[Effects of vaccination against Q-fever in Lower Saxony dairy cattle farms].
Being a notifiable and zoonotic disease, Q-fever is coming under increasing focus of epizootic disease control. Current studies indicate that the disease is more widespread in Germany than the number of notifications suggest. Therefore, since 2013, under certain conditions a hardship allowance is granted by the Animal Diseases Fund of Lower Saxony for the vaccine costs of the basic immunization to support affected farms. Material und methods: All farmers, on whose farms clinical signs of Q-fever and the pathogen Coxiella burnetii had been detected prior to vaccination and who had taken advantage of the hardship allowance during the previous 2 years were surveyed to assess the effectiveness of the measure. The survey was conducted by telephone using a previously compiled questionnaire. The topics included the observed clinical signs in cattle before and after the vaccination and the evaluation of the vaccination. Clinical manifestations indicating a Q-fever infection may differ widely and include aborts and fertility disorders and/or frequently occurring inflammations (pneumonia, mastitis, metritis) and/or unspecific symptoms presenting as higher susceptibility to disease, weakness, and fever attacks. Following vaccination, the vast majority of the farmers (84 %) observed a marked health improvement in their cattle and two thirds of the respondents intend to continue with the vaccination even without financial support from the Animal Diseases Fund. Adverse effects beyond general vaccination reactions, including transiently elevated body temperature, physical weakness and fluctuations in milk performance, were rarely observed. The clinical signs for Q-fever were diverse and often unspecific. According to the assessments by the farmers, clinical problems in most cases were considerably reduced following Q-fever vaccination. Vaccination appears to be a valuable tool in the control of this zoonosis.


Dendrimer Based Binders Enable Stable Operation of Silicon Microparticle Anodes in Lithium-Ion Batteries.
High-capacity anode materials (e.g., Si) are highly needed for high energy density battery systems, but they usually suffer from low initial coulombic efficiency (CE), short cycle life, and low-rate capability caused by large volume changes during the charge and discharge process. Here, a novel dendrimer-based binder for boosting the electrochemical performance of Si anodes is developed. The polyamidoamine (PMM) dendrimer not only can be used as binder, but also can be utilized as a crosslinker to construct 3D polyacrylic acid (PAA)-PMM composite binder for high-performance Si microparticles anodes. Benefiting from maximum interface interaction, strong average peeling force, and high elastic recovery rate of PAA-PMM composite, the Si electrode based on PAA-PMM achieves a high specific capacity of 3590 mAh g-1 with an initial CE of 91.12%, long-term cycle stability with 69.80% retention over 200 cycles, and outstanding rate capability (1534.8 mAh g-1 at 3000 mA g-1 ). This work opens a new avenue to use dendrimer chemistry for the development of high-performance binders for high-capacity anode materials.


Supraventricular antidysrhythmic and electrophysiological effects of bepridil, a new antianginal agent.
We investigated the potential antidysrhythmic effects of bepridil, a new antianginal agent, on dysrhythmias of supraventricular origin. Intravenous bepridil (5 mg/kg) suppressed dysrhythmias evoked by local application of aconitine to the left atria of anesthetized cats. After the aconitine-induced dysrhythmias had subsided, cardiac function was better maintained in animals given bepridil than in the controls. The effects of bepridil on the maximum following frequency (MFF) and transmembrane action potentials of isolated guinea pig atria and on cells displaying phase 4 depolarization were also examined. Both bepridil (5--120 microM) and verapamil (0.02--1 microM) induced a dose-dependent reduction in contractility of driven left atria, whereas only bepridil reduced MFF. The effects of bepridil (10--40 microM) on the cellular action potentials of left atria were a dose-dependent decrease in the maximum rate of depolarization of phase 0 associated with a reduction in action potential height and a marked prolongation of the action potential duration. In similar concentrations, bepridil reduced the spontaneous rate of the right atrium and reduced the slope of phase 4 depolarization. We conclude that the action of bepridil in suppressing supraventricular dysrhythmias may be partly explained by depression of automaticity together with a reduction in the intensity of the inward sodium current.


Prevention of all-terrain vehicle injuries: A systematic review from The Eastern Association for the Surgery of Trauma.
Despite increasing usage since their introduction, there exist no evidence-based guidelines on all-terrain vehicles (ATVs) and injury prevention. While the power and speed of these vehicles has increased over time, advancements in ATV safety have been rare. A priori questions about ATV injury pattern and the effect of helmet and safety equipment use and legislation mandating use were developed. A query of MEDLINE, PubMed, Cochrane Library, and Embase for all-terrain vehicle injury was performed. Letters to the editor, case reports, book chapters, and review articles were excluded. Grading of Recommendations Assessment, Development, and Evaluation methodology was used to perform a systematic review and create recommendations. Twenty-eight studies were included. Helmet use reduced traumatic brain injury (TBI). However, studies examining whether legislation mandating helmet use reduced TBI had mixed results. When ATV safety legislation was enforced, overall injury rates and mortality decreased. However, enforcement varied widely and lack of enforcement led to decreased compliance with legislation and mixed results. There was not enough evidence to determine the effectiveness of non-helmet-protective equipment. Helmet use when riding an ATV reduced the rate of TBI. ATV safety legislation, when enforced, also reduced morbidity and mortality. Compliance with laws is often low, however, possibly due to poor enforcement. We recommend helmet use when riding on an ATV to reduce TBI. We conditionally recommend implementing ATV safety legislation as a means to reduce ATV injuries, noting that enforcement must go hand in hand with enactment to ensure compliance.


Bayesian learning and the psychology of rule induction.
In recent years, Bayesian learning models have been applied to an increasing variety of domains. While such models have been criticized on theoretical grounds, the underlying assumptions and predictions are rarely made concrete and tested experimentally. Here, I use Frank and Tenenbaum's (2011) Bayesian model of rule-learning as a case study to spell out the underlying assumptions, and to confront them with the empirical results Frank and Tenenbaum (2011) propose to simulate, as well as with novel experiments. While rule-learning is arguably well suited to rational Bayesian approaches, I show that their models are neither psychologically plausible nor ideal observer models. Further, I show that their central assumption is unfounded: humans do not always preferentially learn more specific rules, but, at least in some situations, those rules that happen to be more salient. Even when granting the unsupported assumptions, I show that all of the experiments modeled by Frank and Tenenbaum (2011) either contradict their models, or have a large number of more plausible interpretations. I provide an alternative account of the experimental data based on simple psychological mechanisms, and show that this account both describes the data better, and is easier to falsify. I conclude that, despite the recent surge in Bayesian models of cognitive phenomena, psychological phenomena are best understood by developing and testing psychological theories rather than models that can be fit to virtually any data.


Nebulization of Risedronate Sodium Microspheres for Potential Attenuation of Pulmonary Emphysema: a Promising New Insight of Alveolar Macrophage Apoptosis.
Risedronate sodium (RS) is a potent nitrogen-containing bisphosphonate which is known to induce osteoclast apoptosis. As a drug repurposing approach, the current work explored the potential of nebulizable RS-chitosan (CS) microspheres to induce alveolar macrophage apoptosis. RS-CS microspheres were assessed for lung deposition, cytotoxicity, and cellular uptake percentage in Calu-3 cells. The potential of nebulizable microspheres for treating elastase-induced emphysema in rats was investigated, compared to RS marketed oral tablets®, with respect to histopathological, immunohistochemical, and flow cytometric studies. The in vitro lung deposition pattern suggested deep alveolar deposition of RS microspheres, with respect to high FPF% and suitable MMAD (66% and 1.506 μm, respectively, at a flow rate of 28.3 L min-1). No apparent cytotoxicity was observed, with a cell viability > 90%. The inhalation of RS-CS microspheres was suggested to inhibit airspace enlargement and lung rarefaction after elastase instillation and reduce the macrophage accumulation in alveolar parenchyma. Immunohistochemical and cytometric analyses revealed significant low expression levels of CD68 and CD11b surface markers, respectively, with significantly (P < 0.05) lower detected numbers of intact alveolar macrophages following inhalation of RS-CS microspheres. The nebulization of RS-CS microspheres could induce apoptosis in alveolar macrophages and be promisingly adopted for attenuation of pulmonary emphysema.


Antioxidant features of red wine pyranoanthocyanins: experimental and theoretical approaches.
This work is focused on the study of the antioxidant properties of red wine anthocyanin derivatives (carboxypyranoanthocyanins, methylpyranoanthocyanins, oxovitisins, and pyranoanthocyanin-phenolics) derived from malvidin-3-glucoside. Some antioxidant features were determined using the DPPH assay and the ability to delay lipid peroxidation in a liposome membrane system by monitoring oxygen consumption. The pyranoanthocyanin-phenolics have higher antioxidant potential than that of malvidin-3-glucoside, suggesting that the addition of a catechol or flavanol moiety increases the antioxidant capacity. The only derivatives that showed lower antioxidant features than malvidin-3-glucoside were oxovitisins and methylpyranomalvidin-3-glucoside. Also, the radical scavenging capacity of these pyranoanthocyanins was computationally explored using DFT methods. All pyranoanthocyanins were suggested as good candidates as antioxidant compounds because they easily donate an H atom to the free radicals, originating stable species. Altogether, these results support the fact that the antioxidant potential arising from anthocyanins is not impaired by some of their transformations during red wine aging.


Polymers and inflammation: disease mechanisms of the serpinopathies.
Members of the serpin (serine proteinase inhibitor) superfamily play a central role in the control of inflammatory, coagulation, and fibrinolytic cascades. Point mutations that cause abnormal conformational transitions in these proteins can trigger disease. Recent work has defined three pathways by which these conformers cause tissue damage. Here, we describe how these three mechanisms can be integrated into a new model of the pathogenesis of emphysema caused by mutations in the serpin alpha1-antitrypsin.


Multi-Objective Cognitive Model: a Supervised Approach for Multi-subject fMRI Analysis.
In order to decode human brain, Multivariate Pattern (MVP) classification generates cognitive models by using functional Magnetic Resonance Imaging (fMRI) datasets. As a standard pipeline in the MVP analysis, brain patterns in multi-subject fMRI dataset must be mapped to a shared space and then a classification model is generated by employing the mapped patterns. However, the MVP models may not provide stable performance on a new fMRI dataset because the standard pipeline uses disjoint steps for generating these models. Indeed, each step in the pipeline includes an objective function with independent optimization approach, where the best solution of each step may not be optimum for the next steps. For tackling the mentioned issue, this paper introduces Multi-Objective Cognitive Model (MOCM) that utilizes an integrated objective function for MVP analysis rather than just using those disjoint steps. For solving the integrated problem, we proposed a customized multi-objective optimization approach, where all possible solutions are firstly generated, and then our method ranks and selects the robust solutions as the final results. Empirical studies confirm that the proposed method can generate superior performance in comparison with other techniques.


