Goal‐directed behaviors in patients with schizophrenia: Concept relevance and updated model

Goal‐directed behaviors are formulated to pursue a given objective by constructing a plan and selecting actions that lead to the intended goal, either immediately or over an extended period. This concept is important to the study of human behavior because of its involvement in the majority of complex or novel situations that an individual may encounter, regardless of the cognitive, affective, or social abilities required. In this paper, we aim to demonstrate the relevance of goal‐directed behaviors to our understanding of the cognitive deficits and other symptoms associated with schizophrenia. A systematic analysis of this relation may allow us to develop integrative hypotheses regarding positive, negative, and disorganized symptoms of schizophrenia rather than consider them to be distinct issues. In this article, we review previous studies of goal‐directed actions in patients with schizophrenia in order to clarify the relevant concepts and provide a theoretical basis for the integration of existing results. Based on available theoretical models and data, we propose an updated model to facilitate further investigation of schizophrenia‐related impairments in goal‐directed behaviors.     

Insight into the mechanisms underlying tumor response to boron neutron capture therapy in the hamster cheek pouch oral cancer model

Objective: The therapeutic success of different boron neutron capture therapy (BNCT) protocols employing the hamster cheek pouch oral cancer model has been previously reported by our laboratory. The aim of this study was to explore potential mechanisms of BNCT‐induced damage to tumor in terms of potential inhibition in DNA synthesis and induction of apoptosis in the tumors that underwent partial remission following application of the different BNCT protocols in this model. Materials and methods: We evaluated DNA synthesis employing incorporation of 5‐bromo‐2′‐deoxyuridine as an end‐point. Apoptosis was evaluated by immunohistochemistry employing the deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate‐biotin nick end‐labeling technique and Bax and Bcl‐2 labeling. These studies were performed in tumors that underwent partial remission 1–30 days post‐BNCT mediated by boronophenylalanine (BPA), GB‐10 (Na₂¹⁰B₁₀H₁₀) or (BPA + GB‐10). Results: BNCT exerted a marked inhibitory effect on DNA synthesis in tumors for all the protocols under study. The inhibitory effect of BPA‐BNCT occurred as soon as 1 day post‐treatment (P < 0.001). Conversely, the effect of GB‐10‐BNCT became apparent 7–14 days after therapy (P < 0.001) and was sustained until killed at 30 days post‐treatment (P < 0.001). (GB‐10 + BPA)‐BNCT exerted a rapid and persistent effect, conceivably because of the combined effect of BNCT mediated by both boron compounds. The apoptosis studies did not show differences between the pre‐treatment group and any of the BNCT groups. Conclusions: One of the mechanisms involved in BNCT‐induced tumor control in our model would be an inhibitory effect on DNA synthesis. Apoptosis does not seem to have a significant role in BNCT‐induced tumor control in our model.     

Effect of different doses of hexavalent chromium on mandibular growth and tooth eruption in juvenile Wistar rats

Not only workers employed at industrial plants are exposed to intoxication with the element they manipulate, the population at large is also at risk of suffering health problems caused by contaminating wastes inadequately treated for their safe disposal. As a result certain toxic substances, such as hexavalent chromium,has reached the general population including children. The present study sought to evaluate the effect of intoxication with hexavalent chromium on body and mandibular growth and tooth eruption in suckling Wistar rats. Potassium dichromate was administered by gavage in a dose of 6.25 or 12.5 mg/kg body weight (b.w.) to one of the two groups of 4-day-old Wistar rats during 10 days. Our results showed that the effects of chromium are dose-dependent. Morphometric studies of body growth showed lower body weight in both experimental groups and shorter tail length in animals receiving 12.5 mg/kg b.w. dose of chromium, compared with controls. All parameters of mandibular growth were lower in the experimental group receiving 12.5 mg/kg b.w. of chromium. Differences in tooth eruption were observed at the level of the first molar in animals receiving 12.5 mg/kg and of the second molar in those receiving 6.25 mg/kg b.w. of chromium. Chromium was found to affect all the studied parameters.     

Platelet-derived growth factor-D enables liver myofibroblasts to promote tumor lymphangiogenesis in cholangiocarcinoma

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Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.     

Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening

OBJECTIVEAssess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSA total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m²; and HbA_1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.RESULTSThe prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3–4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI).CONCLUSIONSModerate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.     

Epidemiological studies on Echinococcus in Pampas fox (Lycalopex gymnocercus) and European hare (Lepus europaeus) in Buenos Aires province, Argentina

In Argentina, hydatid disease caused by Echinococcus granulosus is widespread. The south of Buenos Aires province, Argentina, is one of the three regions where hydatidosis is endemic. Although domestic dogs and sheep are considered to be the main hosts for E. granulosus, the potential role of wildlife in the local transmission of E. granulosus has not been investigated. The aim of this study was to estimate the hydatidosis/echinococcosis prevalence in European hare (Lepus europaeus) and Pampas fox (Lycalopex gymnocercus), two abundant species with a strong predator–prey relationship in rural areas of Buenos Aires province using different diagnostic tests. A total of 61 fox intestines were examined, finding that 52 (85.2 %) harbored at least one helminth species. However, no adult or immature form of Echinococcus sp. was found in the intestinal contents. Coproparasitological analysis and Copro–ELISA followed by Copro–PCR were used as supplementary diagnostic tests. Only one (1.7 %) of 59 fecal samples was positive to Taeniidae eggs by coproparasitological analysis, but this same sample was negative by the Copro–ELISA test. The analysis by Copro–ELISA showed 6 of 57 (10.6 %) positive samples, but the Copro–PCR tests carried out on these samples were negative to E. granulosus. A total of 6,808 lungs, 3,576 livers, and 3,542 hearts of hunted hares were examined and palpated, but no structure resembling hydatid cysts were detected. Our results suggest that hares and Pampas foxes are not currently important wild reservoirs of E. granulosus in the studied area.