A Markov model assessing the impact on primary care practice revenues and patient's health when using mid-level providers, lesson learned from the United Kingdom.
To evaluate the cost-effectiveness of using mid-level providers for dental "check-up" examinations and the treatment of caries in different NHS settings in the United Kingdom. Mid-level providers are a broad category that describes non-dentist members of dental teams. This study focused on the potential use of Dental Hygiene Therapists undertaking dental "check-up" examinations and simple restorative treatment, instead of dentists. A Markov model was used to construct the natural history of caries development in adults that visit a dental practice every six months over a five-year period. Three cost perspectives are taken: those borne to dental healthcare providers in England and Wales, Northern Ireland and Scotland. These represent three separate forms of retrospective payment system that are currently in use in the United Kingdom. The cost outcome was the average amount of retained practice earnings required to provide healthcare per patient visit. The health outcome was the average length of time in a cavity-free state and the cost-effectiveness outcome was incremental cost for six months in a cavity-free state. No statistical difference was found between dentists and mid-level providers in the length of time in a cavity-free state but the use of the latter saved money in all three NHS health system jurisdictions. This ranged from £7.85 (England and Wales) to £9.16 (Northern Ireland) per patient visit ($10.20 to $11.90, respectively) meaning the incremental cost for six month in a cavity-free state ranged from £261.67 ($339.93) in England and Wales to £305.33 ($369.68) in Northern Ireland. Further, changes in baseline assumptions and parameter values did not change mid-level providers being the dominant service intervention. In a time of limited funds for dental services, these results suggest that resources in public funded systems could be saved using mid-level providers in dental practices, without any health risk to patients or capital investment.


Adverse mucocutaneous reactions related to chemotherapeutic agents: part II.
Events and reactions involving chemotherapy are common in clinical oncology. Chemotherapeutic agents are widely used in therapy. Side effects range from the common to the rare and may be confused with other mucocutaneous manifestations resulting from the oncological treatment. The objective of this paper was to present data on skin reactions to chemotherapy, particularly those cases in which the dermatologist is requested to issue a report and asked to comment on the safety and viability of readministration of a specific drug. The authors describe aspects associated with these events, presenting a detailed analysis of each one of them.


The molecular biology of pelvi-ureteric junction obstruction.
Over recent years routine ultrasound scanning has identified increasing numbers of neonates as having hydronephrosis and pelvi-ureteric junction obstruction (PUJO). This patient group presents a diagnostic and management challenge for paediatric nephrologists and urologists. In this review we consider the known molecular mechanisms underpinning PUJO and review the potential of utilising this information to develop novel therapeutics and diagnostic biomarkers to improve the care of children with this disorder.


Imaging Findings of Axillary Granular Cell Tumor in a Patient with Breast Cancer History: A Case Report.
Granular cell tumors (GCTs) are rare soft tissue tumor, originating from neural or perineural cells. We present a case of axillary GCT in a 69-year-old woman with breast cancer history and discuss the various radiologic findings. US revealed a circumscribed oval heterogeneous iso- and hyperechoic mass in the left axilla. Chest CT showed a well-defined, oval, and mildly enhancing mass in the left axilla on the lateral aspect of the pectoralis muscle. A final diagnosis of GCT was made through US-guided core needle biopsy. Follow-up US showed no significant changes in the axillary GCT. Familiarity with GCT may facilitate early diagnosis and subsequent management.


Transforming growth factor-beta 1 (TGF-beta 1) inhibits DNA synthesis of PWM-stimulated PBMC via suppression of IL-2 and IL-6 production.
The multifunctional cytokine transforming growth factor-beta 1 (TGF-beta 1) is known to inhibit the proliferation of lymphocytes. However, the role of TGF-beta 1 in the production and secretion of various interleukins is not yet clear. In this study we have analysed in parallel the effects of TGF-beta 1 on both DNA synthesis and production of the cytokines IL-1, IL-2, IL-6, and TNF-alpha by pokeweed mitogen-stimulated peripheral blood mononuclear cells. With this stimulation system we show that TGF-beta 1 at a concentration of 15 ng/ml significantly suppresses IL-2 and IL-6 production. The release of IL-1 and TNF-alpha, however, was not influenced under these conditions. Under similar conditions DNA synthesis of PWM-stimulated PBMC was found to be inhibited by 50 +/- 10%. Using flow cytometric methods we could demonstrate that TGF-beta 1 arrested the cells in the G0/G1 phase of the cell cycle. Taken together, these results suggest that TGF-beta 1 may suppress immune responses by inhibiting the endogenous production of IL-2 and IL-6.


Juvenile psammomatoid ossifying fibroma: a rare cause of unilateral proptosis.
This is case of a young girl who presented with unilateral proptosis. Imaging (CT & MRI) revealed an expansile lytic bony tumour involving the left frontal bone and orbital roof. The globe was displaced but uninvolved. Complete surgical resection was done and histopathology revealed psammomatoid bodies diagnostic of juvenile psammomatoid ossifying fibroma (JPOF). JPOF is a rare bone tumour characterised by a predilection for the sino-nasal tract and orbit, a tendency to affect younger patients, a potential for aggressive growth and a high recurrence rate of 30-50%. It warrants a complete surgical resection to avoid recurrence.


Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia.
A National Cancer Institute consensus study on prioritization of cancer antigens ranked the Wilms tumor 1 (WT1) protein as the top immunotherapy target in cancer. We previously reported a pilot study of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia (AML) patients. We have now conducted a phase 2 study investigating this vaccine in adults with AML in first complete remission (CR1). Patients received 6 vaccinations administered over 10 weeks with the potential to receive 6 additional monthly doses if they remained in CR1. Immune responses (IRs) were evaluated after the 6th and 12th vaccinations by CD4+ T-cell proliferation, CD8+ T-cell interferon-γ secretion (enzyme-linked immunospot), or the CD8-relevant WT1 peptide major histocompatibility complex tetramer assay (HLA-A*02 patients only). Twenty-two patients (7 males; median age, 64 years) were treated. Fourteen patients (64%) completed ≥6 vaccinations, and 9 (41%) received all 12 vaccine doses. Fifteen patients (68%) relapsed, and 10 (46%) died. The vaccine was well tolerated, with the most common toxicities being grade 1/2 injection site reactions (46%), fatigue (32%), and skin induration (32%). Median disease-free survival from CR1 was 16.9 months, whereas the overall survival from diagnosis has not yet been reached but is estimated to be ≥67.6 months. Nine of 14 tested patients (64%) had an IR in ≥1 assay (CD4 or CD8). These results indicated that the WT1 vaccine was well tolerated, stimulated a specific IR, and was associated with survival in excess of 5 years in this cohort of patients. This trial was registered at www.clinicaltrials.gov as #NCT01266083.


Closing the loop of deep brain stimulation.
High-frequency deep brain stimulation is used to treat a wide range of brain disorders, like Parkinson's disease. The stimulated networks usually share common electrophysiological signatures, including hyperactivity and/or dysrhythmia. From a clinical perspective, HFS is expected to alleviate clinical signs without generating adverse effects. Here, we consider whether the classical open-loop HFS fulfills these criteria and outline current experimental or theoretical research on the different types of closed-loop DBS that could provide better clinical outcomes. In the first part of the review, the two routes followed by HFS-evoked axonal spikes are explored. In one direction, orthodromic spikes functionally de-afferent the stimulated nucleus from its downstream target networks. In the opposite direction, antidromic spikes prevent this nucleus from being influenced by its afferent networks. As a result, the pathological synchronized activity no longer propagates from the cortical networks to the stimulated nucleus. The overall result can be described as a reversible functional de-afferentation of the stimulated nucleus from its upstream and downstream nuclei. In the second part of the review, the latest advances in closed-loop DBS are considered. Some of the proposed approaches are based on mathematical models, which emphasize different aspects of the parkinsonian basal ganglia: excessive synchronization, abnormal firing-rate rhythms, and a deficient thalamo-cortical relay. The stimulation strategies are classified depending on the control-theory techniques on which they are based: adaptive and on-demand stimulation schemes, delayed and multi-site approaches, stimulations based on proportional and/or derivative control actions, optimal control strategies. Some of these strategies have been validated experimentally, but there is still a large reservoir of theoretical work that may point to ways of improving practical treatment.


The Utility of Flap Coverage for Limb Salvage in Patients With Severe Prosthetic Joint Infections of the Knee Requiring Implant Exchange.
Prosthetic joint infection (PJI) is a challenging complication of knee arthroplasty, which can require amputation in severe cases. This study analyzes the utility of flap reconstruction in PJIs requiring hardware removal and extensive soft tissue debridement. This was a retrospective analysis of patients who were treated according to a multistage extremity salvage protocol between 2018 and 2022. The protocol involved at least 3 planned surgeries including (1) hardware removal with antibiotic spacer placement and soft tissue debridement, (2) spacer exchange with flap coverage, and (3) hardware reimplantation with simultaneous or delayed extensor mechanism reconstruction. All patients had large periprosthetic tissue defects that would necessitate an amputation if not reconstructed. Primary outcomes were extremity salvage and successful defect coverage. Fifty-two patients (25 female) underwent 62 reconstructions (52 primary, 10 salvage). Flap techniques included pedicled muscular (n = 32), fasciocutaneous (n = 4), combined muscular and fasciocutaneous (n = 2), and free flaps (n = 24). Overall rate of successful defect coverage was 95% (98% in primary and 80% in salvage reconstructions). At a median follow-up of 11 months, 41 patients completed the treatment protocol with a 68% (n = 28) extremity salvage rate (reimplantation arthroplasty, n = 15; permanent knee fusion, n = 13). On the multivariate model including demographic factors, defect size, and flap type, no single factor independently predicted limb salvage. Alongside intensive orthopedic surgical treatment, flap coverage may aid in extremity salvage in severe knee PJIs by reestablishing healthy soft tissue coverage and allowing reimplantation arthroplasty. We recommend a multispecialty approach including plastic surgeons for this challenging condition.


