Post-Marketing Surveillance of the World's First Novel Cocktail of Rabies Monoclonal Antibodies: TwinRab™ in Real \-World Setting.

Rabies presents with a high fatality rate, which imposes a significant global public health challenge, and therefore the use of post-exposure prophylaxis (PEP) is crucial for prevention. Monoclonal antibodies (mAbs) have emerged as a promising substitute for rabies immunoglobulins (RIGs) due to their high efficacy and standardized manufacturing process. A prospective, open-label, post-marketing surveillance study (PMS) was conducted at Byramjee Jeejeebhoy Medical College (BJMC), Pune. The study included patients aged more than 2 years who had recently sustained Category III-suspected rabid animal bite exposures. These patients were administered TwinRabTM at a dosage of 40 IU/kg in and around the wound as intralesional transfer, along with the anti-rabies vaccine (ARV). Adverse events (AEs) grading was performed with reference to the Food and Drug Administration (FDA) toxicity grading. In this study, 215 subjects received the TwinRabTM mAb with a 100% completion rate. Out of 215 patients, three (1.3%) patients in the range of 18 to 65 years of age showed solicited local AEs, which were resolved after the appropriate treatment intervention, but causality assessment was non-assessable. The overall tolerability assessment showed positive ratings from doctors (91.63%) and patients (67.91%) for the mAb cocktail. The PMS demonstrated the safety of TwinRabTM in patients who experienced Category III-suspected rabid animal bites, thereby supporting its potential as an alternative option for post-exposure prophylaxis in the management of animal bites for the prevention of rabies.

An Effective Hybrid Deep Learning Model for Single-Channel EEG-Based Subject-Independent Drowsiness Recognition.

Nowadays, road accidents pose a severe risk in cases of sleep disorders. We proposed a novel hybrid deep-learning model for detecting drowsiness to address this issue. The proposed model combines the strengths of discrete wavelet long short-term memory (DWLSTM) and convolutional neural networks (CNN) models to classify single-channel electroencephalogram (EEG) signals. Baseline models such as support vector machine (SVM), linear discriminant analysis (LDA), back propagation neural networks (BPNN), CNN, and CNN merged with LSTM (CNN+LSTM) did not fully utilize the time sequence information. Our proposed model incorporates a majority voting between LSTM layers integrated with discrete wavelet transform (DWT) and the CNN model fed with spectrograms as images. The features extracted from sub-bands generated by DWT can provide more informative & discriminating than using the raw EEG signal. Similarly, spectrogram images fed to CNN learn the specific patterns and features with different levels of drowsiness. Furthermore, the proposed model outperformed state-of-the-art deep learning techniques and conventional baseline methods, achieving an average accuracy of 74.62%, 77.76% (using rounding, F1-score maximization approach respectively for generating labels) on 11 subjects for leave-one-out subject method. It achieved high accuracy while maintaining relatively shorter training and testing times, making it more desirable for quicker drowsiness detection. The performance metrics (accuracy, precision, recall, F1-score) are evaluated after 100 randomized tests along with a 95% confidence interval for classification. Additionally, we validated the mean accuracies from five types of wavelet families, including daubechis, symlet, bi-orthogonal, coiflets, and haar, merged with LSTM layers.

Extra-Fortification of Zinc Upsets Vitellogenin Gene Expression and Antioxidant Status in Female of Clarias magur brooders.

The present experiment was designed to evaluate the effect of graded level of zinc on Vitellogenin gene (Vtg) expression and antioxidant enzymes in threatened catfish, Clarias magur (C. magur). One hundred and eighty female C. magur with an average weight of 145 ± 5 g were allocated in twelve cemented tanks with dimension 4.5 × 2 × 1 m for a period of 60 days. Fish were distributed in four groups with three replicates following the completely randomised design. The first group treated as control (C) fed with basal diet contained normal zinc level, and remaining groups were fed with basal diets having 50, 200 and 300 mg/kg zinc acetate and treated as T1, T2 and T3 respectively. To evaluate the effect of dietary zinc supplementation on Vtg gene expression, three sampling were carried out, I sampling (April, before starting the experimental trail), II sampling (May, after 1 month of feeding trail) and III sampling (June before breeding season). In the present study, a dose-dependent relationship between Vtg gene expression and zinc inclusion in the diet of threatened catfish, C. magur, was reported. Vtg gene expression increased in all groups from I sampling to II sampling but the highest Vtg gene expression was found in T1 group and the lowest in T3 group at II sampling. Vtg gene expression among the treatments differs significantly (P < 0.05) in each sampling. Accumulation of zinc was measured by Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) in C. magur and it was reported that the significantly higher (P < 0.05) zinc was accumulated in the liver and ovary of T3 group as compared to other groups. The antioxidant enzyme activities (superoxide dismutase, SOD, catalase and GST) were also measured in different tissues (liver, gill and ovary) to evaluate the effect of extra-supplementation of zinc on the antioxidant status. In T3 group, SOD, catalase and GST activities were significantly higher than those in other groups. In the current study, serum glucose level was also measured and it was found in increasing trend with inclusion of zinc in the diet of C. magur. In the present study, it can be concluded that the zinc exhibits beneficial effect only up to 50 mg/kg. Thus, it is concluded that supplementation of zinc at 200 mg/kg or more disrupts Vtg gene expression and antioxidant status.

