Selective fasciculation and divergent pathfinding decisions of embryonic chick motor axons projecting to fast and slow muscle regions.
Proper motor function requires the precise matching of motoneuron and muscle fiber properties. The lack of distinguishing markers for early motoneurons has made it difficult to determine whether this matching is established by selective innervation during development or later via motoneuron-muscle fiber interactions. To examine whether chick motoneurons selectively innervate regions of their target containing either fast or slow muscle fibers, we backlabeled neurons from each of these regions with lipophilic dyes. We found that motor axons projecting to fast and slow muscle regions sorted into separate but adjacent fascicles proximally in the limb, long before they reached the muscle. More distally, these fascicles made divergent pathfinding decisions to course directly to the appropriate muscle fiber region. In contrast, axons projecting to different areas of an all-fast muscle did not fasciculate separately and became more intermingled as they coursed through the limb. Selective fasciculation of fast- and slow-projecting motoneurons was similar both before and after motoneuron cell death, suggesting that motoneurons specifically recognized and fasciculated with axons growing to muscle regions containing the appropriate muscle fiber type. Taken together, these results strongly support the hypothesis that "fast" and "slow" motoneurons are molecularly distinct before target innervation and that they use these differences to selectively fasciculate, pathfind to, and branch within the correct muscle fiber region from the outset of neuromuscular development.


Whole exome germline sequencing in early-onset prostate cancer patients: Genomic findings and clinical outcomes.
Whole exome sequencing (WES) furthered our understanding of various tumors. We assessed the occurrence of germline likely pathogenic/pathogenic (LP/P) variants, disease features, and clinical outcomes in early-onset prostate cancer. This retrospective study (N = 134) included consecutive prostate cancer patients who donated blood samples for research purposes to the Kahn-Sagol-Maccabi biobank. Patients diagnosed at >65 years were excluded. Clinical characteristics were extracted from the medical records. Germline WES was performed with analysis reporting on oncogenetic, two immunogenic, and a secondary minimum list panels (121, 468, 76, and 59 genes, respectively). Median age at diagnosis was 61 (range 46-65) years; 131 (98%) were diagnosed with local disease. The median follow-up time from diagnosis was 14 (range <1-25) years. Of the patients with local disease, 32 (24%) and 10 (8%) had biochemical and distant recurrences, respectively. Twenty-five patients (19%) had ≥1 additional cancer (excluding non-melanoma skin cancer), most frequently bladder (6), colorectal (5), and lymphoma (5). Seven (5%) deaths were reported, with only one related to prostate cancer. LP/P variants were identified in 8 patients (6%), all in genes from the oncogenetic panel: ATM, BRCA1 (in two patients), BRCA2 (in two patients), HOXB13, MUTYH, and MYH7. Of these eight patients, with a median follow-up of 7 years (range <1-15), two (25%) had biochemical recurrences, one had (12.5%) distant recurrence, and no deaths were reported. In this cohort of 134 early-onset prostate cancer patients, we identified germline LP/P variants in an oncogenetic panel in 6% of participants, with no unique clinical outcome.


Mechanistic modeling reveals the importance of turgor-driven apoplastic water transport in wheat stem parenchyma during carbohydrate mobilization.
During stem elongation, wheat (Triticum aestivum) increases its stem carbohydrate content before anthesis as a reserve for grain filling. Hydraulic functioning during this mobilization process is not well understood, and contradictory results exist on the direct effect of drought on carbohydrate mobilization. In a dedicated experiment, wheat plants were subjected to drought stress during carbohydrate mobilization. Measurements, important to better understand stem physiology, showed some unexpected patterns that could not be explained by our current knowledge on water transport. Traditional water flow and storage models failed to properly describe the drought response in wheat stems during carbohydrate mobilization. To explain the measured patterns, hypotheses were formulated and integrated in a dedicated model for wheat. The new mechanistic model simulates two hypothetical water storage compartments: one where water is quickly exchanged with the xylem and one that contains the carbohydrate storage. Water exchange between these compartments is turgor-driven. The model was able to simulate the measured increase in stored carbohydrate concentrations with a decrease in water content and stem diameter. Calibration of the model showed the importance of turgor-driven apoplastic water flow during carbohydrate mobilization. This resulted in an increase in stem hydraulic capacitance, which became more important under drought stress.


[Idiopathic collapsing glomerulopathy in children: report of two cases].
Idiopathic collapsing glomerulopathy (ICG) is a clinically and pathologically distinct variant of focal segmental glomerulosclerosis, which is characterized by proteinuria (often nephrotic range) and rapid progression to end-stage renal failure. The typical pathological changes are global/segmental glomerular collapse, hypertrophy and hyperplasia of podocytes and severe tubulointerstitial lesions. Most ICG patients who have been reported in previous published papers are adults. ICG in children is rare. The study aimed to analyze and investigate clinical manifestations, renal histopathological findings, treatment and outcomes of ICG in children. Data of two cases of ICG, a 7-year-old boy and a 12-year-old girl, were analyzed. Both of them were Chinese and Han. Clinical characteristics, results of laboratory tests, renal histopathological findings, treatment, outcomes and prognosis of the two children with ICG were retrospectively analyzed. Results were compared with published data. These two children presented typical clinical features of nephrotic syndrome. The quantity of 24 hr urine protein was 7.6 g/d (0.47 g/kg x d for boy) and 10.67 g/d (0.35 g/kg x d for girl). Both of them had hypertension (blood pressure ranged from 130/90 to 150/110 mmHg) and hypercholesterolemia (15.4 mmol/L for the boy and 11.3 mmol/L for the girl). The serum albumin was 12 g/L for girl and 23 g/L for boy. The creatinine clearance rate gradually decreased from normal range to 30 ml/min for the girl. The histopathological changes in renal biopsy of them were focal segmental or global glomerular collapse, hypertrophy and hyperplasia of podocytes and severe tubulointerstitial lesions. These two cases were steroid-resistant and were treated with pulse intravenous methylprednisolone and pulse intravenous cyclphosphamade in one case, who rapidly progressed to end-stage renal failure and died half a year later. Another one was treated with cyclosporine. He showed continuous hypertention and heavy proteinuria for eight months. ICG in the 2 children was a severe disease which presented steroid-resistant nephrotic syndrome and rapidly progressive renal failure. The pathological characteristics was global/segmental glomerular collapse, hypertrophy and hyperplasia of podocytes and severe tubulointerstitial lesions. In children with ICG treatment was difficult and the prognosis was poor.


New treatment modalities in osteoporosis.
To describe recently discovered agents for the management of osteoporosis. A literature review (PubMed search) was conducted to identify agents at various stages of development for osteoporosis treatment. Agents under study or review for approval were included. In menopause, bone remodeling is increased, and agents that suppress bone resorption can stabilize bone mass. In contrast, agents that target the osteoblast can increase bone formation and bone mass. Novel antiresorptive agents can target the formation or the activity of osteoclasts. They include denosumab, an antibody to receptor activated nuclear factor κB; new selective estrogen receptor modulators, such as bazedoxifene; and cathepsin K inhibitors, such as odanacatib. Src kinase inhibitors are in the early phases of development. Parathyroid hormone is the only approved anabolic agent for the treatment of osteoporosis. Novel anabolic therapies for osteoporosis may include the use of factors with anabolic properties for bone or the neutralization of growth factor antagonists. Recent discoveries have demonstrated that the Wnt/β-catenin signaling pathway has a central role in osteoblastic cell differentiation. Antibodies to Wnt antagonists, such as sclerostin, are under development as new therapeutic approaches for osteoporosis. Anabolic therapies have the potential to enhance bone mass, but their long-term safety must be proven. New developments in the treatment of osteoporosis include novel antiresorptive and anabolic agents. Their success will depend on their long-term effectiveness and safety profile.


Slice Management for Quality of Service Differentiation in Wireless Network Slicing.
Network slicing is a technology that virtualizes a single infrastructure into multiple logical networks (called slices) where resources or virtualized functions can be flexibly configured by demands of applications to satisfy their quality of service (QoS) requirements. Generally, to provide the guaranteed QoS in applications, resources of slices are isolated. In wired networks, this resource isolation is enabled by allocating dedicated data bandwidths to slices. However, in wireless networks, resource isolation may be challenging because the interference between links affects the actual bandwidths of slices and degrades their QoS. In this paper, we propose a slice management scheme that mitigates the interference imposed on each slice according to their priorities by determining routes of flows with a different routing policy. Traffic flows in the slice with the highest priority are routed into shortest paths. In each lower-priority slice, the routing of traffic flows is conducted while minimizing a weighted summation of interference to other slices. Since higher-priority slices have higher interference weights, they receive lower interference from other slices. As a result, the QoS of slices is differentiated according to their priorities while the interference imposed on slices is reduced. We compared the proposed slice management scheme with a naïve slice management (NSM) method that differentiates QoS among slices by priority queuing. We conducted some simulations and the simulation results show that our proposed management scheme not only differentiates the QoS of slices according to their priorities but also enhances the average throughput and delay performance of slices remarkably compared to that of the NSM method. The simulations were conducted in grid network topologies with 16 and 100 nodes and a random network topology with 200 nodes. Simulation results indicate that the proposed slice management increased the average throughput of slices up to 6%, 13%, and 7% and reduced the average delay of slices up to 14%, 15%, and 11% in comparison with the NSM method.


Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation.
Mycophenolate mofetil (MMF) has been widely used for prophylaxis against graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-SCT). However, no clear advantage over methotrexate has been reported, other than reduced incidence of mucositis. We speculated that the wide inter-individual variation of plasma mycophenolic acid (MPA) levels veiled the benefits of MMF. Data from 36 unrelated allogeneic bone marrow (allo-BMT) and cord blood transplantation (CBT) were analyzed retrospectively based on MPA area under the curve (AUC(0-24h)). In allo-BMT, high AUC(0-24h) (>30 μg h/ml) resulted in no incidence of grade II-IV acute/extensive chronic GVHD and tended to show higher overall and disease-free survival, lower relapse rates, and non-relapse mortality. In CBT, AUC(0-24h) less than 30 μg h/ml was sufficient for low incidence of acute/chronic GVHD and high survival. Strong correlation between AUC(0-24h) and C(2h), plasma MPA concentration at 2 h after administration was observed. Single point assessment of C(2h) was shown to provide a useful surrogate of AUC(0-24h) to predict GVHD incidence. The results of this study suggest that individualized MMF dosing in a donor source-dependent fashion may be important for maximizing the benefit of MMF in allo-SCT.


