Diffusion MR microscopy of cortical development in the mouse embryo

Cortical development in the mouse embryo involves complex changes in the microstructure of the telencephalic wall, which are challenging to examine using three-dimensional (3D) imaging techniques. In this study, high-resolution 3D diffusion magnetic resonance (dMR) microscopy of the embryonic mouse cortex is presented. Using diffusion-weighted gradient- and spin-echo based acquisition, dMR microimaging data were acquired from fixed mouse embryos at 7 developmental stages from embryonic day (E)12.5 to E18.5. The dMR imaging (dMRI) contrasts revealed microscopic structural detail in the mouse telencephalic wall, allowing delineation of transient zones in the developing cortex based on their unique diffusion signatures. With the high-resolution 3D data of the mouse embryo, we were able to visualize the complex microstructure of embryonic cerebral tissue and to resolve its regional and temporal evolution during cortical formation. Furthermore, averaged dMRI contrasts generated via deformable registration revealed distinct spatial and temporal gradients of anisotropy variation across the developing embryonic cortical plate and the ventricular zone. The findings of this study demonstrate the potential of 3D dMRI to resolve the complex microstructure of the embryonic mouse cortex, and will be important for investigations of corticogenesis and its disruption in embryonic mouse models

How Good Is Local Search for Capacitated Facility Location Problem: An Experimental Study

Facility location problems have been widely studied since 1960’s. These problems are known to be strongly NP-hard. In capacitated variant of the problem, a capacity constraint is associated with each facility. Capacitated facility location problem (CFLP) instances can be solved exactly using existing MILP solvers but only for small instance sizes. As the size of the problem instance increases beyond few hundred facilities and few hundred clients, it becomes prohibitive to solve these instances exactly. For large problem instances, therefore, other solution methods are used. One approach is to use heuristic methods. These methods usually give good solutions in reasonable time but they do not provide any guarantee about the quality of the solution. Somewhere between these two extremes exist another class of algorithms called approximation algorithms. They also provide only suboptimal solutions to the problem, like heuristic algorithms, in polynomial time. How ever they guarantee worst case upper bounds on the cost of the solution. So, a solution obtained using an approximation algorithm is guaranteed to have its cost between the optimal cost and the upper bound. We present experimental studies done with a local search based approximation algorithm for CFLP given by Bansal et al. [1] to show that this algorithm performs well in practice

Evaluation of axial length and association with morphology of cataract

Background: Cataractogenesis is associated with alteration in the nature of lens epithelium. How a change in morphology of cataract relates to axial length and IOL power is an interesting area to explore. The aim of the study was to evaluate the association between axial length and age-related cataracts, and intra ocular lens (IOL) power in eyes undergoing cataract surgery.Methods: A cross sectional study was conducted from 2019 to 2020 on 550 eyes with age related cataract for morphology of cataract and axial length of eye. Data was analyzed using statistical software One-way ANOVA and Post HOC test.Results: Out of a total 550 eyes, 122 (22.2%) were Nuclear, 79 (14.4%) were PSC, and 349 (63.5%) were of Mixed morphology. Mean age of patients with PSC was 56.41±14.55 years, 58.52±14.16 years with Nuclear, and 62.88±9.86 years in Mixed morphology. This difference was found to be statistically significant with p value of 0.001. In this study, the mean axial length in eyes with only Nuclear, only PSC, and Mixed morphology, was measured to be 23.19±1.29, 23.26±0.91, 23.24±1.47 respectively. This was found to be statistically insignificant with p=0.92. The mean power intraocular lens 20.96±3.03 D in Nuclear Cataract, 21.25±2.39 D in PSC, and 21.25±2.60 D in Mixed cataract, and was statistically insignificant with p value of 1.Conclusions: This study suggests no impact of morphology of cataract on axial length or IOL power.

