Transsexual subtypes: clinical and theoretical significance.
The present study was designed to investigate whether transsexuals can be validly subdivided into subtypes on the basis of sexual orientation, and whether differences between subtypes of transsexuals are similar for male-to-female (MF) and female-to-male transsexuals (FMs). Within a large transsexual sample (n=187), homosexual and nonhomosexual subjects were compared on a number of characteristics before the start of treatment. Differences within MF and FM groups were also investigated. Homosexual transsexuals were found to be younger when applying for sex reassignment, reported a stronger cross-gender identity in childhood, had a more convincing cross-gender appearance, and functioned psychologically better than nonhomosexual transsexuals. Moreover, a lower percentage of the homosexual transsexuals reported being (or having been) married and sexually aroused while cross-dressing. The pattern of findings was different for MFs and FMs. No differences between homosexuals and nonhomosexuals were found in height, weight, or body mass index. A distinction between subtypes of transsexuals on the basis of sexual orientation seems theoretically and clinically meaningful. The results support the notion that in the two groups different factors influence the decision to apply for sex reassignment. The more vulnerable nonhomosexual transsexuals may particularly benefit from additional professional guidance before and/or during treatment.


Predicting RNA secondary structures from sequence and probing data.
RNA secondary structures have proven essential for understanding the regulatory functions performed by RNA such as microRNAs, bacterial small RNAs, or riboswitches. This success is in part due to the availability of efficient computational methods for predicting RNA secondary structures. Recent advances focus on dealing with the inherent uncertainty of prediction by considering the ensemble of possible structures rather than the single most stable one. Moreover, the advent of high-throughput structural probing has spurred the development of computational methods that incorporate such experimental data as auxiliary information.


Effects of solder temperature on pin through-hole during wave soldering: thermal-fluid structure interaction analysis.
An efficient simulation technique was proposed to examine the thermal-fluid structure interaction in the effects of solder temperature on pin through-hole during wave soldering. This study investigated the capillary flow behavior as well as the displacement, temperature distribution, and von Mises stress of a pin passed through a solder material. A single pin through-hole connector mounted on a printed circuit board (PCB) was simulated using a 3D model solved by FLUENT. The ABAQUS solver was employed to analyze the pin structure at solder temperatures of 456.15 K (183(°)C) < T < 643.15 K (370(°)C). Both solvers were coupled by the real time coupling software and mesh-based parallel code coupling interface during analysis. In addition, an experiment was conducted to measure the temperature difference (ΔT) between the top and the bottom of the pin. Analysis results showed that an increase in temperature increased the structural displacement and the von Mises stress. Filling time exhibited a quadratic relationship to the increment of temperature. The deformation of pin showed a linear correlation to the temperature. The ΔT obtained from the simulation and the experimental method were validated. This study elucidates and clearly illustrates wave soldering for engineers in the PCB assembly industry.


Caroli's disease and congenital hepatic fibrosis associated with polycystic kidney disease. A case presenting with acute focal bacterial nephritis.
Congenital cystic dilatation of the intrahepatic biliary ducts (Caroli's disease), until recently, has been infrequently recognized. It is often associated with autosomal recessive polycystic kidney disease (ARPKD) and congenital hepatic fibrosis (CHF). We hereby report a case with Caroli's disease, polycystic kidney disease (PKD), and CHF: This 24-year-old female patient initially presented with acute bacterial nephritis (ABN). Renal ultrasonography revealed bilateral enlarged kidneys with multiple cysts. Because her parents showed no renal cyst on ultrasonographic examination, she received further studies. Abdominal ultrasonography showed cystic dilatation of the biliary tree. Computed tomography (CT) with meglumine lotroxinate (biliscopin) infusion study and hepatobiliary scintigraphy confirmed the diagnosis of Caroli's disease. Liver biopsy revealed CHF: The radiographic and scintigraphic pictures are hereby illustrated and CT with biliscopin infusion study is emphasized. We conclude that if radiologic evidence of renal cystic lesions is absent in the parents of patients with PKD, the coexistence of Caroli's disease and CHF should be considered. The clinical pictures of ABN in this patient are also discussed. As far as we know, this is the first reported case of ABN in a patient with PKD and Caroli's disease, and it showed good response to antibiotic therapy.


Interleukin-13 induces the production of interleukin-1 receptor antagonist (IL-1ra) and the expression of the mRNA for the intracellular (keratinocyte) form of IL-1ra in human myelomonocytic cells.
The aim of this study was to examine the expression of interleukin-1 receptor antagonist (IL-1ra) in human myelomonocytic cells treated with IL-13. IL-13 induced IL-1ra transcripts in human circulating monocytes and polymorphonuclear cells (PMN). Induction by IL-13 was not blocked, but rather superinduced, in the presence of the protein synthesis inhibitor cycloheximide. Actinomycin D blocked induction, suggesting involvement of gene transcription. The half-life of IL-1ra transcripts was prolonged by IL-13 from 1.3 hours to 4.5 hours in monocytes and to 12 hours in PMN. By reverse transcriptase-polymerase chain reaction, IL-13 was found to augment the transcripts coding for the soluble form of IL-1ra, but also to induce the expression of the intracellular (keratinocyte) form of IL-1ra, the latter being extremely low or undetectable in myelomonocytic cells. IL-13 induced production of IL-1ra in myelomonocytic cells, augmenting both cell-associated and released protein. Induction of IL-1ra by IL-13 may represent a further mechanism by which this molecule can counteract the potent proinflammatory properties of IL-1.


Magnetic resonance imaging targeted biopsy in men with previously negative prostate biopsy results.
To evaluate the efficacy of targeted prostate biopsy using magnetic resonance imaging (MRI) and to characterize clinicopathologic features of tumors detected with targeted prostate biopsy in men with previous negative prostate biopsy results. We prospectively studied 87 patients with a persistently increasing level of serum prostate-specific antigen (PSA), at least one previous set of negative 12-core prostate biopsies, and normal digital rectal examination. All patients were examined with combined T2-weighted and diffusion-weighted MRI before undergoing the prostate biopsy. Prostate biopsy was performed using transrectal ultrasonography-guided standard 12 cores plus targeted biopsy to suspicious region(s) as identified on T2 images on their MRI. Of a total of 87 cases, 82 (94.2%) patients had suspicious lesion(s) on their MRI. Of these 82 patients, 46 (56.0%) patients had prostate cancer (PCA) as determined by the biopsy. The patients with PCA showed a significantly higher incidence of having suspicious lesion(s) (the anterior or apex) on MRI than the patients without PCA (P<0.05). On analysis by dividing all biopsy cores into the targeted cores and standard cores, PCA was found in 149/518 (28.8%) MRI-targeted cores and in 32/903 (3.6%) standard cores (P=0.012) Of 43 patients who underwent radical prostatectomy, 37 (86.0%) patients were detected with PCA located at the anterior or apex portion of the prostate. For tumor characteristics according to tumor locations, there was no significant correlation between tumor location and Gleason scores or pathologic stage. Our data suggest that a MRI-targeted prostate biopsy after prostate MRI might be considered for the identification of cancer foci and the detection of PCA, for patients with a previous negative standard prostate biopsy result despite a persistently elevated PSA value.


Patient-derived outcome measures for HIV services in the developed world: a systematic review.
This review sought to establish the themes and approaches used in the measurement of patient satisfaction regarded by HIV service users as crucial to improving service quality. It also investigated how feedback has been measured previously and whether a gold standard instrument exists that is generalizable across HIV inpatient and clinic settings. Twelve databases and other sources yielded 1474 titles. Using a clinically-focused question and pre-defined inclusion and exclusion criteria, 32 articles were retrieved and reviewed for quality using a quality appraisal checklist. Two reviewers used a data extraction form to identify and verify key patient experiences. Thematic analysis revealed that clinic staffs' current knowledge of HIV was an essential factor in positive feedback. Treating patients with dignity and respecting their autonomy and confidentiality were also important. Developments in treatment, extended life expectancy and quality of life have altered patients' experience and level of satisfaction. Three instruments developed to assess patient satisfaction with HIV care were identified but there was no gold standard method of measuring it. There is a need to develop a specific, valid instrument that is easy to complete and analyse, and the data should be used to inform the redesign of services to promote a dynamic model of care.


Sexual and prevention practices in men who have sex with men in the era of combination HIV prevention: results from the Presse Gays et Lesbiennes survey, France, 2011.
To better understand the diversity of practices and behaviours to prevent HIV with casual partners, data from a large convenience sample of men who have sex with men (MSM) in France were categorised into different prevention profiles: no anal intercourse, consistent condom use during anal intercourse, risk-reduction practices (serosorting, seropositioning) and no discernible prevention practice (NDPP). Categories were applied to HIV-positive respondents with controlled (CI; n=672) and uncontrolled infection (UI; n=596), HIV-negative (n=4,734) and untested respondents (n=663). Consistent condom use was reported by 22% (n=148) of HIV-positive-CI respondents, 13% (n=79) of HIV-positives UI, 55% (2,603) of HIV-negatives, and 50% (n=329) of untested (p<0.001). Corresponding figures for NDPP were 45% (n=304), 55% (n=327), 21% (n=984) and 34% (n=227) (p<0.001). Logistic regressions showed that, regardless of respondents' serostatus, NDPP was associated with regularly frequenting dating websites, drug use, exposure to sperm during oral sex, and with HIV diagnosis after 2000 for HIV-positive respondents (CI and UI), with age <30 years for HIV-positive-CI, and with low education for HIV-negatives. Risk-taking remains high, despite implementation of risk-reduction practices. A global health approach should be central to prevention programmes for MSM, to include target behavioural intervention, promotion of condom use, and encouragement of regular HIV testing and early initiation of ART.


Characterization of an intracellular ATP assay for evaluating the viability of live attenuated mycobacterial vaccine preparations.
The viability of BCG vaccine has traditionally been monitored using a colony-forming unit (CFU) assay. Despite its widespread use, results from the CFU assay can be highly variable because of the characteristic clumping of mycobacteria, their requirement for complex growth media, and the three week incubation period needed to cultivate slow-growing mycobacteria. In this study, we evaluated whether an ATP luminescence assay (which measures intracellular ATP content) could be used to rapidly estimate the viability of lyophilized and/or frozen preparations of six different BCG vaccine preparations - Danish, Tokyo, Russia, Brazil, Tice, and Pasteur - and two live attenuated mycobacterial vaccine candidates - a ΔlysAΔpanCD M. tuberculosis strain and a ΔmmaA4 BCG vaccine mutant. For every vaccine tested, a significant correlation was observed between intracellular ATP concentrations and the number of viable attenuated bacilli. However, the extractable intracellular ATP levels detected per cell among the different live vaccines varied suggesting that validated ATP luminescence assays with specific appropriate standards must be developed for each individual live attenuated vaccine preparation. Overall, these data indicate that the ATP luminescence assay is a rapid, sensitive, and reliable alternative method for quantifying the viability of varying live attenuated mycobacterial vaccine preparations.


