Biology of Triatoma carcavalloi Jurberg, Rocha & Lent, 1998 under laboratory conditions.
Triatoma carcavalloi is a wild species that is found in sympatry with Triatoma rubrovaria and Triatoma circummaculata, which are vectors of Trypanosoma cruzi currently found in rural areas of Rio Grande do Sul, Brazil. Fertility was assessed and to determine the incubation period, the eggs were observed until hatching. The first meal was offered to 1st stage nymphs. The intermolt period was also determined. The number of blood meals was quantified at each nymphal stage and the resistance to fasting as the period between ecdysis and death. Mortality was assessed and longevity was determined by recording the time that elapsed from molting to the adult stage and until death. The developmental cycle was assessed by recording the length in days of each stage from molting to adult hood. The average incubation period was 22.7 days. The average first meal occurred 3.1 days after hatching. The 5th stage nymph to adult intermolting period was the longest at 193.4 days. The average number of feedings during nymphal development was 13.4. The resistance to fasting assay indicated that the 3rd, 4th and 5th stage nymphs presented higher resistance than did adults. The highest mortality rate was observed in the 3rd stage nymphs (22.2%). The average length of adult survival was 25.6 weeks, and the average total life cycle lasted 503.4 days. This study is the first report on the biology of T. carcavalloi that fed on mice. The presented findings expand the bionomic knowledge of these species.


General characteristics of the use of silicon diode detectors for clinical dosimetry in proton beams.
The properties of silicon diode detectors, used for dosimetry in clinical proton beams, were investigated with special regard to the measurement of relative dose distributions in water. Different types of silicon diode detector were studied, and the resulting distributions of detector signal versus depth in the water phantom were compared with the corresponding distributions obtained with a plane-parallel NACP ionization chamber. The measurements were performed in a proton beam with an initial energy of 173 MeV. It is shown that the Hi-p silicon detector gives a signal which is proportional to the ionization density in the silicon crystal in all parts of the Bragg curve, and for all levels of accumulated dose to the detector. This is in contrast to detectors based on n-type silicon, or on low resistivity p-type silicon. After pre-irradiation, these latter detectors show a stopping-power dependent recombination, yielding an increase in the detector signal per unit dose with increasing LET. This effect leads to an over-response in the Bragg peak, which increases gradually with the accumulated detector dose. Using the Hi-p silicon diode detector, the depth ionization distribution was found to be equal to the distribution obtained with the plane-parallel NACP ionization chamber at all pre-irradiation levels, within the experimental accuracy. This implies that the quotient between the ionization in the detector and the absorbed dose to the surrounding water is equal for these detectors.


Single-Cell RNA Sequencing Reveals Heterogeneity and Functional Diversity of Lymphatic Endothelial Cells.
Lymphatic endothelial cells (LECs) line the lymphatic vasculature and play a central role in the immune response. LECs have abilities to regulate immune transport, to promote immune cell survival, and to cross present antigens to dendritic cells. Single-cell RNA sequencing (scRNA) technology has accelerated new discoveries in the field of lymphatic vascular biology. This review will summarize these new findings in regard to embryonic development, LEC heterogeneity with associated functional diversity, and interactions with other cells. Depending on the organ, location in the lymphatic vascular tree, and micro-environmental conditions, LECs feature unique properties and tasks. Furthermore, adjacent stromal cells need the support of LECs for fulfilling their tasks in the immune response, such as immune cell transport and antigen presentation. Although aberrant lymphatic vasculature has been observed in a number of chronic inflammatory diseases, the knowledge on LEC heterogeneity and functional diversity in these diseases is limited. Combining scRNA sequencing data with imaging and more in-depth functional experiments will advance our knowledge of LECs in health and disease. Building the case, the LEC could be put forward as a new therapeutic target in chronic inflammatory diseases, counterweighting the current immune-cell focused therapies.


Methods for estimation of statistical properties of envelopes of ultrasonic echoes from myocardium.
Several investigators have characterized various forms of heart disease from the statistical properties of envelopes of ultrasonic echos from myocardium. In particular, the mean-to-standard deviation ratio (MSR), skewness, and kurtosis of the envelope probability density function have been used for the detection of myocardial ischemia, infarction, reperfusion, and hypertrophy. In this paper, the effects of phenomena other than tissue acoustic properties upon estimates of statistical parameters are investigated. These include system characteristics (center frequency, bandwidth, beam width, etc.), sample volume dimensions, and tissue velocity. In myocardium, relatively small amounts of tissue are available for interrogation. It is shown that, under these limited data acquisition conditions, substantial systematic biases in the estimates of statistical parameters may occur. Analytic forms for errors in the envelope variance estimate are derived. Estimation of the envelope mean, variance, MSR, skewness, and kurtosis is investigated experimentally, using a commercial medical ultrasound scanner and a tissue-mimicking phantom.


The importance of Good Clinical Practice guidelines and its role in clinical trials.
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analyses and reporting of clinical trials. It also serves to protect the rights, integrity and confidentiality of trial subjects. It is very important to understand the background of the formation of the ICH-GCP guidelines as this, in itself, explains the reasons and the need for doing so. In this paper, we address the historical background and the events that led up to the formation of these guidelines. Today, the ICH-GCP guidelines are used in clinical trials throughout the globe with the main aim of protecting and preserving human rights.


Molecular Characterization of Virulence Genes in Vancomycin-Resistant and Vancomycin-Sensitive Enterococci.
The aim of this study was to find out the correlation between presence of virulence (gelatinase [gel E], enterococcal surface protein [esp], cytolysin A [cyl A], hyaluronidase [hyl], and aggregation substance [asa1]) and vancomycin-resistant genes (van A and van B) in enterococci, with their phenotypic expression. A total of 500 isolates (250 each clinical and fecal) were processed. Enterococci were isolated from various clinical samples and from fecal specimens of colonized patients. Various virulence determinants namely asa1, esp, hyl, gel E, and cyl were detected by phenotypic methods. Minimum inhibitory concentration (MIC) of vancomycin was determined by agar dilution method. Multiplex polymerase chain reaction (PCR) was used to detect the presence of virulence and van genes. Out of all the samples processed, 12.0% (60/500) isolates carried van A or van B genes as confirmed by MIC test and PCR methods. Genes responsible for virulence were detected by multiplex PCR and at least one of the five was detected in all the clinical vancomycin-resistant enterococci (VRE) and vancomycin-sensitive enterococci (VSE). gel E, esp, and hyl genes were found to be significantly higher in clinical VRE. Of the fecal isolates, presence of gel E, esp, and asa1 was significantly higher in VRE as compared to VSE. The presence of hyl gene in the clinical VRE was found to be statistically significant (P = 0.043) as against the fecal VRE. Correlation between the presence of virulence genes and their expression as detected by phenotypic tests showed that while biofilm production was seen in 61.1% (22/36) of clinical VRE, the corresponding genes, i.e., asa1 and esp were detected in 30.5% (11/36) and 27.8% (10/36) of strains only. Enterococcus faecium isolates were found to carry esp gene, a phenomenon that has been described previously only for Enterococcus faecalis, but we were unable to correlate the presence of esp with their capacity to form biofilms.


Perception of COVID-19 Physical Distancing Effectiveness and Contagiousness of Asymptomatic Individuals: Cross-sectional Survey of Deaf and Hard of Hearing Adults in the United States.
During the COVID-19 pandemic, there has been a rapid increase in the amount of information about the disease and SARS-CoV-2 on the internet. If the language used in video messages is not clear or understandable to deaf and hard of hearing (DHH) people with a high school degree or less, this can cause confusion and result in information gaps among DHH people during a health emergency. The aim of this study is to investigate the relationship between DHH people's perception of the effectiveness of physical distancing and contagiousness of an asymptomatic person. This is a cross-sectional survey study on DHH people's perceptions about COVID-19 (N=475). Items pertaining to COVID-19 knowledge were administered to US deaf adults from April 17, 2020, to May 1, 2020, via a bilingual American Sign Language/English online survey platform. The sample consisted of 475 DHH adults aged 18-88 years old, with 74% (n=352) identifying as White and 54% (n=256) as female. About 88% (n=418) of the sample felt they knew most things or a lot about physical distancing. This figure dropped to 72% (n=342) for the question about the effectiveness of physical distancing in reducing the spread of COVID-19 and 70% (n=333) for the question about the contagiousness of an infected person without symptoms. Education and a knowledge of the effectiveness of physical distancing significantly predicted knowledge about the contagiousness of an asymptomatic individual. Race, gender, and age did not emerge as significant predictors. This results of this study point to the strong connection between education and coronavirus-related knowledge. Education-related disparities can be remedied by making information fully accessible and easily understood during emergencies and pandemics.


Bartonella vinsonii subspecies berkhoffi as a possible cause of anterior uveitis and choroiditis in a dog.
A 2-year old, neutered, female spaniel mixed breed was referred to the North Carolina State University Veterinary Teaching Hospital for evaluation of bilateral anterior uveitis. The dog was febrile and, in addition to anterior uveitis, multifocal hyporeflective lesions were present in the tapetal fundus of both eyes. The antibody titer for Bartonella vinsonii subspecies berkhoffi was positive (1 : 512). Aqueous paracentesis was performed for PCR in an attempt to detect B. vinsonii in the eye but was unsuccessful. The ocular manifestations of Bartonella infection in humans are currently expanding as more sensitive serologic and PCR techniques are being developed to identify Bartonella spp. In addition to optic neuritis and neuroretinitis, retinochoroidal lesions are one of the most common manifestations of B. henselae infection, and are frequently accompanied by vitreous or anterior segment inflammation. Diagnosis of a Bartonella infection in humans can be made on serology alone, in conjunction with ocular examination findings. The ultimate proof of B. vinsonii (berkhoffi) as a direct cause of ocular disease would be detection of the infectious agent in the eye. However, it is unknown at this time whether Bartonella causes ocular disease primarily, secondarily via an autoimmune reaction, or both. Due to the difficulties associated with culture of Bartonella spp. and the limitations of PCR, serology is currently the most useful tool for screening dogs for possible Bartonella spp. infection. In the case presented here, even though the PCR was negative, the clinical signs of anterior uveitis and choroiditis might reasonably be associated with B. vinsonii (berkhoffi) seroreactivity, which was repeatable on three separate occasions. Clinical improvement was also accompanied by a post-treatment decrease in B. vinsonii (berkhoffi) seroreactivity, potentially supporting resolution of Bartonella infection in this dog. This is the first reported case of a possible association between uveitis, choroiditis and Bartonella infection in the dog, without clinical manifestations of other organ or tissue involvement. Future studies based on PCR analysis of intraocular fluids may clarify the involvement of B. vinsonii (berkhoffi) in dogs with intraocular inflammatory disease. Furthermore, performing fluorescein angiography in dogs with elevated Bartonella titers may also prove useful in the identification and characterization of lesions.