Promoting SnTe as an Eco-Friendly Solution for p-PbTe Thermoelectric via Band Convergence and Interstitial Defects.
Compared to commercially available p-type PbTe thermoelectrics, SnTe has a much bigger band offset between its two valence bands and a much higher lattice thermal conductivity, both of which limit its peak thermoelectric figure of merit, zT of only 0.4. Converging its valence bands or introducing resonant states is found to enhance the electronic properties, while nanostructuring or more recently introducing interstitial defects is found to reduce the lattice thermal conductivity. Even with an integration of some of the strategies above, existing efforts do not enable a peak zT exceeding 1.4 and usually involve Cd or Hg. In this work, a combination of band convergence and interstitial defects, each of which enables a ≈150% increase in the peak zT, successfully accumulates the zT enhancements to be ≈300% (zT up to 1.6) without involving any toxic elements. This opens new possibilities for further improvements and promotes SnTe as an environment-friendly solution for conventional p-PbTe thermoelectrics.


When is the processing of data from medical implants lawful? The legal grounds for processing health-related personal data from ICT implantable medical devices for treatment purposes under EU data protection law.
Medicine is one of the biggest use cases for emerging information technologies. Data processing brings huge advantages but forces lawmakers and practitioners to balance between privacy, autonomy, accessibility, and functionality. ICT-connected Implantable Medical Devices plant themselves firmly between traditional medical equipment and software that processes health-related personal data, and these implants face many data management challenges. It is essential that healthcare providers and others can identify and understand the legal grounds they rely on to process data. The European Union is currently updating its framework, and the special provisions in the GDPR, the current ePrivacy Directive, and the coming ePrivacy Regulation all provide enhanced thresholds for processing data. This article provides an overview and explanation of the applicability of the rules and the legal grounds for processing data. We find that only a cumulative application of the GDPR and the ePrivacy rules ensure adequate protection of this data and present the legal grounds for processing in these cases. We discuss the challenges in obtaining and maintaining valid consent and necessity as a legal ground for processing and offer use case-specific discussions of the role of consent long-term and the lack of an adequate 'vital interest' exception in the ePrivacy rules.


Interfacial degradation of biodegradable polyester monolayers at the air/enzyme-containing water interface.
The initial enzymatic degradation behavior of Langmuir monolayer films of a series of biodegradable polyesters at a constant surface pressure was investigated at the air/water interface. The initial degradation of polyester monolayers strongly depended on the structural formula of the polyesters. By the co-polymerization of 3-hydroxyvalerate (3HV) into the poly[(R)-3-hydroxybutyrate] backbone, the critical surface pressure at which the degradation occurs was increased and the rate of enzymatic degradation was retarded because of the inactivity of the enzyme and the hydrophobicity of 3HV. The decrease in the optical purity of poly(l-lactide) (PLLA) delayed the time when the degradation occurred at a constant surface pressure. However, the degradation rate after the critical time was accelerated as the optical purity decreased. These results can be explained by the mutual competition of the preferential degradation of l-lactide units and the density.


A carlactonoic acid methyltransferase that contributes to the inhibition of shoot branching in Arabidopsis.
SignificanceStrigolactones (SLs) are a group of apocarotenoid hormones, which regulates shoot branching and other diverse developmental processes in plants. The major bioactive form(s) of SLs as endogenous hormones has not yet been clarified. Here, we identify an Arabidopsis methyltransferase, CLAMT, responsible for the conversion of an inactive precursor to a biologically active SL that can interact with the SL receptor in vitro. Reverse genetic analysis showed that this enzyme plays an essential role in inhibiting shoot branching. This mutant also contributed to specifying the SL-related metabolites that could move from root to shoot in grafting experiments. Our work has identified a key enzyme necessary for the production of the bioactive form(s) of SLs.


Extent of acute hydrocephalus after subarachnoid hemorrhage as a risk factor for poor functional outcome.
To evaluate the correlation between acute hydrocephalus after subarachnoid hemorrhage (SAH) and functional outcome 1 year after the event. We retrospectively reviewed the clinical and radiological information on consecutive adult patients admitted to our hospital with a diagnosis of acute SAH between 1 January 2002 and 1 January 2008. Patients with early death of any cause, chronic hydrocephalus, or evidence of radiological infarction were excluded. Remaining patients were grouped based on the presence or absence of acute hydrocephalus. The extent of ventricular dilatation was expressed as a function of bicaudate distance. Functional outcomes at 1 year after the hemorrhage were compared between patients with and without acute hydrocephalus. We included 110 patients of whom 57 (52%) had acute hydrocephalus. Acute hydrocephalus was an independent risk factor for poor functional outcome in multivariate analysis (P = 0·006). Patients were categorized into quartiles based on the relative bicaudate index (RBCI). The proportion of patients with poor functional outcome increased in consecutive quartiles (P = 0·0001). The adjusted odds ratio for the highest quartile of RBCI versus the lowest was 7·2 (95% confidence interval: 2·1-25·2). Initiation of treatment at or above an RBCI value of 1·6 (± 0·3) did not significantly improve functional outcome (P = 0·15). The extent of ventricular dilatation after SAH is a strong risk factor for development of poor functional outcome in the year following the event. The proportion of patients with poor outcome was not significantly different with and without cerebrospinal fluid drainage, when treatment was initiated at an RBCI of ≧1·6. Our results suggest that development of acute hydrocephalus after SAH adversely affects long-term functional outcome. Moreover, cerebrospinal fluid flow diversion strategies might best be aimed at preventing ventricular enlargement rather than at treating an established hydrocephalus.


Mosquitoes in Moose Country: A Mosquito Survey of Northern Minnesota.
An adult mosquito survey was conducted at 12 sites using carbon dioxide traps in northern Minnesota throughout the summer of 2012. Specimens were counted, identified to species, sorted into pools, and tested for eastern equine encephalitis (EEEV) and West Nile virus (WNV). Our findings extend the known range of Culiseta melanura, Anopheles barberi, and An. quadrimaculatus and document the presence and abundance of 27 other mosquito taxa in the region. None of the pools tested positive for EEEV or WNV.


Transjugular intrahepatic portosystemic shunt (TIPS): treatment of esophageal variceal bleeding.
Management of esophageal variceal bleeding continues to be a difficult problem for the practicing physician. TIPS is an interventional radiologic procedure that involves creating a channel within the liver between the portal vein and the systemic circulation using an expandable metallic stent. Ten patients underwent TIPS at St Francis Medical Center and the technical success rate was 100%. Complications have been minimal. One patient has died from progressive hepatic failure and carcinoma, and 1 patient underwent liver transplantation. The remaining 8 patients have a patent TIPS in place and have not rebled.


Breast Self-examination and Health Beliefs in Grenadian Women.
Breast cancer incidence and mortality are rising in Grenada, and there is a lack of knowledge about women's beliefs about breast self-examination (BSE). The objective of this study was to quantify and identify patterns of beliefs about health and BSE in Grenadian women to help plan targeted community interventions. In this descriptive cross-sectional study of 110 women in a community parish in Grenada, sociodemographic data and health beliefs were collected using a self-administered questionnaire. The Champion revised Health Belief Model Scale was used to measure general health motivation (5 items), perceived susceptibility to breast cancer (4 items), seriousness of breast cancer (7 items), confidence in performing BSE (7 items), benefits of BSE (2 items), and barriers to BSE (6 items). Younger women were motivated to perform BSE (P = .018), and divorced/separated/widowed women felt more susceptible to breast cancer (P = .014) but perceived fewer benefits in performing BSE (P = .032). Women who did not attend church were more motivated (P = .015) and saw greater benefit (P = .033) in BSE. Frequent church attendees perceived that they were more susceptible (P = .01), were less confident (P < .001), and saw less benefit in BSE (P = .024). There are groups of women in Grenada with belief patterns and sociodemographic characteristics that may benefit from targeted community intervention, perhaps in partnership with other stakeholders such as the church. Beliefs about health and BSE affect BSE uptake and are culture dependent. These data help identify the at-risk population to guide the development of targeted community-based and culturally appropriate breast screening programs.


Vascular function of the mesenteric artery isolated from thyroid hormone receptor-α knockout mice.
This study evaluated the consequences of thyroid hormone receptor-α (TRα) disruption on vascular reactivity. The activity of superior mesenteric arteries isolated from TRα knockout mice generated in the SV129 background (TRα(0/0)SV) or in a pure C57BL/6 background (TRα(0/0)C57) was compared to that of their corresponding wild-type strains (SV129 or C57BL/6 mice). The wild-type SV129 mice exhibited an impaired acetylcholine (Ach)-induced mesenteric artery relaxation compared to C57BL/6 mice, associated with greater responses to angiotensin II (AII) and phenylephrine (PE). The disruption of TRα decreased the vascular response to sodium nitroprusside and PE in both the SV129 and C57BL/6 genetic backgrounds. Responses to Ach and AII were also blunted, but only in TRα(0/0)C57 mice. The administration of 3,3'5-triiodo-L-thyronine sodium salt (T3) elicited a vasodilatation in C57BL/6 mice even at the lowest concentration (10(-9)M); a maximal relaxation of more than 50% was observed with the concentrations between 10(-9) and 10(-8)M. However, the response to T3 was nearly absent in TRα(0/0)C57 mice. TRα is essential for the control of vascular tone, particularly in thyroid hormone-mediated relaxation. The difference in response to Ach observed between the two wild-type mice should be taken into account for interpreting the vascular responses of genetically engineered mice.


Identification of transcriptionally regulated genes in response to cellular iron availability in rat hippocampus.
The present study was attempted to identify transcriptionally regulated genes of the normal neurocytes responsive to iron availability. Postnatal rat hippocampus cells were primarily cultured either under the iron-loaded or depleted conditions. These cultured cells were applied for the generation of subtracted complementary DNA libraries by the suppression subtraction hybridization (SSH) and for the subsequent identification of differentially expressed transcripts by reverse Northern blot. The differentially expressed genes were chosen to perform sequencing, and then some of them were performed by Northern blot analysis for observation of their expression in the hippocampus of rats with the different iron status. The results indicated that five unique transcripts were strong candidates for differential expression in cellular iron repletion, one of them is a novel sequence (GenBank No. AF 433878), while 26 unique transcripts were strong candidates for differential expression in cellular iron deprivation, one of them is a novel sequence (GenBank No. AY 912101). The revealed known genes responsive to iron availability were previously unknown to respond to iron availability, or have not been determined in the brain, have not even been currently determined in their physiological and biological functions. Interestingly, the proteins encoded by most of the known genes are either directly pointed to or indirectly associated with the molecules that play important, even key roles in cellular signal transduction and the cell cycle. These findings lead to the important suggestion that the cellular responses to iron availability involve extensive transcriptional regulation and cellular signal transduction. Therefore, iron may serve as a signal, which directly and/or indirectly regulates or modulates cell functions.