Enhancing brain-machine interface (BMI) control of a hand exoskeleton using electrooculography (EOG).
Brain-machine interfaces (BMIs) allow direct translation of electric, magnetic or metabolic brain signals into control commands of external devices such as robots, prostheses or exoskeletons. However, non-stationarity of brain signals and susceptibility to biological or environmental artifacts impede reliable control and safety of BMIs, particularly in daily life environments. Here we introduce and tested a novel hybrid brain-neural computer interaction (BNCI) system fusing electroencephalography (EEG) and electrooculography (EOG) to enhance reliability and safety of continuous hand exoskeleton-driven grasping motions. 12 healthy volunteers (8 male, mean age 28.1 ± 3.63y) used EEG (condition #1) and hybrid EEG/EOG (condition #2) signals to control a hand exoskeleton. Motor imagery-related brain activity was translated into exoskeleton-driven hand closing motions. Unintended motions could be interrupted by eye movement-related EOG signals. In order to evaluate BNCI control and safety, participants were instructed to follow a visual cue indicating either to move or not to move the hand exoskeleton in a random order. Movements exceeding 25% of a full grasping motion when the device was not supposed to be moved were defined as safety violation. While participants reached comparable control under both conditions, safety was frequently violated under condition #1 (EEG), but not under condition #2 (EEG/EOG). EEG/EOG biosignal fusion can substantially enhance safety of assistive BNCI systems improving their applicability in daily life environments.


Consistent image registration.
This paper presents a new method for image registration based on jointly estimating the forward and reverse transformations between two images while constraining these transforms to be inverses of one another. This approach produces a consistent set of transformations that have less pairwise registration error, i.e., better correspondence, than traditional methods that estimate the forward and reverse transformations independently. The transformations are estimated iteratively and are restricted to preserve topology by constraining them to obey the laws of continuum mechanics. The transformations are parameterized by a Fourier series to diagonalize the covariance structure imposed by the continuum mechanics constraints and to provide a computationally efficient numerical implementation. Results using a linear elastic material constraint are presented using both magnetic resonance and X-ray computed tomography image data. The results show that the joint estimation of a consistent set of forward and reverse transformations constrained by linear-elasticity give better registration results than using either constraint alone or none at all.


Remember the saphenous: ultrasound evaluation and intravenous site selection of peripheral veins in young children.
The primary objective of this study was to measure the width and depth of peripheral veins using bedside ultrasound in children younger than 3 years. Secondary objectives included the evaluation of other vein and patient characteristics that may affect intravenous (IV) site selection. Assessment of nursing preferences for peripheral IV site selection was performed. Sixty children aged 0 to 3 years who presented to an urban pediatric emergency department were enrolled. Ultrasound measurements of the transverse diameter (width) and distance from the top of the vein to the skin (depth) were recorded. Upon examination, veins were categorized as visible, palpable, detectable only by ultrasound, or not detectable. Sixteen staff nurses rated the likelihood of successful IV placement among different peripheral veins. The mean width of saphenous veins was significantly larger than that of hand veins (2.8 vs 1.8 mm, P < 0.0001). When comparing saphenous veins to antecubital veins, no significant difference was measured between the mean width (2.8 vs 2.8 mm). The mean depth of saphenous veins was significantly greater than those of hand veins (1.9 vs 1.4 mm, P < 0.0001) and antecubital veins (1.9 vs 1.6 mm, P = 0.019). Differences in visibility and palpability were observed between different vein types. Hand veins and antecubital veins were rated by the nursing staff as the most likely sites for successful IV placement, whereas saphenous veins were among the least likely (P < 0.0001). In children younger than 3 years, the saphenous vein is larger than hand veins and is similar in size to antecubital veins, although marginal differences in depth exist. The sonographic findings of the saphenous vein and antecubital vein suggest that either should be considered a superior first choice for IV cannulation in this age group. Knowledge of these differences is important when choosing a site for peripheral IV placement. Future studies should evaluate peripheral IV success rates by vein type with or without ultrasound guidance.


Shifts in the epitopes of myelin basic protein recognized by Lewis rat T cells before, during, and after the induction of experimental autoimmune encephalomyelitis.
An epitope present in the 71-90 sequence of basic protein (BP) has been identified as the dominant epitope recognized by most Lewis rat encephalitogenic T cells isolated during experimental autoimmune encephalomyelitis (EAE). In the present study, we investigated the BP epitopes recognized by Lewis rat T cells in naive rats, in rats suffering from acute EAE, and in recovered rats. T cells isolated from the spinal cord lesions and from the lymph nodes were studied using T cell lines and bulk cultures. Virulence of the T cells was assayed by adoptive transfer. We now report that naive and recovered Lewis rats are populated with T cells reactive to a variety of BP epitopes and only a minority are specific for the 71-90 epitope. In contrast, the induction of EAE was associated with a predominance of T cells reactive to the 71-90 epitope. T cells recovered from naive, diseased, or recovered rats were found to be virulent upon passive transfer. Some of these virulent T cells were specific to BP epitopes other than the 71-90 epitope. There was no major difference in the BP specificities of T cells isolated from the lesions and from the lymph nodes. Thus, natural T cell reactivity to BP is heterogeneous and pathogenicity is not confined to one particular epitope, active disease is characterized by a dominant response to the 71-90 epitope, and recovery is marked by a return to heterogeneity.


Construct validity of the Dissociative Experiences Scale: II. Its relationship to hypnotizability.
Undergraduates (n = 311) who volunteered to participate in an experiment on "Hypnotizability and Personality" filled out several personality questionnaires (including the Dissociative Experiences Scale; DES), were administered the Harvard Group Scale of Hypnotic Susceptibility (HGSHS), and completed a self-rating of hypnotizability. The DES overall score correlated significantly with the HGSHS summary score (r(309) = .12, p < .05, two-tailed) and with subject's self-rating of hypnotizability (r(309) = .13, p < .05, two-tailed). The magnitude of these correlations was similar to that observed in a previous study (.14 & .18) and is also similar in magnitude to the correlations typically observed between the HGSHS and the Tellegen Absorption Scale. The potential clinical implications of these findings are discussed.


Melanogenesis and evidence for melanosome transport to the plasma membrane in a CD83 teleost leukocyte cell line.
Visceral organs of ectothermic vertebrates harbour melanin-containing leukocytes termed melanomacrophages. These cells are thought to participate in immune reactions and free-radical trapping. In teleosts, the melanin-producing ability of melanomacrophages has hitherto not been confirmed by molecular techniques. Here, a leukocyte marker and the apparatus for melanosome production and transport were investigated in an Atlantic salmon (Salmo salar) pronephros-derived mononuclear leukocyte (SHK-1) cell line. The SHK-1 cells expressed transcripts specific for a mammalian CD83 homologue, a standard surface marker for activated or differentiated dendritic cells, and dopachrome tautomerase/tyrosinase-related protein-2, a melanocyte specific enzyme essential for melanin production. Reduction potential of melanin or its precursors was demonstrated histochemically after prolonged cultivation. Ultrastructural investigations revealed tyrosinase and acid phosphate activity in identical organelles and BSA-gold co-localized with multilamellar melanosomes after 2 h internalization. Apparently, melanosomes were transported and released through periodically occurring tubules fusing with the plasma membrane. Video monitoring revealed filopodia and macropinocytosis. These results showed that the SHK-1 cell line is capable of melanogenesis and melanosome secretion. Melanin-producing cells in teleost pronephros may represent a distinct CD83(+) leukocyte population consisting of phylogenetically relict multifunctional cells. This is the first report of a melanin-producing leukocyte cell-line.


[The clinico-functional characteristics of pulmonary arterial hypertension in systemic scleroderma].
Electro-, phono-, echo-, and Doppler echocardiography, bulbar biomicroscopy were performed in 54 SS patients aged 18-64. Mean pulmonary arterial pressure (PP) was determined at Doppler echocardiography on Toshiba SSH-40A unit according to techniques developed by M. M. Mirrakhimov et al. in 1989. The diagnosis of pulmonary hypertension (PH) was made in PP above 18 mm Hg. A close relationship was found between SS history and PH registration. With growing SS duration, PH severity increases, microcirculatory disorders progress. Main PH risk factors in SS patients are believed SS duration, activity, Raynaud's syndrome presentation. Doppler echocardiography can effectively diagnose PH in its subclinical stage, is noninvasive.


Racial/ethnic measurement invariance of the School Success Profile (SSP)'s future orientation scale.
Future orientation (FO) has received increasing attention for its positive effects on adolescent well-being and successful transition to adulthood. Although numerous measures of FO exist, most are not developmentally appropriate for diverse populations of adolescents, do not assess all theoretical components of FO, and/or were not developed for administration in schools. Additionally, the invariance of existing measures across racial/ethnic groups has not been examined using appropriately rigorous procedures. Using data from 2575 students in grades 6-9, this study examined the psychometric quality and measurement invariance of the FO scale on the School Success Profile (SSP) across African American (34.8%), Latino (27.0%), and European American (38.1%) subsamples. A one-factor model fit the data well in all three groups. Analyses identified only a small number of noninvariant parameters, supporting the conclusion that the scale has partial measurement invariance across the three groups. On average, African Americans had significantly higher levels of FO than the other two groups; mean scores for Latinos and European Americans were lower and statistically equivalent to each other. Construct validity of the SSP FO scale was also supported by findings of medium-sized relationships of FO scores to scores on five other constructs: low grades, school engagement, parent educational support, psychological distress, and school behavior. Multiple group tests of the magnitude and direction of the validity relationships indicated statistical equivalence across the three groups. Results support the use of the SSP FO scale by school psychologists to assess FO and to evaluate the effects of interventions targeting FO as a promoter of well-being and school success.