Acute ischaemic stroke alters the brain's preference for distinct dynamic connectivity states.
Acute ischaemic stroke disturbs healthy brain organization, prompting subsequent plasticity and reorganization to compensate for the loss of specialized neural tissue and function. Static resting state functional MRI studies have already furthered our understanding of cerebral reorganization by estimating stroke-induced changes in network connectivity aggregated over the duration of several minutes. In this study, we used dynamic resting state functional MRI analyses to increase temporal resolution to seconds and explore transient configurations of motor network connectivity in acute stroke. To this end, we collected resting state functional MRI data of 31 patients with acute ischaemic stroke and 17 age-matched healthy control subjects. Stroke patients presented with moderate to severe hand motor deficits. By estimating dynamic functional connectivity within a sliding window framework, we identified three distinct connectivity configurations of motor-related networks. Motor networks were organized into three regional domains, i.e. a cortical, subcortical and cerebellar domain. The dynamic connectivity patterns of stroke patients diverged from those of healthy controls depending on the severity of the initial motor impairment. Moderately affected patients (n = 18) spent significantly more time in a weakly connected configuration that was characterized by low levels of connectivity, both locally as well as between distant regions. In contrast, severely affected patients (n = 13) showed a significant preference for transitions into a spatially segregated connectivity configuration. This configuration featured particularly high levels of local connectivity within the three regional domains as well as anti-correlated connectivity between distant networks across domains. A third connectivity configuration represented an intermediate connectivity pattern compared to the preceding two, and predominantly encompassed decreased interhemispheric connectivity between cortical motor networks independent of individual deficit severity. Alterations within this third configuration thus closely resembled previously reported ones originating from static resting state functional MRI studies post-stroke. In summary, acute ischaemic stroke not only prompted changes in connectivity between distinct networks, but it also caused characteristic changes in temporal properties of large-scale network interactions depending on the severity of the individual deficit. These findings offer new vistas on the dynamic neural mechanisms underlying acute neurological symptoms, cortical reorganization and treatment effects in stroke patients.


Impact of reinduction regimens on the clinical course of adult acute nonlymphocytic leukemia.
All clinical studies in the English literature from 1976 to mid-1987 that address drug management of refractory or relapsed ANLL are reviewed and summarized. We conclude that, although many regimens may induce a CR, none is clearly superior. New drugs and or drug combinations must be sought if treatment outcomes are to be substantially improved. At present it appears that combination chemotherapy with VP-16 has not been extensively studied and may be active in non-cross-resistant regimens.


Pompholyx as a side effect of intravenous immunoglobulin (IVIg).
Intravenous immunoglobulin (IVIg) is increasingly used across multiple specialties for the treatment of inflammatory and autoimmune diseases. Cutaneous reactions to IVIg are generally minor. Pompholyx is a common eruption of small vesicles on the palms, soles, and/or lateral aspects of the fingers. It has a multifactorial aetiology but is rarely attributed to being a drug-related side effect. We describe a 43-year-old woman presenting with peripheral sensory neuropathy who developed pompholyx eczema on both palms following treatment with IVIg.


A quantitative evaluation of fluid leakage around a polyvinyl chloride tapered endotracheal tube cuff using an in-vitro model.
This study was designed to quantitatively evaluate the sealing effect of a polyvinyl chloride tapered endotracheal tube cuff and to compare the tapered cuff with cylindrical endotracheal tube cuffs using an in vitro viscous fluid model. Five types of 8.0 mm inner diameter endotracheal tubes (TaperGuard, PortexSacett, PortexSoftseal, Sheridan HVT, Sheridan CF) were fixed in vertically placed 20mm internal diameter acrylic tubes. The cuffs were inflated to 25 mmHg pressure and water was added to the top of the cuff. The amount of water leaking around the cuff at five minutes was measured. Afterwards a viscous fluid was poured above the cuff and the amount of fluid passing around the cuff at five minutes and four hours was measured. Each determination was repeated five times and the data analyzed. The median (range) amount (ml) of dyed water passing around the cuff at 5 minutes was TaperGuard tube 0 (0-0.2), PortexSacett 81.1 (44.6-107.9), PortexSoftseal 95.4 (91.4-113.7), Sheridan HVT 46.5 (32.7-74.6) and Sheridan CF 52.6 (31.9-62.2), suggesting that TaperGuard significantly (P<0.05) reduced fluid leakage. The viscous fluid leakage at 5 minutes was not significantly different among the groups while the amount of leaked viscous fluid at 4 hours was 0.2 (0-1.1) for the TaperGuard, 57.6 (11.9-117.4) for the PortexSacett, 23.2 (13.8-33.0) for the PortexSoftseal, 5.5 (2.7-15.4) for the Sheridan HVT and 5.6 (1.8-7.9) for the Sheridan CF. An endotracheal tube with a tapered polyvinyl chloride cuff had significantly less fluid leakage compared to four tubes with cylindrical cuffs.


Incident light immunofluorescence of alcohol-fixed colonies of ruminant mycoplasma.
Two species of ruminant mycoplasma colonies had to be fixed in ethyl alcohol so that incident immunofluorescence method could be applied. In addition, the stain reaction had to be kept for 90 minutes at 37 degrees C. This fluorescent antibody (FA) method was developed to identify colonies of Vom strain of Mycoplasma mycoides var. capri, V-5 strain of M. mycoides var. mycoides, and PG-2 strain of M. agalactiaeon agar, using fluorescent ultraviolet light. Fluorescence was not demonstrated when heterologous conjugates or normal rabbit serum conjugate were applied but the reaction appeared to be specific for each strain of mycoplasma. The FA method was able to differentiate specific mycloplasma colonies in mixed cultures.


Triaxial system in bronchial arterial embolization for haemoptysis using N-butyl-2-cyanoacrylate.
The application of bronchial artery embolization (BAE) using N-butyl-2-cyanoacrylate (NBCA) for haemoptysis was recently reported to be useful. A triple co-axial (triaxial) system consisting of a 4-Fr catheter, 2.7-Fr microcatheter and 1.9-Fr no-taper microcatheter has been developed. The aim of the present study was to evaluate the usefulness of the triaxial system in BAE using NBCA. 12 patients with haemoptysis, 8 males and 4 females with a median age of 64 years (range, 49-88 years), underwent BAE between August 2012 and October 2014. Medical records and images were reviewed, and the technical success rate, clinical success rate, haemoptysis-free rate and complications were evaluated. Technical success was defined as the complete cessation of the target artery as confirmed by digital subtraction angiography, whereas clinical success was defined as the cessation of haemoptysis within 24 h of BAE. Recurrent haemoptysis was defined as a total of >30 ml of bleeding per day. The target artery was embolized successfully in all patients, and the technical success rate was 100% (12/12). The cessation of haemoptysis was achieved in 11 out of 12 patients within 24 h, and thus, the clinical success rate was 92% (11/12). The 6-, 12- and 24-month haemoptysis-free rates were 89%, 89% and 76%, respectively. No patients exhibited any signs of complications such as spinal ischaemia. BAE using the triaxial system and NBCA appears to be a useful and safe procedure for haemoptysis. The triaxial system contributes to safe and effective BAE using NBCA.


Rethinking the cost of healthcare in low-resource settings: the value of time-driven activity-based costing.
Low-income and middle-income countries account for over 80% of the world's infectious disease burden, but <20% of global expenditures on health. In this context, judicious resource allocation can mean the difference between life and death, not just for individual patients, but entire patient populations. Understanding the cost of healthcare delivery is a prerequisite for allocating health resources, such as staff and medicines, in a way that is effective, efficient, just and fair. Nevertheless, health costs are often poorly understood, undermining effectiveness and efficiency of service delivery. We outline shortcomings, and consequences, of common approaches to estimating the cost of healthcare in low-resource settings, as well as advantages of a newly introduced approach in healthcare known as time-driven activity-based costing (TDABC). TDABC is a patient-centred approach to cost analysis, meaning that it begins by studying the flow of individual patients through the health system, and measuring the human, equipment and facility resources used to treat the patients. The benefits of this approach are numerous: fewer assumptions need to be made, heterogeneity in expenditures can be studied, service delivery can be modelled and streamlined and stronger linkages can be established between resource allocation and health outcomes. TDABC has demonstrated significant benefits for improving health service delivery in high-income countries but has yet to be adopted in resource-limited settings. We provide an illustrative case study of its application throughout a network of hospitals in Haiti, as well as a simplified framework for policymakers to apply this approach in low-resource settings around the world.


Anomalous bending of a polyelectrolyte.
We report on a study of the shape of a stiff, charged rod that is subjected to equal and opposite force couples at its two ends. Unlike a neutral elastic rod, which forms a constant curvature configuration under such influences, the charged rod tends to flatten in the interior and accumulate the curvature in the end points, to maximally reduce the electrostatic self-repulsion. The effect of this nonuniform bending on the effective elasticity and on the statistical conformations of a fluctuating charged rod is discussed. An alternative definition for the electrostatic persistence length is suggested. This definition is found to be consistent with a corresponding length that can be deduced from the end-to-end distribution function of a fluctuating polyelectrolyte.


Surgical treatment of secondary fractures after percutaneous vertebroplasty: A retrospective study.
Percutaneous vertebroplasty (PVP) and percutaneous kyphoplasty (PKP) are effective procedures for the treatment of vertebral compression fractures (VCFs). However, recent studies have reported that secondary VCFs develop in patients after PVP or PKP treatment. This study aimed to investigate the clinical characteristics and management of secondary fractures after PVP or PKP. 599 cases who had vertebral compression fracture and underwent PVP or PKP between September 2008 and June 2014 were enrolled, including 121 males and 478 females. Secondary fractures were observed in 52 cases, including 3 males and 49 females, who were treated by re-operation with PVP or PKP. The ratio of secondary fracture after PVP or PKP was 8.68% in all cases. The age ranged from 59 to 92 years (74.41 ± 6.83 average). A composition of 44.44% of the secondary fracture occurred near the initial fracture vertebrae. After re-operation with PVP or PKP, visual analog scale score significantly decreased to 2.72 ± 0.88 or 2.52 ± 1.12, respectively, anterior height of vertebral bodies increased to 24.69 ± 4.59 or 24.54 ± 5.97 mm, respectively, and middle height of vertebral bodies increased to 20.90 ± 3.72 or 20.36 ± 6.33 mm, respectively. There is a high chance of secondary fracture near the initially operated vertebrae after PVP or PKP. Re-operation with PVP or PKP achieves satisfactory outcomes in these patients such as pain relief and the recovery of the vertebrae height.


