Deficiency States Research Articles

Intellectual Potential of Kyrgyzstan

The article is a study of the intellectual potential of Kyrgyzstan, its state and development opportunities. The author proposes a methodology for analyzing intellectual potential based on five groups of criteria: standard indicators of international rankings and indices (human development index, innovative development index, Hirsch index); the state of the socio-cultural environment for the development of intellectual potential; the state of the educational infrastructure for the development of intellectual potential; the level of scientific impetus (the presence of scientific infrastructure and scientific community, scientific elite); state support for science (expenditures on scientific research and development work, state strategies for the development of science and education). Based on the analysis of statistical data and government documents, the most vulnerable areas of the development of the country’s intellectual potential are identified: insufficient environment for the development of intellectual potential, insufficient scientific impetus, insufficient availability and quality of educational infrastructure, insufficient conditions and opportunities for the reproduction and development of the intellectual elite, in particular the scientific elite of the country. It is concluded that Kyrgyzstan has not yet formed the institutional foundations of a unified scientific policy that would contribute to solving the problems of innovative development of the country and ensuring its scientific and technological sovereignty.

Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism

Obesity, characterized by excessive fat accumulation in white adipose tissue (WAT), is linked to numerous health issues, including insulin resistance (IR), and type 2 diabetes mellitus (DM2). The distribution of adipose tissue differs by sex, with men typically exhibiting android adiposity and pre-menopausal women displaying gynecoid adiposity. After menopause, women have an increased risk of developing android-type obesity, IR, and DM2. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) are important in treating obesity and DM2 by regulating insulin secretion, impacting glucose and lipid metabolism. GLP-1Rs are found in various tissues including the pancreas, brain, and adipose tissue. Studies suggest GLP-1RAs and estrogen replacement therapies have similar effects on tissues like the liver, central nervous system, and WAT, probably by converging pathways involving protein kinasesTo investigate these interactions, female rats underwent ovariectomy (OVR) to promote a state of estrogen deficiency. After 20 days, the rats were euthanized and the tissues were incubated with 10 μM of liraglutide, a GLP-1RA. Results showed significant changes in metabolic parameters: OVR increased lipid catabolism in perirenal WAT and basal lipolysis in subcutaneous WAT, while liraglutide treatment enhanced stimulated lipolysis in subcutaneous WAT. Liver responses included increased stimulated lipolysis with liraglutide. Transcriptome analysis revealed distinct gene expression patterns in WAT of OVR rats and those treated with GLP-1RA, highlighting pathways related to lipid and glucose metabolism. Functional enrichment analysis showed estrogen’s pivotal role in these pathways, influencing genes involved in lipid metabolism regulation.Overall, the study underscores GLP-1RA acting directly on adipose tissues and highlights the complex interactions between GLP-1 and estrogen in regulating metabolism, suggesting potential synergistic therapeutic effects in treating metabolic disorders like obesity and DM2.

Machine Learning-based Prediction Analysis of Potential Factors in Traffic Accidents

Machine Learning-based Prediction Analysis of Potential Factors in Traffic Accidents

Growth hormone/insulin-like growth factor I axis in health and disease states: an update on the role of intra-portal insulin

Growth hormone (GH) is the key regulator of insulin-like growth factor I (IGF-I) generation in healthy states. However, portal insulin delivery is also an essential co-player in the regulation of the GH/IGF-I axis by affecting and regulating hepatic GH receptor synthesis, and subsequently altering hepatic GH sensitivity and IGF-I generation. Disease states of GH excess (e.g., acromegaly) and GH deficiency (e.g., congenital isolated GH deficiency) are characterized by increased and decreased GH, IGF-I and insulin levels, respectively, where the GH/IGF-I relationship is reflected by a “primary association”. When intra-portal insulin levels are increased (e.g., obesity, Cushing’s syndrome, or due to treatment with glucocorticoids and glucagon-like peptide 1 receptor agonists) or decreased (e.g., malnutrition, anorexia nervosa and type 1 diabetes mellitus), these changes secondarily alter hepatic GH sensitivity resulting in a “secondary association” with discordant GH and IGF-I levels (e.g., high GH/low IGF-I levels or low GH/high IGF-I levels, respectively). Additionally, intra-portal insulin regulates hepatic secretion of IGFBP-1, an inhibitor of IGF-I action. Through its effects on IGFBP-1 and subsequently free IGF-I, intra-portal insulin exerts its effects to influence endogenous GH secretion via the negative feedback loop. Therefore, it is important to understand the effects of changes in intra-portal insulin when interpreting the GH/IGF-I axis in disease states. This review summarizes our current understanding of how changes in intra-portal insulin delivery to the liver in health, disease states and drug therapy use and misuse that leads to alterations in GH/IGF-I secretion that may dictate management decisions in afflicted patients.

