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Menkes kinky hair disease (MKHD) is a rare inherent error of copper metabolism presenting during early infancy with multi-system involvement. It is associated with high morbidity and mortality in early childhood. Characteristic hair changes mirror internal metabolic alterations. Here, we report a case of 13-month-old male child who presented with peculiar changes of skin and hair along with convulsion and high-grade fever. Dermatoscopy and hair mount examination showing pili torti with pigmentary dilution pointed toward the diagnosis of MKHD, which was further enforced with blood investigations showing low copper and ceruloplasmin levels. Cutaneous findings play a crucial role in early diagnosis, thereby reducing morbidity with timely treatment.

Abstract Complex permittivity of Corn, Jowar, Ashoka and Banana plant leaves was measured using a Vector Network Analyzer (Anritsu Shockline Model-MS46322A) over 500 MHz to 15 GHz frequency range, at different moisture contents. The dielectric constant ( $$\varepsilon$$ ε ′) and dielectric loss ( $$\varepsilon$$ ε ″) of the leaves decrease with decrease in moisture content over this frequency range. For the leaves having moisture content less than certain critical moisture level (CML), the values of $$\varepsilon$$ ε ′ and $$\varepsilon$$ ε ” remain almost constant with frequency variation. $$\varepsilon$$ ε ″ does not increase appreciably with the increase in moisture content up to CML. CML is found to vary for different types of leaves. At higher moisture level, $$\varepsilon$$ ε ′ and $$\varepsilon$$ ε ″ exhibit frequency dependence. Above certain moisture level in the leaves, $$\varepsilon$$ ε ″ starts to increase slowly with the increase in frequency above 3 GHz approaching towards the dielectric relaxation of water. The values of $$\varepsilon$$ ε ′ and $$\varepsilon$$ ε ″ were also measured for the extract of leaves and compared with the values calculated using Stogryn equations for the same salinity, and the results agree with the calculated values. The measured values of $$\varepsilon$$ ε ′ and $$\varepsilon$$ ε ″ for the leaves were compared with the values calculated using Debye–Cole dual dispersion dielectric model and are found to match very well.

A study was carried out to investigate the effect of supplementation of cumin (Cuminum cyminum) seed (CS) on the production performance, nutrient digestibility and hemato-biochemical profiles of lactating Mehsana goats. Twenty lactating Mehsana goats (7 days post-partum) were assigned randomly into two groups (10 animals in each), control (CON: fed basal diet without supplement) and treatment (CS: basal diet supplemented with 10 g/animal/d of CS) for the duration of 60 days. The final body weight was significantly higher (38.09 vs. 34.04 kg) in the animals of CS group than the CON group. Feeding of cumin seed to the lactating goats did not influence daily dry matter intake. However, cumin seed supplementation increased milk yield (985 vs. 859 g/d), 4% FCM (818 vs 623 g/d) and ECM (952 vs. 742 g/d) as compared to the CON group. The percentages of milk fat, SNF, total solids and lactose were also improved by the supplementation of cumin seed. Apparent digestibility of dry matter was comparable in CON and CS groups. However, the digestibilities of crude protein (58.19 vs. 66.97%), crude fibre (47.05 vs. 55.28%), ether extract (67.00 vs.75.82%) and nitrogen free extract (65.25 vs. 75.32%) were significantly improved in cumin supplemented group. There was no effect on haematological parameters between the CON and CS groups. The supplementation of cumin has significantly improved glucose concentration in CS group when compared to the CON group. The concentrations of other estimated blood metabolites were not affected by the cumin supplementation in lactating goats. Based on the results of the present study, it can be concluded that cumin supplementation in the diet of lactating Mehsana goats at the rate of 10 g/d improved milk yield, nutrient digestibility and feed efficiency without any adverse effect on haemato-biochemical parameters

First lactation production records of 7,825 Mehsana buffaloes, sired by 200 sires maintained at Dudhsagar Research and Development Association, Dudhsagar Dairy, Mehsana over a period of 25 years (1989-2013), were utilised for estimation of breeding value of the first lactation milk yield using BLUP - Univariate sire model and animal model using WOMBAT software. The study aimed to find out the optimum number of daughters that may be sufficient for more accurate and unbiased estimate of breeding value of Mehsana buffalo bulls. The effectiveness of different models run with different daughters per sire for sire evaluation was judged on the basis of within-sire variance. The maximum and minimum estimated breeding values were 1924.04 l (BLUP-AM, 5 daughters/sire) and 1855.61 l (BLUP-SM, 30 daughters/sire), respectively. However, error variance estimated was highest when five daughters/sire were evaluated and lowest, when 30 daughters/sire were evaluated. The present study revealed that the sire evaluation with sires having minimum 5, 10 and 15 daughters are equally efficient. However, if we do evaluation with sires having daughters more than 20, 25 or 30, additional accuracy of approximately 2.5%, 3% and 5%, respectively may be obtained.

Endogenous FLOWERING LOCUS T homolog MeFT1 was transgenically overexpressed under control of a strong constitutive promoter in cassava cultivar 60444 to determine its role in regulation of flowering and as a potential tool to accelerate cassava breeding. Early profuse flowering was recorded in-vitro in all ten transgenic plant lines recovered, causing eight lines to die within 21 days of culture. The two surviving transgenic plant lines flowered early and profusely commencing as soon as 14 days after establishment in soil in the greenhouse. Both transgenic lines sustained early flowering across the vegetative propagation cycle, with first flowering recorded 30-50 days after planting stakes compared to 90 days for non-transgenic controls. Transgenic plant lines completed five flowering cycles within 200 days in the greenhouse as opposed to twice flowering event in the controls. Constitutive overexpression of MeFT1 generated fully mature male and female flowers and produced a bushy phenotype due to significantly increased flowering-induced branching. Flower induction by MeFT1 overexpression was not graft-transmissible and negatively affected storage root development. Accelerated flowering in transgenic plants was associated with significantly increased mRNA levels of MeFT1 and the three floral meristem identity genes MeAP1, MeLFY and MeSOC1 in shoot apical tissues. These findings imply that MeFT1 encodes flower induction and triggers flowering by recruiting downstream floral meristem identity genes.

Abstract This study models a joint pricing, inventory, and preservation decision-making problem for deteriorating items subject to stochastic demand and promotional effort. The generalized price-dependent stochastic demand, time proportional deterioration, and partial backlogging rates are used to model the inventory system. The objective is to find the optimal pricing, replenishment, and preservation technology investment strategies while maximizing the total profit per unit time. Based on the partial backlogging and lost sale cases, we first deduce the criterion for optimal replenishment schedules for any given price and technology investment cost. Second, we show that, respectively, total profit per time unit is concave function of price and preservation technology cost. At the end, some numerical examples and the results of a sensitivity analysis are used to illustrate the features of the proposed model.

