Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care.

BACKGROUND: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. METHODS: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. RESULTS: After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001). CONCLUSIONS: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. CLINICAL TRIALS REGISTRATION: NCT04292899 and EUPAS34303.

PET/CT features of extrapulmonary tuberculosis at first clinical presentation: a cross-sectional observational 18F-FDG imaging study across six countries.

BACKGROUND: A large proportion of the huge global burden of extrapulmonary tuberculosis (EPTB) cases are treated empirically without accurate definition of disease sites and extent of multi-organ disease involvement. Positron emission tomography (PET) imaging using 2-deoxy-2-(fluorine-18) fluoro-d-glucose (18F-FDG) in tuberculosis could be a useful imaging technique for localising disease sites and extent of disease. METHODS: We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across eight centres located in six countries: India, Pakistan, Thailand, South Africa, Serbia and Bangladesh, to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/computed tomography (CT) scans were performed within 2 weeks of presentation. FINDINGS: 358 patients with EPTB (189 females; 169 males) were recruited over 45 months, with an age range of 18-83 years (females median 30 years; males median 38 years). 350 (98%) out of 358 patients (183 female, 167 male) had positive scans. 118 (33.7%) out of 350 had a single extrapulmonary site and 232 (66.3%) out of 350 had more than one site (organ) affected. Lymph nodes, skeleton, pleura and brain were common sites. 100 (28%) out of 358 EPTB patients had 18F-FDG PET/CT-positive sites in the lung. 110 patients were 18F-FDG PET/CT-positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites. INTERPRETATION: 18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies.

Sequential 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan findings in patients with extrapulmonary tuberculosis during the course of treatment-a prospective observational study.

BACKGROUND: Initial studies of tuberculosis (TB) in macaques and humans using 18F-FDG positron emission tomography (PET) imaging as a research tool suggest its usefulness in localising disease sites and as a clinical biomarker. Sequential serial scans in patients with extrapulmonary TB (EPTB) could inform on the value of PET-CT for monitoring response to treatment and defining cure. PATIENTS AND METHODS: HIV-negative adults with EPTB from eight sites across six countries had three 18F-FDG PET/CT scans: (i) within 2 weeks of enrolment, (ii) at 2 months into TB treatment and (iii) at end of ATT treatment. Scanning was performed according to the EANM guidelines. 18F-FDG PET/CT scans were performed 60 ± 10 min after intravenous injection of 2.5-5.0 MBq/kg of 18F-FDG. FINDINGS: One hundred and forty-seven patients with EPTB underwent 3 sequential scans. A progressive reduction over time of both the number of active sites and the uptake level (SUVmax) at these sites was seen. At the end of WHO recommended treatment, 53/147 (36.0%) patients had negative PET/CT scans, and 94/147 (63.9%) patients remained PET/CT positive, of which 12 patients had developed MDR TB. One died of brain tuberculoma. INTERPRETATION: Current 18F-FDG PET/CT imaging technology cannot be used clinically as a biomarker of treatment response, cure or for decision-making on when to stop EPTB treatment. PET/CT remains a research tool for TB and further development of PET/CT is required using new Mycobacterium tuberculosis-specific radiopharmaceuticals targeting high-density surface epitopes, gene targets or metabolic pathways.

Design, synthesis and biological evaluation of spiropyrimidinetriones oxazolidinone derivatives as antibacterial agents.

Gram-positive bacteria are among the most common human pathogens associated with clinical infections which range from mild skin infections to sepsis. Resistance towards existing class of drugs by Gram-positive bacteria including methicillin resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE) and vancomycin resistant enterococci (VRE) is a growing concern. There is an urgent need to discover new antibiotics which are active against resistant strains of Gram positive bacteria. We report herein a novel class of spiropyrimidinetrione oxazolidinone derivatives as novel antibacterial agents. Key step towards the synthesis of title compounds involved the use of tert-amino reaction with [1,5]-hydride shift leading to the new CC bond formation. Compound 30n has demonstrated potent antibacterial activity against a panel of Gram-positive microbial strains including MRSA, MRSE, and LNZ and vancomycin resistant strains of E. faecalis. Further, molecular docking studies suggest that 30n has binding mode similar to that of LNZ in 50S RNA ribosome.

