Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells.
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor composed of alpha and beta subunits. HIF-1 is critically involved in cellular responses to hypoxia, glycolysis, and angiogenesis. Here, we show that treatment of prostate cancer PC-3 and LNCaP cells with the benzoquinone ansamycin geldanamycin, an Hsp90-specific inhibitor, induced degradation of HIF-1alpha protein in a dose- and time-dependent manner under both normoxia and hypoxia. This inhibition was also shown in other common cancer types tested. Rapid degradation of nuclear HIF-1alpha protein levels was accompanied by respective inhibition in HIF-1alpha functional transcription activity of VEGF. No difference between HIF-1alpha mRNA levels before or after geldanamycin treatment was found. Moreover, [35S]methionine pulse-chase analysis revealed that HIF-1alpha protein half-life was markedly decreased in the presence of geldanamycin compared with that in control. The geldanamycin-induced degradation of HIF-1alpha was reversed by proteosome inhibitors lactacystin and MG-132. We conclude that geldanamycin induces reduction of HIF-1alpha levels and its downstream transcriptional activity by accelerating protein degradation independent of O2 tension. Thus, benzoquinone ansamycin drugs and their derivatives, such as 17-allyl-aminogeldanamycin, are excellent candidates as small molecule drug inhibitors of HIF-1 overexpression in cancer cells.


Hypopituitarism secondary to cavernous sinus thrombosis.
We present what we believe to be the only documented cases of cavernous sinus thrombosis complicated by acute hypopituitarism and ultimately resulting in limited pituitary ACTH reserve. If pituitary involvement is suspected, replacement therapy should be instituted while awaiting laboratory confirmation. Cavernous sinus thrombosis is a medical and surgical emergency. Its successful therapy is dependent upon prompt recognition, surgical drainage when appropriate, proper antibiotic coverage, and close observation for and prompt treatment of complications and sequelae.


Contra: Contrarian statistics for controlled variable selection.
The holdout randomization test (HRT) discovers a set of covariates most predictive of a response. Given the covariate distribution, HRTs can explicitly control the false discovery rate (FDR). However, if this distribution is unknown and must be estimated from data, HRTs can inflate the FDR. To alleviate the inflation of FDR, we propose the contrarian randomization test (CONTRA), which is designed explicitly for scenarios where the covariate distribution must be estimated from data and may even be misspecified. Our key insight is to use an equal mixture of two "contrarian" probabilistic models in determining the importance of a covariate. One model is fit with the real data, while the other is fit using the same data, but with the covariate being tested replaced with samples from an estimate of the covariate distribution. CONTRA is flexible enough to achieve a power of 1 asymptotically, can reduce the FDR compared to state-of-the-art CVS methods when the covariate distribution is misspecified, and is computationally efficient in high dimensions and large sample sizes. We further demonstrate the effectiveness of CONTRA on numerous synthetic benchmarks, and highlight its capabilities on a genetic dataset.


Cellular and humoral immune response to a phenolic glycolipid antigen (PhenGL-I) in patients with leprosy.
The ability of phenolic glycolipid I (PhenGL-I) of Mycobacterium leprae to stimulate in vitro lymphocyte proliferation (LP) was tested in cultures of peripheral blood cells from 42 patients with leprosy in Chicago and Thailand, 9 individuals with household contact in Thailand, and 10 unexposed North American controls. Only 10 responders (24%) were found among the patients, and the degree of LP was small. Responders were found among patients with lepromatous (18%) or tuberculoid (30%) leprosy without relation to age, complications, duration of treatment, or lepromin responsiveness. The specificity of the response was supported by a lack of response to two other glycolipids, by responses by T cells but not B cells, and by the observation that three of four responders tested maintained their responses to PhenGL-I for at least 1 year. Serum immunoglobulin M (IgM) and IgG antibodies were measured in the same patients by using PhenGL-I or its terminal monosaccharide conjugated to a bovine serum albumin carrier in an enzyme-linked immunosorbent assay. The presence of IgM antibody correlated negatively with LP to lepromin and to PhenGL-I in patients with tuberculoid leprosy. We conclude that circulating T cells from some leprosy patients proliferate in the presence of PhenGL-I in vitro, but the response is weak, possibly due to concomitant suppression or inhibition. The predominance of IgM antibody to PhenGL-I may be related to a lack of a T-helper-cell-mediated switch to IgG antibody response.


Chemical composition and biological activities of the essential oil from Calamintha nepeta plants from the wild in southern Italy.
The chemical composition of the essential oil from aerial parts of Calamintha nepeta (L.) Savi, collected in the Campania Region, was obtained by hydrodistillation and analyzed by GC and GC-MS. In all, 42 compounds were identified. The oil was characterized by a prevalence of the sesquiterpenic fraction (80.8%). The main components were 1,10-di-epi-cubenol (18.5%), allo-aromadendrene epoxide (11.4%) and cadalene (5.7%). The essential oil was evaluated for its in vitro potential phytotoxic activity against germination and initial radical growth of Raphanus sativus L., Lepidium sativum L., Sinapis arvensis L., Triticum durum L. and Phalaris canariensis L. seeds. The essential oil showed no antioxidant activity.


Role of Arbuscular Mycorrhizal Fungi in Plant Growth Regulation: Implications in Abiotic Stress Tolerance.
Abiotic stresses hamper plant growth and productivity. Climate change and agricultural malpractices like excessive use of fertilizers and pesticides have aggravated the effects of abiotic stresses on crop productivity and degraded the ecosystem. There is an urgent need for environment-friendly management techniques such as the use of arbuscular mycorrhizal fungi (AMF) for enhancing crop productivity. AMF are commonly known as bio-fertilizers. Moreover, it is widely believed that the inoculation of AMF provides tolerance to host plants against various stressful situations like heat, salinity, drought, metals, and extreme temperatures. AMF may both assist host plants in the up-regulation of tolerance mechanisms and prevent the down-regulation of key metabolic pathways. AMF, being natural root symbionts, provide essential plant inorganic nutrients to host plants, thereby improving growth and yield under unstressed and stressed regimes. The role of AMF as a bio-fertilizer can potentially strengthen plants' adaptability to changing environment. Thus, further research focusing on the AMF-mediated promotion of crop quality and productivity is needed. The present review provides a comprehensive up-to-date knowledge on AMF and their influence on host plants at various growth stages, their advantages and applications, and consequently the importance of the relationships of different plant nutrients with AMF.


Social impairments in Rett syndrome: characteristics and relationship with clinical severity.
While behavioural abnormalities are fundamental features of Rett syndrome (RTT), few studies have examined the RTT behavioural phenotype. Most of these reports have focused on autistic features, linked to the early regressive phase of the disorder, and few studies have applied standardised behavioural measures. We used a battery of standardised measures of behaviour and functioning to test the following hypotheses: (1) autistic behaviour is prominent throughout childhood in RTT; (2) autistic features are more salient in individuals with milder presentation; (3) severity of autistic behaviour is associated with a wider range of behavioural problems; and (4) specific MECP2 mutations are linked to more severe autistic behaviour. Eighty MECP2 mutation-positive girls with RTT (aged 1.6-14.9 years) were administered: (1) the Screen for Social Interaction (SSI), a measure of autistic behaviour suited for individuals with severe communication and motor impairment; (2) the Rett Syndrome Behaviour Questionnaire (RSBQ), covering a wide range of abnormal behaviours in RTT; (3) the Vineland Adaptive Behavior Scales (VABS); and (4) a modified version of the Rett Syndrome Severity Scale (RSSS). Regression analyses examined the predictive value of age and RSSS on autistic behaviour and other behavioural abnormalities. T-tests further characterised the behavioural phenotype of individual MECP2 mutations. While age had no significant effect on SSI or RSBQ total scores in RTT, VABS Socialization and Composite scores decreased over time. Clinical severity (i.e. RSSS) also increased with age. Surprisingly, SSI performance was not related to either RSSS or VABS Composite scores. Autistic behaviour was weakly linked with the RSBQ Hand behaviour factor scores, but not with the RSBQ Fear/Anxiety factor. Clinical (neurological) severity did not predict RSBQ scores, as evidenced by the analysis of individual MECP2 mutations (e.g. p.R106W, p.R270X and p.R294X). Our data suggest that in RTT, autistic behaviour persists after the period of regression. It also demonstrated that neurological and behavioural impairments, including autistic features, are relatively independent of one another. Consistent with previous reports of the RTT phenotype, individual MECP2 mutations demonstrate complex associations with autistic features. Evidence of persistent autistic behaviour throughout childhood, and of a link between hand function and social skills, has important implications not only for research on the RTT behavioural phenotype, but also for the clinical management of the disorder.


[Clinical competence of the cardiologists working in coronary care units].
Since the early 1970s, intensive cardiac care has been given in coronary care units (CCUs) that were developed to treat lethal arrhythmias in patients with acute myocardial infarction (AMI). Later on, such units have expanded their attitude according to patients' needs. In fact, during the last decades, subjects have become progressively older, with an increasing number of comorbidities. In addition, growing numbers of patients with severe heart failure, rhythm disturbances, massive pulmonary embolism or severe valvular dysfunction need intensive care. Thus, at present admission to CCUs is not limited to patients with AMI, but has extended to a large number of severe cardiac conditions that need highly specialized care and very complex procedures. Therefore, it is not surprising that physicians in charge of these CCUs need to expand their skills. In fact, they should be able to recognize and treat a wide variety of acute cardiac conditions and different comorbidities. In addition, they should be familiar with all the diagnostic and therapeutic options available in a modern CCU (ECG, echocardiography, hemodynamic measurements and their interpretation, cardiac and coronary angiography, cardiac and non-cardiac pharmacotherapy, and interventional cardiology). In addition they should be able to use all the equipment needed like cardiac echocardiography, pulmonary artery catheters, cardiac pacemakers, defibrillators, mechanical ventilators, dialysis equipment, intra-aortic balloon pump and ventricular assist devices). Moreover, CCUs have a crucial role in the management of all cardiac emergencies according to an integrated cardiac network model. In this model, the CCU of a referring center (Hub) plays a central role in keeping continuous and tight relations with the other peripheral hospitals (Spoke) that have a prominent and unique role in the selection and early treatment of acute cardiac patients and their follow-up. Thus, all these evolving needs of acute cardiac patients look for skilled doctors and highly specialized CCUs. Therefore, both the University and the Scientific Societies should re-design the training process of the cardiologists working in the CCUs.


