Do macronutrient intakes affect obesity indices in Jordanian adults?
To determine whether macronutrient intake is associated with novel obesity indices, including the conicity index (CI), body adiposity index (BAI), abdominal volume index (AVI), body roundness index (BRI), and weight-adjusted-waist index (WWI). A cross-sectional survey was conducted with 491 adults (344 males and 147 females) working at different universities in Jordan (July-December 2019). Daily intake of energy (kcal), carbohydrates (g), protein (g), and fat (g) was obtained using 24-h recalls collected over 2 days. Additionally, obesity indices were calculated. Regardless of sex, energy, and carbohydrate intakes had a moderately significant positive association, whereas protein and fat intakes had a weakly significant association with BAI, AVI, and BRI. CI and WWI showed a weakly significant association with all macronutrients in males, a moderate correlation with energy and carbohydrate intake, and a weak association with fat and protein intake in females. Male participants had significant increases in the CI (T1 = 1.29 ± 0.01 vs. T3 = 1.36 ± 0.01, p = .018), AVI (T1 = 17.96 ± 0.52 vs. T3 = 22.81 ± 0.57, p = .011), and WWI (T1 = 10.72 ± 0.11 vs. T3 = 11.29 ± 0.09, p = .047) indices scores through the carbohydrate intake tertiles. Additionally, there was a significant increase in scores of AVI (T1 = 18.60 ± 0.56 vs. T3 = 21.42 ± 0.46, p = .048) and an almost significant increase in CI (T1 = 1.30 ± 0.01vs. T3 = 1.33 ± 0.01, p = .056) through the tertiles of protein intake. Macronutrients were significantly associated with all indices. The effect of macronutrients on obesity indices is sex-based. Among men, CI, AVI, and WWI were the indices most affected by carbohydrate and protein intakes. Future studies should further investigate food sources and macronutrient quality.


Hormonal underpinnings of status conflict: Testosterone and cortisol are related to decisions and satisfaction in the hawk-dove game.
A contribution to a special issue on Hormones and Human Competition.Testosterone is theorized to influence status-seeking behaviors such as social dominance and competitive behavior, but supporting evidence is mixed. The present study tested the roles of testosterone and cortisol in the hawk-dove game, a dyadic economic decision-making paradigm in which earnings depend on one's own and the other player's choices. If one person selects the hawk strategy and the other person selects the dove strategy, the player who selected hawk attains a greater financial pay-off (status differentiation). The worst financial outcome occurs when both players choose the hawk strategy (status confrontation). Ninety-eight undergraduate students (42 men) provided saliva samples and played ten rounds of the hawk-dove game with another same-sex participant. In support of the hypothesis that testosterone is related to status concern, individuals higher in basal testosterone made more hawk decisions - decisions that harmed the other player. Acute decreases in cortisol were also associated with more hawk decisions. There was some empirical support for the dual-hormone hypothesis as well: basal testosterone was positively related to satisfaction in the game among low basal-cortisol individuals but not among high basal-cortisol individuals. There were no significant sex differences in these hormonal effects. The present findings align with theories of hormones and status-seeking behavior at the individual level, but they also open up new avenues for research on hormone profiles at the collective level. Our results suggest that the presence of two or more high-testosterone members increases the likelihood of status confrontations over a limited resource that can undermine collective outcomes.


Model-Based and Model-Free Analyses of the Neural Correlates of Tongue Movements.
The tongue performs movements in all directions to subserve its diverse functions in chewing, swallowing, and speech production. Using task-based functional MRI in a group of 17 healthy young participants, we studied (1) potential differences in the cerebral control of frontal (protrusion), horizontal (side to side), and vertical (elevation) tongue movements and (2) inter-individual differences in tongue motor control. To investigate differences between different tongue movements, we performed voxel-wise multiple linear regressions. To investigate inter-individual differences, we applied a novel approach, spatio-temporal filtering of independent components. For this approach, individual functional data were decomposed into spatially independent components and corresponding time courses using independent component analysis. A temporal filter (correlation with the expected brain response) was used to identify independent components time-locked to the tongue motor tasks. A spatial filter (cross-correlation with established neurofunctional systems) was used to identify brain activity not time-locked to the tasks. Our results confirm the importance of an extended bilateral cortical and subcortical network for the control of tongue movements. Frontal (protrusion) tongue movements, highly overlearned movements related to speech production, showed less activity in the frontal and parietal lobes compared to horizontal (side to side) and vertical (elevation) movements and greater activity in the left frontal and temporal lobes compared to vertical movements (cluster-forming threshold of Z > 3.1, cluster significance threshold of p < 0.01, corrected for multiple comparisons). The investigation of inter-individual differences revealed a component representing the tongue primary sensorimotor cortex time-locked to the task in all participants. Using the spatial filter, we found the default mode network in 16 of 17 participants, the left fronto-parietal network in 16, the right fronto-parietal network in 8, and the executive control network in four participants (Pearson's r > 0.4 between neurofunctional systems and individual components). These results demonstrate that spatio-temporal filtering of independent components allows to identify individual brain activity related to a specific task and also structured spatiotemporal processes representing known neurofunctional systems on an individual basis. This novel approach may be useful for the assessment of individual patients and results may be related to individual clinical, behavioral, and genetic information.


The N-terminus and Tudor domains of Sgf29 are important for its heterochromatin boundary formation function.
Eukaryotic chromosomes are organized into heterochromatin and euchromatin domains. Heterochromatin domains are transcriptionally repressed and prevented from spreading into neighbouring genes by chromatin boundaries. Previously, we identified 55 boundary-related genes in Saccharomyces cerevisiae. In this study, we describe the characterization of one of these boundary genes, named SGF29, which was previously reported as a component of the SAGA, SLIK, ADA and HAT-A2 complex. A domain analysis of Sgf29 identified two minimal regions that can function as individual boundaries. The N-terminal minimal region comprising amino acids 1-12, which has not been defined as a functional domain, showed stronger boundary formation ability than the C-terminal minimal region comprising amino acids 110-255, which contains Tudor domains. Together with Ada2, Ada3 and Sgf29, which are all components of SAGA, Gcn5 acetylates multiple lysine residues on nucleosomal histone H3, which is associated with an open chromatin structure. However, the results presented in this study suggest that the boundary formation ability of the Sgf29 minimal regions is independent of Gcn5. An in vivo analysis also revealed that Sgf29 and Gcn5 perform distinct functions at native telomere boundary regions on the chromosome.


The microRNA cluster miR-106b~25 regulates adult neural stem/progenitor cell proliferation and neuronal differentiation.
In adult mammals, neural stem cells (NSCs) generate new neurons that are important for specific types of learning and memory. Controlling adult NSC number and function is fundamental for preserving the stem cell pool and ensuring proper levels of neurogenesis throughout life. Here we study the importance of the microRNA gene cluster miR-106b~25 (miR-106b, miR-93, and miR-25) in primary cultures of neural stem/progenitor cells (NSPCs) isolated from adult mice. We find that knocking down miR-25 decreases NSPC proliferation, whereas ectopically expressing miR-25 promotes NSPC proliferation. Expressing the entire miR-106b~25 cluster in NSPCs also increases their ability to generate new neurons. Interestingly, miR-25 has a number of potential target mRNAs involved in insulin/insulin-like growth factor-1 (IGF) signaling, a pathway implicated in aging. Furthermore, the regulatory region of miR-106b~25 is bound by FoxO3, a member of the FoxO family of transcription factors that maintains adult stem cells and extends lifespan downstream of insulin/IGF signaling. These results suggest that miR-106b~25 regulates NSPC function and is part of a network involving the insulin/IGF-FoxO pathway, which may have important implications for the homeostasis of the NSC pool during aging.


Broad spectrum of hepatocyte inclusions in humans, animals, and experimental models.
We focus on hepatic inclusions, which are defined as intracellular aggregates of stainable substances. They represent established hallmarks of their respective human disorders, but unlike aggregates found in neurodegenerative disorders are often not well studied. Hepatic inclusions can be subdivided into primary liver aggregates and aggregates found in multiple tissues. The former ones consist of inclusions found in endoplasmic reticulum storage diseases such as α 1-antitrypsin aggregates or ground-glass hepatocytes, p62-containing (Mallory-Denk bodies and intracellular hyaline bodies) and porphyrin-containing inclusions. p62-containing aggregates are not restricted to the liver but are found in multiple other disorders such as Parkinson or Alzheimer disease. Inclusions such as pale bodies or intracellular hyaline bodies are typical for malignant disorders while others (ground-glass hepatocytes and α1-antitrypsin aggregates) are predominantly seen in non-neoplastic tissues. The inclusions, which are not restricted to the liver, are often due to a systemic viral infection, but also due to disruption of glycogen metabolism or systemic inclusion-forming diseases such as polyglutamine disorders or sarcoidosis. Despite their heterogeneity, inclusions share several pathogenic principles such as an imbalance between protein damage/misfolding on one side and repair/degradation on the other side. This is why hepatic aggregates represent a valuable tool to study the aggregation process in general and to improve our understanding of inclusions found in multiple human disorders.


Putative intestinal hyperammonaemia in horses: 36 cases.
Intestinal hyperammonaemia (HA) has been infrequently reported in individual horses; however, there have been no studies describing clinical and laboratory data as well as short- and long-term outcome in a larger number of cases. To describe clinical and laboratory data and short- and long-term outcome in a large group of horses with intestinal HA. Multi-centred, retrospective study; case records of horses with HA were reviewed and any horse with a clinical or post mortem diagnosis of intestinal HA was included. Hyperammonaemia was defined as a blood ammonium (NH(4) (+)) concentration ≥60 µmol/l and horses with a diagnosis of primary hepatic disease were excluded. Relevant data were recorded and, if appropriate, data from survivors were compared to nonsurvivors to identify potential prognostic indicators. Thirty-six cases, 26 mature horses and 10 foals with intestinal HA were identified. Case histories included diarrhoea, colic and neurological signs and the most common clinical diagnosis was colitis and/or enteritis. The most common clinical and laboratory abnormalities included tachycardia, increased packed cell volume, hyperlactataemia and hyperglycaemia. Fourteen horses (39%) survived to discharge; NH(4) (+) concentration on admission was the only parameter significantly associated with survival. All surviving horses and foals for which follow-up information was available recovered completely and returned to their intended use without further complications. Intestinal HA occurs in mature horses and foals and can be associated with severe clinical and laboratory abnormalities; further studies are required to investigate predisposing factors and delineate possible differences in aetiologies.


