Roots and fates of congenital insensitivity to pain and anhidrosis: a human phenotype

Congenital insensitivity to pain is a rare neurological disorder characterized by the inability to perceive physical pain. Individuals with CIP lack the typical nociceptive responses to harmful stimuli, which poses significant challenges to their safety and well-being. This condition is often caused by genetic mutations affecting the nervous system's ability to transmit pain signals. Despite the apparent advantage of not experiencing pain, CIP presents severe risks as affected individuals may unknowingly sustain injuries or develop medical complications without timely intervention. The absence of pain perception hinders the learning of protective behaviour and responses to potentially harmful situations, making daily activities fraught with danger. Understanding the genetic basis of CIP has provided valuable insights into pain perception and the functioning of nociceptive pathways. While this knowledge may pave the way for potential therapeutic interventions, managing CIP remains a complex task. This article provides an overview of CIPA, its genetic basis, clinical manifestations, complications, treatment and the challenges associated with managing this complex condition. A multidisciplinary approach involving genetic counselling, pain management, and specialized care is crucial to support individuals with CIPA and improve their overall well-being.  

FORMULATION AND EVALUATION OF SOLID SELF MICRO EMULSIFYING DISPERSIBLE TABLET OF PIROXICAM

Objective: The aim of this study was to formulate the solid self-micro emulsifying dispersible tablets for promoting the dissolution of Piroxicam. Methods: Solubility study test was performed to know the solubility of various oil phase, surfactants, cosurfactants. Self-emulsifying grading test was done by visual grading system. Ternary phase diagrams and droplet size analysis test were performed to screen and optimize the Piroxicam-self microemulsifying drug delivery system (SMEDS). Then microcrystalline cellulose (KG802) was added as a suitable adsorbent and dispersible tablet were prepared by wet granulation compression method. Results: The final composition of Piroxicam-SMEDS was oil phase (oleic acid, 23%), surfactant (Cremophor R H-40,61%), co-surfactant (PEG-400,16%) based on the result of solubility test, self-emulsifying grading test, droplet size analysis and ternary phase diagrams. Microcrystalline cellulose (KG802) was selected based on dissolution study (98.35%) and added to liquid Piroxicam-Smeds formulation to form dispersible tablets. The in vitro dissolution study showed 98.02 % of drug release from Piroxicam-SMEDS tablets. Conclusion: Piroxicam–Self microemulsifying dispersible tablets have increased the solubility and bioavailability of the Piroxicam to a greater extent. SMEDS formulation can help the solubility of poorly water-soluble drugs

Ranking candidate signals with machine learning in low-latency searches for gravitational waves from compact binary mergers

In the multimessenger astronomy era, accurate sky localization and low latency time of gravitational-wave (GW) searches are keys in triggering successful follow-up observations on the electromagnetic counterpart of GW signals. We, in this work, study the feasibility of adopting a supervised machine learning (ML) method for scoring rank on candidate GW events. We consider two popular ML methods, random forest and neural networks. We observe that the evaluation time of both methods takes tens of milliseconds for ∼45,000 evaluation samples. We compare the classification efficiency between the two ML methods and a conventional low-latency search method with respect to the true positive rate at given false positive rate. The comparison shows that about 10% improved efficiency can be achieved at lower false positive rate ∼2×10⁻⁵ with both ML methods. We also present that the search sensitivity can be enhanced by about 18% at ∼10⁻¹¹  Hz false alarm rate. We conclude that adopting ML methods for ranking candidate GW events is a prospective approach to yield low latency and high efficiency in searches for GW signals from compact binary mergers

Decoding pituitary tumors: a systematic analysis of diagnostic methods and treatment modalities

Pituitary tumors are growths that form in the gland these tumors are rare representing 10-15% of all brain tumors. They can disrupt the production of hormones, in the body leading to symptoms related to hormone imbalance. This review offers an overview of the methods used for diagnosing and treating tumors. It is worth noting that relying solely on references may restrict the scope and depth of discussions about tumors in this paper. Suggestions for research include exploring diagnostic tools like molecular imaging and liquid biopsy to enhance early detection and accurate assessment of these tumors. Additionally, more research is required to understand the long-term effects and quality of life outcomes for patients undergoing treatment options for tumors. In conclusion, significant progress has been made in diagnosing and treating tumors over time. Advances in imaging technologies such as diffusion-weighted imaging and magnetic resonance spectroscopy have enhanced precision and treatment strategies for these tumors. The discussion also covers the roles of surgery, radiation therapy and medical interventions, in managing tumor growth and hormonal imbalances further advancements, in research and innovation are crucial, for enhancing our knowledge and treatment of tumors ultimately bringing outcomes for both patients and healthcare professionals.

