Search

Abstract With the increased next generation sequencing (NGS) based genetic diagnosis due to technological boon, the biomedical world is getting a substantial number of single nucleotide variations (SNVs) every day along with other genetic variations. The detected SNVs may or may not have clinical significance. Based on different levels of study, these SNVs are categorized either as disease associated or not disease associated. However, there exists another category called as “uncertain” where the scientific literature has scanty of data. These “uncertain” or “variants of uncertain significance (VUS)” has become the greatest challenge for the diagnostic fraternity since no specific decision can be taken by them for the persons carrying the VUS. Therefore, there exists a huge knowledge gap that needs to be addressed for better patient care. The present study aims to find out the possible ways of investigation that may help in reducing this knowledge gap so that decisive approaches can be made against VUS for better and accurate patient care.

Abstract Background Dengue fever, a viral illness spread mostly by Aedes mosquitoes, continues to pose a substantial public health issue in Dhaka city, Bangladesh. In Dhaka, climatic and socio-demographic factors like population density affect the spread of dengue. The dengue indexes are greatest in the residential mixed zone. Numerous environmental parameters, such as temperature, relative humidity, rainfall, and the air pollution index, have been linked to mosquito larvae, and dengue prevalence is correlated with urbanization, decreased vegetation, and population expansion. Methods By using an extensive dataset that encompasses a range of years, we use spatial and temporal analytic methodologies to investigate the correlation between land use attributes, climatic variables, and the occurrence of dengue fever. To better understand the dynamics of dengue, the built environment and climatic factors are treated as independent variables in this study. ArcPy is a Python package that facilitates here for geographic data analysis and ArcMap 10.7 also used for visualizing spatial data. Results The results of our study demonstrate that land use significantly influences the spatial patterns of Dengue incidence in Dhaka city. The dengue hotspot Thana are identified and these are Badda, Jatrabari, kadamtali, Mirpur, Mohammadpur, Sobujbagh, Shyampur, Tejgoan, Dhanmondi and Uttara. All of these areas’ population density and residential use as land use is higher than the other Thana of Dhaka city. There exists a significant correlation between climatic characteristics, such as temperature (0.25), rainfall (.803), specific humidity (0.74), relative humidity (0.76), wind speed (0.4) and Dengue incidence patterns. This research emphasizes the structural use and climatic relationship in Dengue epidemics, with climatic conditions playing a significant role as drivers of these variations. Conclusions This research demonstrates the complex relationship between land use, meteorological factors, and the spread of Dengue fever in Dhaka city. The results of this study have significant significance for several domains, including urban planning, public health measures, and vector control tactics. A comprehensive understanding of the temporal and geographical patterns of dengue transmission might aid in the development of accurate and effective prevention measures intended to lessen the effects of dengue in cities, such as Dhaka.

The significance of this study involves the optimisation of the aeration efficiency (AE) of the venturi aerator using an artificial neural network (ANN) technique integrated with an optimisation algorithm, i.e., particle swarm optimisation (PSO) and genetic algorithm (GA). To optimise the effects of operational factors on aeration efficiency by utilising a venturi aeration system, aeration experiments were conducted in an experimental tank with dimensions of 90cm×55cm×45cm. The operating parameters of the venturi aerator include throat length (TL), effective outlet pipe (EOP), and flow rate (Q) to estimate the efficacy of the venturi aerator in terms of AE. A 3–6-1 ANN model was developed and integrated with the PSO and GA techniques to find out the best possible optimal operating variables of the venturi aerator. The coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE) determined from the experimental and estimated data were used to assess and compare the performance of the ANN-PSO and ANN-GA modelling. It is shown that ANN-PSO provides a better result as compared to ANN-GA. The operational parameters, TL, EOP, and Q, were determined to have the most optimum values at 50 mm, 6 m, and 0.6 L/s, respectively. The optimised aeration efficiency of the venturi was found to be 0.105 kg O2/kWh at optimum operational circumstances. In fact, the neural network having an ideal design of (3-6-1) and a correlation coefficient value that is extremely close to unity has validated the results indicated above.

mRNA-based vaccines and candidate therapeutics have great potential in various medical fields. For the delivery of mRNA into target cells and tissues, lipid formulations are often employed. However, this approach could cause the activation of immune responses, making it unsuitable for the treatment of inflammatory conditions. Therefore, alternative delivery systems are highly demanded. In this study, we evaluated the transport efficiency and characteristics of cell-penetrating peptide PepFect14 (PF14) and mRNA nanoparticles in the presence of different additives. Our results show that all PF14-mRNA formulations entered cultured cells, while calcium chloride enhanced the transport and production of the encoded protein in HeLa and HaCaT cell lines, and polysorbate 80 did so in primary human keratinocytes. All formulations had similar physical properties and did not remarkably affect cell viability. By selectively blocking endocytosis pathways, we show that PF14-mRNA nanoparticles primarily entered HeLa cells via macropinocytosis and HaCaT cells via both macropinocytosis and clathrin-mediated endocytosis, while none of the blockers significantly affected the delivery into primary keratinocytes. Finally, subcutaneous injection of PF14-mRNA nanoparticles before inducing mouse irritant contact dermatitis resulted in the expression of a reporter protein without provoking harmful immune responses in the skin. Together, our findings suggest that PF14-mRNA nanoparticles have the potential for developing mRNA-based therapeutics for treating inflammatory skin conditions.

