Efficacy and safety of albumin for the treatment of hepatic encephalopathy: an updated systematic review and meta-analysis of randomized controlled trials.

Background: Albumin acts as a scavenger of reactive oxygen species and an inhibitor of inflammatory processes that underlie hepatic encephalopathy (HE). However, the role of albumin in hepatic encephalopathy is not well-established. The authors performed this meta-analysis to evaluate the efficacy and safety of albumin in the management of hepatic encephalopathy. Methods: The authors carried out an extensive search across multiple databases, including MEDLINE (via PubMed), Embase, CENTRAL, and various trial registries, to identify randomized controlled trials (RCTs) evaluating the impact of albumin administration in HE. The authors used a random-effects model for analyses and presented dichotomous outcomes and continuous outcomes as relative risk and mean difference, along with corresponding 95% CIs, respectively. Heterogeneity was assessed using both the I2 index and χ2 test. Results: Our meta-analysis included 4 RCTs involving 306 patients. Our primary outcomes, mortality, and persistence of HE were reported by all four studies. Albumin was found to significantly decrease mortality in patients with HE [risk ratio (RR) 0.52, 95% CI 0.32-0.83; I2 =0%]. Persistence of HE was found to be comparable between the two groups (RR 0.83, 95% CI 0.68-1.00; I2 =24%). There was no significant difference between the albumin and control groups regarding length of hospital stay (MD -1.55, 95% CI -3.5 to 0.14; I2 =41%), adverse events (RR 1.00, 95% CI 0.87-1.16; I2 =0%), and severe adverse events (RR 0.89, 95% CI 0.59-1.35). Conclusion: Albumin administration in patients with hepatic encephalopathy decreases mortality but does not significantly impact the persistence of HE. Further high-quality, large-scale randomized controlled trials are needed to provide conclusive evidence.

Immunizing hearts: exploring the vaccination frontier in heart failure management.

Heart failure (HF) is a widespread clinical condition that affects numerous individuals globally and is a leading cause of hospitalization, particularly in the elderly population. Despite efforts to manage HF using various pharmacological and nonpharmacological interventions, mortality and hospitalization rates remain alarmingly high. Preventive vaccination has emerged as a key measure endorsed by cardiology societies for reducing the morbidity and mortality associated with HF. This study undertakes an extensive review of existing literature to explore the role of vaccination in managing HF, focusing specifically on the immunological pathways involved and potential benefits offered by immunization in this context. This article highlights the role of various vaccines, including influenza, pneumococcal, and COVID-19 vaccines, in reducing HF-related hospitalization, mortality, and overall disease burden. Additionally, this article will delve into specific vaccines that have shown promise in HF management, such as influenza, pneumococcal, and COVID-19 vaccines, along with the rationale for their use, clinical trials, meta-analyses, and real-world data supporting their effectiveness in patients with HF. This article also considers potential challenges and obstacles to widespread vaccination in individuals with HF, which include vaccine hesitancy, accessibility, and adverse events related to vaccines.

Solitary and multiple thyroid nodules as predictors of malignancy: a systematic review and meta-analysis.

BACKGROUND: The debate on whether or not there is a difference in the incidence of thyroid cancer between the patients with Solitary thyroid Nodule (STN) and Multinodular Goiter (MNG) has been constantly present for the last few decades. With newer studies yielding mixed results, it was imperative to systematically compile all available literature on the topic. METHODS: PubMed/MEDLINE, Cochrane Central, ScienceDirect, GoogleScholar, International Clinical Trials registry, and reference lists of the included articles were systematically searched for article retrieval. No filter was applied in terms of time, study design, language or country of publication. Rigorous screening as per PRISMA guidelines was undertaken by 2 independent reviewers in order to identify the articles that were most relevant to the topic. RESULTS: Twenty-two studies spanning from 1992 to 2018 were included in this analysis and encompassed 50,321 patients, 44.2% of which belonged to the STN subgroup and 55.37% to the MNG subgroup. MNG was found to be associated with a significantly lower risk of thyroid cancer (OR = 0.76; 95% CI 0.61-0.96) when compared with STN. Papillary carcinoma was the most frequently occurring carcinoma across both groups, followed by follicular and medullary carcinomas. A subgroup analysis was performed to assess the efficacy of the two most commonly employed diagnostic tools i.e. surgery and fine needle aspiration cytology (FNAC), however it yielded nonsignificant results, indicating a comparable usefulness of the two. Another subgroup analysis run on the basis of the presumed iodine status of the participants also yielded nonsignificant results. CONCLUSION: There is a higher incidence of thyroid cancer among patients of STN, however, given the low quality of existing evidence on the topic, it is crucial to conduct larger studies that can establish association with a greater precision.