Coffee and tea consumption and the prevalence of coronary heart disease in men and women: results from the Scottish Heart Health Study.
The aim was to determine if there was a relationship between coffee or tea consumption and the prevalence of coronary heart disease in Scotland. The relationship between self reported coffee and tea consumption and the prevalence of coronary heart disease (history, symptoms, or electrocardiographic evidence) was investigated using multiple logistic regression analysis in the Scottish Heart Health Study (SHHS), a cross sectional study. Twenty two Scottish districts were surveyed for the SHHS between 1984 and 1986. A total of 10,359 men and women aged 40-59 years were studied. Of the 9740 subjects who were assigned a category, 21.8% (2122) were classified as having indications of coronary heart disease. Men and women were combined in the odds ratio analysis because they showed almost identical patterns in the prevalence of coronary heart disease across the coffee and tea quarters (grouped according to consumption). Those who did not drink coffee had a significantly higher (p < 0.05) prevalence of coronary heart disease than the three groups for coffee drinkers. Adjustments for risk factors including cigarette smoking, total blood cholesterol, and diastolic blood pressure did not remove the significance of the odds ratios. There was a positive dose-response effect between tea consumption and coronary heart disease which was removed after adjustment for various risk factors. These findings do not support a positive relationship between coffee or tea consumption and coronary heart disease in this British study where most coffee consumed is instant coffee.


Conserved and variable structures in HLA class I molecules: a review.
Amino acid sequences and structural data on HLA class I molecules are now available, making possible a comparison of the serological and structural definitions of allelic series. 1) A hierarchy of differences between molecules is observed. Certain molecules show a low level of differences (1.2% of amino acids) and represent variants of original molecules. Other molecules are recombinants derived from two parent molecules (2.5% difference). Original molecules from an allelic series have a higher level of difference (7.6%). Maximum differences (13.5%) are observed between products from different loci. Serologically related specificities (cross-reacting groups) show a relatively low level of difference (6.4%). 2) In most specificities an exclusive residue can be considered as responsible for the formation of a serologically recognized determinant. Certain specificities do not have an exclusive residue; they can then be characterized either by a unique determinant made by the association of several non-exclusive residues, or by an unique association of several non-exclusive (shared) determinants. There is a significant correlation between the absence of an exclusive residue and the absence of monoclonal antibodies recognizing certain specificities. This suggests two kinds of definition of serological specificities, either by a single exclusive determinant (monotopic recognition) or by several shared determinants (polytopic recognition). Private and public specificities are recognized at the structural level. T-cell receptor (TCR) recognizes either a xenogeneic peptide in the context of self HLA molecules (restricted CTL [Cytotoxic T Lymphocyte]), or allogeneic HLA molecules. Determinants recognized by CTL (restricted or allogeneic) on HLA molecules have been identified. It is not possible to ascertain whether determinants recognized by antibodies and TCRs are identical, but they are probably very similar. 3) HLA class I molecule is made of 75% conserved residues (mostly in the alpha 3 and beta 2-m domains) and of 25% variable residues (mostly in the alpha 1 + alpha 2 domains). Conserved residues maintain the general shape of the molecule, its outward orientation on the cell membrane, its association with T cells CD8 molecule, and the structure of the peptide binding site, a groove at the top of molecule. Variable residues are responsible for the capacity of each molecule to bind and to present a large number of different peptides to the TCR. Each molecule carries several (3-10?) variable sites; certain are localized into the groove and are recognition sites while others, more exposed on the surface of the molecule, are sites recognized by TCRs and antibodies. Both conserved and variable regions are necessary to the function of the HLA molecule.


Calcitonin gene-related peptide predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope.
The vasoconstriction agent midodrine hydrochloride is a vital treatment for pediatric patients diagnosed with vasovagal syncope (VVS), although the efficacy is variable. This study was designed to explore the value of calcitonin gene-related peptide (CGRP) in predicting the effect of midodrine hydrochloride treatment upon VVS patients. In total, 55 children diagnosed with VVS were treated with midodrine hydrochloride for 3 months. Therapeutic response was evaluated using a symptom score system. CGRP levels were significantly higher in VVS patients (68.700 ± 6.460) than in control subjects (43.400 ± 5.810; t = 18.207, P < 0.001) and symptom scores correlated positively with CGRP concentrations (r = 0.779, P < 0.001). Patients treated with midodrine hydrochloride showed a significant reduction in symptom scores [4 (0, 6.5) vs. 1 (1, 2); z = -6.481; P < 0.001]. However, the value of plasma CGRP were potently elevated in the positive-response subjects than in the negative-response subjects (70.080 ± 5.040) vs. (61.150 ± 3.090); t = 5.817; P < 0.001). The area under the ROC curve showed that the value of CGRP for predicting the therapeutic response to midodrine hydrochloride was 0.946 (95% CI: 0.879-0.997, P < 0.001). With high sensitivity (97.7%) and specificity (83.3%), CGRP predicted the therapeutic response to midodrine hydrochloride (cut-off value, 62.56 pg/ml). In conclusion, CGRP can be used to predict the effect of midodrine hydrochloride administration in VVS patients.


A Systematic Analysis of Incidence, Therapeutic Strategies, and In-hospital Mortality of Mallory-Weiss Syndrome in Germany.
Mallory-Weiss syndrome (MWS) is a rare cause of upper gastrointestinal bleeding from gaging or vomiting-induced mucosal lacerations at the gastroesophageal junction. Most cases do not require urgent endoscopic intervention due to the mostly self-limiting course. For more severe cases, different hemostasis techniques have been used. In small MWS cohorts, overall mortality was ~5%, but comprehensive data, as well as population-based incidence, treatment recommendations, and outcome parameters such as in-hospital mortality and adverse events, are largely lacking. We evaluated current epidemiological trends, therapeutic strategies, and in-hospital Mortality of MWS in Germany based on standardized hospital discharge data provided by the German Federal Statistical Office from 2010 to 2019. A total of 59,291 MWS cases, predominately male (62%), were included into analysis. The mean number of MWS cases in Germany was 5929/year and decreased continuously during the observation period (-4.1%/y). The overall annual incidence rate (as hospitalization cases per 100,000 persons) was 7.5 with the highest incidence rate in the New Federal States (8.7). The most common comorbidities were reflux esophagitis (23.6%), diaphragmatic hernia (19.7%), and alcohol abuse (10.9%). The most frequent complication was bleeding anemia (26%), whereas hypovolemic shock (2.9%) was rare. Endoscopic injection was the most commonly performed endoscopic therapy (13.7%), followed by endoscopic clipping (12.8%), whereas the need for surgical therapy was rare (0.1%). Endoscopic combination therapies were used predominantly as a combination of injection and clipping. The overall in-hospital mortality was 2.7% and did not differ through the observation period. The presence of hypovolemic shock, acute kidney injury, sepsis, artificial ventilation, adult respiratory distress syndrome, bleeding anemia, and female sex was associated with a significantly worse prognosis. Our study gives a detailed insight into the incidence, patient-related risk factors, endoscopic treatment, and overall in-hospital mortality as well as regional differences in a large MWS collective in Germany. Furthermore, we were able to identify mortality-associated complications and their impact.


Photodetachment spectrum of OHF-: three-dimensional study of the heavy-light-heavy resonances.
In this work a simulation of the OHF(-) photodetachment spectrum is performed in a three-dimensional potential energy surface recently developed for OHF((3)A(")). The ground (2)A(') state potential of the anion is calculated in three dimensions based on accurate ab initio calculations and the reaction dynamics is studied using a wave packet method. The calculated spectrum shows a sequence of bands associated to vibrational HF(v) up to v=3. Each band is formed by a continuous spectrum and resonant structures. These resonances are associated to the OH-F channel well of the (3)A(") PES, in which fragmentation occurs through vibrational predissociation. Above the OH(v=0) threshold a new resonant pattern appears corresponding to heavy-light-heavy resonances. Special attention is paid to the assignment of these resonances because they mediate the reaction dynamics in the OH+F collision at low kinetic energies. The sequence of bands is in rather good agreement with that appearing in the experimental spectrum, especially at higher electron kinetic energies. At low kinetic energies, however, some other electronic states may contribute. The resonance structures might be washed out by the rotational average and the relatively low energy resolution of the experiment.


1,3-Diarylpyrazolyl-acylsulfonamides as Potent Anti-tuberculosis Agents Targeting Cell Wall Biosynthesis in Mycobacterium tuberculosis.
Phenotypic whole cell high-throughput screening of a ∼150,000 diverse set of compounds against Mycobacterium tuberculosis (Mtb) in cholesterol-containing media identified 1,3-diarylpyrazolyl-acylsulfonamide 1 as a moderately active hit. Structure-activity relationship (SAR) studies demonstrated a clear scope to improve whole cell potency to MIC values of <0.5 μM, and a plausible pharmacophore model was developed to describe the chemical space of active compounds. Compounds are bactericidal in vitro against replicating Mtb and retained activity against multidrug-resistant clinical isolates. Initial biology triage assays indicated cell wall biosynthesis as a plausible mode-of-action for the series. However, no cross-resistance with known cell wall targets such as MmpL3, DprE1, InhA, and EthA was detected, suggesting a potentially novel mode-of-action or inhibition. The in vitro and in vivo drug metabolism and pharmacokinetics profiles of several active compounds from the series were established leading to the identification of a compound for in vivo efficacy proof-of-concept studies.


