Predictors of malaria vaccine uptake among children 6-24 months in the Kassena Nankana Municipality in the Upper East Region of Ghana.
The Malaria Vaccine Implementation Programme (MVIP) coordinates the routine implementation of the RTS,S vaccine pilot in strategically selected locations in Malawi, Kenya, and Ghana. The pilot programme thoroughly assesses the programmatic feasibility of administering the four doses of the RTS,S vaccine. It will also assess the impact on malaria morbidity and mortality, as well as monitor and detect the vaccine's safety for routine usage. The malaria vaccine was introduced into Ghana's routine vaccination programme in May 2019 in seven regions, comprising 42 districts, including Kassena Nankana Municipal in the Upper East region of Ghana. Therefore, this study seeks to assess the predictors of the malaria vaccine uptake in children 6 to 24 months in the Kassena Nankana Municipal in Ghana. The survey used a cross-sectional study design and included 422 mothers/caregivers with children aged 6 to 24 months from the Kassena Nankana Municipality. WHO cluster survey questionnaire was altered for use in data gathering with caregivers as respondents. The Statistical Package for the Social Sciences (SPSS) version 25.0 (for descriptive statistics) and Stata version 13 (for calculating odds ratios) were used to analyse the data. The findings depict that, the mean age of respondents for the study was 27 ± 5 years and average age of children was 15 ± 8 months. The study found that coverage uptake was high (94%). Chi-square and odds ratios testing revealed statistically significant associations between health service factors and vaccine uptake: education on malaria vaccine cOR(Cl); 9.69(3.496-25.425), (P < 0.001), giving caregivers the option to accept malaria vaccine cOR(Cl); 7.04 (2.759-17.476), (P < 0.001). Confidence in the efficiency of the vaccination was found to have a statistically significant association with malaria vaccine uptake (P < 0.005) and (p < 0.001) for 'somewhat confidence' and 'not confidence at all', respectively. Attitude of health workers was found to be significant predictor of malaria vaccine uptake (P < 0.003). Malaria vaccine uptake was high among the study population in the municipality; however, dose four uptake coverage by age two was low. This indicates that mothers/caregivers did not understand the notion of immunization throughout the second year of life. As a result, it is recommended that the municipality raise awareness about immunization services among mothers/caregivers beyond year one in order to improve performance and reduce the risk of disease outbreaks in the municipality.


Identification of an IDO1-based immune classifier for survival prediction of upper tract urothelial carcinoma.
The limited response rate of immunotherapy in upper tract urothelial carcinoma (UTUC) might be attributed to additional immunosuppressive mechanisms in vivo. As a promising immune checkpoint target, the expression and prognostic role of indoleamine 2,3-dioxygenase 1 (IDO1) in UTUC remains unknown. In this study, the expression and prognostic value of IDO1 was analyzed in 251 patients from 3 independent cohorts. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to construct an IDO1-based immune classifier and external validation was performed to further validate the classifier. RNA sequencing and immunofluorescence were used to explore the immune contexture of different risk groups stratified by classifier. We found that high IDO1 expression on tumor cells (TC) indicated a poorer overall survival and disease-free survival in all cohorts. Patients with high expression of IDO1 TC possessed increased infiltration of CD4+ , CD8+ and Foxp3+ T cells. An immune classifier based on intratumoral CD8+ lymphocytes, IDO1 TC, and stromal PD-L1 expression status was developed, with its area under the curves (AUCs) values for overall survival at 5 y being 0.79 (95% confidence interval [CI] 0.65-0.93) in the discovery cohort, 0.75 (95% CI 0.58-0.92) and 0.78 (95% CI 0.65-0.92) in the internal and external validation cohorts, respectively. The high-risk group stratified by the immune classifier was associated with immunosuppressive contexture, accompanied by enhanced CD8+ T cells exhaustion patterns. Our IDO1-based immune classifier can provide a superior accuracy for survival prediction and lead to individual stratification of UTUC immune subtypes.


Day medicine: an urgent internal medicine clinic and medical procedures suite.
During Saskatchewan's healthcare reform of the 1990s, the number of acute hospital beds in Saskatoon District Health was cut in half. The emergency room and outpatient facilities were not able to accommodate an increasing number of patients needing urgent assessments and medical procedures. In this article, we describe the development, implementation and utilization of a day medicine program. This description may be useful to others planning healthcare delivery to medical patients, especially in a setting of resource constraint.


Rabbit retinal organ culture as an in-vitro model of hepatic retinopathy.
In patients with liver insufficiency the blood ammonia concentration is elevated, which induces structural and functional retinal alterations referred to as "hepatic retinopathy". The fact that some of these alterations are reversible after timely liver transplantation rationalizes therapeutic/preventive approaches to maintain the retina before a donor organ is available. Here, we describe further elaboration and characterization of our retinal organ culture model. Retinal pieces of neonatal rabbits were explanted and cultured for up to 22 days. After 7 days in vitro (DIV7), some of the cultures were exposed to 0.25, 0.5, 1.0, 3.0, or 7.0 mM ammonia for varying periods of time and then studied by light and electron microscopy. Untreated (control) cultures underwent several changes during prolonged culturing; these included increased expression of GFAP and of Bcl-2, and decreased levels of glutamine synthetase, in Müller (glial) cells. However, the retinal layering remained intact and even some retinal ganglion cells survived although their axons had been cut. Exposure to elevated levels of ammonia caused morphologic alterations in the explants compatible with those noted in hepatic retinopathy in vivo. Specifically, we observed neuronal cellular degeneration with destruction of retinal layers and formation of rosettes, as well as decreased expression of intermediate filament proteins, migration of cell nuclei, cell swelling, and up-regulation of glutamine synthetase immunoreactivity in (some) Müller cells. Our findings indicate that the organ culture model may be a useful tool for detailed studies on the cellular and subcellular mechanisms underlying hepatic retinopathy and for in vitro testing of measures to alleviate HR symptoms.


Return to Play After Shoulder Replacement Surgery: What Is Realistic and What Does the Evidence Tell Us.
This article analyzes the available literature regarding return to sport following total shoulder arthroplasty (TSA), hemiarthroplasty (HA), and reverse shoulder arthroplasty (RTSA). It examines the quality of the available evidence and areas of future research. Most patients are able to return to preoperative sport activities following TSA, RTSA, and HA. The rates of return for TSA are slightly higher than those reported for HA and RTSA. Patients may be counseled that noncontact, low-demand activities have higher return rates. Most patients can expect to return to sports within 6 months postoperatively.


Occupational exposure to pesticides: Genetic danger to farmworkers and manufacturing workers - A meta-analytical review.
In the last decades, the use of pesticides has grown worldwide. However, there is great worry about the impact of pesticides on human health, due to their wide distribution and possible long-term effects. Complex mixtures with different formulations are often used, including a variety of genotoxic compounds. Thus, genotoxicity tests form an important part of cancer research and risk assessment of potential carcinogens. This study aimed to conduct a meta-analytical review of possible genetic damage resulting from occupational exposure in farmworkers and workers employed in pesticide production, both ever in comparison to non-exposed people, using comet assay (CA), micronucleus test (MN) and telomere length (TL) data available in the scientific literature. A total of 145 datasets were evaluated. The results showed that the occupationally exposed workers had more DNA damage in CA and MN than non-exposed workers. The TL result did not show difference between groups. When the data were categorized by gender (male, female or both), crop (general, tobacco, fruits, soybeans, cotton) and occupation (manufacturing or farmworkers), the study found that the exposed group always presented higher damage than the non-exposed individuals, in CA and MN. More studies with TL are needed to obtain a more precise response, and to segregate the effect of tobacco farming from pesticide exposure. When TL was segregated by gender, women and men presented difference between exposed and non-exposed groups. In general, the publication bias impact was modest. If all relevant studies were included, the key finding (i.e. the effect of pesticide exposure increases the genotoxicity and mutation rate) would probably remain unchanged. Lastly, it is important to highlight the importance of the use of personal protective equipment (PPE), and offer safer options to farmworkers (e.g. organic farming or less toxic alternatives).


Dynamics and mechanism of HSP70 translocation induced by photodynamic therapy treatment.
Heat shock protein 70 (HSP70) is involved in nearly all intracellular compartments. It has been recently shown to be expressed on the outer cellular membrane under photodynamic therapy (PDT) treatment. However, the mechanism and function of HSP70 translocation to the cell surface during PDT treatment are not well understood. In this study, the dynamics and mechanism of HSP70 translocation onto the cell surface and its relationship with several key intracellular events after PDT treatment were investigated using confocal microscopy. HeLa and ASTC-a-1 tumor cells were treated by PDT using different doses. In the case of PDT-induced apoptosis, cytoplasmic HSP70 rapidly translocated to the cell surface after treatment, but it was not released into the medium. Such translocation was found to be dependent on the PDT dose. Moreover, during apoptosis, the translocation of HSP70 was closely related to the changes of mitochondrial transmembrane potential (DeltaPsim). Under non-lethal PDT induced surface stress, HSP70 also translocated to the cell surface, but with a slower rate and a lower final surface concentration. These findings reaffirm the HSP70 translocation onto the cell surface under PDT treatment in living cells. Our results also indicate that the function of the surface expression of HSP70, either initiated by mitochondrial disruption or direct surface stress, is to stabilize the plasma membrane integrity, although such function failed to prevent apoptosis induced by lethal PDT treatment, as evidenced in our study.


Synthesis and biological evaluation of 1,2,5-oxadiazole N-oxide derivatives as hypoxia-selective cytotoxins.
Synthesis and biological evaluation of new 1,2,5-oxadiazole N-oxide derivatives with potential cytotoxic effects are described. From the series of compounds tested, compounds 2 and 6 proved to be very active, although non-selective.


Bile acid sulfates in serum bile acids determination.
Some bile acid sulfates were synthesized and characterized. The configuration of sulfate groups at C-3, C-7 and C-12 positions was confirmed by Nuclear Magnetic Resonance analysis. These sulfates were utilized in a study of their chemical behaviour in different analytical procedures currently used for serum bile acids determination. Procedures for bile acids extraction from serum with ethanol or Amberlite XAD-2 result in an important loss of the most polar sulfated bile acids. Complete separation of unsulfated from sulfated bile acids on Sephadex LH-20 is not achieved when deconjugation of the most polar bile acid sulfate is slow but does not produce artifacts. Enzymatic determination of bile acids gives positive response with some bile acid sulfates. The current procedures of serum bile acids determination are discussed in consideration of these results.


