Feeding behaviors collected from automated milk feeders were associated with disease in group-housed dairy calves in the Upper Midwest United States.
Automated milk feeders (AMF) are an attractive option for producers interested in adopting practices that offer greater behavioral freedom for calves and can potentially improve labor management. These feeders give farmers the opportunity to have a more flexible labor schedule and more efficiently feed group-housed calves. However, housing calves in group systems can pose challenges for monitoring calf health on an individual basis, potentially leading to increased morbidity and mortality. Feeding behavior recorded by AMF software could potentially be used as an indicator of disease. Therefore, the objective of this observational study was to investigate the association between feeding behaviors and disease in preweaning group-housed dairy calves fed with AMF. The study was conducted at a dairy farm located in the Upper Midwest United States and included a final data set of 599 Holstein heifer calves. The farm was visited on a weekly basis from May 2018, to May 2019, when calves were visually health scored and AMF data were collected. Calf health scores included calf attitude, ear position, ocular discharge, nasal discharge, hide dirtiness, cough score, and rectal temperatures. Generalized additive mixed models (GAMM) were used to identify associations between feeding behavior and disease. The final quasibinomial GAMM included the fixed (main and interactions) effects of feeding behavior at calf visit-level including milk intake (mL/d), drinking speed (mL/min), visit duration (min), rewarded (with milk being offered) and unrewarded (without milk) visits (number per day), and interval between visits (min), as well as the random effects of calf age in regard to their relationship with calf health status. Total milk intake (mL/d), drinking speed (mL/min), interval between visits (min) to the AMF, calf age (d), and rewarded visits were significantly associated with dairy calf health status. These results indicate that as total milk intake and drinking speed increased, the risk of calves being sick decreased. In contrast, as the interval between visits and age increased, the risk of calves being sick also increased. This study suggests that AMF data may be a useful screening tool for detecting disease in dairy calves. In addition, GAMM were shown to be a simple and flexible approach to modeling calf health status, as they can cope with non-normal data distribution of the response variable, capture nonlinear relationships between explanatory and response variables and accommodate random effects.


Cochlear Implant Device Failure in the Postoperative Period: An Institutional Analysis.
As the cochlear implant (CI) surgeries are on rise, there is a compelling need to understand its long-term complications and revision surgery protocols. Our experience in the management of CI devices failure is shared in this paper. To review the experience in patients who underwent CI device manipulation/explanation in terms of failure rate, etiology, surgical considerations, and preoperative and postoperative auditory and speech outcome. This was a retrospective study. A retrospective study of 250 patients (201 children and 49 adults) with normal cochlea at a tertiary care center from June 2004 to June 2014 was done. All cases were implanted multichannel devices via Veria technique of CI surgery. Preoperative assessment, surgical considerations, and postoperative auditory and speech outcomes were analyzed. Preoperative and postoperative auditory/speech outcomes were analyzed using Category of Auditory Perception (CAP) and Speech Intelligibility Rating (SIR) scores. Reimplantation rate was 4%. The causes of revision CI surgery were hard device failure (n = 3), surgical site infection (n = 3), magnet displacement (n = 2), and electrode extrusion (n = 2). In one patient, recurrent cutaneous infection on the implanted site ultimately resulted in reimplantation in the opposite ear after multiple surgical interventions on the same side. The preoperative and postoperative CAP and SIR scores showed improvement in the postoperative period with P < 0.05 as compared with the paired t-test. Preoperative counseling for device failure should always be emphasized. The success rate is high in revision surgery with good performance in the postoperative audiological outcome. There is a compelling need for an agreed international definition of CI failure and the adoption of uniform reporting protocols.


A prospective longitudinal brain morphometry study of children with sickle cell disease.
Age-related changes in brain morphology are crucial to understanding the neurobiology of sickle cell disease. We hypothesized that the growth trajectories for total GM volume, total WM volume, and regional GM volumes are altered in children with sickle cell disease compared with controls. We analyzed T1-weighted images of the brains of 28 children with sickle cell disease (mean baseline age, 98 months; female/male ratio, 15:13) and 28 healthy age- and sex-matched controls (mean baseline age, 99 months; female/male ratio, 16:12). The total number of MR imaging examinations was 141 (2-4 for each subject with sickle cell disease, 2-3 for each control subject). Total GM volume, total WM volume, and regional GM volumes were measured by using an automated method. We used the multilevel-model-for-change approach to model growth trajectories. Total GM volume in subjects with sickle cell disease decreased linearly at a rate of 411 mm(3) per month. For controls, the trajectory of total GM volume was quadratic; we did not observe a significant linear decline. For subjects with sickle cell disease, we found 35 brain structures that demonstrated age-related GM volume reduction. Total WM volume in subjects with sickle cell disease increased at a rate of 452 mm(3) per month, while the trajectory of controls was quadratic. There was a significant age-related decrease in total GM volume in children with sickle cell disease. The GM volume reduction was spatially distributed widely across the brain, primarily in the frontal, parietal, and occipital lobes. Total WM volume in subjects with sickle cell disease increased at a lower rate than for controls.


Adolescents provide more complex reasons for lowering the voting age than do adults: Evidence from national convenience samples.
Debates about lowering the voting age often center on whether 16- and 17-year-old adolescents possess sufficient cognitive capacity and political knowledge to participate in politics. Little empirical research has examined age differences in adolescents' and adults' complexity of reasoning about political issues. We surveyed adults (n = 778; Mage = 38.5, SD = 12.5; 50% female; 72% non-Hispanic White) and 16- and 17-year-old adolescents (n = 397; 65% female; 69% non-Hispanic White) concerning judgments and justifications about whether the United States should change the minimum voting age. Justifications for changing the voting age were coded for integrative (i.e., integrating multiple perspectives to form a judgment about changing the voting age), elaborative (i.e., providing multiple reasons to support the same judgment about changing the voting age), and dialectical (i.e., recognizing multiple differing perspectives on changing the voting age) complexity of reasoning. Bayesian regressions indicated that adolescents provided greater integrative and elaborative complexity in their reasoning to change the voting age than adults. Adolescents and adults did not meaningfully differ in their dialectical complexity. Findings are consistent with past research indicating that adolescents possess the cognitive capacity and political knowledge to vote in U.S. elections. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


[Beta-endorphins and bronchial asthma in children].
The content of beta-endorphins was studied in 64 children aged 6 to 14 years with atopic bronchial asthma (BA). The phasic relationship was established in the time course of changes in the content of beta-endorphins. In the paroxysmal period of BA, the concentration of beta-endorphins in blood was lowered, whereas after attacks and in the stage of remission, the level of beta-endorphins was increased and differed significantly from the indicators in the control group. The reduction of the content of beta-endorphins during exacerbation correlated with the disease gravity. The content of endorphins was found to be affected by the age and sex: the greater reduction of the level of beta-endorphins was recorded in children aged 6 to 11 years and in boys. The reduction of the level of beta-endorphins was followed by the impairment of interhormonal relations between ACTH and beta-endorphins, ACTH and hydrocortisone in all the disease phases. A correlation was discovered between the level of beta-endorphins and ACTH, cAMP as well as the level of IgE in blood plasma. It is suggested that derangements in the endorphin system may influence the mechanisms by which bronchial hyperreactivity is formed.


Supracondylar fractures of the humerus. A comparative study of Dunlop's traction versus percutaneous pinning.
A retrospective comparative study was done of two groups of patients with displaced supracondylar fractures of the humerus. The patients in the first group were treated with Dunlop's traction, while those in the second group were treated by percutaneous pin fixation. There were thirty-six patients in the group treated with Dunlop's traction, of whom twenty-seven were seen in follow-up with an average time of 2.7 years. Twenty-eight patients were in the group treated with pin fixation, of whom twenty were seen in follow-up with an average time of 2.9 years. In each case the chart and roentgenograms were reviewed and the patient was examined. The results showed a 33 per cent incidence of cubitus varus (so-called gunstock deformity) in the patients treated with Dunlop's traction as compared with 5 per cent in those pinned percutaneously. The range of elbow motion was also slightly better in the group treated with pin fixation. Furthermore, the costs and hospital stays were significantly less in those treated by pinning. Complications in both groups were few.


Release of vancomycin and gentamicin from a contact lens versus a fibrin coating applied to a contact lens.
To develop a contact lens capable of releasing antibiotics for a minimum of 8 hours for the treatment of bacterial keratitis. Fibrin gel was loaded with vancomycin or gentamicin and then shaped into a curved disc. The disc was then used to coat the surface of a commercial contact lens or was sealed between two lenses. Separate contact lenses were soaked in solutions of vancomycin or gentamicin. The in vitro release kinetics for each system was determined using PBS at 37°C and a particle-enhanced turbidimetric inhibition immunoassay. The bioactivity of the antibiotics released from the fibrin was confirmed by using a microbiological assay. Vancomycin and gentamicin were released at similar rates from soaked contact lenses and a coating of fibrin gel; however, the amounts of antibiotic delivered by the two systems differed considerably. The fibrin coating released over three times more gentamicin but less than one-fifth that of the lenses soaked in vancomycin. When fibrin was encapsulated between two contact lenses, significantly more controlled release was observed. For all systems, bactericidal amounts of vancomycin and gentamicin were released throughout the three-day testing period. As a delivery system, fibrin gel loaded with gentamicin performs better than contact lenses soaked in gentamicin. The opposite is true for vancomycin, where soaked lenses outperform fibrin gel. These systems could potentially be used as a treatment for bacterial keratitis.


