Long-range white matter fibres and post-stroke verbal and non-verbal cognition.

Among stroke survivors, linguistic and non-linguistic impairments exhibit substantial inter-individual variability. Stroke lesion volume and location do not sufficiently explain outcomes, and the neural mechanisms underlying the severity of aphasia or non-verbal cognitive deficits remain inadequately understood. Converging evidence supports the idea that white matter is particularly susceptible to ischaemic injury, and long-range fibres are commonly associated with verbal and non-verbal function. Here, we investigated the relationship among post-stroke aphasia severity, cognition, and white matter integrity. Eighty-seven individuals in the chronic stage of stroke underwent diffusion MRI and behavioural testing, including language and cognitive measures. We used whole-brain structural connectomes from each participant to calculate the ratio of long-range fibres to short-range fibres. We found that a higher proportion of long-range fibres was associated with lower aphasia severity, more accurate picture naming, and increased performance on non-verbal semantic memory/processing and non-verbal reasoning while controlling for lesion volume, key damage areas, age, and years post stroke. Our findings corroborate the hypothesis that, after accounting for age and lesion anatomy, inter-individual differences in post-stroke aphasia severity, verbal, and non-verbal cognitive outcomes are related to the preservation of long-range white matter fibres beyond the lesion.

Acute seizures after spontaneous intracerebral hemorrhage in young individuals: 11-year trends and association with mortality.

BACKGROUND: The rate of spontaneous Intracerebral Hemorrhage (sICH) is rising among young Americans. Trends in acute seizure (AS) incidence in this age group is largely unknown. Further, the association of AS with mortality has not been reported in this age group. The aim of this study is to determine trends in AS among young individuals with sICH. METHODS: The Merative MarketScan® Commercial Claims and Encounters database, for the years 2005 through 2015, served as the data source for this retrospective in-hospital population study. This period was chosen as spontaneous ICH incidence increased among young individuals between 2005 and 2015. Our study population included patients aged 18-64 years with ICH identified using the International Classification of Diseases, Ninth and Tenth Revision (ICD-9/10) codes 430, 431, 432.0, 432.1, 432.9, I61, I61.0, I61.1, I61.2, I61.3, I61.4, I61.5, I61.6, I61.8, and I61.9, excluding those with a prior diagnosis of seizures (ICD-9/10 codes 345.x,780.3x, G40, G41, and R56.8). We computed yearly AS incidence, mortality (in patients with and without seizures), and analyzed trends. We applied a logistic regression model to determine the independent association of AS with mortality accounting for demographic and clinical variables. RESULTS: AS incidence increased linearly between 2005 (incidence rate: 8.1 %) and 2015 (incidence rate: 11.0 %), which represents a 26 % relative increase (P for trends <0.0001). In-hospital mortality rate was 14.3 % among those who developed AS and 11.5 % among those who did not have AS. Overall, between 2005 and 2015, in-hospital mortality decreased from 13.0 % to 9.7 % among patients without AS but remained unchanged among those with AS. Patients who developed AS were 10 % more likely to die than those who did not (OR: 1.10, 95 % confidence interval: 1.02-1.18). CONCLUSIONS: Between 2005 and 2015, the incidence of AS increased by nearly 26 % among young Americans with sICH. In-patient mortality remained unchanged among those who developed seizures but declined among those who did not. The occurrence of AS was independently associated with a 10 % higher risk of in-hospital death.

Clonal hematopoiesis driven by mutated DNMT3A promotes inflammatory bone loss.

Clonal hematopoiesis of indeterminate potential (CHIP) arises from aging-associated acquired mutations in hematopoietic progenitors, which display clonal expansion and produce phenotypically altered leukocytes. We associated CHIP-DNMT3A mutations with a higher prevalence of periodontitis and gingival inflammation among 4,946 community-dwelling adults. To model DNMT3A-driven CHIP, we used mice with the heterozygous loss-of-function mutation R878H, equivalent to the human hotspot mutation R882H. Partial transplantation with Dnmt3aR878H/+ bone marrow (BM) cells resulted in clonal expansion of mutant cells into both myeloid and lymphoid lineages and an elevated abundance of osteoclast precursors in the BM and osteoclastogenic macrophages in the periphery. DNMT3A-driven clonal hematopoiesis in recipient mice promoted naturally occurring periodontitis and aggravated experimentally induced periodontitis and arthritis, associated with enhanced osteoclastogenesis, IL-17-dependent inflammation and neutrophil responses, and impaired regulatory T cell immunosuppressive activity. DNMT3A-driven clonal hematopoiesis and, subsequently, periodontitis were suppressed by rapamycin treatment. DNMT3A-driven CHIP represents a treatable state of maladaptive hematopoiesis promoting inflammatory bone loss.