Frequency of migraine according to the ICHD-3 criteria and its association with sociodemographic and triggering factors in Pakistan: A cross-sectional study.

Background: Migraine is a primary headache disorder marked by episodes of moderate to severe headache that is unilateral, throbbing in character, having a duration of 4 h to three days, and associated with nausea, vomiting, photophobia, and phonophobia. Aims: Our study aims to determine the frequency of migraine in Pakistan, its association with sociodemographic variables and triggering factors, and the coping mechanisms used. Methods: A cross-sectional study was conducted through an online survey from March 19, 2022, to June 15, 2022. The snowball sampling technique was used for data collection. The questions asked included those on sociodemographic information, screening questions, and questions on triggering factors and coping mechanisms. The screening was done using the ICHD-3 criteria and percentages were calculated using SPSS. Results: Of the 986 respondents, 393 suffered from migraine. The majority of them were female (78.1%), belonged to the age group 20-29 years (69.2%), and were students (76.1%). 32.8% of the migraineurs had a family history of migraine. Most frequent triggers included sleep disturbance (70.5%), stress (66.7%) and fatigue (64.4%). Of the female migraineurs, 31.8% had menstruation as a trigger. The coping mechanisms used included taking rest, medication, staying in a quiet and dark place, and doing massage. Conclusion: The findings suggest that young adults, especially females, with a stressful and sleep-deprived lifestyle are more vulnerable to migraine. However, further studies must focus on trigger synergy and interrelation of triggers that precipitate migraine so a better understanding can be developed for the prevention, diagnosis, and treatment of migraine.

Aerosol-Assisted Chemical Vapor Deposition Growth of NiMoO4 Nanoflowers on Nickel Foam as Effective Electrocatalysts toward Water Oxidation.

The fabrication of active and durable catalysts derived from transition metals is highly desired for the realization of efficient water oxidation reactions. This is particularly important to address the slow oxygen evolution reaction (OER) kinetics and hence can contribute to the conversion and storage of sustainable energy. In this study, the deposition of crystalline flowerlike 2D nanosheets of nickel molybdate (NiMoO4) directly on nickel foam (NF) through an aerosol-assisted chemical vapor deposition process is reported. The NiMoO4 nanosheets were developed on NF by altering the deposition time for 60 and 120 min at a fixed temperature of 480 °C. The structural determination by XRD and XPS analyses revealed a highly crystalline single phase NiMoO4. The micrographs of NiMoO4 show that the surface consisted of vertically aligned 2D nanosheets assembled into flowerlike structures. The nanosheets produced after 60 min deposition time on a network of NF is found to perform better for OER as compared to the one developed for 120 min. A reference current density of 10 mA cm-2 was achieved at an overpotential (η) of 320 mV, which was better as compared to that reported for the benchmark OER catalyst in 1.0 M KOH. Moreover, a small Tafel value (75 mV dec-1) and good OER stability for >15 h were also observed.

Rapid antibody diagnostics for SARS-CoV-2 adaptive immune response.

The emergence of a pandemic scale respiratory illness (COVID-19: coronavirus disease 2019) and the lack of the world's readiness to prevent its spread resulted in an unprecedented rise of biomedical diagnostic industries, as they took lead to provide efficient diagnostic solutions for COVID-19. However, these circumstances also led to numerous emergency use authorizations without appropriate evaluation that compromised standards, which could result in a larger than usual number of false-positive or false-negative results, leading to unwanted ambiguity in already confusing realities of the pandemic-hit closures of the world economy. This review is aimed at comparing the claimed or reported clinical sensitivity and clinical specificity of commercially available rapid antibody diagnostics with independently evaluated clinical performance results of the tests. Thereby, we not only present the types of modern antibody diagnostics and their working principles but summarize their experimental evaluations and observed clinical efficiencies to highlight the research, development, and commercialization issues with future challenges. Still, it must be emphasized that the serological or antibody tests do not serve the purpose of early diagnosis but are more suitable for epidemiology and screening populaces with an active immune response, recognizing convalescent plasma donors, and determining vaccine efficacy.

Proteomics analysis reveals that the proto-oncogene eIF-5A indirectly influences the growth, invasion and replication of Toxoplasma gondii tachyzoite.

