Potential therapeutic approaches for the treatment of vaso-occlusion in sickle cell disease.
Vaso-occlusion is the major cause of morbidity and mortality in sickle cell disease. The pathogenesis of vaso-occlusion likely involves many complex steps related to both the primary event of deoxyhemoglobin S polymerization and the many resultant pathologic changes in both the sickle erythrocyte and the vascular endothelium. Several therapeutic approaches have been designed to reduce the extent of deoxyhemoglobin S polymerization. Although direct chemical inhibition of deoxyhemoglobin S polymerization has proven difficult, strategies to increase levels of fetal hemoglobin or reverse sickle erythrocyte dehydration have been more successful. Although gene therapy is actively being pursued, the ability to cure sickle cell disease is currently limited to bone marrow transplantation with its attendant toxicities and limitations. Because the pathophysiology of vaso-occlusion in sickle cell disease is complex, its treatment will likely be optimized using a multifactorial therapeutic approach.


Inhibition of capsular protein synthesis of Pasteurella multocida strain P-1059.
A mutant strain, PBA322, was constructed by electroporation of a phagemid containing the coding region of antisense RNA of the ompH gene, encoding 39 kDa capsular protein or OmpH, into the parental strain P-1059 (serovar A:3) of Pasteurella multocida, and the pathogenicity was determined in mice and chickens. Grayish colonies of the mutant, indicating loss of capsule synthesis, were observed under a stereomicroscope using obliquely transmitted light, while iridescent colonies were observed for the parental strain. Moreover, strain PBA322 showed a low amount of OmpH compared with the parental strain on SDS-PAGE. Additionally, the capsule of strain PBA322 was thinner than that of the parental strain according to electron microscopy, correlating to the attenuation against chickens. In conclusion, strain PBA322, the mutant of P. multocida strain P-1059, was completely attenuated for chickens.


RETINOCHOROIDAL ANASTOMOSIS ASSOCIATED WITH ENHANCED S-CONE SYNDROME.
To describe the phenotype and genotype of a 10-year-old boy affected with enhanced S-cone syndrome associated with neovascularization. Fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral domain optical coherence tomography, full-field electroretinogram and NR2E3 molecular testing were performed. Best-corrected visual acuity was measured as 20/32, right eye and 20/20, left eye. Fluorescein and indocyanine green angiographies showed unilateral macular retinochoroidal anastomosis on his right eye, and spectral domain optical coherence tomography showed typical signs of subretinal exudation and foveolar pseudoschisis consistent with the diagnosis of enhanced S-cone syndrome. Genetic analysis revealed biparental transmission of mutations in the enhanced S-cone syndrome-causing gene, NR2E3, namely, c.194_202del (p.Asn65_Cys67del), and c.932 G>A (p.Arg311Gln), supporting an autosomal recessive inheritance. The patient received three intravitreal injections of anti-VEGF agents. Evidence of retinochoroidal anastomosis in an individual affected with enhanced S-cone syndrome supports the view that neovascularization can occur early in the course of the disease, and raises the question to know whether it might be responsible for previously described enhanced S-cone syndrome-associated hemorrhage-induced fibrosis.


Estimated indirect costs of haemodialysis versus peritoneal dialysis from a patients' perspective at an Academic Hospital in Pretoria, South Africa.
In South Africa (SA), patients with kidney failure can be on either haemodialysis (HD), which is performed by a healthcare professional in a hospital thrice weekly; or peritoneal dialysis (PD), which can performed daily at home. There needs to be more studies within the South African healthcare sector on the cost of kidney failure and especially the indirect costs associated with patients being on dialysis to provide future guidance. This study aimed to determine and compare the indirect costs associated with HD and PD from the patients' perspective at an Academic Hospital in Pretoria. The study used a cross-sectional prospective quantitative study design. The researcher used face-to-face interviews to collect data and the human capital approach to calculate productivity losses. The study population included all patients over 18 receiving HD or PD for over three months; 54 patients participated (28 on HD and 26 on PD). The study lasted seven months, from September 2020 to March 2021. Haemodialysis patients incurred greater productivity losses per annum ($8127.55) compared to PD (R$3365.34); the difference was statistically significant with a P-value of p < 0.001. More HD (96.4%) patients were unemployed than (76.9%) PD patients.


Determinants of exclusive direct breastfeeding using constructs from the breastfeeding relationship scale.
This study examined the relationship among constructs of the Breastfeeding Relationship Scale and exclusive direct breastfeeding (EDBF) while controlling for covariates in US breastfeeding dyads in the first 3 months. The Breastfeeding Relationship Scale was developed to measure mother-infant mutual responsiveness during breastfeeding in response to perceived insufficient milk, but there is no clear understanding about the relationships between the Breastfeeding Relationship Scale's constructs and EDBF. A cross-sectional design was used. The convenience sample of 589 directly breastfeeding mothers in the US whose infants were between 1 and 12 weeks of age were included for analysis using a structural equation model. Covariates for EDBF included mother's age, education, marital status, parity, prior breastfeeding experience, infant's age, weight, and sex. Mother-Infant Breastfeeding Interaction and Breastfeeding Synchronicity were related (β = 0.33, p < .001), as were Breastfeeding Synchronicity and Perceived Adequate Milk Supply (β = 0.35, p < .001) and Mother-Infant Breastfeeding Interaction and Perceived Adequate Milk Supply (β = 0.08, p = .05). The relationship between Mother-Infant Breastfeeding Interaction and Breastfeeding Synchronicity with EDBF was fully mediated by Perceived Adequate Milk Supply, where the odds of EDBF was higher for mothers with higher scores on Perceived Adequate Milk Supply (OR = 1.61, p < .001) and prior breastfeeding experience (OR = 2.31, p = .006). Perceived Adequate Milk Supply and prior breastfeeding experience are major determinants of EDBF in the first 3 months. Breastfeeding Synchronicity can bolster Mother-Infant Breastfeeding Interaction and promote Perceived Adequate Milk. More attention should be paid to breastfeeding relationship to be the result of EDBF.


Wnt proteins contribute to neuromuscular junction formation through distinct signaling pathways.
Understanding the developmental steps that shape formation of the neuromuscular junction (NMJ) connecting motoneurons to skeletal muscle fibers is crucial. Wnt morphogens are key players in the formation of this specialized peripheral synapse, but their individual and collaborative functions and downstream pathways remain poorly understood at the NMJ. Here, we demonstrate through Wnt4 and Wnt11 gain-of-function studies in cell culture or in mice that Wnts enhance acetylcholine receptor (AChR) clustering and motor axon outgrowth. By contrast, loss of Wnt11 or Wnt-dependent signaling in vivo decreases AChR clustering and motor nerve terminal branching. Both Wnt4 and Wnt11 stimulate AChR mRNA levels and AChR clustering downstream of activation of the β-catenin pathway. Strikingly, Wnt4 and Wnt11 co-immunoprecipitate with Vangl2, a core component of the planar cell polarity (PCP) pathway, which accumulates at embryonic NMJs. Moreover, mice bearing a Vangl2 loss-of-function mutation (loop-tail) exhibit fewer AChR clusters and overgrowth of motor axons bypassing AChR clusters. Together, our results provide genetic and biochemical evidence that Wnt4 and Wnt11 cooperatively contribute to mammalian NMJ formation through activation of both the canonical and Vangl2-dependent core PCP pathways.


Management of postgastric bypass noninsulinoma pancreatogenous hypoglycemia.
Postgastric bypass noninsulinoma hyperinsulinemic pancreatogenous hypoglycemia defines a group of patients with postprandial neuroglycopenic symptoms similar to insulinoma but in many cases more severe. There are few reports of patients with this condition. We describe our surgical experience for the management of this rare condition. A retrospective study was performed at St. Vincent Hospital, Indianapolis. Fifteen patients were identified with symptomatic postgastric bypass hypoglycemia for the period 2004-2008. All patients were initially treated with medical therapy for hypoglycemia. Nine patients eventually underwent surgical treatment. The preoperative workup included triple-phase contrast CT scan of the abdomen, endoscopic ultrasound of the pancreas, a 72-h fast followed by a mixed meal test, and calcium-stimulated selective arteriography. Intraoperative pancreatic ultrasound also was performed in all patients. Patients then underwent thorough abdominal exploration, exploration of the entire pancreas, and extended distal pancreatectomy. Nine patients underwent surgery. The mean duration of symptoms was 14 months. The 72-h fast was negative in eight patients (as expected). Triple-phase contrast CT scan of the abdomen was negative in eight patients and showed a cyst in the head of pancreas in one patient. Extended distal (80%) pancreatectomy was performed in all nine patients. The procedure was attempted laparoscopically in eight patients but was converted to open in three. One patient had an open procedure from start to finish. Pathology showed changes compatible with nesidioblastosis with varying degrees of hyperplasia of islets and islet cells. Follow-up ranged from 8-54 (median, 22) months. All patients initially reported marked relief of symptoms. Over time, two patients had complete resolution of symptoms; three patients developed occasional symptoms (once or twice per month), which did not require any medication; two patients developed more frequent symptoms (more than twice per month), which were controlled with medications; and two patients had severe symptoms refractory to medical therapy (calcium channel blockers, diazoxide, octreotide). Postprandial hypoglycemia after gastric bypass surgery with endogenous hyperinsulinemia is being increasingly recognized and reported in the literature. Our experience with nine patients is one of the largest. The etiology of this condition is not entirely understood. There may be yet unknown factors involved but increased secretion of glucagon-like peptide 1 and decreased grehlin are being implicated in islet cell hypertrophy. There is no "gold standard" treatment-medical or surgical-but distal pancreatectomy to debulk the hypertrophic islets and islet cells is the main surgical modality in patients with severe symptoms refractory to medical management.


Altered Brain Functional Network Topology in Lung Cancer Patients After Chemotherapy.
Purpose: This study aimed to explore the topological features of brain functional network in lung cancer patients before and after chemotherapy using graph theory. Methods: Resting-state functional magnetic resonance imaging scans were obtained from 44 post-chemotherapy and 46 non-chemotherapy patients as well as 49 healthy controls (HCs). All groups were age- and gender-matched. Then, the topological features of brain functional network were assessed using graph theory analysis. Results: At the global level, compared with the HCs, both the non-chemotherapy group and the post-chemotherapy group showed significantly increased values in sigma (p < 0.05), gamma (p < 0.05), and local efficiency, E loc (p < 0.05). The post-chemotherapy group and the non-chemotherapy group did not differ significantly in the above-mentioned parameters. At the nodal level, when non-chemotherapy or post-chemotherapy patients were compared with the HCs, abnormal nodal centralities were mainly observed in widespread brain regions. However, when the post-chemotherapy group was compared with the non-chemotherapy group, significantly decreased nodal centralities were observed primarily in the prefrontal-subcortical regions. Conclusions: These results indicate that lung cancer and chemotherapy can disrupt the topological features of functional networks, and chemotherapy may cause a pattern of prefrontal-subcortical brain network abnormality. As far as we know, this is the first study to report that altered functional brain networks are related to lung cancer and chemotherapy.


Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in AIRE gene, which encodes a transcription factor essential for central immune tolerance. Classic diagnosis is determined by the presence of two of the main APECED clinical diseases: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. Non-endocrine autoimmunity, involving the liver, intestine, eyes, and kidneys, is generally reported in a minority of European patients, while American APECED patients have a higher tendency of developing organ-specific non-endocrine manifestations early in life. This observation led to the revision of the diagnostic criteria to permit earlier diagnosis based on the appearance of one classic triad symptom or one non-classical manifestation at a young age in the presence of IFNωAbs or AIRE mutations (Ferre-Lionakis criteria). We analyzed the clinical, genetic, and autoantibody (Ab) profiles in a series of 14 pediatric Italian APECED patients with gastrointestinal manifestations (seven male and seven female patients). Ten patients presented hepatitis (APECED-associated hepatitis (APAH)), while seven were affected by constipation, diarrhea, and malabsorption. Four patients had developed APAH before classic triad symptoms. Based on the age of appearance of non-endocrine manifestations including APAH and gastro-enteropathy, the Ferre-Lionakis criteria would have allowed an expedited diagnosis in 11/14 patients. Abs to tryptophan hydroxylase (TPHAb) and hepatic aromatic l-amino acid decarboxylase (AADC) were significantly associated with APECED patients of the present series. Abs to cP4501A2 were detectable in the serum of 4/8 patients with APAH, and Abs to cP4502A6 were detectable in 3/8 patients. AADC Abs tested positive in 5/7 patients, which is indicative of gastrointestinal dysfunction in APECED and TPHAb in 5/7 patients with gastrointestinal dysfunction. IFNAb was significantly associated with the syndrome. Although Ferre-Lionakis expanded criteria applied to the American cohorts of APECED patients would require validation in independent large cohorts of European patients, the results of this study emphasize the importance to evaluate the presence and the age of appearance of APAH and autoimmune enteropathy even in European cohorts for an earlier APECED diagnosis. An earlier APECED diagnosis would also allow the prevention of episodes of life-threatening hypocalcemic seizures and adrenal crisis, which are the main manifestations of undiagnosed APECED.


Recurrent Ptosis in a Case of Dubowitz Syndrome.
Dubowitz syndrome is a relatively rare genetic and developmental disorder. An eight-year-old female presented with a complaint of drooping in her left eye since birth. She had undergone ptosis surgery two years back. There was a history of delayed speech and delayed dentition. She was of moderate built appropriate to her age. There was microcephaly, sparse hair, flat bridge of the nose with a prominent rounded tip, short stature, low-set ears, and micrognathia with subsequent protrusion of upper two incisors. Based on the clinical features a diagnosis of Dubowitz syndrome with left recurrent ptosis was made. She underwent frontalis sling surgery and had a satisfactory outcome.


The role of recombination and RAD52 in mutation of chromosomal DNA transformed into yeast.
While transformation is a prominent tool for genetic analysis and genome manipulation in many organisms, transforming DNA has often been found to be unstable relative to established molecules. We determined the potential for transformation-associated mutations in a 360 kb yeast chromosome III composed primarily of unique DNA. Wild-type and rad52 Saccharomyces cerevisiae strains were transformed with either a homologous chromosome III or a diverged chromosome III from S. carlsbergensis. The host strain chromosome III had a conditional centromere allowing it to be lost on galactose medium so that recessive mutations in the transformed chromosome could be identified. Following transformation of a RAD+ strain with the homologous chromosome, there were frequent changes in the incoming chromosome, including large deletions and mutations that do not lead to detectable changes in chromosome size. Based on results with the diverged chromosome, interchromosomal recombinational interactions were the source of many of the changes. Even though rad52 exhibits elevated mitotic mutation rates, the percentage of transformed diverged chromosomes incapable of substituting for the resident chromosome was not increased in rad52 compared to the wild-type strain, indicating that the mutator phenotype does not extend to transforming chromosomal DNA. Based on these results and our previous observation that the incidence of large mutations is reduced during the cloning of mammalian DNA into a rad52 as compared to a RAD+ strain, a rad52 host is well-suited for cloning DNA segments in which gene function must be maintained.


When Research "Unravels": One Community Psychologist's Tale of Becoming a Nepantlera.
This is an autoethnography of one community psychologist's reflections on the abrupt conclusion of a project that resulted in the dismantlement of a Latinx Student Union at a public middle school in the Pacific Northwest. Gloria Anzaldúa's (Borderlands/La Frontera: The new mestiza, Aunt Lute Books, San Francisco, 2002) notion of nepantla is used to situate how an individual's personal identities often intersects with their professional identities in ways that collide within the research environment. Drawing on the "heart work" core competencies within the field of community psychology (The Community Psychologist, 45, 2012, 8; American Journal of Community Psychology, 55, 2015, 266) and extending the dialogue of feminist community psychologists engaged in narrative work (American Journal of Community Psychology, 37, 2006, 157; American Journal of Community Psychology, 37, 2006, 267; Feminist research practice: A primer, Sage, Los Angeles, 2014; American Journal of Community Psychology, 28, 2000, 883), the author addresses why it is important for researchers of Color engaged in community collaborations to reflect on projects that have unraveled to understand how their positionality shifts within social contexts.


The use of histologically defined specific biomarkers in drug development with special reference to the glutathione S-transferases.
Failure of drug candidates late in development is very expensive. This can be reduced by using more specific biomarkers of effect and toxicity during the preclinical and development testing. However, traditional toxicity tests have not been developed to study toxicology and so may lack sufficient sensitivity and specificity hence the search for new biomarkers using the many "-omics" technologies. Important aspects of useful biomarkers are that their origin is known and localised so that one knows what is being observed. Furthermore, biomarkers with a localised origin are less likely to be subject to background variation and have a wider dynamic range. This paper will discuss how using biomarkers with a known cellular origin, toxic effects can be found earlier and at lower doses of compound.


A Review of Welfare Assessment Methods in Reptiles, and Preliminary Application of the Welfare Quality® Protocol to the Pygmy Blue-Tongue Skink, Tiliqua adelaidensis, Using Animal-Based Measures.
Reptiles are held at wildlife parks and zoos for display and conservation breeding programs and are increasingly being kept as pets. Reliable indicators of welfare for reptiles need to be identified. Current guidelines for the captive management of reptiles utilize resource-based, rather than animal-based indicators; the latter being a more direct reflection of affective state. In this paper we review the literature on welfare assessment methods in reptiles with a focus on animal-based measures. We conclude that, whilst a number of physiological and behavioral indicators of welfare have been applied in reptiles, there is need for further validation of these methods across the diversity of species within the Class. Methods of positive welfare state assessment are comparatively understudied and need elucidation. Finally, we examine some widely-used welfare assessment tools in mammals and explore the application of the Welfare Quality® Protocol to the endangered pygmy blue-tongue skink, Tiliqua adelaidensis. We propose that this framework can form the basis for the development of taxon-specific tools with consideration of species-specific biology.


Versatile Particle-Based Route to Engineer Vertically Aligned Silicon Nanowire Arrays and Nanoscale Pores.
Control over particle self-assembly is a prerequisite for the colloidal templating of lithographical etching masks to define nanostructures. This work integrates and combines for the first time bottom-up and top-down approaches, namely, particle self-assembly at liquid-liquid interfaces and metal-assisted chemical etching, to generate vertically aligned silicon nanowire (VA-SiNW) arrays and, alternatively, arrays of nanoscale pores in a silicon wafer. Of particular importance, and in contrast to current techniques, including conventional colloidal lithography, this approach provides excellent control over the nanowire or pore etching site locations and decouples nanowire or pore diameter and spacing. The spacing between pores or nanowires is tuned by adjusting the specific area of the particles at the liquid-liquid interface before deposition. Hence, the process enables fast and low-cost fabrication of ordered nanostructures in silicon and can be easily scaled up. We demonstrate that the fabricated VA-SiNW arrays can be used as in vitro transfection platforms for transfecting human primary cells.


Clinical Efficacy and Safety of Methotrexate versus Hydroxychloroquine in Preventing Lichen Planopilaris Progress: A Randomized Clinical Trial.
Lichen planopilaris is an inflammatory cicatricial alopecia, and its management is a challenge for dermatologists. We aimed to compare the efficacy of methotrexate and hydroxychloroquine on refractory lichen planopilaris. In a randomized clinical trial, 29 patients were randomly allocated to receive either 15 mg methotrexate/week or 200 mg hydroxychloroquine twice a day for 6 months. Side effects, symptoms/signs, and laboratory tests were assessed periodically. Lichen Planopilaris Activity Index (LPPAI) was measured before intervention and at 2, 4, and 6 months after. The changes from baseline to the end of the study were analyzed within each group and between the two groups by per-protocol and intention-to-treat analysis. After 2 months, mean (standard deviation [SD]) decrease in LPPAI in methotrexate group was significantly more than that in hydroxychloroquine group (1.68 [1.24] vs. 0.8 [0.71], respectively, P = 0.047). Furthermore, after 6 months, mean (SD) decrease in LPPAI in methotrexate group was significantly higher than that in hydroxychloroquine group (3.3 [2.09] vs. 1.51 [0.91], respectively, P = 0.01). The following symptoms/signs showed significant improvements in frequency and/or severity in methotrexate group after intervention: pruritus (P = 0.007), erythema (P = 0.01), perifollicular erythema (P = 0.01), perifollicular scaling (P = 0.08), spreading (P = 0.001), and follicular keratosis (P = 0.04). In hydroxychloroquine group, only erythema (P = 0.004) showed significant improvement. Methotrexate was more effective than hydroxychloroquine in treating refractory lichen planopilaris.


