COVID-19 Induces Neuroinflammation and Suppresses Peroxisomes in the Brain.

OBJECTIVE: Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune responses and peroxisome biogenesis factors during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using a multiplatform strategy. METHODS: Brain tissues from coronavirus disease 2019 (COVID-19) (n = 12) and other disease control (ODC) (n = 12) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS-CoV-2, were investigated by droplet digital polymerase chain reaction (ddPCR), quantitative reverse transcriptase PCR (RT-qPCR), and immunodetection methods. RESULTS: SARS-CoV-2 RNA was detected in the CNS of 4 patients with COVID-19 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID-19 showed induction of pro-inflammatory transcripts (IL8, IL18, CXCL10, NOD2) and cytokines (GM-CSF and IL-18) compared to CNS tissues from ODC patients (p < 0.05). Peroxisome biogenesis factor transcripts (PEX3, PEX5L, PEX11ß, and PEX14) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID-19 compared to ODC patients (p < 0.05). SARS-CoV-2 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post-infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post-infection (p < 0.05). Pex3 transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS-CoV-2 infected animals (p < 0.05). INTERPRETATION: COVID-19 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS-CoV-2 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post-acute sequelae of COVID-19. ANN NEUROL 2023;94:531-546.

Evaluation of transfer factors of 226Ra, 232Th, and 40K radionuclides from soil to grass and mango in the northern region of Bangladesh.

Bangladesh is a rapidly developing country, which is vulnerable to various types of pollution due to the large-scale industrial and associated human activities that might potentially affect the locally harvested foodstuffs. Therefore, the transfer factor is an essential tool to assess the safety of foodstuffs due to the presence of natural radioactivity in environmental matrix and/or strata. This is a first study of its kind conducted in a well-known region for mango farming in Bangladesh, measuring the uptake of naturally occurring radioactive materials (NORMs) by grass and mango from soil to assess the ingestion doses to humans. The HPGe gamma-ray detector was used to determine the concentrations of NORMs in samples of soil (20), grass (10), and mango (10), which were then used to calculate the transfer factors of soil to grass and soil to mango. Average activity concentrations of 226Ra, 232Th, and 40K in associated soil samples (47.27 ± 4.10, 64.49 ± 4.32, 421.60 ± 28.85) of mango and 226Ra and 232Th in associated soil samples (45.07 ± 3.93, 52.17 ± 3.95) of grass were found to exceed the world average values. The average transfer factors (TFs) for mango were obtained in the order of 40K(0.80) > 226Ra (0.61) > 232Th (0.31), and for grass, it shows the order of 40K (0.78) > 232Th (0.64) > 226Ra (0.56). However, a few values (3 mango samples and 3 grass samples) of the estimated TFs exceeded the recommended limits. Moreover, Bangladesh lacks the transfer factors for most of the food crops; therefore, calculation of TFs in the major agricultural products is required all over Bangladesh, especially the foodstuffs produced near the Rooppur Nuclear Power Plant, which is scheduled to be commissioned in 2023.

Antibacterial effect of kitchen herbs against pathogenic multidrug-resistant E. coli isolates from calf diarrhoea.

Calf diarrhoea remains the biggest challenge both in the small and large farms. Infectious diarrhoea is associated with many pathogens, Escherichia coli being one, but majority are systematically treated with antibiotics. Since antimicrobial resistance (AMR) is a growing menace, the need to find alternative prophylactic solutions using popular kitchen herbs such as Trachyspermum ammi (carom seeds), Curcuma longa (turmeric) and cinnamon (Cinnamomum sp.) extracts is been investigated against virulent form of E. coli isolated from calf diarrhoea. The virulence factors identified in these isolates were ST (32.5%), LT (20%), eaeA (15%), stx1 (2.5%) and stx2 (5%) with the occurrence of the most common serogroups as O18 (15%) followed by O111 (12.5%). Highest resistance was seen with beta lactam + beta lactamase inhibitor (amoxicillin/clavulanic acid) followed by beta lactams (ampicillin, cefuroxime and cefepime). The zone of inhibition due to cinnamon (methanol) and carom seed (ethanol) extracts (500 to 250 µg/mL concentration) on E. coli bacteria was >19 mm, respectively. Turmeric, cinnamon and carom had the potency of inhibiting the pathogenic E. coli which maybe suggestive of its use in calf diets as prophylaxis against diarrhoea.