First lactation data on 7,782 Mehsana buffaloes sired by 184 sires maintained at Dudhsagar Research and Development Association, Dudhsagar Dairy, Mehsana over a period of 24 years (1989–2012) were used to estimate least-squares means (LSM) and breeding value of the first lactation fat yield (FLFY) and average fat percentage (AFP) using univariate and bivariate models with the help of WOMBAT software. The effectiveness of different sire evaluation models using FLFY and AFP were compared on the basis of error variance, coefficient of determination (CV%), R2-value, AIC, BIC and Spearman’s rank correlation. The average estimate of FLFY and AFP was 135.04±0.57 kg and 7.11±0.11% in Mehsana buffaloes. These estimates were significantly affected by period and season of calving, and age at first calving group. The average expected breeding value of Mehsana buffalo bulls for FLFY and AFP were 133.24 kg and 7.14% using sire model (BLUP-SM), 135.71 kg and 7.22% using univariate animal model (BLUP-U-AM) and 133.23 kg and 7.14% from bivariate animal model (BLUP-B-AM), respectively for FLFY and AFP. The spearman’s rank correlation indicated similarity of rankings by BLUP-U-AM and BLUPB- AM. Animal model had a wider range of breeding values indicating the greater differentiating ability of the model. Based on error variance, AIC, BIC, R2 and CV; animal model was found to be superior in comparison to sire model.

Maggot debridement therapy (MDT) is a safe, effective, and controlled method of healing of chronic wounds by debridement and disinfection. In this therapy live, sterile maggots of green bottle fly, Lucilia (Phaenicia) sericata are used, as they prefer necrotic tissues over healthy for feeding. Since centuries, MDT is used in human beings to treat chronic wounds. Lately, MDT came out as a potent medical aid in animals. In animals, although, this therapy is still limited and clinical studies are few. However, with the increasing antibiotic resistance and chronic wound infections in veterinary medicine, maggot therapy may even become the first line of treatment for some infections. This paper will present a brief discussion of MDT and its role in veterinary medicine that may add one more treatment method to utilize in non-healing wounds of animals and overcome the use of amputation and euthanasia. The objective of this review paper is to assemble relevant literature on maggot therapy to form a theoretical foundation from which further steps toward clinical use of maggot therapy in animals for chronic wounds can be taken.

Aim: The present study was conducted to evaluate the dietary addition of Emblica officinalis (Amla) fruit powder as a growth promoter in commercial broiler chickens. Materials and Methods: An experiment was conducted on 135 commercial broiler chicks (Ven-Cobb 400 strain) divided into three groups with three replicates of 15 chicks each. Three treatment groups were as follows – T1: Basal diet as per BIS standards; T2: Basal diet supplemented with 0.4% of E. officinalis fruit powder; and T3: Basal diet supplemented with 0.8% of E. officinalis fruit powder. Results: The average body weights at the end of the 6th week were significantly higher (p

Background: HIV transmission from mother to child continues to be the major source of HIV infection in young children. This study assessed utilization and uptake of PPTCT services among HIV positive antenatal women registered at PPTCT centres of the Surat city. Materials and Methods: This Retro-prospective Cohort study en- rolled a sample of 282 HIV positive antenatal women registered for HIV testing and counseling during January 2007 to Dec 2008 in 5 PPTCT centres of Surat city and conducted from Dec 2008 to Nov 2010. Of these 127 (45%) antenatal women who came to collect their reports were included in the study and given post test coun- seling. Result: There was 55% loss to follow up among the HIV positive antenatal women and out of 127 (45%) women, 98(77%) had been registered in ART centres, from which only 45% started ART, 9% opted for abortion,105 (91%) were institutional delivery, among them only 38% underwent caesarean section,.101 (91%) mother- baby pairs received nevirapine prophylaxis at the time of labour and out of these, only 84 exposed babies were tested at 18 months of age and 5 (5.95%) were found to be positive among them. Conclusion: Utilization and uptake of PPTCT services among the HIV positive antenatal women has remained low even after avail- abilities of 5 PPTCT centres in the study area. Just like mothers, drop out in service utilization was observed among exposed children also.

Aim: This study was undertaken to derive the prevalence rate of Fasciolosis in buffaloes by a collection of fecal and liver samples from Anand and Ahmedabad districts’ local slaughter houses. Materials and Methods: Fecal and liver samples were collected during ante- and post-mortem examination, respectively, and brought to the department laboratory preserved in 10% formalin for further processing. Fecal samples were processed with qualitative examination viz.; sedimentation technique for identification of the ova. Liver samples were also examined for the presence of gross parasites. Results: The highest prevalence rate was observed in the month of December (25.97% fecal and 33.33% liver samples) and lowest in the month of May (10.71% fecal and 11.76% liver samples) at Anand district. In the area of Ahmedabad district, the highest prevalence rate was recorded in the month of October and February (26.98%) and lowest in the month of May (10.34%) for the fecal and highest prevalence was observed in the month of February (26.98%) and lowest in May (11.11%) for the liver samples. Conclusion: It can be concluded that the heavy infection is present in Anand and Ahmedabad districts, especially in the month of winter followed by monsoon and the least in summer.

Aim: The study was undertaken to compare the alterations in the hematological parameters in buffaloes suffering from Amphistomosis with normal buffaloes and to correlate it with the subclinical infection that is hard to diagnose. Materials and Methods: Blood samples from 50 amphistomes infected as well as 50 non-infected buffaloes from slaughter houses were taken into vacutainer tubes containing ethylene diamine tetraacetic acid for estimation of various hematological parameters by Automatic Analyzer Hema-2062 manufactured by Analytical Technologies Ltd. Result: There was a significant reduction in the mean hemoglobin, total leukocyte count, total erythrocyte count and packed cell volume and significant increase in the neutrophils count and eosinophil count of infected buffaloes as compared to the non-infected buffaloes respectively. Conclusion: Amphistomosis is characterized by severe neutrophilia, eosinophilia, and anemia. Anemia of high intensity along with hepatic damage can lead to the death of the animal in severe cases. Alterations in the Hematological parameters can be used as an indicator to diagnose and check the severity of amphistomosis especially in young ones and in subclinical infection.

Aim: This study was undertaken to identify Paramphistomum cervi on the basis of its morphology and histology to be the common cause of paramphistomosis in infected sheep and its differentiation from other similar Paramphistomes in Gujarat. Materials and Methods: Adult rumen flukes were recovered from the rumen of naturally infected sheep slaughtered in various abattoirs in Gujarat. Some adult flukes were flattened and stained in Borax carmine, and some were sectioned in the median sagittal plane and histological slides of the flukes were prepared for detailed morphological and histological studies. Result: Microscopic pictures of the parasite used in identification define the similarity in the morphology and histology of the anterior sucker, pharynx, esophagus, genital atrium, posterior sucker (acetabulum) and testes to the P. cervi. Conclusion: It can be concluded that the most common species found in sheep infected with Paramphistomosis is P. cervi on the basis of its histo-morphological appearance in Gujarat.

