery in the tibialis anterior muscle following maximal isometric contraction for 30 seconds. Results Phosphocreatine recovery following exertion, age-adjusted, was slowest in the frail group (mean=189 sec; 95%CI: 150,228) compared to pre-frail (mean=152 sec; 95%CI: 107,197) and nonfrail subjects (mean=132 sec; 95%CI: 40,224). The pre-frail and frail groups had 20 sec (95%CI: −49,89) and 57 sec (95%CI: −31,147) slower phosphocreatine recovery, respectively, than the non-frail. This response was paralleled by dysregulation in glucose recovery in response to oral glucose tolerance test in women from the same study population. Conclusions Impaired muscle energetics and energy metabolism might be implicated in the physical frailty syndrome.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Lasers in Medical Science

Thank you list 2018

Letter about: nocturnal enuresis in children between laser acupuncture and medical treatment—a comparative study

The effect of low-level laser irradiation on hyperglycemia-induced inflammation in human gingival fibroblasts Abstract Hyperglycemia-induced inflammation can greatly increase the risk of periodontal disease in people with diabetes. Low-level laser irradiation (LLLI) has been used for wound healing and anti-inflammation in many cases, and LLLI is known to inhibit the lipopolysaccharide (LPS)-stimulated inflammatory response. However, the therapeutic effect of LLLI in diabetes patients with periodontitis remains unknown. In this study, we cultured human gingival fibroblasts (HGFs) in high-glucose medium (35 mM) to mimic a hyperglycemic environment, and then measured the anti-inflammatory effect of LLLI by assessing the expression of pro-inflammatory genes including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-8 by quantitative real-time polymerase chain reaction. The results demonstrated no significant inflammatory response in HGFs cultured in mannitol medium and in those treated only with LLLI. However, HGFs cultured only in high-glucose medium showed significantly higher expression of pro-inflammatory cytokine than in those treated together with LLLI. We then observed that LLLI reduced the expression of pro-inflammatory cytokines in HGFs cultured in high-glucose medium by modulating cAMP signaling. We also investigated whether antioxidant (vitamin C) treatment reduced the inflammatory effect of oxidative stress in HGFs cultured in high-glucose medium but found no additive effect upon co-treatment with LLLI, suggesting that LLLI may activate cAMP signaling, but not reactive oxygen species (ROS) signaling, to reduce the high glucose-induced inflammation. In conclusion, LLLI may have an anti-inflammatory effect on HGFs in a high glucose environment and may benefit the treatment of periodontal disease in diabetes patients.

Comparison of two different laser photobiomodulation protocols on the viability of random skin flap in rats Abstract To identify the best low level laser photobiomodulation application site at the same irradiation time to increase the viability of the skin flap in rats. Eighteen male rats (Rattus norvegicus: var. Albinus, Rodentia Mammalia) were randomly distributed into three groups (n = 6). Group I (GI) was submitted to simulated laser photobiomodulation; group II (GII) was submitted to laser photobiomodulation at three points in the flap cranial base, and group III (GIII) was submitted to laser photobiomodulation at 12 points distributed along the flap. All groups were irradiated with an Indium, Galium, Aluminum, and Phosphorus diode laser (InGaAlP), 660 nm, with 50 mW power, irradiated for a total time of 240 s in continuous emission mode. The treatment started immediately after performing the cranial base random skin flap (10 × 4 cm2 dimension) and reapplied every 24 h, with a total of five applications. The animals were euthanized after the evaluation of the percentage of necrosis area, and the material was collected for histological analysis on the seventh postoperative day. GII animals presented a statistically significant decrease for the necrosis area when compared to the other groups, and a statistically significant increase in the quantification of collagen when compared to the control. We did not observe a statistical difference between the TGFβ and FGF expression in the different groups evaluated. The application of laser photobiomodulation at three points of the flap cranial base was more effective than at 12 points regarding the reduction of necrosis area.

