Bone mineral density, vertebral fractures and trabecular bone score in primary ovarian insufficiency.

PURPOSE: Bone health in primary ovarian insufficiency (POI) is under-investigated. We assessed patients with spontaneous POI for vertebral fractures (VFs) and related parameters of bone health. METHODS: 70 cases with spontaneous POI (age 32.5 ± 7.0 years) and an equal number of controls were assessed for BMD, TBS, and VFs. BMD at the lumbar-spine (L1-L4), left hip, non-dominant forearm, and TBS (iNsight software) were measured on a dual-energy X-ray absorptiometry (DXA) machine. VFs were assessed by Genant's classification. Serum FSH, LH, estradiol, T4, TSH, iPTH, serum 25(OH)D, total calcium, and inorganic phosphorus were measured. RESULTS: BMD at the lumbar-spine, hip and forearm was reduced by 11.5%, 11.4% and 9.1% in POI as compared to controls (P < 0.001). Degraded or partially degraded microarchitecture on TBS was observed in 66.7% of patients and 38.2% of controls (P = 0.001). 15.7% of the POI patients had VFs, compared to 4.3% of controls (P = 0.045). Age, duration of amenorrhea and duration of HRT use were the significant predictors of TBS (P < 0.01). Serum 25(OH)D was the significant determinant of VFs. TBS abnormalities were higher in patients with POI and VFs. BMD was not significantly different in patients with and without VFs. CONCLUSION: Thus, lumbar-spine osteoporosis, impaired TBS and VFs were present in 35.7%, 66.7% and 15.7% of patients with spontaneous POI in their early third decade. This indicates need for rigorous investigations for impaired bone health in these young patients and management with HRT, vitamin-D, and possible need for bisphosphonate therapy.

Vertebral fractures, trabecular bone score and their determinants in chronic hypoparathyroidism.

PURPOSE: Patients with hypoparathyroidism are at risk of vertebral fractures (VFs) despite high bone mineral density (BMD). We investigated this paradox by assessing trabecular bone score (TBS) and hip structural analysis (HSA) in non-surgical chronic hypoparathyroidism (cHypoPT) with and without VFs. METHODS: 152 cHypoPT patients (age 40.2 ± 13.4 years, M: F = 81:71) with a median follow-up of 8 (2-13) years were assessed for BMD, VFs, TBS, and HSA and compared with 152 healthy controls. VFs at T7-L4 were assessed by Genant's method. Average serum total calcium and phosphorus during follow-up were assessed. RESULTS: The lumbar spine and hip BMD were higher by 25.4 and 13.4% in cHypoPT than controls (P < 0.001). Paradoxically, VFs (30.9 vs.7.9%), including multiple (12.5 vs. 2.6%) were higher in cHypoPT (P < 0.001). Though overall average TBS (1.411 ± 0.091) was normal in cHypoPT, 25.4% of the females had subnormal TBS, more in post than pre-menopausal women (52.3 vs. 14%, P = 0.002) and as compared to males (6.1%, P = 0.001). TBS correlated with menopausal status and follow-up serum calcium-phosphorus product. For every gm/cm2 rise in BMD, TBS increase was only 0.227 in cHypoPT compared to 0.513 in controls. Frequency of VFs increased with declining TBS (P = 0.004). HSA was comparable between cHypoPT with and without VFs. 23.4% of cHypoPT with VFs had subnormal TBS. CONCLUSION: 31% of cHypoPT patients had VFs. TBS indicated degraded bone microarchitecture in 50% of the post-menopausal cHypoPT women. However, TBS has limitations to detect abnormal bone microarchitecture in cHypoPT as only one-fourth of patients with VFs showed low TBS.

Bioremediation of heavy metals from wastewater: a current perspective on microalgae-based future.

Heavy metals-containing drinking water and wastewater are posing a severe threat to the environment, and living beings on land, air and water. Different conventional, advanced nanomaterials-based and biological method has been employed for the treatment of heavy metals. Among the biological methods, microalgae are an important group of micro-organisms that have numerous environmental applications and can remediate heavy metals from wastewater. Also, it has numerous advantages over conventional remediation processes. Microalgae cells can uptake the heavy metal via different physiological and biological methods and are utilized as a nutrient source to regulate its metabolic process for the production of biomass. Furthermore, the enhancement in heavy metal removal efficiency can be improved using different strategies such as immobilization of algal cells, development of algal consortia and designing of microalgae-based nanocomposite materials. Also, it can significantly contribute towards environmental sustainability and future. Thus, the review provides a critical overview of heavy metals and their existence along with their negative effects on humans. This review provides insight on recent advanced nanomaterial approaches for the removal of heavy metals, overviews of microalgae-based heavy metal uptake mechanisms and their potential for the amputation of different heavy metals. Furthermore, the special focus is on recent strategies that enhance heavy metal removal efficiency and contribute towards sustainability for the development of a microalgae-based future.

