Clinical outcome of acute and chronic hepatitis delta over time: a long-term follow-up study.
Long-term changes in the frequency and outcome of hepatitis delta virus (HDV) infection have seldom been analysed. This retrospective, longitudinal study includes 398 consecutive hepatitis B surface antigen (HBsAg)-positive patients with anti-HDV antibodies who attended our institution between 1983 and 2008. At enrolment, 182 patients had acute and 216 chronic hepatitis. Patients were grouped into two periods. Those who attended between 1983 and 1995 and those between 1996 and 2008. The former group was significantly younger, mainly intravenous drugs users, and had a greater incidence of acute HDV and HIV and HCV coinfection. Patients with acute HBV/HDV coinfection cleared both infections in 90% of cases, while all patients with HDV superinfection evolved to chronic disease. One hundred and fifty-eight patients with chronic HDV were followed for a median period of 158months. Seventy-two per cent of the patients remained stable, 18% had hepatic decompensation, 3% developed hepatocellular carcinoma, and 8% cleared HBsAg. Liver-related death was observed in 13% of patients and mainly occurred in patients from the first period (P=0.012). These results indicate an outbreak of HDV at the end of the 1980s and the beginning of the 1990s, with a large number of acute HDV cases affecting predominately young, male intravenous drug users. Currently, patients with chronic HDV disease are older, and factors associated with worse prognosis include the presence of cirrhosis and age at the time of diagnosis.


Screening for Ovarian Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
Ovarian cancer is relatively rare but the fifth-leading cause of cancer mortality among United States women. To systematically review evidence on benefits and harms of ovarian cancer screening among average-risk women to inform the United States Preventive Services Task Force. MEDLINE, PubMed, Cochrane Collaboration Registry of Controlled Trials; studies published in English from January 1, 2003, through January 31, 2017; ongoing surveillance in targeted publications through November 22, 2017. Randomized clinical trials of ovarian cancer screening in average-risk women that reported mortality or quality-of-life outcomes. Interventions included transvaginal ultrasound, cancer antigen 125 (CA-125) testing, or their combination. Comparators were usual care or no screening. Independent critical appraisal and data abstraction by 2 reviewers. Meta-analytic pooling of results was not conducted because of the small number of studies and heterogeneity of interventions. Ovarian cancer mortality, false-positive screening results and surgery, surgical complications, and psychological effects of screening. Four trials (N = 293 587) were included; of these, 3 (n = 293 038) assessed ovarian cancer mortality, and 1 (n = 549) reported only on psychological outcomes. Evaluated screening interventions included transvaginal ultrasound alone, transvaginal ultrasound plus CA-125 testing, and CA-125 testing alone. Test positivity for CA-125 was defined by a fixed serum level cutpoint or by a proprietary risk algorithm based on CA-125 level, change in CA-125 level over time, and age (risk of ovarian cancer algorithm [ROCA]). No trial found a significant difference in ovarian cancer mortality with screening. In the 2 large screening trials (PLCO and UKCTOCS, n = 271 103), there was not a statistically significant difference in complete intention-to-screen analyses of ovarian, fallopian, and peritoneal cancer cases associated with screening (PLCO: rate ratio, 1.18 [95% CI, 0.82-1.71]; UKCTOCS: hazard ratio [HR], 0.91 [95% CI, 0.76-1.09] for transvaginal ultrasound and HR, 0.89 [95% CI, 0.74-1.08] for CA-125 ROCA). Within these 2 trials, screening led to surgery for suspected ovarian cancer in 1% of women without cancer for CA-125 ROCA and in 3% for transvaginal ultrasound with or without CA-125 screening, with major complications occurring among 3% to 15% of surgery. Evidence on psychological harms was limited but nonsignificant except in the case of repeat follow-up scans and tests, which increased the risk of psychological morbidity in a subsample of UKCTOCS participants based on the General Health Questionnaire 12 (score ≥4) (odds ratio, 1.28 [95% CI, 1.18-1.39]). In randomized trials conducted among average-risk, asymptomatic women, ovarian cancer mortality did not significantly differ between screened women and those with no screening or in usual care. Screening harms included surgery (with major surgical complications) in women found to not have cancer. Further research is needed to identify effective approaches for reducing ovarian cancer incidence and mortality.


Total testosterone density predicts high tumor load and disease reclassification of prostate cancer: results in 144 low-risk patients who underwent radical prostatectomy.
The aim of this study is to evaluate the association between total testosterone density (TTD), defined as the ratio of serum TT to prostate volume (PV), and high tumor load (HTL) in low-risk prostate cancer (PCA) patients who underwent radical prostatectomy. Tumor load was defined as the percentage of prostate volume invaded by cancer (PPI-PCA) in the surgical specimen. Pathologic features including tumor upgrading, upstaging or positive surgical margins in the specimen defined unfavorable disease (UD). PSA, TT, PSA density (PSAD), TTD, percentage of biopsy positive cores (BPC), PV and body mass index (BMI). The association of factors with the risk UD and HTL was evaluated by statistical methods. The cohort included 144 consecutive low-risk PCA patients. Overall, 104 patients (72.2%) had at least one feature indicating UD. TTD was associated with BMI, TT, PSA, PV and PPI-PCA ≥ 20% defined as HTL. A higher PPI-PCA was associated with an increased risk of UD with a fair discriminant power (area under the curve, AUC = 0.775; p < 0.0001). Patients with PPI-PCA > 20% were considered the study group versus patients with a PPI-PCA < 20% (control group). BPC, PSAD and TTD were independently associated with the risk of HTL (PPI-PCA ≥ 20%) with receiver-operating characteristics (ROC) curves indicating the same discriminant power for BPC (AUC = 0.628; p = 0.013), PSAD (AUC = 0.611; p = 0.032) and TTD (AUC = 0.610; p = 0.032). Among low-risk PCA patients, TTD is associated with the risk of HTL, which is an independent predictor of UD and should be evaluated in the management of these patients.


Carbon sequestration efficiency of organic amendments in a long-term experiment on a vertisol in Huang-Huai-Hai Plain, China.
Soil organic carbon (SOC) sequestration is important for improving soil fertility of cropland and for the mitigation of greenhouse gas emissions to the atmosphere. The efficiency of SOC sequestration depends on the quantity and quality of the organic matter, soil type, and climate. Little is known about the SOC sequestration efficiency of organic amendments in Vertisols. Thus, we conducted the research based on 29 years (1982-2011) of long-term fertilization experiment with a no fertilizer control and five fertilization regimes: CK (control, no fertilizer), NPK (mineral NPK fertilizers alone), NPK+1/2W (mineral NPK fertilizers combined with half the amount of wheat straw), NPK+W (mineral NPK fertilizers combined with full the amount of wheat straw), NPK+PM (mineral NPK fertilizers combined with pig manure) and NPK+CM (mineral NPK fertilizers combined cattle manure). Total mean annual C inputs were 0.45, 1.55, 2.66, 3.71, 4.68 and 6.56 ton/ha/yr for CK, NPK, NPKW1/2, NPKW, NPKPM and NPKCM, respectively. Mean SOC sequestration rate was 0.20 ton/ha/yr in the NPK treatment, and 0.39, 0.50, 0.51 and 0.97 ton/ha/yr in the NPKW1/2, NPKW, NPKPM, and NPKCM treatments, respectively. A linear relationship was observed between annual C input and SOC sequestration rate (SOCsequestration rate = 0.16 Cinput -0.10, R = 0.95, P<0.01), suggesting a C sequestration efficiency of 16%. The Vertisol required an annual C input of 0.63 ton/ha/yr to maintain the initial SOC level. Moreover, the C sequestration efficiencies of wheat straw, pig manure and cattle manure were 17%, 11% and 17%, respectively. The results indicate that the Vertisol has a large potential to sequester SOC with a high efficiency, and applying cattle manure or wheat straw is a recommendable SOC sequestration practice in Vertisols.


Dose-dependent differential resistance of inbred chicken lines to avian pathogenic Escherichia coli challenge.
Avian pathogenic E. coli (APEC) cause severe respiratory and systemic disease. To address the genetic and immunological basis of resistance, inbred chicken lines were used to establish a model of differential resistance to APEC, using strain O1 of serotype O1:K1:H7. Inbred lines 72, 15I and C.B12 and the outbred line Novogen Brown were inoculated via the airsac with a high dose (107 colony-forming units, CFU) or low dose (105 CFU) of APEC O1. Clinical signs, colibacillosis lesion score and bacterial colonization of tissues after high dose challenge were significantly higher in line 15I and C.B12 birds. The majority of the 15I and C.B12 birds succumbed to the infection by 14 h post-infection, whilst none of the line 72 and the Novogen Brown birds developed clinical signs. No difference was observed after low dose challenge. In a repeat study, inbred lines 72 and 15I were inoculated with low, intermediate or high doses of APEC O1 ranging from 105 to 107 CFU. The colonization of lung was highest in line 15I after high dose challenge and birds developed clinical signs; however, colonization of blood and spleen, clinical signs and lesion score were not different between lines. No difference was observed after intermediate or low dose challenge. Ex vivo, the phagocytic and bactericidal activity of lung leukocytes from line 72 and 15I birds did not differ. Our data suggest that although differential resistance of inbred lines 72, 15I and C.B12 to APEC O1 challenge is apparent, it is dependent on the infectious dose. Research Highlights Lines 15I and C.B12 are more susceptible than line 72 to a high dose of APEC O1. Differential resistance is dose-dependent in lines 15I and 72. Phagocytic and bactericidal activity is similar and dose independent.