Do children in India grow well into adolescents? Longitudinal analysis of growth transitions from Young Lives panel survey in India.

OBJECTIVES: Studies that examined the growth during late childhood and early adolescence beyond 8 years of age are very limited. Further, most studies have used dichotomized classification of stunting, thereby limiting the understanding of moderate stunting in childhood growth trajectory. We aimed to examine the course of stunting from childhood to adolescence by undertaking robust analyses of the Young Lives Survey (YLS) longitudinal data from India using multilevel categorization of stunting. STUDY DESIGN: Retrospective cohort analysis was undertaken from YLS in India among 1827 children from the younger cohort born in 2001-02 with complete follow-up data in all five rounds of YLS collected in 2002, 2006, 2009, 2013, and 2016. METHODS: A three-state multistate Markov model (not stunted, moderate, severe) was performed to estimate annual transition probabilities, mean sojourn-time, and transition-specific risk factors. RESULTS: Between Round-one and Round-five, cross-sectional prevalence of severe stunting decreased from 10.4% (95% confidence interval [CI]: 7.8%, 13.7%) to 5.3% (95% CI: 3.8%, 7.3%), while moderate stunting increased from 19.9% (95% CI: 16.3%,23.9%) to 21.7% (95% CI: 18.4%, 24.9%). Mean Sojourn time estimation indicated a relatively concise state for moderate stunting. The stunting trajectory had shown gender differential where more faltering to severe stunting and lower recovery to the normal state was observed among girls between 8 and 12 years and among boys between 12 and 15 years. Compared with boys, girls had 40% excess likelihood (Hazard Ratio: 1.40; 95% CI 1.00 to 1.95) for moderate-to-severe stunting transition and also had 19% excess likelihood (Hazard Ratio: 1.19; 95% CI 1.01 to 1.40) of favorable transition (moderate-to-non-stunted). CONCLUSIONS: The transition trajectory highlights preadolescence, especially among girls, as an additional window of opportunity to ensure better nutrition in adolescent life. With a fifth of adolescents living in India, study findings call for coordinated, multisectoral, age-appropriate, and gender-responsive approach to take India closer to meeting SDG-2.

Seasonal variation in photosynthetic rates and satellite-based GPP estimation over mangrove forest.

In view of increasing anthropogenic influences and global changes, quantification of carbon assimilation through photosynthesis has gained tremendous significance. Precise estimation of Gross Primary Productivity (GPP) is essential for several ecosystem models and is typically done using coarser scale satellite data. The mangrove ecosystem, which offers significant protection to the coastal environment, is one of the critical habitats from a global change point of view. Light use efficiency (LUE) was measured using diurnal in situ photosynthetic rate observations for 13 dominant mangrove species for 3 seasons at each of the three mangrove dominant test-sites situated along the east and west coast of India. Variations in photosynthetic rates among these species were studied for 3 seasons that indicated varying responses of mangrove ecosystem at each site. Among all species, Rhizophora mucronata and Sonneratia apetala indicated higher values at two of the test-sites. IRS Resourcesat-2 LISS-IV datasets were used for the estimation of GPP. Mean GPP for all the sites varied from 1.2 to 7.7 g C m-2 day-1 with maximum value of 14.4 g C m-2 day-1. Mean values of GPP varied across the sites, based on its maximum LUE values and available photosynthetically active radiation (PAR). The results provide GPP values at much better spatial resolution for a threatened habitat like mangroves that typically survive in a narrow habitat along the coasts.

Developing a new PI-RADS v2-based nomogram for forecasting high-grade prostate cancer.

