Estimation of differential pathlength factor from NIRS measurement in skeletal muscle.

The utilization of continuous wave (CW) near-infrared spectroscopy (NIRS) device to measure non-invasively muscle oxygenation in healthy and disease states is limited by the uncertainties related to the differential path length factor (DPF). DPF value is required to quantify oxygenated and deoxygenated heme groups' concentration changes from measurement of optical densities by NIRS. An integrated approach that combines animal and computational models of oxygen transport and utilization was used to estimate the DPF value in situ. The canine model of muscle oxidative metabolism allowed measurement of both venous oxygen content and tissue oxygenation by CW NIRS under different oxygen delivery conditions. The experimental data obtained from the animal model were integrated in a computational model of O2 transport and utilization and combined with Beer-Lambert law to estimate DPF value in contracting skeletal muscle. A 2.1 value was found for DPF by fitting the mathematical model to the experimental data obtained in contracting muscle (T3) (Med.Sci.Sports.Exerc.48(10):2013-2020,2016). With the estimated value of DPF, model simulations well predicted the optical density measured by NIRS on the same animal model but with different blood flow, arterial oxygen contents and contraction rate (J.Appl.Physiol.108:1169-1176, 2010 and 112:9-19,2013) and demonstrated the robustness of the approach proposed in estimating DPF value. The approach used can overcome the semi-quantitative nature of the NIRS and estimate non-invasively DPF to obtain an accurate concentration change of oxygenated and deoxygenated hemo groups by CW NIRS measurements in contracting skeletal muscle under different oxygen delivery and contraction rate.

Architecture and potential roles of a delta-class glutathione S-transferase in protecting honey bee from agrochemicals.

The European honey bee, Apis mellifera, serves as the principle managed pollinator species globally. In recent decades, honey bee populations have been facing serious health threats from combined biotic and abiotic stressors, including diseases, limited nutrition, and agrochemical exposure. Understanding the molecular mechanisms underlying xenobiotic adaptation of A. mellifera is critical, considering its extensive exposure to phytochemicals and agrochemicals present in the environment. In this study, we conducted a comprehensive structural and functional characterization of AmGSTD1, a delta class glutathione S-transferase (GST), to unravel its roles in agrochemical detoxification and antioxidative stress responses. We determined the 3-dimensional (3D) structure of a honey bee GST using protein crystallography for the first time, providing new insights into its molecular structure. Our investigations revealed that AmGSTD1 metabolizes model substrates, including 1-chloro-2,4-dinitrobenzene (CDNB), p-nitrophenyl acetate (PNA), phenylethyl isothiocyanate (PEITC), propyl isothiocyanate (PITC), and the oxidation byproduct 4-hydroxynonenal (HNE). Moreover, we discovered that AmGSTD1 exhibits binding affinity with the fluorophore 8-Anilinonaphthalene-1-sulfonic acid (ANS), which can be inhibited with various herbicides, fungicides, insecticides, and their metabolites. These findings highlight the potential contribution of AmGSTD1 in safeguarding honey bee health against various agrochemicals, while also mitigating oxidative stress resulting from exposure to these substances.

Functional and Structural Diversity of Insect Glutathione S-transferases in Xenobiotic Adaptation.

As a superfamily of multifunctional enzymes that is mainly associated with xenobiotic adaptation, glutathione S-transferases (GSTs) facilitate insects' survival under chemical stresses in their environment. GSTs confer xenobiotic adaptation through direct metabolism or sequestration of xenobiotics, and/or indirectly by providing protection against oxidative stress induced by xenobiotic exposure. In this article, a comprehensive overview of current understanding on the versatile functions of insect GSTs in detoxifying chemical compounds is presented. The diverse structures of different classes of insect GSTs, specifically the spatial localization and composition of their amino acid residues constituted in their active sites are also summarized. Recent availability of whole genome sequences of numerous insect species, accompanied by RNA interference, X-ray crystallography, enzyme kinetics and site-directed mutagenesis techniques have significantly enhanced our understanding of functional and structural diversity of insect GSTs.

A National Equity Initiative to Address Noncommunicable Diseases and Injuries: Findings and Recommendation from the Nepal NCDI Poverty Commission.