Background: Higher prevalence of stress in polycystic ovarian syndrome (PCOS) patients may have a critical role in their altered body composition. Aims: The aim is to study the correlation of perceived stress with waist-hip ratio (WHR), lipid profile, and fasting sugar in newly diagnosed patients with polycystic ovarian syndrome in an urban population of West Bengal. Materials and Methods: This cross-sectional pilot project was conducted in the Department of Physiology, Burdwan Medical College, in a time span of 1 year after taking institutional ethical clearance and informed consent of the participants. One hundred newly diagnosed PCOS patients and 100 age-, dietary habit-, and body mass index (BMI)-matched controls were included in the study. The Perceived Stress Scale (PSS) scores of the participants were assessed. Fasting blood samples were drawn from participants for analysis of fasting blood sugar (FBS) and lipid profile. Height, weight, BMI, WHR, resting pulse rate (measured after 15 min of rest with participants in supine posture), and blood pressure (measured by mercury manometer) were measured. The computer software “Statistical Package for the Social Sciences (SPSS) version 16” was used to analyze the data, and unpaired t-test was used to compare different parameters of the two groups. Correlation of PSS with other parameters was assessed. Results: There was a significant difference in PSS, WHR, pulse, blood pressure, FBS, and lipid profile between the two groups. There was a significant positive correlation between PSS and WHR, FBS, and lipid profile, and high-density lipoprotein cholesterol was negatively correlated with PSS. However, no difference in BMI was observed. Conclusion: PCOS patients with higher PSS in spite of having equivalent BMI, dietary habits, and age may have higher WHR, dyslipidemia, and fasting sugar as compared to normal individuals. Stress management programs are need of the day for the highly stressed modernized global population.

Cell-penetrating peptides (CPPs) are highly promising transfection agents that can deliver various compounds into living cells, including nucleic acids (NAs). Positively charged CPPs can form non-covalent complexes with negatively charged NAs, enabling simple and time-efficient nanoparticle preparation. However, as CPPs have substantially different chemical and physical properties, their complexation with the cargo and characteristics of the resulting nanoparticles largely depends on the properties of the surrounding environment, i.e., solution. Here, we show that the solvent used for the initial dissolving of a CPP determines the properties of the resulting CPP particles formed in an aqueous solution, including the activity and toxicity of the CPP–NA complexes. Using different biophysical methods such as dynamic light scattering (DLS), atomic force microscopy (AFM), transmission and scanning electron microscopy (TEM and SEM), we show that PepFect14 (PF14), a cationic amphipathic CPP, forms spherical particles of uniform size when dissolved in organic solvents, such as ethanol and DMSO. Water-dissolved PF14, however, tends to form micelles and non-uniform aggregates. When dissolved in organic solvents, PF14 retains its α-helical conformation and biological activity in cell culture conditions without any increase in cytotoxicity. Altogether, our results indicate that by using a solvent that matches the chemical nature of the CPP, the properties of the peptide–cargo particles can be tuned in the desired way. This can be of critical importance for in vivo applications, where CPP particles that are too large, non-uniform, or prone to aggregation may induce severe consequences.

Background: In patients with primary hypothyroidism, there are increased levels of thyrotropin-releasing hormone (TRH) which can cause rise of prolactin (PRL) levels and these patients may have galactorrhea. Aims: Considering the clinical importance of hyperprolactinemia in ovulation disorders, sterility, and menstruation disorders, the present study was conducted to observe the prevalence of hyperprolactinemia and related galactorrhea in newly diagnosed hypothyroid females and correlate serum PRL level with thyroid-stimulating hormone (TSH) in hypothyroid females in a rural population of East India. Materials and Methods: This pilot study was conducted in Burdwan Medical College on 200 newly diagnosed female hypothyroid participants after taking institutional ethical clearance and informed consent of the participants. Age and gender-matched 100 controls were taken. Serum TSH, serum free thyroxine (fT4), and serum PRL levels were assessed. A questionnaire was designed for the evaluation of hypothyroidism symptoms for all the participants. These symptoms were galactorrhea, dryness of skin, feeling cold, hair loss, weakness, weight gain, constipation, loss of libido, and menstrual abnormalities. A total number of hyperprolactinemic patients were 42; out of them, 30 females were clinical and 12 were subclinical hypothyroid patients. One hundred and fifty-eight patients had normal PRL level. Results: Significant difference was found between clinical and subclinical hypothyroid females for body mass index (BMI) (P = 0.002), TSH (P < 0.0001), fT4 (P < 0.0001), and PRL (P = 0.002). The prevalence of hyperprolactinemia was 21% in hypothyroid females, 23.07% in clinical or overt hypothyroid females, and 17.14% in subclinical hypothyroid females. The prevalence of galactorrhea is 1% in all hypothyroid females and 1.53% in clinical hypothyroid females. A significant positive correlation was found between TSH and PRL in hypothyroid patients. Conclusions: Incidence of hyperprolactinemia is found to be notable in hypothyroid females including clinical and subclinical hypothyroidism, and hypothyroid females show positive correlation between TSH and PRL levels. Hence, PRL levels need to be assessed in all hypothyroid females.

