Soil microbial communities, being situated at the interface of aboveground plant and belowground soil systems, can play a pivotal role in determining ecosystem response to the drivers of global ...environmental change, including invasive species. In mountains, invasive plants occurring along elevational gradients offer a unique natural experimental system to investigate the impact of invasions in determining patterns and relationships of soil microbial diversity and nutrient pools at much shorter spatial distances. Here, we studied the impact of a global plant invader,
Leucanthemum vulgare
, on the diversity of soil microbiome and physico-chemical attributes along an elevational gradient (1760–2880 m) in Kashmir Himalaya. We used Illumina MiSeq platform to characterize the soil microbiome in pair-wise invaded and uninvaded plots at four different sites along the gradient. We found a total of 1959 bacterial operational taxonomic units (OTUs) belonging to 152 species, and a relatively higher number of 2475 fungal OTUs belonging to 589 species. The α-diversity of soil microbiome showed a gradual increase from low to high elevation and differed significantly (
p
< 0.05) between the invaded and uninvaded plots. The β-diversity revealed distinct microbiome clustering among the sampling sites. Plant invasion also altered soil physico-chemical attributes along the elevational gradient. Overall, our findings suggest that the
L. vulgare
-induced shifts in soil microbiome and nutrient pools may be a belowground self-reinforced mechanism to facilitate its successful invasion along the elevational gradient. Our study provides new insights into invasive plant–microbe relationships with wide implications for climate warming-driven elevational range shifts in mountains.
The study aimed to predict pregabalin individualized doses in healthy adults, pediatrics and renal impaired geriatric patients by using physiological based pharmacokinetic (PBPK) model for ...gastroretentive formulation producing comparable pharmacokinetics to that of the immediate release (IR) formulation to obtain doses on basis of their physiological needs.
The PBPK model of pregabalin was developed for a healthy adult, healthy pediatrics, healthy and renal impaired geriatric (with creatinine clearance, CLcr = 90, 60, 30, 15 ml/min) at different once daily doses of the IR and GR formulations. In PBPK adult model, PK parameters were also predicted in fasting and fed condition after administration of pregabalin 300 mg of IR and 330 mg of sustained release (SR) formulations. The doses in the renal impaired geriatrics and healthy pediatric population were computed by a dose decremental method and were selected at which the comparable pharmacokinetics parameters to that of the reported values in healthy adults were obtained.
In healthy adults, comparable PK parameters were obtained after administration of pregabalin 300 mg of IR and 330 mg of SR formulation in fasting and fed state and there was no effect of food on the bioavailability of pregabalin. In neonates to infants and toddlers, the same AUC0-48 to that of the adults was obtained with a 40–82 mg dose of GR formulation of pregabalin. For pre-schooled and schooled virtual populations, a dose of 40–170 mg and for adolescents, 40–330 mg produced the comparable AUC0-48 as that of the normal adults, 42.20 ± 32 μg h/ml. The predicted doses of gastroretentive formulation in renal impaired geriatric with CLcr, 60, 30, and 15 ml/min were 220–330, 110 to 220 and 55–85 mg, respectively to achieve the same level of PK parameters as elder individual with normal CLcr (90 ml/min) after administration of 330 mg of gastroretentive formulation.
PBPK models effectively predicted dose for the modified GR pregabalin formulations in special populations such as pediatrics and elder renal impaired individuals.
Display omitted
Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes presenting within the first 6 months of life. INS gene promoter mutations have been shown to cause both remitting/relapsing and ...permanent NDM. We, herein, present three interesting patients with INS gene promoter mutations. Two cousins with an identical homozygous c.‐331C > G mutation presented with NDM. The first cousin had nonremitting diabetes and still requires multidose insulin injections at the current age of 6.1 years. However, the other cousin's diabetes remitted at the age of 9 months, and she is still in remission at the age of 3 years with no medication or dietary intervention required (latest HbA1c was 4.9%). The third patient had NDM also due to a homozygous INS promoter c.‐331C>A mutation. Her diabetes remitted at the age of 2 months and relapsed at the age of 2.6 years with severe diabetic ketoacidosis (DKA). Distinct clinical phenotype and relapse with severe DKA in one of the three cases suggest that INS promotor mutations can cause a heterogeneous phenotype and even cases exhibiting remission can relapse unpredictably. Therefore, as the age of relapse is unpredictable, close follow‐up and family education on diabetes symptoms are essential for cases with remitting/relapsing diabetes due to INS gene mutations.
The development of excellent photocatalytic material is highly required for energy and environmental applications. In this study, visible light responsive p-n heterojunction photocatalysts based on ...CuO/MoO3 with varying ratios of CuO were prepared by the facile hydrothermal method. The crystalline structure, surface morphology, chemical compositions and optical properties of the synthesized photocatalysts were studied using X-ray powder diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FTIR), photoluminescence (PL) techniques and UV–Vi's absorption spectroscopy. The results showed that the 5%CuO/MoO3 nanocomposite displayed enhanced photocatalytic performance for the production of hydrogen (98.5 μmol h−1g−1) and degradation of dyes rhodamine B (RhB) and alizarine yellow (AY) than all other samples. Furthermore, 5% CuO/MoO3 composite exhibited excellent stability after five consecutive cycles for both RhB and AY dyes. Overall, the improved photocatalytic performance of 5%CuO/MoO3 composite was due to increased adsorption of visible light, good surface morphology, enhanced charge separation/transfer which inhibited recombination of electrons and holes. This study could encourage the synthesis of novel and effective p-n heterojunction photocatalysts for practical applications.
•CuO/MoO3 p-n heterojunction photocatalyst was prepared by hydrothermal method.•Prepared CuO/MoO3 photocatalyst showed superior performance under visible light.•The improved photocatalytic activity was due to synergistic effects of both materials.
The increasing levels of heavy metals in aquatic environments, driven by human activities, pose a critical threat to ecosystems' overall health and sustainability. This study investigates the ...bioaccumulation of heavy metals (Pb, Cu, Cr, and Cd) in water, sediment, and three fish species (Catla catla, Labeo rohita, Cirrhinus mrigala) of different feeding zones within Chashma Barrage, located in the Mianwali district of Punjab, Pakistan, on the Indus River. A comprehensive analysis, including an assessment of associated human health risks, was conducted. Thirty samples from all three sites for each fish species, with an average body weight of 160 ± 32 g, were collected from Chashma Barrage. Water quality parameters indicated suitability for fish growth and health. Heavy metal concentrations were determined using an atomic absorption spectrometer. Results indicated elevated levels of Cd, Cr, and Cu in sediment and Pb and Cd in water, surpassing WHO standard limits. Among the fish species, bottom feeder (C. mrigala) exhibited significantly (P < 0.05) higher heavy metal levels in its tissues (gills, liver, and muscle) compared to column feeder (L. rohita) and surface feeder (C. catla). Liver tissues across all species showed higher heavy metal bioaccumulation, followed by gills. Principal component analysis (PCA) revealed strong correlations among heavy metals in sediment, gills, muscle, and water in every fish species. However, the vector direction suggests that Cr was not correlated with other heavy metals in the system, indicating a different source. The human health risk analysis revealed lower EDI, THQ, and HI values (< 1) for the fish species, indicating no adverse health effects for the exposed population. The study emphasizes the bioaccumulation differences among fish species, underscoring the higher heavy metal concentrations in bottom feeder fish within Chashma Barrage.The increasing levels of heavy metals in aquatic environments, driven by human activities, pose a critical threat to ecosystems' overall health and sustainability. This study investigates the bioaccumulation of heavy metals (Pb, Cu, Cr, and Cd) in water, sediment, and three fish species (Catla catla, Labeo rohita, Cirrhinus mrigala) of different feeding zones within Chashma Barrage, located in the Mianwali district of Punjab, Pakistan, on the Indus River. A comprehensive analysis, including an assessment of associated human health risks, was conducted. Thirty samples from all three sites for each fish species, with an average body weight of 160 ± 32 g, were collected from Chashma Barrage. Water quality parameters indicated suitability for fish growth and health. Heavy metal concentrations were determined using an atomic absorption spectrometer. Results indicated elevated levels of Cd, Cr, and Cu in sediment and Pb and Cd in water, surpassing WHO standard limits. Among the fish species, bottom feeder (C. mrigala) exhibited significantly (P < 0.05) higher heavy metal levels in its tissues (gills, liver, and muscle) compared to column feeder (L. rohita) and surface feeder (C. catla). Liver tissues across all species showed higher heavy metal bioaccumulation, followed by gills. Principal component analysis (PCA) revealed strong correlations among heavy metals in sediment, gills, muscle, and water in every fish species. However, the vector direction suggests that Cr was not correlated with other heavy metals in the system, indicating a different source. The human health risk analysis revealed lower EDI, THQ, and HI values (< 1) for the fish species, indicating no adverse health effects for the exposed population. The study emphasizes the bioaccumulation differences among fish species, underscoring the higher heavy metal concentrations in bottom feeder fish within Chashma Barrage.
