Common genetic polymorphisms and coronary heart disease.
Susceptibility to coronary heart disease (CHD) is to some extent genetically determined, but despite a great deal of effort, in the past decade research has shown little progress towards identifying the genetic variants responsible. This article explores the reasons why this is so, using the ACE insertion/deletion polymorphism, which has been the most extensively studied of all genetic polymorphisms with respect to CHD risk, as an example. It is suggested that issues long recognized as important in epidemiological studies of classical risk factors, such as appropriate sample size, a requirement for high levels of statistical significance, and avoidance of excessive subgroup analysis, have tended to be under-appreciated in case-control studies of genetic polymorphisms and disease thus far. I discuss the consequences of such methodological limitations. Finally, I present a ;;checklist'' of important factors in study design and analysis in order to assist readers who may be unfamiliar with aspects of genetic methodology in the evaluation of these increasingly frequently conducted studies.


The early rise and spread of evolutionary game theory: perspectives based on recollections of early workers.
Though the first attempts to introduce game theory into evolutionary biology failed, new formalism by Maynard Smith and Price in 1973 had almost instant success. We use information supplied by early workers to analyse how and why evolutionary game theory (EGT) spread so rapidly in its earliest years. EGT was a major tool for the rapidly expanding discipline of behavioural ecology in the 1970s; each catalysed the other. The first models were applied to animal contests, and early workers sought to improve their biological reality to compare predictions with observations. Furthermore, it was quickly realized that EGT provided a general evolutionary modelling method; not only was it swiftly applied to diverse phenotypic adaptations in evolutionary biology, it also attracted researchers from other disciplines such as mathematics and economics, for which game theory was first devised. Lastly, we pay attention to exchanges with population geneticists, considering tensions between the two modelling methods, as well as efforts to bring them closer. This article is part of the theme issue 'Half a century of evolutionary games: a synthesis of theory, application and future directions'.


The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells.
We previously identified proline-rich protein 11 (PRR11) as a novel cancer-related gene that is implicated in the regulation of cell cycle and tumorigenesis. Our recent study demonstrated that PRR11 and its adjacent gene, kinetochore associated 2 (SKA2), constitute a classic head-to-head gene pair that is coordinately regulated by nuclear factor Y (NF-Y). In the present study, we further show that the PRR11-SKA2 bidirectional transcription unit is an indirect target of the tumor suppressor p53. A luciferase reporter assay revealed that overexpression of wild type p53, but not mutant p53, significantly represses the basal activity and NF-Y mediated transactivation of the PRR11-SKA2 bidirectional promoter. Deletion and mutation analysis of the PRR11-SKA2 promoter revealed that p53-mediated PRR11-SKA2 repression is dependent on the presence of functional NF-Y binding sites. Furthermore, a co-immunoprecipitation assay revealed that p53 associates with NF-Y in lung cancer cells, and a chromatin immunoprecipitation assay showed that p53 represses PRR11-SKA2 transcription by reducing the binding amount of NF-Y in the PRR11-SKA2 promoter region. Consistently, the ability of p53 to downregulate PRR11-SKA2 transcription was significantly attenuated upon siRNA-mediated depletion of nuclear factor Y subunit beta (NF-YB). Notably, lung cancer patients with lower expression of either PRR11 or SKA2 along with wild type p53 exhibited the best overall survival compared with others with p53 mutation and/or higher expression of either PRR11 or SKA2. Taken together, our results demonstrate that p53 negatively regulates the expression of the PRR11-SKA2 bidirectional transcription unit through NF-Y, suggesting that the inability to repress the PRR11-SKA2 bidirectional transcription unit after loss of p53 might contribute to tumorigenesis.


New Clinical Phenotype of the Post-Covid Syndrome: Fibromyalgia and Joint Hypermobility Condition.
Fibromyalgia can be defined as a chronic pain condition, affecting the musculoskeletal system, etiology and pathophysiology of which is sufficiently understudied. Despite the fact that many authors consider this entity to be a manifestation of central sensitization, and not an autoimmune disease, the high prevalence of fibromyalgia in patients with post-COVID-19 conditions requires taking a fresh look at the causes of the disease development. During the patient examination, the authors identified a combination of symptoms that occurs so often, that they can be carefully described as a clinical pattern. These manifestations include young age, female gender, joint hypermobility, the onset of pain after COVID-19, physical traumatization of one particular tendon and the development of the fibromyalgia pain syndrome during the next several weeks. As well as an increase in the titer of antinuclear antibodies and some other systemic inflammation factors. It can be assumed with great caution that local damage to the connective tissue in patients with joint hypermobility, having COVID-19 as a trigger factor can lead to the development of fibromyalgia syndrome. This article presents three clinical cases that illustrated this hypothesis.


Effect of family support on the success of translocated black-tailed prairie dogs.
Translocation has become a widely used conservation tool but remains only marginally successful. High mortality is often attributed to predation, but for highly social species, founder group composition may also play a critical role in postrelease survival. I compared the fitness of black-tailed prairie dogs translocated with or without their family groups. Animals in the family translocated groups were individually marked and observed until coterie membership was determined. Nonfamily translocated animals were trapped without regard to family membership. I measured fitness by retrapping all marked animals remaining at release sites in the summer following release. Family translocated animals were five times more likely to survive and had significantly higher reproductive success than those translocated without families. Predation was an important impediment of translocation success, but family translocation significantly reduced the success of predators on newly established prairie dog colonies. Postrelease survival was also affected by the timing of release, but appeared to be more important for juveniles than adults. These results demonstrate the importance of considering familiarity when translocations are required. More broadly, these results illustrate the value of applying animal behavior to conservation efforts and suggest that other species dependent on social interactions for survival and reproduction may benefit substantially from the maintenance of social groups during translocations.


Ethanol causes accelerated G1 arrest in differentiating HL-60 cells.
The effects of clinically relevant ethanol concentrations on myeloid differentiation in the HL-60 cell promyelocytic leukemia line have been studied. The exposure of noninduced stem cells to 60 mM ethanol results in an increase in G1 cells, but there is no increase in superoxide production or expression of the Mo1 antigen. When HL-60 cells are induced to differentiate along the myeloid line with dimethylsulfoxide (DMSO) or retinoic acid (RA), there is a shift to smaller cell size, an increase in G1 cells and acquisition of the ability to produce superoxide as reported previously by several authors. When ethanol is present during differentiation, there are further increases in G1 cells, and increases in the percentage of cells which produce superoxide and express Mo1, and decreases in mean cell size and total growth during the incubation period. Regrowth experiments after periods of differentiation indicate that the increased G1 arrest seen in the presence of ethanol represents terminal commitment if inducer is present, but in the absence of inducer the increased G1 percentage is readily reversible. Examination of RNA content by flow cytometry reveals a decrease in both the peak and mean G1 RNA content during DMSO or RA induced differentiation. These decreases are accentuated by the presence of ethanol, resulting in a higher G1A/G1B ratio than in nonexposed cells. These findings indicate that ethanol enhances G1 growth arrest in HL-60 cells exposed to myeloid inducers. Partial differentiation occurs during this process, resulting in terminally arrested cells, some of which have undergone fewer postinduction cell divisions than normal and may not be fully competent.


Functional characteristics of a novel odorant binding protein in the legume pod borer, Maruca vitrata.
Insect olfaction system plays a key role in the foraging food, pollination, mating, oviposition, reproduction and other insect physiological behavior. Odorant binding protein are widely found in the various olfactory sensilla of different insect antennae and involved in chemical signals discrimination from natural environment. In this study, a novel OBP gene, MvitOBP3 is identified from the legume pod borer, Maruca vitrata, which it mainly harms important legume vegetables including cowpea, soybean and lablab bean. Real-time PCR results demonstrated that MvitOBP3 gene was abundantly expressed in the antennal tissue of M. vitrata, while low levels were distributed in the head, thorax, abdomen, leg and wing of adult moths. The recombinant OBP3 protein was purified using the prokaryotic expression and affinity chromatography system. Fluorescence competitive binding experiments indicated that that MvitOBP3 protein exhibited greater binding affinities with host-plant flower volatiles including Butanoic acid butyl ester, Limonene, 1H-indol-4-ol and 2-methyl-3-phenylpropanal, highlighting they may have attractant activities for the oviposition of female moths on the legume vegetables. Moreover, protein homology modeling and molecular docking analysis revealed that there are six amino acid sites of MvitOBP3 involved in the binding of the host-plant volatiles. These findings will further promote to understand the key role of odorant binding protein during host perception and oviposition of M. vitrata moths, which improve the efficiency of semiochemical-based prevention and monitoring for this pest in the legume vegetables field.


Association between caregiver ability and quality of life for people with inflammatory bowel disease: The mediation effect of positive feelings of caregivers.
Inflammatory bowel disease (IBD) is an incurable digestive disease. Since patients have to live with it, improving patients' quality of life is important. Caregiver's positive feelings and closeness may have a positive effect on patients' quality of life. We hypothesized that caregiver's positive feeling affected patient's quality of life through caregiver's caring ability, and closeness might be the upstream of this chain. In this study, we conducted a single-center cross-sectional survey by questionnaire in China to tested the hypothesis. A total of 181 patient-caregiver pairs were included. The short version of the IBD questionnaire (SIBDQ), the twelve-item short-form health survey (SF-12), the positive aspects of caregiving (PAC) and Capacity Scale of caregivers were used to collect data. All the data were collected in one interview. Spearman correlation and Bootstrap method were used to analyze the data. Mediation analysis results indicated that caregiver's caring ability mediated the association between caregiver's positive feelings and patients' quality of life (p < 0.01), which explained 34.1% of the total variation of patients' quality of life. Mediation analysis results also revealed that patient-evaluated or caregiver-evaluated closeness had a positive effect on patients' quality of life through caregiver's positive feeling and caregiver's caring ability (p < 0.05), which explained 2.1 and 2.3% of the variation of patients' quality of life. Caregiver's positive feelings were related to caregivers' quality of life (p < 0.01), but there was no significant association between caregivers' ability and caregivers' quality of life. In summary, our model revealed that caregiver's positive feeling affected patients' quality of life through caregiver's caring ability.


