Chondroprotective Effects of a Single PRP Injection in a Spontaneous Osteoarthritis Model of Dunkin Hartley Guinea Pig: An Immunohistochemical Analysis.

Purpose of the Study: The evaluation of anti-apoptotic and chondroprotective properties of a single injection of PRP using immunohistochemistry (IHC). Methods: This was a placebo-controlled blinded experimental study. Ten healthy Dunkin Hartley guinea pigs were selected. One knee of each animal was injected with a single injection of PRP (Group A); the contralateral knee acted as a control and was injected with a single injection of normal saline (Group B). These groups were further divided into A3 and B3 based on the timeline of animal sacrifice (3 months) and A6 and B6 (6 months). The formalin-preserved articular cartilage blocks were subjected to IHC to stain Aggrecan, Caspase-3, and Collagen-2. Results: The mean IHC score was significantly low for Caspase-3 (p-0.029) in intervention group (A3) in comparison to placebo control group (B3) pointing towards decreased apoptosis. The mean IHC values were significantly higher for Collagen II (p-0.011) for intervention group (A6) in contrast to control group (B6); values were also significantly low for Caspase-3 (p-0.029) in A6 as compared to B6. The mean Caspase-3 values were significantly higher in A6 as compared to A3 (p-0.029). Conclusion: The impact of a solitary injection of PRP on upregulation of anabolic pathways inside cartilage is relatively slower as compared to its effect on downregulation of apoptotic pathways. Even a single PRP injection holds the potential to change cartilage microenvironment, but the effects are not long lasting.

Developing Nepal's medicines pricing policy: evidence synthesis and stakeholders' consultation.

Objectives: The objectives of this paper are to (a) explore stakeholders' opinions regarding Nepal's existing medicines pricing practices/situation and (b) build and present a set of medicines pricing policies for Nepal. Methods: A review of the literature and field visits to community retail pharmacies, hospital pharmacies, wholesalers, and distributor outlets in Kathmandu were conducted to assess the medicines pricing situation. Following the literature review, preliminary meetings with stakeholders and field visits were held and a draft interview guide was prepared. Consultative sessions subsequently were undertaken in Kathmandu, Nepal, in January 2023 with representatives from the Department of Drug Administration, Ministry of Health and Population, Association of Pharmaceutical Producers of Nepal, consumer groups, Transparency International, Medicines Importers Association of Nepal/ Pharmaceutical Distributors Association of Nepal, Nepal Chemist and Druggist Association, and Nepal Pharmaceutical Association. Notes were taken during these meetings regarding issues and concerns raised as well as experiences and recommendations for the future, as outlined in the interview guide. Results: The stakeholders in general stated that they do not have any objection to price regulation; however, they believe such regulation should be subject to periodic review. Both the importers and the Ministry of Health and Population have the view that an independent body/authority should be charged with regulating the prices of medicines. A set of policy options to be considered for use in Nepal include cost-plus pricing, external price referencing, internal reference pricing, and mark-up regulations. Conclusion: Key issues related to pricing were identified and suggest that a set of pricing policies and updated regulations need to be considered to establish changes that are transparent, rational, and acceptable to the related stakeholders. Hence, suggestions made in this paper could be useful to inform a rational and fair pricing structure and to improve access to medicines.

A comparative study of perioperative pain, blood loss, and hospital stay in an Indian population undergoing mini-open oblique lumbar interbody fusion versus open transforaminal lumbar interbody fusion.

