Thioglycolic acid assisted hydrothermal growth of SnS 2D nanosheets as catalysts for photodegradation of industrial dyes.

We present our work on the rapid hydrothermal synthesis of highly crystalline 2D SnS nanostructures. An innovative idea is used in which thioglycolic acid is the sulfur precursor source. Structural studies indicate the material has grown in a single-phase orthorhombic structure. The single-phase formation of the material is also confirmed from the rietveld refinement of the experimental XRD data and by raman spectroscopic analysis. Morphological studies show the formation of 2D sheets having thickness in the nanoscale (100-150 nm) dimensions. Optical absorbance studies show the material is visible-light active exhibiting an indirect bandgap of 1.1 eV and direct band gap ∼1.7 eV. Density functional theory calculations support the experimental bandgap results. Photocatalytic activity of the nanosheets was investigated against methylene blue (MB), rhodamine B (RhB) and methyl orange (MO) dyes employing a solar simulator as the source of photons (light source). The nanosheets were found to photodegrade 80% of MB, 77% of RhB and 60% of MO in 120 min of light illumination. Reusability and post catalytic properties affirm the durability and stability of the nanosheets, which is very important in the context of waste water treatment considering the toxic nature of the effluents from dye industries.

Impact of ciprofloxacin impurities on bacterial growth, antibiotic resistance development and content assays.

In addition to active pharmaceutical ingredient (API), antibiotics may contain small amounts of excipients and impurities and be prone to accumulation of degradation products. There has been limited work characterizing how these substances impact bacterial growth and antibiotic resistance development. We investigated how two ciprofloxacin (CIP) impurities, fluoroquinolonic acid (FQA) and ciprofloxacin ethylenediamine analogue (CEA), impact growth and antibiotic resistance in Escherichia coli. Additionally, we investigated how these impurities impact a frequently used API content assay. Both impurities displayed modest antimicrobial activity compared to the CIP API. The effective antimicrobial activity of a medicine containing increased impurity levels may permit bacterial growth and resistance development. Our results also suggest that increasing exposure concentration and duration to CEA and FQA, independent of CIP, can promote antibiotic resistance development. However, at concentrations of 100% and below the MIC of the API, impurities had limited contributions to resistance development compared to the CIP API. From a methodological standpoint, we found that UV spectrophotometry may be inadequate to account for antibiotic impurities or degradation products. This can lead to incorrect estimations of API content and we propose additional multi-wavelength measures when using UV spectrophotometry to help identify impurities or degradation.

Clinical and laboratory features of seventy-eight UK patients with Good's syndrome (thymoma and hypogammaglobulinaemia).

Good's syndrome (thymoma and hypogammaglobulinaemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case series. We use the national UK-Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were female, were reviewed. Median age of presentation was 54 years. Absolute B cell numbers and serum immunoglobulins were very low in all patients and all received immunoglobulin replacement therapy. All patients had undergone thymectomy and nine (12%) had thymic carcinoma (four locally invasive and five had disseminated disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T cells were significantly lower in these patients with malignant thymoma. Seventy-four (95%) presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic sinusitis, but only eight (10%) had serious invasive fungal or viral infections. Patients with AB-type thymomas were more likely to have bronchiectasis. Twenty (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism, arthritis, myasthenia gravis, systemic lupus erythematosus, Sjögren's syndrome). There was no association between thymoma type and autoimmunity. Seven (9%) patients had died. Good's syndrome is associated with significant morbidity relating to infectious and autoimmune complications. Prospective studies are required to understand why some patients with thymoma develop persistent hypogammaglobulinaemia.

Expansion of a novel lead targeting M. tuberculosis DHFR as antitubercular agents.

