The Lysosomal Calcium Channel TRPML1 Maintains Mitochondrial Fitness in NK Cells through Interorganelle Cross-Talk

Cytotoxic lymphocytes eliminate cancer cells through the release of lytic granules, a specialized form of secretory lysosomes. This compartment is part of the pleomorphic endolysosomal system and is distinguished by its highly dynamic Ca2+ signaling machinery. Several transient receptor potential (TRP) calcium channels play essential roles in endolysosomal Ca2+ signaling and ensure the proper function of these organelles. In this study, we examined the role of TRPML1 (TRP cation channel, mucolipin subfamily, member 1) in regulating the homeostasis of secretory lysosomes and their cross-talk with mitochondria in human NK cells. We found that genetic deletion of TRPML1, which localizes to lysosomes in NK cells, led to mitochondrial fragmentation with evidence of collapsed mitochondrial cristae. Consequently, TRPML1-/- NK92 (NK92ML1-/-) displayed loss of mitochondrial membrane potential, increased reactive oxygen species stress, reduced ATP production, and compromised respiratory capacity. Using sensitive organelle-specific probes, we observed that mitochondria in NK92ML1-/- cells exhibited evidence of Ca2+ overload. Moreover, pharmacological activation of the TRPML1 channel in primary NK cells resulted in upregulation of LC3-II, whereas genetic deletion impeded autophagic flux and increased accumulation of dysfunctional mitochondria. Thus, TRPML1 impacts autophagy and clearance of damaged mitochondria. Taken together, these results suggest that an intimate interorganelle communication in NK cells is orchestrated by the lysosomal Ca2+ channel TRPML1

Logarithmic Corrections to Schwarzschild and Other Non-extremal Black Hole Entropy in Different Dimensions

Euclidean gravity method has been successful in computing logarithmic corrections to extremal black hole entropy in terms of low energy data, and gives results in perfect agreement with the microscopic results in string theory. Motivated by this success we apply Euclidean gravity to compute logarithmic corrections to the entropy of various non-extremal black holes in different dimensions, taking special care of integration over the zero modes and keeping track of the ensemble in which the computation is done. These results provide strong constraint on any ultraviolet completion of the theory if the latter is able to give an independent computation of the entropy of non-extremal black holes from microscopic description. For Schwarzschild black holes in four space-time dimensions the macroscopic result seems to disagree with the existing result in loop quantum gravity.Comment: LaTeX, 40 pages; corrected small typos and added reference

Back reaction, covariant anomaly and effective action

In the presence of back reaction, we first produce the one-loop corrections for the event horizon and Hawking temperature of the Reissner-Nordstr\"om black hole. Then, based on the covariant anomaly cancelation method and the effective action technique, the modified expressions for the fluxes of gauge current and energy momentum tensor, due to the effect of back reaction, are obtained. The results are consistent with the Hawking fluxes of a (1+1)-dimensional blackbody at the temperature with quantum corrections, thus confirming the robustness of the covariant anomaly cancelation method and the effective action technique for black holes with back reaction.Comment: 17 page

Logarithmic Corrections to Extremal Black Hole Entropy from Quantum Entropy Function

We evaluate the one loop determinant of matter multiplet fields of N=4 supergravity in the near horizon geometry of quarter BPS black holes, and use it to calculate logarithmic corrections to the entropy of these black holes using the quantum entropy function formalism. We show that even though individual fields give non-vanishing logarithmic contribution to the entropy, the net contribution from all the fields in the matter multiplet vanishes. Thus logarithmic corrections to the entropy of quarter BPS black holes, if present, must be independent of the number of matter multiplet fields in the theory. This is consistent with the microscopic results. During our analysis we also determine the complete spectrum of small fluctuations of matter multiplet fields in the near horizon geometry.Comment: LaTeX file, 52 pages; v2: minor corrections, references adde

A comparative study of efficacy of epidural versus interpleural bupivacaine for post operative analgesia after open cholecystectomy