Can machine learning predict late seizures after intracerebral hemorrhages? Evidence from real-world data.

INTRODUCTION: Intracerebral hemorrhage represents 15 % of all strokes and it is associated with a high risk of post-stroke epilepsy. However, there are no reliable methods to accurately predict those at higher risk for developing seizures despite their importance in planning treatments, allocating resources, and advancing post-stroke seizure research. Existing risk models have limitations and have not taken advantage of readily available real-world data and artificial intelligence. This study aims to evaluate the performance of Machine-learning-based models to predict post-stroke seizures at 1 year and 5 years after an intracerebral hemorrhage in unselected patients across multiple healthcare organizations. DESIGN/METHODS: We identified patients with intracerebral hemorrhage (ICH) without a prior diagnosis of seizures from 2015 until inception (11/01/22) in the TriNetX Diamond Network, using the International Classification of Diseases, Tenth Revision (ICD-10) I61 (I61.0, I61.1, I61.2, I61.3, I61.4, I61.5, I61.6, I61.8, and I61.9). The outcome of interest was any ICD-10 diagnosis of seizures (G40/G41) at 1 year and 5 years following the first occurrence of the diagnosis of intracerebral hemorrhage. We applied a conventional logistic regression and a Light Gradient Boosted Machine (LGBM) algorithm, and the performance of the model was assessed using the area under the receiver operating characteristics (AUROC), the area under the precision-recall curve (AUPRC), the F1 statistic, model accuracy, balanced-accuracy, precision, and recall, with and without seizure medication use in the models. RESULTS: A total of 85,679 patients had an ICD-10 code of intracerebral hemorrhage and no prior diagnosis of seizures, constituting our study cohort. Seizures were present in 4.57 % and 6.27 % of patients within 1 and 5 years after ICH, respectively. At 1-year, the AUROC, AUPRC, F1 statistic, accuracy, balanced-accuracy, precision, and recall were respectively 0.7051 (standard error: 0.0132), 0.1143 (0.0068), 0.1479 (0.0055), 0.6708 (0.0076), 0.6491 (0.0114), 0.0839 (0.0032), and 0.6253 (0.0216). Corresponding metrics at 5 years were 0.694 (0.009), 0.1431 (0.0039), 0.1859 (0.0064), 0.6603 (0.0059), 0.6408 (0.0119), 0.1094 (0.0037) and 0.6186 (0.0264). These numerical values indicate that the statistical models fit the data very well. CONCLUSION: Machine learning models applied to electronic health records can improve the prediction of post-hemorrhagic stroke epilepsy, presenting a real opportunity to incorporate risk assessments into clinical decision-making in post-stroke care clinical care and improve patients' selection for post-stroke epilepsy research.

Combined 3D DNA FISH, Single-Molecule RNA FISH, and Immunofluorescence.

Nuclear architecture is a potential regulator of gene expression in eukaryotic cells. Studies connecting nuclear architecture to gene expression are often population-averaged and do not report on the cell-level heterogeneity in genome organization and associated gene expression. In this report we present a simple way to combine fluorescence in situ hybridization (FISH)-based detection of DNA, with single-molecule RNA FISH (smFISH) and immunofluorescence (IF), while also preserving the three-dimensional (3D) nuclear architecture of a cell. Recently developed smFISH techniques enable the detection of individual RNA molecules; while using 3D DNA FISH, copy numbers and positions of genes inside the nucleus can be interrogated without interfering with 3D nuclear architecture. Our method to combine 3D DNA FISH with smFISH and IF enables a unique quantitative handle on the central dogma of molecular biology.

Large datasets from Electronic Health Records predict seizures after ischemic strokes: A Machine Learning approach.