Comparison of high-intensity laser therapy and combination of ultrasound treatment and transcutaneous nerve stimulation in patients with cervical spondylosis: a randomized controlled trial Abstract The aim of the study was to compare the effect of high-intensity laser therapy (HILT) and a combination of ultrasound (US) treatment and transcutaneous nerve stimulation (TENS) on pain, range of motion (ROM), and functional activity in patients with cervical spondylosis (CS). A total of 84 patients with a mean age of 51.54 years (52 women and 32 men) affected by CS were enrolled in this study. Patients were randomly divided into two groups. In group A (42 subjects), patients received 12 sessions of HILT plus exercise, while in group B (42 subjects), they received a combination of US, TENS, and exercise. The outcomes measured were cervical segment ROM, pain level measured by visual analogue scale (VAS), and functional activity measured by neck disability index (NDI) at the end of the therapy. The level of statistical significance was set as p < 0.05. In the two groups, cervical ROM, VAS, and functional scores showed significant changes. Both HILT plus exercise and US/TENS plus exercise effectively increased cervical ROM and reduced pain (with a significant greater decrease in group A). Statistically significant differences in NDI scores were observed after treatment sessions with better results for participants enrolled in group A (HILT plus exercise) Both therapeutic modalities demonstrated analgesic efficacy and improved function in patients affected by cervical spondylosis 4 weeks after the therapy. HILT plus exercise was more effective than US/TENS plus exercise. HILT can be promoted and used in this pathology with positive outcomes. However, further studies are needed to optimize the dose and duration of HILT therapy.

Blue light-emitting diode in healthy vaginal mucosa—a new therapeutic possibility Abstract A healthy female genital mucosa has an ecosystem that remains in balance through interactions between endogenous and exogenous factors. The light-emitting diode (LED) is a device that emits light at different wavelengths, with varying color and effects. Blue light in humans is most commonly used for antimicrobial purposes and has been already applied to treat facial acne and gastric bacteria. Although blue LED therapy in humans has been reported, its properties against vaginal infections have not yet been investigated. This study aims to test the safety and effects of 401 ± 5 nm blue LED on healthy vaginal mucosa. Phase I clinical trial involving 10 women between 18 and 45 years old with healthy vaginal mucosa. The participants were illuminated by 401 ± 5 nm blue LED for 30 min and anamnesis, oncotic cytology, and pH measurement were made again after 21/28 days of treatment. In the re-evaluation, adverse effects were investigated. The mean age was 27 ± 5.4 years and one of the women was excluded due to interruption of use of oral contraceptives. Oncotic cytology done before and after therapy showed that the composition of the microflora remained normal in all participants. Vaginal pH remained unchanged in eight of the women and had a reduction in one woman (5.0–4.0). No adverse effects were observed during or after illumination. 401 ± 5 nm blue LED did not generate any adverse effects or pathogenic changes in the microflora and vaginal pH. The effects of 401 ± 5 nm blue LED still need to be tested in vulvovaginal pathogens. Trial registration number: NCT03075046

Effects of UVB and UVC irradiation on cariogenic bacteria in vitro Abstract The aim of this study was to evaluate the bactericidal effect of ultraviolet (UV) light at 265-nm (UVC) and 310-nm (UVB) wavelengths from a newly developed UV light-emitting diode (LED) device against cariogenic bacteria in vitro. Suspensions of Streptococcus mutans (S. mutans) and Streptococcus sobrinus were directly irradiated by UVB or UVC for 2.5 min or 5 min. Numbers of colonies were counted and calculated as colony forming units (CFU) per milliliter. Fluorescence microscopy (FM) and optical density measurements at 490 nm (OD490) were also taken after irradiation. In addition, the bactericidal effects of irradiation against S. mutans under 0.5 mm-thick dentin were compared using culture tests and OD490 measurements. Direct UV-LED irradiation with both UVB and UVC showed strong bactericidal effects. UVB showed superior bactericidal effect through 0.5-mm-thick dentin than did UVC, especially after demineralization. These results suggest that UVB irradiation could be utilized for the prevention and management of dental caries.