What Can Chemical Bonding Tell Us about Photoinduced Phase Transition Reactions in Inorganic Semiconductors? Insight from Bismuth-Antimony Selenide.

Photoreactive self-healing semiconductors with suitable bandgaps for solar energy conversion offer an intriguing path to making resilient and low-cost photovoltaic devices through the introduction of a self-recovery path. However, only a few inorganic photovoltaic materials have such quality, and the underlying chemical properties that enable it are unknown, which poses a significant limit to our ability to study and discover new self-healing semiconductors. Recently, we have found that antimony trichalcogenide (Sb2Se3 and Sb2S3) and chalcohalides (e.g., SbSeI) can undergo a reversible photoinduced phase transition (PIPT) in which the structure is restored after photoinduced damage incurs to the materials. This group of materials offer a unique opportunity for studying PIPT and its limits. In particular, this group of materials facilitate the study of functional permutation to specific crystalline sites and to finding the limits of PIPT occurrence, which sheds light on the origin of the PIPT and self-recovery of this class of materials. Using Raman spectroscopy of thin films, and following signature vibrations of transition species, we have found that the PIPT magnitude decays upon gradual BiSb(1) substitution in a Sb2-xBixSe3 homologous series, until nearly one in five Sb ions is substituted with Bi. Then, the PIPT diminishes completely. The homologous series occurs along a transition from covalent to metavalent chemical bonding. By expanding our search, we find that a correlation between bonding type and photoreactivity does exist but conclude that it is an insufficient condition. Instead, we suggest, based on bond order and additional DFT calculations, that sufficient bonding states at the bottom of the conduction band are also required. This joint experimental and computational study pushes the limits of designing self-healing inorganic semiconductors for various applications and provides tools for further expansion.

Retrospective analysis of ferrotherapy methodology in patients with chronic heart failure and chronic kidney disease

The course of chronic non-infectious diseases is often accompanied by the development of comorbid conditions. In chronic heart failure and chronic kidney disease, special attention is drawn to iron deficiency and anemia. Intravenous iron preparations have become widely used for the prevention and treatment of anemia. Their use contributes to the progression of structural changes in vital organs. However, attempts to implement high-dose intravenous ferrotherapy as a routine strategy for compensating iron deficiency in patients with heart failure, with or without anemia, raise questions related to the search for diagnostic markers of iron deficiency states, goals, and conditions for its use. The article discusses the influences of a combination of opposing factors (inflammation, hypoxia) on the erythron system, its humoral regulators, and iron metabolism based on the author’s own research to justify the choice of strategy and tactics for ferrotherapy in patients with heart failure and chronic kidney disease.

Serum Transcobalamin Concentration in Cats-Method Validation and Evaluation in Chronic Enteropathies and Other Conditions.

Hypocobalaminemia is common in cats with chronic enteropathy (FCE). However, the disruptions in cobalamin metabolism are not fully understood and may vary across species. Cobalamin is distributed to target tissues via binding to transcobalamin (TC) in blood, which has not been evaluated in cats. Thus, an in-house sandwich-ELISA was established to evaluate serum total TC concentrations in cats with FCE. Surplus sera served to analytically validate the assay, and serum TC concentrations were compared among cats with FCE and other diseases (gastrointestinal neoplasia, cholangiohepatopathy, and other neoplastic or non-neoplastic conditions) and healthy controls. Observed-to-expected ratios for serial dilutions ranged from 72.4 to 145.6% and were 75.1-126.7% for spiking-and-recovery. Intra- and inter-assay variability was <17.7% and <17.2% and the preliminary reference interval for feline serum TC was <160-2795 aU/L (lower detection limit: 160 aU/L). Serum TC levels were significantly decreased (p = 0.0067) but not correlated with paired cobalamin concentrations in FCE. Hypertranscobalaminemia predominated with hypercobalaminemia, reaching the highest levels in advanced-stage chronic kidney disease (CKD) cases. TC variations in cobalamin deficiency states with FCE may be linked to inflammation or autoantibodies. This and possible links between serum TC variation in FCE, intracellular cobalamin availability, response to supplementation, and concurrent CKD require further exploration.