Update on therapy for chronic myelogenous leukemia.
Chronic myelogenous leukemia is a clonal disorder of hematopoietic stem cells characterized by granulocytic leukocytosis, splenomegaly, and a specific chromosomal abnormality, the Philadelphia chromosome. Treatment options include the oral agents hydroxyurea or busulfan, subcutaneous interferon-alpha, and bone marrow transplantation. The recent publication of some large, randomized trials and the increased availability of bone marrow transplantation are changing the therapeutic approach to chronic myelogenous leukemia. This paper reviews these recent studies on the management of chronic myelogenous leukemia.


Vascular endothelial growth factor-a promotes peritumoral lymphangiogenesis and lymphatic metastasis.
Metastases are commonly found in the lymphatic system. The molecular mechanism of lymphatic metastasis is, however, poorly understood. Here we report that vascular endothelial growth factor (VEGF)-A stimulated lymphangiogenesis in vivo and that overexpression of VEGF-A in murine T241 fibrosarcomas induced the growth of peritumoral lymphatic vessels, which occasionally penetrated into the tumor tissue. As a result of peritumoral lymphangiogenesis, metastases in lymph nodes of mice were detected. VEGF-A-overexpressing tumors contained high numbers of infiltrating inflammatory cells such as macrophages, which are known to express VEGF receptor (VEGFR)-1. It seemed that in the mouse cornea, VEGF-A stimulated lymphangiogenesis through a VEGF-C/-D/VEGFR-3-independent pathway as a VEGFR-3 antagonist selectively inhibited VEGF-C-induced, but not VEGF-A-induced, lymphangiogenesis. Our data show that VEGF-A contributes to lymphatic mestastasis. Thus, blockage of VEGF-A-induced lymphangiogenesis may provide a novel approach for prevention and treatment of lymphatic metastasis.


Multiple opportunistic infections after high-dose steroid therapy for giant cell arteritis in a patient previously treated with a purine analog.
We present the case of a 74-y-old HIV-negative female who suffered simultaneously from multiple opportunistic infections and a Klebsiella pneumoniae sepsis during high-dose steroids for giant cell arteritis. The patient was treated with a purine analog due to hairy cell leukaemia 10 y previously. Purine analog therapy can lead to long lasting defects in cell-mediated immunity. In these patients, treatment with steroids should be closely monitored with CD4 counts.


Normal calcitonin response to pentagastrin stimulation in patients with chronic renal failure.
High calcitonin levels have been reported in chronic renal failure. To study the C cell response in patients with chronic renal failure, an intravenous bolus of pentagastrin was administered to 11 patients and 11 healthy subjects. Samples were obtained at 0, 1, 2, 3, 5 and 10 min for calcitonin assay. In order to detect only the active monomeric calcitonin, an immunoradiometric assay method was used. The influence of calcium, phosphate, alkaline phosphatase and intact parathyroid hormone was also evaluated. Although basal calcitonin levels were higher (p < 0.01) in chronic renal failure (mean +/- SEM: 10.1 +/- 2.9 pmol/l) versus healthy subjects (1.1 +/- 0.3 pmol/l), the area under the curve showed there to be no differences between the two groups. The rising branch of the area under the curve, employed as an expression of the C cell response capacity, showed no differences either (chronic renal failure vs healthy subjects: 5.6 +/- 2 vs 2.6 +/- 0.7 pmol l-1 min-1, p = 0.28). In the chronic renal failure group, a positive correlation was found (r = 0.625, p < 0.05) between the rising branch of the area under the curve and parathyroid hormone. We conclude that monomeric calcitonin is increased in chronic renal failure, but C cells of the thyroid respond to pentagastrin, as they do in normal subjects. This finding is of great clinical importance when a patient with renal impairment is evaluated for medullary thyroid carcinoma. The calcitonin response to pentagastrin seems to be related directly to the degree of secondary hyperparathyroidism in chronic renal failure.


Comparison study of transoral robotic surgery and radical open surgery for hypopharyngeal cancer.
The oncologic outcome of transoral robotic surgery (TORS) was comparable to radical open surgery. The TORS group showed a better functional recovery and quality of life (QOL) than the radical surgery group. Therefore, TORS was a valid treatment option as a minimally invasive surgery for selected patients with hypopharyngeal cancer. To affirm rapid functional recovery and improved QOL of patients who underwent TORS, which is a minimally invasive surgical technique. Between April 2008 and November 2011, 56 patients were enrolled in the study. During the study period, 30 patients underwent TORS and 26 patients underwent radical open surgery. In the TORS and radical surgery groups, the 3-year overall survival rate was 85% and 78%, respectively, and disease-free survival was 81% and 76%, respectively. Significant differences were not observed in the overall survival and disease-free survival rates. As regards postoperative functional recovery, the TORS group showed statistically better results for decannulation, swallowing, and hospitalization compared with the radical surgery group. On the University of Washington (UW)-QOL, the TORS group showed better results than the radical open surgery group in the domains of pain, activity, recreation, swallowing, speech, anxiety, and health-related QOL.


Primary and secondary prevention of heart failure with statins.
Statins are effective in the prevention of coronary heart disease (CHD), a leading cause of heart failure (HF). Secondary analyses from 11 randomized clinical trials of patients with high-risk acute or stable coronary heart disease, but without HF, suggest that statins may prevent new-onset HF or HF-related hospitalization. In persons with established HF, several cohort studies found an approximate 35% relative risk reduction in all-cause mortality. While ongoing randomized clinical trials will help to determine the efficacy of statins in persons with established HF, it is reasonable to consider this class of medications in patients with a history of cardiovascular disease, dyslipidemia or diabetes mellitus, and who have either developed, or who remain at risk of, HF.


[Graft versus host reaction in an infant with DiGeorge syndrome].
An infant with complete DiGeorge syndrome was treated with blood transfusions and fresh frozen plasma because of severe septicemia and anemia. 9 weeks after the first transfusion and 2 weeks after administration of fresh frozen plasma he died of acute graft-versus-host disease. The blood products were routinely irradiated with 25 gray, the fresh frozen plasma was not irradiated. The diagnosis of GvHD was confirmed on autopsy. All cellular blood products including fresh frozen plasma which are used in the treatment of immuno-deficient patients have to be irradiated to avoid GvHD. Currently 50 gray are recommended.


Impact of new technologies and experience on procedural aspects of surgical aortic valve replacement - a process analysis.
Surgical aortic valve replacement (SAVR) is the treatment of choice in severe symptomatic aortic valve disease. New techniques and prostheses have been recently developed to facilitate the procedure and reduce aortic cross-clamp time (AOx). The aim of this study was to analyse the different procedural steps in order to identify the most time-consuming part during aortic clamping time and to compare impact of experience on procedural aspects. AOx during SAVR was divided into five consecutive steps. Duration of each step was measured. The first procedural step started with clamping of the aorta and ended with the beginning of the second step starting with the resection of the native aortic valve. The third step started with placement of the first valve anchoring suture, the fourth step started with tying of the first suture and the fifth and final step started after the cut of the last suture and ended with removal of the aortic clamp. Surgeons were divided into two groups based on their experience, which in our analysis was defined as a total SAVR experience of more than 100 procedures. From March 2013 to August 2015 57 nonconsecutive patients (33% female; age, median 71.0 years, interquartile range 65.0-76.0) undergoing isolated SAVR for severe aortic valve stenosis in our institution were included in this process analysis. Two different prostheses were implanted. Forty-eight (84%) patients received a tissue valve (Perimount Magna Ease, Edwards Lifesciences, Irvine, USA) and 9 (16%) patients received a mechanical prosthesis (Medtronic AP 360, St-Paul, MN, USA). The mean estimated risk of mortality was 1.1% (0.7-1.6) according to the logistic EUROScore II. Overall duration of AOx was 50.5 ± 13.8 min, with 32.3% (16.4 ± 5.9 min) accounting for placing the sutures into the native annulus and the prosthetic sewing ring and 18.5% (9.2 ± 3.0min) accounting for tying and cutting the sutures. Surgeons with more experience performed 35 operations (61.4%) and needed an average of 44.1 ± 11.5 min versus 60.6 ± 11.0 min (p <0.001) for less experienced surgeons. Surgeons with more experience needed 14.0 ± 5.0 min for the suturing step and 8.4 ± 2.8 min for tying the sutures compared with 20.2 ± 5.2 min and 10.5 ± 3.0 min, respectively, for the less experienced surgeons with (p <0.001 and p = 0.010). Placing and tying sutures in the prostheses accounts for over half (50.8%) of AOx during isolated SAVR. Experienced surgeons have significantly reduced AOx. This shortening is equally distributed between all five procedural steps.


Zinc Photocages with Improved Photophysical Properties and Cell Permeability Imparted by Ternary Complex Formation.
Photocaged complexes can control the availability of metal ions to interrogate cellular signaling pathways. We describe a new photocage, {bis[(2-pyridyl)methyl]amino}(9-oxo-2-xanthenyl)acetic acid (XDPAdeCage, 1), which utilizes a 2-xanthone acetic acid group to mediate a photodecarboxylation reaction. XDPAdeCage photolyzes with a quantum yield of 27%, and binds Zn2+ with 4.6 pM affinity, which decreases by over 4 orders of magnitude after photolysis. For comparison to our previous approach to Zn2+ release via photodecarboxylation, the analogous photocage {bis[(2-pyridyl)methyl]amino}(m-nitrophenyl)acetic acid (DPAdeCage, 2), which uses a m-nitrobenzyl chromophore, was also prepared and characterized. The advantages of the 2-xanthone acetic acid chromophore include red-shifted excitation and a higher extinction coefficient at the preferred uncaging wavelength. The neutral ternary complex of [Zn(XDPAdeCage)]+ with the anionic ligand pyrithione is membrane permeable, which circumvents the need to utilize invasive techniques to introduce intracellular Zn2+ fluctuations. Using fluorescent imaging, we have confirmed transport of Zn2+ across membranes; in addition, RT-PCR experiments demonstrate changes in expression of Zn2+-responsive proteins after photolysis.


