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Background: Malaria is a major cause of mortality among children. Objective: This study determines the clinical profile, outcome (discharge and death), and factors associated with poor outcome in children with severe malaria in a tertiary health facility in Northern Nigeria. Methods: We conducted a descriptive retrospective study of all children (≤14 years) admitted with severe malaria based on positive malaria parasite on thick film and or rapid diagnostic test and the World Health Organization guideline for severe malaria. We extracted relevant data from patients’ case files and departmental records and analyzed with the Statistical Package for the Social Sciences (SPSS) for Windows, version 20.0. (IBM Corp, Armonk, NY). Results: A total of 483 children with severe malaria were admitted with median age interquartile range of 4.0 (2.5–8.0) years. Males were 261 (54.0%). Underfives were 258 (53.4%). Common forms of presentation were cerebral malaria 169 (35.0%), prostration (102; 21.1%), and multiple convulsion (86; 17.8%). Cerebral malaria and prostration were significantly higher among children aged 5 years and older. The mortality rate was 4.3% (21). Multivariate logistic regression analyses showed that impaired consciousness (adjusted odds ratio [aOR] 8.5, 95% confidence interval [CI]: 2.345, 30.484), hypoglycemia (aOR: 21.4, 95% CI: 2.766, 165.410), presence of two or more components (aOR: 4.5, 95% CI: 1.630, 12.522), and duration of hospitalization of 24 h or less (aOR: 4.6, 95% CI: 1.621, 12.782) were independent predictors of poor outcome. Conclusion: Our study showed that cerebral malaria was the most common form of severe malaria with a significant burden in children above 5 years. The presence of impaired consciousness, hypoglycemia, multiple components, and duration of

IntroductionThis study was undertaken to investigate whether sustained rather than a single measure of corneal nerve loss was associated with the onset of diabetic peripheral neuropathy (DPN) and the progression of neuropathic symptoms and deficits in individuals with type 2 diabetes (T2D).MethodsParticipants underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function, and corneal confocal microscopy (CCM) at baseline, 1, 2, and 4–7 years. Sustained corneal nerve loss was defined as abnormal corneal nerve fiber density (CNFD,

Microgrid protection schemes play a vital role in ensuring the reliability and efficiency of power distribution in urban and rural areas, especially as renewable distributed energy resources are increasingly integrated. This paper aims to provide a comprehensive analysis of existing microgrid protection schemes, discussing their advantages and limitations and highlighting key challenges and opportunities for future research. As microgrid systems become increasingly common, the management of power flow in small-community networks equipped with intelligent electronic devices, non-linear loads, and multiple distributed generation sources becomes more complicated. In order to address these challenges, coordination of protective schemes is required to prevent overload and damage to equipment. Firstly, the study discusses microgrid definitions and functional categories, highlighting their benefits and drawbacks. An analysis of microgrid protection literature includes adaptive protection systems as intelligent methods to address coordination challenges. Secondly, this review classifies microgrid protection techniques as modified, new knowledge-based and conventional schemes and provides a systematic analysis of optimization approaches. The study also examines the essential problems associated with the coordination of protective relays within microgrids. Finally, examining the current state of microgrid protection to identify the key research directions and opportunities for future development in this rapidly advancing field. The findings of this comprehensive analysis highlight the importance of effective microgrid protection in ensuring a stable and sustainable energy future.

Pregnancy complicated by gestational diabetes mellitus (GDM) is accompanied by a higher risk of serious obstetric and perinatal complications. The results of the HAPO (Hyperglycemia and Adverse Pregnancy Outcomes) study showed that the previously used criteria for the diagnosis of GDM require revision. Universal standards for the diagnosis and treatment of carbohydrate metabolism disorders during pregnancy are required. GDM is a risk factor for the development of obesity, type 2 diabetes and cardiovascular diseases in the mother and offspring in the future. GDM treatment is based on modification of diet and lifestyle, self-monitoring of glycemia, as well as timely initiated insulin therapy. However, the adherence to glucose self-control among pregnant women with GDM remains quite low, as well as the correctness of filling out handwritten diaries. The wider use of glucose meters with the setting of an individual target range of glycemia, the function of wireless transmission of blood glucose data to an endocrinologist with the formation of reports, as well as the ability to enter information about nutrition, physical activity, insulin dose into a mobile application allows to increase satisfaction with treatment and reduce poor obstetric and perinatal outcomes in GDM.