Introduction: Open fractures are fairly common in developing countries. Causes of open fractures vary widely including road traffic accident, fall from height, gunshot, assault, machine injuries and others. Infection is a common complication of open fractures. Chronic osteomyelitis, nonunion, loss of function or even limb loss are some serious outcome of deep fracture site infections. Primary goal in management of open fractures is prevention of infection of bone and soft tissue by early debridement, irrigation of wound and administration of broad spectrum antibiotics with stabilization of fractures. Aim: The aim of the study is to elucidate pattern of microbial isolates in open fractures so as to form rationale antibiotic regimen for treating open fractures. Methods: 70 patients were taken into study of all ages, both the sexes with open fracture classified according to Gustilo Anderson classification. Primarily wound was examined and description of the wound was recorded with 1st culture swab taken at that time followed by 2nd culture swab on 1st dressing after debridement and 3rd culture swab if infection continues further. Culture and sensitivity reports were collected for studying pattern of bacterial isolate and their sensitivity. Results: Pre-debridement cultures are of no importance. Post-debridement cultures are important in formulating an antibiotic regime. Gram negative organisms are the most probable cause of infection. Aminoglycosides are the most sensitive group of drugs in both gram positive and gram negative bacteria. Cephalosporins or quinolones should be used in combination with aminoglycosides in all cases of open fracture in our vicinity. Conclusion: All institutions and hospitals should find out the most common infecting pathogen in their environment and formulate an antibiotic policy accordingly.

Among the rare bone tumors, the osteoblastoma is a fascinating tumor. The rarity, the predisposition to occur in any bone and the diagnostic dilemma makes this infrequent tumor interesting. It is sporadically reported in the literature and what is rarer is its occurrence in the pelvis. The unusual location and inconclusive radiographic findings with diffused diagnostic evidences delays the management of benign osteoblastoma. We encountered a patient with benign osteoblastoma of the pubic ramus of right side. An excisional biopsy was performed. Peroperatively, the tumor appeared as oval, reddish brown, bony hard mass lying just over the cortex of the right pubic ramus and not breaching the cortex. Histopathological study revealed an osteoid rich lesion. Its presence in pubis must not be ignored and periosteal osteoblastoma should be considered as a differential diagnosis.

An articulated and partially preserved skeleton of an ichthyosaur was found in the Upper Jurassic (Upper Kimmeridgian) Katrol Formation exposed at a site south of the village Lodai in Kachchh district, Gujarat (western India). Here we present a detailed description and inferred taxonomic relationship of the specimen. The present study revealed that the articulated skeleton belongs to the family Ophthalmosauridae. The new discovery from India further improves the depauperate fossil record of ichthyosaurs from the former Gondwanan continents. Based on the preserved length of the axial skeleton and anterior part of the snout and taking into account the missing parts of the skull and postflexural region, it is suggested that the specimen may represent an adult possibly reaching a length of 5.0-5.5 m. The widespread occurrence of ophthalmosaurids in the Upper Jurassic deposits of western Tethys, Madagascar, South America and India points to possible faunal exchanges between the western Tethys and Gondwanan continents through a southern seaway.

SNO+ is a large liquid scintillator-based experiment located 2 km underground at SNOLAB, Sudbury, Canada. It reuses the Sudbury Neutrino Observatory detector, consisting of a 12 m diameter acrylic vessel which will be filled with about 780 tonnes of ultra-pure liquid scintillator. Designed as a multipurpose neutrino experiment, the primary goal of SNO+ is a search for the neutrinoless double-beta decay (0νββ) of 130Te. In Phase I, the detector will be loaded with 0.3% natural tellurium, corresponding to nearly 800 kg of 130Te, with an expected effective Majorana neutrino mass sensitivity in the region of 55–133 meV, just above the inverted mass hierarchy. Recently, the possibility of deploying up to ten times more natural tellurium has been investigated, which would enable SNO+ to achieve sensitivity deep into the parameter space for the inverted neutrino mass hierarchy in the future. Additionally, SNO+ aims to measure reactor antineutrino oscillations, low energy solar neutrinos, and geoneutrinos, to be sensitive to supernova neutrinos, and to search for exotic physics. A first phase with the detector filled with water will begin soon, with the scintillator phase expected to start after a few months of water data taking. The 0νββ Phase I is foreseen for 2017.

Background. This study was performed to evaluate the results of vacuum assisted wound therapy in patients with open musculoskeletal injuries. Study Design and Setting. Prospective, randomized, and interventional at tertiary care hospital, from 2011 to 2012. Materials and Methods. 30 patients of open musculoskeletal injuries underwent randomized trial of vacuum assisted closure therapy versus standard wound therapy around the upper limb and lower limb. Mean patient age was years (range, 18 to 76 years). Necrotic tissues were debrided before applying VAC therapy. Dressings were changed every 3 or 4 days. For standard wound therapy, debridement followed by daily dressings was done. Data Management and Statistical Analysis. The results obtained were subjected to statistical analysis. Results. The size of soft tissue defects reduced more than 5 mm to 25 mm after VAC (mean decrease of 26.66%), whereas in standard wound therapy, reduction in wound size was less than 5 mm. A free flap was needed to cover exposed bone and tendon in one case in standard wound therapy group. No major complication occurred that was directly attributable to treatment. Conclusion. Vacuum assisted wound therapy was found to facilitate the rapid formation of healthy granulation tissue on open wounds in the upper limb and lower limb, thus to shorten healing time and minimize secondary soft tissue defect coverage procedures.

Objective:To determine the percentage of phenylketonuria (PKU) subjects using current treatment strategies whose phenylalanine (Phe) concentrations diverge from the UK target guidelines for PKU.Research design and methods:This retrospective, observational, chart review was conducted between 2004 and 2008 at three specialist PKU treatment centres in the UK, and included 125 eligible subjects: 20 adults (18 years, with ≥4 Phe concentrations measured per year) and 105 children (up to age 17, with ≥6 Phe concentrations measured per year).Results:The mean percentage of subjects with at least 70% of Phe concentrations within the target range for 0––5-year olds, 6––10 year olds and 11––17 year olds was similar across the period 2004––2008 (57.0%, 56.5% and 57.1%, respectively) and lower (39.4%) in the 18 year age group. For all ages, across the period the mean was 54.4%. Further analysis of the adult population showed that some subjects were very good at complying with treatment and reporting Phe concentrations. Overall, the percentage of 100% compliance was 15.7% in females and 13.7% in males. The mean duration that subjects were ‘‘out of range’’ of target Phe concentrations over the study period was approximately 1 year and 3 months and the mean duration for ‘‘significantly out of range’’ values was approximately 9 months. The most common type of contact made with subjects was by telephone, with a mean number of 16 calls per subject per year.Conclusion:The results support current literature showing that a proportion of subjects with PKU, in particular older subjects, are not fully compliant with their treatment and subsequently have Phe concentrations that depart from national recommendations. However, definitive conclusions may not be drawn due to the retrospective nature of the study and the small number of observed subjects. [ABSTRACT FROM AUTHOR]

