Effect of oxidative stress and calcium deregulation on FAM26F (CALHM6) expression during hepatitis B virus infection.

BACKGROUND: Family with sequence similarity 26, member F (FAM26F) is an important innate immunity modulator playing a significant role in diverse immune responses, however, the association of FAM26F expression with HBV infection is not yet known. Thus, the current study aims to explore the differential expression of FAM26F in vitro in HepAD38 and HepG2 cell lines upon HBV infection, and in vivo in HBV infected individuals. The effects of antioxidant and calcium inhibitors on the regulation of FAM26F expression were also evaluated. The expression of FAM26F was simultaneously determined with well-established HBV infection markers: IRF3, and IFN-ß. METHODS: The expression of FAM26F and marker genes was analyzed through Real-time qPCR and western blot. RESULTS: Our results indicate that the differential expression of FAM26F followed the same trend as that of IRF3 and IFN-ß. The in vitro study revealed that, in both HBV infected cell lines, FAM26F expression was significantly down-regulated as compared to uninfected control cells. Treatment of cells with N-acetyl-L-cysteine (NAC), EGTA-AM, BAPTA-AM, and Ru360 significantly upregulated the expression of FAM26F in both the cell lines. Moreover, in in vivo study, FAM26F expression was significantly downregulated in all HBV infected groups as compared to controls (p = 0.0007). The expression was higher in the HBV recovered cases, probably due to the decrease in infection and increase in the immunity of these individuals. CONCLUSION: Our study is the first to show the association of FAM26F with HBV infection. It is proposed that FAM26F expression could be an early predictive marker for HBV infection, and thus is worthy of further investigation.

Effect of Ramadan fasting on disease activity in patients with rheumatoid arthritis presenting in tertiary care hospital.

BACKGROUND AND OBJECTIVE: Rheumatoid Arthritis (RA) is a common inflammatory disorder affected by various factors, including fasting. The objective of the study was to establish the effect of Ramadan fasting on DAS 28 in Rheumatoid Arthritis patients. METHODS: In this observational cohort study done in department of rheumatology, Mayo hospital, Lahore, between May 2019 to July 2019, 240 patients were divided in fasting (n=120) and non-fasting cohort (n=120) based on their own choice. Mean DAS-28 scores before and after Ramadan was compared in both cohorts with appropriate statistical analyses. RESULTS: Two hundred forty participants, (74 males, 166 females), were recruited. Baseline DAS of fasting group was significantly low (4.35±0.9) as compared to non-fasting group (5.07±0.91). Paired t-test showed statistically significant improvement in fasting and non-fasting groups in total and in both genders (p=0.000). Mean improvement in DAS was numerically greater and statistically significant (p=0.000) in non-fasting group (1.08±0.62) as compared to fasting ones (0.86±0.61). Post-Ramadan DAS was, however, significantly low in fasting group (3.49±0.9) versus non-fasting group (3.98±1.0) (p=0.000). CONCLUSION: DAS 28 score decreased in both non-fasting as well as fasting patients of RA during the month of Ramadan. RA patients with moderate disease activity, who want to keep fast, can be allowed to do so without any fear of disease worsening.

A Retrospective Analysis on the Cystic Echinococcosis Cases Occured in Northeastern Punjab Province, Pakistan.

A retrospective study was performed to report the case occurrence of cystic echinococcosis (CE) in three hospitals of north-eastern region in Punjab Province, Pakistan. We reviewed retrospectively the clinical records of patients in 4 hospitals which were diagnosed with CE during 2012-2017. A total of 198 cases, 82 (41.4%) male and 116 (58.6%) females were detected as CE. The most Highest incidence was revealed in.... 21-30 years-old group (24.2%) followed by 41-50 (22.7%), 31-40 (16.2%), 11-20 (13.6%), 51-60 (8.1%), below 10 (5.5%), over 71 (5.1%) and 61-70 year-old group (4.5%). CE was detected in various organs of infected individuals. However, most of CE cases were detected in the liver (47.4%) and lung (18.6%). The present study indicated that CE is more or less prevalent in surveyed areas and one of the most important public health problems in Punjab Province, Pakistan.