On the effects of the ocean on atmospheric CFC-11 lifetimes and emissions.
The ocean is a reservoir for CFC-11, a major ozone-depleting chemical. Anthropogenic production of CFC-11 dramatically decreased in the 1990s under the Montreal Protocol, which stipulated a global phase out of production by 2010. However, studies raise questions about current overall emission levels and indicate unexpected increases of CFC-11 emissions of about 10 Gg ⋅ yr-1 after 2013 (based upon measured atmospheric concentrations and an assumed atmospheric lifetime). These findings heighten the need to understand processes that could affect the CFC-11 lifetime, including ocean fluxes. We evaluate how ocean uptake and release through 2300 affects CFC-11 lifetimes, emission estimates, and the long-term return of CFC-11 from the ocean reservoir. We show that ocean uptake yields a shorter total lifetime and larger inferred emission of atmospheric CFC-11 from 1930 to 2075 compared to estimates using only atmospheric processes. Ocean flux changes over time result in small but not completely negligible effects on the calculated unexpected emissions change (decreasing it by 0.4 ± 0.3 Gg ⋅ yr-1). Moreover, it is expected that the ocean will eventually become a source of CFC-11, increasing its total lifetime thereafter. Ocean outgassing should produce detectable increases in global atmospheric CFC-11 abundances by the mid-2100s, with emission of around 0.5 Gg ⋅ yr-1; this should not be confused with illicit production at that time. An illustrative model projection suggests that climate change is expected to make the ocean a weaker reservoir for CFC-11, advancing the detectable change in the global atmospheric mixing ratio by about 5 yr.


New β-lactam-β-lactamase inhibitor combinations in clinical development.
Tazobactam was the most recent β-lactamase inhibitor to be approved in 1993. Since the approval of piperacillin-tazobactam, the complexity of β-lactamase-mediated resistance among Gram-negative bacilli has increased enormously. After more than 20 years since the first such combination, amoxicillin-clavulanic acid, was approved, several new β-lactam-β-lactamase inhibitor combinations have reached late-stage (phase II and beyond) clinical trials. These include ceftolozane-tazobactam (2:1, ratios of β-lactam to β-lactamase inhibitor in parentheses), ceftazidime-avibactam (4:1), ceftaroline-avibactam (1:1), and imipenem-cilastatin-MK-7655 (2:2:1 and 4:4:1). Avibactam and MK-7655 are diazabicyclooctane (DABCO) inhibitors and thus not β-lactams themselves; they include class A carbapenemases and class C enzymes within their spectra of activity. Ceftolozane is an antipseudomonal cephalosporin, and tazobactam is used to protect it against extended spectrum β-lactamases to which it is labile. Additional novel combinations are in preclinical development. This review will focus on the biochemistry, antimicrobial activity, pharmacodynamics, and clinical development of these novel combinations.


Giving credit to reforestation for water quality benefits.
While there is a general belief that reforesting marginal, often unprofitable, croplands can result in water quality benefits, to date there have been very few studies that have attempted to quantify the magnitude of the reductions in nutrient (N and P) and sediment export. In order to determine the magnitude of a credit for water quality trading, there is a need to develop quantitative approaches to estimate the benefits from forest planting in terms of load reductions. Here we first evaluate the availability of marginal croplands (i.e. those with low infiltration capacity and high slopes) within a large section of the Ohio River Basin (ORB) to assess the magnitude of the land that could be reforested. Next, we employ the Nutrient Tracking Tool (NTT) to study the reduction in N, P and sediment losses from converting corn or corn/soy rotations to forested lands, first in a case study and then for a large region within the ORB. We find that after reforestation, N losses can decrease by 40 to 80 kg/ha-yr (95-97% reduction), while P losses decrease by 1 to 4 kg/ha-yr (96-99% reduction). There is a significant influence of local conditions (soils, previous crop management practices, meteorology), which can be considered with NTT and must be taken into consideration for specific projects. There is also considerable interannual and monthly variability, which highlights the need to take the longer view into account in nutrient credit considerations for water quality trading, as well as in monitoring programs. Overall, there is the potential for avoiding 60 million kg N and 2 million kg P from reaching the streams and rivers of the northern ORB as a result of conversion of marginal farmland to tree planting, which is on the order of 12% decrease for TN and 5% for TP, for the entire basin. Accounting for attenuation, this represents a significant fraction of the goal of the USEPA Gulf of Mexico Hypoxia Task Force to reduce TN and TP reaching the dead zone in the Gulf of Mexico, the second largest dead zone in the world. More broadly, the potential for targeted forest planting to reduce nutrient loading demonstrated in this study suggests further consideration of this approach for managing water quality in waterways throughout the world. The study was conducted using computational models and there is a need to evaluate the results with empirical observations.


Diagnostic Imaging in Vascular Graft Infection: A Systematic Review and Meta-Analysis.
Vascular graft infection (VGI), a serious complication in vascular surgery, has a high morbidity and mortality rate. The diagnosis is complicated by non-specific symptoms and challenged by the variable accuracy of different imaging techniques. The objective of this study was to determine the diagnostic value of various imaging techniques to diagnose VGI. A systematic review was conducted according to the PRISMA guidelines. Data sources included PubMed/Medline, Embase, and Cochrane from January 1997 until October 2017. Observational cohort studies were included. A meta-analysis was conducted on several imaging modalities: computed tomography with or without angiography (CT(A)), 18F-fluoro-d-deoxyglucose positron emission tomography with or without low dose or contrast enhanced CT (FDG-PET(/CT)), and white blood cell scintigraphy with or without single photon emission computed tomography combined with low dose CT (WBC (SPECT/CT)). Of 4259 papers, 14 articles were included, containing eight prospective and six retrospective articles. CTA (I2 7.4%), FDG-PET (I2 36.5%), and FDG-PET/CT (I2 36.6%) showed negligible to moderate heterogeneity, while WBC scintigraphy ± SPECT/CT (I2 78.6%) showed considerable heterogeneity. Pooled sensitivity for CTA was 0.67 (95% CI 0.57-0.75), in contrast to FDG-PET of 0.94 (95% CI 0.88-0.98), FDG-PET/CT of 0.95 (95% CI 0.87-0.99), WBC scintigraphy of 0.90 (95% CI 0.85-0.94), and WBC scintigraphy with SPECT/CT of 0.99 (95% CI 0.92-1.00). The pooled specificities were for CTA 0.63 (95% CI 0.48-0.76), FDG-PET 0.70 (95% CI 0.59-0.79), FDG-PET/CT 0.80 (95% CI 0.69-0.89), WBC scintigraphy 0.88 (95% CI 0.81-1.94), and WBC scintigraphy SPECT/CT 0.82 (95% CI 0.57-0.96). Pre- and post-test results showed that WBC SPECT/CT favours FDG-PET/CT, with a positive post-test probability of 96% versus 83%. This meta-analysis suggests the diagnostic performance of WBC scintigraphy combined with SPECT/CT is the greatest in diagnosing VGI. However, it is a time consuming technique and not always available. Therefore FDG-PET/CT may be favourable as the initial imaging technique. The use of solitary CTA in diagnosing VGI seems to be obsolete.


Adverse Childhood Experience, Genes, and PTSD Risk in Soldiers: A Methylation Study.
Epigenetics can serve as a marker of susceptibility to many known psychiatric diseases. DNA methylation patterns of multiple genes have been studied in both civilian populations and military personnel with post-traumatic stress disorder (PTSD). Many of these genes serve various functions that span the hypothalamic-pituitary-adrenal axis, immune system, and central nervous system (CNS) growth factors and neurotransmission. It is thought that the methylation levels of such genes may be able to identify individuals who are at higher risk of developing PTSD. Our study seeks to establish whether previously reported PTSD genes possess a particular methylation pattern that is predictive of PTSD in active duty military members with combat exposure. This is an institutional review board (IRB)-approved, cross-sectional, case control, gene-environment interaction study. About 170 active military members with and without PTSD were recruited. Patients with a history of structural brain damage, traumatic brain injury (TBI) resulting in loss of consciousness, predeployment diagnosis of PTSD or anxiety disorder, and predeployment prescription of an antidepressant or psychoactive medication were excluded. Validated measures of childhood trauma and adversity (adverse childhood experience [ACE] score), PTSD symptoms (PTSD check-list military version [PCL-M]), and combat exposure scales (CES) were measured via validated questionnaires for all subjects. After extracting DNA from peripheral blood provided by the 170 subjects, we determined methylation percentages, via pyrosequencing assays, for nine target areas within the following seven genes: BDNF, NR3C1, MAN2C1, TLR8, SLC6A4, IL-18, and SKA2. These genes are commonly reported in the literature as being highly correlated with PTSD and early-life traumatic experiences.Methylation levels were measured as a percentage at specific sites within the previously mentioned genes. Data were examined with SPSS v 22.0 Statistics and JMP v13.1 software using a general linear model for methylation × trauma (CES scores) split by diagnosis of PTSD or not, methylation versus childhood trauma (ACE scores), and methylation versus PTSD severity (PCL-M score). Two-way ANOVA was performed to control for antidepressant use. A two-tailed Student t-test was performed for PTSD analyses and was correlated with PTSD diagnosis, demographic information as well as ACE score, PCL-M score, and CES scores. Differentially methylated sites that were highly associated with PTSD diagnosis were found in three of seven candidate genes: BDNF, NR3C1, and MAN2C1. When compared to controls, patients with PTSD diagnosis had significantly lower levels of methylation, even after controlling for antidepressant use. PCL-M, ACE, and CES scores were significantly associated with PTSD diagnosis. Our study suggests that methylation of key genes involved in synaptic plasticity and the hypothalamic-pituitary-adrenal axis is associated with lower levels of methylation in military PTSD subjects exposed to combat when compared to their non-PTSD counterparts. Strengths of this study include controlling for antidepressant use and excluding TBI patients. Similar studies in an active duty population of this size are scarce. What is not clear is whether methylation changes are driving PTSD symptomology or whether they are merely a marker of disease. Future areas of research include prospective studies that measure methylation pre- and postcombat exposure in the same individual.