Sexy males and sexless females: the origin of triploid apomicts.

Apomixis and polyploidy are closely associated in angiosperms, but the evolutionary reason for this association is unknown. Taraxacum officinale, the common dandelion, exists both as diploid sexuals and triploid apomicts. Here, in the context of T. officinale, we provide a model of the evolution of triploid apomicts from diploid sexuals. We posit an apomictic allele that arrests female meiosis in diploids, so that the plant produces diploid egg cells that can develop without fertilization, but haploid pollen. We propose occasional fertilization of diploid egg cells by haploid pollen, resulting in triploid apomicts that produce triploid egg cells but largely nonfunctional pollen. The irreversibility of this process renders diploid partial apomicts evolutionarily short-lived, and results in fixation of triploid apomicts except when they suffer extreme selective disadvantages. Our model can account for the high genetic diversity found in T. officinale triploid populations, because recombinant haploid pollen produced by diploids allows the apomictic allele to spread onto many genetic backgrounds. This leads to multiple clonal lineages in the newly apomictic population, and thereby alleviates some of the usual pitfalls of asexual reproduction.

A Clinico-analytical Study on Seed of Wrightia antidysenterica Linn. as a Therapeutic Emetic Agent (Vamaka Yoga) in the Management of Psoriasis.

OBJECTIVES: Wrightia antidysenterica Linn. (WA) is male variety Kutaja stated to be potent therapeutic emetic agent in skin disorders. Expulsion of doshas through oral route is termed as Vamana Karma (VK) (therapeutic emesis). However, so far, its utility for Vamana is not explored in detail, therefore there is a need to revalidate the utility of WA for Vamana. Hence, the above study was conducted to ascertain the efficacy as a therapeutic emetic agent (vamaka yoga) in the management of psoriasis along with quality control and standardization of this herb. MATERIALS AND METHODS: The drug was standardized as per analytical procedures in Pharmacopeias. Thirty patients of psoriasis fulfilling inclusion criteria were taken for the study and Vamana with WA was conducted. Criteria were prepared to assess the signs and Symptoms of psoriasis. VK was assessed using the classical Lakshanas (features) such as Anthiki shudhi (Ending symptoms of emesis), Vaigiki shudhi (features of vomiting bouts), Maniki shudhi (Quantitative and qualitative purification), complications. RESULT: VK with WA showed significant relief in parameters of psoriasis such as scaling, itching, candle grease sign (P < 0.001), and psoriasis area and severity index score (P = 0.001). In VK with WA, mean number of Vegas (vomiting bouts) was 6.91. 66% patients showing quantitative purification between 301 and 600 ml. 73.33% showed all Symptoms of purification. 73.33% patients showed Kaphanta vamana (Moderate expulsion of desire humor). In the level of biopurification, 66.66% patients showed moderated purification. No complication was noted with moderate drug palatability. CONCLUSION: Pharmacopeial analytical study showed its standardized values for testing the drug used for the study. It is proved as potent therapeutic emetic agent with no complication showed its clinical benefits over skin disorder like psoriasis. SUMMARY: Seeds of Wrightia antidysenterica (WA) Linn. free from any foreign matter were selected for the study. Loss on drying revealed 6.535% moisture content; total ash indicating of total inorganic content was found to be 5.12%; acid insoluble ash is the acid insoluble part of total ash, mainly silica, WA showed 0.393% acid insoluble ash; ethanol and water soluble extractive is indicative of percentage active constituents were found to be 25.66 and 20.854%, respectively. High-performance thin layer chromatography fingerprinting profiles of WA under 254 nm showed the presence of 7 spots (all in green) at Rf values ranging from 0.21 to 0.88. Under 366 nm there were 4 prominent spots (all in fluorescent) at Rf 0.49 to 0.82 and, when scanned under white light 620 nm following derivatization with vanillin sulfuric acid 6 spots (in different colors) were evident at Rf 0.28 to 0.58. Among these spot with Rf of 0.58 was common when visualized under all the three methods. Rf values by densitometric scan of WA showed 12 peaks at 254 nm and 5 peaks at 366 nm. However, in clinical trial, it was found to be a potent emetic agent without any complication. Abbreviations Used: WA: Wrightia antidysenterica; Linn.; VK: Vamana karma; BT: Before treatment; FP: Freidman's P value; CHS: Chi-square value; NR: Negative ranks; PR: Positive ranks; N: Sample number, AS: Austipz sign; CG: Candle grease test; SSL: Samyak Snigdha Lakshana.