We aimed to assess the burden of NCDIs across socioeconomic groups, their economic impact, existing health service readiness and availability, current policy frameworks and national investment, and planned programmatic initiatives in Nepal through a comprehensive literature review. Secondary data from Global Burden of Disease estimates from GBD 2015 and National Living Standard Survey 2011 were used to estimate the burden of NCDI and present the relationship of NCDI burden with socioeconomic status. The Commission used these data to define priority NCDI conditions and recommend potential cost-effective, poverty-averting, and equity-promoting health system interventions. NCDIs disproportionately affect the health and well-being of poorer populations in Nepal and cause significant impoverishment. The Commission found a high diversity of NCDIs in Nepal, with approximately 60% of the morbidity and mortality caused by NCDIs without primary quantified behavioral or metabolic risk factors, and nearly half of all NCDI-related DALYs occurring in Nepalese younger than 40 years. The Commission prioritized an expanded set of twenty-five NCDI conditions and recommended introduction or scale-up of twenty-three evidence-based health sector interventions. Implementation of these interventions would avert an estimated 9680 premature deaths per annum by 2030 and would cost approximately $8.76 per capita. The Commission modelled potential financing mechanisms, including increased excise taxation on tobacco, alcohol, and sugar-sweetened beverages, which would provide significant revenue for NCDI-related expenditures. Overall, the Commission's conclusions are expected to be a valuable contribution to equitable NCDI planning in Nepal and similar resource-constrained settings globally.

Structural and Functional Characterization of One Unclassified Glutathione S-Transferase in Xenobiotic Adaptation of Leptinotarsa decemlineata.

Arthropod Glutathione S-transferases (GSTs) constitute a large family of multifunctional enzymes that are mainly associated with xenobiotic or stress adaptation. GST-mediated xenobiotic adaptation takes place through direct metabolism or sequestration of xenobiotics, and/or indirectly by providing protection against oxidative stress induced by xenobiotic exposure. To date, the roles of GSTs in xenobiotic adaptation in the Colorado potato beetle (CPB), a notorious agricultural pest of plants within Solanaceae, have not been well studied. Here, we functionally expressed and characterized an unclassified-class GST, LdGSTu1. The three-dimensional structure of the LdGSTu1 was solved with a resolution up to 1.8 Å by X-ray crystallography. The signature motif VSDGPPSL was identified in the "G-site", and it contains the catalytically active residue Ser14. Recombinant LdGSTu1 was used to determine enzyme activity and kinetic parameters using 1-chloro-2, 4-dinitrobenzene (CDNB), GSH, p-nitrophenyl acetate (PNA) as substrates. The enzyme kinetic parameters and enzyme-substrate interaction studies demonstrated that LdGSTu1 could catalyze the conjugation of GSH to both CDNB and PNA, with a higher turnover number for CDNB than PNA. The LdGSTu1 enzyme inhibition assays demonstrated that the enzymatic conjugation of GSH to CDNB was inhibited by multiple pesticides, suggesting a potential function of LdGSTu1 in xenobiotic adaptation.

Blood volume versus deoxygenated NIRS signal: computational analysis of the effects muscle O2 delivery and blood volume on the NIRS signals.