Evolution of the Bacillus Calmette-Guerin Scar and Its Association with Birth and Pregnancy Characteristics in a Prospective Cohort of Infants in Iquitos, Peru.
Bacillus Calmette-Guerin (BCG) scar formation is considered a visual marker of vaccination and cell-mediated immune response. This study characterized the association between pregnancy and birth characteristics with BCG scar formation. Pregnant women were enrolled prospectively. Infants were followed up for the first 6 months of life, and the diameter of the BCG scar was recorded. Marginal models were fitted to assess the association of BCG scar diameter with pregnancy and birth characteristics using linear regressions with generalized estimating equations. A total of 307 infants were enrolled, of whom 19.2% (59/307) were of low birth weight. Among those with known gestational age, 7.1% were preterm births (21/295). Overall, 98.7% (303/307) of infants developed a BCG scar. BCG scar trends in a tropical environment, such as the Amazon, differ from the trends evidenced in the capital of Peru. For every additional week of gestational age, the mean scar diameter increased by 0.1 mm (95% confidence interval [CI]: 0.02, 0.24; p = 0.017). Maternal illness during pregnancy impacted BCG scar size, as the infants of mothers who self-report fever had a smaller scar diameter (1 mm, 95% CI: 0.5, 1.8 mm; p = 0.001). The immune reaction to the BCG vaccination is affected by gestational age at birth and systemic inflammatory episodes during pregnancy.


Public Attitudes and Factors of COVID-19 Testing Hesitancy in the United Kingdom and China: Comparative Infodemiology Study.
Massive community-wide testing has become the cornerstone of management strategies for the COVID-19 pandemic. This study was a comparative analysis between the United Kingdom and China, which aimed to assess public attitudes and uptake regarding COVID-19 testing, with a focus on factors of COVID-19 testing hesitancy, including effectiveness, access, risk perception, and communication. We collected and manually coded 3856 UK tweets and 9299 Chinese Sina Weibo posts mentioning COVID-19 testing from June 1 to July 15, 2020. Adapted from the World Health Organization's 3C Model of Vaccine Hesitancy, we employed social listening analysis examining key factors of COVID-19 testing hesitancy (confidence, complacency, convenience, and communication). Descriptive analysis, time trends, geographical mapping, and chi-squared tests were performed to assess the temporal, spatial, and sociodemographic characteristics that determine the difference in attitudes or uptake of COVID-19 tests. The UK tweets demonstrated a higher percentage of support toward COVID-19 testing than the posts from China. There were much wider reports of public uptake of COVID-19 tests in mainland China than in the United Kingdom; however, uncomfortable experiences and logistical barriers to testing were more expressed in China. The driving forces for undergoing COVID-19 testing were personal health needs, community-wide testing, and mandatory testing policies for travel, with major differences in the ranking order between the two countries. Rumors and information inquiries about COVID-19 testing were also identified. Public attitudes and acceptance toward COVID-19 testing constantly evolve with local epidemic situations. Policies and information campaigns that emphasize the importance of timely testing and rapid communication responses to inquiries and rumors, and provide a supportive environment for accessing tests are key to tackling COVID-19 testing hesitancy and increasing uptake.


Successful infection of the common marmoset (Callithrix jacchus) with human varicella-zoster virus.
The common marmoset, Callithrix jacchus, can be infected with human varicella-zoster virus (VZV), both wild-type strain KMcC and attenuated vaccine strain Oka/Merck. Infection was accomplished with either whole-cell-associated or cell extract VZV by combined oral-nasal-conjunctival application and was characterized by substantial and persistent anti-VZV antibody responses. The infectivity of VZV for marmosets was destroyed by treatment of inocula with heat or UV light. Diluted inocula with as few as 40 PFU/ml were infectious for marmosets. The lungs were demonstrated to be a major site of viral replication; both the presence of viral antigens and signs of pneumonia were demonstrated in lung tissues. Four serial passages of VZV KMcC were carried out in C. jacchus by a process of in vitro isolation and culturing of VZV from infected lung tissue and reapplication of the cultured isolates to fresh animals. The isolated viruses were identified as VZV both serologically and by restriction endonuclease analyses. The C. jacchus infectivity model should prove useful for determining the efficacy of subunit and live recombinant VZV vaccines as well as for the study of zoster.


Current and emerging pharmacological targets for medical expulsive therapy.
The primary goals of medical expulsive therapy are to increase the rate of stone expulsion along the ureter to avoid ureteral obstruction and reduce ureteral colic and thus avoid the need for surgical and more invasive interventions. This review focussed on the findings from in vivo and in vitro animal and human studies that have investigated the pharmacological mechanisms controlling ureteral motility and their translation to current and potentially new clinically used drugs for increasing the rate of stone expulsion along the ureter. The complicated contractility profile of the ureter, which alters with age, tissue segment region, orientation and species contributes to the difficulty of interpreting studies on ureteral pharmacology, which translates to the complexity of discovering ideal drug targets for medical expulsive therapy. Nevertheless, the current drug classes clinically used for patients with stone lodgement include α1 -adrenoceptor antagonists, calcium channel blockers and NSAIDS, whilst there are promising targets for drug development that require further clinical investigations including the phosphodiesterase type 5 enzyme, β-adrenoceptors and 5-HT receptors.


Topology, length scales, and energetics of surfactant micelles.
We study the morphology, energetics, and kinetics of a self-associating model cationic surfactant in water using large-scale coarse-grained molecular dynamics simulations over time scales that allow for probing micelle recombination dynamics. We develop an algorithm to track micelle contours and quantify various microstructural features such as contour length distribution, persistence length, and mesh size. We predict reliably the end-cap energy and recombination time of micelles, directly from molecular simulations for the first time. We further consider the variation of solution viscosity as a function of salt concentration and show that branched and multiconnected structures govern the experimentally observed anomalous dependence of zero-shear viscosity on salt concentration. Overall, simulation predictions are in good agreement with experiments.


Genetic and epigenetic control of UNC5C expression in human renal cell carcinoma.
Inappropriate gene silencing and subsequent promiscuous activity define the transformation of many solid tumours including renal cell carcinoma (RCC). Here, we report that UNC5C, one of the Netrin-1 receptors, was frequently inactivated in RCC cell lines and primary tumours. UNC5C protein was expressed in the proximal convoluted tubules of the human kidney, the presumed origin of clear cell RCC (ccRCC) and papillary RCC (pRCC). Compared to paired adjacent non-malignant tissues, both UNC5C mRNA and protein expression were significantly down-regulated in RCC. Immunohistochemical analysis showed that UNC5C was inactivated in 94.3% of the samples and the loss of UNC5C occurred at the early stage of RCC. Methylation specific PCR showed that UNC5C promoter was methylated in two renal carcinoma cell lines. Pharmacologic demethylation alone or in combination with inhibition of deacetylation dramatically induced UNC5C expression. Furthermore, bisulfite genomic sequencing (BGS) confirmed that dense methylation existed in UNC5C promoter. In paired tumour samples, UNC5C methylation was observed in 12 out of 44 patients (27.3%). Moreover, we analysed the loss of heterozygosity (LOH) of UNC5C in renal cell carcinoma, the LOH was observed in 27 out of 44 patients (61.4%). Finally, restoration of UNC5C expression suppressed the colony formation of renal carcinoma cells. In addition, UNC5C inhibited tumour cell proliferation, migration and enhanced chemosensitivity to cisplatin and etoposide. Therefore, UNC5C acts as a tumour suppressor in RCC and is down-regulated in RCC. Loss of heterozygosity and DNA methylation contribute to the inactivation of UNC5C in renal cell carcinoma.


Effect of MPO/H2O2/NO(-) system on nitric oxide-mediated modification of TTR amyloid and serum TTR in FAP ATTR Val30Met patients.
Amyloid deposits consist of protein fibrils and amorphous material, and this deposition is related to oxidative stress. Previously, we demonstrated the presence of high-density lipoproteins and/or lipids in amyloid deposits of familial amyloid polyneuropathy patients. In this study, the presence of myeloperoxidase (MPO) in amyloid deposits was demonstrated using immunohistochemical staining. In contrast, normal surrounding tissues were consistently negative for MPO. Nitrotyrosine was present in amyloid deposits after being exposed to the MPO/H2O2/NO(-) system by immunohistochemical staining, and the oxide mediated modification of serum transthyretin (TTR) was observed upon exposure to the MPO/H2O2 system using two-dimensional gel electrophoresis and TTR Western blotting. This observation revealed that the TTR amyloid deposits and serum TTR were oxidized by the MPO/H2O2/NO(-) system. Nitric oxide-mediated modification of TTR may play a role in amyloidogenesis in vivo.


Examining the aetiopathogenesis of varicoceles: the relationship between retroperitoneal adipose tissue and testicular venous drainage.
This study evaluated the effect of retroperitoneal adipose tissue on testicular venous drainage and tested the nutcracker phenomenon by clinical and imaging findings. A total of 95 patients were included. The patients were evaluated with a detailed medical history and physical examination for varicocele. Their weight, height and waist circumference were also recorded. Body mass index was calculated as weight (kg)/height squared (m(2) ). Pampiniform plexus diameters were measured by scrotal colour Doppler ultrasonography, and retroperitoneal adipose tissue was evaluated by noncontrast abdominal computed tomography. We determined an almost significant correlation between BMI and varicocele presence by physical examination (P = 0.06). However, there was a significant relationship between WC and varicocele identified by physical examination (P = 0.021). There was a positive and significant relationship between BMI and pampiniform plexus diameters. Furthermore, we detected a negative correlation between retroperitoneal adipose tissue measurements and CDU findings. Additionally, there was a significant correlation between WC, pampiniform plexus diameters and CT findings. It is concluded that increasing BMI and increasing WC may play a protective role in the development of varicocele. There is a need for further studies to verify the effect of obesity on varicocele formation.


