Increased utilization of mechanically stable synthetic matrices particularly silica gel as a solid support and its surface modification either by impregnation of organic ligands directly or covalent ...grafting through spacer unit for extractive concentration of trace elements are highlighted in the present article. Experimental evidences for existence of surface silanol and its chemical nature have explored the idea of silica surface modification. Recent methods of development in functionalized silica synthesis by attachment of various ligands or organic reagents to the silica surface and techniques of characterization of the modified surface have been reported. Analytical applications of various modified silica surfaces, in particular, adsorption of trace elements taking separation and preconcentration into account from complex synthetic mixture as well as natural water is presented.
Impairments in fear extinction are thought to be central to the psychopathology of posttraumatic stress disorder, and endocannabinoid (eCB) signaling has been strongly implicated in extinction ...learning. Here we utilized the monoacylglycerol lipase inhibitor JZL184 to selectively augment brain 2-AG levels combined with an auditory cue fear-conditioning paradigm to test the hypothesis that 2-AG-mediated eCB signaling modulates short-term fear extinction learning in mice. We show that systemic JZL184 impairs short-term extinction learning in a CB1 receptor-dependent manner without affecting non-specific freezing behavior or the acquisition of conditioned fear. This effect was also observed in over-conditioned mice environmentally manipulated to re-acquire fear extinction. Cumulatively, the effects of JZL184 appear to be partly due to augmentation of 2-AG signaling in the basolateral nucleus of the amygdala (BLA), as direct microinfusion of JZL184 into the BLA produced similar results. Moreover, we elucidate a short ~3-day temporal window during which 2-AG augmentation impairs extinction behavior, suggesting a preferential role for 2-AG-mediated eCB signaling in the modulation of short-term behavioral sequelae to acute traumatic stress exposure.
Stress is a major risk factor for the development of mood and anxiety disorders; elucidation of novel approaches to mitigate the deleterious effects of stress could have broad clinical applications. ...Pharmacological augmentation of central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy to mitigate the adverse behavioral and physiological consequences of stress. Here we show that acute foot-shock stress induces a transient anxiety state measured 24 h later using the light-dark box assay and novelty-induced hypophagia test. Acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), reverses the stress-induced anxiety state in a cannabinoid receptor-dependent manner. FAAH inhibition does not significantly affect anxiety-like behaviors in non-stressed mice. Moreover, whole brain anandamide levels are reduced 24 h after acute foot-shock stress and are negatively correlated with anxiety-like behavioral measures in the light-dark box test. These data indicate that central anandamide levels predict acute stress-induced anxiety, and that reversal of stress-induced anandamide deficiency is a key mechanism subserving the therapeutic effects of FAAH inhibition. These studies provide further support that eCB-augmentation is a viable pharmacological strategy for the treatment of stress-related neuropsychiatric disorders.
Summary
Good’s syndrome (thymoma and hypogammaglobulinaemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case ...series. We use the national UK‐Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy‐eight patients with a median age of 64 years, 59% of whom were female, were reviewed. Median age of presentation was 54 years. Absolute B cell numbers and serum immunoglobulins were very low in all patients and all received immunoglobulin replacement therapy. All patients had undergone thymectomy and nine (12%) had thymic carcinoma (four locally invasive and five had disseminated disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T cells were significantly lower in these patients with malignant thymoma. Seventy‐four (95%) presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic sinusitis, but only eight (10%) had serious invasive fungal or viral infections. Patients with AB‐type thymomas were more likely to have bronchiectasis. Twenty (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism, arthritis, myasthenia gravis, systemic lupus erythematosus, Sjögren’s syndrome). There was no association between thymoma type and autoimmunity. Seven (9%) patients had died. Good’s syndrome is associated with significant morbidity relating to infectious and autoimmune complications. Prospective studies are required to understand why some patients with thymoma develop persistent hypogammaglobulinaemia.
Good's syndrome (thymoma and hypogammaglobulinemia is a rare secondary immunodeficiency. This is one of the largest series of patients with this condition collating information on the clinical features, laboratory parameters, complications and mortality of this disease. Prospective translational studies are required to better understand the pathogenesis of this disease.