Near-infrared spectroscopy (NIRS) signals quantify the oxygenated (ΔHbMbO2) and deoxygenated (ΔHHbMb) heme group concentrations. ΔHHbMb has been preferred to ΔHbMbO2 in evaluating skeletal muscle oxygen extraction because it is assumed to be less sensitive to blood volume (BV) changes, but uncertainties exist on this assumption. To analyze this assumption, a computational model of oxygen transport and metabolism is used to quantify the effect of O2 delivery and BV changes on the NIRS signals from a canine model of muscle oxidative metabolism (Sun Y, Ferguson BS, Rogatzki MJ, McDonald JR, Gladden LB. Med Sci Sports Exerc 48: 2013-2020, 2016). The computational analysis accounts for microvascular (ΔHbO2, ΔHHb) and extravascular (ΔMbO2, ΔHMb) oxygenated and deoxygenated forms. Simulations predicted muscle oxygen uptake and NIRS signal changes well for blood flows ranging from resting to contracting muscle. Additional NIRS signal simulations were obtained in the absence or presence of BV changes corresponding to a heme groups concentration changes (ΔHbMb = 0-48 µM). Under normal delivery (Q = 1.0 L·kg-1·min-1) in contracting muscle, capillary oxygen saturation (So2) was 62% with capillary ΔHbO2 and ΔHHb of ± 41 µΜ for ΔHbMb = 0. An increase of BV (ΔHbMb = 24 µΜ) caused a ΔHbO2 decrease (16µΜ) almost twice as much as the increase observed for ΔHHb (9 µΜ). When So2 increased to more than 80%, only ΔHbO2 was significantly affected by BV changes. The analysis indicates that microvascular So2 is a key factor in determining the sensitivity of ΔHbMbO2 and deoxygenated ΔHHbMb to BV changes. Contrary to a common assumption, the ΔHHbMb is affected by BV changes in normal contracting muscle and even more in the presence of impaired O2 delivery.NEW & NOTEWORTHY Deoxygenated is preferred to the oxygenated near-infrared spectroscopy signal in evaluating skeletal muscle oxygen extraction because it is assumed to be insensitive to blood volume changes. The quantitative analysis proposed in this study indicates that even in absence of skin blood flow effects, both NIRS signals in presence of either normal or reduced oxygen delivery are affected by blood volume changes. These changes should be considered to properly quantify muscle oxygen extraction by NIRS methods.

Effect of Blood Flow on Hemoglobin and Myoglobin Oxygenation in Contracting Muscle Using Near-Infrared Spectroscopy.

Insufficient O2 delivery to, and uptake by skeletal muscle can produce mobility limitations for patients with chronic diseases. Near-infrared spectroscopy (NIRS) can be used to noninvasively quantify the balance between skeletal muscle O2 delivery and utilization during contraction. However, it is not clear how the oxygenated or deoxygenated NIRS signal should be used to assess muscle O2 changes. This issue is related to the fact that the contributions of hemoglobin (Hb) and myoglobin (Mb) cannot be distinguished. This conundrum can be resolved by quantitative analysis of experimental data by computer simulations with a mechanistic, mathematical model. Model simulations distinguish dynamic responses of the oxygenated (HbO2, MbO2) and deoxygenated (HHb, HMb) contributions to the NIRS signal components (HbMbO2, HHbMb). Simulations of muscle O2 uptake and NIRS kinetics correspond closely to published experimental data (Hernández et al., J Appl Physiol 108: 1169-1176, 2010). Simulated muscle O2 uptake and oxygenation kinetics with different blood flows indicate (1) faster O2 delivery is responsible for slower muscle oxygenation kinetics; (2) Hb and Mb contributions to the HbMbO2 are similar (40-60%); and (3) Hb and Mb contributions to the HHbMb are significantly different, 80% and 20%, respectively. The effect of slow blood flow kinetics on oxygenated Hb and Mb contributions is minimal. However, the effect on the imbalance between O2 delivery and utilization rates causes significant overshoots and undershoots of deoxygenated Hb and Mb contributions. Model analysis in combination with NIRS measurements and information on hemodynamic and microvascular distribution can help to determine the use of NIRS signal in evaluating the factors limiting exercise tolerance in health and disease states.

A randomized controlled trial of motivational interviewing as a tool to enhance secondary prevention strategies in cardiovascular disease (MICIS study).

Physical activity/exercise has consistently been shown to improve objective measures of functional capacity, enhance quality of life, improve coronary risk profile, and reduce mortality for individuals with coronary heart disease. Despite the gains achieved by those who attend cardiac rehabilitation (CR) many individuals fail to maintain lifestyle changes.The aims of this study were to evaluate the effectiveness of motivational interviewing as a strategy for promoting maintenance of cardiac risk factor modification in patients who had participated in standard, 6-week outpatient CR programs.In a randomized controlled trail, participants in usual care and intervention group (Motivational interviewing supplemental to a standard 6-week CR program) were followed up at 6-weeks and 12-months. The primary outcome was distance walked on the six-minute walk test (6MWT), used as both an indicator of functional capacity and habitual physical activity. Secondary outcomes included modifiable coronary risk factors (smoking, self-reported physical activity, waist circumference, body mass index and medication adherence), psychological status (depression, anxiety, stress, perceived cardiac control, perceived social support, exercise self-efficacy) and quality of life.Total 110 patients, usual care (n = 58) and intervention (n = 52), consented to participate in the study. Overall, demographic and clinical characteristics did not differ between groups at baseline. Motivational interviewing was no more likely to promote maintenance of cardiac risk factor modification (both primary and secondary outcomes) than a standard CR program alone. Both intervention and control groups maintained the gains achieved during CR at the 12-month follow-up except for weight loss.Although both groups maintained the gains achieved during CR for physical activity, there was no effect of the intervention on maintenance of cardiac risk factor modification on both primary and secondary outcomes.