Evaluation of complexity and deliverability of IMRT treatment plans for breast cancer.
This study aimed to predict the outcome of patient specific quality assurance (PSQA) in IMRT for breast cancer using complexity metrics, such as MU factor, MAD, CAS, MCS. Several breast cancer plans were considered, including LBCS, RBCS, LBCM, RBCM, left breast, right breast and the whole breast for both Edge and TrueBeam LINACS. Dose verification was completed by Portal Dosimetry (PD). The receiver operating characteristic (ROC) curve was employed to determine whether the treatment plans pass or failed. The area under the curve (AUC) was used to assess the classification performance. The correlation of PSQA and complexity metrics was examined using Spearman's rank correlation coefficient (Rs). For LINACS, the most suitable complexity metric was found to be the MU factor (Edge Rs = - 0.608, p < 0.01; TrueBeam Rs = - 0.739, p < 0.01). Regarding the specific breast cancer categories, the optimal complexity metrics were as follows: MAD (AUC = 0.917) for LBCS, MCS (AUC = 0.681) for RBCS, MU factor (AUC = 0.854) for LBCM and MAD (AUC = 0.731) for RBCM. On the Edge LINAC, the preferable method for breast cancers was MCS (left breast, AUC = 0.938; right breast, AUC = 0.813), while on the TrueBeam LINAC, it became MU factor (left breast, AUC = 0.950) and MCS (right breast, AUC = 0.806), respectively. Overall, there was no universally suitable complexity metric for all types of breast cancers. The choice of complexity metric depended on different cancer types, locations and treatment LINACs. Therefore, when utilizing complexity metrics to predict PSQA outcomes in IMRT for breast cancer, it was essential to select the appropriate metric based on the specific circumstances and characteristics of the treatment.


[Mediastinal angiography. A helpful method to evaluate to operability of mediastinal and lung tumors (author's transl)].
Preoperative mediastinal angiography, as a simple method, shows alterations of pulmonary and venous mediastinal circulation. It enables the surgeon to evaluate the operability of malignant thoracic neoplasms without performance of other diagnostic procedure with a higher rate of complications, e.g. mediastinoscopy or explorative thoractomy.


Nutritional supplements for people being treated for active tuberculosis.
Tuberculosis and malnutrition are linked in a complex relationship. The infection may cause undernutrition through increased metabolic demands and decreased intake, and nutritional deficiencies may worsen the disease, or delay recovery by depressing important immune functions. At present, there are no evidence-based nutritional guidance for adults and children being treated for tuberculosis. To assess the effects of oral nutritional supplements (food, protein/energy supplements or micronutrients) on tuberculosis treatment outcomes and recovery in people on antituberculous drug therapy for active tuberculosis. We searched the Cochrane Infectious Disease Group Specialized Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, LILACS, mRCT, and the Indian Journal of Tuberculosis to July 2011, and checked the reference lists of all included studies. Randomized controlled trials comparing any oral nutritional supplement given for at least four weeks with no nutritional intervention, placebo, or dietary advice only for people being treated for active tuberculosis. Two authors independently selected trials, extracted data, and assessed the risk of bias. Results are presented as risk ratios (RR) for dichotomous variables, and mean differences (MD) for continuous variables, with 95% confidence intervals (CI). Where appropriate, data from trials with similar interventions and outcomes have been pooled. The quality of evidence was assessed using the GRADE methods. Twenty-three trials, with 6842 participants, were included. Macronutrient supplementation Five trials assessed the provision of free food, or high energy supplements, although none were shown to provide a total daily kilocalorie intake above the current daily recommended intake for the non-infected population.The available trials were too small to reliably prove or exclude clinically important benefits on mortality, cure, or treatment completion. One small trial from India did find a statistically significant benefit on treatment completion, and clearance of the bacteria from the sputum, but these findings have not been confirmed in larger trials elsewhere (VERY LOW quality evidence).The provision of free food or high-energy nutritional products probably does produce a modest increase in weight gain during treatment for active tuberculosis (MODERATE quality evidence). Two small studies provide some evidence that physical function and quality of life may also be improved but the trials were too small to have much confidence in the result (LOW quality evidence). These effects were not seen in the one trial which included only human immunodeficiency virus (HIV)-positive patients.Micronutrient supplementation Five trials assessed multi-micronutrient supplementation in doses up to ten times the dietary reference intake, and 12 trials assessed single or dual micronutrient supplementation.There is insufficient evidence to judge whether multi-micronutrients have a beneficial effect on mortality in HIV- negative patients with tuberculosis (VERY LOW quality evidence), but the available studies show that multi-micronutrients probably have little or no effect on mortality in HIV-positive patients with tuberculosis (MODERATE quality evidence). No studies have assessed the effects of multi-micronutrients on cure, or treatment completion.Multi-micronutrient supplements may have little or no effect on the proportion of tuberculosis patients remaining sputum positive during the first eight weeks (LOW quality evidence), and probably have no effect on weight gain during treatment (MODERATE quality evidence). No studies have assessed quality of life.Plasma levels of vitamin A appear to increase following initiation of tuberculosis treatment regardless of supplementation. In contrast, plasma levels of zinc, vitamin D and E, and selenium may be improved by supplementation during the early stages of tuberculosis treatment, but a consistent benefit on tuberculosis treatment outcomes or nutritional recovery has not been demonstrated. There is insufficient research to know whether routinely providing free food or energy supplements results in better tuberculosis treatment outcomes, or improved quality of life. Further trials, particularly from food insecure settings, should have adequate sample sizes to identify, or exclude, clinically important benefits.Although blood levels of some vitamins may be low in patients starting treatment for active tuberculosis, there is currently no reliable evidence that routinely supplementing at or above recommended daily amounts has clinical benefits.


Incidence of whooping cough in Spain (1997-2010): an underreported disease.
Whooping cough is currently the worst controlled vaccine-preventable disease in the majority of countries. In order to reduce its morbidity and mortality, it is essential to adapt vaccination programmes to data provided by epidemiological surveillance. A population-based retrospective epidemiological study to estimate the minimum annual undernotification rate of pertussis in Spain from 1997 to 2010 was performed. The incidence of pertussis cases reported to the National Notifiable Disease Surveillance System was compared with the incidence of hospital discharges for pertussis from the National Surveillance System for hospital data, Conjunto Mínimo Básico de Datos. The overall reported incidence and that of hospitalisation for whooping cough were 1.3 cases × 100,000 inhabitants in both cases. Minimum underreporting oscillated between 3.8 and 22.8 %, according to the year of the study. The greatest underreporting (50 %) was observed in children under the age of 1 year. Spanish epidemiological surveillance system of pertussis should be improved with complementary active systems to ascertain the real incidence. Paediatricians and general practitioners should be sensibilized to the importance of notification because this would be essential for adapting the prevention and control measures of this disease.


Chlorosis caused by two recessively interacting genes reveals a role of RNA helicase in hybrid breakdown in Arabidopsis thaliana.
Hybrids often differ in fitness from their parents. They may be superior, translating into hybrid vigour or heterosis, but they may also be markedly inferior, because of hybrid weakness or incompatibility. The underlying genetic causes for the latter can often be traced back to genes that evolve rapidly because of sexual or host-pathogen conflicts. Hybrid weakness may manifest itself only in later generations, in a phenomenon called hybrid breakdown. We have characterized a case of hybrid breakdown among two Arabidopsis thaliana accessions, Shahdara (Sha, Tajikistan) and Lövvik-5 (Lov-5, Northern Sweden). In addition to chlorosis, a fraction of the F2 plants have defects in leaf and embryo development, and reduced photosynthetic efficiency. Hybrid chlorosis is due to two major-effect loci, of which one, originating from Lov-5, appears to encode an RNA helicase (AtRH18). To examine the role of the chlorosis allele in the Lövvik area, in addition to eight accessions collected in 2009, we collected another 240 accessions from 15 collections sites, including Lövvik, from Northern Sweden in 2015. Genotyping revealed that Lövvik collection site is separated from the rest. Crosses between 109 accessions from this area and Sha revealed 85 cases of hybrid chlorosis, indicating that the chlorosis-causing allele is common in this area. These results suggest that hybrid breakdown alleles not only occur at rapidly evolving loci, but also at genes that code for conserved processes.


Implicit theories of intelligence, perceived academic competence, and school achievement: testing alternative models.
In the present study 3 alternative causal models concerning the relationships between implicit theories of intelligence, perceived academic competence, and school achievement were tested. The direction of changes in implicit theories and perceived competence during early adolescence also was examined. A total of 187 fifth and sixth graders were tested and retested a year later, when they were sixth and seventh graders, respectively. Cross-lagged regression analyses indicated that school achievement determined the adoption of a particular implicit theory through the mediation of perceived competence. Implicit theories were found to change toward the adoption of more incremental beliefs and perceived academic competence declined; however, high achievers, as compared with their low- and middle-level classmates, adopted more incremental beliefs and had significantly higher perceived competence.


Effects of a natural prolyl oligopeptidase inhibitor, rosmarinic acid, on lipopolysaccharide-induced acute lung injury in mice.
Rosmarinic acid (RA), a polyphenolic phytochemical, is a natural prolyl oligopeptidase inhibitor. In the present study, we found that RA exerted potent anti-inflammatory effects in in vivo models of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Mice were pretreated with RA one hour before challenge with a dose of 0.5 mg/kg LPS. Twenty-four hours after LPS was given, bronchoalveolar lavage fluid (BALF) was obtained to measure pro-inflammatory mediator and total cell counts. RA significantly decreased the production of LPS-induced TNF-a, IL-6, and IL-1β compare with the LPS group. When pretreated with RA (5, 10, or 20 mg/kg) the lung wet-to-dry weight (W/D) ratio of the lung tissue and the number of total cells, neutrophils and macrophages in the BALF were decreased significantly. Furthermore, RA may enhance oxidase dimutase (SOD) activity during the inflammatory response to LPS-induced ALI. And we further demonstrated that RA exerts anti-inflammation effect in vivo models of ALI through suppresses ERK/MAPK signaling in a dose dependent manner. These studies have important implications for RA administration as a potential treatment for ALI.