The burden of normality as a model of psychosocial adjustment after deep brain stimulation for Parkinson's disease: A systematic investigation.
Deep brain stimulation (DBS) has become a well-established treatment that significantly improves the motor symptoms of Parkinson's disease (PD). Patients may nevertheless experience psychosocial maladjustment after surgery, as reported by an increasing body of research. Yet, no comprehensive theoretical approach has been proposed to account for this. Initially conceptualized for postsurgical epilepsy, the burden of normality (BoN) may be viewed as a model that is potentially applicable to psychosocial maladjustment after PD-DBS. We systematically examined the literature to verify this assumption by scrutinizing the 3 theoretical levels of the BoN, specifically, precursory conditions for the applicability of the model, clinical manifestations of psychosocial maladjustment, and 2 mediating variables: expectations and discarding the roles associated with the pretreatment condition. The applicability of the BoN to PD-DBS found support for the first 2 of these 3 levels in 88 scientific articles included in the review. The number of studies that addressed the mediating variables was nevertheless insufficient to draw any definitive conclusion. The degenerative condition of PD further limits the distinction between symptoms pertaining to psychosocial maladjustment and disease progression. Considering psychosocial maladjustment through the lens of the BoN is complementary to the traditional medical perspective of PD-DBS and illuminates the potential contribution of specialists from multiple disciplines in clinical rehabilitation. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Oral health of individuals with cerebral palsy in Saudi Arabia: A systematic review.
This systematic review aimed to comprehensively summarize and critically assess studies conducted on oral health outcomes among individuals with cerebral palsy (CP) in Saudi Arabia. This study followed the Participants, Exposure, Control and Outcomes (PECO) framework to formulate a focused research question. We conducted an extensive literature search across multiple databases, including PubMed, Medline, Scopus and Embase, in addition to clinical trial registers. Inclusion criteria encompassed clinical studies conducted in either English or Arabic, focusing on CP as defined by the International Classification of Diseases 10 (ICD10), and examining various oral health conditions and parameters. Nonclinical studies, commentaries, other systematic reviews and letters to the editor were excluded. Data extraction included comprehensive information about the study characteristics, oral health outcomes (dental, oral or periodontal disease; changes in standardized indices; dental trauma and other types of oral diseases) and an assessment of the risk of bias using the Appraisal Tool for Cross-Sectional Studies (AXIS). The initial search yielded a total of 879 articles, ultimately resulting seven studies that met our stringent inclusion criteria. All of these studies were conducted as cross-sectional investigations in different cities within Saudi Arabia. The sample sizes ranged from 46 to 400 participants, all falling within the age range of 2-18 years. Notably, the prevalence of dental caries among individuals with CP in these studies varied significantly, with rates ranging from 52.9% to as high as 98.6%. Additionally, a substantial portion of CP patients exhibited poor oral hygiene, with figures ranging between 34.6% and 66.2%, and dental trauma was reported in 47.5% of the cases. Moreover, these studies underscored the influence of motor function and intellectual disabilities on the oral health status of CP individuals. Furthermore, various secondary outcomes, including periodontal parameters and oral health-related quality of life, were also assessed. However, it is essential to acknowledge that several sources of bias were identified within these studies, raising questions about the generalisability of their findings. In conclusion, the systematic review revealed a concerning pattern of high dental caries prevalence and other oral health issues among individuals with CP in Saudi Arabia. Nevertheless, the need for comparative studies between CP patients and those without CP is evident to establish a definitive understanding of the oral health status of CP individuals. Initiating early interventions such as oral hygiene education, preventive dentistry programs, and orthodontic interventions could potentially contribute to improved oral health outcomes for individuals with CP in Saudi Arabia.


Transvaginal Ultrasound for Endometrial Carcinoma Screening - Current Evidence-based Data.
The value of transvaginal ultrasound in gynaecological examinations is beyond dispute. But it is of particular forensic importance that the validity of this type of imaging with regard to the reliable detection of early-stage malignancy is properly understood. Vaginal ultrasound screening in asymptomatic patients for the early detection of endometrial carcinoma is not useful from a medical point of view, nor is it cost-efficient. However, even though the validity of transvaginal ultrasound for screening has currently not been proven, the method should still be an integral part of gynaecological examinations.


The use of nasal allergen vs allergen exposure chambers to evaluate allergen immunotherapy.
Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment option for allergic rhinitis (AR) patients with persistent moderate-severe AR for whom traditional pharmacotherapies are ineffective. The nasal allergen challenge (NAC) and allergen exposure chamber (AEC) are two translational models of AR that can be used to investigate the properties, safety, and efficacy of AIT. Peer-reviewed, human-centered articles utilizing AEC or NAC models to investigate AIT between 2010 and 2020 were curated from PubMed, EMBASE, and OVID Medline databases. AECs have been used to evaluate traditional subcutaneous and sublingual administrations of AIT, including cross-protective effects and different dosing regimens. More recently, the effectiveness of novel AIT formulations has been evaluated. NACs are another model used to study AIT, including using novel intralymphatic routes of administration. It is an especially powerful and versatile tool to determine if basic science and animal model findings are clinically translatable. The AEC and NAC models both produce clinically relevant and reproducible results. AECs are more effective for studying many participants but are limited because they require a specialized facility. As more AIT therapies and new formulations are developed over time, the versatility of the NAC will be especially useful.


Case-control comparison of at-home to total hospital care for autologous stem-cell transplantation for hematologic malignancies.
One of the most significant limitations of at-home autologous stem-cell transplantation (ASCT) is the necessity for hospital readmission. We developed an at-home ASCT program in which prophylactic ceftriaxone and treatment of febrile neutropenia with piperacillin and tazobactam was introduced to minimize the readmission rate. Between November 2000 and February 2005, 178 consecutive patients underwent ASCT for a hematologic malignancy. Of these, 50 patients fulfilled the requirements for at-home ASCT. Results were compared with those observed in a control group of 50 patients individually matched to the group of patients treated at home for age, sex, diagnosis, stage of disease, conditioning, and source of stem cells. Febrile neutropenia occurred in fewer patients in the at-home group as compared with the hospitalized group (76% v 96%: P = .008), and duration of fever was also shorter in the at-home group (median, 2 and 6 days, respectively; range, 1 to 11 and 1 to 20 days, respectively; P = .00003). Hospital readmission in the at-home group was required in only four cases (8%). This resulted in a reduction of 18.6 days of hospitalization per patient. Likewise, total median charges were approximately half in the at-home group as compared with the in-hospital group (3,345 euro v 6,250 euro, respectively; P < .00001). Results of at-home ASCT with prophylactic administration of ceftriaxone and domiciliary treatment of febrile neutropenia with piperacillin and tazobactam are highly satisfactory and significantly cheaper compared with those obtained with conventional in-hospital ASCT.


Discovery of novel curcumin derivatives targeting xanthine oxidase and urate transporter 1 as anti-hyperuricemic agents.
A series of curcumin derivatives as potent dual inhibitors of xanthine oxidase (XOD) and urate transporter 1 (URAT1) was discovered as anti-hyperuricemic agents. These compounds proved efficient effects on anti-hyperuricemic activity and uricosuric activity in vivo. More importantly, some of them exhibited proved efficient effects on inhibiting XOD activity and suppressing uptake of uric acid via URAT1 in vitro. Especially, the treatment of 4d was demonstrated to improve uric acid over-production and under-excretion in oxonate-induced hyperuricemic mice through regulating XOD activity and URAT1 expression. Docking study was performed to elucidate the potent XOD inhibition of 4d. Compound 4d may serve as a tool compound for further design of anti-hyperuricemic drugs targeting both XOD and URAT1.


Structure of the Ambrosia Beetle (Coleoptera: Curculionidae) Mycangia Revealed Through Micro-Computed Tomography.
Ambrosia beetles (Coleoptera: Curculionidae: Scolytinae and Platypodinae) rely on a symbiosis with fungi for their nutrition. Symbiotic fungi are preserved and transported in specialized storage structures called mycangia. Although pivotal in the symbiosis, mycangia have been notoriously difficult to study, given their minute size and membranous structure. We compared the application of novel visualization methods for the study of mycangia, namely micro-computed tomography (micro-CT) and laser ablation tomography (LATscan) with traditional paraffin sectioning. Micro-CT scanning has shown the greatest promise in new organ discovery, while sectioning remains the only method with sufficient resolution for cellular visualization. All three common types of mycangia (oral, mesonotal, and pronotal) were successfully visualized and presented for different species of ambrosia beetles: Ambrosiodmus minor (Stebbing) 1909, Euplatypus compositus (Say) 1823, Premnobius cavipennis Eichhoff 1878, Scolytoplatypus raja Blandford 1893, Xylosandrus crassiusculus (Motschulsky) 1866 and X. amputatus (Blandford) 1894. A reconstruction of the mycangium and the surrounding musculature in X. amputatus is also presented. The advantages of micro-CT compared to the previously commonly used microtome sectioning include the easy visualization and recording of three-dimensional structures, their position in reference to other internal structures, the ability to distinguish natural aberrations from technical artifacts, and the unprecedented visualizations of the anatomic context of mycangia enabled by the integrated software.


Preconception telomere length as a novel maternal biomarker to assess the risk of spina bifida in the offspring.
Periconception interactions between maternal conditions and environmental and genetic factors are involved in the pathogenesis and prevention of neural tube defects (NTD), such as spina bifida. These factors have in common that they can impair the oxidative pathway, resulting in excessive (chronic) oxidative stress and inflammation. Review of the literature concerning underlying mechanisms and biomarkers of aging particularly during reproduction. A number of molecular markers for biological aging have been identified, including telomere length (TL). Excessive telomere shortening is an index of senescence, causes genomic instability and is associated with a higher risk of age-related diseases. Furthermore, TL shortening is associated with the similar environmental and lifestyle exposures associated with NTD risk. Embryonic mice deficient in the telomerase gene show shorter TL and failure of closure of the neural tube as the main defect, suggesting that this developmental process is among the most sensitive to telomere loss and chromosomal instability. From this background, we hypothesize that preconceptional long term exposure to harmful environmental and lifestyle risk factors accelerates a woman's aging process, which can be measured by TL, and thereby her underlying risk of NTD offspring. Alternatively, it might be that women with an increased NTD risk already exhibit a more advanced biological age before the onset of pregnancy compared to women of identical calendar age.