A brief glimpse of Polylactic acid polymer has been provided. The unique properties of these polymers have attracted considerable attention across the spectrum of plastic applications. These materials provide a rare example of a competitive polymer whose primary building blocks comes from a natural renewable carbohydrate source. [ABSTRACT FROM AUTHOR]

Five different millets (foxtail, little, barnyard, kodo and browntop) with and without sprouting were subjected to flaking. Phytic acid and phenolic content tends to decrease significantly, whereas antioxidant activity increased up to 77.32% on flaking of millets. A significant decrease in peak and final viscosity was observed in millet flakes. A-type diffraction pattern was predominant for unsprouted millets whereas the flaked millets showed V-type crystallinity. The protein digestibility significantly increased up to 37.77% in flakes made from sprouted millets. The mineral bioavailability upon flaking of millets increased, especially Ca (88.22% for little), Fe (43.04% for barnyard) and Zn (61.77% for kodo), which is attributed to the reduction in phytic acid. Flaking, however, led to an increase in rapidly and slowly digestible starch with a corresponding decrease in resistant starch. Among the unsprouted and sprouted millet flakes, foxtail received the highest sensory scores for overall acceptability., Competing Interests: Declaration of competing interest The authors state that they have no personal relationships or conflicting financial interests that could have appeared to have an impact on the work discussed in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The accurate extraction of surgical data from electronic health records (EHRs), particularly operative notes through manual chart review (MCR), is complex, crucial, and time-intensive, limited by human error due to fatigue and the level of training. This study aimed to develop and validate a novel Natural Language Processing (NLP) algorithm integrated with a Large Language Model (LLM; GPT4-Turbo) to automate the extraction of spinal surgery data from EHRs. The algorithm employed a two-stage approach. Initially, a rule-based NLP framework reviewed and classified candidate segments from the text, preserving their reference segments. These segments were then verified in the second stage through the LLM. The primary outcomes of this study were the accurate extraction of surgical data, including the type of surgery, levels operated, number of disks removed, and presence of intraoperative incidental durotomies. Secondary objectives explored time efficiency, tokenization lengths, and costs. The performance of the algorithm was assessed across two validation databases, analyzing metrics such as accuracy, sensitivity, discrimination, F1-score, and precision, with 95% confidence intervals calculated using percentile-based bootstrapping. The NLP + LLM algorithm markedly outperformed all performance metrics, demonstrating significant improvements in time and cost efficiency. These results suggest the potential for widespread adoption of this technology., (© 2024. The Author(s).)

Background: Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE., Methods: In this integrated post-hoc analysis, we pooled data from five phase 3 trials of belimumab (BLISS-76 [NCT00410384], BLISS-52 [NCT00424476], BLISS-NEA [NCT01345253], BLISS-SC [NCT01484496], and EMBRACE [NCT01632241]), in patients with active, autoantibody-positive SLE. Patients were randomly assigned to receive belimumab (10 mg/kg per month intravenously or 200 mg per week subcutaneously) or placebo, plus standard therapy. The proportion of patients with Definitions of Remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) were analysed every 4 weeks from week 4 to week 52 for belimumab versus placebo, using modified Poisson regression adjusted for trial variance, in all patients and in subgroups per baseline SLE Disease Activity Index-2000 score (<10 or ≥10); anti-double stranded DNA positivity (yes or no); low complement 3 (C3) or C4 levels (yes or no); anti-dsDNA positivity or low C3 or C4 levels (yes and no); prednisone-equivalent dose (≤7·5 mg per day or >7·5 mg per day); antimalarial use (yes or no); and by race (Black African ancestry or African American, Asian, Indigenous American, or White)., Findings: Data for 3086 patients (1869 in the belimumab group and 1217 in the placebo group) were analysed. 2913 (94%) of 3086 patients were women and 173 (6%) were men, and the median age was 36 years (IQR 28-45). The proportion of patients with DORIS remission was significantly higher in the belimumab group than the placebo group at weeks 28, 48, and 52 (week 52: 148 [8%] of 1869 participants vs 68 [6%] of 1217 participants; risk ratio 1·51 [95% CI 1·15-1·99]; p=0·0055). The proportion of patients who attained LLDAS was higher in the belimumab group than the placebo group at weeks 8, 24, 32-52 (week 52: 322 [17%] of 1869 participants vs 125 [10%] of 1217 participants; 1·74 [1·44-2·12]; p<0·0001). A higher proportion of patients had DORIS remission at week 52 in the belimumab group than the placebo group among all baseline subgroups denoting high disease activity, with the exception of those on a prednisone-equivalent dose higher than 7·5 mg per day in whom there was no difference for DORIS remission with belimumab versus placebo. The proportion of patients with LLDAS was significantly higher among patients in the belimuab group than those who received placebo from week 44 in all baseline subgroups denoting high disease activity or earlier in some subgroups, and the differences were maintained at week 52., Interpretation: In adults with active SLE, belimumab plus standard therapy yielded greater benefit than placebo plus standard therapy in attaining DORIS remission (for which low rates were attained in both groups) and LLDAS, with differences observed as early as week 28 for DORIS remission and week 8 for LLDAS., Funding: Swedish Rheumatism Association, King Gustaf V's 80-year Foundation, Swedish Society of Medicine, Nyckelfonden, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and the Karolinska Institutet., Competing Interests: Declaration of interests IP reports grants and speaker honoraria from Amgen, AstraZeneca, Aurinia, BMS, Eli Lilly, Gilead, GSK, Janssen, Novartis, Otsuka, and Roche. MZ reports speaker honoraria from Eli Lilly, AstraZeneca, and GSK. AA has received consulting fees from AbbVie, Amgen, AstraZeneca, Aurinia, BMS, Celgene, Eli Lilly, Idorsia, Janssen, Genentech, GSK, Mallinckrodt, Pfizer, and UCB. RvV reports grants from Pfizer and Roche; consulting fees from AbbVie, AstraZeneca, Biogen, Biotest, BMS, Galapagos, Gilead, Janssen, Pfizer, Sanofi, Servier, UCB, and Vielabio; and speaker honoraria from AbbVie, Galapagos, GSK, Janssen, Pfizer, UCB, and Roche. MN reports grants from Janssen Pharmaceuticals; and consulting fees and speaker honoraria from AstraZeneca, Boehringer Ingelheim, GSK, and Janssen Pharmaceuticals. RAL, CH, MK, HAQ, and DC are employees of GSK and hold stocks and shares in the company. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: Myelomeningocele (MMC) is a lifelong condition requiring complex multidisciplinary management. Using the National Spina Bifida Patient Registry (NSBPR), the authors tested the association between sociodemographic variables and odds of undergoing neurosurgical procedures., Methods: The authors extracted sociodemographic, clinical, and neurosurgical procedure data on participants with MMC aged ≥ 1 year who visited an NSBPR clinic between 2009 and 2020. The zip code of the participant's residence at the time of the last spina bifida clinic visit was linked to the Distressed Communities Index (DCI) tier. Multivariate models were built to identify factors associated with undergoing CSF diversion, shunt revision, tethered cord release (TCR), and Chiari decompression., Results: There were 7924 participants with a median visit age of 13 years (IQR 7-20 years); 49.1% were male, 30.2% were non-Hispanic Black or Hispanic, 54.5% had public/supplemental insurance, and 16.9% were from distressed communities. CSF diversion, shunt revision, TCR, and Chiari decompression were performed in 81.8%, 47.7%, 22.9%, and 8.7% of participants, respectively. In multivariate analyses controlling for age, sex, insurance, DCI tier, lesion level, and surgical closure timing, Hispanic individuals were less likely than their non-Hispanic White counterparts to undergo shunt revision (p = 0.013). Non-Hispanic Black and Hispanic individuals were less likely to undergo TCR (p < 0.001 each) or Chiari decompression (p < 0.001 each). Compared with privately insured individuals, publicly insured individuals were more likely to undergo CSF diversion (p = 0.031). Those in distressed communities had increased odds of undergoing CSF diversion (p = 0.004) than those in prosperous communities., Conclusions: Among individuals with MMC participating in the NSBPR, there were differences in receiving neurosurgical procedures by race/ethnicity, insurance type, and DCI tier. Additional prospective studies are necessary to elucidate the reasons for these variations and their impact on long-term outcomes for this patient population in order to created targeted interventions.

