[The microclimate of an unoccupied wintering sett of the badger, Meles meles (Carnivora: Mustelidae), in the Darwin State Nature Reserve, Vologda Region].
Data on the microclimate (air temperature and humidity) within an unoccupied badger sett in the Darwin Reserve (the Vologda Region) between September 2005 and May 2006 have been analyzed in relation to changes in the temperature and humidity of the ground air layer and soil. A positive correlation has been revealed between the temperature regime of the soil and air temperature within the sett. After the establishment of snow cover, air and soil temperatures within the sett vary slightly and barely depend on ambient air temperature.


Fetuin-A in newly detected type 2 diabetes mellitus as a marker of non-alcoholic fatty liver disease.
Fetuin-A has been implicated in the causation of metabolic disorders such as obesity, diabetes, and hepatic steatosis. Numerous studies have shown the association between levels of fetuin-A in type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). The levels of fetuin-A in newly detected type 2 diabetic (NDD) patients and its relationship with the presence of NAFLD have not been studied. To study the fetuin-A levels in patients with NDD and its relationship with NAFLD. A total of 60 NDD patients were studied. The diagnosis of NAFLD was made on the basis of transient elastography. Serum fetuin-A and serum fasting insulin were measured along with other investigations. The percentage of patients with NAFLD in NDD was 53.33%. Fetuin-A levels were significantly higher in NDD with NAFLD compared to those without NAFLD. There was no association of fetuin-A with age, systolic and diastolic blood pressure, fasting blood sugar (FBS), hemoglobin (Hb)A1c, fasting insulin, homeostatic model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and markers of advanced fibrosis. Fetuin-A levels beyond 1166.5 mcg/mL could predict the development of NAFLD with odds ratio (OR) of 4.33 (95% CI: 1.364-13.77), which remained significant after adjustment for various confounding factors. Fetuin-A is a reliable marker of NAFLD in NDD and is positively associated with insulin resistance (IR). The observation in this study suggests that high serum fetuin-A levels in patients with NAFLD do not merely reflect the effects of insulin resistance, but also a more extensive distortion of liver architecture.


A comparison of the cardiac actions of dopamine and noradrenaline in anaesthetized dogs and guinea-pig atria.
1. The positive chronotropic and inotropic actions of dopamine and noradrenaline have been compared in anaesthetized dogs and isolated guinea-pig atria. 2. Inotropic activity was measured with a strain-gauge arch in vagotomized dogs or estimated from max (dp/dt) in dogs with denervated hearts. 3. The effects of propranolol and haloperidol on the concentration-response curves to both amines were studied in isolated atria. 4. In anaesthetized vagotomized dogs noradrenaline was more potent than dopamine but dopamine appeared to have a selective inotropic action, less apparent with noradrenaline. In denervated hearts, doses of noradrenaline and dopamine which caused similar increases in max (dp/dt) also caused similar increases in heart rate. 5. In isolated atrial preparations, concentrations of dopamine and noradrenaline which produced similar increases in force of contraction also had similar chronotropic effects. 6. Propranolol produced a shift to the right of the concentration-response curves to both dopamine and noradrenaline but the antagonism of noradrenaline was quantitatively greater. Haloperidol had not effct in concentrations below those found to cause general tissue depression. 7. It is concluded that neither dopamine nor noradrenaline show any real difference in their relative inotropic and chronotropic activities in the absence of autonomic innervation.


The driving mechanism and targeting value of mimicry between vascular endothelial cells and tumor cells in tumor progression.
The difficulty and poor prognosis of malignant tumor have always been a difficult problem to be solved. The internal components of solid tumor are complex, including tumor cells, stromal cells and immune cells, which play an important role in tumor proliferation, migration, metastasis and drug resistance. Hence, targeting of only the tumor cells will not likely improve survival. Various studies have reported that tumor cells and endothelial cells have high plasticity, which is reflected in the fact that they can simulate each other's characteristics by endothelial-mesenchymal transition (EndMT) and vasculogenic mimicry (VM). In this paper, this mutual mimicry concept was integrated and reviewed for the first time, and their similarities and implications for tumor development are discussed. At the same time, possible therapeutic methods are proposed to provide new directions and ideas for clinical targeted therapy and immunotherapy of tumor.


The natural history of peanut allergy.
Between 1973 and 1985, 114 children, aged 2 to 14 years, underwent double-blind, placebo-controlled, food challenge (DBPCFC) to peanut. Thirty-two of 46 children with symptoms produced by DBPCFC to peanut were included in this longitudinal evaluation. Contact was made with the 32 subjects 2 to 14 years after their positive DBPCFC to peanut. All 32 subjects had exhibited a positive puncture skin test to peanut at the time of the original evaluation. Sixteen subjects had experienced symptoms caused by accidental peanut ingestion in the year before contact. Eight subjects had reacted to accidental ingestion in more than 1 year but less than 5 years before contact. Eight subjects had completely avoided peanut since the original evaluation and positive DBPCFC. No subjects could be demonstrated to have "outgrown" their peanut reactivity. All subjects tested continued to have skin reactivity to a puncture skin test with peanut extract. It appears uncommon for peanut-sensitive patients to lose their clinical reactivity, even after many years have elapsed. In addition, data were collected concerning reactions to other legumes and other (nonlegume) nuts. Only two patients with DBPCFC to peanut reacted on DBPCFC to soy or pea (one each). None of the subjects with a positive DBPCFC to peanut reacted to nonlegume nuts.


Robot-assisted transvaginal peritoneoscopy using confocal endomicroscopy: a feasibility study in a porcine model.
Optical biopsy methods such as probe-based confocal laser endomicroscopy (pCLE) provide useful intraoperative real-time information, especially during minimally invasive surgery with flexible endoscopic or robotic platforms. By translating the probe at constant pressure across the target tissue, undistorted "mosaics" can be produced. However, this poses ergonomic challenges with a conventional flexible endoscope. A 100 μm confocal depth pCLE probe was integrated into a previously described seven degrees-of-freedom articulated endoscopic robot. After estimating the average workspace created by a female pneumoperitoneum, the accessibility of the peritoneal cavity by the device for robot-assisted pCLE peritoneoscopy was calculated. To demonstrate its in vivo feasibility, the robot was inserted transvaginally in a pig, under laparoscopic vision. Optical biopsy was performed of several targets within the peritoneal cavity. The workspace analysis calculated that 88 % of the surface of an estimated average female pneumoperitoneum could be contacted by the probe using the robot transvaginally. In vivo, the robot was manoeuvred to provide views of all abdominal and pelvic organs. At each target there was robotic acquisition of still pCLE images, and slowly translating images for the construction of increased field-of-view mosaics up to 2 mm in length. Optical biopsies took 1-2 min per target, and at 3.5 μm lateral resolution, the mosaic images showed characteristic features of anterior abdominal wall, liver, and spleen. In the porcine model, the robotically actuated method of performing peritoneoscopy and pCLE mosaicked optical biopsy is safe and provides a consistent means of acquiring near-histological grade images of submesothelial tissue. Clinical translation is likely to provide sufficient accessibility of the peritoneal cavity.


Use of restricted significance tests in clinical trials: beyond the one- versus two-tailed controversy.
Whether to use "one-tailed" or "two-tailed" tests for clinical trials is examined in the more general context of restricted tests, developed by J. Neyman. This is complimented by a discussion of theoretical work of Savage and Bahadur. It is concluded that all tests of statistical significance have to be "restricted" in some sense and that failure to recognize the restrictions implied by "standard" methods of analysis can have a negative effect on the ability to detect treatment effects of new drugs in phase II and early phase III clinical trials.


[Event-recorder].
Event or loop recorders monitor heart rhythm using discontinuous ECG storage which enables them to obtain a correlation between symptoms and the underlying heart rhythm in patients with infrequent, short-lasting episodes. External event recorders with intermittent monitoring, i.e., with electrodes within the device, are suitable for patients with palpitations or tachycardia who remain conscious. External event recorders with continuous monitoring are tolerated by patients for a few weeks and have a limited diagnostic impact in patients with recurrent syncope. The implantable loop recorder (ILR) monitors heart rhythm for one year and after patient-triggered or automatic activation stores a one-lead ECG up to 42 minutes prior to device activation. The diagnostic benefit of ILR in comparison to conventional approaches has been demonstrated in randomised studies. Furthermore, an ILR identifies patients with recurrent syncope of unknown origin in whom a pacemaker implantation can avoid further episodes. Additional possible indications are the monitoring of atrial fibrillation, the diagnostics of infrequent palpitations and patients with seizures.


Factors associated with immunoglobulin G subclass polarization in naturally acquired antibodies to Plasmodium falciparum merozoite surface proteins: a cross-sectional survey in Brazilian Amazonia.
We investigated immunoglobulin G (IgG) subclass antibody responses to Plasmodium falciparum merozoite surface protein 1 (MSP-1) and MSP-2 in 112 malaria-exposed subjects in Brazil. IgG3 polarization was primarily epitope driven, being little affected by cumulative or current exposure to malaria and not affected by a subject's age and Fcgamma receptor IIA genotype.


Antifungal resistance in Candida spp within the intra-abdominal cavity: study of resistance acquisition in patients with serial isolates.
Antifungal susceptibility testing is mostly conducted on blood-cultured Candida spp isolates. Because the intra-abdominal cavity has been highlighted as a hidden echinocandin-resistant C. glabrata reservoir, we assessed whether testing sequential isolates from a given patient might increase the chances of detecting antifungal resistance. Intra-abdominal initial and sequential isolates from the same species from patients included in the CANDIdaemia in MADrid study (January 2019 to June 2022) were studied. We assessed antifungal susceptibility to amphotericin B, azoles, anidulafungin, micafungin, and ibrexafungerp using European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology and molecularly characterized resistant isolates. We collected 308 isolates (C. albicans [n = 179/308; 58.1%], C. glabrata [n = 101/308; 32.8%], C. tropicalis [n = 17/308; 5.5%], and C. parapsilosis [n = 11/308; 3.6%]) from 112 patients distributed as incident (n = 125/308) and sequential (n = 183/308). Per patient resistance rates of fluconazole (13.4% [15/112] vs. 8% [9/112]); 5.4% proportions difference (95% CI, -2.7% to 13.5%, p 0.09) and echinocandins (8.9% [10/112] vs. 1.8% [2/112]); 7.1% proportions difference (95% CI; 1.2-12.9%; p 0.01) were higher when considering all available isolates than only incident isolates. Resistance was detected in 18 of 112 patients and would have been overlooked in 11 of 18 (61.1%) patients if only incident isolates had been studied. Of the patients who harboured fluconazole or echinocandin-resistant isolates, 14 of 15 and 8 of 10 had received or were receiving fluconazole or echinocandins, respectively. Testing sequential Candida isolates from intra-abdominal samples is required to detect antifungal resistance, particularly to echinocandins, in patients whose incident isolates turned out to be susceptible. Furthermore, patients with echinocandin-resistant infections had frequently used echinocandins and had common secondary resistance acquisition.