A steered molecular dynamics mediated hit discovery for histone deacetylases.
The inhibitors of class I histone deacetylases (HDACIs) have gained significant interest in cancer therapeutics. Virtual high throughput screening (vHTS) is one of the popular approaches used in the identification of novel scaffolds of HDACIs. However, an accurate description of ligand-protein flexibilities in the vHTS remains challenging. In this work, we implement an integrated approach, which combines the vHTS with the 'state-of-the-art' steered molecular dynamics (SMD). This approach serves as an efficient tool to identify potential hits and characterize their binding potencies against the class I HDACs in a flexible solvent environment. A hybrid pharmacophore-based and structure-based vHTS method identifies the hits with more favourable physico-chemical features against the class I HDACs. Our pharmacophore-based screening enhanced the quality of the vHTS outcomes. Further, the molecular interactions between the hits and the HDACs are investigated using the SMD-driven force profiles, which in turn resulted in filtering the hits with higher binding potencies against the HDACs. Our results, therefore, reveal that vHTS and SMD can be a complementary and effective analytical tool for accelerating the hit identification phase in structure-based drug design.


Functional outcomes following anoxic brain injury: a comparison with traumatic brain injury.
To compare the functional outcomes of patients with anoxic brain injury (ABI) and patients with traumatic brain injury (TBI) following inpatient rehabilitation. Retrospective chart review. Data on 68 patients with brain injury (34 with ABI and 34 with TBI) were collected. The ABI and TBI groups were demographically similar, except that patients with ABI were more likely to be married. Both groups significantly improved their function and were similar upon discharge. For the ABI group, there were trends toward a shorter length of stay, increased total FIM efficiency and decreased cost of stay when compared with the TBI group. The patients with ABI tended to be discharged to a sub-acute rehabilitation facility more than those in the TBI group. This study is important because it shows that patients with ABI benefit from inpatient rehabilitation and made significant functional gains comparable to the gains of patients with TBI.


Web-based survey among animal researchers on publication practices and incentives for increasing publication rates.
Publication bias, non-publication, and selective reporting of animal studies limit progress toward the 3Rs (Replacement, Reduction, and Refinement) that guide ethical animal testing, waste public resources, and result in redundant research, which collectively undermine the public's trust in scientific reliability. In this study, we aimed to 1) validate findings from a previous follow-up study by our team that examined the publication rates of animal studies from protocol to publication and 2) identify incentives for improving publication rates in animal research. The researchers responsible for the animal proposals (n = 210) from our previous study were contacted as participants for a Web-based survey between October 2019 and April 2020. Question types varied between free text questions, answer options based on a 5-point Likert scale and closed yes/no questions. In total, 78 researchers responsible for 101 of 210 animal study proposals participated, yielding a response rate of 48.1%. Results showed that the publication rate increased from 67% in our follow-up study to 70%. According to a 5-point Likert scale (from 1 = "not relevant" to 5 = "extremely relevant"), the most widely accepted suggestions for increasing publication rates were "Publication costs for open access journals are fully covered by funders or universities" (mean 4.02, SD 1.01), "Performance-based allocation of intramural funds for results reporting of animal research not supporting the initial hypothesis (including preprints and repositories)" (mean 3.37, SD 1.05), and "Researchers receive more information from scientific journals that also publish non-significant results" (mean 3.30, SD 1.02). While the extent of publication and publication practices have been thoroughly investigated for clinical trials, less data is available for animal research to date. Therefore, the study contributes in complementing the picture of publication practice in animal research. Suggestions from our survey may help improve the publication rates of animal studies.


[Chief cells of gastric fundal glands in patients with duodenal ulcer before and after vagotomy].
Chief cells were studied ultrastructurally and stereometrically in 93 patients at various intervals (from 2 weeks up to 4 years) after complete vagotomy as well as in 87 patients at the same intervals after selective proximal vagotomy. The chief cell structure indicated their high level of secretory activity in patients with duodenal ulcer regardless of the type of initial secretion (hypo-, normo- or hypersecretion). Vagotomy, apart from the decrease of the chief cell volume in the glands results in the reduction of their intracellular structures. The secretory granule structure was changed indicating the disturbance of cell differentiation, more pronounced after selective proximal vagotomy.


Molecular basis for Poria cocos mushroom polysaccharide used as an antitumor drug in China.
Poria cocos is an edible mushroom known as "Fuling" in Chinese, which belongs to the fungus family of Polyporaceae. Poria cocos has been used as a Chinese traditional medicine for >2000 years. Indications for using it include promoting urination, to invigorate the spleen function, and to calm the mind. The bioactive components in Poria cocos include polysaccharides, triterpenoids, fatty acids, sterols, enzymes, etc. Poria cocos polysaccharide (PCP) accounts for 84% by weight among all constituents in the dried sclerotium. Biochemical and pharmacological studies reveal that PCP is the major bioactive component in Poria cocos and has a wide range of biological activities including antitumor, immunomodulation, anti-inflammation, anti-oxidation, anti-aging, anti-hepatitis, anti-diabetes, and anti-hemorrhagic fever effects. As a result, "Poria cocos polysaccharide oral solution" was developed and sold as an over-the-counter health supplement since 1970s. In 2015, "Polysaccharidum of Poria cocos oral solution" was approved as a drug by Chinese Food and Drug Administration (SFDA) for treating multiple types of cancers, hepatitis, and other diseases alone or during chemo- or radiation therapy for cancer patients. In this article, biochemical, preclinical and clinical studies of Poria cocos polysaccharide from 74 independent studies during the past 46 years (1970-2018) based on PubMed, VIP (Chongqing VIP Chinese Scientific Journals Database), CNKI (China National Knowledge Infrastructure), and Wanfang database searches are summarized. The structure, pharmacological effects, clinical efficacy, immune regulatory molecular mechanisms, and toxicity of PCP are deliberated to provide the data basis for PCP to serve as a clinically used antitumor drug.


Characterization of a population of monozygotic twins with asthma.
Asthma is a complex inflammatory lung disease that results from allergic and nonallergic environmental exposures in genetically susceptible individuals. The interrelationship and impact of environmental and genetic determinants on the development of asthma is still unclear. Monozygotic twins (MZT) have been considered a potentially useful population to investigate the role of genetic and environmental factors on asthma because of their identical genetic background, similar childhood environmental exposures, and expected high concordance rate for asthma. A detailed questionnaire designed to obtain demographic information, medical history/severity of asthma, and environmental exposures was distributed to 43 pairs of MZT pairs where one or both probands had a history of asthma. All twin pairs were clinically evaluated for atopy by skin testing. Asthma was assessed by questionnaire, baseline spirometry, disease severity, airway reactivity, and medication scores. Based on a history of physician-diagnosed asthma, disease severity, airway reactivity, and medication scores, 22 MZT pairs were identified as concordant (C) for asthma while 21 MZT pairs were discordant (D) for asthma. Those MZT-C for asthma were on average older and more often female. Adjusted odds ratios for age and gender revealed that MZT-C for asthma had a 2.3 greater likelihood of childhood tobacco exposure and a 1.8 greater likelihood of early exposure to a pet compared to MZT-D pairs. In addition, MZT-C for asthma had a 2.4 greater likelihood of being full term vs. premature at birth. None of these odds ratios were statistically significant due to a small sample size. However, a trend for a greater likelihood of earlier environmental exposures was observed for MZT-C asthma pairs. Among MZT-D probands, a history of asthma in one proband was supported by a lower FEV1 and higher airway reactivity, disease severity, asthma symptom, and medication scores compared to the nonasthma proband. There was significant intrapair heterogeneity among MZT-C and MZT-D probands in their positive skin test responses to specific aeroallergens. Cross-sectional evaluation of larger MZT populations where one or both proband has asthma with a long-term prospective follow-up may be a feasible way for identifying the impact of environmental determinants as independent risk factors for the development of asthma.


Antigenic uniformity of topotype strains of Thogoto virus from Africa, Europe, and Asia.
Prototype Thogoto virus from Kenya and Thogoto virus isolates from Portugal, Italy, Nigeria, Central African Republic, Cameroon, and Iran were cross-tested by hemagglutination inhibition and serum dilution plaque reduction neutralization. Considering the broad geographic distribution of these strains, the antigenic differences seen appear to be essentially minor. This uniformity suggests that the distribution of Thogoto virus is due to repeated introduction of virus from common sources and that such introduction may depend on the movement of tick-infested domestic animals.


[Symptomatic carriers of dystrophinopathy with chromosome X inactivation bias].
Several studies have recently highlighted the fact that the clinical involvement in females carrying a mutation in the dystrophin gene could be more frequent than usually thought, suggesting the need of a careful cardiac follow-up. Except for the classical chromosomal rearrangements, it was shown that a bias in the X chromosome inactivation process could be found in some affected females. We report two families illustrating different situations. The propositus of the first family, aged 32, presented with a proximal muscular weakness, increasing for three years, as well as elevated muscular enzymes in blood. Her brother suffered from classical Duchenne muscular dystrophy. Her mother was more severely affected, whereas her sister remained asymptomatic. A duplication of exons 3 to 7 of the dystrophin gene was found in all four patients. The affected carrier from the second family was a sporadic case. She has been suffering from proximal muscular weakness for six years. Muscle biopsy showed a mosaic pattern of the immunostaining using specific antidystrophin antibodies. A stop mutation was found in exon 52. Her ten year-old daughter, carrying the mutation, was asymptomatic. In both families, the inactivation profiles were in accordance with the clinical presentation. We discuss the different mechanisms that may lead to the inactivation bias in these patients, as well as the advantage and limits of using the X chromosome inactivation test as a tool for diagnosis and prognosis purpose in symptomatic carriers for dystrophinopathies.


