Category: Nevin Manimala

J Hum Genet. 2023 Apr 3. doi: 10.1038/s10038-023-01146-0. Online ahead of print.

ABSTRACT

Hematologic abnormalities was observationally associated with the susceptibility of primary biliary cholangitis (PBC). However, the conclusion is still controversial and whether there exists a causal association remains elusive. Here we aimed to explore the causative role of hematological traits in the risk of PBC. We conducted two-sample and multivariable Mendelian randomization analyses based on summary statistics from previous large genome-wide association studies. Totally twelve red blood cell and six white blood cell traits were analyzed. Genetically determined higher hemoglobin level was significantly associated with a reduced risk of PBC (OR: 0.62, 95% CI: 0.47-0.81, P: 5.59E-04). Meanwhile, higher hematocrit level was nominally associated with reduced risk of PBC (OR: 0.73, 95% CI: 0.57-0.93, P: 0.01). These results could help better understand the role of hematological traits in the risk of PBC, and provide potential targets for the disease prevention and treatment.

PMID:37012349 | DOI:10.1038/s10038-023-01146-0

Sci Rep. 2023 Apr 3;13(1):5435. doi: 10.1038/s41598-023-31829-9.

ABSTRACT

1st episode drug naïve patients with psychosis might be at higher risk for cardiometabolic disturbances which could affect the different cognitive, and executive functions and domains of social cognition. This study aimed to study the metabolic parameters in 1st episode drug naïve patients with psychosis, to evaluate the relation of these cardiometabolic domains to the cognitive, executive functions, and social cognition. Socio-demographic characteristics of 150 first episode drug naïve patients with psychosis and 120 matched healthy control groups were collected. The current study also assessed the cardiometabolic profile and cognitive functions in both groups. Social cognition was examined by Edinburgh Social Cognition Test. The study revealed a statistically significant difference in parameters of metabolic profile among the studied groups (p < 0.001*), the scores of cognitive and executive tests were statistically significantly different (p < 0.001*). In addition, the patient’s group has lowered scores of domains of social cognition (p < 0.001*). Also, the mean affective theory of mind was negatively correlated with the conflict cost of the Flanker test (r = -.185* p value = .023). The total cholesterol level (r = – 0.241**, p value = .003) and level of triglycerides (r = – 0.241**, p value = 0.003) were negatively correlated with the interpersonal domain of social cognition, the total cholesterol level is positively correlated to the total score of social cognition (r = 0.202*, p value = 0.013). Patients with 1st episode drug naïve psychosis showed disturbed cardiometabolic parameters which have deleterious effects on cognitive functions and social cognition.

PMID:37012300 | DOI:10.1038/s41598-023-31829-9

Sci Rep. 2023 Apr 3;13(1):5400. doi: 10.1038/s41598-023-32004-w.

ABSTRACT

Acrylamide is a toxic reaction product occurring in dry-heated food such as bakery products. To meet the requirements laid down in recent international legal norms calling for reduction strategies in food prone to acrylamide formation, efficient chromatography-based quantification methods are available. However, for an efficient mitigation of acrylamide levels, not only the quantity, but also the contaminant’s distributions are of interest especially in inhomogeneous food consisting of multiple ingredients. A promising tool to investigate the spatial distribution of analytes in food matrices is mass spectrometry imaging (MS imaging). In this study, an autofocusing MALDI MS imaging method was developed for German gingerbread as an example for highly processed and instable food with uneven surfaces. Next to endogenous food constituents, the process contaminant acrylamide was identified and visualized keeping a constant laser focus throughout the measurement. Statistical analyses based on relative acrylamide intensities suggest a higher contamination of nut fragments compared to the dough. In a proof-of-concept experiment, a newly developed in-situ chemical derivatization protocol is described using thiosalicylic acid for highly selective detection of acrylamide. This study presents autofocusing MS imaging as a suitable complementary method for the investigation of analytes’ distributions in complex and highly processed food.