Presence of pre-diabetes in Helicobacter pylori positive versus Helicobacter pylori negative patients having dyspepsia.

Pre-diabetes is a state of intermediate hyperglycaemia. Helicobacter (H) pylori infection is an established risk factor for pre-diabetes. This comparative cross-sectional study was done in Mayo Hospital Lahore from November 2015 to August 2016 in which 270 patients underwent upper gastrointestinal endoscopy with antral biopsy. An oral glucose tolerance test was done half to one hour after endoscopy. Patients were diagnosed having pre-diabetes according to American Diabetic Association criteria. Cases were divided into Group A and B based on the presence or absence of histopathological evidence of H. pylori respectively. Comparison was done to see the occurrence of pre-diabetes in H. pylori positive versus helicobacter negative dyspeptic patients. Results showed that 79 (58.52%) in Group-A and 62 (45.93%) in Group-B had pre-diabetes while remaining 56 (41.48%) in Group-A and 73 (54.07%) in Group-B had no findings of this morbidity, p value was calculated as 0.03 showing a significant difference. It was concluded that H. pylori infection is significantly associated with pre-diabetes.

Efficacy of oral vitamin D on glycated haemoglobin (HbA1c) in type 2 diabetics having vitamin D deficiency - A randomized controlled trial.

OBJECTIVE: To study the efficacy of oral vitamin D in improving glycaemic control of patients with type 2 diabetes by reducing glycated haemoglobin levels. METHODS: This randomised control trial was carried out at Mayo Hospital, Lahore, from February 5 to August 5, 2016, and comprised type 2 diabetes patients aged 40-70 years visiting the outpatient clinics. They were randomly divided into two groups by using the lottery method. Group A received oral vitamin D along with metformin and group B received metformin only. Blood samples of both the groups were tested for glycated haemoglobin at three months to assess the change. SPSS 21 was used for data analysis. RESULTS: There were 140 patients divided into two groups of 70(50%) each. Mean age in Group A was 54.80±8.55 years and 58.40±7.98 years in Group B. No significant difference was seen in glycated haemoglobin levels at baseline (p>0.05). However, after 3 months post-treatment the levels significantly differed (p<0.05) in favour of Group A. CONCLUSIONS: Vitamin D supplementation had a significant effect in lowering glycated haemoglobin level in patients with type 2 diabetes.

Comparison of metformin and pioglitazone in achieving sustained virological response in chronic hepatitis C patients with insulin resistance: A quasi-experimental study.

OBJECTIVE: To compare metformin and pioglitazone with standard interferon and ribavirin in achieving sustained virological response in chronic hepatitis C patients. METHODS: This quasi-experimental, comparative, interventional study was conducted at Mayo Hospital, Lahore, Pakistan, from January 2015 to March 2016, and comprised chronic hepatitis C patients who had insulin resistance. The patients were divided evenly in three groups. Group A had patients treated with interferon 3 million units, three times in a week and ribavirin 400mg three times in a day. In addition to interferon and ribavirin, group B was treated with metformin, and group C received pioglitazone. Polymerase chain reaction was done at the completion of 24 and 48 weeks to assess the end treatment and sustained virological response, respectively. SPSS 20 was used for data analysis. RESULTS: Of the 138 patients, there were 46(33.3%) in each group. The mean age of the patients in group A was 36.83±9.65 years, in group B was 37.72±10.00 years and in group C it was 38.07±8.85 years. Overall, there were 70(50.72%) males and 68(49.28%) females. At the end of 24 weeks, polymerase chain reaction exhibited that in group A, the score was <100 in 28(60.9%) and >100 in 18(39.1%) patients. In group-B, it was <100 in 39(84.8%) and >100 in 7(15.2%) patients. In group-C, it was <100 in 31(67.4%) and >100 in 15(32.6%) patients. The sustained virological response was considerably higher in group B (p=0.003). CONCLUSIONS: Sustained virological response with standard therapy with metformin gave high-end response as compared to other groups.