Genetic effects for femoral biomechanics, structure, and density in C57BL/6J and C3H/HeJ inbred mouse strains.
Genome-wide QTL analysis for bone density, structure, and biomechanical phenotypes was performed in 999 (B6xC3H)F2 mice. Multivariate phenotypes were also derived to test for pleiotropic QTL effects. Highly significant QTLs were detected with pleiotropic effects on many of these phenotypes, and QTLs with unique effects on specific phenotypes were found as well. The inbred C57BL/6J (B6) and C3H/HeJ (C3H) mouse strains were previously shown to segregate quantitative trait loci (QTLs) for femoral bone density. The 999 s filial (F2) mouse progeny were further phenotyped for measures of femoral biomechanics (load to failure, Fu; work to failure, U; stiffness, S), structure (polar moment of inertia, Ip; moment of inertia ratio, Ir), and more specific femoral midshaft bone density measures (cortical and total vBMD). Two novel multivariate phenotypes were computed using principal component analysis, thus aiding in the exploration of pleiotropic effects of the QTLs detected. Results of a genome-wide analysis provided strong evidence of pleiotropic QTL effects on chromosome 4, with six of the seven primary phenotypic measures, representing femoral biomechanics, density, and structure, producing LOD scores greater than 8. Chromosomes 1, 8, 13, and 14 were also identified as harboring QTLs that affect phenotypes in two of the three aspects of bone properties. QTLs uniquely contributing to variability in biomechanical measures were identified on chromosomes 10 and 12, whereas a QTL solely affecting structure was found on chromosome 17. Analysis of the evidence for pleiotropic effects using principal component analysis revealed pleiotropic QTLs on chromosomes 4 and 14, influencing nearly all the bone phenotypes measured and revealed QTLs on chromosomes 1, 8, 13, and 17 with pleiotropic effects restricted to either density or the structure and stiffness phenotypes. The use of multivariate phenotypes has allowed us to identify pleiotropic effects of several QTLs previously linked in studies of other mouse strains and in human studies of bone mineral density and femoral structure, which will provide important insight regarding the importance of allelic variation on the entire skeleton.


Tumor endothelial marker 8 enhances tumor immunity in conjunction with immunization against differentiation Ag.
We have previously shown that xenogeneic DNA vaccines encoding rat neu and melanosomal differentiation Ag induce tumor immunity. Others have developed vaccines targeting tumor neovasculature. Tumor endothelial marker 8 (TEM8) is expressed in the neovasculature of human tumors, and in the mouse melanoma B16, but its expression is limited in normal adult tissues. We describe a DNA vaccine combining xenogeneic tumor Ag and TEM8. In-situ hybridization was used to detect TEM8 RNA in mouse tumors. Mice transgenic for the rat neu proto-oncogene were immunized with DNA vaccines encoding TEM8 and the extracellular domain of rat neu and challenged with the 233-VSGA1 breast cancer cell line. In parallel experiments, C57BL/6 mice were immunized with TEM8 and human tyrosinase-related protein 1 (hTYRP1/hgp75) and challenged with B16F10 melanoma. TEM8 was expressed in the stroma of transplantable mouse breast and melanoma tumors. In both model systems, TEM8 DNA had no activity as a single agent but significantly enhanced the anti-tumor immunity of neu and hTYRP1/hgp75 DNA vaccines when given in concert. The observed synergy was dependent upon CD8+ T cells, as depletion of this cell population just prior to tumor challenge obviated the effect of the TEM8 vaccine in both tumor models. A local immune response to TEM8 may increase inflammation or tumor necrosis within the tumor, resulting in improved Ag presentation of HER2/neu and hTYRP1/hgp75. Alternatively, TEM8 expression in host APC may alter T-cell interactions or homing. In this way, TEM8 may act more as an adjuvant than an immunologic target.


Mapping Verb Retrieval With nTMS: The Role of Transitivity.
Navigated Transcranial Magnetic Stimulation (nTMS) is used to understand the cortical organization of language in preparation for the surgical removal of a brain tumor. Action naming with finite verbs can be employed for that purpose, providing additional information to object naming. However, little research has focused on the properties of the verbs that are used in action naming tasks, such as their status as transitive (taking an object; e.g., to read) or intransitive (not taking an object; e.g., to wink). Previous neuroimaging data show higher activation for transitive compared to intransitive verbs in posterior perisylvian regions bilaterally. In the present study, we employed nTMS and production of finite verbs to investigate the cortical underpinnings of transitivity. Twenty neurologically healthy native speakers of German participated in the study. They underwent language mapping in both hemispheres with nTMS. The action naming task with finite verbs consisted of transitive (e.g., The man reads the book) and intransitive verbs (e.g., The woman winks) and was controlled for relevant psycholinguistic variables. Errors were classified in four different error categories (i.e., non-linguistic errors, grammatical errors, lexico-semantic errors and, errors at the sound level) and were analyzed quantitatively. We found more nTMS-positive points in the left hemisphere, particularly in the left parietal lobe for the production of transitive compared to intransitive verbs. These positive points most commonly corresponded to lexico-semantic errors. Our findings are in line with previous aphasia and neuroimaging studies, suggesting that a more widespread network is used for the production of verbs with a larger number of arguments (i.e., transitives). The higher number of lexico-semantic errors with transitive compared to intransitive verbs in the left parietal lobe supports previous claims for the role of left posterior areas in the retrieval of argument structure information.


A dedicated target capture approach reveals variable genetic markers across micro- and macro-evolutionary time scales in palms.
Understanding the genetics of biological diversification across micro- and macro-evolutionary time scales is a vibrant field of research for molecular ecologists as rapid advances in sequencing technologies promise to overcome former limitations. In palms, an emblematic, economically and ecologically important plant family with high diversity in the tropics, studies of diversification at the population and species levels are still hampered by a lack of genomic markers suitable for the genotyping of large numbers of recently diverged taxa. To fill this gap, we used a whole genome sequencing approach to develop target sequencing for molecular markers in 4,184 genome regions, including 4,051 genes and 133 non-genic putatively neutral regions. These markers were chosen to cover a wide range of evolutionary rates allowing future studies at the family, genus, species and population levels. Special emphasis was given to the avoidance of copy number variation during marker selection. In addition, a set of 149 well-known sequence regions previously used as phylogenetic markers by the palm biological research community were included in the target regions, to open the possibility to combine and jointly analyse already available data sets with genomic data to be produced with this new toolkit. The bait set was effective for species belonging to all three palm sub-families tested (Arecoideae, Ceroxyloideae and Coryphoideae), with high mapping rates, specificity and efficiency. The number of high-quality single nucleotide polymorphisms (SNPs) detected at both the sub-family and population levels facilitates efficient analyses of genomic diversity across micro- and macro-evolutionary time scales.


Does meaning protect against loneliness? Exploring empirical studies and theory.
Research indicates that meaning in life is a protective factor for physical and mental health. Although loneliness is increasingly recognized as an important public health concern, no studies have investigated the potential of meaning in life to protect against loneliness. Based on an explorative interdisciplinary research strategy that comprises data from a cohort study, a strategic review of empirical literature and a conceptual analysis of the concept of meaning in life we explore the support for potential links between meaning in life and the protection against loneliness. We propose three different explanatory mechanisms; (i) that meaning in life promotes a positive orientation toward others, (ii) that meaning in life enhances interpersonal appeal and (iii) that meaning in life promotes a better ability to cope with loneliness. Theoretically, we explore the idea that the value of meaning in life ultimately concerns a social need to contribute to the realization of value that, at least in principle, can be shared and recognized by others. When people realize the value of meaning in life, they partake in a community of shared values, which links them to a social world in a way that may protect against the feeling of loneliness. Jointly the analyses point to the need for prospective studies on the role of meaning in life as a protective factor against loneliness and a potential novel focus for loneliness interventions.


The influences of ambient particle composition and size on particle infiltration in Los Angeles, CA, residences.
Particle infiltration is a key determinant of the indoor concentrations of ambient particles. Few studies have examined the influence of particle composition on infiltration, particularly in areas with high concentrations of volatile particles, such as ammonium nitrate (NH4NO3). A comprehensive indoor monitoring study was conducted in 17 Los Angeles-area homes. As part of this study, indoor/outdoor concentration ratios during overnight (nonindoor source) periods were used to estimate the fraction of ambient particles remaining airborne indoors, or the particle infiltration factor (FINF), for fine particles (PM2.5), its nonvolatile (i.e., black carbon [BC]) and volatile (i.e., nitrate [NO3-]) components, and particle sizes ranging between 0.02 and 10 microm. FINF was highest for BC (median = 0.84) and lowest for NO3- (median = 0.18). The low FINF for NO3- was likely because of volatilization of NO3- particles once indoors, in addition to depositional losses upon building entry. The FINF for PM2.5 (median = 0.48) fell between those for BC and NO3-, reflecting the contributions of both particle components to PM25. FINF varied with particle size, air-exchange rate, and outdoor NO3- concentrations. The FINF for particles between 0.7 and 2 microm in size was considerably lower during periods of high as compared with low outdoor NO3- concentrations, suggesting that outdoor NO3- particles were of this size. This study demonstrates that infiltration of PM2.5 varies by particle component and is lowest for volatile species, such as NH4NO3. Our results suggest that volatile particle components may influence the ability for outdoor PM concentrations to represent indoor and, thus, personal exposures to particles of ambient origin, because volatilization of these particles causes the composition of PM2.5 to differ indoors and outdoors. Consequently, particle composition likely influences observed epidemiologic relationships based on outdoor PM concentrations, especially in areas with high concentrations of NH4NO3 and other volatile particles.


Glutathione and NADH, but not ascorbate, protect lens proteins from modification by UV filters.
Age-dependent human lens colouration and fluorescence may stem primarily from the covalent binding of UV filters to crystallins. The tendency of the kynurenine (Kyn) UV filters to deaminate at neutral pH, with the generation of reactive alpha,beta-ketoalkenes, underlies this phenomenon. In this study the authors examined the ability of small molecular weight antioxidants, which are known to be present in the lens, to inhibit this process. Crystallins were incubated with Kyn at pH 7 in the presence of glutathione (GSH), ascorbate or NADH. Ascorbate, even at high (15 m M) levels, was not found to significantly retard the time-dependent covalent binding of Kyn to the proteins. GSH, and to a lesser extent NADH, however, had a major impact in preventing this modification. The increase in protein UV absorbance and fluorescence was inhibited by GSH intercepting the reactive ketone intermediate, to form a GSH-Kyn adduct. NADH seemed to protect by both reduction of the reactive ketone intermediate and by competing with Kyn for presumably hydrophobic sites on the crystallins. This may indicate that the covalent attachment of aromatic Kyn molecules could be facilitated by initial hydrophobic interactions. Since GSH is present at far greater concentrations than NADH, these results show that in primate lenses, GSH is the key agent responsible for protecting the crystallins from covalent modification.