Response of modified microclimates on growth, yield, and incidence of rhizome rot disease of ginger in Assam, India.

Field experiments were conducted at Biswanath, Assam, India (26° 42' N and 93° 15' E), during 2016, 2017, and 2018, to evaluate the effect of microclimates on growth, yield, and disease incidence in the ginger crop. The ginger variety Nadia was grown under six microclimates, viz., under shade net for the entire crop season (T1), under shade net from planting to mid-October (T2), with pigeon pea (T3), with maize (T4), with okra (T5), and as a sole crop (T6) in three replicated RBD. Photosynthetically active radiation (PAR), net radiation (Rn), temperature above the ginger canopy, soil temperature, and soil moisture were measured during the critical crop growth period under different microclimates. Recording of rhizome rot disease incidence was done periodically and genomic analysis of pathogen was carried out. PAR recorded above the ginger canopy under T6 was 1688.1 µ mol s-1 m-2, which was attenuated up to 80.1% in other microclimates. The Rn load of the ginger canopy was maximum (446.4 W m-2) under T6, which reduced to below 50 W m-2 under both T3 and T4. Both air temperatures above the ginger canopy and soil temperatures under T3 and T4 were reduced by 3.3 °C and 4.6 °C, respectively, as compared to T6. The pathogen causing the disease in the experimental site was identified as Fusarium oxysporum. Considerable increase in soil and air temperature and soil moisture favored disease incidence (90.3%) under shade net (T1 and T2) treatments, while opposite reason causing significant reduction in disease incidence (16.1%) was observed under T3 and T4. More yield of ginger recorded in treatments T3 (6.21 t ha-1) or T4 (6.48 t ha-1) was attributed to better crop growth and diminutive disease incidence, while the crop was almost damaged due to severe disease incidence under shade net (T1 and T2) treatments.

Growth and digestive enzyme activities of rohu labeo rohita fed diets containing macrophytes and almond oil-cake.

The impact of plant-based diets on the digestive physiology of rohu Labeo rohita fingerlings (10.66 ±â€¯0.53 g) was evaluated. A diet with all protein supplied by fishmeal was included as a control (F). Four test diets containing 300 g/kg protein were formulated using the following plant ingredients and fishmeal in a 1:1 blend: almond oil-cake Terminalia catappa (FTC), duckweed Lemna minor (FLM), water fern Salvania molesta (FSM) and combination of these three ingredients (FTCLMSM). The final body weight and specific growth rate were significantly higher in rohu fed diet FLM compared to the other treatments. Significantly lower feed conversion ratio in rohu fed diet FLM showed that diet was utilized efficiently in this feeding regime compared to the other diets. The composition of diets also influenced the digestive enzyme activities of the fish. Thus, amylase, trypsin and chymotrypsin activities were significantly higher in rohu fed diet FLM compared to the rohu fed the other diets. Protease activity was significantly higher in rohu fed diets FTC and F and lipase activity was significantly higher in rohu fed diet FTC compared to the rohu fed the other diets. The inclusion of raw duckweed in feed replaced 300 g/kg of dietary fishmeal without affecting growth.

An IL-10 dominant polarization of monocytes is a feature of Indian Visceral Leishmaniasis.

Leishmania donovani, the causative parasite of Visceral Leishmaniasis (VL), deviously manipulates host monocytes/macrophages to ensure its survival. Although monocytes/macrophages from patients with VL have demonstrated an impaired oxidative burst and antigen presentation, an unanswered yet pertinent question remains as to whether they are deactivated or alternatively activated. The significantly raised plasma levels of IL-4/IL-13 and IL-10 in VL patients suggested a microenvironment conducive for alternative activation of monocytes/macrophages. Accordingly, the classical markers for IL-4-driven monocytes/macrophages [M(IL-4)] were studied namely intramonocytic CD206+ , circulating CCL22 and CCL17, and were unchanged. Furthermore, the mRNA expression of Kruppel-like factor 4 (KLF4), peroxisome proliferator-activated receptors (PPAR)-γ and arginase-I (ARG-I) in peripheral blood mononuclear cells was unaltered. However, markers for IL-10-driven monocytes/macrophages [M(IL-10)], namely soluble CD163, intramonocytic IL-10, and circulating CXCL13 were significantly increased. Monocytes/macrophages of patients with VL demonstrated an increased expression of markers for M(IL-10), along with the absence of markers for M(IL-4). Taken together, in human VL, manipulation of these IL-10 polarized monocytes-macrophages may pave the way for improved therapeutic outcomes.