Abstract Background Central venous pressure (CVP) readings are affected by several factors. The need to test the technology of noninvasive or minimal invasive monitoring during liver surgery to guide fluids intake is the focus of this trial. Adult hepatic patients undergoing elective open liver resection were randomized into transesophageal Doppler (TED, n = 20) or plethysmography variability index (PVI, n = 20). PVI blinded to anesthetist in TED group (gp) and vice versa. During dissection, crystalloids were restricted to keep corrected flow time (FTc) parameter of TED < 330 msec or PVI > 14%, otherwise infused at 6 ml/kg/h. Following resection, colloids infused if FTc < 330 msec or PVI > 14% despite crystalloids infusion. Primary aim is to compare TED-corrected flow time (FTc, msec) parameter to PVI (%) for guiding intravenous fluids during liver resection. Secondary to study their correlations and each parameter effect on blood loss and consumption, morbidity and intensive care unit (ICU) stay. Results It is presented as median [IQ]. Volumes of crystalloids and colloids guided by FTc and PVI were not different (p = 0.3, p = 0.1, respectively) despite negligible correlations. Normovolemic existed during dissection despite 2 h of fluids restriction. FTc was 327 (320–341) msec, PVI was 11.50 (11.00–14.00) %, and CVP in TED gp 11.00 (10.00–12.00) vs. 9.00 (9.00–11.50) mmHg in PVI gp, p = 0.2. Blood loss was 1500 (475–2000) ml in TED vs. 950 (675–1925) in PVI, p = 0.5. Patients’ % in need for blood transfusion and volumes in TED vs. PVI gps were similar: red blood cells: 30%, 350 (350–350) vs. 40%, 525 (350–700) ml, and p = 0.2. Plasma is 20%, 200 (200–300) vs. 40%, and 400 (200–400) ml, p = 0.3. There was no difference in nausea, vomiting, or ICU stay, (p > 0.05). Conclusions Volume of fluids guided by PVI was not different from that by TED, despite lack of correlation. Transfusion-free dissection was possible for a significant number of patients with normovolemia. Trial registration PACTR201808140151322 ( www.pactr.org )

One of the most efficient aminoglycoside is amikacin. Yet, it has been linked to unwanted renal toxicity, which has resulted in negative alterations in various biochemical indicators, particularly those related to oxidative stress, kidney function, and inflammation. The goal of this research was to see how citrus bergamot extract affected hemato-biochemical, inflammatory, and oxidative stress parameters in male rats triggered by acute amikacin toxicity.A total of 30 male rats were divided into five equal groups, each with six rats. The first group received 1 ml DW orally and its represent control group. Group 1 was given 1 ml of DW orally and I.P. AK (1.2 gm/kg) on day seven. Group 2 was given 100 mg/kg CBE orally for ten days. Groups (3) and (4) were given 100 mg/kg and 200 mg/kg of CBE, respectively, orally for ten days. On the seventh day of the experiments, I.P. AK (1.2 gm/kg) was given to the test groups. At the end of the trial, blood samples were used to assess oxidative stress, renal function, inflammatory markers, and some hemato-biochemical parameters.Significantly higher levels of serum MDA, IL-6, urea, and creatinine, and an adversely affect lipid profile, are indications of AK-induced nephrotoxicity. Supplementation of CBE attenuated AK-induced change in these biomarkers.It was concluded that CBE supplementation protects against the nephrotoxic effects of AK because to its antioxidant, anti-inflammatory, and hypolipemic properties.