AIM: To establish a predictive nomogram for high-grade prostate cancer (HGPCa) in biopsy-naive patients based on the Prostate Imaging-Reporting and Data System version 2 (PI-RADS v2), magnetic resonance imaging (MRI)-based prostate volume (PV), MRI-based PV-adjusted prostate-specific antigen density (PSAD), and other classical parameters. MATERIAL AND METHODS: Between August 2014 and August 2015, 158 men who were eligible for analysis were included as the training cohort. A prediction model for HGPCa was built using backward logistic regression and was presented on a nomogram. The prediction model was evaluated by a validation cohort between September 2015 and March 2016 (n=89). Histology of all lesions was obtained with MRI-directed transrectal ultrasound (TRUS)-guided targeted and sectoral biopsy. RESULTS: The multivariate analysis revealed that patient age, PI-RADS v2 score, and adjusted PSAD were independent predictors for HGPCa. The most discriminative cut-off value for the logistic regression model was 0.33; the sensitivity, specificity, positive predictive value, and negative predictive value were 83.3%, 87.4%, 88.4%, and 81.2%, respectively. The diagnostic performance measures retained similar values in the validation cohort (AUC=0.83). CONCLUSION: The nomogram for forecasting HGPCa is effective and potentially reducing harm from unnecessary prostate biopsy and over-diagnosis.

Outcome of Pregnancy Related Acute Kidney Injury Observed in a Tertiary Care Hospital.

This prospective case control study was carried out in Mymensingh Medical College Hospital (MMCH) from April 2011 to March 2012. The main objective of the study was to determine the short term maternal outcome of pregnancy related Acute Kidney Injury and to identify aetiological factors and to observe clinical features of pregnancy related Acute Kidney Injury. Total 60 pregnant women with AKI were included in the study as sample and equal (60) number of pregnant women with normal renal function was taken as control. Mean ages (±SD) of study and control group were observed 31.6±6.9 years and 25.5±4.7 years respectively. It was observed that most patients were from rural area with low income group. Most women were multiparous and presented in third trimester and postpartum period. Majority of the study subjects did not receive antenatal care at any stage of pregnancy. Fifty (86.7%) of the study subjects were oligo-anuric, forty-nine (81.7%) were edematous and fifty one (85%) were anaemic. Twenty-five (41.7%) patients presented with abnormal vaginal bleeding. Sepsis (including septic abortion and puerperal sepsis) was responsible for of Pregnancy Related AKI (PR-AKI) in more than two fifths of cases. Haemorrhage (APH & PPH combined) was the next common cause of Pregnancy Related AKI (PR-AKI). Toxemia of Pregnancy was responsible in one fourth of cases. Dialysis (HD & IPD combined) was required for two fifths of the patients. Rest patients were treated conservatively with antibiotics, blood transfusion, maintenance of fluid and electrolytes balance etc. Maternal outcome of Pregnancy related acute kidney injury was considered for the period of patient's hospital staying. 56.6% patients recovered completely, 15.0% patients recovered partially, 6.7% did not recover at the time of hospital discharge; while 21.7% died. So it can be concluded that, pregnancy related acute kidney injury is a critical condition, associated with worse prognosis.

Comparative evaluation of hormonal protocol on the performance of crossbred cattle.

A total of 60 animals (38 cows, 22 heifers) were selected and were divided into three groups of 20 animals each (containing both anoestrus and repeat breeder) in which treatment was performed for 60 days. Group I: control (farmer practice), T1 group: group I + hormone (double synch), and T2 group: group I + hormone (Estra double synch). The growth performances were measured in terms of body weight and average daily gain (ADG). Blood collection was done at the start and end of the experiment for assessment of blood biochemical, hematological, and reproductive status of the animals. Results revealed significant improvement in growth and reproductive performances in treatment group as compared to control group. Higher percentage of conception was achieved in group III (60%) followed by group II (55%). The least percentage was in group I (15%), i.e., in control group. So it was found that the effect of treating the reproductive-disordered animals with Estra double synch gave comparatively better result than double synch hormonal application.

Incidence of severe diarrhoea due to Vibrio cholerae in the catchment area of six surveillance hospitals in Bangladesh.