Effect of wheat distillers dried grains with solubles or sugar beet pulp on prevalence of Salmonella enterica Typhimurium in weaned pigs.
Salmonella enterica Typhimurium (ST) is of concern in the swine industry with relevance for animal health and consumer safety. Nutritional strategies might help to reduce ST infection and transmission. This study examined the potential of wheat (Triticum aestivum) distillers dried grains with solubles (DDGS) and sugar beet (Beta vulgaris) pulp (SBP) to alter intestinal microbial communities and ST shedding using a Trojan model. Weaned pigs (n = 105; 28.5 ± 3.5 d of age) were separated into 3 treatment groups (7 pigs/pen) and fed a wheat-based control diet or the control diet formulated with 15% wheat DDGS or 6% SBP inclusion. Following 12 d of diet adaptation, 2 pigs/pen were inoculated with 2 x 10(9) cfu ST, resistant to novobiocin and nalidixic acid. Fecal swabs were taken from infected pigs and pen-mates (contact pigs) for 9 d following challenge, enriched in nutrient broth for 24 h, and plated on selective media to determine prevalence of ST. The ranges of prevalence of ST in feces were from 90 to 100% in challenged pigs and 74 to 78% in contact pigs. No influence of treatment on rectal temperature and prevalence of ST in contact pigs were observed. Fifteen contact pigs were euthanized per treatment group on 9 and 10 d postchallenge to enumerate in intestinal contents (ileum, cecum, and proximal colon), Lactobacillus spp., Enterobacteriaceae, and Clostridium clusters I, VI, and XVIa by quantitative PCR (qPCR) and to determine ST prevalence by selective culture. No significant effects of diet were observed with respect to ST prevalence in feces, ileum, cecum, colon, and lymph nodes of contact pigs. Compared with the control diet, DGGS and SBP diets showed a trend towards increased (P < 0.1) number of Lactobacillus species in the cecum and colon. Although both wheat DGGS and SBP tended to increase the Lactobacillus spp. neither of the feed ingredients affected ST prevalence.


The Global and Regional Prevalence of Abdominal Aortic Aneurysms: A Systematic Review and Modeling Analysis.
To estimate the global and regional prevalence and cases of abdominal aortic aneurysms (AAAs) in 2019 and to evaluate major associated factors. Understanding the global prevalence of AAA is essential for optimizing health services and reducing mortality from reputed AAA. PubMed, MEDLINE, and Embase were searched for articles published until October 11, 2021. Population-based studies that reported AAA prevalence in the general population, defined AAA as an aortic diameter of 30 mm or greater with ultrasonography or computed tomography. A multilevel mixed-effects meta-regression approach was used to establish the relation between age and AAA prevalence for high-demographic sociodemographic index and low-and middle-sociodemographic index countries. Odds ratios of AAA associated factors were pooled using a random-effects method. We retained 54 articles across 19 countries. The global prevalence of AAA among persons aged 30 to 79 years was 0.92% (95% CI, 0.65-1.30), translating to a total of 35.12 million (95% CI, 24.94-49.80) AAA cases in 2019. Smoking, male sex, family history of AAA, advanced age, hypertension, hypercholesterolemia, obesity, cardiovascular disease, cerebrovascular disease, claudication, peripheral artery disease, pulmonary disease, and renal disease were associated with AAA. In 2019, the Western Pacific region had the highest AAA prevalence at 1.31% (95% CI, 0.94-1.85), whereas the African region had the lowest prevalence at 0.33% (95% CI, 0.23-0.48). A substantial proportion of people are affected by AAA. There is a need to optimize epidemiological studies to promptly respond to at-risk and identified cases to improve outcomes.


Young children's perspectives on treatment and care: A qualitative study using narrative and play-based interviewing.
To explore young children's (age 3-6 years) own experiences and perceptions of treatment and care when living with a chronic illness. The study employed a qualitative research design using a narrative and play-based interview approach. Individual face-to-face, narrative and play-based interviews were conducted with eight young children age 3-6 years with type 1 diabetes or cystic fibrosis. The play sessions took place at the home of the children and were video recorded. Interpretative phenomenological analysis was used to analyse the data and frame the study. Our analysis identified six main themes: 1. Children understood illness through their bodily experience of treatment and care, 2. Children's experience of care and treatment ranged from a feeling of powerlessness to a sense of agency, 3. Children depended on their parents to provide comfort, advocacy and protection, 4. Children's perceptions of treatment and care were inherently related to their experiences of familiarity, interpersonal relationships and trust, 5. Children with type 1 diabetes did not perceive that they played an active role during consultations, and 6. Children associated medical treatment with receiving tangible rewards or positive feedback. Children expressed a need to feel safe and build agency. They experienced this through participation and interpersonal relationships with healthcare professionals. We should prioritize the establishment and implementation of age-appropriate psychosocial care practices that support young children in participating, forming relationships, and building trust.


Genetic factors in the etiology of mental retardation.
Mental retardation is a condition with multiple, disparate causes, both environmental and genetic. In this article we have tried to characterize, in a general fashion, the nature of the genetic factors through a discussion of polygenic inheritance, single gene errors, and chromosomal anomalies. Despite the existence of a large and complex body of knowledge, which has only been touched upon here, it is sobering to realize that we cannot diagnose almost half of the mentally retarded. Even in those in whom a genetic etiology is obvious, we know little about the intervening processes that operate between the gene and the mental deficiency it produces. Under the conditions, therapy holds little promise, while prevention assumes a high priority. Prevention of mental retardation due to genetic factors requires the physician to have a basis knowledge of genetic principles and syndromes, of prenatal diagnostic technology, and a determination to inform, even when the patient does not ask.


Developmental Exposure to a Human-Relevant Polychlorinated Biphenyl Mixture Causes Behavioral Phenotypes That Vary by Sex and Genotype in Juvenile Mice Expressing Human Mutations That Modulate Neuronal Calcium.
Polychlorinated biphenyls (PCBs) are putative environmental risks for neurodevelopmental disorders. Here, we tested two hypotheses: (1) developmental exposure to a human-relevant PCB mixture causes behavioral phenotypes relevant to neurodevelopmental disorders; and (2) expression of human mutations that dysregulate neuronal Ca2+ homeostasis influence sensitivity to behavioral effects of developmental PCB exposures. To test these hypotheses, we used mice that expressed a gain-of-function mutation (T4826I) in ryanodine receptor 1 (RYR1), the X-linked fragile X mental retardation 1 (FMR1) CGG repeat expansion or both mutations (double mutant; DM). Transgenic mice and wildtype (WT) mice were exposed to the MARBLES PCB mix at 0, 0.1, 1, and 6 mg/kg/day in the maternal diet throughout gestation and lactation. The MARBLES PCB mix simulates the relative proportions of the 12 most abundant PCB congeners found in the serum of pregnant women at increased risk for having a child with a neurodevelopmental disorder. We assessed ultrasonic vocalizations at postnatal day 7 (P7), spontaneous repetitive behaviors at P25-P30, and sociability at P27-P32. Developmental PCB exposure reduced ultrasonic vocalizations in WT litters in all dose groups, but had no effect on ultrasonic vocalizations in transgenic litters. Developmental PCB exposure significantly increased self-grooming and decreased sociability in WT males in the 0.1 mg/kg dose group, but had no effect on WT females in any dose group. Genotype alone influenced ultrasonic vocalizations, self-grooming and to a lesser extent sociability. Genotype alone also influenced effects of PCBs on sociability. PCB levels in the brain tissue of pups increased in a dose-dependent manner, but within any dose group did not differ between genotypes. In summary, developmental PCB exposure phenocopied social behavior phenotypes observed in mice expressing human mutations that modify intracellular Ca2+ dynamics, and expression of these mutations alleviated PCB effects on ultrasonic vocalizations and repetitive behavior, and modified the dose-response relationships and sex-dependent effects of PCB effects on social behavior. These findings suggest that: (1) developmental PCB exposure causes behavioral phenotypes that vary by sex and genotype; and (2) sex-specific responses to environmental factors may contribute to sex biases in the prevalence and/or severity of neurodevelopmental disorders.


A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study.
Adenosine deaminase (ADA) inhibition not only may be applied for the treatment of ischemic injury, hypertension, lymphomas and leukaemia, but also they have been considered as anti- inflammatory drugs. On the other hand according to literatures, ADA inhibitors without a nucleoside framework would improve pharmacokinetics and decrease toxicity. Hence we have carried out a rational pharmacophore design for non-nucleoside inhibitors filtration. A merged pharmacophore model based on the most potent non-nucleoside inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and natural products were generated and applied for compounds filtration. The effects of filtrated compounds based on pharmacophore and docking studies investigated on ADA by UV and Fluorescence spectroscopy techniques. Extracted compounds were find efficiently inhibit ADA, and the most potent (2) shows an inhibition constant equal to 20 μM. Besides, Fluorescence spectroscopy studies revealed that enzyme 3D structure bear further change in lower concentrations of compound 2. 3 non-nucleoside inhibitors for ADA are presented. According to obtained results from UV and fluorescence spectroscopy, such interesting pharmacophore template with multiple approaches will help us to extract or design compound with desired properties.


Meningiomas of the lateral ventricle - a report of 15 cases.
Lateral ventricular meningiomas are rare tumours that pose considerable surgical challenge. This study attempts to analyse some of the important clinical features of these tumours and review technical considerations in surgery for lateral ventricular meningiomas. A retrospective analysis of the case records of patients with lateral ventricular meningiomas operated in our institute since 1998 with a minimum of one year follow up was done. The variables analysed included age, sex, clinical presentation, imaging characteristics, histopathology and operative details. Outcome was analysed using the Glasgow outcome score (GOS). Fifteen patients with a mean age of 40.6 years formed the study group. A female preponderance was observed (M:F 5:10). Raised intracranial pressure was the predominant symptom at presentation (10/15; 66%) followed by visual field deficits (6/15; 40%) and contralateral motor deficits (5/15; 33.3%). One patient presented with evidence of intratumoural bleed. The tumour was on the right side in 7 patients and on the left side in 8 patients. The lesion was located in the trigone of the lateral ventricle in 13 patients and in the body of the ventricle in two. The tumours were excised through a parietooccipital approach in 11 (73.33%) patients and through a middle temporal gyrus approach in 4 (26.66%).The tumour recurred in 2 patients, both tumours being histologically fibroblastic variants. Fresh operative complications included motor deficits in 3, contralateral homonymous hemianopia in 2, dysphasia in 1, refractory seizures in 2 and loculated hydrocephalus in one. We had no operative mortality. At last follow-up for 10 patients were in GOS 5, two were in GOS 4 and three in GOS 3. Lateral ventricular meningiomas are difficult tumours to operate. Total surgical excision through a superior parietal lobule or middle temporal gyrus approach is possible in most cases with minimal morbidity.