Clinical features and management of COVID-19: A systematic review.

Novel coronavirus disease, the latest world pandemic is one of the most contagious viral infections to date. There has been a lack of uniformity on recognizing this condition clinically because of poorly understood pathophysiology and clinical nature. Also due to ongoing clinical trials, its management is also varied. This is a systematic review from evidence-based studies until March 1st, 2020, covering an update on its clinical features and management. This study shows the multisystem involvement of COVID-19 with dominant respiratory features followed by the musculoskeletal, gastrointestinal system and others. The clinical features varied from asymptomatic to severe forms. Major causes of fatality were acute respiratory distress syndrome, shock, acute cardiac injury, acute kidney injury, rhabdomyolysis, and arrhythmia. Major modalities of management included supportive, antiviral and antibiotic therapy. There was no direct relationship between the specific treatment and the outcome.

Clinical features and management of COVID-19: A systematic review

@#Novel coronavirus disease, the latest world pandemic is one of the most contagious viral infections to date. There has been a lack of uniformity on recognizing this condition clinically because of poorly understood pathophysiology and clinical nature. Also due to ongoing clinical trials, its management is also varied. This is a systematic review from evidence-based studies until March 1st, 2020, covering an update on its clinical features and management. This study shows the multisystem involvement of COVID-19 with dominant respiratory features followed by the musculoskeletal, gastrointestinal system and others. The clinical features varied from asymptomatic to severe forms. Major causes of fatality were acute respiratory distress syndrome, shock, acute cardiac injury, acute kidney injury, rhabdomyolysis, and arrhythmia. Major modalities of management included supportive, antiviral and antibiotic therapy. There was no direct relationship between the specific treatment and the outcome.

Slip pulse and resonance of the Kathmandu basin during the 2015 Gorkha earthquake, Nepal.

Detailed geodetic imaging of earthquake ruptures enhances our understanding of earthquake physics and associated ground shaking. The 25 April 2015 moment magnitude 7.8 earthquake in Gorkha, Nepal was the first large continental megathrust rupture to have occurred beneath a high-rate (5-hertz) Global Positioning System (GPS) network. We used GPS and interferometric synthetic aperture radar data to model the earthquake rupture as a slip pulse ~20 kilometers in width, ~6 seconds in duration, and with a peak sliding velocity of 1.1 meters per second, which propagated toward the Kathmandu basin at ~3.3 kilometers per second over ~140 kilometers. The smooth slip onset, indicating a large (~5-meter) slip-weakening distance, caused moderate ground shaking at high frequencies (>1 hertz; peak ground acceleration, ~16% of Earth's gravity) and minimized damage to vernacular dwellings. Whole-basin resonance at a period of 4 to 5 seconds caused the collapse of tall structures, including cultural artifacts.

Prevalence of Occlusal Traits in the Deciduous Dentition of Children of Kaski District, Nepal.

INTRODUCTION: The prevalence of occlusal traits varies among various populations. Ethnic, genetic and environmental factors are the major contributors, with a role in the specific cause of malocclusion. The aim of this epidemiological study was to assess the prevalence of occlusal traits in the deciduous dentition of children of Kaski District,Nepal. METHODS: A total of 506 children (251 girls, 255 boys), aged 3-5 years, were assessed. The occlusion examination was carried out by three examiners, in the school camps,community dental care centre and general health camps, utilizing a mouih mirror and probe. Intra investigator error was calculated using kappa statistics. The data were analyzed by the statistical program SPSS version 17 using the Chi-square test. RESULTS: The present study studied occlusal traits of 506 children (251 girls, 255 boys), aged 3-5 years. The study result showed that bilateral mesial step seen in 40.3%,bilateral flush terminal plane in 33.5%, bilateral distal steps in 8.5%,mesial step one side and flush terminal other side in 12.7%,mesial step one side and distal step other side in 2.6%,flush terminal one side and distal step other side in 2.4%,anterior crossbite in 3%,posterior crossbite in 0.4% and non-spaced dentition in 20% children. CONCLUSIONS: Mesial step was the most prevalent followed by straight terminal plane and the distal terminal plane showed least prevalence. There were diverse traits for malocclusion. There was no significant difference(p>0.05) in occlusal traits between male and female children.