Patients with disabilities as teachers.
Medical schools and residencies lack training in communication skills with patients with disabilities, thereby creating potential barriers to care. To address this shortcoming, the Department of Family Medicine at Lehigh Valley Health Network developed an innovative program in which the patients themselves serve as medical educators. The P-DAT (Patients With Disabilities as Teachers) program is designed to teach basic communication skills and disability etiquette to promote sensitivity to issues unique to this patient population. As such, it conforms to the established principles of the patient-centered medical home. Two persons with disabilities who were patients of the residency-affiliated clinic underwent training to become educators. In the resulting interactive education session with medical students, the P-DAT educators describe their daily routines and health care experiences while encouraging their learners to ease anxieties in interacting with patients with disabilities by asking questions. The 44 student participants evaluated the program by responding to a series of Likert scale and open-ended questions. Tallies of the post-program survey results reveal that prior to the disability etiquette training a majority (89%) felt uncomfortable in communicating with patients with disabilities. The survey revealed that 98% of respondents found the program beneficial because it increased overall awareness and sensitivity (52%) and improved competency for future interactions with patients (46%). Although these evaluation results reflect the early stages of P-DAT implementation, the preliminary feedback indicates that medical students are eager to close the gap in their knowledge about disability etiquette so they can improve their care of this patient population.


[Effects of piperazine ferulate on TGF-beta1-induced renal interstitial fibroblast activation].
To investigate the effects of piperazine ferulate (PF) on TGF-beta1-induced renal interstitial fibroblast activation, and to explore the mechanism of PF in the prevention of renal tubulointerstitial fibrosis. In cultured normal rat renal kidney fibroblast (NRK-49F), the effect of PF on the TGF-beta1-induced cell vitality was observed by MTT. The protein expression levels of a-smooth muscle actin (alpha-SMA), connective tissue growth factor (CTGF) induced by TGF-beta1 were evaluated by immunocytochemistry. The levels of a-SMA, CTGF mRNA expression induced by TGF-beta1, were determined by quantitative real time fluroscent polymerase chain reaction. The levels of collagen type I (Col I) and fibronectin (FN) protein expression were examined by Enzyme Linked Immunosorbent Assay(ELISA). TGF-beta1 may markedly increase the cell vitality, alpha-SMA and CTGF expression, FN and Col I protein expression (P < 0.05). Compared with TGF-beta1-induced group, PF can partly decrease the cell vitality, level of alpha-SMA and CTGF expression and extracellular matrix(ECM) synthesis induced by TGF-beta1 (P < 0.05). PF may inhibit TGF-beta1-induced fibrosis in the renal fibroblast to a certain extent.


Efficacy of hypertonic dextrose infiltrations for pain control in rotator cuff tendinopathy: systematic review and meta-analysis.
The aim of our study was to assess the efficacy of hypertonic dextrose infiltrations for pain control in individuals with rotator cuff tendinopathy and to assess the characteristics of the treatment and the presence of side effects or adverse reactions through a systematic review and meta-analysis. The search for the articles was performed in the electronic databases PUBMED, EMBASE, SCOPUS, SCIELO, DIALNET and Google Scholar, published up to August 2020. The keywords used were "prolotherapy" or "proliferation therapy" or "hypertonic dextrose infiltrations" or "hypertonic dextrose injection" and "Rotator Cuff" or "Rotator Cuff Injury" or "Rotator Cuff Tear" or "Rotator Cuff Tendinosis" or "supraspinatus". The effectiveness of hypertonic dextrose infiltrations was expressed as standardized mean difference (d) and 95% CI. In the pooled analysis, hypertonic dextrose infiltrations were an effective intervention to reduce long-term pain in patients with rotator cuff tendinopathy when compared to controls; furthermore, in the individual analyses, hypertonic dextrose infiltrations were more effective in the short, medium and long terms than non-invasive treatments, and more effective in the long-term than infiltrations with local anesthetics. On the other hand, hypertonic dextrose infiltrations were not more effective than injections with corticosteroids or PRP. Finally, no complications or serious adverse effect were observed when hypertonic dextrose infiltrations were used. We found that hypertonic dextrose infiltrations reduced pain in individuals with rotator cuff in the long-term. Hypertonic dextrose infiltrations could be an alternative to non-invasive treatments when no favorable results can be achieve. However, due to the small number of studies included in this meta-analysis, new studies are necessary to clarify the efficacy and safety of this intervention.


Circadian and homeostatic factors in arousal.
In the course of evolution, mechanisms have evolved to anticipate the timing of regularly occurring events. These mechanisms are encompassed in a circadian timing system that include a master clock localized to the suprachiasmatic nucleus of the hypothalamus and "slave" oscillators distributed throughout the body. This system serves multiple functions so as to ensure that various physiological processes occur at optimal and nonoverlapping times, to synchronize our activities to local environmental time, and to permit changes required to respond to new environmental circumstances. We suggest that a generalized concept of arousal (which includes alterations in responsiveness to homeostatic pressures, sensory stimuli and emotional reactivity, and to changes in motor activity) serves as a rubric in which to explore the multiple ways in which the circadian system modulates behavior.


Smoking and prevalence of COVID-19: Evidence from studies from January 2020 - May 2020.
It is well-known that smoking tobacco harms the respiratory system and can lead to various health problems. Regarding COVID-19, a respiratory illness caused by the novel coronavirus SARS-CoV-2, smoking may have implications for both the risk of infection and the severity of the disease. Several studies have explored the association between smoking and COVID-19. However, findings have been somewhat inconsistent and vary from region to region for sample size. This article aims to study the prevalence of COVID-19 among those affected with their ongoing smoking history by computing pooled estimates of the published research. Fixed effect meta-analysis by following the guidelines of PRISMA has been carried out on 34 studies. The patients with confirmed RT-PCR and CT-scan were included, a total of 13,368; The studies' quality assessment was performed according to the Appraisal Checklist recommended by the Joanna Briggs Institute. The effect sizes of the published research are presented in the form of pooled estimates with their respective confidence intervals. Forest plots are used to represent the effect size graphically. Current smokers' effect sizes are 0.12 (CI = 0.11-0.12); for non-smokers, it is estimated to be 0.88 (CI = 0.88-0.89). The heterogeneity statistic I2 describes 0% of the total variation, meaning no heterogeneity among studies exists. A higher prevalence of COVID-19 among non-smokers is observed than the smokers.


Bone resorptive activity in symptomatic and asymptomatic apical lesions of endodontic origin.
The aim of this study is to assess the levels and diagnostic accuracy of a set of bone resorption biomarkers, including TRAP-5, RANKL, and OPG in symptomatic and asymptomatic apical lesions and controls. Apical tissues from symptomatic and asymptomatic apical periodontitis patients and periodontal ligaments from healthy teeth extracted for orthodontic reasons were processed for tissue homogenization and the levels of TRAP-5, RANKL, and OPG were determined by multiplex assay. Marker levels were analyzed by Kruskal Wallis test, and diagnostic accuracy was analyzed with ROC curves. Higher levels of RANKL, OPG, and RANKL/OPG ratio were determined in both types of apical lesions compared to healthy periodontal ligament, whereas higher TRAP-5 levels were found only in symptomatic apical lesions (p < 0.05). OPG, RANKL, and RANKL/OPG ratio showed diagnostic potential to identify apical lesions versus healthy controls (AUC = 0.69, p < 0.05); while TRAP-5 showed a potential to discriminate symptomatic versus asymptomatic apical periodontitis (AUC = 0.71, p < 0.05) and healthy controls (AUC = 0.83, p < 0.05). Apical lesions showed higher RANKL and OPG levels than healthy tissues. TRAP-5 levels were the highest in symptomatic apical lesions, suggesting that these represent a progressive state, and showed diagnostic potential. Clinically symptomatic apical periodontitis might represent biologically progressive apical lesions based on TRAP5 levels. TRAP5 has diagnostic potential to identify these lesions, representing a candidate prognostic biomarker.


[Regression of cardiac hypertrophy using angiotensin II receptor blocker in patients with chronic kidney diseases].
Cardiovascular complications proportionally increase as chronic kidney diseases (CKD) progress into chronic renal insufficiency or failure. The present study addressed whether the long-term use of angiotensin II receptor blocker (ARB) exerts a cardio-protective effect in CKD patients with mild to moderate renal damage. Fifteen patients with CKD above stage 3 were enrolled in the study. While their previous antihypertensive therapy remained unchanged, the ARB candesartan, was newly added to the concurrent therapy and the patients were followed for 12-24 months thereafter. The main results were as follows: 1) The use of ARB improved the status of BP control classifications, shifting them to the better control categories where there was less morning hypertension. 2) ARB significantly reduced the left ventricular (LV) mass index(LVMI), the relative wall thickness (RWT), the LV intra-dimension in diastole(LVIDd), and as a result, the LV ejection fraction(LVEF) improved. In parallel, the LV mass category shifted to lower categories, indicating a significant improvement. 3) The levels of BNP decreased significantly from 135.2 +/- 136.0 to 85.0 +/- 80.3 pg/mL. 4) ARB reduced urinary protein excretion in all cases. Regardless of an inevitable increase in the serum creatinine(Cr) concentration, the slope of reciprocal serum Cr concentration (l/Cr) in the treatment period with ARB was significantly less steep compared to that in the run-in period. 5) Throughout the observation period, no serious side effects were found in any of the patients. The present study indicated that the long-term use of ARB exerts both cardio-, and renoprotective effects in patients with advanced CKD. This agent could be especially indicative and useful not only for patients with CKD, but also for patients of CKD with cardiac hypertrophy.


In vivo dynamics of the cortical actin network revealed by fast-scanning atomic force microscopy.
Together with lamellipodia and stress fibers, a dynamic network of actin filaments in the cell cortex plays a major role in the maintenance of cell morphology and motility. In contrast to lamellipodia, which have been well studied in various motile cells, the dynamics of actin filaments in the cell cortex have not yet been clarified due to a lack of proper imaging techniques. Here, we utilized high-speed atomic force microscopy for live-cell imaging and analyzed cortical actin dynamics in living cells. We successfully measured the polymerization rate and the frequency of filament synthesis in living COS-7 cells, and examined the associated effects of various inhibitors and actin-binding proteins. Actin filaments are synthesized beneath the plasma membrane and eventually descend into the cytoplasm. The inhibitors, cytochalasin B inhibited the polymerization, while jasplakinolide, inhibited the turnover of actin filaments as well as descension of the newly synthesized filaments, suggesting that actin polymerization near the membrane drives turnover of the cortical actin meshwork. We also determined how actin turnover is maintained and regulated by the free G-actin pool and G-actin binding proteins such as profilin and thymosin β4, and found that only a small amount of free G-actin was present in the cortex. Finally, we analyzed several different cell types, and found that the mesh size and the orientation of actin filaments were highly divergent, indicating the involvement of various actin-binding proteins in the maintenance and regulation of cortical actin architecture in each cell type.