Effects of arsenic toxicity on morphological characters in blackgram (Vigna mungo L.) during early growth stage.

Blackgram is an important pulse crop of the tropic and sub-tropic area and has been identified as a potential crop in many countries. In the south-East Asia arsenic toxicity in soil and water is one of the most environmental problems. Crop productivity is highly affected by cultivation in arsenic polluted soil or irrigation through arsenic polluted water. The present study was conducted to evaluate the effect of arsenic (As) on fresh shoot length, fresh shoot weight, fresh root length, fresh shoot weight and total fresh biomass, The results indicate that root length is more affected than shoot length due to arsenic toxicity. The fresh shoot weight observed was more affected than fresh root weight. This study indicates that arsenic toxicity causes the deleterious effect on blackgram growth. The toxic effect of blackgram depends on the genotypic variability. Some blackgram genotypes show very less toxic effect of arsenic due to its genetic makeup. Experimental findings of study indicate that longer root length and more shoot weight in arsenic stress condition may be tolerant blackgram genotype to arsenic toxicity.

Development of sediment load estimation models by using artificial neural networking techniques.

This study aims at the development of an artificial neural network-based model for the estimation of weekly sediment load at a catchment located in northern part of Pakistan. The adopted methodology has been based upon antecedent sediment conditions, discharge, and temperature information. Model input and data length selection was carried out using a novel mathematical tool, Gamma test. Model training was carried out by using three popular algorithms namely Broyden-Fletcher-Goldfarb-Shanno (BFGS), back propagation (BP), and local linear regression (LLR) using forward selection of input variables. Evaluation of the best model was carried out on the basis of basic statistical parameters namely R-square, root mean squared error (RMSE), and mean biased error (MBE). Results indicated that BFGS-based ANN model outperformed all other models with significantly low values of RMSE and MBE. A strong correlation was also found between the observed and estimated sediment load values for the same model as the value of Nash-Sutcliffe model efficiency coefficient (R-square) was found to be quite high as well.

Induction of interleukin-1ß by activated microglia is a prerequisite for immunologically induced fatigue.

We previously reported that an intraperitoneal (i.p.) injection of synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly-I:C), produced prolonged fatigue in rats, which might serve as a model for chronic fatigue syndrome. The poly-I:C-induced fatigue was associated with serotonin transporter (5-HTT) overexpression in the prefrontal cortex (PFC), a brain region that has been suggested to be critical for fatigue sensation. In the present study, we demonstrated that microglial activation in the PFC was important for poly-I:C-induced fatigue in rats, as pretreatment with minocycline, an inhibitor of microglial activation, prevented the decrease in running wheel activity. Poly-I:C injection increased the microglial interleukin (IL)-1ß expression in the PFC. An intracerebroventricular (i.c.v.) injection of IL-1ß neutralising antibody limited the poly-I:C-induced decrease in activity, whereas IL-1ß (i.c.v.) reduced the activity in a dose-dependent manner. 5-HTT expression was enhanced by IL-1ß in primary cultured astrocytes but not in microglia. Poly-I:C injection (i.p.) caused an increase in 5-HTT expression in astrocytes in the PFC of the rat, which was inhibited by pretreatment with minocycline (i.p.) and rat recombinant IL-1 receptor antagonist (i.c.v.). Poly-I:C injection (i.p.) led to a breakdown of the blood-brain barrier and enhanced Toll-like receptor 3 signaling in the brain. Furthermore, direct application of poly-I:C enhanced IL-1ß expression in primary microglia. We therefore propose that poly-I:C-induced microglial activation, which may be at least partly caused by a direct action of poly-I:C, enhances IL-1ß expression. Then, IL-1ß induces 5-HTT expression in astrocytes, resulting in the immunologically induced fatigue.

