Translating ENIGMA schizophrenia findings using the regional vulnerability index: Association with cognition,symptoms, and disease trajectory

Patients with schizophrenia have patterns of brain deficits including reduced cortical thickness, subcortical gray matter volumes, and cerebral white matter integrity. We proposed the regional vulnerability index (RVI) to translate the results of Enhancing Neuro Imaging Genetics Meta-Analysis studies to the individual level. We calculated RVIs for cortical, subcortical, and white matter measurements and a multimodality RVI. We evaluated RVI as a measure sensitive to schizophrenia-specific neuroanatomical deficits and symptoms and studied the timeline of deficit formations in: early (≤5 years since diagnosis, N = 45, age = 28.8 ± 8.5); intermediate (6–20 years, N = 30, age 43.3 ± 8.6); and chronic (21+ years, N = 44, age = 52.5 ± 5.2) patients and healthy controls (N = 76, age = 38.6 ± 12.4). All RVIs were significantly elevated in patients compared to controls, with the multimodal RVI showing the largest effect size, followed by cortical, white matter and subcortical RVIs (d = 1.57, 1.23, 1.09, and 0.61, all p < 10^?6). Multimodal RVI was significantly correlated with multiple cognitive variables including measures of visual learning, working memory and the total score of the MATRICS consensus cognitive battery, and with negative symptoms. The multimodality and white matter RVIs were significantly elevated in the intermediate and chronic versus early diagnosis group, consistent with ongoing progression. Cortical RVI was stable in the three disease-duration groups, suggesting neurodevelopmental origins of cortical deficits. In summary, neuroanatomical deficits in schizophrenia affect the entire brain; the heterochronicity of their appearance indicates both the neurodevelopmental and progressive nature of this illness. These deficit patterns may be useful for early diagnosis and as quantitative targets for more effective treatment strategies aiming to alter these neuroanatomical deficit patterns.     

Personality traits of volunteer females of normal vaginal delivery or cesarean section based on HEXACO’s personality model: a comparison study

Archives of Gynecology and Obstetrics - Child birth is one of the most important events in a mother’s life. Different factors influence whether a child is delivered by cesarean or normal...     

Green solvent free epoxidation of olefins by a heterogenised hydrazone-dioxidotungsten(vi) coordination compound

A new mononuclear tungsten coordination compound, [WO₂L(CH₃OH)] (1), was synthesized by the reaction of WCl₆ and H₂L (H₂L = (E)-4-amino-N′-(5-bromo-2-hydroxybenzylidene)benzohydrazide) in methanol. Both the H₂L and compound 1 were characterized by elemental analysis and UV-Vis, FT-IR and NMR spectroscopic methods. The molecular structure of compound 1 was also determined by single crystal X-ray analysis which confirmed the compound is a mononuclear coordination compound of cis-dioxidotungsten(vi) containing a free amine functionality on the ligand. Compound 1 was supported on propionyl chloride-functionalized silica gel by amidification reaction to obtain a heterogeneous catalyst. The obtained heterogeneous catalyst was characterized by FT-IR spectroscopy, thermal gravimetric analysis (TGA), diffuse-reflectance spectroscopy (DRS), X-ray diffraction analysis (XRD), energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) and its catalytic activity was investigated in the epoxidation of olefins with hydrogen peroxide under solvent free conditions. The catalyst was successfully recovered several times and the recovered catalyst was also characterized by various methods including FT-IR, DRS, TGA, SEM and EDX analyses. The results indicated this heterogeneous catalytic system is an effective and selective catalyst for epoxidation of olefins and can be reused several times without significant change in its catalytic activity.

In this study the solvent free catalytic oxidation of olefins by a new silica supported hydrazone-dioxidotungsten(vi) coordination compound is investigated.     

Combination cryotherapy and intralesional corticosteroid versus steroid monotherapy in the treatment of keloids

Background

Keloids are common and have significant negative effects on quality of life. There is a need for more effective treatment approaches for keloids.

Aims

We investigated treatment outcomes of intralesional triamcinolone acetonide (IL TAC) compared with combination IL TAC and cryotherapy, including changes in pruritus, pain, and keloid size.