Glycaemic Control Of Type 2 Diabetic Patients During Ramazan Fasting.

BACKGROUND: Among five main pillars of Islam Fasting is one of the key elements, all healthy adult Muslims have to observe fast from dawn till dusk during the holy month of Ramadan. According to a 2009 demographic study, Islam has 1.57 billion believers, making up 23% of the world population of 6.8 billion, and is growing by 3% per year. EPIDIAR (epidemiology of diabetes and Ramadan) study showed that 43% patients with type 1 and 79% patients with type2 diabetes observe fast during the month of Ramadan. Whereas those people who are suffering from diabetes and are fasting may be at risk of adverse outcomes and the risks may rise with longer fasting periods. Ideal management of diabetic patients who wish to fast during Ramadan needs to be done to avoid the complications. The purpose of this study was to observe the effect of fasting on glycaemic control in type 2 diabetic patients during the month of Ramadan. METHODS: This was an observational cross sectional study; it was conducted at outpatient department Jinnah institute of diabetes and endocrinology Jinnah hospital Lahore during the month of Ramadan. Patients were advised to monitor blood sugar levels for two days before and after three meals (lunch, breakfast and dinner) before Ramadan and then during Ramadan blood sugar levels were monitored for four days in first Ashra before and two hours after Sehari, for four days at noon during second Ashra and then for four days pre and two hours after Iftar in last Ashra of Ramadan. Patients were educated Pre-Ramadan about glucose monitoring and drug dosage adjustments were done along with dietary counselling. RESULTS: Blood glucose levels two days before and during Ramadan fell within range of mean glucose level of 150-187 mg/dl showing no extreme fluctuations in blood glucose levels only one patient reported symptomatic and biochemical hypoglycaemia severe enough to break the fast at noon. CONCLUSIONS: We concluded that in Ramadan fasting, type 2 diabetic patients with proper education, dietary counselling and drug dosage adjustments glycaemic control can remain in safe acceptable range preventing any life-threatening complication.

Frequency of Type-2 diabetes mellitus in Nephropathic patients and comparison of mean magnesium levels in Nephropathic patients with and without Type-2 diabetes mellitus.

OBJECTIVE: The objective of this study was to determine the frequency of Type 2 diabetes mellitus (T2DM) in patients with nephropathy (i.e. Chronic Kidney Disease Stage 1 to 3) and to compare the mean magnesium levels in diabetic nephropathic patients and non-diabetic nephropathic patients. METHODS: This cross-sectional study was conducted in department of Medicine, Mayo Hospital Lahore from August 2014 to February 2015. Using non-probability purposive sampling 200 nephropathic (Chronic Kidney Disease Stage 1 to 3) patients were selected. Patients were assessed for T2DM and divided in two groups on the basis of presence or absence of DM. Magnesium levels were recorded in both groups. Percentages, mean, standard deviation and unpaired t-test was used to assess the data. SPSS was used for analysis of information. RESULTS: Total number of cases were 200, 43.5% (n=87) out of them were between 25-50 years of age while 56.5% (n=113) patients were between 51-70 years. The Mean+SD was calculated to be 51.38+11.51 years. The male patients were 48.5 %(n=109) while 51.5 %(n=91) were females. The frequency of DM in patients with nephropathy was 25.5% (n=51). Comparison of mean magnesium levels in nephropathic patients with and without diabetes was done. The results showed nephropathic patients having diabetes had 1.54+0.301 mg/dL magnesium levels while cases without diabetes had 1.92+0.313 mg/dL levels of magnesium, p value was calculated as 0.001 showing a significant difference between the two groups. CONCLUSION: The frequency of diabetes mellitus is higher among patients with nephropathy while on comparison of mean magnesium levels, nephropathic patients with diabetes had significant lower levels of magnesium as compared to without diabetes.