Cholera is an important public health problem in Bangladesh. Interventions to prevent cholera depend on their cost-effectiveness which in turn depends on cholera incidence. Hospital-based diarrhoeal disease surveillance has been ongoing in six Bangladeshi hospitals where a systematic proportion of patients admitted with diarrhoea were enrolled and tested for Vibrio cholerae. However, incidence calculation using only hospital data underestimates the real disease burden because many ill persons seek treatment elsewhere. We conducted a healthcare utilization survey in the catchment areas of surveillance hospitals to estimate the proportion of severe diarrhoeal cases that were admitted to surveillance hospitals and estimated the population-based incidence of severe diarrhoea due to V. cholerae by combining both hospital surveillance and catchment area survey data. The estimated incidence of severe diarrhoea due to cholera ranged from 0.3 to 4.9/1000 population in the catchment area of surveillance hospitals. In children aged <5 years, incidence ranged from 1.0 to 11.0/1000 children. Diarrhoeal deaths were most common in the Chhatak Hospital's catchment area (18.5/100 000 population). This study provides a credible estimate of the incidence of severe diarrhoea due to cholera in Bangladesh, which can be used to assess the cost-effectiveness of cholera prevention activities.

A Breast Lump in an Elderly Lady - Carcinoma or else ?.

Breast tuberculosis (TB) is rare form of extra-pulmonary TB. It is most commonly seen in women of reproductive age group, especially in young, multiparous women who are breast feeding. In geriatric women, breast TB in some cases simulates with breast carcinoma due to common signs which include hard breast lump with nodular surface, ulceration, fixity to skin, discharging sinus, retraction of nipple, axillary lymphadenopathy etc. Hence, it is very difficult to differentiate breast TB from breast cancer, especially in elderly women on clinical ground only, and therefore, histopathological diagnosis is mandatory. Fine needle aspiration cytology is frequently inconclusive due to very small amount of tissue material, and open biopsy or lumpectomy followed by histopathological examination is necessary to confirm the diagnosis of breast TB. Six-month course of anti-tuberculous therapy - ATT (rifampicin, isoniazid, pyrazinamide and ethambutol) is adequate for complete resolution. Here, we report a case of breast TB in an elderly women presenting with left sided breast lump with ulceration of overlying skin and ipsilateral axillary lymphadenopathy. This case of tuberculous mastitis was suspected to be carcinoma due to presence of hard, tender, breast lump with irregular margin, nodular surface, ulceration, purulent discharge and ipsilateral axillary lymphadenopathy in absence of any constitutional symptoms of TB, and heterogenous, hypoechoic mass on USG, which was confirmed by histopathological examination of resected breast lump and responded fully to ATT.

A Rare Case of Bilateral Aspergillomas in a Patient of Ankylosing Spondylitis.

Pulmonary involvement by Aspergillus sp. mainly includes allergic bronchopulmonary aspergillosis, aspergilloma, and invasive aspergillosis. Aspergilloma (Fungal ball) is the most common form of aspergillous pulmonary involvement, which occurs in preexisting pulmonary cavities, especially secondary to pulmonary tuberculosis. Ankylosing spondylitis is a rare cause of upper lobe fibro-cavitary lesions in pulmonary parenchyma. It may also lead to development of fungal balls in pulmonary cavities. Most common presentation is mild to massive hemoptysis; dyspnoea, chronic cough, expectoration may be other presentation; even the patient may remain asymptomatic. Intaracavitary mobile mass is a valuable sign for fungal ball, best detected by computed tomography (CT) scan of thorax. Lobectomy is the treatment of choice to stop the hemoptysis, if the general condition of the patient is fit; otherwise associated co-morbidities complicate the post-operative scenario. In this situation, bronchial artery embolization may be used as a temporary measure to control hemoptysis. Here, we report a case of bilateral aspergillomas within the cavities located in upper lobes of both lungs in a 74 years old male who was suffering from ankylosing spondylitis for last 42 years.