Spatial (E)quality from a User Perspective.
Universal Design (UD) has gained global significance and is in the process of being interpreted and institutionalised in the Nordic Region. Hence a broader understanding of the theoretical basis and practical architectural applicability of UD is advancing. This paper builds a framework for understanding two current notions of UD and accessibility in Denmark. Implications are that understandings and motivations of UD and accessibility from architects' and users' perspective are asymmetrical. In collaborative relationships, UD and accessibility are seen from an architectural design perspective and a human rights perspective respectively. This influences the dialogue and cooperation of the two parties. Reflecting the possibility to further a comprehensive understanding of spatial implication of UD, this paper aims to contribute with a clarification and a discussion of the two perspectives. Within the architectural field, Disabled People's Organisations Denmark (DPOD) is one of the key actors in user participatory processes related to UD and accessibility, and the organisations play an important role in a Danish discourse. Through observations and interviews with DPOD user representation and practicing architects, the paper sheds light on the central notions of UD and accessibility - a spatial quality perception and a spatial equality perception. Along with qualitative research conducted at the Danish Building Research Institute, the on-going PhD research project "Generating Inclusive Built Environments through User Driven Dialogue in the Architectural Design Process" frames current thinking and discusses the process of advancing the dialogue, in direction of furthering both Spatial Quality and Spatial Equality.


Cordycepin inhibits human ovarian cancer by inducing autophagy and apoptosis through Dickkopf-related protein 1/β-catenin signaling.
Cordycepin, the major active component from Cordyceps militaris, has been reported to significantly inhibit some types of cancer; however, its effects on ovarian cancer are still not well understood. In this study, we treated human ovarian cancer cells with different doses of cordycepin and found that it dose-dependently reduced ovarian cancer cell viability, based on Cell counting kit-8 reagent. Immunoblotting showed that cordycepin increased Dickkopf-related protein 1 (Dkk1) levels and inhibited β-catenin signaling. Atg7 knockdown in ovarian cancer cells significantly inhibited cordycepin-induced apoptosis, whereas β-catenin overexpression abolished the effects of cordycepin on cell death and proliferation. Furthermore, we found that Dkk1 overexpression by transfection downregulated the expression of c-Myc and cyclin D1. siRNA-mediated Dkk1 silencing downregulated the expression of Atg8, beclin, and LC3 and promoted β-catenin translocation from the cytoplasm into the nucleus. These results suggest that cordycepin inhibits ovarian cancer cell growth, possibly through coordinated autophagy and Dkk1/β-catenin signaling. Taken together, our findings provide new insights into the treatment of ovarian cancer using cordycepin.


Putting People First: Critical Reforms for Canada's Health Care System.
For over 70 years, since the Dominion Provincial Conferences at the end of the Second World War, Canadians have viewed health care as a right of citizenship. The Canada Health Act (CHA, 1984) formally entrenched the five principles that guide our current publicly operated, single payer, provincially managed system: public administration, comprehensiveness, universality, portability and accessibility. The health care system that has sprung up around the CHA has become increasingly complex, costly and strained. Our gradual descent through the rankings of major health care suggests that we are reaching the limits of what the current health care system can provide. Unfortunately, constructive political debate around this issue is often choked by intense ideological positioning. System reform is urgently needed to address the rapidly changing biological and demographic drivers of health. We do not feel that diverting ever larger flows of money into the status quo is a sustainable solution. Our nation's health and the means to advance it must be seen as assets rather than costs. We believe it is possible to meet increasing demands by expanding the supply and acknowledging the wealth of resources (scientific, human, managerial and educational) that we currently possess. In this paper we propose a cultural shift from an institution-centered system bent on cost control, to a patient-centered system that fosters a true health economy. We identify a series of interventions (some bold and others less so) to achieve a clear and evaluable goal: maximizing the well-being and debility-free life expectancy of each individual. To achieve a patient-centred system-we discuss strategies to address costs and utilization, the setting of real performance standards, the elimination of conflicts of interest and the provision of truly accessible care for all Canadians. To create a health economy, we discuss the importance of innovation, the need for a reinvigorated public health system and steps to overhaul the health care human resources environment. The goal of health care reform in Canada should be a system that is dynamic, evidence based, wealth creating and a global leader. We believe that, with leadership and vision, this goal is eminently achievable.


Cytotoxic T lymphocyte responses in allogeneic radiation bone marrow chimeras. The chimeric host strictly dictates the self-repertoire of Ia-restricted T cells but not H-2K/D-restricted T cells.
The present report has used fully H-2 allogeneic radiation bone marrow chimeras to assess the role of host restriction elements in determining the self-specificity of Ia- and H-2K/D-restricted T cells that participate in the generation of trinitrophenyl (TNP)-specific cytotoxic T lymphocytes (CTL). It was demonstrated that there exists a stringent requirement for the recognition of host thymic-type Ia determinants, but there exists only a preference for host thymic-type H-2K/D determinants. Indeed, once the stringent requirement for recognition of host Ia determinants was fulfilled, anti-TNP CTL were generated in response to TNP-modified stimulators that expressed either donor-type or host-type H-2K/D determinants. The CTL that were generated in response to TNP-modified donor-type stimulators were shown to be specific for TNP and restricted to the non-thymic H-2K/D determinants of the chimeric donor. Thus, these results demonstrate in a single immune response that the thymic hypothesis accurately predicts the self-specificity expressed by Ia-restricted T cells, but does not fully account for the self-specificity expressed by H-2K/D-restricted T cells. These results are consistent with the concept that H-2K/D-restricted T cells, but not Ia-restricted T cells, can differentiate into functional competence either intrathymically or extra-thymically. The present results are also informative for understanding the cellular interactions that are required for the generation of antigen-specific CTL responses. The Ia-restricted T cells that are required for the generation of H-2K/D-restricted anti-TNP CTL were shown to be helper T (TH) cells since (a) like TH cells functioning in antibody responses, they were specific for Ia determinants expressed by accessory cells, and (b) their function could be replaced by either TNP-primed, irradiated TH cells or by nonspecific soluble helper factors. It was also shown that the T-T cell interaction between Ia-restricted TH cells and H-2K/D-restricted precursor CTL (pCTL) is not Ia restricted. Rather, the results demonstrate that the generation of anti-TNP CTL responses involve two parallel sets of major histocompatibility complex-restricted cell interactions, an Ia-restricted TH-accessory cell interaction required for TH cell activation, and an H-2K/D-restricted pCTL-stimulator cell interaction required for pCTL stimulation. The interaction between activated TH cells and stimulated pCTL is mediated, at least in part, by nonspecific soluble helper factors.


Uveitis-Glaucoma-Hyphema Syndrome Following iStent Implantation.
Minimally invasive glaucoma surgery (MIGS) is a subset of glaucoma surgery that is known for its low rate of complications both intraoperatively and postoperatively compared to traditional filtering surgery. We present a case of a patient who, after receiving uncomplicated cataract extraction with posterior chamber intraocular lens implantation and concurrent iStent trabecular bypass stent implantation, experienced recurrent episodes of spontaneous microhyphema and inflammation in the late postoperative period. The patient, who had a history of mild asymmetric exfoliative glaucoma but no identifiable sources of trauma, underwent extensive examination to investigate causes of his episodic anterior segment bleeding and mild inflammation with concurrent elevated intraocular pressure. Given the circumstances of the patient's recurrent symptoms and a negative workup for conventional causes of recurrent hyphema, it was suspected that the patient's iStent was interacting with the patient's peripheral iris, causing microtrauma and hyphema. We hypothesized that this contact was potentially exacerbated by pre-existing exfoliation syndrome, which caused zonular weakness and subsequent anterior movement of the lens-iris diaphragm. After the patient's third recurrence of microhyphema and inflammation, the patient underwent removal of iStent and concurrent OMNI canaloplasty for glaucoma. Six months post-iStent explantation, the patient has had complete resolution of symptoms without recurrence of hyphema. In this case report, we outline the course of this patient's symptoms and diagnosis, discuss the potential of MIGS devices such as iStent to cause recurrent hyphema, and explore treatment options following removal.


Brain Oxygen Optimization in Severe Traumatic Brain Injury (BOOST-3): a multicentre, randomised, blinded-endpoint, comparative effectiveness study of brain tissue oxygen and intracranial pressure monitoring versus intracranial pressure alone.
Management of traumatic brain injury (TBI) includes invasive monitoring to prevent secondary brain injuries. Intracranial pressure (ICP) monitor is the main measurement used to that intent but cerebral hypoxia can occur despite normal ICP. This study will assess whether the addition of a brain tissue oxygenation (PbtO2) monitor prevents more secondary injuries that will translate into improved functional outcome. Multicentre, randomised, blinded-endpoint comparative effectiveness study enrolling 1094 patients with severe TBI monitored with both ICP and PbtO2. Patients will be randomised to medical management guided by ICP alone (treating team blinded to PbtO2 values) or both ICP and PbtO2. Management is protocolised according to international guidelines in a tiered approach fashion to maintain ICP <22 mm Hg and PbtO2 >20 mm Hg. ICP and PbtO2 will be continuously recorded for a minimum of 5 days. The primary outcome measure is the Glasgow Outcome Scale-Extended performed at 180 (±30) days by a blinded central examiner. Favourable outcome is defined according to a sliding dichotomy where the definition of favourable outcome varies according to baseline severity. Severity will be defined according to the probability of poor outcome predicted by the IMPACT core model. A large battery of secondary outcomes including granular neuropsychological and quality of life measures will be performed. This has been approved by Advarra Ethics Committee (Pro00030585). Results will be presented at scientific meetings and published in peer-reviewed publications. ClinicalTrials.gov Registry (NCT03754114).


Complexity and developmental changes in the expression pattern of claudins at the blood-CSF barrier.
The choroid plexus epithelium controls the movement of solutes between the blood and the cerebrospinal fluid. It has been considered as a functionally more immature interface during brain development than in adult. The anatomical basis of this barrier is the interepithelial choroidal junction whose tightness has been attributed to the presence of claudins. We used quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry to identify different claudins in the choroid plexuses of developing and adult rats. Claudin-1, -2, and -3 were highly and selectively expressed in the choroid plexus as compared to brain or parenchyma microvessels and were localized at epithelial junctions. Claudin-6, -9, -19, and -22 also displayed a previously undescribed choroidal selectivity, while claudin-4, -5, and -16 were enriched in the cerebral microvessels. The choroidal pattern of tight junction protein expression in prenatal brains was already complex and included occludin and zonula occludens proteins. It differed from the adult pattern in that the pore-forming claudin-2, claudin-9, and claudin-22 increased during development, while claudin-3 and claudin-6 decreased. Claudin-2 and claudin-11 presented a mirror image of abundance between lateral ventricle and fourth ventricle choroid plexuses. Imunohistochemical analysis of human fetal and postnatal brains for claudin-1, -2, and -3 demonstrated their early presence and localization at the apico-lateral border of the choroid plexus epithelial cells. Overall, choroidal epithelial tight junctions are already complex in developing brain. The observed differences in claudin expression between developing and adult choroid plexuses may indicate developmental differences in selective blood-cerebrospinal fluid transport functions.