Tea and its consumption: benefits and risks.

The recent convention of introducing phytochemicals to support the immune system or combat diseases is a centuries' old tradition. Nutritional support is an emerging advancement in the domain of diet-based therapies; tea and its constituents are one of the significant components of these strategies to maintain the health and reduce the risk of various malignancies. Tea is the most frequently consumed beverage worldwide, besides water. All the three most popular types of tea, green (unfermented), black (fully fermented), and oolong (semifermented), are manufactured from the leaves of the plant Camellia sinensis. Tea possesses significant antioxidative, anti-inflammatory, antimicrobial, anticarcinogenic, antihypertensive, neuroprotective, cholesterol-lowering, and thermogenic properties. Several research investigations, epidemiological studies, and meta-analyses suggest that tea and its bioactive polyphenolic constituents have numerous beneficial effects on health, including the prevention of many diseases, such as cancer, diabetes, arthritis, cardiovascular disease (CVD), stroke, genital warts, and obesity. Controversies regarding beneficialts and risks of tea consumption still exist but the limitless health-promoting benefits of tea outclass its few reported toxic effects. However, with significant rise in the scientific investigation of role of tea in human life, this review is intended to highlight the beneficial effects and risks associated with tea consumption.

Efficacy of Remdesivir on Clinical Outcomes in COVID-19 Patients: A Study in a Tertiary Care Hospital in Pakistan.

Background: As of October 3, 2023, the global COVID-19 case tally exceeded 696 million, with almost 7 million fatalities. Remdesivir, approved for treatment of COVID-19 by regulatory bodies, has seen varying recommendations by the World Health Organization over time. Despite certain studies questioning its efficacy, others highlight potential benefits. The objective of this study was to gauge the impact of remdesivir on clinical outcomes in a Pakistani tertiary care hospital. Methods: An analytical cross-sectional study was conducted on 108 COVID-19 patients at Mayo Hospital Lahore between September 2020 and August 2021. Of these, 52 received remdesivir. The study employed a structured proforma for data collection, with analyses conducted using SPSS version 26, considering a p-value of less than 0.05 as statistically significant. Results: Demographic distribution between remdesivir-treated and untreated groups was similar. Significant improvement was observed in the remdesivir cohort in terms of oxygen saturation (58%), ferritin levels (58.2%), chest X-ray results (67.8%), and discharge rates (66.7%) when compared to the untreated group. Stratification based on disease severity showed that remdesivir was particularly beneficial for moderate illness cases in several parameters. Conclusion: This study suggests that remdesivir can be associated with improved outcomes, especially in patients with moderate COVID-19 severity. The data emphasizes the importance of the disease stage when considering therapeutic interventions and calls for more region-specific research to guide health responses amid diverse epidemiological landscapes.

Colloidal carbon soot templated TiO2/Ag surface functionalized 3D printed metal brushes as new generation surface enhanced Raman scattering substrates.

This present work demonstrated the functional transformation of 3D printed metal substrates into a new family of Surface-enhanced Raman Scattering substrates, a promising approach in developing SERS-based Point-of-care (PoC) analytical platforms. l-Powder Bed Fusion (l-PBF, Additive manufacturing or 3D printing technique) printed metal substrates have rough surfaces, and exhibit high thermal stability and intrinsic chemical inertness, necessitating a suitable surface functionalization approach. This present work demonstrated a unique multi-stage approach to transform l-PBF printed metal structures as recyclable SERS substrates by colloidal carbon templating, chemical vapor deposition, and electroless plating methods sequentially. The surface of the printed metal structures was functionalized using the colloidal carbon soot particles, that were formed by the eucalyptus oil flame deposition method. These carbon particles were shown to interact with the metals present in the printed structures by forming metal carbides and function as an adlayer on the surface. Subsequent deposition of TiO2 onto these templates led to strong grafting of TiO2 and retaining the fractal structure of the soot template onto the metal surface. Electroless deposition of silver nanoparticles resulted in the formation of fractally structured TiO2/Ag nanostructures and these functionalized printed metal structures were shown as excellent SERS substrates in enhancing the vibrational spectral features of Rhodamine B (RhB). The presence of TiO2 photocatalyst on the surface was shown to remove the RhB analyte from the surface under photochemical conditions, which enables the regeneration of SERS activity, and the substrate can be recycled. The migration of metals from the printed metal structures into the fractally ordered TiO2/Ag nanostructures was found to enhance the photocatalytic activity and increase the recyclability of these substrates. This study demonstrates the potential of 3D-printed Inconel metal substrates as next-generation recyclable SERS platforms, offering a substantial advancement over traditional colloidal, thin-film, flexible, and hard SERS substrates.