Pseudomonas putida triggers phosphorus bioavailability and P-transporters under different phosphate regimes to enhance maize growth

The decline of available phosphorus in soil due to anthropogenic activities necessitates utilizing soil microorganisms that influence soil phosphorus levels. However, the specific mechanisms governing their interaction in Zea mays under diverse phosphate regimes remain largely unknown. The present study investigated the dynamics of phosphorus solubilization and the impact of organic acid supplementation in combination with the beneficial rhizobacterium Pseudomonas putida (RA) on maize growth under phosphorus-limiting and unavailable conditions. HPLC analysis revealed gluconic acid as the primary organic acid (OA) produced by P. putida across all three conditions (P-sufficient, P-limiting, and P-unavailable), with the highest production occurring under P-limiting conditions. The study evaluates the effects of RA, OA, and OA + RA on plant growth parameters under P-limiting and insufficient conditions, revealing significant alterations in growth and biochemical parameters (P = 0.05) compared to their respective untreated controls. Additionally, plants treated with organic acids and bacterial inoculation show increased phosphorus concentrations in both roots and shoots. Gene expression analysis of key phosphorus transporter genes (PHT1, PHO1, PTF, PHF1) further supports the role of organic acids and bacterial inoculation in enhancing phosphorus uptake. In conclusion, our study affirms that the secretion of gluconic acid by RA and its plant growth-promoting properties boost phosphorus uptake and maize growth by increasing phosphorus availability and influencing the expression of phosphorus transport-related genes.

Oxygen sensing in the kidney.

The kidneys fulfil several essential homeostatic functions for the body. One of them is the maintenance of sufficient oxygen supply to the organs. For this purpose, the kidneys control the formation of red blood cells by the production of the hormone erythropoietin. This control of red cell formation is not only relevant to prevent states of oxygen deficiency but also to prevent an unwanted increase of red cell numbers causing thromboembolic risks. The adequate production of erythropoietin requires a sensing of the arterial oxygen content and transduction to hormone production. This oxygen sensing is a two-step process which includes a translation of the arterial oxygen content to respective oxygen tension in the tubulointerstitium and a perception of the resulting local interstitial oxygen tension to translate them into specific cellular responses such as the production of erythropoietin. This contribution will describe these steps of oxygen sensing for the healthy kidney and for the changes occurring during states of chronic renal disease, which are commonly associated with anemia. In this context a special focus will also be set on intrarenal hypoxia and oxygen sensing in the diabetic kidney including the treatment with tubular glucose transport (SGLT-2) inhibitors which might influence the oxygen sensing in the kidney. Finally, we will consider the effects of prolylhydroxylase inhibitors (PHD-I), which fundamentally interfere with the cellular oxygen sensing and which are meanwhile treatment options in renal anemia.

Toward a treatment for thyroid hormone transporter MCT8 deficiency - achievements and challenges.

Patients with an inactive thyroid hormone (TH) transporter MCT8 (Allan-Herndon-Dudley Syndrome, AHDS) display severe neurological impairments and motor disabilities, indicating an indispensable function of MCT8 in facilitating TH access to the human brain. Consequently, the CNS of AHDS patients appears to be in a TH deficient state, which greatly compromises proper neural development and function. Another hallmark of this disease is that patients exhibit elevated serum T3 levels, leading to a hyperthyroid situation in peripheral tissues. Several treatment strategies have been developed and evaluated in preclinical mouse models as well as in patients. Here, we discuss these different therapeutic approaches to overcome MCT8 deficiency and summarize the current achievements and challenges in improving brain maturation in the absence of MCT8.