Ischemic cholangitis.
Ischemia-induced bile duct lesions have been collectively labeled as ischemic cholangitis. The biliary epithelium is dependent on arterial blood flow, unlike the hepatic parenchyma with its dual arterial and portal venous blood supply. As such, the biliary epithelium is susceptible to injury when arterial blood flow is compromised. This compromise can occur at the level of the major, named hepatic artery branches or at the microscopic, peribiliary capillary plexus level. Typically, ischemic cholangitis manifests as segmental strictures and cholangiectases with resultant mechanical impairment of bile flow and, occasionally, secondary infection of the biliary system. Ischemic cholangitis after liver transplantation is becoming an important problem and likely is attributable to numerous factors. Hepatic arterial infusion of chemotherapy and systemic vasculitis are other causes of ischemic cholangitis. The role of ischemia in other chronic biliary and ductopenic diseases remains speculative.


Factor structure of the McCarthy scales for males and females.
Determined the factor structure of the McCarthy Scales (1972) for a referred group of male and female children, ages 6 to 81/2, from rural eastern North Carolina and compared their factor structure to that of the standardization sample. Three hundred and one males and 177 females were separated into two groups and examined independently. The 21 individual test scores of the McCarthy were correlated and then subjected to a principal factor analysis followed by Varimax rotation. Three meaningful factors emerged for males and females: Verbal, Perceptual, and Motor factors for males and General-Cognitive, Verbal, and Memory factors for females. The factor analyses for males and females agreed with previous factor analytic studies conducted with referred samples on the absence of a Quantitative factor and inconsistencies in the emergence of General-Cognitive and Memory factors. Coefficients of congruence with Kaufman's (1975) standardization analysis suggest that the McCarthy Scales reflect a general dimension of cognitive ability rather than a measure of distinct abilities for a referred sample of males and females.


Tegumentary leishmaniasis as a manifestation of immune reconstitution inflammatory syndrome in 2 patients with AIDS.
Immune reconstitution inflammatory syndromes (IRISs) have been reported in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (AIDS) since the introduction of highly active antiretroviral therapy (HAART). This syndrome is characterized by clinical manifestations of opportunistic infections when signs of immune reconstitution are observed during therapy. We report on leishmaniasis, suggestive of HAART-induced IRIS, in 2 patients with AIDS. After beginning HAART, 1 patient presented with disseminated, tegumentary lesions, whereas the other patient's preexisting lesions worsened and became more extensive; however, at the same time, their CD4(+) T cell counts were recovering and their virus loads were decreasing significantly. The lesions healed with anti-Leishmania therapy.


Is there a gluteus medius tendon injury during reaming through a modified medial trochanteric portal? A cadaver study.
The purpose of this cadaveric study was to evaluate whether there is any damage to the gluteus medius tendon when reaming through a modified medial trochanteric portal for antegrade intramedullary femoral nailing. Ten cadaver hips were used in this study. A guidewire was placed in the modified medial trochanteric portal using the assistance of C-arm fluoroscopy and a 14-mm reamer was advanced over the wire. After the reaming was complete, each hip was dissected and the gluteus medius muscle and tendon were inspected to evaluate the amount of intrasubstance and medial tendon damage. Precise localization of the modified medial trochanteric portal was achieved in 9 of 10 cadaver hips. Of those nine hips, the use of the modified medial trochanteric portal did not result in any visible damage to the tendinous insertion of the gluteus medius or the medial aspect of the tendon in any of the specimens. There is no damage to the gluteus medius tendon with the use of the modified medial trochanteric portal. Although the clinical implications of this finding are not known with certainty, the use of the modified medial trochanteric entry portal for antegrade femoral nailing could possibly result in less postoperative morbidity because it does not damage the gluteus medius tendon as compared to the traditional more lateral trochanteric portal.


Gestational diabetes predicts the risk of childhood overweight and abdominal circumference independent of maternal obesity.
Gestational diabetes mellitus is believed to be a risk factor for childhood overweight/obesity. We aimed to assess whether this association is either a reflection or independent of confounding by maternal BMI. Data from 7355 mother-child dyads of the German Perinatal Prevention of Obesity cohort with full anthropometric information on mothers and children, gestational diabetes and confounding factors were obtained at school entry health examination. We calculated crude and adjusted logistic regression models for the association of gestational diabetes and childhood overweight/obesity and abdominal adiposity defined by age- and sex-specific percentiles for BMI and waist circumference. Among all children (mean age 5.8 years), 8.1% were overweight, 2.6% were obese and 15.5% had abdominal adiposity. The prevalence of overweight (obesity) was 21% (8.2%) in children of mothers with gestational diabetes and 10.4% (2.4%) in children of healthy mothers. Analyses with adjustment for maternal BMI and other potential confounders yielded an odds ratio of 1.81 (95% CI 1.23-2.65) and 2.80 (95% CI 1.58-4.99) for the impact of gestational diabetes on childhood overweight and obesity, respectively. Similar results were obtained for the risk of childhood abdominal adiposity (odds ratio 1.64, 95% CI 1.16-2.33) by maternal gestational diabetes. The postulated increased risk of overweight and abdominal adiposity in offspring of mothers with gestational diabetes cannot be explained by maternal BMI alone and may be stronger for childhood obesity than for overweight.


Obesity alone should not rule out knee replacement surgery.
The studyEvans JT, Mouchti S, Blom AW, et al. Obesity and revision surgery, mortality, and patient-reported outcomes after primary knee replacement surgery in the National Joint Registry: a UK cohort study. PLoS Med 2021;18:7.


[Clinical observation of traumatically-damaged joint after its repair with transplantation of allogenic joint].
To evaluate the long-term function of the traumatically-damaged joint after its repair with transplantation of a fresh or a frozen allogenic joint. From March 1977 to September 1993, 13 patients (9 males, 4 females; age, 17-55 years) with traumatically-damaged joints underwent transplantation of the fresh or the frozen allogenic joints. Five patients had 5 damaged metacarpophalangeal joints, 6 patients had 9 damaged interphalangeal joints, and 2 patients had 2 damaged elbow joints. So, the traumatic damage involved 13 patients and 16 joints. All the metacarpophalangeal joints and the interphalangeal joints were injured by machines and the 2 elbow joints were injured by road accidents. The patients were randomly divided into 2 groups: Group A (n=7) and Group B (n= 6). The 7 patients with 8 joints in Group A underwent transplantation of fresh allogenic joints; the 6 patients with 8 joints in Group B underwent transplantation of frozen allogenic joints. The allogenic joint transplants were performed in the period from immediately after the injuries to 6 months after the injuries. The motion ranges of the transplanted joints and the X-ray films were examined after operation, and the immunological examination was performed at 8 weeks after operation. The time for synostosis was 5-8 months in Group A, but 4-6 months in Group B. In Group A, at 2 years after operation the metacarpophalangeal flexion was 30-40 degrees and the interphalangeal flexion was 20-30 degrees; however, at 6 or 7 years after operation the interphalangeal flexion was only 10-20 degrees. The patients undergoing the transplantation with fresh elbow joints had the elbow flexion of 60 degrees and the elbow extension of 0 degrees, and had the forearm pronation of 30 degrees and the forearm supination of 30 degrees. But in Group B, at 2 years after operation the metacarpophalangeal flexion was 60-70 degrees and the interphalangeal flexion was 40-50 degrees; at 6 or 7 years after operation the interphalangeal flexion was still 40-50 degrees. However, the patients undergoing the transplantation with frozen elbow joints had the elbow flexion of 90 degrees and the elbow extension of 0 degrees, and had the forearm pronation of 45 degrees and a forearm supination of 45 degrees. The joint motion ranges, the X-ray findings, and the immunological results in the patients undergoing the transplantation of the frozen allogenic joints were significantly better than those in the patients undergoing the transplantation of fresh allogenic joints. There was a significant difference in the immunological examination between Group A and Group B (IL-2, 21.64 +/- 3.99; CD4/CD8, 3.88 +/- 0.82 vs. IL-2, 16.63 +/- 3.11; CD4/CD8, 2.53 +/- 0.23, P<0. 01). Conclusion Repairing the traumatically-damaged joints with frozen allogenic joints is a better method of regaining the contour, movement, and complex motion of the hands.


Distance and near visual acuity improvement after implantation of multifocal intraocular lenses in cataract patients with presbyopia: a systematic review.
To evaluate uncorrected distance visual acuity (UDVA) as well as uncorrected near visual acuity (UNVA) as outcomes in treating presbyopic cataract patients to assist clinicians and ophthalmologists in their decision-making process regarding available interventions. Medline, Embase, and Evidence Based Medicine Reviews were systematically reviewed to identify studies reporting changes in UDVA and UNVA after cataract surgery in presbyopic patients. Strict inclusion/exclusion criteria were used to exclude any studies not reporting uncorrected visual acuity in a presbyopic population with cataracts implanted with multifocal intraocular lenses (IOLs). Relevant outcomes (UDVA and UNVA) were identified from the studies retrieved through the systematic review process. Twenty-nine studies were identified that reported uncorrected visual acuities, including one study that reported uncorrected intermediate visual acuity. Nine brands of multifocal IOLs were identified in the search. All studies identified in the literature search reported improvements in UDVA and UNVA following multifocal IOL implantation. The largest improvements in visual acuity were reported using the Rayner M-Flex lens (Rayner Intraocular Lenses Ltd) (UDVA, binocular: 1.05 logMAR, monocular: 0.92 logMAR; UNVA, binocular and monocular: 0.83 logMAR) and the smallest improvements were reported using the Acri.LISA lens (Carl Zeiss Meditec) (UDVA, 0.21 decimal; UNVA, 0.51 decimal). The results of this systematic review show the aggregate of studies reporting a beneficial increase in UDVA and UNVA with the use of multifocal IOLs in cataract patients with presbyopia, hence providing evidence to support the hypothesis that multifocal IOLs increase UDVA and UNVA in cataract patients.


