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.

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.

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.

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.

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.

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.

Role of magnetic resonance imaging in breast cancer management.

Magnetic resonance imaging (MRI) of the breast is primarily used as a supplemental tool to breast screening with mammography or ultrasound. A breast MRI is mainly used for women who have been diagnosed with breast cancer, to help measure the size of the cancer, look for other tumors in the breast, and to check for tumors in the opposite breast. For certain women at high risk for breast cancer, a screening MRI is recommended along with a yearly mammogram. MRI is known to give some false positive results which mean more test and/or biopsies for the patient. Thus, although breast MRI is useful for women at high risk, it is rarely recommended as a screening test for women at average risk of breast cancer. Also, breast MRI does not show calcium deposits, known as micro-calcifications which can be a sign of breast cancer.

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.

Engineered Peptides for Applications in Cancer-Targeted Drug Delivery and Tumor Detection.

Cancer-targeting peptides as ligands for targeted delivery of anticancer drugs or drug carriers have the potential to significantly enhance the selectivity and the therapeutic benefit of current chemotherapeutic agents. Identification of tumor-specific biomarkers like integrins, aminopeptidase N, and epidermal growth factor receptor as well as the popularity of phage display techniques along with synthetic combinatorial methods used for peptide design and structure optimization have fueled the advancement and application of peptide ligands for targeted drug delivery and tumor detection in cancer treatment, detection and guided therapy. Although considerable preclinical data have shown remarkable success in the use of tumor targeting peptides, peptides generally suffer from poor pharmacokinetics, enzymatic instability, and weak receptor affinity, and they need further structural modification before successful translation to clinics is possible. The current review gives an overview of the different engineering strategies that have been developed for peptide structure optimization to confer selectivity and stability. We also provide an update on the methods used for peptide ligand identification, and peptide- receptor interactions. Additionally, some applications for the use of peptides in targeted delivery of chemotherapeutics and diagnostics over the past 5 years are summarized.

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.

Nanomechanical sandwich assay for multiple cancer biomarkers in breast cancer cell-derived exosomes.

The use of exosomes as cancer diagnostic biomarkers is technically limited by their size, heterogeneity and the need for extensive purification and labelling. We report the use of cantilever arrays for simultaneous detection of multiple exosomal surface-antigens with high sensitivity and selectivity. Exosomes from breast cancer were selectively identified by detecting over-expressed membrane-proteins CD24, CD63, and EGFR. Excellent selectivity however, was achieved when targeting the cell-surface proteoglycan, Glypican-1 at extraordinary limits (∼200 exosomes per mL, ∼0.1 pg mL(-1)).

ASSESSMENT OF INHALATION DOSE FROM THE INDOOR 222Rn AND 220Rn USING RAD7 AND PINHOLE CUP DOSEMETERS.

Radon is the most important source of natural radiation and is responsible for approximately half of the received dose from all sources. Most of this dose is from inhalation of the radon progeny, especially in closed atmospheres. Concentration of radon (222Rn) and thoron (220Rn) in the different villages of Jalandhar and Kapurthala district of Punjab has been calculated by pinhole cup dosemeters and RAD7. On an average, it has been observed from the study that the values of all the parameters calculated are higher in case of active monitoring than the passive monitoring. The calculated equilibrium equivalent 222Rn concentration (EECRn) and equilibrium equivalent 220Rn concentration (EECTh) fluctuate in the range from 5.58 to 34.29 and from 0.35 to 2.7 Bq m-3 as estimated by active technique, respectively. Similarly, the observed mean value of the potential alpha energy concentration of 222Rn (PAECRn) and 220Rn (PAECTh) is 4.55 and 4.34 mWL, respectively. The dose rate to the soft tissues and lung from indoor 222Rn varies from 0.06 to 0.38 and from 0.50 to 3.05 nGy h-1, respectively. The total annual effective dose for the residents of the study area is less than 10 mSv.

G9a histone methyltransferase inhibitor BIX01294 promotes expansion of adult cardiac progenitor cells without changing their phenotype or differentiation potential.