Rapid evaluation of surface sanitation by electrical measurement.
Electrical measurements are easier and faster than traditional methods for evaluating surface sanitation in the food industry. However, the behavior of sublethally damaged bacteria is different in each method. The electrical method is more sensitive to the presence of disinfectant traces in the samples. These issues lead to low correlations between both methods (r2 < 0.7). The use of smaller sample volumes in electrical measurements, together with the addition of a blend of neutralizers to the sample and the subsequent removal by filtration, provide r2 values > 0.9. The developed protocol shows an excellent correlation with traditional methods and facilitates the adaptation of the electrical method to routine monitoring of surface sanitation. It allows for a reduction in holding times and thereby provides the necessary time to make decisions.


Characterization of the J chain from polymeric immunoglobulins (IgA-IgM-immunological specificity-primary structure).
The J chains isolated from polymeric IgA and IgM were shown to be distinct from the other immunoglobulin subunits, including the secretory component, both on the basis of amino-acid content and antigenic determinants. By the same criteria, the J chains were found to be indistinguishable from each other whether they were derived from pentamer IgM, polydisperse myeloma IgA, or dimer colostral IgA. The only differences were observed in (a) the extent of disulfide bond cleavage required for J chain release from the different polymers, and (b) the three-dimensional arrangement of J chains in the different polymers. These data support the hypothesis that the same J chain joins the monomeric units of IgA and IgM to form their respective polymeric molecules.


[The role of Smad signaling pathway in the repair of mucosal epithelium in chronic sinusitis with nasal polyps and without nasal polyps].
Objective:To evaluate the differences in CRS and normal subjects between chronic rhinosinusitis without nasal polys (CRSsNP) and chronic rhinosinusitis with nasal polys (CRSwNP) in the role of TGF-β-Smad pathways in the repair of mucosal epithelium.Method:Ethmoidal mucosal samples collected from CRS and healthy control patients were analyzed for TGF-β1, TGF-β receptorⅠ,TGF-β receptor Ⅱ, Smad3, phospho-Smad3, Smad7, and Smad anchor for receptor activation by Western blot. The proliferation of sinonasal epithelial cells at baseline after TGF-β1 and/or EGF stimulation was evaluated by the MTT assay.Result:In CRSsNP,TGF-β1,TGF-β receptorⅠ,TGF-β receptor Ⅱ and Smad3 protein levels were significantly higher than controls. In CRSwNP, TGF-β1, Smad3 and pSmad3 protein levels were significantly lower than controls. Smad7 protein was significantly higher in CRS than controls. In vitro experiments demonstrated that the baseline proliferation levels of sinonasal epithelial cells were lower in CRS than controls.Conclusion:CRSwNP is characterized by a lower level of TGF-signaling compared with the control. In CRSsNP, although the upstream signaling of TGF-β was enhanced, over expression of Smad7 protein may restrain the downstream signaling components (e.g., pSmad3) and the TGF-β antiproliferative effect on sinonasal epithelium. The difference in the local tissue concentration of TGF-β1 between CRSsNP and CRSwNP patients did not show significant differences in epithelial proliferation.


A user-centred implementation strategy for tuberculosis contact investigation in Uganda: Protocol for a stepped-wedge, cluster-randomised trial.
Background Tuberculosis (TB) is among the leading causes of infectious death worldwide. Contact investigation is an evidence-based, World Health Organisation-endorsed intervention for timely TB diagnosis, treatment, and prevention but has not been widely and effectively implemented. Methods We are conducting a stepped-wedge, cluster-randomised, hybrid Type III implementation-effectiveness trial comparing a user-centred to a standard strategy for implementing TB contact investigation in 12 healthcare facilities in Uganda. The user-centred strategy consists of several client-focused components including 1) a TB-education booklet, 2) a contact-identification algorithm, 3) an instructional sputum-collection video, and 4) a community-health-rider service to transport clients, CHWs, and sputum samples, along with several healthcare-worker-focused components, including 1) collaborative improvement meetings, 2) regular audit-and-feedback reports, and 3) a digital group-chat application designed to develop a community of practice. Sites will cross from the standard to the user-centred strategy in six, eight-week transition steps following a randomly determined site-pairing scheme and timeline. The primary implementation outcome is the proportion of symptomatic close contacts completing TB evaluation within 60 days of TB treatment initiation by the index person with TB. The primary clinical effectiveness outcomes are the proportion of contacts diagnosed with and initiating active TB disease treatment and the proportion initiating TB preventative therapy within 60 days. We will assess outcomes from routine source documents using intention-to-treat analyses. We will also conduct nested mixed-methods studies of implementation fidelity and context and perform cost-effectiveness and impact modelling. The Makerere School of Public Health IRB (#554), the Uganda National Council for Science and Technology (#HS1720ES), and the Yale Institutional Review Board (#2000023199) approved the study with a waiver of informed consent for the main trial implementation-effectiveness outcomes. We will submit trial results for publication in a peer-reviewed journal and disseminate findings to local shareholders, including policymakers and representatives of affected communities. Discussion This pragmatic, quasi-experimental implementation trial will inform efforts to find and prevent undiagnosed persons with TB in high-burden setting using contact investigation. It will help assess the suitability of human-centred design and communities of practice for tailoring implementation strategies and sustain evidence-based interventions in low-and-middle-income countries. Trial registration number ClinicalTrials.gov Identifier: NCT05640648.


Early burn wound excision and skin grafting postburn trauma restores in vivo neutrophil delivery to inflammatory lesions.
This study assessed the effect of early vs delayed postburn wound excision and skin grafting on the in vivo neutrophil delivery to a delayed-type hypersensitivity (DTH) reaction and a bacterial skin lesion (BSL). Male Lewis rats were presensitized to keyhole-limpet hemocyanin. Group 1 comprised sham controls. Groups 2 through 4 were given a 30% 3 degrees scald burn, but the burn wounds were excised, and skin was grafted on days 1, 3, and 7, respectively, after the burn. Group 5 comprised burn controls. Twelve days after burn trauma, all rats were injected at different intervals (during a 24-hour period) with a trio of intradermal injections of keyhole-limpet hemocyanin, Staphylococcus aureus 502A, and saline at different sites. In vivo neutrophil delivery to these dermal lesions was determined by injecting indium in 111 oxyquinoline-labeled neutrophils isolated from similarly treated groups of rats. Neutrophil delivery to DTH and BSL lesions was restored to normal by excision and skin grafting of the burn wound one day after burn trauma. Waiting three days after burn trauma to excise and skin graft the wound partially, but not completely, restored the in vivo neutrophil delivery to DTH and BSL lesions. Waiting one week to excise and skin graft a burn wound resulted in no improvement in neutrophil delivery to DTH and BSL dermal lesions. It was concluded that burn wound excision and skin grafting immediately after burn trauma restored in vivo neutrophil delivery to a BSL and DTH dermal lesion. This may, in part, explain the beneficial effect of early aggressive burn wound debridement in patients with burn injuries.


Is HPV-negative cervical carcinoma a different type of cervical cancer?
Human papillomavirus (HPV), which is known to play a very important role in genital area (vulva, vagina, and cervix) cancers in women, is responsible for almost all cervical cancers. However, a significant proportion of cervical carcinomas (approximately 7%) is HPV-negative. Therefore, there are still two important questions to be answered: 1. Why is HPV Deoxyribonucleic acid (DNA) not found in all cervical carcinomas? 2. Are HPV-DNA-negative cervical cancers a specific subgroup of cervical cancers with different biological behavior (worse prognosis)? In this article, we aimed to evaluate the clinicopathological characteristics and survival of patients with confirmed HPV-negative tumors in order to answer these two questions. A total of 97 patients who underwent HPV-DNA testing and received a histological diagnosis of cervical cancer were included in the study. 14 HPV-DNA negative and 83 HPV-DNA positive cervical carcinoma patients were detected. Demographic profiles, clinicopathological characteristics, progression-free, and overall survival of all patients were analyzed. Women with HPV-negative tumors were diagnosed at an older age range (p=0.05), and their demographic data other than age range were similar to HPV-positive tumors. P16 staining pattern was not observed in any of the HPV-negative tumors (p=0.001), and a positive P53 staining pattern was detected in 35.7% of the HPV-negative tumors. Although disease-free survival (PFS) (p=0.224) and overall survival (OS) (p=0.219) were worse in the HPV-negative patient group, this difference was not statistically significant. HPV-negative cervical cancers do not have a poor prognosis unlike their counterparts in other anatomical regions where HPV-associated tumors are present.


[Medicinal plants and diabetes mellitus].
Diabetes mellitus is a group of chronic metabolic disorders. Hyperglycaemia and other related disturbances in the body's metabolism can result in serious damage to many of the body's systems, especially the blood vessels and nerves. Across the globe, there are an estimated 150 million people suffering from diabetes mellitus, which causes about 5 % of all deaths globally each year. From many reports it is clear that diabetes will be one of the major diseases in the coming years. Existing treatment options are costly, and have limited palliative effects. It stimulates finding new medicines or suitable prophylactic treatments. Plant-based medicinal products known since ancient times have been used to control diabetes in the traditional medicinal systems. Numerous medicinal plants have been studied and validated for their hypoglycaemic properties using diabetic animal models but not so often in clinical studies. Testing of many plant extracts and plant substances continue. This review paper presents selected information on the hypoglycemic and antihyperglycaemic activities of tested preparations of plant origin.


What can we learn from murine models of asthma?
Even though a complex disease such as asthma does not have a comprehensive animal model, some characteristics can be duplicated in mice and guinea-pigs. The murine model offers advantages with respect to strain control and availability of molecular biology tools. We introduced the use of the BP2 'Biozzi' mice, which have high IgE titres and expresses bronchopulmonary hyperresponsiveness (BHR) after a single antigenic provocation. BHR is accompanied by airway sequestration of lymphocytes and eosinophils, and by a newly described IgE-bearing granulocyte, identified to basophils. The murine model permits studies for cellular and molecular biology and to investigate the mode of action of drugs.


Changes to spontaneous otoacoustic emissions (SOAEs) due to cisplatin administration.
We investigated the influence of cisplatin on spontaneous otoacoustic emissions (SOAEs) by measuring SOAEs, before and after cisplatin administration, in 18 ears of nine patients (one female and eight males) who had received chemotherapy with cisplatin for a brain tumor. No hearing loss was observed after cisplatin administration in eight ears. Before cisplatin administration SOAE was present in four out of these eight ears, and only mild frequency fluctuation was observed even after administration. In 10 ears, sensory neural hearing loss was observed after cisplatin administration. Before cisplatin administration SOAE was present in four out of these 10 ears, and SOAE decreased or disappeared in three ears after administration. In two ears, SOAE was not present before cisplatin administration, but newly appeared after administration. It was indicated that SOAE principally disappeared at the frequencies where the region of the outer hair cells responsible for the same frequencies was injured, but new SOAEs appeared at the frequencies where the region of the outer hair cells was not injured after cisplatin administration.