Foliar-applied selenium nanoparticles alleviate cadmium stress through changes in physio-biochemical status and essential oil profile of coriander (Coriandrum sativum L.) leaves.
Since large areas of agricultural soils around the world are contaminated by Cd, a cost-effective and practical method is needed for the safe production of edible plants. The effective role of many nanomaterials to improve plant yield by mitigating environmental pollutions is addressed; however, the impacts of selenium nanoparticles (Se-NPs) have not been well-known yet. The aim of this work was to investigate foliar application of Se-NPs on yield, water content, proline concentration, phenolic content, lipid peroxidation, and essential oil (EO) attributes of coriander (Coriandrum sativum L.) under Cd stress. The plants were exposed to Cd contamination (0, 4, and 8 mg L-1) and foliar application of Se-NPs (0, 20, 40, and 60 mg L-1). The results showed increased Cd accumulation in roots and shoots of coriander plants upon Cd stress; however, Se-NPs alleviated the uptake of Cd. Cd toxicity, particularly 8 mg L-1, decreased shoot and root weight, chlorophyll (Chl), and relative water content (RWC), while Se-NPs improved these attributes. The Cd concentration at 4 mg L-1 and Se-NPs at 40 or 60 mg L-1 increased phenolic and flavonoid contents as well as EO yield. Proline concentration and malondialdehyde (MDA) increased by enhancing Cd stress, but Se-NPs decreased MDA. The GC/MS analysis showed that the main EO constitutes were n-decanal (18.80-29.70%), 2E-dodecanal (14.23-19.87%), 2E-decanal (12.60-19.40%), and n-nonane (7.23-12.87%), representing different amounts under Cd pollution and Se-NPs. To sum up, Se-NPs at 40-60 mg L-1 are effective in alleviating Cd stress.


Salmonella enterica shedding in hospitalized horses and associations with diarrhea occurrence among their stablemates and gastrointestinal-related illness or death following discharge.
To evaluate the potential association between Salmonella enterica shedding in hospitalized horses and the risk of diarrhea among stablemates, and to characterize gastrointestinal-related illness and death following discharge among horses that shed S. enterica while hospitalized. Retrospective cohort study [corrected]. 221 horses (59 that shed S. enterica during hospitalization and 162 that tested negative for S. enterica shedding ≥ 3 times during hospitalization). Information from medical records (signalment, results of microbial culture of fecal samples, clinical status at the time of culture, and treatment history) was combined with data collected through interviews with horse owners regarding formerly hospitalized horses and their stablemates. Data were analyzed to investigate risk factors for death and diarrhea. Occurrence of diarrhea among stablemates of formerly hospitalized horses was not associated with S. enterica shedding in hospitalized horses but was associated with oral treatment with antimicrobials during hospitalization. Salmonella enterica shedding during hospitalization was not associated with risk of death or gastrointestinal-related illness in study horses ≤ 6 months after discharge, but shedding status and history of gastrointestinal illness were associated with increased risk of death during the preinterview period. Stablemates of horses that shed S. enterica during hospitalization did not appear to have an increased risk for diarrhea, but comingling with horses that receive orally administered antimicrobials may affect this risk. Salmonella enterica shedding during hospitalization may be a marker of increased long-term risk of death after discharge. Risks are likely influenced by the S enterica strain involved and biosecurity procedures used.


Simple clinical assessment of colonic response to food.
The colonic response to food (CRF) is an integrated function of the colon that has been poorly studied in clinical practice. This study describes a new method to measure it, based on the progress of radio-opaque markers, and shows the results in healthy subjects and in patients with irritable bowel syndrome (IBS). Thirty healthy subjects and 43 patients suffering from IBS were studied. Two studies of colonic transit time (CTT), at rest and after eating a standard test meal, were performed. CRF was quantified by calculating the variation in number of markers in each zone of interest of the large bowel using X-ray films of the abdomen taken before and after eating. The results were as follows: (1) CRF is characterised by caudal propulsion of the colonic contents in the two groups. In controls, there is emptying of the cecum-ascending colon region and filling of the distal large bowel. In IBS patients, only emptying of the left transverse colon and the splenic flexure is found. (2) IBS patients have a delayed CTT because of slowing in the right and left colon, and this is both before and after a meal. The determination of the movements of markers after eating is a simple method that is useful in clinical practice to evaluate CRF.


Potentially inappropriate use of psychotropic medications in hospitalized elderly patients in France: cross-sectional analysis of the prospective, multicentre SAFEs cohort.
In France, there is evidence to suggest that 50% of elderly individuals are prescribed psychotropic medications. However, it is known that use of these agents increases the risk of falls, fractures and delirium in older people. To study the consumption of 'potentially inappropriate medication' (PIM) among patients aged>or=75 years, paying particular attention to psychotropic drugs and the factors influencing the use of 'potentially inappropriate psychotropics' (PIPs). This was a cross-sectional analysis of a prospective multicentre cohort of 1306 hospitalized French patients aged>or=75 years (the SAFEs [Sujet Agé Fragile: Evaluation et suivi (Frail Elderly Subjects: Evaluation and follow-up)] cohort). The present analysis involved the 1176 patients for whom there was information on the usual treatments being taken in the 2 weeks before hospitalization. The drugs were coded according to the Anatomical Therapeutic Chemical classification; the Beers list as updated in 2003 defined which medications were considered PIPs. Standardized geriatric assessment variables were recorded on inclusion in the study. Logistic regression analysis was performed to identify factors linked to use of psychotropics and PIPs. The mean number of drugs taken was 5.7+/-2.9 per patient. Twenty-eight percent of patients took at least one PIM. The number of patients who had taken at least one psychotropic drug in the 2 weeks before hospitalization (mean 1.6+/-0.9 psychotropics per patient) was 589 (50.1%). More than half of both the 510 patients with a depressive syndrome and the 543 patients affected by dementia were treated with psychotropics. Multivariate analysis showed that prescription of psychotropics was linked to the presence of a dementia syndrome (odds ratio [OR]=1.4; 95% CI 1.1, 1.9; p=0.03), the presence of a depressive syndrome (OR=1.7; 95% CI 1.3, 2.1; p<0.001), living in an institution (OR=2.2; 95% CI 1.5, 3.4; p<0.001), use of more than five drugs (OR=3.2; 95% CI 2.5, 4.2; p<0.001) and Charlson's co-morbidity score>1 (OR=0.6; 95% CI 0.5, 0.8; p=0.001). Nineteen percent of all psychotropics prescribed were PIPs. Of these PIPs, 66.5% were anxiolytics, 28.4% were antidepressants and 5.1% were antipsychotics. Use of PIPs in the multivariate analysis was associated only with consumption of more than five drugs (OR=1.7; 95% CI 1.1, 2.5; p=0.01). PIM use is common among hospitalized older adults in France. The most important determinant of risk of receiving a psychotropic medication or a PIP was the number of drugs being taken. The elderly, who have multiple co-morbidities, complex chronic conditions and are usually receiving polypharmacy, are at increased risk for adverse drug events. These adverse events are often linked to problems that could be preventable such as delirium, depression and falls. Regular review of prescriptions would help optimize prescription of psychotropics in the elderly. The Beers list is a good tool for evaluating PIMs but is too restrictive with respect to psychotropics; in the latter respect, the list could usefully be widened.


The LDL receptor is regulated by membrane cholesterol as revealed by fluorescence fluctuation analysis.
Membrane cholesterol-rich domains have been shown to be important for regulating a range of membrane protein activities. Low-density lipoprotein receptor (LDLR)-mediated internalization of cholesterol-rich LDL particles is tightly regulated by feedback mechanisms involving intracellular sterol sensors. Since LDLR plays a role in maintaining cellular cholesterol homeostasis, we explore the role that membrane domains may have in regulating LDLR activity. We expressed a fluorescent LDLR-mEGFP construct in HEK293T cells and imaged the unligated receptor or bound to an LDL/DiI fluorescent ligand using total internal reflection fluorescence microscopy. We studied the receptor's spatiotemporal dynamics using fluorescence fluctuation analysis methods. Image cross correlation spectroscopy reveals a lower LDL-to-LDLR binding fraction when membrane cholesterol concentrations are augmented using cholesterol esterase, and a higher binding fraction when the cells are treated with methyl-β-cyclodextrin) to lower membrane cholesterol. This suggests that LDLR's ability to metabolize LDL particles is negatively correlated to membrane cholesterol concentrations. We then tested if a change in activity is accompanied by a change in membrane localization. Image mean-square displacement analysis reveals that unligated LDLR-mEGFP and ligated LDLR-mEGFP/LDL-DiI constructs are transiently confined on the cell membrane, and the size of their confinement domains increases with augmented cholesterol concentrations. Receptor diffusion within the domains and their domain-escape probabilities decrease upon treatment with methyl-β-cyclodextrin, consistent with a change in receptor populations to more confined domains, likely clathrin-coated pits. We propose a feedback model to account for regulation of LDLR within the cell membrane: when membrane cholesterol concentrations are high, LDLR is sequestered in cholesterol-rich domains. These LDLR populations are attenuated in their efficacy to bind and internalize LDL. However, when membrane cholesterol levels drop, LDL has a higher binding affinity to its receptor and the LDLR transits to nascent clathrin-coated domains, where it diffuses at a slower rate while awaiting internalization.


A preliminary look at loneliness as a moderator of the link between perfectionism and depressive and anxious symptoms in college students: does being lonely make perfectionistic strivings more distressing?
An integrative model involving perfectionism [Hewitt, P. L., & Flett, G. L. (1991). Perfectionism in the self and social contexts: Conceptualization, assessment, and association with psychopathology. Journal of Personality and Social Psychology, 60, 456-470] and loneliness as predictors of depressive and anxious symptoms was proposed and tested in 383 college students. Beyond the expected additive influences of the two predictors in the prediction of symptoms, loneliness was also hypothesized to moderate the link between perfectionism and symptoms. Results indicated that other-oriented perfectionism predicted anxious symptoms, whereas socially prescribed perfectionism predicted both depressive and anxious symptoms. Loneliness was found to add incremental validity to these predictions. Moreover, the Perfectionism x Loneliness interaction was found to further augment the prediction of depressive and anxious symptoms. These findings are taken to offer support for a more contextual model of perfectionism. Some implications of the present findings are discussed.