Genetic analysis of river, swamp and hybrid buffaloes of north-east India throw new light on phylogeography of water buffalo (Bubalus bubalis).

This study analysed buffaloes from north-east India and compared their nuclear and mitochondrial DNA variations with buffaloes of mainland India, China, Mediterranean and South-East Asia. Microsatellite genotypes of 338 buffaloes including 210 from six north-east Indian buffalo populations and three mainland Indian breeds were analysed to evaluate their genetic structure and evolutionary relationships. Phylogenetic analysis and multidimensional scaling plot of pairwise FST revealed the clustering of all swamp-type buffaloes of north-east India with Lower Assamese (significantly hybrid type) buffaloes in one plane and all the mainland river buffaloes in another plane while the upper Assamese buffaloes being distinct from both these clusters. Analysis of mtDNA D-loop region of 530-bp length was performed on 345 sequences belonging to 23 buffalo populations from various geographical regions to establish the phylogeography of Indian water buffalo. The swamp buffaloes of north-east India clustered with both the lineages of Chinese swamp buffalo. Multidimensional scaling display of pairwise FST derived from mitochondrial DNA data showed clustering of upper Assamese, Chilika and Mediterranean buffaloes distinctly from all the other Indian buffalo populations. Median-joining network analysis further confirmed the distinctness and ancestral nature of these buffaloes. The study revealed north-east region of India forming part of the wider hybrid zone of water buffalo that may probably extend from north-east India to South-East Asia.

Potential contribution of monoamine oxidase a gene variants in ADHD and behavioral co-morbidities: scenario in eastern Indian probands.

Attention deficit hyperactivity disorder (ADHD) is the most frequently diagnosed behavioral disorder in children with a high frequency of co-morbid conditions like conduct disorder (CD) and oppositional defiant disorder (ODD). These traits are controlled by neurotransmitters like dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of amines, has been reported to be associated with aggression, impulsivity, depression, and mood changes. We hypothesized that MAOA can have a potential role in ADHD associated CD/ODD and analyzed 24 markers in a group of Indo-Caucasoid subjects. ADHD probands and controls (N = 150 each) matched for ethnicity and gender were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV. Appropriate scales were used for measuring CD and ODD traits. Markers were genotyped by PCR-based methods and data obtained analyzed using the Cocaphase program under UNPHASED. Only eight markers were found to be polymorphic. rs6323 "G" allele showed higher frequencies in ADHD (P = 0.0023), ADHD + CD (P = 0.03) and ADHD + ODD (P = 0.01) as compared to controls. Haplotype analysis revealed statistically significant difference for three haplotypes in ADHD cases (P < 0.02). Statistically significant differences were also noticed for haplotypes in ADHD + CD and ADHD + ODD cases (P < 0.01). LD analysis showed significant variation in different groups. Multidimensionality reduction analysis showed independent as well as interactive effects of markers. Genotypes showed correlation with behavioral problems in ADHD and ADHD + CD. We interpret that MAOA gene variants may contribute to the etiology of ADHD as well as associated co-morbid CD and ODD in this ethnic group.

Impact of sodium-glucose cotransporter-2 inhibitor use on peak VO2 in advanced heart failure patients.