Solution-phase synthesis of CsPbI3 nanowire clusters via polymer-induced anisotropic growth and self-assembly.
A facile solution-phase synthesis of black γ-phase CsPbI3 nanowire clusters was developed using poly(methyl methacrylate) (PMMA) as surfactant. PMMA was found to efficiently retard the crystal growth, thereby inducing anisotropic growth for formation of the nanowire structure, while the intermolecular hydrogen bonds of PMMA act as a driving force for self-assembly of the nanowires.


Effects of high- and low-intensity exercise training on aerobic capacity and blood lipids.
Sixteen non-obese, non-smoking males, ages 20-30 yr, were assigned to one of two training groups, exercising on a cycle ergometer 3 d/wk for 18 wk: high-intensity (H; N = 7; 80-85% Vo2max, 25 min/session) or low-intensity (L; N = 9; 45% VO2max, 50/min/session). Data were obtained at 3-wk intervals for Vo2max, body weight, percent body fat, and 12-h fasting blood levels of cholesterol (CHOL), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). The average post-training increase in VO2max for group H (0.56 l X min-1, 8.5 ml X min-1 X kg-1) was not significantly (P greater than 0.05) greater than for group L (0.45 l X min-1, 6.5 ml X min-1 X kg-1). Significant reductions in percent body fat occurred in both groups, amounting to an average fat loss of approximately 1.35 kg. No statistically significant changes in CHOL, TG, HDL-C, LDL-C, CHOL/HDL-C, or HDL-C/LDL-C occurred in either group. However, changes in HDL-C after 18 wk of training were inversely correlated (r = -0.57, P less than 0.05) with pre-training levels. We conclude that 1) the minimum exercise training-intensity threshold for improving aerobic capacity is at least 45% Vo2max; 2) 18 wk of high- or low-intensity exercise training is ineffective in significantly altering CHOL, TG, HDL-C, LDL-C, CHOL/HDL-C, and HDL-C/LDL-C in young male subjects with low blood lipid levels, and 3) exercise training-induced changes in HDL-C are dependent upon initial pre-training levels.


Divergent Co-occurrence Patterns and Assembly Processes Structure the Abundant and Rare Bacterial Communities in a Salt Marsh Ecosystem.
Understanding how species interaction and assembly processes structure the abundant and rare bacterial biospheres in soils is crucial for predicting how biodiversity influences ecosystem functioning. Here, we profiled the bacterial communities across a salt marsh ecosystem gradient to investigate the co-occurrence patterns across taxa and the relative influence of ecological processes mediating the assembly of the abundant and rare biospheres in soil. Our results revealed abundant taxa to be ubiquitous across all sites, whereas the distributions of the rare taxa were relatively more site specific. The α-diversity indices and β-diversity of rare subcommunities were significantly higher than those of the abundant subcommunities. Besides, both the taxonomic and functional composition of soil bacterial communities differed significantly between the two biospheres. Furthermore, the influence of stochasticity differed in each subcommunity. In particular, stochastic processes were relatively more important in constraining the assembly of rare taxa. Co-occurrence network analysis revealed that a few abundant taxa occupy central nodes within the networks, possibly indicating crucial roles as keystone taxa. Collectively, these findings suggest that abundant and rare bacterial biospheres have distinct distributions underpinned by a dynamic interplay of ecological processes and taxon co-occurrence patterns.IMPORTANCE Estuarine salt marshes are highly productive ecosystems subjected to regular disturbances by hydrodynamic exchange. However, little is known about how distinct assembly processes and co-occurrence of taxa influence the structure of the abundant and rare bacterial biospheres in these soil systems. This study aims at unravelling these intricacies by studying a typical estuarine salt marsh located in Hangzhou Bay, China. Our study provides important pieces of evidence on the diverse distribution of rare and abundant bacterial biospheres. We show that a few abundant taxa are central nodes in species co-occurrence, potentially playing important roles as keystone species in the system. In addition, we highlight a dynamic interplay of assembly processes structuring these two subcommunities.


A Validated Ultra-Performance Liquid Chromatography Tandem Triple Quadrupole Mass Spectrometric Method for Fast Determination of Losartan in Rabbit Plasma.
A rapid UPLC-MS-MS method was developed and validated for determination of losartan in rabbit plasma. Protonated adducts of losartan and eprosartan (IS) were monitored in multiple reaction monitoring mode. Molecular masses of daughter species of losartan were m/z 423.19 > 207 and m/z 423.19 > 180; and of eprosartan were m/z 425.11 > 135 and m/z 425.11 > 107. Losartan from plasma samples was extracted by protein precipitation method. The mobile phase comprising water (0.1% formic acid) (A) and acetonitrile (0.1% formic acid) (B) was used in gradient mode. Analytes were eluted on Acquity UPLC®BEH C18 1.7 μm, 2.1 × 50 mm column. Sample run time was 3.0 min. The validation parameters: accuracy, precision and recovery were within recommended limits. Losartan as well as internal standard remains stable in benchtop stability study as well as in post-preparative stability study. Pharmacokinetic parameters such as Cmax (182.79 ± 23.80 ng/mL), Tmax (1.16 ± 0.28 h), AUC0-t (1188.57 ± 404.60 ng h/mL) and Kel (0.0954 ± 0.0140 h-1) of losartan were measured. Method was successfully applied for pharmacokinetic investigation in rabbits and can be used for losartan determination in plasma sample obtained from other animals.


VEGF, Flt-1, and microvessel density in primary tumors as predictive factors of colorectal cancer prognosis.
Angiogenesis in the primary tumor is known to be necessary for tumor progression in adenocarcinomas of the colon. However, whether angiogenesis in the primary tumors of patients with colorectal cancer affects their prognosis has yet to be fully elucidated. The aim of the present study was to assess the association between selected pathoclinical parameters and overall survival of resectable colorectal cancer patients with the expression of angiogenesis-promoting factors, including vascular endothelial growth factor (VEGF) and Fms-like tyrosine kinase receptor (Flt-1), and microvessel density (MVD) in the primary tumor. VEGF and Flt-1 expression were assessed, as well as MVD (with anti-CD34) by immunohistochemistry in 139 archived primary colorectal cancer tissue samples. These results were compared with the overall survival of the patients and potential prognostic pathoclinical parameters. A higher MVD in the tumors expressing Flt-1 (P=0.04) was identified. However, there was no correlation between the pathoclinical parameters of colon cancer and Flt-1 expression, VEGF expression, or MVD in the tumor. Furthermore, the intensity of VEGF expression, Flt-1 expression and tumor MVD did not correlate with the overall survival of the patients. Therefore, although increased expression of VEGF and Flt-1 was correlated with an increased expression of MVD in the primary tumors of resectable colorectal cancer patients, these factors were not correlated with prognostic pathoclinical factors and overall survival.


Effects of short-term exposure to simulated microgravity on the physiology of Bacillus subtilis and multiomic analysis.
In our study, Bacillus subtilis was disposed to a simulated microgravity (SMG) environment in high-aspect ratio rotating-wall vessel bioreactors for 14 days, while the control group was disposed to the same bioreactors in a normal gravity (NG) environment for 14 days. The B. subtilis strain exposed to the SMG (labeled BSS) showed an enhanced growth ability, increased biofilm formation ability, increased sensitivity to ampicillin sulbactam and cefotaxime, and some metabolic alterations compared with the B. subtilis strain under NG conditions (labeled BSN) and the original strain of B. subtilis (labeled BSO). The differentially expressed proteins (DEPs) associated with an increased growth rate, such as DNA strand exchange activity, oxidoreductase activity, proton-transporting ATP synthase complex, and biosynthetic process, were significantly upregulated in BSS. The enhanced biofilm formation ability may be related with the DEPs of spore germination and protein processing in BSS, and differentially expressed genes involved in protein localization and peptide secretion were also significantly enriched. The results revealed that SMG may increase the level of related functional proteins by upregulating or downregulating affiliated genes to change physiological characteristics and modulate growth ability, biofilm formation ability (epsB, epsC, epsN), antibiotic sensitivity (penP) and metabolism. Our experiment may gives new ideas for the study of space microbiology.


[Model for the organizational structure of the Regional Service for Animal Health].
The organisational structure of any unit must be a reflection of the way in which work is distributed and of specialisation in the constituent parts. Co-ordination between these parts requires the establishment of standards, strategies, procedures and official controls, as well as a chain of command, in order to attain the desired objectives. The authors present an alternative model for designing an organisational structure for district Veterinary Services of a given country. This model will assist the establishment of basic criteria for evaluating such Services, facilitating their integration into the procedure for planning animal health activities, and providing a better comprehension of their function within the livestock sector.


Predicting and characterizing a cancer dependency map of tumors with deep learning.
Genome-wide loss-of-function screens have revealed genes essential for cancer cell proliferation, called cancer dependencies. It remains challenging to link cancer dependencies to the molecular compositions of cancer cells or to unscreened cell lines and further to tumors. Here, we present DeepDEP, a deep learning model that predicts cancer dependencies using integrative genomic profiles. It uses a unique unsupervised pretraining that captures unlabeled tumor genomic representations to improve the learning of cancer dependencies. We demonstrated DeepDEP's improvement over conventional machine learning methods and validated the performance with three independent datasets. By systematic model interpretations, we extended the current dependency maps with functional characterizations of dependencies and a proof-of-concept in silico assay of synthetic essentiality. We applied DeepDEP to pan-cancer tumor genomics and built the first pan-cancer synthetic dependency map of 8000 tumors with clinical relevance. In summary, DeepDEP is a novel tool for investigating cancer dependency with rapidly growing genomic resources.


Lung transplantation in children.
Fewer than 50 pediatric lung transplants are performed each year. Surgical advances in the field have resulted in improved operative outcomes and in technical innovations that have broadened both the target population and the donor pool. At the same time, late referral of critically ill patients and shortage of donor organs result in death prior to transplantation for many children, and substantial biological barriers exist that prevent achievement of satisfactory long-term outcomes for the many who do undergo a successful surgical procedure. Until we can better understand and overcome these barriers, lung transplantation must be considered a palliative rather than curative procedure. In this article, a brief overview of pediatric lung transplantation is offered, and contributions to the recent literature are summarized.