Background: There are several approaches for lumbar fusion, although there is yet to be a consensus on which approach is the best. This study aimed to evaluate the intraoperative blood loss and acute postoperative pain in single-level mini-open oblique lumbar interbody fusion (OLIF) versus open transforaminal lumbar interbody fusion (TLIF) surgeries for the degenerative spine. Methods: Thirty-two patients were assigned by the surgeon to OLIF or TLIF groups - 16 in mini-open OLIF and 16 in open TLIF groups. The intraoperative blood loss and postoperative hemoglobin, numerical rating scale (NRS) at proposed time intervals for 24 h postoperative, and rescue analgesics used were compared among the groups. The operative duration and hospital stay in both groups were also compared. Results: The OLIF group showed significantly higher postoperative hemoglobin (11.5 vs. 10.5 g %, P = 0.04), lower 24-h postoperative pain scores on movement, (NRS 4 vs. 5.5, P = 0.0001), and shorter hospital stay (4.5 vs. 7 days, P = 0.003) than TLIF group. However, the surgery duration was significantly longer in OLIF than in TLIF (190 vs. 150 min, P = 0.005). Intraoperative hemodynamics, other postoperative pain scores at variable time points, and rescue analgesics given were comparable among groups (P > 0.05). Intraoperative blood loss was lower in OLIF than TLIF (275 vs. 500 mL) but was not statistically significant (P > 0.05). Conclusion: Mini-open OLIF has favorable perioperative outcomes compared to open TLIF. Patients have higher postoperative hemoglobin and lesser pain on movement on the first postoperative day, leading to earlier mobilization and a shorter hospital stay.

Knee Arthrodesis Using Dual-Plate Construct is Following Failed Distal Femur Megaprosthesis-A Case Report.

Introduction: Knee arthrodesis following failed total knee arthroplasty is a viable limb salvage option, and this procedure is reserved for failed two-stage revision surgery in severe comorbid patients with irreparable extensor mechanism disruption, severe instability, and extensive soft tissue loss. Knee arthrodesis using a dual-plate construct has been scarcely reported. We report a case of knee arthrodesis using a dual-plate construct in a male in his 20s who presented to us with a broken distal femur megaprosthesis. Case Report: An anterior midline incision was given. The cement mantle and broken prosthetic components were removed. The bone surfaces were freshened up and fixed using two orthogonal locking plates. After 4 months, there was a solid fusion in the knee, and the patient started walking independently with a short limb gait. The patient was advised limb lengthening for a shortening of 3 cm, but he denied it and managed with a shoe raise. After 4 years, he was pain free, and radiographs revealed a solid knee fusion. The patient was fully satisfied with the procedure, and he resumed manual work. Conclusion: This case report revealed that knee arthrodesis using a dual-plate construct is an economically viable salvage option for failed distal femur megaprosthesis.

Evaluation of Artemisia dubia folium extract-mediated immune efficacy through developing a murine model for acute and chronic stages of atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a biphasic type of skin inflammation characterized by a predominance of type-2 (TH2) and type-1 (TH1) helper T cell-biased immune responses at the acute and persistent chronic phases, respectively. The present study was aimed to evaluate the efficacy of Artemisia dubia folium extract (ADFE) on AD-like skin lesions through developing a murine model for acute and chronic stages of AD. To induce acute phase AD, the dorsal skin of BALB/c mice was sensitized twice a week with 1% 2, 4-dinitrochlorobenzene (DNCB), followed by challenge (twice) in the following week with 0.2% DNCB. To induce persistent chronic AD, some mice were challenged twice a week for 4 more weeks. After the second challenge, the dorsal skin was exposed to 3% ADFE (five times per week) for 2 weeks (acute phase) or 4 weeks (persistent chronic phase). RESULTS: The paradigm of TH2 or TH1 predominance at the acute and chronic phase, respectively, was observed in this mouse model. During the acute phase, we observed an increased IL-4/IFN-γ ratio in splenic culture supernatants, an increased IgG1/IgG2a ratio in serum, and elevated serum IgE levels; however, the skew toward TH2 responses was diminished during the chronic stage. Compared with vehicle controls, ADFE reduced the IL-4/IFN-γ and IgG1/IgG2a ratios in acute AD, but both ratios increased during the chronic stage. CONCLUSIONS: Our results suggest that ADFE concomitantly suppresses the TH2 predominant response in acute AD, as well as the TH1 predominant response in chronic AD. Thus, ADFE is a candidate therapeutic for AD.

Drought, temperature, and moisture availability: understanding the drivers of isotopic decoupling in native pine species of the Nepalese Himalaya.