Effect of simultaneous thawing of multiple 0.5-mL straws of semen and sequence of insemination on conception rate in dairy cattle.
The objectives of this study were to determine 1) the effect of simultaneous thawing of multiple 0.5-mL straws of semen and sequence of insemination (first, second, third, or fourth) on conception rates in dairy cattle, 2) whether the conception rates achieved following AI by professional AI (PAI) technicians and herdsman-inseminators (HI) differed, and 3) the effect of elapsed time from initiation of thawing straws of semen to seminal deposition on conception rates in dairy cattle. Four dairies with PAI and four with HI participated in the study. Initial data recorded included beginning thaw time, cow identification number, and time of seminal deposition. Herd records were retrieved following pregnancy diagnosis. Conception rates of dairy cows (n = 1025) were not affected by sequence of insemination (first, second, third, or fourth). Conception rates for herds using PAI were 40, 47, 41, and 50%. Conception rates for herds using HI were 24, 20, 33, and 30%. Average conception rates of dairy cows differed between PAI and HI (45 vs. 27%, respectively). The difference in mean conception rate achieved by PAI and HI was not attributable to milk production, parity, service number or stage of lactation. The elapsed time from initial thaw to completion of fourth AI was shorter for PAI than for HI, 7.6 vs. 10.9 min, respectively. Although the average conception rate differed between PAI and HI, elapsed time from initial thaw to completion of fourth AI and sequence of insemination (first, second, third, or fourth) had no effect on conception rate within inseminator group.


Neural cells from primary human striatal xenografts migrate extensively in the adult rat CNS.
Primary neural cells do not appear to migrate significantly following transplantation into the adult rodent CNS, which is in contrast to expanded neural precursor cells where migration is well-documented. However, most transplant studies of primary neural tissue have been performed in an allograft situation in which it is difficult to identify graft-derived cells. We have, therefore, used a xenograft paradigm to investigate the potential for cells derived from grafts of primary human fetal striatal tissue (gestational age of 66-72 days) to migrate following intrastriatal transplantation in an athymic adult rat model of Huntington's disease. The use of an antibody specific to human nuclear antigen enabled clear identification of graft-derived cells within the host brain, and specific neural phenotypes were determined using human-specific tau for neurons, glial fibrillary acidic protein for mature astrocytes and Ki67 for proliferative cells. At 6 weeks, the graft mass was very dense with a high proliferative index, few cells had migrated away from the graft, and the cells that had differentiated both within and away from the graft were mainly neurons. In contrast, at 6 months, the graft core was dispersed significantly more and a large number of graft-derived cells had migrated throughout the brain as far rostral as the olfactory bulb and as caudal as the substantia nigra. Cells had differentiated into both neurons and astrocytes and the level of proliferation was significantly lower within the graft. These results demonstrate that primary neural xenografts contain proliferative cells that possess the ability to migrate and differentiate into both neurons and astrocytes, and suggest that these cells could contribute to normal graft function. This property may be a consequence of the xenograft situation and could potentially be exploited to provide the opportunity to target regions of distant pathology in neurodegenerative diseases using xenotransplantation of embryonic neural tissue.


Evaluation of the cranial base in amnion rupture sequence involving the anterior neural tube: implications regarding recurrence risk.
Amniotic bands can cause disruption of the cranial end of the developing fetus, leading in some cases to a neural tube closure defect. Although recurrence for unaffected parents of an affected child with a defect in which the neural tube closed normally but was subsequently disrupted by amniotic bands is negligible; for a primary defect in closure of the neural tube to which amnion has subsequently adhered, recurrence risk is 1.7%. In that primary defects of neural tube closure are characterized by typical abnormalities of the base of the skull, evaluation of the cranial base in such fetuses provides an approach for making a distinction between these 2 mechanisms. This distinction has implications regarding recurrence risk. The skull base of 2 fetuses with amnion rupture sequence involving the cranial end of the neural tube were compared to that of 1 fetus with anencephaly as well as that of a structurally normal fetus. The skulls were cleaned, fixed in 10% formalin, recleaned, and then exposed to 10% KOH solution. After washing and recleaning, the skulls were exposed to hydrogen peroxide for bleaching and photography. Despite involvement of the anterior neural tube in both fetuses with amnion rupture sequence, in Case 3 the cranial base was normal while in Case 4 the cranial base was similar to that seen in anencephaly. This technique provides a method for determining the developmental pathogenesis of anterior neural tube defects in cases of amnion rupture sequence. As such, it provides information that can be used to counsel parents of affected children with respect to recurrence risk.


A Reflection and Discussion Exercise on Racial Justice and Equity.
Residents have valuable perspectives about diversity and equity in medical training, yet many graduate medical education curricula lack dedicated activities focused on such issues. To describe and report feasibility and acceptability of an innovation that uses individual reflection and group discussion to create conversation in our residency program about equity and injustice through the lens of the Black Lives Matter movement. In July 2020, we sent a survey with reflection prompts to all postgraduate year 2 and above internal medicine residents. In the discussion session (during required academic time), we presented 10 of the residents' responses to the reflection prompts. After each response was read aloud, the residents had an open discussion. We used thematic analysis to analyze the responses to the reflection prompts. Acceptability was tracked through free-text comments in the survey. Feasibility was measured by the time and resources needed to conduct the session. We received responses from 24 out of 72 (33%) residents. We identified 10 codes that fell into 4 themes. The most commonly identified codes included anger or frustration toward events, self-reflection on privilege, increased awareness and discussion of racism in daily life, and life being minimally impacted/homeostasis. The 4 overarching themes were (1) awareness, (2) motivation for change, (3) emotional response, and (4) self-reflection. Using a format of reflection and sharing of anonymous responses was an inexpensive and effective method to begin a discussion about equity and injustice in medicine.


Clinical and radiological presentation of 340 adults with smear-positive tuberculosis in The Gambia.
Four clinics in The Gambia. To document clinical and radiographic presentations of sputum smear-positive tuberculosis in adults. Newly diagnosed acid-fast bacilli (AFB) smear, culture-positive tuberculosis patients aged > or = 15 years were interviewed and examined, and underwent tuberculin skin testing, HIV testing and chest X-ray reviewed by a chest physician using set criteria. Of 340 patients enrolled (median age 29 years; males 73%), 8.3% were HIV-positive. One-third reported haemoptysis, > 90% reported weight loss and fever, and wasting was the most common sign (69%). Crepitations were the most frequent auscultatory finding (41%). The most common radiological lesion was a patchy infiltrate (> 90%). Cavitation was present in 206 patients (60.6%), most frequently occurred in the upper lung fields, was associated with increasing bacterial load in the sputum, and was less prevalent in HIV-positive patients (45% vs. 62%; P = 0.07). Auscultatory and chest X-ray findings matched only one-third of the time. In our setting, wasting is the most common clinical sign of sputum smear-positive tuberculosis. Auscultatory findings correlate poorly with radiological abnormalities. Cavitation is associated with increasing bacterial load in the sputum, and is therefore a strong indicator for early treatment.


[High incidence of admissions for schizophrenia in Surinam patients in The Netherlands not caused by preferential immigration of (pre)schizophrenic patients].
To answer the question whether positive selection of (pre)schizophrenic Surinams in Surinam before emigration to the Netherlands can explain the high admission rates for schizophrenia of Surinams in the Netherlands. Retrospective research. 's Lands Psychiatrisch Ziekenhuis (National Psychiatric Hospital) Paramaribo, Surinam (LPZ). The Netherlands Central Bureau of Statistics in Voorburg and the Central Registry Office in Paramaribo provided data on emigration to the Netherlands of the Surinam population and on remigration. Files of (pre)schizophrenic patients were selected from the records of LPZ. Subsequently, these patients were traced and their pattern of migration was studied. Using the chi 2 test the significance of observed differences was assessed. Surinam (pre)schizophrenic patients did not emigrate more frequently to the Netherlands (6.3%) compared with the Surinam population in general (9.6%) and they remigrated more frequently to Surinam than the Surinams in general. The positive selection hypothesis must be rejected.


Ophthalmology Practice During the Coronavirus Disease 2019 Pandemic: The University of Pittsburgh Experience in Promoting Clinic Safety and Embracing Video Visits.
The coronavirus disease 2019 pandemic has led to widespread change as public health strategies for containment have emphasized social distancing and remaining at home. These policies have led to downscaled clinic volumes, cancellation of elective procedures, enhanced personal protective strategies in the clinic, and adoption of telemedicine encounters. We describe the evidence-based practical approach taken in our ophthalmology department to continue delivering eye care during the pandemic by rescheduling visits, enhancing clinic safety, and adopting virtual video encounters.


PTHrP, calcitonin and calcitriol in a case of severe, protracted and refractory hypercalcemia due to a pancreatic neuroendocrine tumor.
A patient with a primary neuroendocrine tumor of the pancreas, presented with severe hypercalcemia. This hypercalcemia of malignancy (HCM) failed to respond to intensive bisphosphonate treatment and needed continuous enhanced diuresis. Only after successful antitumor therapy did the hypercalcemia subside. Hypercalcemia was associated with increased concentrations of plasma PTHrP, calcitonin and 1,25-(OH)(2)D(3). Bone mineral density was markedly increased. We demonstrated the presence of both PTHrP and calcitonin in the tumor at the mRNA and protein level, using RT-PCR, immunohistochemistry and Western blotting. The high levels of plasma PTHrP and the demonstrated predominant renal mechanism in this case of HCM are suspected to be the cause for its refractoriness to bone resorption inhibitors. Our findings furthermore suggest that the tumoral production of calcitonin and PTHrP might have contributed to the increased bone mineral storage of calcium and thus probably attenuated the development of frank hypercalcemia.


Variation of oxide films on titanium induced by osteoblast-like cell culture and the influence of an H2O2 pretreatment.
Variations of titanium oxide films induced by osteoblast-like cells in a rat calvaria culture system and the influence of an H2O2 pretreatment have been investigated by using X-ray photoelectron spectroscopy and electrochemical impedance spectroscopy. For abraded titanium, the results revealed that phosphate and calcium ions may incorporate into the surface oxide film during the cell culture, forming a precipitate with a Ca/P ratio near that of hydroxyapatite. Oxidized carbon also was found in the surface layer, most likely precipitated hydroxylcarbonated apatite (HCA). The H2O2 pretreatment of titanium in a phosphate-buffered saline solution results in a 10-fold thickened porous oxide film and large amounts of surface hydroxyl groups as well as a certain amount of phosphate ions inside the oxide film. During the cell culture, the H2O2-treated titanium surface favors the ion incorporation and precipitation of the HCA-like compound, which probably is inlaid into the oxide film. Osteoblast-like cells on the H2O2-treated titanium showed a more active morphology during the initial stage compared with cells on abraded titanium. Moreover, bone-like nodule formation and mineralization appear to be related to the precipitation of the HCA-like compound on the surface. The results are discussed with respect to corrosion resistance, ion incorporation and precipitation of the HCA-like compound on the surface, osseointegration, and bioactivity of titanium implants.