Prevention of iron deficiency conditions in obese children

Background. Due to the progressive increase in childhood obesity, the effect of iron levels in the body on carbohydrate and lipid metabolism disorders and the relationship between these conditions are actively studied. It is proven that obesity in children is often associated with dysregulation of iron metabolism. The correlation between the body mass index and iron deficiency (ID) in children and adolescents was reported. Therefore, implementing preventive measures to correct the iron deficiency state (IDS), including the enrichment of the diet with foods containing easily digestible iron, is relevant and can be considered as one of the principles of an integrated approach to the treatment of obesity in childhood. Aim. To evaluate the effectiveness of dietary supplements "Kidz Tasty iron" for IDS prevention in obese children. Materials and methods. Thirty children aged 7–14 with exogenous constitutional obesity were followed up, 14 (47%) females and 16 (53%) males. All patients received a dietary supplement (DS), "Kidz Tasty iron," 10 mL once daily with meals according to the label for 1 month. The follow-up included data on signs and symptoms, medical history, evaluation of anthropometric data, evaluation of current nutrition status with the software "Optimal Nutrition 5.0", bioimpedance analysis of body composition, questionnaire on the assessment of ID symptoms and quality of life, general hematology and blood chemistry tests, validated for childhood. Results. The diets of obese children in the study had low iron content (33.3% of patients), which justifies the need for additional iron supplementation. While taking the dietary supplement "Kidz Tasty Iron," there was a positive clinical trend: decreased symptoms related to ID and clinical signs of ID, improved overall well-being, and increased quality of life. The improvement of the body composition of the studied children was represented by preservation and an increase (20% of patients) in the active cell mass in the studied children. Laboratory tests of iron metabolism improved in 9 children (30%). Most children reported the good organoleptic properties of the product. Adherence to the DS was 96.7%. Conclusion. The study results show the "Kidz Tasty iron" dietary supplement to be tolerable, safe, and effective, supporting its use in the complex therapy of children and adolescents with obesity, including for IDS prevention.

Decreased vitamin D levels as a factor of deterioration of osseointegration during dental implantation

Introduction. Decreased vitamin D levels are considered as a possible factor in dental implantation failure. However, there arelack of good quality studies on this topic, some of which were conducted on animal models.Aim. To identify the possible role of vitamin D levels on osseointegration parameters during dental implantation.Materials and methods. A retrospective single-sample cohort observational non-interventional study was conducted. 78 female patients who underwent dental implantation were examined, who were divided into 3 groups: up to 44 years old, group 1 (n = 20), 45-60 years old, group 2 (n = 34), 60 years and older, group 3 (n = 24). All patients were examined before implantation: vitamin D, FSH, estradiol, TSH, free T4, computed tomography of the jaw bones, indices of the gums and periodontium condition, also the implant stability quotient (ISQ) was determined at the time of implant placement and at the time of prosthetics.Results. The concentrations of vitamin D, estradiol, jaw bone density, and ISQ at the time of implantation and at the time of prosthetics were significantly lower in group 3. Vitamin D deficit/insufficiency occurred in 38%, 58%, 88% of patients in groups 1, 2, 3, respectively (p &lt; 0.001). The ratio of chances to detect a decrease in vitamin D was 13.1 (CI 95% 2.9–60.2) in group 3 compared to group 2, and 5.7 (CI 95% 1.4–22.6) compared to group 1. The ratio of the chances for an increase of osseointegration time was 11.6 (CI 95% 2.3–59.1) in case of vitamin D deficiency compared to optimal values, and 5.7 (CI 95% 1.4–24.1) compared to a insufficiency condition. Vitamin D levels significantly inversely correlated with hygienic indices of periodontal condition.Conclusion. A decrease vitamin D levels can be strongly considered as a factor in the deterioration of osseointegration during dental implantation, since this is associated with an extended period of osseointegration due to a decrease in the bone density of the jaw and a worse periodontal condition.

The application and interpretation of laboratory biomarkers for the evaluation of vitamin B12 status.