Aim of this study to evaluate the safety profile, hepatoprotective and in-vivo antioxidant activities of Dicliptera bupleuroides Nees. Toxicity studies were conducted in human RBCs and DNA by using ...standard procedures. Acute hepatoprotective investigation was carried out in albino rats by treated with all six fractions of D. bupleuroides 350 mg/kg/day. ALT, AST, ALP and total bilirubin (TB) were performed. The n-hexane fraction (200 mg/kg/day) exhibited appropriate hepatoprotective activity hence subjected to chronic study (14 days). Paracetamol induced the hepatotoxicity (350mg/kg) and silymarin (50 mg/kg) was standard drug. Liver function tests, liver peroxidation tests and histopathological examination were performed at the end. Hexane fraction showed significant decrease in the level of ALT (88.1±7.8), AST (93.8±7.6), ALP (136.3±8.4) and TB (0.6±0.03) as compared to the standard drug (p>0.05). Rats treated with ethyl acetate fraction showed decrease in MDA (42.8±0.7) while GSH was found to be increased (107.7±1.8) against the toxic group (51.3±2.9), (73.6±4.0) respectively. All the drug extracts decreased the oxidative stress and protect the DNA from free hydroxyl radicals. DNA damage protection activity of these fractions is due to phytochemicals present in these fractions. These results indicate that the plant fractions possess significant hepatoprotective and antioxidant activities with no toxic effects.
Hypoglycaemia is common in patients with diabetes mellitus and is a limiting factor for achieving adequate glycaemic control. In the vast majority of cases, hypoglycaemia develops due to the ...imbalance between food intake and insulin injections. As recurrent hypoglycaemia leads to significant morbidity and mortality, the recognition and immediate treatment of hypoglycaemia in diabetic patients is thus important. In the last 20 years, the introduction of improved insulin analogues, insulin pump therapy, continuous glucose monitoring (CGM), and sensor-augmented pump therapy have all made significant improvements in helping to reduce and prevent hypoglycaemia. In terms of treatment, the American Diabetes Association recommends oral glucose as the first-line treatment option for all conscious patients with hypoglycaemia. The second line of treatment (or first line in unconscious patients) is the use of glucagon. Novel formulations of glucagon include the nasal form, the Gvoke HypoPen which is a ready-to-deliver auto-injector packaged formulation and finally a glucagon analogue, Dasiglucagon. The Dasiglucagon formulation has recently been approved for the treatment of severe hypoglycaemia. It is a ready-to-use, similar to endogenous glucagon and its potency is also the same as native glucagon. It does not require reconstitution before injection and therefore ensures better compliance. Thus, significant improvements including development of newer insulin analogues, insulin pump therapy, continuous glucose monitoring (CGM), sensor-augmented pump therapy and novel formulations of glucagon have all contributed to reducing and preventing hypoglycaemia in diabetic individuals. However, considerable challenges remain as not all patients have access to diabetes technologies and to the newer glucagon formulations to help reduce and prevent hypoglycaemia.
Beckwith-Wiedemann syndrome (BWS) is caused by dysregulation of imprinted genes on chromosome 11.p15.5. The syndrome includes overgrowth, macroglossia, organomegaly, abdominal wall defects, ...hypoglycemia, and long-term malignancy risk. No patient who has BWS has been reported with hypopituitarism. We describe a patient who presented at birth with macrosomia, macroglossia, respiratory distress, jaundice, and hypoglycemia, and who was followed for 4.5 years. Genetic test for BWS was performed, which detected loss of maternal methylation on region KvDMR1 (11p15.5). The hypoglycemia was attributable to hyperinsulinism and was treated with diazoxide and chlorothiazide. She responded well, but the hypoglycemia returned after reducing the diazoxide. It was possible to stop the diazoxide after 2.5 years. On routine follow-up she was noted to be developing short stature. Baseline pituitary and growth hormone (GH) stimulation tests detected GH deficiency and secondary hypothyroidism. A brain MRI showed a small anterior pituitary gland. Thereafter, thyroxine and replacement therapy with GH were started, which resulted in a remarkable improvement in growth velocity. This is the first patient to be reported as having hypopituitarism and BWS. It is unclear if the BWS and the hypopituitarism are somehow connected; however, further investigations are necessary. Hypopituitarism explains the protracted hypoglycemia and the short stature. In our patient, GH therapy seems to be safe, but strict follow-up is required given the increased cancer risk related to BWS.