Blood donors and non-donors: a review of the research.
This review complements a report by Oswalt who reviewed blood donor motivation and recruitment. Thirty-one studies were reviewed that provided insight into blood donor motivation, blood donor characteristics, blood donor personality, and non-donor motivation. From the review, it was possible to draw conclusions regarding: 1) the most often identified reasons why donors give blood; 2) characteristics of donors; 3) personality traits of donors; and 4) the most often identified reasons why non-donors do not give blood.


Alpha-adrenergic blockade in preventing posttransplant edema of lung allograft.
Effect of alpha-adrenergic blockers on pulmonary edema in lung transplantation was studied with a rat model of syngeneic left lung transplantation. Prior to harvesting, 0.1 mg of Prazosin or 0.4 mg of Yohimbine was given to the donor. Pulmonary and systemic hemodynamics were measured under the right pulmonary arterial occlusion (RPAO) at different time points after grafting. Wet to dry weight ratio (W/D) of all transplants was also calculated. Same procedure was conducted in rats with normal and ischemic lung and in transplanted animals without any treatments. While RPAO did not increase W/D in normal lung with a significant elevation in pulmonary arterial pressure (PAP), both these values significantly increased in transplanted lung. Transplanted animals could not tolerate RPAO 24 hours after grafting, but were tolerable later than 48 hours with elevated W/D and PAP. On the contrary, animals given Prazosin or Yohimbine were all tolerable at 24 hours postsurgery. Yohimbine significantly improved W/D. Consequently, it was demonstrated that pulmonary edema of the graft reached its peak during first 24 to 48 hours after transplantation and was alleviated by the blockade of alpha-adrenergic receptor in the graft vessel.


Iodine in Human Milk: A Systematic Review.
Because infants are born with small amounts of stored intrathyroidal iodine, they depend on human-milk iodine for normal physical and neurologic growth and development. The mammary gland concentrates iodide; however, there is a lack of consensus on the concentrations of breast-milk iodine necessary to achieve equilibrium in the infant. The objectives of the present review are to consider trends in breast-milk iodine concentrations over the course of lactation, to determine which maternal factors or interventions influence breast-milk iodine concentrations, to examine the association between breast-milk iodine concentrations and infant iodine status, and to identify how newer data contribute to the literature and inform recommendations for achieving optimal breast-milk iodine concentrations. A systematic search of the published literature was undertaken by using the US National Library of Medicine's MEDLINE/PubMed bibliographic search engine. Observational and intervention studies were included if the research was original, the study had not been included in a previous review, and iodine concentration in human milk was measured at ≥1 time point during the first 12 mo of lactation. Results of the systematic review indicate that breast-milk iodine concentrations vary widely between populations but are highest in colostrum and decrease gradually throughout the lactation period. Included studies did not replicate earlier findings of an inverse correlation between breast-milk iodine and perchlorate concentrations. Supplementation with high-dose or daily iodine during lactation was effective in increasing breast-milk iodine concentrations with some evidence of a dose-response relationship, which is consistent with findings of earlier supplementation trials in pregnancy and lactation. Although additional and globally representative research is needed, data suggest that breast-milk iodine concentrations in the range of 150 μg/L during the first 6 mo of lactation would achieve or exceed infant iodine equilibrium and prevent the developmental consequences of iodine deficiency.


Chlamydia trachomatis pneumonia in the immune, athymic and normal BALB mouse.
This paper compares the histopathology of pneumonia due to murine Chlamydia trachomatis (MoPn, mouse pneumonitis agent) in susceptible athymic nude mice (nu/nu), resistant heterozygous littermates (nu/+) and very resistant immunized nu/+ mice. While all groups had an early heterophil response, successful host defence correlated with the presence of large numbers of plasma cells, lymphocytes, monocytes, and lipid laden macrophages. Reticulate bodies were seen in all groups, predominantly in type I alveolar epithelial cells. By 24 h in the immune nu/+ group, no intact organisms were visible. Optimal control of infection was thus rapid and not clearly related to heterophils. These studies show that the histopathology of chlamydial infection may be quite atypical in the immunocompromised host, mononuclear cells seem critical in host defence, and B cell activation with plasma cell infiltration is dependent on intact T cell function in this model.


ADAMTS-7 inhibits re-endothelialization of injured arteries and promotes vascular remodeling through cleavage of thrombospondin-1.
ADAMTS-7, a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, was recently identified to be significantly associated genomewide with coronary artery disease. However, the mechanisms that link ADAMTS-7 and coronary artery disease risk remain elusive. We have previously demonstrated that ADAMTS-7 promotes vascular smooth muscle cell migration and postinjury neointima formation via degradation of a matrix protein cartilage oligomeric matrix protein. Because delayed endothelium repair renders neointima and atherosclerosis plaque formation after vessel injury, we examined whether ADAMTS-7 also inhibits re-endothelialization. Wire injury of the carotid artery and Evans blue staining were performed in Adamts7(-/-) and wild-type mice. Adamts-7 deficiency greatly promoted re-endothelialization at 3, 5, and 7 days after injury. Consequently, Adamts-7 deficiency substantially ameliorated neointima formation in mice at days 14 and 28 after injury in comparison with the wild type. In vitro studies further indicated that ADAMTS-7 inhibited both endothelial cell proliferation and migration. Surprisingly, cartilage oligomeric matrix protein deficiency did not affect endothelial cell proliferation/migration and re-endothelialization in mice. In a further examination of other potential vascular substrates of ADAMTS-7, a label-free liquid chromatography-tandem mass spectrometry secretome analysis revealed thrombospondin-1 as a potential ADAMTS-7 target. The subsequent studies showed that ADAMTS-7 was directly associated with thrombospondin-1 by its C terminus and degraded thrombospondin-1 in vivo and in vitro. The inhibitory effect of ADAMTS-7 on postinjury endothelium recovery was circumvented in Tsp1(-/-) mice. Our study revealed a novel mechanism by which ADAMTS-7 affects neointima formation. Thus, ADAMTS-7 is a promising treatment target for postinjury vascular intima hyperplasia.


Mutant monoclonal antibodies with alterations in biological functions.
Somatic cell mutants with deletions in the immunoglobulin constant region were isolated from an IgG(2b) Ar-binding hybridoma. Rat anti-mouse immunoglobulins were used to identify the sites of the deletions. The mutant monoclonal antibodies differ from the parental molecule in their assembly states and are defective in various immunoglobulin activities, making them potentially more useful reagents.


Clinical presentation and cardiac imaging findings in patient cases of perimyocarditis and pericarditis with a temporal association to SARS-CoV-2 vaccination.
We aimed to investigate and present cases of perimyocarditis and pericarditis verified by cardiovascular resonance (CMR) imaging in patients with a strong temporal association to SARS-CoV-2 vaccination. We sought to describe the clinical presentation including coronary artery angiography, CMR, transthoracic echocardiography, blood samples, electrocardiography, and symptoms. We included 10 patients admitted with chest pain shortly after vaccination for SARS-CoV-2, who were diagnosed with pericarditis or perimyocarditis by CMR. We reviewed the CMR, echocardiography, electrocardiography, blood samples, coronary artery angiography, vital signs and medical history. The updated Lake Louise Criteria were used to determine the diagnosis by CMR. Eight patients had perimyocarditis and two patients had pericarditis. The mean age was 22 ± 5 years (range 16 to 31 years), 90% were male. The median time from vaccination to hospital admission was 4 days (range 2 to 28 days). Admissions were seen after vaccination with three different SARS-CoV-2 vaccine manufacturers. Nine Patients had ST-elevation on the initial electrocardiography. Peak troponins varied from 357 to 23,547 ng/l, with a median of 4,304 ng/l. Two patients had an LVEF <50% on echocardiography and four patients had left ventricular global longitudinal strain values <18%. CMR revealed preserved left ventricular ejection fraction (LVEF), although one patient had decreased LVEF on CMR. The T1 and T2 mapping values were increased in all patients. Of the 8 patients with perimyocarditis, all patients had signs of myocardial injury in the lateral segments of the left ventricle. This case series of 10 patients supports the emerging evidence of an association between vaccination for SARS-CoV-2 and perimyocarditis and pericarditis, especially in young males. The temporal association was seen after vaccines from three different manufacturers. Imaging data from echocardiography and CMR displayed normal to mildly impaired cardiac function, usually with a mild disease course.


Chromosome 18 pairing behavior in human trisomic oocytes. Presence of an extra chromosome extends bouquet stage.
Little is known about the first meiotic prophase stages in the human female because these occur during fetal life, and only a few studies have addressed aneuploid human oocytes. In this paper, the synaptic process in the meiotic prophase in three 47, XX+18 cases is analyzed. A complete study of the dynamics of centromeres and telomeres, cohesin core and synapsis development in aneuploid female meiosis was performed. Investigation of chromosome dynamics in prophase of trisomy 18 oocytes show that these events follow the major patterns seen earlier in euploid oocytes. However, there is a significant delay in the resolution of bouquet topology which could relate to the presence of a surplus chromosome 18 axial element in zygotene oocytes. Pachytene oocytes displayed normal synapsis among the three chromosome 18s. However, in some oocytes the surplus chromosome 18 core was aligned to the bivalent 18. As ataxia telangiectasia and Rad3 related kinase (ATR) has been described as a marker for late-pairing chromosomes in mice, ATR distribution was analyzed in human meiocytes--spermatocytes, euploid oocytes and trisomic oocytes. In contrast to the observations made in mice, no preferential staining for late-pairing chromosomes was observed in humans. In the cases studied, bivalent synapses progressed as in a normal ovary, contrasting with the hypothesis that a surplus chromosome can modify pairing of other chromosomes.