PMID:37012286 | DOI:10.1038/s41598-023-32004-w

Sci Rep. 2023 Apr 3;13(1):5440. doi: 10.1038/s41598-023-32441-7.

ABSTRACT

There is an ongoing debate on the COVID-19 infection fatality rate (IFR) and the impact of COVID-19 on overall population mortality. Here, we addressed these issues in a community in Germany with a major superspreader event analyzing deaths over time and auditing death certificates in the community.18 deaths that occurred within the first six months of the pandemic had a positive test for SARS-CoV-2. Six out of 18 deaths had non-COVID-19 related causes of death (COD). Individuals with COVID-19 COD typically died of respiratory failure (75%) and tended to have fewer reported comorbidities (p = 0.029). Duration between first confirmed infection and death was negatively associated with COVID-19 being COD (p = 0.04). Repeated seroprevalence essays in a cross-sectional epidemiological study showed modest increases in seroprevalence over time, and substantial seroreversion (30%). IFR estimates accordingly varied depending on COVID-19 death attribution. Careful ascertainment of COVID-19 deaths is important in understanding the impact of the pandemic.

PMID:37012282 | DOI:10.1038/s41598-023-32441-7

Sci Rep. 2023 Apr 3;13(1):5416. doi: 10.1038/s41598-023-31364-7.

ABSTRACT

Wear properties of Al-Mg-Si alloy matrix hybrid composites made with Si-based refractory compounds (SBRC) derived from bamboo leaf ash (BLA) as complimentary reinforcement with alumina have been studied. The experimental result indicate that optimum wear loss was obtained at higher sliding speed. The wear rate of the composites increased with an increase in BLA wt. %, with the composites having 4%SBRC from BLA + 6% alumina (B4) showing the least wear loss for the different sliding speeds and wear loads considered. With increasing BLA weight percent, the composites’ wear mechanism was mostly abrasive wear. Numerical optimization results using central composite design (CCD) reveal that at a wear load of 587.014N, sliding speed of 310.053 rpm and B4 hybrid filler composition level respectively, minimum responses in wear rate (0.572mm²/min), specific wear rate (0.212cm²/g.cm³) and wear loss (0.120 g) would be obtained for the developed AA6063 based hybrid composite. Perturbation plots indicate that the sliding speed have more impact on wear loss, while wear load have significant impact on the wear rate and specific wear rate.

PMID:37012279 | DOI:10.1038/s41598-023-31364-7

Sci Rep. 2023 Apr 3;13(1):5413. doi: 10.1038/s41598-023-31446-6.

ABSTRACT

Onchocerciasis is a parasitic disease transmitted by black flies. Human onchocerciasis is a public health and socioeconomic problem in Nigeria. Its prevalence and morbidity have reduced over the years because of control efforts especially, Mass Drug Administration with ivermectin. The current goal is to eliminate the disease transmission by 2030. Understanding the changes in transmission patterns in Cross River State is critical to elimination of onchocerciasis in Nigeria. This study was designed to determine the transmission dynamics of onchocerciasis in Cross River State after over two decades of mass ivermectin distribution in endemic communities. Agbokim, Aningeje, Ekong Anaku and Orimekpang are four endemic communities from three Local Government Areas of the State selected for this study. Transmission indices such as infectivity rates, biting rates and transmission potentials, parity rates and diurnal biting activities were determined. A total of 15,520 adult female flies were caught on human baits, Agbokim (2831), Aningeje (6209), Ekong Anaku (4364) and Orimekpang (2116). A total of 9488 and 5695 flies were collected during the rainy and dry seasons respectively in the four communities studied. The differences in relative abundance among the communities were statistically significant (P < 0.001). Monthly and seasonal fly numbers varied significantly (P < 0.008). There were differences in diurnal biting activities of flies in this study at different hours of the day and different months. The peak monthly biting rates were 5993 (Agbokim, October), 13,134 (Aningeje, October), 8680 (Ekong Anaku, October) and 6120 (Orimekpang, September) bites/person/month while the lowest monthly biting rates were 400 (Agbokim, November), 2862 (Aningeje, August), 1405 (Ekong Anaku, January) and 0.0 (Orimekpang, November and December) bites/person/month. Differences in biting rates among the study communities were significant (P < 0.001). The peak monthly transmission potential in Aningeje was 160 infective bites/person/month in the month of February while the lowest (except for months with no transmission) was 42 infective bites/person/month in the month of April. All other study sites had no ongoing transmission in this study. Transmission studies showed that there is progress toward transmission interruption especially in 3 out of the four studied areas. Molecular O-150 poolscreen studies is required to confirm the true transmission situation in the areas.