KOH mount as an aid in the management of infectious keratitis at secondary eye care centre.
To report the clinical outcome of infectious keratitis managed after doing 10% KOH mount of corneal smears and reporting done by an ophthalmologist in the secondary eye care centre in South India. 103 consecutive cases of microbial keratitis were studied. Inclusion criteria were presence of corneal infiltrate on slit lamp biomicroscopy. An ophthalmologist carried out microbiological evaluation of 10% KOH mount of corneal scrapings. No cultures were done at secondary centres. Antifungal therapy with 5% Natamycin was initiated when 10% KOH mount was positive for fungal filaments. Else, the patients were started on combined topical ciprofloxacin (0.3%) and fortified cefazolin (5%). 41/103 (39.8%) smears were positive for fungus and 62 (60.2%) were negative. 89 out of 103 patients (86.40%) healed with scarring at an average of 2.95±1.58 weeks. Healing was noted in 39/41 (95.12%) of patients at an average of 3.06±1.19 weeks in patients with KOH smear positive keratitis. 80.64% (50/62) healed with scarring at an average period of 2.86±1.86 weeks in KOH mount negative keratitis. Initial smear examination of KOH mount by an ophthalmologist helped in diagnosis of infectious keratitis caused by fungi and its management and 95.12% of KOH positive patients healed with scarring. Reading of KOH mount by an ophthalmologist helped in initiation of specific therapy with improved clinical outcome.


Antibody precipitation of lipid vesicles containing myelin proteins: dependence on lipid composition.
Antibody binding to human CNS myelin basic protein and to rabbit sciatic nerve myelin P-2 in their lipid-bound and water-soluble conformations has been investigated. 125I-labeled basic protein or P-2 was bound to the surface of liposomes (vesicles) of different acidic lipids, phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidic acid (PA), phosphatidylglycerol (PG), and cerebroside sulfate (CBS). The antibody was prepared against aqueous solutions of basic protein and P-2. Antibody binding to the proteins in liposomes was measured by precipitation of the liposomes by using a double antibody radioimmunoassay. The amount of 125I-basic protein precipitated was lest when the protein was bound to PA and increased in the order PA less than PS less than PG less than CBS less than PE approximately equal to basic protein in solution, suggesting that the antigenic determinants were lest exposed or most altered for PA and most exposed for PE. This agreed fairly well with previously published biophysical studies that suggested that hydrophobic segments of the protein penetrated into the lipid bilayer and that this penetration decreased in the order PA approximately equal to PG greater than PS greater than CBS greater than or equal to PE. The amount of 125I-P-2 precipitated was least for PA and CBS and increased in the order PA approximately equal to CBS less than PS less than PG less than PE approximately equal to P-2 in solution. However, the differences were less than for basic protein and the effect of CBS was different for the 2 proteins. Less is known about the conformation of P-2 in these lipids but it is known that lipids increase its disease-inducing activity. These results indicate that interaction with lipid may sequester or alter the conformation of antigenic determinants such that antibody binding decreases.


[An extended operation for scirrhous gastric cancer--its significance and procedure].
We have been performing an extended operation for scirrhous gastric cancer, namely left upper abdominal exenteration plus Appleby's method, and compared the prognosis among macroscopic subtype classifications. The surgical procedure of left upper abdominal exenteration plus Appleby's method is to resect the neighboring organs of the stomach in an en bloc fashion. It consists of total gastrectomy, partial pancreatectomy, splenectomy, transverse colectomy, cholecystectomy, resection of the left adrenal gland, and ligation and resection of the common hepatic artery. D4 lymph node dissection is carried out. Extended operations were performed for 45 cases of P0-1 scirrhous gastric cancer in 1983-1990. There were 25, 17 and 3 cases of giant fold type, erosive type and stenotic type scirrhous gastric cancers, respectively. Positive lymph node metastases were found in 64% of giant fold type cases and 82% of erosive type cases. In Po, T3-4 cases, cytology of intraoperative peritoneal lavage was positive in 27% of giant fold type cases and 50% of erosive type cases. Although there were no obvious macroscopic invasions found during the operative procedure, later histological study showed invasion to the left adrenal gland in 14% of giant fold type cases and 0% of erosive type cases, and invasion to the transverse colon in 21% of giant fold type cases and 15% of fold type and erosive type scirrhous gastric cancer according to the histological invasion of transverse colon were 25% in positive cases and 27% in negative cases (p = 0.27), 0% in positive cases and 27% in negative cases (p = 0.27), respectively. In giant fold type scirrhous gastric cancer, the extended operation is favorable. In erosive type scirrhous gastric cancer, peritoneal dissemination is observed with a high incidence. Therefore, prophylactic therapy is significant.


A Nonheme Mononuclear {FeNO}7 Complex that Produces N2 O in the Absence of an Exogenous Reductant.
A new nonheme iron(II) complex, FeII (Me3 TACN)((OSiPh2 )2 O) (1), is reported. Reaction of 1 with NO(g) gives a stable mononitrosyl complex Fe(NO)(Me3 TACN)((OSiPh2 )2 O) (2), which was characterized by Mössbauer (δ=0.52 mm s-1 , |ΔEQ |=0.80 mm s-1 ), EPR (S=3/2), resonance Raman (RR) and Fe K-edge X-ray absorption spectroscopies. The data show that 2 is an {FeNO}7 complex with an S=3/2 spin ground state. The RR spectrum (λexc =458 nm) of 2 combined with isotopic labeling (15 N, 18 O) reveals ν(N-O)=1680 cm-1 , which is highly activated, and is a nearly identical match to that seen for the reactive mononitrosyl intermediate in the nonheme iron enzyme FDPnor (ν(NO)=1681 cm-1 ). Complex 2 reacts rapidly with H2 O in THF to produce the N-N coupled product N2 O, providing the first example of a mononuclear nonheme iron complex that is capable of converting NO to N2 O in the absence of an exogenous reductant.


An Ensemble Spatiotemporal Model for Predicting PM2.5 Concentrations.
Although fine particulate matter with a diameter of <2.5 μm (PM2.5) has a greater negative impact on human health than particulate matter with a diameter of <10 μm (PM10), measurements of PM2.5 have only recently been performed, and the spatial coverage of these measurements is limited. Comprehensively assessing PM2.5 pollution levels and the cumulative health effects is difficult because PM2.5 monitoring data for prior time periods and certain regions are not available. In this paper, we propose a promising approach for robustly predicting PM2.5 concentrations. In our approach, a generalized additive model is first used to quantify the non-linear associations between predictors and PM2.5, the bagging method is used to sample the dataset and train different models to reduce the bias in prediction, and the variogram for the daily residuals of the ensemble predictions is then simulated to improve our predictions. Shandong Province, China, is the study region, and data from 96 monitoring stations were included. To train and validate the models, we used PM2.5 measurement data from 2014 with other predictors, including PM10 data, meteorological parameters, remote sensing data, and land-use data. The validation results revealed that the R² value was improved and reached 0.89 when PM10 was used as a predictor and a kriging interpolation was performed for the residuals. However, when PM10 was not used as a predictor, our method still achieved a CV R² value of up to 0.86. The ensemble of spatial characteristics of relevant factors explained approximately 32% of the variance and improved the PM2.5 predictions. The spatiotemporal modeling approach to estimating PM2.5 concentrations presented in this paper has important implications for assessing PM2.5 exposure and its cumulative health effects.


Using Ion Imaging to Measure Velocity Distributions in Surface Scattering Experiments.
We present a new implementation of ion imaging for the study of surface scattering processes. The technique uses a combination of spatial ion imaging with laser slicing and delayed pulsed extraction. The scattering velocities of interest are parallel to the imaging plane, allowing speed and angular distributions to be extracted from a single image. The first results of direct scattering of N2 from a clean, single-crystal Au(111) surface are reported, and the speed resolution is shown to be competitive with current state-of-the-art time-of-flight methods for velocity measurements while providing simultaneous measurements of in-plane angular distributions.


Immune subtypes and neoantigen-related immune evasion in advanced colorectal cancer.
Elimination of cancerous cells by the immune system is an important mechanism of protection from cancer, however, its effectiveness can be reduced owing to development of resistance and evasion. To understand the systemic immune response in advanced untreated primary colorectal cancer, we analyze immune subtypes and immune evasion via neoantigen-related mechanisms. We identify a distinctive cancer subtype characterized by immune evasion and very poor overall survival. This subtype has less clonal highly expressed neoantigens and high chromosomal instability, resulting in adaptive immune resistance mediated by the immune checkpoint molecules and neoantigen presentation disorders. We also observe that neoantigen depletion caused by immunoediting and high clonal neoantigen load are correlated with a good overall survival. Our results indicate that the status of the tumor microenvironment and neoantigen composition are promising new prognostic biomarkers with potential relevance for treatment plan decisions in advanced CRC.


Vaccination and antiviral treatment of neglected diseases caused by flaviviral infections.
Flaviviral infections have a re-emerging impact on the health situation in developing countries with several billions of people living at risk. In the present review, we focus on three members of the genus Flavivirus belonging to the Flaviviridae family. They are transmitted to humans by mosquito bites, namely those viruses leading to Dengue Fever, Yellow Fever and mosquito-borne Japanese encephalitis. All three virus groups have a spherical structure with a diameter of approximately 50 nm. Although sharing a similar genomic structure and intracellular life cycle, they show different clinical manifestations. Infections are incurable, as there is no antiviral treatment available for either of the three viruses. Thus, prevention and vaccination are the best defenses. The most promising vaccines are live attenuated vaccines (LAVs), such as the YF17D strain against Yellow Fever or the SA-14-14-2 strain against Japanese encephalitis. Additionally, recombinant vaccines for Japanese encephalitis are in development. Although Dengue Fever is the most prevalent arthropode-borne flaviviral infection and a lot of research to develop a vaccine against all four Dengue Fever serotypes was undertaken, no vaccine is available on the market yet. Promising tetravalent vaccine candidates are currently undergoing clinical phase trials, including LAVs, recombinant and chimeric candidates as well as non-replicating vaccine approaches. Additionally, encouraging anti-flaviviral approaches target non-structural proteins, virus-specific proteases essential for cellular maturation of viral particles. Peptide inhibitors against the highly conserved NS2B and NS3 proteases are attractive as pan-flaviviral drug candidates.