Gap arthroplasty of temporomandibular joint ankylosis by transoral access: a case series.

This article describes a technique of gap arthroplasty in temporomandibular joint (TMJ) ankylosis performed by transoral access. The treatment of TMJ ankylosis by creating an adequate gap is of paramount importance in preventing any future recurrence and this can be achieved only when good access is gained to this complex anatomical joint. Five patients with TMJ ankylosis (eight TMJ) were treated by gap arthroplasty using an intraoral approach. The average mouth opening before surgery was 8.6mm and the average mouth opening achieved postsurgery was 37.9 mm. The average follow-up time was 13 months and none of the patients had any recurrence or significant complications during or after surgery. Our technique relies on the use of a stable landmark to trace the superior-most extent of the ankylotic mass thereby facilitating the removal of the entire mass including the medial extent. We found that even though transoral access is technically challenging and took an average time of 84 min, it has many advantages over conventional extraoral approaches in terms of facial scars and facial nerve injury. The authors also emphasize the importance of good postoperative physiotherapy and presurgical patient counselling to prevent future recurrences.

Kin-bias, breeding site selection and female fitness in a cannibalistic Neotropical frog.

Resource availability influences sexual selection within populations and determines whether behaviours such as territoriality or resource sharing are adaptive. In Thoropa taophora, a frog endemic to the Atlantic Coastal Rainforest of Brazil, males compete for and defend limited breeding sites while females often share breeding sites with other females; however, sharing breeding sites may involve costs due to cannibalism by conspecific tadpoles. We studied a breeding population of T. taophora to determine (i) whether this species exhibits polygynous mating involving female choice for territorial males and limited breeding resources; (ii) whether limited breeding resources create the potential for male-male cooperation in defence of neighbouring territories; and (iii) whether females sharing breeding sites exhibit kin-biased breeding site choice, possibly driven by fitness losses due to cannibalism among offspring of females sharing sites. We used microsatellites to reconstruct parentage and quantify relatedness at eight breeding sites in our focal population, where these sites are scarce, and in a second population, where sites are abundant. We found that at localities where the appropriate sites for reproduction are spatially limited, the mating system for this species is polygynous, with typically two females sharing a breeding site with a male. We also found that females exhibit negative kin-bias in their choice of breeding sites, potentially to maximize their inclusive fitness by avoiding tadpole cannibalism of highly related kin. Our results indicate that male territorial defence and female site sharing are likely important components of this mating system, and we propose that kinship-dependent avoidance in mating strategies may be more general than previously realized.

Preventing the preventable through effective surveillance: the case of diphtheria in a rural district of Maharashtra, India.