Background. Intra-operative rupture (IOR) of intracranial aneurysms is a critical event affecting the operation course and the patient’s outcome. However, A rupture induced by an avulsion in the aneurysmal neck is exceedingly challenging, as sealing the neck tear by clip application might result in ischemic injury due to parent vessel occlusion. Here we reviewed the literature regarding the intraoperative avulsion of the aneurysmal neck with an illustrative case to provide explanations of its surgical management intricacies. Methods. A Midline PubMed literature review was performed using the following keywords; (Aneurysm) AND (neck) AND (surgery or clipping) AND (tear OR avulsion). Fifty-three results were found initially. After excluding non-human subject studies, and non-English studies, two independent researchers examined the title and the abstract for the cases of neck tear or avulsion with its management. Results. Fourteen articles were found to be included in this study. The average age of the cases is around 57 years. The percentages of females in the review were 62% (8/13), and among the males, 38% (5/13). Regarding the locations, PcomA and AcomA were both 23% (3/13) of the cases; other locations include ACA, 15%, and MCA, 15%. The surgical techniques that opted from the literature include the cotton clip method, clip wrapping, parallel clipping and micro-suturing Conclusion. IOR due to aneurysmal neck avulsion is a devastating surgical complication, and its management may differ according to the extent of the rupture. Choosing the most convenient technique depends on the surgeon’s knowledge and experience.

BACKGROUND: There are major health benefits to physical exercise during pregnancy for mothers and newborns. However, physical inactivity during pregnancy varies worldwide, but it is more common during the third trimester of pregnancy. A positive attitude toward antenatal exercise can reduce physical inactivity. OBJECTIVES: This study aimed to evaluate pregnant women’s knowledge and attitude toward physical exercise during pregnancy and to find out the relationship between pregnant women’s knowledge and attitude. METHODS: This is a descriptive study utilizing a non-probability purposive sample of 200 women. The data were collected by distributing a structured, self-administered questionnaire. The questionnaire comprised 37 questions for knowledge and 15 questions for attitude. This study was conducted from October 2021 to November 2022. RESULTS: The higher percentage of women’s age was 20–24 years, and 30% graduated from primary school. Nearly two-thirds of them were in the second trimester. More than one-third of them have two to three living children. Nearly two-thirds of women have poor knowledge levels about physical exercise during pregnancy, but most of them have a positive attitude. There is a significant relationship between pregnant women’s knowledge and attitude. CONCLUSION: This study indicated that most of the study sample had poor knowledge regarding physical exercise during pregnancy. However, they have a positive attitude toward physical exercise during pregnancy.

Introduction: Propofol is a short-acting medication that lowers awareness and causes a transient memory loss. It is given intravenously. The aim of this study was to assess the prevalence of various side effects of the use of propofol as an anesthetic in various surgical procedures and to compare their prevalence among adults and children. Materials and Methods: One hundred patients were included in the study, fifty adults and fifty of children, who underwent various types of surgery and received propofol anesthesia, at Pediatrics Hospital, Benghazi Medical Center (BMC) and Al-Hawari hospital, from September to November 2019. Results: The mean age was 6.37 ± 4.18 years in the pediatric group (ranging from 1 to 15 years) and 40.0 ± 17.03 years in the adult group (range from 16 to 97 years). The indication of surgery among the adult group was cholecystectomy (14 patients, 28%), followed by ENT operations (12 patients, 24%), while the indication of surgery among the pediatric group was tonsillectomy (20 patients, 40%), followed by hernia repair (15 patients, 30%). Thirty-five adults (70%) and 40 children (80%) suffered different types of complications during the study. Pain at the site of propofol injection was the most common complication. It was observed in 21 adult patients (42%) and 23 children (46%). Bronchospasm developed among 11 children who underwent tonsillectomy. Low blood pressure was more prevalent among adult patients (14 patients, 28%). An arrhythmia was developed in nine patients (six adults and three children). Two adults and five children experienced delayed recovery from anesthesia. The recovery time was 14.67 ± 8.37 min (5â€"45 min), Conclusion: Burning at site of propofol injection is the most common side effect of propofol anesthesia; other complications need further evaluation by more detailed studies.