[Solitary diverticulum of ascending colon induced internal intestinal herniation: report of one case].
Colonic diverticula are generally multiple and occur most commonly in the descending and sigmoid colon. Solitary ascending colonic diverticulum is a rare pathology and presents several features which separate it from colonic diverticulosis. It is a true diverticulum. It is a congenital dysplasia that generally runs an asymptomatic course and becomes clinically important only when inflammatory, perforating, or hemorrhagic complications occurs and presents a difficult problem in diagnosis and management. An unusual case of 4 year old girl with solitary ascending colonic diverticulum was reported here. It caused internal intestinal herniation by forming an adhesion band with mesentery and the clinical course manifested as an acute intestinal obstruction.


Virtual users support forum: do community members really want to help you?
The survival of a virtual community is guaranteed by the users' creation of content. However, the literature has found that the percentage of users who create innovative content is very modest. The content contribution process can also be interpreted as a social collective action in which we-intentions play a primary role. Nevertheless, some people choose not to participate in the collective action, but to benefit from the community's resources and to maximize individual outcomes. In this study (N=250), we investigated the effects of the free-riding tendency, conceived as the willingness to maximize personal outcomes. The specific setting was a virtual support forum, the most common type of web platform, generally used instrumentally by web users to find information and solutions to specific problems. We used the theory of planned behavior theoretical framework, plus social influence variables to test the effect of the free-riding tendency as a drawback for contributions, considering both the role of individual and we-intentions on the observed behavior. Findings showed that neither we-intentions nor I-intentions predicted the actual contribution behavior. Both types of intentions and contribution behavior were negatively influenced only by the free-riding tendency construct. Considerations and future developments of these results are discussed.


Intraosseous spinal glomus tumors: case report.
Glomus tumors are rare lesions that can arise intraosseously along the entire spinal axis. Only four cases have been reported, usually manifesting with severe back pain and involving the midthoracic spine or sacrum. The current report describes the largest such lesion reported in the literature to date and summarizes the clinical and pathological characteristics of these rare tumors. A single, recent case arising from the lumbar vertebra of L3 is described, and the literature of intraosseous spinal glomus tumors is reviewed. The lesion described arose in a 44-year-old man with a 1-year history of neurological symptoms and a large dumbbell-shaped lesion involving the lumbar vertebra, which extended through the neural foramen at L3. The lesion was resected using a two-stage approach. Severe intraoperative hemorrhage necessitated emergent angiographic embolization. Histopathological examination confirmed the presence of a glomus tumor arising from the smooth muscle cells of the glomus body. These rare lesions may extend into the epidural space and through the neural foramina and abdominal compartments; over time, they grow very large. Preoperative embolization may be indicated for large tumors suspected to be glomus tumors.


Telehomecare rewards and risks.
Telehomecare offers improved access to home care at lower costs and promises unique opportunities for home care patient empowerment and improved care outcomes. Telehomecare programs must be carefully designed to comply with licensure requirements, minimize liability risks, protect patient privacy, and capitalize on reimbursement trends. Providers willing to invest in the development of well-designed telehomecare programs and to document the merits of their initiatives should be well-positioned to serve the country's aging population under any of the care models that will dominate health care delivery in the next century.


Design and Usage of the HeartCycle Education and Coaching Program for Patients With Heart Failure.
Heart failure (HF) is common, and it is associated with high rates of hospital readmission and mortality. It is generally assumed that appropriate self-care can improve outcomes in patients with HF, but patient adherence to many self-care behaviors is poor. The objective of our study was to develop and test an intervention to increase self-care in patients with HF using a novel, online, automated education and coaching program. The online automated program was developed using a well-established, face-to-face, home-based cardiac rehabilitation approach. Education is tailored to the behaviors and knowledge of the individual patient, and the system supports patients in adopting self-care behaviors. Patients are guided through a goal-setting process that they conduct at their own pace through the support of the system, and they record their progress in an electronic diary such that the system can provide appropriate feedback. Only in challenging situations do HF nurses intervene to offer help. The program was evaluated in the HeartCycle study, a multicenter, observational trial with randomized components in which researchers investigated the ability of a third-generation telehealth system to enhance the management of patients with HF who had a recent (<60 days) admission to the hospital for symptoms or signs of HF (either new onset or recurrent) or were outpatients with persistent New York Heart Association (NYHA) functional class III/IV symptoms despite treatment with diuretic agents. The patients were enrolled from January 2012 through February 2013 at 3 hospital sites within the United Kingdom, Germany, and Spain. Of 123 patients enrolled (mean age 66 years (SD 12), 66% NYHA III, 79% men), 50 patients (41%) reported that they were not physically active, 56 patients (46%) did not follow a low-salt diet, 6 patients (5%) did not restrict their fluid intake, and 6 patients (5%) did not take their medication as prescribed. About 80% of the patients who started the coaching program for physical activity and low-salt diet became adherent by achieving their personal goals for 2 consecutive weeks. After becoming adherent, 61% continued physical activity coaching, but only 36% continued low-salt diet coaching. The HeartCycle education and coaching program helped most nonadherent patients with HF to adopt recommended self-care behaviors. Automated coaching worked well for most patients who started the coaching program, and many patients who achieved their goals continued to use the program. For many patients who did not engage in the automated coaching program, their choice was appropriate rather than a failure of the program.


Allelotype of pancreatic adenocarcinoma.
Knowledge of the patterns of allelic loss has been useful in identifying the spectrum of the tumor suppressor genes involved in various tumor types. Such analyses in pancreatic carcinoma have been difficult due to the characteristic host desmoplastic reaction to the neoplasm. We have assembled the first allelotype of pancreatic adenocarcinoma, a survey for allelic loss among each chromosomal arm, using seven cryostat-dissected neoplasms. The fractional allelic loss in these seven neoplasms was 0.18, a value similar to that seen previously in colorectal carcinoma. Alleles of chromosome 18q (lost in five of six informative tumors) and of chromosome 17p (lost in four of five informative tumors) were commonly affected. Neither APC mutations (33 neoplasms), allelic shifts of dinucleotide repeats (26 neoplasms), nor immunohistochemical evidence of retinoblastoma protein underexpression (7 neoplasms) were found. Further evaluation of allelic loss in pancreatic cancer would benefit from improved methods for the analysis of lost genetic material which overcome the problems posed by the high admixture of nonneoplastic stromal and inflammatory cells in these tumors.


The Effect of Intracoronary Infusion of Autologous Bone Marrow-Derived Lineage-Negative Stem/Progenitor Cells on Remodeling of Post-Infarcted Heart in Patient with Acute Myocardial Infarction.
Introduction: Regenerative capacity of the heart is limited, and the post-infarct left ventricle (LV) dysfunction is associated with poor prognosis. Administration of stem/progenitor cells (SPCs) is a promising approach for cardiac regeneration. Objectives: In the study, we assessed LV function and post-infarcted remodeling in patients with ST-elevated myocardial infarct (STEMI) who received autologous lineage-negative (LIN-) SPCs. Patients and methods: Patients with STEMI and one-vessel coronary artery disease treated with percutaneous revascularisation were divided into study group (LIN- group, 15 patients) that received standard therapy and autologous BM-derived LIN- SPCs and control group (standard therapy group, 19 patients). The cells were administered intracoronary 24 hours after STEMI. The follow-up was 12 months with subsequent non-invasive tests and laboratory parameter evaluation on days 1st, 3rd, and 7th as well as at 1st, 3rd, 6th and 12th month after STEMI. Results: All procedures related to SPCs administration were well tolerated by the patients. In 12-month follow-up, there were no major adverse cardiac events connected with LIN- SPCs administration. During 12-month follow-up, 9 patients from LIN- group (Responders) achieved an improvement in LV ejection fraction (>10% after 12 months) with no signs of unfavorable LV remodeling. Laboratory parameters analysis showed that Troponin T levels were significantly lower until day 7th in the Responders group, while brain natriuretic peptide (BNP) level remained significantly lower from day 3rd to 12th month respectively. Conclusions: Intracoronary infusion of autologous BM-derived LIN- stem/progenitor cells is feasible and safe for patient. Improvement in LV function and prevention of unfavorable remodeling in the 60% of study group seems relatively promising. Stem cell-based therapy for cardiac regeneration still needs more accurate and extensive investigations to estimate and improve their efficacy.


Automated microscopy for electron tomography.
Instrumentation and methodology for the automatic collection of tomographic tilt series data for the three-dimensional reconstruction of single particles is described. The system consists of a Philips EM 430 TEM, with a Gatan 673 cooled slow-scan CCD camera and a Philips C400 microscope computer control unit attached. The procedure for data collection includes direct digital recording of the images on the CCD camera and the automatic measurement and correction of (a) image shifts resulting from tilting the specimen, (b) variation of defocus and (c) the eucentric height position of the specimen. Experiments are described illustrating the possibilities and limitations of automatic data collection. Data collection at a magnification of 30k shows that the exposure time of the specimen to the beam is reduced by a factor of 10-100 compared to manual operation of the TEM.


Characterization of Mechanical Signature of Eutopic Endometrial Stromal Cells of Endometriosis Patients.
Endometriosis affects 5-10% of women in reproductive age and causes pelvic pain and subfertility. Exact etiology of the disease is unknown. Here, we present a microfluidic platform for characterizing mechanical properties of eutopic endometrial stromal cells of endometriosis patients based on cellular deformability inside narrow microchannels. Primary human endometrial stromal cells were isolated from eutopic endometrium of endometriosis patients (4407 cells, from 7 endometriosis patients) and from disease-free women (4541 cells, from 6 control women) and were pumped through microchannels (formed of polydimethylsiloxane (PDMS) by standard soft lithography, with dimensions of 8 × 20 × 150 μm, as width × height × length) at a constant flow rate of 2 μL/min. High-speed imaging was used to capture videos of cells as they flow inside microchannels, and a computer vision code was used to track cells, measure their area, and calculate the time each cell takes to pass through the microchannel. Compared with their counterparts from control women, eutopic endometrial stromal cells from endometriosis patients showed significantly increased deformation index (1.65 ± 0.2 versus 1.43 ± 0.19, respectively, P value < 0.001), and higher velocity in travelling through narrow microchannels (96.530 ± 0.710 mm/s versus 57.518 ± 0.585 mm/s, respectively, P value < 0.001). The same difference in velocities between the two cell types was maintained after controlling for cell area. Eutopic endometrial stromal cells of endometriosis patients showed a mechanical phenotype characterized by high deformability and reduced stiffness. This mechanical signature can represent basis of a mechanical biomarker of endometriosis.