Screening for diabetes and hypertension in a rural low income setting in western Kenya utilizing home-based and community-based strategies.

BACKGROUND: The burdens of hypertension and diabetes are increasing in low- and middle-income countries (LMICs). It is important to identify patients with these conditions early in the disease process. The goal of this study, therefore, is to compare community- versus home-based screening for hypertension and diabetes in Kenya. METHODS: This was a feasibility study conducted by the Academic Model Providing Access to Healthcare (AMPATH) program in Webuye, a town in western Kenya. Home-based (door-to-door) screening occurred in March 2010 and community-based screening in November 2011. HIV counselors were trained to screen for diabetes and hypertension in the home-based screening with local district hospital based staff conducting the community-based screening. Participants >18 years old qualified for screening in both groups. Counselors referred all participants with a systolic blood pressure (SBP) ≥ 160 mmHg and/or a random blood glucose ≥ 7 mmol/L (126 mg/dL) to a local clinic for follow-up. Differences in likelihood of screening positive between the two strategies were compared using Fischer's Exact Test. Logistic regression models were used to identify factors associated with the likelihood of following-up after a positive screening. RESULTS: There were 236 participants in home-based screening: 13 (6%) had a SBP ≥ 160 mmHg, and 54 (23%) had a random glucose ≥ 7 mmol/L. There were 346 participants in community-based screening: 35 (10%) had a SBP ≥ 160 mmHg, and 27 (8%) had a random glucose ≥ 7 mmol/L. Participants in community-based screening were twice as likely to screen positive for hypertension compared to home-based screening (OR=1.93, P=0.06). In contrast, participants were 3.5 times more likely to screen positive for a random blood glucose ≥ 7 mmol/L with home-based screening (OR=3.51, P<0.01). Rates for following-up at the clinic after a positive screen were low for both groups with 31% of patients with an elevated SBP returning for confirmation in both the community-based and home-based group (P=1.0). Follow-up after a random glucose was also low with 23% returning in the home-based group and 22% in the community-based group (P=1.0). CONCLUSION: Community- or home-based screening for diabetes and hypertension in LMICs is feasible. Due to low rates of follow-up, screening efforts in rural settings should focus on linking cases to care.

Safety of untreated autologous cranioplasty after extracorporeal storage at -26 degrees Celsius.

BACKGROUND: Given the improved survival of patients requiring decompressive craniectomies, the frequency of subsequent cranioplasties are on the rise. The most feared complication of autologous cranioplasty is infection and one method for reducing the rate of infection, is to store the bone flaps at subnormal temperatures. However, to date there is no defined temperature for flap storage and temperature ranges from - 18 to - 83°C have been described in literature. Considering our limited resources it has been the practice at our center to store bone flaps at - 26°C. In this study, we have retrospectively reviewed our practice and have audited this choice of temperature with respect to the frequency of infections. METHODS: A retrospective review was conducted for all cranioplasties performed at our center between January 2001 to March 2011, using autologous bone which was cryopreserved according to institutional protocol. During this period the operative and cryopreservation protocol remained the same. All patient records including charts, notes and laboratory findings were reviewed with a specific focus to identify infections. RESULTS: Of the 88 patients included in the study, only 3 (3.40%) patients were found to show signs of infection. Of these, two patients had superficial surgical site infections which resolved with oral antibiotics (Co-Amoxiclav 1 gm BD for 7 days). However the third patient developed deep surgical site infection requiring re-exploration and washout. All three patients had complete resolution of infection with preservation of autologous bone. CONCLUSION: Despite our method of keeping the bone flap in freezer at - 26°C we have reported an acceptable rate of infection and raised the notion whether there is a justification for sophisticated and costly equipment for bone flap preservation, especially in resource depleted setups.

