Clinical Impact of Weight-Loss Pharmacotherapy in Patients with Atherosclerotic Cardiovascular Disease.
Obesity is associated with the development and progression of multiple cardiovascular risk factors, such as hypertension, dyslipidemia, and type 2 diabetes mellitus, and is an important contributor to the global burden of atherosclerotic cardiovascular disease (CVD). Guidelines suggest that clinicians provide lifestyle counseling and promote lifestyle modifications before considering weight-loss surgery. However, despite lifestyle modifications and increased physical activity, most patients with obesity will not lose significant weight or will experience weight regain. Weight-loss pharmacotherapy added to lifestyle modification has long been perceived as a bridge between lifestyle modifications alone and weight-loss surgery. However, since its inception, weight-loss pharmacotherapy has been plagued by variable efficacy and concern about cardiovascular safety. Following requirements from regulatory authorities, efficacy and cardiovascular safety trials have been conducted for the currently available weight-loss pharmacotherapeutic agents. Overall, these trials have shown that weight-loss pharmacotherapy is only modestly efficient for the inducement of weight loss. Recent trials have also demonstrated the cardiovascular safety of some of these agents. We review these trials with a focus on the clinical impact of these weight-loss pharmacotherapeutic agents in patients with atherosclerotic CVD.


A critical analysis of the routine testing of newborn stools for occult blood and reducing substances.
Stool tests for occult blood or reducing substances were introduced in the neonatal intensive care unit (NICU) as potential aids in the early recognition of necrotizing enterocolitis (NEC) in high-risk neonates, and have been recommended by some as routine nursing procedures. Neither the performance characteristics of these tests with respect to NEC, nor their indirect impact, were evaluated formally before widespread adoption into clinical care. The published evidence suggests that these tests are not useful as diagnostic or screening tools. There is no evidence that routine stool screening for occult blood or reducing substances predicts NEC or decreases the rate or severity of this disease. The direct costs of the tests are significant. A greater concern is their potential unintended consequences, which include the cost of secondary tests, restricted nutritional intake, and the accumulation of distracting, useless data. The logistics of maintaining quality control, the demands on nursing time, and the cost of testing are increasingly important considerations. This installment of Focus on the Physical diverges from a step-by-step systematic physical assessment by addressing the utility of testing neonatal stools for occult blood and reducing substances as aids in the early diagnosis or prevention of NEC. Using the information from these tests requires a framework for understanding their rationale, the test performance characteristics in the NICU setting, and the potential benefits, costs, and risks of their routine use.


Interaction between glutamate and luteinizing hormone-releasing hormone (LHRH) in lordosis behavior and luteinizing hormone release (LH): further studies on NMDA receptor mediation.
The present studies examine the effects of the glutamate agonist N-Methyl-D-Aspartic acid on lordosis responsiveness and LH release in estrogen-primed, ovariectomized rats. Groups of rats previously cannulated in the 3rd ventricle of the brain (IVT) were challenged with saline, NMDA and LHRH. A clear increase in lordosis-to-mount quotients (LQ) after IVT administration of 0.5, 0.75 and 1 microgram NMDA was found. LHRH (150 ng IVT) also enhanced LQ. High plasma LH levels were present in both cases. Intraventricular administration of the selective LHRH antagonist [D-p-Glu1, D-Phe2, D-Trp3,6]-LHRH (100 ng) was unable to prevent NMDA action on lordosis behavior. In contrast, it blunted LHRH enhancement of LQ. LH release evoked by either NMDA and LHRH was blocked by the LHRH antagonist. Present results support our previous view suggesting that glutamate, through NMDA receptors, participates in the regulation of lordosis behavior. Glutamate seems to exert its actions in the behavioral and endocrine patterns through different mechanisms; the first seems not to be mediated by LHRH, but the endocrine effect operates via LHRH release.


Nonselective beta blockers, hepatic decompensation, and mortality in cirrhosis: A national cohort study.
Little is known about the effectiveness of nonselective beta blockers (NSBBs) in preventing hepatic decompensation in routine clinical settings. We investigated whether NSBBs are associated with hepatic decompensation or liver-related mortality in a national cohort of veterans with Child-Turcotte-Pugh (CTP) A cirrhosis with no prior decompensations. In an active comparator, new user (ACNU) design, we created a cohort of new users of carvedilol ( n = 123) versus new users of selective beta blockers (SBBs) ( n = 561) and followed patients for up to 3 years. An inverse probability treatment weighting (IPTW) approach balanced demographic and clinical confounders. The primary analysis simulated intention-to-treat ("pseudo-ITT") with IPTW-adjusted Cox models; secondary analyses were pseudo-as-treated, and both were adjusted for baseline and time-updating drug confounders. Subgroup analyses evaluated NSBB effects by HCV viremia status, CTP class, platelet count, alcohol-associated liver disease (ALD) etiology, and age. In pseudo-ITT analyses of carvedilol versus SBBs, carvedilol was associated with a lower hazard of any hepatic decompensation (HR 0.59, 95% CI 0.42-0.83) and the composite outcome of hepatic decompensation/liver-related mortality (HR 0.56, 95% CI 0.41-0.76). Results were similar in pseudo-as-treated analyses (hepatic decompensation: HR 0.55, 95% CI 0.33-0.94; composite outcome: HR 0.62, 95% 0.38-1.01). In subgroup analyses, carvedilol was associated with lower hazard of primary outcomes in the absence of HCV viremia, higher CTP class and platelet count, younger age, and ALD etiology. There is an ongoing need to noninvasively identify patients who may benefit from NSBBs for the prevention of hepatic decompensation.


Impact of engineered nanomaterials on rice (Oryza sativa L.): A critical review of current knowledge.
After use, a large number of engineered materials (ENMs) are directly or indirectly released into the environment. This may threaten the agricultural ecosystem, especially with crops under high demand for irrigation water, such as rice (Oryza sativa L.), a crop that feeds nearly half of the world's population. However, consistent and detailed information on the effects of nanoparticles in rice is limited. This review is a systematic exploration of the effects of ENMs on rice, with a critical evaluation of the mechanisms reported in the literature by which different nanomaterials cause toxicity in rice. The physiological and biochemical effects engendered by the nanoparticles are highlighted, focusing on rice growth and development, ENMs uptake and translocation, gene expression changes, enzyme activity modifications, and secondary metabolite alterations.


TTX-sensitive Na+ channels and Ca2+ channels of the L- and N-type underlie the inward current in acutely dispersed coeliac-mesenteric ganglia neurons of adult rats.
Inward membrane currents of sympathetic neurons acutely dispersed from coeliac-superior mesenteric ganglia (C-SMG) of adult rats were characterized using the whole-cell variant of the patch-clamp technique. Current-clamp studies indicated that C-SMG neurons retained electrical properties similar to intact ganglia. Voltage-clamp studies designed to isolate Na+ currents revealed that tetrodotoxin (TTX, 1 microM) completely inhibited the large transient inward current. Half activation potential (Vh) and slope factor (K) were -26.8 mV and 6.1 mV, respectively. Inactivation parameters for Vh and K were -65 mV and 8.2 mV, respectively. Voltage-clamp studies also revealed a high-voltage-activated sustained inward Ca2+ current which was blocked by the removal of external Ca2+ or the presence of Cd2+ (0.1 mM). The dihydropyridine agonist, (+)202-791 (1 microM), caused a small increase (20%) in the amplitude of the Ca2+ current at more negative potentials and markedly prolonged the tail currents. omega-Conotoxin GIVA (omega, CgTX, 15 microM) caused a 66% inhibition of the high-voltage-activated Ca2+ current amplitude. Norepinephrine (1 microM) caused a 49% reduction in the peak Ca2+ current. This study is the first demonstration that dispersed C-SMG neurons from adult rats retain electrical characteristics similar to intact ganglia. A TTX-sensitive Na+ current as well as a high voltage-activated sustained Ca2+ current underlie the inward current in C-SMG neurons. The macroscopic Ca2+ current is composed of a small dihydropyridine-sensitive (L-type current) and a large omega-CgTx-sensitive (N-type current) component.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of air displacement plethysmography to hydrostatic weighing for estimating total body density in children.
The purpose of this study was to examine the accuracy of total body density and percent body fat (% fat) using air displacement plethysmography (ADP) and hydrostatic weighing (HW) in children. Sixty-six male and female subjects (40 males: 12.4 +/- 1.3 yrs, 47.4 +/- 14.8 kg, 155.4 +/- 11.9 cm, 19.3 +/- 4.1 kg/m2; 26 females: 12.0 +/- 1.9 yrs, 41.4 +/- 7.7 kg, 152.1 +/- 8.9 cm, 17.7 +/- 1.7 kg/m2) were tested using ADP and HW with ADP always preceding HW. Accuracy, precision, and bias were examined in ADP with HW serving as the criterion method. Lohman's equations that are child specific for age and gender were used to convert body density to % fat. Regression analysis determined the accuracy of ADP and potential bias between ADP and HW using Bland-Altman analysis. For the entire group (Y = 0.835x + 0.171, R2 = 0.84, SEE = 0.007 g/cm3) and for the males (Y = 0.837x + 0.174, R2 = 0.90, SEE = 0.006 g/cm3) the regression between total body density by HW and by ADP significantly deviated from the line of identity. However in females, the regression between total body density by HW and ADP did not significantly deviate from the line of identity (Y = 0.750x + 0.258, R2 = 0.55, SEE = 0.008 g/cm3). The regression between % fat by HW and ADP for the group (Y = 0.84x + 3.81, R2 = 0.83, SEE = 3.35 % fat) and for the males (Y = 0.84x + 3.25, R2 = 0.90, SEE = 3.00 % fat) significantly deviated from the line of identity. However, in females the regression between % fat by HW and ADP did not significantly deviate from the line of identity (Y = 0.81x + 5.17, R2 = 0.56, SEE = 3.80 % fat). Bland-Altman analysis revealed no bias between HW total body density and ADP total body density for the entire group (R = 0.-22; P = 0.08) or for females (R = 0.02; P = 0.92), however bias existed in males (R = -0.37; P < or = 0.05). Bland-Altman analysis revealed no bias between HW and ADP % fat for the entire group (R = 0.21; P = 0.10) or in females (R = 0.10; P = 0.57), however bias was indicated for males by a significant correlation (R = 0.36; P < or = 0.05), with ADP underestimating % fat at lower fat values and overestimating at the higher % fat values. A significant difference in total body density and % fat was observed between ADP and HW in children 10-15 years old with a potential gender difference being detected. Upon further investigation it was revealed that the study was inadequately powered, thus we recommend that larger studies that are appropriately powered be conducted to better understand this potential gender difference.