Leukocyte telomere length positively correlates with duration of lithium treatment in bipolar disorder patients.
Bipolar disorder (BD) has been suggested to be associated with accelerated aging and premature cell senescence. While findings on shorter telomeres in BD are controversial, a recent study showed that long-term lithium treatment correlates with longer telomeres in BD. In our study, we sought to investigate the correlation between leukocyte telomere length (LTL) and long-term lithium treatment in a sample of 200 BD patients characterized for lithium response. We also compared data from two different methods commonly used to measure telomere length, quantitative PCR (qPCR) and quantitative fluorescence in situ hybridization (Q-FISH). We also measured, for the first time, the effect of lithium in vitro on the expression of the telomerase gene in human-derived neural progenitor cells (NPCs). Our findings showed that LTL correlated negatively with age (p=0.0002) and was independent of sex, diagnosis, age at onset, suicidal behavior, number of mood episodes, response to lithium and use of other psychotropic medications. After correcting for age, LTL was positively correlated with lithium treatment duration in patients treated for more than two years (n=150, R=0.17, p=0.037). There was a significant correlation between data measured with qPCR and Q-FISH (p=0.012, R=0.826). Lithium treatment increased telomerase expression in NPCs, though this effect was not statistically significant. Our data support previous findings showing that long-term lithium treatment associates with longer telomeres in BD, though this effect appeared to be independent from clinical response to the treatment. Moreover, we suggested for the first time that lithium increases the expression of telomerase gene in human neural progenitor cells.


A DNA barcoding approach to characterize pollen collected by honeybees.
In the present study, we investigated DNA barcoding effectiveness to characterize honeybee pollen pellets, a food supplement largely used for human nutrition due to its therapeutic properties. We collected pollen pellets using modified beehives placed in three zones within an alpine protected area (Grigna Settentrionale Regional Park, Italy). A DNA barcoding reference database, including rbcL and trnH-psbA sequences from 693 plant species (104 sequenced in this study) was assembled. The database was used to identify pollen collected from the hives. Fifty-two plant species were identified at the molecular level. Results suggested rbcL alone could not distinguish among congeneric plants; however, psbA-trnH identified most of the pollen samples at the species level. Substantial variability in pollen composition was observed between the highest elevation locality (Alpe Moconodeno), characterized by arid grasslands and a rocky substrate, and the other two sites (Cornisella and Ortanella) at lower altitudes. Pollen from Ortanella and Cornisella showed the presence of typical deciduous forest species; however in samples collected at Ortanella, pollen of the invasive Lonicera japonica, and the ornamental Pelargonium x hortorum were observed. Our results indicated pollen composition was largely influenced by floristic local biodiversity, plant phenology, and the presence of alien flowering species. Therefore, pollen molecular characterization based on DNA barcoding might serve useful to beekeepers in obtaining honeybee products with specific nutritional or therapeutic characteristics desired by food market demands.


Intraoperative Pulmonary Embolism: A Case Report Emphasizing the Utility of Electrocardiogram.
Pulmonary embolism (PE) is an important cause of perioperative morbidity and mortality. In patients with suspected PE, electrocardiogram (ECG) alone is thought to have a limited utility due to its low sensitivity and specificity. This case report describes a patient with intraoperative PE presenting with hypotension and hypoxemia for whom the ECG finding of SIQIIITIII was key in identifying acute cor pulmonale. The ECG was paramount in our decision to acquire computed tomography angiography to confirm the diagnosis, reinforcing its invaluable role in early detection of intraoperative PE.


[Neuropathological findings in early-onset Alzheimer's disease (E280a-PS1 mutation)].
Nine brains belonging to early onset Alzheimer disease (E280A-PS1 mutation) affected individuals from Antioquia, Colombia, were analyzed by neuropathological standard techniques. All individuals were ascertained from genealogies descendents from a common ancestor that shows a dominant autosomical pattern of inheritance. All cases analyzed were carriers to the E280A-PS1 mutation. This type of mutation produce beta-amyloid deposits of 42 aminoacids in the CNS. The mean of onset age was 48.4 years with an average of evolution time of 7.55 years and a mean of death age of 56.55. Although, all the cases showed symmetrical atrophy and them was more severe in the hippocampal region, a definitive anterior pattern (temporo-frontal) was showed. The higher the time of evolution of disease the lower the brain weight. All types of senile plaques and abundant neurofibrillary tanggles were found. In the stem, similar lesions were found but they were in lower number. Only the mesencephalic region showed a significative positive correlation between the number of senile plaques and the number of neurofibrillary tanggels (p < 0.05, r = 0.76). Only the parietal region showed a significant positive correlation between the number of senile plaques and the disease evolution time (p < 0.02, r = 0.74). Particularly, the cerebellum only showed senile plaques but neurofibrillary degeneration was not observed. With the exception of the Hirano bodies, all findings traditionally described were observed.


Dendroids, Discrete Covalently Cross-Linked Dendrimer Superstructures.
A versatile method is presented to form dendrimer superstructures by exploiting coacervate-core micelles as a template to confine and organize the hyperbranched macromolecules. First, complex coacervate-core micelles are formed from negative-neutral block copolymers and positively charged polyamidoamine dendrimers. The dendrimers inside the micellar core are then covalently cross-linked with each other upon addition of glutaraldehyde. After removal of the block copolymer from the assembly by increasing the salt concentration, consecutively, the formed Schiff bases cross-linking the dendrimers are reduced to amines, followed by a final dialysis step. This leads to well-defined covalently cross-linked nanostructures, coined dendroids, with a size of around 30 nm in diameter and a molecular weight of approximately 2.5 MDa. By incorporating dendrimer-encapsulated gold nanoparticles (AuDENs) into the micelle template strategy, the aggregation number of dendrimers inside the dendroids is determined by counting the nanoparticles in TEM micrographs. Furthermore, TEM performed at different tilt angles and AFM analysis corroborate formation of stable, covalently linked three-dimensional structures. Reconstruction of the TEM tilt series results in a tomogram further illustrating the 3D distribution of the gold nanoparticles, and hence the individual dendrimers, in the nanostructure. These dendroids appear to have a hard, poorly compressible core and a relatively soft outside. The versatility of the hierarchical building up of the supermolecules is illustrated by the controlled and synchronous incorporation of empty dendrimers and AuDENs into a single hybrid dendroid structure. The presented strategy allows for the preparation of a variety of classes of supermolecules, depending on the type of micellar-core macromolecule, e.g., dendrimer, cross-linker, and nanoparticles, used. Considering the broad interest in dendrimers as well as micelles in a plethora of research areas, e.g., (targeted) drug delivery, biomedical imaging, theragnostics, and catalysis, there is a great potential for dendroids and related classes of covalently linked macromolecules, viz., supermolecules.


Problems with defining cannabis dependence.
Cannabis enjoys a unique social status, widely perceived as a relatively harmless drug, with several benefits reported by the people who use it. Several jurisdictions have opened up access to cannabis to their populations for medicinal and/or recreational reasons. Given this changing regulatory environment, this article is intended to prompt debate about what is known about cannabis dependence and what has still to be revealed. Evidence suggests that 1 in 10 cannabis users are at risk of developing dependence. However, investigation of the way risk is estimated and the diagnosis of cannabis use disorder is constructed highlight some methodological problems, which call into question the incidence and prevalence of this diagnosis. There is scope to improve the way cannabis dependence is defined and counted in at-risk populations. Improving our understanding of this risk could lead to identifying who might be at risk of developing dependence prior to exposure to the drug.


Individual variation in an acute stress response reflects divergent coping strategies in a large herbivore.
Individuals differ in the manner that they cope with risk. When these behavioral differences are manifested in risky or challenging environments (i.e. stressful situations), they are generally interpreted within the "coping style" framework. As studying inter-individual variability in behavior is particularly challenging in the wild, we used a captive facility to explore consistency in the individual behavioral response to an acute stress in roe deer (Capreolus capreolus). Using behavioral and physiological parameters measured six times across a calendar year, we first quantified individual repeatability and, second, explored the correlations among these parameters that might indicate a coherent stress response. Finally, we analyzed the link between the stress response and individual body mass, a reliable indicator of phenotypic quality in roe deer. We found that the measured parameters were highly repeatable across seasons, indicating that the individual stress response is consistent over time. Furthermore, there was considerable covariation among the stress response parameters, describing a proactivity-reactivity gradient at the individual level. Finally, proactive individuals had higher body mass than reactive individuals. We suggest that consistent individual differences in energy metabolism and physiology may promote consistent individual differences in behavioral traits, providing a mechanistic link between food acquisition tactics and demographic performance.


Identifying inefficient strategies in automation-aided signal detection.
Automated diagnostic aids can assist human operators in signal detection tasks, providing alarms, warnings, or diagnoses. Operators often use decision aids poorly, though, falling short of best possible performance levels. Previous research has suggested that operators interact with binary signal detection aids using a sluggish contingent cutoff (CC) strategy (Robinson & Sorkin, 1985), shifting their response criterion in the direction stipulated by the aid's diagnosis each trial but making adjustments that are smaller than optimal. The present study tested this model by examining the efficiency of automation-aided signal detection under different levels of task difficulty. In a pair of experiments, participants performed a numeric decision-making task requiring them to make signal or noise judgments on the basis of probabilistic readings. The mean reading values of signal and noise states differed between groups of participants, producing two levels of task difficulty. Data were fit with the CC model and two alternative accounts of automation-aided strategy: a discrete deference (DD) model, which assumed participants defer to the aid on a subset of trials and a mixture model, which assumed that participants choose randomly between the CC and DD strategies every trial. Model fits favored the mixture model. The results indicate multiple forms of inefficiency in operators' strategies for using signal detection aids. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Vascular endothelium as a regulator of granulopoiesis: production of colony-stimulating activity by cultured human endothelial cells.
Colony-stimulating activity is a regulatory factor(s) that promotes differentiation of hemopoietic stem cells to mature granulocytes and macrophages; in man it has been found that blood monocytes, lymphocytes, and tissue macrophages produce it. In an effort to identify other potenitally physiologic tissue sources of colony-stimulating activity, we have studied the capacity of primary cultures of human vascular endothelial cells to produce colony-stimulating activity. Medium conditioned by incubation with endothelial cultures contained activity that promoted granulocyte-macrophage colony formation of nonadherent human and murine marrow cells. Exposure of endothelial cultures to 0.1-5.0 microgram/ml S. typhosa endotoxin for 6-72 hr enhanced colony-stimulating activity production. Similarly, incubation of endothelial cells with lysates of human blood granulocytes, or cocultivation with intact granulocytes, resulted in increased colony-stimulating activity levels. In 7-14 day cultures, freshly isolated endothelial cells, incorporated into agar underlayers, consistently stimulated more colony formation by nonadherent human marrow cells than comparable numbers of blood monocytes. These data indicate that: (1) cultured human endothelial cells are a potent source of colony-stimulating activity; (2) they respond to endotoxin and granulocytes and their contents by producing increased amounts of CSA; and (3) they produce morea colony-stimulating activity, than human blood monocytes under standardized conditions in vitro. These observations suggest that the vascular endothelium may play a role in the physiologic regulation of granulopoiesis.