FAM26F: An Enigmatic Protein Having a Complex Role in the Immune System.

Mammalian immune system is a complex amalgam of diverse cellular and noncellular components such as cytokines, receptors and co-receptors. FAM26F (family with sequence similarity 26, member F) is a recently identified tetraspanin-like membrane glycoprotein which is predicted to make homophilic interactions and potential synapses between several immune cells including CD4+, CD8+, NK, dendritic cells and macrophages. Various whole transcriptome analyses have demonstrated the differential expression of FAM26F in several bacterial, viral and parasitic infections, in certain pathophysiological conditions such as liver and heart transplantation, and in various cancers. The complete understanding of transcriptional regulation of FAM26F is in its infancy however it is up regulated by various stimulants such as polyI:C, LPS, INF gamma and TNF alpha, and via various proposed pathways including TLR3, TLR4 IFN-ß and Dectin-1. These pathways can merge in STAT1 activation. The synergistic expression of FAM26F on both NK-cells and myeloid dendritic cells is required to activate NK-cells against tumors via its cytoplasmic tail, thus emphasizing therapeutic potential of FAM26F for NK sensitive tumors. Current review provides a comprehensive basis to propose that FAM26F expression level is at least a hallmark for IFN-γ-lead immune responses and thus can proficiently be regarded as an early diagnostic marker. Future investigation dissecting the role of FAM26F in activation of various immune cell populations in local amplification by cell-cell contact is crucial to provide the missing link imperative for elucidating the relevance of this protein in immune responses.

Nanozyme-based pollutant sensing and environmental treatment: Trends, challenges, and perspectives.

Nanozymes are defined as nanomaterials exhibiting enzyme-like properties, and they possess both catalytic functions and nanomaterial's unique physicochemical characteristics. Due to the excellent stability and improved catalytic activity in comparison to natural enzymes, nanozymes have established a wide base for applications in environmental pollutants monitoring and remediation. Nanozymes have been applied in the detection of heavy metal ions, molecules, and organic compounds, both quantitatively and qualitatively. Additionally, within the natural environment, nanozymes can be employed for the degradation of organic and persistent pollutants such as antibiotics, phenols, and textile dyes. Further, the potential sphere of applications for nanozymes traverses from indoor air purification to anti-biofouling agents, and even they show promise in combatting pathogenic bacteria. However, nanozymes may have inherent toxicity, which can restrict their widespread utility. Thus, it is important to evaluate and monitor the interaction and transformation of nanozymes towards biosphere damage when employed within the natural environment in a cradle-to-grave manner, to assure their utmost safety. In this context, various studies have concluded that the green synthesis of nanozymes can efficiently overcome the toxicity limitations in real life applications, and nanozymes can be well utilized in the sensing and degradation of several toxic pollutants including metal ions, pesticides, and chemical warfare agents. In this seminal review, we have explored the great potential of nanozymes, whilst addressing a range of concerns, which have often been overlooked and currently restrict widespread applications and commercialization of nanozymes.

Surface functionalized 3D printed metal structures as next generation recyclable SERS substrates.