[Regulation of Bcl-2 expression in ageing T cells by CD137 and CD28].
To observe the effect of the costimulatory molecules CD137 and CD28 on Bcl-2 expression in T cells of mice with D-galactose-induced aging and natural aging. Seven-week-old male BALB/c mice were injected daily with D-galactose (120 mg/kg) for 5 months to induce subacute aging, and 16-month-old male BALB/c mice served as the natural aging group. The spleen T cells of were isolated from the rats and stimulated in vitro with conA+IgG, conA+CD137 mAb or conA+CD28 mAb for 48 h. Bcl-2 expression of T cells was detected by flow cytometry and semi-quantitative RT-PCR. In the subacute aging group, Bcl-2 protein expression rate in the T cells stimulated with conA+IgG, conA+CD137 mAb and conA+CD28 mAb were (24.4-/+1.5)%, (34.4-/+2.4) %, and (45.1-/+2.7) %, which were (19.6-/+2.0) %, (26.3-/+1.9) %, and (48.5-/+2.2) % in the natural aging group, respectively. In vitro stimulation with conA+IgG, conA+CD137 mAb and conA+CD28 mAb resulted in expression rate of bcl-2 mRNA in the T cells of 0.309-/+0.039, 0.547-/+0.036, and 0.780-/+0.041 in the subacute aging group, and 0.283-/+0.038, 0.535-/+0.041, and 0.771-/+0.063 in the natural aging group, respectively. CD137 and CD28 can promote bcl-2 expression at both mRNA and protein level in T cells in aging mice, which may be one of the mechanisms through which CD137 and CD28 molecules inhibit aging T cell apoptosis and maintain their function.


Psychometric properties of the Assessment Tool for Perceived Agency (ATPA-22) - utility for the rehabilitation of young adults not in education, employment or training (NEETs).
Promoting and supporting agency have been at the heart of the debate multidisciplinary. To promote self-awareness of young people's agency and identify persons in need of support the Assessment Tool for Perceived Agency (ATPA-22) was developed. This study aims to evaluate the psychometric properties of the ATPA-22. Participants were young adults not in education, employment or training (NEETs) and students in higher education (HEI). The main data analysis was implemented by Many Faceted Rasch (MFR) analysis. The ATPA-22 items defined a unidimensional construct with reasonable internal consistency and separation ability. The ATPA-22 was capable of detecting differences between HEI students and young adult NEETs. Nine differential functioning items emerged between the groups. ATPA-22 shows promise as a tool to assess young adults' perceived agency. Anyhow, as the individual life situation affects strongly to perceived agency, research on the stability of the ATPA-22 among different populations is needed. The purpose of the ATPA-22 is to measure perceived agency of individuals, and to identify aspects of agency in need for support. ATPA-22 can be used as a tool for promoting self-awareness of occupational challenges.


Comparison of ovarian function and circulating steroids in estrous cycles of Holstein heifers and lactating cows.
Ovarian function was compared between nulliparous heifers (n = 29; 10 to 16 mo old) and lactating Holstein cows (n = 31; 55.9 +/- 3.5 d postpartum). Follicular dynamics, corpus luteum growth, and regression, and serum steroid concentrations were evaluated through ultrasonography and daily blood sampling. Most heifers (27 of 29) but only 14 of 31 cows had typical spontaneous estrous cycles after cycles were initiated. Twelve cows had atypical cycles, and 5 became anovulatory during the study. The 12 cows with atypical estrous cycles had low serum estradiol after luteolysis and failed to ovulate the dominant follicle present at luteolysis. Heifers and cows with typical cycles were compared directly. Interovulatory intervals were similar between heifers (22.0 +/- 0.4 d) and cows (22.9 +/- 0.7 d). Those animals had estrous cycles with either 2 (15 heifers; 11 cows), 3 (9 heifers; 2 cows), or 4 follicular waves (3 heifers; 1 cow). Cows ovulated later after luteolysis than heifers (5.2 +/- 0.2 vs. 4.6 +/- 0.1 d, respectively), and had more multiple ovulations (17.9 vs. 1.9%). Maximal serum estradiol concentration preceding ovulation was lower in cows than in heifers (7.9 +/- 0.8 vs. 11.3 +/- 0.6 pg/mL) even though ovulatory follicles were larger in cows (16.8 +/- 0.5 vs. 14.9 +/- 0.2 mm). Similarly, maximal serum progesterone concentration was lower for cows (5.6 +/- 0.5 vs. 7.3 +/- 0.4 ng/mL), whereas maximal volume of luteal tissue was larger for cows than heifers (11,120 +/- 678 vs. 7303 +/- 308 mm3). Thus, higher incidence of reproductive anomalies in lactating cows, such as low conception rate, ovulation failure, delayed ovulation, and multiple ovulations, may be due to lower circulating steroid concentrations in spite of larger ovulatory follicles and luteal structures.


Association study of human MTH1 Ile45Thr polymorphism with sporadic Parkinson's disease.
Human MTH1, an oxidized purine nucleoside triphosphatase, hydrolyzes 8-oxo-dGTP thereby preventing its misincorporation into DNA. The present study was designed to investigate a possible link between the MTH1 Ile45Thr polymorphism and the development of sporadic Parkinson disease (PD). This case-control study consisted of 106 PD patients and 135 unrelated controls. MTH1 polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that Ile45/Thr45 heterozygote and Thr45 allele tended to be more frequent in sporadic PD, although statistically not significant (0.085 vs. 0.044, corrected p = 0.591 and 0.052 vs. 0.022, p = 0.080, respectively). Stratification analysis by gender showed that Ile45/Thr45 heterozygote tended to be more frequent in male PD patients than in male controls (0.113 vs. 0.038, corrected p = 0.480). The male PD patients exhibited a borderline statistically significant higher frequency of the Thr45 allele than the controls (0.073 vs. 0.019, corrected p = 0.050). These results suggested to us that the Thr45 allele of MTH1 might be associated with sporadic PD in the Chinese male population.


Incidence, pattern and direction of hair distribution on the dorsum of phalanges of the hands of male medical students of Uttar Pradesh, India.
In the present investigation direction and pattern of hair distribution were observed on the dorsum of phalanges of hands in 115 male medical students from Uttar Pradesh, India. Inproximal phalanges of the hands the direction of hair showed the relation with fingers. Observation of hair from little finger to thumb revealed the changes in direction from ulnar to radial (p less than 0.05). Probability of incidence of hair distribution was also studied among the fingers of both the hands. This correlation was significant on the proximal phalanges (p less than 0.05). However, no significant correlation coefficient was observed in the middle phalanges of the hands.


A community-based study of acute respiratory infections among preschool children in Syria.
A longitudinal community-based study of the epidemiology of acute respiratory infections (ARI) in children less than 5 years old was carried out in a low income peri-urban area of Syria. A total of 1030 children were followed up by weekly morbidity surveillance for a period of 24 weeks, starting September 1989. The results revealed that, on average, a child suffered 3.4 episodes of ARI per 100 child-days at risk. The average prevalence of ARI was 23 per cent of time of observation. The peak age-specific incidence occurred in children 6-12 months old for cough/cold, and in children 0-5 months for pneumonia. Male children experienced higher incidence and prevalence of ARI. The most frequently reported symptoms were nasal discharge and cough.


Phenacetin abuse and chronic pyelonephritis.
A history of phenacetin abuse has been found almost three times more frequently among subjects diagnosed on clinical and functional grounds as suffering from chronic pyelonephritis than among those suffering from other renal diseases or among non-renal controls. The chronic pyelonephritis in subjects admitting phenacetin abuse has been usually characterized by a more frequent intense bacteriuria and leucocyturia, by a slightly more frequent haematuria, history of renal colic, presence of stones and more rapid downhill course of glomerular filtration rate than in subjects without phenacetin abuse. A sterile lesion also without any past evidence of infection was observed only in subjects with the heaviest analgesic abuse. The discontinuation of the abuse in 5 subjects led to an improvement of the renal function.


Twelve tips for developing training programs for international medical graduates.
International Medical Graduates (IMGs) are a diverse group of doctors who provide essential health services in many western countries, and hospitals are increasingly relying upon IMGs to fill vacancies in all staff grades. Clinical skills and experience vary greatly between doctors, and orientation and clinical skills training is a way of addressing any identified deficiencies. This paper relates the experiences of establishing a training program and support services for IMGs working in the public hospital system in Tasmania, Australia, and offers advice for other agencies contemplating establishing similar programs. A 'hub and spoke' model is a useful model to adopt: a central coordinating office designs and implements programs informed by best available evidence, and clinical educators on site at healthcare facilities implement programs and provide direct assistance and orientation. Broad-based programs attending to orientation, doctor's families' needs, communication skills and clinical skills training are required. Support from health administrators is essential.


[HL-A and potential diabetics (type 2)].
21-HLA-A and B antigens were typed in 34 descendants of the parents with diabetes mellitus type 2(maturity-onset type). No relationship between the potential diabetes mellitus type 2 and the HLA system was found.


Green fluorescent protein based pH indicators for in vivo use: a review.
Green fluorescent protein (GFP) and its variants have been used as fluorescent reporters in a variety of applications for monitoring dynamic processes in cells and organisms, including gene expression, protein localization, and intracellular dynamics. GFP fluorescence is stable, species-independent, and can be monitored noninvasively in living cells by fluorescence microscopy, flow cytometry, or macroscopic imaging techniques. Owing to the presence of a phenol group on the chromophore, most GFP variants display pH-sensitive absorption and fluorescence bands. Such behavior has been exploited to genetically engineer encodable pH indicators for studies of pH regulation within specific intracellular compartments that cannot be probed using conventional pH-sensitive dyes. These pH indicators contributed to shedding light on a number of cell functions for which intracellular pH is an important modulator. In this review we discuss the photophysical properties that make GFPs so special as pH indicators for in vivo use and we describe the probes that are utilized most by the scientific community.


Influence of semisynthetic modification of the scaffold of a contact domain of HbS on polymerization: role of flexible surface topology in polymerization inhibition.
A new variant of HbS, HbS-Einstein with a deletion of segment α23-26 in the B-helix, has been assembled by semisynthetic approach. B-helix of the α chain of cis αβ-dimer of HbS plays dominant role in the quinary interactions of deoxy HbS dimer. This B-helix is the primary scaffold that provides the orientation for the side chains of contact residues of this intermolecular contact domain. The design of HbS-Einstein has been undertaken to map the influence of perturbation of molecular surface topology and the flexibility of surface residues in the polymerization. The internal deletion exerts a strong inhibitory influence on Val-6 (β)-dependent polymerization, comparable to single contact site mutations and not for complete neutralization of Val-6(β)-dependent polymerization. The scaffold modification in cis-dimer is inhibitory, and is without any effect when present on the trans dimer. The flexibility changes in the surface topology in the region of scaffold modification apparently counteracts the intrinsic polymerization potential of the molecule. The inhibition is close to that of Le Lamentin mutation [His-20 (α) → Gln] wherein a mutation engineered without much change in flexibility of the contact domain. Interestingly, the chimeric HbS with swine-human chimeric α chain with multiple non-conservative mutations completely inhibits the Val-6(β)-dependent polymerization. The deformabilities of surface topology of chimeric HbS are comparable to HbS in spite of the multiple contact site mutations in the α-chain. We conclude that the design of antisickling Hbs for gene therapy of sickle cell disease should involve multiple mutations of intermolecular contact sites.