Evaluation of Serum Iron Profile in Patients with Pulmonary Tuberculosis.

Approximately 10.0% of tuberculosis (TB) Infected individuals develop clinical disease in the absence of immune suppression suggests that individual factors may play a role in the response to infection. Body's immune function is boosted by micronutrient and also plays a major role in response to tubercular infection. Someone, may argue that cell mediated immunity is compromised in iron deficiency before anemia becomes apparent. This descriptive observational study intended to assess serum iron profile in patients suffering from pulmonary tuberculosis. This study included 56 newly diagnosed sputum smear positive and negative pulmonary tuberculosis patients as per inclusion and exclusion criteria and was conducted at the department of the Internal Medicine, Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh with the collaboration of the Biochemistry department, BSMMU, Bangladesh from February 2017 to January 2018. Collected data were recorded in a structured questionnaire and compiled and appropriate analyses were done by using computer-based software Statistical Package for Social Sciences (SPSS) version 23.0. Out of 56 patients, majority was young and at reproductive age, male was predominant (78.6%) with a male to female ratio of 3.7:1. More than three fourth 43(81.0%) patients were found to have low serum iron concentration. Majority 45(80.4%) patients had normal serum TIBC, 6(10.7%) had low serum total iron binding capacity (TIBC) and 5(8.9%) had high serum TIBC. Almost two third 36(64.3%) patients had low serum transferrin saturation and 20(35.7%) had normal serum transferrin saturation. Majority 31(55.4%) patients had normal serum ferritin, 2(3.6%) had low serum ferritin and 23(41.1%) had high serum ferritin. Serum iron concentration and serum ferritin were significantly associated with chest x-ray abnormalities (p<0.01). Half of the patients were smear positive for acid fast bacilli (AFB) (50.0%). No significant association was found between sputum positive for AFB with iron profile status. In smear positive pulmonary tuberculosis patients, more than three fourth (78.6%) patients had low serum iron concentration at baseline and majority 20(80.0%) patients had normal serum iron concentration after 2(two) months. Mean serum iron concentration was 41.8±17.6mcg/l in baseline and 70.4±29.7mcg/l in at 2(two) month. More than sixty percent (60.7%) patients had low serum transferrin saturation at baseline and 20(80.0%) patients had normal serum transferrin saturation after 2(two) months. Mean serum transferrin saturation was 18.1±7.6% at baseline and 31.2±19.4% in at 2(two) months. After 2(two) months follow up serum iron concentration and serum transferrin saturation had significant improvement (p<0.05). Significant iron deficiency status occurred in pulpmonary tuberculosis and which improved after anti-tubercular treatment without iron supplementation.

Single-Cell Proliferation Microfluidic Device for High Throughput Investigation of Replicative Potential and Drug Resistance of Cancer Cells.

Introduction: Cell proliferation represents a major hallmark of cancer biology, and manifests itself in the assessment of tumor growth, drug resistance and metastasis. Tracking cell proliferation or cell fate at the single-cell level can reveal phenotypic heterogeneity. However, characterization of cell proliferation is typically done in bulk assays which does not inform on cells that can proliferate under given environmental perturbations. Thus, there is a need for single-cell approaches that allow longitudinal tracking of the fate of a large number of individual cells to reveal diverse phenotypes. Methods: We fabricated a new microfluidic architecture for high efficiency capture of single tumor cells, with the capacity to monitor cell divisions across multiple daughter cells. This single-cell proliferation (SCP) device enabled the quantification of the fate of more than 1000 individual cancer cells longitudinally, allowing comprehensive profiling of the phenotypic heterogeneity that would be otherwise masked in standard cell proliferation assays. We characterized the efficiency of single cell capture and demonstrated the utility of the SCP device by exposing MCF-7 breast tumor cells to different doses of the chemotherapeutic agent doxorubicin. Results: The single cell trapping efficiency of the SCP device was found to be ~ 85%. At the low doses of doxorubicin (0.01 µM, 0.001 µM, 0.0001 µM), we observed that 50-80% of the drug-treated cells had undergone proliferation, and less than 10% of the cells do not proliferate. Additionally, we demonstrated the potential of the SCP device in circulating tumor cell applications where minimizing target cell loss is critical. We showed selective capture of breast tumor cells from a binary mixture of cells (tumor cells and white blood cells) that was isolated from blood processing. We successfully characterized the proliferation statistics of these captured cells despite their extremely low counts in the original binary suspension. Conclusions: The SCP device has significant potential for cancer research with the ability to quantify proliferation statistics of individual tumor cells, opening new avenues of investigation ranging from evaluating drug resistance of anti-cancer compounds to monitoring the replicative potential of patient-derived cells. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00773-z.