Drug repurposing based on a Quantum-Inspired method versus classical fingerprinting uncovers potential antivirals against SARS-CoV-2 including vitamin B12.
The COVID-19 pandemic has accelerated the need to identify new therapeutics at pace, including through drug repurposing. We employed a Quadratic Unbounded Binary Optimization (QUBO) model, to search for compounds similar to Remdesivir (RDV), the only antiviral against SARS-CoV-2 currently approved for human use, using a quantum-inspired device. We modelled RDV and compounds present in the DrugBank database as graphs, established the optimal parameters in our algorithm and resolved the Maximum Weighted Independent Set problem within the conflict graph generated. We also employed a traditional Tanimoto fingerprint model. The two methods yielded different lists of compounds, with some overlap. While GS-6620 was the top compound predicted by both models, the QUBO model predicted BMS-986094 as second best. The Tanimoto model predicted different forms of cobalamin, also known as vitamin B12. We then determined the half maximal inhibitory concentration (IC 50 ) values in cell culture models of SARS-CoV-2 infection and assessed cytotoxicity. Lastly, we demonstrated efficacy against several variants including SARS-CoV-2 Strain England 2 (England 02/2020/407073), B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta). Our data reveal that BMS-986094 and different forms of vitamin B12 are effective at inhibiting replication of all these variants of SARS-CoV-2. While BMS-986094 can cause secondary effects in humans as established by phase II trials, these findings suggest that vitamin B12 deserves consideration as a SARS-CoV-2 antiviral, particularly given its extended use and lack of toxicity in humans, and its availability and affordability. Our screening method can be employed in future searches for novel pharmacologic inhibitors, thus providing an approach for accelerating drug deployment.


Non-coplanar 2,2',3,5',6-pentachlorobiphenyl (PCB 95) amplifies ionotropic glutamate receptor signaling in embryonic cerebellar granule neurons by a mechanism involving ryanodine receptors.
The mechanisms by which non-coplanar 2,2',3,5',6-pentachlorobiphenyl (PCB 95) and rapamycin interact with ryanodine receptor (RyR) complexes to alter Ca2+ signaling, were explored in intact cerebellar granule neurons. PCB 95 (10 microM, 20 min) significantly increased the number of neurons responding to caffeine. PCB 95 sensitization of RyR-mediated responses was further supported by the observations that ryanodine pretreatment blocked response to caffeine and coplanar 2,4,4',5-tetrachlorobiphenyl (PCB 66), which lacks RyR activity, failed to sensitize neurons. PCB 95 did not significantly alter levels of resting cytosolic Ca2+ nor thapsigargin-sensitive Ca2+ stores, suggesting a more complex mechanism than sensitization from increased cytosolic Ca2+ or an increased endoplasmic reticulum/cytosolic Ca2+ gradient. The immunosuppressant, rapamycin, sensitized neurons to caffeine in a manner similar to PCB 95, suggesting a common mechanism. PCB 95 or rapamycin significantly enhanced Ca2+ responses following N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl4-isoxasolepropiate (AMPA) receptor activation. Store depletion or direct block of RyR with ryanodine enhanced responses to NMDA. PCB 95 further enhanced these responses to NMDA. These results suggest that PCB 95 and rapamycin enhance NMDA- and AMPA-mediated Ca2+ signals by modifying a functional association of the FKBP12/RyR complex that results in amplification of glutamate signaling in cultured cerebellar granule neurons in culture.


Crucial and diverse role of the interleukin-33/ST2 axis in infectious diseases.
Interleukin-33 (IL-33) has now emerged as a cytokine with diverse and pleiotropic functions in various infectious and inflammatory diseases. IL-33 is expressed by epithelial cells, endothelial cells, fibroblasts, and hepatocytes. The target cells of IL-33 are Th2 cells, basophils, dendritic cells, mast cells, macrophages, NKT cells, and nuocytes, newly discovered natural helper cells/innate lymphoid cells bearing the ST2 receptor. IL-33 has dual functions, both as a traditional cytokine and as a nuclear factor that regulates gene transcription. IL-33 functions as an "alarmin" released following cell death, as a biomarker, and as a vaccine adjuvant, with proinflammatory and protective effects during various infections. The exacerbated or protective role of the IL-33/ST2 axis during different infections is dependent upon the organ involved, type of infectious agent, whether the infection is acute or chronic, the invasiveness of the infectious agent, the host immune compartment, and cellular and cytokine microenvironments. In this review, we focus on recent advances in the understanding of the role of the IL-33/ST2 axis in various viral, bacterial, fungal, helminth, and protozoal infectious diseases gained from animal models and studies in human patients. The functional role of IL-33 and ST2 during experimentally induced infections has been summarized by accumulating the data for IL-33- and ST2-deficient mice or for mice exogenously administered IL-33. In summary, exploring the crucial and diverse roles of the IL-33/ST2 axis during infections may help in the development of therapeutic interventions for a wide range of infectious diseases.


Mutations of Francisella novicida that alter the mechanism of its phagocytosis by murine macrophages.
Infection with the bacterial pathogen Francisella tularensis tularensis (F. tularensis) causes tularemia, a serious and debilitating disease. Francisella tularensis novicida strain U112 (abbreviated F. novicida), which is closely related to F. tularensis, is pathogenic for mice but not for man, making it an ideal model system for tularemia. Intracellular pathogens like Francisella inhibit the innate immune response, thereby avoiding immune recognition and death of the infected cell. Because activation of inflammatory pathways may lead to cell death, we reasoned that we could identify bacterial genes involved in inhibiting inflammation by isolating mutants that killed infected cells faster than the wild-type parent. We screened a comprehensive transposon library of F. novicida for mutant strains that increased the rate of cell death following infection in J774 macrophage-like cells, as compared to wild-type F. novicida. Mutations in 28 genes were identified as being hypercytotoxic to both J774 and primary macrophages of which 12 were less virulent in a mouse infection model. Surprisingly, we found that F. novicida with mutations in four genes (lpcC, manB, manC and kdtA) were taken up by and killed macrophages at a much higher rate than the parent strain, even upon treatment with cytochalasin D (cytD), a classic inhibitor of macrophage phagocytosis. At least 10-fold more mutant bacteria were internalized by macrophages as compared to the parent strain if the bacteria were first fixed with formaldehyde, suggesting a surface structure is required for the high phagocytosis rate. However, bacteria were required to be viable for macrophage toxicity. The four mutant strains do not make a complete LPS but instead have an exposed lipid A. Interestingly, other mutations that result in an exposed LPS core were not taken up at increased frequency nor did they kill host cells more than the parent. These results suggest an alternative, more efficient macrophage uptake mechanism for Francisella that requires exposure of a specific bacterial surface structure(s) but results in increased cell death following internalization of live bacteria.


Review of the genera Paulomanus Young, 1952 and Beamerana Young, 1952 (Hemiptera: Cicadellidae: Typhlocybinae: Empoascini) with description of a new species from Argentina.
The Neotropical microleafhopper genera Paulomanus and Beamerana are redescribed based on study of type material and newly collected specimens. Paulomanus is recorded for the first time from Argentina and a new species, P. falciformis n. sp., is described. Detailed morphological description and illustration of the new species and a key to males of the known species of Paulomanus are provided. A key to genera of the New World Empoascini is also provided.


Noninvasive magnetic resonance-guided focused ultrasound for tendon disruption: an in vivo Animal study.
Surgical resection of the tendon is an effective treatment for severe contracture. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a non-invasive ultrasonic therapy which produces a focal increase in temperature, subsequent tissue ablation and disruption. We evaluated MRgFUS as a clinically translatable treatment modality to non-invasively disrupt in vivo porcine tendons. In vivo Achilles tendons (n = 28) from 15-20kg Yorkshire pigs (n = 16) were randomly assigned to 4 treatment groups of 600, 900, 1200 and 1500 J. Pretreatment range of motion (ROM) of the ankle joint was measured with the animal under general anesthesia. Following MRgFUS treatment, success of tendon rupture, ROM increase, temperature, thermal dosage, skin burn, and histology analyses were performed. Rupture success was found to be 29%, 86%, 100% and 100% for treatment energies of 600, 900, 1200 and 1500 J respectfully. ROM difference at 90° flexion showed a statistically significant change in ROM between 900 J and 1200 J from 16° to 27°. There was no statistical significance between other groups, but there was an increase in ROM as more energy was delivered in the treatment. For each of the respective treatment groups, the maximal temperatures were 58.4 °C, 63.3 °C, 67.6 °C, and 69.9 °C. The average areas of thermal dose measured were 24.3mm2, 53.2mm2, 77.8mm2 and 91.6mm2. The average areas of skin necrosis were 5.4mm2, 21.8mm2, 37.2mm2, and 91.4mm2. Histologic analysis confirmed tissue ablation and structural collagen fiber disruption. This study demonstrated that MRgFUS is able to disrupt porcine tendons in vivo without skin incisions.


A system for documentation of pharmacist interventions with incorporation into performance and quality improvement plans.
Budgetary constraints have compelled hospital administrators to take a more discerning look at the role of the pharmacist within the healthcare team. In 1991, financial difficulties and hospital-wide cutbacks at Northern Michigan Hospital resulted in the loss of pharmacy personnel. Consequently, the department has increasingly found it necessary to document the clinical activities of the pharmacists and their potential effect on patient care. To document therapeutic interventions, two forms specific to this activity were developed. These forms allowed evaluation of both the quantity and quality of interventions. The authors realize it is essential for pharmacists to not only maintain, but to continually update their knowledge base to be prepared for the future. A staff development program was developed to help meet the educational needs of the pharmacists. This article describes how therapeutic interventions were integrated into the quality improvement and performance plans to help motivate staff to continually improve their pharmacy practice skills at this institution.


