Neuronal Expression of Opioid Gene is Controlled by Dual Epigenetic and Transcriptional Mechanism in Human Brain.

Molecular mechanisms that define patterns of neuropeptide expression are essential for the formation and rewiring of neural circuits. The prodynorphin gene (PDYN) gives rise to dynorphin opioid peptides mediating depression and substance dependence. We here demonstrated that PDYN is expressed in neurons in human dorsolateral prefrontal cortex (dlPFC), and identified neuronal differentially methylated region in PDYN locus framed by CCCTC-binding factor binding sites. A short, nucleosome size human-specific promoter CpG island (CGI), a core of this region may serve as a regulatory module, which is hypomethylated in neurons, enriched in 5-hydroxymethylcytosine, and targeted by USF2, a methylation-sensitive E-box transcription factor (TF). USF2 activates PDYN transcription in model systems, and binds to nonmethylated CGI in dlPFC. USF2 and PDYN expression is correlated, and USF2 and PDYN proteins are co-localized in dlPFC. Segregation of activatory TF and repressive CGI methylation may ensure contrasting PDYN expression in neurons and glia in human brain.

Impact of prior cancer history on survival in brain malignancy: A propensity score-adjusted, population-based study.

BACKGROUND: Individuals with a Prior Cancer History (PCH) are often excluded from clinical trials. However, a growing body of evidence suggests that prior cancer history does not present adverse outcomes on cancer patients. The evidence on the survival of brain cancer patients in this regard remains widely unknown. METHODS: We conducted a retrospective cohort study to estimate the prevalence and impact of prior cancer on survival of patients diagnosed with brain cancer. Data of patients who were diagnosed with brain cancer as their first or second primary malignancy between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to ensure comparable baseline characteristics among the patients. Survival analysis was conducted using the Kaplan-Meier method, as well as multivariate Cox proportional hazard and multivariate competing risk models. RESULTS: Out of 42 726 patients, 1189 (2.78%) had PCH. Genitourinary (40.4%), Breast (13.6%), Hematologic and Lymphatic (11.4%), and Gastrointestinal malignancies (11.3%) were the most common types of prior cancer. PCH served as a significant risk factor for Overall Survival (OS) (Adjusted Hazard Ratio [AHR] 1.26; 95% CI [1.15-1.39]; p < .001) but did not have a statistically significant impact on Brain Cancer-Specific Survival (BCSS) (AHR 0.97; 95% CI [0.88-1.07]; p = .54). Glioblastoma exhibited the most substantial and statistically significant impact on survival as compared to other histological types. Of all the organs systems, only prior Gastrointestinal and Hematologic and Lymphatic malignancies had a statistically significant impact on OS of patients. CONCLUSION: Our findings indicate that PCH does not exert a substantial impact on the survival of brain cancer patients, except in cases involving gastrointestinal or hematologic and lymphatic PCH, or when the brain cancer is glioblastoma.

Practical guide in using insulin degludec/insulin aspart: A multidisciplinary approach in Malaysia.

Insulin degludec/insulin aspart (IDegAsp) co-formulation provides both basal and mealtime glycaemic control in a single injection. The glucose level-lowering efficacy of IDegAsp is reported to be superior or non-inferior to that of the currently available insulin therapies with a lower rate of overall hypoglycaemia and nocturnal hypoglycaemia. An expert panel from Malaysia aims to provide insights into the utilisation of IDegAsp across a broad range of patients with type 2 diabetes mellitus (i.e. treatment-naive or insulin-naive patients or patients receiving treatment intensification from basal-only regimens, premixed insulin and basal-bolus insulin therapy). IDegAsp can be initiated as once-daily dosing for the main meal with the largest carbohydrate content with weekly dose adjustments based on patient response. A lower starting dose is recommended for patients with cardiac or renal comorbidities. Dose intensification with IDegAsp may warrant splitting into twice-daily dosing. IDegAsp twice-daily dosing does not need to be split at a 50:50 ratio but should be adjusted to match the carbohydrate content of meals. The treatment of patients choosing to fast during Ramadan should be switched to IDegAsp early before Ramadan, as a longer duration of titration leads to better glycated haemoglobin level reductions. The pre-Ramadan breakfast/lunch insulin dose can be reduced by 30%-50% and taken during sahur, while the preRamadan dinner dose can be taken without any change during iftar. Education on the main meal concept is important, as carbohydrates are present in almost all meals. Patients should not have a misconception of consuming more carbohydrates while taking IDegAsp.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults with Type 2 Diabetes in Malaysia: Results from a Prospective, Non-interventional Real-World Study.