Gender Differences in Perceptions and Attitudes of Medical Students Toward Neurosurgery: A German Nationwide Survey.
Despite advances in gender equity, the paucity of women neurosurgeons remains. In Germany, women accounted for only 24% of the specialists who completed their neurosurgical training in 2019. We sought to explore the perceptions of medical students in Germany toward a neurosurgical career, focusing on gender-specific differences. A digital 26-item questionnaire with a Likert 4-point scale and open-ended questions was distributed to the German medical school student bodies. Data were analyzed to determine statistically significant intragroup variability between women and men. Two hundred ten medical students participated in the survey. Women and men were equally interested in brain pathologies (38% vs. 47%, strongly agreed), whereas interest in neurosurgery was significantly greater in men (12% vs. 26%, strongly agreed). Men were less likely to believe that women neurosurgery residents would face inequality at work. They were also less likely to support a gender quota in neurosurgery. Yet, both women and men were convinced that a rise in the number of women would positively impact the field. No gender dependency was seen in students' strive for success and prestige. Men felt discouraged from pursuing neurosurgery because they feared an unpleasant work environment, whereas women were concerned about neurosurgery not being family-friendly. Regardless of gender, the greatest factor deterring students from neurosurgery was poor work-life balance. Awareness must be raised concerning gender inequity and discrimination in our specialty. A multifaceted approach is imperative to develop neurosurgery into a profession where gender no longer hinders access to training and success in the field.


Baricitinib provides rapid and sustained improvements in absolute EASI and SCORAD outcomes in adults with moderate-to-severe atopic dermatitis.
Baricitinib is an oral selective Janus kinase 1/2 inhibitor approved for moderate-to-severe atopic dermatitis (AD) in adults. To evaluate absolute Eczema Area and Severity Index (EASI) and SCORing of Atopic Dermatitis (SCORAD) outcomes over 16 weeks and to link disease severity categories to quality of life (QoL) improvements. This post-hoc analysis included patients enrolled in Phase3 monotherapy (BREEZE-AD1/AD2) and topical corticosteroid (TCS) combination therapy (BREEZE-AD7) trials and analyzed baricitinib 2 and 4 mg vs. placebo. Categorical outcomes were analyzed using Fisher's exact test. Significantly more baricitinib-treated patients reached EASI ≤ 7 and SCORAD < 25 as early as week 1 in monotherapy and week 2 in TCS combination therapy, compared to placebo. Significant response vs. placebo was sustained until week 16 for EASI ≤ 7 (AD1/2 [p-value vs. placebo]: 2 mg = 19.9%, 4 mg = 25.4% [p = 0.001] and AD7: 2 mg = 40.4% [p = 0.087], 4 mg = 48.6% [p = 0.003]) and SCORAD < 25 (AD1/2: 2 mg = 12.2%, 4 mg = 19.4% [p = 0.001] and AD7: 2 mg = 30.3% [p = 0.025], 4 mg = 34.2% [p = 0.004]) severity categories. These effects were accompanied by rapid improvements in QoL. Baricitinib-treated patients rapidly achieved recommended absolute EASI and SCORAD treatment outcomes which were sustained until week 16. Improvements in QoL were greater than EASI severity categories reflected, indicating that physician-assessed scores do not necessarily correlate with patients' impression of AD severity.


Methods on Skull Stripping of MRI Head Scan Images-a Review.
The high resolution magnetic resonance (MR) brain images contain some non-brain tissues such as skin, fat, muscle, neck, and eye balls compared to the functional images namely positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI) which usually contain relatively less non-brain tissues. The presence of these non-brain tissues is considered as a major obstacle for automatic brain image segmentation and analysis techniques. Therefore, quantitative morphometric studies of MR brain images often require a preliminary processing to isolate the brain from extra-cranial or non-brain tissues, commonly referred to as skull stripping. This paper describes the available methods on skull stripping and an exploratory review of recent literature on the existing skull stripping methods.


Microsolvation of cationic dimers in 4He droplets: geometries of A+2(He)N (A=Li, Na, K) from optimized energies.
Ab initio computed interaction forces are employed to describe the microsolvation of the A+2(2Sigma) (A=Li, Na, K) molecular ion in 4He clusters of small variable size. The minimum energy structures are obtained by performing energy minimization based on a genetic algorithm approach. The symmetry features of the collocation of solvent adatoms around the dimeric cation are analyzed in detail, showing that the selective growth of small clusters around the two sides of the ion during the solvation process is a feature common to all three dopants.


Use of transient elastography in patients with HIV-HCV coinfection: A systematic review and meta-analysis.
Patients with HIV-hepatitis C virus (HCV) coinfection progress towards liver fibrosis and cirrhosis more rapidly compared with HCV mono-infected individuals. This necessitates an accurate assessment of liver stiffness with transient elastography to guide treatment. Searches of PubMed, EMBASE, Web of Science, and the Cochrane Library databases were performed through January 2016 to assess the diagnostic accuracy of transient elastography for liver stiffness in the HIV-HCV population. Included studies were analyzed according to the Cochrane DTA Working Group methodology. Bivariate and hierarchical models were used to compute pooled sensitivity and specificity. Positive and negative likelihood ratios were also determined. A Fagan nomogram was constructed. Meta-regression analysis was performed with assessment of publication bias using Deeks' funnel plot asymmetry testing. A total of six studies (n = 756) met the inclusion criteria. The diagnostic accuracy of elastography for the diagnosis of moderate (≥F2) fibrosis was 88% (95% confidence interval [CI], 0.85-0.90). The pooled sensitivity and specificity of moderate fibrosis was 97% (95% CI, 0.82-0.91) and 64% (95% CI, 0.45-0.79), respectively. The diagnostic accuracy of elastography for the assessment of cirrhosis was 94% (95% CI, 0.91-0.95). The pooled sensitivity and specificity for cirrhosis was 90% (95% CI, 0.74-0.97) and 87% (95% CI, 0.80-0.92), respectively. Meta-regression analysis demonstrated that CD4 cell count did not impact diagnostic accuracy of elastography. Transient elastography is a noninvasive imaging modality with excellent ability to assess for cirrhosis in patients with HIV-HCV coinfection.


Chemo-Photothermal Combination Therapy of HER-2 Overexpressing Breast Cancer Cells with Dual-Ordered Mesoporous Carbon@Silica Nanocomposite.
In cancer treatment, the complexity of tumors seriously affects the therapeutic potential of the treatment. Treatments with combination therapy result in more potent effects than monotherapy or their theoretical combination in cancer treatment. Photothermal therapy (PTT) includes applying phototherapeutic agents that cause local hyperthermia responsible for the thermal ablation of tumor cells after applying near-infrared light and is often applied with other combination therapies. In this study, the chemo-PTT potential of synthesized drug-loaded and targeted GEM/TRA-MC@Si nanocomposite on Her2 positive breast cancer cell line (SK-BR-3) and human triple-negative breast cancer cell line (MDA-MB-231) was investigated using NIR application as in vitro. First, the cell viability (IC50) value of the GEM/TRA-MC@Si nanocomposite was determined as 25 µg/µL. Then, chemo-PTT was performed, and the viability of the cells was evaluated. In addition, the live/dead cell rate was established by staining with the Calcein-AM and EthD-1, and apoptosis tests were completed. When the surface temperature of Her2 positive SK-BR-3 cells exceeded 47 °C during PTT with an irradiation time of > 100 s, it caused cell death. In this study, it was demonstrated that in vitro PTT (1 W/cm2, 180 s) was applied using GEM/TRA-MC@Si nanocomposite (25 µg/mL) on her2 + SK-BR-3 cell line, which contributed to the reduction of cell viability. In addition, this study demonstrates that chemo-PTT with targeted GEM/TRA-MC@Si nanocomposite induced SK-BR-3 cell viability and can initiate cell death through the apoptosis pathway under optimized irradiation conditions. Herewith chemo-PTT combination therapy of targeted GEM-TRA/MC@Si nanocomposite was found to be effective on SK-BR-3 cells as in vitro.


The effects of coupled B1 fields in B1 encoded TRASE MRI - A simulation study.
Transmit Array Spatial Encoding (TRASE) is a novel MRI technique that encodes spatial information by introducing phase gradients in the transmit RF (B1) magnetic field. Since TRASE relies on the use of multiple RF fields (B1 fields with different phase gradients) for k-space traversal, a TRASE pulse sequence requires RF pulses that are produced by switching between the transmit coils (B1 fields). However, interactions among the transmit RF coils can cause un-driven coils to produce unwanted B1 fields that impair the spatial encoding. Therefore, TRASE is sensitive to B1 field perturbations arising from inductive coupling among the RF transmit coils and any B1 field isolation (coil decoupling) technique requires an understanding of the effects of the B1 field interactions. The purpose of this study was to investigate the effects of B1 field coupling using Bloch equation based simulations and to determine the acceptable level of B1 field interactions for 2D TRASE imaging. The simulations show that 2D TRASE MRI (using a 3-coil setup) displays ideal performance for pairwise coupling constant lower than k = 0.01 while having acceptable performance up to k = 0.1. This translates into S12 measurements of range ~(- 50 dB to -30 dB) required for successful 2D TRASE MRI in this study. This result is of crucial importance for designers of practical TRASE transmit array systems.


Inventory management performance for laboratory commodities and their challenges in public health facilities of Gambella Regional State, Ethiopia: A mixed cross-sectional study.
Sustaining an adequate inventory level of laboratory commodities is critical as 70% of medical decisions are made using laboratory-related information. However, millions of populations in developing countries still do not get elementary laboratory services due to the inaccessibility of laboratory commodities. Hence, this study aimed to assess inventory management performance and challenges for laboratory commodities in public health facilities of Gambella regional state, Ethiopia. A health facility-based descriptive cross-sectional study was conducted using a mixed quantitative and qualitative method in seventeen public health facilities of the Gambella regional state between May and July 2021. Data were collected from documents, health professionals, and health care facilities' warehouses. Quantitative data were analyzed using Excel spreadsheets version 14 and SPSS version 23. In the qualitative part, 18 key informants were interviewed, and data were analyzed using thematic analysis techniques. The average availability of laboratory commodities on the day of the visit was 60.39% in health facilities. Over the past year, 12.94% (37,488.76 US$) of laboratory commodities were wasted due to damage and expiration, while the average stock out date was 58 days. The average accuracy, completeness, and timeliness of the report and requisition form were 49%, 71%, and 64%, respectively. The health facilities had attained only, 68.2% of the storage conditions criteria. Lack of adequate and committed staff, budget constraints, insufficient storage space, frequent shortages of commodities from the suppliers, lack of frequent supervision, and feedback from higher officials were the main challenges for inventory management of laboratory commodities. The inventory management for laboratory commodities was inadequate, which was disclosed by inaccurate records and reports, stock-outs, high wastage rate, lack of adequate staff, budget constraints, and unacceptable storage conditions criteria. The study result suggests strict and close monitoring is needed to improve the inventory management performance for laboratory commodities at health facilities.