Genome-wide selection on codon usage at the population level in the fungal model organism Neurospora crassa.
Many organisms exhibit biased codon usage in their genome, including the fungal model organism Neurospora crassa. The preferential use of subset of synonymous codons (optimal codons) at the macroevolutionary level is believed to result from a history of selection to promote translational efficiency. At present, few data are available about selection on optimal codons at the microevolutionary scale, that is, at the population level. Herein, we conducted a large-scale assessment of codon mutations at biallelic sites, spanning more than 5,100 genes, in 2 distinct populations of N. crassa: the Caribbean and Louisiana populations. Based on analysis of the frequency spectra of synonymous codon mutations at biallelic sites, we found that derived (nonancestral) optimal codon mutations segregate at a higher frequency than derived nonoptimal codon mutations in each population; this is consistent with natural selection favoring optimal codons. We also report that optimal codon variants were less frequent in longer genes and that the fixation of optimal codons was reduced in rapidly evolving long genes/proteins, trends suggestive of genetic hitchhiking (Hill-Robertson) altering codon usage variation. Notably, nonsynonymous codon mutations segregated at a lower frequency than synonymous nonoptimal codon mutations (which impair translational efficiency) in each N. crassa population, suggesting that changes in protein composition are more detrimental to fitness than mutations altering translation. Overall, the present data demonstrate that selection, and partly genetic interference, shapes codon variation across the genome in N. crassa populations.


Surface characterization and frictional force between stainless steel brackets and archwires in orthodontic patients using chlorhexidine- and Persica-containing mouthrinses: A randomized controlled trial.
The aim of this study was to compare the effect of chlorhexidine- and Persica-containing mouthrinses on the surface characterization of orthodontic appliance and friction between the orthodontic stainless steel wires and brackets. In this randomized controlled trial, 75 orthodontic patients (aged 13-30) were allocated (n = 25) into two experimental groups (prescribed by Persica- or chlorhexidine-containing mouthrinse) and one control group (no prescription). The ovoid stainless steel archwires were placed, and the maxillary first premolar stainless steel edgewise brackets were ligated to wires by elastomeric rings. The patients were recalled after 2 weeks, and then, the archwires were removed and replaced. The surface analysis of archwires and brackets was evaluated using scanning electron microscopy and atomic force microscopy. The frictional forces between the archwires and brackets were measured using a universal testing machine. The data for surface roughness were analyzed by the nonparametric Kruskal-Wallis and Mann-Whitney tests. The frictional forces data were analyzed using a two-way analysis of variance and Tukey's post hoc test using SPSS software. The level of significance was P < 0.05. The retrieved brackets showed minor changes in their surface topography. The surface roughness of archwires after the intervention was significantly greater for the chlorhexidine than that of Persica (P < 0.05). The friction force between the archwires and brackets was also significantly higher for the chlorhexidine than that of Persica (P < 0.05). The Persica-containing mouthrinse from the biomechanical and biochemical standpoints may be a better option for oral hygiene in orthodontic patients compared with the chlorhexidine.


Adenocarcinoma metastasis of the intertransversarius cervicis muscle eliciting a right forelimb lameness in a dog.
This article describes identification of a metastatic adenocarcinoma to the intertransversarius cervicis muscle using magnetic resonance imaging (MRI) in a dog that presented with chronic lameness of the right forelimb. Magnetic resonance imaging revealed a right sided, ovoid signal abnormality within the intertransversarius cervicis muscle lateral to the sixth cervical (C6) vertebra. The lesion was uniform, hyperintense on T2- and isointense on T1-weighted images to muscle and exhibited uniform contrast enhancement on T1-weighted images. The MRI findings were consistent with a neoplasia. Surgical excision was performed. Histopathological diagnosis was metastatic fibrous adenocarcinoma. The dog recovered rapidly but 6 months post-operatively he was killed because of lung metastases. Necropsy was declined and the primary tumour could not be identified.


Alcohol in excess: CRF₁ receptors in the rat and mouse VTA and DRN.
Manipulation of the stress neuropeptide corticotropin-releasing factor (CRF), specifically central antagonism of the type 1 receptors (CRF-R1), effectively reduces alcoholic-like ethanol drinking in rodents. Escalated consumption is largely controlled by neurocircuitry that is important for reward and affect, such as the ventral tegmental area (VTA) and the dorsal raphé nucleus (DRN). The current studies investigated the role of CRF-R1 within the VTA and DRN and their relation to escalated ethanol drinking in two species. An additional goal was to explore whether high alcohol-drinking individuals would be more affected by CRF-R1 antagonism than low alcohol-drinking individuals. With a two-bottle choice drinking procedure, adult male C57BL/6J mice and Long-Evans rats were given 24-h access to 20 % ethanol and water on an intermittent schedule. Rats and mice were implanted with cannulae targeting the VTA or DRN. Doses of the CRF-R1 antagonist CP-154,526 (butyl-[2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]ethylamine)) were microinfused to modulate drinking of ethanol and water over the course of 24 h. In both mice and rats, intra-VTA CP-154,526 selectively decreased ethanol intake, while identical doses (0.3 and 0.6 μg) infused intra-DRN reduced both ethanol and water drinking. Long-Evans rats displayed a range of individual differences for ethanol preference, and CP-154,526 suppressed ethanol drinking in the high-preferring animals regardless of brain site manipulation. The current findings confirm previous studies that blockade of CRF-R1 efficaciously reduces escalated drinking while also suggesting that the effects of intermittent access on alcohol consumption may require CRF interaction with dopamine in the VTA.


Microplastics in gut contents of coastal freshwater fish from Río de la Plata estuary.
The presence of microplastics (MPs) in gut contents of coastal freshwater fish of the Rio de la Plata estuary was studied. Samples were taken in six sites where 87 fish belonging to 11 species and four feeding habits were captured. Presence of MPs was verified in the 100% of fish. The fibres represented the 96% of MPs found. The number of MPs in gut contents was significantly higher close to sewage discharge. There was not found relationship between number of MPs and fish length, weight or feeding habit. The spatial differences in mean number of MPs in fish observed in this study, suggest that environmental availability of MPs could be of great importance to explain the differences found among sampling sites analysed. This work represents the first study about the interaction between MPs and aquatic organisms in this important estuarine ecosystem of South America.


Interventions promoting physical activity among obese populations: a meta-analysis considering global effect, long-term maintenance, physical activity indicators and dose characteristics.
As the benefits that regular physical activity (PA) have on obesity are well known, many interventions promote active lifestyle adoption among obese populations. This meta-analysis aims to determine (i) the global effect that interventions promoting PA among obese populations have on their PA behaviour; (ii) variations in the effect of interventions depending on the PA indicator used; (iii) the programme's dose characteristics and (iv) maintenance of the intervention effects after the intervention has ended. A comprehensive search through databases and review articles was completed. Forty-six studies met the inclusion criteria. Calculations of effect size (Cohen's d) and a moderator analysis were conducted. The meta-analysis showed that interventions globally have an impact on the PA behaviour of obese populations (d = 0.44; 95% CI = 0.31, 0.57). The moderator analysis revealed that interventions of less than 6 months reported significantly larger effects than longer interventions. Moreover, the interventions had a stronger impact on the number of steps and the PA indexes (i.e. composite scores reflecting PA practice) than on other PA indicators. Finally, the analysis revealed that interventions succeed in maintaining PA behaviour after the intervention is over. However, relatively few studies addressed this issue (n = 9). Despite global positive effects, further research is needed to determine the optimal dose for interventions and to evaluate the maintenance of intervention effects.


Lung and respiratory muscle function in facioscapulohumeral muscular dystrophy.
Pulmonary dysfunction is not a well-recognized feature of facioscapulohumeral muscular dystrophy (FSHD). The aim of this study was to establish the prevalence and type of pulmonary and respiratory muscle dysfunction in FSHD. Sixteen patients with moderately advanced FSHD and 16 healthy controls were evaluated. Standard lung and respiratory muscle function tests were performed. Diaphragm muscle inspiratory action was evaluated with transdiaphragmatic pressure measurements. Lung function tests showed an increased residual volume in five patients. There was a significant difference in global respiratory muscle function in patients versus controls; weakness was mild, and it affected expiratory more than inspiratory muscles. There was no significant difference in the diaphragm inspiratory action of patients versus controls. The dystrophic process that underlies FSHD did not significantly involve the muscles of the diaphragm, but it caused mild global respiratory muscle weakness that affected expiratory more than inspiratory muscles. It is probably not necessary to routinely monitor respiratory muscle function in ambulant FSHD patients who lack symptoms or signs of respiratory impairment.


Evaluation of the suitability of recombinant yeast-based estrogenicity assays as a pre-screening tool in environmental samples.
This paper presents a study evaluating the suitability of recombinant yeast-based estrogenicity assays as a pre-screening tool for monitoring of the chemical status of water bodies in support of the Water Framework Directive (WFD). Three different recombinant yeast-based assays were evaluated; the Yeast Estrogen Screen (YES), the Recombinant Yeast Assay (RYA) and the Rikilt Estrogen bioAssay (REA), of which the YES assay was employed by two different laboratories. No significant difference between the performance of neither the different laboratories, nor the different yeast-assays was observed. Six batches of eleven samples each were analysed one week apart by the four participating laboratories and the robustness, repeatability and reproducibility of the participating yeast-based assays were evaluated. The setup included a correlation between bioassay results and results from chemical target analysis, which gave valuable information in the evaluation of the assays' performance. A good agreement was found between chemical and bioassay results, showing that the yeast-based assays can give valuable information in WFD work. However, the low sensitivity of the assays towards alkylphenols needs to be significantly improved if they are to be used for monitoring of these compounds. The study further led to suggestions on ways to improve traceability and quality assurance of the yeast-based assays.