Nivolumab for the treatment of cancer.
One mechanism by which tumor cells are thought to evade the host's immune system is by inducing negative signals that cause T-cell suppression. An important interaction that results in this phenomenon is the one between programmed death-1 (PD-1) on the T cell and its ligand PD ligand-1 (PD-L1) on the tumor cell. PD-1 pathway blocking agents, such as nivolumab , are therefore capable of reversing T-cell suppression and ultimately induce antitumor responses. In this review, the authors summarize investigations related to the safety and efficacy of nivolumab in a variety of malignancies thus far, including advanced melanoma, renal cell carcinoma (RCC) and NSCLC. The results have been promising with a large number of objective responses and favorable safety profiles inspiring several Phase III trials in these settings. More recent studies are exploring the role of this drug in the treatment of various other cancers. Combination therapies involving nivolumab are also being studied and are yielding interesting results. Finally, the role of tumor PD-L1 expression as a predictive biomarker remains to be ascertained. Thus, with rational refinement through biomarker and combination clinical trials, nivolumab and other PD-1 blocking agents will likely lead to significant improvements in cancer therapeutics.


[Hemorrhagic rectocolitis or ulcerative colitis in the black Senegalese. Apropos of 14 cases].
Ulcerative colitis is exceptional in Africa South of the Sahara. The first case was described in 1964: up to 1982, 46 cases were reported. We report on 14 cases (6 females and 8 males) observed in black Senegalese for three years and a half. The medium age of patients was 30 years. All of them had a high social standard of living. Four patients showed intestinal amebiasis in their previous medical history. Clinical and evolutive patterns of ulcerative colitis in Africa present few differences in comparison with the classical ones. The diagnosis is established by endoscopy (rectosigmoidoscopy and/or colonoscopy) and histopathology. Cryptic abscesses were found in only 2 out of 14 cases. Rectal dysplasia was noted in 2 cases. The course of the disease developed on a fulminating acute mode in one case, on a continuous chronic mode in another case and on a chronic mode with relapses in 11 cases. Irrespective to the clinical form observed, intestinal amebiasis represents the most pressing differential diagnosis. Treatment appears to be difficult in severe acute forms out of an intensive care department, as well as in advanced extensive chronic forms. For the later in black Africa endoscopic and histopathological surveillance appears to be preferable to a total colectomy, made necessary by the important rectal lesions, because the functional sequelae of an ileostomy.


Real-time PCR detection of Didemnum perlucidum (Monniot, 1983) and Didemnum vexillum (Kott, 2002) in an applied routine marine biosecurity context.
Prevention and early detection are well recognized as the best strategies for minimizing the risks posed by nonindigenous species (NIS) that have the potential to become marine pests. Central to this is the ability to rapidly and accurately identify the presence of NIS, often from complex environmental samples like biofouling and ballast water. Molecular tools have been increasingly applied to assist with the identification of NIS and can prove particularly useful for taxonomically difficult groups like ascidians. In this study, we have developed real-time PCR assays suited to the specific identification of the ascidians Didemnum perlucidum and Didemnum vexillum. Despite being recognized as important global pests, this is the first time specific molecular detection methods have been developed that can support the early identification and detection of these species from a broad range of environmental sample types. These fast, robust and high-throughput assays represent powerful tools for routine marine biosecurity surveillance, as detection and confirmation of the early presence of species could assist in the timely establishment of emergency responses and control strategies. This study applied the developed assays to confirm the ability to detect Didemnid eDNA in water samples. While previous work has focused on detection of marine larvae from water samples, the development of real-time PCR assays specifically aimed at detecting eDNA of sessile invertebrate species in the marine environment represents a world first and a significant step forwards in applied marine biosecurity surveillance. Demonstrated success in the detection of D. perlucidum eDNA from water samples at sites where it could not be visually identified suggests value in incorporating such assays into biosecurity survey designs targeting Didemnid species.


Mitochondrial ADCK3 employs an atypical protein kinase-like fold to enable coenzyme Q biosynthesis.
The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. Here, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flips this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.


Incidence of total stroke, stroke subtypes, and myocardial infarction in the Japanese population: the JMS Cohort Study.
Previous reports indicated that the incidence rate of stroke was higher in Japan than in Western countries, but the converse was true in the case of myocardial infarction (MI). However, few population-based studies on the incidence rates of stroke and MI have been conducted in Japan. The Jichi Medical School (JMS) Cohort Study is a multicenter population-based cohort study that was conducted in 12 districts in Japan. Baseline data were collected between April 1992 and July 1995. We examined samples from 4,869 men and 7,519 women, whose mean ages were 55.2 and 55.3 years, respectively. The incidence of stroke, stroke subtypes, and MI were monitored. The mean follow-up duration was 10.7 years. A total of 229 strokes and 64 MIs occurred in men, and 221 strokes and 28 MIs occurred in women. The age-adjusted incidence rates (per 100,000 person-years) of stroke were 332 and 221 and those of MI were 84 and 31 in men and women, respectively. In the case of both sexes, the incidence rates of stroke and MI were the highest in the group of subjects aged > 70 years. We reported current data on the incidence rates of stroke and MI in Japan. The incidence rate of stroke remains high, considerably higher than that of MI, in both men and women. The incidence rates of both stroke and MI were higher in men than in women.


Evolving techniques for the investigation of muscle bioenergetics and oxygenation.
Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are both powerful, non-invasive methodologies and, as such, offer great potential to investigate both human biochemistry and human physiology, and ultimately to contribute significantly to the field of medicine. Consequently there has been much effort devoted to fostering the evolution of these methodologies into distinct and applicable techniques. Here we will highlight several MRI and MRS techniques for the assessment of human biochemistry and physiology that ultimately may provide useful clinical assessments and diagnoses of various muscular and cardiovascular pathologies. Specifically, the evolving techniques that will be discussed are: (1) (1)H MRS of myoglobin to assess the intracellular partial pressure of O(2), (2) (31)P MRS to assess metabolic capacity, and (3) the combination of (31)P chemical shift imaging to assess local metabolic demand (oxygen uptake; .VO(2)) with arterial spin labelling to assess local perfusion (blood flow; .Q), in an effort to characterize the elusive spatial matching of skeletal muscle (.Q/.VO(2)).


Povidone-iodine vs sodium hypochlorite enema for mechanical preparation before elective open colonic or rectal resection with primary anastomosis: a multicenter randomized controlled trial.
The anti-infective actions of povidone-iodine (PVI) and sodium hypochlorite enemas are different. Prospective, randomized, single-blind study. Multicenter. Five hundred seventeen consecutive patients with colorectal carcinoma or sigmoid diverticular disease undergoing elective open colorectal resection, followed by primary anastomosis. All patients received senna (1-2 packages diluted in a glass of water) at 6 pm the evening before surgery. Patients were administered two 2-L aqueous enemas of 5% PVI (n = 277) or 0.3% sodium hypochlorite (n = 240) at 9 pm the evening before surgery and at 3 hours before operation. Intravenous ceftriaxone sodium (1 g) and metronidazole (1 g) were administered at anesthetic induction. Rate of patients with 1 infective parietoabdominal complication or more. The percentages of patients with 1 infective parietoabdominal complication or more did not differ between the 2 groups (13.7% in the PVI-treated group vs 15.0% in the sodium hypochlorite-treated group). Tolerance was better in the PVI-treated group than in the sodium hypochlorite-treated group (79.4% vs 67.9%), with fewer patients experiencing abdominal pain (13.0% vs 24.6%) or discontinuing their preparation (3.0% vs 9.0%) (P=.02 for all). There were more patients with malaise in the PVI-treated group than in the sodium hypochlorite-treated group (9.1% vs 4.9%, P<.05). Three patients in the sodium hypochlorite-treated group had necrotic ulcerative colitis. When antiseptic enemas are chosen for mechanical preparation before colorectal surgery, PVI should be preferred over sodium hypochlorite because of better tolerance and avoidance of necrotic ulcerative colitis.


Health Experiences of African American Mothers, Wellness in the Postpartum Period and Beyond (HEAL): A Qualitative Study Applying a Critical Race Feminist Theoretical Framework.
The objective of this study is to explore the cultural, social, and historical factors that affect postpartum primary care utilization among Black women with cardiometabolic risk factors and to identify the needs, barriers, and facilitators that are associated with it. We conducted in-depth interviews of 18 Black women with one or more cardiometabolic complications (pre-pregnancy chronic hypertension, diabetes, obesity, preeclampsia, or gestational diabetes) within one year of delivery. We recruited women from three early home-visiting programs in Baltimore, Maryland, between May 2020 and June 2021. We used Critical Race Feminism theory and a behavioral model for healthcare utilization as an analytical lens to develop a codebook and code interview transcripts. We identified and summarized emergent patterns and themes using textual and thematic analysis. We categorized our findings into six main themes: (1) The enduring influence of structural racism, (2) personally mediated racism in healthcare and beyond, (3) sociocultural beliefs about preventative healthcare, (4) barriers to postpartum care transitions, such as education and multidisciplinary communication, (5) facilitators of postpartum care transitions, such as patient-provider relationships and continuity of care, and (6) postpartum health and healthcare needs, such as mental health and social support. Critical race feminism provides a valuable lens for exploring drivers of postpartum primary care utilization while considering the intersectional experiences of Black women.