Introduction: Advanced heart failure (HF) is an epidemic that affects multiple organ systems with high morbidity and mortality rates despite optimal medical therapy (OMT) and remains the leading cause of hospitalizations in type 2 diabetes-related cardiovascular disease. The addition of sodium-glucose co-transporter inhibitors (SGLT2i) in treating these patients has seen improved mortality and hospital admission rates. As such, we felt it was important to investigate whether the use of SGLT2i improved functional capacity in patients with HF when compared to OMT by evaluating maximum oxygen consumption (peak VO2) using cardiopulmonary exercise testing (CPET). Methods: We found 94 heart failure patients between August 2020 and August 2021 who underwent CPET before and after treatment at Mayo Clinic in Florida. 50 patients received OMT and 44 received OMT and SGLT2i therapy. CPET results before and after were compared for each group. Results: The baseline ejection fraction was not significantly different between groups, with the OMT group at 38% and the SGLT2i group at 33%, p = 0.10. OMT patients were found to have a significantly lower hemoglobin A1c of 5.7 (5.4-6.1) compared to those with SGLT2i therapy of 6.4 (5.8-7.1), p = 0.01. The baseline peak VO2 was 17.3 ml/kg/min (13.3-21.6) in the OMT group and 17.3 ml/kg/min (14.4-18.9) in the SGLT2i group, p = 0.18, not significantly different. The interesting finding is that the follow-up peak VO2 at one year for the OMT group was 17 ml/kg/min (13.3-21.6), which was not significantly different from the SGLT2i group peak VO2 of 17 ml/kg/min (14.6-19.6), p = 0.19. Our study is the first to compare before and after peak VO2 values of the OMT+SGLT2i group to the patient's own baseline and we found no significant improvement. Conclusion: Our single-center data shows no improvement in functional capacity after the addition of SGLT2i therapy to OMT in patients with advanced heart failure. Improved hospitalization and symptoms may be attributed to other numerous effects of SGLT2i such as volume management.

Molecular monitoring of treatment efficacy in human visceral leishmaniasis.

BACKGROUND: Focused efforts of the visceral leishmaniasis elimination program have led to a drastic decline in cases, and the present challenge is disease monitoring, which this study aimed to assess. METHODS: A Leishmania kinetoplastid-targeted qPCR quantified parasite load at disease presentation, and following treatment completion (n=49); an additional 80 cases were monitored after completion of treatment. RESULTS: The parasite load at disease presentation was 13 461.00 (2560.00-37764.00)/µg gDNA, which upon completion of treatment reduced in 47 of 49 cases to 1(1-1)/µg gDNA, p<0.0001. In 80 cases that presented >2 months post-treatment, their parasite burden similarly decreased to 1(1-1)/µg gDNA except in 6 of 80 cases, which were qPCR positive. CONCLUSION: In 129 cases of visceral leishmaniasis, qPCR by quantification of parasite burden proved effective for monitoring treatment.

A foe incognito: an interesting case of pleurisy.

Though pleuritis and pleural effusion are common in lupus patients they are distinctly rare as the initial manifestation of lupus. Diagnosis of lupus pleuritis is also a difficult task and often costly and lengthy immunological panels are employed to diagnose it. We report one case of systemic lupus erythematosus (SLE) presenting with lupus pleuritis as the first manifestation. We propose that demonstration LE cells have a very prominent role in differentiating lupus pleuritis from other causes of pleural effusions in SLE patients. We believe that our case is the first report from India which shows pleuritis may be a first manifestation of lupus.

Early seizures in first-ever acute stroke patients in India: incidence, predictive factors and impact on early outcome.

BACKGROUND AND PURPOSE: Stroke-associated early seizures (ES) often complicate the initial course of acute stroke. This study intended to estimate the rate of and the predictive factors for ES and the impact of ES on the clinical outcome in patients with first-ever acute stroke. MATERIALS AND METHODS: Consecutive patients with first-ever acute stroke admitted in the Department of Medicine from June 2010 to December 2011 were prospectively included. ES were defined as seizures occurring within 7 days from acute stroke. Patients with history of epilepsy, transient ischaemic attack, subarachnoid haemorrhage and cerebral venous thrombosis were excluded. Clinical outcomes were measured under the subheadings of mortality and disability at discharge, according to modified Rankin score. RESULTS: Of the 441 (56.92% male patients, median age 55 years, 49.43% had haemorrhagic stroke) patients, 79 (17.91%, 95% confidence interval (CI): 14.61-21.78%) suffered from ES. At discharge, 37.64% were disabled, and 19.5% were dead. In multivariate analysis, alcoholism, NIHSS at admission, haemorrhagic stroke and cortical location were significant predictors of ES. Thirty-day mortality was predicted by NIHSS at admission [hazard ratio (HR): 1.14, 95% CI: 1.11-1.18, P < 0.001], history of hypertension (HR: 3.79, 95% CI: 2.1-6.85, P < 0.001), history of alcoholism (HR: 2.43, 95% CI: 1.49-3.95, P < 0.001) and early seizure (HR: 2.58, 95% CI: 1.54-4.34, P = 0.001). CONCLUSIONS: Early seizures occurred in about 18% acute stroke patients. Alcoholism, haemorrhagic stroke, cortical and severe strokes predict development of ES. ES are an independent important risk factor for early mortality.

