Clinico-Pathological Spectrum of Hepatitis A Virus-Induced Autoimmune-Like Hepatitis in Children.

There is limited evidence that hepatitis A virus (HAV) infection can trigger hepatic autoimmunity, but this area remains largely unexplored. This study was thus planned with the aim to compare HAV-induced autoimmune-like hepatitis (HAV-ALH) with HAV-related liver dysfunction (HAV-acute viral hepatitis or HAV-AVH) and classical autoimmune hepatitis (AIH). This was a retrospective review of 46 patients with HAV infection who underwent liver biopsy (including 17 cases of HAV-ALH: diagnosis based on histopathology), and they were compared to 46 cases of age- and gender-matched classical AIH. Overall, HAV cohort (n = 46) had higher prevalence of pruritus, higher bilirubin levels, higher proportion of cholestasis, lower IgG levels, higher seronegativity and lack of disease recurrence, while the classical AIH group had higher proportion/severity of interface hepatitis, fibrosis, necrosis and pseudorosetting (p < 0.05). In comparison to the classical HAV-AVH group, HAV-ALH group had higher AST levels, higher presence of autoantibodies, and higher prevalence of severe zone 3 perivenulitis and marked pseudorosetting on histology (p < 0.05). Also, HAV-ALH group, in comparison to the AIH group, had more pruritus (OR 7.29, p < 0.004) and more seronegativity (41% vs. 13%, p < 0.031), while duration of illness (p < 0.003), IgG (p < 0.001) levels and liver stiffness measurement (p < 0.006) were significantly higher in AIH group (versus the HAV-ALH and HAV-AVH groups). Histologically, in comparison to AIH, HAV-ALH group had significantly less interface hepatitis (OR 0.03, p < 0.001) and fibrosis (OR 0.08, p < 0.001) and significantly more cholestasis (OR 4.5, p < 0.021). HAV infection can act as a potential trigger for immune-mediated hepatic damage, akin to drug-induced autoimmune-like hepatitis. Larger multicentric studies are needed to further explore this aspect.

Development and validation of the chemotherapy adherence assessment scale (CAAS).

BACKGROUND: Adherence to chemotherapy regimens is crucial for achieving optimal treatment outcomes in cancer patients. However, measuring adherence remains a significant challenge. This study aimed to develop and validate a comprehensive self-report tool for assessing chemotherapy adherence. METHODS: The Chemotherapy Adherence Assessment Scale (CAAS) was developed through a multi-stage process involving literature review, expert input, and pilot testing. Face validation was conducted with 23 subject experts, and content validity was assessed using the Content Validity Index (CVI). The CAAS was pilot-tested on 28 cancer patients undergoing chemotherapy. Psychometric properties were evaluated through internal consistency analysis (Cronbach's alpha) and Exploratory Factor Analysis (EFA). RESULTS: Face validation revealed 85% agreement among experts regarding grammar, clarity, and content. The CVI was 0.81 for individual items and 0.83 for the overall scale, indicating good content validity. Cronbach's alpha was 0.789, demonstrating strong internal consistency. The EFA yielded a robust five-factor structure, explaining 94.63% of the total variance. Most items exhibited strong factor loadings (>0.7) and high communalities (>0.7), supporting the construct validity of the CAAS. CONCLUSIONS: The CAAS demonstrated robust psychometric properties, including good content validity, high internal consistency, and a well-defined factor structure capturing key dimensions of chemotherapy adherence. The CAAS represents a valuable contribution to adherence assessment in oncology settings, with potential applications in clinical practice and adherence interventions.

Tunable backward terahertz-wave parametric oscillator centered at a high frequency of 0.87 THz with injection seeding.