Mortality associated with gastroesophageal reflux disease and its non-malignant complications: a systematic review.
The mortality associated with malignant complications of gastroesophageal reflux disease (GERD) is well recognized. The aim of this systematic review was to assess the less well-examined mortality associated with GERD and its non-malignant complications, including esophageal erosions, ulcers, bleeding, perforation and strictures. Studies reporting mortality in GERD and its non-malignant complications were identified via systematic PubMed searches, and previously unpublished population mortality statistics from public access databases. RESULTS. Three countries were examined (USA, UK, Finland). Cohort studies (n=3) in the UK showed a 1.16- to 1.6-fold increase in risk of death in individuals with GERD compared with the general population, the majority of deaths being due to cardiac disease. Population data indicate that GERD and its likely esophageal complications were the cause of death in 685 and 521 cases, respectively, in the USA (year: 2003) (age-adjusted mortality: 2.3/million and 1.8/million, respectively), and in 36 and 349 cases, respectively, in England and Wales (2004) (0.6/million and 5.4/million, respectively). In Finland (2000), GERD-related mortality was 4.6/million. Mortality from GERD and its likely esophageal complications increased with age, and was between 1.2-fold and 1.8-fold higher in men than in women. Cohort studies in the USA are inconsistent on mortality risk associated with surgical therapy. Time-trend data suggest that mortality from GERD and its non-malignant complications has been increasing. Data from Europe and the USA show that GERD and its non-malignant complications can on rare occasions cause death.


New Robust and Reproducible Stereological IHC Ki67 Breast Cancer Proliferative Assessment to Replace Traditional Biased Labeling Index.
There is a pressing need for an objective decision tool to guide therapy for breast cancer patients that are estrogen receptor positive and HER2/neu negative. This subset of patients contains a mixture of luminal A and B tumors with good and bad outcomes, respectively. The 2 main current tools are on the basis of immunohistochemistry (IHC) or gene expression, both of which rely on the expression of distinct molecular groups that reflect hormone receptors, HER2/neu status, and most importantly, proliferation. Despite the success of a proprietary molecular test, definitive superiority of any method has not yet been demonstrated. Ki67 IHC scoring assessments have been shown to be poorly reproducible, whereas molecular testing is costly with a longer turnaround time. This work proposes an objective Ki67 index using image analysis that addresses the existing methodological issues of Ki67 quantitation using IHC on paraffin-embedded tissue. Intrinsic bias related to numerical assessment performed on IHC is discussed as well as the sampling issue related to the "peel effect" of tiny objects within a thin section. A new nonbiased stereological parameter (VV) based on the Cavalieri method is suggested for use on a double-stained Ki67/cytokeratin IHC slide. The assessment is performed with open-source ImageJ software with interobserver concordance between 3 pathologists being high at 93.5%. Furthermore, VV was found to be a superior method to predict an outcome in a small subset of breast cancer patients when compared with other image analysis methods being used to determine the Ki67 labeling index. Calibration methodology is also discussed to further this IHC approach.


Intracytoplasmic lumina of human breast cancer--a microscopic study and practical application in cytological diagnosis.
Intracytoplasmic lumina (ICLs) of breast carcinoma cells are dominantly noted as rather specific structures in various organella of carcinoma cells. The present study deals with the characteristic patterns of ICLs in the ultrastructural and cytological features of breast carcinomas. Ultrastructural analysis of benign and malignant breast lesions for ICLs revealed a high occurrence of such lumina in the carcinomas. Especially the lumina were frequently noted in cells of scirrhous carcinomas (scirrhous carcinoma: 42 ICLs, medullary tubular carcinoma: 24, papillotubular carcinoma: 17 per each 300 carcinoma cells, mastopathy: 7 ICLs, fibroadenoma: 3, normal mammary gland: 1 or 2 per each epithelial cell). In 55.6% of the cytological cases of scirrhous carcinoma, the tumor cells showed ICLs, whereas such lumina were found at a rate of only 3.4% in benign lesions. These results demonstrate that the detection of ICLs by cytological examination can be useful in the establishment of a diagnosis of scirrhous carcinoma, and in the decision on a breast origin for metastatic tumors.


Simultaneous occurrence of multiple neoplasms and hyperplasias in the adrenal and thyroid gland of the horse resembling multiple endocrine neoplasia syndrome: case report and retrospective identification of additional cases.
Neoplastic and hyperplastic disorders that affect multiple endocrine tissues in a single individual are well described in humans but less so in domestic animals. Multiple endocrine neoplasia (MEN) in humans is a genetically determined syndrome characterized by the appearance of benign or malignant proliferations within two or more endocrine glands. The primary endocrine tumors that are characteristic of MEN arise from cells that share the capacity for amine precursor uptake and decarboxylation. Here we describe the case of a 22-year-old Thoroughbred mare that died during an unattended parturition and subsequently was presented for necropsy at the University of California, Davis, Veterinary Medical Teaching Hospital. A C-cell (medullary) thyroid adenoma, pheochromocytoma, and multicentric bilateral nodular hyperplasia of the adrenal medulla were present, findings that are remarkably similar to those of human MEN syndrome. Mortality during pregnancy in women with undiagnosed pheochromocytoma is high (approximately 50%), typically because of hypertension and/or hemorrhage associated with catecholamine release from the tumor. Similarly, the mare in this report died of hemorrhage subsequent to parturition. A retrospective evaluation of endocrine tumors in horses that underwent necropsy at the Veterinary Medical Teaching Hospital from 1987 to 1997 was undertaken to identify additional possible cases of MEN in horses. Data from this retrospective evaluation suggest that coexistence of hyperplasias and neoplasias of the thyroid and adrenal glands, similar to MEN syndrome of humans, also occurs with some frequency in the horse.


Peripheral nerve blocks for the treatment of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) during pregnancy.
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare, primary headache syndrome, which is classified as a subtype of trigeminal autonomic cephalalgias. Although SUNCT is usually refractory to treatment, several antiepileptic drugs have recently shown promising results for its treatment. However, there is a lack of evidence regarding the course of SUNCT during pregnancy and the available treatment options. Here, we present a 30-week pregnant female with SUNCT who was successfully treated with infra- and supraorbital nerve blocks. Headache attacks completely diminished after the injection, and recurrence was not observed. Although lamotrigine may be relatively safe in pregnant patients with SUNCT attacks, peripheral nerve block may be a feasible technique and can be considered as a safe and effective treatment option. This is the first SUNCT case in the literature that was successfully treated with infra- and supraorbital nerve blocks during pregnancy.


The association of family continuity with infant health service use.
Continuity of care is a fundamental component of family medicine that has been shown to improve health care quality. Family continuity, when different family members are seen by the same clinician or practice, has not been well studied. We performed a retrospective cohort study of Medicaid enrollees in Oregon using administrative data. Infants were determined to have family continuity if they received well-baby care at the same clinic as that in which their mothers received prenatal care. Of the 1591 infants identified for participation in this study, 749 (47.1%) had family continuity. Infants had a mean of 4.55 well-child visits, 1.23 emergency department visits, and 0.17 hospitalizations in the first 13 months of life. Multivariate analyses found that infants with family continuity had increased numbers of well-child visits (relative risk, 1.05; P = .041), increased numbers of emergency department visits (relative risk, 1.36; P < .0001), and no difference in the number of hospitalizations (relative risk, 0.85; P = .282) when compared with infants without family continuity. Family continuity, when measured at the clinic level, is associated with a variable effect on infant health service use. This finding suggests that clinic-level continuity is not sufficient for achieving all the benefits of continuity.


The Impact of Mental Illness Stigma on Seeking and Participating in Mental Health Care.
Treatments have been developed and tested to successfully reduce the symptoms and disabilities of many mental illnesses. Unfortunately, people distressed by these illnesses often do not seek out services or choose to fully engage in them. One factor that impedes care seeking and undermines the service system is mental illness stigma. In this article, we review the complex elements of stigma in order to understand its impact on participating in care. We then summarize public policy considerations in seeking to tackle stigma in order to improve treatment engagement. Stigma is a complex construct that includes public, self, and structural components. It directly affects people with mental illness, as well as their support system, provider network, and community resources. The effects of stigma are moderated by knowledge of mental illness and cultural relevance. Understanding stigma is central to reducing its negative impact on care seeking and treatment engagement. Separate strategies have evolved for counteracting the effects of public, self, and structural stigma. Programs for mental health providers may be especially fruitful for promoting care engagement. Mental health literacy, cultural competence, and family engagement campaigns also mitigate stigma's adverse impact on care seeking. Policy change is essential to overcome the structural stigma that undermines government agendas meant to promote mental health care. Implications for expanding the research program on the connection between stigma and care seeking are discussed.


Risk factors for symptomatic hyponatraemia: the role of pre-existing asymptomatic hyponatraemia.
Hyponatraemia is associated with substantial morbidity and mortality. Identification of the risk factors associated with the development of symptomatic hyponatraemia is important in determining preventive strategies. A retrospective analysis of the risks factors associated with the development of severe, symptomatic hyponatraemia requiring hospital admission over the past 3 years at our institution was carried out. Forty-seven patients (26 women, 21 men) with a hospital admission serum sodium <134 mmol/L were identified. Of these patients, 31 (65.9%) had associated changes in the mental status that improved with the treatment of the hyponatraemia suggesting causality. The average admission sodium level of this cohort was 118.8 mmol/L. Symptomatic hyponatraemia was associated with volume depletion (32.6%), congestive heart failure (26%), syndrome of inappropriate antidiuretic hormone (26%), thiazide diuretic use (26%) and selective serotonin re-uptake inhibitor use (26%). In 21.7% of cases, the cause was multifactorial (congestive heart failure, syndrome of inappropriate antidiuretic hormone or medication use with volume depletion). In 11% of cases, patients were taking both thiazide diuretics and serotonin re-uptake inhibitors. Most importantly, 70.9% of all patients admitted with symptomatic hyponatraemia had pre-existing hyponatraemia that was untreated and believed to be asymptomatic (P < 0.05). This was the most common risk factor identified. We next investigated the prevalence of presumed asymptomatic hyponatraemia in the outpatient setting. Out of 27 496 patients analysed, 14% had serum sodium levels less than or equal to 134 mEq/L and 4% had values less than 130 mEq/L. Pre-existing asymptomatic hyponatraemia is a common finding and is associated with a high risk for the development of worsening hyponatraemia with altered mental status.