Temporal Progression of Craniofacial Dysmorphology in Unilateral Coronal Synostosis: A Mechanistic Hypothesis.
This study chronicles skull base and face development in nonsyndromic unilateral coronal synostosis (UCS) during infancy, to characterize the mechanistic progression of facial dysmorphology. Computed tomography scans from 51 subjects were reviewed (26 UCS, 25 controls) and data were reconstructed. Patients were stratified into 5 age groups. A series of measurements were taken from the reconstructions. All patients had a unilaterally fused coronal suture at the time of analysis. Asymmetry of the sphenoid wings was present across all age groups. The sphenoid wing ipsilateral to the fused suture consistently had a more acute angle from the midline. At 19 days of age, ipsilateral nasal root and cribriform plate deviation are noted, as well as increased contralateral zygoma antero-posterior length. Patients younger than 2 months also had elongated posterior cranial bases. At 2 to 3 months of age, the cranial base widens in the anterior portion of the middle cranial fossa with an increased ipsilateral pterion to sella distance. The most delayed change observed was the increase in contralateral orbital rim angle at 7 to 12 months of age compared to normal. After suture fusion, sphenoid wing changes are among the earliest restructural malformations to take place. This suggests that the cascade of dysmorphology in UCS originates in the cranial vault, then progresses to the skull base, and lastly to the facial structures. Ipsilateral orbital changes are early facial changes in UCS that begin before 2 months of age. This is then followed by changes in the contralateral face later in development.


Reducing the residue of retractions in evidence synthesis: ways to minimise inappropriate citation and use of retracted data.
The incorporation of publications that have been retracted is a risk in reliable evidence synthesis. Retraction is an important mechanism for correcting the literature and protecting its integrity. Within the medical literature, the continued citation of retracted publications occurs for a variety of reasons. Recent evidence suggests that systematic reviews and meta-analyses often unwittingly cite retracted publications which, at least in some cases, may significantly impact quantitative effect estimates in meta-analyses. There is strong evidence that authors of systematic reviews and meta-analyses may be unaware of the retracted status of publications and treat them as if they are not retracted. These problems are difficult to address for several reasons: identifying retracted publications is important but logistically challenging; publications may be retracted while a review is in preparation or in press and problems with a publication may also be discovered after the evidence synthesis is published. We propose a set of concrete actions that stakeholders (eg, scientists, peer-reviewers, journal editors) might take in the near-term, and that research funders, citation management systems, and databases and search engines might take in the longer term to limit the impact of retracted primary studies on evidence syntheses.


Assessment of Parents' Perceptions of Childhood Immunization: A Cross-Sectional Study from Pakistan.
Immunization is one of the most cost-effective public health interventions, with considerable impacts on people's health. Parents' perception of their knowledge, attitude, and satisfaction is an important factor, as they may be targeted by interventions for better immunization coverage. Therefore, this study aimed to assess parents' perceptions in terms of their knowledge, attitude, and satisfaction of the immunization of their children aged less than two years of age, in two cities of Pakistan. A descriptive cross-sectional study was conducted in the vicinity of Rawalpindi and Islamabad from March to August 2019. A semi-structured questionnaire was used for the data collection on a convenient sample of parents. The questionnaire was hand-delivered to the parents by data collectors. Descriptive and inferential statistics were used for data analysis via SPSS version 22. A total of n = 382 respondents were included in the data analysis. Statistically significant differences were found between the parents' knowledge scores and their education levels and monthly incomes (p < 0.05). Parents with master's education degrees and low monthly incomes had significantly better knowledge (p < 0.05). Additionally, 96.85% of the respondents believed that child immunization was important. In addition, more than half of the respondents (57.58%) thought that the affordability of vaccines was a principal factor for delays in immunization. Although the parents' knowledge regarding the immunization of their children was not adequate, they had positive perceptions toward it.


Birth by caesarean section and prevalence of risk factors for non-communicable diseases in young adults: a birth cohort study.
Conflicting findings on the risk of obesity among subjects born by caesarean section have been published. Caesarean section should also increase the risk of obesity related cardiovascular risk factors if type of delivery is associated with obesity later in life. This study was aimed at assessing the effect of type of delivery on metabolic cardiovascular risk factors in early adulthood. In 1982, maternity hospitals in Pelotas, southern Brazil, were visited and those livebirths whose family lived in the urban area of the city have been followed. In 2000, when male subjects undertook the Army entrance examination (n=2200), fat mass and fat free mass were estimated through bioimpedance. In 2004-2005, we attempted to follow the whole cohort (n=4297), and the following outcomes were studied: blood pressure; HDL cholesterol; triglycerides; random blood glucose, C-reactive protein, waist circumference and body mass index. The estimates were adjusted for the following confounders: family income at birth; maternal schooling; household assets index in childhood; maternal skin color; birth order; maternal age; maternal prepregnancy weight; maternal height; maternal smoking during pregnancy; birthweight and family income at early adulthood. In the crude analyses, blood pressure (systolic, diastolic and mean arterial pressure) and body mass index were higher among subjects who were delivered through caesarean section. After controlling for confounders, systolic blood pressure was 1.15 mmHg (95% confidence interval: 0.05; 2.25) higher among subjects delivered by caesarean section, and BMI 0.40 kg/m(2) (95% confidence interval: 0.08; 0.71). After controlling for BMI the effect on systolic blood pressure dropped to 0.60 mmHg (95% confidence interval: -0.47; 1.67). Fat mass at 18 years of age was also higher among subjects born by caesarean section. Caesarean section was associated with a small increased in systolic blood pressure, body mass index and fat mass.


Factors associated with time to identify physical problems of nursing home residents with dementia.
This study describes new problems emerging over 6 weeks for nursing home residents with advanced dementia and factors associated with time to identify the problems. The sample of 65 developed 149 new acute problems or exacerbations of existing conditions over the 6 weeks of data collection. The majority of these problems involved uncontrolled pain, new infections, and severe psychoses. Nurse assessment skill was associated with a shorter time to identify the new problem and more time spent on the problem. A higher ratio of new to existing interventions was also associated with a shorter time to identify the problem. Other patient characteristics associated with time to identify problems included nonspecific vocalizations, physical signs, cognitive status, and length of stay. While future research is warranted, findings from this study highlight the frequency of problems requiring treatment and suggest that improved assessment of residents may decrease the time to identify new problems.


Isolation and characterization of ovine mesenchymal stem cells derived from peripheral blood.
Mesenchymal stem cells (MSCs) are multipotent stem cells with capacity to differentiate into several mesenchymal lineages. This quality makes MSCs good candidates for use in cell therapy. MSCs can be isolated from a variety of tissues including bone marrow and adipose tissue, which are the most common sources of these cells. However, MSCs can also be isolated from peripheral blood. Sheep has been proposed as an ideal model for biomedical studies including those of orthopaedics and transmissible spongiform encephalopathies (TSEs). The aim of this work was to advance these studies by investigating the possibility of MSC isolation from ovine peripheral blood (oPB-MSCs) and by subsequently characterizing there in vitro properties. Plastic-adherent fibroblast-like cells were obtained from the mononuclear fraction of blood samples. These cells were analysed for their proliferative and differentiation potential into adipocytes, osteoblasts and chondrocytes, as well as for the gene expression of cell surface markers. The isolated cells expressed transcripts for markers CD29, CD73 and CD90, but failed to express the haematopoietic marker CD45 and expressed only low levels of CD105. The expression of CD34 was variable. The differentiation potential of this cell population was evaluated using specific differentiation media. Although the ability of the cultures derived from different animals to differentiate into adipocytes, osteoblasts and chondrocytes was heterogeneous, we confirmed this feature using specific staining and analysing the gene expression of differentiation markers. Finally, we tested the ability of oPB-MSCs to transdifferentiate into neuronal-like cells. Morphological changes were observed after 24-hour culture in neurogenic media, and the transcript levels of the neurogenic markers increased during the prolonged induction period. Moreover, oPB-MSCs expressed the cellular prion protein gene (PRNP), which was up-regulated during neurogenesis. This study describes for the first time the isolation and characterization of oPB-MSCs. Albeit some variability was observed between animals, these cells retained their capacity to differentiate into mesenchymal lineages and to transdifferentiate into neuron-like cells in vitro. Therefore, oPB-MSCs could serve as a valuable tool for biomedical research in fields including orthopaedics or prion diseases.


Unbalanced germ-line expression of hMLH1 and hMSH2 alleles in hereditary nonpolyposis colorectal cancer.
We analyzed the hMLH1 and hMSH2 genes in 30 unrelated hereditary nonpolyposis colorectal cancer (HNPCC) patients using mutational and immunohistochemical analyses combined whenever possible with primer extension assays, designed to estimate hMLH1 and hMSH2 transcript expression in peripheral blood lymphocytes. Single-strand conformational polymorphism screening and PCR-direct sequencing revealed seven hMLH1 and five hMSH2 sequence variants in 14 unrelated HNPCC patients, including three definite pathogenic mutations, four amino acid substitutions of uncertain pathogenic significance, and five polymorphisms. Immunohistochemistry indicated the lack of either hMLH1 or hMSH2 protein expression in tumors from 13 patients, and the absence of both hMLH1 and hMSH2 immunostaining was observed in the tumor from one additional case. The lack of hMLH1 or hMSH2 immunostaining was associated with the presence of microsatellite instability in the corresponding tumor and was also observed in tumors from patients negative for pathogenic mutations by mutational screening. There was a marked unbalance in the allelic expression of either hMLH1 or hMSH2 transcripts in three of eight unrelated HNPCC patients that could be analyzed, although a less marked unbalance was detected in two additional patients. Tumors from patients with germ-line unbalance in hMLH1 or hMSH2 transcript expression did not express the corresponding mismatch repair protein and displayed microsatellite instability. Our results indicate that constitutional alterations in hMLH1 and hMSH2 transcript expression may represent genetic markers for HNPCC carrier status also in cases in which mutational analysis did not detect a definite pathogenic variant. This suggests that transcript deregulation may represent a relevant mode of germ-line inactivation for mismatch repair genes.