Oleic acid as modulator of oxidative stress in European sea bass (Dicentrarchus labrax) juveniles fed high dietary lipid levels.
Although the benefits of oleic acid (OA) have been established in mammals, its effects on fish remain understudied. The aim of this study was to evaluate the antioxidant potential of OA in the liver, intestine, and muscle of European sea bass juveniles fed diets containing different lipid levels. For that purpose, six diets with 16 or 22% lipids and 0, 1, and 2% OA were formulated and triplicate groups of European sea bass juveniles (21.4 g) were fed with these experimental diets for 9 weeks. Increasing dietary lipid levels or OA supplementation did not affect antioxidant enzyme activity in the liver and muscle. Superoxide dismutase (SOD) activity in the intestine increased with both the dietary lipid and OA levels, while glucose 6 phosphate dehydrogenase (G6PDH) activity increased only with dietary OA supplementation. Reduced glutathione (GSH) and total glutathione (tGSH) content were higher in the liver and intestine of fish fed the low-lipid diets, while in the high-lipid diets it was lower in the muscle than in the liver and intestine. Present findings suggest that OA plays a role in the antioxidant defense mechanisms of European sea bass, particularly at the intestine level, but additional research is required to further assess the potential benefits of incorporating OA into the diets.


Use of fine capillaries for cryopreservation of Caenorhabditis elegans by vitrification.
Caenorhabditis elegans is an exceptional model organism. More than twenty thousand different strains have been developed, increasing knowledge on countless topics. However, the traditional method to cryopreserve this nematode, based on slow freezing, usually reaches recovery rates of around 35% for the L1 and L2 larval stages. Here, we propose two alternative methods to cryopreserve this nematode based on vitrification that are applicable in common laboratories and allow the selective individual cryopreservation of this organism. These new methods require ultra-high warming rates, which are achieved by employing very thin capillaries as the nematode container, and a very low final concentration of cryoprotectants, which, as compared to slow freezing, reduce toxicity damage. The recovery rate was 98.5% for larvae (L1 - L4) and 84.3% for adults. Given these results, our procedures offer an alternative to cryopreserve this nematode (larvae and adults) with higher recovery rates, avoiding expensive requirements. Indeed, it only needed a container with liquid nitrogen and a warming bath for water at 37 °C. The high performance of this approach has been revealed by preserving the long-term memory and, probably, the connectome of this nematode.


The redefinition of aging in American surgery.
Adults aged sixty-five and over account for a large fraction of all surgeries performed in the United States each year. While historical growth in rates of surgery in this population is commonly attributed to financial incentives and technological innovations, the shifts in thought that underpinned the spread of surgery among the U.S. elderly remain largely unexplored. We examined changing perspectives on aging over time in American surgery through two case studies: the expansion of general surgical procedures among older U.S. adults between 1945 and 1965, and the spread of coronary artery bypass grafting (CABG) among the U.S. elderly between 1975 and 1995. For this article, we used close readings of historical journal articles, textbook excerpts, survey reports, and government documents related to surgery and aging. Similar perspectives on aging informed the spread of both general surgical procedures among older adults after World War II and CABG in the elderly from the mid-1970s onward. In each case, surgeons argued against earlier views that surgery was contraindicated in old age using rhetoric that negated the relevance of age to medical decisions. Furthermore, surgeons elevated other types of information-such as the presence or absence of chronic diseases-to supplant age as an explanation for the high operative mortality rates seen among older patients. By stressing the modifiability of operative risk in the elderly, surgeons' arguments positioned old age itself as a new surgical "frontier." Surgeons' arguments for the expansion of surgery among the U.S. elderly over time worked to negate the relevance of age to medical decisions and to portray the wider use of surgery in the elderly as uniformly beneficial. While potentially promoting broader access to surgical care, such perspectives may also have contributed to ongoing health policy challenges by normalizing surgery at any stage in the life-course, with implications for current patterns of surgical utilization and medical spending.


Timeliness of antibiotics for patients with sepsis and septic shock.
For many years, sepsis guidelines have focused on early administration of antibiotics. While this practice may benefit some patients, for others it might have detrimental consequences. The increasingly shortened timeframes in which administration of antibiotics is recommended, have forced physicians to sacrifice diagnostic accuracy for speed, encouraging the overuse of antibiotics. The evidence supporting this practice is based on retrospective data, with all the limitations attached, while the only randomized trial on this subject does not show a mortality benefit from early administration of antibiotics in a population of patients with sepsis as often seen in the emergency department (ED). Physicians are challenged to treat patients suspected of having sepsis within a short period of time, while the real challenge should be to identify patients who would not be harmed by withholding treatment with antibiotics until the diagnosis of infection with a bacterial origin is confirmed and the appropriateness of a course of antibiotics can be evaluated more adequately. Therefore, in the general population of patients with sepsis, taking the time to gather additional data to confirm the diagnosis should be encouraged without a specific timeframe, although physicians should be encouraged to perform an adequate work-up as soon as possible. Patients with suspected sepsis and signs of shock should immediately be treated with antibiotics, as there is no margin for error.


Genome-Wide Small RNA Sequencing Identifies MicroRNAs Deregulated in Non-Small Cell Lung Carcinoma Harboring Gain-of-Function Mutant p53.
Mutations in the TP53 gene are one of the most frequent events in cancers. Certain missense mutant p53 proteins gain oncogenic functions (gain-of-functions) and drive tumorigenesis. Apart from the coding genes, a few non-coding microRNAs (miRNAs) are implicated in mediating mutant p53-driven cancer phenotypes. Here, we identified miRNAs in mutant p53R273H bearing non-small cell lung carcinoma (NSCLC) cells while using small RNA deep sequencing. Differentially regulated miRNAs were validated in the TCGA lung adenocarcinoma patients with p53 mutations and, subsequently, we identified specific miRNA signatures that are associated with lymph node metastasis and poor survival of the patients. Pathway analyses with integrated miRNA-mRNA expressions further revealed potential regulatory molecular networks in mutant p53 cancer cells. A possible contribution of putative mutant p53-regulated miRNAs in epithelial-to-mesenchymal transition (EMT) is also predicted. Most importantly, we identified a novel miRNA from the unmapped sequencing reads through a systematic computational approach. The newly identified miRNA promotes proliferation, colony-forming ability, and migration of NSCLC cells. Overall, the present study provides an altered miRNA expression profile that might be useful in biomarker discovery for non-small cell lung cancers with TP53 mutations and discovers a hitherto unknown miRNA with oncogenic potential.


Preliteracy signatures of poor-reading abilities in resting-state EEG.
The hereditary character of dyslexia suggests the presence of putative underlying neural anomalies already in preliterate age. Here, we investigated whether early neurophysiological correlates of future reading difficulties-a hallmark of dyslexia-could be identified in the resting-state EEG of preliterate children. The children in this study were recruited at birth and classified on the basis of parents' performance on reading tests to be at-risk of becoming poor readers (n = 48) or not (n = 14). Eyes-open rest EEG was measured at the age of 3 years, and the at-risk children were divided into fluent readers (n = 24) and non-fluent readers (n = 24) after reading assessment at their third grade of school. We found that fluent readers and non-fluent readers differed in normalized spectral amplitude. Non-fluent readers were characterized by lower amplitude in the delta-1 frequency band (0.5-2 Hz) and higher amplitude in the alpha-1 band (6-8 Hz) in multiple scalp regions compared to control and at-risk fluent readers. Interestingly, across groups these EEG biomarkers correlated with several behavioral test scores measured in the third grade. Specifically, the performance on reading fluency, phonological and orthographic tasks and rapid automatized naming task correlated positively with delta-1 and negatively with alpha-1. Together, our results suggest that combining family-risk status, neurophysiological testing and behavioral test scores in a longitudinal setting may help uncover physiological mechanisms implicated with neurodevelopmental disorders such as the predisposition to reading disabilities.


The Relationship of Tobacco, Alcohol, and Betel Quid with the Formation of Oral Potentially Malignant Disorders: A Community-Based Study from Northeastern Thailand.
This study's objective was to describe the relationship between the main risk factors for oral cancer, including tobacco (in the form of cigarettes, smokeless tobacco (SLT), secondhand smoking (SS)), alcohol, and betel quid (BQ), and the occurrence of oral potentially malignant disorders (OPMDs). A community-based case-control study was conducted with a population of 1448 adults aged 40 years or above in northeastern Thailand. Patients aged 60 years or above (OR 1.79, p < 0.001) and female patients (OR 2.17, p < 0.001) had a significant chance of having OPMDs. Our multivariate analysis showed that the most potent risk factor for OPMDs occurrence was betel quid (BQ) (adjusted OR 4.65, p < 0.001), followed by alcohol (OR 3.40, p < 0.001). Even former users were at risk of developing OPMDs. The synergistic effect between these main risk factors was significantly shown in the group exposed to SLT, SS, BQ, and alcohol. The most potent synergistic effect was found in the group exposed to SLT, BQ and alcohol with the OR = 20.96.


100 years since the publication of the suramin formula.
Suramin was the first drug developed using the approach of medicinal chemistry by the German Bayer company in the 1910s for the treatment of human African sleeping sickness caused by the two subspecies Trypanosoma brucei gambiense and Trypanosoma brucei rhodesienese. However, the drug was politically instrumentalized by the German government in the 1920s in an attempt to regain possession of its former African colonies lost after the First World War. For this reason, the formula of suramin was kept secret for more than 10 years. Eventually, the French pharmacist Ernest Fourneau uncovered the chemical structure of suramin by reverse engineering and published the formula of the drug in 1924. During the Nazi period, suramin became the subject of colonial revisionism, and the development of the drug was portrayed in books and films to promote national socialist propaganda. Ever since its discovery, suramin has also been tested for bioactivity against numerous other infections and diseases. However, sleeping sickness caused by Trypanosoma brucei rhodesiense is the only human disease for which treatment with suramin is currently approved.