Full-fat field cricket (Gryllus bimaculatus) as a substitute for fish meal and soybean meal for weaning piglets: effects on growth performance, intestinal health, and redox status.
Full-fat field cricket meal (FCP) is an alternative protein ingredient in livestock production; however, the effects of replacing conventional protein sources with FCP in nursery diets have not been determined. In this study, the effects of the partial replacement of either fish meal or soybean meal with FCP on weaning pigs were evaluated, including the analyses of growth performance, nutrient utilization, intestinal morphology, immunity, oxidative stress, and fecal microbial counts. A total of 100 crossbred weaning pigs [(Landrace × Large White) × Duroc] were allotted to one of the following five treatments with five replicates (four pigs/pen) and fed for 28 d postweaning. Treatments were 1) a corn-soybean meal (SBM)-based diet with 5% fish meal (Positive control; PC), 2) a corn-SBM-based diet without fish meal (Negative control; NC), 3) field crickets replacing fishmeal on a total Lys basis (FCP1), 4) field crickets replacing fishmeal on a kg/kg basis (FCP2), and 5) field crickets replacing fish meal and soybean meal (FCP3). The piglets on FCP1 had a higher body weight on days 14 and 28, and an increased average daily gain over the experimental period than NC (P < 0.05); FCP2 and FCP3 were similar to the FCP1 treatment. The incidence of diarrhea was lower under an FCP-supplemented diet than under the NC diet throughout the study (P < 0.05). Pigs fed FCP1 and FCP2 had a higher digestibility of crude protein (P = 0.041), and all FCP groups increased crude fat digestibility (P = 0.024). FCP1 and FCP2 also increased jejunal villus height (P = 0.009), whereas the increase in jejunal villus-to-crypt ratios (P = 0.019) was greater in pigs fed the FCP2 diet than those fed the NC diet. Furthermore, FCP2 supplementation increased serum immunoglobulin A levels on days 14 and 28, including reduced serum interleukin-6 and tumor necrosis factor alpha levels (P < 0.05). Pigs fed an FCP2 diet had reduced malondialdehyde levels than those fed a PC diet, while pigs fed an FCP2 diet had higher superoxide dismutase and glutathione peroxidase levels, and more fecal Lactobacillus spp. than those fed an NC diet (P < 0.05). These results support the use of FCP as an alternative protein ingredient with beneficial effects on growth performance, intestinal morphology, antioxidant capacity, and intestinal microbiota. In particular, FCP can be used as a partial substitute for fish meal and soybean meal without detrimental effects on weaning pigs.


First Report of Severe Autoimmune Hemolytic Anemia During Eltrombopag Therapy in Waldenström Macroglobulinemia-Associated Thrombocytopenia.
Autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) can be observed in Waldenström macroglobulinemia (WM). The autoimmune disorders are primarily mediated by autoimmune monoclonal gammopathy, but drug-induced hemolysis should also be considered. Herein, we presented the case of a 63-year-old female WM patient complicated with ITP, who was admitted to our department with a complaint of abdominal pain. After first half of bortezomib/dexamethasone/rituximab (BRD) chemotherapy, her platelet level recovered, but subsequently decreased to extremely low level (around 1-2×109/L), and the patient suffered from platelet transfusion refractoriness. During the management of refractory thrombocytopenia, the patient developed severe hemolytic anemia, and further tests confirmed warm AIHA. FcγRIIα polymorphism test showed that the patient had FcγRIIα-131RH, which implied that the AIHA may not be WM-related. Given the effects of ibrutinib in controlling WM, secondary AITP and AIHA, ibrutinib single treatment was started, which quickly corrected the thrombocytopenia within five days, but not hemolysis. With a relatively safe platelet level, eltrombopag was stopped, and the hemolysis relieved three days after eltrombopag withdrawal. This is the first report on eltrombopag-induced AIHA in the management of WM-associated ITP.


Dysglycemia in a community sample of people treated for schizophrenia: the Diabetes in Schizophrenia in Central-South Ontario (DiSCO) study.
Despite increasing recognition of schizophrenia as a risk factor for diabetes, the prevalence and correlates of dysglycemia in people with schizophrenia have not been adequately studied. Discerning the modifiable risk factors is crucial for developing diabetes prevention strategies in schizophrenia. Socio-demographic, clinical and recent laboratory data were compiled from the case records and supplemental sources of 1123 people treated for schizophrenia who were living across five different communities in the region. Screening rates for fasting plasma glucose (FPG) varied between 63-100% across the five communities, while other metabolic indices were monitored less frequently. 39 subjects (3.5%) in the sample had an existing diagnosis of type 2 diabetes. Among the others, 845 (78%) had FPG measured in the preceding 6 months, with the following results: FPG < or = 5.6 mmol/l in 474 (56%), 5.6-6.9 mmol/l in 268 (31%), and > or = 7 mmol/l in 103 (12.2%) subjects. Dysglycemia (FPG > or = 5.6 mmol/l) was significantly associated with older age (odds ratio [OR] 1.031), longer duration of schizophrenia (OR 1.062), self reported family history of diabetes (OR 8.87), body mass index (OR 1.081), excess weight (OR 1.014) and independent living status (OR 1.779), while European ethnicity (OR 0.706) and regular physical activity (OR 0.958) lowered the risk. No statistically significant correlations were noted with gender, level of education or functioning, or the type of antipsychotic drug prescribed. There was a two-fold increase in the prevalence of dysglycemia, while there was a substantial under-recognition of and intervention for, diabetes and pre-diabetes in this sample of people treated for schizophrenia.


The regulation of autophagy by the miR-199a-5p/p62 axis was a potential mechanism of small cell lung cancer cisplatin resistance.
Autophagy has been found to be involved in the multidrug resistance (MDR) of cancers, but whether it is associated with resistance of small cell lung cancer (SCLC) has not been studied. Here, we hypothesized that a potential autophagy-regulating miRNA, miR-199a-5p, regulated cisplatin-resistant SCLC. We validated the MDR of H446/EP using CCK-8 and LDH. We tested the binding of miR-199a-5p to p62 using the Dual-Luciferase assay and validated the association of miR-199a-5p and p62 in SCLC samples. We overexpressed (OE) and knocked down (KD) miR-199a-5p in H446 and H446/EP and determined the expression of miR-199a-5p, autophagy-related proteins, and the formation of autophagolysosomes using QPCR, western blotting, and MDC staining respectively. These results were validated in an orthotopic H446 mouse model of SCLC. H446/EP was resistant to cisplatin, etoposide, paclitexal, epirubicin, irinotecan, and vinorelbine. Exposure of cisplatin at 5 μg/ml for 24 h increased LC3II/LC3I, ATG5, p62, and the formation of autophagolysosomes in H446 cells, but not in H446/EP cells. The expression of miR-199a-5p was up-regulated in H446/EP compared to H446. MiR-199a-5p directly targeted the p62 gene. The expression of miR-199a-5p and p62 were correlated in SCLC samples. In H446 and H69PR, the OE of miR-199a-5p increased LC3II/LC3I, p62, and the formation of autophagolysosomes, but not ATG5, while the KD of miR-199a-5p decreased p62, but did not affect LC3II/LC3I, ATG5, and the formation of autophagolysosomes. In H446/EP, the OE of miR-199a-5p decreased p62 only. These results were generally consistent to results in the animal tumor samples. The regulation of autophagy by the miR-199a-5p/p62 axis was a potential mechanism of small cell lung cancer cisplatin resistance.


Unusual insulin binding to cells expressing an insulin receptor mutated at cysteine 524.
The involvement of cysteine 524 of the insulin receptor in an intermolecular (class I) disulfide bond between the two alpha-subunits was investigated using site-directed mutagenesis. The oligomeric structure of the mutated receptor was partially disrupted, although a significant portion of the receptor remained in its heterotetrameric form. Interestingly, the mutated insulin receptor heterotetramer was more susceptible than the wildtype receptor to reduction to heterodimers by low concentrations of dithiothreitol. Insulin binding to solubilized mutant receptors was normal and the mutant receptors had normal affinity for insulin, but insulin binding to cells expressing mutant insulin receptors displayed positive cooperativity. Cysteine 524 is most likely involved in a class I disulfide bond and receptors mutated at this site displayed unusual insulin binding properties only in the cellular environment.


A systematic review of the bimanual examination as a test for ovarian cancer.
An annual bimanual pelvic examination remains widely recommended for healthy women, but its inclusion may discourage attendance. Our goal was to determine the accuracy of the pelvic examination as a screening test for ovarian cancer and to distinguish benign from malignant lesions. PubMed was searched to identify studies evaluating the accuracy of the bimanual pelvic examination for ovarian cancer diagnosis. Data regarding study design, study quality, and test accuracy were abstracted. Heterogeneity was evaluated and meta-analysis performed where appropriate, including bivariate receiver operating characteristic curves. Eight studies in screening populations (n=36,599) and seven studies in symptomatic patients (n=782) were identified. Search was completed in November 2013; included studies were published between 1988 and 2009. Screening studies were homogeneous; the summary estimates of sensitivity and specificity of the pelvic examination as a screening test for ovarian cancer were 0.44 and 0.98 (positive likelihood ratio, 24.7; negative likelihood ratio, 0.57). For distinguishing benign versus malignant lesions, there was considerable heterogeneity, with a range of sensitivity from 0.43 to 0.93 and specificity from 0.53 to 0.91. The bimanual pelvic examination lacks accuracy as a screening test for ovarian cancer and as a way to distinguish benign from malignant lesions. In a typical screening population, the positive predictive value of an abnormal pelvic examination is only 1% (95% CI=0.67%, 3.0%). Its inclusion in a health maintenance examination cannot be justified on the basis of using it to screen for ovarian cancer.


Recent Insights into Notch Signaling in Embryonal Rhabdomyosarcoma.
The Notch signaling pathway is an evolutionarily conserved developmental network critical for embryonic and postnatal regulation of tissue growth, homeostasis, and repair. Signaling is initiated when transmembrane Notch ligands bind to transmembrane Notch receptors on nearby cells. Sequential proteolytic steps generate an activated Notch fragment that translocates to the nucleus, where it drives activation of canonical Notch target genes. In skeletal muscle, Notch signaling governs myogenic cell fate and stem cell maintenance. In the human soft tissue sarcoma rhabdomyosarcoma, which bears markers of skeletal muscle commitment and so is thought to be related to the skeletal muscle lineage, Notch signaling is also found to be upregulated and dysregulated. This review provides an overview of Notch signaling during normal embryonic and postnatal myogenesis, information on the recently discovered aberrant Notch signaling occurring in muscular dystrophies, the upregulation and mechanism of Notch signaling in the embryonal variant of rhabdomyosarcoma and related soft tissue sarcomas, and Notch cross-talk with other metazoan developmental pathways including Hippo, Hedgehog, Wnt, and TGF-β. The review concludes with updates on current promising efforts to target and inhibit Notch signaling in human sarcomas including rhabdomyosarcoma.