Electrodermal activity in euthymic unipolar and bipolar affective disorders. A possible marker for depression.
Skin conductance, heart rate, and resting EEG were examined in 26 patients with unipolar and 24 with bipolar affective disorder (in remission) and 46 medical control patients. The electrodermal activity (EDA) was monitored during a tone series that included a dishabituating stimulus as well as at rest and during respiratory maneuvers. The EDA of the patients with affective disorder was uniformly depressed across all tasks and conditions. Only one of the unipolar and five of the bipolar patients showed an elevated tonic conductance level, compared with about half of the normal subjects. These results suggest that diminished EDA may serve as a marker of susceptibility to affective disorder or, alternatively, that elevated EDA may be a protective factor. There were no EEG differences between groups, and observed cardiac rate differences were attributable to the effects of tricyclic medication.


Variants in the ATM-BRCA2-CHEK2 axis predispose to chronic lymphocytic leukemia.
We conducted a large-scale association study to identify low-penetrance susceptibility alleles for chronic lymphocytic leukemia (CLL), analyzing 992 patients and 2707 healthy controls. To increase the likelihood of identifying disease-causing alleles we genotyped 1467 coding nonsynonymous single nucleotide polymorphisms (nsSNPs) in 865 candidate cancer genes, biasing nsSNP selection toward those predicted to be deleterious. Preeminent associations were identified in SNPs mapping to genes pivotal in the DNA damage-response and cell-cycle pathways, including ATM F858L (odds ratio [OR] = 2.28, P < .0001) and P1054R (OR = 1.68, P = .0006), CHEK2 I157T (OR = 14.83, P = .0008), BRCA2 N372H (OR = 1.45, P = .0032), and BUB1B Q349R (OR = 1.42, P = .0038). Our findings implicate variants in the ATM-BRCA2-CHEK2 DNA damage-response axis with risk of CLL.


Impact of the COVID-19 pandemic on Swiss pregnant and breastfeeding women - a cross-sectional study covering the first pandemic wave.
Information on the impact of the COVID-19 pandemic on pregnancy and breastfeeding experiences, as well as on perinatal mental health in Switzerland is limited. In Switzerland, there are few national studies and little information. Using an anonymous online survey accessible after the first wave of the outbreak in Switzerland, we have investigated how this pandemic affected pregnant and breastfeeding women. Among women who completed the survey, 69.0% (1050/1518) indicated the first wave of the pandemic affected their personal habits, 61.0% (689/1131) were affected in their work and 40.0% (632/1573) reported impaired relations with healthcare services (different denominators correspond to the number of participants who answered the question). 36.8% (110/299) of women reported an impact of the pandemic on their current pregnancy experience or breastfeeding experience (8.2%, 46/555). Overall, 11.6% (170/1467) of participants who completed the validated screening tests for mental health symptoms (Edinburgh Postnatal Depression Scale, Generalized Anxiety Disorder 7, Perceived Stress Scale) presented a score compatible with symptoms of major depression, severe anxiety or high perceived stress, which is higher than in the pre-pandemic period according to literature. Risk factors independently associated with impaired mental health were being hospitalized, having symptoms of COVID-19, living with a person with COVID-19 symptoms, having comorbidities, having experienced reduced healthcare services, having restricted usual activities and being a housewife. Protective factors independently associated were a high level of education and living with a partner. Our findings suggest that the COVID-19 pandemic might have significantly affected the well-being and mental health of pregnant and breastfeeding women, directly in the case of exposure, and indirectly as a result of the potential modifications in their life habits and in healthcare facilities.


Mental health services implementation in Colombia-A systematic review.
Colombia's mental health services have a complex history shaped by 60 years of armed conflict, a predominantly clinical approach to mental health, and social factors such as inequities and stigma. The 1990 Caracas declaration proposed a shift towards decentralised community mental health services and interventions based on the recovery approach and emphasis on social determinants of mental health in the Americas. Colombia has adopted these approaches in its legal and practical framework in recent years, but implementation has been uneven. This systematic review aims to contribute to mental health services understanding in Colombia by examining the barriers and facilitators to the implementation of mental health services in Colombia. A search was conducted to explore available peer-reviewed studies on Colombian mental health services across five databases (Medline, PubMed, Scopus, Scielo and BVS) on quantitative and qualitative research papers published in the last ten years and without language restrictions. The Consolidated Framework for Implementation Research (CFIR) was used to structure the analysis and identify barriers and facilitators during the implementation of mental health services. We adapted the CFIR to attend to gender, race and age informed by the Socio-Political Economy of Global Mental Health framework, given the importance of these factors to the Colombian health landscape. Finally, narrative synthesis was used to summarise the data. 1 530 records were identified, and 12 articles met all inclusion criteria and were included in the analysis. 8 papers described substance use disorders services, 11 involved multidisciplinary healthcare professionals, and 7 were implemented at a local scale. The primary barriers to implementation were the lack of coordination, high workloads, and low funding. Facilitators included the use of protocols, and the involvement of communities, stakeholders, users, and external champions. Findings suggest the continued importance of community and recovery approaches and efforts to improve coordination between multi-sector actors involved in the mental health spaces (e.g., public, and private organisations, users and their families).


Macroscopic magnetic frustration.
Although geometrical frustration transcends scale, it has primarily been evoked in the micro- and mesoscopic realm to characterize such phases as spin ice, liquids, and glasses and to explain the behavior of such materials as multiferroics, high-temperature superconductors, colloids, and copolymers. Here we introduce a system of macroscopic ferromagnetic rotors arranged in a planar lattice capable of out-of-plane movement that exhibit the characteristic honeycomb spin ice rules studied and seen so far only in its mesoscopic manifestation. We find that a polarized initial state of this system settles into the honeycomb spin ice phase with relaxation on multiple time scales. We explain this relaxation process using a minimal classical mechanical model that includes Coulombic interactions between magnetic charges located at the ends of the magnets and viscous dissipation at the hinges. Our study shows how macroscopic frustration arises in a purely classical setting that is amenable to experiment, easy manipulation, theory, and computation, and shows phenomena that are not visible in their microscopic counterparts.


Sinus sternoclavicularis: a congenital cervical sinus.
We try to characterize a previously rather neglected congenital cervical sinus located in the sternoclavicular area in five children. This sinus showed extension to the left sternoclavicular joint in all patients, so we call this congenital lesion "sinus sternoclavicularis." With knowledge of this congenital lesion, diagnosis can easily be established based on case history and clinical examination; no further radiological tests are required. Surgical excision is the treatment of choice. The chance of recurrence seems to be high because of misinterpretation of the lesion.


Platelet transfusion therapy. Optimal donor selection with a combination of lymphocytotoxicity and platelet fluorescence tests.
Although the value of HLA matching for the selection of platelet donors for patients refractory to random platelets is beyond doubt, even perfectly matched combinations sometimes fail to give a satisfactory transfusion response. With HLA typing and negative lymphocytotoxicity crossmatches, 35% of the platelet transfusions administered to 15 patients gave disappointing results (29 of 82). Additional crossmatching with the newly developed platelet fluorescence test described in this paper reduced the unexpected transfusion failures to 7% (6 of 82). Five of these failures were observed in one patient. The target of the antibodies detected with this platelet fluorescence test is not yet fully specified. It seems probable that both HLA and platelet-specific non-HLA antibodies were detected. No correlation of the results of platelet transfusions with the presence or absence of leukoagglutinating antibodies was found.


Dehydroepiandrosterone suppresses elevated hepatic glucose-6-phosphatase mRNA level in C57BL/KsJ-db/db mice: comparison with troglitazone.
Dehydroepiandrosterone (DHEA) is known to improve hyperglycemia of diabetic C57BL/KsJ-db/db mice that are obese and insulin resistant. In a previous study, we reported that DHEA as well as troglitazone suppresses the elevated hepatic gluconeogenic enzymes, glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase) activities in C57BL/KsJ-db/db mice. In the present study, we evaluated the changes in mRNA of G6Pase and FBPase in db/db mice. Despite hyperinsulinemia, the G6Pase mRNA level of db/db mice was elevated as compared to their heterozygote littermate db/+m mice. In contrast, the FBPase mRNA level was not elevated in db/db mice. Administration of DHEA for two weeks significantly decreased the blood glucose level and the elevated G6Pase mRNA level in db/db mice. No significant changes were seen in the FBPase mRNA level after the administration of DHEA. Administration of troglitazone also decreased the blood glucose and G6Pase mRNA level in db/db mice although no changes were seen in the FBPase mRNA level. These results suggest that the elevation of G6Pase mRNA is important in elucidating the cause of insulin resistance, and that the G6Pase gene is at least one target for the hypoglycemic effects of DHEA as an insulin sensitizing agent in db/db mice.


[Effect of vazaprostan on microcirculation in patients with scleroderma systematic].
To investigate the effect of vazaprostan (alprostadil) on skin blood flow in patients with sclerodermia systematica (SS). A total of 51 patients with SS aged 33-70 years were included in the study. 33 of them received a 3-hour infusion of vazaprostan at the standard dose for 20 consecutive days. The rest 18 patients received low molecular dextran solution. Before and at the end of the treatment digital skin microcirculation was measured with a laser Doppler flowmeter. The laser probe was attached to the distal pad of the ring finger on the left hand. Baseline blood flow and vascular reactivity in the tests with sympathetic stimulation, local heating and during orthostasis were evaluated. Baseline blood flow and vascular response to functional tests were significantly reduced in all the patients. At the end of the treatment the flow increased only in patients treated with vazaprostan. Vascular reactivity was not changed after the treatment in both groups of patients. Vazaprostan increases baseline blood flow and contributes to the improvement of microcirculation in patients with SS.


In vivo cytokine production in murine listeriosis. Evidence for immunoregulation by gamma delta+ T cells.
Differential cytokine production by gamma delta+ T cells influences Th1 and Th2 responses. Here, we describe the in vivo kinetics of peritoneal and splenic gamma delta+, CD4+, and CD8+ T cell cytokine responses during primary and secondary Listeria infections. The data show differences in the kinetics of IFN-gamma-producing alpha beta+ splenocytes consistent with immunologic memory. Most noteworthy, however, was the elevated production of IL-10 by splenic gamma delta+ T cells in the red pulp and marginal zones that coincided with maximal IFN-gamma production and with a decrease in inflammation and tissue damage. This result implies a role for gamma delta+ T cells in the control of Th1 responses.


