Variations of great saphenous vein: a cadaveric study in central Indian population

Background: Variations are more commonly seen in venous system as compared to arterial system. Varicosities are more commonly seen in the superficial veins of lower limbs.Methods: In the present study, thirty lower limbs were dissected superficially to study the course, tributaries and perforators of great saphenous vein. After exposing the vein, we took various measurements from saphenofemoral junction to the origin of various tributaries and perforators. Pattern of duplications were also reported.Results: The mean distance of tributaries and perforators were compared with the previous literature available. Patterns of duplication were also reported.Conclusions: Study of variations of great saphenous vein would be of immense help in planning varicose vein treatment and coronary artery bypass procedures where it is used as autograft. Therefore, the study will be helpful for surgeons, cardiologist and interventional radiologist

A Study of Fermions Coupled to Gauge and Gravitational Fields on a Cylinder

Fermions on a cylinder coupled to gravity and gauge fields are examined by studying the geometric action associated with the symmetries of such a system. The gauge coupling constant is shown to be constrained and the effect of gravity on the masses is discussed. Furthermore, we introduce a new gravitational theory which couples to the fermions by promoting the coadjoint vector of the diffeomorphism sector to a dynamical variable. This system, together with the gauge sector is shown to be equivalent to a one dimensional system.Comment: 16 pages, UI-94-2 (Some minor typographical errors are cleaned up.

An improved medium formulation for efficient ex vivo gene editing, expansion and engraftment of hematopoietic stem and progenitor cell populations

Gene editing has emerged as a powerful tool for the therapeutic correction of monogenic diseases. CRISPR/Cas9 applied to hematopoietic stem and progenitor cells (HSPCs) has shown great promise in proof-of-principle preclinical studies to treat hematological disorders, and clinical trials using these tools are now underway. Nonetheless, there remain important challenges that need to be addressed, such as the efficiency of targeting primitive, long-term repopulating HSPCs and their in vitro expansion for clinical application. In this study, we assessed the effect of different culture medium compositions on the ability of HSPCs to proliferate and undergo homology directed repair-mediated knock-in of a reporter gene, while preserving their stemness features during ex vivo culture. We demonstrated that by supplementing the culture medium with stem cell agonists and by fine-tuning its cytokine composition it is possible to achieve high levels of gene targeting in long-term repopulating HSPCs both in vitro and in vivo, with a beneficial balance between preservation of stemness and cell expansion. Overall, the implementation of this optimized ex vivo HSPC culture protocol can improve the efficacy, feasibility and applicability of gene editing as a key step to unlocking the full therapeutic potential of this powerful technology

Formulation Development and Evaluation of Gastroretentive Delivery System (Microspheres) Using Natural Polymer

Microspheres are novel drug delivery approach to control release of pharmacologically active ingredient as per patient need. Natural polymers like fenugreek mucilage are cheap, biodegradable and have been proved safe for pharmaceutical formulation. Higher loading efficiency was observed for all the formulations and also the drug release was observed for the period of 12 hours. Thus, the simvastatin microsphere using fenugreek mucilage showed promising results in retarding the drug release. It can be concluded from whole study that due to the formation of polymeric network system or other active moiety can be easily entrapped with the matrix and hydration and swelling of natural polymer controlled their release patter

Wiskott Aldrich syndrome protein regulates non-selective autophagy and mitochondrial homeostasis in human myeloid cells.

The actin cytoskeletal regulator Wiskott Aldrich syndrome protein (WASp) has been implicated in maintenance of the autophagy-inflammasome axis in innate murine immune cells. Here, we show that WASp deficiency is associated with impaired rapamycin-induced autophagosome formation and trafficking to lysosomes in primary human monocyte-derived macrophages (MDMs). WASp reconstitution in vitro and in WAS patients following clinical gene therapy restores autophagic flux and is dependent on the actin-related protein complex ARP2/3. Induction of mitochondrial damage with CCCP, as a model of selective autophagy, also reveals a novel ARP2/3-dependent role for WASp in formation of sequestrating actin cages and maintenance of mitochondrial network integrity. Furthermore, mitochondrial respiration is suppressed in WAS patient MDMs and unable to achieve normal maximal activity when stressed, indicating profound intrinsic metabolic dysfunction. Taken together, we provide evidence of new and important roles of human WASp in autophagic processes and immunometabolic regulation, which may mechanistically contribute to the complex WAS immunophenotype

ROLE OF MRI IN EVALUATION OF EPILEPSY IN PEDIATRIC AGE GROUP IN A TERTIARY CARE CENTRE OF JHARKHAND, INDIA- A PROSPECTIVE STUDY.