Testing urine samples with rK39 strip as the simplest non-invasive field diagnosis for visceral leishmaniasis: an early report from eastern India.

BACKGROUND: Diagnosis of visceral leishmaniasis (VL) is a major obstacle in the control of this disease. The rK39 strip-test using patient's blood is a breakthrough; however, it still requires a blood sample, which is a concern for safety in the field. We tried to simplify the test using the patient's urine instead of blood. AIMS: To observe the sensitivity and specificity of the urine test in comparison with the blood test. MATERIALS AND METHODS: We tested active and post-treatment VL patients, Post Kala azar dermal leishmaniasis (PKDL), VL/HIV and control subjects (healthy, disease suspects and diseased other than VL) with the rK39 strip-test using blood and urine samples. STATISTICAL ANALYSIS: The level of agreement between the urine and blood testing was calculated by inter-rater agreement (kappa) statistics. RESULTS: Forty-two active VL, 40 treated VL, six PKDL, three VL/HIV and 139 controls (54 healthy, 21 disease suspects and 64 diseased other than VL) were tested. All VL-related cases showed positive results with urine as well as blood samples (100%). The urine testing was found to have 100% sensitivity and 86.33% specificity for the diagnosis of VL. Kappa statistic between the two methods was 0.916 (P<0.001). Urine testing had more false-positive results in comparison with blood testing (13.67% vs. 9.45%), but the test subjects were from VL-endemic areas and they might be exposed to Leishmania donovani infection. CONCLUSIONS: The present study has the potentiality of providing a new, yet simplest non-invasive screening tool for VL in remote rural areas.

First Report of Ascochyta Blight Caused by QoI-Resistant Isolates of Ascochyta rabiei in Chickpea Fields of Nebraska and South Dakota.

Ascochyta blight, caused by Ascochyta rabiei, is a serious disease of chickpea (Cicer arietinum) and fungicide applications are used to manage the disease in the North Central plains (4). During the 2010 growing season, a commercial field near Stanley, SD was treated with pyraclostrobin (Headline, BASF, NC) and called a management failure by the grower. Similarly, limited efficacy of pyraclostrobin was observed in an ascochyta research trial near Scott's Bluff, NE. In both locations, symptoms and signs consistent with A. rabiei infection existed on leaves, stems, and pods; namely, circular brown lesions with concentric rings of dark brown pycnidia. Symptomatic samples were collected, disinfected with 95% ethanol for 1 min, rinsed with sterile water, placed in 0.5% NaOCl for 1 min, and rinsed again with sterile water for 1 min (4). Samples were air dried, placed on potato dextrose agar (PDA) plates for 3 to 7 days, and colonies with morphological characteristics typical of A. rabiei were single-spored and transferred to new PDA plates and incubated for 7 to 14 days. Three and six putative A. rabiei isolates were obtained from South Dakota and Nebraska samples, respectively. Morphological characteristics were consistent with A. rabiei; cultures were brown with concentric rings of dark, pear-shaped pycnidia with an ostiole, and conidia were hyaline, single-celled, and oval-shaped (2). Comparison of the internal transcribed spacer (ITS) region amplified from the genomic DNA of 3-day-old liquid cultures using ITS4/ITS5 primers by BLASTN searches using the nr database in GenBank (Accession Number FJ032643) also confirmed isolates to be A. rabiei. Mismatch amplification mutation assay (MAMA) PCR was used for detection of sensitive and resistant isolates to QoI fungicides (1). Confirmation of the presence of the G143A mutation was carried out by cloning an mRNA fragment of the cytochrome b gene using cDNA synthesized from total RNA of A. rabiei and CBF1/CBR2 (1,3). Total RNA was extracted from 3-day-old liquid cultures and it was used instead of genomic DNA for this PCR to avoid large intronic regions commonly present in mitochondrial genes. The G143A mutation has previously been correlated with resistance to QoI fungicides in other fungal plant pathogens (3). Also, these isolates were determined to be QoI-resistant in vitro by PDA amended with a discriminatory dose of 1 µg/ml of azoxystrobin (4). To our knowledge, this is the first report of QoIresistant A. rabiei isolates causing infections on chickpeas in South Dakota and Nebraska. QoI-resistant isolates were reported in North Dakota and Montana in 2005 and 2007, respectively (4). Of nearly 300 isolates collected from these states from 2005 and 2007, approximately 65% were determined to be QoI resistant (4). The widespread occurrence of QoIresistant isolates and reduction of fungicide performance in fields led the North Dakota State University Cooperative Extension Service to actively discourage the use of QoI fungicides on chickpeas in North Dakota and Montana (4). It is likely that similar recommendations will need to be adopted in South Dakota and Nebraska for profitable chickpea production. References: (1) J. A. Delgado, 2012 Ph.D. Diss. Department of Plant Pathology, North Dakota State University. (2) R. M. Harveson et al. 2011. Online. Plant Health Progress doi:10.1094/PHP-2011-0103-01-DG. (3) Z. Ma et al. Pestic. Biochem. Physiol. 77:66, 2003. (4) K. A. Wise et al. Plant Dis. 93:528, 2009.