A series of 1-(1-benzyl-2-methyl-5-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)-1H-indol-3-yl)ethanone and ethyl 1-benzyl-2-methyl-5-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)-1H-indole-3-carboxylate derivatives were designed based on bioisosteric replacement of previously reported antitubercular agent (IND-07). Twenty ligands were successfully synthesized and some of them were found to have good in vitro activity (MIC < 10 µM) against the H37Rv strain of Mycobacterium tuberculosis. Among these compounds, KC-08 and KC-11 inhibited Mtb-DHFR with 4- and 18-fold selectivity for Mtb-DHFR over h-DHFR, respectively. Compound KC-11 display acceptable ADME, and better pharmacokinetic profiles than IND-07. Docking studies were performed to predict the binding mode of the compounds within the active site of Mtb-DHFR and h-DHFR. The results of our study suggest that compound KC-11 may serve as a valuable lead for the design and development of selective inhibitors of Mtb-DHFR with potential therapeutic application in tuberculosis.

Structural comparison of Mtb-DHFR and h-DHFR for design, synthesis and evaluation of selective non-pteridine analogues as antitubercular agents.

Tuberculosis is an infectious disease that affects millions of population every year. Mtb-DHFR is a validated target that is vital for nucleic acids biosynthesis and therefore DNA formation and cell replication. This paper report identification and synthesis of novel compounds for selective inhibition of Mtb-DHFR and unleash the selective structural features necessary to inhibit the same. Virtual screening of databases was carried out to identify novel compounds on the basis of difference between the binding pockets of the two proteins. Consensus docking was performed to improve upon the results and best ten hits were selected. Hit 1 was subjected to analogues design and the analogues were docked against Mtb-DHFR. From the docking results 11 compounds were selected for synthesis and biological assay against H37Rv. Most potent compound (IND-07) was tested for selectivity using enzymatic assay against Mtb-DHFR and h-DHFR. The compounds were found to have good inhibitory activity (25-200 µM) against H37Rv and in enzyme assay against Mtb-DHFR and h-DHFR the compound was found selective towards Mtb-DHFR with selectivity index of 6.53. This work helped to identify indole moiety as novel scaffold for development of novel selective Mtb-DHFR inhibitors as antimycobacterial agents.

Smokeless tobacco and public health in Bangladesh.

Despite the high prevalence of smokeless tobacco (SLT) use among adults in Bangladesh, SLT was not included in the Tobacco Control Law till 2013. Information on SLT use among Bangladeshi people is inadequate for policymaking and implementing effective control measures. With the aim to identify the prevalence and trends of different SLT products, health and economic impacts, manufacture, and sale of and policies related to SLT in Bangladesh, we carried out a literature review, which involved literature search, data extraction, and synthesis. Evidence suggests that in Bangladesh, SLTs range from unprocessed to processed or manufactured products including Sada Pata, Zarda, Gul, and Khoinee. Over 27% of Bangladeshi adults aged 15 years and older use SLT in one form or other. SLT use is associated with age, sex, education, and socioeconomic status. SLT consumption has reportedly been associated with increased prevalence of heart diseases, stroke, and oral cancer and led to around 320,000 disability adjusted life years lost in Bangladesh in 2010. No cessation service is available for SLT users in public facilities. Compared to cigarettes, taxation on SLT remains low in Bangladesh. The amendment made in Tobacco Control Law in 2013 requires graphic health warnings to cover 50% of SLT packaging, ban on advertisement of SLT products, and restriction to sale to minors. However, implementation of the law is weak. As the use of SLT is culturally accepted in Bangladesh, culturally appropriate public awareness program is required to curb SLT use along with increased tax and cessation services.

Intussusception of Small Intestine as a Result of Inflammatory Fibroid Polyp Causing Small Bowel Obstruction in an Adult Patient.

Intussusception is the telescoping of one segment of bowel into the adjacent segment. It is more commonly seen in children,however rarely encountered in adult patients. Proximal segment of bowel is called intussusceptum which is intussuscepted into the lumen of the adjacent distal segment known as intussuscipiens. There is always a lead point causing this disorder especially in adults. We presented a case of a 45 year old man who presented in emergency department of our institute with history and clinical features of acute intestinal obstruction since 10 days. Patient was resuscitated, investigated and taken for exploratory laparotomy under General anaesthesia. Segment of involved small gut was resected and well circumscribed polypoidal mass was found in intussuscepted bowel. Histopathological examination of the specimen revealed the features of inflammatory fibroid polyp.