Probabilistic health risk assessment of carcinogenic emissions from a MSW gasification plant.
Health risk assessment due to the atmospheric emissions of carcinogenic pollutants (PCDD/Fs and Cd) from a waste gasification plant is performed by means of a probabilistic approach based on probability density functions for the description of the input data of the model parameters involved in the assessment. These functions incorporate both the epistemic and stochastic uncertainty of the input data (namely, the emission rate of the pollutants) and of all the parameters used for individual exposure assessment through the pathways of inhalation, soil ingestion and dermal contact, and diet. The uncertainty is propagated throughout the evaluation by Monte Carlo technique, resulting in the probability distribution of the individual risk. The median risk levels nearby the plant are in the 10(-8)-10(-10) range, ten-fold lower than the deterministic estimate based on precautionary values for the input data; however, the very upper percentiles (>95th) of the risk distribution can exceed the conventional 10(-6) reference value. The estimated risk is almost entirely determined by the Cd exposure through the diet; the pathways arising from PCDD/Fs exposure are without any practical significance, suggesting that the emission control should focus on Cd in order to reduce the carcinogenic risk. Risk variance decomposition shows the prevailing influence on the estimated risk of the Cd concentration at the emission stack: thus, for a more accurate risk assessment the efforts should focus primarily on the definition of its probability density function.


Myelin imaging measures as predictors of cognitive impairment in MS patients: A hybrid PET-MRI study.
Cognitive impairment is one of the concerns of Multiple Sclerosis (MS) and has been related to myelin loss. Different neuroimaging methods have been used to quantify myelin and relate it to cognitive dysfunctions, among them Magnetization Transfer Ratio (MTR), Diffusion Tensor Imaging (DTI), and, more recently, Positron Emission Tomography (PET) with 11C-PIB. To investigate different myelin imaging modalities as predictors of cognitive dysfunction. Fifty-one MS patients and 24 healthy controls underwent clinical and neuropsychological assessment and MTR, DTI (Axial Diffusion-AD and Fractional Anisotropy-FA maps), and 11C-PIB PET images in a PET/MR hybrid system. MTR and DTI(FA) differed in patients with or without cognitive impairment. There was an association of DTI(FA) and DTI(AD) with cognition and psychomotor speed for progressive MS, and of 11C-PIB uptake and MTR for relapsing-remitting MS. MTR in the Thalamus (β= -0.51, p = 0.021) and Corpus Callosum (β= -0.24, p = 0.033) were predictive of cognitive impairment. DTI-FA in the Caudate (β= -26.93, p = 0.006) presented abnormal predictive result. Lower myelin content by 11C-PIB uptake was associated with worse cognitive status. MTR was predictive of cognitive impairment in MS.


Allantoin and allantoic acid titre in the faeces and tissues of the developing larva of the moth, Orthaga exvinacea Hampson.
Allantoin and allantoic acid are investigated in the faeces and tissues of the developing sixth instar larva of the moth, Orthaga exvinacea. The nitrogen excreted as allantoin and allantoic acid is compared with nitrogen excreted as uric acid and ammonia. The larva excretes 2.35-5.14 mumol/g allantoin and 0.74-1.34 mumol/g allantoic acid which account for 0.83 to 2.39% and 0.23 to 0.53%, respectively, of the excreted total nitrogen. Allantoin and allantoic acid are found to be minor nitrogenous end-products of the larva. Allantoin and allantoic acid are also present in the haemolymph and fat body of the larva in varying concentrations. The level of allantoin in the haemolymph shows a negative correlation with the allantoin concentration of faeces and fat body. The allantoin is found to be stored in the fat body at a low level. The results of the present study also indicate the coexistence of uric acid storage and uricolysis.


Monensin is obligatory for the cytotoxic action of a disulfide linked methotrexate-anti-transferrin receptor conjugate.
Methotrexate (MTX) in the form of a gamma-cysteinylglycine derivative was disulfide linked to a monoclonal antibody reactive with the human transferrin receptor to give an antibody-MTX conjugate (anti-TfR-MTX). Antibody directed delivery of MTX to cell surface receptors was readily detected by flow cytometry using an anti-MTX antibody plus a secondary fluorescent antibody probe. Despite the presence of ample drug on the cell membrane, the conjugate alone was not cytotoxic over the course of several days. Expression of specific toxic activity, however, was obtained in conjunction with the carboxylic ionophore monensin, in whose presence anti-TfR-MTX displayed an IC50 of 8 X 10(-8) M. These results suggest that the ionophore causes antibody-drug conjugate to bypass the normal transferrin receptor cyclic pathway, allowing sufficient drug to reach, bind to, and inactivate intracellular dihydrofolate reductase.


Impact of the more restrictive definition of atypical squamous cells introduced by the 2001 Bethesda System on the sensitivity and specificity of the Papanicolaou test: a 5-year follow-up study of Papanicolaou tests originally interpreted as ASCUS, reclassified according to Bethesda 2001 criteria.
The Bethesda 2001 (B2001) classification system raised the threshold for reporting atypical squamous cells. The category of Atypical Squamous Cells of Undetermined Significance (ASCUS)-favor reactive has been eliminated with a recommendation for cytologists to judiciously downgrade those Papanicolaou (Pap) tests that would formerly have been in this category to Negative for Intraepithelial Lesion or Malignancy (NILM). The effect of this change on sensitivity and specificity of the Pap test is not yet known. A total of 535 consecutive SurePath Pap tests interpreted as ASCUS during a period from March 1 through December 31, 2001, with follow-up polymerase chain reaction(PCR)-based human papilloma virus (HPV) testing, were independently reviewed by 3 pathologists and 1 cytotechnologist who reinterpreted these tests according to Bethesda 2001 criteria. Follow-up HPV and biopsy results were compiled for a 5-year period. By consensus of the 4 observers, 169 (32%) of the ASCUS cases were downgraded to NILM. These cases showed a lower rate of underlying high-risk HPV infection (11% vs 30%) and cervical intraepithelial neoplasia of grades 2 to 3 (CIN 2/3) (5% vs 10%) on follow-up than those tests that were reinterpreted as ASCUS or higher. Nine women with follow-up CIN 2/3 would have had the Pap test interpreted as NILM instead of ASCUS under Bethesda 2001 (20% of all CIN 2/3 found). Individual reviewers downgraded 29% to 42% Pap tests to NILM including those of 5 to 10 women with follow-up CIN 2/3. The ASCUS threshold established by B2001 prevents a sizeable subset of women from having follow-up for ASC. However, as a consequence, a few women with CIN 2/3 are downgraded to NILM. The cost savings thus achieved must be weighed against the lost opportunities to detect CIN 2/3.


Intrathecal high-dose morphine induces spinally-mediated behavioral responses through NMDA receptors.
Previous research has demonstrated that intrathecal i.t. morphine in a dose of 60.0 nmol into the spinal subarachnoid space of mice can evoke nociceptive behavioral responses consisting of a severe hindlimb scratching directed toward the flank followed by biting/licking of the hindpaw. The present study was undertaken to examine the involvement of spinal N-methyl-D-aspartate (NMDA) and opioid receptors on the behavioral responses evoked by high-dose i.t. morphine. Pretreatment with naloxone, an opioid receptor antagonist (1.0 and 4.0 mg/kg, s.c.), failed to reverse the morphine-evoked behavioral response, suggesting that the morphine effect is not mediated through the opioid receptors in the spinal cord. The morphine-induced behavior was dose-dependently inhibited by i.t. co-administration of the competitive NMDA receptor antagonists, D(-)-2-amino-5-phosphonovaleric acid (D-APV) (6.25-50.0 pmol) and 3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) (3.125-25.0 pmol). The characteristic behavior was also reduced by co-administration of (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5,10-imine maleate (MK-801) (74.1-250 pmol), an NMDA ion-channel blocker. Ifenprodil, a competitive antagonist of the polyamine recognition site of NMDA receptor ion channel complex, produced a dose-related inhibitory effect on the behavioral response to i.t. morphine with less potency than the competitive and non-competitive antagonists examined. High doses of (+)-HA-966, a glycine/NMDA antagonist, induced a dose-dependent inhibition of morphine-induced response. The effective dose of i.t. 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, needed to reduce the morphine-induced response, was approximately 10-fold greater than that of D-APV. These results suggest that spinal NMDA receptors, but not non-NMDA receptors, may be largely involved in elicitation of the behavioral episode following i.t. injection of morphine in mice.


Mouse skin ornithine decarboxylase induction and tumor promotion by cyclohexane.
Cyclohexane, a frequently used solvent in industry, was assessed for its tumorigenic potential on mouse skin following multistage initiation-promotion protocols. The activity of ornithine decarboxylase (ODC), a marker of tumor promotion was found to be induced by the topical application of cyclohexane. This ODC induction was dependent on the dose of cyclohexane used and the duration of application. Effect of protein synthesis inhibitors and the modifiers of tumor promotion on the cyclohexane induced ODC activity was also studied. ODC induction was inhibited by cycloheximide and also, up to some extent, by actinomycin D. Inhibitors of stage II tumor promotion showed more effect on the ODC induction by cyclohexane as compared to the inhibitors of stage I tumor promotion. In chronic animal bioassay experiments topical application of cyclohexane to DMBA initiated mouse skin resulted in just 10% of tumor bearing animals while prior application of TPA for two weeks resulted in 45% of tumor bearing animals. Collectively, the present study demonstrates that cyclohexane is more effective as a stage II tumor promoter over mouse skin and possibly affects the biochemical events at the molecular level.


Maintained effect of a training program on attitudes towards depression in family physicians.
Family doctors' (FD) attitudes likely play an important role in the recognition and management of depression. The purpose of the study was to prospectively analyse the short-term and long-term impact of a specifically designed training program on attitudes towards depression among FDs. A prospective, educational intervention, single group pre- and post-test study with three assessments (pre, post, and 6-month follow-up) was conducted. Participants included 1322 certified FDs who had enrolled voluntarily in a structured postgraduate training in depression. This course was mainly practical and guided by case reports and real clinical experiences. The course was based on Patient's Unmet Needs and Doctors Educational Needs (PUNS & DENS) methodology. Primary outcome was assessed through the Depression Attitudes Questionnaire (DAQ). In total, 970 subjects completed the pre-post assessments, and 787 also completed the 6-month follow-up. After training, FDs positively changed their attitudes towards the management of depression. A significant change was observed in 18 of 20 items of the DAQ. The distinction between unhappiness and depression was initially found to be difficult in 41% of FDs. After the course, the percentage was reduced to 27%. Agreement with the statement that 'psychotherapy is an exclusive practice of specialists' strikingly changed from 57% to 23%. Minimal differences were noted between the post-training assessment and the 6-month follow-up. Attitudes towards depression in FDs can be modified by a structured training program, and this change is maintained over the long term. A short training in psychotherapy (cognitive-behavioural, problem-solving based and psycho-educative oriented) significantly increases the confidence of FDs in treating depression.


