Tubercular pseudoaneurysm of aorta: a rare association with vertebral tuberculosis.

BACKGROUND CONTEXT: Pseudoaneurysm of the aorta in association with vertebral tuberculosis is a rare phenomenon. With the resurgence of human immunodeficiency virus (HIV) and associated resistant tuberculosis, this life-threatening complication requires greater awareness. PURPOSE: Our purpose is to report the rare presentation and successful management of tubercular pseudoaneurysm of the aorta in association with vertebral tuberculosis, and to highlight the clinicoradiological features for early and prompt diagnosis of this potentially fatal, but treatable, disease. STUDY DESIGN: A single case report and overview of the disease comprises the design of this study. PATIENT SAMPLE: The patient, already surgically intervened, is a 27-year-old male with increasing abdominal and back pain, upper motor neuron signs, and constitutional signs and symptoms. OUTCOME MEASURES: At 33 months follow-up, there is complete resolution of the signs and symptoms, and the patient is back to his previous vocation. METHODS: The diagnosis was confirmed by magnetic resonance imaging and contrast computed tomography. Endoaneurysmorrhaphy of the pseudoaneurysm along with a complete course of antitubercular treatment was given to the patient, and he has presently been followed up for 33 months. RESULTS: The patient's signs and symptoms have been completely resolved without any recurrence. CONCLUSION: Despite the use of modern chemotherapy and imaging techniques, this disastrous complication still occurs and reinforces the need for early suspicion, diagnosis, surgical resection, and antitubercular therapy along with close postoperative follow-up to prevent recurrence. With the resurgence of HIV (and other immunocompromised states) associated and resistant tuberculosis, we should be more alert than ever to this life-threatening complication.     

Increased Ventricular Vulnerability in a Chronic Ethanol Model Despite Reduced Electrophysiologic Responses to Catecholamines

An increased incidence of sudden death has been reported in chronic alcoholism. To assess electrical vulnerability of the heart, action potential responses, and the role of the sympathetic system, a well-nourished canine model has been studied intact under chloralose anesthesia after 1 year of ethanol consumption at 36% of caloric intake. Two alcoholic groups were compared with controls (Group 1). In Group 2 myocardial vulnerability was assessed after chronic EtOH and superimposed acute administration. In Group 3 basal vulnerability was related to circulating norepinephrine and release of neurohormone from the myocardium. Subsequently the responsiveness to catecholamine infusion was determined. To assess vulnerability an electrode catheter was placed in the right ventricular apex. The basal ventricular fibrillation threshold (VFT) was reduced to 27 +/- 3 ma in Group 2 versus 43 +/- 1.0 in Group 1. Acute infusion of ethanol in Group 2 further reduced the threshold. Group 3 had a reduced basal VFT. Baseline arterial plasma levels of norepinephrine were 8-fold higher and coronary venous levels 13 times higher in the alcoholic group than in Group 1. However, VFT was not responsive to infused epinephrine, compared with Group 1 controls. In vitro study of superfused ventricular tissue from Group 3 revealed that basal action potential amplitude, overshoot, and resting potential were comparable with normals. Basal repolarization time (90%) was 198 +/- 12 msec in Group 3 versus 215 +/- 6 msec in Group 1 (p less than 0.05). After acute EtOH, repolarization time was shortened to 170 +/- 8.6 in Group 1 at 90 mg% ethanol (p less than 0.002), with minimal further change up to 280 mg%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children

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Mutations in VMK1, a mitogen-activated protein kinase gene, affect microsclerotia formation and pathogenicity in Verticillium dahliae

Verticillium dahliae is an important soil-borne fungal pathogen that causes vascular wilt diseases in a large variety of important crop plants. Due to its persistence in the soil, control of Verticillium wilt relies heavily on soil fumigation. The global ban on methyl bromide, a highly effective soil fumigant, poses an urgent need to develop alternative control measures against Verticillium wilt; and these might be more forthcoming with a better understanding of the molecular and cellular mechanisms that underpin the pathogenicity of V. dahliae. In this study, we assessed the role in growth, development, and pathogenicity of VMK1, a gene encoding a mitogen-activated protein (MAP) kinase (hence, Verticillium MAP Kinase 1). Disruption of VMK1 via Agrobacterium tumefaciens-mediated transformation, in two V. dahliae isolates, one from lettuce and the other from tomato, resulted in severely reduced virulence in diverse host plants, suggesting that VMK1 is essential for pathogenicity and that the MAP kinase-mediated signaling pathway has a conserved role in fungal pathogenicity. The vmk1 mutants also exhibited reduced conidiation and microsclerotia formation, suggesting that the gene is important for multiple cellular processes. P.R. and R.G.B. equally contributed to the work     

A critical function for type I interferons in cancer immunoediting

'Cancer immunoediting' is a process wherein the immune system protects hosts against tumor development and facilitates outgrowth of tumors with reduced immunogenicity. Although interferon-gamma (IFN-gamma) is known to be involved in this process, the involvement of type I interferons (IFN-alpha/beta) has not been elucidated. We now show that, like IFN-gamma, endogenously produced IFN-alpha/beta was required for the prevention of the growth of primary carcinogen-induced and transplantable tumors. Although tumor cells are important IFN-gamma targets, they are not functionally relevant sites of the actions of the type I interferons. Instead, host hematopoietic cells are critical IFN-alpha/beta targets during development of protective antitumor responses. Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-gamma.     

