“The Role of Hypomagnesemia as Prognostic Indicator in Patients with St Elevation Myocardial Infarction”

Background: Cardiovascular diseases, particularly acute myocardial infarction (AMI), remain a leading cause of mortality worldwide. ST-elevation myocardial infarction (STEMI) is a severe form of AMI associated with significant morbidity and mortality. Hypomagnesemia has been increasingly recognized as a potential prognostic marker in STEMI patients, influencing cardiac function and patient outcomes. However, its role remains underexplored in clinical settings. Aim: To determine whether hypomagnesemia at admission serves as a prognostic indicator in patients with STEMI and to evaluate its association with disease severity and clinical outcomes. Materials and Methods: This prospective cohort study included 110 patients diagnosed with STEMI based on American Heart Association (AHA) criteria. Serum magnesium levels were measured at admission, and patients were categorized into hypomagnesemia and normal magnesium groups. Clinical severity was assessed using Killip classification, and outcomes, including mortality, arrhythmias, and recovery rates, were evaluated at a 30-day follow-up. Statistical analysis was performed using SPSS v23.0, with p<0.05 considered significant. Results: The study cohort had a mean age of 60.3 years, with a male predominance (58.2%). Hypomagnesemia was significantly associated with higher Killip class severity (9.1% in class 3 vs. 1.8% in normal magnesium, p<0.05). At 30-day follow-up, recovery was significantly higher in patients with normal magnesium levels (54.5%) compared to those with hypomagnesemia (23.6%), while mortality was also higher in the hypomagnesemia group (3.6%). Additionally, hypomagnesemia was linked to increased arrhythmias, including ventricular tachycardia (10.9%).” Conclusion: Hypomagnesemia is significantly associated with worse outcomes in STEMI patients, including higher disease severity, increased arrhythmia risk, and lower recovery rates. Routine assessment of magnesium levels in STEMI patients may help in early risk stratification and targeted therapeutic interventions. Further research is required to explore the potential benefits of magnesium supplementation in improving clinical outcomes

An intelligent converter and controller for electric vehicle drives utilizing grid and stand-alone solar photovoltaic power generation systems

In this study, a battery energy management system for electric vehicle (EV) applications is proposed with a standalone photovoltaic (PV) source and controlled based on the availability of grid, PV source, load consumption, and energy stored in the battery. This paper proposes a single-ended primary-inductance converter (SEPIC) DC-DC converter for charging the battery through the utility and PV source that provides good load regulation. The bidirectional nature of the proposed DC-DC converter provides the charging and discharging of the EV battery in the succeeding modes of operation, i) grid-tied charging, ii) PV-tied charging, iii) discharging to the load in the absence of utility and PV source, and iv) regenerative braking. An improved perturb and observe-based maximum power point tracking (MPPT) algorithm is proposed to track the maximum power from the PV source. In addition, to handle the four modes of operation, a dedicated controller is also proposed. Firstly, the proposed system is validated using MATLAB/Simulink software by considering different operating conditions, and the performance is compared with the traditional MPPT algorithms. Finally, the effectiveness of the suggested system is validated through an experimental prototype. The result proved the superiority of the converter and controller over the traditional systems.

