Nevin Manimala

J Ayub Med Coll Abbottabad. 2023 Oct-Dec;35(4):523-529. doi: 10.55519/JAMC-04-11760.

ABSTRACT

BACKGROUND: Recently various combinations of direct acting antivirals (DAAs) have been tried successfully. The Sofosbuvir + Daclatasvir combination has been used with promising results. Recently, resistance has been noticed against DAAs. Therefore, polymorphism at particular sites in the interleukin 28B gene are under study to find possible association with resistance. This study was aimed at finding out any association of SNPs rs8099917 and rs12979860 (IL28B gene) with response and resistance to treatment in HCV genotype 3 patients in Khyber Pakhtunkhwa.

METHODS: This cross sectional, Analytical study was conducted at Gastroenterology/hepatology OPD of Prime Teaching Hospital, Peshawar Medical College. Collected Samples were stored at -20o C in PCR Lab of the College. DNA extraction and genotyping was carried out at BJ Molecular Biology Lab in Rawalpindi. Data was analyzed by using SPSS version 21. Chi-Square Test was used to see the statistically significant differences between rs8099917 T/G and rs12979860 T/C model.

RESULTS: In the IL28-B gene, single nucleotide polymorphism at rs12979860 T/C model, we observed that there are 37.5% CC homozygous, 12.5% TT homozygous and 50% CT heterozygous genotypes in resistant patients and 42.85% CC homozygous, 28.57% TT and 28.57% CT genotype in responder group. In rs12979860 T/C model, genotype of IL28-B in the responder and resistant group significantly varies at p-value =0.00572.

CONCLUSION: We conclude that in SNP at rs12979860, CC genotype is associated with clearance of HCV, while CT genotype was more prevalent in the resistant group and associated with chronicity.

PMID:38406928 | DOI:10.55519/JAMC-04-11760

J Hypertens. 2024 Feb 16. doi: 10.1097/HJH.0000000000003693. Online ahead of print.

ABSTRACT

BACKGROUND: The correlation between systolic blood pressure (SBP) and mortality in hypertensive patients with different phenotypes of heart failure (HF) has not been adequately studied, and optimal blood pressure control targets remain controversial. To explore the link between SBP and prognosis in all or three ejection fraction (EF) phenotypes of HF patients with hypertension.

METHODS: We analyzed 1279 HF patients complicated by hypertension in a retrospective cohort. The SBP <130 mmHg group included 383 patients, and the SBP ≥130 mmHg group included 896 patients. The major end point was all-cause mortality.

RESULTS: Of the 1279 study patients, with a median age of 66.0 ± 12.0 years, 45.3% were female. The proportions of the three subtypes of heart failure complicated with hypertension (HFrEF, HEmrEF, and HFpEF) were 26.8%, 29.3%, and 43.9%, respectively. During the 1-year follow-up, 223 patients experienced all-cause death, and 133 experienced cardiovascular death. Restricted cubic splines showed that the risk of all-cause and cardiovascular death increased gradually as the SBP level decreased in patients with HFrEF and HFmrEF. Furthermore, the multivariate Cox proportional hazards model revealed that SBP <130 mmHg was also associated with an increased risk of all-cause death [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.23-5.20, P = 0.011] and cardiovascular death (HR 1.91, 95% CI 1.01-3.63, P = 0.047) in HFrEF patients. A trend toward increased risk was observed among HFmrEF patients, but it was not statistically significant. This trend was not observed in HFpEF patients.

CONCLUSION: In HFrEF patients, SBP <130 mmHg was associated with an increased risk of all-cause and cardiovascular mortality. A trend toward increased risk was observed among HFmrEF patients, but not among HFpEF patients.

PMID:38406922 | DOI:10.1097/HJH.0000000000003693

J Ayub Med Coll Abbottabad. 2023 Oct-Dec;35(Suppl 1)(4):S721-S725. doi: 10.55519/JAMC-S4-11807.

ABSTRACT

BACKGROUND: The use of unhealthy food and a sedentary lifestyle increases daily health problems. Renal stones are one among others. Endourology promises the minimum complications and the highest stone clearance rate. Indications of the two procedures overlap micro-PCNL and RIRS. The objective was to evaluate stone clearance and complication rate of micro-PCNL and RIRS for lower pole renal stones.

METHODS: The research design of this study was a randomized trial and was done after approval of the ethical review committee. The sampling technique was consecutive sampling at the Urology department. Patients included in the study according to inclusion criteria were 96 in number. Randomization into two groups (RIRS vs micro-PCNL) was done by even odd method. All the procedure was done by a single senior urologist.

RESULTS: Their ratio among males and females was 2:1. Mean LOS in the RIRS group was 2.89±0.86 days and in the micro-PCNL group 2.58±0.65 days (p=0.047). The complication rate in the RIRS group was 6.2% and 8.3% in micro-PCNL (p=0.695). Mean post-operative haemoglobin was 12.30±1.07 g/dL among the RIRS group and among the micro-PCNL group it was 11.21±1.08 g/dL (p<0.001). There was an average haemoglobin drop in the micro-PCNL group of 1.09±0.01 g/dL. 75% clearance of stone after one session was achieved in the RIRS group while 79.2% was achieved in the micro-PCNL group (p=0.627).

CONCLUSION: Length of hospital stay (LOS) and stone clearance rate (SFR) were similar in both groups with insignificant statistical differences. There is a need to conduct more studies with a large number of study participants and involving multi-centers.

PMID:38406900 | DOI:10.55519/JAMC-S4-11807

Diabetes Metab J. 2024 Feb 26. doi: 10.4093/dmj.2022.0443. Online ahead of print.

ABSTRACT

BACKGROUND: The association between low-density lipoprotein (LDL-C) levels and cardiovascular disease (CVD) risk in different age groups within the diabetes mellitus (DM) population remains unclear. The cohort study was conducted to investigate this relationship.

METHODS: We assessed the 2009 to 2012 Korean National Health Screening and National Health Insurance Service records, with follow-up to the primary outcome (myocardial infarction [MI] or stroke) or December 2018. After excluding the participants with a history of MI or stroke, 2,227,394 participants with DM were included and categorized according to baseline LDL-C levels and age. Cox proportional hazards modeling was conducted. The CVD risk of age <40 years and LDL-C <70 mg/dL was set as the reference. In each age group, LDL-C <70 mg/dL was used as a reference for the subgroup analysis.

RESULTS: The cut-off LDL-C value for increased MI risk in each age group varied (<40 years old, LDL-C ≥160 mg/dL: hazard ratios [HR], 2.03; 95% confidence interval [CI], 1.644 to 2.506) (40-49-year-old, LDL-C <115 mg/dL: HR, 1.245; 95% CI, 1.04 to 1.489) (50-59-year-old, LDL-C <115 mg/dL: HR, 1.21; 95% CI, 1.014 to 1.445) (60-69-year-old, LDL-C <145 mg/dL: HR, 1.229; 95% CI, 1.022 to 1.479) (≥70 years old group, LDL-C <100 mg/dL: HR, 1.238; 95% CI, 1.018 to 1.504). The cut-off LDL-C values for increased stroke risk varied in each age subgroup (<40 years old, LDL-C ≥160 mg/dL: HR, 1.395; 95% CI, 1.094 to 1.779) (40-49-year-old, LDL-C <145 mg/dL: HR, 1.13; 95% CI, 1.019 to 1.253) (50-59-year-old, LDL-C <160 mg/dL: HR, 1.079; 95% CI, 1.008 to 1.154) (60-69-year-old, LDL-C <130 mg/dL: HR, 1.07; 95% CI, 1.022 to 1.119) (≥70 years old, LDL-C <115 mg/dL: HR, 1.064; 95% CI, 1.019 to 1.112).

CONCLUSION: The effect of LDL-C on the risk of CVD differs depending on the age of the population with DM.

PMID:38403889 | DOI:10.4093/dmj.2022.0443

Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2024 Jan-Feb;16(1):e1944. doi: 10.1002/wnan.1944.

ABSTRACT

Microbial biofilms are complex three-dimensional structures where sessile microbes are embedded in a polymeric extracellular matrix. Their resistance toward the host immune system as well as to a diverse range of antimicrobial treatments poses a serious health and development threat, being in the top 10 global public health threats declared by the World Health Organization. In an effort to combat biofilm-related microbial infections, several strategies have been developed to independently eliminate biofilms or to complement conventional antibiotic therapies. However, their limitations leave room for other treatment alternatives, where the application of nanotechnology to biofilm eradication has gained significant relevance in recent years. Their small size, penetration efficiency, and the design flexibility that they present makes them a promising alternative for biofilm infection treatment, although they also present set-backs. This review aims to describe the main possibilities and limitations of nanomedicine against biofilms, while covering the main aspects of biofilm formation and study, and the current therapies for biofilm treatment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

PMID:38403876 | DOI:10.1002/wnan.1944

Int J Paediatr Dent. 2024 Feb 25. doi: 10.1111/ipd.13171. Online ahead of print.

ABSTRACT

BACKGROUND: Paediatric-preformed zirconia crowns have been associated with several issues, primarily their inability to be crimped and the need for extensive tooth preparation. Additionally, the capacity to adjust the size, shape, and fit of these crowns is very limited.

AIM: To evaluate and compare the fracture strength of four different types of dental crowns intended for paediatric patients.

DESIGN: The fracture resistance of four types of paediatric crowns was evaluated using the universal testing machine; freshly extracted primary molars received one of the following: preformed zirconia crowns, custom-made computer-aided design and computer-aided manufacturing (CAD-CAM) zirconia crowns, custom-made CAD-CAM ceramic crowns, and custom-made CAD-CAM hybrid composite crowns. Data were statistically compared using the Kruskal-Wallis test followed by the Bonferroni test, and the level of significance was set at 5%.

RESULTS: Results showed that there was a statistically significant difference among the four groups (p < .001). The highest value of fracture force was observed for the milled zirconia crown and the lowest for the prefabricated zirconia.

CONCLUSION: The implementation of the CAD-CAM digital crown fabrication technique has the potential to address issues associated with preformed crowns in paediatric patients, particularly in terms of fracture resistance.

PMID:38403852 | DOI:10.1111/ipd.13171

Clin Genet. 2024 Feb 25. doi: 10.1111/cge.14510. Online ahead of print.

ABSTRACT

Spastic paraplegia type 4 (SPG4), caused by SPAST mutations, is the most predominant subtype of hereditary spastic paraplegia. Most documented SPG4 patients present as pure form, with the complex form rarely reported. We described the clinical and genetic features of 20 patients with complex phenotypes of SPG4 and further explored the genotype-phenotype correlations. We collected detailed clinical data of all SPG4 patients and assessed their phenotypes. SPAST gene mutations were identified by Multiplex ligation-dependent probe amplification in combination with whole exome sequencing. We further performed statistical analysis in genotype and phenotype among patients with various manifestations and different variants. Out of 90 SPG4 patients, 20 patients (male:female = 16:4) with additional neurologic deficits, namely complex form, were included in our study. The bimodal distribution of age of onset at 0-10 and 21-40 years old is concluded. On cranial MRI, obvious white matter lesions can be observed in five patients. We identified 9 novel and 8 reported SPAST mutations, of which 11 mutations were located in AAA (ATPase associated with various cellular activities) domain. The AAA cassette of spastin is the hottest mutated region among complex SPG4. All patients with cognitive impairment (CI) are males (n = 9/9). Additionally, 80% patients with ataxia are due to frameshift mutations (n = 4/5). Overall, our study summarized and analyzed the genetic and phenotypic characteristics of complex SPG4, making up over 1/5 of in-house SPG4 cohort, among which CI and ataxia are the most common features. Further studies are expected to explore the underlying mechanisms.

PMID:38403837 | DOI:10.1111/cge.14510

Environ Sci Pollut Res Int. 2024 Feb 26. doi: 10.1007/s11356-024-32424-9. Online ahead of print.

ABSTRACT

Plastic contamination is widely recognized as a major environmental concern due to the entry of small plastic particles into the food chain, thereby posing potential hazards to human health. However, the current understanding of microplastic (MP; < 5 mm) particles in livestock, which serve as an important food source, is limited. This study aims to investigate the concentration and characteristics of MPs in edible tissues of cow and sheep, namely liver, meat, and tripe, obtained from butcher shops in five areas of Bushehr port, Iran. The mean concentration of MPs in different tissues of cow and sheep were 0.14 and 0.13 items/g, respectively. Among the examined tissues, cow meat exhibited the highest concentration of MPs, with a concentration of 0.19 items/g. Nylon and fiber were identified as the predominant polymer types and shapes of MPs found in cow and sheep tissues, respectively. Furthermore, no statistically significant difference was observed in MP concentration across different tissues of cow and sheep. Significantly, this study highlights the elevated hazards associated with exposure to MPs through the consumption of edible cow and sheep tissues, particularly for children who consume meat. The results underscore the potential transfer of MPs from the environment to livestock bodies through their food, contamination during meat processing, and subsequent health hazards for consumers.