Vitamin B12 (cobalamin; B12) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B12 deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B12 status include the measurement of serum B12 (also known as total B12 or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B12 status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B12 test, which is readily available and highly automated. In some cases, the sequential use of different B12 status biomarkers or the calculation of a composite B12 status score, derived from a panel of B12 biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarizes the utility of B12-related biomarkers and describes approaches to their application and interpretation.

Under which conditions do extreme events support a paradigm shift? Studying focusing events during two centuries of Swiss flood risk management

Extreme weather events affect many areas around the world. How a country or region reacts to it can take many forms. In this article, we concentrate on policy responses, as typically found in laws, acts, or strategies. Recent research in climate change adaptation or environmental governance concluded that the degree of severity of extreme events is a crucial indicator that policy action should be taken. The event alone is a necessary, but insufficient condition for policies to be introduced. In this context, we ask: Which conditions must be at stake so that an extreme event is able to deploy its focal power and induce policy introduction or change? To answer this question, we studied more than two centuries of flood risk management in Switzerland. We relied on qualitative and quantitative data, as well as process tracing techniques, to relate event characteristics, media, political, and policy contexts to policy change in flood risk management. Results indicate that two conditions made floods turn into focusing events and support paradigm shift: high economic damage and a policy subsystem’s actor constellation favorable to change. We are convinced that our results are also replicable for other natural disasters and other countries than only Switzerland.

Regional Electron Delocalization Regulation Internalizes the Reduced‐Order‐Transformation of Polysulfides

AbstractThe step‐order or disproportionation conversion of lithium polysulfides (LiPSs) is still a blind box in LiS batteries (LSBs) system. The cation‐doped electrocatalyst (Fe‐CoS2@HCNF) is designed through modulating electron‐surrounding situation of the central atomic d‐band to promote regional electron‐directed LiPSs reduced‐order‐transformation (especially, Li2S4Li2S). Fe‐CoS2@HCNF satisfies the requirement of mass (electron/ion) transfer reaction, quantizing as multi‐osmosis‐connected transportation channels and an all‐encompassing interior space for sulfur reduction occurring. Based on experiments and DFT calculations, the introduced Fe presents a local electron deficiency state toward regulating regional electron delocalization between Fe and Co matrix, which induces the d‐band state of the metal site, strengthening the metal 3d orbital coupling interaction with S2−of LiPSs, further guiding the order‐transformation of intermediate LiPSs. Consequently, the Fe‐CoS2@HCNF electrode has excellent electrochemical properties, performing at 3.0 C with 0.064 % capacity decay per cycle, and even maintaining super cycle stability at a high sulfur loadings. In addition, the pouch cell assembled can also reach an initial specific capacity of 1070.3 mAh g−1 at 0.1 C, which can still show good long‐term cycle stability. This work provides a valuable prospect for analyzing SRR intermediate state by regional electron flow regulation of electrocatalyst in practical LSBs.

Utility of Reticulocyte Hemoglobin Equivalent in Screening for Iron Deficiency in Pregnancy.

Ferritin, commonly used for diagnosing iron deficiency (ID) in pregnancy, is limited by high cost and false elevations during inflammation. Reticulocyte hemoglobin equivalent (Ret-He), an alternative marker for ID, is unaffected by inflammation and analyzed on the same collection tube as the standard complete blood count (CBC). We aimed to determine the accuracy of Ret-He in detecting ID in pregnancy compared to ferritin in a U.S. This prospective cohort study enrolled 200 pregnant participants, recruited in any trimester if a CBC was drawn as part of routine prenatal care. For those who agreed to participate, Ret-He and ferritin were collected concurrently with the CBC. ID was defined as ferritin level below 30 ng/mL. Patients were classified into three groups based on hemoglobin and ferritin results to determine the severity of ID: no ID, ID alone, and ID anemia (IDA). Four participants with anemia but normal ferritin were excluded. Receiver operating curve analysis, including the area under the curve (AUC), was performed to assess the accuracy of Ret-He in detecting ID. A one-way ANOVA (analysis of variance) with post-hoc analysis was used to compare differences in Ret-He between the three groups of ID severity. The prevalence of ID in our cohort was 82% (161/196). The AUC for Ret-He was 0.65 (95% confidence interval: 0.55-0.75), indicating suboptimal discrimination between patients with and without ID. Ret-He was significantly different among the three groups (p < 0.001). In post-hoc analysis, Ret-He was significantly lower in the IDA group compared to the ID group (p < 0.001) but there was only a trend of lower Ret-He in the ID group compared to the non-ID group (p = 0.38). Ret-He has low accuracy in diagnosing ID in pregnancy. It may be useful in detecting severe ID resulting in anemia but not a mild iron-deficient state resulting in ID only. · The prevalence of ID in our cohort was 82%.. · Ret-He has low accuracy in diagnosing ID in pregnancy.. · Ferritin is preferable when readily available..