Microemulsion Copolymers for Retanning Applications on Leathers

The microemulsion polymerization method is used to synthesize tercopolymers of styrene, methyl methacrylate and methacrylic acid with finer particle dispersions. Four compositions of the monomers mixture are used in these syntheses. The copolymeriztion reactions are carried out at 70oC with potassium persulphate (KPS) as the initiator. Sodium lauryl sulphate (SLS) and n-heptanol (HA) are being used as the surfactant and cosurfactant combinations, respectively, in these reaction media.These experimental products are employed in retanning wet blue goat skins along with the fatliquoring agent, Balmol SXE. The offer of the experimental products are varied in the retanning experiments and the effects of these products on retanned goat skins are observed by measuring tensile strength, tearing strength and bursting strength. The copolymer products II and III containing 5 and 7.5 weight percents of methacrylic acid as comonomer units , respectively, in the copolymers show considerable improvement in these properties. Product I containing no methacrylic acid groups in the copolymer shows improvement in tensile strength and fall in other properties. Product IV containing 10 (%wt) of methacrylic acid groups in the copolymer does not show considerable improvement in these physical properties, the tensile strength decreases with the offer of the product, no uniform variation of tear strength with the offer level and the grain bursting strength increases with the offer of the product. Scanning electron micrographs (SEM) are obtained for the leathers retanned with product I and these SEM analyses reveal good filling of the product I in the leather matrix. RESUMEN El método de polimerización de micro emulsiones se utiliza para sintetizar tercopolímeros [involucran más de dos monómeros] de estireno, metíl meta acrilato y ácido meta acrílico para obtener dispersiones de partícula más fina. Cuatro composiciones de mezcla de monómeros se utilizan en estas síntesis. Las reacciones de copolimerización son efectuadas a 70ºC con persulfato de potasio (KPS) como iniciador. Lauril-sulfato sódico (SLS) y n-heptanol (HA) se emplean en combinaciones como agente y coagente de superficie, respectivamente, en estos medios de reacción. Estos productos experimentales se emplean en recurtición de pieles caprinas curtidas al cromo conjuntamente con el agente de engrase, Balmol SXE. La oferta de de los productos experimentales son variados en ensayos de recurtidos y los efectos de estos productos sobre las pieles caprinas en el recurtido fueron observados al determinar la resistencia a la tracción, la resistencia al rasgado y las resistencias en el lastómetro [estallido de flor y distensión]. Los productos copoliméricos II y III conteniendo 5 y 7,5 por ciento por peso del ácido meta acrílico como una de las unidades co-monoméricas, respectivamente, en los copolímeros, demuestra considerable mejoría en estas propiedades. El producto I que no contiene grupos de ácido meta acrílico en el copolímero, demuestra una mejoría en la resistencia a la tracción y empeoramiento de las otras propiedades. El producto IV conteniendo 10 (% por peso) de grupos de ácido meta acrílico en el copolímero no demuestra significativa mejoría en estas propiedades físicas, y la resistencia a la tracción disminuye con la oferta del producto, ninguna variación uniforme en la resistencia al rasgado con el nivel de oferta [es evidente] y la resistencia al estallido de flor [en el lastómetro] aumenta con la oferta del producto. Microscopía por barrido electrónico (SEM) obtenidos para los cueros recurtidos con el producto I; los análisis por SEM demuestran buena acción de relleno del producto I en la matriz del cuero

Influence of TRPV1 on diabetes-induced alterations in thermal pain sensitivity

A common complication associated with diabetes is painful or painless diabetic peripheral neuropathy (DPN). The mechanisms and determinants responsible for these peripheral neuropathies are poorly understood. Using both streptozotocin (STZ)-induced and transgene-mediated murine models of type 1 diabetes (T1D), we demonstrate that Transient Receptor Potential Vanilloid 1 (TRPV1) expression varies with the neuropathic phenotype. We have found that both STZ- and transgene-mediated T1D are associated with two distinct phases of thermal pain sensitivity that parallel changes in TRPV1 as determined by paw withdrawal latency (PWL). An early phase of hyperalgesia and a late phase of hypoalgesia are evident. TRPV1-mediated whole cell currents are larger and smaller in dorsal root ganglion (DRG) neurons collected from hyperalgesic and hypoalgesic mice. Resiniferatoxin (RTX) binding, a measure of TRPV1 expression is increased and decreased in DRG and paw skin of hyperalgesic and hypoalgesic mice, respectively. Immunohistochemical labeling of spinal cord lamina I and II, dorsal root ganglion (DRG), and paw skin from hyperalgesic and hypoalgesic mice reveal increased and decreased TRPV1 expression, respectively. A role for TRPV1 in thermal DPN is further suggested by the failure of STZ treatment to influence thermal nociception in TRPV1 deficient mice. These findings demonstrate that altered TRPV1 expression and function contribute to diabetes-induced changes in thermal perception

Activation of p38α/β MAPK in myogenesis via binding of the scaffold protein JLP to the cell surface protein Cdo

The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cell differentiation, but the signaling mechanisms by which it is activated during this process are largely unknown. Cdo is an immunoglobulin superfamily member that functions as a component of multiprotein cell surface complexes to promote myogenesis. In this study, we report that the Cdo intracellular region interacts with JLP, a scaffold protein for the p38α/β MAPK pathway. Cdo, JLP, and p38α/β form complexes in differentiating myoblasts, and Cdo and JLP cooperate to enhance levels of active p38α/β in transfectants. Primary myoblasts from Cdo−/− mice, which display a defective differentiation program, are deficient in p38α/β activity, and the expression of an activated form of MKK6 (an immediate upstream activator of p38) rescues the ability of Cdo−/− cells to differentiate. These results document a novel mechanism of signaling during cell differentiation: the interaction of a MAPK scaffold protein with a cell surface receptor

Preclinical formulation for the pharmacokinetics and efficacy of GBO-006, a selective polo like kinase 2 (PLK2) inhibitor for the treatment of triple negative breast cancer