Oral Chinese herbal medicine in combination with phototherapy for vitiligo: A systematic review and meta-analysis of randomized controlled trials.
The aim of this study was to assess the effects of oral Chinese herbal medicine (CHM) combined with phototherapy for vitiligo. We undertook a meta-analysis of relevant randomized controlled trials (RCTs) and searched eight bibliographic databases from inception to December 2015. A total of 5 RCTs with 513 participants which assessed the efficacy of oral CHM in combination with narrow-band ultraviolet B (NB-UVB) in treating vitiligo were included. The meta-analysis revealed a superior effectiveness in those receiving oral CHM plus NB-UVB when compared to phototherapy alone (risk difference 0.22, 95% confidence interval 0.14 to 0.29, P<0.00001). Only mild adverse events were reported without significant renal or liver function impairment. The current evidence demonstrates that oral CHM in combination with NB-UVB has a superior effectiveness in terms of repigmentation rate of vitiligo when compared to NB-UVB alone. Although the overall quality of included trials was low, oral CHM in combination with NB-UVB may be an alternative option of treatment for vitiligo. As to safety, there were only mild adverse events reported without significant renal or liver function impairment. However, there is limited available evidence of long-term follow-up and poor methodological quality of the available trials. Well-designed RCTs of adequate length and sample size that include life quality as an outcome are warranted.


A comprehensive review of the role of immune checkpoint inhibitors in brain metastasis of renal cell carcinoma origin.
The contribution of renal cell carcinoma (RCC) to brain metastases (BM) reaches 7-13%. These patients have limited survival with local control and targeted therapies. Immune checkpoint inhibitors (ICI) revolutionized the treatment landscape of RCC but commonly excluded BM patients from their pivotal trials. The daily clinical practice often imposes the use of ICI in RCC patients with BM in view of the promising survival times and durations of response. Only small prospective trials have included BM patients but rarely reported on the efficacy or safety of ICI in this subgroup. The available data is limited to small retrospective and prospective series that have shown comparable efficacy to that of the pivotal trials. In this review, we will discuss the biological rationale and potential concerns for the use of ICI in BM RCC. Furthermore, we will summarize BM subgroup data from the prospective and retrospective series of ICI in RCC as well as the use of cranial radiation and ICI.


Frailty, Age, and Postdialysis Recovery Time in a Population New to Hemodialysis.
Frailty, a phenotype characterized by decreased physiologic reserve and the inability to recover following confrontation with a stressor like hemodialysis, may help identify which patients on incident hemodialysis will experience longer postdialysis recovery times. Recovery time is associated with downstream outcomes, including quality of life and mortality. We characterized postdialysis recovery times among patients new to hemodialysis and quantified the association between frailty and hemodialysis recovery time. Among 285 patients on hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, frailty was measured using the Fried phenotype. Self-reported recovery time was obtained by telephone interview. We estimated the association of frailty (intermediately frail and frail versus nonfrail) and postdialysis recovery time using adjusted negative binomial regression. Median time between dialysis initiation and study enrollment was 3.4 months (IQR, 2.7-4.9), and that between initiation and recovery time assessment was 11 months (IQR, 9.3-15). Mean age was 55 years, 24% were >65 years, and 73% were Black; 72% of individuals recovered in ≤1 hour, 20% recovered in 1-6 hours, 5% required 6-12 hours to recover, and <5% required >12 hours to recover. Those with intermediate frailty, frailty, and age ≤65 years had 2.56-fold (95% CI, 1.45 to 4.52), 1.72-fold (95% CI, 1.03 to 2.89), and 2.35-fold (95% CI, 1.44 to 3.85) risks, respectively, of longer recovery time independent of demographic characteristics, comorbidity, and dialysis-related factors. In adults new to hemodialysis, frailty was independently associated with prolonged postdialysis recovery. Future studies should assess the effect of frailty-targeted interventions on recovery time to improve clinical outcomes.


Biological conversion of biogas to methanol using methanotrophs isolated from solid-state anaerobic digestate.
The aim of this work was to isolate methanotrophs (methane oxidizing bacteria) that can directly convert biogas produced at a commercial anaerobic digestion (AD) facility to methanol. A methanotrophic bacterium was isolated from solid-state anaerobic digestate. The isolate had characteristics comparable to obligate methanotrophs from the genus Methylocaldum. This newly isolated methanotroph grew on biogas or purified CH4 and successfully converted biogas from AD to methanol. Methanol production was achieved using several methanol dehydrogenase (MDH) inhibitors and formate as an electron donor. The isolate also produced methanol using phosphate with no electron donor or using formate with no MDH inhibitor. The maximum methanol concentration (0.43±0.00gL(-1)) and 48-h CH4 to methanol conversion (25.5±1.1%) were achieved using biogas as substrate and a growth medium containing 50mM phosphate and 80mM formate.


Breast cancer cell-associated endopeptidase EC 24.11 modulates proliferative response to bombesin.
We have investigated the production, growth and inactivation of gastrin-releasing peptide (GRP)-like peptides in human breast cancer cell lines. Radioimmunoassay detected GRP-like immunoreactivity (GRP-LI) in T47D breast cancer cells but not in the conditioned medium, indicating rapid clearance. No GRP-LI was found in the ZR-75-1 or MDA-MB-436 cells or their conditioned medium. High-performance liquid chromatography (HPLC) analysis of the GRP-LI in the T47D cells revealed a major peak, which co-eluted with GRP(18-27), and a minor more hydrophilic peak. In vitro stimulation of T47D cell growth by bombesin (BN) was enhanced to 138% of control levels (bombesin alone) by the addition of the selective endopeptidase EC 184.108.40.206 inhibitor phosphoramidon (0.1 ng ml(-1)). Fluorogenic analysis using whole cells confirmed low levels of this phosphoramidon-sensitive enzyme on the T47D cells. This enzyme, previously unreported in human breast cancer cells, significantly modulates both T47D growth and its response to BN-induced growth.


Comparative studies on the chemical and enzymatic stability of alpha- and beta-arbutin.
The aim of this study was to establish a comparative analysis of the chemical and enzymatic stability of α- and β-arbutins as potential sources of the substance of concern hydroquinone (HQ). The study was performed using an array of techniques including HPLC-PDA, nuclear magnetic resonance (NMR) and optical rotation (OR). Both arbutins are emerging as popular and effective skin whiteners, acting as tyrosinase inhibitors in a fashion similar to the popular whitening agent HQ. Due to their structural similarity to the regulated agent HQ, both arbutins may be regarded as potential sources of the active aglycone after chemical or metabolic conversion. Various cosmetic formulations including creams, sera, gels and lotions were analysed by HPLC-PDA for their arbutin and HQ content in freshly opened and aged samples stored for 16 months. Solutions of pure compounds were also aged and periodically checked for degradation products using 1D and 2D NMR experiments and OR measurements. The metabolic stability was investigated using pear peels as a biological model. Both arbutins were found to be stable in water and methanol solutions in the absence of buffer or stabilizers. Their stability in cosmetic formulations, however, was found to depend on the type of formulation and pH. Both compounds were unstable under strong hydrolytic conditions, with consequent release of HQ. Enzymatic instability of both arbutins was also observed, although no formation of HQ was observed under the chosen experimental conditions. Both arbutins were found to possess similar stability profiles, and to be more prone to in vivo rather than in chemico degradation, although no HQ was found after enzymatic hydrolysis. Also, no epimerization was observed in any of the tested conditions. Diverse experimental approaches can be applied to analyse the chemical and enzymatic stability of arbutins in regard to the potential release of HQ in different types of preparations. These result showed the potential use of NMR and OR as complementary investigative tools for the stability and safety assessment of arbutin along with more established HPLC methods.


W. Zacheus Cande: Evolutionary biologist in cell biologist's clothing. Interview by Ruth Williams.
Zac Cande wants to get to the roots of cell division and cytoskeletal mechanics.


Local Effects Following Single and Repeat Intra-Articular Injections of Triamcinolone Acetonide Extended-Release: Results from Three Nonclinical Toxicity Studies in Dogs.
Single intra-articular (IA) injections of poly(lactic-co-glycolic acid) (PLGA) microsphere-based triamcinolone acetonide extended-release (TA-ER; formerly FX006) demonstrated sustained, clinically relevant benefits in patients with knee osteoarthritis. The local effects of TA-ER were assessed in normal canine knees in three nonclinical studies. Knees were evaluated for up to 6 weeks or 9 months after a single injection of TA-ER (2.1/6.25/18.75 mg TA), or TA crystalline suspension (TAcs, 18.75 mg TA), and for up to 6 months after three injections (every 1 or 3 months) of TA-ER (6.25/18.75 mg TA) or TAcs (18.75 mg). Vehicle-diluent, blank microspheres, and untreated knees were used as controls. Plasma and synovial fluid (SF) TA concentrations and standard histopathological assessment of the synovium were conducted. Articular cartilage morphology was assessed via modified Mankin scoring. Plasma and SF concentrations indicated prolonged dose-dependent TA joint residency with TA-ER compared with TAcs. Effects in articular cartilage were dose- and time-dependent and consistent with known effects of corticosteroids in the normal knee. Loss of Safranin O staining occurred, indicative of a reduction in cartilage matrix proteoglycan, and recovered in a similar manner for TA-ER and TAcs across all studies. Structural lesions were infrequent and generally comparable in severity between TA-ER and TAcs but slightly higher in incidence for TA-ER. Focal/multifocal foreign-body responses (FBR) to PLGA were observed in the superficial layer of the synovium, peaking after 4-6 weeks, with significant recovery or complete resolution by month 6. These findings suggest that the effects of IA injections of TA-ER on cartilage are predominantly transient, and comparable to those observed with TAcs in the normal canine knee joint. These mild effects in the normal joint differ from the beneficial effects observed with TA-ER and other corticosteroids in disease models. The synovial FBR to PLGA microspheres was focal and transient. Flexion Therapeutics, Inc. Plain language summary available for this article.