Association of serum LDL cholesterol level with periodontitis among patients visiting a tertiary-care hospital.

INTRODUCTION: High low-density lipoproteins (LDL) cholesterol is one of the major risk factors for cardiovascular disease. In recent years, some evidence has been presented that periodontitis, an infectious inflammatory condition of the periodontium, is associated with an increased risk of cardiovascular disease. To further elucidate this association, we have studied the levels of LDL cholesterol, a known risk marker for cardiovascular disease, in a periodontally-diseased group. METHODS: The levels of serum LDL cholesterol in 47 subjects with mild to severe (clinical attachment loss equal to or greater than 1 mm) chronic generalized (at least 30% of teeth affected) periodontitis with the mean age of 42.21 ± 1.46 years were measured and compared with those obtained from 42 age (39.83 ± 0.94) and sex matched controls. Both groups were free from systemic illnesses. RESULTS: The mean serum LDL cholesterol in periodontitis patients was found to be significantly higher (P < 0.001) as compared to that of the controls. The mean clinical attachment loss was positively correlated with serum LDL cholesterol (P < 0.01) and gingival index (P<0.05). The frequency of persons with pathologic values of LDL cholesterol was significantly higher in periodontitis patients compared with that of the controls. CONCLUSIONS: These results showed that high serum LDL cholesterol may be associated with periodontitis in healthy people. However, it is unclear whether periodontitis causes an increase in the levels of serum LDL or an increased LDL is a risk factor for both periodontitis and cardiovascular disease.

Tricuspid valve repair: DeVega's tricuspid annuloplasty in moderate secondary tricuspid regurgitation.

BACKGROUND: Moderate secondary tricuspid incompetence has variable natural history if left unattended during mitral valve surgery. Recent data suggest progression of the secondary tricuspid incompetence over time.Secondary moderate tricuspid regurgitation in rheumatic mitral valve disease may regress after mitral valve surgery without direct intervention. OBJECTIVES: The present study was done to assess early result of DeVega tricuspid valve annuloplasty amongst those with moderate tricuspid regurgitation due to rheumatic mitral valve disease. METHODS: Group I(mitral value replacement with tricuspid repair) and group II (mitral value replacement only).The two groups were followed up at three months post-operatively and evaluated for their functional class and echocardiography variables. RESULTS: There were 43 patients who underwent mitral valve replacement with moderate tricuspid regurgitation. 23 underwent mitral valve replacement with tricuspid repair group (Group 1). Most of the patients were women (28/43). The mean age was 31.4 + 14.8 and 25.13 + 9.4 years. Group I had 21(91.3%) and Group II had 17 (85%) in NYHA class III and IV. The pre-operative echocardiographic cardiac left ventricular and left atrial dimensions, Left ventricular function and valve lesions were statistically similar for both groups, except PASP was higher amongst tricuspid repair (Group 1: 38.60 + 12.75 mHg, Group 2: 61.52 + 19.76 mmHg; p equals or less than 0.05). At three month review after surgery, four patients were in NYHA II amongst those without tricuspid repair (Group II), whilst the rest were in NYHA I. Left ventricular dimensions, Left Ventricular function and valve prosthetic valve function were similar between groups. Eleven (47.8%) patients in Group I and only five (25%) of Group II had trace or less TR at the follow-up. This was found to be statistically significant on chi square test (p less than 0.05). There were 7 (16.2%) patients who had persistent moderate TR. Higher PASP and larger LV dimensions at three months were predictive of persistent moderate TR. CONCLUSION: Mitral valve replacement does decrease the severity of tricuspid regurgitation amongst those with secondary moderate tricuspid regurgitation by at least one grade, but DeVega's annuloplasty confers a better repair result.

Impalement injury to the heart.