GBO-006 was shown to be a highly specific and selective PLK2 inhibitor that promoted mitotic arrest in various cancer cell lines, subsequently resulting in their apoptotic death. Intraperitoneal alternate day dosing of GBO-006 using 100 % DMSO as formulation showed significant tumor regression in xenograft models, demonstrating proof of concept of PLK2 inhibition in vivo. These studies necessitated the development of a suitable and GRAS (generally considered as safe) preformulation for pharmacokinetic and efficacy studies. GBO-006 possesses challenging physicochemical and biopharmaceutical properties like poor solubility in aqueous media, low permeability and a crystalline nature. Different methods like cosolvency, complexation and micellar solubilization were employed to improve the solubility of GBO-006. A strategy of co-solvency is used to solubilize the GBO-006 up to 10 mg/mL. A formulation with 20 % DMSO, 40 % PEG 400, 30 % of 100 mM citrate buffer (pH 3.0) and 10 % solutol displayed clear solution without any visual precipitation of the drug even after 2 weeks of storage. GBO-006 showed moderate clearance in rat and high systemic clearance in mouse and dog. It showed poor oral bioavailability across all species. Intraperitoneal dosing of GBO-006 demonstrated the linear exposure. GBO-006 showed significant inhibition of tumor progression

JNK associated leucine zipper protein functions as a docking platform for Polo like kinase 1 and regulation of the associating transcription factor Forkhead box protein K1

JLP (JNK associated Leucine zipper protein) is a scaffolding protein that interacts with various signaling proteins associated with coordinated regulation of cellular process such as endocytosis, motility, neurite outgrowth, cell proliferation and apoptosis. Here we identified Polo like kinase 1 (PLK1) as a novel interaction partner of JLP through mass spectrometric approaches. Our results indicate that JLP is phospho-primed by PLK1 on Thr 351, which is recognized by the PBD of PLK1 leading to phosphorylation of JLP at additional sites. SILAC and quantitative LC-MS/MS analysis was performed to identify PLK1 dependent JLP interacting proteins. Treatment of cells with the PLK1 kinase inhibitor BI2536 suppressed binding of the Forkhead box protein K1 (FOXK1) transcriptional repressor to JLP. JLP was found to interact with PLK1 and FOXK1 during mitosis. Moreover, knockdown of PLK1 affected the interaction between JLP and FOXK1. FOXK1 is a known transcriptional repressor of the CDK inhibitor p21/WAF1 and knockdown of JLP resulted in increased FOXK1 protein levels and a reduction of p21 transcript levels. Our results suggest a novel mechanism by which FOXK1 protein levels and activity are regulated by associating with JLP and PLK1

Downstaging with atezolizumab-bevacizumab: a case series

Backgrounds/Aims Hepatocellular carcinoma (HCC) is generally diagnosed at an advanced stage, which limits curative treatment options for these patients. Locoregional therapy (LRT) is the standard approach to bridge and downstage unresectable HCC for liver transplantation (LT). Atezolizumab-bevacizumab (atezo-bev) can induce objective responses in nearly one-third of patients; however, the role and outcomes of downstaging using atezo-bev remains unknown. Methods In this retrospective single-center study, we included consecutive patients between November 2020 and August 2023, who received atezo-bev with or without LRT and were subsequently considered for resection/LT after downstaging. Results Of the 115 patients who received atezo-bev, 12 patients (10.4%) achieved complete or partial response and were willing to undergo LT; they (age, 58.5 years; women, 17%; Barcelona Clinic Liver Cancer stage system B/C, 5/7) had received 3-12 cycles of atezo- bev, and four of them had received prior LRT. Three patients died before LT, while three were awaiting LT. Six patients underwent curative therapies: four underwent living donor LT after a median of 79.5 days (range, 54-114) following the last atezo-bev dose, one underwent deceased donor LT 38 days after the last dose, and one underwent resection. All but one patient had complete pathologic response with no viable HCC. Three patients experienced wound healing complications, and one required re-exploration and succumbed to sepsis. After a median follow-up of 10 months (range, 4-30), none of the alive patients developed HCC recurrence or graft rejection. Conclusions Surgical therapy, including LT, is possible after atezo-bev therapy in well-selected patients after downstaging

Effects of biofertilizer containing N-fixer, P and K solubilizers and AM fungi on maize growth: A greenhouse trial.

An in vitro study was undertaken to evaluate the compatibility of indigenous plant growth promoting rhizobacteria (PGPR) with commonly used inorganic and organic sources of fertilizers in tea plantations. The nitrogenous, phosphatic and potash fertilizers used for this study were urea, rock phosphate and muriate of potash, respectively. The organic sources of fertilizers neem cake, composted coir pith and vermicompost were also used. PGPRs such as nitrogen fixer; Azospirillum lipoferum, Phosphate Solubilizing Bacteria (PSB); Pseudomonas putida, Potassium Solubilizing Bacteria (KSB); Burkholderia cepacia and Pseudomonas putida were used for compatibility study. Results were indicated that PGPRs preferred the coir pith and they proved their higher colony establishment in the formulation except Azospirillum spp. that preferred vermicompost for their establishment. The optimum dose of neem cake powder

Requirement of argininosuccinate lyase for systemic nitric oxide production

Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases