Does ethyl glucuronide in hair correlate with alcohol consumption? A comparative study with other traditional biomarkers among individuals with alcohol dependence syndrome.
Ethyl glucuronide (EtG) in hair is a direct biomarker proven to be useful for the detection of chronic excessive alcohol use. This study investigated the association of self-reported alcohol consumption with traditional biomarkers: GGT, AST, ALT, CDT, and MCV in blood and a direct biomarker, hair EtG, in a total of 122 patients with alcohol dependence syndrome. The diagnostic accuracy of the biomarkers to differentiate heavy from non-heavy drinkers was also evaluated. GGT, AST, and ALT in serum were measured by Automated Chemistry Analyzer, MCV in blood was measured by Haematology Analyzer, serum CDT was analyzed by ELISA, and EtG in hair was evaluated by gas chromatography-mass spectrometry. The association between the biomarkers and the amount of alcohol consumed (self-reported) was determined using Spearman's rank correlation. All participants showed EtG level above the cut-off (0.03 ng/mg). Hair EtG showed a statistically significant linear and positive correlation with the amounts (in grams) of alcohol consumed (r = 0.60; p < 0.001). No correlation was observed among the traditional biomarkers and the quantity of alcohol consumed. Also, EtG showed an excellent receiver operating characteristic (ROC) curve (98%) with good sensitivity (85%) and specificity (60%) to classify heavy drinkers among individuals with alcohol dependence syndrome. Hair EtG can be helpful to estimate retrospective alcohol consumption in long-term chronic alcohol consumption cases. Hair EtG also provides a reliable diagnostic test to detect heavy drinkers among individuals with alcohol dependence syndrome.


Resection of lung metastasis from gallbladder carcinoma: immunohistochemistry of RCAS1 and CD8+T cells in primary and metastatic tumors.
Advanced Gallbladder cancer has an extremely poor prognosis. We examined a patient with resectable gallbladder cancer with associated lung metastasis. A 64-year-old female patient, diagnosed with gallbladder cancer and a solitary benign lung tumor by imaging, was subjected to extensive cholecystectomy and extrahepatic bile duct resection. After one year, a follow-up CT indicated enlargement of the lung tumor; video-assisted right middle lobectomy was then performed. The lung tumor was diagnosed as a metastasis derived from the gallbladder cancer by pathology and immunohistochemistry. Expression of RCAS1, an independent unfavorable prognostic indicator in gallbladder cancer, was observed in both the gallbladder and lung tumors. However, infiltration of CD8+T cells was only seen in the lung metastatic tumor. She has remained free of any evidence of recurrence in the 10 months and 4 years after the first surgery. The results that metastasis is solitary and infiltrated by CD8+T cells correspond with the present clinical history.


Psychiatric disorders in the U.S. transgender population.
The purpose of the study was to determine the prevalence and odds of mental disorder diagnoses at discharge in U.S. transgender hospital encounters as compared with cisgender hospital encounters using nationally representative data. The National Inpatient Sample was used to identify 25,233 transgender and 254,437,363 cisgender inpatient encounters from 2007 to 2014. Univariate analyses were performed to compare the prevalence of mental disorders and comorbid medical diagnoses at the time of discharge. Multivariable analyses controlling for medical comorbid diagnoses were performed to assess the multivariable odds of mental disorder diagnoses in transgender versus cisgender hospital encounters. The prevalence of medical comorbid diagnoses in transgender encounters with and without mental disorder diagnoses was also compared. The prevalence of mental disorder diagnoses was higher in transgender hospital encounters (77% vs. 37.8%, P < .001). The prevalence of each examined mental disorder diagnosis was significantly higher in transgender hospital encounters. A multivariable analysis demonstrated significantly higher odds of all mental disorder diagnoses (odds ratio [OR] = 7.94; confidence interval [CI], 7.63-8.26; P < .001), anxiety (OR = 3.44; CI, 3.32-3.56; P < .001), depression (OR = 1.63; CI, 1.57-1.70; P < .001), and psychosis (OR = 2.46; CI, 2.36-2.56; P < .001) among transgender versus cisgender inpatient encounters. Transgender encounters with a mental disorder diagnosis had a higher prevalence of chronic medical comorbid diagnoses as compared with transgender encounters without mental disorder diagnoses. Our findings suggest a high prevalence and significantly higher odds of mental disorder diagnoses in the transgender population as compared with the cisgender population using data that are nationally representative of the U.S.


[Susceptibility of Aedes albopictus and Culex pipiens quinquefasciatus to infection with bat Japanese encephalitis virus isolates].
To evaluate the susceptibility of Aedes albopictus and Culex pipiens quinquefasciatus to oral infection with bat Japanese encephalitis virus isolates (GD1 and HN2 strains). Aedes albopictus and Culex pipiens quinquefasciatus were infected orally by GD1 and HN2 strains of bat Japanese encephalitis virus. TaqMan real-time PCR was used to detect the virus and monitor the changes in the viral loads in Aedes albopictus and Culex pipiens quinquefasciatus at a 2-day interval, starting from 4 days till 20 days after the infection. The infected Aedes albopictus and Culex pipiens quinquefasciatus were found positive for the Japanese encephalitis virus from day 4 to day 20. Both Aedes albopictus and Culex pipiens quinquefasciatus were susceptible to infection by GD1 and HN2 strains, but the latter showed a greater susceptibility. The HN2 strain virus appeared to have a greater virulence than the GD1 strain. Aedes albopictus and Culex pipiens quinquefasciatus can carry GD1 and HN2 strains of bat Japanese encephalitis virus isolates.


Small and dangerous? Potential toxicity mechanisms of common exposure particles and nanoparticles.
We are continuously exposed to large numbers of non-biological, persistent particulates through dermal, oral and inhalation routes. At sizes perfect for cell interactions, such modern particle exposures are derived from human engineering either purposefully (e.g. additives/excipients) or inadvertently (e.g. pollution). Whether oral or dermal exposure to common particles has significantly adverse effects is not yet known. However, relationships between increased morbidity or mortality and airborne particle exposure are well established. Large nanoparticles and microparticles adsorb environmental molecules, including antigens and allergens, and deliver them to cells potentially with an adjuvant effect. Smaller nanoparticles may have enhanced redox activity due to increased surface areas or band gap effects. Under some circumstances, ultrasmall nanoparticles can ligate cellular receptors or interact with other cell machinery and drive distinct cell signalling. These, as well as the potential for inflammasome activation, are discussed as feasible pathways to understanding or de-bunking particle toxicity.


CNS cell groups projecting to the submandibular parasympathetic preganglionic neurons in the rat: a retrograde transneuronal viral cell body labeling study.
The retrograde transneuronal viral tracing method was used to study the CNS nuclei that innervate the parasympathetic preganglionic neurons controlling the submandibular gland in the rat. A genetically engineered beta-galactosidase expressing Bartha strain of pseudorabies virus (PRV) was injected into the submandibular gland of rats. After 4 days, PRV infected tissues were reacted with the Bluo-Gal substrate (halogenated indolyl-beta-D-galactoside) and labeled cell bodies were identified throughout the brain. In the medulla oblongata, cell body labeling was seen in the superior salivatory nucleus, and throughout the medullary reticular formation as well as in the nucleus of the solitary tract, spinal trigeminal nucleus, and deep cerebellar nuclei. In the pons, PRV labeled neurons were found bilaterally in the locus ceruleus, subceruleus region, and parabrachial complex. In the mesencephalon, labeled cells were found in the Edinger-Westphal nucleus, deep mesencephalic nucleus, and central grey matter. Several hypothalamic regions were labeled including the lateral, perifornical and paraventricular hypothalamic nuclei. In the telencephalon, PRV-positive cell bodies were observed in the substantia innominata, bed nucleus of the stria terminalis and central nucleus of the amygdala. The results suggest that widespread areas of the CNS are involved in control of salivation.


Stage Ia squamous cell carcinoma as the malignant transformation of giant and unusual mature teratoma of the ovary in an elderly patient.
Mature cystic teratomas of the ovary (MCTO) are a type of germ cell tumor that may contain well-differentiated tissues developed from three germ cell layers and constitute about 20% of ovarian germ cell tumors. They are rare ovarian tumors with an annual incidence variable from 1.2 to 14.2 cases per 100,000 that occur mainly in women of reproductive age. They are frequently benign with a slow growth rate, even if they can undergo a malignant transformation in about 1-2% of cases. Here, we present the case of an elderly woman referred to gynecological first aid for acute abdominal pain and showing a giant and unusual MCTO at rapid growth with malignant transformation in squamous cell carcinoma (FIGO stage Ia). The patient underwent pelvic mass removal trough emergency longitudinal midline laparotomic incision with intraoperative frozen pathologic examination. A complete surgical staging during the first surgery was performed. After about 9 years of follow-up, she died of non-oncological reasons without recurrence. Present case highlights that CMTO with malignant transformation should always be suspected in elderly women in presence of pelvic mass at rapid growth, even if in absence of other clinical and ultrasonographic signs of malignancy. An intraoperative frozen pathologic examination may drive the best treatment.


Influence of naloxone on catecholamine release evoked by nicotinic receptor stimulation in the isolated rat adrenal gland.
The present study was designed to investigate the effect of naloxone, a well known opioid antagonist, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal glands, and to establish its mechanism of action. Naloxone (10(-6) approximately 10(-5) M), perfused into an adrenal vein for 60 min, produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh (5.32 x 10(-3) M), high K+ (5.6 x 10(-2) M), DMPP (10(-4) M) and McN-A-343 (10(-4) M). Naloxone itself also failed to affect the basal CA output. In adrenal glands loaded with naloxone (3 x 10(-6) M), the CA secretory responses evoked by Bay-K-8644, an activator of L-type Ca2+ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic Ca(2+)-ATPase, were also inhibited. In the presence of met-enkephalin (5 x 10(-6) M), a well known opioid agonist, the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Taken together, these results suggest that naloxone greatly inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that these inhibitory effects of naloxone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of Ca2+ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.


Recent Recommendations and Emerging Science in Neonatal Resuscitation.
The Neonatal Resuscitation Program, initially an expertise- and consensus-based approach, has evolved into an evidence-based algorithm. Ventilation remains the key component of successful resuscitation of neonates. Recent changes in recommendations include management of cord clamping, multiple methods to prevent hypothermia, rescinding of mandatory intubation and suction of the nonvigorous meconium-stained infant, electrocardiographic monitoring, and establishing an airway for ventilation before initiation of chest compressions. Emerging science, including issues such as cord milking, oxygen targeting, and laryngeal mask use, may lead to future program modifications. Technology such as video laryngoscopy and telemedicine will affect the way training and care is delivered.