Global Epidemiology of Pediatric Traumatic Spine Injury: A Systematic Review and Meta-Analysis.

OBJECTIVE: Traumatic spine injury (TSI) leads to significant morbidity and mortality in children. However, the global epidemiology of pediatric TSI is currently unknown. We conducted a systematic review and meta-analysis to estimate the global incidence of pediatric TSI and the burden of cases. METHODS: PubMed, Embase, and Scopus were searched for reports in June 2021 and updated in March 2023 with no restrictions on language or year of publication. A meta-analysis was conducted to estimate the global incidence of pediatric TSI and, subsequently, the number of cases of pediatric TSI worldwide and the proportion requiring spine surgery. RESULTS: Of 6557 studies, 25 met the inclusion criteria. Road traffic accidents (64%) were responsible for most cases reported in the literature, followed by falls (18%). The global incidence of TSI in children aged ≤20 years was estimated to be 14.24 of 100,000 children, or 375,734 children, with an estimated 114,975 requiring spine surgery. Across the World Bank income classification groups, lower middle-income countries had the highest pediatric TSI case burden (186,886 cases, with 57,187 requiring spine surgery). Across the World Health Organization regions, countries in the Southeast Asia region had the largest number of projected cases at 88,566, with 27,101 requiring surgical management, followed closely by the African region, with 87,235 projected cases and 26,694 requiring surgical management. CONCLUSIONS: Pediatric TSI represents a large healthcare burden globally. Interventions targeting both injury prevention and strengthening of neurosurgical capacity, especially in low resource settings, are needed to address this global health challenge.

Sudden Vision Loss Secondary to Optic Nerve Infiltration as a Presenting Symptom of Metastatic Lung Adenocarcinoma.

Purpose: To report a rare case of left-sided metastatic optic nerve infiltration and right-sided choroidal mass with exudative retinal detachment caused by EGFR exon 19 deletion positive non-small-cell lung adenocarcinoma that responded to targeted therapy with osimertinib (EGFR-TKI). Our patient demonstrated an excellent response with reduced size of the metastatic choroidal mass of the right orbit and improved visual acuity, in addition to systemic disease control. Case: A 66-year-old male patient with a history of diabetes mellitus, hypertension, and tobacco use presented with sudden vision loss in the left eye secondary to optic nerve infiltration and subacute vision loss in the right eye secondary to exudative retinal detachment from a choroidal metastasis. He was found to have a right lung mass, multiple metastatic pulmonary nodules, and liver and bone metastases. Biopsy from a mediastinal lymph node confirmed the diagnosis of metastatic lung adenocarcinoma. He was found to have exon 19 deletion on next-generation sequencing. We treated him with local radiation therapy to the left eye and systemic osimertinib (EGFR-TKI). Conclusion: To our knowledge, our case is the first report of a patient who initially presented with acute vision loss and was found to have metastatic retrobulbar optic nerve infiltration in one eye and metastatic choroidal lesion with exudative retinal detachment in the fellow eye secondary to lung adenocarcinoma. Due to the rarity of this condition, literature regarding effective treatment is scarce. Our patient demonstrated significant improvement in visual acuity and resolution of exudative retinal detachment in the right eye following osimertinib treatment and radiation therapy to the left eye. Further investigation into the role of tyrosine kinase inhibitors and radiation therapy in treating intraocular metastasis involving the optic nerve is needed.