Analysis of serum Calcium, Magnesium, and Parathyroid Hormone in neonates delivered following preeclampsia treatment.

Due to the approximate clinical and biochemical manifestations of calcium and magnesium disturbances, with regard to the regulatory effects of parathyroid hormone (PTH), this present study is designed to analyze serum calcium (Ca), magnesium (Mg), and (PTH) at the time of birth, 24 hours afterwards in newborns after the mother has been treated with Mg-sulfate. We registered 86 term and preterm neonates (43 in each group) using simple census method delivered through vagina to preeclampsia pregnant women treated with Mg-sulfate immediately before birth in Khoramabad Asali Hospital, Iran. The first specimen was obtained from umbilical cord blood at birth, followed by the second sample of 2cc peripherally obtained from blood 24 hours after birth. The mean serum Mg level was higher than normal for both specimens in both term and preterm groups with no significant difference. The mean serum Ca level was higher in term group at both occasions, which turned out to be statistically significant (P<0.000) and (P=0.001) for the first and second specimens respectively. The mean PTH level was also in normal range for both groups at both times with no statistical significance. On the other hand, magnesium level showed a significant decline at 24 hours (P = 0.005) while PTH increased significantly (p<0.000) and (p=0.005) for term and preterm groups respectively. In contrast, Ca changes were not significantly different between the two specimens. Treatment with Mg-sulfate immediately before vaginal delivery increases Mg in both term and preterm neonates with no effect on Ca and PTH levels.

Association of increasing age with receipt of specialist care and long-term mortality in patients with non-ST elevation myocardial infarction.

BACKGROUND: observational studies suggest that older patients are less likely to receive secondary prevention medicines following acute coronary syndrome (ACS). OBJECTIVES: to examine the association of increasing age with receipt of specialist care and influence of specialist care on long-term mortality in patients with non-ST elevation myocardial infarction (NSTEMI). DESIGN: a cohort study. SETTING: National ACS registry of England and Wales. SUBJECTS: a total of 85,183 patients admitted with NSTEMI between 2006 and 2010. METHODS: logistic regression analyses to assess receipt of secondary prevention medicines (ACE inhibitor, ß-blocker, statin, aspirin) by age group; multivariate Cox regression models to examine longitudinal effect of cardiologist care on all-cause mortality by age group. RESULTS: mean age 72.0 years (SD 13.0 years), mean follow-up was 2.13 years. Older patients received less cardiologist care (70.2% of NSTEMI patients ≥85 years compared with 94.7% of patients <65) years and had more co-morbidity. Cardiologists prescribed more secondary prevention in all age groups than generalists, but this was mostly explained away by co-morbidity (receipt of statin crude OR 1.51 (1.27,1.80), fully adjusted OR 1.11 (0.92,1.33) in patients ≥85 years). Receiving cardiologist care compared with generalist care was associated with a decreased risk of death in all even after adjustment for co-morbidity, disease severity and secondary prevention; this benefit reduced incrementally with older age group (adjusted hazard ratio (HR) 0.58 (0.49,0.68) aged <65; 0.87 (0.82,0.92) aged ≥85). CONCLUSION: older patients with NSTEMI were less likely to see a cardiologist, but reduced treatment by generalists was explained away by co-morbidity. Cardiologist care was associated with lower mortality in all age groups than a generalist, but this survival benefit was less pronounced in older patients.

Incidentally Raised Cardiac Troponin I Has a Worse Prognosis in Older Patients Compared to Those with Normal Cardiac Troponin I and Patients with Acute Coronary Syndrome: A Cohort Study.