Melatonin reduces oxidative damage of neural lipids and proteins in senescence-accelerated mouse.
We investigated whether long-term melatonin administration in the drinking water influences oxidative modification of lipids and proteins and antioxidative enzyme activity in brain of senescence-accelerated mice (SAM). Cerebral cortex was obtained in the middle of the dark period of the daily light cycle from SAMP8, a strain of mice prone to accelerated senescence, and from SAMR1, a senescence-resistant strain, at 3, 6, and 12 months of age. Thiobarbituric acid-reactive substances (TBARS) and protein carbonyls exhibited significant age-related increases in both strains. Glutathione peroxidase (GPx) activity decreased significantly at 12 months of age in SAMP8. No age effect was found in GPx activity in SAMR1, or in superoxide dismutase (SOD) activity in either strain. Melatonin administration (2 microg/mL) via the drinking fluid beginning at 7 months significantly decreased neural TBARS content (over 30%) in both strains and lowered the protein carbonyl content in the brain of SAMP8 mice. Furthermore, melatonin significantly augmented GPx activity (over 20%) in both strains. Melatonin had no effect on SOD activity. These results suggest an age-related increase in cerebral tissue vulnerability to oxidation in SAM that can be modified by melatonin, most likely through the ability of melatonin to scavenge oxygen free radicals and to stimulate antioxidant enzyme activity.


Coexpression of collagens and collagen-binding heat shock protein 47 in human diabetic nephropathy and IgA nephropathy.
The mechanism of structural changes of the kidney in human diabetic nephropathy (DN) and IgA nephropathy (IgAN) is not yet completely known, but excessive deposition of extracellular matrix (ECM), including various collagens, may be crucial to this process. Heat shock protein (HSP) 47 has been identified as collagen-binding stress protein, shown to have a specific role in the intracellular processing of procollagen molecules during collagen assembly. To determine whether increased deposition of collagens in human DN and IgAN is related to HSP47, we investigated the expression of HSP47 in renal biopsy and autopsy sections obtained from 22 DN and 45 IgAN patients. Five renal biopsy specimens, diagnosed as minor glomerular abnormalities, were simultaneously studied as controls. Monoclonal antibodies specific for HSP47, type III collagen and type IV collagen were used to assess the relative expression of their proteins in paraffin-embedded renal sections by immunohistochemistry. Increased deposition of collagens was closely related to the sclerotic activity of the disease process in DN and IgAN; increased deposition of collagens was often present in relation to a strong expression of HSP47, a stress protein known to regulate collagen synthesis/assembly. By double immunostaining, we found colocalization of collagens and their molecular chaperone HSP47 in the sclerotic glomeruli and tubulointerstitium in DN and IgAN. Our results strongly support a pathologic role for HSP47 in both these diseases and that increased levels of HSP47 may play an important role in the excessive assembly of collagens resulting in glomerulosclerosis and interstitial fibrosis found in DN and IgAN patients.


Concurrent cardiac transthyretin and brain β amyloid accumulation among the older adults: The Hisayama study.
Previous studies have revealed risk for cognitive impairment in cardiovascular diseases. We investigated the relationship between degenerative changes of the brain and heart, with reference to Alzheimer's disease (AD) pathologies, cardiac transthyretin amyloid (ATTR) deposition, and cardiac fibrosis. A total of 240 consecutive autopsy cases of a Japanese population-based study were examined. β amyloid (Aβ) of senile plaques, phosphorylated tau protein of neurofibrillary tangles, and ATTR in the hearts were immunohistochemically detected and graded according to the NIH-AA guideline for AD pathology and as Tanskanen reported, respectively. Cerebral amyloid angiopathy (CAA) was graded according to the Vonsattel scale. Cardiac fibrosis was detected by picrosirius red staining, followed by image analysis. Cardiac ATTR deposition occurred after age 75 years and increased in an age-dependent manner. ATTR deposition was more common, and of higher grades, in the dementia cases. We subdivided the cases into two age groups: ≤90 years old (n = 173) and >90 years old (n = 67), which was the mean and median age at death of the AD cases. When adjusted for age and sex, TTR deposition grades correlated with Aβ phase score (A2-3), the Consortium to Establish a Registry for AD score (sparse to frequent), and high Braak stage (V-VI) only in those aged ≤90 years at death. No significant correlation was observed between the cardiac ATTR deposition and CAA stages, or between cardiac fibrosis and AD pathologies. Collectively, AD brain pathology correlated with cardiac TTR deposition among the older adults ≤90 years.


A young age of subspecific divergence in the desert locust inferred by ABC random forest.
Dating population divergence within species from molecular data and relating such dating to climatic and biogeographic changes is not trivial. Yet it can help formulating evolutionary hypotheses regarding local adaptation and future responses to changing environments. Key issues include statistical selection of a demographic and historical scenario among a set of possible scenarios, and estimation of the parameter(s) of interest under the chosen scenario. Such inferences greatly benefit from (a) independent information on evolutionary rate and pattern at genetic markers; and (b) new statistical approaches, such as approximate Bayesian computation-random forest (ABC-RF), which provides reliable inference at a low computational cost and the possibility to measure prediction quality at the exact position of the observed data set. Here, we show full potential of the ABC-RF approach including prior knowledge on microsatellite genetic markers to decipher the evolutionary history of the African arid-adapted pest locust, Schistocerca gregaria, with support for a southern colonization of Africa, from a low number of founders of northern origin, dating back 2.6 Ky (90% CI: 0.9-6.6 Ky). We verify that this divergence time estimate accurately reflected true divergence time values by computing accuracy at a local posterior scale from simulated pseudo-observed data sets. The inferred divergence history is better explained by the peculiar biology of S. gregaria, which involves a density-dependent swarming phase with some exceptional spectacular migrations, rather than a continuous colonization resulting from the continental expansion of open vegetation habitats during more ancient Quaternary glacial climatic episodes.


Pediatric kidney transplantation: outcomes with under and over 6-year-old donors.
Kidney shortage for pediatric kidney transplantation (PKT) entails the need to use low-weight and age donors, despite the apprehension. The aim of this study was to analyze the pediatric deceased donor kidney transplantations (pDDKT) outcomes in the first year after the procedure, stratified by donor age. Retrospective cohort of pDDKTs carried out between January 2013, and January 2018, at a PKT reference hospital in Southern Brazil. Donors were divided into group 1 (≤ 6 years), and group 2 (> 6 years); the analysis of the outcomes was carried out in the same period. There were 143 pDDKTs; 51 (35.66%) in group 1; and 92 (64.34%) in group 2. In both groups there were 17 graft losses (11.8%), with vascular thrombosis as the main cause (group 1: 5; group 2: 4). Among the complications, renal artery stenosis (RAS) with indication for angioplasty and stenting was more frequent in group 1 (7.8%; group 2: 2.2%). The 1-year Renal Transplant Recipients' and graft survival did not show significant differences between the groups, (p = = 0.95). However, the Glomerular Filtration Rate analysis was higher in group 2, reaching, in the 12th month, 79.3 mL/min/1,73m2, compared to 69.7 mL/min/1,73m2 in group 1(p = = 0.033). Small donors can be considered for pDDKTs, as long as there is an expert team to perform the transplantation.


Changing rates for liver and lung cancers in Qidong, China.
Residents of Qidong, China are undergoing a rapid fluctuation in cancer incidence rates at many organ sites, reflecting a dynamic interplay of socio-behavioral, economic, and environmental factors. This Perspective On Statistical Trends examines the China age-standardized incidence rates (CASR), as tracked by the Qidong Cancer Registry for the past 40 years, for the two leading cancer killers in Qidong, liver and lung. Both cancer types are strongly influenced by environmental factors. The CASR for liver cancer has dropped nearly 50% in the last 4 decades, in part from access to deep-well drinking water in the 1970s with consequent diminished exposure to tumor promoting microcystins produced by blue-green algae. There have also been substantive reductions in exposures to dietary aflatoxins, as economic reform in the mid-1980s fostered a wholesale change in dietary staple from maize to rice. In men, lung cancer CASR has trebled over this period, likely driven by a high prevalence of smokers (∼65%) and an ever increasing smoking frequency in this population. Qidong women, by contrast, rarely smoke and have exhibited a flat CASR until the past decade where lung cancer rates have now doubled. This upturn may reflect an increasing burden of indoor and outdoor air pollution.


A multi-level analysis of risk perception, poverty and sexual risk-taking among young people in Cape Town, South Africa.
Various studies have underscored the relevance of community-level factors to sexual behavior and HIV/AIDS prevention efforts in Africa. However, there is a paucity of research and theorizing in this area compared to the preponderance of prevention models that focus solely on individual-level factors. Using data from the Cape Area Panel Survey and hierarchical linear models, this study examines the effects of a combination of individual-level factors and community-level poverty on sexual behaviors. Male and female respondents who perceived themselves to be at great risk of HIV infection were less likely to indulge in risky sexual behaviors. For females, race and community-level poverty were confounded such that race mediated the effects of community-level poverty. Results from this study indicate that multiple rationalities affect sexual behaviors in Cape Town, South Africa and that there is a need to consider both the social embeddedness of sexual behaviors and the rational components of decision making when designing HIV/AIDS prevention programs.


Superoxide mediates reperfusion-induced leukocyte-endothelial cell interactions.
The objective of this study was to determine whether superoxide mediates the leukocyte-endothelial cell interactions elicited by reperfusion (reoxygenation) of ischemic (hypoxic) tissues. Mesenteric and intestinal blood flows were reduced to 20% of control for 1 h, followed by 1 h of reperfusion. Sixty minutes after reperfusion, red blood cell velocity (Vr), leukocyte rolling velocity (Vw), and the number of adherent leukocytes were measured in mesenteric venules. Then, either human superoxide dismutase (hSOD), hydrogen peroxide-inactivated hSOD, or MoAb IB4 (a monoclonal antibody against the leukocyte adhesion molecule CD18) was injected intravenously. Ten minutes later, repeat measurements were obtained and compared with pretreatment values. hSOD attenuated reperfusion-induced neutrophil adherence and increased Vw/Vr, an index of the fracture stress between leukocytes and endothelium. Peroxide-inactivated hSOD did not alter any parameter. MoAb IB4 attenuated reperfusion-induced adherence but did not alter Vw/Vr. In a correlate study, cultured bovine microvascular endothelium was exposed to 30 min of anoxia, followed by 60 min of reoxygenation. Cat neutrophils were added during reoxygenation. Reoxygenation-induced leukocyte adherence was attenuated by either hSOD or MoAb IB4 but not by inactivated hSOD. Adherence of phorbol 12-myristate 13-acetate-activated cat neutrophils to plastic was unaffected by hSOD or inactive hSOD, yet MoAb IB4 virtually abolished the response. These results indicate that superoxide mediates reperfusion-induced leukocyte adherence and that endothelial cells are required for this superoxide-mediated adherence.