Abstract Background Obesity is associated with an increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). However, some obese individuals maintain their insulin sensitivity and exhibit a lower risk of associated comorbidities. The underlying metabolic pathways differentiating obese insulin sensitive (OIS) and obese insulin resistant (OIR) individuals remain unclear. Methods In this study, 107 subjects underwent untargeted metabolomics of serum samples using the Metabolon platform. Thirty-two subjects were lean controls whilst 75 subjects were obese including 20 OIS, 41 OIR, and 14 T2DM individuals. Results Our results showed that phospholipid metabolites including choline, glycerophosphoethanolamine and glycerophosphorylcholine were significantly altered from OIS when compared with OIR and T2DM individuals. Furthermore, our data confirmed changes in metabolic markers of liver disease, vascular disease and T2DM, such as 3-hydroxymyristate, dimethylarginine and 1,5-anhydroglucitol, respectively. Conclusion This pilot data has identified phospholipid metabolites as potential novel biomarkers of obesity-associated insulin sensitivity and confirmed the association of known metabolites with increased risk of obesity-associated insulin resistance, with possible diagnostic and therapeutic applications. Further studies are warranted to confirm these associations in prospective cohorts and to investigate their functionality.

BACKGROUND: The basis of early ultrasound (US) diagnosis of diabetic fetopathy (DF) in pregnant with gestational diabetes mellitus (GDM) is the forehanded detection of macrosomia, especially its asymmetric forms. In pregnant with GDM on a diet therapy, the detection of macrosomia may be an indication for starting the insulin therapy. In pregnant with hyperglycemia due to mutation in the glucokinase gene (GCK), US fetal growth dynamics helps to assume the fetal genotype, as well as to stratify the risks of insulin therapy. AIM: To determine the prognostic significance of asymmetric form of macrosomia and the value of the coefficients of proportionality for the diagnosis of DF in pregnant with GDM, including hyperglycemia due to mutation in the GCK gene. MATERIALS AND METHODS: US fetometry was performed in 95 pregnant with GDM (including 22 pregnant with hyperglycemia caused by mutation in the GCK gene) (main group) and 427 healthy pregnant women (control group). Estimated fetal weight, standard fetometric indicators and coefficients of proportionality were evaluated. Retrospective analysis of US predictors of macrosomia was carried out after evaluating the weight of the newborn and clarifying the signs of DF. RESULTS: In the group with GDM, 51 (53.7%) pregnant had children with phenotypic symptoms of DF, including macrosomia – 66,7% (34 children). We found statistically significant differences in fetal weight between the control group and the main group who gave birth to children with DF starting from 32 weeks. The coefficients of proportionality (femur length/abdominal circumference and the head circumference/abdominal circumference), characterizing the formation of the asymmetric macrosomia were significantly from 34 weeks (Р 90 percentile for gestational age. A specific sign of DF in pregnant with GDM is the asymmetric macrosomia. In pregnant with a mutation in the GCK gene, the tendency to macrosomia was revealed only in the absence of a mutation in the fetus, but insulin therapy in the presence of a similar mutation in fetus did not lead to a significant decrease in its percentile ranges.

MODY1 and MODY3 represent rare causes of diabetes in pregnancy. Establishing a molecular diagnosis of MODY1 or MODY3 during pregnancy may be important for minimizing risk of perinatal complications and for improving glycemic control after pregnancy. The objective of the study was to evaluate the contribution of mutations in HNF4A and HNF1A genes in development of diabetes in pregnancy and to describe clinical characteristics of diabetes in pregnancy associated with these mutations. 230 pregnant women (20-43 years) with different type of glucose intolerance complicated during their current pregnancy were included in the study. A custom NGS panel targeting 28 diabetes causative genes was used for sequencing. Heterozygous mutations in HNF4A and HNF1A genes were detected in 3% of cases. Mutations p.I271T in HNF4A gene and p.L148F, p.Y265C, p.G288W in HNF1A gene were novel. This study includes a description of patients with pregnancy diabetes due to mutations in hepatocyte nuclear factors.