Dental and orofacial mesenchymal stem cells in craniofacial regeneration: The prosthodontist's point of view.
Of the available regenerative treatment options, craniofacial tissue regeneration using mesenchymal stem cells (MSCs) shows promise. The ability of stem cells to produce multiple specialized cell types along with their extensive distribution in many adult tissues have made them an attractive target for applications in tissue engineering. MSCs reside in a wide spectrum of postnatal tissue types and have been successfully isolated from orofacial tissues. These dental- or orofacial-derived MSCs possess self-renewal and multilineage differentiation capacities. The craniofacial system is composed of complex hard and soft tissues derived from sophisticated processes starting with embryonic development. Because of the complexity of the craniofacial tissues, the application of stem cells presents challenges in terms of the size, shape, and form of the engineered structures, the specialized final developed cells, and the modulation of timely blood supply while limiting inflammatory and immunological responses. The cell delivery vehicle has an important role in the in vivo performance of stem cells and could dictate the success of the regenerative therapy. Among the available hydrogel biomaterials for cell encapsulation, alginate-based hydrogels have shown promising results in biomedical applications. Alginate scaffolds encapsulating MSCs can provide a suitable microenvironment for cell viability and differentiation for tissue regeneration applications. This review aims to summarize current applications of dental-derived stem cell therapy and highlight the use of alginate-based hydrogels for applications in craniofacial tissue engineering.


Enhancement of reproductive heat tolerance in plants.
Comparison of average crop yields with reported record yields has shown that major crops exhibit annual average yields three- to seven-fold lower than record yields because of unfavorable environments. The current study investigated the enhancement of pollen heat tolerance through expressing an Arabidopsis thaliana heat shock protein 101 (AtHSP101) that is not normally expressed in pollen but reported to play a crucial role in vegetative thermotolerance. The AtHSP101 construct under the control of the constitutive ocs/mas 'superpromoter' was transformed into cotton Coker 312 and tobacco SRI lines via Agrobacterium mediated transformation. Thermotolerance of pollen was evaluated by in vitro pollen germination studies. Comparing with those of wild type and transgenic null lines, pollen from AtHSP101 transgenic tobacco and cotton lines exhibited significantly higher germination rate and much greater pollen tube elongation under elevated temperatures or after a heat exposure. In addition, significant increases in boll set and seed numbers were also observed in transgenic cotton lines exposed to elevated day and night temperatures in both greenhouse and field studies. The results of this study suggest that enhancing heat tolerance of reproductive tissues in plant holds promise in the development of crops with improved yield production and yield sustainability in unfavorable environments.


TIPT2 and geminin interact with basal transcription factors to synergize in transcriptional regulation.
The re-replication inhibitor Geminin binds to several transcription factors including homeodomain proteins, and to members of the polycomb and the SWI/SNF complexes. Here we describe the TATA-binding protein-like factor-interacting protein (TIPT) isoform 2, as a strong binding partner of Geminin. TIPT2 is widely expressed in mouse embryonic and adult tissues, residing both in cyto- and nucleoplasma, and enriched in the nucleolus. Like Geminin, also TIPT2 interacts with several polycomb factors, with the general transcription factor TBP (TATA box binding protein), and with the related protein TBPL1 (TRF2). TIPT2 synergizes with geminin and TBP in the activation of TATA box-containing promoters, and with TBPL1 and geminin in the activation of the TATA-less NF1 promoter. Geminin and TIPT2 were detected in the chromatin near TBP/TBPL1 binding sites. Together, our study introduces a novel transcriptional regulator and its function in cooperation with chromatin associated factors and the basal transcription machinery.


Associations of serum sclerostin and polymorphisms in the SOST gene with bone mineral density and markers of bone metabolism in postmenopausal Chinese women.
The aims of this study were as follows: 1) to evaluate the association of serum sclerostin with bone mineral density (BMD) and markers of bone metabolism in postmenopausal Chinese women and 2) to observe the relationships of single-nucleotide polymorphisms (SNPs) within the sclerostin (SOST) gene with serum sclerostin, BMD, and markers of bone metabolism. A cross-sectional study was conducted with 703 postmenopausal Chinese women. Ten tagging SNPs (rs1234612, rs1513670, rs1634330, rs1708635, rs2023794, rs7220711, rs74252774, rs851057, rs851058, and rs865429) of the SOST gene were genotyped. Serum sclerostin and markers of bone metabolism were measured, including serum intact PTH, 25-hydroxyvitamin D [25(OH)D], procollagen type 1 N-terminal propeptide, and β-CrossLaps of type I collagen containing cross-linked C-telopeptide (β-CTX). The BMD of the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry. Serum sclerostin was positively correlated with BMD at the lumbar spine, femoral neck, and total hip and with serum 25(OH)D (all P < .01) but negatively correlated with β-CTX (P < .01). The significant relationships between serum sclerostin and BMD and with serum β-CTX persisted, even after adjustments for age, body mass index, and serum 25(OH)D (all P < .01). However, there was no correlation between serum sclerostin and age or serum procollagen type 1 N-terminal propeptide. We failed to identify a significant association between the SNP, haplotypes of SOST and BMD, or serum sclerostin. Our results suggested that serum sclerostin was positively correlated with the BMD at the lumbar spine, femoral neck, and total hip and with serum 25(OH)D but was negatively correlated with serum β-CTX. Genetic polymorphisms of SOST may not be a major contributor to variations in the serum sclerostin or BMD in postmenopausal Chinese women.


[Polio and post-polio syndrome, viewed by patients and health professionals in primary care].
Polio affects the quality of life of those who have suffered from it and causes health problems including the post-polio syndrome. The main goals of this work were to know the patients perspective of how they have been affected by the disease and establish the knowledge of post-polio syndrome among patients and primary health care professionals. Interpretive qualitative research based on the Grounded Theory carried out in two health-care centers in the city of Malaga, one of them with care-rural clinics. Four focal groups were established with the participation of thirteen patients and two focus groups with twenty-six professional participants. Intentional sampling is performed until saturation. The analysis follows an inductive strategy using the Atlas Ti5.2 software. The people affected by polio reports their personal histories of suffering counteracted by strong family support and an active coping attitude, marked by great effort exertion, willpower and endurance. These people made a positive assessment of their lives minimising the limitations. They presented compatible symptoms with post-polio syndrome, which remain unidentified due to the lack of knowledge of it among patients and health-care professionals. The health care provided was considered deficient due to several causes as for instance lack of involvement, communication problems. The day-to-day polio experience is focused on personal overcoming with major roles played by family support, difficult relationships with the healthcare system and lack of knowledge of the post-polio syndrome.


Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression.
Curcumin is a polyphenol and the one of the principle curcuminoids of the spice turmeric. Its antioxidant, anti-cancer and anti-inflammatory effects have been intensively studied. Previous in vivo studies showed that administration of curcumin also decreased cholesterol levels in the blood, and the effects were considered to be related to upregulation of LDL receptor. However, since plasma cholesterol levels are also influenced by the uptake of cholesterol in the gut, which is mediated by a specific transporter Niemann-Pick Cl-like 1 (NPC1L1) protein, the present study is to investigate whether curcumin affects cholesterol uptake in the intestinal Caco-2 cells. Caco-2 cells were cultured to confluence. The micelles composed of bile salt, monoolein, and 14C-cholesterol were prepared. We first incubated the cells with the micelles in the presence and absence of ezetimibe, the specific inhibitor of NPC1L1, to see whether the uptake of the cholesterol in the cells was mediated by NPC1L1. We then pretreated the cells with curcumin at different concentrations for 24 h followed by examination of the changes of cholesterol uptake in these curcumin-treated cells. Finally we determined whether curcumin affects the expression of NPC1L1 by both Western blot analysis and qPCR quantification. We found that the uptake of radioactive cholesterol in Caco-2 cells was inhibited by ezetimibe in a dose-dependent manner. The results indicate that the uptake of cholesterol in this study was mediated by NPC1L1. We then pretreated the cells with 25-100 muM curcumin for 24 h and found that such a treatment dose-dependently inhibited cholesterol uptake with 40% inhibition obtained by 100 muM curcumin. In addition, we found that the curcumin-induced inhibition of cholesterol uptake was associated with significant decrease in the levels of NPC1L1 protein and NPC1L1 mRNA, as analyzed by Western blot and qPCR, respectively. Curcumin inhibits cholesterol uptake through suppression of NPC1L1 expression in the intestinal cells.


Observation of directly interacting coherent two-level systems in an amorphous material.
Parasitic two-level tunnelling systems originating from structural material defects affect the functionality of various microfabricated devices by acting as a source of noise. In particular, superconducting quantum bits may be sensitive to even single defects when these reside in the tunnel barrier of the qubit's Josephson junctions, and this can be exploited to observe and manipulate the quantum states of individual tunnelling systems. Here, we detect and fully characterize a system of two strongly interacting defects using a novel technique for high-resolution spectroscopy. Mutual defect coupling has been conjectured to explain various anomalies of glasses, and was recently suggested as the origin of low-frequency noise in superconducting devices. Our study provides conclusive evidence of defect interactions with full access to the individual constituents, demonstrating the potential of superconducting qubits for studying material defects. All our observations are consistent with the assumption that defects are generated by atomic tunnelling.


