Impact of Lower Versus Higher LDL Cholesterol Targets on Cardiovascular Events After Ischemic Stroke in Patients With Diabetes.
After an ischemic stroke with evidence of atherosclerosis, lipid-lowering treatment with a target LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL reduced the risk of subsequent cardiovascular events. In this analysis, we explored the effect in the subgroup of patients with diabetes compared with the subgroup without, as well as in those with newly diagnosed diabetes. Patients with ischemic stroke in the previous 3 months or transient ischemic attack within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned at a 1:1 ratio to a target LDL cholesterol of <70 mg/dL or 100 ± 10 mg/dL using statin or ezetimibe. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and death resulting from vascular disease. We performed a prespecified analysis to evaluate the effect in patients with diabetes. Of 2,860 patients enrolled, 643 had diabetes at baseline, with a mean age of 66.2 years and baseline LDL cholesterol of 127 mg/dL, and were followed for a median of 3 years. The primary composite end point occurred in 27 (8.2%) of 328 patients in the lower-target group and in 44 (14.0%) of 315 patients in the higher-target group (adjusted hazard ratio [HR] 0.56; 95% CI 0.34-0.89; P = 0.016). In patients without diabetes, the HR was 0.87 (95% CI 0.66-1.14; P = 0.31; interaction P = 0.15). In those with diabetes, there were three intracranial hemorrhages in both randomization groups (0.9% vs. 1.0%, respectively). Newly diagnosed diabetes occurred in 98 (9.2%) of 1,070 and in 80 (7.4%) of 1,085 patients in the lower- and higher-target groups, respectively (HR 1.27; 95% CI 0.94-1.71; P = 0.11), and baseline higher HbA1c was the unique multivariable predictor. In conclusion, after an ischemic stroke with evidence of atherosclerosis, targeting an LDL cholesterol of <70 mg/dL compared with 100 ± 10 mg/dL consistently reduced the risk of subsequent stroke and other major vascular events in patients with and without diabetes, but the higher risk in those with diabetes yielded a higher absolute risk reduction, with number needed to treat of 17.


MLCV: Bridging Machine-Learning-Based Dimensionality Reduction and Free-Energy Calculation.
Importance-sampling algorithms leaning on the definition of a model reaction coordinate (RC) are widely employed to probe processes relevant to chemistry and biology alike, spanning time scales not amenable to common, brute-force molecular dynamics (MD) simulations. In practice, the model RC often consists of a handful of collective variables (CVs) chosen on the basis of chemical intuition. However, constructing manually a low-dimensional RC model to describe an intricate geometrical transformation for the purpose of free-energy calculations and analyses remains a daunting challenge due to the inherent complexity of the conformational transitions at play. To solve this issue, remarkable progress has been made in employing machine-learning techniques, such as autoencoders, to extract the low-dimensional RC model from a large set of CVs. Implementation of the differentiable, nonlinear machine-learned CVs in common MD engines to perform free-energy calculations is, however, particularly cumbersome. To address this issue, we present here a user-friendly tool (called MLCV) that facilitates the use of machine-learned CVs in importance-sampling simulations through the popular Colvars module. Our approach is critically probed with three case examples consisting of small peptides, showcasing that through hard-coded neural network in Colvars, deep-learning and enhanced-sampling can be effectively bridged with MD simulations. The MLCV code is versatile, applicable to all the CVs available in Colvars, and can be connected to any kind of dense neural networks. We believe that MLCV provides an effective, powerful, and user-friendly platform accessible to experts and nonexperts alike for machine-learning (ML)-guided CV discovery and enhanced-sampling simulations to unveil the molecular mechanisms underlying complex biochemical processes.


Safety of in-utero antiretroviral exposure: neurologic outcomes in children who are HIV-exposed but uninfected.
To evaluate whether there is an increased risk of neurologic diagnoses in children who are HIV-exposed but uninfected (CHEU) exposed in utero to specific antiretroviral medications. Prospective cohort study of CHEU enrolled from 2007 to 2017. We evaluated children for neurologic case status, including microcephaly, febrile seizures, seizure disorders, ophthalmologic disorders, and other neurologic disorders. Adjusted relative risks (aRRs) were estimated for the association between in-utero antiretroviral exposure and neurologic case using log-binomial regression, accounting for potential confounders. Sensitivity analyses were conducted to evaluate robustness of findings. Among 3747 eligible CHEU, 231 (6.2%) met neurologic case criteria (95% CI 5.4--7%). Most eligible children (86%) were exposed in utero to combination antiretroviral regimens. In adjusted models, children exposed to efavirenz at any time during pregnancy had higher risk of neurologic case status (aRR = 1.53, 95% CI 0.94--2.51). This association was stronger when comparing efavirenz exposure at conception to no exposure during pregnancy (aRR = 1.92, 95% CI 1.09--3.36) and considering follow-up and case diagnosis only through age 2 (aRR = 2.14, 95% CI 1.11--4.12). Children exposed to didanosine at conception and during the first trimester had increased risk of neurologic case status (aRR = 2.28, 95% CI 1.07--4.87 and aRR = 2.02, 95% CI 1.01--4.04, respectively), compared with didanosine-unexposed children. Children with dolutegravir exposure had some suggestion of increased risk of neurologic case (aRR = 2.43, 95% CI 0.75--7.84), which was observed consistently across several sensitivity analyses. Efavirenz and didanosine exposure during pregnancy were associated with higher risk of neurologic abnormalities in CHEU, and dolutegravir exposure showed some suggestive associations, which warrant further monitoring.


[Role of salivary kallikrein in the pathogenesis of periodontosis].
In patients with parodontosis the distinct increase in salivary kallikrein secretion was found. In Wistar rats the intensity of age atrophy of alveoli dentalis correlated with BAEE-esterase activity of mixed saliva. Desalivation considerably decreased the rate of age atrophy of parodontosis in rats. Salivary kallikrein, penetrating in active form into parodontal tissues, caused the pronounced vasodilation in dogs and golden hamsters. By means of kallikrein preparations an intensive inflammatory-dystrophical process was reproduced in parodontal tissues of Wistar rats. The local treatment of patients with parodontosis by kallikrein inhibitors was found to be especially effective.


Genomics of Recombination Rate Variation in Temperature-Evolved Drosophila melanogaster Populations.
Meiotic recombination is a critical process that ensures proper segregation of chromosome homologs through DNA double-strand break repair mechanisms. Rates of recombination are highly variable among various taxa, within species, and within genomes with far-reaching evolutionary and genomic consequences. The genetic basis of recombination rate variation is therefore crucial in the study of evolutionary biology but remains poorly understood. In this study, we took advantage of a set of experimental temperature-evolved populations of Drosophila melanogaster with heritable differences in recombination rates depending on the temperature regime in which they evolved. We performed whole-genome sequencing and identified several chromosomal regions that appear to be divergent depending on temperature regime. In addition, we identify a set of single-nucleotide polymorphisms and associated genes with significant differences in allele frequency when the different temperature populations are compared. Further refinement of these gene candidates emphasizing those expressed in the ovary and associated with DNA binding reveals numerous potential candidate genes such as Hr38, EcR, and mamo responsible for observed differences in recombination rates in these experimental evolution lines thus providing insight into the genetic basis of recombination rate variation.


[Fibronectins: a possible treatment of therapy-resistant corneal ulcers].
Fibronectin was isolated from a patient's plasma by affinity chromatography using gelatin-agarose. Biochemical and immunological tests proved the homogeneity of the fibronectin fraction. A therapy-resistant corneal ulcer following keratitis neuroparalytica was successfully treated with the isolated fibronectin. The ulcer healed within 26 days of fibronectin treatment (1 drop 6 X daily) and eight months have now passed without it recurring.


[Influenza in heterothermic animals].
The objective was to study Orthomyxovirus in heterothermic animals. Blood samples from snakes (genus Bothrops and Crotalus) and from toads and frogs (genus Bufo and Rana) were collected to evaluate the red cell receptors and antibodies specific to influenza virus by the hemagglutination and hemagglutination inhibition tests, respectively. Both snakes and toads kept in captivity presented receptors in their red cells and antibodies specific to either influenza virus type A (human and equine origin) or influenza type B. The same was observed with recently captured snakes. Concerning the influenza hemagglutination inhibition antibodies protective levels were observed in the reptiles' serum, against influenza type A and type B. Unlike the toads, 83.3% of the frogs presented mean levels of Ab 40HIU for some influenza strains. It was concluded that heterothermic animals could offer host conditions to the influenza virus and also susceptibility to the infection.


Disparities in COVID-19 related outcomes in the United States by race and ethnicity pre-vaccination era: an umbrella review of meta-analyses.
Meta-analyses have investigated associations between race and ethnicity and COVID-19 outcomes. However, there is uncertainty about these associations' existence, magnitude, and level of evidence. We, therefore, aimed to synthesize, quantify, and grade the strength of evidence of race and ethnicity and COVID-19 outcomes in the US. In this umbrella review, we searched four databases (Pubmed, Embase, the Cochrane Database of Systematic Reviews, and Epistemonikos) from database inception to April 2022. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews, version 2 (AMSTAR-2). The strength of evidence of the associations between race and ethnicity with outcomes was ranked according to established criteria as convincing, highly suggestive, suggestive, weak, or non-significant. The study protocol was registered with PROSPERO, CRD42022336805. Of 880 records screened, we selected seven meta-analyses for evidence synthesis, with 42 associations examined. Overall, 10 of 42 associations were statistically significant (p ≤ 0.05). Two associations were highly suggestive, two were suggestive, and two were weak, whereas the remaining 32 associations were non-significant. The risk of COVID-19 infection was higher in Black individuals compared to White individuals (risk ratio, 2.08, 95% Confidence Interval (CI), 1.60-2.71), which was supported by highly suggestive evidence; with the conservative estimates from the sensitivity analyses, this association remained suggestive. Among those infected with COVID-19, Hispanic individuals had a higher risk of COVID-19 hospitalization than non-Hispanic White individuals (odds ratio, 2.08, 95% CI, 1.60-2.70) with highly suggestive evidence which remained after sensitivity analyses. Individuals of Black and Hispanic groups had a higher risk of COVID-19 infection and hospitalization compared to their White counterparts. These associations of race and ethnicity and COVID-19 outcomes existed more obviously in the pre-hospitalization stage. More consideration should be given in this stage for addressing health inequity.