Objective: To develop an artificial intelligence, machine learning prediction model for estimating the risk of seizures 1 year and 5 years after ischemic stroke (IS) using a large dataset from Electronic Health Records. Background: Seizures are frequent after ischemic strokes and are associated with increased mortality, poor functional outcomes, and lower quality of life. Separating patients at high risk of seizures from those at low risk of seizures is needed for treatment and clinical trial planning, but remains challenging. Machine learning (ML) is a potential approach to solve this paradigm. Design/Methods: We identified patients (aged ≥18 years) with IS without a prior diagnosis of seizures from 2015 until inception (08/09/22) in the TriNetX Research Network, using the International Classification of Diseases, Tenth Revision (ICD-10) I63, excluding I63.6 (venous infarction). The outcome of interest was any ICD-10 diagnosis of seizures (G40/G41) at 1 year and 5 years following the index IS. We applied a conventional logistic regression and a Light Gradient Boosted Machine algorithm to predict the risk of seizures at 1 year and 5 years. The performance of the model was assessed using the area under the receiver operating characteristics (AUROC), the area under the precision-recall curve (AUPRC), F1 statistic, model accuracy, balanced accuracy, precision, and recall, with and without anti-seizure medication use in the models. Results: Our study cohort included 430,254 IS patients. Seizures were present in 18,502 (4.3%) and (5.3%) patients within 1 and 5 years after IS, respectively. At 1-year, the AUROC, AUPRC, F1 statistic, accuracy, balanced-accuracy, precision, and recall were respectively 0.7854 (standard error: 0.0038), 0.2426 (0.0048), 0.2299 (0.0034), 0.8236 (0.001), 0.7226 (0.0049), 0.1415 (0.0021), and 0.6122, (0.0095). Corresponding metrics at 5 years were 0.7607 (0.0031), 0.247 (0.0064), 0.2441 (0.0032), 0.8125 (0.0013), 0.7001 (0.0045), 0.155 (0.002) and 0.5745 (0.0095). Conclusion: Our findings suggest that ML models show good model performance for predicting seizures after IS.

Improved naming in patients with Broca's aphasia with tDCS.

BACKGROUND: Language impairment (aphasia) is a common neurological deficit after strokes. For individuals with chronic aphasia (beyond 6 months after the stroke), language improvements with speech therapy (ST) are often limited. Transcranial direct current stimulation (tDCS) is a promising approach to complement language recovery but interindividual variability in treatment response is common after tDCS, suggesting a possible relationship between tDCS and type of linguistic impairment (aphasia type). METHODS: This current study is a subgroup analysis of a randomised controlled phase II futility design clinical trial on tDCS in chronic post-stroke aphasia. All participants received ST coupled with tDCS (n=31) vs sham tDCS (n=39). Confrontation naming was tested at baseline, and 1, 4, and 24 weeks post-treatment. RESULTS: Broca's aphasia was associated with maximal adjunctive benefit of tDCS, with an average improvement of 10 additional named items with tDCS+ST compared with ST alone at 4 weeks post-treatment. In comparison, tDCS was not associated with significant benefits for other aphasia types F(1)=4.23, p=0.04. Among participants with Broca's aphasia, preservation of the perilesional posterior inferior temporal cortex was associated with higher treatment benefit (R=0.35, p=0.03). CONCLUSIONS: These results indicate that adjuvant tDCS can enhance ST to treat naming in Broca's aphasia, and this may guide intervention approaches in future studies.

Dental Caries, Race and Incident Ischemic Stroke, Coronary Heart Disease, and Death.