BACKGROUND: Epidemic diphtheria is still poorly understood and continues to challenge both developing and developed countries. In the backdrop of poor immunization coverage, non-existent adult boosters, weak case based surveillance and persistence of multiple foci, there is a heightened risk of re-emergence of the disease in epidemic forms in India. Investigating each outbreak to understand the epidemiology of the disease and its current status in the country is therefore necessary. Dhule a predominantly tribal and rural district in Northern Maharashtra has consistently recorded low vaccination coverages alongside sporaidic cases of diphtheria over the last years. METHODS: This study reports the findings of an onsite survey conducted to assess a recent outbreak of diphtheria in Dhule district and the response mounted to it. Secondary data regarding outbreak detection and response were obtained from the district surveillance office. Clinical data were extracted from hospital records of eleven lab confirmed cases including one death case. Frequency distributions were calculated for each identified clinical and non- clinical variable using Microsoft™ Excel® 2010. RESULTS: Our findings suggest a shift in the median age of disease to adolescents (10-15 years) without gender differences. Two cases (18%) reported disease despite immunization. Clinical symptoms included cough (82%), fever (73%), and throat congestion (64%). About 64% and 36% of the 11 confirmed cases presented with a well defined pseudomembrane and a tonsillar patch respectively. Drug resistance was observed in all three culture positive cases. One death occurred despite the administration of Anti-Diphtheric Serum in a partially immunized case (CFR 9%). Genotyping and toxigenicity of strain was not possible due to specimen contamination during transport as testing facilities were unavailable in the district. CONCLUSIONS: The outbreak raises several concerns regarding the epidemiology of diphtheria in Dhule. The reason for shift in the median age despite consistently poor immunization coverage (below 50%) remains unclear. Concomitant efforts should now focus on improving and monitoring primary immunization and booster coverages across all age groups. Gradually introducing adult immunization at ten year intervals may become necessary to prevent future vulnerabilities. Laboratory networks for genotyping and toxigenicity testing are urgently mandated at district level given the endemicity of the disease in the surrounding region and its recent introduction in remote Dhule. Contingency funds with pre- agreements to obtain ADS and DT/Td vaccines at short notice and developing standard case management protocols at district level are necessary. Monitoring the disease, emerging strains and mutations, alongside drug resistance through robust and effective surveillance is a pragmatic way forward.

A new sphingolipid from the gorgonian Junceella juncea of the Indian Ocean.

A new sphingolipid, (2S,3R,4E)-1,3-dihydroxy-2-[(nonadecanoyl) amino]-octadec-4-ene (1) along with ubiquitous batyl alcohol is isolated from the gorgonian, Junceella juncea Pallas (Gorgonaceae) of the Indian Ocean. The structure of 1 is determined on the basis of 1H- and 13C-NMR, COSY, FABMS, and GC-EIMS experiments.

New sphingosines from a gorgonian, Pseudopterogorgia australiensis Ridley, of the Indian Ocean.

Two new sphingosines, (2S,3R)-2-(docosanoyl amino)nonadecane-1,3-diol (1) and (2S,3S,4R)-2-[(2'R)-2'-hydroxynonadecanoylamino]nonadecane-1,3,4-triol (3), along with the known (2S,3R,4E)-2-(heptadecanoylamino)octadec-4-ene-1,3-diol, have been isolated from Pseudopterogorgia australiensis, of the Indian Ocean. The structures were deduced from spectral and chemical methods. Compounds 1-3 showed moderate antibacterial activity.

Oxytocin receptor couples to the 80 kDa Gh alpha family protein in human myometrium.

One of the primary functions of the oxytocin receptor is to modulate intracellular calcium levels in myometrium. The oxytocin receptor has been purified and cloned. Although it has been suggested that oxytocin receptor couples with a GTP-binding regulatory protein (G-protein), the identity of this G-protein remains unclear. To elucidate the mechanism of oxytocin receptor signalling, we used the oxytocin-receptor-G-protein ternary complex preparation from human myometrium, and evaluated oxytocin-mediated activation of [35S]guanosine 5'-[gamma-thio]triphosphate ([35S]GTP[S]) binding and [alpha-32P]GTP photoaffinity labelling to a G-protein. Binding of [35S]GTP[S] and the intensity of the [alpha-32P]GTP photoaffinity labelled protein resulting from activation of the oxytocin receptor were significantly attenuated by the selective oxytocin antagonist, desGlyNH2d(CH2)5[Tyr(Me)2,Thr4]OVT. Furthermore, the molecular mass of the specific GTP-binding protein was approximately 80 kDa; homologous with the Gh alpha family, the new class of GTP-binding proteins first identified in rat liver that couples to the alpha 1B-adrenoceptor. Consistent with these observations, in co-immunoprecipitation and co-immunoadsorption of the oxytocin receptor in the ternary complex preparation by anti-Gh7 alpha antibody, the Gh alpha family protein tightly coupled to the oxytocin receptor. These findings demonstrate that oxytocin receptor couples with approximately 80 kDa Gh alpha in signal mediation.