Study on Clinicopathological Features of Gastrointestinal Stromal Tumor and Relevant Prognostic Factors.
The objective of the study is to investigate and analyze clinicopathological features of gastrointestinal stromal tumor (GIST) and relevant prognostic factors. Between September 2008 and April 2014, 168 patients who presented with pathologically confirmed GIST and underwent surgical resection of the tumors in our institution were included in this study. A retrospective study on clinicopathological features of the disease and follow-up study on 1-year, 3-year, and 5-year survival rates were performed. Of 168 patients, 113 were males and 55 females of age ranging from 18 to 78 years (mean age 52.6 ± 10.1 years). Seventy patients (41.7 %) presented abdominal distension, 74 (44.0 %) abdominal pain, and 82 (48.8 %) bloody stools. Of all patients, 115 (68.4 %) developed tumors in GI tract, 51 (30.4 %) presented multiple tumors, 88 (52.4 %) tumors displayed a maximal diameter >5 cm, mitotic count >5/50HPF were observed in 80 patients. Positive rate of CD117 was 92.9 % (156/12), DOG1 97.0 % (163/5), CD34 53.0 % (89/79) and S-100 25.6 % (43/125). Follow-up study achieved in 149 patients. Survival analysis and Cox regression analysis demonstrated that no significant prognostic effects were observed for gender, clinical presentations, tumor location, number of tumors, CD34 and S-100 expression (p > 0.05). However, tumor diameter and mitotic count were factors with significant effect on prognosis of GIST (p < 0.05). Tumors with diameter >5 cm and mitotic count ≥5/50HPF resulted in poor prognosis. Common symptoms of GIST include abdominal pain and blood stools. Tumor diameter and mitotic count are helpful for the evaluation of prognosis with favorable clinical value.


A high-resolution mass spectrometry based proteomic dataset of human regulatory T cells.
Regulatory T cells (Tregs) play a core role in maintaining immune tolerance, homeostasis, and host health. High-resolution analysis of the Treg proteome is required to identify enriched biological processes and pathways distinct to this important immune cell lineage. We present a comprehensive proteomic dataset of Tregs paired with conventional CD4+ (Conv CD4+) T cells in healthy individuals. Tregs and Conv CD4+ T cells were sorted to high purity using dual magnetic bead-based and flow cytometry-based methodologies. Proteins were trypsin-digested and analysed using label-free data-dependent acquisition mass spectrometry (DDA-MS) followed by label free quantitation (LFQ) proteomics analysis using MaxQuant software. Approximately 4,000 T cell proteins were identified with a 1% false discovery rate, of which approximately 2,800 proteins were consistently identified and quantified in all the samples. Finally, flow cytometry with a monoclonal antibody was used to validate the elevated abundance of the protein phosphatase CD148 in Tregs. This proteomic dataset serves as a reference point for future mechanistic and clinical T cell immunology and identifies receptors, processes, and pathways distinct to Tregs. Collectively, these data will lead to a better understanding of Treg immunophysiology and potentially reveal novel leads for therapeutics seeking Treg regulation.


Level Ib sparing intensity-modulated radiation therapy in selected nasopharyngeal carcinoma patients based on the International Guideline.
To investigate the feasibility of level Ib sparing in selected nasopharyngeal carcinoma (NPC) patients during intensity-modulated radiation therapy (IMRT) based on the International Guideline. Patients with histologically-proven NPC who received definitive IMRT at our group were candidates for this analysis. Other eligibility criteria for analysis were designed according to the recommendation of International Guideline for selective coverage of level Ib. Survival outcomes focused on regional recurrence-free survival (RRFS) and level Ib recurrence rate were analyzed. A total of 450 patients were included, 60 of them received level Ib-covering IMRT due to the first three principles of the International Guideline according to our protocol. Of note, patients with level Ib involvement would receive ultrasound guided puncture, only those with positive pathological results would undergo level Ib-covering IMRT. For the remaining 390 patients who only fulfilled the last two criteria and/or level Ib involvement with negative pathological results, level Ib-sparing IMRT was delivered, with a median follow-up time of 112 months (range 6 to 194 months), reported 5- and 10-year RRFS were 95.4% and 92.9%, respectively. Twenty-two patients occurred regional recurrence at censorship (median 44.5 months), only 4(4/390, 1.03%) were recorded as level Ib recurrence. Level Ib-sparing IMRT should be safe and feasible for patients who only had level II involvement with ECE, and/or had a MAD of greater than 2 cm in level II, and/or level Ib involvement with negative pathological results. Further well-designed multi-center prospective trials should be conducted.


Measuring support needs in children with motor disability: Validity and utility of the Supports Intensity Scale (SIS-C).
It is unknown whether the Supports Intensity Scale-Children's version (SIS-C) is valid and useful to assess support needs for children with motor and intellectual disabilities. (a) To assess the structural validity of the SIS-C using factor analyses in a sample of children with motor disabilities; and (b) to analyze the SIS-C's reliability and its discriminative capacity in children with different levels of motor function. A cross-sectional design was used to assess 210 children (aged 5-16 years). Among them, 88% had an intellectual disability and 84% had cerebral palsy, with variations in mobility (Gross Motor Function Classification System; level V: 56.19%), handling of objects (Manual Ability Classification System; level V: 38.09%), and communicating (Communication Function Classification System; level V: 42.86%). The model with seven support needs factors and three method factors showed the best fit. The support needs model was reliable and indicated high convergent validity. However, the SIS-C scores showed a strong ceiling effect in children with more significant limitations in gross and fine motor functions. The seven-dimensional model of support needs could be replicated in children with motor disabilities. However, the usefulness of SIS-C is limited in discriminating between children with greater restrictions in mobility and handling of objects.


A head template for computational dose modelling for transcranial focused ultrasound stimulation.
Transcranial focused Ultrasound Stimulation (TUS) at low intensities is emerging as a novel non-invasive brain stimulation method with higher spatial resolution than established transcranial stimulation methods and the ability to selectively stimulate also deep brain areas. Accurate control of the focus position and strength of the TUS acoustic waves is important to enable a beneficial use of the high spatial resolution and to ensure safety. As the human skull causes strong attenuation and distortion of the waves, simulations of the transmitted waves are needed to accurately determine the TUS dose distribution inside the cranial cavity. The simulations require information of the skull morphology and its acoustic properties. Ideally, they are informed by computed tomography (CT) images of the individual head. However, suited individual imaging data is often not readily available. For this reason, we here introduce and validate a head template that can be used to estimate the average effects of the skull on the TUS acoustic wave in the population. The template was created from CT images of the heads of 29 individuals of different ages (between 20-50 years), gender and ethnicity using an iterative non-linear co-registration procedure. For validation, we compared acoustic and thermal simulations based on the template to the average of the simulation results of all 29 individual datasets. Acoustic simulations were performed for a model of a focused transducer driven at 500 kHz, placed at 24 standardized positions by means of the EEG 10-10 system. Additional simulations at 250 kHz and 750 kHz at 16 of the positions were used for further confirmation. The amount of ultrasound-induced heating at 500 kHz was estimated for the same 16 transducer positions. Our results show that the template represents the median of the acoustic pressure and temperature maps from the individuals reasonably well in most cases. This underpins the usefulness of the template for the planning and optimization of TUS interventions in studies of healthy young adults. Our results further indicate that the amount of variability between the individual simulation results depends on the position. Specifically, the simulated ultrasound-induced heating inside the skull exhibited strong interindividual variability for three posterior positions close to the midline, caused by a high variability of the local skull shape and composition. This should be taken into account when interpreting simulation results based on the template.


Effects of trout on the diel periodicity of drifting in baetid mayflies.
Some benthic invertebrates in streams make frequent, short journeys downstream in the water column (=drifting). In most streams there are larger numbers of invertebrates in the drift at night than during the day. We tested the hypothesis that nocturnal drifting is a response to avoid predation from fish that feed in the water column during the day. We surveyed diel patterns of drifting by nymphs of the mayfly Baetis coelestis in several streams containing (n=5) and lacking (n=7) populations of rainbow trout, Oncorhynchus mykiss. Drifting was more nocturnal in the presence of trout (85% of daily drift occurred at night) than in their absence (50% of daily drift occurred at night). This shift in periodicity is due to reduced daytime drifting in streams with trout, because at a given nighttime drift density, the daytime drift density of B. coelestis was lower in streams occupied by trout than in troutless streams. Large size classes of B. coelestis were underrepresented in the daytime drift in trout streams compared to nighttime drift in trout streams, and to both day and night drift in troutless streams. Differences in daytime drift density between streams with and without trout were the result of differences in mayfly drift behaviour among streams because predation rates by trout were too low to significantly reduce densities of drifting B. coelestis. We tested for rapid (over 3 days) phenotypic responses to trout presence by adding trout in cages to three of the troutless streams. Nighttime drifting was unaffected by the addition of trout, but daytime drift densities were reduced by 28% below cages containing trout relative to control cages (lacking trout) placed upstream. Drift responses were measured 15 m downstream of the cages suggesting that mayflies detected trout using chemical cues. Overall, these data support the hypothesis that infrequent daytime drifting is an avoidance response to fish that feed in the water column during the day. Avoidance is more pronounced in large individuals and is, at least partially, a phenotypic response mediated by chemical cues.


Peer training of safety-related skills to institutional staff: benefits for trainers and trainees.
A peer training program, in which experienced staff trained new staff, was evaluated as a method for teaching and maintaining safety-related caregiver skills in an institutional setting for the developmentally disabled. Three sets of safety-type skills were assessed in simulated emergency situations: responding to facility fires, managing aggressive attacks by residents, and assisting residents during convulsive seizures. Using a multiple-baseline research design, results indicated that the peer training program was an effective method of training the three types of emergency skills to new direct care staff. The program also appeared effective in improving the skills of the peer trainers. Perhaps most importantly, results indicated that if experienced staff functioned as peer trainers for particular emergency skills, then their proficiency in those skills maintained over time whereas their proficiency declined in emergency skills for which they did not act as peer trainers. Social validity information collected from available staff 23 months after the program was completed supported the utility of the training in terms of staff responses during actual emergencies. Also, acceptability measures indicated that staff liked participating in the program. However, some inconsistencies between staff verbal reports and performance-based measures of acceptability were noted. Results are discussed regarding the overall effectiveness of the peer training program, the importance of maintenance strategies for safety-related skills, and the need for multidimensional analyses of staff acceptability in staff training/management research.