BACKGROUND: The proliferative stage (tachyzoite) of Toxoplasma gondii (T. gondii) is critical for its transmission and pathogenesis, and a proto-oncogene eukaryotic translation initiation factor (eIF-5A) plays an important role in various cellular processes such as cell multiplication. METHODS: We performed a proteomic study to evaluate the specific roles of eIF-5A involved in invasion and replication of T. gondii, and both in vivo and in vitro trials using eIF-5A-interfered and wild tachyzoites were performed to verify the proteomic results. RESULTS: The results of our study showed that T. gondii eIF-5A affected tachyzoite growth and also participated in the synthesis of proteins through regulation of both ribosomal and splicing pathways. Inhibition of eIF-5A in T. gondii resulted in the downregulated expression of soluble adhesions, such as microneme protein 1 (MIC1) and MIC4, which in turn decreased the parasite population that adhered to the surface of host cells. The reduced attachment, combined with lower expression of some rhoptry proteins (ROPs) and dense granule antigens (GRAs) involved in different stages of T. gondii invasion such as ROP4 and GRA3, ultimately reduce the invasion efficiency. These processes regulated by eIF-5A eventually affect the replication of tachyzoites. CONCLUSIONS: Our findings showed that eIF-5A influenced tachyzoite survival and was also involved in the process of parasite invasion and replication. These results will provide new clues for further development of targeted drugs to control T. gondii infection.

Fasciola gigantica tegumental calcium-binding EF-hand protein 4 exerts immunomodulatory effects on goat monocytes.

BACKGROUND: The liver fluke Fasciola gigantica secretes excretory-secretory proteins during infection to mediate its interaction with the host. In this study, we investigated the immunomodulatory effects of a recombinant tegumental calcium-binding EF-hand protein 4 of F. gigantica (rFg-CaBP4) on goat monocytes. METHODS: The rFg-CaBP4 protein was induced and purified by affinity chromatography. The immunogenic reaction of rFg-CaBP4 against specific antibodies was detected through western blot analysis. The binding of rFg-CaBP4 on surface of goat monocytes was visualized by immunofluorescence assay. The localization of CaBP4 within adult fluke structure was detected by immunohistochemical analysis. The cytokine transcription levels in response to rFg-CaBP4 were examined using ABI 7500 real-time PCR system. The expression of the major histocompatibility complex (MHC) class-II molecule (MHC-II) in response to rFg-CaBP4 protein was analyzed using Flow cytometry. RESULTS: The isopropyl-ß-D-thiogalactopyranoside-induced rFg-CaBP4 protein reacted with rat sera containing anti-rFg-CaBP4 polyclonal antibodies in a western blot analysis. The adhesion of rFg-CaBP4 to monocytes was visualized by immunofluorescence and laser scanning confocal microscopy. Immunohistochemical analysis localized native CaBP4 to the oral sucker, pharynx, genital pore, acetabulum and tegument of adult F. gigantica. Co-incubation of rFg-CaBP4 with concanavalin A-stimulated monocytes increased the transcription levels of interleukin (IL)-2, IL-4, interferon gamma and transforming growth factor-ß. However, a reduction in the expression of IL-10 and no change in the expression of tumor necrosis factor-α were detected. Additionally, rFg-CaBP4-treated monocytes exhibited a marked increase in the expression of the major histocompatibility complex (MHC) class-II molecule (MHC-II) and a decrease in MHC-I expression, in a dose-dependent manner. CONCLUSIONS: These findings provide additional evidence that calcium-binding EF-hand proteins play roles in host-parasite interaction. Further characterization of the immunomodulatory role of rFg-CaBP4 should expand our understanding of the strategies used by F. gigantica to evade the host immune responses.

Aerosol-assisted nanostructuring of nickel/cobalt oxide thin films for viable electrochemical hydrazine sensing.

Herein, we report the fabrication of NiO-CoO films for the electrochemical detection of hydrazine. An electrochemical sensor was devised where aerosol assisted chemical vapor deposition (AACVD) was employed as a nifty method for synthesizing NiO-CoO films over FTO electrodes. NiO-CoO-nanoparticle (NP) and NiO-CoO-nanowall (NW) films were fabricated over FTO substrates. The electrocatalytic analysis was performed in a standard three-electrode electrochemical setup. NiO-CoO-NW/FTO showed enhanced electro-oxidation for hydrazine at all concentrations tested. XRD, XPS, EDX, and FE-SEM techniques were used to characterize the structural, morphological, and elemental properties of NiO-CoO films. The results showed improved sensitivity, a large dynamic range, and good long-term stability of NiO-CoO-NW films. The amperometric response was used to measure the detection limit, and it was as low as 0.01 µM, and the sensitivity is ∼33 µA µM-1 cm-2. Besides, the NiO-CoO-NW/FTO electrodes showed significant selectivity towards hydrazine upon testing cross-sensitivity to other common interfering molecules. This strategy of using NiO-CoO-NW/FTO electrodes prepared via AACVD has great potential for the direct determination of hydrazine in environmental sensing applications.