We report the first demonstration of a frequency tunable backward THz-wave parametric oscillator (BW-TPO) centered at a high frequency of 0.87 THz using a slant-stripe-type magnesium oxide-doped periodically poled lithium niobate (PPLN) crystal as the nonlinear medium. Down-converted THz and idler beams generate upon excitation of the PPLN with a sub-nanosecond pulsed source of λ = 1064.44 nm. The resulting first idler has a wavelength of 1067.75 nm, equivalent to an oscillation frequency of 0.872 THz as per the spectral line separation from the pump. We also present angle tuning of the BW-TPO frequency ranging from 0.836-0.905 THz through PPLN rotation. The threshold pump intensity for BW-TPO is determined to be 5.6 GW/cm2 while obtaining a conversion efficiency as high as 12.3% at a pump energy (intensity) of 15.25 mJ (8.90 GW/cm2). A reduction of the BW-TPO threshold energy and improved pump-to-idler energy conversion efficiency resulted from injection seeding with a CW laser at the same wavelength as the first idler. The THz output is also directly proportional to seed power.

Bioaerogels, the emerging technology for wastewater treatment: A comprehensive review on synthesis, properties and applications.

Over the past decade use of aerogels has received much attention as an emerging technology for wastewater treatment. However, production of aerogels is not environment-friendly. Owing to its excellent properties such as porosity, three-dimensional structure, being amenable to chemical modifications, it is imperative to devise strategies for their improved production and use. Bioaerogels are non-toxic and most of their precursor compounds are biomass-derived. This review aims to present a comprehensive report on survey of existing literature published on the use of bioaerogels for removal of all major categories of water contaminants, namely, heavy metals, industrial dyes, oil, organic compounds and pharmaceuticals. It also gives critical analysis of the lacunae in the existing knowledge such as lack of studies on domestic sewage, emerging pollutants, toxicity of raw materials and adequate disposal of used adsorbents. Proposals of overcoming the limitations in the applicability of bioaerogels, like combining constructed wetlands with use of bioaerogels, among others have been discussed. In this review, emphasis has been given on production of bioaerogels, with an aim to underscore the potential of valorization of biomass waste to develop novel materials for wastewater treatment in an effort towards creating a circular and green economy.

Nonlinear frequency conversion of 3D optical bottle beams generated using a single axicon.

We demonstrate a novel experimental scheme to generate and study the nonlinear frequency conversion of a three-dimensional (3D) optical Bessel bottle beam (BBB). Using a single axicon and standard optical components and controlling the spot size and divergence of the input Gaussian beam to the axicon, we have generated stable micron-size, high-power optical BBB with tunable spatial characteristics. The BBB has a series of low-intensity regions surrounded by high intensity with diameters of ∼30µm and 17 µm, respectively, at a variable period of 2.3 to 6.4 mm along with the beam propagation. Using the single-pass second harmonic generation (SHG) of femtosecond BBB at 1064 nm in a bismuth triborate nonlinear crystal, we have generated BBB at 532 nm with output power as high as 75 mW and single-pass SHG efficiency of 1.9%. We also observed the self-healing of the BBB at both pump and SHG wavelengths. It is interesting to note that the pump beam truncation shows self-healing in the SHG beam. Such observation proves the direct transfer of the pump's spatial characteristics to the SHG beam in the nonlinear process, potentially useful for imaging even in the turbid medium in biology. This generic scheme can be used at different wavelengths and timescales (continuous-wave to ultrafast).

Lymphocyte-Peppered Sclerotic Collagen: An Additional Histological Clue in Lichen Sclerosus, Morphea, and Systemic Sclerosis.