PMID:37012274 | DOI:10.1038/s41598-023-31446-6

Sci Rep. 2023 Apr 3;13(1):5424. doi: 10.1038/s41598-023-31574-z.

ABSTRACT

Speckle-based phase-contrast X-ray imaging (SB-PCXI) can reconstruct high-resolution images of weakly-attenuating materials that would otherwise be indistinguishable in conventional attenuation-based X-ray imaging. The experimental setup of SB-PCXI requires only a sufficiently coherent X-ray source and spatially random mask, positioned between the source and detector. The technique can extract sample information at length scales smaller than the imaging system’s spatial resolution; this enables multimodal signal reconstruction. “Multimodal Intrinsic Speckle-Tracking” (MIST) is a rapid and deterministic formalism derived from the paraxial-optics form of the Fokker-Planck equation. MIST simultaneously extracts attenuation, refraction, and small-angle scattering (diffusive dark-field) signals from a sample and is more computationally efficient compared to alternative speckle-tracking approaches. Hitherto, variants of MIST have assumed the diffusive dark-field signal to be spatially slowly varying. Although successful, these approaches have been unable to well-describe unresolved sample microstructure whose statistical form is not spatially slowly varying. Here, we extend the MIST formalism such that this restriction is removed, in terms of a sample’s rotationally-isotropic diffusive dark-field signal. We reconstruct multimodal signals of two samples, each with distinct X-ray attenuation and scattering properties. The reconstructed diffusive dark-field signals have superior image quality-as measured by the naturalness image quality evaluator, signal-to-noise ratio, and azimuthally averaged power-spectrum-compared to our previous approaches which assume the diffusive dark-field to be a slowly varying function of transverse position. Our generalisation may assist increased adoption of SB-PCXI in applications such as engineering and biomedical disciplines, forestry, and palaeontology, and is anticipated to aid the development of speckle-based diffusive dark-field tensor tomography.

PMID:37012270 | DOI:10.1038/s41598-023-31574-z

Sci Rep. 2023 Apr 3;13(1):5434. doi: 10.1038/s41598-023-31773-8.

ABSTRACT

Multiple types and classes of medications are administered in the acute management of traumatic spinal cord injury. Prior clinical studies and evidence from animal models suggest that several of these medications could modify (i.e., enhance or impede) neurological recovery. We aimed to systematically determine the types of medications commonly administered, alone or in combination, in the transition from acute to subacute spinal cord injury. For that purpose, type, class, dosage, timing, and reason for administration were extracted from two large spinal cord injury datasets. Descriptive statistics were used to describe the medications administered within the first 60 days after spinal cord injury. Across 2040 individuals with spinal cord injury, 775 unique medications were administered within the two months after injury. On average, patients enrolled in a clinical trial were administered 9.9 ± 4.9 (range 0-34), 14.3 ± 6.3 (range 1-40), 18.6 ± 8.2 (range 0-58), and 21.5 ± 9.7 (range 0-59) medications within the first 7, 14, 30, and 60 days post-injury, respectively. Those enrolled in an observational study were administered on average 1.7 ± 1.7 (range 0-11), 3.7 ± 3.7 (range 0-24), 8.5 ± 6.3 (range 0-42), and 13.5 ± 8.3 (range 0-52) medications within the first 7, 14, 30, and 60 days post-injury, respectively. Polypharmacy was commonplace (up to 43 medications per day per patient). Approximately 10% of medications were administered acutely as prophylaxis (e.g., against the development of pain or infections). To our knowledge, this was the first time acute pharmacological practices have been comprehensively examined after spinal cord injury. Our study revealed a high degree of polypharmacy in the acute stages of spinal cord injury, raising the potential to impact neurological recovery. All results can be interactively explored on the R_XSCI web site ( https://jutzelec.shinyapps.io/RxSCI/ ) and GitHub repository ( https://github.com/jutzca/Acute-Pharmacological-Treatment-in-SCI/ ).