Human Ro ribonucleoprotein particles: characterization of native structure and stable association with the La polypeptide.
Anti-Ro autoantibodies, found in sera of patients with systemic lupus erythematosus, Sjogren's syndrome, and related diseases, target the Ro ribonucleoprotein particles (RNPs). Although the polypeptide and RNA components of the Ro RNPs have been characterized, much less is known about the native structure of these particles. We have now characterized by biochemical techniques intact Ro ribonucleoprotein particles from cultured HeLa cells. These particles segregated in three discrete subpopulations with characteristic physicochemical properties: one containing hY5 RNA (RohY5 particles), one containing only hY4 RNA (RohY4 particles) and one with hY1, hY3, and hY4 RNAs (RohY1-hY4 particles). The RohY5 particles were purified free of contaminating ribonucleoproteins; both the La and the 60-kD Ro polypeptides were stable components of this portion of the Ro RNPs. The La RNPs co-purified with the RohY4 particles and contaminated the RohY1-hY4 RNPs. The stable association between the La and the 60-kD Ro polypeptides provides a potential macromolecular target for the linked set of anti-Ro and anti-La antibodies, and suggests a possible functional association of these polypeptides.


Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization.
We established a sustained vasohibin-1 (a 42-kDa protein), delivery device by a novel method using photopolymerization of a mixture of polyethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and collagen microparticles. We evaluated its effects in a model of rat laser-induced choroidal neovascularization (CNV) using a transscleral approach. We used variable concentrations of vasohibin-1 in the devices, and used an enzyme-linked immunosorbent assay and Western blotting to measure the released vasohibin-1 (0.31 nM/day when using the 10 μM vasohibin-1 delivery device [10VDD]). The released vasohibin-1 showed suppression activity comparable to native effects when evaluated using endothelial tube formation. We also used pelletized vasohibin-1 and fluorescein isothiocyanate-labeled 40 kDa dextran as controls. Strong fluorescein staining was observed on the sclera when the device was used for drug delivery, whereas pellet use produced strong staining in the conjunctiva and surrounding tissue, but not on the sclera. Vasohibin-1 was found in the sclera, choroid, retinal pigment epithelium (RPE), and neural retina after device implantation. Stronger immunoreactivity at the RPE and ganglion cell layers was observed than in other retinal regions. Significantly lower fluorescein angiography (FA) scores and smaller CNV areas in the flat mounts of RPE-choroid-sclera were observed for the 10VDD, VDD (1 μM vasohibin-1 delivery device), and vasohibin-1 intravitreal direct injection (0.24 μM) groups when compared to the pellet, non-vasohibin-1 delivery device, and intravitreal vehicle injection groups. Choroidal neovascularization can be treated with transscleral sustained protein delivery using our novel device. We offer a safer sustained protein release for treatment of retinal disease using the transscleral approach.


Pharmacokinetic and Biodistribution Studies of HPMA Copolymer Conjugates in an Aseptic Implant Loosening Mouse Model.
N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymers were previously found to represent a versatile delivery platform for the early detection and intervention of orthopedic implant loosening. In this article, we evaluated the impact of different structural parameters of the HPMA copolymeric system (e.g., molecular weight (MW), drug content) to its pharmacokinetics and biodistribution (PK/BD) profile. Using 125I, Alexa Fluor 488, and IRDye 800 CW-labeled HPMA copolymer-dexamethasone (P-Dex) conjugates with different MW and dexamethasone (Dex) contents, we found the MW to be the predominant impact factor on the PK/BD profiles of P-Dex, with Dex content as a secondary impact factor. In gamma counter-based PK/BD studies, increased MW of P-Dex reduced elimination, leading to lower clearance, longer half-life, and higher systemic exposure (AUC and MRT). In the semiquantitative live animal optical imaging evaluation, the distribution of P-Dex to the peri-implant inflammatory lesion increased when MW was increased. This result was further confirmed by FACS analyses of cells isolated from peri-implant regions after systemic administration of Alexa Fluor 488-labeled P-Dex. Since the in vitro cell culture study suggested that the internalization of P-Dex by macrophages is generally independent of P-Dex's MW and Dex content, the impact of the MW and Dex content on its PK/BD profile was most likely exerted at physiological and pathophysiological levels rather than at the cellular level. In both gamma counter-based PK/BD analyses and semiquantitative optical imaging analyses, P-Dex with 6 wt % Dex content showed fast clearance. Dynamic light scattering analyses unexpectedly revealed significant molecular aggregation of P-Dex at this Dex content level. The underlining mechanisms of the aggregation and fast in vivo clearance of the P-Dex warrant further investigation.


[Retail food outlets and the association with overweight/obesity in schoolchildren from Florianópolis, Santa Catarina State, Brazil].
The study analyzes retail food outlets and their association with overweight/obesity in schoolchildren from Florianópolis, Santa Catarina State, Brazil. The study used a cross-sectional design with a random sample of 2,506 schoolchildren from public (n = 19) and private schools (n = 11). Overweight and obesity were classified according to World Health Organization guidelines for 2007, and crude and adjusted analyses were performed using Poisson regression. Prevalence of overweight/obesity was 34.2%. In public schools, 19.6% of the children were overweight and 13.5% were obese, as compared to 22.4% and 11.1% in private schools. An association was found in the public school system between overweight/obesity and the use of bakeries for food purchases (p = 0.004). In the private school system, children of families that bought groceries at the supermarket showed 26% less overweight/obesity compared to those who did not (p = 0.003). The data show an association between some types of food outlets (supermarkets and bakeries) and prevalence of overweight/obesity in the school-age population.


[Two cases of acute methyl acetate poisoning].
This article analyzed the clinical data and on-site occupational health survey results of a patient with occupational acute methyl acetate poisoning in Zhejiang. Based on the pathways of methyl acetate poisoning and the characteristics of target organ damage, diagnosis and treatment experience were summarized, providing reference for the diagnosis and treatment of occupational acute methyl acetate poisoning and occupational health monitoring of methyl acetate.


Factors associated with coronary heart disease in COPD patients and controls.
COPD and coronary heart disease (CHD) frequently co-occur, yet which COPD phenotypes are most prone to CHD is poorly understood. The aim of this study was to see whether COPD patients did have a true higher risk for CHD than subjects without COPD, and to examine a range of potential factors associated with CHD in COPD patients and controls. 347 COPD patients and 428 non-COPD controls, were invited for coronary computed tomography angiography (CCTA) and pulmonary CT. Arterial blood gas, bioelectrical impedance and lung function was measured, and a detailed medical history taken. The CCTA was evaluated for significant coronary stenosis and calcium score (CaSc), and emphysema defined as >10% of total area <-950 Hounsfield units. 12.6% of the COPD patients and 5.7% of the controls had coronary stenosis (p<0.01), whereas 55.9% of the COPD patients had a CaSc>100 compared to 31.6% of the controls (p<0.01). In a multivariable model adjusting for sex, age, body composition, pack-years, CRP, cholesterol/blood pressure lowering medication use and diabetes mellitus, the OR (95% CI) for having significant stenosis was 1.80 (0.86-3.78) in COPD patients compared with controls. In a similar model, the OR (95% CI) for having CaSc>100 was 1.68 (1.12-2.53) in COPD patients compared with controls. Examining the risk of significant stenosis and CaSc>100 among COPD patients, no variable was associated with significant stenosis, whereas male sex [OR 2.85 (1.56-5.21)], age [OR 3.74 (2.42-5.77)], statin use [OR 2.23 (1.23-4.50)] were associated with CaSc>100, after adjusting for body composition, pack-years, C-reactive protein, use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), diabetes, emphysema score, GOLD category, exacerbation frequency, eosinophilia, and hypoxemia. COPD patients were more likely to have CHD, but neither emphysema score, lung function, exacerbation frequency, nor hypoxemia predicted presence of either coronary stenosis or CaSc>100.


[Female presence in teaching of dentistry and medicine carrers at the National University of Cordoba].
Social stratification based on gender has undoubtedly a powerful bearing on the division of labor in the area of health. The presence of women has reached significant levels in the Teaching Departments at almost every Institution of Higher Education, although it has been observed that the higher the position, the fewer the women occupying such positions. The purpose of this work is to analyze the evolution of admission and leaving of men and women students as well as the distribution of teaching positions according to sex at the School of Dentistry and at Medical School of the National University of Cordoba. In addition, this study aims at visualizing both the feminine role and the existence of posts in the field of education which are traditionally staffed by women, and also the factors contributing to define these positions. An analysis of the female participation in university education shows that in those programs of study where there is a predominance of female students, the proportion of women teachers is lower. It has also been noticed that the proportion of women working as teaching assistants is higher than that of women occupying leading positions in the management of the Schools. By the year 2003, at the University of Cordoba, 43% of the teachers and 58% of the students enrolled were women. At the School of Dentistry there is a higher percentage (10%) of female teachers, while at the School of Medicine the male teaching staff is 19.3% higher. These data allows us to infer that most probably, the differences observed in our analysis are the result of a held belief that considers that Medicine belongs to men's domain and consequently, women medical doctors find it difficult to gain prestige and reach high-level, well paid positions.