Chronic remote ischemic conditioning treatment in patients with chronic stable angina (EARLY-MYO-CSA): a randomized, controlled proof-of-concept trial.
Chronic remote ischemic conditioning (CRIC) has been shown to improve myocardial ischemia in experimental animal studies; however, its effectiveness in patients with chronic stable angina (CSA) has not been investigated. We conducted a proof-of-concept study to investigate the efficacy and safety of a six-month CRIC treatment in patients with CSA. The EARLY-MYO-CSA trial was a prospective, randomized, controlled trial evaluating the CRIC treatment in patients with CSA with persistent angina pectoris despite receiving ≥ 3-month guideline-recommended optimal medical therapy. The CRIC and control groups received CRIC (at 200 mmHg) or sham CRIC (at 60 mmHg) intervention for 6 months, respectively. The primary endpoint was the 6-month change of myocardial flow reserve (MFR) on single-photon emission computed tomography. The secondary endpoints were changes in rest and stress myocardial blood flow (MBF), angina severity according to the Canadian Cardiovascular Society (CCS) classification, the Seattle Angina Questionnaire (SAQ), and a 6-min walk test (6-MWT). Among 220 randomized CSA patients, 208 (105 in the CRIC group, and 103 in the control group) completed the treatment and endpoint assessments. The mean change in MFR was significantly greater in the CRIC group than in the control group (0.27 ± 0.38 vs. - 0.04 ± 0.25; P < 0.001). MFR increased from 1.33 ± 0.48 at baseline to 1.61 ± 0.53 (P < 0.001) in the CRIC group; however, a similar increase was not seen in the control group (1.35 ± 0.45 at baseline and 1.31 ± 0.44 at follow-up, P = 0.757). CRIC treatment, when compared with controls, demonstrated improvements in angina symptoms assessed by CCS classification (60.0% vs. 14.6%, P < 0.001), all SAQ dimensions scores (P < 0.001), and 6-MWT distances (440 [400-523] vs. 420 [330-475] m, P = 0.016). The incidence of major adverse cardiovascular events was similar between the groups. CSA patients benefit from 6-month CRIC treatment with improvements in MFR, angina symptoms, and exercise performance. This treatment is well-tolerated and can be recommended for symptom relief in this clinical population. [chictr.org.cn], identifier [ChiCTR2000038649].


Dietary α-linolenic acid-rich formula reduces adhesion molecules in rats with experimental colitis.
The ω-3 polyunsaturated fatty acid therapy in inflammatory bowel disease is focused on the effects on fish oil-derived polyunsaturated fatty acids. We speculated that a vegetal oil rich in α-linolenic acid (ALA) might also inhibit colitis. Therefore, we evaluated whether dietary ALA would decrease the expression of adhesion molecules by inducing the protective enzyme heme oxygenase-1 (HO-1) in a rat colitis model. Colitis was induced at day 0 by an intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS), whereas control rats received the vehicle. Rats were fed an ALA-rich formula 450 mg · kg⁻¹ · d⁻¹, whereas the other colitic group (TNBS) and the control group were fed an isocaloric corn oil formula for 14 d (from day -7 to day 7). The colonic expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor A receptor-2 (VEGFR2), and HO-1 were studied by immunohistochemistry. The ALA-rich diet significantly decreased the expression of ICAM-1, VCAM-1, and VEGFR-2 compared the TNBS group, but it did not affect the expression of HO-1. A vegetal ALA-rich formula decreases the expression of ICAM-1, VCAM-1, and VEGFR-2 and independently of HO-1 in rats with TNBS-induced colitis. Further studies are required to evaluate its therapeutic potential in inflammatory bowel disease as an alternative to fish oil.


Comparative Outcomes of Cap Assisted Endoscopic Resection and Endoscopic Submucosal Dissection in Dysplastic Barrett's Esophagus.
Endoscopic resection is an important component of the endoscopic treatment of Barrett's esophagus (BE) with dysplasia and intramucosal adenocarcinoma. Endoscopic resection can be performed by cap-assisted endoscopic mucosal resection (cEMR) or endoscopic submucosal dissection (ESD). We compared the histologic outcomes of ESD vs cEMR, followed by ablation. We queried a prospectively maintained database of all patients undergoing cEMR and ESD followed by ablation at our institution from January 2006 to March 2020 and abstracted relevant demographic and clinical data. Our primary outcomes included the rate of complete remission of dysplasia (CRD): absence of dysplasia on surveillance histology, and complete remission of intestinal metaplasia (CRIM): absence of intestinal metaplasia. Our secondary outcome included complication rates. We included 537 patients in the study: 456 underwent cEMR and 81 underwent ESD. The cumulative probabilities of CRD at 2 years were 75.8% and 85.6% in the cEMR and ESD groups, respectively (P < .01). Independent predictors of CRD were as follows: ESD (hazard ratio [HR], 2.38; P < .01) and shorter BE segment length (HR, 1.11; P < .01). The cumulative probabilities of CRIM at 2 years were 59.3% and 50.6% in the cEMR and ESD groups, respectively (P > .05). The only independent predictor of CRIM was a shorter BE segment (HR, 1.16; P < .01). BE patients with dysplasia or intramucosal adenocarcinoma undergoing ESD reach CRD at higher rates than those treated with cEMR, although CRIM rates at 2 years and complication rates were similar between the 2 groups.


Roles for the tubulin- and PTP-PEST-binding paxillin LIM domains in cell adhesion and motility.
Cell dynamics mediated through cell-extracellular matrix contacts, such as adhesion and motility involve the precise regulation of large complexes of structural and signaling molecules called focal adhesions (FAs). Paxillin is a multi-domain FA adaptor protein containing five amino-terminal paxillin leucine-aspartate repeat (LD) motifs and four carboxyl-terminal Lin-11 Isl-1 and Mec-3 (LIM) domains. The LD motifs support paxillin binding to actopaxin, integrin linked kinase (ILK), FA kinase (FAK), paxillin kinase linker (PKL) and vinculin. Of the LIM domains, LIM2 and 3 comprise the paxillin FA-targeting motif, with phosphorylation of these domains modulating paxillin targeting and cell adhesion to fibronectin (Fn). The identity of the paxillin FA targeting partner remains to be determined; however, the LIM domains mediate interactions with tubulin and the protein-tyrosine phosphatase (PTP)-PEST. PTP-PEST binding requires both LIM3 and 4, whereas, the precise LIM target of tubulin binding is not known. In this report, we demonstrate that the individual paxillin LIM2 and 3 domains support specific binding to tubulin and suggest a potential role for this interaction in the regulation of paxillin sub-cellular compartmentalization. In addition, expression of paxillin molecules with mutations in the tubulin- and PTP-PEST-binding LIM domains differentially impaired Chinese hamster ovary K1 (CHO.K1) cell adhesion and migration to Fn. Perturbation of LIM3 or 4 inhibited adhesion while mutation of LIM2 or 4 decreased cell motility. Interestingly, expression of tandem LIM2-3 inhibited cell adhesion and spreading while LIM3-4 stimulated a well-spread polarized phenotype. These data offer further support for a critical role for paxillin in cell adhesion and motility.


A direct method for detecting proteins in body fluids by Surface-Enhanced Raman Spectroscopy under native conditions.
Surface enhanced Raman spectroscopy (SERS) is widely used in biomolecular detection. However, maintaining the native structure of proteins while obtaining sensitive and reproducible SERS signals of unlabeled proteins remains a challenge. In this study, dichloromethane (DCM) and CaCl2 were used to optimize the aggregation of Ag nanoparticles (AgNPs), and several proteins were analyzed comprehensively. Calcium ions removed citrate ions outside AgNPs, inducing hot spots and achieving high-sensitivity SERS signals of proteins. Furthermore, 20 random samples of 0.5 μg/mL hemoglobin were analyzed by this method. The obtained spectra showed good repeatability and a high quality. Using the peak intensity of DCM as internal parameter, the differences in peak intensities at the same position were analyzed to distinguish different proteins and evaluate changes in protein structure. Subsequently, the protein content in protein mixtures and serum was quantified and a good linear relationship between peak intensity and protein concentration was obtained. This method shows great promise in the fields of food testing and clinical diagnosis.


Dichhaptic recognition of textures in normal adults.
Dichhaptic procedures usually use nonsense shapes or letters as stimuli. The present study was designed to investigate hand asymmetry in a texture recognition task, in male right-handed adults. An overall left hand (right hemisphere) advantage was observed. However, when examining the order-of-report effect, the asymmetry appeared for the first report only. These results are discussed in terms of inter-hemispheric cooperation that can emerge for the second report.


Post-ablative reconstruction of the medial canthus and medial orbital wall using conchal cartilage graft with three illustrative cases.
When the medial third of the upper or lower eyelid has to be reconstructed after full-thickness tumour excision, we usually use Hübner tarsomarginal grafts, but when medial canthal lesions spread to the medial orbital wall without invading the orbital margin, conchal graft becomes our first surgical option. Previously reported solutions to this difficult problem are few and concern more directly medial orbital wall fractures. We found no article dealing specifically with the use of conchal graft in post-ablative reconstruction of the medial orbital wall. Nevertheless the concha presents great advantages over bone grafting or rib cartilage, because it is more flexible and malleable. And it is less prone to extrusion or infection as may be allografts implants. It is a very effective way to repair medial orbital defects, but graft reorientation must be perfect to match exactly the medial orbital wall concavity.


Components of Metabolic Syndrome and the Risk of Disability among the Elderly Population.
The direct relationship between metabolic syndrome (MetS) and function disability has not been established. The aim of the present study was to investigate the relationship between MetS and functional disability in the elderly. This retrospective observational study included 1,778 participants aged 60-84 years from the National Health and Nutrition Examination Survey (1999-2002). Impairments in activities of daily living (ADL), instrumental activities of daily living (IADL), leisure and social activities (LSA), lower extremity mobility (LEM), and general physical activities (GPA) were assessed. Additionally, the associations between the features of MetS and disability were evaluated. MetS was associated with a high prevalence of functional dependence in ADL, IADL, LSA, LEM, and GPA. After adjusting for potential confounders, a high number of MetS components was found to be associated with increased disability (P = 0.002). Additionally, associations were observed between MetS components, including abdominal obesity and high triglycerides levels, and functional dependence in ADL, IADL, LSA, LEM, and GPA (all, P < 0.05). A linear increase in disability might be associated with the number of MetS components in an elderly population. Additionally, MetS abnormalities, particularly abdominal obesity and high triglycerides levels, might be highly predictive of functional dependence in the elderly.


The current status of viscoelastic testing in septic coagulopathy.
Sepsis can be associated with different degrees of coagulopathy, ranging from a mild activation of the coagulation system to disseminated intravascular coagulation (DIC). The evaluation of haemostasis in the context of sepsis is important since it has been shown that anticoagulant therapies were beneficial mainly in patients with sepsis-induced DIC, but not in the general population of septic patients. Sepsis-induced haemostatic disturbances are not adequately reflected by standard coagulation tests (SCTs) which only consider the plasmatic components of the haemostatic system and not the cellular components. In addition, SCTs only assess the initiation phase of coagulation and reflect the activity of pro-coagulant factors, but lack sensitivity for the anticoagulant drive and the fibrinolytic activity. Viscoelastic tests (VET) are whole-blood tests which can assess clot formation and dissociation, and the contribution of both plasmatic and cellular components with a shorter turnaround time compared to SCTs. The use of VET in septic patients has proved useful for the assessment of the fibrinolytic activity, detecting hypercoagulable status and for the diagnosis of DIC and mortality risk prediction. While having relevant advantages over SCTs, the VET also present some blind spots or limitations leaving space for future improvement by the development of new reagents or new viscoelastic parameters.