Climate Change and Its Impact on the Yield of Major Food Crops: Evidence from Pakistan.
Pakistan is vulnerable to climate change, and extreme climatic conditions are threatening food security. This study examines the effects of climate change (e.g., maximum temperature, minimum temperature, rainfall, relative humidity, and the sunshine) on the major crops of Pakistan (e.g., wheat, rice, maize, and sugarcane). The methods of feasible generalized least square (FGLS) and heteroscedasticity and autocorrelation (HAC) consistent standard error were employed using time series data for the period 1989 to 2015. The results of the study reveal that maximum temperature adversely affects wheat production, while the effect of minimum temperature is positive and significant for all crops. Rainfall effect towards the yield of a selected crop is negative, except for wheat. To cope with and mitigate the adverse effects of climate change, there is a need for the development of heat- and drought-resistant high-yielding varieties to ensure food security in the country.


Initial evaluation of Advanced Collapsed cone Engine dose calculations in water medium for I-125 seeds and COMS eye plaques.
To investigate the dose calculation accuracy in water medium of the Advanced Collapsed cone Engine (ACE) for three sizes of COMS eye plaques loaded with low-energy I-125 seeds. A model of the Oncura 6711 I-125 seed was created for use with ACE in Oncentra® Brachy (OcB) using primary-scatter separated (PSS) point dose kernel and Task Group (TG) 43 datasets. COMS eye plaque models of diameters 12, 16, and 20 mm were introduced into the OcB applicator library based on 3D CAD drawings of the plaques and Silastic inserts. To perform TG-186 level 1 commissioning, treatment plans were created in OcB for a single source in water and for each COMS plaque in water for two scenarios: with only one centrally loaded seed, or with all seed positions loaded. ACE dose calculations were performed in high accuracy mode with a 0.5 × 0.5 × 0.5 mm3 calculation grid. The resulting dose data were evaluated against Monte Carlo (MC) calculated doses obtained with MCNP6, using both local and global percent differences. ACE doses around the source for the single seed in water agreed with MC doses on average within < 5% inside a 6 × 6 × 6 cm3 region, and within < 1.5% inside a 2 × 2 × 2 cm3 region. The PSS data were generated at a higher resolution within 2 cm from the source, resulting in this improved agreement closer to the source due to fewer approximations in the ACE dose calculation. Average differences in both investigated plaque loading patterns in front of the plaques and on the plaque central axes were ≤ 2.5%, though larger differences (up to 12%) were found near the plaque lip. Overall, good agreement was found between ACE and MC dose calculations for a single I-125 seed and in front of the COMS plaques in water. More complex scenarios need to be investigated to determine how well ACE handles heterogeneous patient materials.


[Autoimmune hemolytic anemia associated with mesenteric teratoma].
The paper describes a case of autoimmune hemolytic anemia (AIHA) in a 27-year-old woman whose examination revealed mesenteric teratoma. AIHA was characterized by a hypertensive crisis and a temporary response to corticosteroid therapy that was complicated by the development of somatogenic psychosis and discontinued. A relapse of hemolysis developed 6 months later. The patient underwent laparoscopic splenectomy and removal of mesenteric root teratoma. Immediately after surgery, a hematological response was obtained as relief of hemolysis and restoration of a normal hemoglobin level. There is a sustained remission of AIHA for the next 16 months.


Pregnancy intention from men's perspectives: does child support enforcement matter?
Most research on pregnancy intention has focused on women's perspectives and characteristics. Because decisions about sexual activity and contraceptive use usually involve both men and women, it is important to understand factors associated with men's intentions-for example, child support enforcement-to maximize the potential for reducing unwanted pregnancies. Data from the 1982-2002 waves of the National Longitudinal Survey of Youth were used in multinomial logit analyses to examine the determinants of pregnancy intention from men's perspectives. Forty-six percent of pregnancies reported by never-married men were unwanted, compared with 21% of those reported by married men. Stronger child support enforcement was marginally associated with men's decreased likelihood of being involved in an unwanted pregnancy compared with no pregnancy (coefficient, -0.14) and of being involved in an unwanted pregnancy compared with a wanted pregnancy (-0.15). Without the improvement of child support enforcement over the survey period, the rate of unwanted pregnancies would have been an estimated 7% higher than the observed rate. Strengthening child support enforcement may have a positive impact on preventing unwanted pregnancies. Programs designed to reduce unwanted pregnancies and nonmarital births should include information on child support enforcement to increase their success.


A new family of insulin-mimetic vanadium complexes derived from 5-carboalkoxypicolinates.
The reaction of 5-carboalkoxypicolinic acid (5 ROpicH, R=Me, Et, iPr, sBu; 1 a-d) with vanadyl sulfate yielded the complexes [VO(H(2)O)(5 ROpic)(2)], 2 a-d, with H(2)O and one of the picolinato ligands in the equatorial positions, and the second picolinate occupying equatorial (N) and axial (O) positions. Reaction of 1 a with [NH(4)][VO(3)] yielded [NH(4)][VO(2)(5 MeOpic)(2)], [NH(4)]-3, in which the N functions of the picolinates are trans to the doubly bonded, cis-positioned oxo groups. Complexes 1 a.H(2)O, 1 b, 1 c, 2 a.3.5 H(2)O and [NH(4)]-3.4 H(2)O have been structurally characterised. A detailed pH-potentiometric solution speciation analysis of the system VO(2+)-1 a revealed a dominance of VO(5 OMepic)(2) between pH 2 and 6, with the same coordination pattern, evidenced by EPR spectroscopy, as in the crystalline solid state. In ternary systems containing physiological concentrations of the low molecular mass biogenic binders (B) lactate, oxalate, citrate or phosphate, ternary species of general composition VO(5 MeOpic)B dominate at physiological pH, with citrate being the most effective competitor for picolinate. All of the complexes trigger glucose uptake and degradation by simian virus modified mice fibroblasts at non-toxic concentrations (<100 microM), with 2 a, [VO(2)(pic)(2)](-) and [VO(2)(dipic)](-) being at least as effective as insulin. Vanadium uptake by the cells is most effective in the case of 2 a. 2 a also effectively inhibits free fatty acid release by rat adipocytes treated with epinephrine, thus mimicking the inhibition of lipolysis by insulin.


Critical analysis of ineffective post implantation implantable cardioverter-defibrillator-testing.
To test of the implantable-cardioverter-defibrillator is done at the time of implantation. We investigate if any testing should be performed. All consecutive patients between January 2006 and December 2008 undergoing implantable cardioverter-defibrillator (ICD) implantation/replacement (a total of 634 patients) were included in the retrospective study. Sixteen patients (2.5%) were not tested (9 with LA/LV-thrombus, 7 due to operator's decision). Analyzed were 618 patients [76% men, 66.4 + 11 years, 24% secondary prevention (SP), 46% with left ventricular ejection fraction (LVEF) < 20%, 56% had coronary artery disease (CAD)] undergoing defibrillation safety testing (SMT) with an energy of 21 + 2.3 J. In 22/618 patients (3.6%) induced ventricular fibrillation (VF) could not be terminated with maximum energy of the ICD. Six of those (27%) had successful SMT after system modification or shock lead repositioning, 14 patients (64%) received a subcutaneous electrode array. Younger age (P = 0.0003), non-CAD (P = 0.007) and VF as index event for SP (P = 0.05) were associated with a higher incidence of ineffective SMT. LVEF < 20% and incomplete revascularisation in patients with CAD had no impact on SMT. Defibrillation testing is well-tolerated. An ineffective SMT occurred in 4% and two third of those needed implantation of a subcutaneous electrode array to pass a SMT > 10 J.


Single-image structured illumination using Hilbert transform demodulation.
Structured illumination microscopy (SIM) achieves sectioning at depth by removing undesired light from out-of-focus planes within a specimen. However, it generally requires at least three modulated images with discrete phase shifts of 0, 120, and 240 deg to produce sectioning. Using a Hilbert transform demodulation, it is possible to produce both sectioning and depth information relative to a reference plane (i.e., a coverslip) using only a single image. The specimen is modulated at a known frequency, and the unmodulated portion of the image is estimated. These two components are used to provide a high-quality sectioned image containing both axial and lateral information of an object. The sectioning resolution with a single image is on par with that of a control three-image SIM. We are also able to show that when used with three images of discrete phase, this method produces better contrast within a turbid media than the traditional SIM technique. Because the traditional SIM requires alignment of three different phases, small differences in optical path length can introduce strong artifacts. Using the single-image technique removes this dependency, greatly improving sectioning in turbid media. Multiple targets with various depths and opaqueness are considered, including human skin in vivo, demonstrating a quick and useful way to provide noninvasive sectioning in real time.


Dads and Daughters: grassroots advocacy.
Dads and Daughters (DADS) is a grassroots organization of fathers. Its mission is to provide tools to both strengthen father-daughter relationships and to transform the pervasive cultural messages that value girls more for how they look than for who they are. The DADS philosophy is captured in ten "Tips for Fathers with Daughters" which include: (a) listen to girls; (b) encourage their strength and savvy; (c) respect girl's uniqueness, urge them to love their bodies, and discourage dieting; (d) get physically active with girls; (e) get involved in their schools; (f) get involved in their activities; (g) help make the world better for girls; (h) take daughters to work; (i) support positive alternative media for girls; and (j) talk to other fathers. DADS urges health care providers to actively involve fathers in their daughter's preventive health and illness care.


A mechanistic study into the interconversion of rhodium alkyne, alkynyl hydride and vinylidene complexes.
The conversion of the alkyne complex RhCl(PPr(i)3)2(eta2-PhC[triple bond]CH) into its vinylidene isomer RhCl(PPr(i)3)2(=C=CPhH) has been monitored via NMR spectroscopy in a range of solvents. In THF and hexane solution the reaction was observed to proceed via the alkynyl hydride complex Rh(H)Cl(PPr(i)3)2(-C[triple bond]CPh). The kinetic profile of the reaction demonstrates that this species is an intermediate in the formation of the vinylidene complex.


