Usage of vildagliptin among patients with type 2 diabetes mellitus attending a public primary healthcare clinics in Kuala Selangor District, Selangor.

INTRODUCTION: Studies showed that vildagliptin can lower HbA1c levels by 0.8%-1%. However, there is limited data looking at vildagliptin use among suburban populations. The efficacy of vildagliptin use may differ among different populations, especially those with low socio-economic status. Thus, this study aimed to assess the HbA1c reduction after vildagliptin initiation, treatment patterns and the reason for its initiation among patients with type 2 diabetes mellitus attending outpatient clinics in Kuala Selangor District, Selangor. MATERIALS AND METHODS: This is a cross-sectional, retrospective study design. All patients who received vildagliptin in the Pharmacy Integrated Health System (PHIS) registry database from 2016 to 2021 were included as study samples. The exclusion criteria were being less than 18 years old and having type 1 diabetes mellitus. Patients' medical records were retrieved after sampling, and data were collected. One medical record was missing, thus SPSS analysis were performed on 144 vildagliptin users. RESULTS: In total, 84 females (58.3%) and 60 males (41.7%) with a mean age of 62.1 (±10.1) years were analysed in this study. Mean HbA1c pre-therapy was 8.5 ± 2.1%; while posttherapy 6 months demonstrated a mean HbA1c of 7.9 ± 1.8%. Use of vildagliptin alone or as an adjunct was associated with a mean reduction of 0.6% in HbA1c (p = 0.01). Factors influencing this HbA1c reduction were advancing age, specifically individuals aged 62 years and older (p = 0.02), patients who are already receiving insulin therapy (p=0.00) and those who express a willingness to commence insulin treatment during the counselling session prior to initiating the treatment plan (p = 0.00). Reasons for vildagliptin initiation documented by prescribers were non-insulin acceptance (n = 59, 40.97%), frequent hypoglycaemia (n = 6, 4.1%) and non-compliance with medications (n = 23, 15.9%). There was no association between demographic, medical background and reason for starting vildagliptin variables and HbA1c reduction (p < 0.001). CONCLUSION: This study showed that initiating vildagliptin alone or as an adjunct therapy significantly reduced HbA1c and is beneficial for uncontrolled diabetes patients. While advancing age, concurrent administration of insulin and the patients' willingness to accept insulin treatment prior to the commencement of therapy were the factors that influenced HbA1c reduction among patients receiving vildagliptin therapy, we recommend primary care providers prioritise all of the significant variables discovered before initiating vildagliptin for their patients.

A retrospective audit of endoscopic duodenal biopsies to uncover undetected Coeliac disease in Malaysian patients.

BACKGROUND: Coeliac disease, an autoimmune enteropathy related to gluten sensitivity was hitherto thought to be rare in Asia. Recent data however suggests that Celiac disease may be under-diagnosed in Asia. OBJECTIVE: The aim of this audit was to determine the frequency of histological changes compatible with Coeliac disease among patients undergoing elective diagnostic oesaphago-gastro-duodenoscopy (OGDS) under the care of a single practitioner in a Malaysian hospital. MATERIALS AND METHODS: The archived endoscopically obtained duodenal biopsy specimens of 241 consecutive Malaysian subjects undergoing elective diagnostic (OGDS) were reviewed by a pathologist blinded to the clinical data. Based on intra-epithelial lymphocyte counts, crypt hyperplasia and villous atrophy, each subject was assigned to one of the categories of the Modified Marsh classification for the histological diagnosis of Coeliac disease. The clinical charts of all subjects were reviewed by a single gastroenterologist blinded to the findings of the histological review. RESULTS: Of the 241 study subjects, 132 (54.8%) were females. There were 56 (23.2%) Malays, 90 (37.3%) Chinese, 88 (36.5%) Indians and seven (2.9%) from the other category. The median age of the study sample was 49 years (range 15- 88 years). The OGDS was done as part of screening in 15(6.2%) subjects while in the remaining it was part of the investigation of a clinical problem. Based on histological findings, none of the subjects could be assigned to a modified Marsh class of >1. The prevalence of histological changes compatible with Coeliac disease in the study was 0% (binomial exact one-sided 97.5 % confidence interval 0- 1.52%). CONCLUSION: In conclusion, this audit provides no evidence that active Coeliac disease is significantly under-detected among symptomatic patients presenting for diagnostic OGDS. The possibility that a significant number may have potential coeliac disease cannot be excluded.