[Neurootological manifestation of migrainous vertigo].
To analyzed the characteristics of migrainous vertigo (MV), a kind of paroxysmal vertigo, in order to demonstrate the extent of damage and dysfunction in MV and to judge whether MV is peripheral or central vertigo. Twenty-two cases of acute (5 cases) or subacute (17 cases) MV were examined with oto-neurological tests, spontaneous nystagmus, positional nystagmus and auditory tests. There were 6 males and 16 females. Among those patients, 15 had migraine, 17 motion sickness, 15 family history of migraine or motion sickness, 1 visual aura, 7 motion intolerance (vertigo from head movement and body movement), 4 photophobia, 6 phonophobia and 5 vertigo from insomnia and emotion. There were likely to have vertigo in menstrual period in 2 cases. The duration of vertigo lasted from minutes to days. For pure-tone audiometric, 9 were normal which from mild to moderate hearing loss. Three cases had abnormal high frequency ABR bilaterally and 10 abnormal unilaterally. Subjective visual vertical were normal in all of the cases. Vestibular evoked myogenic potentials were abnormal in 14 cases (13 had low amplitude and 1 had longer latency of P13 wave). Bithermal caloric test was abnormal in 3 cases and 11 had abnormal ocular movement (9 with low gain of optokinetic nystagmus, 1 with overshoot in saccade and 1 with vertical nystagmus after head shaking), in which 10 had abnormal high frequency ABR and 1 was normal. MV could be peripheral or central vertigo and MV should be included in the differentiation of peripheral and central vertigo.


Animal venoms as antimicrobial agents.
Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens.


Transient ventriculoperitoneal shunt malfunction in a pediatric patient: An illustrative case.
Ventriculoperitoneal shunt (VPS), the mainstay of the treatment for hydrocephalus, is associated with relatively high revision rates. Transient hydrocephalus due to intermittent VPS obstruction should be recognized as a cause of VPS malfunction. While transient VPS dysfunction is well-recognized complication, there is a relative paucity of well-documented cases in the literature. We present the case of a 4-year-old boy with a history of vascular malformation and hydrocephalus secondary to intraventricular hemorrhage. The patient presented with transient, self-resolving hydrocephalus (without intervention), as documented by clinical and radiological findings. Transient hydrocephalus due to intermittent VPS dysfunction in children is a rare entity, but it should be suspected in certain patients with VPS presenting with transient or self-improving symptoms.


Biological implications of selenium in adolescent rats exposed to binge drinking: Oxidative, immunologic and apoptotic balance.
Alcohol intermittent binge drinking (BD) during adolescence decreases the levels of selenium (Se), a trace element that plays a key biological role against oxidative damage in hepatocytes through different selenoproteins such as the antioxidant enzymes glutathione peroxidases (GPx1 and Gpx4) and selenoprotein P (SelP). In this context, it has been found that GPx4 has an essential antioxidant role in mitochondria modulating the apoptosis and NF-kB activation (a factor intimately related to apoptosis and immune function). To further investigate the effectiveness of selenium supplementation in oxidative balance, inflammation and apoptosis, the present study examined the protective effects of 0.4ppm of dietary selenite administrated to adolescent rats exposed to BD. BD consumption depleted Se deposits in all the tissues studied. In liver, GPx1 activity and expression were decreased leading to protein and lipid hepatic oxidation. Moreover GPx4 and NF-kB expression were also decreased in liver, coinciding with an increase in caspase-3 expression. This hepatic profile caused general liver damage as shown the increased serum transaminases ratio AST/ALT. Proinflammatory serum citokines and chemocines were decreased. Se supplementation therapy used restored all these values, even AST levels. These findings suggest for first time that Se supplementation is a good strategy against BD liver damage during adolescence, since it increases GPx1 and GPx4 expression and avoids NF-kB downregulation and caspase-3 upregulation, leading to a better oxidative, inflammatory and apoptotic liver profile. The therapy proposed could be considered to have a great biological efficacy and to be suitable for BD exposed teenagers in order to avoid future hepatic complications.


Qatari Genotype May Contribute to Complications in Type 2 Diabetes.
There is increasing evidence of a strong genetic component in type 2 diabetes (T2DM) that may contribute to diabetes complications. Given the high prevalence of diabetes with its associated complications in the Middle East, we sought to determine if the genotype within a Middle East population may be contributory. Therefore, three genotype-based Qatari ancestral groups, Q1 Arab Bedouin, Q2 Asian/Persian, and Q3 sub-Saharan African, with a fourth admixed group were correlated with T2DM prevalence and its complications to determine if they differed between the 4 Qatari ancestries, particularly for the SLMAP allele-associated diabetic retinopathy. In this cross-sectional study, 398 Qatari subjects, 220 with and 178 without T2DM, were genotyped by Affymetrix 500k SNP arrays. Ancestry was correlated with diabetes complications. 398 subjects were included, the mean age was 49.8 years, and 56.8% were male. The genotype-based ancestry and T2DM prevalence were as follows: 164 (41.2%) with ancestry Q1, 60.4% with T2DM; 149 (37.4%) with ancestry Q2, 49.7% with T2DM; 31 (7.8%) with ancestry Q3, 61.3% with T2DM; and 54 (13.6%) with "admixed" ancestry, 51.9% with T2DM. For patients with diabetes, hypertension (p < 0.035) and retinopathy (p < 0.016) were greater in the Q3 ancestry. These data suggest that the genotype may contribute to complication risk, as exemplified by the increase in hypertension and retinopathy in the Q3 ancestry, though the SLMAP allele was not implicated; however, diabetes prevalence did not differ between the four Qatari ancestries.


Comparative analysis of experimental testing procedures for the elicitation of rescue actions in ants.
Rescue behavior is observed when 1 individual provides help to another individual in danger. Most reports of rescue behavior concern ants (Formicidae), in which workers rescue each other from various types of entrapment. Many of these entrapment situations can be simulated in the laboratory using an entrapment bioassay, in which ants confront a single endangered nest mate entrapped on a sandy arena by means of an artificial snare. Here, we compared numerous characteristics of rescue actions (contact between individuals, digging around the entrapped individual, pulling at its body parts, transport of the sand covering it, and biting the snare entrapping it) in Formica cinerea ants. We performed entrapment tests in the field and in the laboratory, with the latter under varying conditions in terms of the number of ants potentially engaged in rescue actions and the arena substrate (marked or unmarked by ants' pheromones). Rescue actions were more probable and pronounced in the field than in the laboratory, regardless of the type of test. Moreover, different test types in the laboratory yielded inconsistent results and showed noteworthy variability depending on the tested characteristic of rescue. Our results illustrate the specifics of ant rescue actions elicited in the natural setting, which is especially important considering the scarcity of field data. Furthermore, our results underline the challenges related to the comparison of results from different types of entrapment tests reported in the available literature. Additionally, our study shows how animal behavior differs in differing experimental setups used to answer the same questions.


Cardiac tamponade associated with a peripheral vein central venous catheter.
We present a case of cardiac tamponade associated with placement of a central venous catheter (CVC) via a peripheral vein in a 14-year-old girl with idiopathic scoliosis undergoing corrective surgery. A number of complications have been described in association with CVC misplacement. Sporadic cases of cardiac tamponade from this have been reported, but the actual incidence is unknown. Death from cardiac tamponade attributed to CVCs ranges from 65 to 100%. In our patient, cannulation of the pericardiophrenic vein was probably the cause of cardiac tamponade, based on radiological evidence that the initial location of the catheter was near the right atrium and possibly at the outlet of the pericardiophrenic vein. The catheter could have advanced into the vein and then to the pericardial sac with postural changes. The acute clinical course of cardiac tamponade in our patient had potentially lethal hemodynamic repercussions. The main diagnostic test for this condition is echocardiography and the only effective treatment is drainage of the pericardial effusion. Echocardiography should be performed before pericardiocentesis except in life-threatening situations or high clinical suspicion. Although they are rare, it is important to be aware of the potential for CVC complications.


Bilateral pallidal hemorrhage in toxoplasmosis update of acute symmetric lesions of deep nuclei.
As acute symmetric lesions of deep gray nuclei are often associated with an impaired level of consciousness and neuroimaging by itself cannot distinguish between etiologies, diagnosis may be problematic. Appreciation of the cause of the various neuroimaging patterns in conjunction with the history, examination and laboratory investigations allows for accurate diagnosis in the vast majority of cases. Given the metabolic vulnerability of deep gray nuclei, other than bi-thalamic infarction, it follows that toxic-metabolic and hypoxic-ischemic events account for the majority of cases. Nevertheless, the differential diagnosis is broad and diverse. We here describe two cases of bilateral pallidal hemorrhage in AIDS-associated toxoplasmosis, and review conditions recently described with acute symmetric deep gray nuclei lesions on neuroimaging.


Association between ABO blood groups and SARS-CoV-2 infection in blood donors of Puglia region.
This is an observational multicentric cross-sectional study aiming at assessing the association between ABO blood groups and SARS-CoV-2 seroprevalence among the blood donors in Puglia region. Data on ABO and Rh blood groups and demographic characteristics were obtained from Blood Bank Information System. All donors were screened for SARS-CoV-2 IgG antibodies. Comparison of seroprevalence among blood groups and the association between the recorded variables and seroprevalence were evaluated. A total of 35,709 donors from 22 centers were included, with a seroprevalence of 6.8%. The distribution of ABO phenotypes was blood type O (46.8%), A (34.0%), B (14.7%), and AB (4.5%). Among the 2416 donors reactive for SARS-CoV-2 IgG, the prevalent phenotype was blood type O (43.1%), followed by A (37.7%), B (14.2%), and AB (5%). The seroprevalence of phenotype A and AB was 7.5%, followed by B (6.5%) and O (6.2%). According to the adjusted analysis, there was an increase in seroprevalence in groups A and AB, compared to group O, and an increase in males compared to females. A possible effect modification was observed after stratifying for sex (p = 0.0515). A significantly lower prevalence of blood type O was found compared to A and AB, whereas no association was observed between Rh factor and seroprevalence. We hypothesized that the A antigen present in blood type A and AB can play a role in the binding of SARS-CoV-2 to ACE2 receptors, resulting in an increased risk of infection. Furthermore, natural anti-A/anti-B antibodies produced in group O could block viral adhesion to cells and explain a lower risk of infection.