Quality control and data validation procedure in large-scale quantitative monitoring of mosquito density: the case of Aedes albopictus in Emilia-Romagna region, Italy.
The risk of local transmission of chikungunya, dengue, and Zika viruses from viremic travelers arriving from affected areas is a real possibility in southern Europe, due to the large presence of the vector Aedes albopictus. The first chikungunya outbreak in Europe occurred in the Emilia-Romagna region, Italy, in 2007, prompting the regional public health department to implement an Ae. albopictus monitoring and control plan. This paper presents the procedure developed for the quality control of the data collected by the regional ovitrap monitoring network. The quality control procedure consists of four successive steps; the first step is data acquisition and the second is an automatic data processing step, while skilled technicians according to specific procedures perform the third and fourth steps by checking the exact position of the ovitraps and by conducting human landing collections, respectively. The paper also presents the results of this quality control procedure applied to the data collected through the large-scale Ae. albopictus monitoring operation performed in Emilia-Romagna in 2015.


DNA transposon dynamics in populations of Daphnia pulex with and without sex.
We investigate the role of recombination in transposable element (TE) proliferation in the cyclical parthenogen, Daphnia pulex. Recombination provides a mechanism by which the rate of both TE gain and loss can be accelerated, a duality that has long intrigued many biologists interested in the influence of sex on mutation accumulation. We compared TE loads among populations of D. pulex where sex occurs regularly (cyclical parthenogens or 'sexuals') with those in which the ability to reproduce sexually has been completely lost (obligate 'asexuals') for six different families of DNA transposons. Transposon display assays showed that sexuals have more TEs than asexuals, contrary to the expectations under Muller's ratchet but consistent with the idea that sex facilitates TE spread. Sexuals also exhibit higher insertion site polymorphism among lineages, as predicted because recombination accelerates rates of loss and gain. Asexuals, however, have proportionally more singletons (loci occupied in a single isolate), which differs from previous studies where selfing and outcrossing were used as a proxy for high and low recombination. Our multi-element survey reveals that the impact of sex on TE proliferation is consistent among different Class II TE families and we discuss the genomic consequences of different reproductive strategies over long time periods.


Assembling microtubules disintegrate the postsynaptic density in vitro.
The postsynaptic density (PSD), a disk-shaped protein aggregation of several hundred nm in diameter, plays important roles in the signal transduction and molecular organization of the excitatory synapses in mammalian CNS. The PSD resides in the microfilament-enriched cytoplasm of dendritic spines where the transient appearance of microtubules has been reported. When PSD isolated from porcine brain was incubated with polymerizing alpha,beta-tubulins, its turbidity became greater than that of the original PSD, suggesting that the PSD's structure was altered upon incubating with assembling microtubules. By transmission electron microscopy, smaller PSD fragments and several novel structures, including holes and finger-like extensions, were found in the PSD after incubation with assembling microtubules, but not in the original PSD or in the PSD incubated with alpha,beta-tubulins pretreated with vincristine. The results suggest that the interactions with assembling microtubules may result in the formation of holes in the PSD, and the rupture of these holes subsequently leads to the formation of smaller PSD fragments.


Higher albumin levels on admission predict better prognosis in patients with confirmed COVID-19.
Research surrounding COVID-19 (coronavirus disease 2019) is rapidly increasing, including the study of biomarkers for predicting outcomes. There is little data examining the correlation between serum albumin levels and COVID-19 disease severity. The purpose of this study is to evaluate whether admission albumin levels reliably predict outcomes in COVID-19 patients. We retrospectively reviewed 181 patients from two hospitals who had COVID-19 pneumonia confirmed by polymerase chain reaction (PCR) testing and radiologic imaging, who were hospitalized between March and July 2020. We recorded demographics, COVID-19 testing techniques, and day of admission labs. The outcomes recorded included the following: venous thromboembolism (VTE), acute respiratory distress syndrome (ARDS), intensive care unit (ICU) admission, discharge with new or higher home oxygen supplementation, readmission within 90 days, in-hospital mortality, and total adverse events. A multivariate modified Poisson regression analysis was then performed to determine significant predictors for increased adverse events in patients with COVID-19 pneumonia. A total of 109 patients (60.2%) had hypoalbuminemia (albumin level < 3.3 g/dL). Patients with higher albumin levels on admission had a 72% decreased risk of developing venous thromboembolism (adjusted relative risk [RR]:0.28, 95% confidence interval [CI]:0.14-0.53, p<0.001) for every 1 g/dL increase of albumin. Moreover, higher albumin levels on admission were associated with a lower risk of developing ARDS (adjusted RR:0.73, 95% CI:0.55-0.98, p = 0.033), admission to the ICU (adjusted RR:0.64, 95% CI:0.45-0.93, p = 0.019), and were less likely to be readmitted within 90 days (adjusted RR:0.37, 95% CI:0.17-0.81, p = 0.012). Furthermore, higher albumin levels were associated with fewer total adverse events (adjusted RR:0.65, 95% CI:0.52-0.80, p<0.001). Admission serum albumin levels appear to be a predictive biomarker for outcomes in COVID-19 patients. We found that higher albumin levels on admission were associated with significantly fewer adverse outcomes, including less VTE events, ARDS development, ICU admissions, and readmissions within 90 days. Screening patients may lead to early identification of patients at risk for developing in-hospital complications and improve optimization and preventative efforts in this cohort.


AnaConDa reflection filter: bench and patient evaluation of safety and volatile anesthetic conservation.
The AnaConDa filter permits administration of volatile anesthetic without the use of an anesthesia machine. It is intended for use in the intensive care unit. We studied the AnaConDa reflection filter on the bench and in anesthetized patients. The bench analysis used a test lung, a gas analyzer, an intensive care ventilator, the AnaConDa filter, and a syringe pump. We studied a range of tidal volume, respiratory rate, and positive end-expiratory pressure values. We simulated errors during syringe refilling and patient transportation. In 15 anesthetized patients, we used the AnaConDa with constant ventilation variables, a constant sevoflurane infusion rate (4-5 mL/h), and two consecutive fresh gas flow levels. In the bench study, the expired volatile anesthetic fraction decreased linearly with respiratory frequency at constant minute ventilation, and decreased markedly in a hyperbolical manner when tidal volume increased at a constant respiratory rate. Changing the positive end-expiratory pressure level and inspiration/expiration ratio did not modify the AnaConDa's performance. Several safety failures were observed: refilling caused a transient change in AnaConDa output because of a pumping effect, and a standard Luer lock made it possible to connect the halogenate syringe on an IV infusion line. In anesthetized patients, reducing fresh gas flow from 8 to 1 L/min led to a median 40% increase in the expired volatile anesthetic fraction. This study shows that the device is generally reliable, but that there are several conditions under which it might deliver more anesthetic than intended.


"Knowing that I had HPV, I literally just shut down": A qualitative exploration of the psychosocial impact of human papillomavirus (HPV) in women living with mental health conditions.
Psychological distress after testing positive for human papillomavirus (HPV) at cervical cancer screening is well documented in the general population. However, little is known about the impact of an HPV-positive result on those with pre-existing mental health conditions, who may be at higher risk of experiencing clinically significant distress. This study explored the psychosocial impact of HPV in women with co-morbid mental health conditions, as well as their experience of cervical screening during the COVID-19 pandemic. Semi-structured telephone interviews were conducted with 22 women aged 27-54 who had tested positive for HPV at routine cervical screening in England, and who reported having at least one mental health condition. Data were analysed using thematic analysis. Being informed of an HPV-positive result increased distress and heightened pre-existing psychological challenges. Psychosocial response and duration of HPV-related distress appeared to be influenced by the ability to regulate emotions, number of consecutive HPV-positive results, interactions with health care professionals, and other life stressors. The experience added further complexity to many women's perceptions of self and self-esteem. Women who had received psychological treatment for their mental health condition were best able to self-manage HPV-related distress by applying learned coping skills. Receiving an HPV-positive result at cervical screening appears to be a distressing experience for women with co-morbid mental health conditions. Future hypothesis-driven research is needed to confirm findings and develop effective interventions to reduce psychosocial burden.


Acute Effects of Esports on the Cardiovascular System and Energy Expenditure in Amateur Esports Players.
Esports is practiced by millions of people worldwide every day. On a professional level, esports has been proven to have a high stress potential and is sometimes considered equivalent to traditional sporting activities. While traditional sports have health-promoting effects through muscle activity and increased energy expenditure, amateur esports could represent a purely sedentary activity, which would carry potentially harmful effects when practiced regularly. Therefore, this study aims to investigate the acute effects of esports on the cardiovascular system and energy expenditure in amateur esports players to show whether esports can be considered as physical strain or mental stress or whether amateur esports has to be seen as purely sedentary behavior. Thirty male subjects participated in a 30-min gaming session, playing the soccer simulation game FIFA 20 or the tactical, first-person multiplayer shooter Counter-Strike: Global Offensive. Respiratory and cardiovascular parameters, as well as energy expenditure, blood glucose, lactate, and cortisol, were determined pre-, during, and post-gaming. There were no significant changes in oxygen uptake, carbon dioxide output, energy expenditure, stroke volume, or lactate levels. Heart rate, blood glucose and cortisol decreased through the intervention until reaching their minimum levels 10 min post-gaming (Cortisolpre: 3.1 ± 2.9 ng/ml, Cortisolpost: 2.2 ± 2.3 ng/ml, p < 0.01; HRmin0.5: 82 ± 11 bpm, HRpost: 74 ± 13 bpm, p < 0.01). A 30-min esports intervention does not positively affect energy expenditure or metabolism in amateur esports players. Therefore, it cannot provide the same health-promoting effects as traditional sports participation, but could in the long-term rather cause the same potentially health-damaging effects as purely sedentary behavior. However, it does not trigger a negative stress response in the players. Deliberate physical activity and exercise routines adapted to these demands should therefore be part of the daily life of amateur esports players.


The Integration of Emotions in Memories: Cognitive-Emotional Distinctiveness and Posttraumatic Stress Disorder.
The current study examined cognitive-emotional distinctiveness (CED), the extent to which emotions are linked with event information, in memories associated with PTSD. Participants either with PTSD (n=68) or without PTSD (n=40) completed a modified multidimensional scaling technique to measure CED for their most negative and most positive events. The results revealed that participants in the PTSD group evidenced significantly lower levels of CED. This group difference remained significant when we limited the analysis to traumatic events that led to a PTSD diagnosis (n=33) in comparison to control participants who nominated a traumatic event that did not result in PTSD (n=32). Replicating previous findings, CED levels were higher in memories of negative events, in comparison to positive events. These results provide empirical evidence that memories associated with PTSD do contain special organizational features with respect to the links between emotions and memory. Implications for understanding and treating PTSD are discussed.