Patients/Methods

We performed a prospective study of patients referred to one provider who treated patients with combination therapy and compared them to a historic control cohort treated with IL TAC alone. All patients were seen at Thomas Jefferson University between 2019 and 2021. Patient demographics, location of keloids, and inciting events were recorded. Pruritus and pain scores were self-reported by patients using a 10-point Likert scale administered as standard of care. Changes in keloid size were denoted as “No change,” “up to 50% decrease,” “more than 50% decrease,” and “completely flattened.”

Results

While both treatments produced a significant reduction in mean pruritus and pain scores, there was no difference between the two treatment groups (p = 0.3933 and p = 0.2123, respectively). A greater percentage of keloids in the combination therapy group had a post-treatment size difference greater than 50% compared with those in the IL TAC only treatment group (p = 0.0021). In the subgroup of pubic keloids, all lesions treated with combination IL TAC and cryotherapy responded remarkably well to treatment.

Conclusions

While both IL TAC and IL TAC with cryotherapy were effective at reducing pruritus and pain, combination therapy was more effective in reducing keloid size, specifically for pubic keloids.     

Synthesis of biological based hennotannic acid-based salts over porous bismuth coordination polymer with phosphorous acid tags

In this paper, a novel porous polymer capable of coordinating to bismuth (PCPs-Bi) was synthesized. The Bi-PCPs was then reacted with phosphorous acid to produce a novel polymer PCPs(Bi)N(CH₂PO₃H₂)₂ which is shown to act as an efficient and recyclable catalyst. The mentioned catalyst was applied for the efficient synthesis of new mono and bis naphthoquinone-based salts of piperidine and/or piperazine via the reaction of hennotannic acid with various aldehydes, piperidine and/or piperazine, respectively. The structure of the resulting mono and bis substituted piperazine or piperidine-based naphthoquinone salts was thoroughly characterized spectroscopically. The electrochemical behavior of the products was also investigated. The presented protocol has the advantages of excellent yields (82–95%), short reaction times (4–30 min) and simple work-up.

In this paper, a novel porous polymer capable of coordinating to bismuth (PCPs-Bi) was synthesized.     

Recombinant nanobody against MUC1 tandem repeats inhibits growth,invasion, metastasis,and vascularization of spontaneous mouse mammary tumors

Alteration in glycosylation pattern of MUC1 mucin tandem repeats during carcinomas has been shown to negatively affect adhesive properties of malignant cells and enhance tumor invasiveness and metastasis. In addition, MUC1 overexpression is closely interrelated with angiogenesis, making it a great target for immunotherapy. Alongside, easier interaction of nanobodies (single‐domain antibodies) with their antigens, compared to conventional antibodies, is usually associated with superior desirable results. Herein, we evaluated the preclinical efficacy of a recombinant nanobody against MUC1 tandem repeats in suppressing tumor growth, angiogenesis, invasion, and metastasis. Expressed nanobody demonstrated specificity only toward MUC1‐overexpressing cancer cells and could internalize in cancer cell lines. The IC50 values (the concentration at which the nanobody exerted half of its maximal inhibitory effect) of the anti‐MUC1 nanobody against MUC1‐positive human cancer cell lines ranged from 1.2 to 14.3 nm. Similar concentrations could also effectively induce apoptosis in MUC1‐positive cancer cells but not in normal cells or MUC1‐negative human cancer cells. Immunohistochemical staining of spontaneously developed mouse breast tumors prior to in vivo studies confirmed cross‐reactivity of nanobody with mouse MUC1 despite large structural dissimilarities between mouse and human MUC1 tandem repeats. In vivo, a dose of 3 µg nanobody per gram of body weight in tumor‐bearing mice could attenuate tumor progression and suppress excessive circulating levels of IL‐1a, IL‐2, IL‐10, IL‐12, and IL‐17A pro‐inflammatory cytokines. Also, a significant decline in expression of Ki‐67, MMP9, and VEGFR2 biomarkers, as well as vasculogenesis, was evident in immunohistochemically stained tumor sections of anti‐MUC1 nanobody‐treated mice. In conclusion, the anti‐MUC1 tandem repeat nanobody of the present study could effectively overcome tumor growth, invasion, and metastasis.     