A Compact Review of IPMC as Soft Actuator and Sensor: Current Trends, Challenges, and Potential Solutions From Our Recent Work.
Recently, attempts have been made to develop ionic polymer-metal composite (IPMC), which is garnering growing interest for ionic artificial muscle, as a soft actuator and sensor due to its inherent properties of low weight, flexibility, softness, and particularly, its efficient transformation of electrical energy into mechanical energy, with large bending strain response under a low activation voltage. In this paper, we focused on several current deficiencies of IPMC that restrict its application, such as non-standardized preparation steps, relaxation under DC voltage, solvent evaporation, and poor output force. Corresponding solutions to overcome the abovementioned problems have recently been proposed from our point of view and developed through our research. After a brief introduction to the working mechanism of IPMC, we here investigate the key factors that influence the actuating performance of IPMC. We also review the optimization strategies in IPMC actuation, including those for preparation steps, additive selection for a thick casting membrane, solvent substitutes, water content, encapsulation, etc. With consideration of the role of the interface electrode, its effects on the performance of IPMC are revealed based on our previous work. Finally, we also discuss IPMCs as potential sensors theoretically and experimentally. The elimination of the deficiencies of IPMC will promote its applications in soft robotics.


Differential NDR/LATS interactions with the human MOB family reveal a negative role for human MOB2 in the regulation of human NDR kinases.
MOB proteins are integral components of signaling pathways controlling important cellular processes, such as mitotic exit, centrosome duplication, apoptosis, and cell proliferation in eukaryotes. The human MOB protein family consists of six distinct members (human MOB1A [hMOB1A], -1B, -2, -3A, -3B, and -3C), with hMOB1A/B the best studied due to their putative tumor-suppressive functions through the regulation of NDR/LATS kinases. The roles of the other MOB proteins are less well defined. Accordingly, we characterized all six human MOB proteins in the context of NDR/LATS binding and their abilities to activate NDR/LATS kinases. hMOB3A/B/C proteins neither bind nor activate any of the four human NDR/LATS kinases. We found that both hMOB2 and hMOB1A bound to the N-terminal region of NDR1. However, our data suggest that the binding modes differ significantly. Our work revealed that hMOB2 competes with hMOB1A for NDR binding. hMOB2, in contrast to hMOB1A/B, is bound to unphosphorylated NDR. Moreover, RNA interference (RNAi) depletion of hMOB2 resulted in increased NDR kinase activity. Consistent with these findings, hMOB2 overexpression interfered with the functional roles of NDR in death receptor signaling and centrosome overduplication. In summary, our data indicate that hMOB2 is a negative regulator of human NDR kinases in biochemical and biological settings.


Conditioned place preference associates with the mRNA expression of diazepam binding inhibitor in brain regions of the addicted rat during withdrawal.
The diazepam binding inhibitor (DBI) modulating the functions of the GABAA receptors is involved in the maladaptation of neural system during using opiate, but its role in opiate dependence is not fully understood. Using conditioned place preference (CPP) rat model and in situ hybridization technique, we examined the correlation between opiate dependence and the mRNA expression of DBI. We found that chronic morphine treatment enabled CPP and increased the DBI mRNA expression in crucial brain regions of addiction. Withdrawal for 3 days caused significant physical signs and further increased the DBI mRNA expression. Both the DBI mRNA and CPP expression remained significantly high but physical signs were at control level in the animals withdrawal for 6 days. Remarkably, the DBI mRNA expressions in the CA1 region of the hippocampus (CA1), ventral tagmental area (VTA), nucleus accumbens (NAc) and amygdala (AMG) were positively correlated to CPP during the periods from withdrawal for 3 days to withdrawal for 6 days. These findings suggest that DBI may play a role in both physical and psychological dependence of opiates.


Maternal Vitamin D Levels during Late Pregnancy and Risk of Allergic Diseases and Sensitization during the First Year of Life-A Birth Cohort Study.
Allergic diseases are the most common chronic illness in childhood. Findings from developed countries have reported associations between Vitamin D levels during pregnancy and offspring allergy risk. This prospective cohort study aimed to determine the associations between maternal Vitamin D levels during late pregnancy and allergic diseases in Malaysian infants during the first year of life. Serum 25(OH)D concentrations of 380 pregnant women in the third trimester were measured using a chemiluminescent immunoassay. Children's allergic outcomes were assessed at 3, 6, and 12 months based on parental reports. Specific IgE antibodies against food and inhalant allergens were measured in infants at 12 months of age. A total of 43.2% pregnant women were Vitamin D deficient (<30 nmol/L) and 56.8% were nondeficient (≥30 nmol/L). A total of 27.6% of the infants had eczema, 6.1% had wheeze, 27.4% had food sensitization, 10.8% had inhalant allergen sensitization, and 3.8% had IgE-mediated food allergy during the first year of life. Compared with the nondeficient group, maternal Vitamin D deficiency in late pregnancy was not associated with any allergic outcomes after adjustment for potential confounding factors. In conclusion, the present study does not support an association between maternal Vitamin D levels in late pregnancy and allergic outcomes during the first year of life.


Structural and thermodynamic characterization of the TYK2 and JAK3 kinase domains in complex with CP-690550 and CMP-6.
Janus kinases (JAKs) are critical regulators of cytokine pathways and attractive targets of therapeutic value in both inflammatory and myeloproliferative diseases. Although the crystal structures of active JAK1 and JAK2 kinase domains have been reported recently with the clinical compound CP-690550, the structures of both TYK2 and JAK3 with CP-690550 have remained outstanding. Here, we report the crystal structures of TYK2, a first in class structure, and JAK3 in complex with PAN-JAK inhibitors CP-690550 ((3R,4R)-3-[4-methyl-3-[N-methyl-N-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropionitrile) and CMP-6 (tetracyclic pyridone 2-t-butyl-9-fluoro-3,6-dihydro-7H-benz[h]-imidaz[4,5-f]isoquinoline-7-one), both of which bind in the ATP-binding cavities of both JAK isozymes in orientations similar to that observed in crystal structures of JAK1 and JAK2. Additionally, a complete thermodynamic characterization of JAK/CP-690550 complex formation was completed by isothermal titration calorimetry, indicating the critical role of the nitrile group from the CP-690550 compound. Finally, computational analysis using WaterMap further highlights the critical positioning of the CP-690550 nitrile group in the displacement of an unfavorable water molecule beneath the glycine-rich loop. Taken together, the data emphasize the outstanding properties of the kinome-selective JAK inhibitor CP-690550, as well as the challenges in obtaining JAK isozyme-selective inhibitors due to the overall structural and sequence similarities between the TYK2, JAK1, JAK2 and JAK3 isozymes. Nevertheless, subtle amino acid variations of residues lining the ligand-binding cavity of the JAK enzymes, as well as the global positioning of the glycine-rich loop, might provide the initial clues to obtaining JAK-isozyme selective inhibitors.


Implementing peer-assisted case management to help homeless veterans with mental illness transition to independent housing.
Formerly homeless mentally ill veterans are at an important crossroads when they move from living in an institutional setting such as a shelter or supportive residential facility to independent living. We hypothesized that peer advisors, veterans with severe mental illness who had been homeless previously, graduated from a Healthcare for Homeless Veterans program, and subsequently maintained independent, stable housing could assist other veterans make a successful transition to independent living. Pilot data suggests that participants who received peer advisors were more likely to follow up with assessments than were controls. In this report, we describe a pilot peer advisor program, its implementation, and pilot data on program administration.


Efficacy of photodynamic therapy vs other interventions in randomized clinical trials for the treatment of actinic keratoses: a systematic review and meta-analysis.
IMPORTANCE Photodynamic therapy (PDT) is used extensively to treat actinic keratoses(AKs). An analysis of the effectiveness of PDT compared with other treatments may help physicians decide what role it should play in their own clinical practices.OBJECTIVE To determine the effectiveness of PDT for the treatment of AKs relative to other methods.DATA SOURCES MEDLINE, EMBASE,Web of Knowledge, and Cochrane Central Register. No restrictions on years were placed, and all searches extended to the year of each data base inception. Our search was conducted on March 20, 2013, and included the search terms solar keratosis, actinic keratosis, photodynamic therapy, and photochemotherapy. No restrictions were used for the search string.STUDY SELECTION Only randomized PDT trials that used aminolevulinic acid hydrochloride ormethyl aminolevulinate hydrochloride as stabilizers with 10 or more participants were considered. Two of the authors undertook the search independently.DATA EXTRACTION AND SYNTHESIS Data were extracted independently by the 2 authors.We assessed data quality using the Jadad scoring system and used a random-effects model for pooled data analysis.MAIN OUTCOMES AND MEASURES Primary outcome measures specified a priori were lesion response, cosmetic results, and patient satisfaction after the intervention.RESULTS Our search identified 875 journal articles and meeting abstracts.We excluded 862 owing to lack of adherence to our inclusion criteria or lack of author response to our queries for further information.We assessed 13 studies for inclusion in our final synthesis, of which 4 were eligible for final meta-analysis. The only comparator for which meta-analysis was performed was cryotherapy. The meta-analysis consisted of 641 participants, with a total of 2174 AKs treated with cryotherapy and 2170 AKs treated with PDT. Compared with cryotherapy, the pooled relative risk for the meta-analysis for complete response (lesion clearance) was 1.14 (95%CI, 1.11-1.18) at 3 months after treatment. Visual inspection of a funnel plot revealed no publication bias, which was confirmed by the Begg test (P = .80).CONCLUSIONS AND RELEVANCE Photodynamic therapy has a 14%better chance of complete lesion clearance at 3 months after treatment than cryotherapy for thin AKs on the face and scalp.


Obsessive compulsive disorder in a fishermen community.
To find the prevalence of obsessive compulsive disorder(OCD). Cross-sectional study. Two years at the local community of Manora, Karachi. An initial survey was conducted in a fishermen community at Salehabad which is located in Manora. A questionnaire inquiring about the demographic details of the patients and using the ICD-10 diagnostic research criteria along with Yale-Brown OC scale on a population of 5,000 for a period of 2 years was applied. About 150 positive cases were identified whose details were subjected to analysis. Out of a total population of 5,000, 3% were found to be suffering from OCD. Among these 56% (n=150) were females, 60% were married and 50% of the cases were under the age of 25. Among the obsessions contamination, pathological doubt and need for symmetry were the most common. Regarding the compulsions, checking, washing and counting were the most common. It was concluded that 3% of the population of given community was suffering from OCD, which is a significant finding. More community based studies are needed to assess the real magnitude of this illness.