Development and validation of risk prediction model for premenstrual syndrome in nurses: results from the nurses-based the TARGET cohort study.
Premenstrual syndrome (PMS) stands as a significant concern within the realm gynecological disorders, profoundly impacting women of childbearing age in China. However, the elusive nature of its risk factors necessitates investigation. This study, therefore, is dedicated to unraveling the intricacies of PMS by focusing on nurses, a cohort with unique occupational stressors, to develop and validate a predictive model for assessing the risk of PMS. This investigation employed a multi-center cross-sectional analysis drawing upon data from the TARGET Nurses' health cohort. Utilizing online survey versions of the Premenstrual Syndrome Scale (PMSS), a comprehensive dataset encompassing physiological, social, psychological, occupational, and behavioral variables was collected from 18,645 participants. A stepwise multivariate logistic regression analysis was conducted to identify independent risk factors for PMS. Furthermore, a refined variable selection process was executed, combining the Least Absolute Shrinkage and Selection Operator (LASSO) method with 10-fold cross-validation. The visualization of the risk prediction model was achieved through a nomogram, and its performance was evaluated using the C index, receiver operating characteristic (ROC) curves, and the calibration curves. Among the diverse variables explored, this study identified several noteworthy predictors of PMS in nurses, including tea or coffee consumption, sleep quality, menstrual cycle regularity, intermenstrual bleeding episodes, dysmenorrhea severity, experiences of workplace bullying, trait coping style, anxiety, depression and perceived stress levels. The prediction model exhibited robust discriminatory power, with an area under the curve of 0.765 for the training set and 0.769 for the test set. Furthermore, the calibration curve underscored the model's high degree of alignment with observed outcomes. The developed model showcases exceptional accuracy in identifying nurses at risk of PMS. This early alert system holds potential to significantly enhance nurses' well-being and underscore the importance of professional support.


A systematic review of high-intensity interval training as an exercise intervention for intermittent claudication.
Intermittent claudication (IC) is the most common symptom of peripheral arterial disease, which significantly affects walking ability, functional capacity and quality of life. Supervised exercise programs (SEP) are recommended as first-line treatment, but recruitment and adherence rates are poor. The time required to complete a SEP is the most common barrier to participation cited by patients who decline. High-intensity interval training (HIIT) is more time efficient than current SEPs and therefore has the potential to overcome this barrier. We conducted a systematic review to appraise the evidence for HIIT programs for IC. MEDLINE, Embase, and CENTRAL databases were searched for terms related to HIIT and IC. Randomized and nonrandomized trials that investigated HIIT for the treatment of IC were included, with no exclusions based on exercise modality, protocol, or use of a comparator arm. Outcome measures were walking distances, peak oxygen uptake, recruitment and adherence rates, and quality of life. The risk of bias was assessed using the Cochrane tool and study quality using a modified Physiotherapy Evidence Database scale. Nine articles reporting eight studies were included in the review. HIIT seems to improve walking distances and oxygen uptake in relation to controls, with improvements attainable in just 6 weeks. When HIIT was compared with low-intensity exercise, it seemed that longer low-intensity programs were required to obtain similar benefits to those from short-term HIIT. Initial evidence suggests that HIIT may provide benefits for patients with IC. Initially, pilot studies of low-volume, short-term HIIT vs usual SEPs are required. This strategy will allow for larger randomized, controlled trials to be appropriately designed and adequately powered to further explore the potential benefits of HIIT in IC.


Adjuvant radiotherapy after prostatectomy for prostate cancer in Japan: a multi-institutional survey study of the JROSG.
In Japan, the use of adjuvant radiotherapy after prostatectomy for prostate cancer has not increased compared with the use of salvage radiotherapy. We retrospectively evaluated the outcome of adjuvant radiotherapy together with prognostic factors of outcome in Japan. Between 2005 and 2007, a total of 87 patients were referred for adjuvant radiotherapy in 23 institutions [median age: 64 years (54-77 years), median initial prostate-specific antigen: 11.0 ng/ml (2.9-284 ng/ml), Gleason score (GS): 6, 7, 8, 9, 10 = 13.8, 35.6, 23.0, 27.6, 0%, respectively]. Rates of positive marginal status, seminal vesicle invasion (SVI) and extra-prostatic extension (EPE) were 74%, 26% and 64%, respectively. Median post-operative PSA nadir: 0.167 ng/ml (0-2.51 ng/ml). Median time from surgery to radiotherapy was 3 months (1-6 months). A total dose of ≥ 60 Gy and <65 Gy was administered to 69% of patients. The median follow-up time was 62 months. The 3- and 5-year biochemical relapse-free survival (bRFS) rates for all patients were 66.5% and 57.1%, respectively. The GS and marginal status (P = 0.019), GS and SVI (P = 0.001), marginal status and EPE (P = 0.017), type of hormonal therapy and total dose (P = 0.026) were significantly related. The 5-year bRFS rate was significantly higher in SVI-negative patients than SVI-positive patients (P = 0.001), and significantly higher in patients with post-operative PSA nadir ≤ 0.2 than in patients with post-operative PSA nadir >0.2 (P = 0.02), and tended to be more favorable after radiotherapy ≤ 3 months from surgery than >3 months from surgery (P = 0.069). Multivariate analysis identified SVI and post-operative PSA nadir as independent prognostic factors for bRFS (P = 0.001 and 0.018, respectively).


Development of a combined protein and pharmacophore model for cytochrome P450 2C9.
A combined protein and pharmacophore model for cytochrome P450 2C9 (CYP2C9) has been derived using various computational chemistry techniques. A combination of pharmacophore modeling (using 31 metabolic pathways for 27 substrates), protein modeling (using the rabbit CYP2C5/3 crystal structure), and molecular orbital calculations was used to derive a model that incorporated steric, electronic, and chemical stability properties. The initial pharmacophore model (based on a subset of 17 metabolic pathways for 16 substrates) and the protein model used to construct the combined model were derived independently and showed a large degree of complementarity. The combined model is in agreement with experimental results concerning the substrates used to derive the model and with site-directed mutagenesis data available for CYP2C9. The model has been successfully used to predict the metabolism of substrates not used to construct the model, of which four examples are discussed in detail. The model has also been successful in explaining the differences in substrate specificity between CYP2C9 and CYP2C19.


[Trimetazidine in the Treatment of Chronic HeartFailure].
The review presents data on alterations of mitochondrial oxidative metabolism occuring due to heart failure, mechanisms of cytoprotective agent trimetazidine associated with a partial inhibition of the fatty acid oxidation and increased metabolism of pyruvate, reduction of cardiomyocyte apoptosis and oxidative stress are described. The results of clinical studies showing the effectiveness of trimetazidine therapy in ischemic heart decease are reported, as well as the latest data on the effects of prolonged use of trimetazidine on prognosis in patients with heart failure.


Low-dose curcuminoid-loaded in dextran nanobubbles can prevent metastatic spreading in prostate cancer cells.
Preventing recurrences and metastasis of prostate cancer after prostatectomy by administering adjuvant therapies is quite a controversial issue. In addition to effectiveness, absence of side effects and long term toxicity are mandatory. Curcuminoids (Curc) extracted with innovative techniques and effectively loaded by polymeric nanobubbles (Curc-NBs) satisfy such requirements. Curc-NBs showed stable over 30 d, were effectively internalized by tumor cells and were able to slowly release Curc in a sustained way. Significant biological effects were detected in PC-3 and DU-145 cell lines where Curc-NBs were able to inhibit adhesion and migration, to promote cell apoptosis and to affect cell viability and colony-forming capacity in a dose-dependent manner. Since the favourable effects are already detectable at very low doses, which can be reached at a clinical level, the actual drug concentration can be visualized and monitored by US or MRI, Curc-NBs can be proposed as an effective adjuvant theranostic tool.


Ontogenetic habitat shift, population growth, and burrowing behavior of the Indo-Pacific beach star, Archaster typicus (Echinodermata; Asteroidea).
Archaster typicus, a common sea star in Indo-Pacific regions, has been a target for the ornamental trade, even though little is known about its population biology. Spatial and temporal patterns of abundance and size structure of A. typicus were studied in the Davao Gulf, the Philippines (125°42.7'E, 7°0.6'N), from February 2008 to December 2009. Specimens of A. typicus were associated with intertidal mangrove prop roots, seagrass meadows, sandy beaches, and shoals. Among prop roots, specimens were significantly smaller and had highest densities (131 ind. m-2) between November and March. High organic matter in sediment and a relatively low predation rate seemed to support juvenile life among mangroves. Size and density analyses provided evidence that individuals gradually move to seagrass, sandy habitats, and shoals as they age. Specimens were significantly larger at a shoal (maximum radius R = 81 mm). New recruits were found between August and November in both 2008 and 2009. Timing of recruitment and population size frequencies confirmed a seasonal reproductive cycle. Juveniles had relatively high growth rates (2-7 mm month-1) and may reach an R of 20-25 mm after 1 year. Growth rates of larger specimens (R > 30 mm) were generally <2 mm month-1. The activity pattern of A. typicus was related to the tidal phase and not to time of day: Specimens moved over the sediment surface during low tides and were burrowed during high tides possibly avoiding predation. This is one of the first studies to document an ontogenetic habitat shift for sea stars and provides new biological information as a basis for management of harvested A. typicus populations.


Indirect to Direct Gap Crossover in Two-Dimensional InSe Revealed by Angle-Resolved Photoemission Spectroscopy.
Atomically thin films of III-VI post-transition metal chalcogenides (InSe and GaSe) form an interesting class of two-dimensional semiconductors that feature a strong variation of their band gap as a function of the number of layers in the crystal and, specifically for InSe, an expected crossover from a direct gap in the bulk to a weakly indirect band gap in monolayers and bilayers. Here, we apply angle-resolved photoemission spectroscopy with submicrometer spatial resolution (μARPES) to visualize the layer-dependent valence band structure of mechanically exfoliated crystals of InSe. We show that for one-layer and two-layer InSe the valence band maxima are away from the Γ-point, forming an indirect gap, with the conduction band edge known to be at the Γ-point. In contrast, for six or more layers the band gap becomes direct, in good agreement with theoretical predictions. The high-quality monolayer and bilayer samples enable us to resolve, in the photoluminescence spectra, the band-edge exciton (A) from the exciton (B) involving holes in a pair of deeper valence bands, degenerate at Γ, with a splitting that agrees with both μARPES data and the results of DFT modeling. Due to the difference in symmetry between these two valence bands, light emitted by the A-exciton should be predominantly polarized perpendicular to the plane of the two-dimensional crystal, which we have verified for few-layer InSe crystals.