OBJECTIVES: As a follow-up to our previous reports showing that the G9a histone methyltransferase-specific inhibitor BIX01294 enhances bone marrow cell cardiac potential, this drug was examined for its effects on cardiomyocytes and mouse cardiac progenitor cells (CPCs). MATERIALS AND METHODS: Cardiomyocytes and cardiac explants were cultured ± BIX01294, and examined for changes in cardiac function, protein and gene expression. Additionally, enriched populations of CPCs, contained in the 'phase bright cell' component of explants, were harvested from non-treated and BIX01294-treated cardiac tissue, and assayed for differences in cell phenotype and differentiation potential. Mouse CPCs were cultured with rat cardiomyocytes to allow differentiation of the progenitors to be assayed using species-specific PCR primers. RESULTS: While BIX01294 had no discernible effect on myocyte function and sarcomeric organization, treatment with this drug significantly increased CPC proliferation, as indicated by enhanced MTT metabolization and BrdUrd incorporation (4.1- and 2.0-fold, respectively, P < 0.001) after 48 h labelling, and increased Ki67 expression (4.8-fold, P < 0.001) after 7 days culture. Heart explants exposed to BIX01294 generated 3.6-fold (P < 0.005) greater yields of CPCs by 2 weeks culture. Importantly, CPCs obtained from non-treated and BIX01294-treated cultures did not differ in phenotype or differentiation potential. CONCLUSIONS: These data indicate that BIX01294 can expand CPCs without undermining their capacity as cardiac progenitors, and suggest that this drug may have utility for generating large numbers of CPCs for cardiac repair.

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.

Exploitation of sperm-Escherichia coli interaction at the receptor-ligand level for the development of anti-receptor antibodies as the vaginal contraceptive.

In an earlier work performed in our laboratory, we have been able to isolate a sperm receptor (SR) from human spermatozoa playing critical role in fertilization using sperm--E. coli interactions at the receptor-ligand level. It has been hypothesized that for the development of an immunocontraceptive, antibodies generated against the SR should have the ability to impair sperm parameters. In this league, an attempt was made to generate anti-SR antibodies and their effect on sperm parameters such as motility, viability, Mg(2+) -dependent ATPase activity, acrosome status, and apoptotic index was examined. Loss of sperm motility was observed with 100% agglutination. Interaction of anti-SR antibodies with spermatozoa resulted in reduced Mg(2+) -dependent ATPase activity (1020 ± 0.53%), premature acrosomal loss (61.5 ± 0.67%) as well as induced apoptosis (58.76 ± 2.5%). The induction of sperm damage was specifically because of anti-SR polyclonal antibodies as it could be mitigated by the addition of purified SR. Further, when in vivo efficacy of anti-SR antibodies was checked, results showed that a single intravaginal administration with anti-SR antibodies in female BALB/c mice led to the failure of conception. However, simultaneous administration of SR with anti-SR polyclonal antibodies resulted in sustenance of fertility. Infertility induced by anti-SR antibodies did not show any other tissue pathology; hence the present work highlights the potential of anti-SR polyclonal antibodies to be used as a vaginal contraceptive.

Alterations in mitochondrial DNA copy number and the activities of electron transport chain complexes and pyruvate dehydrogenase in the frontal cortex from subjects with autism.

Autism is a neurodevelopmental disorder associated with social deficits and behavioral abnormalities. Recent evidence suggests that mitochondrial dysfunction and oxidative stress may contribute to the etiology of autism. This is the first study to compare the activities of mitochondrial electron transport chain (ETC) complexes (I-V) and pyruvate dehydrogenase (PDH), as well as mitochondrial DNA (mtDNA) copy number in the frontal cortex tissues from autistic and age-matched control subjects. The activities of complexes I, V and PDH were most affected in autism (n=14) being significantly reduced by 31%, 36% and 35%, respectively. When 99% confidence interval (CI) of control group was taken as a reference range, impaired activities of complexes I, III and V were observed in 43%, 29% and 43% of autistic subjects, respectively. Reduced activities of all five ETC complexes were observed in 14% of autistic cases, and the activities of multiple complexes were decreased in 29% of autistic subjects. These results suggest that defects in complexes I and III (sites of mitochondrial free radical generation) and complex V (adenosine triphosphate synthase) are more prevalent in autism. PDH activity was also reduced in 57% of autistic subjects. The ratios of mtDNA of three mitochondrial genes ND1, ND4 and Cyt B (that encode for subunits of complexes I and III) to nuclear DNA were significantly increased in autism, suggesting a higher mtDNA copy number in autism. Compared with the 95% CI of the control group, 44% of autistic children showed higher copy numbers of all three mitochondrial genes examined. Furthermore, ND4 and Cyt B deletions were observed in 44% and 33% of autistic children, respectively. This study indicates that autism is associated with mitochondrial dysfunction in the brain.