BACKGROUND: Incidentally elevated cardiac troponin I (cTnI) levels are common in acutely unwell older patients. However, little is known about how this impacts on the prognosis of these patients. OBJECTIVE: We aimed to investigate whether incidentally elevated cTnI levels (group 1) are associated with poorer outcome when compared to age- and sex-matched patients without an elevated cTnI level (group 2), and to patients diagnosed with acute coronary syndrome (group 3). PATIENTS AND METHODS: This prospective, matched cohort study placed patients ≥75 years old who were admitted to a University teaching hospital into groups 1-3, based on the cTnI levels and underlying diagnosis. Outcomes were compared between the groups using mixed-effects regression models and adjusted for renal function and C-reactive protein. All-cause mortality at discharge, at 1 month and 3 months, alongside the length of hospital stay (LOS), were recorded. RESULTS: In total, 315 patients were included, with 105 patients in each of the 3 groups. The mean age was 84.8 ± 5.5 years, with 41.9% males. All patients were followed up for 3 months. The percent all-cause mortality at discharge and the LOS for groups 1, 2 and 3 were 12.4, 3.8 and 8.6% and 11.2, 8.5 and 7.7 days, respectively. Group 1 had significantly increased mortality at 3 months [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.12-6.96; p = 0.040] and LOS (OR 1.39, 95% CI 1.08-1.79; p = 0.008) compared to group 2 and did not differ significantly when compared to 3-month mortality (OR 2.39, 95% CI 0.91-6.29; p = 0.079) or LOS (OR 1.26, 95% CI 0.96-1.66; p = 0.097) in group 3. CONCLUSION: There is a significant association between an incidental rise in cTnI level with mortality and LOS in older patients. Further research is required to evaluate whether a more systematic management of these patients would improve the prognosis.

Physical activity levels in Bangladeshi adults: results from STEPS survey 2010.

OBJECTIVES: Physical inactivity is an established risk factor for non-communicable diseases (NCD) and identified as the major public health concern worldwide. However, nationally representative and internationally comparable data on physical activity (PA) are lacking in Bangladesh. The objective of this paper was to determine nationally representative prevalence of PA levels among Bangladeshi adults. STUDY DESIGN: Cross-sectional survey. METHODS: Data, on PA for this paper, were analysed from the NCD risk factors survey 2010 in Bangladesh. A standardized approach known as STEPS (STEPSwise approach to Surveillance for NCD risk factors) was followed for this survey. A total of 9275 adults (aged ≥ 25 years) were interviewed. Data on PA were processed and analysed according to Global Physical Activity Questionnaire (GPAQ) version 2 analysis framework. RESULTS: Of total 9275 respondents 4312 were men and 4963 women with a mean age of 42.4 (±13.5) years. Median MET-minutes of total PA in a typical week was double in rural areas (3360) than urban (1680) areas. The overall country wide prevalence of low PA was 34.5% (95% confidence interval, 33.5-35.5), urban 37.7% (36.3-39.1) and rural 31.6% (30.3-32.9). Women in general were more inactive (women, 53.6% [52.2-55.0], men 15.4% [14.9-17.1]). The main contributions to total PA were from work (urban 47.0%, rural 61.0%), and active commuting (38.0%, 30.0%) domains. Leisure-time PA represented only a small proportion (15.0%, 9.0%). CONCLUSIONS: Insufficient physical activity is highly prevalent among the Bangladeshi adult population. Promoting overall PA at leisure-time and commuting considering country context can be feasible options with special attention to the women.

Serological and coprological analyses for the diagnosis of Fasciola gigantica infections in bovine hosts from Sargodha, Pakistan.

A serological and coprological survey of fasciolosis was conducted in bovine hosts from the Sargodha district, Pakistan using excretory-secretory (ES) antigens of Fasciola gigantica from cattle and buffaloes. Livers, faecal and blood samples of 146 cattle and 184 buffaloes were collected from slaughterhouses and examined for the presence of any Fasciola in bile ducts and ova in faeces. Serum was separated. ES antigens were prepared by incubating adult Fasciola in phosphate-buffered saline for 6-8 h and then filtering using a 0.22-µm syringe filter. Checkerboard titration was performed and optimum concentrations of antigen and serum were determined. Sero-prevalence was found to be 50.00 and 38.35% in buffalo and cattle, respectively. Using liver examination as the gold standard, enzyme-linked immunosorbent assay (ELISA) sensitivity was found to be 100% in both buffalo and cattle as compared with that of coprological examination in buffalo (61.79%) and cattle (54.54%). This indigenous ELISA was also highly specific, with values of 96.84 and 98.90% in buffalo and cattle, respectively. Positive predictive values were calculated as 96.74 and 98.21% in buffalo and cattle, respectively, while negative predictive values were 100%. For the validation of indigenous ELISA in field surveys, faecal and blood samples were collected from six sub-districts (tehsils) in the district of Sargodha. Sera were screened for the presence of anti-fasciola antibodies using both the indigenous and commercial ELISA kits. While both kits were equally sensitive, the indigenous ELISA was found to be more specific. The highest prevalence of fasciolosis was found in December, as ascertained using both serological and coprological examination. Significant differences were found in prevalences of fasciolosis in different sub-districts and age groups, together with feeding and watering systems.