Background The conventional methods of administering the prescribed doses of intramuscular or intravenous analgesics at fixed time intervals results in widely fluctuating and inadequate plasma level leads to poor post operative pain relief. Despite all advances made in the field of medicine, this symptom called &ldquo;Pain&rdquo; has not been combated well. Objective The present study was carried out to compare the efficacy of epidural verses interpleural administration of bupivacaine(0.5%) with adrenaline for post operative pain relieve in patients undergoing open cholecystectomy. Methods We prospectively randomized and compared the post operative pain relieve with the reference of visual analog score (VAS) in patients undergoing elective open cholecystectomy in college of medical sciences-teaching hospital, Bharatpur, Chitwan. Forty adult patients undergoing elective cholecystectomy were divided into two groups. Twenty patients in each group were subjected to a different technique of post-operative analgesia, namely thoracic epidural and interpleural instillation of 0.5% bupivacaine. These two groups were then compared in relation to changes produced in the pain scores, vital parameters and complication and side effects associated with the two techniques. The study was conducted for 24 hour postoperatively. Observation: Both thoracic epidural and interpleural instillation of 0.5% bupivacaine compared favorably with regard to analgesia in the present study. In general, the pain relief following thoracic epidural was more complete compared to interpleural but this was not clinically significant. Conclusion The present study shows that both the techniques are equally effective in providing analgesia following cholecystectomy. However, neither technique rendered the patients completely pain free at all times during first 24 hours. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-4, 15-23 DOI:&nbsp;http://dx.doi.org/10.3126/jcmsn.v9i4.10232</p

Microbial infection and antibiotic patterns among intensive care unit patients in a tertiary hospital in Central Nepal

Aims The present study is a fundamental effort to evaluate the bacteriological and antibiotic patterns in the Intensive Care Unit (ICU) setting in a tertiary care hospital. This study was carried out to guide the clinician in choosing the appropriate antibiotics and to prevent emergence of multidrug resistance bacteria. Materials and Methods Between March 2009 to Feb 2012, the samples from various ICUs that were submitted to the microbiology laboratory for culture and sensitivity were included in this study. All the organisms were identified morphologically and biochemically by standard laboratory procedure and antibiotic susceptibility pattern was determined by disc diffusion methods. Result Of 3,780 specimens, 2,312 (61.1%) isolates were recovered. Single organisms were isolated from 1,746 (75.5%) samples while the remaining 566 (24.4%) had two or more organisms isolated. Pseudomonas aeruginosa was the most common isolate 819 (35.4%), followed by Klebsiella pneumoniae 637 (27.5%). Antibiotics sensitivity of Pseudomonas aeruginosa showed that almost all isolates were resistant to cephalexin (97.8%) and ciprofloxacin (80.3%). However (95.8%) of the isolates were sensitive to tobramycin, (92.0%) to meropenem &amp; (74.80 %) to amikacin. Conclusion It is concluded that Pseudomonas aeruginosa is the predominate pathogen isolated from ICUs of this Hospital. Most of the frequently isolated pathogens are resistant to cephalosporins and quinolone antibiotics as compared to aminoglycosides and carbapenem. Regular surveillance of antibiotic susceptibility pattern is very important for setting a guideline to the clinician in choosing an appropriate therapy of infected patients of ICUs. Journal of College of Medical Sciences-Nepal, 2012, Vol-8, No-3, 1-8 DOI: http://dx.doi.org/10.3126/jcmsn.v8i3.8678</p