Free radicals in the regulation of damage and cell death - basic mechanisms and prevention.
Reactive oxygen (ROS) and nitrogen (RNS) species are known to accumulate intracellularly due to both exogenous and/or endogenous factors. In normal physiological conditions, these reactive species are maintained in an equilibrium state by the cells' antioxidant defence systems. In addition, they are recognised to play important roles in several physiological functions. However, when an imbalance in the equilibrium between oxidants and antioxidants occurs in favour of the former, we come to a situation defined as oxidative stress. ROS/RNS can cause damage to all biomolecules (namely proteins, lipids and DNA) and ultimately participate in the regulation of mechanisms leading to cell death, being implicated in the etiology of several pathologies (like neurodegenerative and cardiovascular diseases). To cope with oxidative stress, cells possess effective enzymatic (e.g. superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (e.g. glutathione, thioredoxin, coenzyme Q) antioxidant systems. In addition, several compounds present in plants and vegetables (e.g. vitamins C and E, polyphenols) have been described to react with free radicals. However, some drawbacks associated to these natural compounds are in part responsible for the undergoing development of novel synthetic compounds capable of acting as antioxidants and protect cells against oxidative stress-induced cell death. Here, we review the basic mechanisms of ROS/RNS formation, as well as their interaction with biomolecules and regulation of cell death, in order to identify possible drug targets. We also report the importance of natural antioxidant systems and the ongoing research leading to the development of more powerful and effective antioxidant drugs.


Induction of superficial zone protein (SZP)/lubricin/PRG 4 in muscle-derived mesenchymal stem/progenitor cells by transforming growth factor-β1 and bone morphogenetic protein-7.
Articular cartilage (AC) is an avascular tissue with precise polarity and organization. The three distinct zones are: surface, middle and deep. The production and accumulation of the superficial zone protein (SZP), also known as lubricin, by the surface zone is a characteristic feature of AC. To date, there is a wealth of evidence showing differentiation of AC from mesenchymal stem cells. Most studies that described chondrogenic differentiation did not focus on AC with characteristic surface marker SZP/lubricin. The present investigation was initiated to determine the induction of SZP/lubricin in skeletal muscle-derived mesenchymal stem/progenitor cells (MDMSCs) by transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein-7 (BMP-7). MDMSCs were cultured as a monolayer at a density of 1 × 105 cells/well in 12-well tissue culture plates. Cell cultures were treated for 3, 7 and 10 days with TGF-β1 and BMP-7. The medium was analyzed for SZP. The cells were used to isolate RNA for RT-PCR assays for SZP expression. The SZP/lubricin increased in a time-dependent manner on Days 3, 7 and 10 in the medium. As early as Day 3, there was a three-fold increase in response to 3 ng/ml of TGF-β1 and 300 ng/ml of BMP-7. This was confirmed by immunochemical localization of SZP as early as Day 3 after treatment with TGF-β1. The expression of SZP mRNA was enhanced by TGF-β1. The present investigation demonstrated the efficient and reproducible induction of SZP/lubricin accumulation by TGF-β1 and BMP-7 in skeletal MDMSCs. Optimization of the experimental conditions may permit the utility of MDMSCs in generating surface zone-like cells with phenotypic markers of AC and, therefore, constitute a promising cell source for tissue engineering approaches of superficial zone cartilage.


A Smartphone App to Reduce Sugar-Sweetened Beverage Consumption Among Young Adults in Australian Remote Indigenous Communities: Design, Formative Evaluation and User-Testing.
The disproportionate burden of noncommunicable disease among Indigenous Australians living in remote Indigenous communities (RICs) is a complex and persistent problem. Smartphones are increasingly being used by young Indigenous adults and therefore represent a promising method to engage them in programs seeking to improve nutritional intake. This study aimed to consult RIC members to inform the content of a smartphone app that can be used to monitor and reduce sugar-sweetened beverage intake in RICs. The study was conducted in two phases. The formative phase involved a simulated grocery selection activity with think aloud ("think aloud shop"), a semistructured interview, a questionnaire outlining current smartphone and app use, and a paper prototyping activity. A preliminary end-user testing phase involved a think aloud prototype test and a semistructured interview regarding user satisfaction. Convenience sampling was used to recruit 20 18- to 35-year-old smartphone users for each phase from two RICs in the Northern Territory, Australia. Thematic analysis of transcribed audio recordings was used to identify determinants of food choice from the think aloud shop; themes related to the Theory of Planned Behavior (TPB) from the eating behaviors interview; and usability, comprehension, and satisfaction with the app from the preliminary end-user testing. Smartphone use in RICs is currently different to that found in urban environments; in particular, extremely low use of Facebook, restricted variety of phone types, and limited Internet access. Findings regarding promoting app engagement indicate that utilizing an opt-in approach to social features such as leader boards and team challenges is essential. The inclusion of games was also shown to be important for satisfaction, as were the use of audio features, contextually embedded dissemination, and streamlined app design for comprehension in this target group. This research provides critical insights and concrete recommendations for the development of lifestyle improvement apps targeted toward disadvantaged young adults in nonurban settings, specifically RICs. It serves as a framework for future app development projects using a consultative user-centered design approach, supporting calls for the increased use of this strategy in app development.


Occupational tropical acne.
Tropical acne, a major problem for military personnel assigned to hot, humid areas, has not been reported previously in the United States. Here, a case of tropical acne is reported in an occupational setting in which the working environment simulated tropical conditions. This raises the possibility that heat and humidity may be contributing factors to inflammatory acne in susceptible individuals.


Low uptake of preventive interventions among malaria cases in Swaziland: towards malaria elimination.
Settings: Swaziland is striving to achieve sustainable malaria elimination. Three preventive interventions are vital for reaching this goal: 1) effective household utilisation of long-lasting insecticide nets (LLINs), 2) indoor residual spraying (IRS), and 3) provision of chemoprophylaxis for those travelling to malaria-endemic areas. Objectives: To assess the uptake of preventive intervention among confirmed malaria cases. Design: A longitudinal study using nation-wide programme data from 2010 to 2015. Data on malaria cases from health facilities were sourced from the Malaria Surveillance Database System. Results: Of a total 2568 confirmed malaria cases in Swaziland, 2034 (79%) had complete data on case investigations and were included in the analysis. Of 341 (17%) individuals who owned LLINs, 169 (8%) used them; 338 (17%) had IRS and 314 (15%) slept in sprayed structures. Of 1403 travellers to areas at high malaria risk, 59 (4%) used any form of malaria prevention, including chemoprophylaxis. Conclusion: The uptake of all three key malaria prevention interventions is low, and could threaten the progress made thus far toward malaria elimination. Efforts to improve this situation, including qualitative research to understand the reasons for low uptake, are urgently needed.


The role of natural killer (NK) cells and NK cell receptor polymorphisms in the assessment of HIV-1 neutralization.
The importance of innate immune cells in HIV-1 pathogenesis and protection has been highlighted by the role of natural killer (NK) cells in the containment of viral replication. Use of peripheral blood mononuclear cells (PBMC) in immunologic studies provides both HIV-1 target cells (ie. CD4+ T cells), as well as anti-HIV-1 effector cells, such as NK cells. In this study, NK and other immune cell populations were analyzed in HIV-negative donor PBMC for an impact on the anti-HIV activity of polyclonal and monoclonal antibodies. NK cell percentages were significantly higher in donor PBMC that supported lower levels of viral replication. While the percentage of NK cells was not directly associated with neutralization titers, NK cell-depletion significantly diminished the antiviral antibody activity by up to three logs, and polymorphisms in NK killer immunoglobulin receptor (KIR) and FcγRIIIa alleles appear to be associated with this affect. These findings demonstrate that NK cells and NK cell receptor polymorphisms may influence assessment of traditional HIV-1 neutralization in a platform where antibody is continuously present. This format appears to simultaneously assess conventional entry inhibition (neutralization) and non-neutralizing antibody-dependent HIV inhibition, which may provide the opportunity to delineate the dominant antibody function(s) in polyclonal vaccine responses.


beta-Catenin regulates intercellular signalling networks and cell-type specific transcription in the developing mouse midbrain-rhombomere 1 region.
beta-Catenin is a multifunctional protein involved in both signalling by secreted factors of Wnt family and regulation of the cellular architecture. We show that beta-catenin stabilization in mouse midbrain-rhombomere 1 region leads to robust up-regulation of several Wnt signalling target genes, including Fgf8. Suggestive of direct transcriptional regulation of the Fgf8 gene, beta-catenin stabilization resulted in Fgf8 up-regulation also in other tissues, specifically in the ventral limb ectoderm. Interestingly, stabilization of beta-catenin rapidly caused down-regulation of the expression of Wnt1 itself, suggesting a negative feedback loop. The changes in signal molecule expression were concomitant with deregulation of anterior-posterior and dorso-ventral patterning. The transcriptional regulatory functions of beta-catenin were confirmed by beta-catenin loss-of-function experiments. Temporally controlled inactivation of beta-catenin revealed a cell-autonomous role for beta-catenin in the maintenance of cell-type specific gene expression in the progenitors of midbrain dopaminergic neurons. These results highlight the role of beta-catenin in establishment of neuroectodermal signalling centers, promoting region-specific gene expression and regulation of cell fate determination.