Ultrahigh Resolution Titanium Deep Reactive Ion Etching.
Titanium (Ti) represents a promising new material for microelectromechanical systems (MEMS) because of its unique properties. Recently, this has been made possible with the advent of processes that enable deep reactive ion etching (DRIE) of high-aspect-ratio (HAR) structures in bulk Ti substrates. However, to date, these processes have been limited to minimum feature sizes (MFS) ≥750 nm. Although this is sufficient for many applications, MFS reduction to the deep submicrometer range opens potential for further device miniaturization and an opportunity for endowing devices with unique functionalities that are derived from precisely defined structures within this length scale regime. Herein, we report results from studies seeking to create means for realizing such opportunities through extension of Ti DRIE to the deep submicrometer scale. The effects of key process parameters on etch performance were investigated, and the understanding gained from these studies formed the development of a new ultrahigh resolution (UHR) Ti DRIE process. Using this process, we demonstrate, for the first time, fabrication of HAR structures in bulk Ti substrates with 150 nm MFS, smooth vertical sidewalls (88°), good etch rate (587 nm/min), and mask selectivity (11.1). This represents a fivefold or greater improvement in MFS relative to our previously reported processes and a 29-fold or greater improvement over more recent processes reported by others. As such, the UHR Ti DRIE process extends the state-of-the-art considerably, and it opens important new opportunities for Ti MEMS, particularly in the implantable medical device realm.


[Differential diagnostic value of real-time tissue elastography and three dimensional ultrasound imaging in breast lumps].
To investigate the real-time tissue elastography and 3D contrast-enhanced ultrasonography(CEUS) in breast lumps differential diagnostic value. A total of 126 patients (180 lumps) with breast mass were retrospectively analyzed from December 2012 to December 2014 in Tumor Hospital Affiliated To Xinjiang Medical University.All patients were divided into three groups by using stratified random method.Each group was detected by real-time tissue elastography, 3D CEUS and two joint inspection.Each group of 42 cases (60 lumps) was confirmed by the pathological results as gold standard.Diagnostic sensitivity, specificity and coincidence rate of different methods were compared. The benign masses of ultrasound contrast showed the punctate, linear and nodular enhancement, and the border of enhancement was smooth.The malignant tumors were mainly dominated by uneven and high enhancement. There was no statistical difference in sensitivity, specificity and coincidence rate between elastography group and 3D CEUS group (64.7% vs 73.5%, 69.2% vs 76.9%, 66.7% vs 75.0%, all P>0.05). The sensitivity, specificity and coincidence rate of two joint inspection group were higher than those of elastography group and 3D CEUS group, the differences were statistically significant (97.1%, 92.3% and 98.3% , all P<0.05). 3D CEUS combined with real-time tissue elastography is of high value in the diagnosis of breast masses.


Perfusion bioreactor for small diameter tissue-engineered arteries.
A scaleable perfusion bioreactor has been developed for tissue engineering of small diameter arterial constructs. This modular bioreactor allows for dynamic sequential seeding of smooth muscle and endothelial cells, biomechanical stimulation of cells during culture, and monitoring of tissue growth and maturation. Bovine aortic smooth muscle and endothelial cells were seeded onto porous tubular poly(glycolic acid) nonwoven scaffolds and cultured in the bioreactor under pulsatile flow conditions for up to 25 days. Cell proliferation was more than 3-fold after 4 days, smooth muscle cells expressed differentiated phenotype after 16 days, and collagen and elastin were distributed throughout the construct after 25 days of culture. In bioreactor experiments in which the construct lumen was seeded with endothelial cells by perfusion after 13 days of smooth muscle cell culture, endothelial cell seeding efficiency was 100%, and a confluent monolayer was observed in the lumen within 48 h. These data demonstrate that this perfusion bioreactor supports sequential seeding of constructs with smooth muscle and endothelial cells. Dynamic culture under pulsatile flow leads to cellular expression of differentiated function and extracellular matrix deposition toward the development of tissue-engineered arterial constructs.


Development in the number of clinical trial applications in Western Europe from 2007 to 2015: retrospective study of data from national competent authorities.
To investigate the development in the number of applications for authorisation of clinical trials of medicines (CTAs) submitted annually to national competent authorities in 10 Western European member states of the European Union from 2007 to 2015. Registry study. Data from national competent authorities. Germany, Italy, Spain, France, the UK, Belgium, the Netherlands, Austria, Denmark and Sweden. Inclusion criteria were Western European member states of the European Union, receiving more than 200 CTAs per year. Summarised number of CTAs and distribution of CTAs by type of sponsor (commercial or non-commercial) and trial phase (I-IV). Average annual growth rates (AAGRs) based on linear regressions. Data were evaluated 2007-2011 and 2012-2015 to compare findings with the European Commission's statement of a 25% decrease in CTAs in the EU from 2007 to 2011. From 2007 to 2011, the summarised number of CTAs decreased significantly (AAGR -3.9% (p=0.02)), primarily due to a decrease in commercially sponsored CTAs. From 2012 to 2015, the change was insignificant (AAGR 2.6% (p=0.27)), however with a 10% increase from 2014 to 2015 after stagnation from 2012 to 2014. Overall, the number of CTAs and distribution by type of sponsor varied considerably between countries. No distinct trends were observed when evaluating CTAs by type of trial phase. This study found a significant decrease in the number of CTAs in Western Europe from 2007 to 2011 (AAGR -3.9%). This development is possibly attributable to several factors such as the European Clinical Trials Directive, national and local political decisions, and a potential global shift in clinical trial activity. From 2014 to 2015, the number of CTAs increased markedly (10%). However, it is yet too soon to determine if this constitutes a transient fluctuation or a new trend.


Increase of cytosolic phospholipase A2 as hydrolytic enzyme of phospholipids and autism cognitive, social and sensory dysfunction severity.
Autism is neurodevelopmental disorder that is characterized by developmental, behavioral, social and sensory abnormalities. Researchers have focused in last years in immunological alteration and inflammation as a hot subject in autism field. This work aims to study the alteration in phospholipids (PE, PS, and PC) together with the change in cPLA2 concentration as the main phospholipid hydrolytic enzyme in autistic patients compared to control. It was also extended to find a correlation between these biomarkers and severity of autism measured as childhood autism rating scale (CARS), Social responsiveness scale (SRS), and Short sensory profile (SSP). Phospholipids (PE, PS, PC) and cPLA2 as biochemical parameters were determined in the plasma of 48 Saudi autistic male patients, categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS), social responsiveness scale (SRS) and short sensory profile (SSP) and compared to 40 age- and gender-matched control samples. The reported data demonstrate significantly lower levels of PE, PS, and PC together with a significant increase in cPLA2. While association between severity of autism and impaired phospholipid concentration was completely lacked, an association between cPLA2 and impaired sensory processing was observed. The impaired phospholipid level and remarkable increased in cPLA2 concentration asserted their roles in the etiology of autism. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of clinical symptoms and provide significant guidance for future therapeutic strategy to re-establish physiological homeostasis.


Analysis of neuroleptic binding affinities and potencies for the different human D2 dopamine receptor missense variants.
Neuroleptics, or antipsychotics, are widely used for the treatment of psychotic symptoms such as hallucinations and delusions in schizophrenia and other psychiatric disorders. Pharmacotherapy of these diseases is frequently complicated by a great variability in the clinical response to neuroleptics and by the development of serious and potentially life-threatening side-effects. Brain D2 dopamine receptors are one of the major targets of neuroleptic treatment. The human D2 dopamine receptor (DRD2) gene has three variants predicting the amino acid substitutions Ser311Cys, Pro310Ser and Val96Ala in the receptor protein. We show that several typical and atypical neuroleptics commonly used in the treatment of psychotic disorders have differences in binding affinities and potencies for the D2 dopamine receptor variants. Functional differences between dopamine receptor variants might be related to genetically determined differences in response to neuroleptic treatment.


Laparoscopic Revision of Ventriculoperitoneal Shunts in Pediatric Patients May Result in Fewer Subsequent Peritoneal Revisions.
Ventriculoperitoneal shunts (VPSs) are the mainstay of treatment of hydrocephalus but frequently need revision. We sought to directly compare the impact of laparoscopic versus open peritoneal shunt revision on the need for subsequent VPS revisions in pediatric patients. A prospectively maintained, externally validated database of pediatric patients who underwent a first peritoneal VPS revision at a single center between 2008 and 2016 was reviewed. Outcomes, including subsequent revisions, shunt infections, operative time, and hospital stay between open and laparoscopic groups, were compared. A total of 148 patients underwent a first peritoneal VPS revision during the time period-40 laparoscopically and 108 open-with no significant difference in age or gender between the groups. Operative time, length of stay after shunt revision, and shunt infection rates did not vary between laparoscopic versus open revisions. There was no significant difference between need for subsequent overall (peritoneal or ventricular) shunt revisions in the laparoscopic (20%) versus the open group (34%), P = .07. However, there were significantly fewer frequent peritoneal revisions in the laparoscopic group (3% versus 15%, P = .04). This first cohort analysis of laparoscopic versus open VPS revision in pediatric patients suggests that laparoscopic peritoneal VPS revision may reduce the rate of subsequent peritoneal revisions without increasing shunt infections or operative time in pediatric patients.


Household food insecurity during pregnancy as a predictor of anthropometric indices failures in infants aged less than 6 months: a retrospective longitudinal study.
To investigate the impact of household food insecurity during the third trimester of pregnancy on the growth indicators of infants aged less than 6 months. Retrospective longitudinal study. 137 healthcare centres (15 cities) in Khorasan Razavi province, Iran. Data were extracted from the Sina Electronic Health Record System (SinaEHR®). This study was conducted on 2481 mother and infant dyads during November 2016-March 2019. The Household Food Insecurity Access Scale (nine-item version) was used to measure food insecurity in the third trimester of pregnancy. Women who delivered singleton infants were included in the study, and anthropometric indices of infants were measured throughout the first 6 months of life. Approximately 67 % of the participants were food secure, while 33 % had varying degrees of food insecurity. The children born to the mothers in the food-insecure households were, respectively, 2·01, 3·03, and 3·83 times more likely to be stunted at birth (95 % CI 1·17, 3·46), 4 months (95 % CI 1·21, 7·61) and 6 months of age (95 % CI 1·37, 10·68) compared to their counterparts in the food-secure households. However, there were no significant differences in mean birth weight, birth height and head circumference at birth between the two groups. Household food insecurity during pregnancy is a risk factor for stunting in infants aged less than 6 months. Therefore, national nutrition programs could considerably support women in food-insecure households during and before pregnancy.