Management of scabies.
Scabies is a common infestation worldwide, affecting persons of any age and socioeconomic status. In Singapore, it is more common in institutions rather than in homes. The two variants are classic scabies and crusted scabies, with the latter having a significantly higher mite burden. Early identification, isolation of index patients and prophylactic treatment of contacts are essential in dealing with the outbreak. Locally, most primary care practitioners make the diagnosis based on visual inspection and clinical examination. A skin scrape is done to confirm the diagnosis, especially in atypical presentations. Scabietic mites, eggs or faeces can be seen on microscopy. The usual treatment for adult scabies in Singapore is the use of topical malathion or permethrin. A combination of topical permethrin and oral ivermectin is used for crusted scabies.


Methylene blue decreases mitochondrial lysine acetylation in the diabetic heart.
Diabetic cardiomyopathy is preceded by mitochondrial alterations, and progresses to heart failure. We studied whether treatment with methylene blue (MB), a compound that was reported to serve as an alternate electron carrier within the mitochondrial electron transport chain (ETC), improves mitochondrial metabolism and cardiac function in type 1 diabetes. MB was administered at 10 mg/kg/day to control and diabetic rats. Both echocardiography and hemodynamic studies were performed to assess cardiac function. Mitochondrial studies comprised the measurement of oxidative phosphorylation and specific activities of fatty acid oxidation enzymes. Proteomic studies were employed to compare the level of lysine acetylation on cardiac mitochondrial proteins between the experimental groups. We found that MB facilitates NADH oxidation, increases NAD+, and the activity of deacetylase Sirtuin 3, and reduces protein lysine acetylation in diabetic cardiac mitochondria. We identified that lysine acetylation on 83 sites in 34 proteins is lower in the MB-treated diabetic group compared to the same sites in the untreated diabetic group. These changes occur across critical mitochondrial metabolic pathways including fatty acid transport and oxidation, amino acid metabolism, tricarboxylic acid cycle, ETC, transport, and regulatory proteins. While the MB treatment has no effect on the activities of acyl-CoA dehydrogenases, it decreases 3-hydroxyacyl-CoA dehydrogenase activity and long-chain fatty acid oxidation, and improves cardiac function. Providing an alternative route for mitochondrial electron transport is a novel therapeutic approach to decrease lysine acetylation, alleviate cardiac metabolic inflexibility, and improve cardiac function in diabetes.


Effectively starting and titrating intrathecal analgesic therapy in patients with refractory cancer pain.
Patients continue to suffer from pain despite their analgesic regimen and frequently from symptoms related to these interventions. This article describes the role that intrathecal analgesia may play in improving comfort for individuals experiencing refractory pain and/or symptoms of opioid therapy. Patient selection, staff education, institution requirements, medications, and titration guidelines also will be reviewed. Patients with cancer clearly deserve to achieve comfort; therefore, intrathecal therapy, which is a safe intervention, must be considered when refractory pain or symptoms occur.


The Experience of Women Veterans Coming Back from War.
Issues surrounding mental health are common for women veterans who have served in Iraq and Afghanistan wars. The goal of this phenomenological study was to document themes in the stories gathered from eight women veterans who had come back from war. Themes in the stories were: arriving with mixed sentiments; evolving to a changed view of self; permeating aggravation; confounding broken relationships, frequent deployments, and change in military status; remembering war experiences; and seeking opportunity for what is possible. Mental health issues can be observed in the themes. Including story as part of the mental health visit with veterans may be beneficial to veterans as they deal with the transition of coming back.


[Sideroblastic anemia after prolonged linezolid therapy].
Linezolid is an effective and well-tolerated antibiotic for the treatment of infections caused by Gram-positive pathogens. Some reports have shown that linezolid treatment for more than 2 weeks has been associated with reversible bone marrow suppression, especially thrombocytopenia and anemia. We encountered a case of sideroblastic anemia following prolonged linezolid therapy in a laryngeal cancer patient. He received linezolid therapy for multiple abscesses due to MRSA. Before treatment, the Hb level was 12.5 g/dl and then slowly decreased to 5.9 g/dl for 2 months during treatment. Ringed sideroblasts were detected in the bone marrow. Linezolid was discontinued and the Hb level was slowly increased. This case was considered to reflect a rare complication of linezolid therapy.


Prediction of diuretic response to tolvaptan by a simple, readily available spot urine Na/K ratio.
Tolvaptan is vasopressin type 2 receptor antagonist that inhibits water reabsorption. It is used in combination with standard diuretics to treat ascites unresponsive to standard diuretic therapy or hyponatremia because of liver cirrhosis. This study evaluated the effectiveness and safety of tolvaptan in clinical practice and aimed to determine the factors related to its effectiveness. Tolvaptan was administered to 88 consecutive cirrhotic patients with ascites unresponsive to standard diuretic therapy. An effective treatment response was a ≥2% reduction in body weight on day 7. The association of patient pretreatment characteristics with therapeutic effects was analyzed. Mean weight reduction on day 7 of tolvaptan therapy was -2.9% ± 3.2%, and treatment was effective in 52% of patients. Multivariate analysis revealed that spot urine Na/K ratio ≥2.5 at baseline was the only factor independently related to therapeutic effect, with an odds ratio of 7.85 (95% confidence interval 2.64-23.40, p = 0.0002). Weight reduction percentage on day 7 was -4.0% ± 2.8% in patients with spot urine Na/K ≥2.5, which was significantly greater than the 0.7% ± 2.7% loss in those with urine Na/K < 2.5 (p < 0.05). A spot urine Na/K ratio ≥2.5 had a sensitivity of 85% and specificity of 60% for predicting effective treatment. No adverse events of treatment led to treatment discontinuation. Baseline spot urine Na/K was predictive of an effective response to tolvaptan therapy. It is simple to perform and readily available and might serve as an indicator of optimal timing of tolvaptan administration in patients with inadequate response to conventional Na diuretic therapy.


The Institute for Global Orthopedics and Traumatology: A Model for Academic Collaboration in Orthopedic Surgery.
In 2006, surgeons at the University of California, San Francisco (UCSF) established the Institute for Global Orthopedics and Traumatology (IGOT), an initiative within the department of orthopedic surgery. The principal aim of IGOT is to create long-term, sustainable solutions to the growing burden of musculoskeletal injury in low- and middle-income countries (LMICs) through academic partnership. IGOT currently has relationships with teaching hospitals in Ghana, Malawi, Tanzania, Nicaragua, and Nepal. The organizational structure of IGOT is built on four pillars: Global Surgical Education (GSE), Global Knowledge Exchange (GKE), Global Research Initiative (GRI), and Global Leadership and Advocacy. GSE focuses on increasing surgical knowledge and technical proficiency through hands-on educational courses. The GKE facilitates the mutual exchange of surgeons and trainees among IGOT and its partners. This includes a global resident elective that allows UCSF residents to complete an international rotation at one of IGOT's partner sites. The GRI strives to build research capacity and sponsor high-quality clinical research projects that address questions relevant to local partners. The fourth pillar, Global Leadership and Advocacy aims to increase awareness of the global impact of musculoskeletal injury through national and international courses and events, such as the Bay Area Global Health Film Festival. At the core of each tenet is the collaboration among IGOT and its international partners. Over the last decade, IGOT has experienced tremendous growth and maturation in its partnership model based on cumulative experience and the needs of its partners.


Participation of mercuric conjugates of cysteine, homocysteine, and N-acetylcysteine in mechanisms involved in the renal tubular uptake of inorganic mercury.
Mechanisms involved in the renal uptake of inorganic mercury were studied in rats administered a nontoxic 0.5 mumol/kg intravenous dose of inorganic mercury with or without 2.0 mumol/kg cysteine, homocysteine, or N-acetylcysteine. The renal disposition of mercury was studied 1 h after treatment in normal rats and rats that had undergone bilateral ureteral ligation. In addition, the disposition of mercury (including the urinary and fecal excretion of mercury) was evaluated 24 h after treatment. In normal rats, coadministering inorganic mercury plus cysteine or homocysteine caused a significant increase in the renal uptake of mercury 1 h after treatment. The enhanced renal uptake of mercury was due to increased uptake of mercury in the renal outer stripe of the outer medulla and/or renal cortex. Ureteral ligation caused reductions in the renal uptake of mercury in all groups except for the one treated with inorganic mercury plus N-acetylcysteine. Thus, it appears that virtually all of the mercury taken up by the kidneys of the normal rats treated with inorganic mercury plus N-acetylcysteine occurred at the basolateral membrane. Urinary excretory data also support this notion, in that the rate of excretion of inorganic mercury was greatest in the rats treated with inorganic mercury plus N-acetylcysteine. Our data also indicate that uptake of inorganic mercury in the kidneys of rats treated with inorganic mercury plus cysteine occurred equally at both luminal and basolateral membranes. In addition, the renal uptake of mercury in rats treated with inorganic mercury plus homocysteine occurred predominantly at the basolateral membrane with some component of luminal uptake. The findings of the present study confirm that there are at least two distinct mechanisms involved in the renal uptake of inorganic mercury, with one mechanism located on the luminal membrane and the other located on the basolateral membrane. Our findings also show that cysteine and homologs of cysteine, when coadministered with inorganic mercury, greatly influence the magnitude and/or site of uptake of mercuric ions in the kidney.


Differences in lung function and chest dimensions in school-age girls and boys.
The present analysis was undertaken to find out whether differences in the performance of the lungs of boys and girls of the same height are explicable by differences in thoracic size. We measured forced vital capacity (FVC), peak expiratory flow (PEF) and forced expiratory flows (FEFs), when 50% and 75% of FVC had been exhaled (FEF50, FEF75), and standing height, chest width and depth and biacromial diameter in 1187 schoolchildren aged 6-18 years. Thoracic dimensions were usually greater in boys than in girls of the same height, except for the height range of 150.0-164.9 cm. For this height range, the pulmonary function variables (PEF, FEF50, FEF75 and PEF/FVC) were significantly higher in girls, and for FVC almost as high as the male values. For FEF50/FVC and FEF75/FVC, the female values were larger over the whole height range (115.0-184.9 cm), but even for these parameters the differences were greatest for the height range 150.0-164.9 cm. In conclusion, very similar growth patterns of lung function and thoracic parameters can suggest that differences in the lung function parameters of boys and girls of the same height may be explained by differences in the thorax size.