Variation in the pattern of nucleotide substitution across sites.
A model of nucleotide substitution that allows the transition/transversion rate bias to vary across sites was constructed. We examined the fit of this model using likelihood-ratio tests by analyzing 13 protein coding genes and 1 pseudogene. Likelihood-ratio testing indicated that a model that allows variation in the transition/transversion rate bias across sites provided a significant improvement in fit for most protein coding genes but not for the pseudogene. When the analysis was repeated with parameters estimated separately for first, second, and third codon positions, strong heterogeneity was uncovered for the first and second codon positions; the variation in the transition/transversion rate was generally weaker at the third codon position. The transition rate bias and branch lengths are underestimated when variation in the transition/transversion rate was not accommodated, suggesting that it may be important to accommodate variation in the pattern of nucleotide substitution for accurate estimation of evolutionary parameters.


Evaluation of the effects of extremely low frequency electromagnetic field on the levels of some inflammatory cytokines in post-stroke patients.
Activation of immunologically competent cells results in the overproduction of pro-inflammatory factors, and causes progression of nerve tissue damage. However, the potential neuroprotective effects of these factors in brain damage have not been well investigated. To evaluate the effect of extremely low frequency electromagnetic field (ELF-EMF) treatment on the molecular mechanism of inflammatory cytokine activity in post-stroke patients. All patients underwent the same rehabilitation program, but the ELF-EMF group were also given ELF-EMF treatment. Both groups have been used in our previous studies. In order to determine the plasma level of cytokines, the levels of interleukin 1β (IL-1β), interleukin 2 (IL-2), interferon-γ (INF-γ) and transforming growth factor β (TGF-β) were evaluated, and the level of IL-1β mRNA expression was determined. After ELF-EMF treatment, both IL-1β plasma level and IL-1β mRNA expression level, as well as IL-2 plasma level increased, while IFN-γ and TGF-β levels did not change. The increased expression of IL-1β found in this study may be a response to ELF-EMF stimulation. It is hypothesized that a neuroprotective role of this cytokine may occur due to IL-1β-dependent regulation of neurotrophic factors. Further research is needed to explore this hypothesis.


Nature, extent, and impact of Superfund hazardous waste sites.
Uncontrolled hazardous waste sites are major environmental and public health concerns in the United States and elsewhere. The identification and remediation of and public health responses to these sites are mandated by the U.S. federal Superfund statute. Since its enactment into law in 1980, approximately 40,000 uncontrolled waste sites have been identified in the United States. Approximately 1,300 of these sites constitute the current national Superfund priority list of sites for remediation. Results from analyses are described that characterize the priority hazardous substances released from Superfund sites and the extent of hazard posed to residential communities. Findings from the United States' experience in responding to uncontrolled waste sites are relevant to other countries as they address similar environmental and public health concerns.


Pentafluorosulfanyl-containing flufenamic acid analogs: Syntheses, properties and biological activities.
Pentafluorosulfanyl-containing analogs of flufenamic acid have been synthesized in high yields. Computationally, pKa, LogP and LogD values have been determined. Initial bioactivity studies reveal effects as ion channel modulators and inhibitory activities on aldo-keto reductase 1C3 (AKR1C3) as well as COX-1 and COX-2.


GO-Tibia: a masked, randomized control trial evaluating gentamicin versus saline in open tibia fractures.
The rate of open tibia fractures is rapidly increasing across the globe due to a recent rise in road traffic accidents, predominantly in low- and low-middle-income countries. These injuries are orthopedic emergencies associated with infection rates as high as 40% despite the use of systemic antibiotics and surgical debridement. The use of local antibiotics has shown some promise in reducing the burden of infection in these injuries due to increasing local tissue availability; however, no trial has yet been appropriately powered to evaluate for definitive evidence and the majority of current studies have taken place in a high-resource countries where resources and the bio-burden may be different. This is a prospective randomized, masked, placebo-controlled superiority trial designed to evaluate the efficacy of locally administered gentamicin versus placebo in the prevention of fracture-related infection in adults (age > 18 years) with primarily closeable Gustillo-Anderson class I, II, and IIIA open tibia fractures. Eight hundred ninety patients will be randomized to receive an injection of either gentamicin (treatment group) or saline (control group) at the site of their primarily closed open fracture. The primary outcome will be the occurrence of a fracture-related infection occurring during the course of the 12-month follow-up. This study will definitively assess the effectiveness of local gentamicin for the prevention of fracture-related infections in adults with open tibia fractures in Tanzania. The results of this study have the potential to demonstrate a low-cost, widely available intervention for the reduction of infection in open tibia fractures. Clinicaltrials.gov NCT05157126. Registered on December 14, 2021.


Outcomes and patient satisfaction following individualized physical therapy treatment for patients diagnosed with temporomandibular disc displacement without reduction with limited opening: A cross-sectional study.
To investigate physical therapy treatment outcomes and patient satisfaction in patients with a diagnosis of disc displacement without reduction with limited opening (DDWoR wLO). Records of 97 patients with DDWoR wLO who received physical therapy in one outpatient clinic were used in this cross-sectional study. Outcomes included number of visits, maximum active interincisal opening, self-reported pain, and patient satisfaction. The average number of physical therapy visits per patient was 5.5, and there were significant improvements in pain rating and interincisal opening following physical therapy. Effect sizes for these comparisons were large (>1.0). Mean patient satisfaction responses across all symptom areas was consistent with patients being more than less satisfied following treatment. Individualized physical therapy treatment is an effective conservative intervention to improve mouth opening, reduce pain, and provide patient satisfaction in patients with one specific sub-type of temporomandibular disorder (TMD), DDWoR wLO.


Taurine deficiency in the kitten subcellular distribution of taurine and [35S]taurine in brain.
Taurine concentration decreases rapidly in the tissues and physiological fluids of kittens fed a diet of partially purified casein which lacks taurine. We have studied the subcellular distribution in cerebrum of taurine and [35S]taurine administered intravenously to these animals. The taurine concentration of all the fractions isolated from the cerebrum of taurine-deficient kittens was approximately sevenfold less than that observed in the fractions of cerebrum isolated from control kittens. The [35S]taurine was approximately twofold greater in all the brain fractions isolated from the taurine-deficient kittens compared with those isolated from the control kittens. The percent distributions of taurine and [35S]taurine in the fractions isolated from the cerebrum of control and deficient kittens were identical. Thus, in the face of a severe diet-induced deficiency of taurine in kitten brain, there appears to be no conservation of taurine by any particular subcellular pool of taurine. These studies provide no evidence for differences in compartmentation of taurine in cerebrum of taurine-deficient kittens compared with control kittens.


Changes in psychological well-being during postmenopause as a result of estrogen therapy.
A study of the effects of a conjugated estrogen (Femipren) upon various climacteric symptoms, depression and anxiety scores and psycho-social factors in 120 women around the menopause, was carried out in a Menopause Clinic. In order to participate in this study, the women had to meet very strict criteria. A climacteric symptom list, the MMPI and a psycho-social questionnaire were used for assessment, and were employed before, during and at the end of 1 yr of hormone replacement therapy. Typical vasomotor and psychic symptoms changed significantly as did such factors as self-image, optimism, perception of the future and satisfaction with personal appearance, in those patients who received hormonal replacement therapy for 1 yr. As the psychological factors changed only in those patients who received long-term estrogen therapy, a tentative hypothesis of direct psychotropic effect of estrogen was formulated.


A syntelog-based pan-genome provides insights into rice domestication and de-domestication.
Asian rice is one of the world's most widely cultivated crops. Large-scale resequencing analyses have been undertaken to explore the domestication and de-domestication genomic history of Asian rice, but the evolution of rice is still under debate. Here, we construct a syntelog-based rice pan-genome by integrating and merging 74 high-accuracy genomes based on long-read sequencing, encompassing all ecotypes and taxa of Oryza sativa and Oryza rufipogon. Analyses of syntelog groups illustrate subspecies divergence in gene presence-and-absence and haplotype composition and identify massive genomic regions putatively introgressed from ancient Geng/japonica to ancient Xian/indica or its wild ancestor, including almost all well-known domestication genes and a 4.5-Mbp centromere-spanning block, supporting a single domestication event in main rice subspecies. Genomic comparisons between weedy and cultivated rice highlight the contribution from wild introgression to the emergence of de-domestication syndromes in weedy rice. This work highlights the significance of inter-taxa introgression in shaping diversification and divergence in rice evolution and provides an exploratory attempt by utilizing the advantages of pan-genomes in evolutionary studies.


Measurement of renal cortical fibrosis by CT scan.
The accurate, non-invasive, and rapid measurement of renal cortical fibrosis is needed for well-defined benchmarks of permanent injury and for use of anti-fibrotic agents. It is also needed for non-invasive and rapid assessment of the chronicity of human renal diseases. We have used a non-human primate model of radiation nephropathy to develop a novel method of size-corrected CT imaging to quantify renal cortical fibrosis. Our method has an area under the receiver operating curve of 0.96, which is superior to any other non-invasive method of measuring renal fibrosis. Our method is suitable for immediate translation to human clinical renal diseases.


Changes in cell surface glycoproteins on non-differentiating L6 rat myoblasts selected for resistance to concanavalin A.
Four independently selected conA-resistant, non-differentiating rat L6 myoblast cell lines and their parental wild-type populations were examined for cell surface alterations. [3H]conA-binding studies indicated that the variant myoblasts bound significantly less lectin than wild-type cells at 4 and at 37 degrees C. Scatchard analysis revealed two general types of binding sites (high and low affinity sites) on wild-type cells; the variants appeared to be deficient in the high affinity sites. These changes in conA binding probably play an important role in determining the conA-resistant phenotype. Lectin-binding results could be significantly modified by altering the composition of the serum in the growth medium used to culture myoblasts prior to performing binding experiments, suggesting the existence of productive and non-productive lectin-binding sites on the cell surface. SDS slab gel electrophoresis of [3H]mannose-labelled surface membranes prepared from variant and wild-type cells showed that several glycoproteins of the conA-resistant myoblasts were defective in mannosylation. The conA-binding abilities of a pronase digest of one of these altered regions from variant separations, with a molecular weight of 44500 D, was found to contain glycopeptides with reduced affinity for the lectin, supporting the idea that variant membranes are deficient in a set of high affinity lectin-binding sites. Studies on [GDP-14C]mannose incorporation into lipid by membranes from variant and wild-type myoblasts indicated that the biosynthetic lesion likely involved a mannosyl transferase enzyme directly, rather than a lack of free dolichol-PO4. These studies link conA resistance, cell surface glycoprotein alterations, and defective mannosyl transferase activity with the inability to carry out normal cellular differentiation to form multinucleated myotubes.