Risk management of sediment stress: a framework for sediment risk management research.
Research related to the ecological risk management of sediment stress in watersheds is placed under a common conceptual framework in order to help promote the timely advance of decision support methods for aquatic resource managers and watershed-level planning. The proposed risk management research program relies heavily on model development and verification, and should be applied under an adaptive management approach. The framework is centered on using best management practices (BMPs), including eco-restoration. It is designed to encourage the development of numerical representations of the performance of these management options, the integration of this information into sediment transport simulation models that account for uncertainty in both input and output, and would use strategic environmental monitoring to guide sediment-related risk management decisions for mixed land use watersheds. The goal of this project was to provide a sound scientific framework based on recent state of the practice in sediment-related risk assessment and management for research and regulatory activities. As a result, shortcomings in the extant data and measurement and modeling tools were identified that can help determine future research direction. The compilation of information is beneficial to the coordination of related work being conducted within and across entities responsible for managing watershed-scale risks to aquatic ecosystems.


[Critical remarks on the surgical treatment of syndactylia (author's transl)].
The technique of surgery for syndactylia is described in detail. The author's opinion about the optimal age for surgical correction of equally or unequally long fingers is reported. The importance of early intervention in case of complicated syndactylia is stressed. Until growth has come to an end, continuous follow-up is necessary for early recognizing late contractures.


The heparan sulfates of Swiss mouse 3T3 cells. The effect of transformation.
Three major pools of heparan sulfate have been isolated from cultures of Swiss mouse 3T3 and SV40-transformed 3T3 cells: cell-surface, medium, and intracellular heparan sulfates. The cell-surface heparan sulfate is a high molecular weight proteoglycan which is partially degraded by pronase. Before pronase treatment, it has a peak molecular weight (as estimated by gel filtration) of approx. 7.2 . 10(5) in contrast to only 2.4 . 10(5) after pronase treatment. The medium heparan sulfate appears to be similar in structure to the cell-surface heparan sulfate, since they coelute on Bio-Gel A-15m and DEAE-cellulose, and are both proteoglycans. In contrast, the intracellular heparan sulfate has a low molecular weight (6.0 . 10(3)) and has little if any attached protein. Both the medium and intracellular heparan sulfate exhibit the transformation-associated change in structure reported earlier for cell-surface heparan sulfate (Underhill, C.B. and Keller, J.M. )1975) Biochem. Biophys. Res. Commun. 63, 448--454). This transformation-associated change, detected by DEAE-cellulose chromatography is not the result of changes in either molecular weight or protein core. Cellulose acetate electrophoresis of the cell-surface heparan sulfate at pH 1 suggests that the transformation-associated change in structure is due to a difference in sulfate content. Both types of heparan sulfate are produced in mixed cultures of 3T3 and SV3T3 cells, indicating that neither serum factors in the culture medium nor secreted cell products are responsible for the transformation-associated change in heparan sulfate structure. The presented data are discussed with respect to the postulated role of heparan sulfate in cell social behavior.


Investigating biochemical and structural changes of glycated collagen using multimodal multiphoton imaging, Raman spectroscopy, and atomic force microscopy.
Advanced glycation end products (AGEs) form extracellular crosslinking with collagenous proteins, which contributes to the development of diabetic complications. In this study, AGEs-related pentosidine (PENT) crosslinks-induced structural and biochemical changes are studied using multimodal multiphoton imaging, Raman spectroscopy and atomic force microscopy (AFM). Decellularized equine pericardium (EP) was glycated with four ribose concentrations ranging between 5 and 200 mM and monitored for up to 30 days. Two-photon excited fluorescence (TPEF) and second harmonic generation (SHG) microscopic imaging probed elastin and collagen fibers, respectively. The glycated EP showed a decrease in the SHG intensities associated with loss of non-centrosymmetry of collagen and an increase of TPEF intensities associated with PENT crosslinks upon glycation. TPEF signals from elastin fibers were unaffected. A three-dimensional reconstruction with SHG + TPEF z-stack images visualized the distribution of collagen and elastin within the EP volume matrix. In addition, Raman spectroscopy (RS) detected changes in collagen-related bands and discriminated glycated from untreated EP. Furthermore, AFM scans showed that the roughness increases and the D-unit structure of fibers remained unchanged during glycation. The PENT crosslinked-induced changes are discussed in the context of previous studies of glutaraldehyde- and genipin-induced crosslinking and collagenase-induced digestion of collagen. We conclude that TPEF, SHG, RS, and AFM are effective, label-free, and non-destructive methods to investigate glycated tissues, differentiate crosslinking processes, and characterize general collagen-associated and disease-related changes, in particular by their RS fingerprints.


Comprehensive and Methodical: Diagnostic and Management Approaches to Rapidly Progressive Dementia.
Purpose of review The sudden emergence of a change in cognitive abilities or behavior is an important symptom that warrants medical evaluation and may represent the early stages of a rapidly progressive dementia (RPD). To correctly ascertain the cause of RPD in a given patient, the clinician must be methodical and knowledgeable about the range of potential causes and must move forward with supportive treatment, and in some cases empiric treatment, based on clinical features alone. Recent findings Significant advances in prion disease biomarkers, the molecular features of rapidly progressive Alzheimer's disease, and new detection of autoimmune limbic encephalitis disease entities have caused a shift in the diagnostic and treatment framework of RPD. Additionally, in the past decade, emerging retrospective data have led to suggested treatments in autoimmune encephalitis that, if instituted early, can protect patients against residual deficits and disease relapse. Summary Here, we provide an integrative clinical and diagnostic treatment approach that is applicable to the various forms of RPD. We have highlighted the clinical features of selected types of RPD that have experienced advances in the last 10-15 years.


[Deep brain stimulation of subthalamic nucleous in Parkinson's disease].
We present the preliminary results in patients well selected to be implanted by deep brain stimulation (DBS) for Parkinsons's disease (PD). 8 PD patients with disabled tremor, akinetic/bradikinetic and rigidity, in spite of best therapeutic assay with poor response were referred to surgery. It was implanted DBS Itrell 2. Theses patients were evaluated by the following scales: UPDRS, Schwab and England. The preliminary results in 6 months showed significant improvement of motor performance and it is shown by the scores. There were no complications so far with these procedures. The preliminary results indicate that DBS is highly effective, with benefit to those patients and it is according to literature.


1,25(OH)2D deficiency induces temporomandibular joint osteoarthritis via secretion of senescence-associated inflammatory cytokines.
1,25-Dihydroxyvitamin D [1,25(OH)(2)D] insufficiency appears to be associated with several age-related diseases. Insufficient levels of serum 25-hydroxyvitamin D has been shown to lead to the progression of osteoarthritis (OA) while underlying biological mechanisms remain largely unknown. In this study, we sought to determine whether 1,25(OH)(2)D deficiency has a direct effect on the process of murine temporomandibular joint (TMJ) OA in 25-hydroxyvitamin D 1α-hydroxylase knockout [1α(OH)ase(-/-)] mice that had been fed a rescue diet (high calcium, phosphate, and lactose) from weaning until 6 or 18 months of age. Our results showed that the bone mineral density and subchondral bone volume were reduced in mandibular condyles, articular surfaces were collapsed, the thickness of articular cartilage and cartilage matrix protein abundance were progressively decreased and eventually led to an erosion of articular cartilage of mandibular condyles. We also found that DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines were increased significantly in 1α(OH)ase(-/-) mice. This study demonstrates that 1,25(OH)(2)D deficiency causes an erosive TMJ OA phenotype by inducing DNA damage, cellular senescence and the production of senescence-associated inflammatory cytokines. Our results indicate that 1,25(OH)(2)D plays an important role in preventing the development and progression of OA.


Subnational responsibilities for healthcare and Austria's rejection of the EU's patients' rights directive.
In 2011, Member States and the European Parliament brought into force a Directive on the application of patients' rights in cross-border healthcare within the EU. Austria voted against this directive even though its national legislation was already in line with the rulings of the European Court of Justice which had triggered the negotiations on the directive. Why then, in the absence of any legal constraints on adapting to it, did Austria vote against the directive? The article argues that it was the federal structure of financing hospital infrastructure and the subnational level's influence on national position building which led to the rejection of the directive. The article retraces the process of position building by analyzing the interaction between the national and the subnational levels and concludes that Austria's position mirrors the national struggle between both levels of government over control of the hospital sector.


Ethanol modulates epidermal growth factor-stimulated tyrosine kinase and phosphorylation of PLC-gamma 1.
A431 cells have an abundance of Epidermal Growth Factor (EGF) receptors which possess intrinsic tyrosine kinase activity. Treatment of membranes isolated from A431 cells with EGF caused a 2-3 fold increase in phosphorylation of a synthetic peptide (Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly) which is a substrate for tyrosine kinase. Treatment of these membranes with 0.1 to 100 mM ethanol altered basal tyrosine kinase activity in a biphasic manner; increase at 10 mM and decrease at 100 mM ethanol. The treatment of the membranes with the same concentrations of ethanol also altered EGF's ability to stimulate tyrosine kinase activity: increase at 0.1 mM ethanol and decrease at 10 mM. Strikingly, EGF-stimulated tyrosine kinase was more sensitive to ethanol than the basal activity. Experiments with other alcohols showed a relationship between chain length and the inhibitory ability of the alcohol. These data demonstrate a biochemical effect of low concentrations of ethanol on tyrosine kinase. Interestingly, ethanol treatment of A431 cells inhibited EGF-stimulated phosphorylation of PLC-gamma 1 which is a substrate for EGF receptor tyrosine kinase. It is concluded that ethanol at low concentrations has significant modulatory effect on basal and EGF-stimulated tyrosine kinase, as well as PLC-gamma 1 phosphorylation.