Background: Stress-related diseases are becoming the number one killer in the modern age. Aims: The aim of the study is to identify the effects of yoga on cardiorespiratory profile and stress levels of young adult Indian males residing in West Bengal. Materials and Methods: This cross-sectional pilot project was conducted after taking institutional ethical clearance and informed consent of the participants. Hundred healthy young adult Indian males in the age group of 18–30 years performing yoga regularly were selected as study population, and hundred age- and sex-matched participants from local population not performing any type of yoga were selected as control. Life event stress and perceived stress scores of the participants were measured using presumptive life event stress scale and perceived stress scale (PSS), respectively. Fasting blood sugar (FBS) and lipid profile were analyzed. Anthropometric measurements, resting pulse rate, blood pressure, electrocardiogram, and pulmonary function test were recorded. Unpaired t-test was used to analyze the data. Results: Weight, waist–hip ratio, and body mass index were significantly raised in participants not practicing yoga. Resting pulse rate, systolic blood pressure, and diastolic blood pressure were significantly lower in participants practicing yoga. PSS scores were significantly less in participants practicing yoga. FBS, total cholesterol, triglyceride, and low-density lipoprotein level in serum were significantly lower in participants practicing yoga, and high-density lipoprotein value was significantly raised. Duration of QRS complex, P-R interval, Q-T interval, and R-R interval were significantly raised in participants practicing yoga. The amplitude of T-wave and amplitude of S-T segment were significantly lowered in participants practicing yoga. Forced expiratory volume in 1 s and forced vital capacity values were found to be significantly raised in participants practicing yoga. Conclusions: Perceived stress adversely affects cardiovascular and respiratory profile of healthy young adult males, and regular practice of yoga may decrease perceived stress levels and help in modulating cardiorespiratory profile.

We demonstrate self-similar stable propagation of parabolic optical pulses through a highly nonlinear specialty Bragg fiber at 2.8 μm by a numerical approach. To obtain such propagation characteristics over a longer length of a Bragg fiber, we propose and verify a fiber design scheme that underpins passive introduction of a rapidly varying group-velocity dispersion around its zero dispersion wavelength and modulated nonlinear profile through suitable variation in its diameter. To implement the proposed scheme, we design a segmented and tapered chalcogenide Bragg fiber in which a Gaussian pulse is fed. Transformation of such a launched pulse to a self-similar parabolic pulse with full-width-at-half-maxima of 4.12 ps and energy of ~39 pJ is obtained at the output. Furthermore, a linear chirp spanning across the entire pulse duration and 3 dB spectral broadening of about 38 nm at the output are reported. In principle, the proposed scheme could be implemented in any chosen set of materials.

Background: Femoral shaft fractures account for 1.6% of all bony injuries in children, and the mode of treatment for children between 6 and 16 years of age is still debatable. Objectives: To compare the merits and demerits of operative and conservative managements of fracture shaft femur in children in a rural population in a developing country. Materials and Methods: Forty patients in the age group of 6-14 years with transverse fractures of shaft of the femur and two different treatment protocols were selected. The patients treated in skeletal traction or fixed traction in Thomas′ splint were included in one group and patients who were treated operatively with titanium elastic nails comprised the other group. Data was analyzed using Chi-square test. Results: The commonest cause of injury was motor vehicle accident, accounting for 70% of the cases, with left femur (60%) more commonly injured. All fractures in the operative group united clinically by 8 weeks and radiologically by 10 weeks, and, in the conservative group, by 9 weeks clinically and 12 weeks radiologically. The difference was statistically significant. Shortening and angular mal alignments were found more commonly in the conservative group, and the difference was significant. The follow-up for 1 year of all cases were uneventful. Conclusion: Internal fixation with titanium elastic nails provides better results than conservative treatment in traction.