Cardiac impalement injury is rare and one of the most severe penetrating chest injuries, often fatal. The management of penetrating cardiac injuries is a challenging one. The success in management of impaling cardiac trauma requires stabilization of the impaling object, expeditious transfer to a facility for open heart surgery, rapid imaging, access to blood and blood products and a ready surgical team. We report a case of impalement injury to the heart by a stick, transfixing the right ventricle and its successful treatment.

A study on complication and monitoring of warfarin in post-valve surgery.

INTRODUCTION: This study was carried out to determine the incidence of complication related to warfarin in patients with valve surgery and identify potential risk factors for complication and study its monitoring aspects. METHODS: A combined retrospective and prospective observational study including a total of 185 patients who underwent mechanical valve replacement in Shahid Gangalal National Heart Centre. The study was conducted from 4 November 2006 till 1 February 2007. RESULTS: There were a total of 141 episodes of bleeding. Among them significant bleeding occurred in 15.7% patients, major bleeding was 3.2 per 100 patient-years (3.8%) and minor bleeding was 11.8 per 100 patient-years (11.9%). Epistaxis (16.8%) was the most common bleeding complication. Menorrhagia was the most common bleeding complication in females with 20.5 per 100 patient-years (27.4%). Thromboembolic complications occurred at the rate of 2.3 per 100 patient-years. Patients on warfarin were outside the INR target range 67.8% of the time, with 21% INR values above range and 46.8% INR values below range. However, dose adjustment was done only 31.8% of times when INR was outside range. CONCLUSIONS: There is high incidence of bleeding complication in patients on warfarin and hypertension is significantly associated with bleeding. Difficulty in tightly controlling INR probably is related to high incidence of bleeding. Better patient education, stricter adjustment of INR, frequent monitoring of INR at peripheral hospitals and standardization of the test at different hospitals are suggested to reduce the warfarin related complications.

Erosive oral lichen planus and its management: a case series.

Lichen planus (LP), although a dermatosis, is more common in the oral mucous membrane than in the skin. Lesions of oral LP are classically found on the buccal mucosa and gingiva. Among the various types, the reticular lesions are asymptomatic and require no treatment, but pain and severe discomfort accompany the erosive or ulcerative lesions. Malignant transformation to squamous cell carcinoma developing in areas of erosive oral LP (EOLP) being a possibility, it is important for clinicians to maintain a high index of suspicion for all intraoral lichenoid lesions. Therefore, periodic follow-up of all patients with EOLP is recommended. In view of the above, this paper highlights the management of four cases of EOLP with topical corticosteroid and CO2 laser surgery.

Patients choice for method of early abortion among comprehensive abortion care (CAC) clients at Kathmandu Medical College Teaching Hospital (KMCTH).

OBJECTIVE: The over all objective of the study was to determine different methods of abortion opted by CAC clients at KMCTH. The specific objective of the study was to know the reasons for pregnancy termination and to know the reasons opted for either medical or surgical method of abortion. METHODOLOGY: A hospital based prospective study was carried out for a period of six months at KMCTH from 1st January 2006 to 31st June 2006. All the patient undergoing CAC services were included for the study. Clients were provided with written and verbal information regarding the methods of terminating early abortion and its associated complications. After that they were asked to give their informed choice and decision. All the pertinent information was entered on pre-structured questionnaire. RESULTS: During the study period a total of 100 patients underwent CAC services. The commonest reason for termination pregnancy was no desire for additional children (60%) followed by youngest child too small or short spacing (21%). 74% of the patients opted for surgical abortion, 23% patient opted for medical abortion and 3% of the patient remain undecided. Reasons for favouring surgical method of abortion was that surgical abortion is complete (35), repeated visits are avoided (18), quick (10) would be with service provider and feel safe (5), lack of expectancy (2) side effect of medical treatment (1), twin pregnancy (1), easy (1), fear of pain (1). Medical method of abortion was favoured due to fear of surgery (9), easy and less painful (8) and maintains privacy (6). CONCLUSION: Factors affecting the choice of abortion method appear to be numerous and complex. Providers need to be sensitive to differences in women's values and life circumstances when counselling them about an abortion method. In particular, providers should incorporate into their counselling sessions what women need to know about the characteristics of abortion methods and help women to identify what is the best option for them. Key words: Early abortion medical methods, surgical methods, choice.