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.

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.

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.

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.

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.

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.

Polyacrylamide Bead Sensors for in vivo Quantification of Cell-Scale Stress in Zebrafish Development.

Mechanical stress exerted and experienced by cells during tissue morphogenesis and organ formation plays an important role in embryonic development. While techniques to quantify mechanical stresses in vitro are available, few methods exist for studying stresses in living organisms. Here, we describe and characterize cell-like polyacrylamide (PAAm) bead sensors with well-defined elastic properties and size for in vivo quantification of cell-scale stresses. The beads were injected into developing zebrafish embryos and their deformations were computationally analyzed to delineate spatio-temporal local acting stresses. With this computational analysis-based cell-scale stress sensing (COMPAX) we are able to detect pulsatile pressure propagation in the developing neural rod potentially originating from polarized midline cell divisions and continuous tissue flow. COMPAX is expected to provide novel spatio-temporal insight into developmental processes at the local tissue level and to facilitate quantitative investigation and a better understanding of morphogenetic processes.

Non-genetic factors affecting pre-weaning growth and morphometric traits in Assam Hill goat.

AIM: This study aimed to determine the genetic and non-genetic factors affecting pre-weaning body weight (BW) and morphometry in Assam Hill goat along with the genetic parameters. MATERIALS AND METHODS: The detailed information in respect of BW and body measurements of 960 animals at birth and 3 months of age belonging to three different populations of Assam Hill goat maintained at field units, namely, Batabari, Nahira, and Tetelia under "All India Coordinated Research Project on Goat Improvement" were utilized in the present study. The data were analyzed using least squares technique. RESULTS: The least squares means for BW, height at withers (HW), heart girth (HG), and body length (BL) were 1.166±0.008 kg, 26.198±0.070 cm, 26.695±0.096 cm, and 29.482±0.119 cm at birth and 4.590±0.083 kg, 36.850±0.105 cm, 40.741±0.115 cm, and 39.703±0.108 cm at 3 months of age, respectively. Location had a significant effect on BW, HW, and BL at both birth and 3 months and on HG at 3 months of age. Season of birth exerted significant effect only on BL at birth, whereas the significant effect of sex was observed on HG and BL at 3 months of age. The heritability estimates for BW and body measurements were moderate indicating the scope of selection. The phenotypic and genetic correlations among BWs and body measurements at birth and 3 months of age were positive in direction and high in magnitude. CONCLUSION: On the basis of the present findings, it could be concluded that the weaning weight of kids can be considered for the selection of parent stock to increase productivity and eventually the economic efficiency. Further, animals with higher body measurements at initial phases of growth will perform better with respect to even BW at later stages of growth.