The Himalayas experienced long-term climate changes and recent extreme weather events that affected plant growth and the physiology of tree species at high-elevation sites. This study presents the first statistically robust δ18OTR chronologies for two native pine species, Pinus roxburghii, and Pinus wallichiana, in the lower Nepalese Himalaya. The isotope chronologies exhibited 0.88‰ differences in overall mean isotope values attributed to varying elevations (460-2000 m asl). Comparative analysis of climate response using data sets from different sources and resolutions revealed the superiority of the APHRODITE (Asian Precipitation - Highly-Resolved Observational Data Integration Towards Evaluation) data set calibrated for the South Asian Summer Monsoon (SASM)-dominated region. Both species exhibited negative correlations with monsoon precipitation and positive correlations with temperature. However, during the peak monsoon season (July-August), daily resolved climate data disentangled statistically insignificant relationships, and revealed that δ18OTR is influenced by atmospheric moisture. Both congeneric species showed a decoupling between the chronologies after 1995. However, no significant change in air moisture origin and monsoon regime between the study sites was observed, indicating a consistent dominant moisture source during different monsoon seasons. Besides, we also observed the decreased inter-series correlation of both δ18OTR chronologies after 1995, with P. wallichiana experiencing a steeper decrease than P. roxburghii. The weakening correlations between and within the chronologies coincided with a regional drought during 1993-1995 in both sites, highlighting the strong regulation of local climate on the impact of regional extreme climate events. Our findings emphasise the importance of employing climate data with optimal spatial and temporal resolution for improved δ18OTR-climate relationships at the intra-annual scale while considering the influence of site-specific local environmental conditions. Assessing climate data sets with station data is vital for accurately interpreting climate change's impact on forest response and long-term climate reconstructions.

Insights from in silico study of receptor energetics of SARS-CoV-2 variants.

The emergence of new variants of the novel coronavirus SARS-CoV-2 with increased infectivity, superior virulence, high transmissibility, and unmatched immune escape has demonstrated the adaptability and evolutionary fitness of the virus. The subject of relative order of the binding affinity of SARS-CoV-2 variants with the human ACE2 (hACE2) receptor is hotly debated and its resolution has implications for drug design and development. In this work, we have investigated the energetics of the binding of receptor binding domain (RBD) of SARS-CoV-2 variants of concern (VOCs): Beta (B.1.351), Delta (B.1.617.2), Omicron (B.1.1.529), variant of interest (VOI): Kappa (B.1.617.1), and Delta Plus (B.1.617.2.1) variant with the human ACE2 receptor by using the umbrella sampling (US) method. Our work indicates that Delta and Delta Plus variants have greater values of the US binding free energy than Wild-type (WT), whereas Beta, Kappa, and Omicron variants have lower values. Further analysis of hydrogen bonding, salt bridges, non-bonded interaction energy, and contact surface area at the RBD-hACE2 interface establish Delta as the variant with the highest binding affinity among these variants.

Predicting the current habitat refugia of Himalayan Musk deer (Moschus chrysogaster) across Nepal.

Himalayan Musk deer, Moschus chrysogaster is widely distributed but one of the least studied species in Nepal. In this study, we compiled a total of 429 current presence points of direct observation of the species, pellets droppings, and hoofmarks based on field-based surveys during 2018-2021 and periodic data held by the Department of National Park and Wildlife Conservation. We developed the species distribution model using an ensemble modeling approach. We used a combination of bioclimatic, anthropogenic, topographic, and vegetation-related variables to predict the current suitable habitat for Himalayan Musk deer in Nepal. A total of 16 predictor variables were used for habitat suitability modeling after the multicollinearity test. The study shows that the 6973.76 km2 (5%) area of Nepal is highly suitable and 8387.11 km2 (6%) is moderately suitable for HMD. The distribution of HMD shows mainly by precipitation seasonality, precipitation of the warmest quarter, temperature ranges, distance to water bodies, anthropogenic variables, and land use and land cover change (LULC). The probability of occurrence is less in habitats with low forest cover. The response curves indicate that the probability of occurrence of HMD decreases with an increase in precipitation seasonality and remains constant with an increase in precipitation of the warmest quarter. Thus, the fortune of the species distribution will be limited by anthropogenic factors like poaching, hunting, habitat fragmentation and habitat degradation, and long-term forces of climate change.

Primary Aneurysmal Bone Cyst in the Iliac Bone: A Case Report.