Evaluation of antimicrobial photodynamic therapy on wounds infected by Staphylococcus aureus in animal models.
Antibiotic-resistant Staphylococcus aureus bacteria are one of the expanding challenges. The purpose of current study is to evaluate the antimicrobial effect of photodynamic therapy (aPDT) on wounds infected to Staphylococcus aureus. In this study, 40 six-month-old rats were divided into 4 groups: control, photosensitizer (PS), laser, and aPDT. A full-thickness wound was created on their skin and it was infected by Staphylococcus aureus. For aPDT, the Indocyanine Green (Germany, Nürnberg, A.R.C. Laser, EmunDo) photosensitive agent and laser diod 810 nm (Germany, Nürnberg, A.R.C. Laser) was utilized. The wound healing procedure was monitored every 24 h until the 12th day with photography. The number of the bacteria was counted on the 12th day also. All results were compared using ANOVA and Tukey post hoc tests. Significance level was considered P-Value < 0.05. The average area of wound reduced in days 5-11th in photosensitizer, laser, and aPDT, respectively. The absolute colonization rate of bacteria in the wounds showed a significant decrease in two groups laser and aPDT compared to the control group. However, the lowest value was for the aPDT. In the conditions of this study, it emerged that aPDT and laser have an antimicrobial effect against antibiotic-resistant bacteria (particularly Staphylococcus aureus) and improve wound healing.


Multidimensional scaling analysis of virus diseases.
Viruses are infectious agents that replicate inside organisms and reveal a plethora of distinct characteristics. Viral infections spread in many ways, but often have devastating consequences and represent a huge danger for public health. It is important to design statistical and computational techniques capable of handling the available data and highlighting the most important features. This paper reviews the quantitative and qualitative behaviour of 22 infectious diseases caused by viruses. The information is compared and visualized by means of the multidimensional scaling technique. The results are robust to uncertainties in the data and revealed to be consistent with clinical practice. The paper shows that the proposed methodology may represent a solid mathematical tool to tackle a larger number of virus and additional information about these infectious agents.


Systematic review and meta-analysis of the efficacy and hypoglycemic safety of gliclazide versus other insulinotropic agents.
Sulfonylureas are well positioned in treating type 2 diabetes, after lifestyle modification and metformin. The sulfonylurea gliclazide was given preference over glibenclamide in older people with type 2 diabetes in the World Health Organization model list of essential medicines. Consequently, a systematic review and meta-analysis of randomized controlled trials of the efficacy and safety of gliclazide versus other oral insulinotropic agents (sulfonylureas, dipeptidyl peptidase-4 inhibitors, and glinides) was performed. Two reviewers searched MEDLINE for studies of ≥12 weeks duration in adults with type 2 diabetes. The key search word was "gliclazide", filtered with "randomized controlled trial", "human" and "19+ years". Differences were explored in mean change in glycated hemoglobin (HbA(1c)) from baseline (primary outcome) and risk of hypoglycemia (secondary outcome) between gliclazide and other oral insulinotropic agents; and other sulfonylureas. Nine out of 181 references reported primary outcomes, of which 7 reported secondary outcomes. Gliclazide lowered HbA1c more than other oral insulinotropic agents, with a weighted mean difference of -0.11% (95%, CI -0.19 to -0.03%, P=0.008, I(2)=60%), though not more than other sulfonylureas (-0.12%; 95%, CI -0.25 to 0.01%, P=0.07, I(2)=77%). Risk of hypoglycemia with gliclazide was not different to other insulinotropic agents (RR 0.85; 95%, CI 0.66 to 1.09, P=0.20, I(2)=61%) but significantly lower than other sulfonylureas (RR 0.47; 95%, CI 0.27 to 0.79, P=0.004, I(2)=0%). Compared with other oral insulinotropic agents, gliclazide significantly reduced HbA1c with no difference regarding hypoglycemia risk. Compared with other sulfonylureas, HbA1c reduction with gliclazide was not significantly different, but hypoglycemia risk was significantly lower.


Basal autonomic activity, stress reactivity, and increases in metabolic syndrome components over time.
Basal autonomic nervous system (ANS) functioning has been linked to the metabolic syndrome (MetS), but the role of ANS reactivity in response to stress remains unclear. To examine cross-sectionally and longitudinally to what extent ANS basal level and stress reactivity are related to MetS. 2-year and 6-year data from a prospective cohort: the Netherlands Study of Depression and Anxiety. Participants were recruited from the general community, primary care, and mental health care organizations. 1922 respondents (mean age=43.7years). Indicators of ANS functioning were heart rate (HR), respiratory sinus arrhythmia (RSA) and pre-ejection period (PEP). ANS stress reactivity was measured during a cognitively challenging stressor and a personal-emotional stressor. MetS components included triglycerides, high-density lipoprotein cholesterol, blood pressure, glucose and waist circumference. Cross-sectional analyses indicated that higher basal HR, lower basal values of RSA and PEP, and higher RSA reactivity during cognitive challenge were related to less favorable values of almost all individual MetS components. Longitudinal analyses showed that higher basal HR and shorter basal PEP predicted 4-year increase in many MetS abnormalities. Higher RSA stress reactivity during cognitive challenge predicted 4-year increase in number of MetS components. Higher basal sympathetic, lower basal parasympathetic activity, and increased parasympathetic withdrawal during stress are associated with multiple MetS components, and higher basal sympathetic activity predicts an increase in metabolic abnormalities over time. These findings support a role for ANS dysregulation in the risk for MetS and, consequently, the development of cardiovascular disease.


Associations Between Diabetic Retinal Microvasculopathy and Neuronal Degeneration Assessed by Swept-Source OCT and OCT Angiography.
Purpose: To provide clinical evidence of the associations between retinal neuronal degeneration and microvasculopathy in diabetic retinopathy (DR). Methods: This case-control study included 76 patients (76 eyes) with type 2 diabetes mellitus (DM), and refraction error between -3.0 and +3.0 D. The eyes were assigned into DM (without DR), non-proliferative DR (NPDR), and proliferative DR (PDR) groups. Age-, sex-, and refractive error-matched normal subjects were enrolled as controls. The mean retinal thickness (mRT), the relative mean thickness of the retinal nerve fiber layer (rmtRNFL, mtRNFL/mRT), ganglion cell layer (rmtGCL), ganglion cell complex (rmtGCC) layer, foveal avascular zone area (FAZa), FAZ perimeter (FAZp), FAZ circularity index (FAZ-CI), and vessel density (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP) were assessed by swept-source optical coherence tomography (OCT) and OCT angiography (OCTA). Group comparison and Spearman's partial correlation coefficient analysis were applied to evaluate the correlation between these morphological parameters. Results: rmtRNFL, FAZa, and FAZp in SCP and DCP increased with the DR severity (p rmtRNFL < 0.001; p FAZa, SCP = 0.001; p FAZa , DCP = 0.005; p FAZp , SCP < 0.001; p FAZp , DCP < 0.001). The rmtGCL, FAZ-CI in SCP and DCP, and VD in DCP decreased with the DR severity (p rmtGCL = 0.002, p FAZ-CI , SCP = 0.002; p FAZ-CI, DCP < 0.001, p VD , DCP < 0.001). After controlling age, sex, duration of diabetes, and hypertension, the rmtRNFL, FAZa in SCP and DCP, and FAZp in SCP and DCP were correlated with the severity of DR (p < 0.05), while VD in SCP and DCP, FAZ-CI, and rmtGCL were negatively correlated with the severity of DR (p < 0.05). The rmtGCL was negatively correlated with the FAZa in SCP (r = -0.34, p = 0.002) and DCP (r = -0.23, p = 0.033), and FAZp in SCP (r = -0.37, p = 0.001) and DCP (r = -0.32, p = 0.003), but positively correlated with VD in SCP (r = 0.26, p = 0.016), VD in DCP (r = 0.28, p = 0.012), and FAZ-CI in DCP (r = 0.31, p = 0.006). Conclusions: rmtRNFL, FAZ-CI in SCP and DCP, and FAZp in SCP are strong predictors of the severity of DR. The ganglion cell body loss is highly correlated with increased FAZp and FAZa, decreased FAZ-CI, and reduced VD with the severity of DR.


Hotspot and trend analysis of forest fires and its relation to climatic factors in the western Himalayas.
Forest fire is one of the main issues of forest ecosystems around the world which has resulted in loss of biodiversity, forest degradation, soil erosion, and greenhouse gas emission. Ironically, the information on the forest fire regime and its pattern are still lacking in the Himalayan region. In this study, Moderate-Resolution Imaging Spectroradiometer active fire data products from 2001 to 2020 have been analysed for understanding the forest fire trends and its hotspots patterns during the active fire season (February to June). About 1347 average fire counts/year were recorded in six natural vegetations with the highest number of fires observed during the year 2012 (n = 3096) and minimum in 2011 (n = 210). Mann-Kendall trends analysis for the spatial and temporal pattern of fires indicated that there is a significant increase of forest fires towards higher elevation. Forest fire hotspot analysis using fire radiative power, fire frequency, and fire density showed that Uttarakhand is the most forest fire-prone state as compared to other north-western Himalayan states. It is also revealed that the May month has a higher number of fire counts and the evergreen needle forests have higher fire frequencies amongst the forest types. The forest fires were found to be more influenced by land surface temperature as compared to rainfall. The outcomes in this study on the temporal and spatial patterns for forest fire can be used for forest fire modelling. The online version contains supplementary material available at 10.1007/s11069-022-05530-5.


Intravenous Immunoglobulin as a Treatment for Intractable Epilepsy Secondary to Focal Cortical Dysplasia: A Meta-analysis.
The observation of a dramatic response to intravenous immunoglobulin (IVIG) by a child from our center with intractable epilepsy due to focal cortical dysplasia prompted us to perform a meta-analysis on the efficiency of IVIG in this condition. Focal cortical dysplasia is a common cause of intractable epilepsy. Microglial activation and upregulation of neuroinflammatory pathways have been documented in brain specimen from surgically treated patients with intractable epilepsy and focal cortical dysplasia. IVIG has been used for decades to treat patients with intractable epilepsy; however, there is little evidence regarding its efficacy, possibly because of the pathophysiological heterogeneity of patients included in most of the published studies. A search for studies in patients from 0 to 18 years was performed in databases. We found four observational studies-prospective or retrospective-including patients with focal cortical dysplasia with intractable epilepsy treated with IVIG. The primary outcome was a reduction of seizure frequency by more than 50%. A total of eight patients were included in this meta-analysis. The intravenous immunoglobulin doses ranged from 0.2 to 1 g/kg/day, repeated three to six times over one to 14 months (median: five months). Intravenous immunoglobulin was associated with reduced seizure frequency in six out of eight patients (P < 0.05). Among these six patients, the reduction of seizure frequency lasted for nine months to nine years (median: 3.7 years). There were either no or mild adverse effects of IVIG infusion including postinfusion paresthesia (n = 1) and a transient increase in temperature (n = 1). Despite obvious limitations, mainly because of the small number of patients, and the selection biases, this study suggests that, based on the available data, IVIG might be effective in the treatment of intractable epilepsy secondary to focal cortical dysplasia. Further therapeutic trials are mandatory to further clarify the efficacy of IVIG in this condition.