Clotting factor activity in thawed Octaplas® LG during storage at 2-6°C for 6 days from a quality assurance point of view.
Octaplas® LG is a second-generation solvent/detergent-treated plasma that offers an additional safety benefit by prion elimination. The stability of clotting factors of the new S/D plasma after thawing has not been investigated yet. This study intended to measure the time course of fibrinogen, FII, FV, FVII, FVIII, FIX, PC, fPS and PI through storage at 2-6°C over 6 days. We investigated 20 plasma bags (five bags per blood group) and measured fibrinogen, FII, FV, FVII, FVIII, FIX, PC, fPS and PI immediately after thawing and after 2, 4, 6, 24, 48, 72, 96, 120 and 144 h storage at 2-6°C. Five separate plasma bags were thawed and stored at 2-6°C for microbiological assessment. After 6 days samples were drawn for blood cultures that were incubated for six more days. After 6 days FII, FIX and PC showed no significant changes. FV (-16%, p<0.001), FVII (-19%, p<0.001), FVIII (-19%, p<0.001), FXI (-13%, p<0.0001) and fPS (-4%, p<0.0007) decreased significantly. PI levels were stable at 56%. The microbiological investigation showed no bacterial contamination. In Octaplas® LG plasma clotting factors decreased slightly through storage of 6 days. PI levels were remarkably higher and stable over time in the new Octaplas® LG. Stability of stored Octaplas® LG was limited by the decrease of FVIII to 53%, which may warrant storage up to 24h from a quality assurance point of view. This could result in reduced plasma wastage and costs for healthcare givers.


Sodium sparing effect of alanine in fasting obese females.
In obese females, 50 g of alanine given orally on the fifth day of fasting, produced a decrease in urinary sodium that persisted the following day. Plasma renin did not increase the day following alanine intake.


Ascarid infections of cats and dogs.
The ascarids Toxocara canis, Toxocara cati, and Toxascaris leonina are probably the most common gastrointestinal helminths encountered in small animal practice. Both T. canis and T. cati can cause serious disease in kittens and puppies; T. leonina is generally less pathogenic. Prenatal transmission assures that virtually all puppies are born infected with T. canis. Transmammary transmission is probably the major route of infection for kittens with T. cati. In addition, all three species of worm produce resistant eggs and use paratenic hosts to facilitate transmission. Much is now known about the complex biology and life history of T. canis. However, many questions, such as those concerning the mechanisms of larval survival within host tissues and of larval reactivation and migration during pregnancy, await further study. The mechanism of resistance to ascarid infections in cats and dogs has not been clearly defined. Ascariasis is traditionally thought to be a disease of young animals, with older animals being considered immune. However, at least in the case of T. canis, adult dogs can be repeatedly infected. A wide range of anthelmintics is available with extremely high efficacy against patent ascarid infections. The problem of prenatal infection with T. canis may be overcome by strategic use of the newer benzimidazole-carbamates, and the production of ascarid-free puppies now seems possible. However, complete larvicidal activity against somatic stages has not been convincingly demonstrated. Visceral larva migrans-like syndromes are now being recognized in dogs and cats. In addition, visceral larva migrans in children due to T. canis continues to be a significant zoonotic disease in North America and underscores the need for the veterinary profession to control ascarid infections in cats and dogs at every opportunity.


Comparison between resveratrol and cabergoline in preventing ovarian hyperstimulation syndrome in a rat model.
The aim of this study is to investigate the effects of resveratrol in a rat model of ovarian hyperstimulation syndrome (OHSS) and compare with cabergoline. Randomized controlled, animal study. Female Wistar rats. A rat OHSS model was used to investigate the effects of resveratrol compare with cabergoline administration for preventing OHSS. Body weight, ovary weight, diameter, vascular permeability (VP), vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) expression (immunohistochemistry), and serum estradiol (E2) levels were then compared. The ovarian VEGF concentration was significantly increased in the OHSS Groups (Groups 3-5) compared with the control groups (1 and 2). But vascular permeability, VEGF, and COX-2 expressions were reduced in animals treated with the resveratrol group compared with the cabergoline group (group 5) and the severe OHSS (group 3) group. Blood E2 levels were decreased in group treated with the resveratrol group compared with the cabergoline group (group 5) and severe the OHSS (group 3) group. Our results in a rat model suggest that resveratrol has a beneficial effect on OHSS by reducing the increases in ovarian daimeter, VP, and VEGF expression associated with OHSS. These effects may be mediated by the COX-2 inhibitory capacity of resveratrol.


Horner's syndrome in dogs and cats: 49 cases (1980-1986).
Medical records of 49 dogs and cats with Horner's syndrome were reviewed. Causes included head, neck, and chest trauma, chronic otitis, cranial thoracic mass, and injury attributable to cleaning of the external ear canal. Cause could not be delineated in 54.5% of the dogs. Numerous diagnostic tests and pharmacologic challenge exposure with epinephrine were used to localize the site of injury. Resolution of all clinical signs was observed in 36 animals and required a mean of 7.7 weeks.


Associations of maternal metabolic profile with placental and fetal cerebral and cardiac hemodynamics.
Maternal obesity and metabolic health affect pregnancy outcomes. We examined whether maternal metabolic profiles are associated with placental and fetal hemodynamics. In a population-based prospective cohort study among 1175 women we examined the associations of an adverse maternal metabolic profile in early pregnancy with placental, fetal cerebral and cardiac hemodynamic development. We obtained maternal pre-pregnancy BMI by questionnaire and measured blood pressure, cholesterol, triglycerides and glucose concentrations at a median gestational age of 12.6 (95 % range 9.6-17.1) weeks. An adverse maternal metabolic profile was defined as ≥4 risk factors. Placental and fetal hemodynamics were measured by pulsed-wave-Doppler at a median gestational age of 30.3 (95 % range 28.8-32.3) weeks. An adverse maternal metabolic profile was associated with a 0.29 Z-score higher (95 %CI 0.08-0.50) fetal cerebral middle artery pulsatility index (PI), but not with placental or fetal cardiac hemodynamic patterns. When the individual components of an adverse maternal metabolic profile were assessed, we observed that higher maternal total cholesterol and triglyceride concentrations were associated with a higher cerebral middle artery PI (Z-score, 0.09 (95 %CI 0.02-0.15), 0.09 (95 %CI 0.03-0.15) per Z-score increase). Higher total and HDL maternal cholesterol concentrations were also associated with a higher aorta ascendens peak systolic velocity (PSV) Z-score, 0.08 (95 %CI 0.01-0.14)), and a larger left cardiac output (Z-score, 0.08 (95 %CI 0.00-0.15), respectively). An adverse maternal metabolic profile, especially higher cholesterol and triglycerides concentrations, are associated with increased fetal cerebral vascular resistance and larger fetal aorta ascendens diameter, PSV and left cardiac output, but not with placental vascular resistance indices. Further studies are needed to identify long-term consequences of the observed associations.


Development and behavior of non-handicapped preterm children from a developing country.
There are many studies, mainly conducted in industrialized countries, concerning developmental and behavioral outcomes of preterm children. However, little is known about the outcomes of preterm children from developing countries. Forty-three non-handicapped Turkish preterm children, 15 with very low birth weight and 28 with low birth weight at preschool age, as well as 36 term controls were compared on rates of developmental, emotional and behavioral impairments. Data were collected by review of hospital records and application of various questionnaires and inventories to both children and their parents. Preterm children had significant delays in general development and significant rise in somatic complaints with unknown medical etiologies. The very low birth weight group also had significant delay in language and cognitive development. Parents of the preterm children displayed significantly higher rates of democratic attitudes. Developmental outcome was significantly associated with birth weight and authoritarian parental attitudes where behavioral outcome was significantly influenced by birth weight. Presence of developmental delay is in accordance with existing data on the outcomes of preterm children from industrialized countries. An isolated increase in somatic complaints is an uncommon finding which might also be related to cultural factors.


Fauna of Culicidae in rural areas of Porto Velho and the first record of Mansonia (Mansonia) flaveola (Coquillet, 1906), for the state of Rondônia, Brazil.
Knowledge concerning the fauna of Culicidae in the Brazilian Amazon States contributes to current understanding of the bionomics of the insects collected and makes it possible to observe changes in the fauna over time. The Culicidae were captured with a BG-Sentinel® trap in extra-domiciliary area of two rural regions of Porto Velho in June and July of 2007 and 2008. A total of 10,695 Culicidae was collected, belonging to nine genera: Coquillettidia, Culex, Mansonia, Psorophora, Aedes, Aedeomyia, Anopheles, Uranotaenia and Wyeomyia. The presence of Mansonia (Mansonia) flaveola was recorded in the State of Rondônia for the first time.


Petit mal epilepsy and parkinsonian tremor: hypothesis of a common pacemaker.
Rhythmic oscillation in neuronal systems may serve physiological purposes or may interfere with normal functions of the brain. In disorders of petit mal epilepsy and parkinsonian tremor, centrally and peripherally observable rhythmic patterns are due to network oscillations of thalamocortical cells. This article reviews the afferent mechanisms that might be critically involved in controlling the ionic conductances of thalamic neurons in the behaving organism. We propose that during active behavior the subcortical aminergic and cholinergic inputs to the thalamus act as anti-burst and anti-oscillation mechanisms. We suggest further that the thalamopetal GABAergic inputs (pars reticulata of substantia nigra, entopeduncular nucleus, pallidum) are burst- and oscillation-promoting systems, whose output is controlled by the striatum. Experimental or disease-related decrease of the striatal dopamine levels is hypothesized to increase the efficacy of the GABAergic burst-promoting systems resulting in rhythmic network oscillation of thalamocortical neurons during rest. The recognition of the overlapping neuronal mechanisms in petit mal epilepsy and parkinsonian tremor, and the multistage control of thalamic oscillation suggests that drugs effectively used in petit mal attacks may be effective in levodopa-refractory parkinsonian tremor, and conversely, epileptic patients may benefit from drugs acting on the extrapyramidal system.