A FUS-LATS1/2 Axis Inhibits Hepatocellular Carcinoma Progression via Activating Hippo Pathway.
The roles and related mechanisms of RNA binding protein FUS (fused in sarcoma/translocated in liposarcoma) are unclear in numerous cancers, including hepatocellular carcinoma (HCC). Quantitative reverse transcription PCR (qRT-PCR), western blot, cell viability, transwell migration and invasion, tumor spheres formation and in vivo tumor formation assays were used to examine the effects of FUS on HCC progression in HuH7 and MHCC97 cells. Additionally, transcriptome analysis based on RNA-sequencing data, qRT-PCR, western blots, luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays were used to explore the LATS1/2 (large tumor suppressor kinases 1/2)-related mechanisms contributing to FUS functions. Finally, qRT-PCR and western blot analysis were used to detect the levels of FUS and LATS1/2 in HCC and adjacent normal tissues, and the correlation between them in HCC tissues. Overexpression of FUS decreased cell viability, migration, invasion and stemness. Moreover, FUS interacted and stabilized LATS1/2 stability, and thus promoted LATS1/2 expression and activated Hippo pathway. Finally, FUS and LAST1/2 levels were positively correlated and significantly down-regulated in HCC tissues. We demonstrate that FUS/LATS1/2 axis inhibits HCC progression via activating Hippo pathway.


Crotofolane-Type Diterpenoids: Crotocascarins R-V, Rearranged Trinorcrotofolane: Crotocascarin δ and a Phorbol Derivative from the Leaves of Croton cascarilloides.
Five new crotofolanes, named crotocascarins R-V (1-5), one rearranged trinorcrotofolane, crotocascarin δ, and one phorbol derivative were isolated from the EtOAc-soluble fraction of the MeOH extract of the leaves of Croton cascarilloides. Crotocascarins R (1), T (3), and U (4) possessed isobutyric acid as an acyl moiety and crotocascarin B (2) an acetyl group, whereas crotocascarin V (5) was elucidated to be a hydroxylated compound of crotocascarin K at the 9-position. Crotocascarin δ (6) was a trinor rearranged crotofolane with a tertiary hemiketal functional group at the 8-position. The absolute configuration of the 8-position was determined by the comparison of the experimental electronic circular dichroism (ECD) spectrum and calculated ECD spectra. Compound 7 was a phorbol ester derivative with a peroxide functional group. The fatty acid attached at the 12-position was found to be a single species-i.e., lauric acid (C-12)-from the evidence of the mass spectral data.


The perioperative role of the neurosurgical service coordinator.
At one institution, the development of a position of Neurosurgical Service Coordinator was implemented to expedite the neurosurgical procedures in the operating room. The position required a registered nurse experienced in the field of neurosurgical nursing, who could schedule surgical cases, train personnel, manage budgetary requests, and coordinate a department of 10 neurosurgeons performing 1,500 cases annually.


Optimizing therapy of seizures in women who use oral contraceptives.
There is no evidence that oral contraceptives (OCs) increase seizure activity, and OC use in the setting of antiepileptic drug (AED) treatment provides pregnancy prevention at among the highest rates of any available contraceptive method. One concern, however, is the increased risk for OC failure with the use of cytochrome P450 3A4 enzyme-inducing AEDs, such as phenobarbital, carbamazepine, phenytoin, felbamate, topiramate, and oxcarbazepine. Felbamate induces metabolism of only the progestogenic component, whereas topiramate induces metabolism of only the estrogenic component. There is preliminary evidence that lamotrigine induces the metabolism of a progestin, levonorgestrel. It is unclear whether the estrogenic or the progestogenic component is more clinically important in preventing pregnancy. To ensure maximal pregnancy prevention, it is therefore recommended that women taking enzyme-inducing AEDs should receive OCs containing at least 50 mug of ethinyl estradiol and that low-dose formulations in general should not be used. AEDs that do not induce cytochrome P450 3A4 enzymes, including valproic acid, gabapentin, levetiracetam, tiagabine, vigabatrin, zonisamide, and pregabalin, do not interact with OCs. There are no concerns regarding the treatment of seizures or increased pregnancy risk with the use of OCs and these non-enzyme-inducing AEDs. Lamotrigine levels, however, are reduced by 50% in the setting of OC use. Therefore, women with epilepsy taking lamotrigine need to be monitored carefully for seizures when OCs are started and for toxicity when OCs are discontinued. Dose adjustment to maintain clinical stability may be necessary in these settings. The placebo or pill-free week of the OC regimen may also be a period when clinical toxicity can occur. Even with the considerations discussed in this review, OCs are a reasonable contraceptive option for women with epilepsy taking AEDs.


Comparative study of submerged and surface culture acetification process for orange vinegar.
The two main acetification methodologies generally employed in the production of vinegar (surface and submerged cultures) were studied and compared for the production of orange vinegar. Polyphenols (UPLC/DAD) and volatiles compounds (SBSE-GC/MS) were considered as the main variables in the comparative study. Sensory characteristics of the obtained vinegars were also evaluated. Seventeen polyphenols and 24 volatile compounds were determined in the samples during both acetification processes. For phenolic compounds, analysis of variance showed significant higher concentrations when surface culture acetification was employed. However, for the majority of volatile compounds higher contents were observed for submerged culture acetification process, and it was also reflected in the sensory analysis, presenting higher scores for the different descriptors. Multivariate statistical analysis such as principal component analysis demonstrated the possibility of discriminating the samples regarding the type of acetification process. Polyphenols such as apigenin derivative or ferulic acid and volatile compounds such as 4-vinylguaiacol, decanoic acid, nootkatone, trans-geraniol, β-citronellol or α-terpineol, among others, were those compounds that contributed more to the discrimination of the samples. The acetification process employed in the production of orange vinegar has been demonstrated to be very significant for the final characteristics of the vinegar obtained. So it must be carefully controlled to obtain high quality products. © 2017 Society of Chemical Industry.


Dynamic and quantitative evaluation of degenerative mitral valve disease: a dedicated framework based on cardiac magnetic resonance imaging.
Accurate quantification of mitral valve (MV) morphology and dynamic behavior over the cardiac cycle is crucial to understand the mechanisms of degenerative MV dysfunction and to guide the surgical intervention. Cardiac magnetic resonance (CMR) imaging has progressively been adopted to evaluate MV pathophysiology, although a dedicated framework is required to perform a quantitative assessment of the functional MV anatomy. We investigated MV dynamic behavior in subjects with normal MV anatomy (n=10) and patients referred to surgery due to degenerative MV prolapse, classified as fibro-elastic deficiency (FED, n=9) and Barlow's disease (BD, n=10). A CMR-dedicated framework was adopted to evaluate prolapse height and volume and quantitatively assess valvular morphology and papillary muscles (PAPs) function over the cardiac cycle. Multiple comparison was used to investigate the hallmarks associated to MV degenerative prolapse and evaluate the feasibility of anatomical and functional distinction between FED and BD phenotypes. On average, annular dimensions were significantly (P<0.05) larger in BD than in FED and normal subjects while no significant differences were noticed between FED and normal. MV eccentricity progressively decreased passing from normal to FED and BD, with the latter exhibiting a rounder annulus shape. Over the cardiac cycle, we noticed significant differences for BD during systole with an abnormal annular enlargement between mid and late systole (LS) (P<0.001 vs. normal); the PAPs dynamics remained comparable in the three groups. Prolapse height and volume highlighted significant differences among normal, FED and BD valves. Our CMR-dedicated framework allows for the quantitative and dynamic evaluation of MV apparatus, with quantifiable annular alterations representing the primary hallmark of severe MV degeneration. This may aid surgeons in the evaluation of the severity of MV dysfunction and the selection of the appropriate MV treatment.


Valvular endocarditis associated with Helcococcus ovis infection in a bovine.
A 12-month-old Angus bull calf with a history of fever and lethargy of several weeks' duration was necropsied. Macroscopic findings included general dehydration, congestion, and edema within the craniodorsal lobes of the lung, multifocal ecchymotic hemorrhages on the dorsal epaxial and gluteal muscles, bloody ingesta within the gastrointestinal tract, and a 4- x 4- x 5-cm irregular plaque located on the right atrioventricular heart valve. Microscopically, there were focally extensive pulmonary alveolar infiltrates of histiocytes and neutrophils, large numbers of necrotic hypereosinophilic hepatocytes located within the centrilobular and midzonal regions of the liver, and, within the plaque from the right atrioventricular valve, a large mass formed by abundant laminated fibrin that contained numerous small multifocal aggregates of gram-positive cocci. This report describes the first apparent isolation of Helcococcus ovis from cattle.


[Reconstruction of medial and lateral column periosteal hinge using Kirschner wire to assist in closed reduction of multi-directional unstable humeral supracondylar fractures in children].
To investigate the effectiveness of medial and lateral column periosteal hinge reconstruction using Kirschner wire in the closed reduction of multi-directional unstable humeral supracondylar fractures in children. A clinical data of 43 children with multi-direction unstable humeral supracondylar fractures, who met the selection criteria and were admitted between August 2020 and August 2022, was retrospectively analyzed. Twenty-one cases of fractures were treated wuth closed reduction after medial and lateral column periosteal hinge reconstruction using Kirschner wire and percutaneous Kirschner wires fixation (study group), while 22 cases of fractures were treated by traditional closed reduction technique and percutaneous Kirschner wire fixation (control group). There was no significant difference in gender, age, cause of injury, fracture side, and interval from injury to operation between the two groups ( P>0.05). The operation time, intraoperative fluoroscopy times, the number of children who were changed to open reduction after closed reduction failure, fracture healing time, complications within 2 months after operation, and the Flynn score of elbow joint function at last follow-up were compared between the two groups. All the fractures in the study group were successfully closed reduction, and 4 cases in the control group were changed to open reduction and completed the operation, the difference between the two groups was significant ( P=0.040). The operation time and intraoperative fluoroscopy times of the study group were significantly less than those of the control group ( P<0.05). All children in both groups were followed up 6-18 months with an average of 9.0 months in the study group and 9.8 months in the control group. Imaging review showed that the fractures of both groups healed, and the difference in the healing time between the two groups was not significant ( P=0.373). According to Flynn score at last follow-up, the excellent and good rate of elbow joint function was 95.2% (20/21) in the study group and 86.4% (19/22) in the control group, with no significant difference ( P=0.317). There was no complication such as infection or irritation at the end of Kirchner wire within 2 months after operation. For children with multi-directional unstable humeral supracondylar fractures, the use of Kirschner wires to reconstruct the medial and lateral column periosteal hinge to assist in closed reduction has the advantages of shortening operation time, reducing intraoperative fluoroscopy times, and effectively reducing the incidence of open reduction, and can achieve similar postoperative elbow joint function when compared with traditional closed reduction technique.