rRNA-based analysis to monitor succession of faecal bacterial communities in Holstein calves.
To quantitatively analyse the faecal bacterial communities of Holstein calves and track their succession up to 12 weeks of age. Faecal samples obtained from four female Holstein calves were analysed by the RNA-based, sequence-specific rRNA cleavage method. Twelve scissor probes covering major rumen bacterial groups were used, detecting c. 60-90% of the total 16S rRNAs. At 1 week of age, 16S rRNAs from members of the Bacteroides-Prevotella group (40·0% of the total 16S rRNAs), Faecalibacterium (21·7%), the Clostridium coccoides-Eubacterium rectale group (16·7%) and the Atopobium cluster (10·9%) were detected at high levels. Throughout the 12-week period, rRNAs of the Bacteroides-Prevotella and the Cl. coccoides-Eu. rectale groups constituted the major fraction of microbiota (c. 50-70% of the total). The relative abundances of the Atopobium cluster, Faecalibacterium, and some probiotic bacteria (such as those of the genera Lactobacillus and Bifidobacterium) decreased as the animal aged. Instead, an uncultivated rumen bacterial group, as well as Ruminococcus flavefaciens and Fibrobacter emerged at the detectable levels (1-2%) in the faeces sampled at a postweaning age. In addition, certain bacterial groups that were not covered by the probe suite increased as the animals aged. Young calves undergo dynamic changes in their intestinal bacterial community during the first 12 weeks of life. As young ruminants undergo metabolic and physiological development in their digestive tracts in the transition from a monogastric to a ruminant animal at an early age, the intestinal bacterial community may reflect such development. The succession of the bacterial communities in the faeces of calves was quantitatively monitored in the present study for the first time. The approach used here was demonstrated to be a useful means for determining the populations of predominant faecal bacterial groups in a variety of calf experiments in response to diet, stress and disease.


Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication.
The ability of PRC1 and PRC2 to promote proliferation is a main feature that links polycomb (PcG) activity to cancer. PcGs silence the expression of the tumour suppressor locus Ink4a/Arf, whose products positively regulate pRb and p53 functions. Enhanced PcG activity is a frequent feature of human tumours, and PcG inhibition has been proposed as a strategy for cancer treatment. However, the recurrent inactivation of pRb/p53 responses in human cancers raises a question regarding the ability of PcG proteins to affect cellular proliferation independently from this checkpoint. Here we demonstrate that PRCs regulate cellular proliferation and transformation independently of the Ink4a/Arf-pRb-p53 pathway. We provide evidence that PRCs localize at replication forks, and that loss of their function directly affects the progression and symmetry of DNA replication forks. Thus, we have identified a novel activity by which PcGs can regulate cell proliferation independently of major cell cycle restriction checkpoints.


Successful treatment of refractory brain metastases from ALK-positive lung cancer with lorlatinib.
A 44-year-old woman with ALK-positive advanced adenocarcinoma of the lung was treated with crizotinib, and the lung lesions disappeared. The patient was treated with alectinib and chemotherapy, but brain metastases worsened; therefore, we performed an ALK resistance gene mutation test using plasma samples. Since no ALK resistance gene mutations were detected, we speculated that ALK inhibitors failed to achieve therapeutic effects due to poor transport to the central nervous system. Therefore, we switched to lorlatinib, and found a reduction in brain metastases. In ALK-positive advanced lung cancer, plasma-based resistance gene testing may be useful for treatment decisions.


Chloramphenicol-promoted increase in resistance to UV damage in Escherichia coli B/r WP2 trpE65: development of the capacity for successful repair of otherwise mutagenic or lethal lesions in DNA.
The ultraviolet radiation survival curve of exponentially growing cultures of Escherichia coli B/r WP2 trpE65 was modified by a short period (20 min) of chloramphenicol treatment before UV exposure, which produced an extended exponential section of intermediate slope between the shoulder and the final exponential slope. More prolonged incubation with chloramphenicol (up to 90 min) resulted in little further extension of the intermediate exponential slope, but caused a progressive expansion of the shoulder region. With each period of chloramphenicol pretreatment, a major surge of mutation to tryptophan independence always occurred after that UV fluence promoting the transition from the shoulder to the intermediate exponential slope of the survival curve, and another major surge occurred after that fluence promoting the transition from the intermediate exponential slope to the final exponential slope. A minor surge of mutation occurred after low fluences. The 3 surges in mutation and the increased slopes of the survival curve are ascribed to UV-inactivation of 3 qualitatively different DNA-repair systems, each with differentially increased resistances to UV caused by pretreatment by chloramphenicol.


[Nursing students, the poor relation of the health care system].
Even if nursing students have obtained social progress following different periods of mobilization and negotiations, we must admit that their situation remains worrying. Many of them live in precariousness and undergo very difficult training conditions. Instrumentalized, even mistreated, by caregivers who are at the end of their rope because they work in institutions that are in a critical situation, the students no longer learn and perform the tasks of the missing staff. The Covid-19 crisis is a striking example of this.


[Papillary cystadenoma of the epididymis. Apropos of a rare case in a patient with grade III varicocele].
Primary tumours of the epididymis are rare and one of the rarest is papillary cysto-adenomas. For this reason, a case arising in a patient with Grade III varicocele seemed worth reporting. The report discusses the clinical case and describes the histological characteristics of the tumour.


The nutritional state of male tsetse flies, Glossina pallidipes, at the time of feeding.
The feeding intervals of tsetse flies have been estimated from the nutritional state of flies caught in traps. However, such estimates have been disputed on the grounds that traps catch a biased, hungry sample of the flies which are seeking hosts and will feed. In this paper we present data on the nutritional state of tsetse flies caught approaching and feeding on oxen. Individual oxen were surrounded with an incomplete ring of electric nets which caught Glossina pallidipes Austen that were approaching, departing unfed and departing fed from an ox. Non-teneral males caught in this way were analysed for their fat and haematin contents. The feeding interval was estimated from a comparison of the frequency distributions of the pre- and post-feed haematin contents of the flies which fed. The former was not measured directly, and was deduced from the frequency distributions of the haematin contents of the male flies caught approaching and departing unfed from the oxen, since it is assumed that the departing unfed and fed flies together form a sample of the approaching flies. There was no difference between the frequency distributions of haematin contents of flies caught approaching and departing unfed, and therefore the pre-feed haematin contents of the males which fed should have the same frequency distribution. Comparison of this distribution with that of the post-feed haematin contents of the males which fed indicated that the majority of male G.pallidipes were returning to feed after digesting on average 1.4 log haematin units of the previous bloodmeal.(ABSTRACT TRUNCATED AT 250 WORDS)


Implementing biofuels on a global scale.
Is the introduction of renewable biofuels a simple problem of technology development and diffusion or does it require an industrial revolution?


A validated software application to measure fiber organization in soft tissue.
The mechanical behavior of soft connective tissue is governed by a dense network of fibrillar proteins in the extracellular matrix. Characterization of this fibrous network requires the accurate extraction of descriptive structural parameters from imaging data, including fiber dispersion and mean fiber orientation. Common methods to quantify fiber parameters include fast Fourier transforms (FFT) and structure tensors; however, information is limited on the accuracy of these methods. In this study, we compared these two methods using test images of fiber networks with varying topology. The FFT method with a band-pass filter was the most accurate, with an error of [Formula: see text] in measuring mean fiber orientation and an error of [Formula: see text] in measuring fiber dispersion in the test images. The accuracy of the structure tensor method was approximately five times worse than the FFT band-pass method when measuring fiber dispersion. A free software application, FiberFit, was then developed that utilizes an FFT band-pass filter to fit fiber orientations to a semicircular von Mises distribution. FiberFit was used to measure collagen fibril organization in confocal images of bovine ligament at magnifications of [Formula: see text] and [Formula: see text]. Grayscale conversion prior to FFT analysis gave the most accurate results, with errors of [Formula: see text] for mean fiber orientation and [Formula: see text] for fiber dispersion when measuring confocal images at [Formula: see text]. By developing and validating a software application that facilitates the automated analysis of fiber organization, this study can help advance a mechanistic understanding of collagen networks and help clarify the mechanobiology of soft tissue remodeling and repair.


Blood lactate concentration after exposure to conducted energy weapons (including TASER® devices): is it clinically relevant?
In previous studies, blood lactate concentration (BLac) consistently increased in anesthetized animals and in human subjects after exposures to TASER(®) conducted energy weapons (CEWs). Some have suggested the increased BLac would have detrimental consequences. In the current review, the following are evaluated: (a) the nature of muscle contractions due to CEWs, (b) general aspects of increased BLac, (c) previous studies of conventional neuromuscular electrical stimulation and CEW exposures, and (d) BLac in disease states. On the basis of these analyses, one can conclude that BLac, per se (independent of acidemia), would not be clinically relevant immediately after short-duration CEW applications, due to the short time course of any increase.


Describing clinical teachers' characteristics and behaviours using critical incidents and repertory grids.
Completion of a rating questionnaire is the method used most frequently to evaluate a teacher's performance. Questionnaires that largely assess 'high-inference' teaching characteristics, such as 'enthusiasm' and 'friendliness', require the observer to make a judgement about the teacher but do not describe what the teacher actually did and so have limited use in providing feedback. Measures of 'low-inference' teaching behaviours (i.e. those that are concrete and observable), such as frequency, amount or types of verbal interaction, do not demonstrate how these are linked to good teaching. To describe high-inference teacher characteristics and define the associated low-inference behaviours. A purposive sample of consultants, postgraduate and undergraduate students, nurse lecture practitioners and patients were selected for semistructured interviews using repertory grids and critical incidents to elicit preferred characteristics and behaviours of clinical teachers. Interviews were audiotaped, transcribed and then content-analysed using a framework to pair teachers' characteristics and their behaviours. We identified a variety of preferred high-inference characteristics and their associated observable and recordable low-inference behaviours. We carried out a study that included all participants in clinical teaching and found that participants differed in their preferred characteristics and behaviours. It is important for future research to look at behaviours interdependently, rather than alone, and to take into account the evidence that participants tend to infer characteristics rather than think in terms of behaviours. This information will be used to inform the development of a formative tool for evaluating clinical teaching.