Polymorphism G1359A of the cannabinoid receptor gene (CNR1): allelic frequencies and influence on cardiovascular risk factors in a multicentre study of Castilla-Leon.
A polymorphism (1359 G/A) of the CNR1 gene was reported as a common polymorphism in Caucasian populations and was related to cardiovascular risk factors. The present study aimed to investigate the allelic distribution of polymorphism (G1359A) of the CB1 receptor gene in a geographical area of Spain (Community of Castilla y Leon) and to evaluate the influence of this polymorphism on obesity anthropometric parameters and cardiovascular risk factors in the fasted state in obese patients. A population of 341 obese subjects was analysed. Tetrapolar electrical bioimpedance measurement, blood pressure measurement, a serial assessment of nutritional intake with 3 days of written food records and a biochemical analysis were all performed. One hundred and seventy-seven patients (51.9%) had the genotype G1359G (wild-type group) and 164 (48.1%) patients were A carriers: G1359A (136 patients; 39.9%) or A1359A (28 patients; 8.2%) (mutant type group). The Health Area of Palencia had a lower frequency of wild-type genotype and G allelic frequency than all the other Health Areas. Segovia and Burgos Areas had a higher frequency of wild-type genotype and G allelic frequency than the other Health Areas. High-density lipoprotein (HDL) cholesterol was higher in the mutant type group and blood tryglicerides were lower in the same group. In conclusion, the novel finding of the present study is the association of the mutant type group G1359A and A1359A with a better lipid profile (triglycerides and HDL cholesterol) than the wild-type group. The frequencies of this polymorphism are different among Health Areas of Castilla y Leon (Spain).


A randomized controlled evaluation of alveolar ridge preservation following tooth extraction using deproteinized bovine bone mineral and demineralized freeze-dried bone allograft.
Alveolar ridge preservation could be performed immediately following tooth extraction to limit dimensional changes of alveolar process due to bone resorption. The aim of this study was to compare the clinical and histologic outcomes of socket preservation using two different graft materials; deproteinized bovine bone mineral (DBBM) and demineralized freeze-dried bone allograft (DFDBA) with absorbable collagen membrane. Twenty extraction sockets in 20 patients were randomly divided into 2 treatment groups: 10 sockets were augmented with DBBM and collagen membrane whereas 10 sockets were filled with DFDBA and covered by collagen membrane. Primary closure was achieved over extraction sockets by flap advancement. Horizontal and vertical ridge dimensional changes were assessed at baseline and after 4-6 months at the time of implant placement. For histological and histomorphometrical analysis, bone samples were harvested from the augmented sites with trephine during implant surgery. All data were analyzed using SPSS version 18 (α=0.05). Clinical measurements revealed that average horizontal reduction was 2.3 ± 0.64 mm for DFDBA and 2.26 ± 0.51 mm for DBBM. Mean vertical ridge resorption at buccal side was 1.29 ± 0.68 mm for DFDBA and 1.1 ± 0.17 mm for DBBM. Moreover, mean vertical ridge reduction at lingual site was 0.41 ± 0.38 mm and 0.35 ± 0.34 mm for DFDBA and DBBM, respectively. No significant differences were seen between two groups in any of those clinical parameters. Histologic analysis showed statistically significant more new bone deposition for DFDBA compared to DBBM (34.49 ± 3.19 vs. 18.76 ± 3.54) (P < 0.01). Residual graft particles were identified significantly more in DBBM (12.77 ± 1.85) than DFDBA (6.06 ± 1.02). Based on the findings of this study, both materials have positive effect on alveolar ridge preservation after tooth extraction, but there was more new bone formation and less residual graft particles in DFDBA group than in DBBM group.


The effect of food packaging elements on children's food choices and intake: A systematic review.
Little can be added about the worldwide concern over the exponential increase in obesity and child overweight problems. Much of the unhealthy eating habits occur at the time of food choice. The enormous influence of marketing strategies in general, and packaging in particular, has been highlighted here. In this respect, public policies that tend to direct choices toward healthier options have been developed. However, the usefulness of such policies will depend on evidence of how different packaging elements can influence children. This systematic review (SR) aims to compile the knowledge available to date on the influence of packaging on food choices and eating behaviours in children. Methodologically, the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines have been followed to select papers. We also assessed the risk of bias in the studies analysed using the Newcastle-Ottawa Quality Assessment Scale (NOS). The initial search strategy found 2,627 articles, although only 20 of them met the eligibility criteria. Data from the studies were extracted, categorised, and analysed. The results indicate that most of the packaging elements have some effect on children's food choices or food intake. The use of Cartoon is the element with the most consistent evidence of influence. Despite the number of studies and public initiatives developed to promote this informative and persuasive element, less consistency has been found regarding the effect of Nutrition Labelling. Therefore, the results found should be considered by both governments and organisations when promoting public policies that work for the wellbeing of children.


Thyroid hormone action at the cellular level.
Thyroid hormones influence numerous physiological and biochemical functions. The expression of the hormonal effects involves several events. The interaction of T3 with nuclear receptors, and the stimulation of mRNA production appears to be a major step. Extranuclear binding of thyroid hormones could account for early responses. Plasma membrane receptors may play a role in the cellular uptake of T3 and the stimulation of amino acids and sugar transport. A direct control of oxidative phosphorylation through binding of T3 to mitochondrial binding sites has been proposed. The role of cytosolic binding proteins remains unclear. The understanding of the mode of action of thyroid hormones requires a better knowledge of the molecular events occurring at the nuclear level, and the relation between the nuclear and extranuclear binding sites in the hormonal expression.


Women with dysmenorrhea are hypersensitive to experimental deep muscle pain across the menstrual cycle.
Primary dysmenorrhea is a common painful condition in women that recurs every month across the reproductive years. The recurrent nociceptive input into the central nervous system that occurs during menstruation each month in women with dysmenorrhea is hypothesized to lead to increased sensitivity to painful stimuli. We investigated whether women with primary dysmenorrhea are hyperalgesic to deep muscle pain induced by a cleanly nociceptive method of hypertonic saline injection. Pain stimulation was applied both within an area of referred menstrual pain (lower back) and at a remote site outside of referred menstrual pain (forearm) in 12 healthy women with severe dysmenorrhea and 9 healthy women without dysmenorrhea, at 3 phases of the menstrual cycle: menstruation and follicular and luteal phases. Women rated their pain severity on a 100-mm visual analog scale every 30 seconds after injection until the pain subsided. In both groups of women, menstrual cycle phase had no effect on the reported intensity and duration of muscle pain. However, women with dysmenorrhea had increased sensitivity to experimental muscle pain both at the site of referred pain and at a remote nonpainful site, as assessed by peak pain severity visual analog scale rating, area under the visual analog scale curve, and pain duration, compared to women without dysmenorrhea. These data show that women with severe primary dysmenorrhea, who experience monthly menstrual pain, are hyperalgesic to deep muscle pain compared to women without dysmenorrhea. Our findings that dysmenorrheic women are hyperalgesic to a clinically relevant, deep muscle pain in areas within and outside of referred menstrual pain indicates lasting changes in pain sensitivity outside of the painful period during menstruation.


Predictive value of the Ishii score for sarcopenia and the prognosis of older patients hospitalized with heart failure.
Although sarcopenia is common and associated with poor outcomes in patients with heart failure, its simple screening methods remain unclear. We aimed to investigate the predictive value of the Ishii score, which includes age, grip strength, and calf circumference, for sarcopenia and its prognostic predictability in patients with heart failure. This was a subanalysis of the FRAGILE-HF study. Receiver operating characteristic curves were used to evaluate the predictive value for sarcopenia. Patients were stratified into the high and low Ishii score groups based on the cutoff values of the Ishii score determined by the Youden index for sarcopenia, and the 1-year mortality rates were compared. Of the 1262 study participants, 936 were evaluated with sarcopenia, and 184 (55 women, 129 men) were diagnosed with sarcopenia. The areas under the receiver operating characteristic curves for sarcopenia were 0.73 and 0.87 for women and men, respectively. The optimal cutoff values for predicting sarcopenia were 165 and 141 for women and men, respectively. Using these cutoff values, the sensitivity and specificity for sarcopenia were 70.9% and 68.5% for women and 88.4% and 69.7% for men, respectively. At 1 year, 151 (low Ishii score group, 98; high Ishii score group, 53) deaths were observed. Adjusted Cox proportional hazards analysis showed that the high Ishii score group was significantly associated with 1-year mortality. Among older patients hospitalized for heart failure, the Ishii score is useful for predicting sarcopenia and 1-year mortality. Geriatr Gerontol Int 2023; ••: ••-••.


Assessing Prolongation of the Heart Rate Corrected QT Interval in Users of Tricyclic Antidepressants: Advice to Use Fridericia Rather Than Bazett's Correction.
A prolonged heart rate corrected QT interval (QTc) increases the risk of sudden cardiac death. Some methods of heart rate correction (notably Bazett) overestimate QTc in people with high heart rates. Studies suggest that tricyclic antidepressants (TCAs) can prolong the QTc and increase heart rate. Therefore, we aimed to study whether TCA-induced QTc prolongation is a false-positive observation due to overestimation at high heart rates. For this, we included 12,734 participants from the prospective population-based Rotterdam Study, with a total of 27,068 electrocardiograms (ECGs), of which, 331 during TCA use. Associations between use of TCAs, QTc, and heart rate were studied with linear repeated measurement analyses. QT was corrected for heart rate according to Bazett (QTcBazett), Fridericia (QTcFridericia), or a correction based on regression coefficients obtained from the Rotterdam Study data (QTcStatistical). On ECGs recorded during TCA use, QTcBazett was 6.5 milliseconds (95% confidence interval, 4.0-9.0) longer, and heart rate was 5.8 beats per minute (95% confidence interval, 4.7-6.9) faster than during nonuse. QTcFridericia and QTcStatistical were not statistically significantly longer during TCA use than during nonuse. Furthermore, QTcBazett was similar for ECGs recorded during TCA use and nonuse after statistical adjustment for heart rate. According to our results, TCA use does not seem to be associated with QTc prolongation. Therefore, the current advice of regulatory authorities to restrict the use of these drugs and to do regular checkups of the QTc may need to be revised. Other formulas, like Fridericia's, might be preferred.


