Link N suppresses interleukin-1ß-induced biological effects on human osteoarthritic cartilage.

Osteoarthritis (OA) is a disease of diarthrodial joints associated with extracellular matrix proteolytic degradation under inflammatory conditions, pain and disability. Currently, there is no therapy to prevent, reverse or modulate the disease course. The present study aimed at evaluating the regenerative potential of Link N (LN) in human OA cartilage in an inflammatory milieu and determining if LN could affect pain-related behaviour in a knee OA mouse injury model. Osteo-chondro OA explants and OA chondrocytes were treated with LN in the presence of interleukin-1ß (IL-1ß) to simulate an osteoarthritic environment. Quantitative von Frey polymerase chain reaction and Western blotting were performed to determine the effect of LN on matrix protein synthesis, catabolic enzymes, cytokines and nerve growth factor expression. Partial medial meniscectomy (PMM) was performed on the knee of C57BL/6 mice and, 12 weeks post-surgery, mice were given a 5 µg intra-articular injection of LN or phosphate-buffered saline. A von Frey test was conducted over 24 h to measure the mechanical allodynia in the hind paw. LN modulated proteoglycan and collagen synthesis in human OA cartilage through inhibition of IL-1ß-induced biological effects. LN also supressed IL-1ß-induced upregulation of cartilage-degrading enzymes and inflammatory molecules in OA chondrocytes. Upon investigation of the canonical signalling pathways IL-1ß and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), LN resulted to significantly inhibit NF-κB activation in a dose-dependent manner. In addition, LN suppressed mechanical allodynia in an OA PMM mouse model. Results supported the concept that LN administration could provide therapeutic potential in OA.

Diagnostic and Treatment Delays among the Tuberculosis Patients in the Urban Area of Western Nepal.

Background Diagnosis and treatment of tuberculosis is vital for health system to identify, treat patients as early as possible and to reduce frequency of new cases of a disease among the contacts of known cases. Objective To determine the diagnostic and treatment delay in the urban population of the western, Nepal and factors associated to it. Method An institutional based cross-sectional study was conducted in urban area of Western Nepal. Category I 142 TB patients aged over 15 years visiting DOTs centre during period of three months were included in study. Interview schedule was designed to elicit information on socio- demographic characteristics and history of symptoms. Diagnostic and treatment delay was calculated, chi square test was applied to find associations and non - parametric tests (Mann Whitney U test and Kruskal Wallis H test) for evaluating group differences. Result Out of 142 TB clients, mean age was 38.12 years. Majority (58%) were males. Around 44% belong to upper, 30% middle and 26% lower economic class. Study showed median diagnostic delay 34 days (Q3 =68 Days, Q1 =19 Days), treatment delay less than a day (Q3 =1 Day, Q1 =0 Day) and total delay 33.50 days (Q3 =71 Days, Q1 =19 Days). Smear positive patients had significantly higher risk of diagnostic delay compared to negative (OR=2.18. P=0.035). However, no significant associations found between socio-economic/demographic classes with delay. Median delays was more amongst married (Q3 =86 Days, Median =72 days, Q1=24 Days compared to single/separated (Q3 =74 Days, Median =57 days, Q1 =15 Days) and other socio-demographic variables had no significant differences. Conclusion Delay in diagnosis and treatment in Urban region of Western, Nepal was shorter compared to other places in Nepal and neighboring countries. Shorter delay for smear negative pulmonary tuberculosis raises doubt that cases are not examined according to the national TB control programs manual.

Detection of nucleotide-specific CRISPR/Cas9 modified alleles using multiplex ligation detection.

CRISPR/Cas9 genome-editing has emerged as a powerful tool to create mutant alleles in model organisms. However, the precision with which these mutations are created has introduced a new set of complications for genotyping and colony management. Traditional gene-targeting approaches in many experimental organisms incorporated exogenous DNA and/or allele specific sequence that allow for genotyping strategies based on binary readout of PCR product amplification and size selection. In contrast, alleles created by non-homologous end-joining (NHEJ) repair of double-stranded DNA breaks generated by Cas9 are much less amenable to such strategies. Here we describe a novel genotyping strategy that is cost effective, sequence specific and allows for accurate and efficient multiplexing of small insertion-deletions and single-nucleotide variants characteristic of CRISPR/Cas9 edited alleles. We show that ligation detection reaction (LDR) can be used to generate products that are sequence specific and uniquely detected by product size and/or fluorescent tags. The method works independently of the model organism and will be useful for colony management as mutant alleles differing by a few nucleotides become more prevalent in experimental animal colonies.