Adenocarcinoma predominant pattern subtyping and nuclear grading in cytology: Is there a role in prognostication of advanced pulmonary adenocarcinomas?

INTRODUCTION: Primary lung adenocarcinomas (ADs) show varied architectural patterns, and pattern-based subtyping of ADs is currently recommended due to prognostic implications. Predicting AD patterns on cytology is challenging; however, cytological nuclear features appear to correlate with histological grade and survival in early stage lung ADs. The feasibility and value of AD pattern prediction and nuclear grading on cytology in advanced lung ADs is not known. We aimed to predict patterns and analyse nuclear features on cytology and evaluate their role in prognostication. METHODS: One-hundred patients of Stage III/IV lung AD with available matched cytology and histology samples were included. Cyto-patterns based on cell arrangement patterns (flat sheets vs three-dimensional clusters vs papillae) and cyto-nuclear score based on nuclear features (size, shape, contour), nucleoli (macronucleoli vs prominent vs inconspicuous), and nuclear chromatin were determined, and correlated with predominant histological-pattern observed on the matched small biopsy and outcome. RESULTS: Higher cyto-nuclear scores were observed with high-grade histo-patterns (solid, micropapillary and cribriform), while the predicted cyto-patterns did not correspond to the predominant pattern on histology in 77% cases. Highest cyto-histo agreement was observed for solid pattern (72%). High grade histo-patterns and cyto-nuclear scores > 3 showed a trend towards inferior survival (not significant). CONCLUSIONS: Nuclear grade scoring on cytology is simple to perform, and is predictive of high grade patterns. Its inclusion in routine reporting of cytology samples of lung ADs may be valuable.

Myofibroblastoma of the breast.

INTRODUCTION: Myofibroblastoma is a rare benign mesenchymal tumour arising from the stromal elements of the breast tissue. Histopathological variants such as classic, cellular, collagenous / fibrous, lipomatous, infiltrative, myxoid and epithelioid have been identified. Most myofibroblastomas are immunoreactive for CD34, actin, CD10 and desmin, usually express oestrogen receptor (ER), progesterone receptor (PR) and variably express androgen receptor (AR). CASE REPORT: We report a case of myofibroblastoma in an octogenarian male presenting with painless solitary breast lump. Mammography (digital tomosynthesis) and ultrasound showed a well-circumscribed hyperdense mass and hypoechoic, solid, oval mass with peripheral vascularity respectively. Patient underwent wide local excision. DISCUSSION: Diverse characteristics of myofibroblastoma on imaging necessitates histopathological analysis for an accurate diagnosis. Myofibroblastoma are often confused with fibroadenomas due to the benign imaging characteristics and with malignant neoplasia due to their wide morphological spectrum. Surgical excision is considered curative.

Leaf spot disease adversely affects human health-promoting constituents and withanolide biosynthesis in Withania somnifera (L.) Dunal.