The rate of aneuploidy is altered in spermatids from infertile mice.
It is now possible for infertile males to father their own genetic children through the technique of ICSI. This prospect has consequently prompted several investigations into the quality of sperm being retrieved from infertile males. One potential risk is the use of aneuploid sperm or spermatids, which might then be transferred to the fertilized oocyte. In this investigation, aneuploidy of spermatids was assessed through immunocytochemistry using antibodies directed against chromosome centromeric regions and complexes. Three different types of infertile male mice with phenotypes closely resembling those described in human non-obstructive azoospermia [PP1cgamma-deficient mice, CREM-deficient mice and C57BL/6J.MAC-17(0--23) mice] were examined for chromosome numbers by counting the number of kinetochores in round spermatids using a CREST antiserum. PP1cgamma(-/-) and CREM(-/-) spermatids from infertile mice showed highly significant elevated levels in the rate of aneuploidy compared with wild-type animals (P < 0.0001). Thus infertile males with independent genetic mutations resulting in different histopathologies showed a high risk in the level of aneuploidy in their spermatids. These results suggest that impaired spermatogenesis may lead to production of aneuploid gametes. Analysis of aneuploidy in gametes from infertile men, coupled with appropriate genetic counselling, is recommended prior to ICSI.


Adenosine-induced ventricular fibrillation in a patient with supraventricular tachycardia.
Adenosine is frequently used for paroxysmal supraventricular tachycardia (PSVT) treatment in the emergency department (ED). Atrial and ventricular pro-arrhythmic effects of adenosine were described in the literature, but ventricular fibrillation (VF) secondary to adenosine administration was rarely reported (with an incidence of < 1%). Reported herein is the first case of a 72-year-old female patient who developed VF hemodynamic collapse after an intravenous administration of adenosine for PSVT treatment. She had no known pre-excitation or accessory pathway, nor any underlying structural heart disease or prolonged QT syndrome. Raising awareness of this potential life-threatening pro-arrhythmic effect of adenosine is important, given its frequent use for PSVT treatment in the ED.


Is implementation fidelity associated with improved access to care in a school-based Child and Family Team model?
Effective child and family centered service planning is crucial to addressing vulnerable children's needs. However, there is limited evidence about what facets of these processes improve service use and outcomes. The current study used a Poisson random effects hazard model to test correlations between fidelity to NC's Child and Family Support Team model and time to service receipt, using case management data for 3396 children served by that program during the 2008-2009 school year. Students were more likely to receive recommended services more quickly when caregivers and the students attended planning meetings, when their plans included services for caregivers, and when child and family team leaders followed up after meetings to verify service receipt. Contrary to the Child and Family Support Team theory of change, match between student needs and the lead agency of the meeting was not associated with the odds of quicker service receipt, nor was attendance by natural supports. Findings from this study demonstrate the potential effectiveness of using case management systems to measure service planning process fidelity, as well as how results thereof can both inform process improvement and potential refinements to models' theories of change.


Function, mass, and replication of porcine and rat islets transplanted into diabetic nude mice.
Well-characterized aliquots of adult porcine and rat islets of comparable beta-cell mass were transplanted under the kidney capsule of streptozotocin-induced diabetic nude mice. In both porcine and rat islet grafts, beta-cell mass decreased significantly in the first 2 months and stabilized thereafter. As with beta-cell mass, insulin content decreased significantly in the first 2 months to almost 40% of that originally implanted. In porcine grafts, however, insulin content at 4 months was significantly higher than at 2 months. The endocrine non-beta-cell mass of grafts also decreased significantly after transplantation: in porcine grafts, the decrease was less than in rat and was limited to the first 2 months. beta-cell replication of engrafted islets was significantly lower in porcine than in rat grafts. Although beta-cell mass of porcine and rat grafts was similar at all time periods, recipients of porcine islets required a significantly longer time to reach normal glucose levels; nonetheless, their blood glucose levels continued to decrease and stabilized at levels significantly lower than those of normal mice. During oral and intraperitoneal glucose tolerance tests, blood glucose increased only slightly in both the recipients of porcine and rat grafts. When graft-bearing kidneys were perfused in situ, porcine islet grafts showed a 20-fold increase in insulin release in response to both glucose and arginine. In conclusion, this evidence that adult porcine islet grafts can bring glucose levels to those that are normal for humans provides further support of their potential for human islet replacement therapy.


Predictors of dysphagia screening and pneumonia among patients with acute ischaemic stroke in China: findings from the Chinese Stroke Center Alliance (CSCA).
Guidelines recommend dysphagia screening to identify those at high risk of pneumonia. However, little is known about the prevalence and predictors of dysphagia screening and pneumonia among patients with acute ischaemic stroke in China. Using data from the Chinese Stroke Center Alliance, which is a multicentre, prospective, consecutive patient enrolment programme, univariate and multivariate analyses were conducted to identify patient and hospital characteristics associated with dysphagia screening and pneumonia during acute hospitalisation. Of 790 811 patients admitted to 1476 hospitals, 622 718 (78.7%) underwent dysphagia screening, and 64 398 (8.1%) developed pneumonia. Patients in stroke units were more likely to be screened for dysphagia than those not in stroke units (OR 1.50; 95% CI 1.48 to 1.52), while patients with a past history of stroke were less likely to be screened (OR 0.87; 95% CI 0.86 to 0.88). Dysphagia screening (OR 1.46; 95% CI 1.30 to 1.65), dysphagia (OR 7.31; 95% CI 7.15 to 7.46), and admission to stroke units (OR 1.17; 95% CI 1.14 to 1.19) were significantly associated with a greater risk of pneumonia. Dysphagia was a critical factor in the development of pneumonia. Nearly one in five patients with acute ischaemic stroke in the Chinese Stroke Center Alliance were not screened for dysphagia. Pneumonia prevention during acute hospitalisation is dependent not only on dysphagia screening but also on the effectiveness of subsequent dysphagia management interventions. Further studies are needed to elucidate the relationship between dysphagia screening, stroke unit care and pneumonia in patients with acute ischaemic stroke.


Stigma, Resilience, and Health Care Use Among Transgender and Other Gender Diverse Youth in the United States.
Purpose: To understand the relationships between stigma, resilience, and health care use among transgender and other gender diverse youth (TGDY). Methods: Data include a national sample of 171 TGDY (ages 15-24). Previously developed Gender Minority Stress Theory scales were used to measure experiences of stigma and resilience. Health care use included two outcomes: difficulty accessing care and medical gender affirmation service use (e.g., hormones and surgery). Principal components analysis (PCA) was used to reduce data. Logistic regression was used to test relationships between components and the outcomes; interactions between components were also tested. Results: The PCA determined three components representing (1) enacted stigma, (2) a positive sense of identity, and (3) social support. Two scales (mis-gendering and anticipated stigma) did not fit into any components and were included as separate variables. In the main effects model, none of the minority stress variables were associated with difficulty accessing care. However, an interaction between enacted stigma and a positive sense of identity indicated that having a more positive sense of identity was only associated with reduced difficulty accessing care for participants experiencing less stigma. For medical gender affirmation services, participants who experienced more anticipated stigma were less likely to use these services and participants with a more positive sense of identity were more likely to use them. Conclusions: Findings suggest that stigma and resilience experienced both inside and outside of health care settings can play a role on access to care for TGDY. Interventions should consider how to reduce stigma and promote resilience across multiple contexts.


Impact of Cryoablation on Pectus Excavatum Repair in Pediatric Patients.
Minimally invasive repair of pectus excavatum (MIRPE) involves placement of a transthoracic, retrosternal support bar under thoracoscopic guidance. Despite its minimally invasive technical approach, postoperative pain is a significant morbidity that often results in increased length of stay. Multi-modal pain control strategies have been used in the past with limited success. Recently, the use of intraoperative intercostal nerve cryoablation (CA) has been added. In the present study, we aim to evaluate the effects of CA on postoperative pain control, opioid requirements, and perioperative outcomes. A single-center, retrospective chart review of all patients (less than 18 years old) who underwent MIRPE from 2009 to 2020 was performed. CA was started in June 2018. Data collection included demographics, preoperative characteristics, intraoperative findings, and postoperative outcomes. We hypothesized that CA would be associated with improved pain scores, lower doses of total inpatient opioid requirement, and shorter length of stay (LOS). One hundred sixty-one patients met inclusion criteria: 75 underwent intraoperative CA and 86 underwent MIRPE without CA (NCA group). CA significantly decreased median LOS from 4 days in NCA to 2 days; the use of CA was the only significant predictor of LOS on linear regression. CA was also associated with decreased total PCA, intravenous opioid, and oral opioid dosages. There was no difference in inpatient pain scores and a slight increase in mean procedure time. However, CA was associated with significantly decreased postoperative complications. The use of cryoablation during MIRPE significantly decreases LOS, perioperative opioid requirements, and postoperative complications, with a minimal increase in operative time. Cryoablation is an effective pain control modality in the surgical management of chest wall deformities in children.


Neurogenic hyperacute ascites in mice.
Four groups of mice were subjected to controlled fatal head trauma and then evaluated for the presence of ascites (neurogenic hyperacute ascites, NHA). The animals died virtually instantaneously and without evidence of maintained pain or suffering. The volume of ascites was determined in one group of animals. Two of the traumatized groups were pretreated, one with the beta-blocker propranolol and the other with the alpha-blocker phentolamine. A fifth, non-traumatized, group which was killed with either inhalation served as a control group. Two more groups of non-traumatized mice were administered either the alpha-adrenergic agonist methoxamine hydrochloride or the beta-agonist isoethrane mesylate before killing by ether inhalation, and then evaluated for ascites. Transudative ascitic fluid was found in 87-100% of untreated traumatized mice and in no control animals. Pretreatment with phentolamine had no effect on the prevalence of ascites. Pretreatment with propranolol produced a significant decrease in the prevalence of ascites compared with trauma alone (P less than 0.001). Isoethrane (beta-agonist) administration caused ascites in 100% of the treated animals. Methoxamine (alpha-agonist) administration did not cause ascites. A previously undescribed consequence of acute brain trauma is described (NHA) which appears to be mediated by beta-sympathetic activity of central origin. NHA is inhibited by beta-blockade and can be simulated with beta-agonist administration.