Effects of Intensive versus Non-Intensive Physical Therapy on Children with Cerebral Palsy.

Cerebral Palsy (CP) is one of the most common causes of all childhood disorders. There are tone, posture and movements difficulty due to non-progressive damage to the immature brain in CP. The hallmark of CP is a disability in the development of gross motor function (GMF). The influence of gross motor development on fine motor development is more important in early developmental period, specially under three years old and in children with CP. Various therapeutic interventions have been used in the management of GMF development. Among them physical therapy is the most common intervention in CP and is usually a component of mandated programs. Physical therapy means physical stimulations in the form of various therapeutic exercises, touch, massage, limbs and trunk movement, balancing and coordination training, gait and ambulation training, cognitive stimulation as well as speech, language and occupational therapy. Our study focused to see the effect by short term intensive versus non-intensive physical therapy on children GMF development by using gross motor function measure (GMFM) Score sheet, GMFM-88, version 1.0. Study provides the information that physical therapy intervention is effective in GMF development and intensive interventions are more effective in children with spastic CP than non-intensive one. Study also inform that the more early treatment the more effective result.

Quinoline based furanones and their nitrogen analogues: Docking, synthesis and biological evaluation.

A small library of twenty-four quinoline based butenolides also known as furanones and their nitrogen analogues was prepared by using two different aroylpropionic acids, viz. 3-(2-naphthoyl)propionic acid (3) and 3-(biphenyl-4-yl)propionic acid (4), as starting materials. The 3-aroylpropionic acids were reacted with different 6-substituted-2-chloroquinolin-3-carbaldehydes (2a-d) to obtain the corresponding furan-2(3H)-ones (5a-h). The purified and characterized furanones were then converted into their corresponding 2(3H)-pyrrolones (6a-h) and N-benzyl-pyrrol-2(3H)-ones (7a-h). The antimicrobial activities of the title compounds were evaluated against two strains of each Gram +ve (Staphylococcus aureus and Bacillus subtilis), Gram -ve bacteria (Escherichia coli and Pseudomonas aeruginosa) and against fungal strains of Aspergillus niger and Aspergillus flavus. In vivo anti-inflammatory potential of the title compounds was investigated by standard method. Majority of the compounds showed significant antibacterial activity against both the Gram +ve strains. Eight most potent anti-inflammatory compounds (5b, 5d, 5h, 6b, 7b, 7d, 7f, 7h) which exhibited >53% inhibition in edema, were also screened for their in vivo analgesic activity. All the tested compounds were found to have significant reduction in ulcerogenic action but only three compounds (5d, 5h and 7h) showed comparable analgesic activity to standard drug, diclofenac. The results were also validated using in silico approach and maximum mol doc score was obtained for compounds 7a-h. On comparing the in vivo and in silico anti-inflammatory results of synthesized compounds, N-benzyl pyrrolones (7a-h) emerged as the potent anti-inflammatory agents. It was also observed that compounds that possess electron withdrawing group such as -Cl or NO2 are more biologically active.

Pharmacophore based virtual screening, synthesis and SAR of novel inhibitors of Mycobacterium sulfotransferase.

A planned 3D-pharmacophore mapping was carried out on the basis of chemical features associated with known Stf0 inhibitors. Four models (model 1-4) were obtained after GASP (Genetic Algorithm Similarity Program) refinement of seven models (D-1 to D-7) generated by using DISCOtech. The selected GASP model-1 has two hydrogen bond acceptor, two hydrogen bond donor and four hydrophobic points. This model was used for virtual screening (VS) of large public databases along with in house generated knowledge base database. VS followed by docking of selected compounds on Stf0 active site was carried and pose analysis done. Seven hits were identified after all the computational studies, of which 2 hits were synthesized along with their analogs and evaluated for antitubercular activity. IH-45 was found promising after in vitro assay.