Mouse splenocyte blast transformation in the presence of plasma γ-globulin fraction proteins and their complexes with copper and zinc.
Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes formed by these cations and human serum γ-globulin induce blast transformation of splenocytes from BALB/c mice at a level comparable to that induced by concanavalin A. Zinc bound to γ-globulin reduces by 25% and copper in complex with this protein stimulates by 1.6 times its capacity to induce blast transformation. Combinations with concanavalin A reproduce the effects of γ-globulin-metal complex under conditions of mitogen induction. Incorporation of(3)H-thymidine in splenocytes incubated with combinations of γ-globulin-copper metalcomplex, copper cations, and control protein with concanavalin A was by 1.4, 1.3 (p<0.1), and 1.25 times higher (p<0.05), respectively, than after incubation with concanavalin A alone.


ALOX5AP suppresses osteosarcoma progression via Wnt/β-catenin/EMT pathway and associates with clinical prognosis and immune infiltration.
Osteosarcoma (OS) is one of the most common malignant neoplasms in children and adolescents. Immune infiltration into the microenvironment of the tumor has a positive correlation with overall survival in patients with OS. The purpose of this study was to search for potential diagnostic markers that are involved in immune cell infiltration for OS. Patients with OS who acquired metastases within 5 years (n = 34) were compared to patients who did not develop metastases within 5 years (n = 19). Differentially expressed genes (DEGs) were tested for in both patient groups. To discover possible biomarkers, the LASSO regression model and the SVM-RFE analysis were both carried out. With the assistance of CIBERSORT, the compositional patterns of the 22 different types of immune cell fraction in OS were estimated. In this research, a total of 33 DEGs were obtained: 33 genes were significantly downregulated. Moreover, we identified six critical genes, including ALOX5AP, HLA-DOA, HLA-DMA, HLA-DRB4, HCLS1 and LOC647450. ROC assays confirmed their diagnostic value with AUC > 0.7. In addition, we found that the six critical genes were associated with immune infiltration. Then, we confirmed the expression of ALOX5AP was distinctly decreased in OS specimens and cell lines. High expression of ALOX5AP predicted an advanced clinical stage and overall survival of OS patients. Functionally, we found that overexpression of ALOX5AP distinctly suppressed the proliferation, migration, invasion and EMT via modulating Wnt/β-catenin signaling. Overall, we found that ALOX5AP overexpression inhibits OS development via regulation of Wnt/β-catenin signaling pathways, suggesting ALOX5AP as a novel molecular biomarker for enhanced therapy of OS.


Mechanical properties of brain tissue related to oedema development in rabbits.
We studied the mechanical properties of the brain in anaesthetized rabbits by application of a standard external load to the exposed cerebral surface. The experimental model used allows one to eliminate potential circulatory factors. Brain oedema was produced by repeated episodes of ischaemia secondary to a decrease of the arterial blood pressure to zero. The development of brain oedema was assessed by an increase of the cerebral water content. In the course brain oedema development brain fluidity was found to steadily rise, while the brain compliance and the index of hysteresis decreased from the control value found at the onset of the experiment. Most important both, brain compliance and the index of hysteresis were already markedly elevated prior to the manifestation of brain oedema.


[Optimization of high flip angle for late gadolinium enhancement magnetic resonance imaging by phase-sensitive inversion recovery sequence].
This study focuses on optimization of the flip angle (FA) of phase-sensitive inversion recovery (PSIR) reconstruction (PSIR-FA) to achieve improved tissue contrast. Intensity normalization removes the larger variations in image intensity caused by falloff, thus improving the visualization of tissue contrast. We evaluated tissue contrast for images in healthy volunteers using the phantom influence of T1 relaxation and FA. T1 relaxation is improved due to the T1(*) effect and enables a high PSIR-FA to be set. The contrast-to-noise ratio (CNR) of the PSIR-FA 20° image is good, since magnetization is almost fully restored to normal. The usefulness of PSIR-FA 20 images was proved statistically. PSIR-FA 20° shows improved tissue contrast as a result of the high accuracy of intensity normalization.


Regional changes in GnRH immunoreactivity with puberty in the male Syrian hamster.
Gonadotropin-releasing-hormone immunopositive (GnRH+) neurons were identified in juvenile and adult male Syrian hamsters. There were significantly fewer GnRH+ cells in the diagonal band of Broca/organum vasculosum of the lamina terminalis (DBB/OVLT) and medial septum (MS) in adults as compared to juvenile males, while no cell number difference was found in the preoptic area (POA). The decrease in cell number likely reflects reduced somal stores of GnRH in DBB/OVLT and MS, suggesting that these subpopulations promote increased GnRH release during pubertal maturation in male hamsters.


Rapid duplex immunoassay for wound biomarkers at the point-of-care.
In this study we describe a novel method of sampling and quantifying wound biomarkers for clinical settings. We believe the chosen format will allow rapid assessments of wound healing and provide biomarker evidence-based decision points for treatment of the wound at the time of presentation. The wound monitoring principle uses a proprietary sample collection tool (a thermally reversible hydrogel) to sample and isolate biomarkers within a wound environment without further sample extraction/preparation steps. We show how gel samples can be analysed in a lateral flow assay format utilising fluorescent microspheres with optically discrete emission characteristics and demonstrate quantitative detection of two analytes (duplexing) achieved in a single test line. As a model assay, the chronic wound biomarkers interleukin 6 (IL6) and tumour necrosis factor alpha (TNFα) are used. Limits of detection of 48.5 pg/mL and 55.5 pg/mL respectively in hydrogel samples and 7.15 pg/mL and 10.7 pg/mL respectively in plasma are reported. We believe this is the first literature example of quantitative detection of multiple analytes within a single test line using spectral separation to distinguish the analytes.


Neurocognitive effects of CNS tumors.
There is ample evidence that many children treated for brain tumors experience long-term neurocognitive deficits. The severity of those deficits is determined by a complex interaction of the child's genetic make-up and age, neuroanatomical damage caused by tumor and surgery, radiotherapy and chemotherapy, the psychosocial environment, and the intensity of targeted rehabilitation. The consequences of neurocognitive deficits are moderated by the number and severity of other deficits, including neurological and endocrine impairments, and this wider context must be considered. The impact of intellectual decline on academic functioning is evident, and underlies, for example, poor reading, writing, and mathematical skills. The effects of early brain damage on development are cumulative as more functions are expected to mature. Many survivors of CNS tumors can be expected to grow into deficits that have far-reaching consequences not only for academic achievement but also for their psychological and social development and their ability to be self-sufficient. Because the problems typically only become apparent over time, surveillance for their detection is an essential prerequisite for early educational and other interventions to support learning and successful transition to independent adult life.


Prevalence of HFE (hemochromatosis) gene mutations in patients with cluster headache.
To evaluate whether polymorphisms of the HFE gene would modify the occurrence and the clinical features of cluster headache (CH). Recent studies suggested that iron metabolism may be involved in the pathophysiology of primary headaches. The HFE gene encodes for a protein that modulates iron absorption. Mutations in this gene are responsible for toxic iron overload in several body organs. Genomic DNA was extracted from 109 CH patients and 211 age and sex-matched healthy controls and genotyped for the C282Y and H63D mutations of the HFE gene. Allele and genotype frequencies of the HFE gene were compared between cases and controls. The clinical characteristics of the disease were compared according to the different HFE gene genotypes. No C282Y mutation was found in both cases and controls. The prevalence of the H63D mutation was nearly identical in cases and controls. The four patients carrying the HFE D63D genotype showed a significantly (P < .001) later age at onset of the disease in comparison with both H63H and H63D patients. The remaining clinical characteristics of the disease did not significantly differ in the presence or absence of the H63D mutation. Our data do not support the hypothesis that genetic variations within the HFE gene are associated with CH. However, the HFE gene may influence the disease phenotype and may be regarded as a disease modifier gene.


Statistical 4D graphs for multi-organ abdominal segmentation from multiphase CT.
The interpretation of medical images benefits from anatomical and physiological priors to optimize computer-aided diagnosis applications. Diagnosis also relies on the comprehensive analysis of multiple organs and quantitative measures of soft tissue. An automated method optimized for medical image data is presented for the simultaneous segmentation of four abdominal organs from 4D CT data using graph cuts. Contrast-enhanced CT scans were obtained at two phases: non-contrast and portal venous. Intra-patient data were spatially normalized by non-linear registration. Then 4D convolution using population training information of contrast-enhanced liver, spleen and kidneys was applied to multiphase data to initialize the 4D graph and adapt to patient-specific data. CT enhancement information and constraints on shape, from Parzen windows, and location, from a probabilistic atlas, were input into a new formulation of a 4D graph. Comparative results demonstrate the effects of appearance, enhancement, shape and location on organ segmentation. All four abdominal organs were segmented robustly and accurately with volume overlaps over 93.6% and average surface distances below 1.1mm.


Tips and tricks of fetal MR imaging.
The technique of performing fetal MR examinations differs from routine pelvic MR imaging because the fetus is in motion, and image planes must be selected orthogonal to fetal anatomy. The small size of the fetus also increases examination difficulty because thin slices (limited by SNR) are often needed for adequate examination of anatomy and pathology. Knowledge of fetal anatomy and neonatal anatomy/ pathology are needed in the assessment of fetal MR imaging. Knowledge of MR artifacts aids in image interpretation.