Objectives: Insulin degludec (IDeg)/insulin aspart (IAsp; IDegAsp) is a co-formulation of 70% IDeg and 30% IAsp. According to several randomized controlled trials, IDegAsp is effective and safe for patients with type 2 diabetes mellitus (T2DM). A subgroup analysis of the ARISE study was conducted to explore the safety and efficacy of IDegAsp among Malaysian patients with T2DM in real-world settings. Methodology: ARISE, an open-label, multicenter, non-interventional, prospective study was conducted between August 2019 and December 2020. Adult Malaysian patients with T2DM who were enrolled from 14 sites received IDegAsp as per the local label for 26 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) levels from baseline to end of study (EOS). Results: Of the 182 patients included in the full analysis set, 159 (87.4%) completed the study. From baseline to EOS, HbA1c (estimated difference [ED]: -1.3% [95% CI: -1.61 to -0.90]) and fasting plasma glucose levels (ED: -1.8 mmol/L [95% CI: -2.49 to -1.13]) were significantly reduced (p<0.0001). The patient-reported reduced hypoglycemic episodes (overall and nocturnal) during treatment. Overall, 37 adverse events were observed in 23 (12.6%) patients. Conclusion: Switching or initiating IDegAsp treatment resulted in significant improvements in glycemic control and a reduction in hypoglycemic episodes.

Radioiodine I-131 for the therapy of graves' disease.

Graves' disease is a common cause of hyperthyroidism. Treatment options for Graves' disease include antithyroid medication, surgery or radioactive iodine (I-31) or RAI. This review will focus on the approach to RAI therapy; discussing dose selection, patient preparation, and consideration before and after administering RAI, examining aspects of pre-treatment with antithyroid medication as well as discussing possible adverse events including hypothyroidism and possible worsening of thyroid-associated opthalmopathy. Follow-up is lifelong with the aim of ensuring the patient remains euthyroid or on replacement therapy if there is evidence of hypothyroidism. While there are controversies in treatment of thyrotoxicosis with RAI, with appropriate patient selection and regular follow-up, radioiodine is a safe and effective modality in achieving high cure rates.

A summary of the Malaysian Clinical Guidance on the management of postmenopausal and male osteoporosis, 2015.

AIM: This Clinical Guidance is aimed to help practitioners assess, diagnose and manage their patients with osteoporosis (OP), using the best available evidence. METHODS: A literature search using PubMed (MEDLINE) and The Cochrane Library identified all relevant articles on OP and its assessment, diagnosis and treatment, from 2011, to update from the 2012 edition. The studies were assessed and the level of evidence assigned. For each statement, studies with the highest level of evidence were used to frame the recommendation. RESULTS: This article summarizes the diagnostic and treatment pathways for postmenopausal and male OP, while addressing the risk-benefit ratio for OP treatment. Recognising the limitation of only depending on bone mineral density in assessing fracture risk, a move to assess 10 year fracture risk using tools such as FRAX, is recommended as a guide to decision-making on when to start treatment. A re-evaluation was done of the position of calcium supplementation and on the importance of vitamin D. There has been concern about the potential adverse effects of the long-term usage of bisphosphonates, which have been discussed fully. Algorithms for the management of postmenopausal and male OP have been updated. CONCLUSIONS: Adequate intake of calcium (1000 mg from both diet and supplements) and vitamin D (800 IU) daily remain important adjuncts in the treatment of OP. However, in confirmed OP, pharmacological therapy with anti-resorptives is the mainstay of treatment in both men and postmenopausal women. Patients need to be regularly assessed while on medication and treatment adjusted as appropriate.

Back pain in patients with severe osteoporosis on teriparatide or antiresorptives: a prospective observational study in a multiethnic population.

INTRODUCTION: We evaluated reduced back pain in a multiethnic population treated with teriparatide and/or antiresorptives in real-life clinical settings over 12 months. METHODS: This prospective observational study comprised 562 men and postmenopausal women (mean age 68.8 years) receiving either teriparatide (n = 230), antiresorptives (raloxifene or bisphosphonates; n = 322), or both (n = 10) for severe osteoporosis. The primary endpoint was the relative risk of new/worsening back pain at six months. RESULTS: At baseline, a higher proportion of teriparatide-treated than antiresorptive-treated patients had severe back pain (30.9% vs. 17.7%), extreme pain/discomfort (25.3% vs. 16.8%), extreme anxiety/depression (16.6% vs. 7.8%) and were confined to bed (10.0% vs. 5.3%). Teriparatide-treated patients had higher visual analog scale (VAS) scores for pain (5.8 ± 2.42 vs. 5.1 ± 2.58) and lower mean European Quality of Life-5 Dimensions (EQ-5D) scores (37.7 ± 29.15 vs. 45.5 ± 31.42) than antiresorptive-treated patients. The incidence of new/worsening back pain at six months for patients on teriparatide and antiresorptives was 9.8% and 10.3% (relative risk 0.99, 95% confidence interval 0.80-1.23), respectively. The incidence of severe back pain at 12 months was 1.3% and 1.6% in the teriparatide and antiresorptive treatment groups, respectively. Teriparatide-treated patients had lower mean VAS (2.71 ± 2.21 vs. 3.30 ± 2.37) and EQ­5D (46.1 ± 33.18 vs. 55.4 ± 32.65) scores at 12 months. More teriparatide-treated patients felt better (82.7% vs. 71.0%) and were very satisfied with treatment (49.4% vs. 36.8%) compared to antiresorptive-treated patients. CONCLUSION: Patients treated with either teriparatide or antiresorptives had similar risk of new/worsening back pain at six months.

The Malaysian Clinical Guidance on the management of postmenopausal osteoporosis, 2012: a summary.

AIM: This Clinical Guidance is aimed to help practitioners assess, diagnose and manage their patients with osteoporosis (OP), using the best available evidence. METHODS: A literature search using PubMed (MEDLINE) and The Cochrane Library identified all relevant articles on OP and its assessment, diagnosis and treatment, from 2005, to update from the previous edition published in 2006. The studies were assessed and the level of evidence assigned; for each statement, studies with the highest level of evidence were used to frame the recommendation. RESULTS: This article summarizes the diagnostic and treatment pathways for OP, highlighting the new data that have changed the way we assess and treat OP. Instead of starting treatment based on bone mineral density alone, there has been a move to assessing 10-year fracture risk before treatment, using tools such as the Fracture Risk Assessment Tool (FRAX). There has been a re-evaluation on calcium supplementation and more emphasis on the importance of vitamin D. There has been concern about the potential adverse effects of the long-term usage of bisphosphonates, which we have discussed fully. New drugs that have been licensed since 2006 in Malaysia have been included. CONCLUSIONS: Adequate intake of calcium (1000 mg from both diet and supplements) and vitamin D (800 IU) daily remain important in the treatment of OP. However, in confirmed OP, pharmacological therapy with anti-resorptives is the mainstay of treatment. Patients need to be regularly assessed while on medication and treatment adjusted as required.