A clinical comparison of high dose and low dose of Suxamethonium

Background:&nbsp;Suxamethonium having its rapid onset and short duration of action makes this drug unique amongst the neuromuscular blocking drugs described so far. However, use of suxamethonium is associated with a large number of undesirable side effects. Objective:&nbsp;To evaluate clinical effects of high and low dose of suxamethonium and to determine whether lower dose of suxamethonium can be used for any beneficial effects in terms of its various adverse effects e.g. cardiovascular responses, post-operative muscle pains and intraocular pressure. Methods:&nbsp;A total of 100 patients were included in this prospective study. All these patients on preoperative clinical evaluation were assessed to have adequate airway. All the patients were divided in two groups, low dose group (group I) and High dose group (group II) with 50 patients in each at random. A standard anesthetic technique was adhered to all the patients and following parameters were observed on comparative basis: a. Fasciculation and post operative myalgia. b. Cardiovascular effects, c. Intraocular pressure. Observation:&nbsp;The incidence of post Suxamethonium pain was significantly greater in group II. Increase in heart rate from baseline was significant in both groups. There was no significant difference between the two groups in the diastolic pressure but rise in systolic blood pressure was significant at all assessment times in both groups. This rise from control was statistically significant. Conclusion:&nbsp;Suxamethonium can be used in lower doses (0.5 mg/kg) in elective cases without airway compromise. It gives benefits of reduced muscle pains, cardiovascular responses and intraocular hypertension. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-2, 1-8 DOI: http://dx.doi.org/10.3126/jcmsn.v9i2.9677</p

A comparison of serum potassium level between high dose and low dose of Succinylcholine

Aims:&nbsp;Succinylcholine is a depolarizing type of neuromuscular blocking drug. Aim of this study is to evaluate and compare serum potassium level with upper dose limit of succinylcholine (1.5mg/kg), which is used normally in anesthetic practice with low dose of succinylcholine (0.5mg/kg). Materials and methods:&nbsp;A total of 100 patients attending for elective surgery in College of Medical Sciences -Teaching Hospital( CMSTH)), Bharatpur, Chitwan, Nepal were studied. Two blood samples were collected, one before surgery and another at 4 min after injection of succinylcholine and send to central lab for estimation of serum potassium level. Result:&nbsp;The serum potassium levels recorded during the study showed that there were neither significant differences observed within the groups nor was there any difference between the groups. Conclusion:&nbsp;In absence of pathological conditions related to raised serum potassium level, both high and low doses of succinylcholine can be used safely as there is no statistically significant differences in serum potassium level between high and low dose of succinylcholine. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-1, 19-22 DOI: http://dx.doi.org/10.3126/jcmsn.v9i1.9669</p

Not Available

Not AvailableA detailed investigation on mass mortality of fishes was conducted in a small tropical reservoir- Derjang (20o50’32.0”N, 85o01’14.8″E), Odisha, India. Mortality mostly occurred in Systomus sarana followed by Labeo rohita, Cirrhinus mrigala, Labeo catla, Ompok bimaculatus, Labeo calbasu and Mastacembelus armatus. During 20 days of disease occurrence in May–June 2019, a total of about 3000 kg of fish died. The clinical signs in Cyprinid group were haemorrhagic spots, ulcerative lesions, rotten and pale patches in gills due to septicemic disease whereas haemorrhagic spots were the only prominent symptoms observed in Silurid group. Bacteriological isolation and identification through conventional and molecular techniques revealed that Klebsiella pneumoniae was the most common pathogen recovered from S. sarana, C. mrigala and O. bimaculatus. Further Aeromonas hydrophila, Acinetobacter baumannii were isolated from L. rohita and L. catla respectively. The role of these pathogens for this disease outbreak in multiple fish species is discussed in perspective of environmental factors. Sudden environmental alternation by the supercyclone Fani (3rd May 2019) on the coastal part of Odisha might have played a key role to translate the aquatic bacteria into the virulent infective pathogens. In the experimental challenge study, isolated bacteria showed pathogenicity in respective hosts as that in the reservoir. Thus this further revealed both bacteria and fish specific virulency with a variation in LD50 values. All the gram negative bacterial isolates were found to resist ampicillin and amoxicillin-clavulanic acid and most of them were TEM gene positive. However, the bacteria were found to be susceptible to the rest of the nineteen antibiotics. These findings suggested that the sudden cyclone is an enormous threat to reservoir aquaculture, and should be taken into consideration before breeding, stocking and harvesting of fishes.Not Availabl