The diagnosis of MODY as a subtype of gestational diabetes mellitus (GDM) is important for an adequate management during pregnancy and the postnatal period. The present report describes a case of GDM caused by a synonymous с.666C>G р.V222V substitution in the GCK gene. The variant, which was initially ranked as ‘likely benign’, was later proven to be pathogenic by in vitro studies. The с.666C>G substitution led to the use of a new donor splice site and synthesis of the aberrant mRNA with deletion of 16 base pairs. The case illustrates that additional clinical and experimental data may be required for the correct interpretation of sequence variants pathogenicity.

Md Khalid Anwer,1 Muqtader Mohammad,1 Essam Ezzeldin,2,3 Farhat Fatima,1 Ahmed Alalaiwe,1 Muzaffar Iqbal2,3 1Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia; 2Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 3Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia Background: Apremilast (APM) is a novel, orally administered small molecule drug approved for treatment of psoriasis or psoriatic arthritis. Due to its low solubility and permeability, it is classified as a class IV drug according to BCS classification. Dose titration is recommended during APM treatment due to its tolerability and twice-daily dosing regimen issues. Materials and Methods: In this study, three different APM-loaded PLGA nanoparticles (F1–F3) were prepared by single emulsion and evaporation method. Based on particle size, PDI, zeta potential (ZP), entrapment efficiency (%EE), drug loading (%DL), and spectral characterization, the nanoparticles (F3) were optimized. The F3 nanoparticles were further evaluated for in vitro release and in vivo pharmacokinetic studies in rats. Results: The optimized nanoparticles (F3) had particles size 307.3±8.5 nm with a low PDI value 0.317, ZP of -43.4±2.6 mV, EE of 61.1±1.9% and DL of 1.9±0.1%. The in vitro release profile showed a sustained release pattern of F3 nanoparticles of APM. The pharmacokinetic results showed 2.25 times increase in bio-availability of F3 nanoparticles compared to normal APM suspension. Moreover, significant increase in half-life and mean residence time confirms long-term retention of F3 nanoparticles. Conclusion: Bioavailability enhancement along-with long-term retention of the APM-loaded PLGA nanoparticles might be helpful for the once-daily regimen treatment. Keywords: apremilast, Poly(D,L-lactide-coglycolide), nanoparticles, bioavailability, sustained release

Background. Gestational diabetes (GDM) due to GCK gene mutations is the most frequent form of monogenic diabetes mellitus (DM) presenting during pregnancy. It has been suggested that the use of insulin in pregnancies with fetuses carrying GCK mutations may lead to intrauterine growth retardation. In the present study we evaluated the effect of insulin therapy during pregnancy on birth weight and length in the offsprings of mothers with GDM due to GCK mutations. Aims. The aim was to study birth weight and length in offsprings of mothers with gestational diabetes mellitus due to mutations in GCK, depending on the therapy during pregnancy. Materials and methods. The study included 38 patients with GDM caused by GCK gene mutations (18.7%) and the 45 offsprings. To define molecular basis of GDM in pregnant women we used a targeted NGS. ‘Diabetes panel’ genes were sequenced using a custom Ion Ampliseq gene panel and PGM semiconductor sequencer (Ion Torrent). To found the same mutations in their offsprings was used Sanger sequencing. All children were divided into 3 groups depending of their genotype and therapy received by the mothers during pregnancy. Results. We found statistically significant differences in birth length (p=0.04) and weight (p=0,031) depending on the genotype of the child and therapy in the mother. The risk of macrosomia was shown in non-mutation-carrying offsprings only. The birth weight in children with GCK gene mutations whose mothers received insulin during pregnancy was significantly lower. However, the birth weight remained in the normal range. Conclusions. Since prenatal diagnostics in the mothers with GCK gene mutations is not always justified, we recommend insulin therapy in order to prevent fetal macrosomia, which, however, should be less aggressive than in GDM due to other causes.

The present work include preparation of three ligands (Schiff base) by condensation of (Phthaldialdehyde) with 1,3-diamino-2-propanol) to give ligands (L) L: (1Z,6Z)-4,5-dihydro -3H-2,6-benzodiazonin-4-ol o characterize the structure of prepared ligands and their complexes, elemental analysis (C.H.N),Infrared Spectroscopy (IR), Nuclear Magnetic Resonance Spectroscopy( 1 H-NMR),Mass Spectra and Molar conductivity echniques were applied . The results showed that: - The complexes of [Co(III) and Cr(III)] for ligand have shown octahedral configuration. - Complexes of [ Ni(II)] with ligands have shown tetrahedral configuration.

