Pathophysiology of X-Linked Adrenoleukodystrophy: Updates on Molecular Mechanisms.

X-ALD, an inherited monogenic metabolic disorder affecting the CNS and adrenal white matter, is caused by mutations in ABCD1 gene leading to defective fatty acid oxidation in the peroxisomes. This results in accumulation of very long-chain fatty acids, VLCFA, into brain, spinal cord, and body fluids. A single ABCD1mutation does not clearly explain the severity and diverse clinical spectrum of X-ALD phenotypes which suggests that not only genetic but also other modifier genes, epigenetic factors, and environmental factors play a role and contribute to neuroinflammation, mitochondrial dysfunctions, oxidative stress, and metabolic defects seen in phenotypes of ALD. In this review we discuss genotype and phenotype correlation and clinical spectra of X-ALD, previous and recent modifier genetic factors of X-ALD, including novel role of microRNAs (miRNAs) in pathology and as biomarkers. We also discuss the mechanistic interplay of miRNAs and metabolic pathways and potential of targeting miRNAs for X-ALD.

Generating human AMN and cALD iPSC-derived astrocytes with potential for modeling X-linked adrenoleukodystrophy phenotypes.

X-adrenoleukodystrophy (X-ALD) is a peroxisomal metabolic disorder caused by mutations in the ABCD1 gene encoding the peroxisomal ABC transporter adrenoleukodystrophy protein (ALDP). Similar mutations in ABCD1 may result in a spectrum of phenotypes in males with slow progressing adrenomyeloneuropathy (AMN) and fatal cerebral adrenoleukodystrophy (cALD) dominating the majority of cases. Mouse model of X-ALD does not capture the phenotype differences and an appropriate model to investigate mechanism of disease onset and progress remains a critical need. Induced pluripotent stem cell (iPSC)-derived and cell models derived from them have provided useful tools for investigating cell-type specific disease mechanisms. Here, we generated induced pluripotent stem cell (iPSC) lines from skin fibroblasts of two each of apparently healthy control, AMN and cALD patients with non-integrating mRNA-based reprogramming. iPSC lines expanded normally and expressed pluripotency markers Oct4, SOX2, Nanog, SSEA and TRA-1-60. Expression of markers SOX17, brachyury, Desmin, Oxt2 and beta tubulin III demonstrated the ability of the iPSCs to differentiate into all three germ layers. iPSC-derived lines from CTL, AMN and cALD male patients were differentiated into astrocytes. Differentiated AMN and cALD astrocytes lacked ABCD1 expression and accumulated VLCFA, a hallmark of X-ALD. These patient astrocytes provide disease-relevant tools to investigate mechanism of differential neuroinflammatory response and metabolic reprogramming in X-ALD. Further these patient-derived human astrocyte cell models will be valuable for testing new therapeutics.

Protein Nutrition: Understanding Structure, Digestibility, and Bioavailability for Optimal Health.

This review discusses different protein sources and their role in human nutrition, focusing on their structure, digestibility, and bioavailability. Plant-based proteins, such as those found in legumes, nuts, and seeds, may contain anti-nutritional factors that impact their bioavailability apart from structural and compositional differences from animal proteins. Animal proteins are generally highly digestible and nutritionally superior to plant proteins, with higher amino acid bioavailability. Alternative protein sources are also processed in different ways, which can alter their structure and nutritional value, which is also discussed.

Comparison of Clinical and Radiological Outcomes of Total Knee Arthroplasty in Osteoarthritic Patients.

Background The knee is the joint most commonly affected by osteoarthritis, more than any other. Osteoarthritis is a progressive, long-term condition that leads to the deterioration of joint tissue and cartilage, resulting in pain and impairment. Total knee arthroplasty (TKA) is a successful intervention that improves functional capability, decreases pain, and enhances quality of life. We conducted this study to evaluate whether radiological parameters following TKA influence the clinical outcomes of patients with knee osteoarthritis. Methods The study was conducted on patients treated for knee osteoarthritis at the Department of Orthopedics, Rajindra Hospital and Government Medical College, Patiala, Punjab, in collaboration with the Department of Radiology over a period of 1.5 years. A total of 152 patients diagnosed with knee osteoarthritis were included in the study; all underwent TKA. Patients underwent clinical evaluation and were graded using the Knee Society Score (KSS) during follow-up examinations. Pain was evaluated using the Visual Analog Scale (VAS). Postoperative X-rays were obtained, and various angles, including the distal femoral angle (DFA), the proximal tibial angle (PTA), and the posterior slope angle (PSA), were measured. Patient follow-up was conducted at three days, three months, and six months. Subsequently, a comparison of the clinical and radiological outcomes of TKA was performed. Results In this study, a total of 152 patients participated, with the majority falling into the 61-70 age group. Of these patients, 40.13% were female and 59.87% were male. The average medial DFA was 94.05°, the average medial PTA was 89.31°, and the PSA was 6.6°. Patients with a medial DFA of 94.05° (±3), a medial PTA of 89.31° (±3), and a PSA of 6.6° (±3) were categorized into the normal group. Conclusion Patients with DFA, PTA, and PSA in the normal range demonstrate improved KSS and clinical outcomes.