Nomogram and recursive partitioning analysis to predict overall survival in patients with stage IIB-III thoracic esophageal squamous cell carcinoma after esophagectomy.
We have developed statistical models for predicting survival in patients with stage IIB-III thoracic esophageal squamous cell carcinoma (ESCC) and assessing the efficacy of adjuvant treatment. From a retrospective review of 3,636 patients, we created a database of 1,004 patients with stage IIB-III thoracic ESCC who underwent esophagectomy with or without postoperative radiation. Using a multivariate Cox regression model, we assessed the prognostic impact of clinical and histological factors on overall survival (OS). Logistic analysis was performed to identify factors to include in a recursive partitioning analysis (RPA) to predict 5-year OS. The nomogram was evaluated internally based on the concordance index (C-index) and a calibration plot. The median survival time in the training dataset was 30.9 months, and the 5-year survival rate was 33.9%. T stage, differentiated grade, adjuvant treatment, tumor location, lymph node metastatic ratio (LNMR), and the presence of vascular carcinomatous thrombi were statistically significant predictors of 5-year OS. The C-index of the nomogram was 0.70 (95% CI 0.67-0.73). RPA resulted in a three-class stratification: class 1, LNMR ≤ 0.15 with adjuvant treatment; class 2, LNMR ≤ 0.15 without adjuvant treatment and LNMR > 0.15 with adjuvant treatment; and class 3, LNMR > 0.15 without adjuvant treatment. The three classes were statistically significant for OS (P < 0.001). Thus, the nomogram and RPA models predicted the prognosis of stage IIB-III ESCC patients and could be used in decision-making and clinical trials.


[Clinical application of the single radial immunodiffusion (SRID) technic to detect antitubercle bacillus antibody].
Using the Tubercle bacillus Danish D1331 atoxic species as antigen and by single radial immunodiffusion (SRID) technic, the serum anti-TB-Ab of 454 patients with tuberculosis or other diseases were assayed and the results were reported. It was demonstrated that the sensitivity, specificity and accuracy of this method to diagnose tuberculosis were 81.78%, 97.92% and 90.31%; the positive and negative predictivities of this method were 97.22% and 85.77%, and the diagnostic efficiency was 80.08%. It was suggested this method had significant clinical value for diagnosing of tuberculosis.


[n]Cyclo-3,6-phenanthrenylenes: Synthesis, Structure, and Fluorescence.
Five congeners of [n]cyclo-3,6-phenanthrenylene with 3, 4, 5, 7, and 8 panels were obtained from one-pot macrocyclization of dibromophenanthrene, and their crystal structures with diverse molecular shapes were revealed by X-ray crystallography. The compounds, except the four-panel congener, were highly fluorescent in solution, with quantum yields up to 85 %. The least fluorescent four-panel congener showed the smallest change in its absorption spectrum from that of monomeric phenanthrene, which provided an interesting structure-activity relationship for fluorescent macrocycles to guide future studies.


Intramedullary Screw Fixation of Metacarpal Fractures Results in Excellent Functional Outcomes: A Literature Review.
Intramedullary fixation of a comminuted subcapital metacarpal fracture using a headless compression screw was first described in 2010. The purpose of this study was to identify and evaluate all studies reporting clinical outcomes of intramedullary screw fixation of metacarpal fractures. A comprehensive search of the literature was performed under Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify all relevant studies. Outcome measures included mean follow-up, evidence of radiographic union, functional outcomes, and quality-of-life measures. Nine articles for a total of 169 metacarpal fractures were identified. Average patient age was 32 years; 86.5 percent of the patients were men; and the majority of fractures occurred in the small finger (74 percent). Most fractures occurred in the neck (n = 66), followed by shaft (n = 31) and head (n = 10). The average follow-up was 11 months, with an average metacarpophalangeal joint flexion of 86 degrees (n = 83) and digit total active motion of 251 degrees (n = 72). Radiographic union was achieved in 100% of reported cases (n = 132) at or before the latest follow-up. Grip strength in four studies showed an average of 96 percent compared to the contralateral hand. No serious complications were reported. Nine minor complications were reported, including four cases of hardware removal in asymptomatic patients. The review of the literature suggests intramedullary fixation of metacarpal neck and shaft fractures using headless compression screws has thus far proven to be a safe and successful surgical treatment option resulting in excellent clinical outcomes.


Expressional changes of neuropeptide Y and cholecystokinin in the arcuate and paraventricular nuclei after capsaicin administration.
Despite its toxicity, a great deal of attention has been paid to the anorexic effect of capsaicin in the treatment of obesity-related neurotransmitters/neuromodulators. To determine if capsaicin has any effects on the orexigenic or anorexigenic peptides, the neuropeptide Y (NPY)- and cholecystokinin (CCK)-immunoreactivities were demonstrated in the rat hypothalamus by immunohistochemistry after capsaicin administration. There was a significantly lower concentration of NPY immunopositive cells in the arcuate and paraventricular nuclei of the capsaicin treated rats. In contrast, the CCK expressions level was higher in the paraventricular nucleus of the capsaicin treated rats than in the control rats. These results suggest that capsaicin influence neuropeptides such as orexigenic NPY and anorexigenic CCK related to control food intake.


Quantitative immunoelectron microscopic localization of (Na+,K+)ATPase on rat exocrine pancreatic cells.
Distribution of (Na+,K+)ATPase in rat exocrine pancreatic cells was investigated quantitatively by immunoelectron microscopy using the post-embedding protein A-gold technique. We found that in acinar and duct cells (Na+,K+)ATPase exists on both the luminal and the basolateral surfaces, with higher particle density on the luminal surface (4.4 times in the acinar cells and 5.6 times in the duct cells). According to Bolender (J Cell Biol 61:269, 1974), the luminal surface represents only 5% of the total cell surface of an average pancreatic acinar cell. It is roughly estimated, therefore, that approximately 80% of the plasma membrane (Na+,K+)ATPase in the acinar cells exists on the basolateral surface. When the acinar and duct cells were compared, more than twice as many particles were found on acinar cells than on duct cells. The enzyme existed on all the cell surfaces, preferentially on the microvilli or on the cell membrane folds, and no clustering was detected. We suggest that the (Na+,K+)ATPase on the basolateral surface is mainly responsible for the extrusion of a large number of sodium ions that are incorporated into the cytoplasm accompanying the secondary active transport of various organic substances and inorganic ions, whereas that on the luminal surface is responsible for active extrusion of sodium ions that are partially responsible for the fluid secretion of the pancreatic cells.


Lead(II) Complexes of Amino Acids, Peptides, and Other Related Ligands of Biological Interest.
Lead(II) forms (NH2,COO-)-chelated mono- and bis-complexes with simple amino acids, while mono-complexes with pH-dependent coordination modes exist with simple dipeptides. These mostly hemidirected complexes have moderate stability. While a weak interaction of side chain imidazole and carboxylate in lead(II)-aminoacidato complexes is found, the thiolate group has an exceptionally high affinity to this metal ion. For example, tridentate (NH2,COO-,S-)-coordination of penicillamine (Pen) and cysteine (Cys) results in an extremely strong interaction with lead(II), but, owing to the sterical effect of the 6s2 pair, a second ligand is not able to coordinate in the above mentioned tridentate way. Although there is no example for a lead(II)-induced deprotonation and coordination of a peptide-amide and the side-chain thiolate in oligopeptides has a somewhat lower basicity compared to that of Pen or Cys, still the Cys-containing peptides interact rather strongly with lead(II). Interestingly, the position of Cys in the peptide influences significantly both the lead-binding ability via different bonding modes and the selectivity for lead(II) against other metal ions, like zinc(II) or cadmium(II). At high ligand excess, however, coordination of three sulfur donors to lead(II) is found with thiolate-containing amino acids and oligopeptides. High basicity oxygens of hydroxamates, hydroxypyronates, and hydroxypyridinonates are also effective lead-binding donors. Some factors affecting the complexation of these ligands with lead(II) are: (i) A larger extent of delocalization along the ring in hydroxypyridinonate results in a more favored metal-binding ability over hydroxypyronate. (ii) Even monohydroxamates are good ligands and form mono- and bis-complexes with lead(II). (iii) In general, dihydroxamates and trihydroxamate-based siderophores, like desferrioxamine B (DFB) and desferricoprogen (DFC), are better binding agents for Pb(II) than the monohydroxamates, but the length and structure of linkers connecting the hydroxamate moieties have a significant impact on the complexation and selectivity for lead(II). (iv) The corresponding thio derivatives are significantly better ligands for lead than their parent oxo molecules, but polymeric complexes with poor water solubility are formed in most cases. (v) Out of the hydroxamate derivatives of amino acids the α-ones are the most effective ligands, provided polynuclear species involving the hydroxamate-oxygens, amino-N and hydroxamate-N can be formed.


Water quality assessment and modeling of an effluent-dominated stream, the Notwane River, Botswana.
In an effort to assess current and future water quality of the only perennial river in southeastern Botswana, this study presents water quality monitoring and modeling results for the effluent-dependent Notwane River. The water quality along the Notwane River, pre- and post-implementation of secondary wastewater treatment, was compared and results demonstrated that water quality improved after the new wastewater treatment plant (WWTP) went online. However, stream standards for chemical oxygen demand, total dissolved phosphorous, and fecal coliform were exceeded in most locations and the critical dissolved oxygen (DO) reached concentrations of less than 4 mg L(-1). High dissolved P concentrations and intense macrophyte growth at the impounding ponds and at sites within 30 km of the effluent waste stream confluence suggest that eutrophication was a function of P release from the ponds. Results of DO modeling demonstrated that an unpolluted inflow at approximately 10 km downstream of the confluence was responsible for raising DO concentrations by 2.3 mg L(-1), while SOD was responsible for a decline in DO concentrations of 1.4 mg L(-1) at 6 km downstream of the confluence. Simulations also showed higher DO concentrations during winter months, when water temperatures were lower. Simulations, in which the distributed biochemical oxygen demand (BOD) loading from cattle excrement was decreased, produced nominal increases in DO concentrations. An increase in WWTP BOD loadings to projected 2020 values resulted in a 1.3 mg L(-1) decrease in the critical DO concentration. Furthermore, a decrease in treatment plant efficiency, from 94% to 70% BOD removal, produced critical DO concentrations and anoxia along much of the modeled reach. This has significant implications for Gaborone, especially if decreased WWTP efficiency occurs as a result of the expected future increase in pollutant loadings.