An erratum on «A synonymous variant in GCK gene as a cause of gestational diabetes mellitus» by Natalya A. Zubkova, Petr M. Rubtsov, Liudmila I. Ibragimova, Nina A. Makretskaya, Evgeny V. Vasiliev, Vasily M. Petrov, Anatoly N. Tiulpakov (2019). Diabetes mellitus. 22(2). doi: 10.14341/DM9938An error was made in the list of authors: Fatima F. Burumkulova was not indicated as author of this article. The correct list of authors: Natalya A. Zubkova, Petr M. Rubtsov, Fatima F. Burumkulova, Liudmila I. Ibragimova, Nina A. Makretskaya, Evgeny V. Vasiliev, Vasily M. Petrov, Anatoly N. Tiulpakov.The editorial board apologize for this error and state that this does not change the scientific conclusions of the article in any way.The original article has been updated.

The effect of glycemic state on status epilepticus (SE) development was studied in animals of different ages, submitted to pilocarpine model of epilepsy. Groups: I- Rats with 9-day-old (P9): IA. Submitted to 1SE; IB. Saline-treated; IC. Induced- hyperglycemia; ID. Induced- hyperglycemia+SE; II- Rats submitted to three consecutive episodes of SE at P7, P8 and P9; III- Rats submitted to 1SE at P17; IV- Rats submitted to 1SE at P21. Hippocampal cell death and the expression of glucose transporter GLUT3 were analyzed in group I. The results demonstrated normoglycemia in the groups IA, IB and II, hypoglycemia in group III and hyperglycemia in group IV, showing that the glycemia during SE is age dependent. Induced hyperglycemia during SE in P9 protected the hippocampal neurons from death and both groups IC and ID presented increased GLUT3 expression, showing high glucose consumption by the hippocampus.O efeito do estado glicêmico sobre o desenvolvimento do status epilepticus (SE) foi estudado em animais de diferentes idades, submetidos ao modelo de epilepsia por pilocarpina. Grupos: I- Ratos com nove dias (P9): IA- Submetidos a 1SE; IB- Tratados com salina; IC- Hiperglicemia induzida; ID- Hiperglicemia induzida+SE; II- Ratos submetidos a 3 episódios consecutivos de SE em P7, P8 e P9; III- Ratos submetidos a 1SE em P17; IV- Ratos submetidos a 1SE em P21. Foram analisados no grupo I a morte celular hipocampal e a expressão do transportador de glicose GLUT3. Os resultados mostraram haver normoglicemia nos grupos IA, IB e II, hipoglicemia no grupo III e hiperglicemia no grupo IV, sendo a glicemia durante o SE, idade dependente. A hiperglicemia induzida durante o SE em P9 protegeu neurônios hipocampais e os grupos IC e ID apresentaram expressão aumentada de GLUT3, mostrando aumento no consumo de glicose pelo hipocampo.

Major dengue epidemics have been observed in the Indian subcontinent since the 1980s and have occurred with increased hospitalizations and mortality. In 2011, the first major epidemic of dengue occurred in Lahore, the second largest city in Pakistan, and resulted in 21,685 confirmed cases and 350 deaths. To investigate the possible viral causes for the increased epidemic activity, we determined the predominant serotype and characterized the viruses genetically. Of 50 patients carefully selected as probable dengue fever or dengue hemorrhagic fever, 34 were positive by virologic testing (i.e. PCR and/or virus isolation). DENV-2 was detected in 32 patients and DENV-1 in two. A total of 24 partial and three full DENV genomes were sequenced. Phylogenetic analyses of the capsid (C), pre-membrane (prM), and envelope genes comprising 2500 nucleotides in length indicated that all DENV-2 isolates in Pakistan since 2007 form a monophyletic lineage that is endemic in the country. These viruses were all of the cosmopolitan genotype (IV) and most closely related to viruses isolated in India and Sri Lanka in the past two decades. Phylogenetic analyses of data currently available in GenBank suggest that the Cosmopolitan genotype has diverged into two geographically distinct sub-lineages: sub-lineage IV-a has only been observed in Southeast Asia, China and Oceania, while IV-b is prevalent in the Indian subcontinent. These results highlight the increased diversity of dengue viruses as they spread geographically within the region.