Modulation of Activity of a Carotenoid Pathway Through the Use of the TeT-on Regulatory System: Application in the Fungus Fusarium fujikuroi.
Carotenoids are widespread pigments in photosynthetic species, but they are also found in nonphotosynthetic microorganisms, such as bacteria and fungi. The amenability of fungi to genetic studies have made some fungal species advantageous models in the study of the genetics and biochemistry of carotenoid biosynthesis, while others have been used for biotechnological carotenoid production. The availability of molecular techniques that allow modulating the expression of target genes is a powerful tool in the manipulation of carotenoid synthesis. An example of an adjustable gene expression is based on the tetracycline-controlled transcriptional activation system, known as Tet-on. We describe here the material and protocols for the construction of a Tet-on regulated gene, its introduction in the filamentous fungus F. fujikuroi, and its use to modulate the expression of a negative regulator of carotenoid biosynthesis.


AUA Consensus Statement on Advanced Practice Providers: Executive Summary.
The purpose of this document is to provide guidance for urologists on the integration of advanced practice providers into the urological care setting with a focus on the current state and federal regulatory environment, reimbursement considerations, core competency benchmarks, patient satisfaction with the advanced practice provider-physician team approach and proposed models of team based integrative care. Since 1983, the AUA (American Urological Association) has issued its position on allied health professionals, recognizing that in some areas allied health personnel contribute to the care of the patient with genitourinary disease and, therefore, encourages the proper use of allied health personnel. A 2013 AUA survey on workforce revealed that 62% of urologists surveyed were using an advanced practice provider in their practice. In 2012 there were nearly 8,000 advanced practice providers working in urology departments and practices in the United States, including more than 3,300 nurse practitioners and more than 4,000 physician assistants. In 2013 the AUA convened an ad hoc work group of a diverse set of urology providers, including physicians, nurse practitioners and physician assistants. The consensus statement was drafted over 10 months and approved by the AUA Board of Directors in November 2014. Urologists work with advanced practice providers frequently but many may not know the most efficient way to incorporate them into their practice. The consensus statement examines advanced practice provider integration from a regulatory and practice management approach, as well as provides several applicable examples of how this applies to urologists in various clinical settings throughout the United States. This document supports the AUA's policy statement that in a team based approach with a board certified urologist in a supervisory role, allied health personnel contribute to the care of the patient with genitourinary disease and, therefore, encourages the proper use of allied health personnel.


Data mining in psychiatric research.
Mathematical sciences and computational methods have found new applications in fields like medicine over the last few decades. Modern data acquisition and data analysis protocols have been of great assistance to medical researchers and clinical scientists. Especially in psychiatry, technology and science have made new computational methods available to assist the development of predictive modeling and to identify diseases more accurately. Data mining (or knowledge discovery) aims to extract information from large datasets and solve challenging tasks, like patient assessment, early mental disease diagnosis, and drug efficacy assessment. Accurate and fast data analysis methods are very important, especially when dealing with severe psychiatric diseases like schizophrenia. In this paper, we focus on computational methods related to data analysis and more specifically to data mining. Then, we discuss some related research in the field of psychiatry.


Can birth outcome inequality be reduced using targeted caseload midwifery in a deprived diverse inner city population? A retrospective cohort study, London, UK.
(1) To report maternal and newborn outcomes of pregnant women in areas of social deprivation in inner city London. (2) To compare the effect of caseload midwifery with standard care on maternal and newborn outcomes in this cohort of women. Retrospective observational cohort study. Four council wards (electoral districts) in inner city London, where over 90% of residents are in the two most deprived quintiles of the English Index of Multiple Deprivation (IMD) (2019) and the population is ethnically diverse. All women booked for antenatal care under Guys and St Thomas' National Health Service Foundation Trust after 11 July 2018 (when the Lambeth Early Action Partnership (LEAP*) caseload midwifery team was implemented) until data collection 18 June 2020. This included 523 pregnancies in the LEAP area, of which 230 were allocated to caseload midwifery, and 8430 pregnancies from other areas. To explore if targeted caseload midwifery (known to reduce preterm birth) will improve important measurable outcomes (preterm birth, mode of birth and newborn outcomes). There was a significant reduction in preterm birth rate in women allocated to caseload midwifery, when compared with those who received traditional midwifery care (5.1% vs 11.2%; risk ratio: 0.41; p=0.02; 95% CI 0.18 to 0.86; number needed to treat: 11.9). Caesarean section births were significantly reduced in women allocated to caseload midwifery care, when compared with traditional midwifery care (24.3% vs 38.0%; risk ratio: 0.64: p=0.01; 95% CI 0.47 to 0.90; number needed to treat: 7.4) including emergency caesarean deliveries (15.2% vs 22.5%; risk ratio: 0.59; p=0.03; 95% CI 0.38 to 0.94; number needed to treat: 10) without increase in neonatal unit admission or stillbirth. This study shows that a model of caseload midwifery care implemented in an inner city deprived community improves outcome by significantly reducing preterm birth and birth by caesarean section when compared with traditional care. This data trend suggests that when applied to targeted groups (women in higher IMD quintile and women of diverse ethnicity) that the impact of intervention is greater.


Accommodative dysfunction.
A retrospective review of the records of 114 subjects with accommodative dysfunction has been completed. Most subjects (N = 96) were found to have accommodative insufficiency. Lesser numbers of subjects were categorized in the class of infacility of accommodation (N = 14), spasm of accommodation (N = 3) and fatigue of accommodation (N = 1). A majority of the subjects presented with complaints of blur, headaches and/or asthenopia while attempting nearwork. Most subjects presented with reduced abilities in one or more of the following areas: accommodative amplitude and facility, fusional vergences, near point of convergence and stereo acuities. The clinical characteristics of the group as a whole and the major subgroups have been examined both before and after treatment of the condition with orthoptic exercises and/or plus lenses at the nearpoint. The result of the treatment indicates that although most subjects (96%) experienced some relief with treatment only about half (53%) had their problems totally solved. The importance of these findings is briefly discussed.


Spheno-orbital meningioma with unusual radiological features.
We report a patient with a spheno-orbital meningioma having unusual clinical and radiological features. Eight days before consultation, this 66-year-old female developed right exophthalmos associated with periorbital pain. Neuroradiological features included, (1) multilocular intratumoral cyst on enhanced CT, (2) preferential extradural growth with prominent bony destruction and intratumoral hemorrhage on MRI. and (3) early venous draining on CAG. Histopathology including immunohistochemistry and electron microscopy revealed typical transitional meningioma. The only uncommon pathological feature was that the attachment consisted of the outer (periosteal) layer of the dura, and the microscopic structure of the inner (meningeal) layer was normal.


Current status of prenatal management of fetal spina bifida in the world: worldwide cooperative survey on the medico-ethical issue.
The management of congenital CNS anomalies differs among countries. This paper reports on a worldwide survey of individual experience and regimens for treating spina bifida (SB) in different patient populations and cultural backgrounds. Ten representative members of the International Society for Pediatric Neurosurgery (ISPN) in individual countries registered their experience, prenatal management, and care system for SB. The information collected contained the following major items: intrauterine diagnosis, prophylaxis, and legal termination in prenatal management. The prenatal diagnosis of SB is extensively performed throughout the world, but the marker alpha-fetoprotein is not widely accepted in Asia, nor is the prophylactic administration of folic acid, which is not part of the routine care in Asia. Morphological analyses by neuroimaging, especially using an advanced technique of magnetic resonance imaging (MRI), are well developed in Asian countries, e.g., Japan and Korea. The prenatal management of SB fetuses differed depending upon the region, i.e., more support for aggressive and intensive treatment in Asia than in Europe and North America. The regional and racial difference in management of and care for spina bifida fetuses will be discussed further based on the data analysis.


Detection of K-complexes in EEG waveform images using faster R-CNN and deep transfer learning.
The electroencephalography (EEG) signal carries important information about the electrical activity of the brain, which may reveal many pathologies. This information is carried in certain waveforms and events, one of which is the K-complex. It is used by neurologists to diagnose neurophysiologic and cognitive disorders as well as sleep studies. Existing detection methods largely depend on tedious, time-consuming, and error-prone manual inspection of the EEG waveform. In this paper, a highly accurate K-complex detection system is developed. Based on multiple convolutional neural network (CNN) feature extraction backbones and EEG waveform images, a regions with faster regions with convolutional neural networks (Faster R-CNN) detector was designed, trained, and tested. Extensive performance evaluation was performed using four deep transfer learning feature extraction models (AlexNet, ResNet-101, VGG19 and Inceptionv3). The dataset was comprised of 10948 images of EEG waveforms, with the location of the K-complexes included as separate text files containing the bounding boxes information. The Inceptionv3 and VGG19-based detectors performed consistently high (i.e., up to 99.8% precision and 0.2% miss rate) over different testing scenarios, in which the number of training images was varied from 60% to 80% and the positive overlap threshold was increased from 60% to 90%. Our automated method appears to be a highly accurate automatic K-complex detection in real-time that can aid practitioners in speedy EEG inspection.


High intrahepatic HHV-6 virus loads but neither CMV nor EBV are associated with decreased graft survival after diagnosis of graft hepatitis.
In liver transplant recipients with graft hepatitis, the relevance of herpesviruses is not well defined. Viral loads of CMV, EBV, and HHV-6 were determined in blood and liver biopsies of 170 liver transplant recipients with graft hepatitis by quantitative PCR. HHV-6-, CMV-, and EBV-DNA were detected in 58%, 14%, and 44% of the biopsies, respectively, with coinfections in 34%. High intrahepatic HHV-6 DNA levels (>75th percentile, 11.27 copies/1000 cells) and detection of HHV-6 DNAemia were significantly associated with decreased graft survival after diagnosis of graft hepatitis (p=0.014 and p=0.003, respectively, median follow-up was 23.8 months). Multivariate analysis confirmed high intrahepatic HHV-6 loads as an independent factor associated with reduced graft survival (adjusted hazard ratio 2.61, 95%confidence interval 1.16-5.87). Low concentrations of HHV6 DNA in the liver, indicating latent infection, did not influence graft survival. Neither CMV nor EBV (qualitative detection and high virus loads) nor acute rejection (according to the BANFF score) affected graft survival. However, patients had been treated for CMV reactivations and acute rejections in this retrospective study. High age and high bilirubin levels were the other independent factors associated with reduced graft survival (adjusted hazard ratio 3.56CI 1.52-8.34 and 3.23CI 1.50-6.96, respectively). High intrahepatic HHV-6-DNA levels are associated with decreased graft survival in liver transplant recipients with graft hepatitis. The significance of HHV-6 as potential etiology of graft hepatitis needs further evaluation.