Background: Lupus nephritis (LN), a severe organ manifestation of systemic lupus erythematosus (SLE), significantly impacts health-related quality of life (HRQoL). Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) and Lupus Quality of Life (LupusQoL) have been validated to measure HRQoL in SLE, but not specifically in LN. Patient-reported symptoms of LN are not well-reported. We assessed the content validity and relevance of these measures in evaluating patients with LN and their LN-related experiences., Methods: This qualitative, interview-based study enrolled patients with LN from three US sites from a larger, retrospective survey study. The interview comprised an open-ended concept elicitation part and a more structured cognitive part. Concept elicitation was used to identify relevant themes describing the patients' experiences. Patients were asked to describe their LN-related symptoms, the severity and impact of those symptoms and their satisfaction with treatment. A cognitive interview approach evaluated the appropriate understanding of the items, instructions, and response options and asked patients about their understanding of the FACIT-Fatigue or LupusQoL measures, their relevance to the condition, and any aspects of confusion or need for better clarity of the questionnaires. All interviews were recorded and transcribed. The concept elicitation data were coded, while the cognitive interview data were tabulated to present the participants' responses next to the interview questions to support the evaluation of their understanding of the questionnaire items., Results: Overall, 10 patients participated in FACIT-Fatigue and another 10 in LupusQoL interviews; 18 patients were female, 10 were Black (self-reported) and 17 were receiving maintenance treatment for LN with stable disease activity. When patients recalled their symptoms, 670 expressions of varying symptoms were reported. All patients described pain, discomfort, and energy-related symptoms. Urinary frequency and non-joint swelling were most frequently attributed to LN rather than SLE. Patients felt the questions asked in the FACIT-Fatigue and LupusQoL surveys were relevant to their LN experience., Conclusions: The symptoms reported by patients with LN were consistent with symptoms reported by the overall SLE population. However, patients indicated that some symptoms of LN were more profound than symptoms of SLE alone, affecting a broad range of areas of daily life activity and resulting in a higher burden on their HRQoL. FACIT-Fatigue and LupusQoL demonstrated content relevance as meaningful tools for patients with LN. However, further quantitative data collection is needed to ensure that these patient-reported outcome tools demonstrate good measurement properties in an LN population., (© 2024. The Author(s).)

Background : DNA-dependent protein kinase (DNA-PK) is a validated cancer therapeutic target involved in DNA damage response (DDR) and non-homologous end-joining (NHEJ) repair of DNA double-strand breaks (DSBs). Ku serves as a sensor of DSBs by binding to DNA ends and activating DNA-PK. Inhibition of DNA-PK is a common strategy to block DSB repair and improve efficacy of ionizing radiation (IR) therapy and radiomimetic drug therapies. We have previously developed Ku-DNA binding inhibitors (Ku-DBis) that block in vitro and cellular NHEJ activity, abrogate DNA-PK autophosphorylation, and potentiate cellular sensitivity to IR. Results and Conclusions : Here we report the discovery of oxindole Ku-DBis with improved cellular uptake and retained potent Ku-inhibitory activity. Variable monotherapy activity was observed in a panel of non-small cell lung cancer (NSCLC) cell lines, with ATM-null cells being the most sensitive and showing synergy with IR. BRCA1-deficient cells were resistant to single-agent treatment and antagonistic when combined with DSB-generating therapies. In vivo studies in an NSCLC xenograft model demonstrated that the Ku-DBi treatment blocked IR-dependent DNA-PKcs autophosphorylation, modulated DDR, and reduced tumor cell proliferation. This represents the first in vivo demonstration of a Ku-targeted DNA-binding inhibitor impacting IR response and highlights the potential therapeutic utility of Ku-DBis for cancer treatment.

Tetranuclear [2 × 2] square-grid-like Ln III clusters have been synthesized by reacting LnCl 3 ·6H 2 O salts with bis[α-hydroxy( p -bromophenyl)methyl]phosphinic acid [R 2 PO 2 H, where R = CH(OH)PhBr] and pivalic acid. Single-crystal X-ray diffraction studies show the formation of [Me 4 N] 2 [Ln 4 (μ 2 -η 1 :η 1 -PO 2 R 2 ) 8 (η 2 -CO 2 Bu t ) 4 (μ 4 -CO 3 )] [Ln = Er ( 1 ), Dy ( 2 ), and Tb ( 3 )]. Direct-current studies reveal significant ferromagnetic interactions between Dy III in 2 and Tb III in 3 and an antiferromagnetic interaction between Er III in 1 . Dynamic magnetic susceptibility measurements confirm a single-molecule magnet (SMM) behavior in both 0 and 1200 Oe applied magnetic fields for 2 . Complexes 2 and 3 show single molecular toroic (SMT) behavior with a mixed magnetic moment.