[Pro general hospital].
Trauma operative systems were created in United States to optimize polytrauma patients' treatment. These systems include prehospital polytrauma care. They determine hospital requirements to treat this kind of patients, standardize physicians' training and implement hospital registries. Initially, this system was applied only in monographic centers. However, trauma services of General Hospitals that fulfill the requirements were authorized progressively by the American Surgery Academy to fulfill this function. This is the model followed in Europe at present. Accreditation requires the qualification of the stay, with specific health care resources and a detailed trauma program. The director is responsible for organizing the creation of the trauma teams, operating 24h, for teaching, protocols and guides and the coordination of pre-hospital emergency groups. In Spain, there is an extensive network of tertiary hospitals that have trauma programs and their consequent accreditation could make it possible to take advantage of their existing resources. An accreditation system should be elaborated in order to homogenize professional training in trauma emergencies and to create a National Polytraumatic Registry. The high level of technology of these hospitals and of their human resources that include all the medical, surgical specialties and central services provide an added value. Care to the trauma patients is complex and multidisciplinary. Thus, we believe that General Hospitals, within a traumas program, are the best setting to offer it with excellent conditions.


Curcumin inhibits neuronal and vascular degeneration in retina after ischemia and reperfusion injury.
Neuron loss, glial activation and vascular degeneration are common sequelae of ischemia-reperfusion (I/R) injury in ocular diseases. The present study was conducted to explore the ability of curcumin to inhibit retinal I/R injury, and to investigate underlying mechanisms of the drug effects. Different dosages of curcumin were administered. I/R injury was induced by elevating the intraocular pressure for 60 min followed by reperfusion. Cell bodies, brn3a stained cells and TUNEL positive apoptotic cells in the ganglion cell layer (GCL) were quantitated, and the number of degenerate capillaries was assessed. The activation of glial cells was measured by the expression level of GFAP. Signaling pathways including IKK-IκBα, JAK-STAT1/3, ERK/MAPK and the expression levels of β-tubulin III and MCP-1 were measured by western blot analysis. Pre-treatment using 0.01%-0.25% curcumin in diets significantly inhibited I/R-induced cell loss in GCL. 0.05% curcumin pre-treatment inhibited I/R-induced degeneration of retinal capillaries, TUNEL-positive apoptotic cell death in the GCL, brn3a stained cell loss, the I/R-induced up-regulation of MCP-1, IKKα, p-IκBα and p-STAT3 (Tyr), and down-regulation of β-tubulin III. This dose showed no effect on injury-induced GFAP overexpression. Moreover, 0.05% curcumin administered 2 days after the injury also showed a vaso-protective effect. Curcumin protects retinal neurons and microvessels against I/R injury. The beneficial effects of curcumin on neurovascular degeneration may occur through its inhibitory effects on injury-induced activation of NF-κB and STAT3, and on over-expression of MCP-1. Curcumin may therefore serve as a promising candidate for retinal ischemic diseases.


NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes.
Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1β plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1β is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1β secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1β in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1α, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with α-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1β by microglia, despite a weak pro-inflammatory effect. Amyloid-β peptides were able to activate the NLRP3 inflammasome in microglia and IL-1β secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions.


Sulfur- and acyl chain-dependent influence of 2-methoxy-lysophosphatidylcholine analogues on β pancreatic cells.
Nutrient-induced increase in intracellular Ca(2+) concentration ([Ca(2+)]i) is one of the key mechanisms responsible for insulin release from pancreatic islet β cells. Lysophosphatidylcholine (LPC) was demonstrated to induce insulin secretion from β cells, activate glucose uptake and effectively lower blood glucose levels in mouse models of type 1 and 2 diabetes mellitus. The article hereby presents the results of a characterization of 2-OMe-LPC sulfur analogues with defined acyl residues in terms of their effect on intracellular Ca(2+) concentration and cellular membrane integrity in the murine βTC-3 cell model. Active LPC series that could induce calcium flux in βTC-3 cell model include unmodified LPC 12:0, 14:0, 16:0, and 18:0 as well as phosphorothioate analogues of LPC 12:0, 14:0 and 16:0. However, in the case of species bearing mirystoyl and palmitoyl residues [Ca(2+)]i was associated with membrane permeabilization as demonstrated by propidium iodide incorporation and lactate dehydrogenase release. LPC 12:0 (both unmodified and a sulfurcontaining counterpart) and unmodified LPC 18:0 did not demonstrate membrane disruption but acted as calcium inducers. Interestingly, no stimulation of calcium flux or membrane disruption was observed in the case of LPC analogues with two sulfur atoms introduced into a phosphate group. Experiments with nitrendipine and NiCl2 blocking voltage-dependent calcium channels and the general calcium influx, respectively, revealed remarkably that the compounds studied were involved in different signaling mechanisms while administered to the cell culture, which is clearly related to their chemical structure, both acyl chain and modification dependently.


Fecal microbial transplant effect on clinical outcomes and fecal microbiome in active Crohn's disease.
Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbial transplant (FMT) is a potential therapeutic option for individuals with CD based on the hypothesis that changing the fecal dysbiosis could promote less intestinal inflammation. Nine patients, aged 12 to 19 years, with mild-to-moderate symptoms defined by Pediatric Crohn's Disease Activity Index (PCDAI of 10-29) were enrolled into a prospective open-label study of FMT in CD (FDA IND 14942). Patients received FMT by nasogastric tube with follow-up evaluations at 2, 6, and 12 weeks. PCDAI, C-reactive protein, and fecal calprotectin were evaluated at each study visit. All reported adverse events were graded as mild except for 1 individual who reported moderate abdominal pain after FMT. All adverse events were self-limiting. Metagenomic evaluation of stool microbiome indicated evidence of FMT engraftment in 7 of 9 patients. The mean PCDAI score improved with patients having a baseline of 19.7 ± 7.2, with improvement at 2 weeks to 6.4 ± 6.6 and at 6 weeks to 8.6 ± 4.9. Based on PCDAI, 7 of 9 patients were in remission at 2 weeks and 5 of 9 patients who did not receive additional medical therapy were in remission at 6 and 12 weeks. No or modest improvement was seen in patients who did not engraft or whose microbiome was most similar to their donor. This is the first study to demonstrate that FMT for CD may be a possible therapeutic option for CD. Further prospective studies are required to fully assess the safety and efficacy of the FMT in patients with CD.


Hepatitis C virus chronic infection and oral lichen planus: an Italian case-control study.
The aim of the study was to investigate the possible epidemiological relationship between hepatitis C virus (HCV) chronic infection and oral lichen planus (OLP) in centre-south Italy. In a case-control study three groups of patients were investigated: group 1 (82 patients): patients with histologically confirmed OLP were tested for HCV infection; group 2 (165 patients): patients with chronic HCV infection were examined for OLP; group 3 (466 participants): control group: healthy individuals who had been hospitalized in the Trauma-Orthopaedic Ward and had been tested for HCV. In group 1, 11.4% of the participants were HCV-positive and HCV was found in 10.8% of the patients above 50 years of age. Eight participants (5.5%) of group 2 showed lesions possibly related to OLP: only two had a histology consistent with OLP. In group 3, 5.4% participants had chronic HCV infection, but HCV was found in 10% of the participants of 50 years and above. A weak overall association between HCV and OLP (odds ratio 2.27; 95% confidence interval 0.94, 5.35; P<0.05) was seen and the result was not statistically significant in participants aged 50 years and above (odds ratio 1.08; 95% confidence interval 0.39, 2.88; P=0.86). Our data suggest that no clear association exists between OLP and chronic HCV disease. It is possible that the association is mainly due to the frequency of each disease in the population.


Nano-lead particle synthesis from waste cathode ray-tube funnel glass.
Waste cathode ray-tube (CRT) funnel glass is classified as hazardous waste since it contains high amount of lead. In the present study, a novel process for lead nanopowder synthesis from this type of glass was developed by combining vacuum carbon-thermal reduction and inert-gas consolidation procedures. The key trait of the process was to evaporate lead out of the glass to obtain harmless glass powder and synchronously produce lead nanoparticles. In the synthesis process, lead oxide in the funnel glass was firstly reduced to elemental lead, and evaporated rapidly in vacuum circumstance, then quenched and formed nano-size particles on the surface of the cooling device. Experimental results showed that temperature, pressure and argon gas flow rate were the major parameters controlling lead evaporation ratio and the morphology of lead nanoparticles. The maximum lead evaporation ratio was 96.8% and particles of 4-34 nm were successfully obtained by controlling the temperature, holding time, process pressure, argon gas flow rate at 1000°C, 2-4h, 500-2000 Pa, 50-200 ml/min, respectively. Toxicity characteristic leaching procedure (TCLP) results showed that lead leaching from the residue glass met the USEPA threshold. Accordingly, this study developed a practical and environmental-friendly process for detoxification and reclamation of waste lead-containing glass.


[Types of hypertension in pregnant women of Benin admitted to the National University Hospital of Cotonou].
We carried out a retrospective and prospective study between January 1995 and August 1996, of pregnant women with high blood pressure. The aim of this work was to determine the prevalence of each type of hypertension according to the classification of the American College of Obstetricians and Gynecologists (ACOG) and to evaluate the prognosis for the mother and child. The prevalence of hypertension in pregnancy was found to be 7.65%. A family history of hypertension, obesity and a personal history of hypertension in pregnancy were all risk factors. Severe hypertension (diastolic blood pressure (DBP) > 110 mm Hg) affected 59.4% of the women. Chronic hypertension occurred in 41.51% of cases, preeclampsia in 26.41% of cases, associated preeclampsia in 18.87% of cases and isolated hypertension in 13.21% of cases. Eclampsia (70.6%) was the principal maternal complication in this study population. Fifty-four of the women gave birth to normal babies, 21 to hypotrophic babies, 15 gave birth prematurely and 3 had miscarriages. Six of the seven deaths involved women with DBP above 110 mm Hg.


Fasting blood glucose and HbA1c in children with ADHD.
Reports of hypocortisolism and overweight in pediatric ADHD motivate an investigation of blood glucose regulation in this group. Fasting blood glucose and HbA1c were investigated in 10 children (10-15 years) with ADHD and 22 comparisons. Fasting blood glucose was similar in both groups. HbA1c values were higher in the ADHD-group. BMI-SDS was also higher in the ADHD-group but did not predict HbA1c. The results suggest an association between ADHD and an altered blood glucose homeostasis.