Acceptability, feasibility, and efficacy of Internet cognitive behavioral therapy (iCBT) for pediatric obsessive-compulsive disorder: a systematic review.
Obsessive-compulsive disorder (OCD) is a chronic mental health disorder characterized by recurring obsessions and compulsions affecting 1-3% of children and adolescents. Current treatment options are limited by accessibility, availability, and quality of care. New technologies provide opportunities to address at least some of these challenges. This paper aims to investigate the acceptability, feasibility, and efficacy of traditional cognitive behavioral therapy with Internet cognitive behavioral therapy (iCBT) for pediatric OCD according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched EMBASE, Medline, PsycINFO, CENTRAL, LILACS, CINAHL, and Scopus. Results include articles from 1987 to March 2018. Main inclusion criteria were patients aged 4-18, primary diagnosis of OCD, and iCBT. Of the 2323 unique articles identified during the initial search, six studies with a total of 96 participants met our inclusion criteria: three randomized controlled trials, one single-case multiple-baseline design, one open-label trial, and one case series. Four studies reported a significant decrease in OCD severity on the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) following iCBT, one study reported significant decrease in CY-BOCS scores for iCBT relative to waitlist, and the case series reported (some) symptom reduction in all participants. Six studies reported high rates of feasibility, and five studies reported good acceptability of iCBT. At present, evidence regarding acceptability, feasibility, and efficacy of iCBT for pediatric OCD is limited. Results are promising but need to be confirmed and refined in further research. PROSPERO CRD4201808587.


A nonfunctioning single nucleotide polymorphism in olfactory receptor gene family is associated with the forced expiratory volume in the first second/the forced vital capacity values of pulmonary function test in a Japanese population.
The forced expiratory volume in the first second (FEV1.0)/the forced vital capacity (FVC) is an important index of a single forced expiration. Ectopic expression of the human olfactory receptor (OR) gene family in the lungs has suggested its potential involvement of respiratory physiology. We hypothesized that the individual variability of FEV1.0/FVC value may be attributed to the genetic variance of the OR gene family caused by the nonfunctioning SNPs (nSNPs). We conducted quantitative trait locus (QTL) analyses of population having the 7 OR gene nSNPs and FEV1.0/FVC values by ANOVA, in 2970 samples in the Yamagata Takahata cohort. We found significant association of one nSNP [rs10838851, OR, family 4, subfamily X, member 1 (OR4X1) gene, Tyr273Ter*] with FEV1.0/FVC (%) (P = 0.008). The FEV1.0/FVC value (%) of population having OR4X1 gene nSNP Ter*/Ter*, Ter*/Tyr, and Tyr/Tyr were 78.9 +/- 0.2, 78.2 +/- 0.2, and 77.7 +/- 0.4, respectively. Haplotype-based analysis of the OR4X1 gene with FEV1.0/FVC values demonstrated that two exclusive haplotypes [Hap-1/Hap-2 (frequency 0.669/0.330): SNP1 (rs7106648)T/A-SNP2 (rs871249)G/A-SNP3 (rs713325)G/A-SNP4 (rs10838851)A (Ter*)/T (Tyr)-SNP5 (rs4752923)G/A-SNP6 (rs960640)G/A] were significantly associated with FEV1.0/FVC values (global P = 0.005). These results suggest that OR4X1 may be one of the genes that contribute to the individual variability of FEV1.0/FVC value in pulmonary function test.


A liquid chromatography-mass spectroscopy-based untargeted metabolomic study of the rat cochlear nucleus at various stages of maturity.
The cochlear nucleus receives numerous inputs from auditory and nonauditory systems. This extensive innervation of the cochlear nucleus is involved in sound source localization and the integration of auditory signals with other sensory modalities. The dorsal cochlear nucleus may also have an important role in tinnitus. Although its gross anatomy and function have been extensively studied, the metabolome of the cochlear nucleus remains poorly understood, particularly at different stages of auditory maturity. Here, we present a protocol for untargeted metabolomics analysis of the rat cochlear nucleus, then discuss differences in the metabolome of the rat cochlear nucleus between postnatal day (PD) 14 (hearing onset) and PD60 (hearing maturation). Cochlear nucleus samples collected from rats at PD14 or PD60 were analyzed by liquid chromatography-tandem mass spectrometry (LCMS). In total, 344 metabolites were identified. Principal component analysis and orthogonal partial least-square discriminant analysis showed that the metabolic profiles at these two stages had distinct distribution patterns. Moreover, 91 significantly differential metabolites (62 upregulated and 29 downregulated) were identified at PD60 vs. PD14. N-acetylaspartylglutamic acid (NAAG), γ-aminobutyric acid (GABA), taurine, adenosine monophosphate (AMP), and choline were significantly upregulated at PD60. Pathway enrichment analysis suggested that alanine, aspartate, and glutamate metabolism; glycine, serine, and threonine metabolism; the mammalian target of rapamycin (mTOR) signaling pathway; and the AMP-activated protein kinase (AMPK) signaling pathway may be involved in key developmental events during maturation of the cochlear nucleus. Taken together, the metabolic profiles identified in this study could lead to the identification and understanding of specific key biomarkers and metabolic pathways involved in the maturation of hearing. Moreover, LC-MS-based metabolomics provides an alternative approach for the characterization of auditory maturation and auditory diseases.


Polarization optical analysis of blood cell membranes.
The present study deals with investigations of membrane structure using polarization topo-optical reactions. Polarization microscopy is a special field of biological submicroscopic morphology. It represents a powerful tool well able to reveal the features of organization of biological structures, and the regularity of macromolecules building cells and tissues - properties that cannot directly be studied by other approaches to complex biological systems. Only in "pure" systems can X-ray diffraction, or the analysis of circular dichroism and the dispersion of optical rotability provide data equivalent to those obtained by polarization microscopy in complex systems. One of the main drawbacks of molecular biology is that most information is relevant to isolated, purified particles or macromolecules. Thus, no conclusions can be drawn concerning the original arrangement of molecules. The gap between biochemical-biophysical and morphological approaches to molecular arrangement in complex structures is bridged by the polarization optical technique. As was pointed out in the introduction, polarization microscopy became a routine biological research method following the pioneering work of Romhányi. His enlightening topo-optical reactions (Romhányi 1960, 1963, 1966) were based on the oriented dye binding of the original charge carriers of regularly arranged tissue constituents. The second group of Romhányi's topo-optical reactions comprised procedures such as sulfation (Romhányi et al. 1973, 1974), the aldehyde-bisulfite-toluidine blue (ABT) reaction (Romhányi et al. 1974, 1975), the permanganate-bisulfite-toluidine blue (PBT) reaction (Fischer 1979, 1979a), and the sialic acid-specific reaction (Makovitzky 1980) all of which operate with induced dye-binding groups; i.e. dye-binding moieties on biological macromolecules are produced by specific chemical reactions.


Failure of haemoperfusion and haemodialysis to prevent death in paraquat poisoning. A retrospective review of 42 patients.
In this review the efficacy of haemoperfusion in the treatment of paraquat poisoning is addressed. 42 reports containing sufficient information of paraquat-poisoned patients were evaluated. These reports, from 35 patients reported in the literature and 7 new cases, were chosen for the following reasons: the timed plasma paraquat concentrations were known, patient outcome was known, and details of haemoperfusion were available. In some cases, haemodialysis was also performed. The plasma paraquat concentrations and the specific times post-ingestion were plotted on a contour graph that predicts the probability of survival. Comparison of the predicted probability of survival versus the actual outcome showed that haemoperfusion, single or repeated, did not affect patient survival. None of the patients whose initial plasma concentrations were greater than 3 mg/L paraquat survived, regardless of the time after ingestion that the concentrations were measured, and despite haemoperfusion. Therefore, such patients might not be considered for haemoperfusion because of their uniformly bad prognosis, despite the procedure being used, and because of the morbidity, discomfort and cost associated with it. Clearly, the need for better techniques to remove paraquat and to prevent the consequences of the metabolic effects of the compound are required urgently before the treatment of the paraquat-poisoned patient will be successful.


The structure and expression of a preprohormone of a neuropeptide, Hym-176 in Hydra magnipapillata.
Hym-176 (APFIFPGPKVamide) is a novel myoactive neuropeptide which was identified in systematic screening of signaling peptides in Hydra magnipapillata. By using PCR and library screening, we cloned and sequenced a full length cDNA which encoded a preprohormone of Hym-176. In the preprohormone, a typical signal sequence, one copy of Hym-176 precursor peptide and one copy of precursor sequence of another novel peptide, Hym-357 (KPAFLFKGYKPamide), were detected. In situ hybridization analysis revealed a strong signal in peduncle neurons. Signals were also detected, though weaker, in neurons in the gastric region and around the mouth. No signals were detected in the two extremities of the body, tentacles and basal disk. The expression pattern is correlated with the distribution of Hym-176 and its myoactive function.


Decoding successive computational stages of saliency processing.
An important requirement for vision is to identify interesting and relevant regions of the environment for further processing. Some models assume that salient locations from a visual scene are encoded in a dedicated spatial saliency map [1, 2]. Then, a winner-take-all (WTA) mechanism [1, 2] is often believed to threshold the graded saliency representation and identify the most salient position in the visual field. Here we aimed to assess whether neural representations of graded saliency and the subsequent WTA mechanism can be dissociated. We presented images of natural scenes while subjects were in a scanner performing a demanding fixation task, and thus their attention was directed away. Signals in early visual cortex and posterior intraparietal sulcus (IPS) correlated with graded saliency as defined by a computational saliency model. Multivariate pattern classification [3, 4] revealed that the most salient position in the visual field was encoded in anterior IPS and frontal eye fields (FEF), thus reflecting a potential WTA stage. Our results thus confirm that graded saliency and WTA-thresholded saliency are encoded in distinct neural structures. This could provide the neural representation required for rapid and automatic orientation toward salient events in natural environments.


[Epidemiology and classification of congenital malformations].
The relation highlights the principal congenital anomalies affecting the penis and the scrotum. These anomalies could be caused by genetic alterations and/or by hormonal mechanisms involved in the genitals' development.


Sensitive and selective determination of gallic acid in green tea samples based on an electrochemical platform of poly(melamine) film.
In this work, an electrochemical sensor coupled with an effective flow-injection amperometry (FIA) system is developed, targeting the determination of gallic acid (GA) in a mild neutral condition, in contrast to the existing electrochemical methods. The sensor is based on a thin electroactive poly(melamine) film immobilized on a pre-anodized screen-printed carbon electrode (SPCE*/PME). The characteristics of the sensing surface are well-characterized by field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS) and surface water contact angle experiments. The proposed assay exhibits a wide linear response to GA in both pH 3 and pH 7.0 phosphate buffer solutions (PBS) under the optimized flow-injection amperometry. The detection limit (S/N = 3) is 0.076 μM and 0.21 μM in the pH 3 and pH 7 solutions, respectively. A relative standard deviation (RSD) of 3.9% is obtained for 57 successive measurements of 50 μM GA in pH 7 solutions. Interference studies indicate that some inorganic salts, catechol, caffeine and ascorbic acid do not interfere with the GA assay. The interference effects from some orthodiphenolic compounds are also investigated. The proposed method and a conventional Folin-Ciocalteu method are applied to detect GA in green tea samples using the standard addition method, and satisfactory spiked recoveries are obtained.