Controlling Supramolecular Fiber Formation of Nucleopeptide by Guanosine Triphosphate.
Cells use dynamic self-assembly to construct functional structures for maintaining cellular homeostasis. However, using a natural biological small molecule to mimic this phenomenon remains challenging. This work reports the dynamic microfiber formation of nucleopeptide driven by guanosine triphosphate, the small molecule that controls microtubule polymerization in living cells. Deactivation of GTP by enzyme dissociates the fibers, which could be reactivated by adding GTP. Molecular dynamic simulation unveils the mystery of microfiber formation of GBM-1 and GTP. Moreover, the microfiber formation can also be controlled by diffusion-driven GTP gradients across a semipermeable membrane in bulk conditions and the microfluidic method in the defined droplets. This study provides a new platform to construct dynamic self-assembly materials of molecular building blocks driven by GTP.


Shape-Tunable Charge Carrier Dynamics at the Interfaces between Perovskite Nanocrystals and Molecular Acceptors.
Hybrid organic/inorganic perovskites have recently emerged as an important class of materials and have exhibited remarkable performance in photovoltaics. To further improve their device efficiency, an insightful understanding of the interfacial charge transfer (CT) process is required. Here, we report the first direct experimental observation of the tremendous effect that the shape of perovskite nanocrystals (NCs) has on interfacial CT in the presence of a molecular acceptor. A dramatic change in CT dynamics at the interfaces of three different NC shapes, spheres, platelets, and cubes, is recorded. Our results clearly demonstrate that the mechanism of CT is significantly affected by the NC shape. More importantly, the results demonstrate that complexation on the NC surface acts as an additional driving force not only to tune the CT dynamics but also to control the reaction mechanism at the interface. This observation opens a new venue for further developing perovskite NCs-based applications.


Seven years of zero central-line-associated bloodstream infections.
Many hospitals feel they have adequately addressed the issue of bloodstream infection prevention if they mandate a conventional central-line bundle. Yet central-line-associated bloodstream infections (CLABSIs) persist as a major problem in health care today. Sutter Roseville Medical Center (SRMC) in Roseville, California has achieved unprecedented success in eliminating CLABSIs by approaching the issue more broadly than most institutions. The SRMC bundle is more comprehensive and innovative than conventional bundles. It is applied by a dedicated vascular access team, and the team's efforts are supported by a safety-first culture enforced by senior leadership. All of this is accomplished without losing sight of the financial implications of infection prevention. SRMC is committed to substantial up-front investments in patient safety to realise long-term cost-effectiveness.


BCI-Based Rehabilitation on the Stroke in Sequela Stage.
Stroke is the leading cause of serious and long-term disability worldwide. Survivors may recover some motor functions after rehabilitation therapy. However, many stroke patients missed the best time period for recovery and entered into the sequela stage of chronic stroke. Studies have shown that motor imagery- (MI-) based brain-computer interface (BCI) has a positive effect on poststroke rehabilitation. This study used both virtual limbs and functional electrical stimulation (FES) as feedback to provide patients with a closed-loop sensorimotor integration for motor rehabilitation. An MI-based BCI system acquired, analyzed, and classified motor attempts from electroencephalogram (EEG) signals. The FES system would be activated if the BCI detected that the user was imagining wrist dorsiflexion on the instructed side of the body. Sixteen stroke patients in the sequela stage were randomly assigned to a BCI group and a control group. All of them participated in rehabilitation training for four weeks and were assessed by the Fugl-Meyer Assessment (FMA) of motor function. The average improvement score of the BCI group was 3.5, which was higher than that of the control group (0.9). The active EEG patterns of the four patients in the BCI group whose FMA scores increased gradually became centralized and shifted to sensorimotor areas and premotor areas throughout the study. Study results showed evidence that patients in the BCI group achieved larger functional improvements than those in the control group and that the BCI-FES system is effective in restoring motor function to upper extremities in stroke patients. This study provides a more autonomous approach than traditional treatments used in stroke rehabilitation.


Osteochondral tissue engineering: scaffolds, stem cells and applications.
Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral tissue engineering, which are focused on the application of various materials forming bilayered composite scaffolds, including polymers and ceramics, discussing the variety of scaffold designs and fabrication methods being developed. Additionally, cell sources and biological protein incorporation methods are discussed, addressing their interaction with scaffolds and highlighting the potential for creating a new generation of bilayered composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment.


Practical usefulness of IgA-containing immune complex determination in the serum of patients with primary Sjögren's syndrome.
To evaluate the relevance of IgA-containing immune complexes (IC) as a predictor of lymphocytic infiltration of the minor salivary glands, and thus to determine the necessity of the minor salivary gland biopsy as a diagnostic test for primary Sjögren's syndrome (SS) in patients complaining of dryness of the mouth. IgA-containing IC, as well as anti-SSA and anti-SSB antibodies, were measured using enzyme-linked immunosorbent assays in 116 consecutive patients presenting with dry mouth but no connective tissue disease. The specificity, sensitivity, and positive (PPV) and negative predictive values (NPV) of these tests were calculated in relation to the results of the minor salivary gland biopsy and to the criteria for primary SS. Sixty-five patients had a focus score > or = 1.IgA-containing IC were detected in 45 of them, compared with five of the remainder (specificity 89%, sensitivity 69%, PPV = 88% and NPV = 69%). When the IgA-containing IC, and the anti-SSA and anti-SSB tests were associated, the sensitivity and NPV were improved (81 and 79%, respectively), while specificity and PPV were maintained (88 and 90%, respectively). Given the reliability of this combination of tests for the diagnosis of primary SS, the minor salivary gland biopsy might be indicated only in those patients without any serological abnormality.


A cochrane systematic review of transcutaneous electrical nerve stimulation for cancer pain.
Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management has been the biomedical approach. There is a need for nonpharmacological and innovative pain management strategies. Transcutaneous electrical nerve stimulation (TENS) may have a role. The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, and PEDro databases were searched for randomized controlled trials (RCTs) investigating the use of TENS for the management of cancer-related pain in adults. Once relevant studies were identified, two pairs of reviewers assessed eligibility for inclusion in the review based on a study eligibility form and using the 5-point Oxford Quality Scale. Two RCTs met the study eligibility criteria (these involved 64 patients). These studies were heterogeneous with respect to study population, methodology, and outcome measures. This prevented meta-analysis. In one RCT, there were no significant differences between TENS and placebo in women with chronic pain secondary to breast cancer treatment. In the other RCT, there were no significant differences between acupuncture-like TENS (AL-TENS) and sham in palliative care patients; this study was significantly underpowered. There is insufficient available evidence to determine the effectiveness of TENS in treating cancer-related pain. Further research is needed to help guide clinical practice, and large multi-center RCTs are required to assess the value of TENS in the management of cancer-related pain in adults.


Resting global myocardial work can improve interpretation of exercise stress echocardiography.
Sensitivity and specificity of ESE to determine hemodynamically significant coronary artery disease (CAD) is limited by subjective qualitative interpretation resulting in false-positive results. The objective of this study was to determine whether resting myocardial work estimated from non-invasive left ventricular pressure-strain loops can help improve the interpretation of exercise stress echocardiography (ESE). Resting global myocardial work was performed on 288 patients referred for clinically indicated ESE with no resting regional wall motion abnormalities and normal ejection fraction (≥ 55%). Coronary angiography was used to validate the presence of significant CAD in those with a positive ESE. Resting global myocardial work index (GWI) was significantly reduced (p < 0.001) in patients with true-positive (1544 ± 354 mmHg%) compared to negative (1819 ± 317 mmHg%) and false-positive (1857 ± 344 mmHg%) ESE. A GWI of ≤ 1391 mmHg (AUC 0.73; sensitivity 94%; specificity 73%) predicted true-positive ESE. Predictors of a true-positive ESE were (1) lower myocardial work efficiency (odds ratio 0.731, 95% CI 0.58-0.92, p = 0.007), (2) lower GWI (odds ratio 0.997, 95% CI 0.996-0.999, p = 0.006) (3) male gender (odds ratio 5.47, 95% CI 1.84-16.31, p = 0.002) and (4) E/e' ratio (odds ratio 1.15, CI 1.01-1.31, p = 0.032). Myocardial work is a potentially valuable quantitative parameter that provides incremental value over qualitative ESE interpretation and improves appropriate patient selection for coronary angiography.


[Psychogenic death and suicide (author's transl)].
In psychogenic death, the persons finds himself in a seriously distressing situation of which he believes that he has been thrown into this helpless position and that there is no way out. Humans behave passively and die quietly. In suicide, on the other hand, a person ends his life actively. The problem of why, on the one hand, people bring about death actively while in psychogenic death they "let themselves die" is enquired into. In psychogenic death, the difficulties of the emergencies produced by external factors can no longer be coped with mentally: the person wants to live but he cannot go on. In suicide, it seems to the person that the projection of the future, produced by inner factors, is no longer worth living: the person does not want to live, although he could.


Opportunities and Challenges Arising from Holiday Clubs Tackling Children's Hunger in the UK: Pilot Club Leader Perspectives.
With the school holidays being recognised as a high-risk time for children to experience food insecurity, there is a growing prevalence of school holiday initiatives that include free food. However, information is lacking into what constitutes effective practice in their delivery, and how this can be evaluated. This paper provides insight from individuals who implemented a pilot of a national project which provided free food for children at UK community summer holiday sports clubs in 2016. Focus groups were conducted with all 15 leaders of the holiday clubs that participated in the pilot to understand: (1) what opportunities are provided by community holiday sports clubs which include free food; (2) what challenges arose as a result of offering free food within a broader community holiday club sports offer. Results indicate that offering free food at such clubs creates multiple opportunities for attending children, including: experiencing social interactions around food; enhancing food experiences and food confidence; and promoting positive behaviour. However, free food provision is associated with challenges including resource constraints and tensions around project aims. Future work should determine whether holiday clubs can positively impact children's wellbeing and healthy eating.