Abundance, habitat distribution and content of reserve energy substances in shrews (Sorex caecutiens, Sorex isodon) within the Seymchan-Buyundinskaya Depression (Upper Kolyma River region)

This research examined the influence of interspecific interactions among shrew species on their territorial distribution and trophic conditions within larch and poplar-chosenia forests along the upper Kolyma River. The study specifically analyzed the biotopic characteristics associated with the relative abundance and energy reserve content, including fat tissue mass and glycogen levels in the liver, of Sorex caecutiens and S. isodon. Fieldwork was conducted in the Seymchan- Buyunda depression during July and August in 2003 and 2010. A total of 1,588 individuals from both species were captured using pitfall traps. The assessment of energy reserve content in S. caecutiens (n = 736) and S. isodon (n = 113) was carried out between 2006 and 2010. The abundance of S. caecutiens in the examined habitats exhibited consistent trends and a strong correlation (RS = 0.95, p &lt; 0.01). Conversely, S. isodon displayed asynchronous fluctuations in abundance across various habitats, likely attributable to competition with Laxmann’s shrew, which tends to displace S. isodon from its preferred larch forest during periods of elevated population density. The interannual variations in energy reserve content for both shrew species were remarkably similar, with no significant differences observed between habitats. The nature of these variations suggested insufficient feeding conditions for the animals during years of high overall abundance, with the dominant species, S. caecutiens, contributing most significantly to this phenomenon in both habitats of the upper Kolyma. The results indicate that interspecific relationships play a crucial role in shaping both territorial distribution and food availability for these shrew species.

A-144 Liquid chromatography multiple reaction monitoring-based assay for quantitative assessment of fibrinogen levels in clinical samples

Abstract Background Fibrinogen plays a critical role in hemostasis and is essential to clot formation. Changes in the quantity or activity of fibrinogen can lead to disorders affecting coagulation. Thus, it is essential to precisely quantify fibrinogen levels to differentiate between hyperfibrinogenemia in hypercoagulable disorders and dysfibrinogenemia, hypo/afibrinogenemia, and irregular bleeding. Current diagnostic tests that use antibodies to detect fibrinogen or activity-based measures are susceptible to interference from heparin contamination, hemolysis, and hyperbilirubinemia. Here, we evaluated the use of targeted proteomics for developing a quantitative assay for fibrinogen in plasma samples. Methods Four peptides each for alpha and gamma chains of fibrinogen were synthesized using FMOC chemistry on a Liberty Blue (CEM Corp) peptide synthesizer. A targeted multiple reaction monitoring (MRM) assay was developed and optimized using Dionex Ultimate 3000 HPLC connected to a TSQ Altis triple quadrupole mass spectrometer (Thermo Scientific). Evaluations were conducted using a range of standards, such as pure protein, WHO plasma and commercially available plasma with known fibrinogen amounts for the accurate quantitation of fibrinogen. Calibration curves were generated using different dilutions in various matrices. The repeatability and precision of the assay were evaluated across five different days. The plasma samples were processed and digested in a 96-well plate and subjected to C18 clean-up using a Bravo automated liquid handler (Agilent). All samples were spiked-in with corresponding heavy-labeled peptides prior to digestion with trypsin. Multiple reaction monitoring assays were performed on tryptic digests of plasma samples. Results Calibration curves using commercial plasma for all peptides showed linearity from 20 mg/dl to 1,308 mg/dl. This covers the entire clinical range including normal (200-350 mg/dl), deficient states (&amp;lt;100 mg/dl) and excess production (&amp;gt;350 mg/dl) that can be used for evaluation of bleeding disorders including consumption coagulopathy and hyperfibrinogenemia. Based on the overall performance in terms of linearity, limit of detection/quantitation, carryover and coefficient of variation (CV) across five different days, two peptides per chain were finally selected for developing the quantitative assay. The intra-assay variability was &amp;lt;5% and intra-day CV was ∼20%. This assay is currently being tested on a variety of clinical samples representing a range of fibrinogen levels. Conclusions Our study focused on assessing whether multiplexed MRM assay could be implemented to measure fibrinogen levels in plasma. Our data indicate the feasibility of MRM-based assays for determining fibrinogen levels as an alternative to existing non-mass spectrometry-based activity or antigen assays.