Investigating the Electromechanical Behavior of Unconventionally Ferroelectric Hf0.5Zr0.5O2-Based Capacitors Through Operando Nanobeam X-Ray Diffraction

Understanding various aspects of ferroelectricity in hafnia-based nanomaterials is of vital importance for the development of future nonvolatile memory and logic devices. Here, the unconventional and weak electromechanical response of epitaxial La0.67Sr0.33MnO3/Hf0.5Zr0.5O2/La0.67Sr0.33MnO3 ferroelectric capacitors is investigated, via the sensitivity offered by nanobeam X-ray diffraction experiments during application of electrical bias. It is shown that the pristine rhombohedral phase exhibits a linear piezoelectric effect with piezoelectric coefficient (|d33|) ≈ 0.5–0.8 pmV−1. It is found that the piezoelectric response is suppressed above the coercive voltage. For higher voltages, and with the onset of DC conductivity throughout the capacitor, a second-order effect is observed. The work sheds light into the electromechanical response of rhombohedral Hf0.5Zr0.5O2 and suggests its (un)correlation with ferroelectric switching

Progress in adolescent health and wellbeing: tracking 12 headline indicators for 195 countries and territories, 1990–2016

Background: Rapid demographic, epidemiological, and nutritional transitons have brought a pressing need to track progress in adolescent health. Here, we present country-level estimates of 12 headline indicators from the Lancet Commission on adolescent health and wellbeing, from 1990 to 2016. Methods: Indicators included those of health outcomes (disability-adjusted life-years [DALYs] due to communicable, maternal, and nutritional diseases; injuries; and non-communicable diseases); health risks (tobacco smoking, binge drinking, overweight, and anaemia); and social determinants of health (adolescent fertility; completion of secondary education; not in education, employment, or training [NEET]; child marriage; and demand for contraception satisfied with modern methods). We drew data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016, International Labour Organisation, household surveys, and the Barro-Lee education dataset. Findings: From 1990 to 2016, remarkable shifts in adolescent health occurred. A decrease in disease burden in many countries has been offset by population growth in countries with the poorest adolescent health profiles. Compared with 1990, an additional 250 million adolescents were living in multi-burden countries in 2016, where they face a heavy and complex burden of disease. The rapidity of nutritional transition is evident from the 324·1 million (18%) of 1·8 billion adolescents globally who were overweight or obese in 2016, an increase of 176·9 million compared with 1990, and the 430·7 million (24%) who had anaemia in 2016, an increase of 74·2 million compared with 1990. Child marriage remains common, with an estimated 66 million women aged 20–24 years married before age 18 years. Although gender-parity in secondary school completion exists globally, prevalence of NEET remains high for young women in multi-burden countries, suggesting few opportunities to enter the workforce in these settings. Interpretation: Although disease burden has fallen in many settings, demographic shifts have heightened global inequalities. Global disease burden has changed little since 1990 and the prevalence of many adolescent health risks have increased. Health, education, and legal systems have not kept pace with shifting adolescent needs and demographic changes. Gender inequity remains a powerful driver of poor adolescent health in many countries. Funding: Australian National Health and Medical Research Council, and the Bill & Melinda Gates Foundatio

Improvements in vascular health by a low-fat diet, but not a high-fat diet, are mediated by changes in adipocyte biology

<p>Abstract</p> <p>Background</p> <p>Low-fat (LF) and high-fat (HF) weight loss diets improve brachial artery flow-mediated dilation (FMD) in obese individuals, although results are conflicting. Moreover, the role that adipose tissue plays in mediating these diet-related effects are unknown.</p> <p>Objective</p> <p>This study examined how modulations in FMD by HF and LF diets relate to changes in adipocyte parameters.</p> <p>Design</p> <p>Obese subjects (n = 17) were randomized to a HF diet (60% kcal as fat) or a LF diet (25% kcal as fat) for 6 weeks. Both groups were restricted by 25% of energy needs.</p> <p>Results</p> <p>Body weight decreased (<it>P <</it>0.05) in both groups (HF: -6.6 ± 0.5 kg, LF: -4.7 ± 0.6 kg). Fat mass and waist circumference were reduced (<it>P <</it>0.05) in the LF group only (-4.4 ± 0.3 kg; -3.6 ± 0.8 cm, respectively). FMD improved (<it>P <</it>0.05) in the LF group (7.4 ± 0.8% to 9.8 ± 0.8; 32% increase) and was impaired in the HF group (8.5 ± 0.6% to 6.9 ± 0.7; 19% reduction). Increases in plasma adiponectin (<it>P <</it>0.05, 16 ± 5%), and decreases in resistin (<it>P <</it>0.05, -26 ± 11%), were shown by the LF diet only. Greater decreases in leptin were observed with LF (-48 ± 9%) versus HF (-28 ± 12%) (<it>P <</it>0.05, diet × time). Increased FMD by the LF diet was associated with increased adiponectin, and decreased fat mass, waist circumference, leptin, and resistin.</p> <p>Conclusion</p> <p>Beneficial modulations in vascular health by LF diets may be mediated by improvements in adipocyte parameters.</p

An accurate and interpretable model for siRNA efficacy prediction

BACKGROUND: The use of exogenous small interfering RNAs (siRNAs) for gene silencing has quickly become a widespread molecular tool providing a powerful means for gene functional study and new drug target identification. Although considerable progress has been made recently in understanding how the RNAi pathway mediates gene silencing, the design of potent siRNAs remains challenging. RESULTS: We propose a simple linear model combining basic features of siRNA sequences for siRNA efficacy prediction. Trained and tested on a large dataset of siRNA sequences made recently available, it performs as well as more complex state-of-the-art models in terms of potency prediction accuracy, with the advantage of being directly interpretable. The analysis of this linear model allows us to detect and quantify the effect of nucleotide preferences at particular positions, including previously known and new observations. We also detect and quantify a strong propensity of potent siRNAs to contain short asymmetric motifs in their sequence, and show that, surprisingly, these motifs alone contain at least as much relevant information for potency prediction as the nucleotide preferences for particular positions. CONCLUSION: The model proposed for prediction of siRNA potency is as accurate as a state-of-the-art nonlinear model and is easily interpretable in terms of biological features. It is freely available on the web a