AIMS: The present work investigates the implication of leaf spot disease on the antioxidant potential and commercial value of pharmaceutically important constituents of Withania somnifera, a high-valued medicinal plant. METHODS AND RESULTS: Leaf spot disease was induced in W. somnifera by inoculating Alternaria alternata (Fr.) Keiss. pathogen. Total polyphenolic content and antioxidant potential showed a significant decrease during leaf spot disease. Evaluation of pharmaceutically active constituents withaferin A, withanone and withanolide A utilizing high-performance liquid chromatography showed a significant decrease in diseased samples as compared to healthy ones. Quantitative expression of major genes involved in withanolide biosynthesis also showed down-regulation in diseased samples. Alterations in the ultra-structure of chloroplasts were also analysed under transmission electron microscopy to get a better insight into the changes of withanolide biosynthesis in leaf during disease infestation. CONCLUSIONS: The present work suggests that when the pathogenic fungus invades the host plants, it evokes multiple responses, which could be studied at various levels. The knowledge gained from this work will provide appropriate rationale for controlling the bio-deterioration of the pharmaceutically active metabolites in W. somnifera and development of suitable strategies against leaf spot disease. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to investigate the effect of leaf spot disease on the human health-promoting constituents and withanolide biosynthesis in this high-valued medicinal plant.

Flip-chip assembly of VCSELs to silicon grating couplers via laser fabricated SU8 prisms.

This article presents the flip-chip bonding of vertical-cavity surface-emitting lasers (VCSELs) to silicon grating couplers (GCs) via SU8 prisms. The SU8 prisms are defined on top of the GCs using non-uniform laser ablation process. The prisms enable perfectly vertical coupling from the bonded VCSELs to the GCs. The VCSELs are flip-chip bonded on top of the silicon GCs employing the laser-induced forward transfer (LIFT)-assisted thermocompression technique. An excess loss of < 1 dB at 1.55 µm measured from the bonded assemblies is reported in this paper. The results of high speed transmission experiments performed on the bonded assemblies with clear eye openings up to 20 Gb/s are also presented.

Atypical phenotype associated with reported GCK exon 10 deletions: Clinical judgement is needed alongside appropriate genetic investigations.

BACKGROUND: Maturity-onset diabetes of the young (MODY) caused by heterozygous mutations in the glucokinase (GCK) gene typically presents with lifelong, stable, mild fasting hyperglycaemia. With the exception of pregnancy, patients with GCK-MODY usually do not require pharmacological therapy. We report two unrelated patients whose initial genetic test results indicated a deletion of GCK exon 10, but whose clinical phenotypes were not typical of GCK-MODY. CASE REPORTS: In case 1, the patient was hyperglycaemic at diagnosis (glucose > 30 mmol/l) and elevated glucose levels > 10 mmol/l persisted after withdrawal of insulin therapy. The patient in case 2 was also hyperglycaemic at diagnosis [HbA1c > 86 mmol/mol (10%)], which improved with the introduction of oral hypoglycaemic agents. These clinical features were not consistent with GCK-MODY. Both patients had a single nucleotide variant that prevented multiplex ligation-dependent probe analysis, which generated a false positive result of a GCK exon 10 deletion. CONCLUSION: False positive genetic results in these two unrelated cases were attributable to the presence of a rare single nucleotide variant that prevented ligation of the probe in the multiplex ligation-dependent probe analysis kit used and falsely indicated deletion of exon 10 within GCK. Both cases had clinical features that did not tally with the typical GCK-MODY phenotype. These cases emphasize the need to interpret the results of definitive genetic tests within the specific clinical context. Increased medical sequencing is likely to lead to more reports of novel mutations of uncertain significance. If genetic investigations do not agree with the clinical picture, clinicians should exercise caution when making therapeutic changes based on these results.

Absence of cancer-associated changes in human fibroblasts immortalized with telomerase.

The ectopic expression of telomerase in normal human cells results in an extended lifespan, indicating that telomere shortening regulates the timing of cellular senescence. As telomerase expression is a hallmark of cancer, we investigated the long-term effects of forced expression of human telomerase catalytic component (hTERT) in normal human fibroblasts. In vitro growth requirements, cell-cycle checkpoints and karyotypic stability in telomerase-expressing cells are similar to those of untransfected controls. In addition, co-expression of telomerase, the viral oncoproteins HPV16 E6/E7 (which inactivate p53 and pRB) and oncogenic HRAS does not result in growth in soft agar. Thus, although ectopic expression of telomerase in human fibroblasts is sufficient for immortalization, it does not result in changes typically associated with malignant transformation.