High-resolution structural studies of the retinal--Glu113 interaction in rhodopsin.
The key to understanding the reaction mechanism of rhodopsin lies in determining the structure of the retinal binding site and in defining the charge interactions between Glu113 and the retinal protonated Schiff base chromophore. We have been using 13C-NMR chemical shift data to determine the location of the Glu113 carboxyl side chain in relation to the retinal. The NMR data constrain one of the carboxylate oxygens of Glu113 to be ca. 3 A from the C12 position of the retinal with the second oxygen oriented away from the conjugated chain. A water molecule forming a hydrogen bond with the Schiff base is incorporated into the model to account for the high C = N stretching frequency [Han et al., Biophys. J., 65 (1993) 899]. In this study, we have refined the counterion position and have shown that it can reproduce the observed chemical shift data as well as the red-shifted absorption maximum of rhodopsin. Furthermore, the retinal binding site geometry derived from the NMR constraints can be readily incorporated into a recent structural model of the apoprotein.


Inferred miRNA activity identifies miRNA-mediated regulatory networks underlying multiple cancers.
MicroRNAs (miRNAs) play a key role in regulating tumor progression and metastasis. Identifying key miRNAs, defined by their functional activities, can provide a deeper understanding of biology of miRNAs in cancer. However, miRNA expression level cannot accurately reflect miRNA activity. We developed a computational approach, ActMiR, for identifying active miRNAs and miRNA-mediated regulatory mechanisms. Applying ActMiR to four cancer datasets in The Cancer Genome Atlas (TCGA), we showed that (i) miRNA activity was tumor subtype specific; (ii) genes correlated with inferred miRNA activities were more likely to enrich for miRNA binding motifs; (iii) expression levels of these genes and inferred miRNA activities were more likely to be negatively correlated. For the four cancer types in TCGA we identified 77-229 key miRNAs for each cancer subtype and annotated their biological functions. The miRNA-target pairs, predicted by our ActMiR algorithm but not by correlation of miRNA expression levels, were experimentally validated. The functional activities of key miRNAs were further demonstrated to be associated with clinical outcomes for other cancer types using independent datasets. For ER(-)/HER2(-) breast cancers, we identified activities of key miRNAs let-7d and miR-18a as potential prognostic markers and validated them in two independent ER(-)/HER2(-) breast cancer datasets. Our work provides a novel scheme to facilitate our understanding of miRNA. In summary, inferred activity of key miRNA provided a functional link to its mediated regulatory network, and can be used to robustly predict patient's survival. the software is freely available at http://research.mssm.edu/integrative-network-biology/Software.html. email@example.com Supplementary data are available at Bioinformatics online.


WITHDRAWN: Co-administration of CCL5 and IL4 enhances DNA vaccine-induced protective immunity to Ascaris suum infection in mice.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Impaired lipid and glucose homeostasis in male mice offspring after combined exposure to low-dose bisphenol A and arsenic during the second half of gestation.
In this study, we used a 1H NMR based metabolomics strategy combined with gene expression analysis to determine the combined effects of gestational exposure of mice to BPA (10 μg/kg body weight by subcutaneous injection) and arsenic (10 ppb sodium arsenite in drinking water). Results showed that exposure to either BPA or, arsenic or their combination induced age-dependent metabolic disruptions in male mice offspring, and the combined exposure could exacerbate the metabolic changes induced by either BPA or arsenic alone. Moreover, this combined exposure influenced both glucose tolerance and insulin tolerance in mice, along with changing the expression of genes involved in lipid and glucose homeostasis. Specifically, the combined exposure to BPA and arsenic promoted the uptake of glucose and fatty acid from serum to liver, and genes involved in glycogenesis, glucogenesis, and fatty acid oxidation were activated in the liver in the combined exposure group. Taken together, these experimental results highlight the importance of considering the combined toxicity of environmental pollutants at levels relevant to human exposure, especially during the early life stages of mammals.


Association of ABCB1, ABCC5 and xanthine oxidase genetic polymorphisms with methotrexate adverse reactions in Mexican pediatric patients with ALL.
Acute lymphoblastic leukemia (ALL) is one of the most frequent oncological disorders in pediatric populations. To date, the drug of choice for the treatment of ALL is methotrexate, a drug associated with a high risk of adverse reactions (ADRs). The xanthine oxidase (XO) polymorphisms, 1936A>G and 2107A>G, as well as the polymorphic variants derived from ATP-binding cassette transporter gene subfamilies, ABCB1 and ABCC5, of drug resistant codifying genes, are implicated as precursors of drug-related neurologic, hepatic, and renal toxicities. Our aim was to determine whether the mentioned polymorphisms are risk or protective factors for the development of adverse reactions by methotrexate in our pediatric population with ALL. A total of 35 Mexican children from Centro Estatal de Cancerología-Durango, Mexico, with ALL and the previously noted polymorphisms as determined qPCR were studied. At the same time, a 12-month drug monitoring program was conducted in accordance with WHO-PAHO guidelines for pharmacovigilance. The ABCB11936A>G and 2107A>G and ABCC5 3414+434A>C polymorphisms were not associated with methotrexate ADRs. Single nucleotide polymorphisms (SNPs) of ABCB1 1236C>T (OR 0.19, 95% CI: 0.03-0.9, p<0.05) and ABCC5 3933+313T>C (OR 0.12, 95% CI: 0.027-0.58, p<0.05) were associated with methotrexate ADRs. SNPs 1236C>T of ABCB1 and ABCC5 3933+313T>C are not associated with the development of typical ADRs by methotrexate, rather, they showed a protective factor for myelosuppression in the studied sick population.


Assuring Clonality on the Beacon Digital Cell Line Development Platform.
During biomanufacturing cell lines development, the generation and screening for single-cell derived subclones using methods that enable assurance of clonal derivation can be resource- and time-intensive. High-throughput miniaturization, automation, and analytic strategies are often employed to reduce such bottlenecks. The Beacon platform from Berkeley Lights offers a strategy to eliminate these limitations through culturing, manipulating, and characterizing cells on custom nanofluidic chips via software-controlled operations. However, explicit demonstration of this technology to provide high assurance of a single cell progenitor has not been reported. Here, a methodology that utilizes the Beacon instrument to ensure high levels of clonality is described. It is demonstrated that the Beacon platform can efficiently generate production cell lines with a superior clonality data package, detailed tracking, and minimal resources. A stringent in-process quality control strategy is established to enable rapid verification of clonal origin, and the workflow is validated using representative Chinese hamster ovary-derived cell lines stably expressing either green or red fluorescence protein. Under these conditions, a >99% assurance of clonal origin is achieved, which is comparable to existing imaging-coupled fluorescence-activated cell sorting seeding methods.


Acupuncture combined with traditional Chinese medicine preparation for the treatment of marrow suppression after chemotherapy: A protocol for systematic review and meta-analysis.
From the perspective of evidence-based medicine, the efficacy and safety of combined therapy for marrow suppression after chemotherapy is still unclear. Given that there is no high-quality meta-analysis to incorporate existing evidence, the purpose of this protocol is to design a systematically review and meta-analysis of the level I evidence to ascertain the efficacy and safety of acupuncture combined with traditional Chinese medicine preparation for marrow suppression after chemotherapy. The following databases will be searched electronically by keyword combination mode: 4 British literature databases including PubMed, EMBASE, Scopus, and Cochrane Library, and 4 Chinese literature databases, including Chinese national knowledge infrastructure, VIP, and Wan fang database. The randomized controlled trials on acupuncture plus traditional Chinese medicine preparation for marrow suppression after chemotherapy will be included. The primary outcome is the elevation of hemoglobin, platelets, leukocytes, and neutrophils. The other outcomes include clinical symptoms, quality of life, and absolute value of reticulocyte. Risk bias analysis of the studies will be performed independently by 2 reviewers using the Cochrane Risk of Bias Assessment Tool. The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. This protocol will provide a reliable theoretical basis for the following research.


Treatment of Wilms tumor using carboplatin compared to therapy without carboplatin.
Wilms tumor (WT) is the most common pediatric malignant primary renal tumor. One of the main drugs used in treatment is actinomycin-D. This was not readily available in Turkey at one time. Carboplatin was used in the primary treatment of WT in order to prevent delays in treatment. The aim of this study is to present the results of patients with WT receiving carboplatin or actinomycin-D therapy. Forty-eight consecutive patients with WT treated between July 2005 and December 2011 were included in this retrospective study. The patients were treated according to Turkish Pediatric Oncology Group guidelines. Nineteen patients were treated with actinomycin-D and 29 with carboplatin (500 mg/m(2) /dose). The two groups were then compared in terms of 2- and 4-year overall survival (OS), event-free survival (EFS) and disease-free survival (DFS). Two- and four-year OS rates in the carboplatin group were 90.0% and 90.0%, compared to 100.0% and 88.0%, respectively, in the non-carboplatin group. Two- and four-year EFS levels in the carboplatin group were 92.0% and 88.0%, respectively, compared to 82.0% and 76.0% in the non-carboplatin group. Two-and four-year DFS levels in the carboplatin group were 92.0% and 86.0%, respectively, compared to 77.0% and 77.0% in the non-carboplatin group. The findings show that the carboplatin can be used as an alternative drug in the primary treatment of WT in the event that actinomycin-D is unavailable or not tolerated.


Image-guided Endoscopic Parathyroidectomy Using the Axillo-breast Approach in the Treatment of Primary Hyperparathyroidism.
Focused parathyroidectomy is currently performed using minimal access techniques. Here, we aim to evaluate the outcomes of the axillo-breast totally endoscopic approach (ABTEA) in patients with primary hyperparathyroidism caused by a single parathyroid adenoma. Ten patients with primary hyperparathyroidism were retrospectively evaluated. In all patients, the presence of a single parathyroid adenoma was confirmed using cervical ultrasonography by an expert radiologist with or without the use of parathyroid scintigraphy. All patients underwent focused parathyroidectomy using ABTEA. Clinicopathologic characteristics, surgical outcomes, biochemical cure rates, and cosmetic outcomes were evaluated. The parathyroid adenoma was successfully excised in all patients without significant complications and without conversion to open approach. All patients were cured, with ≥6 months of follow-up. Temporary hoarseness of the voice was observed in 1 case. The mean surgical time was 91±17.61 minutes. The mean blood loss was 20 mL. The postoperative pain scores were satisfactory and 90% of patients were extremely satisfied with the procedure. With accurate preoperative sonographic localization of a single parathyroid adenoma, focused parathyroidectomy using ABTEA is a safe and feasible technique even for posteriorly located parathyroid adenomas.