Severe abacavir hypersensitivity reaction in a patient with human immunodeficiency virus infection: a case report.

BACKGROUND: Abacavir is a nucleoside reverse transcriptase inhibitor that is used as a component of the antiretroviral treatment regimen in the management of the human immunodeficiency virus for both adults and children. It is efficacious, but its use may be limited by a hypersensitivity reaction linked with the HLA-B*57:01 genotype. HLA-B*57:01 has been reported to be rare in African populations. Because of the nature of its presentation, abacavir hypersensitivity is prone to late diagnosis and treatment, especially in settings where HLA-B*57:01 genotyping is not routinely done. CASE REPORT: We report a case of a severe hypersensitivity reaction in a 44-year-old Kenyan female living with the human immunodeficiency virus and on abacavir-containing antiretroviral therapy. The patient presented to the hospital after recurrent treatment for a throat infection with complaints of fever, headache, throat ache, vomiting, and a generalized rash. Laboratory results evidenced raised aminotransferases, for which she was advised to stop the antiretrovirals that she had recently been started on. The regimen consisted of abacavir, lamivudine, and dolutegravir. She responded well to treatment but was readmitted a day after discharge with vomiting, severe abdominal pains, diarrhea, and hypotension. Her symptoms disappeared upon admission, but she was readmitted again a few hours after discharge in a hysterical state with burning chest pain and chills. Suspecting abacavir hypersensitivity, upon interrogation she reported that she had taken the abacavir-containing antiretrovirals shortly before she was taken ill. A sample for HLA-B*57:01 was taken and tested positive. Her antiretroviral regimen was substituted to tenofovir, lamivudine, and dolutegravir, and on subsequent follow-up she has been well. CONCLUSIONS: Clinicians should always be cognizant of this adverse reaction whenever they initiate an abacavir-containing therapy. We would recommend that studies be done in our setting to verify the prevalence of HLA-B*57:01.

Dogs cloned from adult somatic cells.

Several mammals--including sheep, mice, cows, goats, pigs, rabbits, cats, a mule, a horse and a litter of three rats--have been cloned by transfer of a nucleus from a somatic cell into an egg cell (oocyte) that has had its nucleus removed. This technology has not so far been successful in dogs because of the difficulty of maturing canine oocytes in vitro. Here we describe the cloning of two Afghan hounds by nuclear transfer from adult skin cells into oocytes that had matured in vivo. Together with detailed sequence information generated by the canine-genome project, the ability to clone dogs by somatic-cell nuclear transfer should help to determine genetic and environmental contributions to the diverse biological and behavioural traits associated with the many different canine breeds.

Terrorist bombings: medical response in a developing country.

OBJECTIVE: To evaluate the process of transport and immediate Emergency Department (ER) management of mass casualties following the recent bomb blasts in Karachi and review in detail the medical response and management of victims undertaken in these two incidents. METHODS: Eyewitness accounts of the victims, medical personnel and newspaper clippings were used to understand and identify difficulties faced during the rescue process. Data regarding presenting injuries and their outcomes was also collected from all victims presenting to the emergency department at Aga Khan University Hospital. RESULTS: Seventy nine individuals died and over 250 victims were injured in the two incidents. All victims and dead bodies were shifted to the nearest public sector hospital overwhelming the health care facility. Subsequently all victims were evacuated to private sector hospitals creating similar difficulties. Over half of the victims presenting at the emergency department had minor injuries and did not require admission. Most patients requiring admission needed orthopaedic intervention. CONCLUSION: A comprehensive disaster plan with a centralized command and control system is required for the city of Karachi, involving all stake holders including charity ambulance services, security agencies, and trauma management facilities. Training courses and exercises for health care personnel should also be made mandatory to achieve professional excellence.