Preparedness of adolescents departing from Athens International Airport to Africa or Asia: A five-year airport-based prospective study.
The number of adolescents who travel has increased. We estimated the preparedness of adolescents (12-18 years) departing from Athens to Africa and Asia. An airport-based survey was conducted from 2011 to 2015. Sixty-eight adolescents participated; 27/68 (40%) had the Greek nationality. Their main destinations were the Indian subcontinent (37%) and South-East Asia (32%). Most adolescents planned to stay for <1 month (69%) or for 1-3 months (22%). Their main purpose for travel was to visit friends and relatives (VFRs) (60%). Compared to non-VFR adolescents, VFRs more frequently travelled to sub-Saharan Africa and Southeast Asia, stayed in local residences and for longer periods. Twenty-one (31%) adolescents sought pre-travel counseling (in 57% of cases 8-14 days before departure). Having the Greek nationality was the only significant factor associated with an increased probability for seeking pre-travel counseling. Vaccination against rabies, typhoid fever, Japanese encephalitis and meningococcus was highly inadequate for adolescents travelling to endemic areas. Significant gaps in malaria chemoprophylaxis were found in those travelling to the Indian subcontinent. Less than one third of adolescents travelling to Africa and Asia seek counseling. There is a need to access adolescent travellers in Greece and improve pre-travel vaccinations and malaria chemoprophylaxis.


Transitional cell carcinoma of bladder originating from transitional cell carcinoma of anus.
A unique case of transitional cell carcinoma of the bladder with the primary being in the anus is reported. The patient presented with acute urinary retention from a large bladder tumor, which was thought to be primary to the bladder. Biopsy of the bladder revealed transitional cell carcinoma, microscopically indistinguishable from the primary cloacogenic carcinoma diagnosed seven years previously.


Systematic review of pre-clinical models assessing implant integration in locally compromised sites and/or systemically compromised animals.
The aim was to systematically search the dental literature for pre-clinical models assessing implant integration in locally compromised sites (part 1) and systemically compromised animals (part 2), and to evaluate the quality of reporting of included publications. A Medline search (1966-2011) was performed, complimented by additional hand searching. The quality of reporting of the included publications was evaluated using the 20 items of the ARRIVE (Animals in Research In Vivo Experiments) guidelines. One-hundred and seventy-six (part 1; mean ARRIVE score = 15.6 ± 2.4) and 104 (part 2; 16.2 ± 1.9) studies met the inclusion criteria. The overall mean score for all included studies amounted to 15.8 ± 2.2. Housing (38.3%), allocation of animals (37.9%), numbers analysed (50%) and adverse events (51.4%) of the ARRIVE guidelines were the least reported. Statistically significant differences in mean ARRIVE scores were found depending on the publication date (p < 0.05), with the highest score of 16.7 ± 1.6 for studies published within the last 2 years. A large number of studies met the inclusion criteria. The ARRIVE scores revealed heterogeneity and missing information for selected items in more than 50% of the publications. The quality of reporting shifted towards better-reported pre-clinical trials within recent years.


Hydrogeochemistry of seasonal variation of Urmia Salt Lake, Iran.
Urmia Lake has been designated as an international park by the United Nations. The lake occupies a 5700 km2 depression in northwestern Iran. Thirteen permanent rivers flow into the lake. Water level in the lake has been decreased 3.5 m in the last decade due to a shortage of precipitation and progressively dry climate. Geologically the lake basin is considered to be a graben of tectonic origin. Na, K, Ca, Li and Mg are the main cations with Cl, SO4, and HCO3 as the main anions. F & Br are the other main elements in the lake. A causeway crossing the lake is under construction, which may affect the lake's annual geochemistry. The main object of this project is mainly to consider the potential of K-mineral production along with ongoing salt production. Seven hundred and four samples were taken and partially analyzed for the main cations and anions. Surface water (0.5 m. depth) was analyzed for Na, K, Mg, Ca, Br and Li, and averaged 87.118 g/lit, 1.48 g/lit, 4.82 g/lit, 4.54 g/lit, 1.19 ppm and 12.7 ppm respectively for the western half of the lake. Sodium ranged between 84 to 91.2 g/lit, and showed higher concentrations in the south than in the north. This unexpected result may be caused by shallower depth in the south and a higher net evaporation effect. Calcium ranged between 4.2 to 5 g/lit, apparently slightly higher in the north. K is higher in the south, possibly due to rivers entering from south that may carry slightly higher K in solution. In the middle-range samples (0.5-5 m.), K averaged 1.43 g/lit and ranged from 1.40 to 1.46 g/lit. At this intermediate depth the distribution of K is clearly higher to the south of the causeway that is currently under construction. It is not clear whether this increase is the effect of the causeway or the effect of the salty Aji-Chay River to the east, and the Khoy salt domes to the north of the lake. At depth (5 m-10 m), K averaged 1.48 g/lit and ranged from 1.4 to 1.49 g/lit, differing only in the second decimal from the average of the middle and surface samples. Ignoring the small difference between the averages of the three sample depths, the distribution of K is highly homogeneous in the lake water due to the mixing process. Therefore causeway construction has not yet strongly affected K distribution, or it may be at the starting point. Magnesium concentration ranged from 4.6 to 5-g/lit, and was elevated in the south. This differs somewhat compared to calcium. Lithium, with an average of 12-13 ppm, is slightly higher in the south, and has not shown any significant variation in all three seasons. Iodine was below the detection limit in the lake. Urmia Lake, geochemically, is highly uniform both to the south and north of the causeway, in both the surface and deep brines. K and Mg, which average 1.48 and 6.6 g/lit in order, could be elements worth production in addition to the NaCl currently being produced from the lake. Br, F, Li and B in the limit of <50 ppm don't look to be in the economical range.


Altered amygdala shape trajectories and emotion recognition in youth at familial high risk of schizophrenia who develop psychosis.
Relatives of individuals with schizophrenia have a higher risk of developing the illness compared to the general population. Thus, youth at familial high risk (FHR) offer a unique opportunity to identify neuroimaging-based endophenotypes of psychosis. Previous studies have identified lower amygdalo-hippocampal volume in FHR, as well as lower verbal memory and emotion recognition. However, whether these phenotypes increase the risk of transition to psychosis remains unclear. To determine if individuals who develop psychosis have abnormal neurodevelopmental trajectories of the amygdala and hippocampus, we investigated longitudinal changes of these structures in a unique cohort of 82 youth FHR and 56 healthy controls during a 3-year period. Ten individuals from the FHR group converted to psychosis. Longitudinal changes were compared using linear mixed-effects models. Group differences in verbal memory and emotion recognition performance at baseline were also analyzed. Surface-based morphometry measures revealed variation in amygdalar shape (concave shape of the right dorsomedial region) in those who converted to psychosis. Significantly lower emotion recognition performance at baseline was observed in converters. Percent trial-to-trial transfer on the verbal learning task was also significantly impaired in FHR, independently of the conversion status. Our results identify abnormal shape development trajectories in the dorsomedial amygdala and lower emotion recognition abilities as phenotypes of transition to psychosis. Our findings illustrate potential markers for early identification of psychosis, aiding prevention efforts in youth at risk of schizophrenia.


Unlike mammalian GRIFIN, the zebrafish homologue (DrGRIFIN) represents a functional carbohydrate-binding galectin.
Galectins, a family of beta-galactoside-binding proteins, participate in a variety of biological processes, such as early development, tissue organization, immune regulation, and tumor evasion and metastasis. Although as many as fifteen bona fide galectins have been identified in mammals, but the detailed mechanisms of their biological roles still remain unclear for most. This fragmentary knowledge extends to galectin-like proteins such as the rat lens crystallin protein GRIFIN (Galectin-related inter fiber protein) and the galectin-related protein GRP (previously HSPC159; hematopoietic stem cell precursor) that lack carbohydrate-binding activity. Their inclusion in the galectin family has been debated, as they are considered products of evolutionary co-option. We have identified a homologue of the GRIFIN in zebrafish (Danio rerio) (designated DrGRIFIN), which like the mammalian equivalent is expressed in the lens, particularly in the fiber cells, as revealed by whole mount in situ hybridization and immunostaining of 2 dpf (days post fertilization) embryos. As evidenced by RT-PCR, it is weakly expressed in the embryos as early as 21 hpf (hour post fertilization) but strongly at all later stages tested (30 hpf and 3, 4, 6, and 7 dpf). In adult zebrafish tissues, however, DrGRIFIN is also expressed in oocytes, brain, and intestine. Unlike the mammalian homologue, DrGRIFIN contains all amino acids critical for binding to carbohydrate ligands and its activity was confirmed as the recombinant DrGRIFIN could be purified to homogeneity by affinity chromatography on a lactosyl-Sepharose column. Therefore, DrGRIFIN is a bona fide galectin family member that in addition to its carbohydrate-binding properties, may also function as a crystallin.


Infrequent genetic alterations of the PTEN gene in Japanese patients with sporadic prostate cancer.
Prostate cancer is a major cause of cancer death among elderly men in America, Europe, and Japan. However, the molecular mechanism of carcinogenesis is not yet well characterized. Frequent loss of heterozygosity (LOH) on chromosome 10q was reported in prostate cancer, and a candidate tumor suppressor gene, PTEN, was isolated on chromosome band 10q23.3. To investigate the genetic alterations of PTEN, we examined 45 primary prostate cancer specimens. LOH at the PTEN locus was observed in two (11.1%) of 18 tumors. However, no mutations were observed in any of the primary prostate cancers. These data suggest that mutation of the PTEN gene does not play a major role in prostate carcinogenesis of Japanese patients.


Electrochemically Promoted Fluoroalkylation-Distal Functionalization of Unactivated Alkenes.
Difunctionalization of olefins represents a powerful synthetic tool and yet a challenging task. This work describes an electrochemically enabled fluoroalkylation-migration reaction of unactivated olefins in the absence of a strong oxidant or heavy metal catalyst, affording fluorinated (hetero)aryl ketones in good yields and excellent regioselectivities. The efficient and sustainable electrochemical strategy provides a rapid access to a dual functionalized fluorine-containing heterocyclic manifold.


IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES).
Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5' untranslated regions (UTRs). Experimental demonstration of IRES in UTR remains a challenging task. Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). The predictive model was built using 35 features that are based on sequence and structural properties of UTRs and the probabilities of interactions between UTR and small subunit ribosomal proteins (SSRPs). The model was found to have 75.51% accuracy, 75.75% sensitivity, 75.25% specificity, 75.75% precision and Matthews Correlation Coefficient (MCC) of 0.51 in blind testing. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The IRESPred server is freely available at http://bioinfo.net.in/IRESPred/.


Acute hospital costs of pediatric trauma in the United States: how much and who pays?
National estimates of the numbers and expenditures associated with hospitalization due to injury among children (aged 0 to 14) were derived using data from the 1984, 1985, and 1986 National Hospital Discharge Surveys (NHDS) and the 1980 National Medical Care Utilization and Expenditures Study (NMCUES). In this report, age- and sex-specific estimates of the numbers of hospital admissions and expenditures are reported for subgroup of patients defined by external cause of the injury and by nature and severity of the injury. In 1985, over 266,000 children sustained a traumatic injury resulting in hospitalization (rate of 51 per 10,000 children). Expenditures totaled nearly $1 billion. Over 80% of the hospitalizations and two thirds of total expenditures were for minor (Maximum AIS = 1.2) trauma. Moderate (Maximum AIS = 3) and severe (Maximum AIS = 4,5) trauma accounted for 18% and 2% of admissions and 31% and 8% of expenditures, respectively. Falls ranked first in expenditures and admissions (36% of the total). Motor vehicle-related injuries accounted for 19% of trauma admissions and 24% of expenditures. Other less common causes included bicycle injuries, penetrating injuries and injuries caused by the child being hit by an object or person. An estimated 28% of the total hospital charges were paid for by public sources (15% from federal government programs, 13% from state and local programs). An additional 63% of total expenditures were paid for by private sources, with the remaining 9% considered uninsured care.(ABSTRACT TRUNCATED AT 250 WORDS)


Transfer learning for segmentation with hybrid classification to Detect Melanoma Skin Cancer.
Melanoma is an abnormal proliferation of skin cells that arises and develops in most of the cases on surface of skin that is exposed to copious amounts of sunlight. This common type of cancer may develop in areas of the skin that are not exposed to a much abundant sunlight. The research addresses the problem of Segmentation and Classification of Melanoma Skin Cancer. Melanoma is the fifth most common skin cancer lesion. Bio-medical Imaging and Analysis has become more promising, interesting, and beneficial in recent years to address the eventual problems of Melanoma Skin Cancerous Tissues that may develop on Skin Surfaces. The evolved research finds that Attributes Selected for Classification with Color Layout Filter model. The research has produced an optimal result in terms of certain performance metrics accuracy, precision, recall, PRC (what is PRC? Expansion is needed in Abstract), The proposed method has yielded 90.96% of accuracy and 91% percent of precise and 0.91 of recall out of 1.0, 0.95 of ROC AUC, 0.87 of Kappa Statistic, 0.91 of F-Measure. It has been noticed a lowest error with reference to proposed method on certain dataset. Finally, this research recommends that the Attribute Selected Classifier by implementing one of the image enhancement techniques like Color Layout Filter is showing an efficient outcome.


Effects of unilateral naris closure on the olfactory epithelia of adult mice.
This study demonstrates, for the first time, that prolonged unilateral breathing can be harmful to the adult olfactory epithelium. Mice at least 5 months old had one naris closed by cautery and suture. These were divided into 5 groups of 10 mice which had unilateral naris closure for 1, 3, 6, 8 or 12 weeks. A control group of 10 mice was untreated. Variables that were assessed included the thicknesses and numbers of cells spanning olfactory epithelia in hematoxylin and eosin stained paraffin sections. Olfactory marker protein (OMP) immunohistochemistry was used to further visualize the differential impact of naris closure on the two sides of the nose. Unilateral naris closure for 6 weeks or longer caused dramatic losses of olfactory receptor cells in the rostral third of the open-side olfactory epithelia, but did not affect numbers of cells in caudal regions or on the closed sides. The thicknesses of the open and closed-side olfactory epithelia were significantly different for only the 8-week closure group. In most mice with unilateral naris closure for longer than 6 weeks there was little or no staining of the olfactory receptor neurons or their axon bundles for OMP in the affected regions of the open side.


Survival, Reproduction and Growth of the Marine Amphipod, Leptocheirus plumulosus, Following Laboratory Exposure to Copper-Spiked Sediment.
Leptocheirus plumulosus was exposed for 28 days to Cu-spiked sediment at mean concentrations ranging from 44.4 to 605 mg Cu/kg dry sediment in a sediment/water test system designed to simulate natural conditions. The NOEC (no observed effect concentration)-LOEC (lowest observed effect concentration) range for the most sensitive endpoint of growth was 199-414 mg Cu/kg sediment. An IC50 for reproduction was estimated at 187 mg Cu/kg sediment. Mean Cu concentrations in pore water (PW) where significant effects were observed were 25.8 and 59.0 µg/L, while their respective concentrations in overlying water (OW) were 22.1 and 28.0 µg Cu/L. Copper concentrations were ≤19.1 and <16.6 µg/L in PW and OW, respectively, at lower exposures where effects were not evident. Concentrations of Cu in marine sediment lower than sediment quality guidelines based on geochemical factors of acid volatile sulfide, organic carbon content (f OC), and sediment grain size (i.e., silt + clay) would appear not to result in adverse effects toward L. plumulosus.


Identifying inflammatory phenotypes to target mechanism-specific treatments in sepsis.
A clinical trial by Leventogiannis et al.1 suggests that ferritin and HLA-DR monocyte receptor expression can identify septic patients with macrophage-activation-like syndrome (MALS), or immunoparalysis, and that targeting IL-1ra treatment with this strategy may improve outcomes.


The effect of hydrocortisone and cyclosporin A on bacillus Calmette-Guérin epitheloid cell granulomas.
The injection of bacillus Calmette-Guérin (BCG) intradermally into the ear of guinea pigs leads to the formation in the draining lymph node of granulomas containing epithelioid cells with rough endoplasmic reticulum (RER) and an absence of phagocytosed material. BCG granulomas in hydrocortisone- or cyclosporin A (CsA)-treated animals contain mononuclear phagocytes with no RER. In CsA-treated animals, these cells contain fragments of phagocytosed organisms. CsA was given at two doses, 25 mg/kg orally and 50 mg/kg ip. The higher dose completely suppressed the delayed hypersensitivity (DH) response to purified protein derivative (PPD) but the lower dose did not affect the level of the DH response, but had a profound effect on epithelioid cell formation. The role of lymphokines in the maturation of the monocyte/macrophage to epithelioid cells is discussed.


Sleep-Disordered Breathing and 24-Hour Ambulatory Blood Pressure Monitoring in Renal Transplant Patients: Longitudinal Study.
Background Sleep-disordered breathing (SDB) is considered a strong risk factor for hypertension in the general population. This disturbance is common in end-stage kidney disease patients on long-term hemodialysis and improves early on after renal transplantation. Whether SDB may be a risk factor for hypertension in renal transplant patients is unclear. Methods and Results We investigated the long-term evolution of simultaneous polysomnographic and 24-hour ambulatory blood pressure (BP) monitoring recordings in a cohort of 221 renal transplant patients. Overall, 404 paired recordings were made over a median follow-up of 35 months. A longitudinal data analysis was performed by the mixed linear model. The apnea-hypopnea index increased from a median baseline value of 1.8 (interquartile range, 0.6-5.0) to a median final value of 3.6 (interquartile range, 1.7-10.4; P=0.009). Repeated categorical measurements of the apnea-hypopnea index were directly associated with simultaneous 24-hour, daytime, and nighttime systolic ambulatory BP monitoring (adjusted analyses; P ranging from 0.002-0.01). In a sensitivity analysis restricted to 139 patients with at least 2 visits, 24-hour, daytime, and nighttime systolic BP significantly increased across visits (P<0.05) in patients with worsening SDB (n=40), whereas the same BP metrics did not change in patients (n=99) with stable apnea-hypopnea index. Conclusions In renal transplant patients, worsening SDB associates with a parallel increase in average 24-hour, daytime, and nighttime systolic BP. These data are compatible with the hypothesis that the link between SDB and hypertension is causal in nature. Clinical trials are, however, needed to definitively test this hypothesis.


Anxiolytic-induced attenuation of thigmotaxis in the Elevated Minus Maze.
Findings using exploration models of anxiety such as the Elevated Plus Maze (EPM) and Elevated Zero Maze (EZM) are remarkably consistent given the differences in layout and number of walls used to describe their closed areas. These factors therefore do not appear to be critical. The present studies were conducted to determine if anxiolytic activity could be detected using an apparatus that presented animals with only one wall. Mice were pre-treated with either vehicle, diazepam (2-4 mg/kg) or 5-10 mg/kg chlordiazepoxide (CDP) and placed for 5 min onto a square platform containing a 12 cm × 14 cm wall. Measures were taken of frequency/duration of contacts with the wall and of general activity. Time spent in contact with the wall was selectively reduced by 4 mg/kg diazepam. 10 mg/kg CDP also decreased this measure but increased measures of general activity, indicating a possible mild stimulant effect. The closed areas of the EPM are described by 3 walls. The EZM uses 2. Current findings show that anxiolytic effects can also be detected in a model with just one wall. It could and these data provide further evidence that variations in the layout of these mazes are not critical for detecting anxiolytic action. Thigmotactic cues remain present regardless of the physical characteristics of these mazes or the local conditions they are employed under. Hence, it is suggested that thigmotactic cues may be the common source of motivation to behave in these models and that this may explain their robustness.


Least-squares support vector machines and near infrared spectroscopy for quantification of common adulterants in powdered milk.
This paper proposes the use of the least-squares support vector machine (LS-SVM) as an alternative multivariate calibration method for the simultaneous quantification of some common adulterants (starch, whey or sucrose) found in powdered milk samples, using near-infrared spectroscopy with direct measurements by diffuse reflectance. Due to the spectral differences of the three adulterants a nonlinear behavior is present when all groups of adulterants are in the same data set, making the use of linear methods such as partial least squares regression (PLSR) difficult. Excellent models were built using LS-SVM, with low prediction errors and superior performance in relation to PLSR. These results show it possible to built robust models to quantify some common adulterants in powdered milk using near-infrared spectroscopy and LS-SVM as a nonlinear multivariate calibration procedure.