Acute respiratory infection and pneumonia in India: a systematic review of literature for advocacy and action: UNICEF-PHFI series on newborn and child health, India.
Scaling up of evidence based management of childhood acute respiratory infection/pneumonia, is a public health priority in India, and necessitates robust literature review, for advocacy and action. To identify, synthesize and summarize current evidence to guide scaling up of management of childhood acute respiratory infection/pneumonia in India, and identify existing knowledge gaps. A set of ten questions pertaining to the management (prevention, treatment, and control) of childhood ARI/pneumonia was identified through a consultative process. A modified systematic review process developed a priori was used to identify, synthesize and summarize, research evidence and operational information, pertaining to the problem in India. Areas with limited or no evidence were identified as knowledge gaps. Childhood ARI/pneumonia is a significant public health problem in India, although robust epidemiological data is not available on its incidence. Mortality due to pneumonia accounts for approximately one-fourth of the total deaths in under five children, in India. Pneumonia affects children irrespective of socioeconomic status; with higher risk among young infants, malnourished children, non-exclusively breastfed children and those with exposure to solid fuel use. There is lack of robust nation-wide data on etiology; bacteria (including Pneumococcus, H. influenzae, S. aureus and Gram negative bacilli), viruses (especially RSV) and Mycoplasma, are the common organisms identified. In-vitro resistance to cotrimoxazole is high. Wheezing is commonly associated with ARI/pneumonia in children, but difficult to appreciate without auscultation. The current WHO guidelines as modified by IndiaCLEN Task force on Penumonia (2010), are sufficient for case-management of childhood pneumonia. Other important interventions to prevent mortality are oxygen therapy for those with severe or very severe pneumonia and measles vaccination for all infants. There is insufficient evidence for protective or curative effect of vitamin A; zinc supplementation could be beneficial to prevent pneumonia, although it has no therapeutic benefit. There is insufficient evidence on potential effectiveness and cost-effectiveness of Hib and Pneumococcal vaccines on reduction of ARI specific mortality. Case-finding and community-based management are effective management strategies, but have low coverage in India due to policy and programmatic barriers. There is a significant gap in the utilization of existing services, provider practices as well as family practices in seeking care. The systematic review summarizes current evidence on childhood ARI and pneumonia management and provides evidence to inform child health programs in India.


Costs, emissions reductions, and vehicle repair: evidence from Arizona.
The Arizona inspection and maintenance (I/M) program provides one of the first opportunities to examine the costs and effectiveness of vehicle emission repair. This paper examines various aspects of emission reductions, fuel economy improvements, and repair costs, drawing data from over 80,000 vehicles that failed the I/M test in Arizona between 1995 and the first half of 1996. We summarize the wealth of data on repair from the Arizona program and highlight its limitations. Because missing or incomplete cost information has been a serious shortcoming for the evaluation of I/M programs, we develop a method for estimating repair costs when they are not reported. We find surprising evidence that almost one quarter of all vehicles that take the I/M test are never observed to pass the test. Using a statistical analysis, we provide some information about the differences between the vehicles that pass and those that do not. Older, more polluting vehicles are much more likely never to pass the I/M test, and their expected repair costs are much higher than those for newer cars. This paper summarizes the evidence on costs and emission reductions in the Arizona program, comparing costs and emissions reductions between cars and trucks. Finally, we examine the potential for more cost-effective repair, first through an analysis of tightening I/M cut points and then by calculating the cost savings of achieving different emission reduction goals when the most cost-effective repairs are made first.


Spontaneous cytotoxicity. III. Inhibition of human monocyte mediated cytotoxicity by pokeweed mitogen.
We have shown that human mononuclear cells become spontaneously cytotoxic to a variety of erythrocyte targets after 7 days of in vitro culture. This phenomenon of spontaneous cytotoxicity occurs in low concentration of either autologous serum of FCS and is independent of any known stimulant. It does not require exogenous antibody, mitogen, or antigen. Once expressed, the cytotoxic cell has little, if any, specificity. Monocytes appear to be responsible for this observed in vitro cytotoxicity. We now present evidence that the development of spontaneous monocyte-mediated cytotoxicity in vitro is completely reversed by the addition of optimally mitogenic doses of PWM. PWM appears to reverse monocyte-mediated killing by stimulating a potent cell-mediated suppressor. This suppressor cell is radiosensitive and its action is blocked by inhibitors of protein synthesis. In contrast to other mitogen-driven suppressor models, PWM will inhibit spontaneous monocyte-mediated cytotoxicity even when added as late as 6 hr before the end of a 7-day culture.


Severe anaphylactic reaction to human insulin in a diabetic patient.
A 46-year-old nonatopic woman who had been suffering from type 2 diabetes for 17 years was hospitalized at the Endocrinology Department of Selcuk University due to very high glucose levels after recovery from acute hepatitis A infection. She had never used insulin before. After first subcutaneous dose of human regular insulin, severe local allergic reaction developed. Desensitization to insulin was tried. One day later, ketoacidosis developed. Human regular insulin was again subcutaneously injected to the patient. Severe anaphylactic reaction occurred, and in spite of all the medical attempts to save the patient, she died.


Management of a Concealable Stigmatized Identity: A Qualitative Study of Concealment, Disclosure, and Role Flexing Among Young, Resilient Sexual and Gender Minority Individuals.
Disclosure of a sexual or gender minority status has been associated with both positive and negative effects on wellbeing. Few studies have explored the disclosure and concealment process in young people. Interviews were conducted with 10 sexual and/or gender minority individuals, aged 18-22 years, of male birth sex. Data were analyzed qualitatively, yielding determinants and effects of disclosure and concealment. Determinants of disclosure included holding positive attitudes about one's identity and an implicit devaluation of acceptance by society. Coming out was shown to have both positive and negative effects on communication and social support and was associated with both increases and decreases in experiences of stigma. Determinants of concealment included lack of comfort with one's identity and various motivations to avoid discrimination. Concealment was also related to hypervigilance and unique strategies of accessing social support. Results are discussed in light of their clinical implications.


The 5-HT5A receptor regulates excitability in the auditory startle circuit: functional implications for sensorimotor gating.
Here we applied behavioral testing, pharmacology, and in vivo electrophysiology to determine the function of the serotonin 5-HT5A receptor in goldfish startle plasticity and sensorimotor gating. In an initial series of behavioral experiments, we characterized the effects of a selective 5-HT5A antagonist, SB-699551 (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), on prepulse inhibition of the acoustic startle response. Those experiments showed a dose-dependent decline in startle rates in prepulse conditions. Subsequent behavioral experiments showed that SB-699551 also reduced baseline startle rates (i.e., without prepulse). To determine the cellular mechanisms underlying these behaviors, we tested the effects of two distinct selective 5-HT5A antagonists, SB-699551 and A-843277 (N-(2,6-dimethoxybenzyl)-N'[4-(4-fluorophenyl)thiazol-2-yl]guanidine), on the intrinsic membrane properties and synaptic sound response of the Mauthner cell (M-cell), the decision-making neuron of the startle circuit. Auditory-evoked postsynaptic potentials recorded in the M-cell were similarly attenuated after treatment with either 5-HT5A antagonist (SB-699551, 26.41 ± 3.98% reduction; A-843277, 17.52 ± 6.24% reduction). This attenuation was produced by a tonic (intrinsic) reduction in M-cell input resistance, likely mediated by a Cl(-) conductance, that added to the extrinsic inhibition produced by an auditory prepulse. Interestingly, the effector mechanisms underlying neural prepulse inhibition itself were unaffected by antagonist treatment. In summary, these results provide an in vivo electrophysiological characterization of the 5-HT5A receptor and its behavioral relevance and provide a new perspective on the interaction of intrinsic and extrinsic modulatory mechanisms in startle plasticity and sensorimotor gating.


Inhibition of Shiga toxin 2 (Stx2) in apple juices and its resistance to pasteurization.
In the present study, we evaluated Shiga toxin (Stx2) activity in apple juices by measuring a decrease in dehydrogenase activity of Vero cells with the microculture tetrazolium (MTT) assay. Freshly prepared juice from Red Delicious apples and Golden Delicious apples inhibited the biological activity of the bacterial toxin Stx2 produced by E. coli O157:H7 strains. Studies with immunomagnetic beads bearing specific antibodies against the toxin revealed that Stx2 activity was restored when removed from the apple juice. SDS gel electrophoresis revealed no difference (P < 0.05) in the densities or molecular weights between Stx2 in either PBS or apple juices. These results suggest that Stx2 may be reversibly bound to small molecular weight constituents in the juice. The Stx2 toxin was not inactivated on exposure to heat programs (63 degrees C for 30 min, 72 degrees C for 15 s, 89 degrees C for 1 s) commonly used to pasteurize apple juice, but lost all activity when exposed to 100 degrees C for 5 min. The results suggest that pasteurization of apple juice used to inactivate E. coli O157:H7 has no effect on Stx2, and that food-compatible and safe antitoxin compounds can be used to inhibit the biological activity of the Shiga toxin.


Detection of Hydrocarbons by Laser Assisted Paper Spray Ionization Mass Spectrometry (LAPSI MS).
Here we introduce a new ambient ionization technique named laser assisted paper spray ionization mass spectrometry (LAPSI MS). In it, a 532 ± 10 nm, ≤10 mW laser pointer was shone on a triangularly cut paper along with high voltage, to effect ionization. The analyte solution was continuously pushed through a fused silica capillary, using a syringe pump, at a preferred infusion rate. LAPSI MS promises enhanced ionization with high signal intensity of polycyclic aromatic hydrocarbons (PAHs), which are normally not ionizable with similar ionization methods involving solvent sprays. LAPSI MS works both in positive and negative modes of ionization. A clear enhancement of signal intensity was visualized in the total ion chronogram for most analytes in the presence of the laser. We speculate that the mechanism of ionization is field assisted photoionization. The field-induced distortion of the potential well can be large in paper spray as the fibers comprising the paper are separated at tens of nanometers apart, and consequently, the analyte molecules are subjected to very large electric fields of the order of 107 Vcm-1. Ionization occurs from their distorted electronic states of reduced ionization energy, using the laser. Negative ion detection is also demonstrated, occurring due to the capture of produced photoelectrons. LAPSI MS can be used for monitoring in situ photoassisted reactions like the decarboxylation of mercaptobenzoic acid in the presence of gold and silver nanoparticles and the dehydrogenation reaction of 2,3-dihydro-1 H-isoindole, which were chosen as examples. As an application, we have shown that paraffin oil, which is usually nonionizable by paper spray or by electrospray ionization can be efficiently detected using this technique. Impurities like mineral oils were detected easily in commercially available coconut oil, pointing the way to applications of social relevance.


High-Flow Nasal Oxygen in Patient With Obstructive Sleep Apnea Undergoing Awake Craniotomy: A Case Report.
Patients with obstructive sleep apnea are frequently considered unsuitable candidates for awake craniotomy due to anticipated problems with oxygenation, ventilation, and a potentially difficult airway. At present, only a handful of such accounts exist in the literature. Our report describes the novel use of high-flow nasal oxygen therapy for a patient with moderate obstructive sleep apnea who underwent an awake craniotomy under deep sedation. The intraoperative application of high-flow nasal oxygen therapy achieved satisfactory oxygenation, maintained the partial carbon dioxide pressure within a reasonable range even during periods of deep sedation, permitted responsive patient monitoring during mapping, and provided excellent patient and surgeon satisfaction.


