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BackgroundPediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM.MethodsTBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL).ResultsOf 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P

AbstractGenistein (GEN), an isoflavonoid, offers multifunctional biological activities. However, its poor oral bioavailability, aqueous solubility, extensive metabolism, and short half-life restricted its clinical use. Therefore, the Phospholipon®90H complex of genistein (GPLC) was prepared to enhance its biopharmaceutical properties and anti-inflammatory activity. GPLC was characterized by employing particle size and zeta potential, Fourier transforms infrared spectrophotometry, differential scanning calorimetry, powder x-ray diffractometry, proton nuclear magnetic resonance, aqueous solubility, in vitro dissolution, ex vivo permeation, oral bioavailability and in vivo anti-inflammatory activity. The complex showed high entrapment of GEN (∼97.88% w/w) within the Phospholipon®90H matrix. Particle size and zeta potential studies confirmed the small particle size with the modest stability of GPLC. The characterization analysis supported the formation of GPLC through the participation of hydrogen bonding between GEN and Phospholipon®90H. GPLC significantly enhanced the aqueous solubility (∼2-fold) compared to GEN. Dissolution studies revealed that GPLC drastically improved the GEN dissolution rate compared to GEN. Likewise, the complex improved the permeation rate across the membrane compared to GEN. GPLC formulation significantly enhanced the oral bioavailability of GEN via improving its Cmax, tmax, AUC, half-life and mean residence time within the blood circulation compared to GEN. The GPLC (∼20 mg/kg, p.o.) remarkably inhibited the increase in paw edema up to 5 h, compared to GEN and diclofenac. Results suggest that the Phospholipon®90 complex is a superior and promising carrier for enhancing the biopharmaceutical parameters of GEN and other bioactive with similar properties.

Intra-osseous vascular lesions occur rarely in jaw bones. Intra-osseous hemangioma of the facial bones is even rarer and occurs more predominantly in the mandible than the maxilla. Diagnosis of these lesions is challenging due to inconsistent clinical and radiographic presentation. Here, we present a rare case report of a boy, aged 16 years, with an intra-osseous cavernous hemangioma of the left maxilla.

An AA6061 alloy plate surface was reinforced with zirconia (ZrO2) nanoparticles and graphene nanoplatelets (GNP) by friction stir processing (FSP) to produce a surface nanocomposite. The processing was carried out under optimum FSP parametric conditions to ensure the uniform distribution of the reinforced particles. The processed samples were subjected to solution treatment and then subsequently artificially aged at different temperatures (160, 180, 200, and 220 °C). Microstructural and mechanical investigations were carried out for the FSPed AA6061 surface nanocomposite sample and the samples aged at different temperatures after FSP. The sample aged at 200 °C shows a peak hardness of 82.6 HV, which is 27.3% higher than non-heat treated sample. A maximum tensile strength of 207.3 MPa along with 75% wear resistance improvement has been attained with a sample aged at 200 °C. Samples aged at 220 °C show relatively coarser grains (31.46 µm) which indicates over aging. [ABSTRACT FROM AUTHOR]

Crohn's disease is a chronic inflammatory disease of the intestines. It primarily causes ulcerations (breaks in the lining) of the small and large intestines, but can affect the digestive system anywhere from the mouth to the anus. It causes a wide variety of symptoms like abdominal pain, diarrhoea (even bloody if inflammation is severe), vomiting, weight loss. It may also cause complications outside the gastrointestinal tract such as skin rashes, arthritis, and inflammation of the eye, tiredness, and lack of concentration. Crohn's disease is related closely to another chronic inflammatory condition that involves only the colon called ulcerative colitis. Together, Crohn's disease and ulcerative colitis are frequently referred to as inflammatory bowel disease (IBD). Crohn's disease is caused by interactions between environmental, immunological and bacterial factors in genetically susceptible individuals. This result in a chronic inflammatory disorder, in which the body's immune system attacks the gastrointestinal tract possibly directed at microbial antigens. Crohn's disease has traditionally been described as an autoimmune disease, but recent investigators have described it as an immune deficiency state. According to Ayurveda, Crohn's can be compared to 'Ghrahani' disease. Ghrahani in Ayurveda, is actually an anatomical term to describe small intestines (specifically Ileum and jejunam). Any vitiation or inflammation to this particular part by imbalanced Doshas (Vata, Pitta, Kapha) can cause a wide variety of symptom similar to that of Crohn's disease, anywhere across the digestive system. Degree and nature of symptoms may vary as per the doshic predominance & involvement. At CHARAKA, we are providing very effective treatment for Crohn's disease based on the classical principle of Ayurveda and our research. Treatment involves internal research medicines, strict diet regime and life style modifications. In more severe and chronic cases, Panchakarma therapy is selectively done along with these. Pichha Basti indicated in Parvahika, Ghrahani and Atisara by Acharya Charaka and Vagbatta. This Basti reduce inflammation due to its Grahi, Deepandravya and Picchila Guna [ABSTRACT FROM AUTHOR]

Phase-locked loop (PLL) operates at a high frequency and due to the increased switching rate of the circuits, the power consumption is high. Designing a PLL which consumes less power without compromising the frequency of operation is essential. The sub-components of PLL such as the phase frequency detector, charge pump, loop filter, voltage-controlled oscillator, and the frequency divider have to be designed for reduced power consumption. The proposed PLL along with its sub-components have been designed using the CMOS 180nm technology library in the Cadence Virtuoso and simulated using Cadence Spectre with a supply voltage of 1.8V resulting in a 20% reduction in power with a higher frequency of operation compared to the reference PLL architecture. The capture range and lock range of the proposed PLL are 2.09 to 2.14 GHz and 1 to 3.5GHz, respectively. The designed PLL consumes less power and operates at a higher frequency.