BACKGROUND: "Line sign," "cookie cutter sign," "square biopsy sign," "high eccrine glands sign" have been previously described in morphoea and lichen sclerosus. We found focal areas of thickened collagen bundles with lymphocytes interspersed between them in several biopsies of these conditions. MATERIALS AND METHODS: We reviewed slides of sclerosing disorders obtained from the archives of the pathology department in our hospital for the period 2013-2019. RESULTS: A total of 73 slides including 40 of lichen sclerosus, 24 of morphea, 2 of lichen sclerosus-morphea overlap, and 7 of systemic sclerosis were evaluated. Lymphocytes were noted between sclerotic collagen bundles in 46 (63%) slides, being most common in lichen sclerosus (80%, 32/40) followed by morphea (50%, 12/24), whereas it was seen in one case each of lichen sclerosus with morphea overlap (50%, 1/2) and systemic sclerosis (14.3%, 1/7). The finding was noted in the upper dermis in 20 of 32 (62.5%) slides of lichen sclerosus and in both the superficial and deep dermis in 11 (91.7%) of 12 slides of morphea. CONCLUSION: Lymphocyte-peppered sclerotic collagen may be a useful histological clue to the diagnosis of lichen sclerosus, morphea, and systemic sclerosis.

Watt-level, ultrafast, tunable yellow source based on single-pass, fourth-harmonic generation of Cr2+:ZnS laser at 2360 nm.

We report a compact source of high power, tunable, ultrafast yellow radiation using fourth-harmonic generation of a mid-IR laser in two-stage frequency-doubling processes. Using Cr2+:ZnS laser at 2360 nm frequency-doubled in a multi-grating MgO:PPLN crystal, we have generated near-IR radiation tunable across 1137-1200 nm with average output power as high as 2.4 W and pulse width of ∼60fs. Subsequently, the near-IR radiation is frequency-doubled using a bismuth triborate (BIBO) crystal to produce coherent yellow radiation tunable across 570-596 nm with a maximum average power of ∼1W. The source has a maximum mid-IR to yellow (near-IR to yellow) single-pass conversion efficiency as high as ∼29.4% (∼47%). Without any pulse compression, the yellow source has output pulses at a repetition rate of 80 MHz with a pulse width of ∼130fs in Gaussian-shaped and a spectral width of ∼4nm corresponding to a time-bandwidth product of 0.45. The generated output beam has a Gaussian transverse beam profile with measured M2 values of Mx2∼1.07 andMy2∼1.01.

Synthesis and evaluation of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-one derivatives as vasorelaxing agents.

A series of substituted 8,8-dimethyl-8H-pyrano[2,3-f]chromen-2-ones (chromeno-coumarin hybrids) was synthesized from scopoletin (11) as vasorelaxing agents. The synthesized compounds 21a-f, 22, 23a-e and scopoletin (11) were evaluated for vasorelaxation in endothelium intact rat main mesenteric artery (MMA). Compounds 11, 21a, 21c-f and 22 showed significant vasorelaxation in precontracted MMA within the range of EC50 value 1.58-5.02 µM. These derivatives presented 29.40-70.89 fold increased sensitivity for experimental tissue compared to scopoletin (11), the parent molecule. Among others, 22 was found to be the most active compound which had EC50 1.58 µM with 70.89 fold increased sensitivity. The mechanistic evaluation of 22 showed that it exerted vasorelaxation through Ca2+-activated K+ (BKca) channel and the effect was endothelium-independent.

Induced osteoblast differentiation by amide derivatives of stilbene: The possible osteogenic agents.

A series of amide derivatives of stilbene was synthesized and investigated for osteogenic activity. Out of sixteen, seven compounds viz19c, 19g, 19i, 24b, 25a, 25c and 26a showed significant osteoblast differentiation within 1 pM-1 µM concentrations. Amongst all, 26a was identified as most active molecule which presented effective mineralization of osteoblasts and expression of mRNA of osteogenic marker gene such as BMP-2, ALP, and Runx-2 at 1 pM. In estrogen-deficient balb/c mice, 26a showed significant osteogenic activity at 5 mg-kg-1 body weight dose. The protein expression study for estrogen receptors α and ß (ER-α & ER-ß) using mouse calvarial osteoblasts (MCOs) and molecular docking analyses showed preferential expression of ER-ß by 26a indicating the possibility of ER-ß mediated osteogenic activity of 26a.