Fetal growth and prenatal exposure to bisphenol A: the generation R study.
Prenatal exposure to bisphenol A (BPA) has been associated with adverse birth outcomes, but findings of previous studies have been inconsistent. We investigated the relation of prenatal BPA exposure with intrauterine growth and evaluated the effect of the number of measurements per subject on observed associations. This study was embedded in a Dutch population-based prospective cohort study, with urine samples collected during early, mid-, and late pregnancy. The study comprised 219 women, of whom 99 had one measurement, 40 had two measurements, and 80 had three measurements of urinary BPA. Fetal growth characteristics were repeatedly measured by ultrasound during pregnancy and combined with measurements at birth. Linear regression models for repeated measurements of both BPA and fetal growth were used to estimate associations between urinary concentrations of creatinine-based BPA (BPACB) and intrauterine growth. The relationship between BPACB and fetal growth was sensitive to the number of BPA measurements per woman. Among 80 women with three BPA measurements, women with BPACB > 4.22 μg/g crea (creatinine) had lower growth rates for fetal weight and head circumference than did women with BPACB < 1.54 μg/g crea, with estimated differences in mean values at birth of -683 g (20.3% of mean) and -3.9 cm (11.5% of mean), respectively. When fewer measurements were available per woman, the exposure-response relationship became progressively attenuated and statistically nonsignificant. Our findings suggest that maternal urinary BPA may impair fetal growth. Because previous studies have shown contradictory findings, further evidence is needed to corroborate these findings in the general population.


Results from data mining in a radiology department: the relevance of data quality.
This work is part of an ongoing effort to examine and improve clinical workflows in radiology. Classical workflow analysis is time consuming and expensive. Here we present a purely data-driven approach using data mining techniques to detect causes for poor data quality and areas with poor workflow performance. Data has been taken from a operational RIS system. We defined a set of four key indicators for both data quality and workflow performance. Using several mining techniques such as cluster analysis and correlation tests we were able to detect interesting effects regarding data quality and an abnormality in the workflow for some organizational units of the examined radiology departments. We conclude that data-driven data mining approaches may act as a valuable tool to support workflow analysis and can narrow down the problem space for a manual on-site workflow analysis. This can save time and effort and leads to less strain for clinicians and workflow analysts during interviews.


Decision-making deficits in alcohol-dependent patients with and without comorbid personality disorder.
Impairments in decision making are a consistent finding in substance use disorder (SUD) populations. However, decision-making deficits are not specific for SUDs and are also reported in the context of other psychiatric disorders such as antisocial and borderline personality disorders (PDs). Given the frequent comorbidity between SUD and cluster B PD, it might be questioned whether the decision-making impairments typically reported in SUD populations reflect the addictive disorder, the cluster B PD, or a combination of the 2. In the current study, we compare the decision-making performance of non-substance-abusing controls (n=53) on the Iowa Gambling Task (IGT) with the decision-making performance of 3 abstinent alcohol-dependent samples, i.e., alcoholic patients without any PD (n=38), alcoholic patients with a cluster A or C PD (n=19), and alcoholic patients with a cluster B PD (n=23). Overall, all 3 alcohol-dependent subsamples performed inferior compared with controls. Between alcoholic subsamples, the alcoholic patients with a cluster A or C PD had the highest IGT score, followed by the alcoholic patients without a PD, while the cluster B alcoholic patients were the most impaired. These findings suggest that impairments in decision making underlie both alcohol dependence and cluster B PD, and alcoholic patients with a comorbid cluster B PD are particularly impaired in their decision making. These deficits may underlie the severe problems that characterize cluster B alcoholic patients specifically in inappropriate behaviors (e.g., poly substance abuse, legal, and professional dysfunction).


Alzheimer's Disease Drug Discovery--11th International Conference--Targeting Pathological Tau. 27-28 September 2010, Jersey City, NJ, USA.
The 11th Alzheimer's Disease Drug Discovery International Conference, held in Jersey City, NJ, USA, included topics covering new therapeutic developments in the field of Alzheimer's disease. This conference report highlights selected presentations on targeting pathological tau for the prevention or treatment of Alzheimer's disease. Investigational approaches discussed include aminothienopyridazine inhibitors of tau aggregation, the alternative splicing of tau pre-mRNA, protein phosphatase 2A as a potential therapeutic target, and immunotherapy and macroautophagy approaches for clearing aberrant tau protein from the brain.


Analysis of the correlation between the expression of miR-655 and esophageal cancer prognosis.
The correlation between the expression level of microRNA (miR)-655 in esophageal cancer with proliferation, invasion and prognosis was investigated. Reverse transcription-quantitative polymerase chain reaction technique was used to detect the expression level of miR-655 in esophageal cancer cell lines KYSE410 and EC9706, tumor tissues and normal cancer-adjacent tissues of 63 cases of patients with esophageal squamous cell carcinoma (ESCC). The expression of miR-655 was upregulated in ESCC cells through the transfection of miR-655 mimics, and the influence of miR-655 on proliferation and invasion ability of ESCC cells was observed. Combined with the clinical data, the correlation between the expression of miR-655 and the prognosis of esophageal cancer was analyzed. The expression of miR-655 was downregulated in 2 ESCC cell lines and 73.02% of ESCC tissues. The results showed that the increased expression of miR-655 via transfection of mimics inhibited the proliferation and invasion ability of ESCC cells. Combined with clinical data analysis, it was found that the low-expression of miR-655 was related to poorer progression-free survival. In conclusion, the high-expression of miR-655 can inhibit the proliferation and invasion of ESCC, and plays a negative regulation role in the prognosis process of tumor patients. The targeted regulation of miR-655 can be used as a new treatment method of ESCC.


Phylogenetic relationships in the stone fruit group of Prunus as revealed by restriction fragment analysis of chloroplast DNA.
In order to clarify the genetic relationships among stone fruits, a restriction fragment analysis of chloroplast DNAs (cpDNAs) was applied to cultivated Prunus species, whose genetic diagnoses are difficult because of their heterogeneity and long life span. Chloroplast DNAs (cpDNAs) were extracted from leaves of nine stone fruit accessions covering six species of Prunus. A restriction fragment analysis was conducted by gel electrophoresis after digestion with these endonucleases. The genome sizes of the cpDNAs were about 135-139 kbp, and the fruits were classified into seven chloroplast genome types according to their restriction fragment patterns. Two peach cultivars and nectarine were found to harbor identical plastomes, differing from those of two wild peaches and the European plum. This suggests that two cultivated peaches (P. persica) did not receive the cytoplasm from the wild peaches, P. mira and P. davidiana. Phylogenetic relationships among these types were then estimated based on the shared common fragments among the species.


Biologic agents in the management of inflammatory eye diseases.
Biologics are a new class of drugs that comprise recombinant cytokines and monoclonal antibodies directed against selected cell-surface markers. They include the tumor necrosis factor-alpha inhibitors infliximab, etanercept, and adalimumab; the antilymphocyte drugs rituximab and alemtuzumab; the interleukin-2 receptor blocker daclizumab; and recombinant interferon-alpha. This article reviews the rationale and current evidence for their use in uveitis, scleritis, and orbital inflammation.


Autoimmune Pancreatitis: A Multiorgan Disease Presenting a Conundrum for Clinicians in the West.
Autoimmune pancreatitis (AIP), a clinical entity originally described in East Asia and more recently recognized in the United States and Europe, poses a diagnostic conundrum for clinicians in the West due to immunoglobulin G4 seronegativity. Although expert panels classify this disease into 2 types, it remains difficult to stratify the disease given that both types share most clinical, biochemical, and imaging characteristics. The classic presentation of AIP can mimic that of pancreatic carcinoma, which increases the urgency of evaluation, diagnosis, and treatment. In this article, we elucidate the differences between the 2 types of AIP, highlight the shortcomings of the current classification system, and propose a more inclusive view of the disorder.


Choroideremia: molecular mechanisms and therapies.
Choroideremia (CHM) is a monogenic X-linked chorioretinal dystrophy affecting the photoreceptors, retinal pigment epithelium (RPE), and choroid; it is caused by mutations involving the CHM gene. CHM is characterized by night blindness in early childhood, progressing to peripheral visual field loss and eventually to complete blindness from middle age. CHM encodes the ubiquitously expressed Rab escort protein 1 (REP1), which is responsible for prenylation of Rab proteins and is essential for intracellular trafficking of vesicles. In this review we explore the role of REP1 in the retina and its newly discovered systemic manifestations, and discuss the therapeutic strategies for tackling this disease, including the outcomes from recent clinical trials.


Obesity does not affect the number of retrieved lymph nodes and the rate of intraoperative complications in gynecologic cancers.
Lymphadenectomy, in general, is a safe and well-tolerated procedure in gynecologic oncology. However, some technical difficulties may be experienced in obese women which may result in inadequate lymphadenectomy and increased complications. The purpose of this study is to retrospectively evaluate the effect of obesity on lymph node counts retrieved and complication rates observed during lymphadenectomy in gynecologic cancers. Patients with ovarian, endometrial or cervical cancers treated with initial surgery including bilateral pelvic and paraaortic lymph node dissection were grouped as non-obese and obese. These two groups were compared in terms of the number of retrieved lymph nodes and the rate of intraoperative complications directly related to lymph node dissection. One hundred twenty-three patients were eligible with a mean age of 55.1 years and mean body mass index of 29.2 kg/m(2). Fifty-nine patients were obese while 64 were non-obese. Lymph node counts obtained in different stations and in total were similar among non-obese and obese patients. Rates of lymphadenectomy-related intraoperative complications including vascular, neural, intestinal, and bladder injury were also similar in non-obese and obese patients. The obesity does not affect the lymph node counts and intraoperative complication rates adversely in women with gynecologic cancers. Therefore, adequate lymph node dissection should not be omitted based solely upon obesity in gynecologic oncology patients.