A B cell-, T cell-linked epitope located on the adhesin of Mycoplasma pneumoniae.
The identification of specific T cell and B cell epitopes of the P1 protein, which functions as an adhesin and as a major antigen of Mycoplasma pneumoniae, has become of central interest for the design of synthetic vaccines. Here we report the isolation from guinea pigs infected intranasally with M. pneumoniae of hilar and bronchial T lymphocytes which proliferated after in vitro stimulation with sonicated M. pneumoniae whole-cell antigen and with the isolated P1 protein. For more detailed information on T cell epitopes, a 51-amino-acid region (histidine 821 to glycine 871; numbered from the NH2-terminal end) of the P1 protein was analyzed for a T cell epitope. An octapeptide, S-G-S-R-S-F-L-P (starting at amino acid 845), stimulated in vitro lymphocytes of bronchial washings and of hilar lymph nodes. Furthermore, this T cell-stimulating amino acid sequence was located at the C-terminal end of a B cell epitope with the sequence T-N-T (starting at amino acid 842).


Increasing applicability of liver transplantation for patients with hepatitis B-related liver disease.
Liver transplantation in patients with hepatitis B has been under discussion for 20 years because of inferior results without reinfection prophylaxis; therefore, we analyzed our overall experience with liver transplantation in hepatitis B patients with immunoprophylaxis, particularly the influence of the available antiviral treatment in different periods. From 1988 to 2000, 228 liver transplants in 206 hepatitis B patients were performed. Indications were acute liver failure (10%), hepatitis B virus (HBV) cirrhosis alone (67%) or with hepatitis D virus (HDV) (13%), or hepatitis C virus (HCV) coinfection (7%). All patients received long-term immunoprophylaxis (anti-HBs > 100 U/L). HBV DNA-positive patients were treated before and after surgery with famciclovir or lamivudine since 1993 and 1996, respectively. Since 1993, antivirals also were used for HBV reinfection. The 1-, 5-, and 10-year patient survival rates were 91%, 81%, and 73%. In patients with hepatocellular carcinoma (HCC) (60% 5-year survival, P <.01) or HBV reinfection (69% 5-year survival, P <.01) survival was significantly impaired. Those with HDV or HCV coinfection had a slightly better survival than with HBV monoinfection (P >.05, not significant). Preoperative positive HBV DNA (hybridization-assay) test results were associated with a slightly impaired patient survival (78% 5-year survival, P >.05, not significant versus DNA-negative). Preoperative positive hepatitis B e antigen (HBeAg) predicted significantly worse survival (P <.05 versus negative HBeAg). Graft loss caused by reinfection was most frequent before the availability of antiviral drugs. Two-year patient survival increased from 85% in era I (1988-1993) to 94% in era III (1997-2000, P <.05). The 2-year recurrence rates in these 2 periods were 42% and 8% (P <.05). In conclusion, excellent long-term results can be achieved in hepatitis B patients after liver transplantation with modern strategies, and survival rates are similar to other indications. Based on our experience, hepatitis B patients, including those with active viral replication, should not be excluded from liver transplantation.


Identification of differentially expressed reproductive and metabolic proteins in the female abalone (Haliotis laevigata) gonad following artificial induction of spawning.
Inefficient control of temperate abalone spawning prevents pair-wise breeding and production of abalone with highly marketable traits. Traditionally, abalone farmers have used a combination of UV irradiation and application of temperature gradients to the tank water to artificially induce spawning. Proteins are known to regulate crucial processes such as respiration, muscle contraction, feeding, growth and reproduction. Spawning as a pre-requisite of abalone reproduction is likely to be regulated, in part, by endogenous proteins. A first step in elucidating the mechanisms that regulate spawning is to identify which proteins are directly involved during spawning. The present study examined protein expression following traditional spawning induction in the Haliotis laevigata female. Gonads were collected from abalone in the following physiological states: (1) spawning; (2) post-spawning; and (3) failed-to-spawn. Differential protein abundance was initially assessed using two-dimensional difference in-gel electrophoresis coupled with mass spectrometry for protein identification. A number of reproductive proteins such as vitellogenin, vitelline envelope zona pellucida domain 29 and prohibitin, and metabolic proteins such as thioredoxin peroxidase, superoxide dismutase and heat shock proteins were identified. Differences in protein abundance levels between physiological states were further assessed using scheduled multiple reaction monitoring mass spectrometry. Positive associations were observed between the abundance of specific proteins, such as heat shock cognate 70 and peroxiredoxin 6, and the propensity or failure to spawn in abalone. These findings have contributed to better understand both the effects of oxidative and heat stress over abalone physiology and their influence on abalone spawning.


Intramuscular injection of islet neogenesis-associated protein peptide stimulates pancreatic islet neogenesis in healthy dogs.
Diabetes is a serious health problem. It has been proposed that islet neogenesis from pancreatic progenitor cells may restore insulin secretion in diabetic mammals. Islet neogenesis- associated protein (INGAP) stimulates islet neogenesis; therefore, we hypothesized that it would stimulate islet neogenesis in dogs. Forty nondiabetic beagle dogs were randomly divided into 4 groups. Group 1 received daily intramuscular injections of vehicle, whereas the other 3 groups received daily INGAP injections of 0.5, 1.5, or 10 mg/kg. After 30 days, pancreatic tissues were collected, and RNA and histological sections were analyzed. In dogs treated with 1.5 mg/kg INGAP, there was a significant (P < 0.001) increase in the percentage of insulin-positive cells (P < 0.001) and insulin gene expression. There was a trend to increased insulin-positive cells and gene expression with treatments of 0.5 and 10 mg/kg peptide. Protein gene product 9.5-positive cells were increased with treatment. These results indicate that INGAP stimulates cells in the pancreatic duct epithelium of healthy dogs (putative islet progenitor cells) to develop along a neuroendocrine pathway and form new islets in response to INGAP peptide. The INGAP might be an effective therapy for diabetes.


Treatment with the angiogenesis inhibitor endostatin: a novel therapy in rheumatoid arthritis.
An endostatin that inhibits angiogenesis dependent tumor growth is being tested as an antitumor agent. The neoangiogenesis condition of cancer is essentially identical to that of rheumatoid arthritis (RA). Thus antiangiogenic treatment has potential for treatment of RA. We investigated the effects of human recombinant endostatin on human RA synovial tissue by use of a novel model of RA, in which human RA tissue is grafted into SCID mice (SCID-HuRAg). Ten or 50 mg/kg of human recombinant endostatin was administered by percutaneous direct intrasynovial injection in each of 7 SCID-HuRAg mice. We examined the volume of the grafted tissue mass and the histological changes 7 days after endostatin administration. Six control mice received phosphate buffered saline in the same manner. The grafted synovial volume of SCID-HuRAg mice was significantly decreased by endostatin administration. The number of inflammatory cells (macrophages and lymphocytes) was also significantly reduced in a dose dependent manner. The number of vessels that were counted by von Willebrand factor VIII and type IV collagen positive cells was decreased, although apoptotic cells were increased in RA synovia. The results suggest that antiangiogenesis treatment using endostatin represents a potential new therapeutic strategy for RA.


Effects of manure compost application on soil microbial community diversity and soil microenvironments in a temperate cropland in China.
The long-term application of excessive chemical fertilizers has resulted in the degeneration of soil quality parameters such as soil microbial biomass, communities, and nutrient content, which in turn affects crop health, productivity, and soil sustainable productivity. The objective of this study was to develop a rapid and efficient solution for rehabilitating degraded cropland soils by precisely quantifying soil quality parameters through the application of manure compost and bacteria fertilizers or its combination during maize growth. We investigated dynamic impacts on soil microbial count, biomass, basal respiration, community structure diversity, and enzyme activity using six different treatments [no fertilizer (CK), N fertilizer (N), N fertilizer + bacterial fertilizer (NB), manure compost (M), manure compost + bacterial fertilizer (MB), and bacterial fertilizer (B)] in the plowed layer (0-20 cm) of potted soil during various maize growth stages in a temperate cropland of eastern China. Denaturing gradient electrophoresis (DGGE) fingerprinting analysis showed that the structure and composition of bacterial and fungi communities in the six fertilizer treatments varied at different levels. The Shannon index of bacterial and fungi communities displayed the highest value in the MB treatments and the lowest in the N treatment at the maize mature stage. Changes in soil microorganism community structure and diversity after different fertilizer treatments resulted in different microbial properties. Adding manure compost significantly increased the amount of cultivable microorganisms and microbial biomass, thus enhancing soil respiration and enzyme activities (p<0.01), whereas N treatment showed the opposite results (p<0.01). However, B and NB treatments minimally increased the amount of cultivable microorganisms and microbial biomass, with no obvious influence on community structure and soil enzymes. Our findings indicate that the application of manure compost plus bacterial fertilizers can immediately improve the microbial community structure and diversity of degraded cropland soils.


Structural Insights into RNA Dimerization: Motifs, Interfaces and Functions.
In comparison with the pervasive use of protein dimers and multimers in all domains of life, functional RNA oligomers have so far rarely been observed in nature. Their diminished occurrence contrasts starkly with the robust intrinsic potential of RNA to multimerize through long-range base-pairing ("kissing") interactions, self-annealing of palindromic or complementary sequences, and stable tertiary contact motifs, such as the GNRA tetraloop-receptors. To explore the general mechanics of RNA dimerization, we performed a meta-analysis of a collection of exemplary RNA homodimer structures consisting of viral genomic elements, ribozymes, riboswitches, etc., encompassing both functional and fortuitous dimers. Globally, we found that domain-swapped dimers and antiparallel, head-to-tail arrangements are predominant architectural themes. Locally, we observed that the same structural motifs, interfaces and forces that enable tertiary RNA folding also drive their higher-order assemblies. These feature prominently long-range kissing loops, pseudoknots, reciprocal base intercalations and A-minor interactions. We postulate that the scarcity of functional RNA multimers and limited diversity in multimerization motifs may reflect evolutionary constraints imposed by host antiviral immune surveillance and stress sensing. A deepening mechanistic understanding of RNA multimerization is expected to facilitate investigations into RNA and RNP assemblies, condensates, and granules and enable their potential therapeutical targeting.