Diagnostic laparoscopy for patients with potentially resectable pancreatic adenocarcinoma: is it cost-effective in the current era?
For patients with potentially resectable pancreatic cancer, diagnostic laparoscopy may identify liver and peritoneal metastases that are difficult to detect with other staging modalities. The aim of this study was to utilize a population-based pancreatic cancer database to assess the cost effectiveness of preoperative laparoscopy. Data from a state cancer registry were linked with primary medical record data for years 1996-2003. De-identified patient records were reviewed to determine the role and findings of laparoscopic exploration. Average hospital and physician charges for laparotomy, biliary bypass, pancreaticoduodenectomy, and laparoscopy were determined by review of billing data from our institution and Medicare data for fiscal years 2005-2006. Cost-effectiveness was determined by comparing three methods of utilization of laparoscopy: (1) routine (all patients), (2) case-specific, and (3) no utilization. Of 298 potentially resectable patients, 86 underwent laparoscopy. The prevalence of unresectable disease was 14.1% diagnosed at either laparotomy or laparoscopy. The mean charge per patient for routine, case-specific, and no utilization of laparoscopy was $91,805, $90,888, and $93,134, respectively. Cost analysis indicates that the case-specific or routine use of laparoscopy in pancreatic cancer does not add significantly to the overall expense of treatment and supports the use of laparoscopy in patients with known or suspected pancreatic adenocarcinoma.


An engineered transcriptional reporter of protein localization identifies regulators of mitochondrial and ER membrane protein trafficking in high-throughput CRISPRi screens.
The trafficking of specific protein cohorts to correct subcellular locations at correct times is essential for every signaling and regulatory process in biology. Gene perturbation screens could provide a powerful approach to probe the molecular mechanisms of protein trafficking, but only if protein localization or mislocalization can be tied to a simple and robust phenotype for cell selection, such as cell proliferation or fluorescence-activated cell sorting (FACS). To empower the study of protein trafficking processes with gene perturbation, we developed a genetically encoded molecular tool named HiLITR (High-throughput Localization Indicator with Transcriptional Readout). HiLITR converts protein colocalization into proteolytic release of a membrane-anchored transcription factor, which drives the expression of a chosen reporter gene. Using HiLITR in combination with FACS-based CRISPRi screening in human cell lines, we identified genes that influence the trafficking of mitochondrial and ER tail-anchored proteins. We show that loss of the SUMO E1 component SAE1 results in mislocalization and destabilization of many mitochondrial tail-anchored proteins. We also demonstrate a distinct regulatory role for EMC10 in the ER membrane complex, opposing the transmembrane-domain insertion activity of the complex. Through transcriptional integration of complex cellular functions, HiLITR expands the scope of biological processes that can be studied by genetic perturbation screening technologies.


The development, characterization, and cellular response of a novel electroactive nanostructured composite for electrical stimulation of neural cells.
Electrical stimulation is a primary method to repair or restore neurological functions. In this regard, we describe the underlying strategy, chemical/structural design, and gifted attributes of a novel nanostructured electroactive composite electrode comprising organic (highly conducting polymer) and inorganic (carbon nanotubes) components. The electrode was characterized in terms of electrical properties, structure and neural cell response. First, the electrical probe is robust and characterized by low impedance, high charge injection capacity, and is biocompatible to facilitate cellular interactions. Second, the combination of in vitro experiments, fluorescence, and electron microscopy of electrically stimulated cells (NB-39-Nu human neuroblastoma cells) at different applied electric field strengths demonstrated that the electrochemically synthesized hybrid nanostructured coating is conducive to neurite growth. Third, the study on the effects of electrical field strength on protein synthesis and mechanism implied cell-to-cell communication based on the change in the regulation of endogenous cytoskeletal proteins, actin, vinculin, and fibronection involving cell mobility and cell adhesion. The cell-to-cell communication is of significant relevance to functional neuronal circuits in cell translational therapy. Taken together, the results also point to the potential of nanostructured composites for use as substrates to modulate cellular activity via electrical stimulation.


Intracellular pH, transepithelial pH gradients, and ADH-induced water channels.
Urinary bladders of frogs were exposed to a transepithelial proton and osmotic gradient (serosal pH 8.1, Tris or bicarbonate buffer; mucosal pH 5.8, unbuffered) while the alkalinization rate of the mucosal bath and the net water movement were simultaneously monitored. It was observed that 1) the mucosal alkalinization rate was dependent on serosal pH and buffer; 2) oxytocin increased the mucosal alkalinization rate only when serosal bicarbonate was employed, whereas the net water movement augmented both when serosal bicarbonate or Tris buffers were used; 3) amiloride did not modify the mucosal alkalinization rate either before or after oxytocin; 4) the increases in the mucosal alkalinization rate and in the net water movement induced by oxytocin (serosal bicarbonate) were negatively correlated. In other experiments intracellular pH (pHi) was estimated with the DMO distribution technique with the following results. 1) Oxytocin increased the pHi when either serosal bicarbonate or Tris buffers was used and even in the presence of a low mucosal pH (Tris buffer, pH 5.8). 2) Important cellular acidification was observed when CO2 was bubbled (to pH 5.8), whereas the hydrosmotic response to 8-bromo-cAMP was clearly inhibited. These results indicate that cellular alkalinization could play a pivotal role in action of ADH, show that ADH can modify the transepithelial pH equilibrium mechanism, and suggest that intracellular pH regulation and water permeability control can be linked regulatory processes.


Characteristics of Excitable Dog Behavior Based on Owners' Report from a Self-Selected Study.
Past research has found that excitable dog behavior is prevalent among sheltered and owned dogs and many times is a reason for canine relinquishment. In spite of its prevalence in the canine population, excitable behavior is relatively unstudied in the scientific literature. The intent of this research was to understand the experience of owners of excitable dogs through the analysis of self-administered online questionnaires completed by owners as part of another study. We found that certain daily scenarios tended to prompt excitable behavior, with excitability most common when the owner or other people came to the dog's home. All owners experienced some level of frustration with their dog's excitable behavior, with the majority being very frustrated. Many dogs in the sample had other behavior problems, with disobedient, destructive, chasing and barking behaviors being the most commonly reported. Other characteristics of excitable dogs also are discussed. Although the ability to generalize from these results is likely limited, due to targeted recruitment and selection of owners of more excitable dogs, this research provides valuable insights into the owner's experience of excitable behavior. We hope this study prompts more research into canine excitable behavior which would expand our understanding of this behavior and help behaviorists, veterinarians, and shelters develop tools for managing it, as well as provide better education to owners of excitable dogs.


Effects of various operations on the electrical activity of the human stomach recorded during the postoperative recovery period.
This study attempts to characterize any changes occurring in the human gastric control electrical rhythm (CER), following a variety of gastric surgical procedures. Pairs of electrodes were implanted in selected specific sites on the stomachs of 57 patients undergoing either antrectomy and vagotomy, proximal gastric vagotomy (PGV), vagotomy and drainage, gastric resection without vagotomy, or fundoplication. Five patients undergoing nongastric operations served as controls. After operation recordings were obtained with differential preamplifiers, an oscilloscope, and a dual-channel tape recorder. An electrical signal compatible with a CER was found almost always in the distal body or antrum, regardless of whether vagotomy was performed. In contrast, a CER was found only occasionally in the fundus, and was never found following PGV. Although there was a difference in the frequency of occurrence of fundic CER in patients with and without vagotomy, it was not statistically significant (p = 0.0668). Patients with prolonged postoperative convalescence because of gastric atony were compared with patients with normal postoperative courses regarding the presence or absence of CER in the gastric antrum or fundus. A statistically significant relationship between abnormal gastric motility and absence of CER was not established.


Effect of arabinosyl cytosine on the level of DNA polymerase and thymidine kinase activity in PHA-stimulated human tonsillar lymphocytes.
The effect of arabinosyl cytosine (ara-C) was studied on the uptake, phosphorylation and incorporation of 3H-thymidine in human tonsillar lymphocyte cultures is described along with its effect on the level of DNA polymerase and thymidine Kinase activities induced by phytohaemagglutinin (PHA). Freshly isolated tonsillar lymphocytes are stimulated cells with a remarkably high activity of DNA polymerase alpha and thymidine kinase. During in vitro culture, these stimulated cells are transformed to the resting state with low DNA polymerase and thymidine kinase activity. However, a new DNA synthesising cycle can be induced by PHA with maximum at 48 h. 10(-6) M ara-C inhibited the incorporation of 3H-thymidine by 90-95%. This inhibition may be reversed by rinsing the cells. The inhibition of the transport of 3H-thymidine seems to be only a consequence of the inhibitory effect of ara-C on the DNA polymerisation reaction, because at 10 degrees C, where DNA synthesis was arrested, ara-C does not influence the uptake and the phosphorylation of 3H-thymidine. Ara-C (10(-6) M) abolished also the PHA induced elevation of DNA polymerase alpha and thymidine kinase activities without influencing protein synthesis of the cell. This supports a coordinated regulation mechanism between DNA synthesis and the synthesis of enzymes involved in DNA replication.


[Frequency and clinical associations of antineutrophil cytoplasmic antibodies. A regional experience].
Serologic and clinical aspects of 50 positives patients for antineutrophil cytoplasmic antibodies (ANCA) have been evaluated (age range 7-94 years, mean age 43 years). 40 (80%) were females. Antineutrophil nuclear antibodies (pANNA), in which the antigenic specificity is unknown, were detected in seventeen patients (34%). About half of these cases (8 patients) had primary sclerosing cholangitis and other 7 patients had severe ulcerative colitis. Two pANNA patients, with increased susceptibility to infections, had undefined diagnosis. Both had thalassemic trait. Anti MPO were detected in 9 patients in which segmental lesions prevail and anti-PR3 were detected in 9 patients with granulomatous component. The patients with higher levels of these autoantibodies (40%) had the typical syndromes described in literature (vasculitis ANCA-related) although patients with lower autoantibodies levels (60%) mostly present variable clinical symptoms with unspecified diagnosis. Fourteen patients were positive for atypical ANCA detectable with commercial kits. They present variable clinical symptoms with unspecified diagnosis but show granulomatous or neoplastic lungs and bowel involvement. Both have mostly contact with environmental microorganisms. All cases are characterized by chronic inflammatory lesions in which the relapses correlate with infectious disorder.