Adipose tissue gene expression and metabolic health of obese adults.

Obese subjects with a similar body mass index (BMI) exhibit substantial heterogeneity in gluco- and cardiometabolic heath phenotypes. However, defining genes that underlie the heterogeneity of metabolic features among obese individuals and determining metabolically healthy and unhealthy phenotypes remain challenging. We conducted unsupervised hierarchical clustering analysis of subcutaneous adipose tissue transcripts from 30 obese men and women ⩾40 years old. Despite similar BMIs in all subjects, we found two distinct subgroups, one metabolically healthy (group 1) and one metabolically unhealthy (group 2). Subjects in group 2 showed significantly higher total cholesterol (P=0.005), low-density lipoprotein cholesterol (P=0.006), 2-h insulin during oral glucose tolerance test (P=0.015) and lower insulin sensitivity (SI, P=0.029) compared with group 1. We identified significant upregulation of 141 genes (for example, MMP9 and SPP1) and downregulation of 17 genes (for example, NDRG4 and GINS3) in group 2 subjects. Intriguingly, these differentially expressed transcripts were enriched for genes involved in cardiovascular disease-related processes (P=2.81 × 10(-11)-3.74 × 10(-02)) and pathways involved in immune and inflammatory response (P=8.32 × 10(-5)-0.04). Two downregulated genes, NDRG4 and GINS3, have been located in a genomic interval associated with cardiac repolarization in published GWASs and zebra fish knockout models. Our study provides evidence that perturbations in the adipose tissue gene expression network are important in defining metabolic health in obese subjects.

Aetiologies of diarrhoea in adults from urban and rural treatment facilities in Bangladesh.

The objective of our analysis was to describe the aetiology, clinical features, and socio-demographic background of adults with diarrhoea attending different urban and rural diarrhoeal disease hospitals in Bangladesh. Between January 2010 and December 2011, a total of 5054 adult diarrhoeal patients aged ⩾20 years were enrolled into the Diarrhoeal Disease Surveillance Systems at four different hospitals (two rural and two urban) of Bangladesh. Middle-aged [adjusted odds ratio (aOR) 0·28, 95% confidence interval (CI) 0·23-0·35, P < 0·001] and elderly (aOR 0·15, 95% CI 0·11-0·20, P < 0·001) patients were more likely to present to rural diarrhoeal disease facilities than urban ones. Vibrio cholerae was the most commonly isolated pathogen (16%) of the four pathogens tested followed by rotavirus (5%), enterotoxigenic Escherichia coli (ETEC) (4%), and Shigella (4%). Of these pathogens, V. cholerae (19% vs. 11%, P < 0·001), ETEC (9% vs. 4%, P < 0·001), and rotavirus (5% vs. 3%, P = 0·013) were more commonly detected from patients presenting to urban hospitals than rural hospitals, but Shigella was more frequently isolated from patients presenting to rural hospitals than urban hospitals (7% vs. 2%, P < 0·001). The isolation rate of Shigella was higher in the elderly than in younger adults (8% vs. 3%, P < 0·001). Some or severe dehydration was higher in urban adults than rural adults (P < 0·001). Our findings indicate that despite economic and other progress made, conditions facilitating transmission of V. cholerae and Shigella prevail in adults with diarrhoea in Bangladesh and further efforts are needed to control these infections.

Determinants of percent expenditure of household income due to childhood diarrhoea in rural Bangladesh.

There is limited information on percent expenditure of household income due to childhood diarrhoea especially in rural Bangladesh. A total of 4205 children aged <5 years with acute diarrhoea were studied. Percent expenditure was calculated as total expenditure for the diarrhoeal episode divided by monthly family income, multiplied by 100. Overall median percent expenditure was 3·04 (range 0·01-94·35). For Vibrio cholerae it was 6·42 (range 0·52-82·85), for enterotoxigenic Escherichia coli 3·10 (range 0·22-91·87), for Shigella 3·17 (range 0·06-77·80), and for rotavirus 3·08 (range 0·06-48·00). In a multinomial logistic regression model, for the upper tertile of percent expenditure, significant higher odds were found for male sex, travelling a longer distance to reach hospital (⩾median of 4 miles), seeking care elsewhere before attending hospital, vomiting, higher frequency of purging (⩾10 times/day), some or severe dehydration and stunting. V. cholerae was the highest and rotavirus was the least responsible pathogen for percent expenditure of household income due to childhood diarrhoea.