Evaluation of hospital environment for presence of Mucorales during COVID-19-associated mucormycosis outbreak in India - a multi-centre study.

BACKGROUND: An unprecedented rise in the number of COVID-19-associated mucormycosis (CAM) cases has been reported in India. Myriad hypotheses are proposed for the outbreak. We recently reported uncontrolled diabetes and inappropriate steroid therapy as significant risk factors for the outbreak. However, Mucorales contamination of hospital environment was not studied. AIM: To perform a multi-centre study across India to determine possible Mucorales contamination of hospital environment during the outbreak. METHODS: Eleven hospitals from four zones of India representing high to low incidence for mucormycosis cases were included in the study. Samples from a variety of equipment used by the patients and ambient air were collected during May 19th, 2021 through August 25th, 2021. FINDINGS: None of the hospital equipment sampled was contaminated with Mucorales. However, Mucorales were isolated from 11.1% air-conditioning vents and 1.7% of patients' used masks. Other fungi were isolated from 18% of hospital equipment and surfaces, and 8.1% of used masks. Mucorales grew from 21.7% indoor and 53.8% outdoor air samples. Spore counts of Mucorales in air were significantly higher in the hospitals of North and South zones compared to West and East zones (P < 0.0001). Among Mucorales isolated from the environment, Rhizopus spp. were the most frequent genus. CONCLUSION: Contamination of air-conditioning vents and hospital air by Mucorales was found. Presence of Mucorales in these areas demands regular surveillance and improvement of hospital environment, as contamination may contribute to healthcare-associated mucormycosis outbreaks, especially among immunocompromised patients.

Waveguide mode filters fabricated using laser-induced forward transfer.

Titanium (Ti)-in-diffused lithium niobate waveguide mode filters fabricated using laser-induced forward transfer followed by thermal diffusion are presented. The mode control was achieved by adjusting the separation between adjacent Ti segments thus varying the average value of the refractive index along the length of the in-diffused channel waveguides. The fabrication details, loss measurements and near-field optical characterization of the mode filters are presented. Modeling results regarding the device performance are also discussed.

A prospective randomised phase II trial of thalidomide with carboplatin compared with carboplatin alone as a first-line therapy in women with ovarian cancer, with evaluation of potential surrogate markers of angiogenesis.

OBJECTIVES: To compare the safety and efficacy of thalidomide in combination with carboplatin to carboplatin alone as a first-line therapy in women with ovarian cancer and to evaluate the anti-angiogenic effects of thalidomide by measurement of surrogate markers of angiogenesis. METHODS: Forty patients with Stage IC-IV ovarian cancer were randomly assigned to receive either carboplatin (AUC 7) intravenously every four weeks for up to six doses (n = 20) or carboplatin at the same dose and schedule, plus thalidomide 100 mg orally daily for six months (n = 20). RESULTS: After median follow-up of 1.95 years, there was no difference in the overall response rate (90% in carboplatin arm, 75% in combination arm; p = 0.41). Increased incidence of symptoms of constipation, dizziness, tiredness and peripheral neuropathy was observed in the combination arm. There was a significant fall in CA-125 and E-selectin in both arms after treatment and VCAM-1 in the carboplatin arm. No significant difference between the two arms was observed in any of the markers analysed. CONCLUSIONS: In our trial the addition of thalidomide to carboplatin was well tolerated with no increased efficacy. The fall in some of the angiogenic markers in both groups may reflect tumour response rather than any specific anti-angiogenic effect of thalidomide.

Synergistic induction of local glucocorticoid generation by inflammatory cytokines and glucocorticoids: implications for inflammation associated bone loss.