Identification of potential human pancreatic α-amylase inhibitors from natural products by molecular docking, MM/GBSA calculations, MD simulations, and ADMET analysis.
Human pancreatic α-amylase (HPA), which works as a catalyst for carbohydrate hydrolysis, is one of the viable targets to control type 2 diabetes. The inhibition of α-amylase lowers blood glucose levels and helps to alleviate hyperglycemia complications. Herein, we systematically screened the potential HPA inhibitors from a library of natural products by molecular modeling. The modeling encompasses molecular docking, MM/GBSA binding energy calculations, MD simulations, and ADMET analysis. This research identified newboulaside B, newboulaside A, quercetin-3-O-β-glucoside, and sasastilboside A as the top four potential HPA inhibitors from the library of natural products, whose Glide docking scores and MM/GBSA binding energies range from -9.191 to -11.366 kcal/mol and -19.38 to -77.95 kcal/mol, respectively. Based on the simulation, among them, newboulaside B was found as the best HPA inhibitor. Throughout the simulation, with the deviation of 3Å (acarbose = 3Å), it interacted with ASP356, ASP300, ASP197, THR163, ARG161, ASP147, ALA106, and GLN63 via hydrogen bonding. Additionally, the comprehensive ADMET analysis revealed that it has good pharmacokinetic properties having not acutely toxic, moderately bioavailable, and non-inhibitor nature toward cytochrome P450. All the results suggest that newboulaside B might be a promising candidate for drug discovery against type 2 diabetes.


Immunobiotic lactobacilli reduce viral-associated pulmonary damage through the modulation of inflammation-coagulation interactions.
The exacerbated disease due to immune- and coagulative-mediated pulmonary injury during acute respiratory viruses infection results in severe morbidity and mortality. Identifying novel approaches to modulate virus-induced inflammation-coagulation interactions could be important alternatives for treating acute respiratory viruses infections. In this study we investigated the effect of the probiotic strain Lactobacillus rhamnosus CRL1505 on lung TLR3-mediated inflammation, and its ability to modulate inflammation-coagulation interaction during respiratory viral infection. Our findings reveal for the first time that a probiotic bacterium is able to influence lung immune-coagulative reaction triggered by TLR3 activation, by modulating the production of proinflammatory and anti-inflammatory cytokines as well as expression of tissue factor and thrombomodulin in the lung. We also demonstrated that the preventive treatment with the probiotic bacteria beneficially modulates the fine tune balance between clearing respiratory viruses (respiratory syncytial virus and influenza virus) and controlling immune-coagulative responses in the lung, allowing normal lung function to be maintained in the face of a viral attack. Our data also pinpoint a crucial role for IL-10 in the immune protection induced by L. rhamnosus CRL1505 during respiratory viral infections. These observations might be helpful to propose new preventive or therapeutic approaches to better control virus-inflammatory lung damage using probiotic functional foods.


Single-molecule spectroscopy exposes hidden states in an enzymatic electron relay.
The ability to query enzyme molecules individually is transforming our view of catalytic mechanisms. Quiescin sulfhydryl oxidase (QSOX) is a multidomain catalyst of disulfide-bond formation that relays electrons from substrate cysteines through two redox-active sites to molecular oxygen. The chemical steps in electron transfer have been delineated, but the conformational changes accompanying these steps are poorly characterized. Here we use single-molecule Förster resonance energy transfer (smFRET) to probe QSOX conformation in resting and cycling enzyme populations. We report the discovery of unanticipated roles for conformational changes in QSOX beyond mediating electron transfer between redox-active sites. In particular, a state of the enzyme not previously postulated or experimentally detected is shown to gate, via a conformational transition, the entrance into a sub-cycle within an expanded QSOX kinetic scheme. By tightly constraining mechanistic models, smFRET data can reveal the coupling between conformational and chemical transitions in complex enzymatic cycles.


Developing a Measure to Quantify Ocular Pain Postoperatively: The Adaptation of the Ocular Pain Assessment Survey.
Since quantification and communication of ocular pain is important for a healthier patient follow-up and postoperative guidance, reliable measures like the Ophthalmic Pain Assessment Survey (OPAS) are needed to assess the outcome and management of different operations. To address that need, we carried out the adaptation of OPAS into Turkish to reach different age groups and backgrounds, widening the use of OPAS on patients who underwent an ophthalmic operation. We used back-translation method and achieved cultural adaptation through content validity scoring by 5 independent ophthalmologists. The survey is then administered three times: preoperatively, postoperatively within 24 hours, and finally a week later in the follow-up visit. Validity is measured in comparison to Visual Analog Scale using Spearman's correlation coefficient and reliability is measured using Cronbach's alpha. Factor analysis is performed by principal component analysis and rotation is performed using Varimax method when necessary. We reached a total of 132 patients with a mean age of 64.2 years. Most of them underwent phacoemulsification (n = 83), followed by PRK (n = 37). Overall, the T-OPAS demonstrated good reliability (mean C. alpha: 0.830) and its correlation with the VAS was especially high (S. coeff. >0.5) in the first three sections in all three surveys. Factor analysis yielded 5 subscales, allowing us to shape the final form of T-OPAS. Through this adaptation of OPAS into a foreign language, we present a reliable and valid tool for postoperative pain quantification, allowing objective measurement of pain in different populations such as the elderly.


The potential of virtual reality-based training to enhance the functional autonomy of Alzheimer's disease patients in cooking activities: A single case study.
Impairments in performing activities of daily living occur early in the course of Alzheimer's disease (AD). There is a great need to develop non-pharmacological therapeutic interventions likely to reduce dependency in everyday activities in AD patients. This study investigated whether it was possible to increase autonomy in these patients in cooking activities using interventions based on errorless learning, vanishing-cue, and virtual reality techniques. We recruited a 79-year-old woman who met NINCDS-ADRDA criteria for probable AD. She was trained in four cooking tasks for four days per task, one hour per day, in virtual and in real conditions. Outcome measures included subjective data concerning the therapeutic intervention and the experience of virtual reality, repeated assessments of training activities, neuropsychological scores, and self-esteem and quality of life measures. The results indicated that our patient could relearn some cooking activities using virtual reality techniques. Transfer to real life was also observed. Improvement of the task performance remained stable over time. This case report supports the value of a non-immersive virtual kitchen to help people with AD to relearn cooking activities.


Affective response to 5 microT ELF magnetic field-induced physiological changes.
Research into effects of weak magnetic fields (MFs) at biologically relevant frequencies has produced ambiguous results. Although they do affect human physiology and behaviour, the direction of effects is inconsistent, with a range of complex and unrelated behaviours being susceptible. A possible explanation is that these effects, rather than being directly caused, are instead related to changes in affective state. A previous study showed that MFs altered the affective content of concurrent perceptions, but it was unclear whether the emotional response was direct or indirect. Here it is shown that exposure to a 0-5 microT MF (DC-offset sinudsoidal wave form) within EEG alpha-band frequencies (8-12 Hz), results in a reported change in emotional state. This relates to a decrease global field power but lacks the frontal alpha-asymmetry that would physiologically indicate a directly induced emotional state, suggesting that participant experiences are due to an interpretation of the effects of MF exposure.


Pathological interactions between hematopoietic stem cells and their niche revealed by mouse models of primary myelofibrosis.
Primary myelofibrosis (PMF) belongs to the Philadelphia-negative myeloproliferative neoplasms and is a hematological disorder caused by abnormal function of the hematopoietic stem cells. The disease manifests itself with a plethora of alterations, including anemia, splenomegaly and extramedullary hematopoiesis. Its hallmarks are progressive marrow fibrosis and atypical megakaryocytic hyperplasia, two distinctive features used to clinically monitor disease progression. In an attempt to investigate the role of abnormal megakaryocytopoiesis in the pathogenesis of PMF, several transgenic mouse models have been generated. These models are based either on mutations that interfere with the extrinsic (thrombopoietin and its receptor, MPL) and intrinsic (the GATA1 transcription factor) control of normal megakaryocytopoiesis, or on known genetic lesions associated with the human disease. Here we provide an up-to-date review on the insights into the pathobiology of human PMF achieved by studying these animal models, with particular emphasis on results obtained with Gata1(low) mice.


Sterilization of Silastic Capsules Containing 17β-Estradiol for Effective Hormone Delivery in Mus musculus.
Silastic capsules are frequently used to study the physiologic effects of estrogen exposure in animal models. The Officeof Laboratory Animal Welfare requires the sterilization of nonpharmaceutical-grade compounds before use. We compared 2commonly used terminal sterilization methods-ionizing radiation (IR) and ethylene oxide (EO)-for their utility in sterilizingsilastic capsules containing 0.05 or 0.1 mg 17β-estradiol (E2). E2-specific ELISA demonstrated that serum estrogen levelsdid not differ between mice implanted with 0.05-mg E2 capsules that were sterilized with IR or EO and those implanted withnonsterilized capsules. Likewise, mammary gland morphology and progesterone receptor expression and proliferation inmammary epithelium were similar among mice treated with E2 capsules, regardless of sterilization method, and pregnant day15 mice. In addition, IR-sterilized 0.1-mg E2 pellets provided high serum E2. We conclude that neither ionizing radiation norethylene oxide degraded E2 or the cellulose matrix, suggesting that these methods of sterilization are appropriate to provideeffective sterile hormone capsules for animal research.


Serial block face SEM visualization of unusual plant nuclear tubular extensions in a carnivorous plant (Utricularia, Lentibulariaceae).
In Utricularia nelumbifolia , the nuclei of placental nutritive tissue possess unusually shaped projections not known to occur in any other flowering plant. The main aim of the study was to document the morphology and ultrastructure of these unusual nuclei. In addition, the literature was searched to find examples of nuclear tubular projections in other plant groups, and the nuclei of closely related species of Utricularia (i.e. sects Iperua , Orchidioides , Foliosa and Utricularia ) were examined. To visualize the complexity of the nuclear structures, transmission electron microscopy (TEM) was used, and 3-D ultrastructural reconstructions were made using the serial block face scanning electron microscopy (SBEM) technique. The nuclei of 11 Utricularia species, i.e. U. nelumbifolia , U. reniformis , U. cornigera , U. nephrophylla (sect. Iperua ), U. asplundii , U. alpina , U. quelchii (sect. Orchidioides ), U. longifolia (sect. Foliosa ), U. intermedia , U. minor and U. gibba (sect. Utricularia ) were examined. Of the 11 Utricularia species examined, the spindle-like tubular projections (approx. 5 μm long) emanating from resident nuclei located in placental nutritive tissues were observed only in U. nelumbifolia . These tubular nuclear extensions contained chromatin distributed along hexagonally shaped tubules. The apices of the projections extended into the cell plasma membrane, and in many cases also made contact at the two opposing cellular poles, and with plasmodesmata via a short cisterna of the cortical endoplasmic reticulum. Images from the SBEM provide some evidence that the nuclear projections are making contact with those of neighbouring cells. The term chromatubules (chromatin-filled tubules) for the nuclear projections of U. nelumbifolia placental tissue was proposed here. Due to the apparent association with the plasma membrane and plasmodesmata, it was also speculated that chromatubules are involved in nucleus-cell-cell communication. However, further experimental evidence is required before any functional hypothesis can be entertained.