Essential Role of mTOR Signaling in Human Retinal Pigment Epithelial Cell Regeneration After Laser Photocoagulation Abstract This study assessed the role of mechanistic target of rapamycin (mTOR) pathway in the human adult retinal pigment epithelial (ARPE) cell response after laser photocoagulation (LP). The effect of mTOR inhibition on ARPE-19 cell was investigated by rapamycin treatment after LP. Cell viability and proliferation were explored using MTT and EdU assays, respectively. The expression of mTOR-related proteins and epithelial-mesenchymal transition (EMT) markers was verified by Western blot. Rapamycin retarded the LP area recovery in a dose-dependent manner by the 120 h, while LP+DMSO vehicle-treated cells completely restored the lesion zone (P ≤ 0.01). ARPE-19 cell viability is significantly lower in LP + rapamycin 80 and 160 ng/ml treated cultures compared to LP control at 120 h (P ≤ 0.001). LP control group demonstrated significantly more proliferative cells compared to untreated cells at the 72 and 120 h, whereas EdU-positive cell numbers in cultures treated with rapamycin at concentrations of 80 and 160 ng/ml were similar to baseline values (P ≤ 0.01). mTOR pathway activation is essential for regulation of the RPE cell migration and proliferation after LP. mTOR inhibition with rapamycin effectively blocks the migration and proliferation of the RPE cells. Our results demonstrate that mTOR has an important role in ARPE-19 cell as a regulator of cell behavior under stress conditions, suggesting that mTOR could be a promising therapeutic target for numerous retinal diseases.

Influence of Er,Cr:YSGG laser, associated or not to desensitizing agents, in the prevention of acid erosion in bovine root dentin Abstract This in vitro study evaluated the influence of the Er,Cr:YSGG laser, associated or not to desensitizing agents, in the prevention of acid erosion in bovine root dentin. Eighty dentin specimens were selected and divided into eight groups (n = 10): G1: negative control; G2: positive control (5% fluoride varnish-FV); G3: Er,Cr:YSGG laser; G4: FV + laser; G5: 3% potassium oxalate; G6: 3% potassium oxalate + laser; G7: biphasic calcium silicate/phosphate gel (gel); G8: gel + laser. Laser parameters: 0.5 W, 6.25 J/cm2 at 1-mm distance. The erosive drink used was a cola soft-drink (pH = 2.42 at 4 °C), lasting 5 min, twice a day, with 6-h intervals between the challenges, during 14 days. Kolmogorov-Smirnov and Levene's tests were satisfied. The surface roughness data were submitted to ANOVA and Tukey post hoc tests. For the wear profile, Kruskal-Wallis and Dunn post hoc tests were used. Afterwards, the Spearman correlation test was performed. All statistical tests assumed a significance level of 5% (α = 0.05). G1 presented the highest surface roughness value after the erosive challenge (3.586 μm2 ± 0.205 μm2) and the G7 presented the lowest surface roughness value after the erosive challenge (1.071 μm2 ± 0.180 μm2). For the lost volume, G4 presented the lowest percentage (9.7% ± 0.9%), while G1 had the highest percentage (41.8% ± 2.5%), both with p < 0.05. There was a weak correlation between the response variables (ρ = 0.33). All groups presented lower values of surface roughness and loss of volume when compared to the negative control group. For the surface roughness, the biphasic calcium silicate/phosphate gel presented the best result. For volume loss, the 5% fluoride varnish + Er,Cr:YSGG laser showed the best results compared to the other groups.

The effect of the debulking by excimer laser coronary angioplasty on long-term outcome compared with drug-coating balloon: insights from optical frequency domain imaging analysis Abstract This study evaluated the 1-year efficacy of excimer laser coronary angioplasty (ELCA) before drug-coated balloon (DCB) dilatation for the treatment of in-stent restenosis (ISR). Forty consecutive patients with ISR were treated by DCB with or without the use of ELCA (ELCA plus DCB, N = 20; DCB alone, N = 20). Debulking efficiency (DE) value was defined as the neointima area on optical frequency domain imaging (OFDI) debulked by ELCA. The patients in the ELCA plus DCB group were divided into two groups (greater DE (GDE), N = 10; smaller DE (SDE), N = 10) based on the median value of DE. Thereafter, the ISR segment was prepared with a scoring balloon, followed by DCB. At follow-up, binary restenosis and target lesion revascularization (TLR) were evaluated. There were no significant differences in baseline characteristics such as age, comorbidity, and ISR type. Overall, the incidence of neoatherosclerosis in the ISR segment was 17.5%. Post-PCI, acute gain of minimum lumen diameter on quantitative coronary angiography and of minimum lumen area on OFDI was numerically higher in the GDE than in the SDE and the DCB alone group. At follow-up, the occurrences of binary restenosis and TLR in the ELCA plus DCB group were 20.0% and 10.0%; these values in the DCB alone group were 20.0% and 20.0%, respectively. Two patients from the SDE and none from the GDE developed TLR. DCB alone treatment was inferior to ELCA plus DCB treatment. However, greater ELCA debulking might be required to obtain optimal outcomes.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com