Fitness evaluations and fitness findings in competitive junior tennis players.
Elite tennis players, as well as a large number of active recreational players, are involved in a sport that applies high repetitive loads that can create tension overload situations in certain key anatomic areas of the body and add to possible overload situations in other areas of the body. This results in patterns of inflexibility and weakness that can be demonstrated on a tennis-specific musculoskeletal exam, and that can be correlated with areas of increased injury occurrence. These players report conditioning programs that are, for the most part, inadequate to confer total conditioning of all the muscular parameters important in playing tennis. All of these factors, in addition to the frequency and type of playing, contribute to the occurrence of the overload injuries noted. These aspects need to be addressed in a preventative program for injury reduction. We do not believe that major changes in the way that tennis is played should be implemented until the effects of a proper preventative conditioning program are evaluated. The "ideal" conditioning program has not yet been found. While the exact composition of the program is in doubt, our studies allow us to recommend flexibility, strength, and endurance training for all athletes playing tennis at frequent intervals. This program should be guided by the findings on the preparticipation exam.


Proenkephalin-A derived peptides do not modulate cardiovascular effects of epinephrine on the isolated rat atrial preparations.
The catecholamines and the opioid peptides are found to be co-localized in the adrenomedullary chromaffin cells. They are co-secreted from the chromaffin granules in response to various stimuli. The stress-induced released of epinephrine is known to exert its effect on the cardiovascular system resulting in the changes in heart rate and blood pressure. However, the role of the co-released proenkephalin-A derived peptides has not been extensively characterized. Previous work from several investigators suggested that the peptides modulate cardiac functions of the catecholamines. There is considerable conflicting results among these reports. Results from the isolated rat atrial preparation indicated that enkephalins attenuated the increase in atrial rate induced by norepinephrine through restriction of the calcium fluxes. Nonetheless, others reported insensitivity of the enkephalins in similar or different test systems. We further re-examined these discrepancies using the isolated rat atrial preparation to investigate the opioid peptide modulatory effect on the cardiovascular changes induced by exogenous epinephrine. Alterations in rate and force of contraction resulting from epinephrine and the peptides were both studied in parallel. The opioid peptides used in this study were [Met5]-enkephalin (ME), [Leu5]-enkephalin (LE), FMRFamide, [Met5]-enkephalyl-Arg6-Phe7 (MEAP), peptide E, and the non-selective opioid agonist, etorphine. We report here that none of the opioid peptides were effective in alleviating or attenuating the increase in heart rate and developed tension caused by epinephrine. The peptides did not affect the basal beating rate nor the force of contraction. Thus, the present results clearly demonstrate the insensitivity of the enkephalins in modulating the cardiac effects of epinephrine. They further indirectly support the prejunctional synaptic nerve endings as the potential peripheral site of action of the peptides.


Endocardial Hemangioma of the Right Ventricle: Complete Excision With Right Ventricular Restoration.
Primary cardiac tumor can arise from any location in the right and left cardiac chamber. Complete excision is generally recommended because of uncertainty regarding malignancy; however it is important to minimize the resultant functional deterioration after surgery. We report a case of endocardial hemangioma (4 × 3 × 3 cm) on the free wall of the right ventricle, located between the anterior and posterior papillary muscles. We describe details of the procedure to preserve the right ventricular volume and competence of the tricuspid valve.


Neuronal effects of glabellar botulinum toxin injections using a valenced inhibition task in borderline personality disorder.
Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement.


Electrolyte conditioning-enhanced electrokinetic remediation of arsenic-contaminated mine tailing.
Feasibility of electrolyte conditioning with strong acidic or alkaline solution on electrokinetic remediation of arsenic-contaminated mine tailing was investigated in the laboratory. The mine tailing contained calcium oxide of more than 50%. At alkaline condition, arsenic was precipitated with calcium, and formed calcium arsenate which is very stable solid. Catholyte conditioning with strong acidic solution and anolyte conditioning with strong alkaline solution showed similar efficiency to remove arsenic. At 4mAcm(-2) of current density, the removal efficiency of arsenic was 62% after 28 days operation with catholyte conditioning with 0.1M nitric acid.


Clinical long-term study of complete denture wearers.
Thirty-two patients initially treated with a complete denture in the maxilla or mandible were examined after 21 years. The examination included a questionnaire plus clinical and radiographic examinations. Denture function was assessed in general as very good or fairly good by the patients, but about half of the subjects also felt that the dentures needed some attention. The patients generally had a high evaluation of their chewing ability. The functional state of the masticatory system, both according to patients' reports and the clinical signs, was generally good compared with previously published epidemiologic studies. The denture quality and tissue health were far from optimum according to prosthodontic criteria. By overall judgment, 14 patients needed new dentures and six needed relining, occlusal adjustment, or repair. Tracing of cephalometric radiographs showed wide variations in bone resorption among patients.


[Hodgkin's disease in HIV infection--detection of Epstein-Barr virus DNA in tongue epithelium and lymphoma].
We present an HIV-infected patient with lymphadenopathy syndrome in whom an unusually aggressive case of Hodgkin's disease developed. Examination of tissue excised from the lymphoma and of epithelial cells scraped from the tongue of the patient revealed Epstein-Barr virus (EBV). The relationship between an enhanced replication of EBV in the epithelium of the tongue and the elevated frequency of Hodgkin's lymphomas containing EBV-DNA among HIV-infected patients is discussed.


Dental erosion: in vitro model of wine assessor's erosion.
Wine makers and assessors frequently experience severe dental erosion. The objectives of this study were to develop an in vitro model of dental erosion caused by frequent wine contact with teeth, and to use this model to assess the effectiveness of a variety of methods which might protect against this form of erosion. An initial pilot study found that riesling style wine was more erosive than champagne style, and both more than claret. Wine tasting was simulated by subjecting exposed windows of enamel and root surfaces on 50 intact, extracted human teeth to 1400 one minute exposures to white wine (ph 3.2). A variety of dental materials were applied to the exposed windows on groups of teeth prior to erosive challenge, to assess their protective ability. Protective resin coatings and fluoride varnishes protected both enamel and roots against wine induced erosion. A high degree of protection was provided by apf gel, with less by naf gel. It was concluded that dentists may be able to help minimise erosion resulting from frequent wine-tasting in their patients by the clinical application of one or a combination of these agents at times prior to prolonged assessment periods.


Geographic and temporal trends in the management of occult primary breast cancer: a systematic review and meta-analysis.
Management of occult primary breast cancer (OPBC), including the role of magnetic resonance imaging (MRI), is controversial. We conducted a pooled analysis of OPBC patients and a meta-analysis of MRI accuracy in OPBC in order to elucidate current practices. A literature search yielded 201 studies. Patient-level data for clinically/mammographically OPBC from studies published after 1993 and from our institution were pooled; logistic regression examined associations between patient/study data and outcomes, including treatments and recurrence. We report adjusted odds ratios (OR) and 95 % confidence intervals (95 % CI) significant at 2-tailed p < 0.05. Meta-analysis included data for patients who received MRIs for workup of clinically/mammographically OPBC. We report pooled sensitivity and specificity with 95 % CIs. The pooled analysis included 92 patients (15 studies [n = 85] plus our institution [n = 7]). Patients from Asia were more likely to receive breast surgery (OR = 5.98, 95 % CI = 2.02-17.65) but not chemotherapy (OR = 0.32, 95 % CI = 0.13-0.82); patients from the United States were more likely to receive chemotherapy (OR = 13.08, 95 % CI = 2.64-64.78). Patients from studies published after 2003 were more likely to receive radiotherapy (OR = 3.86, 95 % CI = 1.41-10.55). Chemotherapy recipients were more likely to have distant recurrence (OR = 9.77, 95 % CI = 1.10-87.21). More patients with positive MRIs received chemotherapy than patients with negative MRIs (10 of 12 [83.3 %] vs 5 of 13 [38.5 %]; p = 0.0414). In the MRI-accuracy meta-analysis (10 studies, n = 262), pooled sensitivity and specificity were 96 % (95 % CI = 91-98 %) and 63 % (95 % CI = 42-81 %), respectively. OPBC management varied geographically and over time. We recommend establishing an international OPBC patient registry to facilitate longitudinal study and develop global treatment standards.


Combined use of two rapid tests for the conclusive diagnosis of Chagas disease: a systematic scoping review.
The goal of this systematic scoping review is to collect and summarise scientific evidence regarding the validity of two simultaneous immunochromatographic tests for the conclusive diagnosis of Chagas disease. The research was informed by the following review questions: Will the use of two rapid tests be a valid method for the definitive diagnosis of Chagas disease when compared with conventional serological tests? In what type of population has the operation of two rapid tests been tried for the diagnosis of Chagas disease? What are the biomedical and public health advantages of the diagnostic method resulting from the combination of two rapid tests over the conventional serological method? Will it be a cost-benefit strategy for the diagnosis of Chagas with respect to conventional serological tests? Systematic scoping review. A search of the published and unpublished literature in five databases was carried out, in order to identify, screen and select the studies included in this review. 468 studies were identified, of which 46 were screened with a full-text reading, and finally, three articles were included in the review. All studies were in endemic countries with adult and paediatric populations (n=1133) and, together, they evaluated four different rapid tests. The rapid tests showed good sensitivity (97.4%-100%) and specificity (96.1%-100%) for the diagnosis of Chagas when used in combination and compared with the reference tests. The simultaneous use of at least two immunochromatographic rapid tests is a valid option for the definitive diagnosis of chronic Chagas in endemic rural areas, as long as there are studies that previously evaluate their performance on the areas of implementation. Therefore, this could be an alternative to the current diagnostic standard. However, additional studies are still needed in more countries in order to provide further evidence and to investigate the cost-benefit.