A hybrid effective medium description for nanoporous gold films and thickness-mediated control of optical absorption.

With the increasing demand for sensing platforms operating across UV, visible, and near-infrared wavelengths, nanoporous gold has emerged as an ideal substrate for rapid, quantitative detection of analytes with excellent specificity and high sensitivity. This study investigates thickness-mediated compositional changes and their impact on scattering characteristics of thin nanoporous gold films fabricated using selective chemical etching. Specifically, we observe thickness-induced morphological and structural changes across different fabricated samples from 25 to 100 nm in thickness. Upon their optical characterization across UV-VIS-NIR spectral regime, we notice that the constitutional differences among samples manifest distinctively & deterministically in their total optical scattering response. In order to gain insights into these observed scattering responses and to fathom the subtle connections between structural properties of NPG films and their optical response, a hybrid theoretical model comprising Maxwell-Garnett & Bruggeman effective medium approximations has been adopted. Our approach not only allows to appropriately account for the inhomogeneous nature of these films, but also corroborates well with the atomic force microscopy characterizations of the fabricated samples. Furthermore, tracing such a theoretical model is important as it helps in systematically ascertaining additional loss terms emerging in the complex dielectric function of films due to their nanoscale porosity & roughness, permitting a good reproduction of measured optical spectra. We believe, our approach will not only facilitate accurate regulation of losses in NPG thin films but will also aid in deriving customized optical performance from them, thereby advancing their potential applications in sensing and beyond.

Trace Analysis of C4F7N Insulating Gas Mixtures by Spontaneous Raman Spectroscopy and Gas Chromatography.

2,3,3,3-Tetrafluoro-2-(trifluoromethyl) propanenitrile (C4F7N) is being researched as an alternative to sulfur hexafluoride (SF6) for applications in gas-insulated switchgear. We independently assessed the effectiveness of gas chromatography-mass spectrometry (GC-MS) and a novel method of feedback-assisted multipass cavity spontaneous Raman spectroscopy (SRS) for the trace quantification of impurities in C4F7N and its related byproducts. A total of 14 gases were identified with estimated concentrations as low as 20 ppm (ppm) for C3F6 using GC-MS and 7.4 ppm for CH4 using SRS and as high as 500 ppm for CF4 using GC-MS and 1430 ppm for CO using SRS. While GC-MS is highly effective in selectively detecting and quantifying trace contaminants, it necessitates separate detectors for various gases, such as CH4 and H2. SRS succeeded in detecting CF4 and C2F6 at concentrations of 465 and 100 ppm, respectively, and in placing an upper bound of several hundred ppm for the other analytes. Crucially, SRS holds potential for portability-and thus for field applications-in gas-insulated switchgear equipment diagnostics.

Nanopatterning Induced Si Doping in Amorphous Ga2O3 for Enhanced Electrical Properties and Ultra-Fast Photodetection.

Ga2O3 has emerged as a promising material for the wide-bandgap industry aiming at devices beyond the limits of conventional silicon. Amorphous Ga2O3 is widely being used for flexible electronics, but suffers from very high resistivity. Conventional methods of doping like ion implantation require high temperatures post-processing, thereby limiting their use. Herein, an unconventional method of doping Ga2O3 films with Si, thereby enhancing its electrical properties, is reported. Ion-beam sputtering (500 eV Ar+) is utilized to nanopattern SiO2-coated Si substrate leaving the topmost part rich in elemental Si. This helps in enhancing the carrier conduction by increasing n-type doping of the subsequently coated 5 nm amorphous Ga2O3 films, corroborated by room-temperature resistivity measurement and valence band spectra, respectively, while the nanopatterns formed help in better light management. Finally, as proof of concept, metal-semiconductor-metal (MSM) photoconductor devices fabricated on doped, rippled films show superior properties with responsivity increasing from 6 to 433 mA W-1 while having fast detection speeds of 861 µs/710 µs (rise/fall time) as opposed to non-rippled devices (377 ms/392 ms). The results demonstrate a facile, cost-effective, and large-area method to dope amorphous Ga2O3 films in a bottom-up approach which may be employed for increasing the electrical conductivity of other amorphous oxide semiconductors as well.

Deep Earth Chronicles: High-Pressure Investigation of Phenakite Mineral Be2SiO4.