Placental vascularization alterations in hypertensive disorders complicating pregnancy (HDCP) and small for gestational age with HDCP using three-dimensional power doppler in a prospective case control study.
Hypertensive disorders complicating pregnancy (HDCP) continues to be a leading cause of maternal and neonatal mortality and morbidity. The clinical value of placental three-dimensional power Doppler (3DPD) in assessing HDCP requires further confirmation. The research was developed to assess changes of placental vascularity in HDCP using 3DPD and to investigate the placental vascularity in small for gestational age (SGA) compared with not-SGA in patients with HDCP. There were 126 normotensive and 128 hypertensive pregnant women included in this prospective case-control study from March 2011 to March 2013. Pregnant women underwent 3DPD. Vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were obtained. The placental 3DPD indices, umbilical artery systolic and diastolic ratio (S/D) and pregnancy outcomes were compared between the groups. The placental VI and VFI were significantly lower in hypertensive women compared with normotensive women (P < 0.001 and P = 0.014, respectively), and these parameters were significantly reduced in severe preeclampsia (P < 0.001 and P = 0.003, respectively). A weak correlation was found between VI and umbilical artery S/D in HDCP group (r = -0.277, P = 0.001). In HDCP population, neonates who were postnatally diagnosed with SGA had lower VI (P = 0.041) and higher S/D (P < 0.001). The placental vascularity indices decreased in hypertensive women and the reduction inplacental perfusion was consistent with the severity of the hypertensive disorder. The associations betweenplacental vascularization and umbilical artery impedance may be valuable for further researches and arerequired confirmation. The significant differences in the 3DPD placental vascularization between SGA andnot-SGA in hypertensive pregnancy population may show some clinical importance that we could use tobetter assess or predict the progression and adverse outcomes in the future. Although 3DPD quantificationhas been widely used in multiple publications, we have to acknowledge its limitations. The intraplacental vascularization was poor in HDCP, and especially in severe preeclampsia. Neonates with SGA had poor placental vascularization and higher umbilical artery S/D. Further studies should focus on the clinical assessment of placental 3DPD as well as a combination of placental 3DPD and other fetal Doppler indices to better predict the development and outcomes of preeclampsia.


Rescue of BDNF expression by the thalamic parafascicular nucleus with chronic treatment with the mGluR2/3 agonist LY379268 may contribute to the LY379268 rescue of enkephalinergic striatal projection neurons in R6/2 Huntington's disease mice.
We have found that daily subcutaneous injection with a maximum tolerated dose of the mGluR2/3 agonist LY379268 (20 mg/kg) beginning at 4 weeks of age dramatically improves the motor, neuronal and neurochemical phenotype in R6/2 mice, a rapidly progressing transgenic model of Huntington's disease (HD). We also previously showed that the benefit of daily LY379268 in R6/2 mice was associated with increases in corticostriatal brain-derived neurotrophic factor (BDNF), and in particular was associated with a reduction in enkephalinergic striatal projection neuron loss. In the present study, we show that daily LY379268 also rescues expression of BDNF by neurons of the thalamic parafascicular nucleus in R6/2 mice, which projects prominently to the striatum, and this increase too is linked to the rescue of enkephalinergic striatal neurons. Thus, LY379268 may protect enkephalinergic striatal projection neurons from loss by boosting BDNF production and delivery via both the corticostriatal and thalamostriatal projection systems. These results suggest that chronic treatment with mGluR2/3 agonists may represent an approach for slowing enkephalinergic neuron loss in HD, and perhaps progression in general.


Shikonin induces an anti‑tumor effect on murine mammary cancer via p38‑dependent apoptosis.
Breast cancer is the most common malignancy in women. Apoptosis is important for tumor suppression and may delay cancer progression. It was found that shikonin induced apoptosis in 4T1 murine mammary cancer cells and MDA‑MB‑231 human breast cancer cells in vitro. Total p38 and c‑Jun N‑terminal kinase (JNK) levels were maintained in 4T1 cells, and p38 phosphorylation, but not JNK phosphorylation, was significantly increased. Caspase‑3/7 activity was detected, which suggested that the p38 pathway, but not the JNK signaling pathway, induced apoptosis in 4T1 cells. The anti‑tumor effects of shikonin on orthotopic mouse models were also examined. On day 7 after inoculation of 4T1 cells into mice, tumor volumes in the shikonin‑treated and the control groups began to differ. On day 13, tumors were weighed, and shikonin was revealed to suppress tumor growth in the orthotopic 4T1 model in vivo. In conclusion, shikonin is a potential anti‑tumor drug for breast cancer.


Age and burnout syndrome in nursing professionals: moderating role of emotion-focused coping.
This study examined whether the association between age and the three burnout dimensions (emotional exhaustion, depersonalisation and reduced personal accomplishment) depend on the extent of nursing professionals' use of emotion-focused coping strategy. Participants were 283 nurses (Mage = 35 years, SD = 8.17, Range = 23-66 years) from a tertiary healthcare institution in south-eastern Nigeria. They completed self-report measures of relevant variables in paper and pencil form. Increased age was associated with reduced personal accomplishment for nurses with high emotion-focused coping, but not for those who were low or moderate in use of emotion-focused coping. Such moderation effects were not found for emotional exhaustion and depersonalisation. Findings clarify the conditions under which age may be associated with reduced sense of achievement at work among nursing professionals. The study adds to knowledge in combating burnout in nursing and could guide health managers in developing strategies that might prevent or ameliorate nurses' burnout.


Pediatric IgA Nephropathy in Europe.
In Europe IgA nephropathy (IgAN) is detected in 20% of children with glomerular diseases diagnosed by renal biopsy. The outcome during childhood is generally good, but progression in the long-term follow-up may occur in about 20% of children after 20 years. In Europe, urine screening programs are not active, and there is variability in the policy to perform renal biopsies in oligo-symptomatic children. Hence, a suitable observational approach to pediatric IgAN is offered by the VALIGA study which included 174 children aged < 18 years from 13 European countries followed over a median of 4.4 (2.5-7.5) years. Renal pathology lesions were centrally scored according to the Oxford Classification of IgAN (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T; crescents, C [MEST-C]). Children had renal biopsy mostly with normal estimated glomerular filtration rate (eGFR) and moderate proteinuria of a median of 0.84 g/day/1.73 m2 (< 0.30 g/day/1.73 m2 in 30% of the cases). Children showed M1 in 21.8%, E1 in 13.8%, S1 in 42.5%, T1-2 in 6.3%, and C1 in 14.9%. The survival at the combined endpoint of 50% eGFR decrease or end-stage renal disease at 15 years was 94%. The slow progression rate and the limited number of cases progressing to the combined endpoint (6.4%) did not allow the detection of a predictive value of the MEST-C score. Moreover, the predictive value of clinical and pathological features was likely blunted by the use of corticosteroid/immunosuppressive treatment (CS/IS) in 50% of the cases. The survival tree analysis also proved that children < 16 years old with IgAN without mesangial hypercellularity (M0) and well preserved eGFR (> 90 mL/min/1.73 m2) had a high probability of proteinuria remission during follow-up. Moreover, in this subgroup of children, the benefits of CS/IS therapy reached statistical significance. In Europe, the use of CS/IS treatment in IgAN is still a debated issue, but most children tend to be treated more commonly than adults with CS/IS. A recent uncontrolled study reports a favorable outcome in European children with IgAN and very active acute forms of IgAN with improvement in eGFR and reduction in proteinuria. In Europe, children with IgAN have a favorable prognosis in the short term, and this may be due also to the frequently adopted CS/IS therapy, particularly with acute and active pathological features. The risk of progression over decades of follow-up remains an unsolved problem which needs to be addressed by controlling subtle chronic pathogenetic factors which work in children as well as in adult cases of IgAN.


The activated nerve growth factor receptor p-TrkA is selectively expressed in advanced-stage ovarian carcinoma.
The objective of this study was to compare the expression of the nerve growth factor (NGF) receptors TrkA and p75 in ovarian borderline tumors, International Federation of Gynecology and Obstetrics (FIGO) stage I carcinomas and advanced-stage (FIGO stage III-IV) carcinomas, and to assess a possible association between NGF receptor expression and mitogen-activated protein kinase (MAPK) activation in borderline tumors and FIGO stage I carcinomas. Sections from 119 borderline tumors, 57 FIGO stage I invasive ovarian carcinomas, and 56 advanced-stage carcinomas were evaluated for expression of activated phospho-TrkA (p-TrkA) and p75 using immunohistochemistry. MAPK activation was analyzed in stage I carcinomas and borderline tumors using phospho-specific antibodies against the extracellular-regulated kinase (p-ERK), the high osmolarity glycerol response kinase (p-p38), and the c-jun amino-terminal kinase (p-JNK). p-TrkA membrane expression was significantly more frequent in advanced-stage carcinomas compared with both borderline and stage I carcinomas (P < .001). p75 membrane expression was comparable in the 3 groups (P > .05). p-ERK and p-p38 expression was comparable in borderline and stage I carcinomas, whereas p-JNK was more frequently expressed in stage I ovarian carcinomas (P < .001). NGF receptor expression showed no association with MAPK activation in borderline and stage I carcinomas. In conclusion, expression of biologically active p-TrkA receptor at the cell membrane is up-regulated along tumor progression in ovarian carcinoma, whereas p75 expression remains unaltered. These data provide further evidence regarding the clinical role of p-TrkA in ovarian carcinoma. NGF receptors probably signal via MAPK-independent pathways in ovarian carcinoma.


Task-related arousal of type A and type B persons: level of challenge and response specificity.
To determine whether different levels of challenge had differential effects on the arousal levels of Type A and Type B persons, 30 Type A and 30 Type B male subjects worked on an intelligence test task (digits backwards recall) that was easy, moderately difficult, or extremely difficult. Arousal was measured in terms of systolic blood pressure, diastolic blood pressure, pulse rate, pulse volume, skin resistance, and subjective arousal. Results indicated that while working on the extremely difficult task, the Type A subjects evidenced reliably higher systolic blood pressure than did the Type B subjects (p = 0.1; difference = 7.52 mm of Hg) and that there were not reliable differences between the subjects in systolic blood pressure at other levels of challenge or on other measures of arousal.