THE MESOPTERYGIAL VEIN: A RELIABLE VENIPUNCTURE SITE FOR INTRAVASCULAR ACCESS IN BATOIDS.
Intravascular access in batoid species is commonly achieved using the ventral coccygeal or radial wing vessels. However, these approaches can be difficult because of the presence of cartilage, lack of specific landmarks, species variation, and small vessel size in many species. This study used postmortem contrast radiography and gross dissection to develop landmarks for a new, dependable vascular access in three Myliobatiform species commonly maintained in captivity: Atlantic stingray (Hypanus sabinus), cownose ray (Rhinoptera bonasus), and smooth butterfly ray (Gymnura micrura). The mesopterygial vein provides quick vascular access and is suitable for administration of large fluid volumes and intravascular drugs. It is located immediately ventrolateral to the metapterygium cartilage, which sits adjacent to the coelomic cavity and supports the caudal half of the pectoral fin. Using the pectoral girdle and cranial third of the metapterygium cartilage as landmarks, vascular access can be achieved by directing a needle medially at approximately a 30° (adult cownose rays) or 45° angle (Atlantic stingrays, juvenile cownose rays, smooth butterfly rays) toward the metapterygium cartilage. Differences in the degree of needle direction are due to species and age-specific shapes of the metapterygium cartilage. The mesopterygial vein is an alternate site of quick and reliable venous access in batoid species.


Comparison of Intact Knee Cartilage Thickness in Patients with Traumatic Lower Extremity Amputation and Nonimpaired Individuals.
The aim of this study was to assess the femoral articular cartilage thickness of the intact knee in patients with traumatic lower extremity amputation compared with nonimpaired individuals. A total of 30 male patients with traumatic lower extremity amputation (mean [SD] age, 31.2 [6.3] yrs) and a random sample of 53 age-matched and body mass index-matched male nonimpaired individuals (mean [SD] age, 29.8 [6.3] yrs) participated in the study. Exclusion criteria were age younger than 18 yrs, history of significant knee injury, previous knee surgery, or rheumatic disease. The femoral articular cartilage thickness was measured using ultrasound at the midpoints of the medial condyle, the intercondylar notch, and the lateral condyle. Ultrasonographic cartilage measurement was performed on the intact side of the patients with amputation and on both sides of the nonimpaired individuals. The femoral articular cartilage thickness of the intact knees of the patients with amputation was significantly decreased at the lateral and medial condyles compared with the nonimpaired individuals (P < 0.05). There was no significant difference in the measurements at the intercondylar notch between the patients with amputation and the nonimpaired individuals (P > 0.05). There was a premature cartilage loss in the intact limb knee of the patients with traumatic amputation. This result supports the view that patients with traumatic lower extremity amputation are at increased risk for developing knee osteoarthritis in the intact limb.


Lentivirus‑mediated overexpression of CD97/ADGRE5 reverses dysregulated high glucose‑induced endothelial cell migration.
Elevated blood glucose levels contribute to a series of complications in patients with diabetes mellitus, including chronic ulcers and accelerated atherosclerosis. Dysregulated endothelial migration induced by high glucose is important in vascular‑associated complications. In the present study, cluster of differentiation (CD)97/adhesion G protein‑coupled receptor 5 (ADGRE5), a member of the G protein‑coupled receptor protein family, stimulated angiogenesis was investigated to determine its role in cell models of diabetes mellitus using lentivirus‑mediated overexpression and siRNA transfection. The results revealed reduced expression in high glucose‑treated human umbilical vein endothelial cells and in the endothelium of diabetic mice. Among the three CD97 isoforms, the majority of the expression of CD97 (EGF1,2,5) in the endothelial cells was regulated by high levels of glucose. Using stable lentivirus‑mediated transfection and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‑associated protein 9 (Cas9) technology, the present study constructed CD97‑overexpression and CD97‑knockout endothelial cell lines. Migration assays showed that the lentivirus‑mediated overexpression of CD97/ADGRE5 improved the inhibition of high glucose‑induced endothelial cell migration. In addition, using cytoskeleton staining, it was found that CD97 promoted membrane ruffling and lamellipodia formation. Cell division cycle 42, a small GTP‑binding protein, and its downstream factor, actin‑related protein 2, were involved in CD97‑induced actin reorganization in endothelial cells. Additionally, the use of transcription factor filter plate assays revealed that the nuclear translocation of signal transducer and activator of transcription 1 stimulated by high glucose contributed to the inhibited transcription of CD97. In conclusion, the present study established that the overexpression of CD97 improved high glucose‑induced dysfunction of endothelial cell migration. These findings provide insight to assist in identifying therapeutic targets with potential to ameliorate certain vascular complications of diabetes.


Peau d'orange and angioid streaks: manifestations of Bruch membrane pathology.
The aim of this study was to characterize peau d'orange and angioid streaks, characteristic findings in eyes of patients with pseudoxanthoma elasticum, by examining fundus photography and optical coherence tomography imaging. Color photographs were evaluated directly as were the component red and green channels. Optical coherence tomography images were evaluated for reflectivity pattern of the band corresponding to the retinal pigment epithelium-Bruch membrane complex. Eighteen eyes of 9 patients with a mean age of 48.7 years (range, 31-61 years) were examined; 7 of them were women. Color photographs showed areas of yellowish opacification that obscured visualization of the underlying choroid. At the outer edges of this confluent area, opacification were nonconfluent changes with similar appearance and these regions were typical peau d'orange. Angioid streaks occurred within and extended up to the outer border of the confluent opacification. Underlying choroidal details could be seen through the regions of peau d'orange and through the gaps in angioid streaks. The red channel image showed increased reflectivity from the confluent deposit and improved visualization of the choroidal vasculature, except where the confluent opacification was located. Optical coherence tomography imaging showed increased reflectivity from the outer border of the retinal pigment epithelium-Bruch membrane complex. The findings suggest that the confluent region is the relevant lesion, not the subconfluent zone known as peau d'orange. Imaging characteristics of the confluent area of opacity are consistent with diffuse infiltration with calcium, a chief histologic abnormality of pseudoxanthoma elasticum. The name coquille d'oeuf was suggested for the confluent area of opacity as a consequence.


Accommodation in cerebral palsy: function and remediation.
Accommodation function, in a population of severely involved cerebral palsied children, is significantly lowered or absent. This observation suggests that lowered amplitudes and accommodation facility could be part of the cerebral palsy syndrome and untrainable . This paper looks at the accommodative function and the results of vision training on such a population.


Effects of K(ATP) channel modulators on acetylcholine release from guinea-pig isolated atria and small intestine.
The effects of K(ATP) channel blockers (glibenclamide, HMR 1883, HMR 1372) and openers (cromakalim, pinacidil, diazoxide) on the electrically-evoked (5 Hz) release of [(3)H]acetylcholine were studied in isolated guinea-pig atria and myenteric plexus-longitudinal muscle preparations which had been preincubated with [(3)H]choline. Atria: Cromakalim (0.3 microM and 1 microM), pinacidil (10 microM) and diazoxide (30 microM) significantly reduced the stimulation-evoked release of [(3)H]acetylcholine. The inhibition produced by cromakalim and pinacidil was prevented by 1 microM of either HMR 1883, HMR 1372 or glibenclamide. The blockers alone significantly increased the release at concentrations of 30 microM, whereas 1 microM and 10 microM had no effect. Myenteric plexus-longitudinal muscle preparation: The electrically-evoked release of [(3)H]acetylcholine was not affected by K(ATP) channel blockers or openers. In contrast, the contractions of the longitudinal muscle caused by electrical stimulation or by carbachol were strongly inhibited by 1 microM cromakalim which suggests that the relaxant effect of the K(ATP) channel openers is exclusively a direct effect on intestinal smooth muscle. The findings suggest that blockade of activated K(ATP) channels in vagal nerves of guinea-pig atria stimulates acetylcholine release, and that this effect may contribute to the antiarrhythmic actions of K(ATP) channel blockers. By contrast, release of acetylcholine from guinea-pig myenteric plexus is not modulated by K(ATP) channels which suggests heterogeneity of K(ATP) channel distribution in peripheral autonomic nerves.


A parsimonious threshold-independent protein feature selection method through the area under receiver operating characteristic curve.
Protein expression profiling for differences indicative of early cancer holds promise for improving diagnostics. Due to their high dimensionality, statistical analysis of proteomic data from mass spectrometers is challenging in many aspects such as dimension reduction, feature subset selection as well as construction of classification rules. Search of an optimal feature subset, commonly known as the feature subset selection (FSS) problem, is an important step towards disease classification/diagnostics with biomarkers. We develop a parsimonious threshold-independent feature selection (PTIFS) method based on the concept of area under the curve (AUC) of the receiver operating characteristic (ROC). To reduce computational complexity to a manageable level, we use a sigmoid approximation to the empirical AUC as the criterion function. Starting from an anchor feature, the PTIFS method selects a feature subset through an iterative updating algorithm. Highly correlated features that have similar discriminating power are precluded from being selected simultaneously. The classification rule is then determined from the resulting feature subset. The performance of the proposed approach is investigated by extensive simulation studies, and by applying the method to two mass spectrometry data sets of prostate cancer and of liver cancer. We compare the new approach with the threshold gradient descent regularization (TGDR) method. The results show that our method can achieve comparable performance to that of the TGDR method in terms of disease classification, but with fewer features selected. Supplementary Material and the PTIFS implementations are available at http://staff.ustc.edu.cn/~ynyang/PTIFS. Supplementary data are available at Bioinformatics online.


Lung abscess: a neglected cause of life threatening haemoptysis.
Three cases who presented with life threatening haemoptysis are reported, all of whom required surgery to control the bleeding. In all three patients chronic lung abscess was responsible for the haemoptysis. Even in the absence of typical clinical or radiographic features of an abscess this diagnosis should be considered in any patient presenting with life threatening haemoptysis.