BACKGROUND: Dental caries is a highly prevalent disease worldwide. In the United States, untreated dental caries is present in >1 in 5 adults. The objective of this study was to determine the relationship between dental caries and incident ischemic stroke, coronary heart disease (CHD) events, and death. METHODS: The dental cohort (n=6351) of the ARIC study (Atherosclerosis Risk in Communities) was followed for incident ischemic stroke, CHD event, and all-cause mortality. Of all the participants at visit 4 (n=11 656), those who were unable to go through dental examination, or with prevalent ischemic stroke and CHD events, were excluded. The full-mouth dental examination was conducted at visit 4 (1996-1998), assessing dental caries. The dose response of decayed, missing, and filled surfaces due to caries was assessed and related to the outcome. Outcomes were assessed through the end of 2019. Additionally, the effect of regular dental care utilization on dental caries was evaluated. RESULTS: Participants with ≥1 dental caries had an increased risk of stroke (adjusted hazard ratio [HR], 1.40 [95% CI, 1.10-1.79]) and death (adjusted HR, 1.13 [95% CI, 1.01-1.26]) but not for CHD events (adjusted HR, 1.13 [95% CI, 0.93-1.37]). The association of dental caries and ischemic incident stroke was significantly higher in the African American population compared with the White subgroup (interaction term P=0.0001). Increasing decayed, missing, and filled surfaces were significantly associated with stroke (adjusted HR, 1.006 [95% CI, 1.001-1.011]) and death (adjusted HR, 1.003 [95% CI, 1.001-1.005]) but not CHD (adjusted HR, 1.002 [95% CI, 1.000-1.005]). Regular dental care utilization lowered (adjusted odds ratio, 0.19 [95% CI, 0.16-0.22]; P<0.001) the chance of caries. CONCLUSIONS: Among the cohort, dental caries was independently associated with the risk of ischemic stroke and death, with the effect higher in African American participants. Regular dental care utilization was associated with a lower chance of caries, emphasizing its relevance in the prevention of these events.

Association of Dental Infections with Intracranial Atherosclerotic Stenosis.

INTRODUCTION: Periodontal disease (PD) and dental caries are oral infections leading to tooth loss that are associated with atherosclerosis and cerebrovascular disease. We assessed the hypothesis that PD and caries are associated with asymptomatic intracranial atherosclerosis (ICAS) in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Full-mouth clinical periodontal measurements (7 indices) collected at 6 sites per tooth from 6,155 subjects from the Dental Atherosclerosis Risk in Communities Study (DARIC) without prior stroke were used to differentiate seven PD stages (Periodontal Profile Class [PPC]-I to -VII) and dental caries on coronal dental surface (DS) and dental root surface (DRS). A stratified subset underwent 3D time-of-flight MR angiogram and 3D high isotropic-resolution black blood MRI. ICAS was graded according to the criteria established by the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. We evaluated the relationship between PD stage and dental caries with asymptomatic ICAS, graded as no ICAS, <50% ICAS, and ≥50% ICAS. RESULTS: Among dentate subjects who underwent vascular imaging, 801 (70%) had no ICAS, 232 (20%) had <50% ICAS, and 112 (10%) had ≥50% ICAS. Compared to participants without gum disease (PPC-I), participants with mild-moderate tooth loss (PPC-VI), severe tooth loss (PPC-VII), and severe PD (PPC-IV) had higher odds of having <50% ICAS. Participants with extensive gingivitis (PPC-V) had significantly higher odds of having ≥50% ICAS. This association remained significant after adjusting for confounding variables: age, gender, race, hypertension, diabetes, dyslipidemia, 3-level education, and smoking status. There was no association between dental caries (DS and DRS) and ICAS <50% and ≥50%. CONCLUSION: We report significant associations between mild-moderate tooth loss, severe tooth loss, and severe PD with <50% ICAS as well as an association between extensive gingivitis and ≥50% ICAS. We did not find an association between dental caries and ICAS.

Dental Caries a Risk Factor for Intracerebral Hemorrhage.

INTRODUCTION: Streptococcus mutans is a known cause of dental caries that contains a collagen-binding protein, Cnm, and exhibits inhibition of platelet aggregation and matrix metalloproteinase-9 activation. This strain has been linked to aggravation of experimental intracerebral hemorrhage (ICH) and may be a risk factor for ICH. The purpose of this study was to test the association between dental caries and incident ICH. METHODS: The presence of dental caries and periodontal disease was assessed in subjects from the Dental Atherosclerosis Risk in Communities (DARIC) study without prior stroke or ICH. This cohort was followed for incident ICH over a period of 10 years. Cox regression was used to compute crude and adjusted hazards ratio from the dental assessment. RESULTS: Among 6,315 subjects, dental surface caries and/or root caries were recorded in 1,338 (27%) subjects. Of those, 7 (0.5%) had incident ICH over a period of 10 years following the visit 4 assessment. Of the remaining 4,977 subjects, 10 (0.2%) had incident ICH. Those with dental caries versus those without dental caries were slightly younger (mean age 62.0 ± 5.7 vs. 62.4 ± 5.6, p = 0.012), had a greater proportion of males (51 vs. 44%, p < 0.001), African Americans (44 vs. 10%, p < 0.001), and were hypertensive (42 vs. 31%, p < 0.001). The association between caries and ICH was significant (crude HR 2.69, 95% CI 1.02-7.06) and strengthened after adjustment for age, gender, race, education level, hypertension, and periodontal disease (adjusted HR 3.88, 95% CI 1.34-11.24). CONCLUSION: Dental caries is a potential risk for incident ICH after caries detection. Future studies are needed to determine if treatment of dental caries can reduce the risk of ICH.