Initiation with once-daily BIAsp 30 results in superior outcome compared to insulin glargine in Asians with type 2 diabetes inadequately controlled by oral anti-diabetic drugs.

We compare the efficacy and safety of once-daily biphasic insulin aspart 70/30 (BIAsp 30) and insulin glargine in Asian subjects with type 2 diabetes inadequately controlled with oral anti-diabetic drugs (OADs). In a 26-week, open-labelled, randomised, parallel-group, multinational, multicentre, treat-to-target trial, 155 insulin-naïve Asian subjects were treated with either BIAsp 30 or insulin glargine, both in combination with metformin and glimepiride. Change in HbA(1c) at end of treatment with BIAsp 30 was superior to insulin glargine (BIAsp 30-glargine=-0.36%, 95% CI [-0.64; -0.07], p=0.015). Mean self-measured plasma glucose (SMPG) at bedtime was significantly lower with BIAsp 30 than insulin glargine (7.98+/-0.34 mmol/L vs. 9.16+/-0.33 mmol/L, p=0.0078). Incidences of minor and daytime hypoglycaemia were higher with BIAsp 30 than those with glargine, but the difference did not reach the statistical significance. No difference was seen in nocturnal hypoglycaemia. The incidence of adverse events was comparable between treatments, with low incidence of serious adverse events and major hypoglycaemia. Mean body weight increased slightly in both groups. In insulin-naïve Asian subjects with type 2 diabetes who are inadequately controlled with OADs, once-daily BIAsp 30 is superior to insulin glargine.

Prevalence, risk factors, and clinical features of thyroid-associated ophthalmopathy in multiethnic Malaysian patients with Graves' disease.

BACKGROUND: The prevalence of thyroid-associated ophthalmopathy (TAO) has been reported to be lower in several Asian populations than in Caucasians. The risk factors for TAO that have been demonstrated in Caucasians have not been studied in Asian populations. The aim of this study, therefore, was to determine the prevalence, risk factors, and clinical features of TAO in a cohort of multiethnic Malaysian patients with Graves' disease (GD). METHODS: This was a cross-sectional study of 167 consecutive patients with GD who attended two endocrine clinics from October 2003 to September 2004. The patients were classified as Malay, Chinese, and Indian based on their ethnic characteristics as detailed in the national identity card. The patients were examined by a single individual for the presence and characteristics of TAO. Thyroid function tests were performed, and smoking history and the extent of smoking history were recorded. RESULTS: The prevalence rate of TAO using the American Academy of Ophthalmology diagnostic criteria was 34.7%. This increased to 46.7% if lower lid retraction was added as an alternate criterion. The observed prevalence rate was higher than expected in the Chinese patient population based on a comparison with the Malay and Indian patients, but this was not statistically significant. Smokers with GD were at 2.75 times greater risk of TAO than nonsmokers (p = 0.019). Male gender was shown to confer higher risk of TAO on univariate analysis (p = 0.003), but not on multivariate analysis. The percentage of males who smoked in the study group was relatively high (79%). The most common presentation of TAO was exophthalmos, followed by lid retraction. CONCLUSIONS: TAO has relatively high prevalence rate (34.7%) in three populations of Asian patients with GD. This is similar to that reported for Caucasian patients with GD. As in Caucasian patients, smoking increases the risk of TAO. In the Asian populations we studied, exophthalmos was the most common eye sign. However, lower lid retraction was also common and present in 60% of cases with other signs of TAO. In Chinese, Malay, and Indian Asians with GD, lower lid retraction should be a diagnostic criterion for TAO.

Parvo B 19 myocarditis in immunocompetent patient

Parvo B19 virus can cause different diseases in human. It can cause myocarditis which if not treated in time can prove fatal. Here we are presenting a case of 43 years old immune-competent male who was found to be infected with Parvo B 19 virus, which was diagnosed by positive serology and PCR technique. He was successfully treated and ison regular follow up. Every clinician should consider the possibility of PVB 19 in any patient presenting with acute myocarditis

slit-skin smear an alternate to histopathology in the diagnosis of cutaneous leishmaniasis?