Introduction: This study was undertaken to investigate whether sustained rather than a single measure of corneal nerve loss was associated with the onset of diabetic peripheral neuropathy (DPN) and the progression of neuropathic symptoms and deficits in individuals with type 2 diabetes (T2D). Methods: Participants underwent clinical, metabolic testing and assessment of neuropathic symptoms, vibration perception threshold (VPT), sudomotor function, and corneal confocal microscopy (CCM) at baseline, 1, 2, and 4-7 years. Sustained corneal nerve loss was defined as abnormal corneal nerve fiber density (CNFD, <24 fibers/mm²), corneal nerve branch density (CNBD, <21 branches/mm²), and corneal nerve fiber length (CNFL, <16 mm/mm²) persisting for =50% of the study duration. Results: A total of 107 participants with a mean duration of T2D of 13.3 ± 7.3 years, aged 54.8 ± 8.5 years, underwent baseline and follow-up assessments over a median duration of 4 years, ranging from 1 to 7 years. The DPN prevalence at baseline was 18/107 (16.8%), and of the 89 participants without DPN at baseline, 13 (14.6%) developed DPN during follow-up. Approximately half of the cohort had sustained corneal nerve damage, and corneal nerve measures were significantly lower in this group than those without sustained damage (p < 0.0001). Sustained corneal nerve damage was associated with the development of DPN (p < 0.0001), a progressive loss of vibration perception (p = 0.05), an increased incidence of burning pain, numbness, or a combination of both (p = 0.01-0.001), and a borderline association with progressive sudomotor dysfunction (p = 0.07). Sustained abnormal CNFL effectively distinguished between participants who developed DPN and those who did not (AUC: 76.3, 95% CI: 65.9-86.8%, p < 0.0001), while baseline and other sustained measures did not predict DPN onset. Conclusion: Sustained abnormal CCM is associated with more severe corneal nerve damage, DPN development, and the progression of neuropathic symptoms and deficits. Regular CCM monitoring may enable the identification of those at greater risk of developing and worsening DPN who may benefit from more aggressive risk factor reduction. [ABSTRACT FROM AUTHOR]

Background Skin secretions of toads are widely used in medicine all over the world for their antiviral, anti-infective, and cardiotonic properties. Because these secretions are mostly employed to combat blood parasite infection, it is important to understand their potential toxic effects on human erythrocytes. Therefore, the objective of the current investigation was to elucidate the effects of Duttaphrynus melanostictus (Schneider) skin extracts on the physiology of human erythrocytes. Methods Toads captured from their natural habitat were separated into three groups according to their body size. Hydroalcoholic extracts of toad skin were prepared by reflux heating. These extracts were then evaluated for their hemolytic and hemoglobin denaturation potential. The effects of the extracts on cytosolic and membrane-bound enzymes of human erythrocytes were assessed. Results The hemolysis and hemoglobin denaturation caused by these extracts correlated positively with the respective toad sizes. Extracts from medium and large toads led to increased osmotic fragility even at near iso-osmotic concentrations. Biochemical analysis of hemolysate showed that the treatment induced a shift of metabolic flux toward the glutathione pathway. Analysis of membrane-bound enzymes revealed a significant decrease in the activity of Na+/K+ ATPase and acetylcholinesterase. SDS-PAGE analysis of the erythrocyte membrane did not show the band of tropomodulin for the cells treated with 1000 휇g/ml extract from large toads. Conclusions In conclusion, the present study demonstrates that the toxicity of toad skin secretions aggravates with the size of the animal and interferes with the physiology of human erythrocytes, leading to their membrane disruption and rapid lysis. [ABSTRACT FROM AUTHOR]

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