Stigma, deforming metaphors and patients' moral experience of multibacillary leprosy in Sobral, Ceará State, Brazil.
In response to the call for a new Science of Stigma, this anthropological study investigates the moral experience of patients diagnosed with severe multibacillary leprosy. From 2003 to 2006, fieldwork was conducted in the so-called 'United-States-of-Sobral', in Ceará State, Northeast Brazil. Sobral is highly endemic for leprosy, despite intensified eradication efforts and a 30% increase in primary care coverage since 1999. Of 329 active leprosy cases at two public clinics, 279 multibacillary patients were identified and six information-rich cases selected for in-depth ethnographic analysis, utilizing illness narratives, key-informant interviews, home visits, participant-observation of clinical consultations and semi-structured interviews with physicians. A 'contextualized semantic interpretation' revealed four leprosy metaphors: a repulsive rat's disease, a racist skin rash, a biblical curse and lethal leukemia. Far from value-free pathology, the disease is imbued with moral significance. Patients' multivocalic illness constructions contest physicians' disease discourse. 'Skin Spot Day' discriminates more than educates. Patients' 'non-compliance' with effective multi-drug therapy is due to demoralizing stigma more than a rejection of care. 'Social leprosy' in Northeast Brazil deforms patients' moral reputations and personal dignity.


The Effect of Leukocyte Concentration on Platelet-Rich Plasma Injections for Knee Osteoarthritis: A Network Meta-Analysis.
It is hypothesized that leukocyte-poor (LP) platelet-rich plasma (PRP) is preferred over leukocyte-rich (LR) PRP for the treatment of knee osteoarthritis (OA). The MEDLINE, Embase, and Cochrane databases were reviewed for all English-language studies comparing LP-PRP or LR-PRP with relevant controls or each other. The follow-up periods were 6 months and 12 months. The primary outcome measure was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score between baseline and follow-up. The secondary outcome measures were changes in the WOMAC pain subscale, visual analog scale (VAS) for pain, and International Knee Documentation Committee (IKDC) subjective score between baseline and follow-up, and the incidence of local adverse reactions. Treatment outcomes were analyzed using the mean difference between treatments for continuous outcomes and the odds ratio for binary outcomes, with 95% credibility intervals. Treatment modalities were ranked using the surface under the cumulative ranking (SUCRA) probabilities. Risk of bias was assessed using the relevant Cochrane tools, RoB 2 (version 2 of the Cochrane risk-of-bias tools) for randomized controlled trials (RCTs) and ROBINS-I (Risk of Bias in Non-Randomized Studies - of Interventions) for prospective comparative studies (PCSs). This network meta-analysis included 23 studies: 20 RCTs and 3 PCSs, with a total of 2,260 patients and a mean follow-up period of 9.9 months. The overall risk-of-bias assessment of the RCTs revealed that 9 studies had low risk, 7 had some concerns, and 4 had high risk. The overall risk-of-bias assessment of the PCSs revealed that 1 study had low risk and 2 had moderate risk. We found no significant (p < 0.05) difference in all outcome measures and local adverse reactions between LP-PRP and LR-PRP. SUCRA rankings revealed that, for all outcome measures, LP-PRP is preferred to LR-PRP across follow-up periods. Leukocyte concentration of PRP does not play a significant role in patient-reported outcome measures for knee OA. LP-PRP is preferred to LR-PRP according to SUCRA rankings, but this preference may not be important in clinical practice. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.


Undergraduate pediatric nursing education: issues, challenges and recommendations.
The topic is a national review of content and clinical experiences in undergraduate pediatric nursing education with recommendations for strengthening the pediatric nursing curriculum. American Association of Colleges of Nursing member programs (N = 596) were surveyed with 344 schools responding. A 39-item survey collected school demographics, faculty characteristics, pediatric classroom and clinical information, and actual and perceived barriers to implementing the pediatric curriculum. Recommendations for change were offered by participants attending the 2011 Institute of Pediatric Nursing Nursing Forum. A mean of 33 (SD = 27) total undergraduate faculty included an average of 3.1 (SD = 3.11) faculty with graduate specialization and/or recent clinical experience in pediatrics. Within a mean of 43 (range = 0-136 hours) pediatric classroom hours, more than 59% of programs reported 2 hours or less in pediatric genetics, environmental health, and child nutrition. Content focused on acute and specialty care with programs using pediatric inpatient medical (68%) and surgical units (40%) for clinical learning. Recruiting pediatric faculty was a common issue and reported as extremely (23%) to moderately difficult (26%). Competition for clinical practice sites (76%) was a reported barrier. Adjustments in the pediatric undergraduate curriculum are recommended to highlight current health issues experienced by children including expansion of clinical learning experiences to settings where children live, learn, and play.


Understanding food insecurity risk in the United States: A longitudinal analysis.
Food insecurity, lack of consistent access to the food needed for an active, healthy life, harms population health. Although substantial biomedical evidence examines the connections between food insecurity and health, fewer studies examine why food insecurity occurs. We propose a conceptual understanding of food insecurity risk based on institutions that distribute income-the factor payment system (income distribution stemming from paid labor and asset ownership), transfers within households, and the government tax-and-transfer system. A key feature of our understanding is 'roles' individuals inhabit in relation to the factor payment system: child, older adult, disabled working-age adult, student, unemployed individual, caregiver, or paid laborer. A second feature is that the roles of others in an individual's household also affect an individual's food insecurity risk. We tested hypotheses implied by this understanding, particularly hypotheses relating to role, household composition, and income support programs, using nationally-representative, longitudinal U.S. Current Population Survey data (2016-2019). There were 16,884 participants (year 1 food insecurity prevalence: 10.0%). Inhabiting roles of child (Relative Risk [RR] 1.79, 95% Confidence Interval [95%CI] 1.67 to 1.93), disabled working age-adult (RR 3.74, 95%CI 3.25 to 4.31), or unemployed individual (RR 3.29, 95%CI 2.51 to 4.33) were associated with a greater risk of food insecurity than being a paid laborer. Most food insecure households, 74.8%, had members inhabiting roles of child or disabled working age-adult, and/or contained individuals who experienced job loss. Similar associations held when examining those transitioning from food insecurity to food security in year 2. The proposed understanding accords with the pattern of food insecurity risk observed in the U.S. An implication is that transfer income programs for individuals inhabiting roles, such as childhood and disability, that limit factor payment system participation may reduce food insecurity risk for both those individuals and those in their household.


Universal combination antiretroviral regimens to prevent mother-to-child transmission of HIV in rural Zambia: a two-round cross-sectional study.
To evaluate if a pilot programme to prevent mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV) was associated with changes in early childhood survival at the population level in rural Zambia. Combination antiretroviral regimens were offered to pregnant and breastfeeding, HIV-infected women, irrespective of immunological status, at four rural health facilities. Twenty-four-month HIV-free survival among children born to HIV-infected mothers was determined before and after PMTCT programme implementation using community surveys. Households were randomly selected and women who had given birth in the previous 24 months were asked to participate. Mothers were tested for HIV antibodies and children born to HIV-infected mothers were tested for viral deoxyribonucleic acid. Multivariable models were used to determine factors associated with child HIV infection or death. In the first survey (2008-2009), 335 of 1778 women (18.8%) tested positive for HIV. In the second (2011), 390 of 2386 (16.3%) tested positive. The 24-month HIV-free survival in HIV-exposed children was 0.66 (95% confidence interval, CI: 0.63-0.76) in the first survey and 0.89 (95% CI: 0.83-0.94) in the second. Combination antiretroviral regimen use was associated with a lower risk of HIV infection or death in children (adjusted hazard ratio: 0.33, 95% CI: 0.15-0.73). Maternal knowledge of HIV status, use of HIV tests and use of combination regimens during pregnancy increased between the surveys. The PMTCT programme was associated with an increased HIV-free survival in children born to HIV-infected mothers. Maternal utilization of HIV testing and treatment in the community also increased.


Comparison of pulmonary neutrophils in the adult and neonatal rat after hyperoxia.
The mechanisms of the increased tolerance to hyperoxia of neonatal animals of many species is incompletely understood. To investigate the etiology of this difference we compared neutrophil entry into the lungs of neonatal and adult rats after hyperoxic exposure. Adult rats were studied after exposure to > or = 98% O2 for 60 h and neonatal rats after 3 and 7 d. Neonatal survival was prolonged compared with that reported for adult rats (77% after 7 d of exposure). In adult rats, there were significant increases in pulmonary neutrophils after 60 h of O2 exposure. In neonatal rats, these changes were not evident after 72 h of exposure, but pulmonary neutrophils increased after 7 d of hyperoxia. Before mortality, pulmonary neutrophils were distributed differently in the age groups. After 7 d of O2 exposure in the neonates, total neutrophil counts in lung tissue (21.92 +/- 7.29 per cm2 grid) and lung myeloperoxidase (0.085 +/- 0.02 U/mg protein) remained significantly lower than in adults after 60 h of O2 exposure (41.44 +/- 9.08 per cm2 grid and 0.411 +/- 0.085 U/mg protein, respectively). However, in histologic specimens, O2-exposed neonates had higher percentages of neutrophils free in the alveolar air space than did adults, corresponding to a trend toward higher neutrophil counts in bronchoalveolar lavage fluid in the neonates. It appears that, in addition to delay in neutrophil influx into the lung, neonatal rats have lowered retention of neutrophils to the alveolar tissue.


Comparison of three methods of evaluating glare.
A Humphrey Automatic Refractor Model 570 was used to measure the impairment of visual acuity for low contrast optotypes as a result of glare for normal subjects and for subjects with cataracts. This was compared with a direct measure of intraocular light scatter as measured by a compensating technique and with a subjective assessment of glare determined by a questionnaire. Only a weak correlation (r = 0.28) was found between the decrease in low contrast letter acuity and intraocular light scatter. The subjective assessment of glare sensitivity was not correlated with the decrease in low contrast letter acuity, but correlated to some extent (r = 0.55) with the measurement of intraocular light scatter.