Farm typology for planning targeted farming systems interventions for smallholders in Indo-Gangetic Plains of India.

Due to complexity of smallholder farms, many times technologies with great potential fail to achieve the desired impact in leveraging productivity and profitability of the farming community. In the Indo-Gangetic Plains there is an urgent need to understand the diversity of farm households, identifying the main drivers deciding their system thus, classifying them into homogenous groups. In the present study, the diversity of smallholder farms was assessed using crop, livestock and income related characteristics and associated farm mechanization. Using principal component analysis and cluster analysis for 252 farm households, 4 farm types were identified i.e. Type 1. Small Farm households with cereal-based cropping system and subsistence livestock (39%), Type 2. Small Farm households with diversified cropping system dominated by cereal and fodder crops with only cattle herd (9%), Type 3. Marginal Farm household with diversified cropping system dominated by cash crop and herd comprising of only cattle (39%), Type 4. Marginal Farm household with diversified cropping system dominated by cereal crops and herd dominated by small ruminants (12%). Based on the constraints identified for different components of farming systems, low-cost interventions were planned for each farm type. These interventions have resulted in 84.8-103.2 per cent increase in the income of the farm HH under study suggesting usefulness of typology-based intervention planning in increasing income of small farm holders.

Targeted brachyury degradation disrupts a highly specific autoregulatory program controlling chordoma cell identity.

Chordomas are rare spinal tumors addicted to expression of the developmental transcription factor brachyury. In chordomas, brachyury is super-enhancer associated and preferentially downregulated by pharmacologic transcriptional CDK inhibition, leading to cell death. To understand the underlying basis of this sensitivity, we dissect the brachyury transcription regulatory network and compare the consequences of brachyury degradation with transcriptional CDK inhibition. Brachyury defines the chordoma super-enhancer landscape and autoregulates through binding its super-enhancer, and its locus forms a transcriptional condensate. Transcriptional CDK inhibition and brachyury degradation disrupt brachyury autoregulation, leading to loss of its transcriptional condensate and transcriptional program. Compared with transcriptional CDK inhibition, which globally downregulates transcription, leading to cell death, brachyury degradation is much more selective, inducing senescence and sensitizing cells to anti-apoptotic inhibition. These data suggest that brachyury downregulation is a core tenet of transcriptional CDK inhibition and motivates developing strategies to target brachyury and its autoregulatory feedback loop.

UNIQUE PRESENTATION OF DUPLICATION OF THE PITUITARY GLAND-PLUS SYNDROME.

OBJECTIVE: To shed light on a unique presentation of duplication of the pituitary gland (DPG)-plus syndrome. METHODS: We present the case report gathered from the patient. RESULTS: This patient uniquely had DPG-plus syndrome with a concurrent dermoid cyst. CONCLUSION: DPG is a very rare developmental anomaly and there are not many case reports published in the literature. The presence of DPG with dermoid cyst in our patient has not been reported previously. This case report discusses the various presentations of the syndrome and also provides an overview of investigations and management of these patients.

Moxifloxacin induced encephalopathy in disseminated tuberculosis: A case report.

Moxifloxacin is a third-generation fluoroquinolone antibiotic with broad spectrum activity and also used as component of anti-tubercular therapy (ATT). Though frequently prescribed, moxifloxacin induced encephalopathy is uncommonly seen. Here we describe a forty four year old male, with features of disseminated tuberculosis (TB) and suspected case of multi-drug resistance (MDR), who developed acute encephalopathy. Extensive laboratory investigations, neuroimaging of brain, cerebrospinal fluid analysis was unremarkable. On stopping moxifloxacin, which was being administerd as part of ATT for MDR TB, encephalopathy resolved completely, thereby proving it to be a case of moxifloxacin induced encephalopathy. To conclude, by presenting this case, we wish to raise awareness about moxifloxacin induced encephalopathy among healthcare providers.