Introduction: Aneurysmal bone cysts (ABCs) are non-neoplastic expansile, vascular, osteolytic benign tumors in the long bone, spine, and sternum. The location in the pelvis is sparse. Case Report: A 12-year-old female presented with pain in her left pelvis for 6 months. On radiological examination, we found an expansile balloting lytic lesion involving almost the whole ilium and sparing the hip joint. There were multiple fluid levels seen on magnetic resonance imaging. The initial biopsy suggested ABC. Curettage and bone grafting were done along with electrocauterization and chemical cauterization. At 1-year follow-up, she is doing well without any complaints. Conclusion: This case report demonstrates a rare ABC of the ilium that was managed with curettage and bone grafting.

Multi-century (635-year) spring season precipitation reconstruction from northern Pakistan revealed increasing extremes.

The Hindu Kush Himalaya region is experiencing rapid climate change with adverse impacts in multiple sectors. To put recent climatic changes into a long-term context, here we reconstructed the region's climate history using tree-ring width chronologies of climate-sensitive Cedrus deodara and Pinus gerardiana. Growth-climate analysis reveals that the species tree-growth is primarily limited by moisture stress during or preceding the growing season, as indicated by a positive relationship between the chronology and precipitation and scPDSI, and a negative one with temperature. We have reconstructed 635 years (1384-2018 CE) of February-June precipitation using a robust climate reconstruction model that explains about 53% variance of the measured precipitation data. Our reconstruction shows several dry and wet episodes over the reconstruction period along with an increase in extreme precipitation events during recent centuries or years. Long, very wet periods were observed during the following years: 1392-1393, 1430-1433, 1456-1461, 1523-1526, 1685-1690, 1715-1719, 1744-1748, 1763-1767, 1803-1806, 1843-1846, 1850-1855, 1874-1876, 1885-1887, 1907-1909, 1921-1925, 1939-1944, and 1990-1992, while long dry periods were observed during the following years: 1398-1399, 1464-1472, 1480-1484, 1645-1649, 1724-1727, 1782-1786, 1810-1814, 1831-1835, 1879-1881, 1912-1918, 1981-1986, 1998-2003, and 2016-2018 CE. We found predominantly short-term periodicity cycles of 2.0, 2.2, 2.3, 2.4, 2.6-2.7, 2.9, 3.3, 4.8, 8.1-8.3, and 9.4-9.6 years in our reconstruction. Spatial correlation analyses reveal that our reconstruction is an effective representation of the precipitation variability in the westerly climate-dominated areas of Pakistan and adjacent regions. In addition to the influence of regional circulation systems like western disturbances, we found possible teleconnections between the precipitation variability in northern Pakistan and broader-scale climate modes or phases like AMO and ENSO. The study also highlights the prospects of tree-ring application to explore linkages between western disturbance, increasing intensity and frequency of extreme climate events, and analysis of long-term atmospheric circulation over the western Himalayan region.

An Update on Pharmacological and Phytochemical Aspects of Costus pictus D. Don - A Promising Anti-diabetic Plant.

BACKGROUND: The genus Costus is the largest genus in the family Costaceae and encompasses about 150 known species. Among these, Costus pictus D. Don (Synonym: Costus mexicanus) is a traditional medicinal herb used to treat diabetes and other ailments. Currently, available treatment options in modern medicine have several adverse effects. Herbal medicines are gaining importance as they are cost-effective and display improved therapeutic effects with fewer side effects. Scientists have been seeking therapeutic compounds in plants, and various in vitro and in vivo studies report Costus pictus D. Don as a potential source in treating various diseases. Phytochemicals with various pharmacological properties of Costus pictus D. Don, viz. anti-cancer, anti-oxidant, diuretic, analgesic, and anti-microbial have been worked out and reported in the literature. OBJECTIVE: The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research. METHODS: This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, Sci-Finder, other online journals and books for detailed analysis. RESULTS: Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare. CONCLUSION: This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.

Base flipping mechanism and binding strength of methyl-damaged DNA during the interaction with AGT.