Low back pain (LBP), a globally prevalent musculoskeletal condition, affects mobility, mental well-being, and overall quality of life. It is generally caused by disc degeneration, muscular strain, ligamentous sprain, or a disease located at the lumbar spine. Owing to this disability, the social and occupational interactions of an individual might get affected. Modern medicine frequently combines exercise therapy with light amplification by stimulated emission of radiation (LASER) therapy, especially high intensity LASER therapy (HILT) or low level LASER therapy (LLLT), to increase the efficacy of the treatment modalities for LBP. This review aimed to determine the effect of the combined approach of LASER and exercise therapies in managing pain and reducing disability in patients with LBP. PubMed, Google Scholar, Cochrane Library, MEDLINE, and PEDro were searched for full-text research articles published from 2000 to 2023. Overall, 3,913 records were screened from these databases and six high methodological quality studies (PEDro ≥ 5) were included in this review after eligibility assessment. Review manager 5.4.1 was utilized to evaluate the overall quality of the review articles. In conclusion, HILT and LLLT serve as effective adjuncts to exercise therapy in treating LBP, contributing to pain reduction and disability alleviation., Competing Interests: • Conflicts of Interest: No conflict of interest., (© 2024 Journal of Lifestyle Medicine.)

Competing Interests: Conflicts of interest None to declare.

Chronic kidney disease-induced secondary hyperparathyroidism (CKD-SHPT) heightens fracture risk through impaired mineral homeostasis and elevated levels of uremic toxins (UTs), which in turn enhance bone remodeling. Etelcalcetide (Etel), a calcium-sensing receptor (CaSR) agonist, suppresses parathyroid hormone (PTH) in hyperparathyroidism to reduce excessive bone resorption, leading to increased bone mass. However, Etel's effect on bone quality, chemical composition, and strength is not well understood. To address these gaps, we established a CKD-SHPT rat model and administered Etel at a human-equivalent dose concurrently with disease induction. The effects on bone and mineral homeostasis were compared with a CKD-SHPT (vehicle-treated group) and a control group (rats without SHPT). Compared with vehicle-treated CKD-SHPT rats, Etel treatment improved renal function, reduced circulating UT levels, improved mineral homeostasis parameters, decreased PTH levels, and prevented mineralization defects. The upregulation of mineralization-promoting genes by Etel in CKD-SHPT rats might explain its ability to prevent mineralization defects. Etel preserved both trabecular and cortical bones with attendant suppression of osteoclast function, besides increasing mineralization. Etel maintained the number of viable osteocytes to the control level, which could also contribute to its beneficial effects on bone. CKD-SHPT rats displayed increased carbonate substitution of matrix and mineral, decreased crystallinity, mineral-to-matrix ratio, and collagen maturity, and these changes were mitigated by Etel. Further, Etel treatment prevented CKD-SHPT-induced deterioration in bone strength and mechanical behavior. Based on these findings, we conclude that in CKD-SHPT rats, Etel has multiscale beneficial effects on bone that involve remodeling suppression, mineralization gene upregulation, and preservation of osteocytes., Competing Interests: Declaration of competing interest There is no known conflict of interest related to this research work and no competing financial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Societal guidelines support atrial fibrillation (AF) treatment during surgical aortic valve replacement (SAVR). Recently, many patients with AF at low to intermediate risk are managed by transcatheter aortic valve replacement (TAVR). Therefore, we evaluated longitudinal outcomes in these populations., Methods: The United States Centers for Medicare and Medicaid Services inpatient claims database was evaluated for all beneficiaries with AF undergoing TAVR or SAVR with/without AF treatment (2018-2020). Treatment of AF included concomitant left atrial appendage obliteration, with/without surgical ablation, or endovascular appendage occlusion and/or catheter ablation at any time. Diagnosis-related group and International Classification of Diseases, 10th Revision, codes defined procedures with doubly robust risk adjustment across each group., Results: A total of 24,902 patients were evaluated (17,453 TAVR; 7,449 SAVR). Of patients undergoing SAVR, 3176 (42.6%) underwent AF treatment (SAVR+AF). Only 656 TAVR patients (4.5%) received AF treatment. Comparing well-balanced SAVR+AF vs SAVR vs TAVR, there were no differences in the in-hospital incidence of renal failure, bleeding, or stroke, but increased pacemaker requirement (odds ratio [OR], 3.45; P < .0001) and vascular injury (OR, 9.09; P < .0001) were noted in TAVR and higher hospital mortality (OR, 4.02; P < .0001) in SAVR+AF. SAVR+AF was associated with lower readmission for stroke compared with SAVR alone (hazard ratio [HR], 0.87; P = .029) and TAVR (HR, 0.68; P < .0001) and with improved survival vs TAVR (HR, 0.79; P = .019)., Conclusions: In Medicare beneficiaries with AF requiring aortic valve replacement, SAVR+AF was associated with improved longitudinal survival and freedom from stroke compared with TAVR. SAVR+AF treatment should be considered first-line therapy for patients with AF requiring aortic valve replacement., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Anaplasma phagocytophilum is an intracellular tick-transmitted bacterial pathogen that infects neutrophils in mammals and causes granulocytic anaplasmosis. In this study, we investigated the molecular chaperones ClpB and DnaK from A. phagocytophilum. In Escherichia coli, ClpB cooperates with DnaK and its co-chaperones DnaJ and GrpE in ATP-dependent reactivation of aggregated proteins. Since ClpB is not produced in metazoans, it is a promising target for developing antimicrobial therapies, which generates interest in studies on that chaperone's role in pathogenic bacteria. We found that ClpB and DnaK are transcriptionally upregulated in A. phagocytophilum 3-5 days after infection of human HL-60 and tick ISE6 cells, which suggests an essential role of the chaperones in supporting the pathogen's intracellular life cycle. Multiple sequence alignments show that A. phagocytophilum ClpB and DnaK contain all structural domains that were identified in their previously studied orthologs from other bacteria. Both A. phagocytophilum ClpB and DnaK display ATPase activity, which is consistent with their participation in the ATP-dependent protein disaggregation system. However, despite a significant sequence similarity between the chaperones from A. phagocytophilum and those from E. coli, the former were not as effective as their E. coli orthologs during reactivation of aggregated proteins in vitro and in supporting the survival of E. coli cells under heat stress. We conclude that the A. phagocytophilum chaperones might have evolved with distinct biochemical properties to maintain the integrity of pathogenic proteins under unique stress conditions of an intracellular environment of host cells., Competing Interests: Declarations of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nitroimidazoles comprise a class of broad-spectrum anti-microbial drugs with efficacy against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. Among these drugs, metronidazole (MTZ) is commonly used with other antibiotics to prevent infection in open fractures. However, the effect of MTZ on bone remains understudied. In this paper, we evaluated six nitroimidazole drugs for their impact on osteoblast differentiation and identified MTZ as having the highest osteogenic effect. MTZ enhanced bone regeneration at the femur osteotomy site in osteopenic ovariectomized (OVX) rats at the human equivalent dose. Moreover, in OVX rats, MTZ significantly improved bone mass and strength and improved microarchitecture compared to the vehicle-treated rats, which was likely achieved by an osteogenic mechanism attributed to the stimulation of the Wnt pathway in osteoblasts. To mitigate the reported neurological and genotoxic effects of MTZ, we designed an injectable sustained-release in situ gel formulation of the drug that improved fracture healing efficacy by 3.5-fold compared to oral administration. This enhanced potency was achieved through a significant increase in the circulating half-life and bioavailability of MTZ. We conclude that MTZ exhibits osteogenic effects, further accentuated by our sustained-release delivery system, which holds promise for enhancing bone regeneration in open fractures.