Lifestyle chemical carcinogens associated with mutations in cell cycle regulatory genes increases the susceptibility to gastric cancer risk.
In the present study, we correlated the various lifestyle habits and their associated mutations in cell cycle (P21 and MDM2) and DNA damage repair (MLH1) genes to investigate their role in gastric cancer (GC). Multifactor dimensionality reduction (MDR) analysis revealed the two-factor model of oral snuff and smoked meat as the significant model for GC risk. The interaction analysis between identified mutations and the significant demographic factors predicted that oral snuff is significantly associated with P21 3'UTR mutations. A total of five mutations in P21 gene, including three novel mutations in intron 2 (36651738G > A, 36651804A > T, 36651825G > T), were identified. In MLH1 gene, two variants were identified viz. one in exon 8 (37053568A > G; 219I > V) and a novel 37088831C > G in intron 16. Flow cytometric analysis predicted DNA aneuploidy in 07 (17.5%) and diploidy in 33 (82.5%) tumor samples. The G2/M phase was significantly arrested in aneuploid gastric tumor samples whereas high S-phase fraction was observed in all the gastric tumor samples. This study demonstrated that environmental chemical carcinogens along with alteration in cell cycle regulatory (P21) and mismatch repair (MLH1) genes may be stimulating the susceptibility of GC by altering the DNA content level abnormally in tumors in the Mizo ethic population.


Interbipolar contacts in the dorsal inner plexiform layer in the retina of Callionymus lyra L.
Several types of direct contacts have been observed between the square pattern-arranged bipolar synaptic buttons in the P layers in the dorsal inner plexiform layer of the Callionymus retina. These contacts are not randomly occurring interconnections, but they are systematically formed throughout the whole of the dorsal retinal zone and they may be the site of direct synaptic interactions between similar as well as dissimilar bipolar axons. Reciprocal ribbon synapses have been found in the P2,2 layer. Morphologically mixed synapses occur in the P5,1 layer. These contact zones show morphologic characteristics of both chemical and electronic synapses. Morphologically mixed synaptic complexes, representing a triple coupling between two adjacent similar bipolar buttons and an amacrine cell process, have been observed in the P1,1, the P2,1 and the P5,2 layer. The morphology of the interbipolar contacts in the P3,2 layer does not clearly point to a synaptic function. Our results suggest a high degree of functional stratification in the inner plexiform layer.


Platelet Transfusion and In-Hospital Mortality in Veno-Arterial Extracorporeal Membrane Oxygenation Patients.
Thrombocytopenia is common during extracorporeal membrane oxygenation (ECMO), and platelets are sometimes transfused to meet arbitrary goals. We performed a retrospective cohort study of veno-arterial (VA) ECMO patients from a single academic medical center and explored the relationship between platelet transfusion and in-hospital mortality using multivariable logistic regression. One hundred eighty-eight VA ECMO patients were included in the study. Ninety-one patients (48.4%) were transfused platelets during ECMO. Patients who received platelet transfusion had more coronary artery disease, lower platelet counts at cannulation, higher predicted mortality, lower nadir platelet counts, more ECMO days, and more red blood cell (RBC) and plasma transfusion. Mortality was 19.6% for patients who received no platelets, 40.8% for patients who received 1-3 platelets, and 78.6% for patients who received 4 or more platelets ( P < 0.001). After controlling for confounding variables including baseline severity of illness, central cannulation, postcardiotomy status, RBC and plasma transfusion, major bleeding, and total ECMO days, transfusion of 4 or more platelets remained associated with in-hospital mortality; OR = 4.68 (95% CI = 1.18-27.28), P = 0.03. Our findings highlight the need for randomized controlled trials that compare different platelet transfusion triggers, so that providers can better understand when platelet transfusion is indicated in VA ECMO patients.


A method for the quantitative analysis of nerve growth in vitro.
A method is described for the quantitative analysis of the nerve-growth-promoting activity of biological molecules in tissue culture. The criteria used for the evaluation of this activity is based on the neurite length as well as the total number of neurites produced by the explant of whole dorsal root ganglia from 12-d-old chick embryos. A nerve growth index (NGI) is given to each ganglion during each of a 5-d culture period. The NGI is defined as the product of average neurite length in millimeters and the total number of neurites. We report that with increasing concentrations of fetal bovine serum, there was a proportional increase in NGI due to increased neurite density while the neurite length was not greatly affected. The NGI of several proteins with known nerve growth promoting activity, namely nerve growth factor, insulin, transferrin, and fibronectin were investigated for their activity and compared with that of fetal bovine serum.


Patients with adrenal insufficiency have cardiovascular features associated with hypovolemia.
Patients with adrenal insufficiency (AI) have excess mortality and morbidity, mainly due to cardiovascular (CV) diseases. The mechanisms for this is unclear. To assess CV structure and function in AI patients on conventional replacement therapy and after switching to once-daily, modified-release hydrocortisone (OD-HC) in comparison with healthy matched controls. This was a retrospective analysis of 17 adult AI patients (11 with primary AI, 6 with secondary AI) on stable replacement with cortisone acetate [median (minimum, maximum) 33.5 (12.5-50) mg] and, if needed, fludrocortisone [0.1 (0.05-0.2) mg], and 17 healthy matched controls. Ten patients were switched to an equivalent dose of OD-HC. Data from echocardiography, 24 h Holter-ECG and 24 h blood pressure monitoring were collected at baseline and 6 months after the switch to OD-HC. At baseline, AI patients had smaller left ventricular diastolic diameter (47.1 ± 4.2 vs. 51.6 ± 2.3 mm; P = 0.001) and left atrial diameter (34.9 ± 4.7 vs. 38.2 ± 2.6 cm; P = 0.018), and a higher ejection fraction (62.5 ± 6.9% vs. 56.0 ± 4.7%; P = 0.003) than controls. AI patients had lower nocturnal systolic and diastolic blood pressure than controls (108 ± 15 mmHg vs. 117 ± 8 mmHg; P = 0.038 and 65 ± 9 mmHg vs. 73 ± 7 mmHg; P = 0.008, respectively). After the switch to OD-HC, nocturnal diastolic blood pressure normalised. No significant changes were observed in echocardiographic and Holter-ECG parameters following the switch. AI patients on conventional treatment display cardiovascular abnormalities that could be related to hypovolemia. Switch to OD-HC seems to have beneficial effect on blood pressure profile, but no effect on cardiovascular structure and function.


Swimming prevents cell death of chondrocytes via PI3K/AKT pathway in an experimental model.
Knee Osteoarthritis (KOA) is one of the main causes of disability in the elderly and with limited treatment options. Swimming was considered as an ideal form of non-surgical management of KOA. Nevertheless, the mechanism of swimming intervene OA remains unclear. ACLT induced OA model was often used to study the pathogenesis and treatment of OA. Thus, we evaluated the protective effect of swimming on KOA mouse and tried to explore the underlying mechanism. Forty C57BL/6 mice were randomly divided into five groups: Blank group, ACLT group, ACLT + Swim group, Sham group and Sham + Swim group (n = 8). OA model was established by Anterior Cruciate Ligament Transection surgery (ACLT). After modeling, mice in ACLT + Swim and Sham + Swim groups were trained with a moderate swimming program, 5 d/week, for 6 weeks. HE and Safranin-O/fast staining, Immunohistochemistry, TUNEL assay and Western blot were used to detect the effect of swimming on pathological changes, cell death and the mechanism in KOA mouse. Swimming significantly enhanced CoII expression and suppressed ADAMTS5 expression in cartilage of KOA mouse, thus ameliorated KOA development. Apoptotic and autophagic processes were enhanced in OA cartilage, which might be caused by down-regulation of PI3K/AKT pathway; swimming could activate PI3K/AKT pathway and thus regulate apoptosis and autophagy processes of chondrocytes. Swimming could prevent cell death of chondrocytes via PI3K/AKT pathways, thus delayed the progression of KOA in an experimental model.


Familial nephrosis, nerve deafness, and hypoparathyroidism.
Two male siblings with nephrotic syndrome, nerve deafness, and hypoparathyroidism are described. Each child, one at five years of age and the other at eight years, died in renal failure. At autopsy the parathyroid glands were absent in one child and hypoplastic in the other one. Two twin male siblings presented with similar findings and died at the age of three years. At autopsy their parathyroid glands were fibrotic, and glomerular basement membranes were thickened. This may be the first recorded association of familial nephrosis, nerve deafness, and hypoparathyroidism. The mode of transmission is compatible with autosomal recessive inheritance.


Urological anomalies and chronic kidney disease in children with anorectal malformations.
This study aims to predict risk factors for urological anomalies in children with anorectal malformations (ARM) and describes the clinical features of patients who have developed chronic kidney disease. We retrospectively reviewed infants with ARM who received surgery and were followed at the Sabah Women and Children's Hospital, Malaysia, from 1986 to 2010. One hundred and twenty-two children with anorectal malformations were studied, after excluding 24 children with incomplete data. Three factors were significant as predictors of the presence of a urological anomaly: high ARM lesion (OR 3.12, 95%CI 1.1-8.9), the presence of genital abnormality (OR 2.95, 95%CI 1.10-7.91) and cloacal anomaly in girls (OR 8.27, 95% CI 1.91-35.6). The most common anomalies were vesicoureteric reflux, single kidney and neurogenic bladder. Chronic kidney disease (CKD) was noted in 5.7%, in children who had recurrent urinary tract infections, neurogenic bladder or complex renal tract pathology; end-stage renal failure was seen in only 0.8% of children with ARM. Urological anomalies were seen in 23% of patients, but the overall incidence of CKD and end-stage renal disease is low. Early identification of infants with ARM at risk of renal failure may be important for renal survival.


[Mondini dysplasia: traumatic cerebrospinal fluid otorrhea with meningitis].
Mondini dysplasia is a rare malformation of the inner ear commonly associated with loss of hearing and vestibular function. Children with Mondini dysplasia are predisposed to developing a spontaneous cerebrospinal fluid (CSF) leak and recurrent meningitis. If there is no CSF leak but a unilateral hearing loss, the condition may go undiagnosed for years. We describe a 65-year-old man with unrecognized unilateral Mondini dysplasia who presented with CSF leak and meningoencephalitis after minor head trauma. Two operative interventions were undertaken to close the defect properly. Patients with Mondini dysplasia or their parents should be cautioned about the potential hazards of any head trauma.