Determinants of tree assemblage composition at the mesoscale within a subtropical eucalypt forest.
A variety of environmental processes, including topography, edaphic and disturbance factors can influence vegetation composition. The relative influence of these patterns has been known to vary with scale, however, few studies have focused on environmental drivers of composition at the mesoscale. This study examined the relative importance of topography, catchment flow and soil in influencing tree assemblages in Karawatha Forest Park; a South-East Queensland subtropical eucalypt forest embedded in an urban matrix that is part of the Terrestrial Ecosystem Research Network South-East Queensland Peri-urban SuperSite. Thirty-three LTER plots were surveyed at the mesoscale (909 ha), where all woody stems ≥1.3 m high rooted within plots were sampled. Vegetation was divided into three cohorts: small (≥1-10 cm DBH), intermediate (≥10-30 cm DBH), and large (≥30 cm DBH). Plot slope, aspect, elevation, catchment area and location and soil chemistry and structure were also measured. Ordinations and smooth surface modelling were used to determine drivers of vegetation assemblage in each cohort. Vegetation composition was highly variable among plots at the mesoscale (plots systematically placed at 500 m intervals). Elevation was strongly related to woody vegetation composition across all cohorts (R2: 0.69-0.75). Other topographic variables that explained a substantial amount of variation in composition were catchment area (R2: 0.43-0.45) and slope (R2: 0.23-0.61). Soil chemistry (R2: 0.09-0.75) was also associated with woody vegetation composition. While species composition differed substantially between cohorts, the environmental variables explaining composition did not. These results demonstrate the overriding importance of elevation and other topographic features in discriminating tree assemblage patterns irrespective of tree size. The importance of soil characteristics to tree assemblages was also influenced by topography, where ridge top sites were typically drier and had lower soil nutrient levels than riparian areas.


Characteristics of young men with clustering risk factors for coronary heart disease: The cardiovascular risk in young finns study.
The majority of coronary heart disease (CHD) arises from a population with only moderately elevated risk factor levels. This study addressed the issue of whether clustering of moderately adverse levels of serum low density lipoprotein cholesterol (LDL-C), serum high density lipoprotein cholesterol (HDL-C), and diastolic blood pressure (DBP) was detectable in children and young adults. Significant clustering of these factors was observed in young men (ages 18-24 years) (Observed/Expected [O/E] ratio = 1.5, p = 0.014), whereas in young women or children no clustering greater than due to chance was found. In males, clustering tended to increase with age. Compared to young women, young men had a higher relative intake of dietary fat, and smoked and used alcohol more often. Compared to men without risk factors, the men at risk were significantly more obese, consumed more dietary fat, and smoked more often. The highest degree of clustering was seen in the highest quartile for the subscapular skinfold thickness (O/E ratio = 2.4). In conclusion, high LDL-C, low HDL-C, and high DBP cluster in young adult males. The clear sex difference observed in clustering may be one of the causes for the susceptibility of adult men to CHD. Am. J. Hum. Biol. 9:565-571, 1997. © 1997 Wiley-Liss, Inc.


Neurostimulation for fecal incontinence after correction of repair of imperforate anus.
We are reporting the case of a 32-year-old female who had suffered from fecal incontinence (FI). She was born with an imperforate anus and a recto-vaginal fistula; she underwent repair at 6 mo of age. At 29 years of age, she was still fecally incontinent despite extensive pelvic floor reeducation. A magnetic resonance imaging and an anal electromyography were performed. Because her symptoms were considered to be probably due to extra-sphincteric implantation of the neo-anus, a redo was performed of the recto-neo-anal intra-sphincteric anastomosis. A neurostimulator device was subsequently implanted for persistent incontinence. Solid and liquid FI resolved, and her quality of life improved markedly. Combining surgery to correct the position of the neo-anus within the anal sphincter complex and neurostimulation could thus become a new approach in cases of refractory FI for patients with imperforate anus as a newborn. Follow-up into adulthood after pediatric imperforate anus surgery should be recommended for adult patients with persistent FI.


Ongoing diversification of the global fish pathogen Piscirickettsia salmonis through genetic isolation and transposition bursts.
The management of bacterial pathogens remains a key challenge of aquaculture. The marine gammaproteobacterium Piscirickettsia salmonis is the etiological agent of piscirickettsiosis and causes multi-systemic infections in different salmon species, resulting in considerable mortality and substantial commercial losses. Here, we elucidate its global diversity, evolution, and selection during human interventions. Our comprehensive analysis of 73 closed, high quality genome sequences covered strains from major outbreaks and was supplemented by an analysis of all P. salmonis 16S rRNA gene sequences and metagenomic reads available in public databases. Genome comparison showed that Piscirickettsia comprises at least three distinct, genetically isolated species of which two showed evidence for continuing speciation. However, at least twice the number of species exist in marine fish or seawater. A hallmark of Piscirickettsia diversification is the unprecedented amount and diversity of transposases which are particularly active in subgroups undergoing rapid speciation and are key to the acquisition of novel genes and to pseudogenization. Several group-specific genes are involved in surface antigen synthesis and may explain the differences in virulence between strains. However, the frequent failure of antibiotic treatment of piscirickettsiosis outbreaks cannot be explained by horizontal acquisition of resistance genes which so far occurred only very rarely. Besides revealing a dynamic diversification of an important pathogen, our study also provides the data for improving its surveillance, predicting the emergence of novel lineages, and adapting aquaculture management, and thereby contributes towards the sustainability of salmon farming.


Cardiorespiratory and sensory responses to exercise in well-controlled asthmatics.
The purpose of this study was to evaluate detailed ventilatory, cardiovascular and sensory responses to cycle exercise in sedentary patients with well-controlled asthma and healthy controls. Subjects included sedentary patients meeting criteria for well-controlled asthma (n = 14), and healthy age- and activity-matched controls (n = 14). Visit 1 included screening for eligibility, medical history, anthropometrics, physical activity assessment, and pre- and post-bronchodilator spirometry. Visit 2 included spirometry and a symptom limited incremental cycle exercise test. Detailed ventilatory, cardiovascular and sensory responses were measured at rest and throughout exercise. Asthmatics and controls were well matched for age, body mass index and physical activity levels. Baseline forced expiratory volume in 1 second (FEV(1)) was similar between asthmatics and controls (98 ± 10 versus 95 ± 9% predicted, respectively, p > 0.05). No significant differences were observed between asthmatics and controls for maximal oxygen uptake (31.8 ± 5.6 versus 30.6 ± 5.9 ml/kg/min, respectively, p > 0.05) and power output (134 ± 35 versus 144 ± 32 W, respectively, p > 0.05). Minute ventilation (V(E)) relative to maximum voluntary ventilation (V(E)/MVV) was similar between groups at maximal exercise with no subjects showing evidence of ventilatory limitation. Asthmatics and controls achieved similar age-predicted maximum heart rates (92 ± 7 versus 93 ± 8% predicted, respectively, p > 0.05). Ratings of perceived breathing discomfort and leg fatigue were not different between groups throughout exercise. The results of this study indicate that sedentary patients with well-controlled asthma have preserved sensory and cardiorespiratory responses to exercise with no evidence of exercise impairment or ventilatory limitation.


Testicular torsion and low relative humidity in a tropical country.
One hundred and thirty one patients with testicular torsion were reviewed retrospectively to investigate the association of testicular torsion with air temperature and low relative humidity in Zaria, Nigeria. The incidence of testicular torsion was significantly increased during the harmattan season (November to February), when relative humidity is low and temperature decreased. Relative humidity was more closely correlated with the incidence of testicular torsion than was air temperature. Testicular torsion is a major contributor to male infertility in Zaria, and further study of its causes is required.


Pathogenesis-oriented approaches for the management of corticosteroid-resistant or relapsedprimary immune thrombocytopenia.
Primary immune thrombocytopenia (ITP) is a complex autoimmune disorder in which the patient's immune system reacts with platelet autoantigens resulting in immune-mediated platelet destruction and/or suppression of platelet production. Corticosteroids can induce sustained remission rates in 50% to 75% of patients with active ITP. For these patients who are unresponsive to glucocorticoids, or relapsed after an initial response, multiple second-line treatment modalities can be chosen. However, how to make an optimal therapeutic strategy for a specific patient still remains a major challenge. As the pathogenetic heterogeneity of the ITP is increasingly identified, pathogenesis-oriented approach might offer an opportunity to improve the outcome of corticosteroid-resistant or relapsed ITP.


Use of 5% sulfamylon (mafenide) solution after excision and grafting of burns.
In previous reports, 5% sulfamylon solution has been utilized on unexcised burns and granulation tissue. We prospectively evaluated 67 burn patients to determine graft take and the incidence of side effects with use of sulfamylon solution dressings after excision and grafting. Of patients excised and grafted, the mean graft take for a total of 100 procedures was 86%. Rash occurred in 18% of patients and sulfamylon was discontinued with no sequelae. Twenty-five percent had at least one positive fungal wound culture, yet only 3% required treatment for candidemia. Those patients who developed a rash and fungal colonization had a significantly larger percent burn and were treated with sulfamylon for a longer period of time. Pain intensity was rated on a Visual Analog Scale with a mean score of 2.4; in no case was the pain considered severe enough by the patient to terminate treatment. Acidosis was present in 3% of patients but felt to be unrelated to the sulfamylon treatment. As an antimicrobial agent, 5% sulfamylon solution is a viable alternative for fresh autografts with excellent graft take and acceptable side effects.