Does the disclosure of medical insurance information affect patients' willingness to adopt the diagnosis related groups system.
Medical insurance information disclosure is not only a direct way for the public to understand and master social insurance information and resource use benefits, but also an important way for the public to participate in medical service governance and supervision. Some studies have shown that information disclosure can significantly reduce the risk perception of user groups, strengthen their trust and reduce the negative impact of information asymmetry. Based on risk perception and trust perception theories, this paper focuses on the mechanisms influencing patients' attitudes in the process of implementing a Diagnosis Related Groups payment system. Using medical insurance information disclosure from a governance perspective as the research object, the impact of medical insurance information disclosure on patients' willingness to adopt the Diagnosis Related Groups payment system was analyzed by means of a questionnaire survey, Data analysis and hypothesis testing via SPSS while the mechanism of the impact of medical insurance information disclosure on patients' attitudes was explored in depth. It was found that medical insurance information disclosure had a significant positive effect on patients' trust perceptions and a significant negative effect on patients' risk perceptions. The more comprehensive information patients received, the stronger their trust and the lower their perceived risk. This paper conducts an empirical study from patients' perspective, broadens the scope of research on medical insurance Diagnosis related groups, enriches the application of risk perception and trust perception theories in the medical field, and provides management suggestions for medical institutions in the management of medical insurance information disclosure.


Scale to Assess Leaders' Perceptions about their Workers' Digital Addiction.
With the evolution of technologies and the mobility factor, new digital devices have emerged, influencing human behavior and provoking diverse dependencies due to their abusive use. Collective environments begin to exhibit the symptoms of such dependencies, compromising people's quality of life (QOL). The objective of the present study was to validate the scale to evaluate the perception of leaders on digital employee addiction (EPLDDE) initially with 17 questions. The scale was constructed with real situations of digital addiction and through the evaluation of the semantic comprehension and consistency of the items by judges until final formatting of the instrument. Data collection was done via the internet. The sample consisted of 312 volunteers from a federal state-owned company. After data collection, a database was created for statistical analysis. Statistical program R was used. Bartlett's and Kaiser-Meyer-Olkin (KMO) tests confirmed adequacy for factorial analysis. Three statistical criteria were used, and scree plot presented adequate commonalities indicating 5 factors and the withdrawal of 3 questions from the scale. In the second AF, results ratified 14 questions. Cronbach's alpha showed a positive result of 0.8131717. The 14-item EPLDDE scale was validated for the evaluation of the perception of leaders regarding digital dependence of employees in organizations. This scale can contribute to studies on organizational QOL. The limitations found did not compromise the results.


Overview of immigrant worker occupational health and safety for the agriculture, forestry, and fishing (AgFF) sector in the southeastern United States.
Manual labor in the Agriculture, Forestry, and Fishing (AgFF) Sector is provided primarily by immigrant workers. Limited information is available that documents the demographic characteristics of these manual workers, the occupational illnesses, injuries and fatalities they experience; or the risk factors to which they are exposed. A working conference of experts on occupational health in the AgFF Sector was held to address information limitations. This paper provides an overview of the conference. Other reports address organization of work, health outcomes, healthcare access, and safety policy. This report addresses how best to define the population and the AgFF Sector, occupational exposures for the sector, data limitations, characteristics of immigrant workers, reasons for concern for immigrant workers in the AgFF Sector, regulations, a conceptual model for occupational health, and directions for research and intervention.


What have we learned from prospective cohort studies of asthma in children?
Prospective cohort studies have provided a useful tool for the study of the natural history of asthma and lung function and for the development of concepts of asthma phenotypes during childhood. However, although observational epidemiology has indicated a large number of credible associations between environmental variables and asthma onset in childhood, it can be argued that it has yet to fulfill the promise of identifying modifiable, causal risk factors that are amenable to intervention for the primary or secondary prevention of disease. The development of efficient, high-throughput genotyping that can be applied to large, longitudinal cohorts with detailed data on exposures and phenotypic outcomes, opens the way for studies of genetic effects and gene-environment interactions that may come closer to identifying causal pathways between exposure and disease. Therefore, there continues to be an important role for large-scale, observational studies with careful attention to definition and evaluation of outcomes and plausible risk factors.


Effect of glucamylase on tissue glycogen and tissue glucamylase in the rat.
1. A fungal glucamylase (alpha-1,4-glucan glucohydrolase, EC 184.108.40.206) from Aspergillus niger depresses liver glycogen stores after intraperitoneal injection into the rat. The injected enzyme rapidly disappears (within about 8hr.) from the serum; less than 1% is excreted in the urine, but it is rapidly taken up in the liver, spleen, kidney, cardiac and skeletal muscle. Elevated glucamylase concentrations could be demonstrated in liver and spleen tissues for 1-4 days after injection, but in kidney, cardiac and skeletal muscle elevated glucamylase concentrations could be shown only for periods of less than 24hr. after injection of the enzyme.


Prevalence and genetic diversity of Bartonella strains in rodents from northwestern Mexico.
Bartonella infections were investigated in wild rodents from northwestern Chihuahua, Mexico. A total of 489 rodents belonging to 14 species were surveyed in four areas. Bartonella bacteria were cultured from 50.1% of rodent samples (245/489). Infection rates ranged from 0% to 83.3% per rodent species, with no significant difference between sites except for Cynomys ludovicianus. Phylogenetic analyses of the citrate synthase gene (gltA) of the Bartonella isolates revealed 23 genetic variants (15 novel and 8 previously described), clustering into five phylogroups. Three phylogroups were associated with Bartonella vinsonii subsp. vinsonii, B. vinsonii subsp. arupensis, and B. washoensis, respectively. The other two phylogroups were not genetically related to any known Bartonella species. The genetic variants and phylogenetic groups exhibited a high degree of host specificity, mainly at the genus and family levels. This is the first study that describes the genetic diversity of Bartonella strains in wild rodents from Mexico. Considering that some variants found in this study are associated with Bartonella species that have been reported as zoonotic, more investigations are needed to further understand the ecology of Bartonella species in Mexican wildlife and their implications for human health.


Clustering properties of a generalized critical Euclidean network.
Many real-world networks exhibit a scale-free feature, have a small diameter, and a high clustering tendency. We study the properties of a growing network, which has all these features, in which an incoming node is connected to its ith predecessor of degree k(i) with a link of length l using a probability proportional to k(beta)(i)l(alpha). For alpha>-0.5, the network is scale-free at beta=1 with the degree distribution P(k) proportional to k(-gamma) and gamma=3.0 as in the Barabási-Albert model (alpha=0,beta=1). We find a phase boundary in the alpha-beta plane along which the network is scale-free. Interestingly, we find a scale-free behavior even for beta>1 for alpha<-0.5, where the existence of a different universality class is indicated from the behavior of the degree distribution and the clustering coefficients. The network has a small diameter in the entire scale-free region. The clustering coefficients emulate the behavior of most real networks for increasing negative values of alpha on the phase boundary.


Ab-lnitio study of neutral indium diffusion in uniaxially- and biaxially-strained silicon.
In this paper, we present our ab-initio study on energy configurations, minimum energy path (MEP), and migration energy for neutral indium diffusion in a uniaxial and biaxial tensile strained {100} silicon layer. Our ab-initio calculation of the electronic structure allowed us to figure out transient atomistic configurations during the indium diffusion in strained silicon. We found that the lowest-energy structure (Ins - SiTd) consists of indium sitting on a substitutional site while stabilizing a silicon self-interstitial in a nearby tetrahedral position. Our ab-initio calculation implied that the next lowest energy structure is Inj(Td), the interstitial indium at the tetrahedral position. We employed the nudged elastic band (NEB) method for estimating the MEP between the two structures. The NEB method allowed us to find that that diffusion pathway of neutral indium is kept unchanged in strained silicon while the migration energy of indium fluctuates in strained silicon.


Efficacy and prognosis of adalimumab for Crohn's disease at different disease locations: a systematic review and meta-analysis.
For over ten years, adalimumab (ADA) has been approved for treating active moderate to severe Crohn's disease (CD), showing irreplaceable efficacy. However, the difference in efficacy and prognosis when the disease pathology occurs in different locations of the body is still unclear. This study used systematic meta-analysis to assess the efficacy of ADA and prognosis in CD in different locations of disease pathology. We used "Adalimumab OR ADA OR HUMIRA OR IgG1 monoclonal antibody" AND "Crohn disease OR Crohn's disease OR CD OR IBD OR inflammatory bowel disease" as search strategies for searching electronic databases in the Embase, PubMed and CNKI databases. A systematic meta-analysis of proportions was performed to analyze the data. A total of 1,253 patients in 15 articles were included in our study. The results showed that treatment with ADA led to overall remission rates that were elevated (70%, 95% CI: 58%-79%) but a nonnegligible overall relapse rate (28%, 95% CI: 12%-53%) in patients with CD. More importantly, we indicated that the use of ADA in patients with colon only (L2), ileum and colon (L3) and upper gastrointestinal tract (L4) CD led to significantly lower clinical remission rates. The use of ADA in patients with L2 led to significantly higher relapse rates, but the use of ADA in patients with ileum only (L1) and L3 CD led to significantly lower relapse rates. Our findings clarify different remission and relapse rates depending on the location of the disease pathology and may be useful for clinicians' choice of treatment strategies.


Optimization of extraction and analytical protocol for mass spectrometry-based metabolomics analysis of hepatotoxicity.
Drug-induced liver injury is a clinically leading side-effect of drugs. In the present study, a liquid chromatography mass spectrometry-based metabolomics protocol was optimized for extraction and analysis of endogenous metabolites from liver tissue during hepatotoxicity. Various extraction solutions, resuspension solutions, extraction folds and dissolution methods for the supernatant were compared using the number of extracted total ions, relative response and relative extraction efficiency of targeted metabolites from liver tissue. The polar and nonpolar endogenous metabolites associated with liver injury were analyzed by hydrophilic interaction chromatography and reversed-phase liquid chromatography with UPLC-QTOFMS. The results indicated that extraction with 10-fold 50% acetonitrile in water and the supernatant diluted (1:1) with 100% acetonitrile rather than resuspension was the optimal extraction protocol. Subsequently, the optimized method was able to examine the change in metabolites in mouse liver tissue resulting from treatment with a toxic natural product, toosendanin. Taken together, the optimized extraction and analytical protocol provides high reliability and reproducibility for polar and nonpolar metabolites in liver tissue and may be suitable for metabolomics analysis of liver injury induced by drugs or chemicals.