The therapeutic potential for targeting CSE/H2S signaling in macrophages against Escherichia coli infection.
Macrophages play a pivotal role in the inflammatory response to the zoonotic pathogen E. coli, responsible for causing enteric infections. While considerable research has been conducted to comprehend the pathogenesis of this disease, scant attention devoted to host-derived H2S. Herein, we reported that E. coli infection enhanced the expression of CSE in macrophages, accompanied by a significantly increased inflammatory response. This process may be mediated by the involvement of excessive autophagy. Inhibition of AMPK or autophagy with pharmacological inhibitors could alleviate the inflammation. Additionally, cell model showed that the mRNA expression of classic inflammatory factors (Il-1β, Il-6), macrophage polarization markers (iNOS, Arg1) and ROS production was significantly down-regulated after employing CSE specific inhibitor PAG. And PAG is capable of inhibiting excessive autophagy through the LKB1-AMPK-ULK1 axis. Interestingly, exogenous H2S could suppress inflammation response. Our study emphasizes the importance of CSE in regulating the macrophage-mediated response to E. coli. Increased CSE in macrophages leads to excessive inflammation, which should be considered a new target for drug development to treat intestinal infection.


Amperometric immunosensor developed for sensitive detection of SARS-CoV-2 spike S1 protein in combined with portable device.
In this present study, an amperometric immunosensor was developed based on disposable screen-printed carbon electrode (SPCE) for specific and sensitive detection of SARS-CoV-2 S1 protein. Anti-SARS-CoV-2 S1 monoclonal antibody was firstly immobilized onto the electrode surface. Then, the sandwich complex was formed by addition of S1 protein, secondary antibody and HRP-IgG, respectively. Chronoamperometry measurements were done in the presence of TMB mediator and the detection of SARS-CoV-2 S1 protein was performed by using 10 μL sample. The limit of detection (LOD) was found to be 0.19 ng/mL (equals to 24.7 amol in 10 μL sample) in the linear range of 0.5-10 ng/mL obtained in buffer medium. The applicability of this assay was investigated in the linear range of 0.5-3 ng/mL S1 protein in artificial saliva medium with the LOD as 0.13 ng/mL (equals to 16.9 amol in 10 μL sample). The selectivity study was examined in the presence of Hemagglutinin antigen (HA) in both mediums; buffer and artificial saliva while resulting with the successful discrimination between S1 protein and HA. The one of ultimate goals of our study is to present the possible implementation of this assay to point of care (POC) analysis. Under this aim, this assay was performed in combination with a portable device that is the commercial electrochemical analyzer. Amperometric detection of S1 protein in the range of 0.5-5 ng/mL was also successfully performed in artificial saliva medium with a resulting LOD as 0.15 ng/mL (equals to 19.5 amol in 10 μL sample). In addition, a selectivity study was similarly carried out by portable device.


A new acroeimerian (Apicomplexa: Eimeriidae) in spotted house gecko, Gekko monarchus (Schlegel) (Sauria: Gekkonidae) from Peninsular Malaysia.
A new species of Acroeimeria Paperna & Landsberg, 1989 is described from the spotted house gecko, Gekko monarchus (Schlegel) from Peninsular Malaysia. Oöcysts of Acroeimeria grismeri n. sp. are spheroidal to subspheroidal with a smooth bi-layered wall, measure on average 18.4 × 17.3 µm, and have a length/width (L/W) ratio of 1.1; a micropyle and an oöcyst residuum are absent but variable polar granule(s) are present, commonly in Brownian movement. Sporocysts are ellipsoidal and measure on average 8.6 × 6.7 µm, L/W 1.3; Stieda, sub-Stieda and para-Stieda bodies are absent. The sporocyst residuum is composed of numerous spheroidal granules in the center of the sporocyst. This is the initial species of coccidian reported from G. monarchus and one of the few reported from any reptile from Peninsular Malaysia.


Oscillatory Activity in the Cortex, Motor Thalamus and Nucleus Reticularis Thalami in Acute TTX and Chronic 6-OHDA Dopamine-Depleted Animals.
The motor thalamus (MTh) and the nucleus reticularis thalami (NRT) have been largely neglected in Parkinson's disease (PD) research, despite their key role as interface between basal ganglia (BG) and cortex (Cx). In the present study, we investigated the oscillatory activity within the Cx, MTh, and NRT, in normal and different dopamine (DA)-deficient states. We performed our experiments in both acute and chronic DA-denervated rats by injecting into the medial forebrain bundle (MFB) tetrodotoxin (TTX) or 6-hydroxydopamine (6-OHDA), respectively. Interestingly, almost all the electroencephalogram (EEG) frequency bands changed in acute and/or chronic DA depletion, suggesting alteration of all oscillatory activities and not of a specific band. Overall, δ (2-4 Hz) and θ (4-8 Hz) band decreased in NRT and Cx in acute and chronic state, whilst, α (8-13 Hz) band decreased in acute and chronic states in the MTh and NRT but not in the Cx. The β (13-40 Hz) and γ (60-90 Hz) bands were enhanced in the Cx. In the NRT the β bands decreased, except for high-β (Hβ, 25-30 Hz) that increased in acute state. In the MTh, Lβ and Hβ decreased in acute DA depletion state and γ decreased in both TTX and 6-OHDA-treated animals. These results confirm that abnormal cortical β band are present in the established DA deficiency and it might be considered a hallmark of PD. The abnormal oscillatory activity in frequency interval of other bands, in particular the dampening of low frequencies in thalamic stations, in both states of DA depletion might also underlie PD motor and non-motor symptoms. Our data highlighted the effects of acute depletion of DA and the strict interplay in the oscillatory activity between the MTh and NRT in both acute and chronic stage of DA depletion. Moreover, our findings emphasize early alterations in the NRT, a crucial station for thalamic information processing.


Left Atrial Reverse Remodeling in Dilated Cardiomyopathy.
Left atrial (LA) dilation is associated with a worse prognosis in several cardiovascular settings, but therapies can promote LA reverse remodeling. The aim of this study was to characterize and define the prognostic implications of LA volume index (LAVI) reduction in patients with dilated cardiomyopathy (DCM). Consecutive patients with DCM from two tertiary care centers, with available echocardiograms at baseline and at 1-year follow-up, were retrospectively analyzed. LA dilation was defined as LAVI > 34 mL/m2, and change in LAVI (ΔLAVI) was defined as the 1-year relative LAVI reduction. The outcome was a composite of death, heart transplantation (HTx), or heart failure hospitalization (HFH). Five hundred sixty patients were included (mean age, 54 ± 13 years; mean left ventricular ejection fraction, 31 ± 10%; mean LAVI, 45 ± 18 mL/m2). Baseline LAVI had a non-linear association with the risk for death, HTx, or HFH, independent of age, left ventricular ejection fraction, mitral regurgitation, and medical therapy (P < .01). At 1-year follow-up, LAVI decreased in 374 patients (67%; median ΔLAVI, -24%; interquartile range, -37% to -11%). Factors independently associated with ΔLAVI were higher baseline LAVI and lower baseline left ventricular ejection fraction. After multivariable adjustment, ΔLAVI showed a linear association with the risk for death, HTx, or HFH (hazard ratio, 0.96 per 5% decrease; 95% CI, 0.93-0.99; P = .042). At 1-year follow-up, patients with reductions in LAVI of >10% and LAVI normalization (i.e., follow-up LAVI ≤ 34 mL/m2; 31% of the overall cohort) were at lower risk for death, HTx, or HFH (hazard ratio, 0.37; 95% CI, 0.35-0.97; P = .028). In a large cohort of patients with DCM, 1-year reduction in LAVI was observed in a number of patients. The association between reduction in LAVI and death, HTx, or HFH suggests that LA structural reverse remodeling might be considered an additional parameter useful in the individualized risk stratification of patients with DCM.


Reliability of changes in neck pain and cervical rotation range following manual scapular repositioning.
Manual scapular repositioning may result in change in neck pain and cervical rotation range. However, the reliability of such changes performed by examiners remains unknown. To evaluate the reliability of changes in neck pain and cervical rotation range following manual scapular repositioning performed by two examiners and the agreement between these measures and patients' perceptions of change. Cross-sectional study. Sixty-nine participants with neck pain and altered scapular position were recruited. Two physiotherapists performed the manual scapular repositioning. Neck pain intensity was measured using a 0-10 numerical scale and cervical rotation range with a cervical range of motion (CROM) device at baseline and in the modified scapular position. Participants' perceptions of any change were rated on a five-item Likert scale. Clinically relevant changes in pain (>2/10) and range (≥7°) were defined as "improved" or "no change" for each measure. ICCs for changes in pain and range between examiners were 0.92 and 0.91. For clinically relevant changes, percent agreement and kappa values between examiners were 82.6%, 0.64 for pain and 84.1%, 0.64 for range. Percent agreement and kappa values between participants' perceptions and measured changes were 76.1%, 0.51 for pain and 77.5%, 0.52 for range. Changes in neck pain and rotation range following manual scapular repositioning demonstrated good reliability between examiners. There was moderate agreement between the measured changes and patients' perceptions.


Effect of the perineurial vascular net on experimental grafting of the inferior alveolar nerve.
For optimum nerve repair, it is imperative that free autogenous nerve grafts be used in cases when peripheral nerve loss is great. This study was performed to determine the influence of the perineurial vascular net on nerve regeneration in such grafts. It was concluded that nerve grafting is more likely to be successful if suturing of the epineurium and perineurium is precise and if a dense vascular net in the recipient bed, but not around the graft, is retained.


Our Retroperitoneal Cystic Echinococcosis Surgery Experiences at Mehmet Akif İnan Training and Research Hospital in Şanlıurfa
This study aimed to discuss the place of surgical technique in patients who were operated for retroperitoneal hydatid cyst at our clinic, in the light of current literature. Data from seven patients who were operated for retroperitoneal hydatid cyst between May 2012 and May 2019 were retrospectively collected and evaluated. Two patients were operated for isolated retroperitoneal hydatid cyst, one for liver hydatid cyst accompanying renal hydatid cyst and four patients were operated only for renal hydatid cyst. Recurrence was not observed in the follow-up. In our study, emphasis was laid on the fact that cysts can be treated successfully by using total, subtotal and partial cystectomy methods based on the organ and tissue neighbourhood.