Genetic regulation of liver alcohol dehydrogenase in Peromyscus.
Data from genetic crosses of Peromyscus maniculatus and P. polionotus suggests that electrophoretic variants of liver alcohol dehydrogenase are coded by alleles at a single locus. These alleles, designated AdhF, AdhS, and AdhN, determine, respectively, the fast, slow, and not detectable (null) ADH electrophoretic phenotype. Heterozygotes (AdhF/AdhS) exhibit three bands on zymograms, suggesting a dimeric subunit structure for the enzyme. However, AdhF/AdhN and AdhS/AdhN animals exhibit a single band, suggesting that the AdhN allele does not produce a polypeptide subunit capable of dimerizing into an active molecule. Fast and slow electrophoretic phenotypes exhibit multiple bands which can be converted into single major fast and slow bands, respectively, upon treatment with oxidized or reduced NAD. Addition of NAD also stabilizes both the fast and slow enzyme to heat inactivation at 60 C for at least 30 min.


Speciosaperoxide, a new triterpene acid, and other terpenoids from Chaenomeles speciosa.
Investigation on the EtOH extract of the fruits of Chaenomeles speciosa led to the isolation of a new triterpene acid bearing an unusual hydroperoxyl substitute group at C-11, speciosaperoxide (1), along with six known triterpenoids, 3beta-acetoxyurs-11-en-13beta,28-olide (2), 3-O-acetyl ursolic acid (3), oleanolic acid (4), ursolic acid (5), masilinic acid (6), and tormentic acid (7), and three known norsesquiterpenoids, roseoside (8), vomifoliol (9) and (6S,7E,9R)-6,9-dihydroxy-4,7-megastigmadien-3-one 9-O-[beta-d-xylopyranosyl (1 --> 6)-glucopyranoside] (10). Their structures were elucidated on the basis of spectroscopic data and comparison with reference data. Besides compound 1, compounds 2, 8-10 were obtained from this genus for the first time. None of these compounds exhibited inhibitory activity against T-and B-lymphocyte proliferation.


Ascending Aorta 4D Time to Peak Distention Sexual Dimorphism and Association with Coronary Plaque Burden Severity in Women.
Coronary artery disease (CAD) risk and plaque scores are often subjective and biased, particularly in mid-age asymptomatic women, whose CAD risk assessment has been historically underestimated. In this study, a new automatic ascending aorta time-to-peak-distention (TPD) analysis was developed for fast screening and as an independent surrogate for subclinical atherosclerosis in asymptomatic women. CCTA was obtained in 50 asymptomatic adults. Plaque burden segment involvement score (SIS) and automatic TPD were obtained from all subjects. Logistic regression analyses were performed to investigate the association between CAD risk scores and TPD with severe coronary plaque burden (SIS>5). TPD, individually, was found to be a significant predictor of SIS>5. Additionally, sex was a significant effect modifier of TPD, with a stronger statistically significant association with women. Four-dimensional aortic time-to-peak distention could supplement conventional CCTA analysis and offer a quick objective screening tool for plaque burden severity and CAD risk stratification, especially in women.


Metabolism of [U-14C]-4-hydroxybutyric acid to intermediates of the tricarboxylic acid cycle in extracts of rat liver and kidney mitochondria.
The metabolism of [U-14C]-4-hydroxybutyric acid (GHB) was investigated in sonicates of mitochondria of rat heart, kidney and liver. The conversion of this precursor to 14C-organic acids was monitored and quantified by sequential liquid-partition chromatography on hydrated columns of silicic acid using a concave-upward gradient of 2-methylbutan-2-ol in chloroform. Sonicates of liver and kidney mitochondria, but not heart, readily converted [U-14C]-GHB to 14C organic acids via a pathway of conversion to 14C-succinic acid, followed by further metabolism through the tricarboxylic acid cycle. This conversion was facilitated by exogenous NAD+ and NADP+. No evidence for the beta-oxidation of GHB was obtained in any of the mitochondrial sonicates. Studies with exogenous non-labelled succinic semialdehyde indicated that this compound was an intermediate in the conversion of GHB to succinic acid.


Effect of intervention using a messaging app on compliance and duration of treatment in orthodontic patients.
This study aims to determine the effectiveness of a messaging app (WeChat) in improving patients' compliance and reducing the duration of orthodontic treatment (DOT). A randomized controlled trial was performed in a dental hospital and a clinic from August 2012 to May 2015. Orthodontic patients were included at the beginning of treatment. Patients with multiphase treatment or braceless technique were excluded. Participants were randomized to WeChat group (received regular reminders and educational messages) or control group (received conventional management) and were followed up until the treatment was completed. Primary outcome measure was DOT. Others were late and failed attendance, bracket bond failure, and oral hygiene condition. One hundred twelve patients in each group participated and completed the trial. DOT in WeChat group were 7.3 weeks shorter (P = 0.007). There were less failed attendance (3.1 vs. 10.9 %, P < 0.001), late attendance (20.1 vs. 29.9 %, P < 0.001), and bracket bond failure (11.8 vs. 16.1 %, P < 0.001) in WeChat group than control. There was no difference in orthodontic plaque index nor modified gingivitis index between the two groups before and after treatment. Number of failed attendances was identified as an independent factor affecting DOT (P = 0.004; HR = 0.89, 95 % CI 0.84 to 0.95). The intervention with WeChat is effective in reducing the treatment duration and bracket bond failure, and improving the attendance in orthodontic patients. DOT can be reduced by improving patient's compliance. The messaging app is useful for outpatient education and management.


Nonablative laser skin resurfacing for periorbital wrinkling-A case series of 16 patients.
Many modalities have been described for the treatment of periorbital wrinkling. The purpose of this study is to quantify the improvement of periorbital wrinkling achieved by current nonablative modalities, using a fractional 1565 nm Er:glass fiber laser. Our study is a retrospective two-center case series including 16 patients treated with nonablative laser for periorbital wrinkling at the Tel-Aviv Sourasky Medical Center in Israel and Laserplast Aesthetic Medicine Center in Italy between 2017 and 2019. Patients were assessed for objective and subjective improvement, patient satisfaction, side effect profile, and downtime. Improvement in average Fitzpatrick Wrinkle Scale scores (from 4.3 to 2.7 by ranking physician 1 and 3.8 to 2.4 by ranking physician 2, P < .001) was observed after 8 weeks. Global Assessment Improvement Scale scores were 2.6 (physician 1) and 2.2 (physician 2) on average. This correlated to mild-moderate subjective sense of improvement by patients. Side effects and downtime were minimal. Our study suggests that current nonablative laser skin resurfacing technology offers a mild-moderate improvement in periorbital wrinkling.


The contribution of bone to whole-organism physiology.
The mouse genetic revolution has shown repeatedly that most organs have more functions than expected. This has led to the realization that, in addition to a molecular and cellular approach, there is a need for a whole-organism study of physiology. The skeleton is an example of how a whole-organism approach to physiology can broaden the functions of a given organ, reveal connections of this organ with others such as the brain, pancreas and gut, and shed new light on the pathogenesis of degenerative diseases affecting multiple organs.


[Colonic stenosis with primary resection (author's transl)].
A primary resection and reanastomosis of the colon is often the procedure of choice, even in the presence of a significant stenotic element, provided there are no mayor disturbances of water-electrolyte homeostasis. In a series of 100 consecutive colonic resections (23 complicated by perforation, 9 by ileus, and 2 by bleeding), 97 patients were treated by primary resection (92 without a protective colostomy). No untoward effects were noted specifically due to this technique. The overall mortality rate was 4%, a favorable result when compared with the cumulative risk of a multiple stage procedure.


Cancer Risk and its Association With Diabetes Mellitus in Patients With Acromegaly: A Two Center-based Study.
To compare the incidence of cancer in patients with acromegaly with that of the local population in China and explore possible risk factors. Data from 117 patients diagnosed with acromegaly at 2 centers between 2011 and 2022 were analyzed, and their cancer diagnoses were recorded. The cancer standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated by comparison with those of the local population. The patients were divided into 2 groups, having cancer diagnosis or not. The relationships between cancer and sex, body mass index, age, growth hormone levels, diagnosis delay, tumor size, disease duration, treatment, disease status, and other comorbidities were analyzed. Eight (6.8%) of 117 patients were diagnosed with cancer. The incidence of overall (SIR = 3.29, 95% CI = 1.42-6.94), colorectal (SIR = 16.67, 95% CI = 4.45-42.67), and thyroid cancers (SIR = 14.29, 95% CI = 1.73-51.60) was increased, but that of lung cancer (SIR = 4.17, 95% CI = 0.50-15.05) was not. Diagnostic delay (10.1[8.6-14.3] vs 3.8[1.3-9.0]; P = .005) and duration of acromegaly (12.8[8.9-16.4] vs 5.6[2.3-10.9]; P = .008) were prolonged in the cancer group. Diabetes mellitus (odds ratio = 7.01, 95% CI = 1.23-39.99) was an independent risk factor for acromegaly with cancer. Acromegaly patients are at a higher risk of cancer and its association with diabetes mellitus. Considering the rarity of the disease, an Acromegaly Cancer Registry Center should be established in China as soon as possible.


[Home telemonitoring of CPAP: a feasibility study].
The most commonly used treatment for the sleep apnoea syndrome (SAS) is the application of constant positive airway pressure (CPAP) during sleep. Compliance is an essential element in the efficiency of CPAP. This is dependent on the quality of the management of care and on the education of the patients. With the emergence of telemedicine, telemonitoring of CPAP has been developed in France. This study will be observational and multicentered. The main aim is to evaluate the feasibility of CPAP telemonitoring in SAS patients (n=90). During the installation of the equipment, the patients will be instructed how to connect the CPAP Secure Digital card to a data transmitting box every week for two months. The actual number and frequency of remote-monitoring box connections will be recorded. The data transmission will be made to the study coordinator, the home care provider SADIR, by the way of a telemedicine platform, located in France. This study will allow measurement of the adherence of the patients to their CPAP treatment by telemonitoring using this new tool of data transmission and the impact of this on CPAP compliance.


Prenatal screening: invasive diagnostic approaches.
Fetal invasive procedures provide ovular samples that are helpful in establishing diagnosis, etiology, and prognosis when ultrasonography and MRI show a central nervous system (CNS) anomaly or when the fetus is at high risk of such pathology. Invasive procedure techniques are amniocentesis, fetal blood sampling (FBS), and chorionic villous sampling (CVS). They provide material for fetal DNA, biochemical analysis, or identification of various infectious agents. The main complications are miscarriage and premature delivery. Counseling the parents about the risks and benefits of these procedures is therefore mandatory. Amniocentesis may be performed as early as 15 weeks' gestation and is the most widely used invasive technique. FBS is performed after 18 to 20 weeks of pregnancy and CVS may be carried out after 11 weeks. Indications for invasive techniques include DNA and cytogenetic analysis, diagnosis of neural tube defects, identification of infectious agents (toxoplasmosis, cytomegalovirus, rubella, and varicella), and etiology of intracerebral hemorrhage (fetal platelets and coagulation factors).