Background: Childhood epilepsy is a prevalent neurological disorder. Imaging, especially MRI of the brain, plays a pivotal role in diagnosing the underlying cause. This study aimed to assess the frequency of causative factors of epilepsy detected in MRI. Materials and Methods: This hospital-based prospective observational study was conducted in the Radiology Department at Rajendra Institute of Medical Sciences (RIMS), Ranchi, Jharkhand, India from November 2021 to October 2022 in 100 children of 0 to 12 years of age referred from Pediatrics department for an MRI brain scan. MRI of the brain was performed in all cases and findings were analyzed and causes of epilepsy were assessed. Magnetic resonance spectroscopy (MRS) was also done when required for confirmation of diagnosis. Results: Positive findings in MRI were detected in 87% of children, and no abnormalities were detected in 13%. The majority of children belonged to the age group of 10-12 years (37%) and were predominantly males (66%). The most common cause of epilepsy was infections (27%) followed by hypoxic ischemic encephalopathy (22%). Tuberculoma was the most common infective cause of epilepsy in 59.3%. These were further followed by temporal lobe epilepsy and congenital malformations (11% each). The rest were other miscellaneous and idiopathic causes. Conclusion: MRI findings were specific to various conditions, helping in the localization and characterization of etiologies and playing a significant role in the evaluation of children who were newly diagnosed with epilepsy, especially those with partial seizures. Recommendation: Further research with a larger sample size and meta-analysis is recommended for more conclusive results

Leishmania aethiopica cell‐to‐cell spreading involves caspase‐3, AkT, and NF‐κB but not PKC‐δ activation and involves uptake of LAMP‐1‐positive bodies containing parasites

Development of human leishmaniasis is dependent on the ability of intracellular Leishmania parasites to spread and enter macrophages. The mechanism through which free promastigotes and amastigotes bind and enter host macrophages has been previously investigated; however, little is known about intracellular trafficking and cell-to-cell spreading. In this study, the mechanism involved in the spreading of Leishmania aethiopica and Leishmania mexicana was investigated. A significant increase in phosphatidylserine (PS) exhibition, cytochrome C release, and active caspase-3 expression was detected (P < 0.05) during L. aethiopica, but not L. mexicana spreading. A decrease (P < 0.05) of protein kinase B (Akt) protein and BCL2-associated agonist of cell death (BAD) phosphorylation was also observed. The nuclear factor kappa-light-chain enhancer of activated B cells (NF-kB) signaling pathway and pro-apoptotic protein protein kinase C delta (PKC-δ) were downregulated while inhibition of caspase-3 activation prevented L. aethiopica spreading. Overall suggesting that L. aethiopica induces host cell’s apoptosis during spreading in a caspase-3-dependent manner. The trafficking of amastigotes within macrophages following cell-to-cell spreading differed from that of axenic parasites and involved co-localization with lysosomal-associated membrane protein 1 (LAMP-1) within 10 min postinfection. Interestingly, following infection with axenic amastigotes and promastigotes, co-localization of parasites with LAMP-1-positive structures took place at 1 and 4 h, respectively, suggesting that the membrane coat and LAMP-1 protein were derived from the donor cell. Collectively, these findings indicate that host cell apoptosis, demonstrated by PS exhibition, caspase-3 activation, cytochrome C release, downregulation of Akt, BAD phosphorylation, NF-kB activation, and independent of PKC-δ expression, is involved in L. aethiopica spreading. Moreover, L. aethiopica parasites associate with LAMP-rich structures when taken up by neighboring macrophages