PMID:37012257 | DOI:10.1038/s41598-023-31773-8

Spectrochim Acta A Mol Biomol Spectrosc. 2023 Mar 24;296:122662. doi: 10.1016/j.saa.2023.122662. Online ahead of print.

ABSTRACT

The UV spectra of Diclofenac Potassium DIC and Methocarbamol MET are superimposed making their analysis using direct or derivative spectrophotometric methods quite complicated. This study presents four effective spectrophotometric methods that enable simultaneous determination of both drugs without interference. The first method is based on application of simultaneous equation method on their zero order spectra where DIC has shown absorbance maxima at 276 nm and MET displays two absorbances maxima at 273 nm and 222 nm in distilled water. The second method relies on dual wavelength method, the two wavelengths (232 and 285 nm) were chosen for determination of DIC where the absorbance differences at these wavelengths are proportional to DIC concentration while the absorbance differences of MET are equal to zero. For the determination of MET, the two wavelengths (212 and 228 nm) were selected. The third method of first-derivative ratio has been applied where the derivative ratio absorbances of DIC and MET were measured at 286.1 and 282.4 nm, respectively. The fourth method utilizing ratio difference spectrophotometric (RD) method was eventually performed on the binary mixture. The amplitude difference between the two wavelengths (291and 305 nm) was calculated for DIC estimation while the amplitude difference between the two wavelengths (227and 273 nm) for MET determination. All methods show linearity range from 2.0-25 μg. mL^-1 and 6.0-40 μg. mL^-1 for DIC and MET respectively. The developed methods have been statistically compared with a reported method based on first derivative method and the results of statistical comparison confirm the accuracy and precision of the proposed methods therefore they can be effectively applied for determination of MET and DIC in pharmaceutical dosage form.

PMID:37011438 | DOI:10.1016/j.saa.2023.122662

J Am Chem Soc. 2023 Apr 3. doi: 10.1021/jacs.3c00734. Online ahead of print.

ABSTRACT

Criegee intermediates (CIs) are important carbonyl oxides that may react with atmospheric trace chemicals and impact the global climate. The CI reaction with water has been widely studied and is a main channel for trapping CIs in the troposphere. Previous experimental and computational reports have largely focused on reaction kinetic processes in various CI-water reactions. The molecular-level origin of CI’s interfacial reactivity at the water microdroplet surface (e.g., as found in aerosols and clouds) is unclear. In this study, by employing the quantum mechanical/molecular mechanical (QM/MM) Born-Oppenheimer molecular dynamics with the local second-order Møller-Plesset perturbation theory, our computational results reveal a substantial water charge transfer up to ∼20% per water, which creates the surface H₂O⁺/H₂O^– radical pairs to enhance the CH₂OO and anti-CH₃CHOO reactivity with water: the resulting strong CI-H₂O^– electrostatic attraction at the microdroplet surface facilitates the nucleophilic attack to the CI carbonyl by water, which may counteract the apolar hindrance of the substituent to accelerate the CI-water reaction. Our statistical analysis of the molecular dynamics trajectories further resolves a relatively long-lived bound CI(H₂O^–) intermediate state at the air/water interface, which has not been observed in gaseous CI reactions. This work provides insights into what may alter the oxidizing power of the troposphere by the next larger CIs than simple CH₂OO and implicates a new perspective on the role of interfacial water charge transfer in accelerating molecular reactions at aqueous interfaces.

PMID:37011411 | DOI:10.1021/jacs.3c00734