Delayed splenic rupture: diagnosed by culdocentesis.
Culdocentesis is a valuable asset in the diagnosis of hemoperitoneum in women. A case report of delayed splenic rupture diagnosed by this means emphasizes its usefulness. When compared to paracentesis and peritoneal lavage, culdocentesis is more rapid, theoretically more sensitive, and easier to perform. It is a valuable diagnostic tool.


Individualized clinical management of patients at risk for Alzheimer's dementia.
Multidomain intervention for Alzheimer's disease (AD) risk reduction is an emerging therapeutic paradigm. Patients were prescribed individually tailored interventions (education/pharmacologic/nonpharmacologic) and rated on compliance. Normal cognition/subjective cognitive decline/preclinical AD was classified as Prevention. Mild cognitive impairment due to AD/mild-AD was classified as Early Treatment. Change from baseline to 18 months on the modified Alzheimer's Prevention Cognitive Composite (primary outcome) was compared against matched historical control cohorts. Cognitive aging composite (CogAging), AD/cardiovascular risk scales, and serum biomarkers were secondary outcomes. One hundred seventy-four were assigned interventions (age 25-86). Higher-compliance Prevention improved more than both historical cohorts (P = .0012, P < .0001). Lower-compliance Prevention also improved more than both historical cohorts (P = .0088, P < .0055). Higher-compliance Early Treatment improved more than lower compliance (P = .0007). Higher-compliance Early Treatment improved more than historical cohorts (P < .0001, P = .0428). Lower-compliance Early Treatment did not differ (P = .9820, P = .1115). Similar effects occurred for CogAging. AD/cardiovascular risk scales and serum biomarkers improved. Individualized multidomain interventions may improve cognition and reduce AD/cardiovascular risk scores in patients at-risk for AD dementia.


Effect of oxytocin on neuroblastoma cell viability and growth.
Oxytocin, released in response to different physiological stimuli, could play a key role in reducing stress reaction. It was suggested that it has protective effect against inflammation and consequences of oxidative stress. Mechanisms how oxytocin effects mediated in the brain tissue are unclear. In this study, oxytocin effect on cell growth and neuronal viability was examined. Human neuroblastoma (SH-SY5Y and SK-N-SH) and glioblastoma (U87MG) cells were exposed to different concentrations of oxytocin for 12-96 h. Potential protective effect of oxytocin treatment was investigated after exposing cells to oxidative stress using hydrogen peroxide (50 mM, 2 h) or 6-hydroxydopamine (25 μM, 24 h). Cell proliferation was measured by cell counting and cell viability was examined by MTT assay. Protein expression of selected neurotrophic factors was measured as an additional parameter. Oxytocin (1 μM) significantly increased cell number in all three cell types. Viability of SH-SY5Y cells was increased in the presence of oxytocin without significant effect of dose (0.01-1 μM). Cell death induced by hydrogen peroxide was not prevented by incubation with oxytocin. Oxytocin pretreatment blunted neurotoxin 6-OHDA reduction of cell viability in SH-SY5Y cells. Oxytocin (1 μM, 12 h) elevated amount of total proteins without increasing levels of brain-derived neurotrophic factor and neurotrophic growth factor. In conclusion, oxytocin increases growth and viability of neuroblastoma and glioblastoma cells without activation of neurotrophic factors. Oxytocin does not have protective effect in oxidative stress; however, it might be important for neuroprotection to dopaminergic neurons. Its proliferative effect might be important in native cell life, euplastic processes, and tumor progression.


Reproductive ovarian testing and the alphabet soup of diagnoses: DOR, POI, POF, POR, and FOR.
There are large variations in the number of oocytes within each woman, and biologically, the total quantity is at its maximum before the woman is born. Scientific knowledge is limited about factors controlling the oocyte pool and how to measure it. Within fertility clinics, there is no uniform agreement on the diagnostic criteria for each common measure of ovarian reserve in women, and thus, studies often conflict. While declining oocyte quantity/quality is a normal physiologic occurrence as women age, some women experience diminished ovarian reserve (DOR) much earlier than usual and become prematurely infertile. Key clinical features of DOR are the presence of regular menstrual periods and abnormal-but-not-postmenopausal ovarian reserve test results. A common clinical challenge is counseling patients with conflicting ovarian reserve test results. The clinical diagnosis of DOR and the interpretation of ovarian reserve testing are complicated by changing lab testing options and processing for anti-mullerian hormone since 2010. Further, complicating the diagnostic and research scenario is the existence of other distinct yet related clinical terms, specifically premature ovarian failure, primary ovarian insufficiency, poor ovarian response, and functional ovarian reserve. The similarities and differences between the definitions of DOR with each of these four terms are reviewed. We recommend greater medical community involvement in terminology decisions, and the addition of DOR-specific medical subject-heading search terms.


The Effectiveness of Silodosin for Nocturnal Polyuria in Elderly Men With Benign Prostatic Hyperplasia: A Multicenter Study.
To investigate improvement in nocturia and nocturnal polyuria in nocturnal polyuria patients after silodosin administration by using a 3-day frequency volume chart. This was a prospective multicenter study. We enrolled nocturnal polyuria patients (nocturnal polyuria index [NPi]>0.33), aged ≥60 years, diagnosed with the 3-day frequency volume charts of patients with benign prostatic hyperplasia taking α-blockers. Of the 54 patients, 30 (55.6%) completed the study according to the study protocol (per-protocol group), and 24 dropped out (dropout group). Of the 24 patients in the dropout group, 5 withdrew consent due to side effects or lack of efficacy, 7 were lost to follow-up at 4 weeks, 8 were lost to follow-up at 12 weeks, and 4 dropped out due to failure to complete 3-day frequency volume charts at 12 weeks. In the per-protocol group, there was significant improvement in the International Prostate Symptom Score (IPSS), especially question numbers 1, 3, 4, 5, 6, 7, and the quality of life question (P=0.001, P=0.007, P<0.001, P=0.003, P=0.049, P<0.001, and P<0.001, respectively). The Leeds sleep evaluation questionnaire (LSEQ) score for the sleep question improved from 64.36 to 70.43 (P=0.039). The NPi reduced from 0.4005 to 0.3573 (P=0.027); however, in many cases, there was no improvement in nocturnal polyuria itself. In intention-to-treat analysis, there were significant improvements in IPSS and LSEQ in 45 patients. In elderly nocturnal polyuria patients, silodosin monotherapy exhibits good efficacy in improving nocturia and nocturnal polyuria; however, the mean NPi was still >0.33. Considering the high dropout rate of our study due to no implementation of 3-day frequency volume charts, prospective and large-scale studies are needed to confirm our results.


Health risks and benefits of bottled water.
Health and safety concerns have dramatically increased the consumption of bottled water in developed countries, including the United States. The economic and environmental impact of the many different bottled water products on the market is considerable, and the role and impact of bottled water for routine use is unclear, outside the setting of emergencies or natural disasters, when routine water sources may be unsafe. Evidence for routine health risks or benefits from using bottled water is limited. Patients who have specific health needs may wish to use bottled or filtered water. Physicians can use background information regarding the regulation, production, and possible health impact of bottled water to counsel patients.


Combined NMR and X-ray diffraction study of structural aspects, dynamics and charge ordering mechanism in LixVOPO4.2H2O intercalation compounds.
We carried out a detailed investigation of the local ordering and dynamics of the lithium intercalation in paramagnetic LixVOPO4.2H2O (with 0 < x ≤ 1) materials. This question was addressed using a combination of X-ray diffraction, 31P and 7Li MAS NMR experiments. We first studied the structure of the fully ordered end-member of the series, Li1VOPO4.2H2O, revisiting the X-ray single crystal diffraction data on the basis of the information provided by 31P MAS NMR. We then carried out 7Li MAS and exchange NMR experiments and 31P MAS experiments on the polycrystalline powders obtained after partial lithium insertion in VOPO4.2H2O phases. These experiments evidenced an unexpected ageing of the material related with lithium dynamics between the VOPO4 layers and a V4+/V5+ charge ordering mechanism within the layers.


Rational Design of the Lotus-Like N-Co2 VO4 -Co Heterostructures with Well-Defined Interfaces in Suppressing the Shuttle Effect and Dendrite Growth in Lithium-Sulfur Batteries.
The shuttle effect caused by soluble lithium polysulfides (LiPSs) and intrinsic slow electrochemical transformation from LiPSs to Li2 S/Li2 S2 will induce undesirable cycling performance, which is the primary obstruct limiting the practical applications of lithium-sulfur (Li-S) batteries. Here a convenient method is designed to fabricate the 2D louts-like N-Co2 VO4 -Co heterostructures with well-abundant interfaces and oxygen vacancies (Vo ), endowing the materials with both "sulfiphilic" and "lithiophilic" features. When employed as the modification layer coated on commercial Celgard 2400 separator, the as-prepared N-Co2 VO4 -Co/PP with synergistic adsorption-electrocatalysis effects achieves desirable sulfur electrochemistry, thus showing a high initial discharge capacity of 1466.4 mAh g-1 at 0.1 C and stable cycle life with a fade rate of 0.03% per cycle over 1000 cycle at 3.0 C. Moreover, a superior areal capacity of 12.84 mAh cm-2 is preserved under high sulfur loading of 14.3 mg cm-2 .


The role of hydrophobic interactions in the molten globule state of globular protein modulated by surfactants.
In order to highlight the role of hydrophobic interactions in the molten globule (MG) state of globular protein modulated by surfactants, the interactions of bovine α-lactalbumin (α-LA) with alkyl trimethylammonium bromides (CnTAB, n = 10, 12, 14, and 16) have been studied by experimental and theoretical techniques. Isothermal titration calorimetry (ITC) showed that the enthalpy changes (ΔH) and area of the enthalpogram increased with increasing the chain length of CnTAB. The result of fluorescence, circular dichroism (CD) and 1H nuclear magnetic resonance (NMR) spectrum suggested that C10TAB and C12TAB unfolded α-LA partially, C14TAB reconstructed protein with a native-like secondary structure content, and C16TAB induced an MG state α-LA. The SAXS results confirmed that the tertiary structure of α-LA was disrupted by C16TAB forming an MG state complex with a micelle-like structure even at the surfactants concentrations below CMC. As indicated by MD results, the β-domain and unstructured region(s) were involved in the MG state α-LA modulated by CnTAB. This work not only provides molecular insights into the role of hydrophobic interactions in the MG state of a globular protein but also helps understand the mechanism of preparing α-LA based biomacromolecule modulated by hydrophobic interactions.