Successfully managed case of celphos poisoning: a case report and review.

Aluminium phosphide poisoning is one of the major causes of suicidal deaths in developing countries like Nepal. It is one of the common fumigant available and is within easy access. It is primarily used for crop protection. However, it is one of the misused chemicals to commit suicide. In this case, the patient had hyperglycaemia, atrial fibrillation, severe metabolic acidosis, and shock and yet survived. The key to her survival was aggressive supportive management. Therefore, knowing all the prognostic factors along with aggressive management can be life saving in conditions when no antidotes are available.

Iodized Salt Use and Salt Iodine Content among Household Salts from Six Districts of Eastern Nepal.

BACKGROUND: Universal salt iodization is considered the best strategy for controlling iodine deficiency disorders in Nepal. This study was done to find iodized salt use among Nepalese population and the iodine content of household salts. METHODS: Six districts (Siraha, Saptari, Jhapa, Udayapur, Ilam and Panchthar) were chosen randomly from 16 districts of eastern Nepal for the study. In each district, three schools (private and government) were chosen randomly for sample collection. A total of 1803 salt samples were collected from schools of those districts. For sample collection a clean air tight plastic pouch was provided to each school child and was asked to bring approximately 15 gm of their kitchen salt. The information about type of salt used; 'two child logo' iodized salt or crystal salt was obtained from each child and salt iodine content was estimated using iodometric titration. RESULTS: At the time of study, 85% (n=1533) of Nepalese households were found to use iodized salt whereas 15% (n=270) used crystal salt. The mean iodine content in iodized and crystal salt was 40.8±12.35 ppm and 18.43±11.49 ppm respectively. There was significant difference between iodized and crystal salts use and salt iodine content of iodized and crystal salt among different districts (p value <0.001 at confidence level of 95%). Of the total samples, only 169 samples (9.4% of samples) have iodine content<15 ppm. CONCLUSIONS: Most Nepalese households have access to iodized salt most salt samples have sufficient iodine content.

Health in Nepalese media.

BACKGROUND: Coverage of health in Nepali print media is quite a recent phenomenon despite readers' ample appetite for it. Dominated by politics, Nepal's print media has been marginally publishing news pieces, features, editorials and op-ed articles, photographs and cartoons on health, though marginally. But the media did not wake up to the issues of human resources for health until lately. METHODS: We content analysed the coverage of health issues including, human resources for health in select Nepali print media Kantipur, Nagarik and Annapurna Post of select three months in 2012 April, August and December. News pieces and their placements, Op-eds, editorials, features, letters to the editor, photos and cartoons were subjected to analysis. RESULTS: Over the study period, the papers covered 544 health news pieces, 44% of political news pieces. Health workforce news pieces contributed 24% to it. However, only 10% of the health news made to the front pages. Coverage of health in editorials, features, Op-eds, photographs, cartoons and letters to the editor is even more meager. For example, only 7% of the editorials are relating to health. CONCLUSIONS: Health is prioritized far less by the print media than politics despite the reader's appetite for it. Print media should give health a top priority, particularly in those areas that relate to health systems like human resources for health, for their massive impact on the lives of the people.

Fatal neutropenic enterocolitis due to Clostridium septicum / Enterocolitis neutropénica fatal a causa de Clostridium septicum

We describe a case of Clostridium septicum enterocolitis in a patient with pre-B acute lymphoblastic leukaemia undergoing autologous stem cell transplant. In the setting of neutropenia, Clostridium septicum should be suspected in patients who develop signs and symptoms of acute abdomen.

Se describe el caso de una enterocolitis por Clostridium septicum en un paciente con leucemia linfoblástica aguda (LLA) pre-B sometido a trasplante de células madre autológico. En el marco de una neutropenia, debe sospecharse la presencia de Clostridium septicum en pacientes que desarrollan signos y síntomas de abdomen agudo.

Fatal neutropenic enterocolitis due to clostridium septicum.

We describe a case of Clostridium septicum enterocolitis in a patient with pre-B acute lymphoblastic leukaemia undergoing autologous stem cell transplant. In the setting of neutropenia, Clostridium septicum should be suspected in patients who develop signs and symptoms of acute abdomen.