Summary
B1 B cells represent a unique subset of B lymphocytes distinct from conventional B2 B cells, and are important in the production of natural antibodies. A potential human homologue of murine ...B1 cells was defined recently as a CD20+CD27+CD43+ cell. Common variable immunodeficiency (CVID) is a group of heterogeneous conditions linked by symptomatic primary antibody failure. In this preliminary report, we examined the potential clinical utility of introducing CD20+CD27+CD43+ B1 cell immunophenotyping as a routine assay in a diagnostic clinical laboratory. Using a whole blood assay, putative B1 B cells in healthy controls and in CVID patients were measured. Peripheral blood from 33 healthy donors and 16 CVID patients were stained with relevant monoclonal antibodies and underwent flow cytometric evaluation. We established a rapid, whole blood flow cytometric assay to investigate putative human B1 B cells. Examination of CD20+CD27+CD43+ cells is complicated by CD3+CD27+CD43hi T cell contamination, even when using stringent CD20 gating. These can be excluded by gating on CD27+CD43lo–int B cells. Although proportions of CD20+CD27–CD43lo–int cells within B cells in CVID patients were decreased by 50% compared to controls (P < 0·01), this was not significant when measured as a percentage of all CD27+ B cells (P = 0·78). Immunophenotypic overlap of this subset with other innate‐like B cells described recently in humans is limited. We have shown that putative B1 B cell immunophenotyping can be performed rapidly and reliably using whole blood. CD20+CD27+CD43lo–int cells may represent a distinct B1 cell subset within CD27+ B cells. CVID patients were not significantly different from healthy controls when existing CD27+ B cell deficiencies were taken into account.
Covid-19 pandemic is in a massive second wave in India. The new variant is considered more infectious. Diabetic patients are considered more vulnerable to develop some of the complications of acute ...Covid-19 infections. Furthermore, steroids are being used in the treatment of Covid-19 related pneumonia in a large number of patients. Hence, secondary fungal infections are being increasing observed, with very high mortality. We present the clinical, imaging and histopathological features in a diabetic patient who recovered from acute Covid-19 infection. However, he developed palatal and maxillary mucormycosis. Mucosal debridement, sinus surgery and antifungal treatment led to a satisfactory outcome.
Aim
To compare the accuracy of film and digital periapical radiography (PR) in detecting apical periodontitis (AP) using histopathological findings as a reference standard.
Methodology
Jaw sections ...containing 67 teeth (86 roots) were collected from nine fresh, unclaimed bodies that were due for cremation. Imaging was carried out to detect AP lesions using film and digital PR with a centred view (FP and DP groups); film and digital PR combining central with 10˚ mesially and distally angled (parallax) views (FPS and DPS groups). All specimens underwent histopathological examination to confirm the diagnosis of AP. Sensitivity, specificity and predictive values of PR were analysed using rater mean (n = 5). Receiver operating characteristics (ROC) analysis was carried out.
Results
Sensitivity was 0.16, 0.37, 0.27 and 0.38 for FP, FPS, DP and DPS, respectively. Both FP and FPS had specificity and positive predictive values of 1.0, whilst DP and DPS had specificity and positive predictive values of 0.99. Negative predictive value was 0.36, 0.43, 0.39 and 0.44 for FP, FPS, DP and DPS, respectively. Area under the curve (AUC) for the various imaging methods was 0.562 (FP), 0.629 (DP), 0.685 (FPS), 0.6880 (DPS).
Conclusions
The diagnostic accuracy of single digital periapical radiography was significantly better than single film periapical radiography. The inclusion of two additional horizontal (parallax) angulated periapical radiograph images (mesial and distal horizontal angulations) significantly improved detection of apical periodontitis.
Overexpression of casein kinase-2 (CK2) has been implicated in several carcinomas, mainly lung, prostate and acute myeloid leukaemia. The smaller nucleotide pocket compared to related kinases ...provides a great opportunity to discover newer ATP-competitive CK2 inhibitors. In this study, we have employed an integrated structure- and fragment-based design strategy to design 2-amino-6-methyl-pyrimidine benzoic acids as ATP-competitive CK2 inhibitors. A statistically significant four features-based E-pharmacophore (ARRR) model was used to screen 780,092 molecules. Further, the retrieved hits were considered for molecular docking study to identify essential binding interactions. At the same time, fragment-based virtual screening was performed using a dataset of 1,542,397 fragments. The identified hits and fragments were used as structure templates to rationalize the design of 2-amino-6-methyl-pyrimidine benzoic acids as newer CK2 inhibitors. Finally, the binding interactions of the designed hits were identified using an induced fit docking (IFD) study, and their stability was estimated by a molecular dynamics (MD) simulation study of 100 ns.
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