Refurbishing Pacemakers: A Viable Approach

Cardiologists implant permanent pacemakers widely for indications like sick sinus syndrome and complete heart block. The guidelines for such implantations are well established1. However, in developing countries like India, all patients who need pacemakers do not receive them because of financial constraints. Even when such patients get a pacemaker, it is often a more affordable VVI pacemaker rather than the costly DDD pacemaker. The lack of a health insurance scheme and improper social support programs prevent the more widespread implantation of appropriate pacemakers. However, in the developed countries and in affluent pockets of developing countries like India, the pacemaker implantation rates are quite high. Often permanent pacemakers are implanted in the very old and people with predicted brief longevities, due to medico-legal and other social reasons. There are quite a few instances when pacemakers are explanted within a year or even within a few months. This is often due to the unfortunate death of the patient due to unrelated causes. Such pacemakers have battery lives, which are near normal. These can be explanted from the dead patient after taking consent from the relatives and “refurbished” for use in another needy patient. Refurbishing involves proper re-sterilization, checking of battery life, pacing mode and other parameters and re-labelling with the current parameters including predicted battery life. These refurbished pacemakers are a suitable alternative for the financially ‘no option’ group of patients who otherwise would not afford a pacemaker. These can last nearly as long as the original pacemakers. Even pulse generators whose shelf lives have expired can also be resterilised and used gainfully for the economically deprived

MOMORDICA CHARANTIA NANO DRY POWDER ORAL FORMULATION IN CONTROLLING HISTAMINE-INDUCED BRONCHOSPASM

Objective: Momordica charantia (MC) (bitter gourd) is known traditionally to possess medicinal values. This edible vegetable is known for its anti-inflammatory properties and has been studied for its bronchospasm preventive action. With the recent development in nanoformulations, this study was done to identify the effectiveness of MC nanoformulation in comparison to crude MC formulation in protecting animal from histamine-induced bronchospasm. Methods: The optimized MC nanoformulation was prepared with polyethylene glycol and soy phosphatidylcholine. The MC crude powder was prepared by drying in hot air oven and grinding in a blender. Eight guinea pigs of both sexes were given once daily MC nanoformulation per oral by mixing with water for 7 days. Evaluation of the formulation was done on the 2nd, 4th, and 6th h on day 1 and day 7 after administration of MC for protection in developing pre-convulsive dyspnea due to histamine-induced bronchospasm. Results: An analysis of variance test revealed statistically significant results in the protection of animals from developing bronchospasm after treatment with the MC nanoformulation in comparison to the control values. About 75% of animals were protected from developing bronchospasm on day 7 attributing to the cumulative effect of nanoformulation. Conclusion: The study proved that the MC nanoformulation could effectively prevent histamine-induced bronchospasm in guinea pigs

Thermal comfort in a closed space based on closed loop temperature control

In modern office buildings, the common trend is to use state of the technology to ensure the users to get thermally comfortable in order to produce maximum work efficiency. From the statistical studies so far on comfort index vs. work efficiency of users, the most widely adopted index is the Predicted Mean Vote (PMV). Based on this index, this work proposes a control scheme on neural network and fuzzy logic, for modifying the environmental conditions of a closed indoor space, by regarding not only the climatic indoor variables but also the activity level and clothing index of the space users. In this work along with temperature control the speed of the fan has also been taken into consideration

Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment

Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis. PCPG have few infiltrating lymphocytes but abundant macrophages. While neoplastic cells transcriptionally resemble mature chromaffin cells, early chromaffin and neuroblast markers are also features of some PCPG subtypes. The gene-expression profile of metastatic SDHx-related PCPG indicates these tumors have elevated cellular proliferation and a lower number of non-neoplastic Schwann-cell-like cells, while GPR139 is a potential theranostic target. Our findings therefore clarify the diverse transcriptional programs and cellular composition of PCPG and identify biomarkers of potential clinical significance.Magnus Zethoven, Luciano Martelotto, Andrew Pattison, Blake Bowen, Shiva Balachander, Aidan Flynn, Fernando J. Rossello, Annette Hogg, Julie A.Miller, Zdenek Frysak, Sean Grimmond, Lauren Fishbein, Arthur S. Tischler, Anthony J. Gill, Rodney J. Hicks, Patricia L. M. Dahia, Roderick Clifton-Bligh, Karel Pacak, Richard W. Tothil

Status, challenges and pathways to the sustainable use of wild species

DATA AVAILABILITY : Data will be made available on request.The use of wild species is extensive in both high- and low-income countries. At least 50,000 wild species are used by billions of people around the world for food, energy, medicine, material, education or recreation, contributing significantly to efforts to achieve the United Nations Sustainable Development Goals. However, overexploitation remains a major threat to many wild species. Ensuring and enhancing the sustainability of use of wild species is thus essential for human well-being and biodiversity conservation. Globally, the use of wild species is increasing due to growing human demand and efficiency, but its sustainability varies and depends on the social-ecological contexts in which the use occurs. Multiple environmental and social (including economic) drivers affect the sustainability of use of wild species, posing major current and future challenges. In particular, climate change has already increased the vulnerability of many uses and is expected to increase it further in the coming decades, while global and illegal trades are, in many cases, key drivers of unsustainability. There is no single “silver bullet” policy to address these and other major challenges in the sustainable use of wild species. Rather, effective policies need to integrate inclusive actions at multiple scales that adopt right-based approaches, pay attention to equitable distribution of access and costs and benefits, employ participatory processes, strengthen monitoring programs, build robust customary or government institutions and support context-specific policies, as well as adaptive management.http://www.elsevier.com/locate/gloenvchahj2023Plant Production and Soil Scienc

To be financed or not : the role of patents for venture capital financing

This paper investigates how patent applications and grants held by new ventures improve their ability to attract venture capital (VC) financing. We argue that investors are faced with considerable uncertainty and therefore rely on patents as signals when trying to assess the prospects of potential portfolio companies. For a sample of VC-seeking German and British biotechnology companies we have identified all patents filed at the European Patent Office (EPO). Applying hazard rate analysis, we find that in the presence of patent applications, VC financing occurs earlier. Our results also show that VCs pay attention to patent quality, financing those ventures faster which later turn out to have high-quality patents. Patent oppositions increase the likelihood of receiving VC, but ultimate grant decisions do not spur VC financing, presumably because they are anticipated. Our empirical results and interviews with VCs suggest that the process of patenting generates signals which help to overcome the liabilities of newness faced by new ventures

Sequence-selective detection of double-stranded DNA sequences using pyrrole-imidazole polyamide microarrays

We describe a microarray format that can detect double-stranded DNA sequences with a high degree of sequence selectivity. Cyclooctyne-derivatized pyrrole-imidazole polyamides were immobilized on azide-modified glass substrates using microcontact printing and a strain-promoted azide-alkyne cycloaddition (SPAAC) reaction. These polyamide-immobilized substrates selectively detected a seven-base-pair binding site incorporated within a double-stranded oligodeoxyribonucleotide sequence even in the presence of an excess of a sequence with a single-base-pair mismatc

The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T-1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered (https://osf.io/73dvy) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status