Combining the design flexibility and rapid prototyping capabilities of additive manufacturing with photocatalytic and plasmonic functionalities is promising for the development of next-generation SERS applications such as point of care diagnostics and in situ monitoring of chemical reactions in fuels and chemical processing. Laser powder bed fusion (LPBF) is a well-matured additive manufacturing technique which generates metallic structures through localised melting and joining of metal powders using a laser. LPBF reduces material wastage during manufacturing, is applicable to a wide range of metals and alloys, and allows printing of complex internal structures. This feature article elaborates the use of soot templating, chemical vapour deposition and electroless plating techniques for grafting plasmonic and semiconductor nanoparticles on the surface of LPBF manufactured metallic substrates. The capability to fabricate different types of intricate metallic lattices using additive manufacturing is demonstrated and technical challenges in their adequate functionalization are elaborated. The developed methodology allows tailoring of the substrate structure, composition, morphology, plasmonic and photocatalytic activities and thus unveils a new class of recyclable SERS substrates.

Conservative Management of Thyroid Eye Disease.

The aim of the study was to determine the result of conservative management of Graves ophthalmopathy in a multi-disciplinary setting by a team of ophthalmologists and endocrinologists. Twenty-seven patients of thyroid eye disease were included in the study who underwent complete ocular examination and complete thyroid biochemical profile. Each patient was advised lubrication with artificial tears, cool compresses, sleeping with elevated head at bed, taping of the eyelids while sleeping and avoidance of smoking. Follow-ups were done at one and six months. EUGOGO classification was used to classify severity of the disease in mild, moderate, severe, and very severe; whereas, clinical activity score (CAS) was implied to categorise the disease activity. Mild to moderate Graves ophthalmopathy responded very well to conservative management. Moderate cases required additional steroids. Whereas, severe and very severe cases require additional surgical intervention. Key Words: Graves ophthalmology, Conservative management, Lubrication, Multidisciplinary approach.

Determining the clinical significance of computer interpreted electrocardiography conclusions.

BACKGROUND: Computerized electrocardiogram (EKG) interpretation technology was developed in the mid-20th century, but its use continues to be controversial. This study aims to determine clinical factors which indicate greater odds of clinical significance of an abnormal computerized EKG interpretation. METHODS: The inclusion criteria for this retrospective study were patients who underwent outpatient echocardiography for the indication of an abnormal EKG and had an EKG abnormality diagnosed by the computerized EKG system. Qualifying patients had the results of their computerized EKG, echocardiogram, and charted patient characteristics collected. Computerized diagnoses and patient characteristics were assessed to determine if they were associated with increasing or decreasing the odds of an echocardiographic abnormality via logistic regression. Chi-square and t-test analyses were used for categorical and continuous variables, respectively. Odds ratios are presented as odds ratio [95% confidence interval]. A P-value of ≤ 0.05 was considered statistically significant. RESULTS: A total of 515 patients were included in this study. The population was 59% women with an average age of 57 ± 16 years, and a mean BMI of 30.1 ± 7.3 kg/m2. Patients with echocardiographic abnormalities tended to have more cardiac risk factors than patients without abnormalities. In our final odds ratio model consisting of both patient characteristics and EKG diagnoses, age, coronary disease (CAD), and diabetes mellitus (DM) increased the odds of an echocardiographic abnormality (1.04 [1.02-1.06], 2.68 [1.41-5.09], and 1.75 [1.01-3.04], respectively). That model noted low QRS voltage decreased the odds of an abnormal echocardiogram (0.31 [0.10-0.91]). CONCLUSION: Our findings suggest that in patients with an abnormal computerized EKG reading, the specific factors of older age, CAD, and DM are associated with higher odds of abnormalities on follow-up echocardiography. These results, plus practitioner overreading, can be used to determine more appropriate management when faced with an abnormal computerized EKG diagnosis.

Unveiling the Physical and Functional Niches of FAM26F by Analyzing Its Subcellular Localization and Novel Interacting Partners.