Racial Disparities in Utilization of Emergency Medical Services and Related Impact on Poststroke Disability.

BACKGROUND: Prompt seeking of emergency medical services (EMS) assistance at stroke onset is critical to minimize poststroke disability. OBJECTIVE: The aim was to study how racial differences in EMS decision-relevant factors and EMS use impact stroke care and disability outcomes. DESIGN: A prospective observational study. PARTICIPANTS: A total of 1168 acute ischemic stroke patients discharged from April 2016 to October 2017 at a safety net hospital were included; 108 patients were surveyed before discharge. MEASURES: (1) Prehospital delay: EMS use, timely hospital arrival; (2) Stroke care: alteplase receipt and inpatient rehab; (3) Outcomes: Functional improvement at discharge (admission minus discharge scores on National Institutes of Health Stroke Scale), 90-day modified Rankin Scale; (4) EMS decision-relevant factors: Stroke symptom knowledge, source of knowledge, unfavorable past EMS/care experiences, and financial barriers to EMS use. RESULTS: Despite more Black patients using EMS than Whites/Asians (56% vs. 48%, P =0.003), their timely hospital arrival was 30% less likely. Adjusted for stroke severity, receipt of alteplase, and inpatient rehab were similar, but Black patients fared worse on functional improvement at discharge (among severe strokes, 2.4 National Institutes of Health Stroke Scale points less improvement, P <0.01), and on functional normalcy at 90 days (modified Rankin Scale score 0-1 being 60% less likely across severity categories) ( P <0.01). Fewer Black patients knew any stroke symptoms before the stroke (72% vs. 87%, P =0.03), and fewer learned about stroke from providers ( P =0.01). Financial barriers and provider mistrust were similar. CONCLUSIONS: Black patients had less knowledge of stroke symptoms, more care-seeking delay, and poorer outcomes. Including stroke education as a standard of chronic disease care may mitigate stroke outcome disparities.

Periodontal Disease Treatment After Stroke or Transient Ischemic Attack: The PREMIERS Study, a Randomized Clinical Trial.

BACKGROUND: Patients with stroke/transient ischemic attack and periodontal disease (PD) are at increased risk for cardiovascular events. PD treatments that can improve stroke risk factors were tested if they might assist patients with cerebrovascular disease. METHODS: In this multicenter phase II trial, patients with stroke/transient ischemic attack and moderately severe PD were randomly assigned to intensive or standard PD treatment arms. The primary outcome measure was a composite of death, myocardial infarction, and recurrent stroke, as well as adverse events. Secondary outcome included changes in stroke risk factors. RESULTS: A total of 1209 patients with stroke/transient ischemic attack were screened, of whom 481 met the PD eligibility criteria; 280 patients were randomized to intensive arm (n=140) and standard arm (n=140). In 12-month period, primary outcome occurred in 11 (8%) in the intensive arm and 17 (12%) in the standard arm. The intensive arm was nonsuperior to the standard arm (hazard ratio, 0.65 [95% CI, 0.30-1.38]) with similar rates of adverse events (sepsis 2.1% versus 0.7%; dental bleeding 1.4% versus 0%; and infective endocarditis 0.7% versus 0%). Secondary-outcome improvements were noted in both arms with diastolic blood pressure and high-density lipoprotein cholesterol (P<0.05). CONCLUSIONS: In patients with recent stroke/transient ischemic attack and PD, intensive PD treatment was not superior to standard PD treatment in prevention of stroke/myocardial infarction/death. Fewer events were noted in the intensive arm and the 2 arms were comparable in the safety outcomes. Secondary-outcome measures showed a trend toward improvement, with significant changes noted in diastolic blood pressure and high-density lipoprotein in both the treatment arms.

Taxonomic notes on the crab spider genus Oxytate L. Koch, 1878 (Araneae: Thomisidae) from India.