[Olecranon osteotomy].
In recent years the increase of interest for surgery of the elbow has fostered the development of new and modified triceps sparing approaches. Olecranon osteotomy is a widely accepted method especially for open reduction and internal fixation of displaced intra-articular fractures because it provides excellent exposure of the joint surfaces. Due to several reports describing numerous complications, the enthusiasm for this procedure is currently limited. Several intra-articular and extra-articular techniques for refixation of the olecranon have been developed to limit these complications and good results have been obtained. This paper describes various techniques, analyzes advantages and disadvantages and shows alternative ways and solutions for different indications.


Understanding altered contractile properties in advanced age: insights from a systematic muscle modelling approach.
Age-related alterations of skeletal muscle are numerous and present inconsistently, and the effect of their interaction on contractile performance can be nonintuitive. Hill-type muscle models predict muscle force according to well-characterised contractile phenomena. Coupled with simple, yet reasonably realistic activation dynamics, such models consist of parameters that are meaningfully linked to fundamental aspects of muscle excitation and contraction. We aimed to illustrate the utility of a muscle model for elucidating relevant mechanisms and predicting changes in output by simulating the individual and combined effects on isometric force of several known ageing-related adaptations. Simulating literature-informed reductions in free Ca2+ concentration and Ca2+ sensitivity generated predictions at odds qualitatively with the characteristic slowing of contraction speed. Conversely, incorporating slower Ca2+ removal or a fractional increase in type I fibre area emulated expected changes; the former was required to simulate slowing of the twitch measured experimentally. Slower Ca2+ removal more than compensated for force loss arising from a large reduction in Ca2+ sensitivity or moderate reduction in Ca2+ release, producing realistic age-related shifts in the force-frequency relationship. Consistent with empirical data, reductions in free Ca2+ concentration and Ca2+ sensitivity reduced maximum tetanic force only slightly, even when acting in concert, suggesting a modest contribution to lower specific force. Lower tendon stiffness and slower intrinsic shortening speed slowed and prolonged force development in a compliance-dependent manner without affecting force decay. This work demonstrates the advantages of muscle modelling for exploring sources of variation and identifying mechanisms underpinning the altered contractile properties of aged muscle.


Assessing environmental risk of pharmaceuticals in Portugal: An approach for the selection of the Portuguese monitoring stations in line with Directive 2013/39/EU.
In line with the Directive 2013/39/EU the most representative surface waters, regarding pharmaceuticals contamination, were selected based on a Portuguese nationwide monitoring exercise. To meet this purpose, and given that wastewater treatment plants (WWTPs) are regarded as the major point sources of pharmaceuticals environmental contamination, the occurrence, fate and environmental risk assessment (ERA) of eleven of the most consumed pharmaceuticals, belonging to several therapeutic classes were assessed in 15 WWTPs (influents (WWIs) and effluents (WWEs)), from five different regions during one year (4 sampling campaigns). Results showed that all samples were contaminated with at least 1, and up to 8 from the 11 targeted pharmaceuticals. The highest concentrations observed were 150 and 33 μg L(-1) for WWI and WWE, respectively. Regarding temporal and spacial influence, winter, Alentejo, Algarve and Center regions presented higher mass loads. The ERA posed by 7 of the selected pharmaceuticals presented a risk quotient higher than 1 to the three trophic levels. Our findings highlighted that the rivers Mondego, Tagus, Ave, Trancão, Fervença and Xarrama should be selected as surface water monitoring stations. This study gives a good overview on pharmaceuticals contamination in WWTPs and its impact on surface waters in Portugal. Thus, a more integrative approach to rank and prioritize pharmaceuticals, based on an integrated assessment of ERA and exposure of surface water, was provided to support the future selection of the 6 most representative monitoring stations in Portugal, as required by the above mentioned directive.


Postnatal development of pituitary-thyroid function in male and female rats: comparison of plasma and thyroid T3 and T4 concentration.
Plasma T4, T3, and TSH, and total and 131l-labeled T4 and T3 in thyroid digests were determined in male and female rats from birth to 30--45 days postnatally. Mothers and offspring were fed a high-iodine Purina diet throughout. In both sexes, plasma T4 was less than 1 microgram/100ml at birth but rose linearly to a peak of 6--7 micrograms/100 ml at day 15. Plasma T3 remained low at 30--40 ng/100 ml until day 10, then rose steeply to 80--100 ng/100 ml at day 20--30. Plasma TSH had a bimodal distribution with an early peak in the intial 1--2 weeks of life and a second rise after day 30. Adult pattern sex differences in plasma TSH appeared by day 30. Labeled T3 was undetectable in thyroid digests until after day 7. Both labeled and stable T3 and T4 concentration and T3/T4 ratios rose progressively during the first 2 weeks of life. After day 7, stable and labeled intrathyroidal T3/T4 ratios were significantly correlated, but the latter was always higher than the former for any given age.


Interfacial Coupling SnSe2 /SnSe Heterostructures as Long Cyclic Anodes of Lithium-Ion Battery.
Tin selenide (SnSe2 ) is considered a promising anode of the lithium-ion battery because of its tunable interlayer space, abundant active sites, and high theoretical capacity. However, the low electronic conductivity and large volume variation during the charging/discharging processes inevitably result in inadequate specific capacity and inferior cyclic stability. Herein, a high-throughput wet chemical method to synthesize SnSe2 /SnSe heterostructures is designed and used as anodes of lithium-ion batteries. The hierarchical nanoflower morphology of such heterostructures buffers the volume expansion, while the built-in electric field and metallic feature increase the charge transport capability. As expected, the superb specific capacity (≈911.4 mAh g-1 at 0.1 A g-1 ), high-rate performance, and outstanding cyclic stability are obtained in the lithium-ion batteries composed of SnSe2 /SnSe anodes. More intriguingly, a reversible specific capacity (≈374.7 mAh g-1 at 2.5 A g-1 ) is maintained after 1000 cycles. The internal lithium storage mechanism is clarified by density functional theory (DFT) calculations and in situ characterizations. This work hereby provides a new paradigm for enhancing lithium-ion battery performances by constructing heterostructures.


Increases in symptoms associated with obsessive-compulsive disorder among university students during the COVID-19 pandemic.
The long-term consequences of the COVID-19 pandemic on college students' mental health remains unknown. The current study explored self-reported Obsessive-Compulsive symptomatology among college student cohorts from pre-, peak-, and later-pandemic time points. Undergraduate college students (N = 524) who volunteered for course credit. Self-report responses on the Dimensional Obsessive-Compulsive Scale (DOCS), which includes subscales for contamination, unacceptable thoughts, harm responsibility, and symmetry, were collected from November 29, 2016 through April 27, 2021 and assessed for differences between the pre-, peak-, and later-pandemic cohorts. Peak-pandemic responders reported higher symptomatology for contamination and unacceptable thoughts compared to pre-pandemic responders (and for pre- vs. later-pandemic for contamination), with no significant effects for symmetry or harm responsibility. Although the longer-term consequences of the COVID-19 pandemic on students remains unknown, a greater shift in college mental health services from prevention to assessing and addressing more immediate challenges may be necessary.


Development and validation of prediction models for neurocognitive disorders in adult patients admitted to the ICU with sleep disturbance.
Neurocognitive disorders (NCDs) and sleep disturbance are highly prevalent in the perioperative period and intensive care unit (ICU). There has been a lack of individualized evaluation tools designed for the high-risk NCDs in critically ill patients with sleep disturbance. The aim of this study was to develop and validate prediction models for NCDs among adult patients with sleep disturbance. The R software was used to analyze the dataset of adult patients admitted to the ICU with sleep disturbance, who were diagnosed following the codes of the International Classification of Diseases, 9th Revision (ICD-9) and 10th Revision (ICD-10) using the MIMIC-IV database. We used logistic regression and LASSO analyses to identify important risk factors associated with NCDs and develop nomograms for NCDs predictions. We measured the performances of the nomograms using the bootstrap resampling procedure, sensitivity, specificity of the receiver operating characteristic (ROC), area under the ROC curves (AUC), and decision curve analysis (DCA). The prediction models shared the 10 risk factors (age, gender, midazolam, morphine, glucose, diabetes diseases, potassium, international normalized ratio, partial thromboplastin time, and respiratory rate). Cardiovascular diseases were included in the logistic regression, the sensitivity was 74.1%, and specificity was 64.6%. When platelet and Glasgow Coma Score (GCS) were included and cardiovascular diseases were removed in the LASSO prediction model, the sensitivity was 86.1% and specificity was 82.8%. Discriminative abilities of the logistic prediction and LASSO prediction models for NCDs in the validation set were evaluated as the AUC scores, which were 0.730 (95% CI 0.716-0.743) and 0.920 (95% CI 0.912-0.927). Net benefits of the prediction models were observed at threshold probabilities of 0.567 and 0.914. The LASSO prediction model showed better performance than the logistic prediction model and should be preferred for nomogram-assisted decisions on clinical risk management of NCDs among adult patients with sleep disturbance in the ICU.


Insight into the treatment of vulvar pain: a survey of clinicians.
The purpose of this investigation was to determine practice patterns among clinicians who frequently treat patients with vulvar pain syndromes. A cross-sectional survey was distributed to providers in the United States whose names were on a referral list of clinicians that care for women with vulvar pain (National Vulvodynia Association, Silver Springs, MD). The survey included 2 clinical vignettes. Clinicians were asked to report what treatments they would use to treat women with generalized vulvodynia and localized vulvodynia. Data were analyzed with descriptive statistics. A comparison of categoric data was accomplished with the Fisher's exact test. Surveys were mailed to 327 providers; 167 completed surveys were returned, for an overall response rate of 51%. The most commonly used treatment for vulvodynia was tricyclic antidepressants. There was no difference in the use of physical therapy, estrogens, injected or topical steroids, interferon, or laser therapy to treat generalized and localized vulvodynia. Respondents were more likely to use tricyclic antidepressants (P < .001), gabapentin (P < .001), and psychiatric care (P < .001) and less likely to use local anesthesia (P < .001) and vestibulectomy (P = .007) for the clinical scenario that represented generalized vulvodynia than they were for the scenario that represented localized vulvodynia. Most clinicians reported screening for vaginal infections, and many clinicians perform colposcopy and/or vulvar biopsy. Respondents recommend a variety of lifestyle modifications in the treatment of vulvodynia. Clinicians use a wide variety of treatments for vulvar pain and use different therapies for variants of vulvodynia.