Muscle Activity Pattern Dysfunction During Sit to Stand and Stand to Sit in the Movement System Impairment Subgroups of Low Back Pain

Objective

To investigate impairment in the activity pattern of some muscles involved in sit to stand (STD) and stand to sit (STS) among 2 low back pain (LBP) subgroups of the Movement System Impairment (MSI) model.

Altered antioxidant capacity in human renal cell carcinoma: role of glutathione associated enzymes

PURPOSE: We aimed to discern the role of glutathione (GSH) associated enzymes in maintaining high GSH levels in renal cell carcinoma (RCC) of the clear cell type and analyze RCC enzyme antioxidant capacity. Since changes in cellular redox balance in RCC might also be related to alterations of glutathione S-transferase (GST) phenotype, GST class alpha and pi expression was also explored. METHODS AND MATERIALS: Human kidney specimens of tumor and distant nontumor regions were obtained from 15 patients with RCC at the time of surgery. The activities of GSH-replenishing enzymes, gamma-glutamylcysteine synthetase (gamma-GCS), gamma-glutamyl transferase (gamma-GT), and glutathione reductase (GR), as well as the activities of antioxidant enzymes glutathione peroxidase (GPX) and catalase (CAT) were determined spectrophotometrically. GST alpha and pi class expression was determined by immunoblot. RESULTS: In the course of renal cancerization, significant changes appear in the activities of GSH-replenishing and antioxidant enzymes. The activity of the key enzyme of GSH synthesis, gamma-GCS, is up-regulated (P < 0.001), while the activities of gamma-GT and GR are down-regulated in renal tumors compared to nontumor tissue (P < 0.001 and P < 0.05, respectively). Activities of GPX and CAT were also down-regulated (P < 0.001 and P < 0.05, respectively) in RCC. Changes in enzyme antioxidant capacity in RCC were associated with decreased GST class alpha (P < 0.001) and unchanged GST pi expression at the protein level. CONCLUSIONS: Changes in redox status in RCC as a consequence of decreased enzyme antioxidant capacity, together with altered GST alpha expression, may be important factors in development and tumor growth. The up-regulation of gamma-GCS and high levels of GSH in RCC may be an attempt to limit injury caused by oxidative stress.     

G cells and gastrin in chronic alcohol-treated rats.

Numerous reports have described gastric mucosal injury in rats treated with high ethanol concentrations. However, to the best of our knowledge, ultrastructural characteristics of G cells and antral gastrin levels have not been previously reported, either in rats that chronically consumed alcohol or in human alcoholics. The goal of this study was to examine the effect of ethanol consumption (8.5 g/kg) over a 4-month period, under controlled nutritional conditions, on antral and plasma levels of gastrin, ultrastructure of G cells, morphometric characteristics of G cells by stereological methods, and analysis of endocrine cells in the gastric mucosa by immunohistochemistry. The chronic alcohol consumption resulted in a nonsignificant decrease in gastrin plasma levels and unchanged antral gastrin concentrations. A slightly damaged glandular portion of the gastric mucosa and dilatation of small blood vessels detected by histological analysis, suggests that ethanol has a toxic effect on the mucosal surface. Chronic alcohol treatment significantly decreased the number of antral G cells per unit area, and increased their cellular, nuclear, and cytoplasmatic profile areas. In addition, the volume density and diameter of G-cell granules, predominantly the pale and lucent types, were increased, indicating inhibition of gastrin release. Ethanol treatment also decreased the number of gastric somatostatin-, serotonin-, and histamine-immunoreactive cells, except the somatostatin cells in the pyloric mucosa, as well as both G: D: enterochromaffin cells (EC) cell ratios in the antrum and D: ECL cell ratios in the fundus. These results indicate that the change of morphometric parameters in G cells may be related to cellular dysfunction. Our findings also suggest that regulation of G-cell secretion was not mediated by locally produced somatostatin in ethanol-consuming rats, but may involve gastric luminal content and/or neurotransmitters of gastric nerve fibers.