Methyl damage to DNA bases is common in the cell nucleus. O6-alkylguanine-DNA alkyl transferase (AGT) may be a promising candidate for direct damage reversal in methylated DNA (mDNA) at the O6 point of the guanine. Indeed, atomic-level investigations in the contact region of AGT-DNA complex can provide an in-depth understanding of their binding mechanism, allowing to evaluate the silico-drug nature of AGT and its utility in removing methyl damage in DNA. In this study, molecular dynamics (MD) simulation was utilized to examine the flipping of methylated nucleotide, the binding mechanism between mDNA and AGT, and the comparison of binding strength prior and post methyl transfer to AGT. The study reveals that methylation at the O6 atom of guanine weakens the hydrogen bond (H-bond) between guanine and cytosine, permitting for the flipping of such nucleotide. The formation of a H-bond between the base pair of methylated nucleotide (i.e., cytosine) and the intercalated arginine of AGT also forces the nucleotide to rotate. Following that, electrostatics and van der Waals contacts as well as hydrogen bonding contribute to form the complex of DNA and protein. The stronger binding of AGT with DNA before methyl transfer creates the suitable condition to transfer methyl adduct from DNA to AGT.

Gastro-intestinal parasites of urban rhesus macaques (Macaca mulatta) in the Kathmandu Valley, Nepal.

Intestinal parasitic infections such as amoebiasis, ascariasis, hookworm infection, and trichuriasis are the most common infections among non-human primates (NHPs). There are always the possibilities of transmission these parasites between humans and NHPs. Multiple groups of rhesus macaques (Macaca mulatta) live in the urban area of Kathmandu Valley near human settlements, however the gastrointestinal (GI) parasitic infections in those macaques are understudied. This study aimed to explore the GI parasites in free-ranging macaques from Pashupatinath, Swayambhunath, Tripureshwor, Nilbarahi temples and a group of captive rhesus macaques in the Central Zoo, Kathmandu. Fecal samples were collected from the macaques between October 2021 to September 2022 and assessed for parasites by the both wet mount method and concentration technique. There is high prevalence of GI parasite infection; out of 121 fecal samples examined, 87.6% of samples were positive. Six species of protozoans and eight species of helminths were identified from the fecal samples including the first report of Iodamoeba butschlii in monkeys of Nepal. Among the protozoan parasites, Entamoeba coli (54.71%) showed the highest prevalence followed by Balantioides coli (44.33%), E. histolytica (19.81%), and Iodamoeba butschlii (10%). Among the helminths, Trichuris spp. (31.13%) and Strongyloides spp. (31.13%) showed the highest prevalence followed by Hookworm (24.52%), and Strongyle spp. (23.58%). The likelihood ratio test suggested that the prevalence differed significantly with the seasons for Iodamoeba butschlii, Giardia spp., Strongyles spp., Hookworm, and Trichostrongylus spp. The prevalence of E. histolytica, E. coli, Iodamoeba. butschlii, Trichuris spp., Trichostrongylus spp., and Unknown spp.1 differed with sampling localities. The high prevalence of GI parasites found in the macaques living in the densely urbanized Kathmandu presents a potential threat to humans and warrants further study as well as increased education of the public and management of the human-macaque interface in the urban landscape of the Valley.

INTRAGRO: A machine learning approach to predict future growth of trees under climate change.

The escalating impact of climate change on global terrestrial ecosystems demands a robust prediction of the trees' growth patterns and physiological adaptation for sustainable forestry and successful conservation efforts. Understanding these dynamics at an intra-annual resolution can offer deeper insights into tree responses under various future climate scenarios. However, the existing approaches to infer cambial or leaf phenological change are mainly focused on certain climatic zones (such as higher latitudes) or species with foliage discolouration during the fall season. In this study, we demonstrated a novel approach (INTRAGRO) to combine intra-annual circumference records generated by dendrometers coupled to the output of climate models to predict future tree growth at intra-annual resolution using a series of supervised and unsupervised machine learning algorithms. INTRAGRO performed well using our dataset, that is dendrometer data of P. roxburghii Sarg. from the subtropical mid-elevation belt of Nepal, with robust test statistics. Our growth prediction shows enhanced tree growth at our study site for the middle and end of the 21st century. This result is remarkable since the predicted growing season by INTRAGRO is expected to shorten due to changes in seasonal precipitation. INTRAGRO's key advantage is the opportunity to analyse changes in trees' intra-annual growth dynamics on a global scale, regardless of the investigated tree species, regional climate and geographical conditions. Such information is important to assess tree species' growth performance and physiological adaptation to growing season change under different climate scenarios.