Involvement of Ras/extracellular signal-regulated kinase, but not Akt pathway in risedronate-induced apoptosis of U937 cells and its suppression by cytochalasin B.
Although risedronate, a nitrogen containing bisphosphonate (BPs), strongly inhibits bone resorption by enhanced apoptosis of osteoclasts, its mechanism remained unclear. In this study, we investigated the molecular mechanism of risedronate-induced apoptosis of U937 cells, with a focus on extracellular signal-regulated kinase 1/2 (ERK 1/2) and protein kinase B (Akt) pathways, mitochondria-mediated apoptosis, and the effect of disruption of the actin cytoskeleton. Risedronate facilitated the relocation of Ras from membrane to cytosol through inhibited isoprenylation. Accordingly, risedronate suppressed the phosphorylation of ERK 1/2, a downstream survival signaling kinase of Ras, affected the intracellular distribution of Bcl-xL, and induced the mitochondrial membrane depolarization, cytochrome c release, activated caspase cascade and DNA fragmentation. The risedronate-induced apoptosis was effectively suppressed with cyclosporine A plus trifluoperazine, potent inhibitors of mitochondrial membrane permeability transition (MPT). The risedronate-induced apoptosis was independent of Akt, another cAMP-dependent survival signaling kinase. Risedronate facilitated dephosphorylation of Bad at Ser112, an ERK phosphorylation site, but not at Ser136, an Akt phosphorylation site. All of these apoptosis-related changes induced by risedronate were strongly suppressed by cytochalasin B, an inhibitor of actin filament polymerization. These results indicate that risedronate-induced apoptosis in U937 cells involves Ras/ERK, but not Akt signaling pathway, and is dependent on MPT, and that disruption of the actin cytoskeleton inhibits the risedronate-induced apoptosis at its early step.


[2Fe-2S] proteins in Chlorosomes: CsmI and CsmJ participate in light-dependent control of energy transfer in Chlorosomes of Chlorobaculum tepidum.
Chlorosomes of Chlorobaculum tepidum are formed from stacks of syn-anti coordinated bacteriochlorophyll c dimers, which form a suprastructure comprised of coaxial nanotubes and are surrounded by a glycolipid monolayer envelope containing 10 proteins. Three of these proteins, CsmI, CsmJ, and CsmX, have sequences very similar in their N-terminal domains to those of [2Fe-2S] ferredoxins of the adrenodoxin/putidaredoxin subfamily. The roles of these proteins in chlorosomes were studied in single-, double-, and triple-mutant strains. In each mutant, only the protein(s) corresponding to the mutated gene(s) was missing, and the amounts of other chlorosome proteins did not vary significantly. Electrophoretic analyses and immunoblotting showed that CsmX was much less abundant than CsmI or CsmJ. The growth rates and the pigment and isoprenoid quinone contents of isolated chlorosomes of the mutants were similar to wild-type values. Quenching and recovery of energy transfer in isolated chlorosomes and intact cells were studied by measuring fluorescence emission after exposure to or removal of oxygen. Oxygen-induced activation of the quencher in isolated chlorosomes or in intact cells was largely independent of CsmI and CsmJ. This may be because oxygen can diffuse across the chlorosome envelope easily and directly reacts with the quencher. However, CsmI and CsmJ were required to restore energy transfer fully after isolated chlorosomes were exposed to oxygen. Studies with intact cells suggested that cells contain both light-dependent and light-independent pathways for reducing the quenching species in chlorosomes and that CsmI and CsmJ are components of a light-dependent pathway.


[Increase of alpha 1-adrenoreactivity of the rat heart in adaptation to periodic hypoxia].
There is a possibility that the cardioprotective effect of adaptation to intermittent hypoxia is due to changes in receptors apparatus of the heart. In this connection the effect of preliminary adaptation to intermittent hypoxia (4 hours per day at the altitude of 4000 m during 40 days) on the state of beta-receptors-adenylate-cyclase system and same other receptors of the heart were studied. It was shown that at the end of the course of adaptation the number of beta-adrenoceptors in the heart was increased with simultaneous decrease in basal adenylate-cyclase activity, accompanied by the diminution of its response to beta-agonist. The number of beta-adrenoceptors was increased by 48% and their affinity to ligand was increased by almost 2 times. The revealed decrease in the reactivity of beta-receptor-adenylate-cyclase system and increase of alpha 1-adrenoreactivity can play a certain role in the mechanism of cardioprotective effect of adaptation to hypoxia.


The concentrations of polycyclic aromatic hydrocarbons in fish: A systematic review.
This study was conducted on the concentrations of PAHs, including benzo[a]pyrene and the sum of four PAHs (benz[a]anthracene, chryseno, benzo[b]fluoranthene, and benzo[a]pyrene), in unsmoked fish tissues. The values were related to the time period, locality (country and region), living habits, eating habits, and types of environments of the fish species. The data obtained has been also compared with the limits established by the United States Environmental Protection Agency (U.S. EPA) and European Union (E.U.) legislation. The data were collected through a PRISMA systematic review (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) from 1982 to 2020. Only documents that presented the PAHs concentration values were selected. China, Nigeria, and Iran had the highest number of studies. The species Coptodon zillii, Siganus punctatus, and Liza abu were the most commonly used bioindicators. Fish inhabiting demersal and pelagic environments showed the highest concentrations of PAHs. The majority of PAH concentrations of the analyzed documents fell within permissible limits for human consumption, representing a total percentage of 79.49 % for benzo[a]pyrene and 82.86 % for the sum of the 4 PAHs. Although some studies identified concentrations of benzo[a]pyrene alone and benzo[a]pyrene, benz[a]anthracene, chryseno, benzo[b]fluoranthene above the legislation limits, in most of them, the concentrations reported in fish tissue were below the limits defined by European Legislation for human consumption.


Concentration of Microparticles Using Flexural Acoustic Wave in Sessile Droplets.
Acoustic manipulation of microparticles and cells has attracted growing interest in biomedical applications. In particular, the use of acoustic waves to concentrate particles plays an important role in enhancing the detection process by biosensors. Here, we demonstrated microparticle concentration within sessile droplets placed on the hydrophobic surface using the flexural wave. The design benefits from streaming flow induced by the Lamb wave propagated in the glass waveguide to manipulate particles in the droplets. Microparticles will be concentrated at the central area of the droplet adhesion plane based on the balance among the streaming drag force, gravity, and buoyancy at the operating frequency. We experimentally demonstrated the concentration of particles of various sizes and tumor cells. Using numerical simulation, we predicted the acoustic pressure and streaming flow pattern within the droplet and characterized the underlying physical mechanisms for particle motion. The design is more suitable for micron-sized particle preparation, and it can be valuable for various biological, chemical, and medical applications.


The Influence of Medial Comminution in the Treatment Choice of Radial Head Fracture.
The aim of our retrospective study was to investigate the role of the medial side involvement in the treatment choice of radial head fractures. We searched the databases of our institutions for the surgical procedures diagnosed as "fracture of the radial head" and for the procedures related to "prosthesis of the radial head" and "osteosynthesis of the radial head" in the period from May 2014 to October 2017. The fractures were first classified according to the Mason classification . We then allocated the patients into three study groups according to the site of the fracture, either the medial or lateral side of the radial head : Group A, with an isolated lateral fracture of the radius head; Group B1, with a medial fracture of the radius head with two medial fragments; and Group B2, with a medial fracture of the radius head with multiple medial fragments. We performed a multivariate analysis to identify statistically significant correlation between the pre-operative classifications of Mason and our study, the type of surgical procedure, and the clinical outcome. Mayo Elbow Performance (MEP) scores determined at the final follow-up of the study (mean 16.6 months, range 12-26 months) was excellent in 17 patients (4 in Group A, 6 in Group B1 and 7 in Group B2), and good in 12 patients (3 in Group A, 7 in Group B1, and 2 in Group B2). One patient showed a poor result in MEP score probably because of an infection and implant removal. Regarding medial fractures of the radial head, our study showed satisfactory results with a radial head prosthesis for comminuted or multifragmentary radial head fractures. For surgeons with advanced elbow fracture expertise, osteosynthesis could be attempted in a fracture pattern that involved only two medial fragments.


Individualized discrimination of tumor progression from treatment-related changes in different types of adult-type diffuse gliomas using [11C]methionine PET.
This study aimed to assess the ability of [11C]methionine (MET) PET in distinguishing between tumor progression (TP) and treatment-related changes (TRCs) among different types of adult-type diffuse gliomas according to the 2021 World Health Organization classification and predict overall survival (OS). We retrospectively selected 113 patients with adult-type diffuse gliomas with suspected TP who underwent MET PET imaging. Maximum and mean tumor-to-background ratios (TBRmax, TBRmean) and metabolic tumor volume (MTV) were calculated. Diagnoses were verified by histopathology (n = 50) or by clinical/radiological follow-up (n = 63). The diagnostic performance of MET PET parameters was evaluated through receiver operating characteristic (ROC) analysis and area under the curve (AUC) calculation. Survival analysis employed the Kaplan-Meier method and Cox proportional-hazards regression. TP and TRCs were diagnosed in 76 (67%) and 37 (33%) patients, respectively. ROC analysis revealed TBRmax had the best performance in differentiating TP from TRCs with a cut-off of 1.96 in IDH-mutant astrocytoma (AUC, 0.87; sensitivity, 93%; specificity 69%), 1.80 in IDH-mutant and 1p/19q-codeleted oligodendroglioma (AUC, 0.96; sensitivity, 100%; specificity, 89%), and 2.13 in IDH wild-type glioblastoma (AUC, 0.89; sensitivity, 89%; specificity, 78%), respectively. On multivariate analysis, higher TBRmean and MTV were significantly correlated with shorter OS in all IDH-mutant gliomas, as well as in IDH-mutant astrocytoma subgroup. This work confirms that MET PET has varying diagnostic performances in distinguishing TP from TRCs within three types of adult-type diffuse gliomas, and highlights its high diagnostic accuracy in IDH-mutant and 1p/19q-codeleted oligodendroglioma and potential prognostic value for IDH-mutant gliomas, particularly IDH-mutant astrocytoma.


Computational Study of Ortho-Substituent Effects on Antioxidant Activities of Phenolic Dendritic Antioxidants.
Antioxidants are an important component of our ability to combat free radicals-an excess of which leads to oxidative stress, which is related to aging and numerous human diseases. Oxidative damage also shortens the shelf-life of foods and other commodities. Understanding the structure-activity relationship of antioxidants and their mechanisms of action is important for designing more potent antioxidants for potential use as therapeutic agents as well as preservatives. We report the first computational study on the electronic effects of ortho-substituents in dendritic tri-phenolic antioxidants, comprising a common phenol moiety and two other phenol units with electron-donating or electron-withdrawing substituents. Among the three proposed antioxidant mechanisms, sequential proton loss electron transfer (SPLET) was found to be the preferred mechanism in methanol for the dendritic antioxidants based on calculations using Gaussian 16. We then computed the total enthalpy values by cumulatively running SPLET for all three rings to estimate electronic effects of substituents on overall antioxidant activity of each dendritic antioxidant and establish their structure-activity relationships. Our results show that the electron-donating o-OCH3 group has a beneficial effect while the electron-withdrawing o-NO2 group has a negative effect on the antioxidant activity of the dendritic antioxidant. The o-Br and o-Cl groups did not show any appreciable effects. These results indicate that electron-donating groups such as o-methoxy are useful for designing potent dendritic antioxidants while the nitro and halogens do not add value to the radical scavenging antioxidant activity. We also found that the half-maximal inhibitory concentration (IC50) values of 2,2-diphenyl-1-picrylhydrazyl (DPPH) better correlate with the second step (electron transfer enthalpy, ETE) than the first step (proton affinity, PA) of the SPLET mechanism, implying that ETE is the better measure for estimating overall radical scavenging antioxidant activities.


[Theoretical analysis of causes for prolonged delay of decompression sickness onset in divers].
The analysis of probable causes for anomalously prolonged latent time of developing decompression sickness in divers after completion of air dives was carried out in the content of the theory of formation and subsequent evolution of gas bubbles in body tissues. This phenomenon gives grounds to consider that certain of the decompression bubbles have a prolonged lifetime and gradually increase their affect on adjacent tissues. The main causes of increasing the lifetime of these bubbles are the increase of their sires due to the reduction of tissue perfusion during decompression and the coalescence them to one another, as well the encrustation of bubbles by a layer of intercellular fluid elements that reduces the rate of nitrogen diffusion from bubbles to tissues and retards their dissolution. The bubble layer decreases also the gas pressure inside bubbles due to reduction of the surface tension action of intercellular fluid that results in additional reduction of the diffusion flow of nitrogen from bubbles and the rate of their dissolution. Moreover, taken alone, the process of bubble layer formation seems as one of the main mechanisms of tissue lesions by gas bubbles.


Adaptive and Ultrahigh-Affinity Recognition in Water by Sulfated Conjugated Corral[5]arene.
The pursuit of synthetic receptors with high binding affinities has long been a central focus in supramolecular chemistry, driven by their significant practical relevance in various fields. Despite the numerous synthetic receptors that have been developed, most exhibit binding affinities in the micromolar range or lower. Only a few exceptional receptors achieve binding affinities exceeding 109 M-1, and their substrate scopes remain rather limited. In this context, we introduce SC[5]A, a conjugated corral-shaped macrocycle functionalized with ten sulfate groups. Owning to its deep one-dimensional confined hydrophobic cavity and multiple sulfate groups, SC[5]A displays an extraordinarily high binding strength of up to 1011 M-1 towards several size-matched, rod-shaped organic dications in water. Besides, its conformation exhibits good adaptability, allowing it to encapsulate a wide range of other guests with diverse molecular sizes, shapes, and functionalities, exhibiting relatively strong affinities (Ka = 106~108 M-1). Additionally, we've explored the preliminary application of SC[5]A in alleviating blood coagulation induced by hexadimethrine bromide invitro and in vivo. Therefore, the combination of ultrahigh binding affinities (towards complementary guests) and adaptive recognition capability (towards a wide range of functional guests) of SC[5]A positions it as exceptionally valuable for numerous practical applications.


Potential role of lycopene in targeting proprotein convertase subtilisin/kexin type-9 to combat hypercholesterolemia.
Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of the proprotien convertase (PC) family that has profound effects on plasma low density lipoprotein cholesterol (LDL-C) levels, the major risk factor for coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R) protein degradation and reduced recycling to the surface of hepatocytes. Thus, the current study was premeditated not only to evaluate the role of lycopene in targeting the inhibition of PCSK-9 via modulation of genes involved in cholesterol homeostasis in HFD rats but also to examine a correlation between HFD induced inflammatory cascades and subsequent regulation of PCSK-9 expression. Besides the effect of lycopene on hepatic PCSK-9 gene expression, PPI studies for PCSK-9-Lycopene complex and EGF-A of LDL-R were also performed via molecular informatics approach to assess the dual mode of action of lycopene in LDL-R recycling and increased removal of circulatory LDL-C. We for the first time deciphered that lycopene treatment significantly down-regulates the expression of hepatic PCSK-9 and HMGR, whereas, hepatic LDL-R expression was significantly up-regulated. Furthermore, lycopene ameliorated inflammation stimulated expression of PCSK-9 via suppressing the expression of inflammatory markers. The results from our molecular informatics studies confirmed that lycopene, while occupying the active site of PCSK-9 crystal structure, reduces the affinity of PCSK-9 to complex with EGF-A of LDL-R, whereas, atorvastatin makes PCSK-9-EGF-A complex formation more feasible than both of PCSK-9-EGF-A alone and Lycopene-PCSK-9-EGF-A complex. Based on above results, it can be concluded that lycopene exhibits potent hypolipidemic activities via molecular mechanisms that are either identical (HMGR inhibition) or distinct from that of statins (down-regulation of PCSK-9 mRNA synthesis). To the best of our knowledge, this is the first report that lycopene has this specific biological property. Being a natural, safer and alternative therapeutic agent, lycopene could be used as a complete regulator of cholesterol homeostasis and ASCVD.


Compressed sampling and dictionary learning framework for wavelength-division-multiplexing-based distributed fiber sensing.
We propose a compressed sampling and dictionary learning framework for fiber-optic sensing using wavelength-tunable lasers. A redundant dictionary is generated from a model for the reflected sensor signal. Imperfect prior knowledge is considered in terms of uncertain local and global parameters. To estimate a sparse representation and the dictionary parameters, we present an alternating minimization algorithm that is equipped with a preprocessing routine to handle dictionary coherence. The support of the obtained sparse signal indicates the reflection delays, which can be used to measure impairments along the sensing fiber. The performance is evaluated by simulations and experimental data for a fiber sensor system with common core architecture.


Preclinical modeling of low energy X-rays radiological burn: Dosimetry study by monte carlo simulations and EPR spectroscopy.
Interventional radiology has grown considerably over the last decades and become an essential tool for treatment or diagnosis. This technique is mostly beneficial and mastered but accidental overexposure can occur and lead to the appearance of deterministic effects. The lack of knowledge about the radiobiological consequences for the low-energy X-rays used for these practices makes the prognosis very uncertain for the different tissues. In order to improve the radiation protection of patients and better predict the risk of complications, we implemented a new preclinical mouse model to mimic radiological burn in interventional radiology and performed a complete characterization of the dose deposition. A new setup and collimator were designed to irradiate the hind legs of 15 mice at 30 Gy in air kerma at 80 kV. After irradiation, mice tibias were collected to evaluate bone dose by Electron Paramagnetic Resonance (EPR) spectroscopy measurements. Monte Carlo simulations with Geant4 were performed in simplified and voxelized phantoms to characterize the dose deposition in different tissues and evaluate the characteristics of secondary electrons (energy, path, momentum). 30 mice tibias were collected for EPR analysis. An average absorbed dose of 194.0 ± 27.0 Gy was measured in bone initially irradiated at 30 Gy in air kerma. A bone to air conversion factor of 6.5 ± 0.9 was determined. Inter sample and inter mice variability has been estimated to 13.9%. Monte Carlo simulations shown the heterogeneity of the dose deposition for these low X-rays energies and the dose enhancement in dense tissue. The specificities of the secondary electrons were studied and showed the influence of the tissue density on energies and paths. A good agreement between the experimental and calculated bone to air conversion factor was obtained. A new preclinical model allowing to perform radiological burn in interventional radiology-like conditions was implemented. For the development of new preclinical radiobiological model where the exact knowledge of the dose deposited in the different tissues is essential, the complementarity of Monte Carlo simulations and experimental measurements for the dosimetric characterization has proven to be a considerable asset.


Screening for rectal cancer.
Although screening for rectal cancer remains a controversial topic, the case for screening has been strengthened by the demonstration that screening can reduce mortality from the disease. Three randomized controlled trials based on fecal occult blood testing have shown a significant reduction in overall colorectal cancer mortality in those offered testing. The case for screening based on flexible sigmoidoscopy is not as strong. Evidence from randomized controlled trials will not be available for another 8-10 years. Whatever screening method is chosen, factors such as the level of participation and the cost-effectiveness of protocols for adenoma follow-up will have major effects on the success of screening.


DNA damage in buccal epithelial cells from individuals chronically exposed to arsenic via drinking water in Inner Mongolia, China.
The purpose of this pilot study was to assess DNA damage in buccal cells from individuals chronically exposed to arsenic via drinking water in Ba Men, Inner Mongolia. Buccal cells were collected from 19 Ba Men residents exposed to arsenic at 527.5 +/- 23.7 micrograms/L (mean +/- SEM) and 13 controls exposed to arsenic at 4.4 +/- 1.0 micrograms/L. DNA fragmentation by the DNA ladder and TUNEL assay were used to detect DNA damage in buccal cells. In the DNA ladder assay, 89% (17/19) of the arsenic-exposed group showed < 100 bp DNA fragments, in contrast to 15% (2/13) of the controls (p < 0.0001). For the TUNEL assay, the mean frequencies of positive cells were higher in the exposed group (15.1%) than in the controls (2.0%) (p < 0.0001). This study showed that high arsenic exposure via drinking water resulted in DNA damage and DNA fragmentation in buccal cells thus may be an appropriate biomarker for assessing chronic effects of arsenic in humans. A study investigating DNA fragmentation from the individuals with low levels of arsenic exposure in this population is in progress.