Improving the Diagnosis, Management, and Outcomes of Children with Pneumonia: Where are the Gaps?
Pneumonia is the greatest contributor to childhood mortality and morbidity in resource-poor regions, while in high-income countries it is one of the most common reasons for clinic attendance and hospitalization in this age group. Furthermore, pneumonia in children increases the risk of developing chronic pulmonary disorders in later adult life. While substantial advances in managing childhood pneumonia have been made, many issues remain, some of which are highlighted in this perspective. Multiple studies are required as many factors that influence outcomes, such as etiology, patient characteristics, and prevention strategies can vary between and within countries and regions. Also, outside of vaccine studies, most randomized controlled trials (RCTs) on pneumonia have been based in resource-poor countries where the primary aim is usually prevention of mortality. Few RCTs have focused on medium to long-term outcomes or prevention. We propose different tiers of primary outcomes, where in resource-rich countries medium to long-term sequelae should also be included and not just the length of hospitalization and readmission rates.


Kinematic comparison of baseball batting off of a tee among various competition levels.
Determining and understanding baseball batting mechanics at various competition levels may help players and coaches identify key kinematics crucial to being a successful hitter. The purpose of this study was to compare batting kinematics across competition levels. Kinematic and temporal data were analysed for 170 male batters (youth n = 33; high school n = 69; college n = 22; professional n = 46) using 3D motion capture (480 Hz). The results showed differences in angular positions between competition levels during the five phases of the swing, with the greatest differences seen between the youth and professional batters. At the instant of ball contact, professional batters held the bat farther away from their body, with greater back shoulder abduction (35°) and less back elbow flexion (78°) compared to youth (27° and 89°, respectively). These differences were associated with greater back elbow extension velocity for professionals (1539°/s) compared to youth (1174°/s). Additionally, higher level batters had higher bat angular and linear velocities compared to the youth batters. As batters progress through their career, they should focus on their back arm by keeping their elbow up and their arm extended in front of them.


Venous gangrene of the upper extremity.
Venous gangrene of the upper extremity is a rare entity and is the result of massive occlusion of all venous outflow of the extremity. The syndrome is strongly associated with hypercoagulable states including malignancy, low cardiac output states, and hereditary or acquired hematological abnormalities. Diagnosis can be straightforward but must be made early in the course of the process for treatment to be effective. Treatment has historically produced only modest results, and patients continue to suffer a high morbidity and mortality. We present a series of 6 patients with venous gangrene or impending venous gangrene of the upper extremities--a relatively large series. Two patients suffered from malignancy, 3 patients suffered from low-flow cardiac states, and 1 patient suffered from an overdose of calcium channel blockers. Hematological abnormalities included heparin-induced thrombocytopenia and thrombosis in 3 patients, activated protein C resistance in 1 patient, and lupus anticoagulant in 1 patient. Three patients experienced other major venous thrombotic complications, two of whom died (renal and cerebral venous infarction). Venous gangrene of the upper extremity remains a rare occurrence but one in which early identification and intervention may lead to improved outcomes.


Inter-rater reliability of the extended Composite Quality Score (CQS-2).
To establish the inter-rater reliability of the Composite Quality Score (CQS-2) and to test the null hypothesis that it did not differ significantly from that of the first CQS version (CQS-1). Four independent raters were selected to rate 45 clinical trial reports using CQS-1 and CQS-2. The raters remained unaware of each other's participation in this study until all rating had been completed. Each rater received only one rating template at a time in a random sequence for CQS-1 and CQS-2 rating. Raters completed each template and sent these back to the principal investigator. Each rater received their next template 2 weeks after submission of the completed previous template. The inter-rater reliabilities for the overall appraisal score of the CQS-1 and the CQS-2 were established by using the Brennan-Prediger coefficient (BPC). The coefficients of both CQS versions were compared by using the two-sample z-test. During secondary analysis, the BPCs for every criterion and each corroboration level for both CQS versions were established. The BPC for the CQS-1 was 0.85 (95% CI: 0.64-1.00) and for the CQS-2 it was 1.00 (95% CI: 0.94-1.00), suggesting a very high inter-rater reliability for both. The difference between the two CQS versions was statistically not significant (p = 0.17). The null hypothesis was accepted. The CQS-2 is still under development, This study shows that it is associated with a very high inter-rater reliability, which did not statistically significantly differ from that of the CQS-1. The promising results of this study warrant further investigation in the applicability of the CQS-2 as an appraisal tool for prospective controlled clinical therapy trials.


New methods for quantifying the spatial storage effect: an illustration with desert annuals.
Recent theory supports the long-held proposition that coexistence is promoted by species-specific responses to a spatially varying environment. The underlying coexistence mechanism, the spatial storage effect, can be quantified by the covariance between response to the environment and competition. Here, "competition" is generalized to encompass similar processes such as facilitation and apparent competition. In the present study, we use a model field system of desert annual plants to demonstrate this method and to provide insight into the dynamics of the field system. Specifically, we use neighborhood competition experiments to quantify the spatial storage effect and compare it to the separate (but not mutually exclusive) process of neighborhood-scale resource partitioning. As our basic experimental design has been used frequently in community ecology, these methods can be applied to many existing data sets, as well as future field studies.


Impact of in-home defibrillators on postmyocardial infarction patients and their significant others: an interview study.
To investigate the impact of automated external defibrillator (AED) placement in the homes of postmyocardial infarction (MI) patients and their significant others. This qualitative study used a semistructured interview to examine a nonrandomized convenience sample recruited from a larger study of home AEDs. Patients (and their significant others) were recruited from an ongoing study of AED use in the home. Seventeen interviews with 15 patients (14 men, 1 woman) and 16 significant others (1 man, 15 women) aged 39 to 80 years were performed in patients' homes. Verbatim transcripts of audiotaped interviews were reviewed, and responses were categorized. Other data were obtained from hospital chart abstraction. The majority of subjects noted only positive effects of the presence of home AEDs (eg, giving them feelings of security and control). There was no evidence that AED presence in the home caused excessive anxiety or stress either in patients or their significant others, nor were they perceived to cause relationship stress. On average, patients and their significant others estimated a 38% and 43% (respectively) risk of cardiac arrest and a 92% and 87% likelihood of a successful resuscitation with the use of the AED. Subjects' perceived risk of cardiac arrest were subjectively related to their estimate of current health status, size of infarction, and symptoms during their MI. Subjects also related their estimates of risk to their likelihood of traveling with their AED and whether they would consider purchasing one. Significant others had high confidence in their ability to properly use the AED. AEDs were valued highly by subjects and enhanced their perceived control over their heart disease. This was especially true for subjects who believed that their risk of cardiac arrest was high. The possible effects of providing education regarding expert estimates of the likelihood of cardiac arrest and of a successful resuscitation at the time of AED placement are discussed.


A case of new-onset rheumatoid vasculitis becoming evident in the course of treatment for Pneumocystis jirovecii pneumonia.
When patients with autoimmune diseases, such as rheumatoid arthritis (RA), are treated with potent immunosuppressive therapy, the risk of opportunistic diseases inevitably increases. If patients have the misfortune to suffer from both opportunistic and active autoimmune diseases, correct diagnosis could sometimes be difficult since both diseases have inflammatory nature. The choice of treatment is another challenge in that aggressive immunosuppressive therapy can fuel the opportunistic infection. Here we report a case of RA patient with new onset rheumatoid vasculitis that was diagnosed in the process of treatment of Pneumocystis jirovecii pneumonia.


A double-blind placebo-controlled trial of indobufen in the prophylaxis of migraine.
In a double-blind randomized trial of 42 patients with classic or common migraine, indobufen, an antiplatelet drug that inhibits platelet cyclo-oxygenase, was compared with placebo in the prevention of migraine. The duration of treatment was 3 months, and the efficacy was assessed on the basis of the following variables: frequency and duration of attacks, headache index (intensity x frequency); 35 completed the investigation. Indobufen at an oral dose of 200 mg b.i.d. reduced all the variables considered, where placebo did not. The drug was generally well tolerated. The findings of the preliminary trial suggest that indobufen might be an useful alternative in the prophylaxis of migraine.


Three-dimensional echocardiography vs. computed tomography for transcatheter aortic valve replacement sizing.
The accuracy of transcatheter aortic valve replacement (TAVR) sizing using three-dimensional transoesophageal echocardiography (3D-TEE) compared with the gold-standard multi-slice computed tomography (MSCT) remains unclear. We compare aortic annulus measurements assessed using these two imaging modalities. We performed a single-centre prospective cohort study, including 53 consecutive patients undergoing TAVR, who had both MSCT and 3D-TEE for aortic annulus sizing. Aortic annular dimensions, expected transcatheter heart valve (THV) oversizing, and hypothetical valve size selection based on CT and TEE were compared. 3D-TEE and CT cross-sectional mean diameter (r = 0.69), perimeter (r = 0.70), and area (r = 0.67) were moderately to highly correlated (all P-values <0.0001). 3D-TEE-derived measurements were significantly smaller compared with MSCT: perimeter (68.6 ± 5.9 vs. 75.1 ± 5.7 mm, respectively; P < 0.0001); area (345.6 ± 64.5 vs. 426.9 ± 68.9 mm(2), respectively; P < 0.0001). The percentage difference between 3D-TEE and MSCT measurements was around 9%. Agreement between MSCT- and 3D-TEE-based THV sizing (perimeter) occurred in 44% of patients. Using the 3D-TEE perimeter annular measurements, up to 50% of patients would have received an inappropriate valve size according to manufacturer-recommended, area-derived sizing algorithms. Aortic annulus measurements for pre-procedural TAVR assessment by 3D-TEE are significantly smaller than MSCT. In this study, such discrepancy would have resulted in up to 50% of all patients receiving the wrong THV size. 3D-TEE should be used for TAVR sizing, only when MSCT is not available or contraindicated. The clinical impact of this information requires further study.


Hepatitis B virus related membranous glomerulonephritis and proteinuria treated with lamivudine and tenofovir.
Membranous glomerulonephritis is the most common histological renal lesion associated with hepatitis B virus (HBV) infection. The authors describe here a case of a patient presenting with the nephrotic syndrome and HBV infection but without progressive liver disease. The use of lamivudine and tenofovir resulted in arrest of proteinuria and stabilisation of renal function.