Type specimens of poorly known Indian Oxytate species deposited in the National Zoological Collection, Zoological Survey of India, Kolkata, and the National Museum of Natural History (MNHN), Paris are re-examined and described. Oxytate subvirens (Strand, 1907) is recorded for the first time from India and the current distribution of the genus in India is also mapped.

Cerebral blood flow in patients recovered from mild COVID-19.

BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been described in both severe and mild forms of symptomatic Coronavirus Disease 2019 (COVID-19) infection. The purpose of this study was to investigate global and regional cerebral blood flow (CBF) in asymptomatic COVID-19 patients. METHODS: Cases with mild COVID-19 infection and age-, sex-, and race-matched healthy controls were drawn from the Aging Brain Consortium at The University of South Carolina data repository. Demographics, risk factors, and data from the Montreal Cognitive Assessment were collected. Mean CBF values for gray matter (GM), white matter (WM), and the whole brain were calculated by averaging CBF values of standard space-normalized CBF image values falling within GM and WM masks. Whole brain region of interest-based analyses were used to create standardized CBF maps and explore differences between groups. RESULTS: Twenty-eight cases with prior mild COVID-19 infection were compared with 28 controls. Whole-brain CBF (46.7 ± 5.6 vs. 49.3 ± 3.7, p = .05) and WM CBF (29.3 ± 2.6 vs. 31.0 ± 1.6, p = .03) were noted to be significantly lower in COVID-19 cases as compared to controls. Predictive models based on these data predicted COVID-19 group membership with a high degree of accuracy (85.2%, p < .001), suggesting CBF patterns are an imaging marker of mild COVID-19 infection. CONCLUSION: In this study, lower WM CBF, as well as widespread regional CBF changes identified using quantitative MRI, was found in mild COVID-19 patients. Further studies are needed to determine the reliability of this newly identified COVID-19 brain imaging marker and determine what drives these CBF changes.

Effects of early human immunodeficiency virus infection on cerebral white matter blood flow autoregulation.

Blood flow autoregulation in cerebral white matter was measured before and after acute nicardipine-induced changes in mean arterial pressure of 10-21% in 21 treatment naïve HIV-positive adults and 32 controls. The autoregulatory index (-% cerebral blood flow change/% mean arterial pressure change) was not different at baseline ( P  = 0.71) or after 1 year of treatment ( n  = 11, P  = 0.17). We found no autoregulatory defect to explain the increased stroke risk or the development of cerebral white damage in people with HIV.

Taxonomic notes on the nursery-web spider genus Dendrolycosa Doleschall, 1859 (Araneae: Pisauridae) from India, with the description of a new species.

A new species of the nursery-web spider genus Dendrolycosa Doleschall, 1859, D. sahyadriensis spec. nov. () is described from the Mookambika Wildlife Sanctuary, Karnataka, India. Detailed morphological descriptions, diagnoses and illustrations of the copulatory organs of both sexes are provided. The status of the Dendrolycosa species in India is also given, along with a distribution map.

Taxonomic notes on the placement of Tibellus elongatus Tikader, 1960 and Apollophanes bangalores Tikader, 1963 (Araneae: Philodromidae).

Tibellus elongatus Tikader, 1960 is redescribed, and the male is described for the first time. Examination of the types and newly collected specimens reveal that the species is misplaced in Tibellus and is hereby assigned to the genus Thanatus C. L. Koch, 1837T. elongatus (Tikader, 1960) comb. nov. Another new combination is proposed: Lycopus bangalores (Tikader, 1963) comb. nov. (ex. Apollophanes).

Preclusion of methemoglobinemia caused by nitrate drugs in diabetics and nondiabetics: Possible role of Vitamin C.

The drugs containing nitrates like isosorbide dinitrate, isosorbide mononitrate and glyceryl trinitrate, etc., trigger the oxidation of hemoglobin which is manifested in the pathological disorder named methemoglobinemia. It was considered interesting to investigate the preventive roles of vitamin C towards the toxic effects of nitrate containing drugs used for the treatment of angina. The aim is to find whether these drugs need to be administered with special care to diabetic patients who are more prone to develop methemoglobinemia. Vitamin C (500 mg/day) was administered orally to reduce the methemoglobin (metHb) level in both the diabetic and nondiabetic patients consuming nitrate containing drugs regularly, keeping diabetic and nondiabetic patients not on nitrate drugs as control. Concentration of metHb and hemoglobin A (HbA) was estimated spectrophotometrically assuming the molar extinction coefficient values of metHb as 3.78 mM--1 cm--1 at 630 nm and HbA as 125,000 M --1 cm --1 at 415 nm. MetHb level was found to be lower after the treatment with vitamin C for 30 consecutive days than that before the trial with statistically significant two tailed p value. Additionally, fasting insulin level was also found to decrease after 4 weeks of consumption of vitamin C with moderate lowering of fasting serum glucose level as well, indicating a higher insulin sensitivity for the treated patients.