A broader view of trauma: a biopsychosocial-evolutionary view of the role of the traumatic stress response in the emergence of pathology and/or growth.
The main goal of this paper is to articulate a biopsychosocial evolutionary approach to understanding the traumatic stress response. The secondary goal of this paper is to draw out the general clinical implications of this approach. I articulate seven interconnected and overlapping empirically grounded theoretical conclusions: (1) Stress is best understood as a prerational form of biopsychological feedback regarding the organism's relationship with its environment; (2) The normal outcome of traumatic stress is growth, rather than pathology; (3) Most psychopathology is a function of the maladaptive modulation of the stress response; (4) Trauma always leaves the individual transformed on a biological, as well as psychological, level; (5) The general biological process underlying stress responses is universal, but the specific dynamics are always a function of the unique sociocultural environment and psychological makeup of the individual; (6) The biology underlying stable psychopathological symptoms may change even as the psychological symptoms remain the same; and (7) Rationality is humanity's evolutionarily newest and most sophisticated stress-reduction behavioral mechanism, and the most important aspect of restoring psychological health to the trauma victim.


Artificial neural networks in chest radiography: application to the differential diagnosis of interstitial lung disease.
The authors evaluated the usefulness of artificial neural networks (ANNs) in the differential diagnosis of interstitial lung disease. The authors used three-layer, feed-forward ANNs with a back-propagation algorithm. The ANNs were designed to distinguish between 11 interstitial lung diseases on the basis of 10 clinical parameters and 16 radiologic findings extracted by chest radiologists. Thus, the ANNs consisted of 26 input units and 11 output units. One hundred fifty actual clinical cases, 110 cases from previously published articles, and 110 hypothetical cases were used for training and testing the ANNs by using a round-robin (or leave-one-out) technique. ANN performance was evaluated with receiver operating characteristic (ROC) analysis. The Az (area under the ROC curve) obtained with actual clinical cases was 0.947, and both the sensitivity and specificity of the ANNs were approximately 90% in terms of indicating the correct diagnosis with the two largest output values among the 11 diseases. ANNs using clinical parameters and radiologic findings may be useful for making the differential diagnosis of interstitial lung disease on chest radiographs.


[Generic drugs: quality, efficacy, safety and interchangeability].
Since the introduction of generic drugs to the pharmaceutical market a sometimes emotional debate exists whether they are well-investigated and of high quality. There is some uncertainty about whether evidence of bioequivalence is enough to guarantee efficacy and safety of generic drugs. Some physicians ask the question if competent authorities are able to ascertain that the pharmaceutical quality of generics is acceptable. Doctors and patients sometimes are ill at ease about the interchangeability of innovator and generic products. This article describes how the European Union legislation ensures that a generic drug is only approved if its risk-benefit relationship is favourable and that it is essentially similar to the innovator product. In this context pharmacokinetic parameters are accepted as surrogates for clinical results because bioequivalence means therapeutic equivalence as well. For most drugs, current bioequivalence testing generally enables clinicians to routinely substitute generic for innovator products. Published findings, however, suggest that particular drugs may not be ideally suited for generic substitution when a patient is already on that drug. These are the so called critical dose medicinal products (drugs with a narrow therapeutic range). When starting a new therapy with any generic drug, however, its similarity to the innovator drug in terms of efficacy, safety and quality is guaranteed.


Recurrence risk of a hypotonic hyporesponsive episode in two Australian specialist immunisation clinics.
A hypotonic hyporesponsive episode (HHE) is a well-described adverse event following immunisation (AEFI) in young children. There is limited data regarding recurrence post re-vaccination. A retrospective analysis of HHEs reported to two tertiary paediatric hospitals in Australia: The Royal Children's Hospital, Melbourne [2006-11] and the Children's Hospital Westmead, Sydney [1997-2014]. HHE definition level of confidence was allocated according to Brighton Collaboration (BC) criteria and defined immediate if within 30 min post vaccination. The Australian Immunisation Register (AIR) was utilised to document current immunisation status. 235 HHE cases (135 Melbourne, 100 Sydney) were identified: 47% were female and 67% (157/235) occurred following the routine dose one vaccines at 6-8 weeks of age. Median time following immunisation was 120 min (range 1 min to 14 days) An immediate HHE occurred in 43% (102/235) and by BC criteria, 74% (173/235) were level 1 (definite). Subsequent vaccines were administered under supervision in hospital in 37% overall (86/235); 43% (58/135) in Melbourne and 28% (28/100) in Sydney. HHE recurrence rate was 3% (7/235) [95% confidence interval 1-6%]. AIR records were available in 94% (221/235). At a median age of 3.1 years, 84% (186/221) were up-to-date with recommended vaccines. This study highlights the importance of specialist immunization clinics in supporting the National Immunisation Program, through follow-up and management of serious adverse events following immunization.


Macrophage inflammatory protein-related protein-2, a novel CC chemokine, can regulate preadipocyte migration and adipocyte differentiation.
Adipocytes not only store energy, but also secrete biologically active molecules called adipocytokines, which play a pivotal role in adipocyte-related pathological processes such as diabetes and cardiovascular disease. Recent studies have shown that preadipocyte/adipocyte expresses chemokines (e.g. monocyte chemoattractant protein-1, macrophage inflammatory protein-1 alpha) which alter adipocyte function, indicating the involvement of chemokines in adipocyte-related pathologies. The current study investigated the potential of macrophage inflammatory protein-related protein-2 (MRP-2), a novel CC chemokine, to modulate preadipocyte trafficking and adipocyte differentiation. MRP-2 and its receptors were highly expressed in preadipocytes and differentiated adipocytes as well as in the mouse fat pad. Chemotaxis assays revealed that MRP-2 was a specific chemotactic regulator in preadipocyte migration. The levels of MRP-2 expression in adipose tissue were enhanced in obese mice compared to lean mice. MRP-2 secretion by preadipocytes was suppressed during differentiation. MRP-2 suppressed the expression of adipocyte differentiation markers such as adipocyte fatty acid-binding protein and glycerol-3 phosphate dehydrogenase. Taken together, our data suggest that MRP-2 plays a role in the regulation of preadipocyte migration and adipocyte differentiation during adipose tissue development. MRP-2 may be another adipocytokine, which can be involved in the adipocyte-related pathological process.


Randomised trial of endoscopy with testing for Helicobacter pylori compared with non-invasive H pylori testing alone in the management of dyspepsia.
To compare the efficacy of non-invasive testing for Helicobacter pylori with that of endoscopy (plus H pylori testing) in the management of patients referred for endoscopic investigation of upper gastrointestinal symptoms. Randomised controlled trial with follow up at 12 months. Hospital gastroenterology unit. 708 patients aged under 55 referred for endoscopic investigation of dyspepsia, randomised to non-invasive breath test for H pylori or endoscopy plus H pylori testing. Glasgow dyspepsia severity score at one year. Use of medical resources, patient oriented outcomes, and safety were also assessed. In 586 patients followed up at 12 months the mean change in dyspepsia score was 4.8 in the non-invasive H pylori test group and 4.6 in the endoscopy group (95% confidence interval for difference -0.7 to 0.5, P=0.69). Only 8.2% of patients followed up who were randomised to breath test alone were referred for subsequent endoscopy. The use of non-endoscopic resources was similar in the two groups. Reassurance value, concern about missed pathology, overall patient satisfaction, and quality of life were similar in the two groups. The patients found the non-invasive breath test procedure less uncomfortable and distressing than endoscopy with or without sedation. No potentially serious pathology requiring treatment other than eradication of H pylori was missed. In this patient group, non-invasive testing for H pylori is as effective and safe as endoscopy and less uncomfortable and distressing for the patient. Non-invasive H pylori testing should be the preferred mode of investigation.


The distribution of olfactory input in the opossum mediodorsal nucleus.
Discharges of single cells in the thalamic mediodorsal nucleus (MD) of the opossum were recorded during electrical stimulation of the lateral olfactory tract. Responsive sites were histologically localized throughout the entire mediolateral extent of MD. In both rabbit and squirrel monkey responses are confined to the medial half of MD. Thus the lateral non-olfactory nuclear subdivision, common to both rabbit and squirrel monkey, was not found in the opossum. Firing patterns of cells were similar to those observed in rabbit and squirrel monkey. They commonly consisted of an early spike or burst of spikes, followed by a period of inactivity and then, in many cells, by a later period of response or of resumed spontaneous activity. The results indicate that olfactory input is characteristic of MD in a diverse sample of mammals but that topographic organization of the input is distinctly different in the opossum.


Serum phospholipase A in hospitalized patients.
Threehundred and thirty sera from hospitalized patients were analyzed for phospholipase A (PLA) activity. About 30% of unselected patients showed values above the normal range (0 to 10 U/l). The ratio of pathological to normal results was even higher in intensive care patients (around 1:1) and in patients with severe infections (2:1). 'Hyperphospholipasemia' was not typical for any defined organ system. From an etiological viewpoint, infectious diseases were most often related to increased PLA, followed by myocardial infarction and insufficiency and by malignant diseases. It is suggested that phospholipase A is a marker enzyme for the phagocytic activity in inflammation and necrosis.