Prediction of aortic annulus diameter by two-dimensional echocardiography. Application in the preoperative selection and preparation of homograft aortic valves.
The preoperative selection and preparation of an appropriately sized homograft aortic valve would allow delay of surgery if a suitable valve were unavailable, thus pre-emptying inventory limitations, and a decrease of ischemic time in cases of isolated aortic valve replacement. An accurate preoperative measurement of the aortic annulus diameter is the prerequisite for such selection. The aortic annulus diameter was measured retrospectively in a blinded fashion from the two-dimensional echocardiograms of 62 patients who underwent aortic valve replacement with mechanical or bioprosthetic valves. Measurements were obtained with electronic calipers by two observers. Confidence in the accuracy of the measurement obtained was ranked on a scale from 1 to 5. The mean difference between echocardiographic measurements and prosthetic valve sizes was 0.39 +/- 0.46 mm (mean +/- 2SD) for observer 1 and -0.26 +/- 1.44 mm for observer 2. Ninety-eight percent of observer 1 measurements and 80% of observer 2 measurements were within 1.5 mm of the prosthetic valve size (p less than 0.01 for differences between observers). Confidence scores were higher for observer 1 and for both observers were related to accuracy. The aortic annulus diameter of eight patients scheduled for homograft aortic valve replacement was measured prospectively with the same technique. There was an excellent agreement between the two-dimensional echocardiographic measurements and the surgical measurements. In the last 5 consecutive patients, the echocardiographic measurement was used for the preoperative selection and preparation of the appropriate valve. In conclusion, measurement of the aortic annulus diameter by two-dimensional echocardiography is feasible and clinically useful for the preoperative selection and preparation of homograft aortic valves.(ABSTRACT TRUNCATED AT 250 WORDS)


Brain Disorders and Chemical Pollutants: A Gap Junction Link?
The incidence of brain pathologies has increased during last decades. Better diagnosis (autism spectrum disorders) and longer life expectancy (Parkinson's disease, Alzheimer's disease) partly explain this increase, while emerging data suggest pollutant exposures as a possible but still underestimated cause of major brain disorders. Taking into account that the brain parenchyma is rich in gap junctions and that most pollutants inhibit their function; brain disorders might be the consequence of gap-junctional alterations due to long-term exposures to pollutants. In this article, this hypothesis is addressed through three complementary aspects: (1) the gap-junctional organization and connexin expression in brain parenchyma and their function; (2) the effect of major pollutants (pesticides, bisphenol A, phthalates, heavy metals, airborne particles, etc.) on gap-junctional and connexin functions; (3) a description of the major brain disorders categorized as neurodevelopmental (autism spectrum disorders, attention deficit hyperactivity disorders, epilepsy), neurobehavioral (migraines, major depressive disorders), neurodegenerative (Parkinson's and Alzheimer's diseases) and cancers (glioma), in which both connexin dysfunction and pollutant involvement have been described. Based on these different aspects, the possible involvement of pollutant-inhibited gap junctions in brain disorders is discussed for prenatal and postnatal exposures.


Leishmania (infantum) chagasi in canine urinary sediment.
Canine visceral leishmaniasis (CVL) is difficult to diagnosis, mainly due to the presence of asymptomatic animals, the diversity of clinical symptoms and the difficulty in obtaining diagnostic evidence of high sensitivity and specificity. The purpose of this study was to diagnose CVL in urinary sediment of 70 dogs of different breeds, sexes and ages from the veterinary hospital of the Federal University of Piauí and Zoonosis Control Center of Teresina, Brazil. The serological tests were TR DPP® for CVL and enzyme-linked immunosorbent assay (ELISA) for CVL, parasitological exams of bone marrow and lymph nodes and urine sediment cultures. Leishmania was detected in the bone marrow and/or lymph node of 61.0% of the animals (43/70), and urine sediment culture was positive in 9.30% (4/43) of these animals. In the serological exams, 70.0% (49/70) were reactive using the DPP and 78.2% (55/70) were reactive using ELISA. The goal of this study was to diagnose the presence of L. (infantum) chagasi in a culture of urinary sediment.


Coexistent lepromatous leprosy and reactive perforating collagenosis.
The cases of two young men with coexistent lepromatous leprosy and reactive perforating collagenosis are reported. Although both patients' parents were consanguineous, experimental induction of Koebner's phenomenon by superficial scratching failed to produce the lesions of reactive perforating collagenosis. The lesions of reactive perforating collagenosis showed a satisfactory response to treatment with topical retinoic acid.


Glucose-induced Release of Amino Acids from Saccharomyces carlsbergensis by Action on the Cytoplasmic Membrane.
When washed yeast cells grown under appropriate conditions were suspended in glucose solution there was a sudden release of alpha-amino nitrogen into the medium. This released material was of low molecular weight, and its composition was closely similar to that of the intracellular free amino acid pool. During the leakage of amino acids, the yeast did not efficiently absorb labeled amino acids added to the test medium, despite the rapid uptake and metabolism of glucose. Uptake of a labeled amino acid and reabsorption of the released alpha-amino nitrogen occurred almost simultaneously. When these yeast cells were exposed to glucose in the presence of calcium ions, leakage was strongly inhibited. Butanol under the same conditions increased glucose-induced leakage of cell contents. The adenosine triphosphatase activity of intact yeast cells exposed to glucose was greater than that of cells exposed to water. Yeast cells treated with glucose prior to equilibration with sorbose exhibited less ability to retain the sorbose when washed at 0 C than did cells pretreated with water. It was concluded that glucose-induced leakage of amino acids was the result of two factors acting together. These were (i) a change in membrane permeability associated with glucose uptake, and (ii) a temporary shortage of energy for amino acid uptake or retention.


Microfluidic co-culture of epithelial cells and bacteria for investigating soluble signal-mediated interactions.
The human gastrointestinal (GI) tract is a unique environment in which intestinal epithelial cells and non-pathogenic (commensal) bacteria coexist. It has been proposed that the microenvironment that the pathogen encounters in the commensal layer is important in determining the extent of colonization. Current culture methods for investigating pathogen colonization are not well suited for investigating this hypothesis as they do not enable co-culture of bacteria and epithelial cells in a manner that mimics the GI tract microenvironment. Here we describe a microfluidic co-culture model that enables independent culture of eukaryotic cells and bacteria, and testing the effect of the commensal microenvironment on pathogen colonization. The co-culture model is demonstrated by developing a commensal Escherichia coli biofilm among HeLa cells, followed by introduction of enterohemorrhagic E. coli (EHEC) into the commensal island, in a sequence that mimics the sequence of events in GI tract infection.


The role and pathophysiological relevance of membrane transporter PepT1 in intestinal inflammation and inflammatory bowel disease.
Intestinal inflammation is characterized by epithelial disruption, leading to loss of barrier function and the recruitment of immune cells, including neutrophils. Although the mechanisms are not yet completely understood, interactions between environmental and immunological factors are thought to be critical in the initiation and progression of intestinal inflammation. In recent years, it has become apparent that the di/tripeptide transporter PepT1 may play an important role in the pathogenesis of such inflammation. In healthy individuals, PepT1 is primarily expressed in the small intestine and transports di/tripeptides for metabolic purposes. However, during chronic inflammation such as that associated with inflammatory bowel disease, PepT1 expression is upregulated in the colon, wherein the protein is normally expressed either minimally or not at all. Several recent studies have shown that PepT1 binds to and transports various bacterial di/tripeptides into colon cells, leading to activation of downstream proinflammatory responses via peptide interactions with innate immune receptors. In the present review, we examine the relationship between colonic PepT1-mediated peptide transport in the colon and activation of innate immune responses during disease. It is important to understand the mechanisms of PepT1 action during chronic intestinal inflammation to develop future therapies addressing inappropriate immune activation in the colon.


Assessing the efficacy and mechanisms of glycol-contaminated water treatment through floating treatment wetlands.
The growing concerns surrounding water pollution and the degradation of ecosystems worldwide have led to an increased use of nature-based solutions (NbSs). This study assessed the feasibility of using floating treatment wetlands (FTWs) as an NbS to treat propylene glycol-contaminated water and quantitatively investigated different removal pathways. With an environmentally relevant concentration of propylene glycol (1,250 mg/L), FTWs containing Acorus calamus and mixed species demonstrated the highest average glycol mass removal efficacy (99%), followed by Carex acutiformis (98%), Juncus effusus (93%), and the control group without plants (10%) after 1 week. Additional mesocosm-scale experiments with varying FTW configurations, including surface coverage to reduce evaporation and photodegradation processes, and the addition of antibiotics to inhibit microbial activity, were conducted to quantify glycol removal pathways. Mass balance analysis results revealed that microbial biodegradation (33.3-39.7%) and plant uptake (37.9-45.2%) were the primary pathways for glycol removal. Only 15.5-19.5% of the glycol removal via evaporation and photodegradation was accounted in this study, which may be attributed to the mesocosm experimental setup (static water and no wind). Aligned with the broader discussion regarding biodiversity improvements and carbon storage capacity, this study demonstrated that FTWs are an environmentally friendly and effective NbS for addressing glycol-contaminated water.


The patterns of glomerulonephritis in "Tjikini" Hospital Jakarta.
A pattern of primary glomerulonephritis (GN), derived from 94 patients admitted to Tjikini Hospital Jakarta, between 1976-1980 is presented. The ratio of male to female patients was 1:1.2 with mean age of 25.9 and 27.1 years respectively. The morphologic types of glomerulonephritis were analysed. This paper presents data on sex distribution, mean age, onset before hospitalisation, serum immunoglobulin, C3 complement, immunohistological deposits and clinical features. Serum Ig G levels were increased in all types of nephritis except Focal and Segmental GN. Diffuse Mesangial Proliferative (DMesP) GN was associated with a high frequency of Ig M deposits. Distribution of the different types of GN and clinical presentation were compared with other series. DMesP GN and MCGN accounted for 77% of Acute Nephritic Syndrome. It seems to be universal that the most common clinical presentation of GN patients is Nephrotic Syndrome.