PMID:38403824 | DOI:10.1007/s11356-024-32424-9

BJU Int. 2024 Feb 25. doi: 10.1111/bju.16303. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the cumulative incidence proportion of disseminated or local Bacillus Calmette-Guérin (BCG) infections after adjuvant BCG instillations in patients with non-muscle-invasive bladder cancer (NMIBC).

PATIENTS AND METHODS: We analysed the timing and occurrence of BCG infections and absolute and relative risk in relation to patient characteristics available in the Swedish nationwide database ‘BladderBaSe 2.0’. The cumulative incidence proportion of a BCG infection was indicated by a reported diagnosis of tuberculosis (TB) in the patient registry or filing a prescription for tuberculostatic drugs.

RESULTS: The cumulative incidence proportion was 1.1% at the 5-year follow-up in 5033 patients exposed to adjuvant BCG instillations. The incidence rate was highest during the first 2 years after start of BCG instillations. Women had a lower risk than men (hazard ratio 0.23, 95% confidence interval 0.07-0.74). Age and calendar time at diagnosis, comorbidity, tumour risk group, previous medication with corticosteroids, immunosuppressive drugs, or time between transurethral resection of the bladder tumour and commencing the adjuvant BCG instillation were not associated with risk.

CONCLUSIONS: These data further supports that the overall risk of a BCG infection after BCG-instillation treatment for NMIBC is low. The great majority of infections occur in the first 2 years, calling for an awareness of the diverse symptoms of BCG infection during this period. We provide evidence for male sex as a risk factor; however, the statistical precision is low and with a risk of selection bias, making it difficult to rule out the other suggested risk factors without further studies with different approaches.

PMID:38403809 | DOI:10.1111/bju.16303

NMR Biomed. 2024 Feb 25:e5124. doi: 10.1002/nbm.5124. Online ahead of print.

ABSTRACT

Advanced intraoperative MR images (ioMRI) acquired during the resection of pediatric brain tumors could offer additional physiological information to preserve healthy tissue. With this work, we aimed to develop a protocol for ioMRI with increased sensitivity for arterial spin labeling (ASL) and diffusion MRI (dMRI), optimized for patient positioning regularly used in the pediatric neurosurgery setting. For ethical reasons, ASL images were acquired in healthy adult subjects that were imaged in the prone and supine position. After this, the ASL cerebral blood flow (CBF) was quantified and compared between both positions. To evaluate the impact of the RF coils setups on image quality, we compared different setups (two vs. four RF coils) by looking at T1-weighted (T1w) signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), as well as undertaking a qualitative evaluation of T1w, T2w, ASL, and dMR images. Mean ASL CBF did not differ between the surgical prone and supine positions in any of the investigated regions of interest or the whole brain. T1w SNR (gray matter: p = 0.016, 34% increase; white matter: p = 0.016, 32% increase) and CNR were higher (p = 0.016) in the four versus two RF coils setups (18.0 ± 1.8 vs. 13.9 ± 1.8). Qualitative evaluation of T1w, T2w, ASL, and dMR images resulted in acceptable to good image quality and did not differ statistically significantly between setups. Only the nonweighted diffusion image maps and corticospinal tract reconstructions yielded higher image quality and reduced susceptibility artifacts with four RF coils. Advanced ioMRI metrics were more precise with four RF coils as the standard deviation decreased. Taken together, we have investigated the practical use of advanced ioMRI during pediatric neurosurgery. We conclude that ASL CBF quantification in the surgical prone position is valid and that ASL and dMRI acquisition with two RF coils can be performed adequately for clinical use. With four versus two RF coils, the SNR of the images increases, and the sensitivity to artifacts reduces.

PMID:38403798 | DOI:10.1002/nbm.5124