Single-pass, second-harmonic generation of high-power, ultrafast mid-IR Cr2+:ZnS laser at 2360 nm.

We report on a compact and simple ultrafast source producing tunable radiation in the near-IR wavelength range. Based on single-pass frequency doubling of an ultrafast Cr2+:ZnS laser at 2360 nm with pulse width of 43 fs at a repetition rate of 80 MHz in MgO:PPLN crystal, the source produces maximum average output power of ∼2.43 W tunable across 1137-1200 nm with a maximum single-pass conversion efficiency as high as 65%. Without use of any pulse compression technique, the source produces output pulses in Gaussian shape with measured pulse width of ∼60 fs and spectral width of 39 nm centered at 1180 nm corresponding to a time-bandwidth product of 0.5. The output beam has a Gaussian spatial profile with measured M2<1.32 and a peak-to-peak power fluctuation of 3% over 2 h. Using MgO:PPLN crystal of two different lengths, 1 mm and 2 mm, we have observed that the optimum second-harmonic generation efficiency of an ultrafast pulse laser, even in the presence of temporal walk-off, appears in the low pump focusing condition.

Utility of Horizontal Sections of Scalp Biopsies in Differentiating between Androgenetic Alopecia and Alopecia Areata.

BACKGROUND: Androgenetic alopecia (AGA) and alopecia areata (AA) are common causes of alopecia which can sometimes be difficult to differentiate clinically. Horizontal sections of scalp biopsies are used to study non-cicatricial alopecias due to the ability to perform both quantitative and morphometric analysis of hair follicles on them. METHODS: It was a prospective, cross-sectional study conducted to assess the utility of horizontal sections to differentiate between the alopecias. Fifty-two cases were included: 20 cases of male AGA, 11 of female AGA and 21 cases of AA. After clinical examination and dermoscopy, a skin biopsy was taken and subjected to transverse sectioning. Histopathological assessment was done by two dermatopathologists blinded to clinical details. RESULTS: Among the quantitative parameters, terminal:vellus hair ratio (3.08 in AGA and 1.83 in AA, p = 0.0091) and anagen:non-anagen hair ratio (9.25 in AGA and 3.56 in AA, p = 0.0021) were significantly lower in AA. In qualitative parameters, peribulbar inflammation was seen in 63% of AA cases (p = 0.0001). Pigment casts were seen in twice the number of AA (57%) than AGA (26%) cases. Broad avascular stelae and focal trichomalacia were seen in 9.5% of AA cases. CONCLUSION: Besides peribulbar inflammation, we found a lower anagen:non-anagen hair ratio and presence of pigment casts in transverse sections of scalp biopsies favouring AA over AGA.

Vector-Mediated Delivery of Transgenes and RNA Interference-Based Gene Silencing Sequences to Astrocytes for Disease Management: Advances and Prospectives.

Astrocytes are a type of important glial cell in the brain that serve crucial functions in regulating neuronal activity, facilitating communication between neurons, and keeping everything in balance. In this abstract, we explore current methods and future approaches for using vectors to precisely target astrocytes in the fight against various illnesses. In order to deliver therapeutic cargo selectively to astrocytes, researchers have made tremendous progress by using viral vectors such as adeno-associated viruses (AAVs) and lentiviruses. It has been established that engineered viral vectors are capable of either crossing the blood-brain barrier (BBB) or being delivered intranasally, which facilitates their entrance into the brain parenchyma. These vectors are able to contain transgenes that code for neuroprotective factors, synaptic modulators, or anti-inflammatory medicines, which pave the way for multiple approaches to disease intervention. Strategies based on RNA interference (RNAi) make vector-mediated astrocyte targeting much more likely to work. Small interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) are two types of RNA that can be made to silence disease-related genes in astrocytes. Vector-mediated delivery in conjunction with RNAi techniques provides a powerful toolkit for investigating the complex biological pathways that contribute to disease development. However, there are still a number of obstacles to overcome in order to perfect the specificity, safety, and duration of vector-mediated astrocyte targeting. In order to successfully translate research findings into clinical practise, it is essential to minimise off-target effects and the risk of immunogenicity. To demonstrate the therapeutic effectiveness of these strategies, rigorous preclinical investigation and validation are required.