Shock-induced melting of (100)-oriented nitromethane: structural relaxation.
Molecules subjected to shock waves will, in general, undergo significant intramolecular distortion and exhibit large amplitude orientational and translational displacements relative to the unshocked material. The analysis of molecular dynamics simulations of strongly perturbed materials is complicated, particularly when the goal is to express time-dependent molecular-scale properties in terms of structural or geometric descriptors/properties defined for molecules in the equilibrium geometry. We illustrate the use of the Eckart-Sayvetz condition in a molecular dynamics study of the response of crystalline nitromethane subjected to supported shock waves propagating normal to (100). The simulations were performed with the nonreactive but vibrationally accurate force field due to Sorescu et al. [J. Phys. Chem. B 104, 8406 (2000)]. Shocks were initiated with impact velocities of U(p)=0.5, 1.0, 2.0, and 3.0 km s(-1) in crystals at initial temperatures of T0=50 and 200 K. Statistical precision in the analysis was enhanced through the use of a spatiotemporal reference frame centered on the advancing shock front, which was located as a function of time using the gradient of the kinetic energy along the shock direction. The Eckart-Sayvetz condition provides a rigorous approach by which the alignment can be obtained between a coordinate frame for a perturbed molecule and one in a convenient reference frame (e.g., one based on the equilibrium crystal structure) for analyses of the molecules in the material as the system evolves toward equilibrium. Structural and dynamic properties of the material corresponding to orientation in the lattice, translational symmetry, and mass transport (orientational order parameters, two dimensional radial distribution functions, and self-diffusion coefficients, respectively) were computed as functions of time with 4 fs resolution. The results provide clear evidence of melting for shocks initiated by impacts of at least U(p)=2.0 km s(-1) and provide insights into the evolution of changes at the molecular-mode level associated with the onset of the melting instability in shocked crystal.


Perinatal Microbiomes' Influence on Preterm Birth and Preterms' Health: Influencing Factors and Modulation Strategies.
Microbial communities inhabiting the human host play important roles in maintaining health status, including reproduction and early life programming, which is particularly important in the context of preterm neonates' health. Preterm birth (PTB) is often the result of a microbial dysbiosis or infection. In addition, preterm neonates experience different levels of organ immaturity and an abnormal gut microbiota establishment, as compared to full-term neonates. This exacerbates their developmental problems and can have negative consequences at systemic level. In addition, preterm babies are commonly exposed to delayed enteral feeding and hospital environments, which increases the risk of short- and long-term health problems. Some of these clinical conditions, such as necrotizing enterocolitis or sepsis, may be life threatening, whereas others may translate into life-long conditions, including cognitive problems. Increasing scientific interest has focused on understanding developmental problems in preterm neonates related to abnormalities in the settlement of their microbial communities, with the final goal of selecting appropriate microbiome-targeted strategies (eg, probiotics), to reduce preterm health risks and improve overall quality of life.This review aims to summarize current knowledge on microbiological factors influencing PTB initiation and gastrointestinal development, and on the health consequences to the preterm neonate. Scientific evidences on dietary strategies reducing PTB incidence and minimizing sequelae in this particularly sensitive human group subpopulation are also discussed.


[Interlabyrinthine otolithic symmetry and asymmetry as factors in canal-otolith interaction].
The intact and operated (unilateral cutting of utricular or saccular nerve branches) pigeons were exposed to rotations in the horizontal plane. The position of the pigeon with respect to the rotation axis was such that horizontal canal afferents were activated either separately or together with otolith afferents. The results of canal-otolith interaction did not depend directly on enhancement or diminishing of the otolith afferentation but rather on a relative amount of the otolith signal alterations from the two labyrinths. Any variations of the nystagmus duration (increasing or decreasing) could result from different changes of the otolith signals from the two labyrinths.


Therapeutic monitoring of gastroenteropancreatic neuroendocrine tumors: the challenges ahead.
Gastroenteropancreatic neuroendocrine tumors (NETs), a heterogeneous family of tumors arising in a variety of anatomic sites, are generally well differentiated and often metastatic at diagnosis. Morphologic and functional imaging modalities have vastly improved the understanding and diagnosis of NETs. However, use of conventional imaging techniques and response criteria to assess treatment response is often complicated by the clinical course and cytostatic nature of oncologic treatments for NETs. The means of therapeutic monitoring discussed in this review were based on a PubMed search of the medical literature and on the clinical expertise of the authors. Morphology-based criteria for assessing tumor response in general oncology are presented, along with their limitations for assessing response in gastrointestinal and pancreatic NETs. Functional imaging and preliminary response criteria incorporating functional imaging are presented as possible solutions to monitoring treatment response in NETs. Morphology-based criteria to assess tumor response have limitations for NETs, which are often slow growing and frequently demonstrate low response rates when based on conventional radiological criteria. Furthermore, many NET treatments do not induce cytotoxic effects despite demonstrated clinical benefit. Novel imaging techniques are available which have the potential to measure changes in tumor physiology and metabolism. These include (68)Ga-labelled somatostatin analogs for PET/CT-based monitoring of NET, molecular imaging with PET tracers that are not based on somatostatin receptor targeting, and functional MRI. These techniques should be explored as options for monitoring treatment in patients with NET.


Luminescent zero-dimensional organic metal halide hybrids with near-unity quantum efficiency.
Single crystalline zero-dimensional (0D) organic-inorganic hybrid materials with perfect host-guest structures have been developed as a new generation of highly efficient light emitters. Here we report a series of lead-free organic metal halide hybrids with a 0D structure, (C4N2H14X)4SnX6 (X = Br, I) and (C9NH20)2SbX5 (X = Cl), in which the individual metal halide octahedra (SnX64-) and quadrangular pyramids (SbX52-) are completely isolated from each other and surrounded by the organic ligands C4N2H14X+ and C9NH20+, respectively. The isolation of the photoactive metal halide species by the wide band gap organic ligands leads to no interaction or electronic band formation between the metal halide species, allowing the bulk materials to exhibit the intrinsic properties of the individual metal halide species. These 0D organic metal halide hybrids can also be considered as perfect host-guest systems, with the metal halide species periodically doped in the wide band gap matrix. Highly luminescent, strongly Stokes shifted broadband emissions with photoluminescence quantum efficiencies (PLQEs) of close to unity were realized, as a result of excited state structural reorganization of the individual metal halide species. Our discovery of highly luminescent single crystalline 0D organic-inorganic hybrid materials as perfect host-guest systems opens up a new paradigm in functional materials design.


Development and classification of an operational definition of complementary and alternative medicine for the Cochrane collaboration.
During the past decade, the Cochrane Collaboration has been an increasingly important source of information on complementary and alternative medicine (CAM) therapies. From 2007 to 2008, the Cochrane CAM Field developed a topics list that allowed us to categorize all 396 Cochrane reviews related to CAM (as of The Cochrane Library, Issue 4, 2009). This topics list is an advance in making Cochrane reviews on CAM topics accessible to the public. In this article, we discuss challenges in developing the topics list, including developing an operational efinition of CAM, deciding which reviews should be included within the CAM Field's scope, developing the structured list of CAM Field-specific topics, and determining where in the topics list the reviews should be placed. Although aspects of our operational definition of CAM are open to revision, a standardized definition provides us with an objective, reproducible, and systematic method for defining and classifying CAM therapies.


Gauging acceptance of a hepatitis C test by family planning clinic attendees in Glasgow, UK.
In the UK, pregnant women are not offered and recommended a hepatitis C virus (HCV) test because no effective intervention to prevent vertical transmission of HCV exists following conception. Mother-to-child transmission of HCV could, however, be reduced if infected women planning to have children underwent a course of therapy prior to conception. To determine what proportion of female family planning clinic (FPC) attendees would hypothetically accept an HCV test if they were offered it and to identify the factors associated with such a decision. Opportunistic sampling was used to recruit 1000 women attending FPCs in Glasgow during 2002/2003. Participants were asked to self-complete a brief questionnaire about HCV and testing. Of 964 participants, 62% reported that they would accept an HCV test if it was offered in the family planning setting and 24% indicated that they were undecided. Only 4% of women reported that they would be offended if offered an HCV test. The highest rates of hypothetical acceptance of an HCV test were reported among those who had ever injected drugs (88%) and those who felt that they were at risk of being infected with HCV (84%). Women who were single [adjusted odds ratio (OR) 1.4, 95% CI 1.1-1.8] and who were of non-white ethnic origin (adjusted OR 2.5, 95% CI 1.0-6.2) were also significantly more inclined to hypothetically accept an HCV test. Selective HCV testing to those women at high risk of HCV infection should be encouraged in the family planning setting.


A residential labeled dataset for smart meter data analytics.
Smart meter data is a cornerstone for the realization of next-generation electrical power grids by enabling the creation of novel energy data-based services like providing recommendations on how to save energy or predictive maintenance of electric appliances. Most of these services are developed on top of advanced machine-learning algorithms, which rely heavily on datasets for training, testing, and validation purposes. A limitation of most existing datasets, however, is the scarcity of labels. The SustDataED2 dataset described in this paper contains 96 days of aggregated and individual appliance consumption from one household in Portugal. The current and voltage waveforms were sampled at 12.8 kHz, and the individual consumption of 18 appliances was sampled at 0.5 Hz. The dataset also contains the timestamps of the ON-OFF transitions of the monitored appliances for the entire deployment duration, providing the necessary ground truth for the evaluation of machine learning problems, particularly Non-Intrusive Load Monitoring. The data is accessible in easy-to-use audio and comma-separated formats.


Attrition and the management of pediatric obesity: an integrative review.
A key challenge in managing pediatric obesity is the high degree of program attrition, which can reduce therapeutic benefits and contribute to inefficient health services delivery. Our aim was to document and characterize predictors of, and reasons for, attrition in pediatric obesity management. We searched literature published until January 2014 in five databases (CINAHL, EMBASE, MEDLINE, PsycINFO, and Scopus). Articles were included if they were English, included participants 0-18 years of age, focused on pediatric obesity management, incorporated lifestyle and behavioral changes without pharmacotherapy, provided attrition data, and reported information about predictors of, and/or reasons for, attrition from family-based interventions provided in research or clinical settings. Twenty-three articles (n=20 quantitative; n=2 qualitative; n=1 mixed methods) met our inclusion criteria. Clarity of study aims, objectives, methods, and data analysis were appraised using Bowling's checklist. Attrition varied according to definition (minimum to maximum, 4-83%; median, 37%). There were few consistent predictors of attrition between studies, although dropout was higher among US-based families receiving public health insurance. Older children were also more likely to discontinue care, but sex and baseline weight status did not predict attrition. The most commonly reported reasons for attrition were logistical barriers and programs not meeting families' needs. Developing and evaluating strategies designed to minimize the risk of attrition, especially among families who receive public health insurance and older boys and girls, are needed to optimize the effectiveness of pediatric obesity management.