Characterization and Pathogenicity of Rhizoctonia solani Isolates Affecting Pisum sativum in North Dakota.

Acreage of dry field pea (Pisum sativum) in North Dakota has increased approximately eightfold from the late 1990s to the late 2000s to over 200,000 ha annually. A coincidental increase in losses to root rots has also been observed. Root rot in dry field pea is commonly caused by a complex of pathogens which included Fusarium spp. and Rhizoctonia solani. R. solani isolates were obtained from roots sampled at the three- to five-node growth stage from North Dakota pea fields and from symptomatic samples received at the Plant Diagnostic Lab at North Dakota State University in 2008 and 2009. Using Bayesian inference and maximum likelihood analysis of the internal transcribed spacer (ITS) region of the ribosomal DNA (rDNA), 17 R. solani pea isolates were determined to belong to anastomosis group (AG)-4 homogenous group (HG)-II and two isolates to AG-5. Pathogenicity of select pea isolates was determined on field pea and two rotation hosts, soybean and dry bean. All isolates caused disease on all hosts; however, the median disease ratings were higher on green pea, dry bean, and soybean cultivars when inoculated with pea isolate AG-4 HG-II. Identification of R. solani AGs and subgroups on field pea and determination of relative pathogenicity on rotational hosts is important for effective resistance breeding and appropriate rotation strategies.

Monitoring of intracellular nitric oxide in leishmaniasis: its applicability in patients with visceral leishmaniasis.

Nitric oxide (NO) has been demonstrated to be a principal effector molecule responsible for mediating intracellular killing of Leishmania parasites, the causative organism of leishmaniasis. As measurement of intracellular NO remains a challenge to biologists, we have developed a flow cytometric approach to perform real time biological detection of NO within Leishmania parasites and parasitized macrophages using a membrane permeable derivative of diaminofluorescein [4,5-diaminofluorescein diacetate (DAF-2DA)]. Initially, assay optimization was performed in Leishmania donovani promastigotes, assay specificity being confirmed using both a NO donor [S-nitroso-N-acetyl-penicillamine (SNAP)] and a NO scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, C-PTIO]. Using 40 µM DAF-2DA, basal levels of intracellular NO were measured which varied in different Leishmania species; addition of conventional anti-leishmanial drugs, antimony and miltefosine translated into a dramatic increase in DAF-2T fluorescence. Furthermore, the assay also measured levels of NO in macrophages, but needed a 20 fold lower concentration of DAF-2DA, being 2 µM. Following parasitization, levels of NO decreased which was normalized following treatment with anti-leishmanial drugs. Similarly monocytes of patients with visceral leishmaniasis at disease presentation showed decreased levels of NO which too reverted on completion of treatment. Taken together, this study opens new perspectives of research regarding monocyte function and provides a real time approach for monitoring the effect of anti-leishmanial compounds.

Adrenergic and myogenic regulation of viscoelasticity in the vascular bed of the human forearm.