Attention-deficit/hyperactivity disorder (ADHD) and obesity: a systematic review of the literature.
Recent studies suggest a possible comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity. To gain insight into this potential association, we performed a systematic review of the literature excluding case reports, non-empirical studies, and studies not using ADHD diagnostic criteria. Empirically based evidence suggests that obese patients referred to obesity clinics may present with higher than expected prevalence of ADHD. Moreover, all reviewed studies indicate that subjects with ADHD are heavier than expected. However, data on the prevalence of obesity in subjects with ADHD are still limited. As for the mechanisms underlying the potential association between ADHD and obesity, ADHD might lead to obesity via abnormal eating behaviors, impulsivity associated with binge eating might contribute to ADHD in obese patients, or, alternatively, both obesity and ADHD might be the expression of common underlying neurobiological dysfunctions, at least in a subset of subjects. In patients with obesity and ADHD, both conditions might benefit from common therapeutic strategies. Further empirically based studies are needed to understand the potential comorbidity between obesity and ADHD, as well as the possible mechanisms underlying this association. This might allow a more appropriate clinical management and, ultimately, a better quality of life for patients with both obesity and ADHD.


Prevention of nosocomial aspergillosis.
Unfiltered outside air averages 1-15 pathogenic Aspergillus sp. colony forming units (cfu) m-3 although short-term fluctuations are substantial. Seasonal variation reflects increased spore prevalence during periods of greater availability of non-viable matter. In hospital, airborne spores reflect incomplete filtration, infiltration of outside air and shedding of adherent spores from introduced objects. In highly protected hospital areas supplied with air filtered at high efficiency, where aspergillus cfus may be as low as 0.01 cfu m-3, infiltration and shedding contribute a high fraction of ambient spores. Nosocomial aspergillosis occurs in linear proportion to the mean ambient hospital airborne spore content. An analysis presuming a steady-state dynamic equilibrium is imperfect because repeated sampling produces occasional high counts which violate a Poisson distribution. 'Mini-bursts' arise from disturbance of settled spores in dust, shedding spores from clothes or other subtle sources. These sources are best mitigated by increasing the air change rate. It is most important to protect bone marrow transplant patients, leukaemia and lymphoma patients undergoing intensive, potentially curative therapy. The optimal protective environments include high filtration efficiency, point-of-use filters, protection against infiltration and filter bypass, elimination of in-hospital sources, and high air change rates.


Gender differences in grant and personnel award funding rates at the Canadian Institutes of Health Research based on research content area: A retrospective analysis.
Although women at all career stages are more likely to leave academia than men, early-career women are a particularly high-risk group. Research supports that women are less likely than men to receive research funding; however, whether funding success rates vary based on research content is unknown. We addressed gender differences in funding success rates for applications directed to one or more of 13 institutes, representing research communities, over a 15-year period. We retrospectively reviewed 55,700 grant and 4,087 personnel award applications submitted to the Canadian Institutes of Health Research. We analyzed application success rates according to gender and the primary institute selected by applicants, pooled gender differences in success rates using random effects models, and fitted Poisson regression models to assess the effects of gender, time, and institute. We noted variable success rates among grant applications directed to selected institutes and declining success rates over time. Women submitted 31.1% and 44.7% of grant and personnel award applications, respectively. In the pooled estimate, women had significantly lower grant success (risk ratio [RR] 0.89, 95% confidence interval [CI] 0.84-0.94; p < 0.001; absolute difference 3.2%) compared with men, with substantial heterogeneity (I2 = 58%). Compared with men, women who directed grants to the Institutes of Cancer Research (RR 0.86, 95% CI 0.78-0.96), Circulatory and Respiratory Health (RR 0.74, 95% CI 0.66-0.84), Health Services and Policy Research (RR 0.78, 95% CI 0.68-0.90), and Musculoskeletal Health and Arthritis (RR 0.80, 95% CI 0.69-0.93) were significantly less likely to be funded, and those who directed grants to the Institute of Aboriginal People's Health (RR 1.67, 95% CI 1.0-2.7) were more likely to be funded. Overall, women also had significantly lower personnel award success (RR 0.75, 95% CI 0.65-0.86; p < 0.001; absolute difference 6.6%). Regression modelling identified that the effect of gender on grant success rates differed by institute and not time. Study limitations include use of institutes as a surrogate identifier, variability in designation of primary institute, and lack of access to metrics reflecting applicants, coapplicants, peer reviewers, and the peer-review process. Gender disparity existed overall in grant and personnel award success rates, especially for grants directed to selected research communities. Funding agencies should monitor for gender differences in grant success rates overall and by research content.


Biomass Allocation in Response to Nitrogen and Phosphorus Availability: Insight From Experimental Manipulations of Arabidopsis thaliana.
Allocation of biomass to different organs is a fundamental aspect of plant responses and adaptations to changing environmental conditions, but how it responds to nitrogen (N) and phosphorus (P) availability remains poorly addressed. Here we conducted greenhouse fertilization experiments using Arabidopsis thaliana, with five levels of N and P additions and eight repeat experiments, to ascertain the effects of N and P availability on biomass allocation patterns. N addition increased leaf and stem allocation, but decreased root and fruit allocation. P addition increased stem and fruit allocation, but decreased root and leaf allocation. Pooled data of the five levels of N addition relative to P addition resulted in lower scaling exponents of stem mass against leaf mass (0.983 vs. 1.226; p = 0.000), fruit mass against vegetative mass (0.875 vs. 1.028; p = 0.000), and shoot mass against root mass (1.069 vs. 1.324; p = 0.001). This suggested that N addition relative to P addition induced slower increase in stem mass with increasing leaf mass, slower increase in reproductive mass with increasing vegetative mass, and slower increase in shoot mass with increasing root mass. Further, the levels of N or P addition did not significantly affect the allometric relationships of stem mass vs. leaf mass, and fruit mass vs. vegetative mass. In contrast, increasing levels of N addition increased the scaling exponent of shoot to root mass, whereas increasing levels of P addition exerted the opposite influence on the scaling exponent. This result suggests that increasing levels of N addition promote allocation to shoot mass, whereas the increasing levels of P addition promote allocation to root mass. Our findings highlight that biomass allocation of A. thaliana exhibits a contrasting response to N and P availability, which has profound implications for forecasting the biomass allocation strategies in plants to human-induced nutrient enrichment.


Measuring mitochondrial respiration in adherent cells infected with Trypanosoma cruzi Chagas, 1909 using Seahorse extracellular flux analyser.
Infection with Trypanosoma cruzi Chagas, 1909 is reported to increase the production of reactive oxygen species in patients with Chagas disease. Mitochondria dysfunction, host inflammatory response and inadequate antioxidant response are described as the main factors leading to oxidative stress during acute and chronic stages of the disease. The Seahorse XFe24 extracellular flux platform allows energy metabolism determination through mitochondrial respiration and glycolysis measurements. XFe24 platform can be used in in vitro models of T. cruzi-infected cells, which allow the assessment and even modulation of endogenous conditions of infected cells, generating readouts of real-time cellular bioenergetics changes. In this protocol, we standardised the use of XFe24 technology in T. cruzi infected AC16 cardiomyocytes and SGHPL-5 trophoblasts. In addition, we provide a list of optimised assay specifications, advantages and critical steps to be considered during the process. Cardiomyocytes and trophoblasts are attractive target cells to evaluate the metabolic environment in acute, chronic and congenital Chagas transmission scenarios.


A Single Bout of High-intensity Interval Exercise Increases Corticospinal Excitability, Brain-derived Neurotrophic Factor, and Uncarboxylated Osteolcalcin in Sedentary, Healthy Males.
Exercise induces neuroplasticity in descending motor pathways facilitating motor learning, and as such it could be utilized as an intervention in neurorehabilitation, for example when re-learning motor skills after stroke. To date, however, the neurophysiological and molecular mechanisms underlying exercise-induced neuroplasticity remain largely unknown impeding the potential utilization of exercise protocols as 'motor learning boosters' in clinical and non-clinical settings. Here, we assessed corticospinal excitability, intracortical facilitation (ICF) and short-interval intracortical inhibition (SICI) using transcranial magnetic stimulation (TMS) and serum biochemical markers including brain-derived neurotrophic factor (BDNF), total and precursor cathepsin B (tCTSB, proCTSB), uncarboxylated and carboxylated osteocalcin (unOCN, cOCN) and irisin using ELISA. Measurements were carried out in sedentary, healthy males before and after a single session of high-intensity interval exercise (HIIE) or in individuals who rested and did not perform exercise (No Exercise). We found that HIIE increased corticospinal excitability, BDNF and unOCN, and decreased cOCN. We also determined that greater increases in BDNF were associated with increases in unOCN and irisin and decreases in cOCN only in participants who underwent HIIE, suggesting that unOCN and irisin may contribute to exercise-induced BDNF increases. Conversely, no changes other than a decrease in serum unOCN/tOCN were found in No Exercise participants. The present findings show that a single session of HIIE is sufficient to modulate corticospinal excitability and to increase BDNF and unOCN in sedentary, healthy males.


[Diagnosis of bronchogenic carcinoma with MRI].
MRI anatomy of 15 normal chests and features of 24 patients with bronchogenic carcinoma confirmed by surgery or exfoliative cell examination of sputum were analysed. The authors preliminarily conclude that MRI is of remarkable diagnostic value in demonstrating tumor size, its location and extent, exhibiting the relationship between tumor mass and its surrounding such as greater vessel, trachea and bronchi and so forth. It is also more efficient in detecting hilar or mediastinal metastatic lymphadenopathy.


Reproducibility and Reliability of the Radiographic Angles Used to Assess Tailor's Bunions.
Tailor's bunion, or bunionette, deformity is a common condition of the lateral forefoot. To aid in assessing the deformity, radiographic angular measurements are frequently used. The objective of this study was to determine the reliability and reproducibility of these angular measurements. Thirty unique weightbearing dorsoplantar digital radiographs of pathologic feet were compiled. For these 30 radiographs and for ten repeated radiographs, six practicing clinicians measured the following angles: the fourth to fifth intermetatarsal angle, the lateral deviation angle, and the fifth metatarsophalangeal angle. Both traditional and modified versions of the fourth to fifth intermetatarsal angle were included. Intraclass correlation coefficient values were calculated for each of the angles studied. Intrarater reliability was highest for the fifth metatarsophalangeal angle and lowest for the lateral deviation angle. Intrarater reliability was higher for the traditional fourth to fifth intermetatarsal angle than for the modified version. The interrater reliability calculations revealed parallel findings. Accurate assessment is critical when planning for surgical intervention. Awareness of the relative reliability of these radiographic angular measurements can aid in preoperative planning and may be of benefit in procedure selection.