Analysis of daphnane orthoesters in poisonous Australian pimelea species by liquid chromatography-tandem mass spectrometry.
Cattle grazing in arid rangelands of Australia suffer periodic extensive and serious poisoning by the plant species Pimelea trichostachya, P. simplex, and P. elongata. Pimelea poisoning (also known as St. George disease and Marree disease) has been attributed to the presence of the diterpenoid orthoester simplexin in these species. However, literature relating to previous studies is complicated by taxonomic revisions, and the presence of simplexin has not previously been verified in all currently recognized taxa capable of inducing pimelea poisoning syndrome, with no previous chemical studies of P. trichostachya (as currently classified) or P. simplex subsp. continua. We report here the isolation of simplexin from P. trichostachya and the development of a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method to measure simplexin concentrations in pimelea plant material. Simplexin was quantified by positive-ion atmospheric pressure chemical ionization (APCI) LC-MS/MS with selected reaction monitoring (SRM) of the m/z 533.3 > 253.3 transition. LC-MS/MS analysis of the four poisonous taxa P. trichostachya, P. elongata, P. simplex subsp. continua, and P. simplex subsp. simplex showed similar profiles with simplexin as the major diterpenoid ester component in all four taxa accompanied by varying amounts of related orthoesters. Similar analyses of P. decora, P. haematostachya, and P. microcephala also demonstrated the presence of simplexin in these species but at far lower concentrations, consistent with the limited reports of stock poisoning associated with these species. The less common, shrubby species P. penicillaris contained simplexin at up to 55 mg/kg dry weight and would be expected to cause poisoning if animals consumed sufficient plant material.


Foot Reflexology: An Intervention for Pain and Nausea Among Inpatients With Cancer.
Pain and nausea affect a significant number of patients with cancer. Applying foot reflexology to this population has had some positive effects, but more studies are needed to confirm its efficacy. The purpose of this study was to conduct a randomized controlled trial to evaluate the effects of foot reflexology on pain and nausea among inpatients with cancer as compared to traditional nursing care alone. A pilot study was conducted with adult patients with cancer hospitalized on a 24-bed inpatient oncology unit. Using convenience sampling, 40 patients provided consent and were randomized into either the intervention or control group. Each group had a treatment session of 20-25 minutes in which pre- and postsession surveys were completed, with reflexology performed in the intervention group only. Results show that foot reflexology significantly decreases pain for inpatients with cancer as compared to traditional nursing care alone. Although the effects on nausea are not statistically significant, they may be clinically relevant; the mean changes in pre- and postsession nausea ratings indicate at least some decreased nausea among patients in the intervention group.


Heterotrimeric kinesin-II is required for the assembly of motile 9+2 ciliary axonemes on sea urchin embryos.
Heterotrimeric kinesin-II is a plus end- directed microtubule (MT) motor protein consisting of distinct heterodimerized motor subunits associated with an accessory subunit. To probe the intracellular transport functions of kinesin-II, we microinjected fertilized sea urchin eggs with an anti-kinesin-II monoclonal antibody, and we observed a dramatic inhibition of ciliogenesis at the blastula stage characterized by the assembly of short, paralyzed, 9+0 ciliary axonemes that lack central pair MTs. Control embryos show no such defect and form swimming blastulae with normal, motile, 9+2 cilia that contain kinesin-II as detected by Western blotting. Injection of anti-kinesin-II into one blastomere of a two-cell embryo leads to the development of chimeric blastulae covered on one side with short, paralyzed cilia, and on the other with normal, beating cilia. We observed a unimodal length distribution of short cilia on anti-kinesin-II-injected embryos corresponding to the first mode of the trimodal distribution of ciliary lengths observed for control embryos. This short mode may represent a default ciliary assembly intermediate. We hypothesize that kinesin-II functions during ciliogenesis to deliver ciliary components that are required for elongation of the assembly intermediate and for formation of stable central pair MTs. Thus, kinesin-II plays a critical role in embryonic development by supporting the maturation of nascent cilia to generate long motile organelles capable of producing the propulsive forces required for swimming and feeding.


Mycotoxin concentrations in rice from three climatic locations in Africa as affected by grain quality, production site, and storage duration.
Information on the mycotoxin contamination of rice in Africa is limited although the risk of contamination is high. In this study, domestic milled rice processed by actors using suboptimal methods was purchased and total fumonisin (FUM), zearalenone, and aflatoxin concentrations determined at 0, 90, and 180 days after storage. Three different climatic locations, Cotonou (Benin) in the Guinea savanna, Yaoundé (Cameroon) in the Tropical forest, and N'diaye (Senegal) in the Sahel, were selected as storage sites. Subsets of the samples collected from Glazoue (Benin), Ndop (Cameroon), and Dagana (Senegal) were stored in plastic woven bags under room conditions in the respective sites with or without calcium oxide (burnt scallop shell-BSS, 0.1% w/w) treatment. Multivariance analysis showed that FUM concentration was positively influenced by the duration of storage only while zearalenone concentration was negatively influenced by relative humidity and head rice but positively by impurities. Zearalenone concentration was also influenced by sample collection/storage location, processing type, and duration of storage. Aflatoxin concentration was influenced negatively by storage room temperature and head rice but positively by impurities and chalky grains. In addition, aflatoxin concentration was influenced by collection/storage location and processing type. BSS treatment followed by storage for 6 months had no effect on the concentration of the three assessed mycotoxins. Strategies to reduce the risk of mycotoxin contamination in study sites will include the improvement of physical rice quality through better pre- and postharvest practices and proper packaging of both treated rice and untreated rice in hermetic systems before marketing and storage.


Two Swedish screening instruments for exhaustion disorder: cross-sectional associations with burnout, work stress, private life stress, and personality traits.
To examine the relationships of two screening instruments recently developed for assessment of exhaustion disorder (ED) with some other well-known inventories intended to assess ED-related concepts and self-reports of job demands, job control, job support, private life stressors, and personality factors. A cross-sectional population sample ( n = 1355) completed: the Karolinska Exhaustion Disorder Scale (KEDS), Self-reported Exhaustion Disorder Scale (s-ED), Shirom-Melamed Burnout Questionnaire (SMBQ), Utrecht Work Engagement Scale (UWES-9), Job Content Questionnaire (JCQ), Big Five Inventory (BFI), and items concerning family-to-work interference and stress in private life. Compared to participants without any indication of ED, participants classified as having ED on KEDS or s-ED had higher scores on all four SMBQ subscales, lower scores on the UWES-9 subscales vigor and dedication, higher JCQ job demands scores, lower JCQ job support scores, higher degrees of family-to-work interference and stress in private life, and higher BFI neuroticism and openness scores. In addition, participants classified as having ED on KEDS had lower scores on the UWES-9 absorption subscale, the JCQ job control scale, and lower BFI extraversion, agreeableness and conscientiousness scores, compared to the subgroup not classified as having ED. As expected, we observed an overall pattern of associations between the ED screening inventories KEDS and s-ED and measures of burnout, work engagement, job demands-control-support, stress in private life, family-to-work interference, and personality factors. The results suggest that instruments designed to assess burnout, work engagement, and ED share common ground, despite their conceptual differences.


Design Procedure and Fabrication of Reproducible Silicon Vernier Devices for High-Performance Refractive Index Sensing.
In this paper, we propose a generalized procedure for the design of integrated Vernier devices for high performance chemical and biochemical sensing. In particular, we demonstrate the accurate control of the most critical design and fabrication parameters of silicon-on-insulator cascade-coupled racetrack resonators operating in the second regime of the Vernier effect, around 1.55 μm. The experimental implementation of our design strategies has allowed a rigorous and reliable investigation of the influence of racetrack resonator and directional coupler dimensions as well as of waveguide process variability on the operation of Vernier devices. Figures of merit of our Vernier architectures have been measured experimentally, evidencing a high reproducibility and a very good agreement with the theoretical predictions, as also confirmed by relative errors even lower than 1%. Finally, a Vernier gain as high as 30.3, average insertion loss of 2.1 dB and extinction ratio up to 30 dB have been achieved.


Increased IL-17A expression in granulomas and in circulating memory T cells in sarcoidosis.
Sarcoidosis is a systemic inflammatory disorder characterized by granulomas. Although the aetiology is unknown, sarcoidosis is thought to be mediated by Th1 lymphocytes. Recently, IL-17A has been implicated in granuloma formation in various diseases, including tuberculosis. Therefore, we hypothesized that Th17 cells play a role in sarcoidosis, paralleling recent findings in autoimmune diseases such as RA. The aim of our study was to investigate the role of Th17 cells in sarcoidosis. T cells were investigated by intracellular flow cytometry and immunohistochemistry, in blood, bronchoalveolar lavages (BALs) and bronchial mucosal biopsies from a cohort of newly diagnosed sarcoidosis patients and healthy controls. Circulating memory CD4(+) T-cell populations of sarcoidosis patients contained significantly increased proportions of IL-17A(+) cells when compared with healthy controls. Interestingly, proportions of IL-17A/IFN-γ and IL-17A/IL-4 double-producing cells were significantly increased in blood of sarcoidosis patients and were present in substantial numbers in BAL. In granuloma-containing, but not in non-granulomatous sarcoidosis biopsies, we found significantly increased numbers of IL-17A(+) T cells, located in and around granulomas throughout the lamina propria. IL-22(+) T cells were increased in the subepithelial layer. Enhanced IL-17A expression in granulomas and the presence of IL-17A(+), IL-17A(+)IFN-γ(+) and IL-17A(+)IL-4(+)memory Th cells in the circulation and BAL indicate Th17 cell involvement in granuloma induction or maintenance in sarcoidosis. Therefore, neutralization of IL-17A activity may be a novel strategy to treat sarcoidosis.