OBJECTIVES: Synovial fibroblasts and osteoblasts generate active glucocorticoids by means of the 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme. This activity increases in response to proinflammatory cytokines or glucocorticoids. During inflammatory arthritis synovium and bone are exposed to both these factors. This study hypothesised that glucocorticoids magnify the effects of inflammatory cytokines on local glucocorticoid production in both synovium and bone. METHODS: The effects of inflammatory cytokines (IL-1beta/tumour necrosis factor alpha; TNFalpha) and glucocorticoids, alone or combined, were assessed on the expression and activity of 11beta-HSD1 in primary synovial fibroblasts, primary human osteoblasts and MG-63 osteosarcoma cells. A range of other target genes and cell types were used to examine the specificity of effects. Functional consequences were assessed using IL-6 ELISA. RESULTS: In synovial fibroblasts and osteoblasts, treatment with cytokines or glucocorticoids in isolation induced 11beta-HSD1 expression and activity. However, in combination, 11beta-HSD1 expression, activity and functional consequences were induced synergistically to a level not seen with isolated treatments. This effect was seen in normal skin fibroblasts but not foreskin fibroblasts or adipocytes and was only seen for the 11beta-HSD1 gene. Synergistic induction had functional consequences on IL-6 production. CONCLUSIONS: Combined treatment with inflammatory cytokines and glucocorticoids synergistically induces 11beta-HSD1 expression and activity in synovial fibroblasts and osteoblasts, providing a mechanism by which synovium and bone can interact to enhance anti-inflammatory responses by increasing localised glucocorticoid levels. However, the synergistic induction of 11beta-HSD1 might also cause detrimental glucocorticoid accumulation in bone or surrounding tissues.

Hand hygiene compliance of patients' family members in India: importance of educating the unofficial 'fourth category' of healthcare personnel.

INTRODUCTION: In India, due to manpower constraints, patients' family members are often actively involved in healthcare activities of their near and dear ones. They have significant contact with the patient at all World Health Organization (WHO) 'five moments for hand hygiene'. This study analysed the impact of decade-long awareness campaigns on the hand hygiene compliance (HHC) by our patients' carers. METHODS: Trained infection control nurses observed the HHC at each of the five moments for patients' attendants in different hospital settings from January 2014 to December 2018. Compliance was calculated as percentage of events divided by total opportunities. FINDINGS: A total of 7302 opportunities were observed with an overall compliance of 46.1% (35.5% in 2014 to 48.2% in 2018, P < 0.0001). Compliance at WHO moments 1, 2, 3, 4, and 5 was 51.0%, 47.4%, 67.6%, 48.8%, and 24.3% respectively. Among family members, mothers of newborns had a much higher HHC (77%) than others (44.5%) (P < 0.0001). Also, the compliance was higher in medical versus surgical wards and in paediatric wards versus adult wards (P < 0.0001 in both). CONCLUSION: This is the first study on family members' HHC in a hospital setting in a low- and middle-income country. The study shows that family members, once trained, exhibit fairly good HHC while caring for their patients, especially mothers of newborns. It is worthwhile empowering and educating patient attendants about the importance and process of hand hygiene as it is likely to result in immense benefit for patients.

Development of a calibration chamber to evaluate the performance of low-cost particulate matter sensors.