Gross and cellular analysis of 6-mercaptopurine-induced cleft palate in hamster

The present study analyzes the morphological, histochemical, and ultrastructural aspects of the pathogenesis of 6-mercaptopurine (6MP)-induced cleft palate in hamster fetuses. Gross and light microscopic observations indicated that 6MP stunts the growth of vertical palatal shelves and thus induces cleft palate. Ultrastructural analysis showed that, in contrast to controls, 6MP-induced alterations were first seen in the mesenchymal cells 24 hr after drug administration. The initial alterations were characterized by swelling of the nuclear membrane. During the next 12 hr, lysosomes were seen first in the mesenchymal cells and then in the cells of the medial edge epithelium (MEE) of the developing palatal primordia. The appearance of lysosomes was temporally abnormal and was interpreted as a sublethal response to 6MP treatment. Subsequently, the nuclear alterations and the lysosomes diminished; and 48 hr after 6MP administration, they were absent from the palatal tissues. Ninety hours after 6MP administration, unlike the controls (in which the palatal shelves were already fused), changes were seen at the epithelial-mesenchymal interface in the developing cleft palatal shelves. These changes were characterized by breakdown of the basal lamina and epithelial-mesenchymal contacts. Eventually, at term, the MEE of the vertical shelf stratified. It was suggested that 6MP affected cytodifferentiation in the palatal tissues during the critical phase of early vertical shelf development and thereby induced cleft palate.     

Double Electroconvulsive Therapy for Resistant Depression

A case is described of psychotic depression that worsened during a course of three bilateral ECTs per week, but responded to administration of two bilateral ECTs three times per week. For some patients, ECTs may need to be given more than three times per week to obtain remission.     

Mobile methadone dispensing in Delhi,India: implementation research

ObjectiveTo assess the implementation of a mobile dispensing service to improve opioid users’ access to methadone maintenance therapy.MethodsIn March 2019, we started mobile methadone dispensing in an urban underprivileged locality in Delhi, India. The doctor was available only at the main community drug treatment clinic for clinical services, while the nurse dispensed methadone from a converted ambulance. We involved patients in identifying community leaders for sensitization and in deciding the location and timings for dispensing. We conducted a retrospective chart review of the programme data collected during delivery of clinical services. We compared the numbers of patients registered for methadone therapy and their retention and adherence to therapy in the 12-month periods before and after implementation of the mobile service.FindingsThe number of patients registered for therapy at the clinic increased from 167 in the year before implementation to 671 in the year after. A significantly higher proportion of patients were retained in therapy at 3, 6 and 9 months after enrolment; 9-month retention rates were 19% (32/167 patients) and 45% (44/97 patients) in the year before and after implementation, respectively. There was no significant difference in patients’ adherence to therapy between the two periods. Challenges included providing suitable dispensing hours for patients in employment and concerns of local community near to the dispensing sites.ConclusionIt is feasible to dispense methadone by a mobile team in an urban setting, with better retention rates in therapy compared with dispensing through a stationary clinic.     

In Vitro and In Vivo Activity of 16,17-dehydro-epipregnanolones: 17,20-Bond Torsional Energy Analysis and D-ring Conformation

Purpose. Certain neuroactive pregnane steroids (also known as “epalons”) are allosteric modulators of the GABA_A receptor and have been shown to be potent anticonvulsants, anxiolytics, sedative/hypnotics, and anesthetic agents. The purpose of this study was to calculate the structural consequences of introduction of a double bond in the 16,17-position and to determine if this modification would selectively reduce sedative activity, but maintain the potent anticonvulsant activity of neuroactive steroids. Methods. We have studied the biochemical and behavioral effects of introducing a 16,17 double bond into the naturally occurring neuroactive steroids, 3α-hydroxy-5α-pregnan-20-one (3α,5α-P) and 3α-hydroxy-5β-pregnan-20-one (3α,5β-P) and three synthetic neuroactive steroid derivatives, 3α-hydroxy-3β-methyl-5α-pregnan-20-one (3α,3βMe,5α-P), 3α-hydroxy-5α-androstane (3α,5α-A), and alphaxalone (3α,5α-11-one-P). Results. The 16-ene analogs of most of these neuroactive steroids were found to be 7- and 16-fold less potent in inhibiting [³⁵S]TBPS binding to GABA_A receptors and in a similar fashion, had reduced anticonvulsant and sedative potency in proportional amounts. The exception was the androstane (3α,5α-A) without a 17-acetyl group, that had virtually identical IC₅₀ and ED₅₀ values for the saturated and unsaturated derivatives. Calculation of the torsional energy profile for each of the 17-acetyl side chain conformations showed that the conformational energy minima found in the α,β-unsaturated keto systems, produce an orientation of the 20-keto group that is rotated by 165 degrees when compared to the non-conjugated acetyl group (determined by X-ray crystallography and its minimum energy conformation). Conclusions. The modified orientation of the 20-keto group of neuroactive steroids containing a 16-ene, provides an explanation for their decreased biological activity overall, but did not lead to an enhanced protective index.