This study tested the hypothesis that the compliance (C) and viscoelasticity (K) of the forearm vascular bed are controlled by myogenic and/or α-adrenergic receptor (αAR) activation. Heart rate (HR) and waveforms of brachial artery blood pressure (Finometer) and forearm blood flow (Doppler ultrasound) were measured in baseline conditions and during infusion of noradrenaline (NA; αAR agonist), with and without phentolamine (αAR antagonist; n = 10; 6 men and 4 women). These baseline and αAR-agonist-based measures were repeated when the arm was positioned above or below the heart to modify the myogenic stimulus. A lumped Windkessel model was used to quantify the values of forearm C and K in each set of conditions. Baseline forearm C was inversely, and K directly, related to the myogenic load (P < 0.001). Compared with saline infusion, C was increased, but K was unaffected, with phentolanine, but only in the 'above' position. Compliance was reduced (P < 0.001) and K increased (P = 0.06) with NA infusion (main effects of NA) across arm positions; phentolamine minimized these NA-induced changes in C and K for both arm positions. Examination of conditions with and without NA infusion at similar forearm intravascular pressures indicated that the NA-induced changes in C and K were due largely to the concurrent changes in blood pressure. Therefore, within the range of arm positions used, it was concluded that vascular stiffness and vessel wall viscoelastic properties are acutely affected by myogenic stimuli. Additionally, forearm vascular compliance is sensitive to baseline levels of αAR activation when transmural pressure is low.

Mechanical properties of cell- and microgel bead-laden oxidized alginate-gelatin hydrogels.

3D-printing technologies, such as biofabrication, capitalize on the homogeneous distribution and growth of cells inside biomaterial hydrogels, ultimately aiming to allow for cell differentiation, matrix remodeling, and functional tissue analogues. However, commonly, only the mechanical properties of the bioinks or matrix materials are assessed, while the detailed influence of cells on the resulting mechanical properties of hydrogels remains insufficiently understood. Here, we investigate the properties of hydrogels containing cells and spherical PAAm microgel beads through multi-modal complex mechanical analyses in the small- and large-strain regimes. We evaluate the individual contributions of different filler concentrations and a non-fibrous oxidized alginate-gelatin hydrogel matrix on the overall mechanical behavior in compression, tension, and shear. Through material modeling, we quantify parameters that describe the highly nonlinear mechanical response of soft composite materials. Our results show that the stiffness significantly drops for cell- and bead concentrations exceeding four million per milliliter hydrogel. In addition, hydrogels with high cell concentrations (≥6 mio ml-1) show more pronounced material nonlinearity for larger strains and faster stress relaxation. Our findings highlight cell concentration as a crucial parameter influencing the final hydrogel mechanics, with implications for microgel bead drug carrier-laden hydrogels, biofabrication, and tissue engineering.

Presence of impaired intestinal calcium absorption in chronic hypovitaminosis D and its change after cholecalciferol supplementation: assessment by the calcium load test.

BACKGROUND: Hypovitaminosis D is common in Asian Indians and its functional significance is currently under investigation. Previous studies have reported on the effect of low serum 25(OH)D levels (<50 nmol L(-1)) on bone mineral density and serum parathyroid hormone values. The present study assessed the effect of chronic hypovitaminosis D in Asian Indians on intestinal calcium absorption and its change after cholecalciferol supplementation. METHODS: Subjects included 29 healthy volunteers [mean (SD) age, 28.4 +/- 6.4 years] with low serum 25(OH)D levels on screening. Intestinal calcium absorption was assessed by the 'calcium load test' with 1 g of oral elemental calcium. Subjects were put on a calcium restricted diet 1 week prior to the test. The calcium load test was repeated in 26 of them after 8 weeks of supplementation with oral cholecalciferol (60 000 IU week(-1)). RESULTS: The mean urinary calcium/creatinine ratio of the study subjects was 0.027 +/- 0.023 mg mg(-1) under fasting conditions and increased to 0.035 +/- 0.032 mg mg(-1) after calcium loading (delta change = 29.6%, P = 0.33). After 8 weeks of cholecalciferol supplementation, the mean serum 25(OH)D increased from 18.9 +/- 11.9 to 84.4 +/- 34.9 nmol L(-1) (P < 0.0001). Concomitantly, the mean urinary calcium/creatinine ratio of the study subjects increased from 0.030 +/- 0.024 mg mg(-1) under fasting conditions to 0.059 +/- 0.045 mg mg(-1) after calcium loading (delta change = 96.6%, P = 0.008). CONCLUSIONS: The results obtained in the present study show that chronic hypovitaminosis D in Asian Indians has functional relevance in terms of its effect on intestinal calcium absorption, which improves with cholecalciferol supplementation. These findings support the need for improving the vitamin D status of Asian Indians through dietary supplementation and exposure to sunshine.