A late adenovirus factor induces eIF-4E dephosphorylation and inhibition of cell protein synthesis.
Adenovirus prevents host cell protein synthesis during its late phase of replication in large part by causing the underphosphorylation of translation initiation factor eIF-4E, a component of initiation factor eIF-4F (cap-binding protein complex). Late adenovirus mRNAs are preferentially translated because they possess a reduced requirement for eIF-4F. This study continues the characterization of the mechanism by which adenovirus inhibits cellular protein synthesis. First it is shown that adenovirus blocks the addition of phosphate to eIF-4E rather than enhancing its removal, establishing that the virus impairs a signalling pathway or protein kinase activity involved in eIF-4E phosphorylation. It is then shown that shutoff of cell protein synthesis and translation of late viral mRNAs are uncoupled, in that shutoff actually occurs a short time (1 to 3 h) after late adenovirus mRNAs are already undergoing translation. Finally, by using a variety of genetic mutants stalled at different stages in the viral life cycle, it was found that dephosphorylation of eIF-4E and inhibition of cell translation are not caused by early adenovirus gene products acting at late times or by events related to viral DNA replication. Instead, it is shown that inhibition of eIF-4E phosphorylation and cell translation are mediated upon activation of the viral major late transcription unit. These and other results presented indicate that the adenovirus signal which induces eIF-4E dephosphorylation and shutoff of cell protein synthesis is linked either to an activity of one or more late viral polypeptides, to double-stranded RNA produced by opposition of the early and late viral transcription units, or to both.


Current tendencies in the nutrition of women and pregnant women of industrial region of ukraine and their influence on microelements supply.
Introduction: During recent decades there has been observed a violation in the structure of nutrition of the population with a significant decrease in the consumption of biologically valuable products, resulting in the development of the so-called "latent hunger", particularly in sensitive groups of population - women of reproductive age and pregnant women. The aim: To study nutritional peculiarities and the level of biotic and abiotic trace elements intake into the body of the female population, residents of the industrial region. Materials and methods: Physiological and hygienic nutritional assessment was carried out in 185 women and pregnant women, residents of industrial and non-industrial cities of Dnipropetrovsk region of Ukraine. Actual nutrition was studied using the 24-hour food reproduction method recommended by the WHO. Calculation of the content of trace elements in the diet was carried out using well-known techniques, followed by the assessment of their compliance by the level of permissible daily load for toxic trace elements - lead and cadmium and daily requirements - for essential elements, zinc and copper. Results: Studies performed have found significant violations of the requirements of rational nutrition in relation to its regime and the average daily food package, which is excessive in consumption of bread and bakery products, sugar and confectionery products by 9,9%-67,6% and is characterized by a shortage of other groups of foodstuff with various degree of evidence. On the background of deformation of nutrition there is observed an increased income of xenobiotics - lead and cadmium into the female body, which is by 3,8-7,8 times higher than the level of so-called "optimal one". At the same time the level of income of essential micronutrients - zinc and copper was by 9,5-45,7% lower than the RDI. Conclusions: Nutrition of fertile age and pregnant women, residents of industrial regions of Ukraine, does not meet the requirements of rational nutrition due to violations in diet, in quantitative and qualitative nutritional budget, excessive intake of xenobiotics and deficiency of essential micronutrients.


[Forensic pediatric autopsy and medical responsibility].
The integrity of the human body is an intangible human right acknowledged to persist after death. Violating the integrity of the human corpse is a penal act sanctioned by the 1994 version of the French Penal Code. There are only three exceptions: for science (medical autopsy), for public health (organ removal for graft), and for justice (forensic autopsy). The parents' written agreement is needed to perform a pediatric medical autopsy but not for a forensic autopsy. For the forensic pathologist, taking oath does not imply an authorization to override the precepts of humanity nor the Hippocratic Oath. The forensic pathologist remains subject to civil and penal law. This is why forensic pathologists have an obligation of excellence besides their obligation of means. A pediatric autopsy is a specific procedure compared with an adult autopsy and requires specific training. Forensic pathologists, like all pathologists, who does not have sufficient expertise should not perform pediatric autopsy but rather call in a qualified pediatric pathologist. Tissues or organs removed during a forensic autopsy can be used only for diagnostic purposes, and the parents' agreement must be obtained for any other use.


Differences in health-related quality of life between elderly and younger patients on hemodialysis.
It has been demonstrated that elderly patients have a great capacity of adaptation to renal replacement therapy (RRT). The aim of this study was to assess the health-related quality of life (HRQoL) of a cohort of patients at 3 and 12 months after the start of hemodialysis, searching for differences between elderly (aged>or=65 years) and younger (aged <65 years) patients. This was a longitudinal prospective study of 93 patients starting RRT. HRQoL was assessed using the SF-36 health survey and the physical symptom dimension of the Kidney Disease Questionnaire (KDQ) at 3 and 12 months from the start of RRT. Physical component summary (PCS), mental component summary (MCS) and standardized scores, in which a lower score indicated lower HRQoL, by age and sex were obtained. Mean (SD) age was 66 years (12.26 years). At 3 months, differences between younger patients and elderly ones were statistically significant in the general health dimension, and at 12 months in physical functioning, role physical, general health dimensions and PCS, indicating less loss of HRQoL in elderly patients. At 3 months it was found that the functional state measured on the Karnofsky scale was independently associated with PCS (p=0.003), and hematocrit to MCS (p=0.036). At 1 year, PCS was independently associated with age (p=0.043) and Karnofsky score (p=0.039). Using scores standardized by age and sex, elderly patients had less loss of HRQoL in the physical aspects, than younger patients at 1 year from the start of hemodialysis.


Influence of recording site on CMAP amplitude on its variation over a length of nerve.
The distinctions between blocking, abnormal temporal dispersion, and normal conduction require delineation of the normal change in amplitude of the compound muscle action potential (CMAP) over a length of nerve. Effects of the recording site on CMAP amplitude and on its variation were studied in median and ulnar nerves of 13 healthy subjects. CMAPs were recorded from three sites: halfway along the muscles and 1 cm distal and proximal. Elbow-wrist amplitude percentages (CMAP%) were calculated. CMAP amplitudes varied considerably between sites and subjects. Amplitudes were maximal at the middle site in only 16 of 26 nerves. The site of maximal amplitude could not be identified on the basis of thumb anatomy. CMAP% was not related to CMAP amplitude, and differed by up to 32% between adjacent sites. CMAP formation involves spatial factors (electrode site, limb position, and limb anatomy), temporal factors (dispersion), and their interaction, explaining why CMAP% can exceed 100%. The site of the recording electrode affects CMAP amplitude and CMAP% to clinically relevant degrees. Standardization of the recording site may improve reliability of CMAP% studies.


A Novel Mobilizing Tool Based on the Conjugative Transfer System of the IncM Plasmid pCTX-M3.
Conjugative plasmids are the main players in horizontal gene transfer in Gram-negative bacteria. DNA transfer tools constructed on the basis of such plasmids enable gene manipulation even in strains of clinical or environmental origin, which are often difficult to work with. The conjugation system of the IncM plasmid pCTX-M3 isolated from a clinical strain of Citrobacter freundii has been shown to enable efficient mobilization of oriTpCTX-M3-bearing plasmids into a broad range of hosts comprising Alpha-, Beta-, and Gammaproteobacteria We constructed a helper plasmid, pMOBS, mediating such mobilization with an efficiency up to 1,000-fold higher than that achieved with native pCTX-M3. We also constructed Escherichia coli donor strains with chromosome-integrated conjugative transfer genes: S14 and S15, devoid of one putative regulator (orf35) of the pCTX-M3 tra genes, and S25 and S26, devoid of two putative regulators (orf35 and orf36) of the pCTX-M3 tra genes. Strains S14 and S15 and strains S25 and S26 are, respectively, up to 100 and 1,000 times more efficient in mobilization than pCTX-M3. Moreover, they also enable plasmid mobilization into the Gram-positive bacteria Bacillus subtilis and Lactococcus lactis Additionally, the constructed E. coli strains carried no antibiotic resistance genes that are present in pCTX-M3 to facilitate manipulations with antibiotic-resistant recipient strains, such as those of clinical origin. To demonstrate possible application of the constructed tool, an antibacterial conjugation-based system was designed. Strain S26 was used for introduction of a mobilizable plasmid coding for a toxin, resulting in the elimination of over 90% of recipient E. coli cells.IMPORTANCE The conjugation of donor and recipient bacterial cells resulting in conjugative transfer of mobilizable plasmids is the preferred method enabling the introduction of DNA into strains for which other transfer methods are difficult to establish (e.g., clinical strains). We have constructed E. coli strains carrying the conjugation system of the IncM plasmid pCTX-M3 integrated into the chromosome. To increase the mobilization efficiency up to 1,000-fold, two putative regulators of this system, orf35 and orf36, were disabled. The constructed strains broaden the repertoire of tools for the introduction of DNA into the Gram-negative Alpha-, Beta-, and Gammaproteobacteria, as well as into Gram-positive bacteria such as Bacillus subtilis and Lactococcus lactis The antibacterial procedure based on conjugation with the use of the orf35- and orf36-deficient strain lowered the recipient cell number by over 90% owing to the mobilizable plasmid-encoded toxin.


HLA-DQ2/DQ8 and HLA-DQB1*02 homozygosity typing by real-time polymerase chain reaction for the assessment of celiac disease genetic risk: evaluation of a Spanish celiac population.
Celiac disease (CD) is a complex autoimmune disorder caused by ingestion of gluten in genetically susceptible individuals. Different genetic risk factors have been identified, but virtually all patients are human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 positive. We describe a new, fast, accurate and simple real-time polymerase chain reaction (PCR)-based assay for the genotyping and homozygosity analysis of the CD-related HLA alleles. The assay overcomes the major limitations of protocols currently in use, allowing HLA-DQ2/DQ8 genotyping by using only three real-time PCR reactions. For the appraisal of DQ2 homozygosity, only one more reaction is needed. These reactions are easily automated and suitable for large screening studies in diagnostic procedures, as it is demonstrated by their successful application in our HLA diagnostic laboratory. Finally, we assessed the clinical relevance of this real-time PCR-based assay by studying a cohort of fully characterized patients. As expected, all CD patients had at least one of the CD-associated alleles, and the highest CD risk was indicated by the presence of the HLA-DQ2.5 heterodimer (HLA-DQA1*05-DQB1*02) with HLA-DQB1*02 in homozygosity.