Vitamin D Deficiency Prevalence in Pakistan: Common, Important, and Neglected: A Comprehensive Meta-Analysis

Abstract Vitamin D is crucial for normal body metabolism. Two important vitamin D sources are synthesis in the lower layers of the skin (90%) and diet (10%). This systematic review and meta-analysis attempted to determine the incidence of vitamin D deficiency in Pakistan by using the findings of numerous cross-sectional studies. For subgroup analysis, a population-based subgroup analysis and a geographical location-based subgroup analysis were done. Different search techniques were utilized on various databases using the terms “vitamin D deficiency,” “Pakistan,” and “prevalence.” The article names and abstracts were scrutinized, and associated complete texts were evaluated. The articles that satisfied the inclusion requirements were chosen for the meta-analysis. The I 2 test was used to determine heterogeneity. They were combined with the random-effect method. Out of 429 articles, 37 studies, with a total sample size of 19,338, were selected for the final analysis. The highest and lowest reported percentages observed were 100% and 15%, respectively. The overall pooled prevalence reported was 78% (95% CI = 74.2–82%). In subgroup analysis, children/adolescents showed a higher pooled prevalence of 84% (95% CI = 76.1–93.6%), and among province-wise subgroup analysis, Punjab province has shown a higher pooled prevalence of 84% (95% CI: 74–94%). Meta-analysis of the data showed a higher proportion of the population with deficient states. Interventions in public health are essential to address the high incidence of vitamin D insufficiency. Vitamin D levels can be increased, and related health concerns can be minimized through dietary supplementation, recommended sun exposure, and awareness initiatives.

Euglycemic Ketoacidosis Associated with SGLT-2 Inhibitors in Non-diabetic Patients-A Narrative Review.

Euglycemic ketoacidosis is an acute, life-threatening emergency that is characterized by euglycemia, metabolic acidosis, and ketonemia. It is a well-recognized adverse event in diabetic patients taking sodium-glucose cotransporter-2 inhibitor (SGLT-2 inhibitor). However, there is limited data on SGLT-2 inhibitor-related euglycemic ketoacidosis in non-diabetic patients. The mechanism behind SGLT-2 inhibitor-associated euglycemic ketoacidosis involves a general state of starvation or relative insulin deficiency, which exacerbates the mild baseline ketonemia caused by this class of medications while normoglycemia is maintained. The incidence of euglycemic ketoacidosis will likely increase with the increasing use of SGLT-2 inhibitors for various indications in addition to diabetes mellitus type 2, predominantly for congestive heart failure (CHF). Recognizing the signs and symptoms of this life-threatening condition is essential to treat it effectively. Our objective is to comprehensively revisit the pathophysiology of euglycemic ketoacidosis associated with SGLT-2 inhibitors and the risk factors for the condition, review the available data, and summarize the reported cases of euglycemic ketoacidosis in non-diabetic patients on SGLT-2 inhibitors. Our literature search identified five articles with six cases of euglycemic ketoacidosis in non-diabetic patients who were on SGLT-2 inhibitors for heart failure with reduced ejection fraction. The common risk factor in five out of the six cases was decreased oral intake due to acute illness, fasting, or a perioperative state.