Cognitive behavior therapy for panic disorder.
Panic Disorder affects around 3.5% of the population during their lifetime, affecting twice as many women. It is often comorbid with depression and other anxiety disorders. Panic disorder can be assessed by a variety of interviews and self-report questionnaires. The theoretical model underlying CBT explains panic from both a learning perspective as well as a cognitive one. Treatment comprises of both behavioral and cognitive components. Treatment outcome studies show that CBT is an effective, acceptable and cost-effective treatment for Panic Disorder.


Primary Salmonella aortic graft infection. First reported case.
The first spontaneous Salmonella aortic graft infection is reported, being due to graft contamination via a graft enteric erosion. The high mortality of Salmonella aortic infection and gram-negative graft infections is noted.


Psychological changes after coronary angiographic intervention: pre-post comparison and follow-up.
Epidemiological studies demonstrate the relevance of cardiovascular diseases for health policies and medical care, especially coronary heart diseases and myocardial infarction. Research has shown that a significant proportion of patients undergoing coronary angiography suffer from clinically relevant mental stress. The aim of this study is to investigate to what extent the psychological state of cardiology patients changes in short- and mid-term periods after coronary angiography has been performed. The study design is naturalistic, longitudinal and comparative about consecutively admitted patients undergoing coronary angiography (N = 419; consenting patients fulfilling inclusion criteria n = 68) at four measurement points: before and after angiography and 6 weeks and 6 months after discharge. The statistical analysis includes paired t-tests, chi-square tests, effect sizes and random effects regression models. The sample was representative of the target population. The prevalence of risk factors were: 84% heart attack, 31% diabetes and 84% hypertension. There were no angiographic pathological findings in 12% of the sample. The neuroticism levels of the sample was higher than in the general population. There were almost no pre-post differences for depression, anxiety, psychological well-being, self-efficacy, resilience or locus of control. At the mid-term, well-being and anxiety decreased and internal locus of control increased. Neuroticism was negatively and extraversion and openness were positively associated with mental state and resources. The sample showed persistent adverse subsyndromal depressivity. At the mid-term, patients realised that their prognosis also depends on their own behaviour (internal attribution). Special psychosomatic attention should be given to people with subsyndromal depression, higher emotional instability and those with angina pectoris symptoms displaying normal coronary angiography.


Decision procedure for indefinite hypergeometric summation.
Given a summand a(n), we seek the "indefinite sum" S(n) determined (within an additive constant) by [Formula: see text] or, equivalently, by [Formula: see text] An algorithm is exhibited which, given a(n), finds those S(n) with the property [Formula: see text] With this algorithm, we can determine, for example, the three identities [Formula: see text] [Formula: see text] and [Formula: see text] and we can also conclude that [Formula: see text] is inexpressible as S(m) - S(0), for any S(n) satisfying Eq. 2.


Secondary mania in patients with HIV infection: are antiretrovirals protective?
A case-control study of 19 patients with HIV-associated mania and 57 HIV-seropositive control patients matched by CD4 cell count, age, and year of treatment was undertaken to investigate associations with risk factors for human immunodeficiency virus (HIV) infection, treatment, and disease. There was no significant difference between groups for HIV exposure category, baseline health status, or drugs other than antiretrovirals. Zidovudine therapy provided a significant protective effect against the development of mania, whether administered at or prior to diagnosis of mania. In a 3-year follow-up study, incident AIDS dementia was significantly more common in patients with mania, despite no apparent difference in survival between cases and controls. These findings strengthen the evidence of an etiological association of HIV neuropathology with AIDS mania by demonstrating a protective effect of an antiretroviral agent able to penetrate the central nervous system.


[Litter production and breakdown in swamps dominated by palms (Arecaceae) in northeastern Costa Rica].
In Raffia (Raphia taedigera) palm-swamps, it is frequent to observe high mounds at the base of the palm clumps. These mounds are formed by the accumulation of litter and organic matter, or might result from upturned roots of wind-thrown trees. The mounds serve as anchorage site for the palms, and could be important for the establishment of woody tree species in the swamp. The formation of these mounds might be explained by the unequal accumulation of organic matter in the wetland, or by differences in decomposition rates between Raffia litter versus the litter produced in adjacent mixed forests. To distinguish between these hypotheses, I compared the spatial distribution of litter in a R. taedigera swamp with the litter distribution on an adjacent slope forest, where litter distribution is expected to be homogeneous. In addition, I compared decomposition rates of major components of fine litter in three different environments: two wetlands dominated by palms (R. taedigera and Manicaria saccifera) and a slope forest that experiences lower inundation effects. On the palm swamp, noticeable concentration of litter was observed near the bases of clumps of palm as opposed to the swamp floor. In the adjacent slope forest, the magnitude of the differences in the distribution of litter is small and there is no accumulation at the base of emergent trees. It was also found that litter production increases during heavy rains and storms that follow dry periods. The swamp environment, independent of the litter, showed significantly lower decomposition rates than the surrounding forest slope. Furthermore, R. taedigera litter decomposes as fast as the slope forest litter. Overall, these results suggest that resistance to decomposition is not a major factor in the formation of mounds at the bases of R. taedigera clumps. Instead, litter accumulation contributes to the formation of the mounds that rise above the surface of the swamp.


Assessment of yeast diversity in a marine environment in the south of Portugal by microsatellite-primed PCR.
The occurrence and diversity of yeasts in seawater was investigated in a study site located 20 Km off Faro, Portugal, above the Alvares Cabral Trench. A total of 43 water samples from different layers (above the permanent thermocline, under the thermocline and near the bottom) and directly from the surface, originated 234 isolates. All the isolates were identified using a molecular approach that included, in a first stage, MSP-PCR fingerprinting. A total of 31 MSP-PCR classes were formed, 8 for the pigmented yeasts and 23 for the non-pigmented yeasts. The pink coloured isolates were identified by direct comparison of the new fingerprints with those obtained for representative strains of the various species. For identification of the non-pigmented yeasts, a representative isolate of each MSP-PCR class was selected for sequence analysis and compared with reference sequences. The five most abundant yeast species were Sakaguchia dacryoidea, Pseudozyma aphidis, Rhodosporidium babjevae, R. diobovatum and Debaryomyces hansenii. The distribution of isolates and species in the major taxonomic groups indicated that the number of basidiomycetous yeasts and their diversity are prevalent in relation to their ascomycetous counterpart. Diversity indices were determined and superficial water and water near the bottom had the highest diversity. The sampling effort effectiveness was estimated, and found to correspond to approximately 60% of the species present. MSP-PCR identification proved suitable for pigmented basidiomycetous yeasts and, when used in conjunction with sequence analysis, was effective for the characterization of non-pigmented populations. Our results indicate that the MSP-PCR fingerprinting method is appropriate for the characterization of large groups of isolates due to its simplicity and good reproducibility.


Incidence and predictors of severe anemia in Asian HIV-infected children using first-line antiretroviral therapy.
There are limited data on treatment-related anemia in Asian HIV-infected children. Data from Asian HIV-infected children aged <18 years on first-line highly active antiretroviral therapy (HAART) were used. Children who had pre-existing severe anemia at baseline were excluded. Anemia was graded using the United States Division of AIDS (DAIDS) 2004 table. Potential risk factors for severe anemia were assessed by logistic regression. Data from 1648 children (51.9% female, 62.8% World Health Organization (WHO) stage 3/4) were analyzed. Median (interquartile range) age was 6.8 (3.7-9.6) years, CD4% was 9 (3-16)%, and plasma HIV-RNA was 5.2 (4.7-5.6) log10 copies/ml at HAART initiation in those with available testing. The most common regimens were stavudine/lamivudine/nevirapine (42%) and zidovudine/lamivudine/nevirapine (25%). Severe anemia was identified in 47 (2.9%) children after a median time of 6 months after HAART initiation, with an incidence rate of 5.4 per 100 child-years. Mild anemia or moderate anemia at baseline (p = 0.024 and p = 0.005, respectively), previous or current use of zidovudine (p < 0.0001 and p = 0.013, respectively), and male sex (p = 0.008) were associated with severe anemia. Higher weight-for-age z-score (p = 0.004) was protective. The incidence of severe anemia in Asian HIV-infected children after HAART initiation was low and mainly occurred during the first few months after HAART initiation. Mild to moderate anemia at baseline and using zidovudine were independent risk factors for the development of severe anemia.


Is circumferential injection advantageous for ultrasound-guided popliteal sciatic nerve block?: A proof-of-concept study.
Ultrasound (US) guidance, in some instances, can increase the success rate and reduce the onset and procedure times for peripheral nerve blockade compared with traditional nerve localization techniques. The presumptive mechanism for these benefits is the ability to accurately inject local anesthetic circumferentially around the target nerve. We aimed to determine whether ensuring circumferential spread of local anesthetic is advantageous for US-guided popliteal sciatic nerve block. Sixty-four adult patients undergoing US-guided popliteal sciatic block for elective foot and ankle surgery were randomly assigned to 1 of 2 groups, circumferential or single-location injection. Using a short-axis nerve view and out-of-plane needle approach, the needle tip was advanced to the posterior external surface of the sciatic nerve. A 30-mL local anesthetic admixture (1:1 lidocaine 2%/bupivacaine 0.5% with 1:200,000 epinephrine) was injected either entirely at this location (single location) or incrementally at multiple locations to ensure circumferential spread around the sciatic nerve (circumferential). Sensory and motor functions were assessed by a blinded observer at predetermined intervals. The primary outcome was sensory block defined as loss of sensation to pinprick in the distribution of both tibial and common peroneal nerves at 30 mins after injection. Sensory block was achieved in 94% of patients in the circumferential injection group compared with 69% in the single-location injection group (P = 0.010). There were no differences detected in block performance time, pain during block performance, or block-related complications between groups. Ultrasound-guided circumferential injection of local anesthetic around the sciatic nerve at the popliteal fossa can improve the rate of sensory block without an increase in block procedure time or block-related complications compared with a single-location injection technique.


Stochastic properties of gustatory impulse discharges in rat chorda tympani fibers.
1. The present study was intended to elucidate the role of temporal patterns of impulse discharges of the gustatory primary afferents in the coding of taste qualities by the use of simultaneous analyses of the across-neuron patterning (5) and the temporal patterning of impulses. 2. Impulse discharges of 43 rat chorda tympani fibers elicited by gustatory stimulation (0.1 M NaCl, 0.5 M sucrose, 0.01 N HCl, 0.02 M quinine hydrochloride, 0.3 M KCl, and 0.02 M saccharin sodium) were recorded. The temporal patterns of impulse discharges elicited by these stimuli were statistically analyzed both in an initial dynamic phase and a succeeding stationary phase of responses. In the dynamic phase, the time courses of firing frequency were studied; however, these were not clearly associated with the qualities of taste stimuli. In the stationary phase, the stochastic properties of impulse trains were studied regarding the impulse trains as a stochastic point process (30). In this study, interspike interval histograms (ISI histograms), joint interval histograms, serial correlograms, and autocorrelograms were computed. 3. In general, the distribution patterns of ISI histogram were not absolutely specific to the taste qualities. However, the gamma or the exponential distribution occurred most often with 0.1 M NaCl, and the bimodal or the skewed distribution was dominated with 0.5 M sucrose stimulation among the stimuli tested. The rhythmic discharges did not occur exclusively with the sweet taste stimulation, though they occurred more often with the sweet taste stimulation than with other taste stimulations. The joint interval histogram and the serial correlogram were used to examine the stochastic properties of impulse trains with particular reference to the time dependence in the impulse trains. Generally, the time dependence was not concerned with the taste qualities. 4. The chorda tympani fibers were classified into three types according to the magnitude of responses and the temporal patterns of impulse discharges. The neurons predominantly responsive to NaCl and unresponsive to sucrose were classified as type I neurons. The remaining neurons, which moderately responded to both NaCl and sucrose, were further categorized into type II neurons and type III neurons, depending on their temporal patterns of impulse discharge. The type II neurons tended to show the rhythmic or burstlike firing of impulses in response to more than one kind of taste stimuli. 5. The results showed that the taste quality was represented in the characteristic temporal patterning of impulses as well as in the across-neuron patterning of responses. The possible origin of the temporal discharge pattern and its significance in gustatory information processing were discussed on the basis of the neuron types described above.


Application of 3D Printing Technology in Increasing the Diagnostic Performance of Enzyme-Linked Immunosorbent Assay (ELISA) for Infectious Diseases.
Enzyme-linked Immunosorbent Assay (ELISA)-based diagnosis is the mainstay for measuring antibody response in infectious diseases and to support pathogen identification of potential use in infectious disease outbreaks and clinical care of individual patients. The development of laboratory diagnostics using readily available 3D printing technologies provides a timely opportunity for further expansion of this technology into immunodetection systems. Utilizing available 3D printing platforms, a '3D well' was designed and developed to have an increased surface area compared to those of 96-well plates. The ease and rapidity of the development of the 3D well prototype provided an opportunity for its rapid validation through the diagnostic performance of ELISA in infectious disease without modifying current laboratory practices for ELISA. The improved sensitivity of the 3D well of up to 2.25-fold higher compared to the 96-well ELISA provides a potential for the expansion of this technology towards miniaturization and Lab-On-a-Chip platforms to reduce time, volume of reagents and samples needed for such assays in the laboratory diagnosis of infectious and other diseases including applications in other disciplines.


Identification of L1CAM, Jagged2 and Neuromedin U as ovarian cancer-associated antigens.
In order to identify tumor-associated genes of ovarian carcinoma, we have investigated the transcriptional profile of 11 ovarian tumor cell lines and 2 immortalized ovarian surface epithelial cell lines (IOSE) derived from normal ovarian epithelium with Affymetrix GeneChip technology. We have analyzed the expression profile of 12652 genes. A total of 136 genes were up-regulated and 165 were down-regulated in at least 7 out of 11 ovarian tumor cell lines in comparison to the transcriptional profile of the IOSE cell lines with a change factor of +/-2 as the threshold level. We have focused on up-regulated genes encoding for transmembrane receptors and secreted proteins as possible markers for diagnosis and targets for therapy of ovarian carcinoma. We have identified the transmembrane Notch ligand Jagged2, cell adhesion molecule L1CAM and the secreted polypeptide Neuromedin U as possible candidates. Immunohistochemical analysis revealed expression of L1CAM predominantly in ovarian carcinomas, in borderline tumors to a lesser extent, and very rarely in ovarian non-epithelial types of cancer. Further analysis of L1CAM revealed that a splice variant lacking exons 2 and 27 is predominantly expressed in ovarian carcinoma cell lines DW and GG. Functional investigation of stable Delta(2,27)L1CAM transfectants of the ovarian tumor cell line OV-MZ-2 revealed significantly stronger adhesion to laminin in comparison to mock transfectants.


The Evolution of Complex Muscle Cell In Vitro Models to Study Pathomechanisms and Drug Development of Neuromuscular Disease.
Many neuromuscular disease entities possess a significant disease burden and therapeutic options remain limited. Innovative human preclinical models may help to uncover relevant disease mechanisms and enhance the translation of therapeutic findings to strengthen neuromuscular disease precision medicine. By concentrating on idiopathic inflammatory muscle disorders, we summarize the recent evolution of the novel in vitro models to study disease mechanisms and therapeutic strategies. A particular focus is laid on the integration and simulation of multicellular interactions of muscle tissue in disease phenotypes in vitro. Finally, the requirements of a neuromuscular disease drug development workflow are discussed with a particular emphasis on cell sources, co-culture systems (including organoids), functionality, and throughput.


Regulatory T Cell Inhibition by P60 Combined with Adenoviral AFP Transduced Dendritic Cells for Immunotherapy of Hepatocellular Carcinoma.
Vaccination with tumor-associated antigen-pulsed dendritic cells leads to specific T-cell response against hepatocellular carcinoma. However, clinical response has been shown to be limited. High regulatory T-cell count is associated with poor prognosis and seems to mediate immune tolerance in hepatocellular carcinoma. Forkhead box P3-peptide inhibitor P60 has been shown to specifically inhibit regulatory T-cell function in murine models. Aim of this study was to investigate whether P60 can improve the immune response induced by vaccination with adenovirus-transduced dendritic cells expressing alpha-fetoprotein in subcutaneous and orthotopic murine models for hepatocellular carcinoma. Mice developing subcutaneous or orthotopic HCC received daily treatment with P60 starting at different tumor stages. Additionally, mice were vaccinated twice with dendritic cells expressing alpha-fetoprotein. In a preventive setting prior to tumor engraftment, vaccination with alpha-fetoprotein-expressing dendritic cells significantly decreased tumor growth in a subcutaneous model (p = .0256), but no further effects were achieved by addition of P60. However, P60 enhanced the antitumoral effect of a vaccination with alpha-fetoprotein-expressing dendritic cells in established subcutaneous and orthotopic hepatocellular carcinoma characterized by high Treg levels (p = .011). In this study, we showed that vaccination with alpha-fetoprotein-expressing dendritic cells in combination with a specific inhibition of regulatory T-cells by using P60 leads to synergistic tumor inhibition and prolonged survival. This emphasizes the importance of regulatory T-cells inhibition for obtaining an effective antitumoral immune response in hepatocellular carcinoma.


Outcomes of behavioral intervention for children with autism in mainstream pre-school settings.
We evaluated outcomes for 31 children with autism (2-6 years of age at intake) who received behavioral intervention in mainstream pre-school settings and a comparison group of 12 children receiving treatment as usual. After 2 years, children receiving behavioral intervention had higher IQ scores (Hedges g = 1.03 (95% CI = .34, 1.72) and adaptive behavior composite scores (Hedges g = .73 (95% CI = .05, 1.36). Despite probably fewer intervention hours, these group level outcomes were comparable to studies providing more intensive intervention. Individual child data also showed positive results with 19.4% achieving change at a reliable level for IQ; but a lower percentage than found in recent meta-analysis research. Strengths and weaknesses of the mainstream pre-school delivery model are discussed.


Prioritized Research for the Prevention, Treatment, and Reversal of Chronic Disease: Recommendations From the Lifestyle Medicine Research Summit.
Declining life expectancy and increasing all-cause mortality in the United States have been associated with unhealthy behaviors, socioecological factors, and preventable disease. A growing body of basic science, clinical research, and population health evidence points to the benefits of healthy behaviors, environments and policies to maintain health and prevent, treat, and reverse the root causes of common chronic diseases. Similarly, innovations in research methodologies, standards of evidence, emergence of unique study cohorts, and breakthroughs in data analytics and modeling create new possibilities for producing biomedical knowledge and clinical translation. To understand these advances and inform future directions research, The Lifestyle Medicine Research Summit was convened at the University of Pittsburgh on December 4-5, 2019. The Summit's goal was to review current status and define research priorities in the six core areas of lifestyle medicine: plant-predominant nutrition, physical activity, sleep, stress, addictive behaviors, and positive psychology/social connection. Forty invited subject matter experts (1) reviewed existing knowledge and gaps relating lifestyle behaviors to common chronic diseases, such as cardiovascular disease, diabetes, many cancers, inflammatory- and immune-related disorders and other conditions; and (2) discussed the potential for applying cutting-edge molecular, cellular, epigenetic and emerging science knowledge and computational methodologies, research designs, and study cohorts to accelerate clinical applications across all six domains of lifestyle medicine. Notably, federal health agencies, such as the Department of Defense and Veterans Administration have begun to adopt "whole-person health and performance" models that address these lifestyle and environmental root causes of chronic disease and associated morbidity, mortality, and cost. Recommendations strongly support leveraging emerging research methodologies, systems biology, and computational modeling in order to accelerate effective clinical and population solutions to improve health and reduce societal costs. New and alternative hierarchies of evidence are also be needed in order to assess the quality of evidence and develop evidence-based guidelines on lifestyle medicine. Children and underserved populations were identified as prioritized groups to study. The COVID-19 pandemic, which disproportionately impacts people with chronic diseases that are amenable to effective lifestyle medicine interventions, makes the Summit's findings and recommendations for future research particularly timely and relevant.