Seasonal Prey Abundance and Food Plasticity of the Vulnerable Snow Leopard (Panthera uncia) in the Lapchi Valley, Nepal Himalayas.

Conservation strategies for apex predators, like the snow leopard (Panthera uncia), depend on a robust understanding of their dietary preferences, prey abundance, and adaptability to changing ecological conditions. To address these critical conservation concerns, this study presents a comprehensive evidence on prey availability and preferences for snow leopards in the Lapchi Valley in the Nepal Himalayas from November 2021 to March 2023. Field data were collected through the installation of twenty-six camera traps at 16 strategically chosen locations, resulting in the recording of 1228 events of 19 mammalian species, including domesticated livestock. Simultaneously, the collection of twenty snow leopard scat samples over 3800 m above sea level allowed for a detailed dietary analysis. Photo capture rate index and biomass composition analysis were carried out and seasonal prey availability and consumption were statistically analyzed. A total of 16 potential prey species for the snow leopard were documented during the study period. Himalayan musk deer (Moschus leucogaster) was the most abundant prey species, but infrequent in the diet suggesting that are not the best bet prey for the snow leopards. Snow leopards were found to exhibit a diverse diet, consuming eleven prey species, with blue sheep (Pseudois nayaur) being their most consumed wild prey and horses as their preferred livestock. The Pianka's index of dietary niche overlap between the summer and winter seasons were 0.576, suggesting a pronounced seasonal variation in food preference corroborating with the prey availability. The scarcity of larger preys in winter is compensated by small and meso-mammals in the diet, highlighting the snow leopard's capacity for dietary plasticity in response to the variation in resource availability. This research suggests for the utilization of genetic tools to further explore snow leopard diet composition. Additionally, understanding transboundary movements and conducting population assessments will be imperative for the formulation of effective conservation strategies.

Enhanced therapeutic efficacy of Piperlongumine for cancer treatment using nano-liposomes mediated delivery.

Piperlongumine (PL) is a well-known bioactive alkaloid that has been reported as a potent anticancer molecule but has failed to provide potential activity in translational and clinical applications due to some drawbacks like low bioavailability, hydrophobicity, and rapid degradation. However, nano-formulation is a good choice to increase the bioavailability and enhance cellular uptake of PL. In this study, PL loaded nano-liposomes (NPL) were formulated using the thin-film hydration method and analyzed by Response Surface Methodology (RSM) in order to treat cervical cancer. The NPL were thoroughly characterized using particle size, PDI, zeta potential, drug loading capacity, encapsulation efficiency, SEM, AFM and FTIR. Different assays viz. MTT, AO/PI, DAPI, MMP, cell migration, DCFDA and apoptotic assay using Annexin V-FITC/PI were performed for anticancer potential of NPL in human cervical carcinoma cells (SiHa and HeLa). NPL showed enhanced cytotoxicity, diminished cell proliferation, reduced cell viability, enhanced nuclear condensation, reduction in mitochondrial membrane potential, inhibited cell migration, increased ROS level and promoted more apoptosis in both human cervical cancer cell lines. These findings demonstrated that NPL may be a potential therapeutic option for cervical cancer.

Anti-inflammatory, anti-proliferative and anti-psoriatic potential of apigenin in RAW 264.7 cells, HaCaT cells and psoriasis like dermatitis in BALB/c mice.