Lack of BCG vaccination and other risk factors for bacteraemia in severely malnourished children with pneumonia.

We sought to examine the factors associated with bacteraemia and their outcome in children with pneumonia and severe acute malnutrition (SAM). All SAM children of either sex, aged 0-59 months, admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh with radiologically confirmed pneumonia from April 2011 to July 2012 were enrolled (n = 405). Comparison was made between pneumonic SAM children with (cases = 18), and without (controls = 387) bacteraemia. The death rate was significantly higher in cases than controls (28% vs. 8%, P < 0·01). In logistic regression analysis, after adjusting for potential confounders, the SAM children with pneumonia and bacteraemia more often had a history of lack of bacillus Calmette-Guérin (BCG) vaccination (odds ratio 7·39, 95% confidence interval 1·67-32·73, P < 0·01). The results indicate the importance of continuation of BCG vaccination which may provide benefit beyond its primary purpose.

Epidemiology of epilepsy and its burden in Kolkata, India.

BACKGROUND: Disability-adjusted life year (DALY) is a time-based measure of disease burden incorporating both disability and mortality. Our study aimed to determine the DALY lost from epilepsy in an Indian metropolis. METHODS: A population-based prospective study on epilepsy was conducted over 5 years (2003-8) in Kolkata, India, on randomly selected 100,802 subjects (males 53,209, females 47,593) to assess prevalence as well as to capture incident cases of epilepsy and those incident cases that died. Standard case definitions were used. The data were used to estimate years of life lost (YLL) due to premature mortality, years of life lived with disability (YLD), and DALY, utilizing the prevalence-based Global Burden of Disease (GBD) 2010 approach. Age- and gender-specific figures were computed. RESULTS: During 2003-2004, a total of 476 subjects with active epilepsy were detected and the age-adjusted prevalence rate was 4.71 per 1000. Over 5 years, there were 197 incident cases of epilepsy of whom 26 died. The age-adjusted annual incidence rate of epilepsy was 38.3 per 100,000. The all-cause standardized mortality rate (SMR) of epilepsy was 2.4. The burden of epilepsy in the year 2007-8 revealed the overall YLL was 755 per 100,000, and the overall YLD ranged from 14.45 to 31.0 per 100,000 persons depending on the clinical severity of the epilepsy. Both YLL and YLD values were higher in males than in females. The overall DALY lost due to epilepsy in 2007-8 was found to be 846.96 (males 1183.04, females 463.81) per 100,000. CONCLUSIONS: This is the first study in India to determine the DALY of epilepsy using GBD 2010. The results reveal a substantial burden of epilepsy in our setting. Similar such studies are needed in other parts of India in both urban and rural settings.

Oxidative stress and antioxidative parameters in patients with spinal cord injury: implications in the pathogenesis of disease.

STUDY DESIGN: Oxygen-derived free radicals have been implicated in the pathogenesis of spinal cord injury (SCI) after trauma. OBJECTIVE: In this review we will elucidate the importance of oxidative stress and antioxidants and its possible relationship with SCI. METHODS: Literature analysis of oxidative stress, antioxidative parameters based on its implications in the pathogenesis along with devastating effect of oxidative stress parameters on SCI patients and its suggested proposed treatment by antioxidants have been performed. RESULTS: SCI remains a major health problem despite advances in neurotechnology. Previous studies have reported oxidative stress in SCI patients, but the results were inconsistent. Furthermore, increased free radical levels are reported in SCI. Moreover, we have also mentioned in this review that oxidative stress is supposed to be increased in patients with SCI, which is related to the severity of SCI pain. CONCLUSION: Oxidative stress was commonly seen in SCI patients, which may provide useful information to augment the understanding of pathophysiology of SCI patients. However, complete understanding of the biochemical events occurring at a cellular level that influence oxidative damage is required to guide future therapeutic advances. Furthermore, supplementation of antioxidants may also be considered in these patients.