A Comparison of Diets Supplemented with a Feed Additive Containing Organic Acids, Cinnamaldehyde and a Permeabilizing Complex, or Zinc Oxide, on Post-Weaning Diarrhoea, Selected Bacterial Populations, Blood Measures and Performance in Weaned Pigs Experimentally Infected with Enterotoxigenic E. coli.
The effects of feeding a diet supplemented with zinc oxide (ZnO) or a blend of organic acids, cinnamaldehyde and a permeabilizing complex (OACP) on post-weaning diarrhoea (PWD) and performance in pigs infected with enterotoxigenic E. coli (ETEC) were examined. Additionally, changes in selected bacterial populations and blood measures were assessed. A total of 72 pigs weaned at 22 d of age and weighing 7.2 ± 1.02 kg (mean ± SEM) was used. Treatments were: base diet (no antimicrobial compounds); base diet + 3 g ZnO/kg; base diet + 1.5 g OACP/kg. Dietary treatments started on the day of weaning and were fed ad libitum for 3 weeks. All pigs were infected with an F4 ETEC on d 4, 5 and 6 after weaning. The incidence of PWD was lower in pigs fed ZnO ( p = 0.026). Overall, pigs fed ZnO grew faster ( p = 0.013) and ate more ( p = 0.004) than the base diet-fed pigs, with OACP-fed pigs performing the same ( p > 0.05) as both the ZnO- and base diet-fed pigs. Feed conversion ratio was similar for all diets ( p > 0.05). The percentage of E. coli with F4 fimbriae was affected a day by treatment interaction ( p = 0.037), with more E. coli with F4 fimbriae found in pigs fed ZnO on d 11 ( p = 0.011) compared to base diet-fed pigs. Only significant time effects ( p < 0.05) occurred for blood measures. Under the conditions of this study, inclusion of OACP gave statistically similar production responses to pigs fed ZnO, however pigs fed ZnO had less PWD compared to OACP- and the base diet-fed pigs.


The effect of preoperative 18f Fdg-Pet on staging and treatment protocols in breast cancer patients.
We aimed to evaluate the effect of PET taken before surgery on the treatment protocol in patients diagnosed with BC and whether PET resulted in changes in the disease stage. BC patients in our hospital who underwent surgery between 2016-2020 were retrospectively analyzed. The effect of preoperative PET on the treatment protocol was evaluated in all. Patients were divided into subgroups depending on whether they underwent direct surgery without CTX or were operated on after CTX initiation. In addition, in the group that did not receive CTX, axillary findings of PET were compared with postoperative histopathological results, and axillary PPV, NPV, sensitivity and specificity of PET were determined. In this subgroup, the preoperative PET stage was compared with the postoperative histopathological stage, and any changes in the disease stage were compared. In our study, PET affected the treatment protocol of 19 patients (20%). PET resulted in staging differences in 57.6% overall, increased staging in four patients (8.8%) who did not receive early-stage CT, and lower staging in 22 (48.8%) patients in the group. In early-stage BC of PET, the PPV for axilla was 81.2%, the NPV was 65.5%, sensitivity was 56.5%, and specificity was 86.3%. Although PET has many limitations, the determination of the size of the primary tumor and the multiple foci at different locations according to PET findings helped us to easily determine the treatment protocol for patients planned for BCS. The preoperative routine use of PET, which can provide more information about metastasis and stage than other methods in patients undergoing BC surgery, may improve the management of treatment in these patients. Breast cancer, 18F FDG-PET/CT, Chemotherapy, Staging.


Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic-ischemic white matter damage.
White matter damage (WMD) is the main cause of cerebral palsy and cognitive impairment in premature infants. Although caffeine has been shown to possess neuroprotective effects in neonatal rats with hypoxic-ischemic WMD, the mechanisms underlying these protective effects are unclear. Herein, proteins modulated by caffeine in neonatal rats with hypoxic-ischemic WMD were evaluated. We identified differential proteins and performed functional enrichment analyses between the Sham, hypoxic-ischemic WMD (HI), and HI+caffeine-treated WMD (Caffeine) groups. Confirmed the changes and effect of proteins in animal models and determined cognitive impairment via water maze experiments. In paraventricular tissue, 47 differential proteins were identified between the Sham, HI, and Caffeine groups. Functional enrichment analyses showed that these proteins were related to myelination and axon formation. In particular, the myelin basic protein (MBP), proteolipid protein, myelin-associated glycoprotein precursor, and sirtiun 2 (SIRT2) levels were reduced in the hypoxic-ischemic WMD group, and this effect could be prevented by caffeine. Caffeine alleviated the hypoxic-ischemic WMD-induced cognitive impairment and improved MBP, synaptophysin, and postsynaptic density protein 95 protein levels after hypoxic-ischemic WMD by preventing the HI-induced downregulation of SIRT2; these effects were subsequently attenuated by the SIRT2 inhibitor AK-7. Caffeine may have clinical applications in the management of prophylactic hypoxic-ischemic WMD; its effects may be mediated by proteins related to myelin development and synapse formation through SIRT2.


Alkanols inhibit voltage-gated K(+) channels via a distinct gating modifying mechanism that prevents gate opening.
Alkanols are small aliphatic compounds that inhibit voltage-gated K(+) (K(v)) channels through a yet unresolved gating mechanism. K(v) channels detect changes in the membrane potential with their voltage-sensing domains (VSDs) that reorient and generate a transient gating current. Both 1-Butanol (1-BuOH) and 1-Hexanol (1-HeOH) inhibited the ionic currents of the Shaker K(v) channel in a concentration dependent manner with an IC50 value of approximately 50 mM and 3 mM, respectively. Using the non-conducting Shaker-W434F mutant, we found that both alkanols immobilized approximately 10% of the gating charge and accelerated the deactivating gating currents simultaneously with ionic current inhibition. Thus, alkanols prevent the final VSD movement(s) that is associated with channel gate opening. Applying 1-BuOH and 1-HeOH to the Shaker-P475A mutant, in which the final gating transition is isolated from earlier VSD movements, strengthened that neither alkanol affected the early VSD movements. Drug competition experiments showed that alkanols do not share the binding site of 4-aminopyridine, a drug that exerts a similar effect at the gating current level. Thus, alkanols inhibit Shaker-type K(v) channels via a unique gating modifying mechanism that stabilizes the channel in its non-conducting activated state.


Adhesion prevention by solutions of sodium carboxymethylcellulose in the rat. I.
Solutions of sodium carboxymethylcellulose (SCMC) were studied in rats to determine their longevity within the peritoneal cavity and their potential for prevention of postoperative intraperitoneal adhesions. In 18 rats, test solutions of SCMC and 10% dextran 40 were instilled at laparotomy. At 48 hours copious amounts of SCMC remained, whereas no 10% dextran 40 could be detected. In addition, standardized surgical injury was produced on the ceca of 100 rats at laparotomy. All control animals had significant adhesions at 2 weeks. Eighty-two percent of the 10% dextran 40 group had significant adhesions, while only 16% of the 0.9 wt% SCMC and 17% of the 1.0 wt% SCMC groups had significant adhesions. Solutions of SCMC were significantly more effective than 10% dextran 40 in the prevention of adhesions (P less than 0.001). Properties of SCMC and a possible mechanism for its striking effectiveness in adhesion prevention in this study are discussed.


The French way of voice rehabilitation post total laryngectomy: current clinical practices and tendencies.
Vocal rehabilitation post total laryngectomy (TL) lacks clinical guidelines, especially with the presence of multiple modalities. To describe the tendencies of vocal rehabilitation post TL in France and compare it with other countries. We try to identify the most practiced modalities and recognize statistically significant influencing factors. An electronic anonymous survey was answered by 75 ENT surgeons from France. The survey outlined the common practiced vocal rehabilitation modalities and had two versions depending on if the participant practices the tracheoesophageal speech (TES) or not. 96% use TES in their practice. Single modality TES and double modality TES with esophageal speech (ES) are the two most practiced modalities. 99% agreed that there is no age limit for the TES. Single modality ES was offered 92% more when more than 10 TL were performed per year (p < .05). No influencing factors found for single modality TES or double modality TES with ES (p > .05).Conclusion: In line with tendencies from other countries, the TES is the most practiced modality of vocal rehabilitation coupled or not with the ES. TES has no age limit as per our participants. The least practiced modality is the singe modality ALS.


The role of target muscles in the expression of calcitonin gene-related peptide mRNA in the spinal nucleus of the bulbocavernosus.
Previous studies have shown that calcitonin gene-related peptide (CGRP) mRNA steady-state levels and CGRP immunoreactivity in motoneurons of the spinal nucleus of the bulbocavernosus (SNB) are inversely related to the gonadal steroid environment in male rats. Since both the SNB motoneurons and their target muscles, the bulbocavernosus and the levator ani, are steroid sensitive, gonadal steroids may act at either site to regulate CGRP expression. In the present study, we tested the hypothesis that gonadal steroids influence CGRP expression in SNB motoneurons through their effects on the bulbocavernosus and levator ani muscles. We determined the levels of alpha-CGRP mRNA and immunoreactive CGRP in SNB motoneurons of adult male rats following injection of the bulbocavernosus with muscle extracts from bulbocavernosus/levator ani of castrated rats, paralysis of the bulbocavernosus or pudendal nerve cuts. Following injection of the bulbocavernosus/levator ani with extracts from castrated rats, the level of CGRP expression and the number of SNB motoneurons with alpha-CGRP message were increased. These studies suggest that the bulbocavernosus/levator ani muscles from castrated rats produce a factor that increases levels of CGRP. Injections of extract prepared from the bulbocavernosus and levator ani muscles of gonadally intact rats did not change the expression of alpha-CGRP mRNA in the SNB. Paralysis of the bulbocavernosus/levator ani with a local anesthetic increased the number of SNB motoneurons expressing alpha-CGRP mRNA and CGRP immunoreactive neurons. To determine whether nerve damage accounted for the observed effects following injection of anesthetic, the pudendal nerves were cut bilaterally.(ABSTRACT TRUNCATED AT 250 WORDS)


Confirmatory factor analysis of the Questionnaire on the Health Staff's Perceptions Regarding Doutores da Alegria's Interventions.
A confirmatory analysis was performed to validate the Questionnaire on the Health Staff's Perceptions Regarding Doutores da Alegria's Intervention, a 40-item instrument designed to assess pediatric staff's perceptions regarding the effects of Doutores da Alegria, a Brazilian hospital clowning professional organization. Eight dimensions were evaluated: the permanence of Doutores da Alegria's interventions; Doutores da Alegria's intrapersonal and interpersonal effects on their relation to health staff; themselves; staff-children; and staff-family relationships; as well as their effect on staff's cultural development; children's relation to their own disease; and families' attitude regarding their child's condition. In all, 567 health professionals from 13 Brazilian hospitals participated. The instrument's good psychometric features are acknowledged.