A comparative trial of ordinary metoprolol tablets and metoprolol sustained-release tablets in hypertensive patients at rest and on exercise.
An open, randomized crossover trial was carried out in 10 patients with hypertension to compare the degree and duration of antihypertensive effect of metoprolol given as 100 mg ordinary tablets twice daily and as single daily doses of a 200 mg sustained-release tablet. Blood pressures and heart rate were measured, at rest and during maximum exercise effort, before treatment, at the second hour after the start of each treatment sequence, and at the end of both 14-day treatment periods: after 12 hours in the case of ordinary metoprolol and after 24 hours with sustained-release metoprolol. The results showed that heart rate was greatly reduced (less than 0.001) both at rest and on exercise at all times studied with both treatments. At rest, blood pressure was significantly reduced except by sustained-release metoprolol at 2 hours. On exercise, blood pressure was also significantly reduced except for the 12-hour value for diastolic pressure with ordinary metoprolol. It is concluded that, for similar reductions in heart rate reflecting satisfactory beta-receptor blockade, the antihypertensive effect of metoprolol given at a dosage of 200 mg per day was more rapid in onset after the ordinary tablet formulation but less marked at 12 hours than at 24 hours after the sustained-release formulation.


Global patterns of leaf construction traits and their covariation along climate and soil environmental gradients.
Leaf functional traits and their covariation underlie plant ecological adaptations along environmental gradients, but there is limited information on the global covariation patterns of key leaf construction traits. To explore how leaf construction traits co-vary across diverse climate and soil environmental conditions, we compiled a global dataset including cell wall mass per unit leaf mass (CWmass ), leaf carbon (C) and calcium (Ca) concentrations, and specific leaf area (SLA) for 2348 angiosperm species from 340 sites world-wide. Our results demonstrated negative correlations between leaf C and Ca concentrations and between leaf C and SLA across diverse nongraminoid angiosperms. Leaf C concentration increased with increasing mean annual temperature (MAT) and mean annual precipitation (MAP) and with decreasing soil pH and calcium carbonate (CaCO3 ) concentration, whereas leaf Ca concentration and SLA exhibited the opposite responses to these environmental variables. The covariations of leaf Ca-C and of leaf SLA-C were stronger in habitats with lower MAT and MAP, and/or higher soil CaCO3 content. This global-scale analysis demonstrates that the leaf C and Ca concentrations and SLA together govern the C and biomass investment strategies in leaves of nongraminoids. We conclude that environmental conditions strongly shape leaf construction traits and their covariation patterns.


Climate and environmental factors influencing Echinococcus multilocularis occurrence in the Slovak Republic.
During the period of 2000-2004, 3,096 red foxes from the whole territory of the Slovak Republic were sampled and examined parasitologically for infections with Echinococcus multilocularis, causative agent of serious alveolar echinococcosis in humans. Relations between prevalence of the parasite in individual regions of Slovakia and some environmental factors were weighted. During the study period, great differences of prevalence and infection intensity were found on a regional level and significant between-year fluctuation of both parameters was observed. High-endemic foci with an estimated prevalence of more than 30 % were detected in the northern and central part of the country. Climatic conditions, including low mean annual air temperature, high mean annual rainfall and the high humidity of the soil, showed to be important for E. multilocularis distribution. Significant correlation was calculated between prevalence of the tapeworm, mean annual precipitation values, and population density of small mammals.


Langerhans cells in verruciform xanthomas: an immunoperoxidase study of 10 oral cases.
Ten oral verruciform xanthomas were studied using an immunoperoxidase stain for S-100 protein. All cases exhibited positively stained dendritic cells among the mononuclear inflammatory cell infiltrate at the base of the lesions and to a lesser extent among the "foam cells". The foam cells were, however, negative for S-100 staining. We suggest that, based on these findings, verruciform xanthomas belong to a new category of "non-X histiocytoses" in which the presence of Langerhans cells suggests an immunologic pathogenesis.


Constipation: Prevalence and Associated Factors in Adults Living in Londrina, Southern Brazil.
The aims of this study were to estimate the prevalence of constipation and identify associated factors among adults living in an urban area in Londrina, Brazil. This was a secondary analysis of an epidemiological, population-based study on bowel habit performed in 2008 with 2,162 individuals selected through cluster sampling. Interviews were administered using a sociodemographic questionnaire and the adapted and validated Brazilian version of the "Bowel Function in the Community" tool. Variables from the original database were used to determine the prevalence of constipation (according to the Rome Criteria III) and associated factors. The chi-square test and multivariate logistic regression were used for data analysis. The overall prevalence of constipation (14.6%; n = 315) was higher among women than among men (21.9% vs. 5.3%), increased with age among men, and was inversely related to family income. Overall, female gender, low socioeconomic status, history of anal fissure, anorectal surgery, stroke, nervous system disease, fistulae, and hemorrhoids were factors significantly associated with constipation. The variables low social economic status, stroke, anal fissure history, and anorectal surgery were statistically significant in all three tested statistical models.


Plasminogen activator is involved in the hCG-induced neutrophil extravasation and vasopermeability increase in the rat testis.
The role of proteolytic enzymes in the hCG-induced increase in testicular vasopermeability and neutrophil extravasation was studied using protease inhibitors. An intra-testicular injection of hCG together with incubation medium conditioned by polymorphonuclear leucocytes (PMNs) caused a significant increase in vasopermeability and a coincident extravasation of PMN's from the postcapillary venules in the rat testis. When p-aminobenzamidine, a serine protease inhibitor which inhibits urokinase-type plasminogen activator, was administered together with hCG in the incubation medium, both the permeability increase and PMN extravasation were prevented. Aprotinin, another serine protease inhibitor, and Eglin C, a specific neutrophil elastase and cathepsin G inhibitor were, however, without effect. None of these inhibitors caused any non-specific vascular effects in the testis at the concentrations used. These results support the concept that the hCG-induced increase in vasopermeability in the rat testis is related to extravasation of PMNs and suggest that urokinase-type plasminogen activator is involved in migration of these cells through the postcapillary venular walls.


Influence of family income on hospital visits for asthma among Canadian school children.
A study was undertaken to investigate the mechanisms by which socioeconomic status may influence asthma morbidity in Canada. A total of 2968 schoolchildren aged 5-19 years with reported asthma were divided into three family income ranges. Hospital visits and risk factors for asthma, ascertained by questionnaire, were compared between the three groups. The mean (SE) annual period prevalence of a hospital visit was 25.0 (3.1)% among schoolchildren with household incomes of less than $20 000 Canadian compared with 16.0 (1.3)% among those with incomes of more than $60 000 (p<0.05). Students with asthma from lower income households were more likely to be younger and exposed to environmental tobacco smoke and cats, and their parents were more likely to have a lower educational attainment and be unmarried (p<0.05). Across all income groups, younger age, lower parental education, having unmarried parents, and regular exposure to environmental tobacco smoke were each associated with an increase in risk of a hospital visit (p<0.05). No increased risk was detected due to sex, having pets, and not taking dust control measures. Although not statistically significant at p<0.05, there may have been an interactive effect between income and susceptibility to environmental tobacco smoke. In the lower income group those children who were regularly exposed to second hand smoke had a 79% higher risk of a hospital visit compared with a 45% higher risk in the higher income group. In a logistic regression model the association between income and hospital visit was no longer significant after adjusting for differences in reported exposure to passive smoking. Socially disadvantaged Canadian schoolchildren have increased asthma morbidity. Exposure to cigarette smoke appears to be one important explanation for this observation.


Disparities in health, obesity and access to care among an insured population of Asian and Pacific Islander Americans in Hawai'i.
To examine differences in health status, obesity and access among Asian and Pacific Islander Americans in Hawai'i using data from a 2007 health plan survey, including Caucasians, Puerto Ricans, American Indian and Alaska Natives, Chinese, Filipinos, Japanese, Koreans, Native Hawai'ians, Samoans, and Other Pacific Islanders. Data were collected through a stratified random sample of adult members of a health plan in Hawai'i (n = 119,563) who saw a physician in the past 12 months. Multivariable logistic and ordinary least squares regression analyses were used to examine racial/ethnic differences in health status, access, and obesity and the impact of obesity and access on health status, after controlling for age, gender, and education. The highest obesity rates were found among Samoans (50%), Puerto Ricans (37%), Native Hawai'ians (36%), and Other Pacific Islanders (35%). Puerto Ricans and Samoans reported the highestnumber of poor physical health days (5.4). Samoans reported the highest number of poor mental health days (4.4). Obesity had a stronger impact than access on self-reported health status. Samoans had the highest rate of obesity, low health ratings, and a high number of days of poor health. Targeted interventions may be needed for this group.


Sentinel node localization in head and neck tumors.
Sentinel lymph node biopsy (SLNB) is a minimally invasive method that was developed to stage the regional lymphatics of patients with cutaneous melanoma. Many studies performed worldwide have shown that SLNB is a feasible method to stage the cervical lymphatics in patients with head and neck squamous cell carcinoma (HNSCC). The accuracy of SLNB in patients with HNSCC is currently under investigation in a multicenter study sponsored by the American College of Surgeons Oncology Group that compares the results of SLNB with standard elective neck dissection. Research to date has also shown that multiple SLNs and individualized drainage patterns characterize head and neck mucosal sites. These findings suggest that lymphoscintigraphy alone may be useful to delineate the lymphatic basins that require treatment in patients with HNSCC and in patients whose head and neck lymphatics are disrupted because of prior surgery or irradiation.


Gun safety practices of trauma center workers in a southern city.
We designed a study to assess the personal gun ownership and safety practices of trauma center workers in Birmingham, Alabama. Survey questionnaires administered to nurses, physicians, and other workers in pediatric and adult trauma centers showed that two thirds (65%) owned a gun and 56% owned a handgun. Gun owners with children were less likely to have loaded, unlocked guns in their homes than those without children (33% vs 56%). Loaded guns were carried in cars by 48% of workers. Worker title and attitude regarding handgun restrictions were the strongest predictors of unsafe gun ownership in a logistic regression model. Workers with loaded, unlocked guns in their home considered themselves and their family at no greater risk of gun injury from family-owned guns than workers without guns. We conclude that many trauma workers had unsafely stored guns and failed to recognize the associated risks.