Background: Despite prospective randomized evidence supporting concomitant treatment of atrial fibrillation (AF) during mitral valve (MV) surgery, variation in surgical management of AF remains. We assessed longitudinal outcomes after surgical treatment of persistent or paroxysmal AF during MV surgery in Medicare beneficiaries., Methods: All Medicare beneficiaries with a diagnosis of AF undergoing MV surgery (2018-2020) were evaluated. Patients were stratified by no AF treatment, left atrial appendage obliteration (LAAO) alone, or surgical ablation and LAAO (SA+LAAO). Doubly robust risk adjustment and subgroup analysis by persistent or paroxysmal AF were performed., Results: A total of 7517 patients with preoperative AF underwent MV surgery (32.1% no AF treatment, 23.1% LAAO alone, 44.7% SA+LAAO). After doubly robust risk adjustment, AF treatment with SA+LAAO or LAAO alone were associated with lower 3-year readmission for stroke or bleeding. However, SA+LAAO was associated with reduced 3-year mortality and readmission for AF or heart failure compared with no AF treatment or LAAO alone. Compared with no AF treatment or LAAO alone, SA+LAAO was associated with lower composite end point of stroke (hazard ratio, 0.75) or death (hazard ratio, 0.83) at 3 years. Subgroup analysis identified similar longitudinal benefits of SA+LAAO in patients with persistent or paroxysmal AF., Conclusions: In Medicare beneficiaries with AF undergoing MV surgery, SA+LAAO was associated with improved longitudinal outcomes compared with LAAO alone or no AF treatment in patients with paroxysmal or persistent AF. These contemporary real-world data further clarify the benefit of SA+LAAO during MV surgery across all types of AF., Competing Interests: Disclosures J. Scott Rankin reports financial support was provided by AtriCure Inc. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: National Medical Commission (NMC) in their recent notification included Family Adoption Program (FAP) in the undergraduate curriculum to provide a learning opportunity towards community-based health care to Indian medical graduates. This study is carried out to explore and know strengths, weaknesses, opportunities, and challenges of FAP., Materials and Methods: FAP were used to gather data using Focus Group Discussion (FGD) and in-depth interviews of the stakeholders of the program. FGD of students was conducted. In-depth interviews of families, Sarpanch, Panchayat members, ASHA workers of the village, faculties, and Head of the Department of Community Medicine were conducted. Data analysis was done by using deductive-inductive content analysis method using computer software NVivo., Results: Four main categories or themes were formed: strengths, weaknesses, opportunities, and challenges. Strengths include increased understanding about Community Medicine subject, beneficence to students, and community. Weakness includes difficulties in field with respect to time and availability and implementation of programs. Opportunities include early field exposure and FAP as a platform for primary healthcare. Challenges include competencies not aligned with phasewise curriculum and difficulties in adopting five families per student., Conclusions: The family adoption program needs to be adopted and implemented as a part of curriculum for MBBS students as there are many strengths and opportunities, while weaknesses and challenges need to be addressed., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Community Medicine.)

Phytosomes (phytophospholipid complex) are dosage forms that have recently been introduced to increase the stability and therapeutic effect of herbal medicine. Currently, bioactive herbs and the phytochemicals they contain are considered to be the best remedies for chronic diseases. One promising approach to increase the efficacy of plant-based therapies is to improve the stability and bioavailability of their bio-active ingredients. Phytosomes employ phospholipids as their active ingredients, and use their amphiphilic properties to solubilize and protect herbal extracts. The unique properties of phospholipids in drug delivery and their use in herbal medicines to improve bioavailability results in significantly enhanced health benefits. The introduction of phytosome nanotechnology can alter and revolutionize the current state of drug delivery. The goal of this review is to explain the application of phytosomes, their future prospects in drug delivery, and their advantages over conventional formulations. Please cite this article as: Chauhan D, Yadav PK, Sultana N, Agarwal A, Verma S, Chourasia MK, Gayen JR. Advancements in nanotechnology for the delivery of phytochemicals. J Integr Med. 2024; 22(4): 385-398., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

We report a 5-year-old girl with transient complete atrioventricular (AV) block following surgical closure of a symptomatic conoventricular ventricular septal defect (VSD) which recovered on post-operative day 9. She later presented with exertional dizziness and fatigue. While congenital cardiac defect repairs are occasionally complicated by complete heart block, this patient was found to have intra-Hisian Wenckebach which is rare in the pediatric population and can be very difficult to discern from surface electrocardiograms and by Holter monitoring. Mechanisms of post-surgical AV block, including intra-Hisian Wenckebach, are not well characterized in the pediatric population., (© 2023 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Synthesis of nonameric cationic clusters [Dy 9 (acac) 16 (μ 3 -OH) 8 (μ 4 -OH) 2 ]OH·6H 2 O ( 1 ), [Dy 8 Tb (acac) 16 (μ 3 -OH) 8 (μ 4 -OH) 2 ]OH·2H 2 O ( 2 ), and [Gd 9 (acac) 16 (μ 3 -OH) 8 (μ 4 -OH) 2 ]OH·6H 2 O ( 3 ) (acac = acetylacetonate) is reported. The emission spectrum of 1 shows Dy(III) ion characteristic bands assignable to the 4 F 9/2 → 6 H J ( J = 15/2 to 9/2) transitions. Emission due to both Dy(III) and Tb(III) ions is observed for 2 in the visible range, with Tb(III) specific bands appearing due to the 5 D 4 → 7 F J ( J = 6, 4, and 3) transitions. Cluster 3 exhibits a significant magnetocaloric effect (MCE), with -Δ S m values increasing with decrease in temperature and increase in field, reaching -Δ S m max = 20.98 J kg -1 K -1 at 2 K and 9 T. Isotropic magnetic coupling constants ( J s ) in 3 derived from density functional theory (DFT) calculations reveal that the exchange interactions are antiferromagnetic and weak. Compound 3 possesses S = 7/2 ground state arising from the central Gd(III) ion along with several nested excited states due to competing antiferromagnetic interactions that yield reasonably large MCE values. Utilizing computed exchange coupling interactions, we have performed ab initio CASSCF/RASSI-SO/POL&#95;ANISO calculations on antiferromagnetic 1 and 2 to estimate the exchange interactions using the Lines model. For 2 , Dy(III)···Tb(III) exchange interactions were extracted for the first time and were found to be weakly antiferromagnetically coupled.