The impact of COVID-19 on microbiological profile and antibiotic consumption in ICU: a retrospective study in an infectious disease hospital in Brazil.
The COVID-19 pandemic has triggered crises in the public health sector that have complex and multifaceted interrelationships with antimicrobial resistance. It is important to evaluate the impact of COVID-19 on microbiological profile, antibiotic and alcohol gel consumption in Intensive Care Units (ICU). This is a retrospective study undertaken in an infectious disease hospital located in Bahia/Brazil during three periods: from March 2019 to February 2020; from March 2020 to February 2021; and from March 2021 to February 2022. It was evaluated the incidence density of Candida spp and of multidrug-resistant Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE group) in blood, urine and tracheal secretion isolated 48 h after the patient's admission to the ICU, as well as the use of alcohol gel (in milliliters) and consumption of antibiotics in Defined Daily Dose (DDD) per 1,000 ICU patient-days in the previous year and in the first two years of COVID-19 pandemic. There was an increase in Candida spp. (5.81, p < 0.001, IRR = 10.47, 95 % CI 2.57‒42.62) and in carbapenem-resistant A. baumannii in clinical cultures (4.71, p < 0.001, IRR = 8.46, 95 % CI 2.07‒34.60), the latter mainly in tracheal secretions (3.18, p = 0.02, IRR = 11.47, 95 % CI 1.58‒83.39). A rise in the consumption of ceftriaxone and piperacillin-tazobactam, along with an increase in the utilization of alcohol gel were observed. The shifting microbiological profile can be attributed to both the unique characteristics of patients with COVID-19 and the adjustments made to healthcare facilities' structural and work routines. Understanding these changes is essential in addressing the accelerated impact of antimicrobial resistance during the pandemic. Therefore, conducting thorough reviews of institutional practices and routines becomes critical in mitigating the consequences of antimicrobial resistance and its implications for patient care.


[Clinical manifestations of polyposis and polyps of the large intestine and "risk groups"].
In processing of 1603 clinical observations, studied dynamically during 15 years, using the multifactor analysis of clinico-morphological, roentgenological and statistic parallels, there were registered 156 different possible variants in a combination of the forms and clinical manifestations of polyposis and polyps of the colon. The degree of the malignant transformation risk for various forms of polyposis and polyps of the colon is extremely variable.


[Heterogeneity of monoclonal antibody affinity].
In experiments with Pasteurella pestis monovalent capsular antigen and hybridoma monoclonal antibodies obtained after cloning and recloning the heterogeneity of the active centers of antibodies with respect to their affinity was revealed. In ascitic fluids obtained from the animals inoculated with different hybridoma clones 5 groups of antibodies, differing in their affinity, were determined in each fluid sample.


From osmotic second virial coefficient (B22 ) to phase behavior of a monoclonal antibody.
Antibodies are complex macromolecules and their phase behavior as well as interactions within different solvents and precipitants are still not understood. To shed some light into the processes on a molecular dimension, the occurring self-interactions between antibody molecules were analyzed by means of the osmotic second virial coefficient (B22 ). The determined B22 follows qualitatively the phenomenological Hofmeister series describing the aggregation probability of antibodies for the various solvent compositions. However, a direct correlation between crystallization probability and B22 in form of a crystallization slot does not seem to be feasible for antibodies since the phase behavior is strongly dependent on their anisotropy. Kinetic parameters have to be taken into account due to the molecular size and complexity of the molecules. This is confirmed by a comparison of experimental data with a theoretical phase diagram. On the other hand the solubility is thermodynamically driven and therefore the B22 could be used to establish a universal solubility line for the monoclonal antibody mAb04c and different solvent compositions by using thermodynamic models.


A 20-year study of autoimmune polyendocrine syndrome type II and III in Taiwan.
Autoimmune polyendocrine syndrome (APS) is a rare immune-endocrinopathy characterized by the failure of at least two endocrine organs. Clinical characteristics have mainly been described in the Western population. This study comprehensively analyzed the demographic and clinical manifestations of APS II and APS III in Taiwan. Patients aged ≥20 years with a diagnosis of APS II or APS III in ten hospitals between 2001 and 2021 were enrolled. The clinical and serological characteristics of the patients were retrospectively reviewed. Among the 187 enrolled patients (45 men and 142 women); only seven (3.7%) had APS II, while the others had APS III. Fifty-five patients developed hyperthyroidism and 44 patients developed hypothyroidism. Men were diagnosed with APS at a younger age than women (16.8 vs 27.8 years old, P = 0.007). Most patients were initially diagnosed with type 1 diabetes mellitus. There was a positive correlation between age at diagnosis and the likelihood of developing thyroid dysfunction. For every year older patients were diagnosed with APS III, the risk of developing hyperthyroidism increased by 3.6% (P = 0.002), and the risk of developing hypothyroidism increased by 3.7% (P = 0.035). Positive anti-parietal cell antibodies (APCA) were associated with a higher risk of anemia in patients with APS III (P < 0.001). This study provides the most comprehensive analysis of APS II and APS III in Asia. The percentage of patients with APS II was significantly lower than in the Western population. A second autoimmune endocrinopathy may develop several years after the first one. APCA examination is valuable when evaluating anemia in patients with APS.


Role of unfolded protein response in lipogenesis.
The signal transduction network in regulating lipid metabolism is a hot topic of biomedical research. Recent research endeavors reveal that intracellular stress signaling from a cellular organelle called endoplasmic reticulum (ER) is critically involved in lipid homeostasis and the development of metabolic disease. The ER is a site where newly-synthesized proteins are folded and assembled into their three-dimensional structures, modified and transported to their precise cellular destinations. A wide range of biochemical, physiological and pathological stimuli can interrupt the protein folding process in the ER and cause accumulation of unfolded or misfolded proteins in the ER lumen, a condition referred to as ER stress. To cope with this stress condition, the ER has evolved highly-specific signaling pathways collectively termed Unfolded Protein Response (UPR) or ER stress response. The UPR regulates transcriptional and translational programs, affecting broad aspects of cellular metabolism and cell fate. Lipogenesis, the metabolic process of de novo lipid biosynthesis, occurs primarily in the liver where metabolic signals regulate expression of key enzymes in glycolytic and lipogenic pathways. Recent studies suggest that the UPR plays crucial roles in modulating lipogenesis under metabolic conditions. Here we address some of recent representative evidence regarding the role of the UPR in lipogenesis.


Multi-Scale Label-Free Human Brain Imaging with Integrated Serial Sectioning Polarization Sensitive Optical Coherence Tomography and Two-Photon Microscopy.
The study of aging and neurodegenerative processes in the human brain requires a comprehensive understanding of cytoarchitectonic, myeloarchitectonic, and vascular structures. Recent computational advances have enabled volumetric reconstruction of the human brain using thousands of stained slices, however, tissue distortions and loss resulting from standard histological processing have hindered deformation-free reconstruction. Here, the authors describe an integrated serial sectioning polarization-sensitive optical coherence tomography (PSOCT) and two photon microscopy (2PM) system to provide label-free multi-contrast imaging of intact brain structures, including scattering, birefringence, and autofluorescence of human brain tissue. The authors demonstrate high-throughput reconstruction of 4 × 4 × 2cm3 sample blocks and simple registration between PSOCT and 2PM images that enable comprehensive analysis of myelin content, vascular structure, and cellular information. The high-resolution 2PM images provide microscopic validation and enrichment of the cellular information provided by the PSOCT optical properties on the same sample, revealing the densely packed fibers, capillaries, and lipofuscin-filled cell bodies in the cortex and white matter. It is shown that the imaging system enables quantitative characterization of various pathological features in aging process, including myelin degradation, lipofuscin accumulation, and microvascular changes, which opens up numerous opportunities in the study of neurodegenerative diseases in the future.


Shelf life extension, safety, and quality of fresh pork loin treated with high hydrostatic pressure.
The optimal conditions of pressure, time, and processing temperature required to eliminate Listeria monocytogenes Scott A and Salmonella typhimurium ATCC 13311 in fresh pork loin and the effect of these optimal conditions on quality and shelf life were determined. Twenty-five grams of fresh pork loin were inoculated with either of the two organisms and were subjected to pressures between 414 and 827 MPa at either 2 or 25 degrees C for 30 min. The D414MPa(25 degrees C) was determined to be 2.17 min for L. monocytogenes and the D414 MPa (2 degrees C) was determined to be 1.48 min for S. typhimurium. Samples subjected to a 6D process were evaluated by sensory and objective tests as well as for shelf life. These samples were found to be different (P < 0.05) from controls when evaluated after cooking by a triangle test of difference, but only when the pressure was applied at 2 degrees C and not at 25 degrees C. The descriptive analysis test showed that cooked samples treated at 25 degrees C were not different (P > 0.05) from controls in flavor, juiciness, and firmness. Color, peak load, water-holding capacity, and moisture were not found to be different (P > 0.05) between samples treated at 25 degrees C and controls when both were cooked. However, in the raw state, differences were found in the values for color parameters L and b. The level of psychrotrophs was 5.7 log CFU/g for samples treated at 25 degrees C after 33 days of storage at 4 degrees C, as compared with 7.0 log CFU/g for controls. The color and peak load (texture) did not change over the storage period (P > 0.05) in any of the samples. All samples spoiled in 5 days when stored at 25 degrees C.


Outcome for invasive Staphylococcus aureus infections.
We report a survey of invasive Staphylococcus aureus (ISA) infections concerning outcome variables such as mortality, recurrence and residual symptoms. A prospective, population-based study of all cases of ISA was conducted in the catchment area of Skaraborg Hospital (population 255,109) in western Sweden during the period from 1st March 2003 to 28th February 2005. One hundred and fifty-seven patients were included. Recurrences were seen in 13 cases (9.3%). Thirty patients (19.1%) died during the first 28 days. Mortality rates for complicated bacteraemia and severe sepsis were 32% and 54%, respectively. Older patients (>65 years of age), patients with concomitant heart disease and patients with endovascular infections all suffered higher mortality. Line-associated infections had a higher recurrence rate. Residual symptoms were common, with 34% of the living patients reporting incomplete recovery. Accessory gene regulator (agr) type within the bacteria did not affect disease presentation. We conclude that ISA infections are of major medical importance, with high rates of mortality (19.1%), recurrence (9.3%) and residual functional impairment (34%).