Impedance Spectroscopic Study of Nickel Sulfide Nanostructures Deposited by Aerosol Assisted Chemical Vapor Deposition Technique.

This research aims to synthesize the Bis(di-isobutyldithiophosphinato) nickel (II) complex [Ni(iBu2PS2)] to be employed as a substrate for the deposition of nickel sulfide nanostructures, and to investigate its dielectric and impedance characteristics for applications in the electronic industry. Various analytical tools including elemental analysis, mass spectrometry, IR, and TGA were also used to further confirm the successful synthesis of the precursor. NiS nanostructures were grown on the glass substrates by employing an aerosol assisted chemical vapor deposition (AACVD) technique via successful decomposition of the synthesized complex under variable temperature conditions. XRD, SEM, TEM, and EDX methods were well applied to examine resultant nanostructures. Dielectric studies of NiS were carried out at room temperature within the 100 Hz to 5 MHz frequency range. Maxwell-Wagner model gave a complete explanation of the variation of dielectric properties along with frequency. The reason behind high dielectric constant values at low frequency was further endorsed by Koops phenomenological model. The efficient translational hopping and futile reorientation vibration caused the overdue exceptional drift of ac conductivity (σac) along with the rise in frequency. Two relaxation processes caused by grains and grain boundaries were identified from the fitting of a complex impedance plot with an equivalent circuit model (Rg Cg) (Rgb Qgb Cgb). Asymmetry and depression in the semicircle having center present lower than the impedance real axis gave solid justification of dielectric behavior that is non-Debye in nature.

Dense Deployment of LoRa Networks: Expectations and Limits of Channel Activity Detection and Capture Effect for Radio Channel Access.

With worldwide deployment of LoRa/LoRaWAN LPWAN networks in a large variety of applications, it is crucial to improve the robustness of LoRa channel access which is largely ALOHA-like to support environments with higher node density. This article presents extensive experiments on LoRa Channel Activity Detection and Capture Effect property in order to better understand how a competition-based channel access mechanisms can be optimized for LoRa LPWAN radio technology. In the light of these experimentation results, the contribution continues by identifying design guidelines for a channel access mechanism in LoRa and by proposing a channel access method with a lightweight collision avoidance mechanism that can operate without a reliable Clear Channel Assessment procedure. The proposed channel access mechanism has been implemented and preliminary tests show promising capabilities in increasing the Packet Delivery Rate in dense configurations.

Nanoparticles (PLGA and Chitosan)-Entrapped ADP-Ribosylation Factor 1 of Haemonchus contortus Enhances the Immune Responses in ICR Mice.

ADP-ribosylation factor 1 (HcARF1) is one of the Haemonchus contortus (H. contortus) excretory/secretory proteins involved in modulating the immune response of goat peripheral blood mononuclear cells (PBMC). Here, we evaluated the immunogenic potential of recombinant HcARF1 (rHcARF1) against H. contortus infection in Institute of Cancer Research (ICR) mice. Briefly, rHcARF1 was entrapped in poly (D, L-lactide-co-glycolide) (PLGA) and chitosan (CS) nanoparticles (NP) and injected into mice as a vaccine. Fifty-six ICR mice were assigned randomly into seven groups, with eight animals in each group, and they were vaccinated subcutaneously. At the end of the experiment (14th day), the blood and the spleen were collected from euthanized mice to detect lymphocyte proliferation, cytokine analysis, and the production of antigen-specific antibodies. Scanning electron microscope was used to determine the size, morphology, and zeta potential of nanoparticles. Flow cytometry was performed, which presented the increase percentages of CD4+ T cells (CD3e+CD4+), CD8+ T cells (CD3e+CD8+) and dendritic cells (CD11c+CD83+, CD11c+CD86+) in mice vaccinated with rHcARF1+PLGA NP. Immunoassay analysis show raised humoral (Immunoglobulin (Ig)G1, IgG2a, IgM) and cell-mediated immune response (Interleukin (IL)-4, IL-12, and IL-17, and Interferon (IFN)-γ) induced by rHcARF1+PLGA NP. Experimental groups that were treated with the antigen-loaded NP yield higher lymphocyte proliferation than the control groups. Based on these results, we could propose that the rHcARF1 encapsulated in NP could stimulate a strong immune response in mice rather than administering alone against the infection of H. contortus.

Facile and scalable fabrication of nanostructured nickel thin film electrodes for electrochemical detection of formaldehyde.