The staging concept--an approach to the assessment of outcome of ambulatory care.
The paper describes a method to evaluate patient care. The technique is based on the staging concept. Its basic premise is that the seriousness of a patient's condition at some point in the treatment process is a good indicator of the outcome of the previous parts of the process. Data were collected for 5,000 patients who had been admitted to a sample of hospitals in two California cities with a primary diagnosis matching one of the diseases for which staging criteria had been developed. The results indicate that the staging technique can be used to distinguish between the outcomes of ambulatory care received by different population groups.


Suppression of Disease-Associated B Lymphocytes by GAD65 Epitope-Carrying Protein-Engineered Molecules in a Streptozotocin-Induced Mouse Model of Diabetes.
Type 1 diabetes mellitus is an autoimmune syndrome defined by the presence of autoreactive T and B cells, which results in destruction of insulin-producing beta cells. Autoantibodies against GAD65 (glutamic acid decarboxylase 65)-a membrane-bound enzyme on pancreatic beta cells, contribute to beta cells' destruction and the loss of pancreatic functions. Mouse FcγRIIb on B lymphocytes possesses an inhibitory effect on the activity of these cells. We hypothesized that it may be possible to suppress GAD65-specific B cells in mice with diabetes using chimeric molecules, containing an anti-FcγRIIb antibody, coupled to peptide B/T epitopes derived from the GAD65 protein. With these engineered chimeras, we expect to selectively co-cross-link the anti-GAD65-specific B cell receptor (BCR) and FcγRIIb, thus delivering a suppressive signal to the targeted B cells. An anti-FcγRIIb monoclonal antibody and two synthetic peptide epitopes derived from the GAD65 molecule were used for chimeras' construction. The suppressive activity of the engineered molecules was tested in vivo in mice with streptozotocin (STZ)-induced type 1 diabetes. These chimeric molecules exclusively bind disease-associated B cells by recognizing their GAD65-specific BCR and selectively deliver a strong inhibitory signal through their surface FcγRIIb receptors. A reduction in the number of anti-GAD65 IgG antibody-secreting plasmocytes and an increased percentage of apoptotic B lymphocytes were observed after treatment with protein-engineered antibodies of mice with STZ-induced type 1 diabetes.


Comparison of Bipolar vascular sealing and conventional back-table dissection in terms of post-renal transplant drainage and back-table preparation times.
The usage of vessel sealing devices has been gaining popularity in all surgical specialties. Post-renal transplant drain placement is a common practice among transplant surgeons. However, prolonged drainage accompanied by surgical wound complications and perirenal fluid collections is a frequent complication experienced by the recipients. This study aimed to compare Bipolar vascular sealing with conventional back-table dissection in terms of post-renal transplant drainage duration, amount, surgical wound complication, and back-table preparation time. A double-blind clinical study randomizes recipients into 2 groups, using Bipolar vascular sealing (Group 1) and conventional ligation (Group 2) back-table dissection. Variables such as recipient age, gender, body mass index (BMI), cause of end-stage renal disease, amount and duration of surgical drainage, back-table time, and cold ischemia time (CIT) were collected prospectively. Ninety-eight consecutive living donor (M/F: 69/29) renal transplant recipients were enrolled in this prospective randomized clinical trial. There were 49 patients in each group. The mean BMI was 26.76±4.57. There was no difference among the groups regarding recipient age, BMI, total drainage, and surgical drainage duration. The surgical site infection rate was not different between the two groups. Group 1 had significantly shorter back-table time, with mean back-table time being 15.26±2.51 minutes in Group 1 and 28.83±6.27 minutes in Group 2 (p<0.001). The CIT was also significantly different between the 2 groups (p<0.001). In Group 1, the recorded CIT was 43.3±11.4, and in Group 2, 57.1±13.3 minutes. The use of Bipolar vascular sealing to seal lymphatic vessels at the back-table is feasible, safe, and easy to perform. It also expedites the dissection and shortens the time required for back-table graft preparation.


Genetic similarity between species of Akodon (Rodentia, Cricetidae).
Genetic similarity between species of rodents of the Akodon genus (A. dolores, A. molinae, and A. azarae) has been estimated by analysis of electrophoretic zymograms corresponding to 23 loci. Nei's coefficient between A. dolores and A. molinae was within the range usually found in conspecific populations. This evidence plus the successful production of "hybrids" (Merani et al., J. Exp. Zool., 206:343-346, '78) suggests that A. dolores and A. molinae may represent geographic races of the same species.


High Bacterial Agglutination Activity in a Single-CRD C-Type Lectin from Spodoptera exigua (Lepidoptera: Noctuidae).
Lectins are carbohydrate-interacting proteins that play a pivotal role in multiple physiological and developmental aspects of all organisms. They can specifically interact with different bacterial and viral pathogens through carbohydrate-recognition domains (CRD). In addition, lectins are also of biotechnological interest because of their potential use as biosensors for capturing and identifying bacterial species. In this work, three C-type lectins from the Lepidoptera Spodoptera exigua were produced as recombinant proteins and their bacterial agglutination properties were characterized. The lowest protein concentration producing bacterial agglutination against a panel of different Gram+ and Gram- as well as their carbohydrate binding specificities was determined for the three lectins. One of these lectins, BLL2, was able to agglutinate cells from a broad range of bacterial species at an extremely low concentration, becoming a very interesting protein to be used as a biosensor or for other biotechnological applications involving bacterial capture.


The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus.
Long-lasting synaptic plasticity and memory requires mRNA translation, yet little is known as to how this process is regulated. To explore the role that the translation repressor 4E-BP2 plays in hippocampal long-term potentiation (LTP) and learning and memory, we examined 4E-BP2 knock-out mice. Interestingly, genetic elimination of 4E-BP2 converted early-phase LTP to late-phase LTP (L-LTP) in the Schaffer collateral pathway, likely as a result of increased eIF4F complex formation and translation initiation. A critical limit for activity-induced translation was revealed in the 4E-BP2 knock-out mice because L-LTP elicited by traditional stimulation paradigms was obstructed. Moreover, the 4E-BP2 knock-out mice also exhibited impaired spatial learning and memory and conditioned fear-associative memory deficits. These results suggest a crucial role for proper regulation of the eIF4F complex by 4E-BP2 during LTP and learning and memory in the mouse hippocampus.


Ultrathin Cellulose Nanofiber Assisted Ambient-Pressure-Dried, Ultralight, Mechanically Robust, Multifunctional MXene Aerogels.
Ambient-pressure-dried (APD) preparation of transition metal carbide/nitrides (MXene) aerogels is highly desirable yet remains highly challenging. Here, ultrathin, high-strength-to-weight-ratio, renewable cellulose nanofibers (CNFs) are efficiently utilized to assist in the APD preparation of ultralight yet robust, highly conductive, large-area MXene-based aerogels via a facile, energy-efficient, eco-friendly, and scalable freezing-exchanging-drying approach. The strong interactions of large-aspect-ratio CNF and MXene as well as the biomimetic nacre-like microstructure induce high mechanical strength and stability to avoid the structure collapse of aerogels in the APD process. Abundant functional groups of CNFs facilitate the chemical crosslinking of MXene-based aerogels, significantly improving the hydrophobicity, water resistance, and even oxidation stability. The ultrathin, 1D nature of the CNF renders the minimal MXenes' interlayered gaps and numerous heterogeneous interfaces, yielding the excellent conductivity and electromagnetic interference (EMI) shielding performance of aerogels. The synergies of the MXene, CNF, and abundant pores efficiently improve the EMI shielding performance, photothermal conversion, and absorption of viscous crude oil. This work shows great promises of the APD, multifunctional MXene-based aerogels in electromagnetic protection or compatibility, thermal therapy, and oil-water separation applications.


Effects of hypoxia on the immunomodulatory properties of human gingiva-derived mesenchymal stem cells.
The environment of bone marrow mesenchymal stem cells (MSCs) is hypoxic, which plays an important role in maintaining their self-renewal potential and undifferentiated state. MSCs have been proven to possess immunomodulatory properties and have been used clinically to treat autoimmune diseases. Here, we tested the effects of hypoxia on the immunomodulatory properties of MSCs and examined its possible underlying mechanisms. We found that hypoxic stimulation promoted the immunomodulatory properties of human gingiva-derived mesenchymal stem cells (hGMSCs) by enhancing the suppressive effects of hGMSCs on peripheral blood mononuclear cells (PBMCs). The proliferation of PBMCs was significantly inhibited, while the apoptosis of PBMCs was increased, which was associated with the Fas ligand (FasL) expression of hGMSCs. The in vivo study showed that systemically infused hGMSCs could enhance skin wound repair, and 24-h hypoxic stimulation significantly promoted the reparative capacity of hGMSCs. For mechanism, hGMSC treatment inhibited the local inflammation of injured skin by suppressing the inflammatory cells, reducing the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), and increasing anti-inflammatory cytokine interleukin-10 (IL-10), which was promoted by hypoxia. Hypoxia preconditioning may be a good optimizing method to promote the potential of MSCs for the future cell-based therapy.


Irinotecan therapy for small-cell lung cancer.
The DNA topoisomerase inhibitor irinotecan (CPT-11, Camptosar) is being evaluated as a novel chemotherapeutic agent that may complement other agents and treatment modalities for small-cell lung cancer (SCLC). Combination chemotherapy is the most effective means of improving the survival of patients with extensive disease, but until recently, no combination demonstrated superior efficacy. In a recent Japanese phase III study, irinotecan in combination with cisplatin significantly improved the survival of previously untreated patients with extensive SCLC compared to standard etoposide/cisplatin therapy (median progression-free survival: 6.9 vs 4.8 months, P = .003; median overall survival: 12.8 vs 9.4 months, P = .002). Two additional phase III trials have been planned in the United States to confirm these results, and to investigate how the administration schedule of irinotecan/cisplatin may be modified to improve its therapeutic index. The results of phase I/II studies have shown that other irinotecan-based combinations demonstrate promising activity in this disease as both first- and second-line therapy. This article reviews the rationale for the use of irinotecan in SCLC, examines key findings from recent clinical studies of irinotecan-based therapy, and discusses how the use of irinotecan in combination with new noncytotoxic anticancer agents can and will be further explored.


Cell types in the pituitary of the roach, Rutilus rutilus (L.), (Teleostei).
The pituitary of roach, Rutilus rutilus (L.), is pear-shaped and situated in the sella turcica. It is characterised by a large pars nervosa, which penetrates deep into the other regions, splitting the proximal pars distalis. Spatial localisation of nerve fibre types and glandular cell types occurs. Using a variety of staining techniques six glandular cell types have been localised and their distribution is disucssed in relation to those of the other teleost pituitaries.