Effect of caffeine on the possible amelioration of diabetic neuropathy: A spectroscopic study.

IMPORTANCE: One of the consequential and alarming complications of diabetes mellitus is diabetic neuropathy (DN). DN is assured to be caused chiefly by excess sorbitol levels in the body. The harmful consequences of DN alike peripheral nerve damage with extremity ulcers may be dodged with timely detection and treatment. The therapeutic methods for DN are scarce and expensive. Therefore economic and user friendly methodologies to prevent acquiring the disease need proper attention. OBJECTIVE: The present research has been conducted (1) to analyse the levels of sorbitol in diabetic blood samples and compare them with non-diabetic ones and (2) to study the reduction in sorbitol levels upon addition of an important biochemical compounds caffeine in both sample groups. RESEARCH DESIGN, SETTING, PARTICIPANTS AND METHOD: Sorbitol-caffeine interaction analysis of blood samples of 16 patients with type 2 diabetes from KPC Medical College, Kolkata, India was made. The spectroscopic analysis and their interpretations were compared with 16 healthy subjects. MAIN OUTCOMES AND MEASURES: Present work describes that caffeine can be helpful in reducing the sorbitol level in diabetics, so the chances of development and progression of diabetic neuropathy can be controlled with the introduction of caffeine. RESULTS: A total number of 32 blood samples of patients (aged 35-70 years); mean age ranges were 52.06 ± 2.68 and 53.50 ± 2.66 years for non-diabetic and diabetic ones respectively, glucose and sorbitol screening examination were done by enzymatic methodologies where concentrations were assessed by means of either absorption or fluorescence spectroscopy. The calibration range was 18.2-1119.3 mg/dL (Linear regression analysis r2 = 0.996). The sensitivity of this screening program in detecting DN with the healthy adults has been inquired and found efficient. Results of fasting insulin analyses have also been analysed for HOMA-IR (homeostasis model assessment - insulin resistance) and HOMA-B (homeostasis model assessment - pancreatic ß cell function) values. Statistical significance of the results in non-diabetic and diabetic groups were performed and found to be statistically significant. CONCLUSIONS: We have defined the relationship between blood glucose level, insulin level, sorbitol and caffeine in human body and utilized them in the plausible remediation of DN.

Free serum sorbitol and its interaction with caffeine: A suggestive approach for plausible remediation of diabetic neuropathy.

The measure of sorbitol in serum can act as a good indicator in the monitoring of the diabetic complications. To analyze the sorbitol level in serum medium, fluorometric enzymatic assay was performed. To remove the excess sorbitol from the body, proposed binding of sorbitol with caffeine was investigated. Their interaction in serum medium was studied and established by UV-Vis, fluorescence spectrophotometry, and time-correlated single photon counting (TCSPC). The linear calibration of sorbitol (in the range 10-50 mM) was done using UV-Vis spectrophotometry. Time scan experiments furnished the reaction rate of sorbitol assayed solution as well as sorbitol-caffeine complex as 0.021 min-1 and 0.018 min-1 , respectively. A sudden drop was observed in the fluorescence lifetime of reduced nicotinamide adenine dinucleotide (NADH) present in sorbitol assayed solution upon complexation with caffeine, that is, from 1.774 × 10-09 to 1.23 × 10-10 Sec, which indicates the hindrance in the formation of NADH and the probable formation of some other species. Isothermal titration calorimetric experiments clearly indicate the number of binding sites (i.e., 3.89, 1.40, and 2.07) that exist between sorbitol and caffeine at the complexation ratio of 1:1.2, 1:1.5, and 1:3. The present method can be helpful in pharmacological and therapeutic studies of sorbitol using caffeine for treating diabetic neuropathy.