An investigation of physicians' prescribing behaviors related to antidiabetic agents for Type 2 diabetes mellitus patients and associated factors in Taiwan.
This study aimed to examine the factors that may influence physicians' choice of antidiabetic agents. In addition, we investigated physicians' decision-making process and treatment of T2DM patients with chronic kidney disease (CKD). Finally, we wanted to determine whether physicians knew the latest recommendations for T2DM treatment. The study was conducted as a cross-sectional survey using an online self-administered questionnaire to collect data from physicians in Taiwan. We enrolled licensed physicians who worked in hospitals or clinics with an average monthly T2DM patient load of 100 patients. Descriptive statistics, the independent samples t-test, and the Chi-square test were used for data analysis. Moreover, the association was examined between respondents' demographics and the proportion of respondents who answered each T2DM treatment question correctly. A total of 986 invitations were sent out, and 324 completed questionnaires were received. The most important factors that may influence physicians' choice of antidiabetic agents in each factor category were major comorbidities of patients, coverage of insurance, guideline recommendations, cardiovascular disease benefit, and whether a drug is the brand-name drug, respectively. When choosing second-line antidiabetic agents for T2DM patients with CKD, the most common reasons for doing so were recommendations of clinical guidelines (83.6%) and patients' renal function (59.6%) while SGLT2is were respondents' most commonly chosen treatment. Respondents were more familiar with ADA recommendations for patients with certain major comorbidities than with the drugs' labeled indications. Moreover, physicians who were younger, female, specialty in diabetes, or working in medical centers were more likely to give correct answers to certain questions about ADA guidelines (all p < .05). This study provides a better understanding of the influential factors, treatment choices, and reasoning related to physicians' prescribing of antidiabetic agents in Taiwan. In addition, knowledge gaps in various physician groups were identified.


Assessment of antiviral and antibiotic combination treatment in influenza-A H1N1 induced acute kidney injury among hospitalized patients.
The aim of the study is to assess and compare the impact of antiviral drug alone and in combination with antibiotic for prevention of Influenza-A H1N1 induced acute kidney injury (AKI) in hospitalized patients. Hospitalized admitted patients with confirmed diagnosis of Influenza-A H1N1 infection were divided into two groups: group 1, which received antiviral (oseltamivir) drug alone and group 2, which received antiviral (oseltamivir) in combination with empirically prescribed antibiotic. Patients of both groups were assessed for incidences of AKI by two criteria i.e Acute Kidney Injury Network (AKIN) and RIFLE. A total of 329 patients (176 for group 1 and 153 for group 2) were enrolled. According to RIFLE criteria, 23(13%) of group 1 and 9(6%) patients of groups 2 were suffered from AKI with statistically significant difference (P<0.05). Also as per AKIN criteria, the incidence of AKI is statistically significantly difference (P<0.05) between both groups with 18(10%) patients and 6(4%) patients of group 1 and 2 respectively. Length of hospitalization was statistically less (P<0.05) in group 2 patients. The incidences of AKI in Influenza-A H1N1 treated with antiviral and antibiotic combination was statistically less as compared to patients who were given antiviral alone for treatment of influenza infection.


GROSS AND HISTOPATHOLOGIC CORRELATION OF LOW-FIELD MAGNETIC RESONANCE IMAGING FINDINGS IN THE STIFLE OF ASYMPTOMATIC HORSES.
With the recent introduction of a 0.25T rotating MRI system, clinical evaluation of the equine stifle joint is now possible in the average equine athlete. A recent publication described common abnormalities of horses with stifle lameness detected with a low-field MRI system; however, postmortem corroboration of the lesions detected was not possible. Therefore, our objective was to compare postmortem findings with low-field MRI findings in equine cadaver stifle joints. Ten fresh cadaver stifle joints from horses without clinical signs of stifle disease were evaluated using low-field MRI, gross dissection, and histopathology. In eight stifles, either the lateral or medial cranial meniscotibial ligament had an irregular shape, fiber separation, or moderate abnormal signal intensity (SI) on all sequences. In five stifles, the medial femoral condyle had articular cartilage fibrillation with or without an osteochondral defect over the weight bearing surface of the medial femoral condyle. All stifles had abnormal SI on all sequences within the patellar ligaments that corresponded with adipose tissue infiltrating between the collagen bundles. Other abnormalities identified included articular cartilage fibrillation of the tibial condyles in three stifles, and articular cartilage fibrillation with chondral defects in the patella in three stifles. All abnormalities detected with low-field MRI were corroborated by gross dissection. Findings from the current study supported the use of low-field MRI for detection of stifle joint lesions in horses and demonstrated that some stifle joint pathologies may be subclinical in horses.


Adherence to protocols for the use of reversal agents in patients treated with direct oral anticoagulants.
This study aimed to evaluate the adherence to protocols for the use of reversal agents in direct oral anticoagulant (DOAC) users in Dutch hospitals. A retrospective cohort study was conducted in seven hospitals in the Netherlands. Treatment protocols for bleeding and (urgent) procedures in patients on DOAC were collected from each hospital. All patient data on the use of reversal agents were retrospectively collected from September 2021 to April 2022 and compared to the protocols. The degree of per-protocol adherence (compliance score) was categorized into four levels as follows: poor (<45%), moderate (45-79%), high (80-89%), and full (> 90%) adherence rates. A total of 290 patients were included in our study. In patients with bleeding under DOAC, the protocol adherence for prothrombin complex concentrate (PCC) was "moderate" (61%). In the remaining cases (39%), non-adherence was mainly caused by underdosing (68%), overdosing (12%), and a lack of indication (14%). Furthermore, idarucizumab was administered for bleeding with "full" adherence (96%). For andexanet alfa, adherence to the hospital bleeding protocol was "moderate" (67%), with a lack of indication being the only reason for non-adherence. In case of reversal for an urgent procedure, the protocol adherence for PCC was "low" (45%), with underdosing, a lack of indication, and missing lab data being the main reasons for non-adherence. Missing lab data on dabigatran plasma concentration before reversal was the main reason for "low" adherence (26%) in idarucizumab. The adherence for andexanet alfa was also "low" (0%). In case of reversal for bleeding under DOAC, overall adherence to the protocol was "moderate"; however, in patients needing an urgent procedure, it was "low." The major reasons for non-adherence were underdosing, off-label use, and a lack of specific lab testing. The results of this study can assist in improving the implementation of hospital protocols.


Hox genes in normal and neoplastic mouse mammary gland.
Homeobox-containing genes regulate embryonic developmental programs and are expressed in certain adult tissues and cancers. There has been no report of expression in the breast. We amplified homeobox complementary DNA from mouse mammary gland and found expression of members from each of the four major Hox gene clusters. The regulation of expression of two Hox genes was examined in greater depth. Hoxc-6 transcripts were present in the glands of pubescent and mature mice and decreased during pregnancy. Levels were increased substantially following ovariectomy, indicating possible negative regulation by steroid hormones. Hox expression was studied in mammary adenocarcinomas and in transplant lines of the benign, precancerous tissues from which the cancers arose. Hoxc-6 was expressed at low levels in the precancerous tissue but was not expressed in cancers. In contrast, Hoxa-1 was expressed only in cancers, not in normal gland or in precancerous mammary tissues, suggesting that Hox genes may play a role in a late stage in the stepwise development of mammary malignancies.


New records of Amblyomma multipunctum and Amblyomma naponense from Ecuador, with description of A. multipunctum nymph.
We provide new data for the ticks Amblyomma multipunctum and Amblyomma naponense from Ecuador. In addition, we describe the nymph of A. multipunctum for the first time. During December 2012, ticks were collected by dragging in forest trails of 1 locality at Puyo, Pastaza Province (elevation 979 m), and another locality at Papallacta, Napo Province (3,474 m). A total of 10 adults of A. naponense were collected at Puyo, whereas 27 adults and 3 nymphs of A. multipunctum were collected at Papallacta. Compared to sequences of a fragment of the mitochondrial 16S rDNA gene of adult and nymphal ticks, the sequence of an Amblyomma nymph was identical to the sequences generated from the A. multipunctum adults. The 3 collected nymphs (including the 1 used for molecular analysis) had the same morphotype, and were used for the first morphological description of the nymphal stage of A. multipunctum. Sequences generated from the A. naponense specimens were closest (97% identity by BLAST) to a corresponding sequence of A. naponense from Brazil, whereas the A. multipunctum sequences were closer to (90-91% identity) several Neotropical Amblyomma species. Herein, we provide just the second record of A. naponense in Ecuador, more than 100 yr after this tick was reported in this country. Adults and nymphs of A. multipunctum were found in highland, humid montane forest areas, in agreement with the only 2 previous reports of A. multipunctum in Ecuador and Colombia. No genetic differences were found among A. multipunctum ticks that presented significant morphological differences, suggesting intraspecific polymorphism in the adult stages of this species.


HeartMate II Left Ventricular Assist Device Pump Exchange: A Single-Institution Experience.
Background Left ventricular assist devices (LVADs) have revolutionized the treatment of patients with end-stage heart failure. These devices are replaced when pump complications arise if heart transplant is not possible. We present our experience with HeartMate II (HMII (Thoratec, Plesanton, California, United States)) LVAD pump exchange. Materials and Methods We retrospectively reviewed all cases that required pump exchange due to LVAD complication from November 2011 until June 2016 at a single high-volume institution. The indications, demographics, and outcome were extracted and analyzed. Results Of 250 total patients with implanted HMII LVADs, 16 (6%) required pump exchange during the study period. The initial indications for LVAD placement in these patients were bridge to transplantation (n = 6 [37.5%]) or destination therapy (n = 10 [62.5%]). Fifteen patients (93.8%) required pump exchange due to pump thrombosis and 1 (6.2%) due to refractory driveline infection. Nine patients (56.2%) underwent repeat median sternotomy while a left subcostal approach was used in the remaining seven patients. Fifteen patients (93.7%) survived until hospital discharge. During the follow-up period (median, 155 days), 11 patients remained alive and 4 of these underwent successful cardiac transplantation. Conclusion HMII LVAD pump exchange can be safely performed for driveline infection or pump thrombosis when heart transplantation is not an option.