Maternal obesity and baseline vitamin D insufficiency alter the response to vitamin D supplementation: a double-blind, randomized trial in pregnant women.
The achievement of target 25-hydroxyvitamin D [25(OH)D] concentrations in pregnancy may be altered by maternal obesity. The authors examined the effects of maternal supplementation of 10 μg compared with 20 μg vitamin D3/d on maternal and umbilical cord 25(OH)D. The secondary aim was to investigate the influence of maternal BMI (in kg/m2) on the response of the primary outcomes. The authors performed a 2-arm parallel double-blind randomized trial with 240 pregnant women recruited throughout the year in Northern Ireland. Women were stratified by BMI to receive 10 or 20 µg vitamin D3/d from 12 gestational wk (GW) until delivery. Maternal blood samples collected at 12, 28, and 36 GW and from the umbilical cord were analyzed for total serum 25(OH)D. A total of 166 women completed the study. Mean ± SD 25(OH)D at 36 GW was 80.8 ± 28.2 compared with 94.4 ± 33.2 nmol/L (P < 0.001) (10 compared with 20 µg vitamin D3/d, respectively). In those classified with 25(OH)D <50 nmol/L at baseline and assigned 10 µg vitamin D3/d, mean 25(OH)D concentrations remained <50 nmol/L at 36 GW, whereas those <50 nmol/L at baseline and assigned 20 µg vitamin D3/d, had mean 25(OH)D concentrations ≥50 nmol/L at 28 and 36 GW. In women with obesity and 25(OH)D <50 nmol/L at baseline, the related mean umbilical cord 25(OH)D was deficient (<25 nmol/L) in both treatment groups, whereas those with obesity and 25(OH)D ≥50 nmol/L at baseline had an average umbilical cord 25(OH)D between 25 and 50 nmol/L in both treatment groups. Supplementation of 20 µg vitamin D3/d is needed to attain maternal and umbilical cord 25(OH)D concentrations ≥50 nmol/L on average, in those who start pregnancy with low 25(OH)D concentrations (<50 nmol/L). Under current recommendations, women with obesity and low 25(OH)D in early pregnancy are particularly vulnerable to maintaining a low 25(OH)D concentration throughout pregnancy and having an infant born with deficient 25(OH)D concentrations. This trial was registered at ClinicalTrials.gov as NCT02713009.


[Computed tomography diagnostics of acute and chronic mesenteric ischemia].
Chronic mesenteric ischemia is more often accompanied by clinical signs characteristic of colitis. Acute mesenteric ischemia, unlike chronic, is accompanied by nonspecific symptoms and is a serious disease that requires urgent diagnosis. The aim of the study was to evaluate the effectiveness of MSCT in the diagnosis of acute and chronic mesenteric ischemia based on our observations. The retrospective study included 135 patients with abdominalgia and suspected mesenteric ischemia who underwent multiphase CT of the abdominal cavity with intravenous bolus contrast enhancement. Group 1 included 105 patients with mesenteric ischemia; group 2 included 30, without confirmed mesenteric ischemia, with the presence of a symptom of mesenteric ischemia in the form of abdominalgia. We studied 135 patients, including 105 patients with mesenteric ischemia, 59 women and 46 men of average age 60±14.9 years. The acute form of ischemia (58%) was determined 1.5 times more often than the chronic one. Occlusive and nonocclusive acute mesenteric ischemia occurred in equal proportions. Mesenteric arterial thrombosis was the cause of acute mesenteric ischemia in 23% of cases. Mesenteric venous thrombosis was the cause of chronic intestinal ischemia in 61%, in 5% - acute form. Mixed arterial-venous genesis of mesenteric ischemia was determined in 4% against the background of strangulation obstruction. Dunbar syndrome as a cause of chronic intestinal ischemia was diagnosed in 16%. Chronic ischemic enterocolitis accounted for 10% of all cases of mesenteric ischemia and 23% of chronic ischemia. Symptoms and symptom complexes characteristic of the studied series of diseases with acute or chronic mesenteric ischemia were delineated. Sensitivity, specificity and prognostic value of CT with intravenous bolus contrast enhancement in diagnostics of diseases accompanied by mesenteric ischemia reached 100%. Multiphase CT of the abdominal cavity with bolus contrast enhancement is highly informative in the diagnosis of acute and chronic forms of mesenteric ischemia. Direct CT signs of impaired blood flow in the arteries or veins of the mesentery were indisputable. Indirect signs of mesenteric ischemia were aimed at a thorough analysis of the condition of mesenteric vessels.


Transfusion Practice in Trauma Resuscitation.
Recognition of the acute coagulopathy of trauma and the limits of reconstituting whole blood with conventional blood components has led to a radical change in the way trauma patients with severe injuries are resuscitated. Massive transfusion protocols (MTP) have evolved toward the administration of conventional blood components in fixed ratios. Administration of a 1:1:1 unit ratio of fresh frozen plasma to whole-blood-derived platelets to packed red blood cells is now the most common strategy and the stated goal of directors of >80% of the level I trauma centers in the United States. Various physiologic scoring systems exist to guide early activation of an MTP. After activation of an MTP, more goal-directed therapy follows as soon as laboratory results are available. Hemostatic resuscitation using defined blood component ratios modified by early laboratory results can lead to more efficient blood product usage and improved patient outcomes.


Surgical dressings and turbulent years of cotton industry.
Everyday use of a simple cotton bud should remind us of our not so distant past and of the appalling trade in people. Harvesting this precious commodity required forced labour eventually leading to a key turning point in the history of surgery, as civil war raged in America during the 1860s. The fight to end slavery was to reveal a new weapon against disease and certain death. A material used in this struggle against wound infection was the available stockpiles of redundant cotton. Once boiled to make softer, its use on patients in military hospitals proved to be the first clinical application of sterile surgical dressings.


Bioinformatic Identification of the Pyroptosis-Related Transcription Factor-MicroRNA-Target Gene Regulatory Network in Angiotensin II-Induced Cardiac Remodeling and Validation of Key Components.
Accumulative evidence suggests that pyroptosis plays a key role in mediating angiotensin II (Ang II)-induced cardiac remodeling However, the potential role of pyroptosis-related transcription factor (TF)-microRNA (miRNA)-gene regulatory networks in mediating Ang II-associated cardiac remodeling remains largely unknown. Therefore, we identified the pyroptosis-related hub genes and constructed a transcription factor (TF)-miRNA-target gene regulatory network using bioinformatic tools to elucidate the pathogenesis of Ang II-induced cardiac remodeling. The pyroptosis-related differentially expressed genes (DEGs) were identified from the cardiac remodeling-related dataset GSE47420. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis were performed to identify the pyroptosis-related hub DEGs. A TF-miRNA-target gene network was constructed and further validated by quantitative real-time polymerase chain reaction (qRT-PCR) in animal experiments. The correlation between the pyroptosis-related hub DEGs and cardiac remodeling was evaluated using comparative toxicogenomics database. The drug-gene interaction analysis was performed to identify potential drugs that target the pyroptosis-related hub DEGs. A total of 32 pyroptosis-related DEGs were identified and enriched in the inflammation-related pathways by KEGG analysis. 13 of the 32 pyroptosis-related DEGs were identified as hub DEGs. Furthermore, a TF-miRNA-target gene regulatory network containing 16 TFs, 6 miRNAs, and 5 hub target genes was constructed. The five pyroptosis-related hub target genes (DDX3X, ELAVL1, YWHAZ, STAT3, and EED) were identified as crucial cardiac remodeling-related genes using the comparative toxicogenomics database (CTD) database. Five drugs including celecoxib were identified as potential drugs for the treatment of cardiac remodeling. Finally, the expression levels of two top-ranked TF-miRNA-target genes axis were verified by qRT-PCR in mice with Ang II-induced cardiac remodeling and found to be generally consistent with the microarray results. This study constructed a pyroptosis-related TF-miRNA-target gene regulatory network for Ang II-induced cardiac remodeling. Five pyroptosis-related genes (DDX3X, ELAVL1, YWHAZ, STAT3, and EED) can be considered the core genes associated with pyrotposis-related cardiac remodeling. The findings of this study provide new insights into the molecular mechanisms of Ang II-induced cardiac remodeling and may serve as potential biomarkers or therapeutic targets for Ang II-induced cardiac remodeling.


Type IV spinal arteriovenous malformation in association with familial pulmonary vascular malformations: case report.
Type IVc arteriovenous malformations (AVMs) of the spinal cord consist of multiple high-flow feeding vessels, and they often present a challenging management situation. Their location is intradural and extramedullary, and they are rare malformations that are difficult to treat owing to the risk of thrombosis of the anterior spinal artery. The authors report a case of Type IVc spinal AVM in a patient with a family history of three siblings with pulmonary AVMs. Spinal AVMs have been reported to be associated with inherited syndromes such as familial cutaneous hemangiomas and Kartagener's syndrome, but an association with pulmonary AVMs has not previously been described. A 27-year-old man presented with sudden onset of occipital headache with cervical radiation while weightlifting. Results of computed tomography of the brain were normal, but lumbar puncture revealed a subarachnoid hemorrhage. The patient had a 1-year history of a neurogenic bladder and exhibited marked left calf muscle wasting. The patient underwent spinal magnetic resonance imaging, which revealed the AVM in the conus region. Selective spinal angiography was performed for diagnostic purposes. A laminectomy was performed, and the vessels feeding the AVM were clipped, as was the fistula. The patient remained neurologically stable, and angiography confirmed obliteration of the AVM. This is the first case report of a patient with a spinal AVM who had multiple siblings with pulmonary malformations or AVMs.


[Barriers in health care to breast cancer: perception of women].
Identifying the barriers in the access to health care to breast cancer perceived by women undergoing chemotherapy. An exploratory descriptive study. The sample consisted of 58 women with breast cancer receiving chemotherapy and registered in the public oncology ambulatory of Aracaju-Sergipe. Data collection was carried out between October 2011 and March 2012 by semistructured interviews, and data were processed using the SPSS, version 17. Among the interviewed women, 37 (63.8%) reported at least a barrier in the trajectory of care for breast cancer. The organizational and health services barriers were the most reported in the periods of investigation and treatment of breast cancer. In face of these findings, the barriers should be considered in public health policies and programs for the control of breast cancer in Sergipe.