The knowledge of a protein's subcellular localization and interacting partners are crucial for elucidating its cellular function and associated regulatory networks. Although FAM26F (family with sequence similarity 26, member F) has been recognized as a vital player in various infections, stimulation studies, cancer, and immune pathogenesis, the precise location and function of FAM26F are not well understood. The current study is the first to focus on functional characterization of FAM26F by analyzing its subcellular localization and identifying its novel interacting partners using advanced proteome approaches. The immunofluorescence and confocal microscopy results revealed FAM26F to be largely localized within the Golgi apparatus of the cell. However, its minor presence in endoplasmic reticulum (ER) pointed toward the probable retrograde transfer of FAM26F from Golgi to ER during adverse conditions. Moreover, co-immunoprecipitation and MS/MS results demonstrated a total of 85 proteins, 44 of which significantly copurified with FAM26F. Interestingly, out of these 44 MS/MS identified proteins, almost 52% were involved in innate immunity, 38.6% in neutrophil degranulation, and remaining 10% were either involved in phosphorylation, degradation, or regulation of apoptosis. Further characterization through Ingenuity Pathway Analysis showed that majority of these proteins was involved in maintaining calcium homeostasis of cell. Consequently, the validation of selected proteins uncovered the key interaction of FAM26F with Thioredoxin, which essentially paved the way for depicting its mechanism of action under stress or disease conditions. It is proposed that activation and inhibition of the cellular immune response is essentially dependent on whether FAM26F or Thioredoxin considerably interact with CD30R.

Identification of Differentially Expressed Proteins from Smokeless Tobacco Addicted Patients Suffering from Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the eight most common malignancy worldwide with an incidence rate of 40% in south-east Asia. Lack of effective diagnostic tools at early stage and disease recurrence despite extensive treatments are main reasons for high mortality and low survival rates. The aim of current study was to identify differentially expressed proteins to explore potential candidate biomarkers having diagnostic significance. We performed comparative proteomic analysis of paired protein samples (cancerous buccal mucosa and adjacent normal tissue) from OSCC patients using a combination of two dimensional gel electrophoresis and Mass spectrometric analysis. On the basis of spot intensity, seventeen proteins were found to be consistently differentially expressed among most of the samples which were identified through mass spectrometry. For validation of identified proteins, expression level of stratifin was determined using immuno-histochemistry and Western blot analysis. All identified proteins were analyzed by STRING to explore their interaction. Among uniquely identified proteins in this study, at least two candidate markers (Ig Kappa chain C region and Isoform 2 of fructose bisphosphate aldolase A) were found to be novel with respect to OSCC which can be explored further. Results presented in current study are likely to contribute in understanding the involvement of these molecules in carcinogenesis apart from their plausible role as diagnostic/prognostic markers.

Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis.

We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score (PRS) was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD) and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including coronary heart disease (CHD), CKD, PAD and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes.

Cutaneous manifestations in chronic myeloid leukemia in chronic phase treated with imatinib.

OBJECTIVE: The aim of this study was to see the patterns of skin changes in chronic myeloid leukemia (CML) in chronic phase treated with different doses of imatinib. METHODS: This cross-sectional study was conducted in the Oncology Department of Jinnah Hospital, Lahore, over a period of 6 months. Patients aged 7-70 years diagnosed either by fluorescence in situ hybridization (FISH) for BCR-ABL or cytogenetics for Philadelphia (Ph) chromosomes and consuming different doses of imatinib for the treatment of CML were randomly selected. Skin manifestations were analyzed and recorded on a predesigned proforma by a dermatologist. RESULTS: A total of 132 patients were enrolled; 65 male (49.24%) and 67 female (50.75%). Periorbital edema was found in 48.5% of cases, and hyperpigmentaion and melasma were found in 76.5% of cases. Pruritus was diagnosed in 6.8% of cases, alopecia in 5.3% of cases, and photosensitivity in 43.9% of cases. CONCLUSIONS: It was concluded that imatinib is associated with many adverse cutaneous side effects which should be overcome or reduced by either decreasing the duration of treatment with imatinib or switching to other treatment options.