Development of a web-based and mobile app to support physical activity in individuals with rheumatoid arthritis: results from the second step of a co-design process.
Long-term adherence to physical activity recommendations remains challenging for most individuals with rheumatoid arthritis (RA) despite evidence for its health benefits. The aim of this study was to provide basic data on system requirement specifications for a Web-based and mobile app to self-manage physical activity. More specifically, we explored the target user group, features of the future app, and correlations between the system requirements and the established behavior change techniques (BCTs). We used a participatory action research design. Qualitative data were collected using multiple methods in four workshops. Participants were 5 individuals with RA, a clinical physiotherapist, an officer from the Swedish Rheumatism Association, a Web designer, and 2 physiotherapy researchers. A taxonomy was used to determine the degree of correlation between the system requirements and established BCTs. Participants agreed that the future Web-based and mobile app should be based on two major components important for maintaining physical activity: (1) a calendar feature for goal setting, planning, and recording of physical activity performance and progress, and (2) a small community feature for positive feedback and support from peers. All system requirements correlated with established BCTs, which were coded as 24 different BCTs. To our knowledge, this study is the first to involve individuals with RA as co-designers, in collaboration with clinicians, researchers, and Web designers, to produce basic data to generate system requirement specifications for an eHealth service. The system requirements correlated to the BCTs, making specifications of content and future evaluation of effectiveness possible.


Vestibular findings in relapsing, remitting multiple sclerosis: a study of thirty patients.
Our objective was to describe vestibular abnormalities in patients with relapsing and remitting multiple sclerosis. Thirty patients (6 men and 24 women) between 27 and 64 years of age underwent neurological and otolaryngological examinations, complete anamnesis, and electronystagmography. Patients with psychological or oculomotor paresis (or both), internuclear ophthalmoparesis, severe visual disturbances, or locomotion restrictions were excluded. The difference-of-proportion test was used to compare affected patients with controls, with a significance level of 5%. Vestibular alterations were found in 26 (86%) of the evaluated patients, from which 25 presented peripheral etiology and only 1 presented a problem of central origin. There was a prevalence of bilateral peripheral irritative vestibulopathy (20%), followed by bilateral peripheral deficit vestibulopathy (20%) and left peripheral deficit vestibulopathy (17%). The high incidence of vestibular disorders observed in this study indicates that this population might benefit from specific rehabilitation programs. Studies with larger samples are still required and may contribute to the understanding of this pathology.


INDUCTION OF PARTIAL SPECIFIC HETEROTYPIC IMMUNITY IN MICE BY A SINGLE INFECTION WITH INFLUENZA A VIRUS.
Schulman, Jerome L. (Cornell University Medical College, New York, N.Y.), and Edwin D. Kilbourne. Induction of partial specific heterotypic immunity in mice by a single infection with influenza A virus. J. Bacteriol. 89:170-174. 1965.-Mice infected 4 weeks previously with influenza A virus were found to be partially immune when challenged with influenza A2 virus. This partial immunity was demonstrated by reduced titers of pulmonary virus, decreased mortality, and less extensive lung lesions. A specific immunological basis for this protection was suggested by the absence of any protection in animals previously infected with influenza B virus when challenged with A2 virus, or in animals previously infected with influenza A virus when challenged with influenza B virus. Parenteral inoculation with inactivated influenza A virus did not induce partial immunity to A2 virus challenge. An accelerated rise of hemagglutinating-inhibiting antibody after A2 virus challenge was demonstrated in animals previously infected with influenza A virus.


Children born after unplanned pregnancies and cognitive development at 3 years: social differentials in the United Kingdom Millennium Cohort.
Children born after an unplanned pregnancy have poorer developmental scores. This could arise from less favorable parenting but also could reflect confounding from the socioeconomic circumstances. In a large representative sample in the United Kingdom, the Millennium Cohort Study (2001-2005), cognitive delay at 3 years was explored with the Bracken Assessment. Its association with unplanned pregnancy was studied in logistic models controlling for demographic and socioeconomic characteristics of the family, the child's characteristics, and parenting behavior. Stratification by the mother's educational level (grouped into 3 categories) was explored. Of 12,182 children included in the analysis, 41% were born after a pregnancy reported by the mother to have been a "surprise." Such unplanned pregnancies were associated in univariate analysis with more cognitive delay. Among mothers with a low or middle level of education, this association vanished when socioeconomic circumstances were controlled. Among mothers with a high level of education, the risk of cognitive delay remained significantly and unexplainedly raised after unplanned pregnancies, despite controlling for socioeconomic characteristics and parental behavior. In conclusion, for socially disadvantaged children, having resulted from an unplanned pregnancy does not seem to increase their already disproportionate risk of cognitive delay. Births after unplanned conceptions are mainly a symptom rather than a source of disadvantage.


Oral health-related risk behaviours and attitudes among Croatian adolescents--multiple logistic regression analysis.
The aim of this study was to explore the patterns of oral health-related risk behaviours in relation to dental status, attitudes, motivation and knowledge among Croatian adolescents. The assessment was conducted in the sample of 750 male subjects - military recruits aged 18-28 in Croatia using the questionnaire and clinical examination. Mean number of decayed, missing and filled teeth (DMFT) and Significant Caries Index (SIC) were calculated. Multiple logistic regression models were crated for analysis. Although models of risk behaviours were statistically significant their explanatory values were quite low. Five of them--rarely toothbrushing, not using hygiene auxiliaries, rarely visiting dentist, toothache as a primary reason to visit dentist, and demand for tooth extraction due to toothache--had the highest explanatory values ranging from 21-29% and correctly classified 73-89% of subjects. Toothache as a primary reason to visit dentist, extraction as preferable therapy when toothache occurs, not having brushing education in school and frequent gingival bleeding were significantly related to population with high caries experience (DMFT > or = 14 according to SiC) producing Odds ratios of 1.6 (95% CI 1.07-2.46), 2.1 (95% CI 1.29-3.25), 1.8 (95% CI 1.21-2.74) and 2.4 (95% CI 1.21-2.74) respectively. DMFT> or = 14 model had low explanatory value of 6.5% and correctly classified 83% of subjects. It can be concluded that oral health-related risk behaviours are interrelated. Poor association was seen between attitudes concerning oral health and oral health-related risk behaviours, indicating insufficient motivation to change lifestyle and habits. Self-reported oral hygiene habits were not strongly related to dental status.


Highly efficient gene tagging in the bryophyte Physcomitrella patens using the tobacco (Nicotiana tabacum) Tnt1 retrotransposon.
Because of its highly efficient homologous recombination, the moss Physcomitrella patens is a model organism particularly suited for reverse genetics, but this inherent characteristic limits forward genetic approaches. Here, we show that the tobacco (Nicotiana tabacum) retrotransposon Tnt1 efficiently transposes in P. patens, being the first retrotransposon from a vascular plant reported to transpose in a bryophyte. Tnt1 has a remarkable preference for insertion into genic regions, which makes it particularly suited for gene mutation. In order to stabilize Tnt1 insertions and make it easier to select for insertional mutants, we have developed a two-component system where a mini-Tnt1 with a retrotransposition selectable marker can only transpose when Tnt1 proteins are co-expressed from a separate expression unit. We present a new tool with which to produce insertional mutants in P. patens in a rapid and straightforward manner that complements the existing molecular and genetic toolkit for this model species.


Plc1p is required for proper chromatin structure and activity of the kinetochore in Saccharomyces cerevisiae by facilitating recruitment of the RSC complex.
High-fidelity chromosome segregation during mitosis requires kinetochores, protein complexes that assemble on centromeric DNA and mediate chromosome attachment to spindle microtubules. In budding yeast, phosphoinositide-specific phospholipase C (Plc1p encoded by PLC1 gene) is important for function of kinetochores. Deletion of PLC1 results in alterations in chromatin structure of centromeres, reduced binding of microtubules to minichromosomes, and a higher frequency of chromosome loss. The mechanism of Plc1p's involvement in kinetochore activity was not initially obvious; however, a testable hypothesis emerged with the discovery of the role of inositol polyphosphates (InsPs), produced by a Plc1p-dependent pathway, in the regulation of chromatin-remodeling complexes. In addition, the remodels structure of chromatin (RSC) chromatin-remodeling complex was found to associate with kinetochores and to affect centromeric chromatin structure. We report here that Plc1p and InsPs are required for recruitment of the RSC complex to kinetochores, which is important for establishing proper chromatin structure of centromeres and centromere proximal regions. Mutations in PLC1 and components of the RSC complex exhibit strong genetic interactions and display synthetic growth defect, altered nuclear morphology, and higher frequency of minichromosome loss. The results thus provide a mechanistic explanation for the previously elusive role of Plc1p and InsPs in kinetochore function.


Influence of Prevalent and Incident Atrial Fibrillation on Post-Trial Major Events in ALLHAT.
Limited information is available on long-term antihypertensive and lipid-lowering therapy effects on hypertensive patients with atrial fibrillation/flutter (AF/AFL) compared to those without. AF/AFL at baseline or during the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (mean follow-up 4.9 years) markedly increased risk of stroke, heart failure, CHD, and all-cause mortality. We aimed to determine if AF/AFL continued to impact outcomes during post-trial follow-up (mean 3.8 years). Patients were randomized to chlorthalidone, amlodipine, or lisinopril, and to pravastatin vs. usual care in the lipid-lowering trial (LLT). Of 31,473 available subjects, AF/AFL occurred in 854; 383/14,371 chlorthalidone (2.7%), 247/8565 amlodipine (2.9%), and 224/8537 lisinopril (2.6%). Post-hoc analyses utilized administrative databases for post-trial data. Individuals with AF/AFL were compared to those without during post-trial. Outcomes were analyzed by treatment groups for the antihypertensive and LLT trials. Among 854 AF/AFL participants, 491 (57.5%) died: 220 in-trial, 271 post-trial. Ten-year all-cause mortality rates for those with in-trial AF/AFL were similar for chlorthalidone and lisinopril, but lower for amlodipine (68, 66, and 49 per 100 persons, respectively); adjusted HR for amlodipine vs. chlorthalidone was 0.68 (95% CI, 0.54-0.87). Ten-year all-cause mortality rates were 57 vs. 65 per 100 persons (pravastatin vs. usual care); non-CVD mortality rates, 18 vs. 39 per 100 persons (pravastatin vs. usual care) (adjusted HR = 0.46, 95% CI, 0.24-0.86). Post-trial follow-up revealed continued deleterious AF/AFL effects. The amlodipine (ALLHAT) and pravastatin (ALLHAT-LLT) treatment groups showed lower all-cause and non-CVD mortality compared to the chlorthalidone and usual-care groups, respectively.