Low-cost particulate matter (PM) air quality sensors are becoming widely available and are being increasingly deployed in ambient and home/workplace environments due to their low cost, compactness, and ability to provide more highly resolved spatiotemporal PM concentrations. However, the PM data from these sensors are often of questionable quality, and the sensors need to be characterized individually for the environmental conditions under which they will be making measurements. In this study, we designed and assessed a cost-effective (∼$700) calibration chamber capable of continuously providing a uniform PM concentration simultaneously to multiple low-cost PM sensors and robust calibration relationships that are independent of sensor position. The chamber was designed and evaluated with a Computational Fluid Dynamics (CFD) model and a rigorous experimental protocol. We then used this new chamber to calibrate 242 Plantower PMS 3003 sensors from two production lots (Batches I and II) with two aerosol types: ammonium nitrate (for Batches I and II) and alumina oxide (for Batch I). Our CFD models and experiments demonstrated that the chamber is capable of providing uniform PM concentration to 8 PM sensors at once within 6% error and with excellent reliability (intraclass correlation coefficient > 0.771). The study identified two malfunctioning sensors and showed that the remaining sensors had high linear correlations with a DustTrak monitor that was calibrated for each aerosol type (R2 > 0.978). Finally, the results revealed statistically significant differences between the responses of Batches I and II sensors to the same aerosol (P-value<0.001) and the Batch I sensors to the two different aerosol types (P-value<0.001). This chamber design and evaluation protocol can provide a useful tool for those interested in systematic laboratory characterization of low-cost PM sensors.

Seroprevalence of Neospora caninum antibodies in dogs in India.

Neospora caninum is one of most important causes of abortion in cattle worldwide, and dogs are an important risk factor for N. caninum infection in cattle. Antibodies to N. caninum were determined in 184 (126 rural, 58 urban) dogs from the Punjab State, India, using commercial monoclonal antibody-based competitive ELISA and found in 16.8% of the animals. The prevalence of N. caninum antibodies was significantly higher in rural dogs (21.4%, 27 of 126) than city dogs (6.9%, 4 of 58). To our knowledge this is the first report of N. caninum infection in canines from India.

Lipid peroxidation and the levels of antioxidant enzymes in coronary artery disease.

Coronary Artery Disease is the major cause of mortality and morbidity worldwide. Traditional risk factors account for only half of the morbidity and mortality from coronary artery disease. There is substantial evidence that oxidative stress plays the major role in the atherosclerotic process. The present study was undertaken to evaluate the level of lipid peroxidation (by measuring malondialdehyde) and antioxidant enzymes (ceruloplasmin, glutathione, superoxide dismutase) in coronary artery disease. Serum malondialdehyde levels and serum ceruloplasmin levels were significantly raised in all the subgroups of study group as compared to control group (p<0.001). Whole blood glutathione levels and hemolysate superoxide dismutase activity was significantly decreased in all the subgroups of study group as compared to control group (p<0.001). Above results suggests that the patients of coronary artery disease show increased oxidative stress and decreased levels of antioxidant enzymes. So it is recommended that the management protocol for coronary artery disease patients should include antioxidant supplementation along with simultaneous lowering of lipid peroxidation.

Mycobacterium tuberculosis H37Rv expresses differential proteome during intracellular survival within alveolar epithelial cells compared with macrophages.

Mycobacterium tuberculosis survives within the infected host cells by escaping phagolysosomal fusion and adaptation to hosts' intracellular milieu. Recently, the role of alveolar epithelial cells (AECs) in the survival of intracellular M. tuberculosis has gained importance. It has been reported that M. tuberculosis causes cytotoxicity in AECs, a phenotype attributed to M. tuberculosis virulence that could be due to the differential gene/protein expression of bacilli in these cells. Thus, the present study focused on comparative proteomic analysis of intracellular mycobacteria within macrophages and epithelial cells. Intracellular mycobacteria from infected alveolar epithelial (A549) and macrophage (THP-1) cell lines were harvested, and two-dimensional polyacrylamide gel electrophoresis of mycobacterial proteins was performed. The protein spots of interest were picked and MALDI-TOF/MS was performed to identify proteins. Differential expression of 11 mycobacterial proteins was found in infected AECs, out of which six proteins were confirmed by MS/MS analysis. The identified proteins mainly belonged to functional categories of virulence, detoxification and adaptation, and are known to take part in metabolism and respiration, maintenance of virulence and survival during stress. These proteins were predicted to contain peptide motifs possessing cell-penetration ability. Expression of such proteins by intracellular mycobacteria could be essential for survival and persistence in AECs in its virulent state, thus contributing to disease pathogenesis.