Pros and Cons of Telemedicine for Inherited Metabolic Disorders in a Developing Country During the COVID-19 Pandemic.
Introduction: The COVID-19 pandemic has led to considerable changes in the health care system. Experts suggested that individuals protect themselves through social isolation during the pandemic, and consequently, the importance of telemedicine came to be understood for patients with chronic diseases. Telemedicine started to be used in developing countries where the appropriate infrastructure was lacking earlier. The present study investigates the level of satisfaction of patients with inherited metabolic disorders (IMDs) with telemedicine. Methods: This prospective study was conducted by making use of a new video appointment program that ensures the privacy of the patients in video-based consultations. The sociodemographic characteristics of the patients, their clinical status, their views on the telemedicine system, and their levels of satisfaction were questioned. Results: Overall, 174 patients were included in the study. The most common diagnoses were aminoacidopathies, lipid metabolism disorders, biotinidase deficiency, and lysosomal/peroxisomal diseases. More than half of the parents (67.6%) who lived in another city reported accommodation issues when coming to the hospital, and most believed telemedicine would save them time (93.1%) and money for travel (81.6%). The lack of laboratory and radiological tests (83.9%) was stated as the main disadvantage by most parents. Almost all the parents (96.6%) stated that they would opt for telemedicine if it became available in daily practice. The overall satisfaction rate was 94.6 (±10.1)/100. Conclusions: The present research is the most extensive cohort study to date assessing telemedicine in patients with IMDs and it highlights the importance of telemedicine, especially in developing countries during the COVID-19 pandemic.


Poor accuracy of stroke scoring systems for differential clinical diagnosis of intracranial haemorrhage and infarction.
The differentiation of cerebral infarction and cerebral haemorrhage is the most important first step in the management of acute stroke, because clinical management of the two disorders differs substantially. The Guy's Hospital and Siriraj stroke diagnostic scores were developed to aid clinicians in this decision. We have tested the performance of the two scores on a group of 1059 patients admitted to the acute stroke unit (ASU) at the Western Infirmary, Glasgow, with suspected stroke between May, 1990, and December, 1993. The diagnosis was confirmed as stroke by computed tomography (CT) scanning or necropsy (n = 10) in 991 patients. For each clinical score we subjectively identified the cut-off point that maximised sensitivity to cerebral haemorrhage with the smallest loss of specificity. At its optimum cut-off point the Guy's Hospital score had a sensitivity for the diagnosis of haemorrhage of 70% and specificity of 64%. The corresponding figures for the Siriraj score at its optimum cut-off point were 68% sensitivity and 64% specificity. The overall predictive accuracy of both scores was 64%. The greater complexity of the Guy's Hospital score (thirteen variables included) did not result in substantially superior performance to the Siriraj score (five variables). This validation study suggests that neither score is useful for exclusion of haemorrhage before anticoagulant treatment is initiated or as a diagnostic screening procedure for trials of low-risk treatments such as aspirin. Our findings emphasise the need for routine CT scanning in this setting, since this method remains the most accurate for differentiating between haemorrhage and infarction.


Munc13-independent vesicle priming at mouse photoreceptor ribbon synapses.
Munc13 proteins are essential regulators of exocytosis. In hippocampal glutamatergic neurons, the genetic deletion of Munc13s results in the complete loss of primed synaptic vesicles (SVs) in direct contact with the presynaptic active zone membrane, and in a total block of neurotransmitter release. Similarly drastic consequences of Munc13 loss are detectable in hippocampal and striatal GABAergic neurons. We show here that, in the adult mouse retina, the two Munc13-2 splice variants bMunc13-2 and ubMunc13-2 are selectively localized to conventional and ribbon synapses, respectively, and that ubMunc13-2 is the only Munc13 isoform in mature photoreceptor ribbon synapses. Strikingly, the genetic deletion of ubMunc13-2 has little effect on synaptic signaling by photoreceptor ribbon synapses and does not prevent membrane attachment of synaptic vesicles at the photoreceptor ribbon synaptic site. Thus, photoreceptor ribbon synapses and conventional synapses differ fundamentally with regard to their dependence on SV priming proteins of the Munc13 family. Their function is only moderately affected by Munc13 loss, which leads to slight perturbations of signal integration in the retina.


Lipaemic serum in Hb E-Beta thalassaemia major: A rare case of hypertriglyceridaemia thalassaemia syndrome.
A 1-year-old Malay girl presented with pallor, failure to thrive and hepatosplenomegaly. Her blood was sent for thalassaemia screening and it was incidentally found that her blood appeared lipaemic. Primary and secondary causes of hyperlipidaemia were investigated. Her blood was sent for fasting lipid profile, thyroid function test (TFT), fasting plasma glucose (FPG), liver function test (LFT), renal profile (RP) and HIV screening. Lipaemic interference was removed by high-speed centrifugation. She is a product of non-consanguineous marriage. She is staying together with her stepfather who is HIV positive. Her mother's infective status was negative with no dyslipidaemic features and a normal lipid profile. Lipid profile of her biological father was not known. No other lipid stigmata such as eruptive xanthoma or lipaemia retinalis was seen in the patient. Haemoglobin analysis showed Hb E-Beta thalassaemia major. Her triglycerides was 9.05 mmol/L with normal total cholesterol, 2.85 mmol/L and high-density lipoprotein cholesterol (HDL-c), 0.26 mmol/L. Calculated low-density lipoprotein cholesterol (LDL-c) was invalid as triglycerides was >4.5 mmol/L. TFT, RP, FPG, LFT were normal and HIV status was negative. She was transfused with 10 ml/kg packed cell and her blood post transfusion appeared non lipaemic. Primary hypertriglyceridaemia was excluded based on insignificant family history of dyslipidaemia. Secondary causes of hypertriglyceridaemia were ruled out based on unremarkable laboratory investigations. Thus, we conclude that this patient is having hypertriglyceridaemia thalassaemia syndrome (HTS) which is a rare disorder with unknown pathogenesis. Further research may be required to explore this unknown association.


The glial sodium-calcium exchanger: a new target for nitric oxide-mediated cellular toxicity.
The plasma membrane Na(+)/Ca(2+) exchanger (NCX) is a bidirectional ion transporter that couples the translocation of Na(+) in one direction with that of Ca(2+) in the opposite direction. This system contributes to the regulation of intracellular Ca(2+) concentration via the forward mode (Ca(2+) efflux) or the reverse mode (Ca(2+) influx). We have previously demonstrated that the Ca(2+) paradox, an in vitro reperfusion model, causes the sustained activation of the reverse mode of the NCX, the disruption of Ca(2+) homeostasis, and subsequent delayed apoptotic-like death in astrocytes. In addition, we found that the nitric oxide (NO)-cyclic GMP signaling pathway inhibits Ca(2+) paradox-mediated astrocyte apoptosis, while a high concentration of NO induces cytotoxicity. In this way, Ca(2+) and NO may work together in the pathogenesis of several cells in the central nervous system. Concerning the role of NCX in NO cytotoxicity, we have found, using the specific inhibitor of NCX 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400), that NCX is involved in NO-induced cytotoxicity in cultured microglia, astrocytes, and neuronal cells. This review summarizes the pathological roles of the NCX as a new target for NO-mediated cellular toxicity, based on our studies on NO-NCX-mediated glial toxicity.


Cartilaginous end plates: Quantitative MR imaging with very short echo times-orientation dependence and correlation with biochemical composition.
To measure the T2* of the human cartilaginous end plate by using magnetic resonance (MR) imaging with very short echo times and to determine the effect of the orientation of the end plate on T2* and on relationships between T2* and biochemical composition. This study was exempt from institutional review board approval, and informed consent was not required. Thirty-four samples of three cadaveric lumbar spines (from subjects who died at ages 51, 57, and 66 years) containing cartilaginous end plates and subchondral bone were prepared. Samples were imaged with a 3-T imager for T2* quantification by using a three-dimensional very short echo time sequence (repetition time msec/echo times msec, 30/0.075, 2, 5, 12, 18). Samples were imaged with the end plate at three orientations with respect to the constant magnetic induction field: 0°, 54.7°, and 90°. After imaging, the cartilage was assayed for its water, glycosaminoglycan, and collagen content. Pearson correlations were used to investigate the effect of orientation on the relationships between T2* and biochemical composition. T2* was significantly longer when measured at an orientation of 54.7° (21.8 msec ± 2.8 [± standard error of the mean]) than at 0° (10.0 msec ± 0.7, P < .001) or 90° (9.9 msec ± 0.4, P < .001). At 54.7°, T2* was highly correlated with glycosaminoglycan content (r = 0.85, P < .001), the collagen-to-glycosaminoglycan ratio (r = -0.79, P < .001), and water content (r = 0.62, P = .02); at 0° and 90°, there were no significant differences in these relationships, with a minimum P value of .19. T2* evaluation can allow noninvasive estimation of the degeneration of the cartilaginous end plate; however, the accuracy of T2*-based estimates of biochemical composition depends on the orientation of the end plate.


Trypanosoma brucei ornithine decarboxylase: enzyme purification, characterization, and expression in Escherichia coli.
Ornithine decarboxylase from the African trypanosome is an important target for antitrypanosomal chemotherapy. Despite this, the enzyme had not been previously purified or extensively characterized as it is a very low level protein. In this paper we describe the purification of Trypanosoma brucei brucei ornithine decarboxylase from bloodstream form trypomastigotes by 107,000-fold to a specific activity of 2.7 x 10(6) nmol CO2/h/mg of protein in the parasite. T. brucei ornithine decarboxylase had a native molecular weight of 90,000 and a subunit molecular weight of 45,000. The isoelectric point of the protein was 5.0. The Km for ornithine was 280 microM and the Ki for the irreversible inhibitor alpha-difluoromethylornithine (DFMO) was 220 microM with a half-time of inactivation at saturating DFMO concentration of 2.7 min. T. brucei ornithine decarboxylase appears similar to mouse ornithine decarboxylase, further supporting our previous suggestion that the selective toxicity of DFMO to the parasite is not due to catalytic differences between the two proteins. Although a small quantity of T. brucei ornithine decarboxylase was purified from T. brucei, extensive structural and kinetic studies will require a more ample source of the enzyme. We therefore expressed our previously cloned T. brucei ornithine decarboxylase gene in Escherichia coli using a vector that contains an inducible lambda promoter. T. brucei ornithine decarboxylase activity was induced in E. coli to levels that were 50 to 200 fold of that present in the long-slender bloodstream form of T. brucei. Ornithine decarboxylase activity in the crude E. coli lysate was 1500-6000 nmol of CO2/h/mg of protein and represented 0.05-0.2% of the total cell protein. The recombinant T. brucei ornithine decarboxylase was purified to apparent homogeneity from the transformed E. coli. The purified recombinant enzyme had kinetic and physical properties essentially identical to those of the native enzyme.