AIMS: Psoriasis is an immune-mediated skin disease characterized by keratinocytes hyperproliferation, abnormal differentiation and inflammation. Therefore, this study aimed to investigate in-vitro and in-vivo anti-inflammatory and anti-proliferative activity to evaluate anti-psoriatic potential of apigenin. MAIN METHODS: For in-vivo study, 5 % imiquimod cream was used to induce psoriasis-like skin inflammation in BALB/c mice to mimic human psoriatic conditions. PASI score, CosCam score, histopathology, immunohistochemistry, qRT-PCR, and ELISA were done to evaluate the anti-psoriatic potential of topically applied apigenin. For in-vitro studies, LPS-induced inflammation in RAW 264.7 was done, and qRT-PCR, ELISA, and immunofluorescence were conducted to evaluate the anti-inflammatory activity of apigenin. Migration and cell doubling assay in HaCaT cells were performed to assess the anti-proliferative effect of apigenin. Acute dermal toxicity profile of apigenin has also been done as per OECD guidelines. KEY FINDINGS: Results showed that apigenin significantly reduce the PASI and CosCam scores, ameliorate the deteriorating histopathology, and effectively downregulated the expression of CCR6, IL-17A, and NF-κB. Apigenin effectively downregulated the expression and secretion of pro-inflammatory cytokines through IL-23/IL-17/IL-22 axis. Apigenin suppressed nuclear translocation of NF-κB in LPS-induced RAW 264.7 cells. Cell migration and cell doubling assay in HaCaT cells showing the anti-proliferative potential of apigenin and it was found safe in acute dermal toxicity study. SIGNIFICANCE: Apigenin was found effective against psoriasis in both in-vitro and in-vivo models suggesting apigenin as a potential candidate for the development of anti-psoriatic agent.

A novel technique of reconstruction of the distal tibia using allograft after resection of giant cell tumor: A case report with literature review.

Giant cell tumor (GCT) of the distal tibia can result in significant bone loss and soft tissue compromise, which can present a challenge for reconstruction. Various techniques have been described for the reconstruction of large defects, including the use of allografts. In this article, we describe a novel technique of reconstruction of a large defect in the distal tibia using two femoral head allografts after resection of GCT. The technique involves using two femoral head allografts, which are shaped to fit the defect and secured with a locking plate and screws. Using this technique, we present a case report of a patient with GCT of the distal tibia who underwent resection and reconstruction. At the 18-month follow-up, the patient had good functional outcomes and no evidence of tumor recurrence. This technique offers a viable option for reconstructing large defects in the distal tibia after GCT resection, particularly in cases where autograft is not available or not feasible. Further studies are needed to evaluate the long-term outcomes and complications associated with this technique.

Correlation of bone mineral density using the dual energy x-ray absorptiometry and the magnetic resonance imaging of the lumbar spine in Indian patients.

Background: Dual-energy x-ray absorptiometry (DEXA) scan is extensively used to diagnose osteoporosis. But surprisingly, osteoporosis remains an underdiagnosed condition with many fragility fracture patients who have failed to undergo DEXA or received concomitant treatment for osteoporosis. Magnetic resonance imaging (MRI) of the lumbar spine is a routine radiological investigation bring done for low back pain. MRI can detect changes in the bone marrow signal intensity on the standard T1-weighted images. This correlation can be explored to measure osteoporosis in elderly and post-menopausal patients. The present study aims to find any correlation of bone mineral density using the DEXA and MRI of the lumbar spine in Indian patients. Methods: Five regions of interest (ROI) of size 130-180 mm2 were placed in the vertebral body in the mid-sagittal section and parasagittal sections on either side (four in L1-L4 and one outside body) of elderly patients who underwent MRI for back pain. They also underwent a DEXA scan for osteoporosis. Signal to Noise Ratio (SNR) was calculated by dividing the mean signal intensity obtained for each vertebra by the standard deviation of the noise. Similarly, SNR was measured for 24 controls. An MRI-based "M score" was calculated by getting the difference in SNR patients to SNR controls and then dividing it by the control's standard deviation (SD). Correlation between the T score on DEXA and M scores on MRI was found out. Results: With the M score greater than or equal to 2.82, the sensitivity was 87.5%, and the specificity was 76.5%. M scores negatively correlated with the T score. With the increase in the T score, the M score decreased. The Spearman correlation coefficient for the spine T score was -0.651, with a p-value of <0.001, and the hip T score was -0.428, with a p-value of 0.013. Conclusion: Our study indicates that MRI investigations are helpful in Osteoporosis assessments. Even though MRI may not replace DEXA, it can give insight into elderly patients who get an MRI routinely for back pain. It may also have a prognostic value.