Phylogenomics Reveals Convergent Evolution of Lifestyles in Close Relatives of Animals and Fungi.
The Opisthokonta are a eukaryotic supergroup divided in two main lineages: animals and related protistan taxa, and fungi and their allies [1, 2]. There is a great diversity of lifestyles and morphologies among unicellular opisthokonts, from free-living phagotrophic flagellated bacterivores and filopodiated amoebas to cell-walled osmotrophic parasites and saprotrophs. However, these characteristics do not group into monophyletic assemblages, suggesting rampant convergent evolution within Opisthokonta. To test this hypothesis, we assembled a new phylogenomic dataset via sequencing 12 new strains of protists. Phylogenetic relationships among opisthokonts revealed independent origins of filopodiated amoebas in two lineages, one related to fungi and the other to animals. Moreover, we observed that specialized osmotrophic lifestyles evolved independently in fungi and protistan relatives of animals, indicating convergent evolution. We therefore analyzed the evolution of two key fungal characters in Opisthokonta, the flagellum and chitin synthases. Comparative analyses of the flagellar toolkit showed a previously unnoticed flagellar apparatus in two close relatives of animals, the filasterean Ministeria vibrans and Corallochytrium limacisporum. This implies that at least four different opisthokont lineages secondarily underwent flagellar simplification. Analysis of the evolutionary history of chitin synthases revealed significant expansions in both animals and fungi, and also in the Ichthyosporea and C. limacisporum, a group of cell-walled animal relatives. This indicates that the last opisthokont common ancestor had a complex toolkit of chitin synthases that was differentially retained in extant lineages. Thus, our data provide evidence for convergent evolution of specialized lifestyles in close relatives of animals and fungi from a generalist ancestor.


Family Caregivers of Veterans Experience High Levels of Burden, Distress, and Financial Strain.
To describe the caregiving experiences and physical and emotional needs of family members and friends who provide care to veterans with mental, physical, and cognitive comorbidities. Cross-sectional study. National telephone surveys administered from 2017 to 2019. Family caregivers of veterans enrolled in the Veterans Affairs (VA) Program of General Caregiver Support Services between October 2016 and July 2018 who responded to a telephone survey (N = 1,509; response rate = 39%). We examined caregiver burden, depressive symptoms, financial strain, satisfaction with care, amount and duration of caregiving, life chaos, loneliness, and integration of caregiver with the healthcare team using validated instruments. We also collected caregiver demographic and socioeconomic characteristics and asked caregivers to identify the veteran's condition(s) and provide an assessment of the veteran's functioning. Average caregiver age was 62.2 (standard deviation [SD] = 13.7) and 69.8 (SD = 15.6) for veterans. Among caregivers, 76.7% identified at White, and 79.9% were married to the veteran. Caregivers reported having provided care for an average of 6.4 years and spending on average 9.6 hours per day and 6.6 days per week providing care. Average Zarit Subjective Burden score was 21.8 (SD = 9.4; range = 0-47), which is well above the cutoff for clinically significant burden (>16). Caregivers reported high levels of depressive symptoms; the sample average Center for Epidemiologic Studies Depression 10-item Scale score was 11.5 (SD = 7.1; range = 0-30). Caregivers also reported high levels of loneliness and financial strain. Caregivers who care for veterans with trauma-based comorbidities reported intensive caregiving and significant levels of distress, depressive symptoms, and other negative consequences. These caregivers require comprehensive support services including access to health care, financial assistance, and enhanced respite care. Planned expansion of VA caregiver support has the potential to provide positive benefits for this population and serve as a model for caregiver support programs outside the VA health care system.


Mesenchymal stem cells promote hard-tissue repair after direct pulp capping.
The aim of this study was to investigate the potential of autologous mesenchymal bone marrow stem cells (BMSCs) to promote hard-tissue formation after direct pulp capping procedures. Bone marrow was aspirated from the iliac crest of healthy dogs of nonspecific race. Mononuclear cells were obtained using the Histopaque (Sigma-Aldrich, St Louis, MO) protocol and cultured for 21 days. Direct pulp capping procedures were performed in posterior teeth, and then mineral trioxide aggregate (MTA), hydroxyapatite/tricalcium phosphate, or BMSCs were used as direct pulp capping agents. After 3 months, animals were sacrificed, and jaw segments were processed for radiographic examination using cone-beam computed tomography scanning and histologic examination to assess the formation of a hard-tissue barrier according to a scoring system. The longitudinal and cross-sectional radiophotographs and histologic sections confirmed the formation of an evident calcific barrier after direct pulp capping with MTA and BMSCs. Statistical analysis of the scores given for radiographic and histologic calcific bridge formation showed that both MTA and BMSCs had a comparable tendency to produce a hard-tissue barrier that was significantly higher than hydroxyapatite tricalcium phosphate (P < .05). Autologous mesenchymal BMSCs were able to promote hard-tissue formation after direct pulp capping procedures.


Re-engineering of carbon fixation in plants - challenges for plant biotechnology to improve yields in a high-CO2 world.
Source and sink strength control plant carbon gain and yield. Source strength was recently engineered by modifying the large subunit of Rubisco, replacing the small subunit, and creating improved thermostable Rubisco activases. This technological breakthrough makes Rubisco engineering feasible at last. Enhancement of leaf transitory starch synthesis or induction of artificial sinks in leaves increased biomass and yield. Importantly, such approaches also had a positive feedback on source strength. In addition, novel targets for the improvement of carbon gain in crops have been identified that are especially relevant in the light of climate change.


[Technical aspects of guided biopsy following placement of a "harpoon" for infra-clinical, radiologically suspect breast lesions].
The importance of systematic mammography in cancer screening had been well demonstrated. "Harpooning" under radiological control improves the precision of the surgical technique of excisional biopsy of infra-clinical mammary lesions. Among the 20 patients subjected to this technique at the Bordet Institute, 6 cases were malignant tumors (30%). Only once did this technique not allow the excision of the mammographically visualized lesion. No surgical complications have been noted. The neoplastic lesions had been essentially represented radiologically as grouped, dense and irregular microcalcifications.


Haploidization in Saccharomyces cerevisiae induced by a deficiency in homologous recombination.
Diploid Saccharomyes cerevisae strains lacking the RAD52 gene required for homologous recombination have a very high rate of chromosome loss. Two of four isolates subcultured ∼20 times (∼500 cell divisions) became haploid. These strains were capable of mating with wild-type haploids to produce diploid progeny capable of undergoing meiosis to produce four viable spores.


PEEP--a rapid chemical-shift imaging method.
The phase-encoded echo-planar (PEEP) technique, a variant of echo-planar imaging, is used to achieve simultaneous high-speed spatial and chemical-shift data acquisition. This technique is the 2DFT equivalent of the projection reconstruction echo-planar method for chemical-shift imaging. Examples of images and spectra obtained using the PEEP method are presented.


Laboratory animal technicians. Their role in stress reduction and human-companion animal bonding.
The physical and emotional well-being of laboratory animals is often dependent upon the knowledge and ability of the responsible technician. Management has the obligation to place only technicians who are well-trained, compassionate, and highly motivated in responsible positions of animal care and to recognize the legitimacy of, and strongly support, the emotional and behavioral needs of both technicians and animals.


Direct projection from the dorsal hypothalamic area to the nucleus raphe pallidus: a study using anterograde transport with Phaseolus vulgaris leucoagglutinin in the rat.
A hypothalamic projection to the nucleus raphe pallidus of the medulla was examined using the anterograde tracing technique based on Phaseolus vulgaris leucoagglutinin (PHA-L) in the rat. After the iontophoretic application of PHA-L to the dorsal hypothalamic area, labeled fibers that finally ended in the nucleus raphe pallidus were observed descending through the most medial part of the ventral tegmental area and the nucleus reticularis tegmenti pointis to reach the medial aspect of the pyramid. Many varicose fibers forming a loose plexus were observed in the nucleus raphe pallidus, especially ventrally. The ventral surface of the pyramid and the most ventral region of the nucleus reticularis paragigantocellularis lateralis (PGCL) contained labeled varicose fibers. At the electron microscopic level, the labeled profiles in the nucleus raphe pallidus were small-sized unmyelinated axons and axon terminals. Labeled axon terminals containing spherical synaptic vesicles formed synapses on spine-like protrusions or small-sized dendritic shafts. These results strongly indicate that neurons in the dorsal hypothalamic area have a direct connection with neurons in the nucleus raphe pallidus and the ventral part of the PGCL. The possible involvement of this pathway in cardiovascular regulation was discussed.


Comparing Quality of Life of General Population and Orthopedic Patients in Slovenia.
To our knowledge this is the first study presenting descriptive EQ-5D health profile and VAS scores for orthopedic patients in Slovenia. Furthermore, EQ-5D-3L population norms for Slovenia are presented. The aims of this study are (1) to provide population norms for EQ-5D-3L in Slovenia according to age and sex and (2) to compare different groups of orthopaedic patients' health state among themselves as well as to the general population. Data on orthopedic patients' preoperative health status assessment were recorded (n = 1118). The health status of 4 groups of orthopedic patients was analyzed and compared using EQ VAS and the EQ-5D descriptive profile. The results were compared with Slovenian population norms, which were calculated using the EQ-5D valuation set database from year 2000 (n = 708). As expected, a higher proportion of patients than the general population report problems on all dimensions. The opposite is true only for mobility and anxiety/depression dimension for shoulder surgery patients. Hip endoscopy patients have the lowest health-related quality of life (HRQoL) out of all patient groups using EQ VAS and EQ-5D descriptive profiles. The population norms presented will be useful for many researchers trying to compare HRQoL among various patient groups or the general population. Separate use of the descriptive profile of the EQ-5D is informative when assessing HRQoL in orthopedic patients and is in line with VAS values. The results can support further studies on health needs assessment as well as decisions on funds allocation among groups of orthopedic patients.


Evaluation of a rapid physical-chemical method for the determination of extant soluble COD.
Characterization of total chemical oxygen demand (COD) in wastewater is critical for accurate modeling of constituent biotransformation steps. We evaluated the accuracy and precision of a commonly used soluble COD determination technique (coagulation using ZnSO4 at pH 10.5) in relation to three other physical-chemical separation techniques: destabilization with a non-hydrolyzing trivalent cation (LaCl3), sequential filtration, and ultracentrifugation. Samples of deionized water and domestic wastewater were spiked with aliquots of synthetic soluble COD and recoveries using the different separation methods were compared. Although mechanisms of coagulation using LaCl3 and ZnSO4 are different, the mean COD recoveries using these methods were in close agreement. Further, sorption of soluble COD onto zinc hydroxide precipitate flocs appeared to be negligible. The two coagulation methods yielded statistically different (p = 0.05) soluble COD values when applied to nine independent wastewater samples (obtained on nine different days). but the difference was less than 10%. The COD quantified by the coagulation techniques corresponded most closely with the < 1,000 Da molecular weight fraction defined as "truly soluble COD". Centrifugation of wastewater samples amended with mercuric chloride (HgCl2) at 10 mg/L overestimated the soluble COD concentration. Our results confirm that coagulation using either ZnSO4 or LaCI3 is appropriate for the rapid determination of soluble COD fraction in wastewater matrices.