Comparison of Urinary Beta-2 Microglobulin Levels in Children with SSNS and Calcineurin Inhibitor-Treated SRNS.

Background: While the utility of beta-2 microglobulin (ß2M) has been explored in various renal conditions to identify tubulointerstitial damage, it has not been adequately studied in nephrotic syndrome. The primary objective of the study was to compare urinary ß2M levels in children with steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) in disease remission. Materials and Methods: This cross-sectional study was done at a tertiary care hospital between April 2019 and March 2020. Sixty children (2-18 years) with SSNS and SRNS (30 in each group) in remission were enrolled. SRNS patients were included after ≥1 year of treatment with calcineurin inhibitors (CNIs). Biochemical investigations were done to confirm remission; spot samples for urinary ß2M were collected and estimation was done by an enzyme-linked immunosorbent assay (ELISA)-based kit. Results: Of the 60 children, 63% were boys. The median (interquartile range [IQR]) age at enrollment for SSNS and SRNS patients was 7 (4.1-9) and 11 (8.3-12) years, respectively. Urinary ß2M levels were significantly higher in SRNS patients compared to SSNS patients (2.6 vs. 0.75 mg/ml, P < 0.0001). Patients who received cyclosporine for >2 years had higher median urinary ß2M levels compared to those who received it for a shorter period (2.63 vs. 1.83 mg/ml, P = 0.03). Median ß2M levels were higher in focal segmental glomerulosclerosis than minimal change disease (3.5 vs. 2.5 mg/ml). Conclusion: Urinary ß2M levels were higher in SRNS compared to SSNS disease in remission, and ß2M levels correlated well with CNI use of >2 years. It appears to be a promising noninvasive tool to identify early tubular damage and progression in patients with nephrotic syndrome, especially SRNS.

Splicing DNA Damage Adaptations for the Management of Cancer Cells.

Maintaining a tumour cell's resistance to apoptosis (organized cell death) is essential for cancer to metastasize. Signal molecules play a critical function in the tightly regulated apoptotic process. Apoptosis may be triggered by a wide variety of cellular stresses, including DNA damage, but its ultimate goal is always the same: the removal of damaged cells that might otherwise develop into tumours. Many chemotherapy drugs rely on cancer cells being able to undergo apoptosis as a means of killing them. The mechanisms by which DNA-damaging agents trigger apoptosis, the interplay between pro- and apoptosis-inducing signals, and the potential for alteration of these pathways in cancer are the primary topics of this review.

The Potential of Stem Cells in Treating Breast Cancer.

There has been a lot of interest in stem cell therapy as a means of curing disease in recent years. Despite extensive usage of stem cell therapy in the treatment of a wide range of medical diseases, it has been hypothesized that it plays a key part in the progression of cancer. Breast cancer is still the most frequent malignancy in women globally. However, the latest treatments, such as stem cell targeted therapy, are considered to be more effective in preventing recurrence, metastasis, and chemoresistance of breast cancer than older methods like chemotherapy and radiation. This review discusses the characteristics of stem cells and how stem cells may be used to treat breast cancer.

Correction: Singh et al. Nanotechnology-Aided Advancement in Combating the Cancer Metastasis. Pharmaceuticals 2023, 16, 899.

In the original publication [...].

Prevalence and correlates of depression, anxiety, and stress among adolescents in urban and rural areas of Mysuru, South India.