Clustering of non-communicable diseases risk factors in Bangladeshi adults: An analysis of STEPS survey 2013.

BACKGROUND: Non-communicable diseases (NCDs) have already become major killers in Bangladesh. Once NCDs are developed, they become chronic health and economic problems. Their primary prevention is linked to their common risk factors. This study was conducted to determine the prevalence of NCD risk factors with a focus on their clustering in Bangladeshi adults. METHODS: This nationally representative study was done in 4,073 (1,812 men and 2,261 women) adults aged 25 years or older selected from rural and urban households. Multistage cluster sampling design was used. Selected variables were in line with steps I and II of WHO stepwise surveillance except alcohol. RESULTS: Forty-four percent used tobacco in any form. Almost 93% did not consume adequate fruit and vegetables (5 servings or more). Thirty eight percent had low physical activity level (<600 MET-minutes/week). One-quarter (26%) were overweight (body mass index > =25 kg/m^2). Twenty-one percent had hypertension (blood pressure > =140/90 mmHg or medication) and about 5% had documented diabetes. Upon examination of risk factor clustering, we observed that 38% had at least three risk factors. After this threshold, clustering suddenly dropped down to a fairly low level. Using this threshold as a cut-off, clustering of risk factors was associated with age, male gender, urban residence, educational levels and quality of house in multivariate analysis. CONCLUSION: Prevalence of NCD risk factors is fairly high in Bangladeshi adults with a tendency of clustering. If a risk factor such as hypertension is detected, a closer look for other risk factors has to be given in both at clinical and public health settings. Clustering raises risk by more than a summation of risk factors. Our findings, therefore, suggest that Bangladesh could expect a significant increase in NCDs in near future.

Influenza, influenza-like symptoms and their association with cardiovascular risks: a systematic review and meta-analysis of observational studies.

AIMS: To synthesise the evidence relating influenza and influenza-like symptoms to the risks of myocardial infarction (MI), heart failure (HF) and stroke. METHODS: We conducted a systematic review and meta-analysis of the evidence relating influenza and influenza-like symptoms to the risks of MI, HF and stroke. We systematically searched all MEDLINE and EMBASE entries up to August 2014 for studies of influenza vs. the cardiovascular outcomes above. We conducted random effects meta-analysis using inverse variance method for pooled odds ratios (OR) and evaluated statistical heterogeneity using the I(2) statistic. RESULTS: We identified 12 studies with a total of 84,003 participants. The pooled OR for risk of MI vs. influenza (serologically confirmed) was 1.27 (95% CI, confidence interval 0.54-2.95), I(2)  = 47%, which was significant for the only study that adjusted for confounders (OR 5.50, 95% CI 1.31-23.13). The pooled OR for risk of MI vs. influenza-like symptoms was 2.17 (95% CI 1.68-2.80), I(2)  = 0%, which was significant for both unadjusted (OR 2.23, 95% CI 1.65-3.01, five studies) and adjusted studies (OR 2.01, 95% CI 1.24-3.27, two studies). We found one study that evaluated stroke risk, one study in patients with HF, and one that evaluated mortality from MI - all of these studies suggested increased risks of events with influenza-like symptoms. CONCLUSIONS: There is an association between influenza-like illness and cardiovascular events, but the relationship is less clear with serologically diagnosed influenza. We recommend renewed efforts to apply current clinical guidelines and maximise the uptake of annual influenza immunisation among patients with cardiovascular diseases, to decrease their risks of MI and stroke.

The association between older age and receipt of care and outcomes in patients with acute coronary syndromes: a cohort study of the Myocardial Ischaemia National Audit Project (MINAP).