The implications of endemic IMP-4 carbapenemase for clinical laboratory susceptibility testing.
A local predominance of carbapenemase producing Enterobacteriaceae with low minimum inhibitory concentrations (MIC) to meropenem prompted a review of methods available for carbapenemase detection. We report on results using two selective media, temocillin discs, CarbaNP test, GeneXpert Carba-R assay and an in-house PCR assay.


Improvement of exercise capacity by sarpogrelate as a result of augmented collateral circulation in patients with effort angina.
The purpose of this study was to evaluate whether a serotonin blocker, sarpogrelate, improves exercise capacity as a result of vasodilation of coronary collateral channels in patients with effort angina. Serotonin has been reported to decrease coronary collateral blood flow by collateral vasoconstriction in a canine model, suggesting that platelet activation in feeding coronary arteries of the collateral network has the potential to cause collateral vasoconstriction. The subjects consisted of 22 patients with effort angina and reproducible ischemic threshold (group A, 11 patients with thrombolysis in myocardial infarction (TIMI) grade 2 or 3 flow of the ischemia-related coronary artery and Rentrop's collateral index 0 or 1; group B, 11 patients with TIMI grade 0 or 1 flow and Rentrop's collateral index 2 or 3). We repeated the symptom-limited treadmill exercise test using the Balke-Ware protocol and exercise tetrofosmin myocardial perfusion scintigraphy with and without pretreatment with 200 mg orally administered sarpogrelate. Each exercise test was performed at 9:00 a.m. on different days. The order of tests with and without sarpogrelate was randomized. In group A, sarpogrelate increased neither exercise time at 0.1 mV ST depression nor double product at 0.1 mV ST depression. In contrast, in group B sarpogrelate increased the exercise duration at 0.1 mV ST depression from 181+/-112 (SD) to 248+/-131 s (p < 0.05) and also increased the double product at 0.1 mV ST depression by 21% (p < 0.01). The severity score using myocardial perfusion scintigraphy at the same workload was significantly (p < 0.01) decreased by 37% in group B, but not in group A (11%), due to the sarpogrelate treatment. Sarpogrelate augments flow reserve of the collateral circulation and improves exercise capacity in anginal patients with well-developed collaterals. These findings indicate that a serotonin blocker, sarpogrelate, is useful not only as an antiplatelet drugs, but as an antianginal drug.


The Relationship between Smoking and Depression Post-Acute Coronary Syndrome.
The purpose of the current paper is to review research on the relationship between smoking cessation and depressed mood post-Acute Coronary Syndrome (Myocardial infarction or unstable angina; ACS). Emerging evidence regarding the effect of anhedonia-a specific subcomponent of mood disturbance characterized by reduced pleasure-on post-ACS outcomes is also discussed. There is strong evidence that depression prospectively predicts post-ACS relapse to smoking. Weaker evidence suggests that smoking at the time of ACS is related to post-ACS depression. Bupropion is a particularly promising treatment for this population because of its smoking cessation and anti-depressant effects. Future research should focus on the relative risk of using nicotine replacement therapies post-ACS, the efficacy of bupropion for smoking cessation and depression reduction in post-ACS patients, the role of anhedonia in post-ACS smoking cessation, and the development and testing of integrated behavioral treatments (smoking cessation plus interventions targeting mood management) for ACS patients.


Pyruvate:NADP+ oxidoreductase from Euglena gracilis: mechanism of O2-inactivation of the enzyme and its stability in the aerobe.
O2-inactivation of pyruvate:NADP+ oxidoreductase from mitochondria of Euglena gracilis was studied in vitro, and a mechanism which consists of two sequential stages was proposed. Initially, the enzyme is inactivated by the direct action of O2 in a process obeying second-order kinetics. Although the catalytic activity for pyruvate oxidation is lost by this initial inactivation, NADPH oxidation with artificial electron acceptors still occurs. Subsequently, a secondary, O2-independent inactivation occurs, rendering the enzyme completely inactive. Pyruvate stimulates the O2-inactivation while CoA and NADP+ protect the enzyme from O2. The O2-inactivation is accelerated by reduction of the enzyme with pyruvate and CoA. Reactivation of the O2-inactivated enzyme was studied in Ar by incubation with Fe2+ in the presence of some other reducing reagent such as dithiothreitol. The evidence obtained indicates that the partially inactivated enzyme, which retains catalytic activity for NADPH oxidation, can be reactivated, but the completely inactivated enzyme is not. When Euglena cells were exposed to 100% O2 the enzyme in the cells was inactivated by O2, but the rate was quite slow compared with that observed in vitro. The enzyme inactivated by O2 in the cells was almost completely reactivated in vitro by incubation with Fe2+ and other reducing reagents in Ar, suggesting that the secondary, O2-independent inactivation does not occur in situ. When the cells were returned to air, reactivation of the O2-inactivated enzyme in the cells began immediately. The enzyme, kept in isolated, intact mitochondria, was stable in air; however, the enzyme was inactivated by O2 when the mitochondria were incubated with a high concentration of pyruvate.


Graft immunologic events in deceased donor kidney transplant recipients with preformed HLA-donor specific antibodies.
Pretransplant donor-specific HLA alloantibodies detected with the Single Antigen Bead (SAB) assay reflect an increased risk for acute antibody-mediated rejection (AMR). We herein report the incidence of both acute AMR and acute cellular rejection (ACR) during the first year posttransplantation, in a cohort of kidney transplant recipients (KTR) of deceased donor (DD) grafts, according to their DSA status. Pretransplant DSA do not preclude DD-KT in negative CDC-XM recipients at our center. 246 KT were performed at our center between 01/2012 and 12/2015 and 100 KTR obtained from a DD were analyzed; 24% harbored DSA by SAB assay, MFI values >500 were considered positive. All recipients received thymoglobulin induction and generic tacrolimus-based maintenance therapy. Graft biopsies were performed by protocol on months 3 and 12 as well as per indication. The incidence of AMR and ACR was correlated with the existence of pretransplant DSA. Overall, 34% of patients developed an acute rejection episode, 54.2% in the DSA group versus 27.6% in the non-DSA group (p=0.032), and most of these events were detected as subclinical conditions in protocol biopsies. AMR events developed in 33.3% and 19.7% (p=0.176) in the DSA and the non-DSA groups, respectively. ACR events were found in 16.6% and 6.6% (p=0.127) in the DSA and non-DSA groups, respectively. Graft function was similar between groups at the end of the 1st year posttransplant and no immunological graft loss occurred. Despite the use of depleting induction therapy and adequate tacrolimus trough levels along with MMF and steroids, a high rate of rejection events was observed during the first year post-transplantation.


Comparison of ofloxacin and ceftriaxone in the treatment of uncomplicated gonorrhea caused by penicillinase-producing and non-penicillinase-producing strains.
Eighty-nine patients with uncomplicated gonorrhea, including 31 patients (34.8%) infected with penicillinase-producing strains of Neisseria gonorrhoeae, were treated with oral ofloxacin (single 400-mg dose) or intramuscular ceftriaxone (250-mg dose). All 47 patients who received ofloxacin and 41 of 42 patients who received ceftriaxone were cured.


Experience with a modification of the Cloutier technique for hypospadias repair.
A modification of the Cloutier technique of hypospadias repair is described. The technique is applicable to all but the most minor degree of the anomaly. When free of complications the final result approximates a cosmetically and functionally normal penis. Since June 1985, 35 children have undergone both stages of the repair. The only complication encountered was fistula formation in 5, for a complication rate of 14.3 per cent.


Pharmacokinetics of XEN496, a Novel Pediatric Formulation of Ezogabine, Under Fed and Fasted Conditions: A Phase 1 Trial.
XEN496 is a novel, granular, immediate-release formulation of ezogabine intended for pediatric use. The objective of this study was to assess the effect of food on the pharmacokinetics (PK) of XEN496 and its N-acetyl metabolite (NAMR) in healthy volunteers. Twenty-four adult subjects were enrolled in this phase 1, single center, open-label, randomized, single-dose, two-way crossover study. Subjects received 400 mg XEN496 as an oral suspension in both fed and fasted states separated by a 6-day washout period. Serial blood samples were collected up to 48 h post-administration. PK parameters evaluated included maximum observed plasma concentration (Cmax), time of maximum observed plasma concentration (Tmax), and area under the concentration-time curve (AUC(0-t) and AUCinf). Safety was assessed by laboratory evaluations, physical exam, and adverse event monitoring. For XEN496, median Tmax was 3 and 2 h in the fed and fasted states, respectively. AUC parameters in the fed and fasted states were equivalent, whereas food decreased Cmax of XEN496 by 32% compared to the fasted state. The ratio of geometric means [90% CI] for Cmax was 72% [64-82%]. For NAMR, food delayed Tmax by 1 h, while Cmax and AUC parameters were equivalent in the fed and fasted states. The safety profile of XEN496 in this study appeared comparable to that previously reported for ezogabine tablets. The biopharmaceutical performance of XEN496 in this study was as expected for an immediate-release, granular dosage formulation, and generally comparable to that reported for ezogabine tablets. Future studies are needed to characterize the efficacy, safety, and PK of XEN496 in a pediatric population.


A review of therapeutic impacts of saffron (Crocus sativus L.) and its constituents.
Application of herbal medicines in the treatment of diseases is in the center of attention of medical scientific societies. Saffron (Cricus sativus L.) is a medicinal plant belonging to the Iridaceae family with different therapeutic properties. The outcomes of human and animal experiments indicate that therapeutic impacts of saffron and its constituents, crocin, crocetin, and safranal, mainly are mediated via inhibiting the inflammatory reactions and scavenging free radicals. It has been suggested that saffron and crocin extracted from it also up-regulate the expression of sirtuin 1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2), down-regulate nuclear factor kappa B (NF-κB) signaling pathway and untimely improve the body organs dysfunction. Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 (COX2) also is attributed to crocin. The current review narrates the therapeutic effects of saffron and its constituents on various body systems through looking for the scientific databases including Web of Science, PubMed, Scopus, and Google Scholar from the beginning of 2010 until the end of 2022.


Sclerosing angioma of the lung. Case report and electron microscope investigation.
Electron microscopy of a sclerosing angioma of the lung, a coincidental finding in the upper lobe of a 32-year-old woman. The rare, benign tumor, whose vascular proliferation by light microscopy is reminiscent of an angioma, exhibits a clear epithelial structure by electron microscopy. The tumor may develop out of immature pneumocytes. The paper discusses histogenesis and problems of differential diagnosis (potential confusion with carcinomas).