SYNERGISTIC ACTION OF PENETRATION ENHANCERS IN TRANSDERMAL DRUG DELIVERY

Transdermal drug delivery system is a desirable form of drug delivery because of the obvious advantages over other routes of delivery. One promising challenge in designing transdermal drug delivery system is to overcome the natural transport barrier of the skin i.e. the stratum corneum which is the rate limiting step in percutaneous absorption of drugs. Various penetration enhancers are now being used alone or in combinations to enhance the penetration of the drug through the skin. The main objective of the present study is to review the synergistic action of various penetration enhancers on the efficacy and safety of the drug. It has been found from the literature study that systems employing synergistic mixtures of penetration enhancers offer superior skin permeation enhancement as compared to those employing single penetration enhancer. Various chemical, physical and carrier approaches have also been reviewed to increase skin permeation of the drug. Keywords: Transdermal, penetration enhancers, synergistic mixtures, permeation enhancement

Considerations and recommendations from the ISMRM diffusion study group for preclinical diffusion MRI: Part 1: In vivo small-animal imaging

Diffusion MRI; Diffusion tensor; Small animalResonancia magnética de difusión; Tensor de difusión; Animal pequeñoRessonància magnètica de difusió; Tensor de difusió; Animal petitSmall-animal diffusion MRI (dMRI) has been used for methodological development and validation, characterizing the biological basis of diffusion phenomena, and comparative anatomy. The steps from animal setup and monitoring, to acquisition, analysis, and interpretation are complex, with many decisions that may ultimately affect what questions can be answered using the resultant data. This work aims to present selected considerations and recommendations from the diffusion community on best practices for preclinical dMRI of in vivo animals. We describe the general considerations and foundational knowledge that must be considered when designing experiments. We briefly describe differences in animal species and disease models and discuss why some may be more or less appropriate for different studies. We, then, give recommendations for in vivo acquisition protocols, including decisions on hardware, animal preparation, and imaging sequences, followed by advice for data processing including preprocessing, model-fitting, and tractography. Finally, we provide an online resource that lists publicly available preclinical dMRI datasets and software packages to promote responsible and reproducible research. In each section, we attempt to provide guides and recommendations, but also highlight areas for which no guidelines exist (and why), and where future work should focus. Although we mainly cover the central nervous system (on which most preclinical dMRI studies are focused), we also provide, where possible and applicable, recommendations for other organs of interest. An overarching goal is to enhance the rigor and reproducibility of small animal dMRI acquisitions and analyses, and thereby advance biomedical knowledge.We acknowledge financial support from the National Institutes of Health (K01EB032898, R01AG057991, R01NS 125020, R01EB017230, R01EB019980, R01EB031954, R01 CA160620, R01NS109090, R01NS119605, U54AG054349, P50MH096889); the National Institute of Biomedical Imaging and Bioengineering (R01EB031765, R56EB031765); the National Institute on Drug Abuse (P30DA048742); the Secretary of Universities and Research (Government of Catalonia) Beatriu de Pinós postdoctoral fellowship (2020 BP 00117); “la Caixa” Foundation (ID 100010434); the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 847648; Junior Leader fellowship codes (LCF/BQ/PR22/11920010; CF/BQ/PI20/11760029); the European Union's Horizon Europe Programme for Research Infrastructures under the specific grant agreement no. 101147319 (EBRAINS 2.0); the Research Council of Norway under grant agreement no. 333157 (INCF Norwegian Node 2022-2027); the Research Foundation Flanders (FWO: 12M3119N); the Belgian Science Policy Prodex (Grant ISLRA 2009–1062); the μNEURO Research Center of Excellence of the University of Antwerp, the Institutional research chair in Neuroinformatics (Sherbrooke, Canada); the NSERC Discovery Grant; the European Research Council Consolidator grant (101044180); the Canada Research Chair in Quantitative Magnetic Resonance Imaging (950-230815); the Canadian Institute of Health Research (CIHR FDN-143263); the Canada Foundation for Innovation (32454, 34824); the Fonds de Recherche du Québec - Santé (322736); the Natural Sciences and Engineering Research Council of Canada (RGPIN-2019-07244); the Canada First Research Excellence Fund (IVADO and TransMedTech); the Courtois NeuroMod project; the Quebec BioImaging Network (5886, 35450); the Mila-Tech Transfer Funding Program; and the Swiss National Science Foundation (Eccellenza Fellowship PCEFP2_194260)

Etiological evaluation of amenorrhea: a cross-sectional study from a tertiary care center in India