Restriction fragment primed phi X174 single-stranded DNA as template for DNA polymerase alpha and beta. Detection and partial purification of a polymerase alpha stimulating factor.
Template-primers constructed of phiX174 single-stranded viral DNA hybridized to a restriction fragment of phiX174 RF DNA can be used for extensive polymerization by DNA polymerase alpha. Polymerization is dependent upon a restriction fragment containing a 3'OH. The products of the reaction have been identified by agarose gel electrophoresis. Polymerization of 150--400 nucleotides can be obtained in 1h depending upon the restriction fragment used as primer. Synthesis may be limited by barriers in the primary or secondary structure of the template. A factor which stimulates the rate of alpha polymerase activity on these templates was partially purified. This factor does not stimulate alpha polymerase on activated DNA. The stimulating factor sediments at 5.5 S in glycerol gradients containing 0.4M potassium phosphate and has an apparent molecular weight of 70 000 on Sephadex G-100.


A review of the genetic epidemiology of resistance to parasitic disease and atopic asthma: common variants for common phenotypes?
An inverse relationship between resistance to certain parasitic diseases and measures of atopy and asthma has long been observed. A possible explanation is that genetic determinants which confer protection against detrimental worm burdens are the same determinants involved in atopic asthma. The focus of this review is to consider the potential candidate genes that have been elucidated as part of molecular, genomic and genetic studies of parasite biology, host-parasite interactions and classic genetic epidemiology studies on parasitic disease and allergic asthma. Comparative studies of the Plasmodium and Schistosoma spp. genomes have revealed a number of proteins that are homologous to humans. A number of linkage and association studies on susceptibility/resistance to parasitic diseases, including malaria and schistosomiasis, overlap with associations that have been identified for susceptibility to atopy and asthma. In response to parasitic approaches in maintaining survival, the human host has evolved genetic adaptations that minimize severe manifestations of disease, which conversely appear to contribute to allergic disease. A clearer understanding of this process will elucidate the complex pathways and mechanisms involved in these traits.


Possible genotoxic activity of extracts of Bryonia alba roots on human lymphocytes and transformed cells.
Bryonia alba roots (BAR) are widely used as an adaptogenic and restorative drug with immunomodulatory and stress-protective properties that increase the non-specific resistance of an organism toward harmful stimuli. Potential genotoxic activity of aqueous and methanol extracts of BAR was studied on human normal (lymphocytes) and transformed (HeLa and Caco-2) cells using single cell gel electrophoresis (the comet assay). The results obtained did not show any evidence of genotoxic effects of BAR.


Robust numerical evaluation of circular dichroism from chiral medium/nanostructure coupled systems using the finite-element method.
It has been demonstrated that circular dichroism (CD) signals from chiral molecules can be boosted by plasmonic nanostructures inducing strong local electromagnetic fields. To optimize nanostructures to improve CD enhancement, numerical simulations such as the finite element method (FEM) have been widely adopted. However, FEM calculations for CD have been frequently hampered by unwanted numerical artifacts due to improperly discretizing problem spaces. Here, we introduce a new meshing rule for FEM that provides CD simulations with superior numerical accuracy. We show that unwanted numerical artifacts can be suppressed by implementing the mirror-symmetric mesh configuration that generates identical numerical artifacts in the two-opposite circularly polarized waves, which cancel each other out in the final CD result. By applying our meshing scheme, we demonstrate a nanostructure/chiral molecule coupled system from which the CD signal is significantly enhanced. Since our meshing scheme addresses the previously unresolved issue of discriminating between very small CD signals and numerical errors, it can be directly applied to numerical simulations featuring natural chiral molecules which have intrinsically weak chiroptical responses.


Cellular and molecular mechanisms of internalization of mycobacteria by host cells.
Mycobacteria are intracellular pathogens capable of invading mononuclear phagocytes, mucosal epithelial cells (including M cells) and Schwann cells. To enter cells, mycobacteria have been shown to interact with several molecules on macrophage and epithelial cell surfaces. This suggests adaptation to the host environment. In this review we address the strategies used by pathogenic mycobacteria to gain access to the intracellular environment.


Single or bilateral lung transplantation for emphysema?
Most programs favor single lung transplantation for emphysema. However, this is controversial, and we have favored bilateral lung transplantation, confining single lung transplantation mainly to use in older patients and those of small stature. A retrospective analysis was done of 119 consecutive lung transplantation procedures for emphysema at Barnes Hospital between 1989 and 1994 (50 single lung, 69 bilateral lung transplants) to (1) identify outcome differences between the two groups and (2) define the appropriate role of these two procedures. The single lung transplantation group was older and had a higher proportion of female patients. However, baseline pulmonary function (forced expiratory volume in 1 second), arterial oxygen tension, and exercise tolerance (6-minute walk distance) were similar. After transplantation, 90-day mortality (single lung transplantation 10% versus bilateral lung transplantation 7.2%; p = 0.74) and duration of mechanical ventilation, intensive care unit stay, and hospitalization were similar. Both groups achieved a significant and sustained improvement in forced expiratory volume, arterial carbon dioxide tension, arterial oxygen tension, and exercise tolerance within 3 months. However, the improvements in forced expiratory volume, arterial oxygen tension, and exercise tolerance were consistently significantly better in recipients of bilateral transplants at and beyond 6 months. Obliterative bronchiolitis was equally prevalent in both groups. Survival was similar but showed a trend toward better late survival in recipients of bilateral transplants (5-year actuarial survival: bilateral lung transplantation 53% versus single lung transplantation 41%). We conclude that (1) both procedures are satisfactory options in emphysema, producing durable results; (2) bilateral lung transplantation is not associated with increased operative mortality or morbidity and achieves superior improvements in spirometry findings, oxygenation, exercise tolerance, and possibly late survival; and (3) the superior improvements in function (and late survival) after bilateral lung transplantation may be attributed to the presence of more pulmonary reserve after the onset of obliterative bronchiolitis.


Computational aberration correction of VIS-NIR multispectral imaging microscopy based on Fourier ptychography.
Due to the chromatic dispersion properties inherent in all optical materials, even the best-designed multispectral objective will exhibit residual chromatic aberration. Here, we demonstrate a multispectral microscope with a computational scheme based on the Fourier ptychographic microscopy (FPM) to correct these effects in order to render undistorted, in-focus images. The microscope consists of 4 spectral channels ranging from 405 nm to 1552 nm. After the computational aberration correction, it can achieve isotropic resolution enhancement as verified with the Siemens star sample. We image a flip-chip to show the promise of our system to conduct fault detection on silicon chips. This computational approach provides a cost-efficient strategy for high quality multispectral imaging over a broad spectral range.


Intracellular calcium transients and developed tension in rat heart muscle. A mechanism for the negative interval-strength relationship.
The purposes of the present study were to determine (a) whether changes of intracellular [Ca2+] (Cai) can account for the decrease of developed tension observed in rat heart muscle when stimulation rate is increased, and (b) whether the effect of stimulation rate on Cai is altered in conditions in which the rate of repriming of the sarcoplasmic reticulum (SR) is altered, as when perfusate [Ca2+] (Cao) is increased, and in heart muscle from senescent animals. The photoprotein aequorin was used to monitor Cai in rat papillary muscles. In muscles from 6-mo-old rats, increasing the stimulation rate in the range 0.2-0.66 Hz led to parallel decreases of both the aequorin light transient and developed tension when Cao was 2 mM. When Cao was increased to 4 mM, changes in the stimulation rate had less effect on both the light transient and tension. At 8 mM Cao, changing the stimulation rate had no effect on either the light transient or developed tension. Papillary muscles from 24-mo-old rats, in which SR function is likely to be depressed, exhibited a prolonged Ca2+ transient and twitch. At a Cao of 4 or 8 mM, increasing the stimulation rate from 0.33 to 0.66 Hz still led to decreases in the size of the aequorin light transient and developed tension in these muscles. Developed tension and aequorin light responded to increases of Cao in the same way in both groups of muscles. We conclude that under the conditions of our experiments, developed tension is determined by Cai. The negative interval-strength relationship observed when Cao is in the physiological range can be accounted for by a time-dependent recycling of Ca2+ by the SR. The effects of increasing Cao and the age-related differences observed at high Cao can also be accounted for using this model.


Phantom touch: How to unmask sensory unawareness after stroke.
Comprehending the nature of tactile disorders following brain damage is crucial to understand how the brain constructs sensory awareness. Stroke patients may be unaware of being touched on the affected hand if, simultaneously, they are touched on the unaffected hand (i.e., tactile extinction). More rarely, they feel touches on the two hands, when they are solely touched on the unaffected hand (i.e., synchiria). Using a novel assessment tool, we investigated whether in stroke patients with apparent intact tactile awareness on standard evaluation, tactile extinction might be possibly masked by phantom (synchiric) sensations (i.e., elicited by ipsilesional stimulation) arising exclusively during Double Simultaneous Stimulation (DSS). Patients with right (n = 17) and left (n = 8) hemisphere lesions and age-matched healthy controls (n = 13) were tested with the Tactile Quadrant Stimulation test, consisting in delivering unilateral or bilateral touches to one of four quadrants, identified on the participants' hands. In DSS trials, stimuli were applied to asymmetric quadrants. Participants reported the side(s) and then pointed to the site(s) of stimulation. We found that, with the exception of one patient who showed tactile extinction, about 50% of patients with overall intact tactile perception on classical evaluation, although reporting two stimuli in DSS, failed in pointing to the correct contralesional stimulated site. They reported the felt sensation in positions that corresponded to the ipsilesional stimulated sites. Thus apparent detections of contralesional touches in DSS were accounted for by 'phantom' sensations of ipsilesional stimulation that masked unawareness of contralesional touches when classic assessment was applied. Preliminary lesion analyses indicate that the symptom was associated with damage to structures often affected in tactile extinction. These findings, while unveiling important underestimation of the patients' neurological condition, provide a framework for investigating bihemispheric contributions to altered tactile perception following stroke.