To determine how effective is slit-skin smear as a diagnostic test in comparison with the histopathology. This was a validation study, carried out in Combined Military Hospital [CMH] Kohat from 1st September 2011 to 30th June 2012. The study population was the patients who were clinically diagnosed as cutaneous leishmaniasis. Slit-skin smears were performed in all and a biopsy was sent for histopathology. The results were analyzed by cross tabs and chi square test. A total of 50 patients were included. They were all adult males. Leishman-Donovan [LD] bodies were seen in histopathology slides in 31 patients [62%] and were not detected in 19 patients [38%]. The slit-smear showed LD bodies in 18 smears [36%] and negative in 32 smears [64%] [p=0.048]. Histopathology is statistically superior investigation than slit-skin smear in the diagnosis of cutaneous leishmaniasis

Surgery in a temporary setup- sharing an experience of 16 months

Sharing an experience of surgery in a temporary set up. Descriptive study. This study was carried out at Combined Military Hospital Muzaffarabad after the earthquake of October 2005 over a period of 16 months. The workload that this hospital has managed over the period despite running under tents. The hospital was functioning under the temporary set up. Patients were earth quake victims requiring different surgical procedure. A total of 2887 major and 7471 minor surgical procedures pertaining to the specialty of General Surgery, Orthopedics, ENT, EYE and Gynecology were carried out over a period of 16 months. Though the load was comparable to any [C] class and most of the [B] class hospitals, despite being under tents, there was not a single case of post operative infection. The importance of single-use-only surgical disposables in the good management of surgical patients has also been highlighted. The basic sterilization techniques, if followed religiously stand good in preventing postoperative infection, even in compromised working condition

Dry eye syndrome frequency in adult patients attending the eye clinic in Military Hospital Rawalpindi

To determine the frequency of dry eye syndrome in adult patients. A descriptive study. Eye Department Military Hospital Rawalpindi. From June 2004 to December 2004. A total of hundred patients were randomly selected from the daily OPD at eye department, MH Rawalpindi. They were tested for the presence of dry eye syndrome by Rose Bengal staining, Schirmer tear strip measurements and Tear film break up time. A total of 67 males and 33 females were recruited. Out of these 10 males and 6 females were found to be having dry eye syndrome. Mean patient age was 34.3 +/- 1.3 years [range 20-60 years]. The frequency of dry eye syndrome in adult patients attending the eye clinic of Military Hospital Rawalpindi is 16%. To determine the frequency of dry eye syndrome in adult patients. A descriptive study. Eye Department Military Hospital Rawalpindi. From June 2004 to December 2004. A total of hundred patients were randomly selected from the daily OPD at eye department, MH Rawalpindi. They were tested for the presence of dry eye syndrome by Rose Bengal staining, Schirmer tear strip measurements and Tear film break up time. A total of 67 males and 33 females were recruited. Out of these 10 males and 6 females were found to be having dry eye syndrome. Mean patient age was 34.3 +/- 1.3 years [range 20-60 years]. The frequency of dry eye syndrome in adult patients attending the eye clinic of Military Hospital Rawalpindi is 16%

Gronblad-Standberg syndrome: a case report and review of literature

Gronblad-Strandberg syndrome is a rare congenital hereditary dysplasic disorder of the connective tissue, characterized by a progressive abnormal mineralization and dystrophic calcification of elastic tissue and collagen. The term Gronblad-Strandberg syndrome is used when angioid streaks in eye occur in association with pseudoxanthoma elasticum [PXE] of skin. We report a young patient having characteristic skin and eye manifestations of the syndrome. He was evaluated thoroughly regarding extent and potential systemic complications of the disease and was counseled accordingly. Since dermatologists are generally not familiar with historical background and ocular findings of the disease, a brief review of these two aspects is also made