Management of asthma in children.
Management of chronic asthma has changed significantly in recent years. Most of the changes in management are the result of an increased recognition of the importance of the inflammatory component in the pathogenesis and treatment of asthma. The National Heart, Lung, and Blood Institute issued guidelines for the management of asthma in 1991. Beta agonists, cromolyn and nedocromil are mainstays of treatment in patients with mild to moderate asthma. Inhaled steroids are useful in the treatment of patients with moderate to severe asthma. Nonpharmacologic management of asthma includes avoidance of allergens and irritants, the use of peak flow meters, and patient and family education.


T-cell-based Immunotherapy: Adoptive Cell Transfer and Checkpoint Inhibition.
Tumor immunotherapy has had demonstrable efficacy in patients with cancer. The most promising results have been with T-cell-based therapies. These include adoptive cell transfer of tumor-infiltrating lymphocytes, genetically engineered T cells, and immune checkpoint inhibitor antibodies. In this review, we describe the different T-cell-based strategies currently in clinical trials and put their applications, present and future, into perspective.


High expression of two genes selected by iAFLP: a new prognostic factor of estrogen receptor-positive breast cancer.
To detect patients with poor prognosis among those with estrogen receptor (ER)-positive breast cancer, who generally show good prognosis, we analyzed gene expression profiles of 35 ER-positive tumors by using a high through-put RT-PCR technique, iAFLP. High expression of six genes out of 7,508 was related to poor prognosis in this group. From these six genes, NFE2L2 and TIAL1 were selected as genes associated with poor prognosis by means of a validation study with another set of 56 ER-positive breast cancers. High expression of these two genes was determined to be significantly predictive for poor prognosis of patients with ER-positive breast cancer, and may help to achieve optimal selection of adjuvant treatment for such patients.


The relation between air pollution and respiratory deaths in Tehran, Iran- using generalized additive models.
Some epidemiological evidence has shown a relation between ambient air pollution and adverse health outcomes. The aim of this study was to investigate the effect of air pollution on mortality from respiratory diseases in Tehran, Iran. In this ecological study, air pollution data was inquired from the Tehran Province Environmental Protection Agency and the Tehran Air Quality Control Company. Meteorological data was collected from the Tehran Meteorology Organization and mortality data from the Tehran Cemetery Mortality Registration. Generalized Additive Models (GAM) was used for data analysis with different lags, up to 15 days. A 10-unit increase in all pollutants except CO (1-unit) was used to compute the Relative Risk of deaths. During 2005 until 2014, 37,967 respiratory deaths occurred in Tehran in which 21,913 (57.7%) were male. The strongest relationship between NO2 and PM10and respiratory death was seen on the same day (lag 0), and was respectively (RR = 1.04, 95% CI: 1.02-1.07) and (RR = 1.03, 95% CI: 1.02-1.04). O3 and PM2.5 had the strongest relationship with respiratory deaths on lag 2 and 1 respectively, and the RR was equal to 1.03, 95% CI: 1.01-1.05 and 1.06, 95% CI: 1.02-1.10 respectively. NO2, O3, PM10 and PM2.5 also showed significant relations with respiratory deaths in the older age groups. The findings of this study showed that O3, NO2, PM10 and PM2.5 air pollutants were related to respiratory deaths in Tehran. Reducing ambient air pollution can save lives in Tehran.


Small-molecule inhibitors of NF-kappaB for the treatment of inflammatory joint disease.
Recent advances in our understanding of the role of cytokine networks in inflammatory processes have led to the development of novel biological agents for the treatment of chronic inflammatory diseases. At the present time, significant efforts are focused on characterizing the complex signal transduction cascades that are activated by these cytokines and, in turn, regulate their expression. The transcription factor NF-kappaB is a pivotal regulator of the inducible expression of key proinflammatory mediators, and activated NF-kappaB has been observed in several debilitating inflammatory disorders, including rheumatoid arthritis and osteoarthritis. In light of its central role in inflammation, the identification of inhibitors of NF-kappaB should provide novel therapeutics for the treatment of chronic joint disease.


Issues Most Important to Parents After Their Children's Suicide Attempt: A Pilot Delphi Study.
Suicide is the third leading cause of death for people aged 15-24 and results in 4,600 lives lost each year. One important risk factor for completed suicide is a nonlethal suicide attempt. To date, little research has been conducted on the needs of parents of adolescents who have made a nonlethal suicide attempt. The goal of this pilot study was to describe the most important concerns of parents whose children have made a nonlethal suicide attempt from the perspective of adolescent mental health professionals. A two-round Delphi technique was utilized with an interdisciplinary panel of adolescent mental health experts to gain consensus on what issues are most important to parents after their children's suicide attempt. Panelists described the following as most important to parents after their children's nonlethal suicide attempt: keeping their children safe; identifying what caused or triggered the suicide attempt; strategies to prevent another suicide attempt; and communication and building trust for the future. An advanced understanding of the issues most important to parents whose children have made a nonlethal suicide attempt has implications for clinicians in creating acceptable and useful interventions aimed at preventing youth suicide.


Irisin Improves Myocardial Performance and Attenuates Insulin Resistance in Spontaneous Mutation (Leprdb ) Mice.
Irisin, a newly identified peptide, is critical to regulating metabolism, thermogenesis, and reducing oxidative stresses. Our recent works demonstrated that irisin protected the heart against myocardial ischemic injury and preserved the function of mitochondria. However, whether irisin preserves myocardial performance and attenuates insulin resistance in type II diabetes remains unknown. Effects of irisin on type II diabetes-induced cardiac dysfty unction and insulin resistance in db/db mice were studied. Methods: Homozygous db/db mice (n=5/each group) for spontaneous mutation (Leprdb ) and heterozygous (heterozygous) mice (n=5/each group) for control were used to assess for cardiac performance and impairment of insulin resistance. Homozygous and heterozygous controls received a treatment with either irisin (100 mg/kg, intraperitoneal injection, every other day) or vehicle control (PBS) for 4 weeks at 16 weeks of age. Insulin tolerance test and glucose tolerance test were employed to determine insulin resistance in mice. Cardiac function was assessed by echocardiography. Metabolic features including hyperglycemia and body growth were also examined. Immunohistochemical analysis was employed to determine myocardial hypertrophy and interstitial fibrosis. Immunoblots were employed to determine the signaling pathway associated with irisin treatment. Homozygous db/db mice developed an impairment in insulin sensitivity as indicated by Insulin tolerance test (ITT), glucose tolerance test (GTT) (p<0.05 vs non-irisin treatment), hyperglycemia (p<0.05 vs heterozygous control), and hyperinsulinemia (serum insulin: 0.81 ± 0.065 ng/ml in heterozygous control vs. 8.33 ± 0.69 ng/ml in homozygous db/db control, p<0.0001), which were attenuated by the administration of irisin (serum insulin 8.32 ± 0.68 ng/ml in homozygous db/db control vs 6.56 ± 0.38 ng/ml in homozygous db/db irisin treatment, p<0.0001). Furthermore, as compared to heterozygous control, db/db mice manifested a depression in cardiac performance [ejection fraction (EF): 91.9% ± 0.44 in heterozygous control vs 79.1% ± 2.0 in homozygous db/db control, p< 0.001] in associated myocardial remodeling (cardiac fibrosis 1.89% ± 0.09 in heterozygous control vs. 5.39% ± 0.22 in homozygous db/db control, p<0.001). Notably, the depression of cardiac function in EF (79.2% ± 2.0 homozygous db/db control vs. 88.6% ± 1.9 in homozygous db/db + irisin, p<0.01) and fractional shortening (FS) (42.2% ± 1.8 in homozygous db/db control vs. 53.2% ± 2.7 in homozygous db/db+irisin, p<0.01) and remodeling were markedly attenuated by the administration of irisin. Western blotting shows that irisin treatment prevented an approximate two-fold decrease in p38 phosphorylation and increase in histone deacetylase 4 (HDAC4) in the homozygous db/db myocardium (p<0.05 vs homozygous db/db control). Irisin preserves myocardial performance and insulin resistance in db/db mice, which is related to p38 phosphorylation and HDAC reduction.


Selenium deficiency associations with gender, breed, serum vitamin E and creatine kinase, clinical signs and diagnoses in horses of different age groups: a retrospective examination 1996-2011.
Selenium and vitamin E deficiency have been associated with nutritional myopathy, more commonly known as white muscle disease (WMD) in horses. However, correlations between selenium concentrations and presenting clinical signs, age, breed, gender, serum vitamin E, creatine kinase (CK) and final diagnosis, have not previously been evaluated. To determine the number of hospitalised horses in 3 age groups that were selenium tested and the proportions of horses with categorised presenting clinical signs; the association/odds risk of final diagnosis with selenium deficiency and to examine the association between selenium status, vitamin E status and serum CK in adult horses. Two hundred and seventy-one hospitalised horses with a selenium concentration evaluated between 1996 and 2011 were examined retrospectively. Records were examined in order to ascertain selenium and vitamin E concentrations, age, breed, gender, CK values, presenting clinical signs and final diagnosis. Data were analysed with proportions, Fisher's exact t test, odds ratios and multivariate linear regressions. Within the < 30 day old age group, 13/20 animals had low selenium concentrations. There were 18/42 horses in the 30 days to 2 years old age group with low selenium and 77/209 horses more than 2 years of age with low selenium. There was an association between low selenium and myopathy in the < 30-day-old animals (P = 0.017), all of which were classified as having WMD. No associations were identified between nutritional myopathy and selenium status in horses between 30 days and 2 years of age or in horses more than 2 years of age. This study indicates that WMD occurs most commonly in foals < 30 days old and is associated with low selenium concentrations (7 out of 8 affected foals had blood Selenium levels < 1.26 microm/l). Low serum selenium concentrations are common in hospitalised adult horses while nutritional myopathy is rare in these animals.