Multiuser acoustic communications with mobile users.
A multiuser receiver is developed that is capable of separating receptions from independent, mobile users whose transmissions overlap in both time and frequency. With respect to any one user's Doppler corrected signal, the other communication signals appear as multiple-access interference distributed across the Doppler dimension. A previously developed receiver composed of an adaptive time-reversal processor embedded within a successive interference cancellation framework is limited to stationary users. This paper extends the receiver to properly remove the interference from moving sources by modeling the effects of Doppler through the interference cancellation receiver. The combined receiver has the ability to remove interference in both the temporal and spatial domains, and this property is shown to be preserved even when users are in motion. When applied to data collected during a recent shallow water experiment (KAM11), the receiver is shown to be capable of separating packets in a two user system where one user is moving while the other is stationary.


ReCell® Spray-On Skin System for Treating Skin Loss, Scarring and Depigmentation after Burn Injury: A NICE Medical Technology Guidance.
The gold standard treatment for deep burns is an autologous skin graft; in larger burns this may be meshed to increase the area covered. However, long-term aesthetic and functional outcomes of graft scars may be poor. ReCell® is a medical device that processes skin samples in the operating theatre into a cell suspension to be sprayed or dripped onto a wound. It is claimed to improve healing and scar appearance. This device was evaluated by the National Institute for Health and Care Excellence (NICE) Medical Technologies Evaluation Programme. Two groups were defined: ReCell compared to conventional dressings in shallower burns, and meshed grafts plus ReCell compared to meshed grafts alone in larger deeper burns. The manufacturer's clinical evidence submission included three papers and eight conference abstracts. The External Assessment Centre (EAC) excluded two of these and added seven abstracts. In general, the evidence did not fit the defined groups, but suggested that ReCell was clinically comparable to skin grafts for partial thickness burns; however, ReCell is not used in this way in the UK. The manufacturer submitted an economic model in which ReCell treatment of partial thickness burns reduced the requirement for later skin grafts. This indicated that ReCell alone was cost saving in comparison to conventional dressings. The EAC indicated that this model was clinically inappropriate, but data were not available to populate a new model. NICE Medical Technologies Guidance 21 recommended that additional research was needed to address the uncertainties regarding the potential benefits of ReCell.


Relatively high rates of cefotaxime- and ceftriaxone-non-susceptible isolates among group B streptococci with reduced penicillin susceptibility (PRGBS) in Japan.
We have previously identified group B Streptococcus (GBS) clinical isolates with reduced penicillin susceptibility (PRGBS) that were non-susceptible to cefotaxime; however, the rates of cefotaxime and ceftriaxone non-susceptibility among PRGBS isolates have never been reported. Therefore, we first determined the MICs of 22 antibacterial drugs/compounds for 74 PRGBS isolates and then determined the rates of cefotaxime and ceftriaxone non-susceptibility among these isolates. We used 74 clinical PRGBS isolates, previously collected in Japan and confirmed to harbour relevant amino acid substitutions in PBP2X. We also used 80 penicillin-susceptible GBS (PSGBS) clinical isolates as controls. The MICs of 22 antibacterial drugs/compounds for all 154 GBS isolates were determined via microdilution and/or agar dilution methods, as recommended by the CLSI. The rates of non-susceptibility/resistance to ampicillin, cefotaxime, ceftriaxone and levofloxacin for the 80 PSGBS isolates were 0%, 0%, 0% and 30%, respectively, but were 15% (P = 0.0003), 28% (P < 0.0001), 36% (P < 0.0001) and 93% (P < 0.0001) for the 74 PRGBS isolates, respectively. No PRGBS isolates were identified to be non-susceptible to meropenem, doripenem, vancomycin, quinupristin/dalfopristin, daptomycin or linezolid. We found that cefotaxime- and ceftriaxone-non-susceptible PRGBS isolates occur at relatively high rates in Japan. Importantly, this finding suggests that the range of drugs likely to be effective in treating PRGBS infections may be limited compared with those available for PSGBS infections; therefore, clinicians should exercise care when considering drug choice and efficacy for PRGBS infections.


Treatment with L-valine ameliorates liver fibrosis and restores thrombopoiesis in rats exposed to carbon tetrachloride.
It has been reported that treatment with branched chain amino acids (BCAAs) increases the survival rates in cirrhotic patients. In this study, we investigated the effect of L-valine, one of BCAAs, on liver fibrosis in rat. To induce liver fibrosis, male Wistar rats were injected carbon tetrachloride (CCl(4)) intraperitoneally (2.0 mL/kg) twice a week for 12 weeks. The rats (seven to fifteen rats for each group) were then administered 1.688 g/kg/day of L-valine intravenously for 7 days or 10% amino acid preparation that provided the same amount of nitrogen. Seven days after the last administration, blood platelet counts and bone marrow megakaryocyte counts were significantly higher in the valine group than in the control group (131.2 +/- 38.3 vs. 106.3 +/- 14.5 x 10(4)/microL, p = 0.04; 18.0 +/- 2.1 vs. 13.5 +/- 2.2 per field, p < 0.01, respectively). Importantly, the mRNA level of thrombopoietin, a key regulator of thrombopoiesis, was significantly higher in the liver of the valine group than the control group. Furthermore, hepatic fibrosis was significantly reduced in the valine group, and the mRNA levels of factors associated with liver fibrosis such as procollagen alpha1(III), transforming growth factor-beta1 and connective tissue growth factor were significantly lower in the liver of the valine group 10 days after the last administration. These results indicate that L-valine treatment ameliorates liver fibrosis and restores thrombopoiesis in rats exposed to CCl(4). Therefore, L-valine supplementation may be helpful for patients with liver cirrhosis.


Recency and projection biases in air quality valuation by Chinese residents.
We combine survey responses to subjective well-being (SWB) questions with air pollution data to recover Chinese residents' valuation of air quality improvements. Motivated by theoretical models of 'projection bias' and 'recency bias', we posit that one's SWB (and valuation) is affected disproportionately by more recent experiences with air pollution, even though long-term air pollution is more detrimental to one's actual well-being. Towards this end, we find that valuation for a unit improvement in PM2.5 is twice as large when air quality on the day of survey is used as the explanatory variable compared to air quality averaged over a year. Our findings have far-reaching research and policy implications as they call into question the appropriate temporal scale of air quality conditions when conducting valuation studies or policy evaluations. Furthermore, our results imply that policymakers could conceivably exploit this behavioral bias to introduce more stringent air quality management policies when air quality is extremely poor.


Estradiol valerate and alcohol intake: dose-response assessments.
An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from .001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies. With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake. The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries.


PRODUCTION OF HYDROGEN SULFIDE BY STREPTOMYCES ODORIFER.
By use of various trapping systems, as well as lead acetate papers, Streptomyces odorifer was shown to produce hydrogen sulfide. Other sulfur-containing compounds may be produced by S. odorifer, but the amounts obtained were too small for detailed analysis. It was suggested that hydrogen sulfide might be a part of the earthy-odor complex produced by S. odorifer.


Regulatory rewiring confers serotype-specific hyper-virulence in the human pathogen group A Streptococcus.
Phenotypic heterogeneity is commonly observed between isolates of a given pathogen. Epidemiological analyses have identified that some serotypes of the group A Streptococcus (GAS) are non-randomly associated with particular disease manifestations. Here, we present evidence that a contributing factor to the association of serotype M3 GAS isolates with severe invasive infections is the presence of a null mutant allele for the orphan kinase RocA. Through use of RNAseq analysis, we identified that the natural rocA mutation present within M3 isolates leads to the enhanced expression of more than a dozen immunomodulatory virulence factors, enhancing phenotypes such as hemolysis and NAD(+) hydrolysis. Consequently, an M3 GAS isolate survived human phagocytic killing at a level 13-fold higher than a rocA complemented derivative, and was significantly more virulent in a murine bacteremia model of infection. Finally, we identified that RocA functions through the CovR/S two-component system as levels of phosphorylated CovR increase in the presence of functional RocA, and RocA has no regulatory activity following covR or covS mutation. Our data are consistent with RocA interfacing with the CovR/S two-component system, and that the absence of this activity in M3 GAS potentiates the severity of invasive infections caused by isolates of this serotype.


Why despite the lower prevalence, is asthma more severe in the semiarid region?
Asthma is a chronic inflammatory disease which is very prevalent throughout the world, and climatic factors, especially air humidity, have been considered fundamental to its development. This study aims to evaluate the relationship between the climate factor and the severity of asthma episodes in the semiarid region, comparing it to the coast and an intermediate climate region, considering the use of medication as an intervening factor. Ecological study in cities with different climatic conditions (semiarid, intermediate region and Coast). Prevailing data was obtained from the International Study of Asthma and Allergies in Childhood (ISAAC) protocol. We evaluated the temperature, humidity and use of drugs for asthma/100,000 inhabitants. The prevalence of asthma was lower in the semiarid (14%; 95%CI=12.1-15.7) than the intermediate region (19.1%; 95%CI=17.7-20.6) and coast (17.9%; 95%CI=16.6-19.2). Episodes of severe asthma attacks were surprisingly higher in semiarid (10.4%; 95%CI=8.9-11.9) when compared to coast (4.1%; 95%CI=3.4-4.9) and intermediate region (5.0%; 95%CI=4.3-5.8). In the semiarid region, the humidity was lower and the temperature higher than the other cities evaluated. The dispensing of medications was lower in the semiarid region. Temperature and humidity may have contributed to a lower prevalence and greater severity of asthma in the semiarid region. The dispensing of medications was lower in the semiarid region, indicating that access to both relief and control drugs was lower in this city. The possibility of lack of health care in the semiarid region can also be another explanatory factor associated.


Standard weight for height curves in achondroplasia.
Standard curves developed for the general population cannot be used to assess the growth of an individual who has a condition that results in disproportionate short stature. For this reason, efforts have been made to develop growth curves specific for several of the chondrodysplasias. However, data concerning weight for height have been largely lacking, although they may be of particular importance for conditions such as achondroplasia, where there is some consensus that an increased prevalence of obesity is a particular problem. In this paper we provide standard weight for height curves for males and females with achondroplasia, and discuss the use of several indices which have been applied to the assessment of body fat in the general population.