A case of paraneoplastic bullous pemphigoid in association with squamous cell carcinoma of lung.

Bullous pemphigoid is a chronic, autoimmune, acquired subepidermal blistering disorder. It is idiopathic in origin, and mainly seen in elderly individuals. Association between bullous pemphigoid and internal malignancies is reported in the literature, but the exact causal relation is not established. Paraneoplastic bullous pemphigoid is rarely reported in lung cancers, especially in squamous cell variety. So their presence should raise the suspicion of various internal malignancies including lung cancer. It is presented mainly with tense, large blisters over the erythematous base or over normal skin. Subepidermal blisters with tissue eosinophilia are characteristic histopathological features of bullous pemphigoid. Direct immunofluorescence shows linear deposits of IgG - complement complex along the dermoepidermal junction. Conventional treatment of bullous pemphigoid along with treatment of lung cancer (surgery, chemotherapy, radiotherapy) may result in successful resolution of skin lesions. Here, we report a rare association of paraneoplastic bullous phemphigoid and squamous cell carcinoma of lung in a 76-year-old male to increase the awareness among the clinicians regarding this variety of cutaneous paraneoplastic manifestation of lung cancer.

BI-69A11 enhances susceptibility of colon cancer cells to mda-7/IL-24-induced growth inhibition by targeting Akt.

BACKGROUND: Akt and its downstream signalling pathways contribute to the aetiology and progression of colorectal carcinoma (CRC). Targeting the Akt pathway is an attractive strategy but few chemotherapeutic drugs have been used to treat CRC with only limited success. BI-69A11, a small molecule inhibitor of Akt, efficiently inhibits growth in melanoma cells. Melanoma differentiation associated gene-7 (mda-7)/interleukin-24 promotes cancer-selective apoptosis when delivered by a tropism-modified replication incompetent adenovirus (Ad.5/3-mda-7). However, Ad.5/3-mda-7 displays diminished antitumour efficacy in several CRC cell lines, which correlates with the expression of K-RAS. METHODS: The individual and combinatorial effect of BI-69A11 and Ad.5/3-mda-7 in vitro was studied by cell viability, cell cycle, apoptosis and invasion assays in HT29 and HCT116 cells containing wild type or mutant K-ras, respectively. In vivo HT29 tumour xenografts were used to test the efficacy of the combination treatment. RESULTS: BI-69A11 inhibited growth and induced apoptosis in CRC. However, combinatorial treatment was more effective compared with single treatment. This combination showed profound antitumour and anti angiogenic effects in vitro and in vivo by downregulating Akt activity. CONCLUSIONS: BI-69A11 enhances the antitumour efficacy of Ad.5/3-mda-7 on CRC overexpressing K-RAS by inducing apoptosis and regulating Akt activity thereby warranting further evaluation in treating CRC.

Changing patient population in Dhaka Hospital and Matlab Hospital of icddr,b.

The Diarrhoeal Disease Surveillance System of icddr,b noted increasing number of patients ≥60 years at urban Dhaka and rural Matlab from 2001 to 2012. Shigella and Vibrio cholerae were more frequently isolated from elderly people than children under 5 years and adults aged 5-59 in both areas. The resistance observed to various drugs of Shigella in Dhaka and Matlab was trimethoprim-sulphamethoxazole (72-63%), ampicillin (43-55%), nalidixic acid (58-61%), mecillinam (12-9%), azithromycin (13-0%), ciprofloxacin (11-13%) and ceftriaxone (11-0%). Vibrio cholerae isolated in Dhaka and Matlab was resistant to trimethoprim-sulphamethoxazole (98-94%), furazolidone (100%), erythromycin (71-53%), tetracycline (46-44%), ciprofloxacin (3-10%) and azithromycin (3-0%).