Fluorine doped tin oxide (FTO) substrates were deposited with thin metallic nickel films, having distinguishable surface morphologies, via a rapid, facile, and scalable approach i.e., aerosol assisted chemical vapor deposition (AACVD). The growth patterns of the nickel deposits were studied, showing a coalescing behavior as a function of the deposition time in a hierarchical fashion. These studies were followed by electrochemical measurements to design an efficient sensor for formaldehyde detection. The electrochemical responses were correlated with the surface characteristics of the films, whereas the optimized parameters were subjected to the evaluation of sensing performances. The developed sensor demonstrated a detection limit of 8.3 × 10-6 M and a sensitivity of 0.18 A M-1 within a linear range of 0-6.5 mM. Further, the sensor showed a response time of less than 5 s, selectivity against similar concentrations of methanol and formaldehyde, and recovery of ∼102% in a spiked fruit juice sample. Finally, the commercial viability of the fabrication procedure is tested using batch production analysis, and the high reproducibility of the data shows a promising future in mass production. It is envisaged that such low-cost fabrication procedures can be converted into many useful applications in the future.

Taenia solium insulin receptors: promising candidates for cysticercosis treatment and prevention.

Insulin signaling pathway is an ancient and highly conserved pathway known to play critical roles in cell growth, control and metabolic regulation. In this study, we identified and characterized two insulin receptor genes (TsIR-1316 and TsIR-4810) from Taenia solium. TsIR-1316 was grouped with E. multilocularis insulin receptor (EmIR-1) and TsIR-4810 was closer to Taenia pisiformis insulin-like growth factor receptor (TpIR) on the same branch with a very high bootstrap value. TsIR-1316 was located on the integument of larvae and adult worms, as well as the ovary of adults and eggs. Alternatively, TsIR-4810 was located in the parenchyma and reproductive organs of the adult worms. By using in vitro cultivation systems with Cysticercus pisiformis as a model, we demonstrated that anti-TsIRs-LBD antibodies could effectively block the insulin signaling pathway, resulting in reduced phosphorylation of the insulin receptor as well as lower levels of glucose uptake and glycogen synthesis. The rabbits immunized with TsIR-1316-LBD, TsIR-4810-LBD and TsIR-1316-LBD + TsIR-4810-LBD produced protection against infection of T. pisiformis as demonstrated by a 94.6%, 96% and 80% reduction of establishment of larvae, respectively. These data suggested that TsIR-1316-LBD and TsIR-4810-LBD are promising vaccine candidates or novel drug targets against swine cysticercosis.

Highly cytotoxic gold(i)-phosphane dithiocarbamate complexes trigger an ER stress-dependent immune response in ovarian cancer cells.

Ovarian cancer is a highly aggressive disease which is treated by surgery and platinum chemotherapy. However, a significant proportion of treated patients develop resistance to platinum treatment resulting in tumor relapse. Acquired platinum resistance has been recently correlated with activation of pro-survival endoplasmic reticulum (ER) stress responses. We hypothesized that Au complexes that induce severe ER stress might counteract pro-survival cellular attempts leading to the ER stress-mediated apoptosis and reduced platinum resistance. In this work, we prepared a series of highly cytotoxic AuI-dialkyldithiocarbamate complexes and investigated their anticancer potential in ovarian cancer cells. Complexes demonstrated surprisingly low stability in chloroform, resulting in the formation of an Au chain polymer, which also displayed excellent cytotoxicity. Lead complex 2 induced oxidative stress and ER stress-mediated p53-independent apoptosis associated with PARP cleavage and cell cycle arrest at G2/M phase. Importantly, 2 caused the surface exposure of calreticulin (CRT), which is the first step in the activation of cellular immunogenic response.

Single-molecule functional anatomy of endogenous HER2-HER3 heterodimers.

Human epidermal growth factor receptors (HERs) are the primary targets of many directed cancer therapies. However, the reason a specific dimer of HERs generates a stronger proliferative signal than other permutations remains unclear. Here, we used single-molecule immunoprecipitation to develop a biochemical assay for endogenously-formed, entire HER2-HER3 heterodimers. We observed unexpected, large conformational fluctuations in juxta-membrane and kinase domains of the HER2-HER3 heterodimer. Nevertheless, the individual HER2-HER3 heterodimers catalyze tyrosine phosphorylation at an unusually high rate, while simultaneously interacting with multiple copies of downstream signaling effectors. Our results suggest that the high catalytic rate and multi-tasking capability make a concerted contribution to the strong signaling potency of the HER2-HER3 heterodimers.