Background: Adolescence, a volatile period of growth between the ages of 10 and 19, is associated with increased vulnerability to mental health problems. Factors such as academic pressure can contribute to these challenges. Objectives: The current study aimed to evaluate the factors and prevalence of depression, anxiety, and stress among adolescents in the urban and rural areas of Mysuru district. Materials and Methods: A cross-sectional study was conducted in private high schools in both urban and rural regions. Prior permission and informed consent were obtained from participants and their legal guardians aged 18 years and older. Results: The gender distribution in urban areas was 60.2% female and 39.8% male, while in rural areas, it was 51% male and 49% female. The prevalence of depression was higher in rural (39.3%) than in urban areas (24.2%), while anxiety was more prevalent in urban (50.6%) than in rural areas (49%). Stress was also more common in rural (16.6%) than urban adolescents (14.6%). Factors significantly associated with mental health outcomes included monthly family income, parenting practices, academic pressures, and self-esteem. Key needs identified were mobile mental health applications, online counseling services, and access to school counselors. Conclusion: This study provides insights into the prevalence and correlates of common mental health issues among adolescents in this region of South India. The findings emphasize the necessity of providing mobile applications and offline counseling services to effectively support and meet the needs of adolescents in these settings.

Anticancer Potential of Pineapple and its Bioactive Compound Bromelain.

Various ailments have been treated with pineapple [Ananas comosus (L.) Merr.] throughout medicinal history. Pineapple and its bioactive compound bromelain possess health-promoting benefits. Detailed information on the chemotherapeutic activities of pineapple and its bioactive compound bromelain is provided in this review, which analyses the current literature regarding their therapeutic potential in cancer. Research on disease models in cell cultures is the focus of much of the existing research. Several studies have demonstrated the benefits of pineapple extract and bromelain for in vitro and in vivo cancer models. Preliminary animal model results show promise, but they must be translated into the clinical setting. Research on these compounds represents a promising future direction and may be well-tolerated.

Mass Spectrometric and Artificial Intelligence-Based Identification of the Secretome of Plasmodium falciparum Merozoites to Provide Novel Candidates for Vaccine Development Pipeline.

PURPOSE: Merozoites are the only extracellular form of blood stage parasites, making it a worthwhile target. Multiple invasins that are stored in the merozoite apical organelles, are secreted just prior to invasion, and mediates its interaction with RBC. A comprehensive identification of all these secreted invasins is lacking and this study addresses that gap. EXPERIMENTAL DESIGN: Pf3D7 merozoites were enriched and triggered to discharge apical organelle contents by exposure to ionic conditions mimicking that of blood plasma. The secreted proteins were separated from cellular contents and both the fractions were subjected to proteomic analysis. Also, the identified secreted proteins were subjected to GO, PPI network analysis, and AI-based in silico approach to understand their vaccine candidacy. RESULTS: A total of 63 proteins were identified in the secretory fraction with membrane and apical organellar localization. This includes various MSPs, micronemal EBAs and rhoptry bulb proteins, which play a crucial role in initial and late merozoite attachment, and majority of them qualified as vaccine candidates. CONCLUSION AND CLINICAL RELEVANCE: We, for the first time, report the secretory repertoire of merozoite and its status for vaccine candidacy. This information can be utilized to develop better invasion blocking multisubunit vaccines, comprising of immunological epitopes from several secreted invasins.

Current Vaccination Practice in Diabetic (Diabetes I) Patients.

The worldwide prevalence of diabetes, an endocrine condition, is rising quickly. The alarming rise of diabetes in recent years has emerged as a major contributor to premature death and illness among persons of working age. The potential use of immunomodulatory drugs to prevent diabetes has been a source of worry in light of recent advances in our understanding of the role of autoimmune responses in the development of diabetes. Vaccines can work in a variety of ways, including by eliminating autoreactive T-cells or by blocking the connections between immune cells. Most diabetes vaccines that have been created so far have only been evaluated in animal models, with just a small number having undergone successful human trials. In this article, the authors also look at the clinical trial research that are currently being conducted to create a prototype diabetes vaccine.