Background: To determine the prevalence of etiological causes in cases with primary and secondary amenorrhea in a tertiary care center in Western India. Methods: A retrospective analysis of 170 medical records of non-pregnant women who presented with either primary or secondary amenorrhea to the Department of Obstetrics and Gynecology, IKDRC-ITS, Ahmedabad, Gujarat from Jan 2014 to December 2022 was done. The clinical profile, presentation, development of secondary sexual characteristics, physical examinations, hormone profile, imaging and cytogenetic study including karyotyping was done. Results: The most common causes of primary amenorrhea identified were end organ failure (71.49%), among these 69.41% had some form of Mullerian anomalies while three were cases of complete androgen insensitivity syndrome. This was followed by hormonal abnormalities (15.97%) and gonadal failure (7.63%). There were two cases of gonadal dysgenesis, three cases of Turner's syndrome, three cases of complete androgen insensitivity, one case of Swyers syndrome, two cases of ring X chromosomes. Hypergonadotropic hypogonadism was the most common cause of secondary amenorrhea. Three patients had premature ovarian failure. Single kidney was the most common association seen in eleven patients. Conclusions: This is one of the large studies exploring causes of both primary and secondary amenorrhea in Western India. Mullerian anomaly was the commonest cause of primary amenorrhea followed by hormonal abnormalities and gonadal failure. Hypergonadotropic hypogonadism was the most common cause of secondary amenorrhea. Role of racial, genetic, epigenetic and environmental factors could be an area of future research

Role of cetrorelix in the prevention and treatment of ovarian hyperstimulation syndrome: a prospective case control study

Background: Ovarian hyperstimulation syndrome (OHSS) has intrigued clinicians for many years because of its devastating consequences. As an iatrogenic condition resulting from elective ovarian stimulation in the quest for pregnancy, the need to completely prevent the syndrome is evident. Gonadotropin releasing hormone (GnRH) antagonist Cetrorelix has found to be effective in treatment of OHSS and some studies have found it to be helpful in prevention of this condition. Hence, we designed a hospital-based study to investigate the effect of Cetrorelix in preventing and treating OHSS in in-vitro fertilization – embryo transfer (IVF–ET) patients at risk of OHSS undergoing long and short protocol. Methods: The study includes total 102 patients undergoing controlled ovarian stimulation COS for IVF/ICSI. All cases were stimulated using long and short protocol. Depending on whether a GnRH antagonist was given after ovum pick-up (OPU) the patients were divided in two groups: Cetrorelix (antagonist) group (n=51) and control group (n=51). The study group was treated with Cetrorelix 0.25 mg for 5 days commencing on the day of ovum pick up. Results: Incidence of mild OHSS was significantly higher (p=0.01) whereas moderate to severe OHSS was significantly lower in the antagonist group (p<0.05). None of the patients had critical OHSS. Conclusions: GnRH antagonist Cetrorelix administration in early luteal phase in patients undergoing long or short protocol is effective in prevention and treatment of OHSS

Isolation Rate and Antifungal Susceptibility Patterns of Bloodstream Candida Species in a North Indian Hospital Setting between 2017-2021

Background: Candidemia is an increasingly important healthcare-associated fungal infection that is associated with high morbidity and mortality. The epidemiology of candidemia varies according to geographical region, period and the population involved. An increased incidence of non-albicans candidemia has been reported in recent studies. Aim: To study the prevalence of Candida species and their susceptibility profile over a period of five years (2017– 2021). Material and Methods: This retrospective study was performed in the microbiology laboratory. Specimens were collected and culture was performed using the BacTAlert3D / BacTec culture system. All the isolates were identified and their antifungal susceptibility testing was performed. Results: Year-wise positivity rates of candidemia were 0.85%, 0.68%, 0.73%, 0.82% and 0.71%. Majority of the isolates were from the age group 51-60 years with male predominance. Candida tropicalis was the most common species followed by C. albicans & C. parapsilosis. Candida isolates showed good susceptibility to Amphotericin B & Echinocandins whereas increased resistance to azoles (20-30%) was observed in C. tropicalis & C. parapsilosis. Conclusion: The emergence of a few Candida species, which were not previously isolated is alarming. NAC being more resistant / intrinsically resistant to fluconazole strengthens the need for antifungal susceptibility testing on a priority basis