Loaded Handgun Carrying Among US Adults, 2015.
To determine the frequency of loaded handgun carrying among US adult handgun owners, characterize those who carry, and examine concealed carrying by state concealed carry laws. Using a nationally representative survey of US adults in 2015, we asked handgun owners (n = 1444) about their past-30-day carrying behavior. Among surveyed handgun owners, 24% (95% confidence interval[CI] = 21%, 26%) carried loaded handguns monthly, of whom 35% (95% CI = 29%, 41%) did so daily; 82% (95% CI = 77%, 86%) carried primarily for protection. The proportion of handgun owners who carried concealed loaded handguns in the past 30 days was 21% (95% CI = 12%, 35%) in unrestricted states, 25% (95% CI = 21%, 29%) in shall issue-no discretion states, 20% (95% CI = 16%, 24%) in shall issue-limited discretion states, and 9% (95% CI = 6%, 15%) in may-issue states. We estimate that 9 million US adult handgun owners carry loaded handguns monthly, 3 million do so every day, and most report protection as the main carrying reason. Proportionally fewer handgun owners carry concealed loaded handguns in states that allow issuing authorities substantial discretion in granting carrying permits.


The Complete Chloroplast Genome of Plukenetia volubilis Provides Insights Into the Organelle Inheritance.
Plukenetia volubilis L. (Malpighiales: Euphorbiaceae), also known as Sacha inchi, is considered a promising crop due to its high seed content of unsaturated fatty acids (UFAs), all of them highly valuable for food and cosmetic industries, but the genetic basis of oil biosynthesis of this non-model plant is still insufficient. Here, we sequenced the total DNA of Sacha inchi by using Illumina and Nanopore technologies and approached a de novo reconstruction of the whole nucleotide sequence and the organization of its 164,111 bp length of the chloroplast genome, displaying two copies of an inverted repeat sequence [inverted repeat A (IRA) and inverted repeat B (IRB)] of 28,209 bp, each one separating a small single copy (SSC) region of 17,860 bp and a large single copy (LSC) region of 89,833 bp. We detected two large inversions on the chloroplast genome that were not presented in the previously reported sequence and studied a promising cpDNA marker, useful in phylogenetic approaches. This chloroplast DNA (cpDNA) marker was used on a set of five distinct Colombian cultivars of P. volubilis from different geographical locations to reveal their phylogenetic relationships. Thus, we evaluated if it has enough resolution to genotype cultivars, intending to crossbreed parents and following marker's trace down to the F1 generation. We finally elucidated, by using molecular and cytological methods on cut flower buds, that the inheritance mode of P. volubilis cpDNA is maternally transmitted and proposed that it occurs as long as it is physically excluded during pollen development. This de novo chloroplast genome will provide a valuable resource for studying this promising crop, allowing the determination of the organellar inheritance mechanism of some critical phenotypic traits and enabling the use of genetic engineering in breeding programs to develop new varieties.


Features and treatment modality of iliopsoas abscess and its outcome: a 6-year hospital-based study.
Percutaneous drainage (PCD) and surgical intervention are two primary treatment options for iliopsoas abscess (IPA). However, there is currently no consensus on when to use PCD or surgical intervention, especially in patients with gas-forming IPA. This study compared the characteristics of patients with gas-forming and non-gas forming IPA and their mortality rates under different treatment modalities. An algorithm for selecting appropriate treatment for IPA patients is proposed based on our findings. Eighty-eight IPA patients between July 2007 and February 2013 were enrolled in this retrospective study. Patients < 18 years of age or with an incomplete course of treatment were excluded. Demographic information, clinical characteristics, and outcomes of different treatment approaches were compared between gas-forming IPA and non-gas forming IPA patients. Among the 88 enrolled patients, 27 (31%) had gas-forming IPA and 61 (69%) had non-gas forming IPA. The overall intra-hospital mortality rate was 25%. The gas-forming IPA group had a higher intra-hospital mortality rate (12/27, 44.0%) than the non-gas forming IPA group (10/61, 16.4%) (P < 0.001). Only 2 of the 13 patients in the gas-forming IPA group initially accepting PCD had a good outcome (success rate = 15.4%). Three of the 11 IPA patients with failed initial PCD expired, and 8 of the 11 patients with failed initial PCD accepted salvage operation, of whom 5 survived. Seven of the 8 gas-forming IPA patients accepting primary surgical intervention survived (success rate = 87.5%). Only 1 of the 6 gas-forming IPA patients who accepted antibiotics alone, without PCD or surgical intervention, survived (success rate = 16.7%). In the non-gas forming IPA group, 23 of 61 patients initially accepted PCD, which was successful in 17 patients (73.9%). The success rate of PCD was much higher in the non-gas forming group than in the gas-forming group (P <0.01). Based on the high failure rate of PCD and the high success rate of surgical intervention in our samples, we recommend early surgical intervention with appropriate antibiotic treatment for the patients with gas-forming IPA. Either PCD or primary surgical intervention is a suitable treatment for patients with non-gas forming IPA.


Sex-specific transgenerational plasticity: developmental temperatures of mothers and fathers have different effects on sons and daughters.
Each parent can influence offspring phenotype via provisioning of the zygote or sex-specific DNA methylation. Transgenerational plasticity may therefore depend on the environmental conditions experienced by each parent. We tested this hypothesis by conducting a fully factorial experiment across three generations of guppies (Poecilia reticulata), determining the effects of warm (28°C) and cold (21°C) thermal backgrounds of mothers and fathers on mass and length, and thermal performance (sustained and sprint swimming speeds, citrate synthase and lactate dehydrogenase activities; 18, 24, 28, 32 and 36°C test temperatures) of sons and daughters. Offspring sex was significant for all traits except for sprint speed. Warmer mothers produced sons and daughters with reduced mass and length, and warmer fathers produced shorter sons. Sustained swimming speed (Ucrit) of male offspring was greatest when both parents were raised at 28°C, and warmer fathers produced daughters with greater Ucrit. Similarly, warmer fathers produced sons and daughters with greater metabolic capacity. We show that the thermal variation experienced by parents can modify offspring phenotype, and that predicting the impacts of environmental change on populations would require knowledge of the thermal background of each mother and father, particularly where sexes are spatially segregated.


Modeling the 3D geometry of the cortical surface with genetic ancestry.
Knowing how the human brain is shaped by migration and admixture is a critical step in studying human evolution [1, 2], as well as in preventing the bias of hidden population structure in brain research [3, 4]. Yet, the neuroanatomical differences engendered by population history are still poorly understood. Most of the inference relies on craniometric measurements, because morphology of the brain is presumed to be the neurocranium's main shaping force before bones are fused and ossified [5]. Although studies have shown that the shape variations of cranial bones are consistent with population history [6-8], it is unknown how much human ancestry information is retained by the human cortical surface. In our group's previous study, we found that area measures of cortical surface and total brain volumes of individuals of European descent in the United States correlate significantly with their ancestral geographic locations in Europe [9]. Here, we demonstrate that the three-dimensional geometry of cortical surface is highly predictive of individuals' genetic ancestry in West Africa, Europe, East Asia, and America, even though their genetic background has been shaped by multiple waves of migratory and admixture events. The geometry of the cortical surface contains richer information about ancestry than the areal variability of the cortical surface, independent of total brain volumes. Besides explaining more ancestry variance than other brain imaging measurements, the 3D geometry of the cortical surface further characterizes distinct regional patterns in the folding and gyrification of the human brain associated with each ancestral lineage.


Understanding social role participation: what matters to people with arthritis?
To assess the importance of different social roles in the lives of people with osteoarthritis (OA), and satisfaction with time spent in roles and role performance, as well as the relationship of demographic, health, and psychological factors to role perceptions. Sixty women and 27 men (age 42-86 yrs) with hip or knee OA were recruited from rehabilitation programs and community advertising. Participants completed interview-administered questionnaires measuring demographics, OA symptoms, activity limitations, and well-being (e.g., depression). They also completed the Social Role Participation Questionnaire (SRPQ) assessing the influence of arthritis on role salience and satisfaction across diverse role domains (e.g., close relationships, employment). Participants reported many salient roles, but low to moderate satisfaction with them related to OA. SRPQ dimensions of salience and satisfaction were distinct; satisfaction with time spent in roles and with role performance was highly correlated (r = 0.83). Lower role salience was associated with being older, having less education and income, and greater illness intrusiveness. Less satisfaction with time spent in roles due to OA was associated with being younger, greater pain, and greater illness intrusiveness, whereas less satisfaction with role performance was associated with greater illness intrusiveness and depression. This study addresses a gap -- the influence of OA on social role participation. It underscores the importance of taking into account individual perceptions of roles, and that these perceptions are multifaceted. Understanding diverse factors related to social roles may help identify individuals at risk for role difficulties and provide targets for interventions to improve role participation.


Outcomes of children with chronic myeloid leukemia: A population-based cohort study.
Chronic myeloid leukemia (CML) is a rare disease in childhood. While hematopoietic stem cell transplant (HSCT) was the treatment of choice for CML prior to 2000, the introduction of tyrosine kinase inhibitors (TKIs) changed the management of this disease. This population-based analysis was conducted in the province of Ontario, Canada to gather information on treatment choices and outcomes of childhood CML. Using a provincial childhood cancer registry and retrospective review of patient medical records for patients < 18 years diagnosed with CML between 1985 and 2018, data on presenting features, treatment, and outcomes were collected from 52 patients. Patients treated before the introduction of TKIs (before 2002) mainly received HSCT and had an overall survival (OS) of 64% at a median follow up of 6 years. The OS of all patients treated in the TKI era (2002 and after) was 90% at a median follow up of 3 years. All three deaths in the TKI era were related to HSCT complications. Survival of patients who remained on a TKI was significantly improved compared to those who underwent HSCT post-TKI therapy (100% vs 66%, P = .008). TKIs were well tolerated. Given the increased mortality associated with HSCT in our cohort, further advances in HSCT may be required to outweigh the benefits of a TKI monotherapy approach in the majority of childhood CML patients. We believe HSCT should be considered in only a limited subset of pediatric patients with CML.


Single attosecond pulse generation with intense mid-infrared elliptically polarized laser pulses.
We have studied theoretically high-harmonic-order and single attosecond pulse generation with elliptically polarized laser pulses at wavelengths ranging from the visible to the mid-infrared. Results of ab initio simulations of the time-dependent Schrödinger equation show that the ellipticity dependence of the high-harmonic signal intensifies with increasing wavelength of the driving pulse and saturates in the mid-infrared. The isolation of single attosecond pulses using the polarization gating method in the mid-infrared is due to an effective suppression of side pulses as compared with an operation at Ti:sapphire wavelengths.