Nonalcoholic fatty liver disease accelerates kidney function decline in patients with chronic kidney disease: a cohort study.
This study aimed to investigate the association of nonalcoholic fatty liver disease (NAFLD) and its severity with the decline in kidney function in patients with chronic kidney disease (CKD). We conducted a cohort study of 1,525 CKD patients who underwent repeated health check-up examinations from January 2003 through December 2013. NAFLD was diagnosed by ultrasonography and its severity was assessed by the NAFLD fibrosis score. At baseline, the prevalence of NAFLD was 40.9%, and the mean estimated glomerular filtration rate (eGFR) was 59.1 ml/min/1.73 m2. The average follow-up was 6.5 years. The age- and sex-adjusted decline in eGFR was greater in patients with NAFLD (-0.79% per year, 95% CI -1.31%, -0.27%) compared to those without it (0.30%, 95% CI -0.14%, 0.76%; p = 0.002). In multivariable adjusted models, the average difference in annual percent change in decline in eGFR comparing patients with NAFLD to those without NAFLD was -1.06% (-1.73%, -0.38%; p = 0.002). The decline in eGFR associated with NAFLD was greater in patients with higher NAFLD fibrosis score, in those with proteinuria or with low eGFR at baseline ( <45 ml/min/1.73 m2), and in those who were smokers and hypertensive. Therefore, NAFLD is independently associated with CKD progression.


Normative versus consequential ethics in sexually violent predator laws: an ethics conundrum for psychiatry.
Nineteen states and the federal government have statutes for the civil commitment of sexually violent predators (SVP). The American Psychiatric Association has vigorously opposed SVP laws, citing the abuse of both individual civil rights and of psychiatry in forwarding preventive detention. Those who support the laws underscore that the statutes target highly dangerous sex offenders. There are two different approaches to understanding ethics-based problems and their solutions. The normative approach assumes that there is a universal, intuitive, abstract, correct answer to a given question. However, there is no universal right way to balance the important normative ethic of protecting individual rights with the equally important normative ethic of protecting public safety. A less universal approach, consequential ethics, becomes necessary when abstract normative values conflict and lead to opposing conclusions. In this commentary, we examine and attempt to resolve the conflicting positions raised by the SVP statutes by using consequential versus normative ethics.


Sexual and Gender Identity-Based Microaggressions: Differences by Sexual and Gender Identity, and Sex Assigned at Birth Among Dutch Youth.
Research describes several sexual and gender identity-based microaggressions that sexual and gender minority (SGM) people might experience. We aimed to examine the occurrence of different sexual and gender identity-based microaggressions among SGM youth and to identify differences by sexual and gender identity, and sex assigned at birth. Open-ended questions about daily experiences were coded for 16 types of sexual and gender identity-based microaggressions in two daily diary studies among Dutch SGM youth (Study 1: N = 90, M age = 17.64 SD = 1.78; Study 2: N = 393, M age = 18.36 SD = 2.65). Several types of microaggressions were identified, and there was sizable variability in the reported frequency. Overall, lesbian women and bisexual youth were less likely to report microaggressions than gay youth. Bisexual youth were less likely to report use of heterosexist or transphobic terminology than gay youth and youth assigned male at birth were less likely to report invalidation of LGBTQ identity than youth assigned female at birth. Last, gender minority youth were more likely to report familial microaggressions, invalidation of LGBTQ identity, and threatening behaviors than cisgender youth. Overall, this study provides empirical support using mixed qualitative and quantitative methods for theorized typologies of microaggressions among Dutch SGM youth.


Regional differences and similarities of familial amyloidotic polyneuropathy (FAP) presentation in Brazil.
Familial amyloidotic polyneuropathy (FAP) is a worldwide disease with various clinical presentations according to geographical origin of the cases. Brazil is a country of Portuguese colonization and Portuguese descendants are estimated to be more than 25 millions. The Brazilian FAP population was characterized in this text as having basically the same diseases characteristics as the most common Portuguese FAP type I patients.


Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components.
Polarized trafficking of synaptic proteins to axons and dendrites is crucial to neuronal function. Through forward genetic analysis in C. elegans, we identified a cyclin (CYY-1) and a cyclin-dependent Pctaire kinase (PCT-1) necessary for targeting presynaptic components to the axon. Another cyclin-dependent kinase, CDK-5, and its activator p35, act in parallel to and partially redundantly with the CYY-1/PCT-1 pathway. Synaptic vesicles and active zone proteins mostly mislocalize to dendrites in animals defective for both PCT-1 and CDK-5 pathways. Unlike the kinesin-3 motor, unc-104/Kif1a mutant, cyy-1 cdk-5 double mutants have no reduction in anterogradely moving synaptic vesicle precursors (SVPs) as observed by dynamic imaging. Instead, the number of retrogradely moving SVPs is dramatically increased. Furthermore, this mislocalization defect is suppressed by disrupting the retrograde motor, the cytoplasmic dynein complex. Thus, PCT-1 and CDK-5 pathways direct polarized trafficking of presynaptic components by inhibiting dynein-mediated retrograde transport and setting the balance between anterograde and retrograde motors.


Tsukuba science city: Japan tries planned innovation.
Tsukuba Science City is Japan's new municipal complex of research laboratories and educational facilities. About 30 percent of the nation's government research laboratories and more than 40 percent of its government research manpower are concentrated in the community. A brief history of the monumental project is presented and problems confronting the city are discussed.


[Critical areas and suture incompetence in interintestinal anastomoses].
Clinical observations confirming the presence of critical zones in blood supply of the intestine are presented. It was shown that exclusion of the vessels of the right half of the colon is responsible for the disturbance of blood supply in the terminal part of the small intestine. Suture bands should be displaced to the level at which the intramural pressure ensures the viability of the intestine in the anastomosis zone. This should be taken into account in resections of the transverse colon, left-side hemicolectomy, abdominal resection and frontal resection of the rectum.


Features and roles of T helper 22 cells in immunological diseases and malignancies.
T helper 22 (Th22) cell populations are a newly identified subset of CD4+ T cells that primarily mediate biological effects on the epithelial barrier through interleukin (IL)-22. Although, new studies showed that both Th22 and IL-22 are closely associated with the pathogenesis of inflammatory, autoimmune and allergic disease as well as malignancies. In this review, we aim to describe the development and characteristics of Th22 cells as well as their roles in the immunopathogenesis of immune-related disorders and cancer.


A cash-based intervention and the risk of acute malnutrition in children aged 6-59 months living in internally displaced persons camps in Mogadishu, Somalia: A non-randomised cluster trial.
Somalia has been affected by conflict since 1991, with children aged <5 years presenting a high acute malnutrition prevalence. Cash-based interventions (CBIs) have been used in this context since 2011, despite sparse evidence of their nutritional impact. We aimed to understand whether a CBI would reduce acute malnutrition and its risk factors. We implemented a non-randomised cluster trial in internally displaced person (IDP) camps, located in peri-urban Mogadishu, Somalia. Within 10 IDP camps (henceforth clusters) selected using a humanitarian vulnerability assessment, all households were targeted for the CBI. Ten additional clusters located adjacent to the intervention clusters were selected as controls. The CBI comprised a monthly unconditional cash transfer of US$84.00 for 5 months, a once-only distribution of a non-food-items kit, and the provision of piped water free of charge. The cash transfers started in May 2016. Cash recipients were female household representatives. In March and September 2016, from a cohort of randomly selected households in the intervention (n = 111) and control (n = 117) arms (household cohort), we collected household and individual level data from children aged 6-59 months (155 in the intervention and 177 in the control arms) and their mothers/primary carers, to measure known malnutrition risk factors. In addition, between June and November 2016, data to assess acute malnutrition incidence were collected monthly from a cohort of children aged 6-59 months, exhaustively sampled from the intervention (n = 759) and control (n = 1,379) arms (child cohort). Primary outcomes were the mean Child Dietary Diversity Score in the household cohort and the incidence of first episode of acute malnutrition in the child cohort, defined by a mid-upper arm circumference < 12.5 cm and/or oedema. Analyses were by intention-to-treat. For the household cohort we assessed differences-in-differences, for the child cohort we used Cox proportional hazards ratios. In the household cohort, the CBI appeared to increase the Child Dietary Diversity Score by 0.53 (95% CI 0.01; 1.05). In the child cohort, the acute malnutrition incidence rate (cases/100 child-months) was 0.77 (95% CI 0.70; 1.21) and 0.92 (95% CI 0.53; 1.14) in intervention and control arms, respectively. The CBI did not appear to reduce the risk of acute malnutrition: unadjusted hazard ratio 0.83 (95% CI 0.48; 1.42) and hazard ratio adjusted for age and sex 0.94 (95% CI 0.51; 1.74). The CBI appeared to increase the monthly household expenditure by US$29.60 (95% CI 3.51; 55.68), increase the household Food Consumption Score by 14.8 (95% CI 4.83; 24.8), and decrease the Reduced Coping Strategies Index by 11.6 (95% CI 17.5; 5.96). The study limitations were as follows: the study was not randomised, insecurity in the field limited the household cohort sample size and collection of other anthropometric measurements in the child cohort, the humanitarian vulnerability assessment data used to allocate the intervention were not available for analysis, food market data were not available to aid results interpretation, and the malnutrition incidence observed was lower than expected. The CBI appeared to improve beneficiaries' wealth and food security but did not appear to reduce acute malnutrition risk in IDP camp children. Further studies are needed to assess whether changing this intervention, e.g., including specific nutritious foods or social and behaviour change communication, would improve its nutritional impact. ISRCTN Registy ISRCTN29521514.


Hypoparathyroidism: an uncommon adverse effect of treatment with durvalumab.
Immune checkpoint inhibitors (ICIs) are monoclonal antibodies approved for the treatment of numerous cancer types. Toxicities induced by ICIs may affect any organ system and manifest as endocrinopathy. The main side effects related to treatment are immune-related adverse events (irAEs), especially thyroid dysfunction and hypophysitis. Rare endocrine irAEs are diabetes insipidus, hypoparathyroidism, thyrotoxic crisis and hypogonadism. We report a case of hypoparathyroidism induced by ICI treatment with durvalumab, which has not previously been described. Treatment with immune checkpoint inhibitors (ICIs) is associated with many endocrine side effects.It is recommended that patients treated with ICIs are observed by an endocrinologist.If side effects are treated accordingly, ICI therapy can continue.