AIMS: Older people increasingly constitute a large proportion of the acute coronary syndrome (ACS) population. We examined the relationship of age with receipt of more intensive management and secondary prevention medicine. Then, the comparative association of intensive management (reperfusion/angiography) over a conservative strategy on time to death was investigated by age. METHODS AND RESULTS: Using data from 155 818 patients in the national registry for ACS in England and Wales [the Myocardial Ischaemia National Audit Project (MINAP)], we found that older patients were incrementally less likely to receive secondary prevention medicines and intensive management for both ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). In STEMI patients ≥85 years, 55% received reperfusion compared with 84% in those aged 18 to <65 [odds ratio 0.22 (95% CI 0.21, 0.24)]. Not receiving intensive management was associated with worse survival [mean follow-up 2.29 years (SD 1.42)] in all age groups (adjusted for sex, cardiovascular risk factors, co-morbidities, healthcare factors, and case severity), but there was an incremental reduction in survival benefit from intensive management with increasing age. In STEMI patients aged 18-64, 65-74, 75-84, and ≥85, adjusted hazard ratios (HRs) for all-cause mortality comparing conservative treatment to intensive management were 1.98 (1.78, 2.19), 1.65 (1.51, 1.80), 1.62 (1.52, 1.72), and 1.36 (1.27, 1.47), respectively. In NSTEMI patients, the respective HRs were 4.37 (4.00, 4.78), 3.76 (3.54, 3.99), 2.79 (2.67, 2.91), and 1.90 (1.77, 2.04). CONCLUSION: We found an incremental reduction in the use of evidence-based therapies with increasing age using a national ACS registry cohort. While survival benefit from more intensive management reduced with older age, better survival was associated with intensive management at all ages highlighting the requirement to improve standard of care in older patients with ACS.

Inhibitory effect of post-micellar SDS concentration on thermal aggregation and activity of papain.

Papain, a cysteine protease isolated from the latex of Carica papaya, is known to undergo irreversible thermal unfolding. In this study, we found that thermal unfolding of papain is accompanied by a simultaneous self-assembly process where this protein is observed to aggregate above 50°C. The extent of aggregation increased with increasing protein concentration from 3-40 µM. The aggregation was confirmed by enhanced turbidity, light scattering intensity, 1-anilino-8-naphthalene sulfonate (ANS) fluorescence intensity and by transmission electron microscopy. Furthermore, we noted that post-micellar concentration of sodium dodecyl sulfate (SDS) remarkably suppresses the thermal aggregation of papain. Far-UV circular dichroism studies revealed that SDS significantly enhances α-helical content of the protein and also tends to prevent its unfolding, and thus inhibits aggregation. Additionally, papain showed maximal activity at 65°C in neutral buffer. However, in the presence of 6 mM SDS (above its critical micellar concentration), the enzyme lost activity by about 10-fold. Thus, promoting the helical propensity of the protein does not appear to be a suitable strategy to overcome the aggregation related problems of industrially important proteins such as papain, which are not only required to be protected against aggregation but also need to remain functionally active in the presence of aggregation inhibitors.

Modeling of adhesion, protrusion, and contraction coordination for cell migration simulations.

Cell migration is a highly complex, dynamical biological phenomenon that involves precise spatio-temporal coordination of distinctive sub-processes including adhesion, protrusion, and contraction of the cell. Observations of individual tumor cell migration reveal that cells generally exhibit either mesenchymal-type or amoeboid-type migration modes in native like environments. However, it has also been observed that some migrating cells are capable of morphologically adapting to their environment by modifying their type of migration. Recent studies suggest in fact that changes in biophysical and biomechanical properties of tumor cells can reversibly control their transition from one type of migration to the other. These changes may be caused by internal cell biomechanical mechanisms as well as mechanical and topological properties of the extracellular matrix. In order to understand the complex transition between the two modes and the role played by internal cellular mechanics during migration, we have developed a novel axisymmetric hyperviscoelastic cell model to simulate the dynamical behavior of a migrating cell. Numerical results from our study quantitatively demonstrate that the biomechanical properties of the cell may play an important role in the amoeboid-mesenchymal transition during migration. Our study will therefore not only help in creating a new platform for simulating cellular processes but will also provide insights into the role of sub-cellular mechanics in regulating various modes of migration during tumor invasion and metastasis.