Delayed implantation of intramedullary chitosan channels containing nerve grafts promotes extensive axonal regeneration after spinal cord injury.
We describe a new strategy to promote axonal regeneration after subacute or chronic spinal cord injury consisting of intramedullary implantation of chitosan guidance channels containing peripheral nerve (PN) grafts. Chitosan channels filled with PN grafts harvested from green fluorescent protein rats were implanted in the cavity 1 week (subacute) or 4 weeks (chronic) after 50-g clip injury at T8 and were compared with similarly injured animals implanted with either unfilled channels or no channels. Functional recovery was measured weekly for 12 weeks by open-field locomotion, after which histological examination was performed. The implanted channels with PN grafts contained a thick tissue bridge containing as many as 35,000 myelinated axons in both the subacute and chronic spinal cord injury groups, with the greatest number of axons in the channels containing PN grafts implanted subacutely. There were numerous green fluorescent protein-positive donor Schwann cells in the tissue bridges in all animals with PN grafts. Moreover, these Schwann cells had high functional capacity in terms of myelination of the axons in the channels. In addition, PN-filled chitosan channels showed excellent biocompatibility with the adjacent neural tissue and no obvious signs of degradation and minimal tissue reaction at 14 weeks after implantation. In control animals that had unfilled chitosan channels implanted, there was minimal axonal regeneration in the channels; in control animals without channels, there were large cavities in the spinal cords, and the bridges contained only a small number of axons and Schwann cells. Despite the large numbers of axons in the chitosan channel-PN graft group, there was no significant difference in functional recovery between treatment and control groups. Intramedullary implantation of chitosan guidance channels containing PN grafts in the cavity after subacute spinal cord injury resulted in a thicker bridge containing a larger number of myelinated axons compared with chitosan channels alone. A chitosan channel containing PN grafts is a promising strategy for spinal cord repair.


[The ordinal localization of multiple mono-type carpal bones].
The case study was based on the osteologic collection of the chair for anthropology, State Moscow University, including the male carpal bones (67) and female carpal bones (13), aged above 18 to 20. Four measurements were made according to Martin's scheme for metacarpal bones and finger phalanxes. A diagnostic method was worked out on the bases of the discriminative analysis, with such method enabling the remodeling of the ordinal localization of metacarpal bones as well as of main, medium and distal phalanxes. The maximally accurate classification was ensured for metacarpal bones, ranging from 81.5% to 100%; and the minimally accurate one was achieved for distal phalanxes, ranging from 20% to 95%. The discriminative analysis results were checked for distal phalanxes by Neklyudov's series (male--100, female--85); they were described according to 7 sizes. However, an attempt to enhance the accuracy of the classification of these phalanxes failed. The offered method should be applied in combination with the traditional anatomic-and-morphological method; besides, if possible, it is necessary to check the congruence of joint surfaces in the metacarpal interphalangeal joints.


Comparing behavioral treatment of feeding difficulties and tube dependence in children with cerebral palsy and autism spectrum disorder.
Feeding disorders are multifaceted with behavioral components often contributing to the development and continuation of food refusal. In these cases, behavioral interventions are effective in treating feeding problems, even when medical or oral motor components are also involved. Although behavioral interventions for feeding problems are frequently employed with children with autism, they are less commonly discussed for children with cerebral palsy. The purpose of this study was to compare the effectiveness of using applied behavior analytic interventions to address feeding difficulties and tube dependence in children with autism and children with cerebral palsy. Children ages 1 to 12 years who were enrolled in an intensive feeding program between 2003 and 2013, where they received individualized behavioral treatment, participated. Behavioral treatment components were similar across groups, predominately consisting of escape extinction (e.g., nonremoval of the spoon) and differential reinforcement. For both groups, behavioral treatment was similarly effective in increasing gram consumption and in decreasing refusal and negative vocalizations. A high percentage of individualized goals were met by both groups as well as high caregiver satisfaction reported. Behavioral interventions for food refusal are effective for children with cerebral palsy with behavioral refusal, just as they are for children with autism.


Photo-Fenton reaction of graphene oxide: a new strategy to prepare graphene quantum dots for DNA cleavage.
Graphene quantum dots (GQDs) are great promising in various applications owing to the quantum confinement and edge effects in addition to their intrinsic properties of graphene, but the preparation of the GQDs in bulk scale is challenging. We demonstrated in this work that the micrometer sized graphene oxide (GO) sheets could react with Fenton reagent (Fe(2+)/Fe(3+)/H(2)O(2)) efficiently under an UV irradiation, and, as a result, the GQDs with periphery carboxylic groups could be generated with mass scale production. Through a variety of techniques including atomic force microscopy, X-ray photoelectron spectroscopy, gas chromatography, ultraperformance liquid chromatography-mass spectrometry, and total organic carbon measurement, the mechanism of the photo-Fenton reaction of GO was elucidated. The photo-Fenton reaction of GO was initiated at the carbon atoms connected with the oxygen containing groups, and C-C bonds were broken subsequently, therefore, the reaction rate depends strongly on the oxidization extent of the GO. Given the simple and efficient nature of the photo-Fenton reaction of GO, this method should provide a new strategy to prepare GQDs in mass scale. As a proof-of-concept experiment, the novel DNA cleavage system using as-generated GQDs was constructed.


Macro- and microstructural organization of the rabbit's celiac-mesenteric ganglion complex (Oryctolagus cuniculus).
The macro- and microstructures of the rabbit celiac-mesenteric ganglion complex are described in 20 young animals. We found ten celiac ganglia, twenty-seven cranial mesenteric ganglia and eleven celiac-mesenteric ganglia. The celiac ganglia had a rectangular shape in nine cases (90%) and a circular one in one case (10%). The cranial mesenteric ganglia presented triangular (66.7%), rectangular (11.1%), L-shape (18.5%) and semi-lunar (3.7%) arrangements. The celiac-mesenteric ganglia were organized in three patterns: a single left celiac-mesenteric ganglion having a caudal portion (72.7%); celiac-mesenteric ganglia without a caudal portion (18.2%) and a single celiac-mesenteric ganglion with two portions: left and right (9.1%). The microstructure was investigated in nine celiac-mesenteric ganglia. The results showed that the celiac-mesenteric ganglion is actually a ganglion complex constituted of an agglomerate of ganglionic units separated by nerve fibers, capillaries and septa of connective tissue. Using the semi-thin section method we described the cellular organization of the celiac-mesenteric ganglion complex. Inside of each ganglionic unit, there were various cell types: principal ganglion neurons (PGN), glial cells (satellite cells) and SIF cells (small intensely fluorescent cells or small granular cells), which are the cytologic basis for each ganglionic unit of the rabbit's celiac-mesenteric ganglion complex.


The contribution of male and female partners' substance use to sexual risks and STDs among African American HIV serodiscordant couples.
Growing evidence suggests that drug and alcohol use are fueling the heterosexual transmission of HIV among African Americans. This study aims to examine the relative contribution of drug and alcohol use of male and female partners to risks of heterosexual transmission of HIV among 535 African American HIV serodiscordant couples (N = 1,070 participants) who participated in an HIV prevention trial. Associations found between use of drugs and alcohol by one or both partners and sexual risk indicators varied by type of substance and whether male or female partner or both partners reported use. The findings suggest multiple ways in which substance use of male and female partners may be contributing to the heterosexual transmission of HIV and other STDs among African Americans and underscore the need for HIV prevention strategies to address dyadic patterns of substance use that lead to sexual risks.


l-Glutamic acid release from a series of aluminum-based isoreticular porous coordination polymers.
We investigated the encapsulation of bioactive molecules such as l-glutamic acid (Glu) into a series of porous coordination polymers (PCPs) based on aluminum hydroxy dicarboxylates [Al(OH)(L)]n (L = dicarboxylate ligand) and the molecular release therefrom. The use of 2,6-naphthalene dicarboxylate (2,6-ndc), 1,4-benzene dicarboxylate (1,4-bdc) and 1,4-naphthalene dicarboxylate (1,4-ndc) as ligands allows us to systematically tune the pore size and the flexibility of frameworks while keeping the same topology and thus to investigate the effect of those parameters upon both adsorption and release of Glu. We revealed the impact of zwitterionic nature of Glu upon loading efficiency; optimal loading pH was shown to be that for which Glu bears both positive and negative charges. Whereas the loading capacity of PCPs is governed by the pore size ([Al(OH)(2,6-ndc)]n > [Al(OH)(1,4-bdc)]n > [Al(OH)(1,4-ndc)]n), the adsorption isotherm clearly revealed that small or flexible pores induce the stronger Glu-PCP interaction. The release experiments of Glu from PCPs in a physiological media (pH = 7.4, 37 °C) demonstrated the exceptional stabilization of Glu within [Al(OH)(1,4-bdc)]n, compared to those within the other frameworks; whereas the rigid frameworks of [Al(OH)(2,6-ndc)]n and [Al(OH)(1,4-ndc)]n spontaneously released almost the entire Glu contents within 10 h, 70% of Glu loaded within [Al(OH)(1,4-bdc)]n still remained therein over 24 h. Interestingly, the burst release of Glu was triggered by increasing temperature up to 80 °C, at which the framework changed its structure from a closed phase to the open phase.


Sensory attenuation is modulated by the contrasting effects of predictability and control.
Self-generated stimuli have been found to elicit a reduced sensory response compared with externally-generated stimuli. However, much of the literature has not adequately controlled for differences in the temporal predictability and temporal control of stimuli. In two experiments, we compared the N1 (and P2) components of the auditory-evoked potential to self- and externally-generated tones that differed with respect to these two factors. In Experiment 1 (n = 42), we found that increasing temporal predictability reduced N1 amplitude in a manner that may often account for the observed reduction in sensory response to self-generated sounds. We also observed that reducing temporal control over the tones resulted in a reduction in N1 amplitude. The contrasting effects of temporal predictability and temporal control on N1 amplitude meant that sensory attenuation prevailed when controlling for each. Experiment 2 (n = 38) explored the potential effect of selective attention on the results of Experiment 1 by modifying task requirements such that similar levels of attention were allocated to the visual stimuli across conditions. The results of Experiment 2 replicated those of Experiment 1, and suggested that the observed effects of temporal control and sensory attenuation were not driven by differences in attention. Given that self- and externally-generated sensations commonly differ with respect to both temporal predictability and temporal control, findings of the present study may necessitate a re-evaluation of the experimental paradigms used to study sensory attenuation.