Enterobacter cloacae cardiac implantable electronic device infections are rare but can be associated with significant morbidity and mortality. We report an 11-year-old female with Enterobacter cloacae infection of a dual-chamber transvenous pacemaker pocket. The report is supplemented by a comprehensive review of the literature on Enterobacter cloacae cardiac implantable electronic device infections., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Immunogenic cell death (ICD) is a form of cell death by which cancer treatments can induce a clinically relevant antitumor immune response in a broad range of cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib is an ICD inducer and creates durable therapeutic responses in patients. However, eventual relapse and resistance to bortezomib appear inevitable. Here, by integrating patient transcriptomic data with an analysis of calreticulin (CRT) protein interactors, we found that GABA type A receptor-associated protein (GABARAP) is a key player whose loss prevented tumor cell death from being perceived as immunogenic after bortezomib treatment. GABARAP is located on chromosome 17p, which is commonly deleted in patients with high risk MM. GABARAP deletion impaired the exposure of the eat-me signal CRT on the surface of dying MM cells in vitro and in vivo, thus reducing tumor cell phagocytosis by dendritic cells and the subsequent antitumor T-cell response. Low GABARAP was independently associated with shorter survival in patients with MM and reduced tumor immune infiltration. Mechanistically, we found that GABARAP deletion blocked ICD signaling by decreasing autophagy and altering Golgi apparatus morphology, with consequent defects in the downstream vesicular transport of CRT. Conversely, upregulating autophagy using rapamycin restored Golgi morphology, CRT exposure, and ICD signaling in GABARAPKO cells undergoing bortezomib treatment. Therefore, coupling an ICD inducer, such as bortezomib, with an autophagy inducer, such as rapamycin, may improve patient outcomes in MM, in which low GABARAP in the form of del(17p) is common and leads to worse outcomes., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Bisphenols (BP), including BPA and "BPA-free" structural analogs, are commonly used plasticizers that are present in many plastics and are known endocrine disrupting chemicals. Prenatal exposure to BPA has been associated with negative neurodevelopmental and behavioral outcomes in children and in rodent models. Prenatal BPA exposure has also been shown to impair postnatal maternal care provisioning, which can also affect offspring neurodevelopment and behavior. However, there is limited knowledge regarding the biological effects of prenatal exposure to bisphenols other than BPA and the interplay between prenatal bisphenol exposure and postnatal maternal care on adult behavior. The purpose of the current study was to determine the interactive impact of prenatal bisphenol exposure and postnatal maternal care on neurodevelopment and behavior in rats. Our findings suggest that the effects of prenatal bisphenol exposure on eye-opening, adult attentional set shifting and anxiety-like behavior in the open field are dependent on maternal care in the first five days of life. Interestingly, maternal care might also attenuate the effects of prenatal bisphenol exposure on eye opening and adult attentional set shifting. Finally, transcriptomic profiles in male and female medial prefrontal cortex and amygdala suggest that the interactive effects of prenatal bisphenol exposure and postnatal maternal care converge on estrogen receptor signaling and are involved in biological processes related to gene expression and protein translation and synthesis. Overall, these findings indicate that postnatal maternal care plays a critical role in the expression of the effects of prenatal bisphenol exposure on neurodevelopment and adult behavior. Understanding the underlying biological mechanisms involved might allow us to identify potential avenues to mitigate the adverse effects of prenatal bisphenol exposure and improve health and well-being in human populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lauby et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Vestibular schwannomas (VS) are the most common tumor of the skull base with available treatment options that carry a risk of iatrogenic injury to the facial nerve, which can significantly impact patients' quality of life. As facial nerve outcomes remain challenging to prognosticate, we endeavored to utilize machine learning to decipher predictive factors relevant to facial nerve outcomes following microsurgical resection of VS. A database of patient-, tumor- and surgery-specific features was constructed via retrospective chart review of 242 consecutive patients who underwent microsurgical resection of VS over a 7-year study period. This database was then used to train non-linear supervised machine learning classifiers to predict facial nerve preservation, defined as House-Brackmann (HB) I vs. facial nerve injury, defined as HB II-VI, as determined at 6-month outpatient follow-up. A random forest algorithm demonstrated 90.5% accuracy, 90% sensitivity and 90% specificity in facial nerve injury prognostication. A random variable (rv) was generated by randomly sampling a Gaussian distribution and used as a benchmark to compare the predictiveness of other features. This analysis revealed age, body mass index (BMI), case length and the tumor dimension representing tumor growth towards the brainstem as prognosticators of facial nerve injury. When validated via prospective assessment of facial nerve injury risk, this model demonstrated 84% accuracy. Here, we describe the development of a machine learning algorithm to predict the likelihood of facial nerve injury following microsurgical resection of VS. In addition to serving as a clinically applicable tool, this highlights the potential of machine learning to reveal non-linear relationships between variables which may have clinical value in prognostication of outcomes for high-risk surgical procedures., (© 2024. The Author(s).)

Background and Objectives: Neural tube defects (NTDs) are an important cause of global morbidity worldwide. Well-planned global neurosurgery and public health efforts can aid vulnerable communities, but there is a need to elucidate the global burden of NTDs and identify regions without available data to better target interventions., Methods: A scoping review to quantify worldwide NTD prevalence using the PubMed/Medline and birth defects surveillance registries was conducted. Data published after January 1, 1990, encompassing prevalence values of at least the 2 most prevalent NTDs-spina bifida and encephalocele-were abstracted. Average NTD prevalence rates were aggregated by World Health Organization (WHO) region and World Bank classification, and differences were determined using the analysis of variance test. Differences in availability of nationally representative data by WHO region and World Bank classification were determined using χ2 tests., Results: This review captured 140 studies from a total of 93 of 194 WHO member countries. The percentage of countries within a geographic region with available NTD prevalence data was highest in the Eastern Mediterranean (EMR) (85.7%) and lowest in Africa (AFR) (31.3%). The NTD prevalence range was 0.9-269.6 per 10 000 births. Statistically significant differences in reported NTD prevalence rates existed by WHO Region (P = .00027) and World Bank income level of study country (P = .00193). Forty countries (43%) had conducted national-level studies assessing NTD prevalence. There was a statistically significant difference in the availability of nationally representative prevalence data depending on the WHO region (P = .0081) and World Bank classification of study country (P = .0017)., Conclusion: There is a gap in availability of NTD prevalence data worldwide, with many WHO member states lacking national-level NTD prevalence estimates. These findings highlight the need for greater NTD surveillance efforts to identify the countries with the greatest need for targeted global intervention., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)