Serum levels of gonadotropins, prolactin, and testosterone in oligo/azoospermic Nigerian males.
To determine the frequency of hormonal abnormalities in a Nigerian population of male partners of infertile relationships, serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone were estimated using radioimmunoassay techniques in 454 oligo/azoospermic male partners of infertile marriages. Of these men, 272 (59.9%) had an abnormal serum level of one or more of the hormones. Hyperprolactinemia, found in 144 patients, was the most common hormonal disorder in the group. Elevated serum gonadotropins associated with low serum testosterone were found in 120 (26.4%) patients, while 32 (7%) had a reduced serum testosterone concentration in association with low serum gonadotropins. Since hyperprolactinemic, hypogonadotropic, and normogonadotropic testicular failures are amenable to treatment, routine hormonal evaluation of male partners of infertile marriages is suggested in Nigeria and other places where this practice is uncommon at present.


Fibronectin Promotes the Malignancy of Glioma Stem-Like Cells Via Modulation of Cell Adhesion, Differentiation, Proliferation and Chemoresistance.
Glioma stem-like cells (GSCs) are regarded as the sources of oncogenesis, recurrence, invasion and chemoresistance in malignant gliomas. Growing evidence suggests that the microenvironment surrounding GSCs interacts with tumor cells to influence biological behavior; however, the functional mechanisms involved are still unclear. In the present study, we investigated the modulation of GSCs triggered by fibronectin (FN), a main component of the extracellular matrix (ECM), in terms of cell adhesion, differentiation, proliferation and chemoresistance. We demonstrated that pre-coated FN prompted increased adherence by GSCs, with increased matrix metallopeptidases (MMPs)-2 and -9 expression, in a concentration-dependent manner. Decreases in sox-2 and nestin levels, and increased levels of glial fibrillary acidic protein (GFAP) and β-tubulin were also found in GSCs, indicating cell differentiation driven by FN. Further investigation revealed that FN promoted cell growth, as demonstrated by the elevation of Ki-67, with the activation of p-ERK1/2 and cyclin D1 also evident. In addition, FN suppressed p53-mediated apoptosis and upregulated P-glycoprotein expression, making GSCs more chemoresistant to alkylating agents such as carmustine. In contrast, this effect was reversed by an integrin inhibitor, cilengitide. Activation of the focal adhesion kinase/paxillin/AKT signaling pathway was involved in the modulation of GSCs by FN. Focusing on the interactions between tumor cells and the ECM may be an encouraging aspect of research on novel chemotherapeutic therapies in future.


Pantoprazole-Induced Delirium: Review of a Case and Associated Literature.
Proton pump inhibitors (PPIs) are frequently prescribed antiulcer agents in hospitals and are shown to be safer than H-2 blockers. We present a case report of PPI-induced delirium, regarding which not much has been written in the literature. We present a case of a 93-year-old woman with no known past psychiatric history, who was hospitalized for syncope workup and who developed delirium after a double dose of pantoprazole. Very few reports of PPI-induced delirium exist in the literature. In this case report, we attempt to highlight the mechanism of PPI induced delirium which in our case was most likely due to the primary effects of PPI and drug-drug interactions. Given the paucity of literature on this topic, we encourage further research into relationship between PPI and delirium and urge caution while using PPIs in geriatric population.


[Kinetics of prothrombin activation by factor Xa].
It is shown that activation of prothrombin by factor Xa with the presence of the substrate low concentrations occurs as two-stage reaction described by Michaelis-Mentene equation for stationary conditions. The rate constant of the complex formation is 2 and 3 order higher than the constant of dissociation and decay, respectively. Judging from a two-stage character of the process, it is possible to conclude that the second intermediate product (enzyme-modified substrate) in not form in the reaction: the both links in prothrombin sensitive to factor Xa might be attacked simultaneously. In the presence of the substrate high concentrations an inhibition may be observed due to formation of a complex, which involves one enzyme molecule and 1 + n substrate molecules. This complex preserves the enzymic activity because the constant of changes in its decay (beta) rate is larger than 0, but less than 1. The inhibition of factor Xa by the prothrombin surplus may be considered as a self-regulation element in the coagulation system at the level of molecular interactions.


Quantitative hippocampal structural changes following electroconvulsive seizure treatment in a rat model of depression.
The pathophysiology of depression and the effects of antidepressant treatment are hypothesized to be related to hippocampal structural changes. This study aims to investigate the effect of electroconvulsive seizures on behavior and hippocampal structure in a rat model of depression. Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were treated daily for 10 days with either electroconvulsive seizures or sham treatment. The behavior was evaluated using the forced swim test. Design-based stereological methods were used to quantify the hippocampal volume and the numbers of neurons and glial cells in specific hippocampal subregions. The basal level of hippocampal volume and neuron number differed significantly between the two rat strains, and a trend toward the FSL strain having more glial cells was found. The structural differences found between the sham-treated animals were counteracted by electroconvulsive seizure (ECS) treatment, which also normalized the behavior. ECS treatment increased the number of glial cells in hilus significantly in the FRL rats and with the same tendency for the FSL rats. Our results indicate that along with hippocampal neurogenesis, gliogenesis may also be involved in the pathophysiology of depression and in the effect of antidepressant treatment. The underlying mechanisms remain unknown, and further investigations are required to clarify whether the structural changes are necessary to induce a therapeutic effect of antidepressant treatment or if they rather represent an epiphenomenon.


Effects of Mindfulness-Based Interventions on Depression in Patients With Breast Cancer: A Systematic Review and Meta-Analysis.
We examined the effects of Mindfulness-based interventions (MBIs) on depressive symptoms in women with breast cancer and examined the moderating effects of participant characteristics, research methodologies, and features of interventions. We systematically searched 12 databases through November 2022 without date restrictions using the following search terms: (mindful* or meditation) AND (cancer OR neoplasm) AND (depress*). Studies included were primary studies evaluating MBIs in women with breast cancer who also had depression. Studies were included if they used a control group and were written in English. We used a random-effects model to compute effect sizes (ESs) using Hedges' g, forest plot, and Q and I2 statistics as measure of heterogeneity. We also requested moderator analyses. We found 19 studies with 2139 participants (49.4 ± 8.3 years old) that met inclusion criteria for this meta-analysis and systematic review. Overall, women in MBI groups demonstrated significantly lower levels of depression (g = 0.48, 95% CI:0.159, 0.792, P < .001) compared to women in control groups. Regarding moderators, providing MBIs with a home assignment component showed a significantly greater effect on decreasing depressive symptoms (g = 1.75) compared to MBIs without a home assignment component (g = 0.20). When researchers used concealed allocation technique, the interventions demonstrated lower effects on depression than when concealed allocation (g = 0.11vs g = 1.33, P ≤ .001) was not reported. Additionally, when researchers reported high rates of sample attrition, they found a lower effect size on depression (β = -.019, Q = 3.97, P = .046) indicating that attrition moderates the effect. MBIs are moderately effective interventions to reduce depressive symptoms among women with breast cancer. Clinicians might consider encouraging MBIs as adjunct/alternative treatments for women with breast cancer to manage symptoms of depression. Interventions that incorporat home assignments for practicing mindfulness are likely to have a greater effect on reducing depressive symptoms. Additionally, methods including concealed allocation and attrition rate were moderators of the effects of MBIs on depression in women with breast cancer.


Symptom trajectories in the first 18 months and autism risk in a prospective high-risk cohort.
Although early autism spectrum disorder (ASD) detection strategies tend to focus on differences at a point in time, behavioral symptom trajectories may also be informative. Developmental trajectories of early signs of ASD were examined in younger siblings of children diagnosed with ASD (n = 499) and infants with no family history of ASD (n = 177). Participants were assessed using the Autism Observation Scale for Infants (AOSI) from 6 to 18 months. Diagnostic outcomes were determined at age 3 years blind to previous assessments. Semiparametric group-based modeling using AOSI scores identified three distinct trajectories: Group 1 ('Low', n = 435, 64.3%) was characterized by a low level and stable evolution of ASD signs, group 2 ('Intermediate', n = 180, 26.6%) had intermediate and stable levels, and group 3 ('Inclining', n = 61, 9.3%) had higher and progressively elevated levels of ASD signs. Among younger siblings, ASD rates at age 3 varied by trajectory of early signs and were highest in the Inclining group, membership in which was highly specific (94.5%) but poorly sensitive (28.5%) to ASD. Children with ASD assigned to the inclining trajectory had more severe symptoms at age 3, but developmental and adaptive functioning did not differ by trajectory membership. These prospective data emphasize variable early-onset patterns and the importance of a multipronged approach to early surveillance and screening for ASD.


The prevalence of musculoskeletal troubles among car drivers.
In order to explore the relationship between car driving and musculoskeletal troubles, a cross-sectional structured-interview survey of low- to high-mileage drivers (including individuals who drove as part of their job) was conducted based on the Nordic Musculoskeletal Questionnaire. The results clearly showed that exposure to car driving was associated with reported sickness absence due to low back trouble and that those who drive as part of their job appear to be more at risk from low back trouble than those whose jobs primarily involve sitting (not driving) and standing activities. The frequency of reported discomfort also increased with higher annual mileage. In addition, drivers of cars with more adjustable driving packages had fewer reported musculoskeletal troubles. This identifies an urgent need for the training of managers of fleet vehicles in the importance of developing measures to reduce this problem, for example, the selection of an individual's car with respect to comfort and postural criteria.