Beryllium silicate, recognized as the mineral phenakite (Be2SiO4), is a prevalent constituent in Earth's upper mantle. This study employs density-functional theory (DFT) calculations to explore the structural, mechanical, dynamical, thermodynamic, and electronic characteristics of this compound under both ambient and high-pressure conditions. Under ideal conditions, the DFT calculations align closely with experimental findings, confirming the mechanical and dynamical stability of the crystalline structure. Phenakite is characterized as an indirect band gap insulator, possessing an estimated band gap of 7.83 eV. Remarkably, oxygen states make a substantial contribution to both the upper limit of the valence band and the lower limit of the conduction band. We delved into the thermodynamic properties of the compound, including coefficients of thermal expansion, free energy, entropy, heat capacity, and the Gruneisen parameter across different temperatures. Our findings suggest that Be2SiO4 displays an isotropic behavior based on estimated anisotropic factors. Interestingly, our investigation revealed that, under pressure, the compression of phenakite is not significantly affected by bond angle bending.

Impact of Obesity on Outcomes Associated With Acute Alcoholic Pancreatitis.

The incidence and prevalence of obesity have been rising in the United States, negatively impacting the population's overall health. This study seeks to better understand the impact of obesity on patients presenting with acute alcoholic pancreatitis (AAP). Data collected using the National Inpatient Sample (NIS) from the fourth quarter of 2015 to 2019 with a principal diagnosis of AAP and secondary obesity were analyzed. Confounders were adjusted for multivariate regression analysis using a multitude of factors. A total of 229,510 patients were identified with a diagnosis of AAP, among which 14,150 were also identified as obese. A majority of the sample, both obese and non-obese patients with AAP, were middle-aged white females. The average comorbidity index (CCI) was lower in the non-obese cohort compared to the obese cohort. Compared to non-obese patients, patients with AAP who were obese had higher hospital charges and a longer LOS (p<0.05. Additionally, compared to non-obese patients, obese patients with AAP had higher odds of mortality and adverse events, such as acute renal failure and respiratory failure (p<0.05). Current research supports these complications, which have shown an association with increased visceral fat in or around the pancreas that can ultimately worsen acute pancreatitis outcomes and aggravate AAP by damaging the intestinal mucosal barrier. These findings should be considered when treating obese patients who develop AAP. Strategies to increase surveillance of such patients should be implemented to reduce complications and mortality in this population.

Monocular Painless Vision Loss in the Emergency Department: Multipurpose Utility of Point-of-Care Ultrasound.

BACKGROUND: Eye-related symptoms are a common presentation in the emergency department (ED). The cases range from simple viral conjunctivitis to trauma-related eye injuries. One pathological condition that could lead to vision loss is retinal artery occlusion (RAO). Evaluating a patient with an eye symptom requires thorough eye examination and advanced imaging in certain instances. Consultation with an ophthalmologist is also necessary for cases that require treatment recommendations and further testing. In the ED, point-of-care ultrasound (POCUS) is a commonly used diagnostic tool that can be used for ocular examination. CASE REPORT: We reported a case of a 60-year-old man who presented with painless partial right-eye vision loss. POCUS showed decreased flow in the right central retinal artery with an area of the pale retina seen on the image from the retinal camera, suggesting a possible branch RAO. Further examination with POCUS showed plaque formation at the carotid bifurcation, a potential cause of the patient's symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians and other providers should be encouraged to use POCUS to diagnose eye symptoms accurately and promptly. Abnormal findings will prompt immediate specialty consult and early appropriate management. Our case and other reported cases highlight POCUS's reliability and rapid diagnostic ability.

Potential Biotechnological Applications of Cyanobacterial Exopolysaccharides

Abstract The cyanobacterial exopolysaccharides (EPSs) are considered as one of the important group of biopolymers having significant ecological, industrial, and biotechnological importance. Cyanobacteria are regarded as a very abundant source of structurally diverse, high molecular weight polysaccharides having variable composition and roles according to the organisms and the environmental conditions in which they are produced. Due to their structural complexity, versatility and valuable biological properties, they are now emerging as high-value compounds. They are possessing exceptional properties and thus are being widely explored for various applications like in food and pharmaceutical industries, in bioremediation for removal of heavy metals, for soil conditioning, as biopolymers, bioadhesives, and bioflocculants. However, poor understanding of their complex structural properties, lack of concrete information regarding the genes encoding the proteins involved in the EPS biosynthetic pathways, their process of production and about the associated factors controlling their structural stability, strongly limits their commercialization and applications in the various fields of biotechnology. Owing to the above context, the present review is aimed to organize the available information on applications of cyanobacterial EPSs in the field of biotechnology and to identify the research gaps for improved industrial utilization and commercialization of these biomaterials.

Ethanol mediated enhancement in bacterial transformation

In molecular biology, transformation using E. coli as a host plays a key role in synthesizing gene libraries. The present study demonstrated a new ethanol-based method for transformation of plasmid DNA to E. coli. Ethanol at 10 percent concentration (v/v) showed best results. Further, as compared with traditional CaCl2 method, the transformation rate, using protocol outlined in this study, was very high, suggesting amenable for further applications.