Preparation of polymeric and ceramic porous capsules by a novel electrohydrodynamic process.
The preparation of capsules for medical and industrial use can be achieved via several conventional routes, yielding either hard or soft receptacles, depending on the type and the content of the material to be encapsulated. Together with tablets, capsules are amongst the most commonly used means of administering medication and this makes progress in capsule preparation technology a key area of drug delivery research. Here we uncover new technology for the preparation of capsules with porous chambers. The novelty is signified in the use of an electrohydrodynamic process engineering route and its potential is elucidated using a polymeric material; polymethylsilsesquioxane, which can be converted into an identical ceramic form by means of simple pyrolysis. Thus, both polymeric and ceramic capsules have been prepared. The effects of process control parameters such as the applied voltage and flow rate, on the characteristics of the capsules prepared are discussed.


Rutin inhibits DRP1-mediated mitochondrial fission and prevents ethanol-induced hepatotoxicity in HepG2 cells and zebrafish.
Excessive alcohol consumption causes the cellular and tissue damage. The toxic metabolites of ethanol are harmful to multiple organ systems, such as the central nervous system, skeletal muscles, and liver, and cause alcohol-induced diseases like cancer, as well as induce hepatotoxicity, and alcoholic myopathy. Alcohol exposure leads to a surge in hepatic alcohol metabolism and oxygen consumption, a decrease in hepatic ATP, and the rapid accumulation of lipid within hepatocytes. Several pathologies are closely linked to defective mitochondrial dynamics triggered by abnormal mitochondrial function and cellular homeostasis, raising the possibility that novel drugs targeting mitochondrial dynamics may have therapeutic potential in restoring cellular homeostasis in ethanol-induced hepatotoxicity. Rutin is a phytochemical polyphenol known to protect cells from cytotoxic chemicals. We investigated the effects of rutin on mitochondrial dynamics induced by ethanol. We found that rutin enhances mitochondrial dynamics by suppressing mitochondrial fission and restoring the balance of the mitochondrial dynamics. Mitochondrial elongation following rutin treatment of ethanol exposed cells was accompanied by reduced DRP1 expression. These data suggest that rutin plays an important role in remodeling of mitochondrial dynamics to alleviate hepatic steatosis and enhance mitochondrial function and cell viability.


The mycobiome in HIV.
There are a limited number of studies investigating the association between the microbiome and HIV. Although the majority of these published investigations have focused on the role of the bacterial community (bacteriome) in this setting, a handful of studies have also characterized the role of the mycobiome in HIV-infected individuals. This review will summarize the most recent reports pertaining to the role of the fungal community in HIV. Differences in the composition of the oral and respiratory mycobiome in HIV-infected individuals compared with uninfected individuals have been reported. Our review shows that studies investigating the role of the mycobiome in the setting of HIV are severely lacking. With recent advances in our understanding of the composition of the human microbiome, investigations into the role of the bacteria and fungus comprising the overall microbiota and how the two interact to influence each other and the host is crucial.


Low Vocal Pitch Preference Drives First Impressions Irrespective of Context in Male Voices but Not in Female Voices.
Vocal pitch has been found to influence judgments of perceived trustworthiness and dominance from a novel voice. However, the majority of findings arise from using only male voices and in context-specific scenarios. In two experiments, we first explore the influence of average vocal pitch on first-impression judgments of perceived trustworthiness and dominance, before establishing the existence of an overall preference for high or low pitch across genders. In Experiment 1, pairs of high- and low-pitched temporally reversed recordings of male and female vocal utterances were presented in a two-alternative forced-choice task. Results revealed a tendency to select the low-pitched voice over the high-pitched voice as more trustworthy, for both genders, and more dominant, for male voices only. Experiment 2 tested an overall preference for low-pitched voices, and whether judgments were modulated by speech content, using forward and reversed speech to manipulate context. Results revealed an overall preference for low pitch, irrespective of direction of speech, in male voices only. No such overall preference was found for female voices. We propose that an overall preference for low pitch is a default prior in male voices irrespective of context, whereas pitch preferences in female voices are more context- and situation-dependent. The present study confirms the important role of vocal pitch in the formation of first-impression personality judgments and advances understanding of the impact of context on pitch preferences across genders.


Teaching educational assistants to facilitate the multisymbol message productions of young students who require augmentative and alternative communication.
Many classroom educational assistants (EAs) have a significant amount of responsibility in carrying out educational plans for children who use augmentative and alternative communication (AAC), but they receive little instruction on how to do so (Kent-Walsh & Light, 2003). This study investigates the impact of using a communication partner instructional program to teach EAs how to teach their students to produce symbol combinations on their speech-generating devices. A single-subject multiple-probe-across-participants design was used to evaluate the effectiveness of the instructional program on (a) the EAs' implementation of an interaction strategy with their students who used AAC and (b) the rates of multisymbol message productions for the students who used AAC. All 3 participating EAs learned to use the interaction strategy appropriately, and all 3 participating students who used AAC increased their multisymbol message production rates. Results provide further evidence (a) of the viability of using a communication partner instructional program for teaching partners how to facilitate the communication skills of children who use AAC and (b) that the interaction strategy can be an effective tool for increasing expressive multisymbol message rates for children who use AAC.


Sonar Signals of the Sea Lion.
Tape recordings were made of the underwater noises of captive sea lions swimming in a concrete pool at night. When approaching pieces of fish that were thrown into the water, the sea lions emitted trains of sound signals like those of the bat and the porpoise. A detailed analysis of these noises shows that they meet the criteria of a pulse-modulated sonar system and, in fact, reveal an amazing sophistication so far as echo ranging is concerned.


Parental optimism versus parental pessimism in plants: how common should we expect pollen limitation to be?
Many organisms exhibit parental optimism, producing more of the initial stages of offspring (e.g., eggs, embryos) than they can usually mature. For plants, parental optimism may be linked to the risk of seed production being limited by pollen receipt (pollen limitation). Here we elaborate a stochastic model of pollen limitation developed by Haig and Westoby ( 1988 ) and Burd ( 2008 ) and link it with published data on the magnitudes of prepollination costs versus postpollination costs of seed production in 80 plant species. We demonstrate that parental optimism should be expected when prepollination costs of seed production are small relative to postpollination costs. This was observed for most (62 of 80) of the plant taxa surveyed. Under parental optimism, plants overinvest in securing fertilized ovules, and consequently pollen limitation is predicted to be uncommon. However, for a sizable minority of plant species (18 of 80), prepollination costs approach or exceed postpollination costs. For these species, parental pessimism is instead optimal. Parents initiate fewer zygotes than they can usually mature, and pollen limitation is predicted to be severe. Because the relative magnitudes of prepollination and postpollination costs vary by more than 1,000-fold across plant taxa, parental outlook (optimism vs. pessimism) and levels of pollen limitation are predicted to vary widely.


Innovations of surgical techniques for the management of inferior vena cava tumor thrombus of renal cell carcinoma.
Surgery for renal cell carcinoma with inferior vena cava thrombus is challenging. Cardiopulmonary bypass and deep hypothermic circulatory arrest significantly decreased the morbidity and mortality but associated with considerable postoperative complications. Debates still exist in one- or two-stage operations on which of the cardiac and urologic parts should be performed first. Modified maneuvers with main pulmonary artery clamping, vena cystoscope, transesophageal echocardiographic incorporation, and inferior vena cava interruptions are good for reduced perioperative morbidities. Surgical innovations have greatly facilitated the resection of renal cell carcinoma and inferior vena cava involvement. The advantages have been remarkable in less trauma, more cosmetic advantages, shorter hospital stay, and quicker recovery over the conventional open surgery with or without the use of bypass techniques. Such procedures have brought about improved long-term survivals. However, novel minimally invasive techniques such as robotic-assisted and hybrid approaches remain to gain further popularity in larger patient population. This article aims at a collection of the innovations of the surgical techniques in relation to the management of inferior vena cava tumor thrombus.


The Long Non-Coding RNA HOTAIR Is a Critical Epigenetic Mediator of Angiogenesis in Diabetic Retinopathy.
Diabetic retinopathy (DR) remains a pressing issue worldwide. Abnormal angiogenesis is a distinct vascular lesion in DR, and research has established that vascular endothelial growth factor A (VEGF-A) is a primary mediator of such changes. However, limitations in current anti-VEGF therapies suggest that our understanding of molecular networks underlying ocular angiogenesis remains far from complete. Based on our long non-coding RNA (lncRNA) array analyses, HOX antisense intergenic RNA (HOTAIR) was identified as one of the top upregulated lncRNAs in high glucose-cultured human retinal endothelial cells (HRECs). Given the well-documented roles of HOTAIR in cancer, no studies have examined the epigenetic implications of HOTAIR in DR, and we investigated such relationships herein. We used HRECs exposed to various glucose concentrations and epigenetic modulators to examine HOTAIR, angiogenic, and DR-related molecular markers. Oxidative stress, angiogenesis, and mitochondrial dysfunction were assessed. Retinal tissues of diabetic rodents and the vitreous humor and serum of patients with proliferative DR were also investigated. Hyperglycemia significantly augmented HOTAIR expression in HRECs and promoted angiogenesis, oxidative damage, and mitochondrial aberrations. Similarly, vitreous humor and serum from proliferative DR patients and retinas from diabetic animals demonstrated increased HOTAIR expression compared to non-diabetic controls. HOTAIR knockdown protected against glucose-induced increases of angiogenic and diabetes-associated molecules in the retina. Mechanistically, we showed that HOTAIR exerts its capabilities by preventing oxidative stress and modulating epigenetic pathways involving histone methylation, histone acetylation, DNA methylation, and transcription factors. Our findings suggest that HOTAIR is a critical lncRNA in the pathogenesis of DR and may potentially be important for diagnostic and therapeutic targeting.


Post-translational Modifications of the CARMA1-BCL10-MALT1 Complex in Lymphocytes and Activated B-Cell Like Subtype of Diffuse Large B-Cell Lymphoma.
Piracy of the NF-κB transcription factors signaling pathway, to sustain its activity, is a mechanism often deployed in B-cell lymphoma to promote unlimited growth and survival. The aggressive activated B-cell like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) exploits a multi-protein complex of CARMA1, BCL10, and MALT1 (CBM complex), which normally conveys NF-κB signaling upon antigen receptors engagement. Once assembled, the CBM also unleashes MALT1 protease activity to finely tune the immune response. As a result, ABC DLBCL tumors develop a profound addiction to NF-κB and to MALT1 enzyme, leaving open a breach for therapeutics. However, the pleiotropic nature of NF-κB jeopardizes the success of its targeting and urges us to develop new strategies. In this review, we discuss how post-translational modifications, such as phosphorylation and ubiquitination of the CBM components, as well as, MALT1 proteolytic activity, shape the CBM activity in lymphocytes and ABC DLBCL, and may provide new avenues to restore vulnerability in lymphoma.