Generation of RORγt+ Antigen-Specific T Regulatory 17 Cells from Foxp3+ Precursors in Autoimmunity.
Th17 cells are potent mediators in autoimmune diseases, and RORγt is required for their development. Recent studies have shown that RORγt+ Treg cells in the gut regulate intestinal inflammation by inhibiting effector T cell function. In the current study, we report that RORγt+ Treg cells were also found in lymph nodes following immunization. Not only distinct from intestinal RORγt+ Treg cells in their transcriptomes, peripheral RORγt+ Treg cells were derived from Foxp3+ thymic Treg cells in an antigen-specific manner. Development of these RORγt+ Treg cells, coined T regulatory 17 (Tr17) cells, depended on IL-6/Stat3 signaling. Tr17 cells showed suppressive activity against antigen-specific effector T cells in vitro. In addition, Tr17 cells efficiently inhibited myelin-specific Th17-cell-mediated CNS auto-inflammation in a passive EAE model. Collectively, our study demonstrates that Tr17 cells are effector Treg cells that potentially restrict autoimmunity.


Coordinate system requirements to determine motions of the tibiofemoral joint free from kinematic crosstalk errors.
The relative rigid body motions between the femur and the tibia (termed tibiofemoral kinematics) during flexion activities can provide an objective measure of knee function. Clinically meaningful tibiofemoral kinematics are defined as the six relative rigid body motions expressed in a joint coordinate system where the motions about and along the axes conform to clinical definitions and are free from kinematic crosstalk errors. To obtain clinically meaningful tibiofemoral kinematics, coordinate systems must meet certain requirements which neither have been explicitly stated nor in fact satisfied in any previous publication known to the author. Starting with the joint coordinate system of Grood and Suntay (1983) where motions conform to clinical definitions, the body-fixed axes must correspond to the functional (i.e. actual) axes in flexion-extension and internal-external axial rotation to avoid kinematic crosstalk errors in rotations and both functional axes must be body-fixed throughout knee flexion. To avoid kinematic crosstalk errors in translations, the origins of the femoral and tibial Cartesian coordinate systems, which serve as stepping stones for computing translations, must lie on the functional body-fixed axes. Neither the paper by Grood and Suntay nor the ISB recommendation (Wu et al., 2002) which adopted the joint coordinate system of Grood and Suntay explains these requirements. Indeed meeting these requirements conflicts with the ISB recommendation thus indicating the need for revision to this recommendation. Future studies where clinically meaningful tibiofemoral kinematics are of interest should be guided by the requirements described herein.


[Cancer of the breast at a remote time after segmental resection].
An analysis of 72 case histories of breast cancer treated by surgery for nodular dyshormonal hyperplasia established that all cases of lumpectomy should be followed up. Particular care should be exercised in monitoring cases of multi-factor risk for breast cancer and preceding proliferation.


IκBζ: A key protein in the pathogenesis of psoriasis.
Psoriasis is an immune-mediated chronic inflammatory skin disease with a complex etiology. The proinflammatory cytokine IL-17A is known to play key role in the pathogenesis of psoriasis, and recently anti-IL-17A antibodies have been approved for psoriasis treatment. Here, we discuss our recent findings demonstrating that IκBζ, a transcriptional co-activator, plays a crucial role in the development of psoriasis by mediating IL-17A-driven effects. These findings have significant implications as they uncover a novel crucial regulatory mechanism involved in psoriasis development, and identify IκBζ as a possible future target in the treatment of psoriasis and other IL-17A-driven diseases.


Nutritional value and antioxidant capacity of organic and conventional vegetables of the genus Allium.
There are indications that organically grown plants are safer for health and have higher antioxidant content than conventional ones. Vegetables of the genus Allium L. are a valuable source of health-promoting substances, including compounds with antioxidant properties. The aim of the study was to compare the antioxidant potential and nutritional value of four species of Allium L. vegetables obtained from organic and conventional production: garlic, leek and red and yellow onion. Their proximate and mineral composition were determined, as well as the content of bioactive substances and antioxidant potential. The study showed that the cultivation method significantly influenced the parameters tested. Comparison of organic vegetables with conventional ones in terms of content of dry matter, crude protein and crude fibre revealed no general trend indicating the superiority of one method over the other. However, all organic vegetables analysed were more abundant in minerals (Ca, Mg, Fe, Zn, Cu and Mn) and bioactive compounds. They also exhibited higher antioxidant capacity as measured by the FRAP and DPPH. tests. Their consumption (especially organic garlic and leek) may therefore strengthen the body's natural antioxidant defences and is beneficial for health.


Locomotion in rats transplanted with noradrenergic neurons.
It is known that catecholaminergic drugs can induce both locomotion and a late flexion reflex in spinalized animals. We studied spinal reflexes and locomotor activity in five adult spinal rats which had received a suspension of fetal noradrenergic (NA) neurons below the transection and in three control spinal rats. A rhythmical activity similar to the one of locomotion was regularly observed in three of the grafted rats held above a moving belt. In two of them, the step frequency was increased when the velocity of the moving belt was increased. This was not observed in control rats. A late flexion reflex was obtained in grafted rats that displayed locomotor activity, as well as in two controls. In the two rats which exhibited locomotor activity, analysis showed numerous immunoreactivite (against NA) cells and processes with terminals concentrated around the perikarya of motoneurones.


muI Na+ channels expressed transiently in human embryonic kidney cells: biochemical and biophysical properties.
We describe the transient expression of the rat skeletal muscle muI Na+ channel in human embryonic kidney (HEK 293) cells. Functional channels appear at a density of approximately 30 in a 10 microns 2 patch, comparable to those of native excitable cells. Unlike muI currents in oocytes, inactivation gating is predominantly (approximately 97%) fast, although clear evidence is provided for noninactivating gating modes, which have been linked to anomalous behavior in the inherited disorder hyperkalemic periodic paralysis. Sequence-specific antibodies detect a approximately 230 kd glycopeptide. The majority of molecules acquire only neutral oligosaccharides and are retained within the cell. Electrophoretic mobility on SDS gels suggests the molecules may acquire covalently attached lipid. The channel is readily phosphorylated by activation of the protein kinase A and protein kinase C second messenger pathways.


The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis.
Humans and microbes have developed a symbiotic relationship over time, and alterations in this symbiotic relationship have been linked to several immune mediated diseases such as inflammatory bowel disease, type 1 diabetes and spondyloarthropathies. Improvements in sequencing technologies, coupled with a renaissance in 16S rRNA gene based community profiling, have enabled the characterization of microbiomes throughout the body including the gut. Improved characterization and understanding of the human gut microbiome means the gut flora is progressively being explored as a target for novel therapies including probiotics and faecal microbiota transplants. These innovative therapies are increasingly used for patients with debilitating conditions where conventional treatments have failed. This review discusses the current understanding of the interplay between host genetics and the gut microbiome in the pathogenesis of spondyloarthropathies, and how this may relate to potential therapies for these conditions.


Isolated prolapse of the tricuspid valve.
Tricuspid valve prolapse has remained a poorly defined entity. Some authors have stated that prolapse isolated to the tricuspid valve has not been documented. This report contains three cases of isolated tricuspid valve prolapse including the first pathologically confirmed case. A review of worldwide literature including all reported cases of isolated tricuspid valve prolapse is also presented. Although signs and symptoms are similar to those found with mitral valve prolapse, tricuspid valve prolapse may occasionally be differentiated by auscultation. The diagnostic criteria of tricuspid valve prolapse are thoroughly discussed for each of the presently available invasive and noninvasive techniques. Right heart catheterization can define such prolapse but is invasive and requires meticulous technique. Two-dimensional echocardiography supersedes M-mode because of the superior spatial evaluation of the tricuspid leaflets in relation to the right atrium and ventricle. Multiple views including a long-axis view of the right ventricular inflow are often required. This parasternal echocardiographic window is often the only one which permits adequate visualization of the posterior leaflet. The pathologic findings of tricuspid valve prolapse are similar to those of mitral valve prolapse. This report concludes with a description of associated conditions. Severe tricuspid regurgitation has not been noted with tricuspid valve prolapse in the absence of superimposed disease, yet much remains undefined concerning the clinical significance of this condition.


Effect of suramin on pinocytosis by resident rat peritoneal macrophages: an analysis using four different substrates.
The effect of suramin on pinocytosis and intralysosomal proteolysis by resident rat peritoneal macrophages cultured in vitro has been studied. Suramin had little effect on the rate of pinocytic uptake of two non-adsorptive substrates [14C]sucrose and [3H]dextran, but unexpectedly enhanced uptake of a third, 125I-labelled polyvinylpyrrolidone (PVP). Since this enhanced uptake was completely abolished by NaF at a concentration known to inhibit pinocytosis, it clearly represented an increased internalization of substrate and not merely a superficial binding to the cell surface. It was concluded that suramin (i) does not affect the rate of formation of pinocytic vesicles but (ii) acts as a bivalent ligand, binding to both the macrophage surface and the 125I-labelled polyvinylpyrrolidone, thus converting a non-adsorptive into an adsorptive substrate. Suramin (500 micrograms/ml) decreased both the rate of uptake of formaldehyde-denatured 125I-labelled bovine serum albumin (BSA) (an adsorptive substrate) and the rate of its subsequent intracellular degradation. Thus, depending on the substrate chosen to measure pinocytosis, the same modifier may stimulate or inhibit uptake or be without effect.


Assessment of smoking topography generalization across laboratory, clinical, and naturalistic settings.
A three-study series was conducted to examine smoking topography across clinical, laboratory, and naturalistic settings for 24 smokers who were patients in an alcohol treatment program. Experiments 1 and 2 included surreptitious observation of smoking in group therapy sessions (naturalistic), and obtrusive observation of smoking in a smoking clinic setting. The third study added a laboratory smoking condition to the clinic and group conditions. Puffing patterns in clinical and laboratory settings tended to be similar, and both differed from smoking in the naturalistic setting. Subjects generally took more puffs, longer puffs, and had shorter cigarette durations in clinical and laboratory settings than in the naturalistic setting. The implications of these findings for assessment of intake and health risk are discussed.


Homeobrain, a novel paired-like homeobox gene is expressed in the Drosophila brain.
The homeobrain (hbn) gene is a new paired-like homeobox gene which is expressed in the embryonic brain and the ventral nerve cord. Expression of homeobrain initiates during the blastoderm stage in the anterior dorsal head primordia and the gene is persistently expressed in these cells which form parts of the brain during later embryonic stages. An additional weaker expression pattern is detected in cells of the ventral nerve cord from stage 11 on. The homeodomain in the Homeobrain protein is most similar to the Drosophila proteins DRx, Aristaless and Munster. In addition, the localized brain expression patterns of homeobrain and DRx resemble each other. Two other homeobox genes, orthopedia and DRx are clustered in the 57B region along with homeobrain. The current evidence indicates that homeobrain, DRx and orthopedia form a homeobox gene cluster in which all the members are expressed in specific embryonic brain subregions.