A rare case of acute non puerperal complete uterine inversion in nulliparous virgin female

Non-puerperal uterine inversion (NPUI) is extremely rare and accounts for 17% of all uterine inversion cases. A few more than 150 cases have been reported amongst which 10-15 have been reported in nulliparous females and 3-4 have been reported in virgin females from 1914 till date. A 40 years unmarried nulliparous female denying sexual activity presented to our hospital with acute non puerperal complete uterine inversion with something coming out per vaginum of sudden onset while straining at defecation, lower abdominal pain and minimal bleeding per vaginum with history of uterine fibroid and chronic constipation. Diagnosis was confirmed with ultrasonography and examination under anaesthesia after written informed valid consent. After detailed counselling and obtaining written informed valid consent, the patient underwent exploration with a combined abdominal-vaginal approach. Following vaginal myomectomy, the uterus was repositioned using Haultain procedure after a failed attempt of Huntington procedure. Total abdominal hysterectomy with bilateral salpingectomy with vaginal vault suspension was done sparing bilateral ovaries. Diagnosis requires a high index of suspicion and their management is a challenge to gynaecologists due to its rare occurrence, distorted pelvic anatomy and associated pelvic organ injuries during surgery. Good anatomical and clinical knowledge along with surgical skills is of utmost importance for successful outcomes

An inclusive approach to designing a multi-epitope chimeric vaccine for Taenia infections by integrating proteomics and reverse vaccinology

BackgroundSoil- and water-transmitted helminths are a major concern in the developing world due to their high prevalence. More than a quarter of the population were estimated to be infected with helminths in these endemic zones.Research designAn in silico approach was used to design a vaccine construct against the Taenia genus utilizing the proteomic information and evaluation of the construct using immune-informatics.ResultsOur study identified 451 conserved proteins in Taenia spp. using the existing proteome; out of these, 141 were found to be expressed in cysticerci. These proteins were screened for antigenic epitopes and a multi-subunit vaccine was constructed. The constructed vaccine was assessed for its efficacy in mounting the appropriate immune response. Our constructed vaccine showed stability and optimal performance against the TLR 4 receptor, which is reported to be upregulated in Taenia infections in hosts.ConclusionImmune-informatics tools help design vaccines for neglected diseases such as those attributed to helminths, which are known to cause widespread morbidity. Our vaccine construct holds tremendous potential in conferring protection against all Taenia spp. of clinical relevance to human

The interplay of helminthic neuropeptides and proteases in parasite survival and host immunomodulation.

Neuropeptides comprise a diverse and broad group of neurotransmitters in vertebrates and invertebrates, with critical roles in neuronal signal transduction. While their role in controlling learning and memory in the brains of mammals is known, their extra-synaptic function in infection and inflammation with effects on distinct tissues and immune cells is increasingly recognized. Helminth infections especially of the central nervous system (CNS), such as neurocysticercosis, induce neuropeptide production by both host and helminth, but their role in host-parasite interplay or host inflammatory response is unclear. Here, we review the neurobiology of helminths, and discuss recent studies on neuropeptide synthesis and function in the helminth as well as the host CNS and immune system. Neuropeptides are summarized according to structure and function, and we discuss the complex enzyme processing for mature neuropeptides, focusing on helminth enzymes as potential targets for novel anthelminthics. We next describe known immunomodulatory effects of mammalian neuropeptides discovered from mouse infection models and draw functional parallels with helminth neuropeptides. Last, we discuss the anti-microbial properties of neuropeptides, and how they may be involved in host-microbiota changes in helminth infection. Overall, a better understanding of the biology of helminth neuropeptides, and whether they affect infection outcomes could provide diagnostic and therapeutic opportunities for helminth infections

E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration

Cells regularly synthesize new proteins to replace old or damaged proteins. Deposition of various aberrant proteins in specific brain regions leads to neurodegeneration and aging. The cellular protein quality control system develop various defense mechanisms against the accumulation of misfolded and aggregated proteins. The mechanisms underlying the selective recognition of specific crucial protein or misfolded proteins are majorly governed by quality control E3 ubiquitin ligases mediated through ubiquitin-proteasome system. Few known E3 ubiquitin ligases have shown prominent neurodevelopmental functions, but their interactions with different developmental proteins play critical roles in neurodevelopmental disorders. Several questions are yet to be understood properly. How E3 ubiquitin ligases determine the specificity and regulate degradation of a particular substrate involved in neuronal proliferation and differentiation is certainly the one, which needs detailed investigations. Another important question is how neurodevelopmental E3 ubiquitin ligases specifically differentiate between their versatile range of substrates and timing of their functional modulations during different phases of development. The premise of this article is to understand how few E3 ubiquitin ligases sense major molecular events, which are crucial for human brain development from its early embryonic stages to throughout adolescence period. A better understanding of these few E3 ubiquitin ligases and their interactions with other potential proteins will provide invaluable insight into disease mechanisms to approach toward therapeutic interventions

Taenia solium cysticerci's extracellular vesicles Attenuate the AKT/mTORC1 pathway for Alleviating DSS‐induced colitis in a murine model

Abstract The excretory–secretory proteome plays a pivotal role in both intercellular communication during disease progression and immune escape mechanisms of various pathogens including cestode parasites like Taenia solium. The cysticerci of T. solium causes infection in the central nervous system known as neurocysticercosis (NCC), which affects a significant population in developing countries. Extracellular vesicles (EVs) are 30–150‐nm‐sized particles and constitute a significant part of the secretome. However, the role of EV in NCC pathogenesis remains undetermined. Here, for the first time, we report that EV from T. solium larvae is abundant in metabolites that can negatively regulate PI3K/AKT pathway, efficiently internalized by macrophages to induce AKT and mTOR degradation through auto‐lysosomal route with a prominent increase in the ubiquitination of both proteins. This results in less ROS production and diminished bacterial killing capability among EV‐treated macrophages. Due to this, both macro‐autophagy and caspase‐linked apoptosis are upregulated, with a reduction of the autophagy substrate sequestome 1. In summary, we report that T. solium EV from viable cysts attenuates the AKT–mTOR pathway thereby promoting apoptosis in macrophages, and this may exert immunosuppression during an early viable stage of the parasite in NCC, which is primarily asymptomatic. Further investigation on EV‐mediated immune suppression revealed that the EV can protect the mice from DSS‐induced colitis and improve colon architecture. These findings shed light on the previously unknown role of T. solium EV and the therapeutic role of their immune suppression potential

Designing and development of multi-epitope chimeric vaccine against Helicobacter pylori by exploring its entire immunogenic epitopes: an immunoinformatic approach

Abstract Background Helicobacter pylori is a prominent causative agent of gastric ulceration, gastric adenocarcinoma and gastric lymphoma and have been categorised as a group 1 carcinogen by WHO. The treatment of H. pylori with proton pump inhibitors and antibiotics is effective but also leads to increased antibiotic resistance, patient dissatisfaction, and chances of reinfection. Therefore, an effective vaccine remains the most suitable prophylactic option for mass administration against this infection. Results We modelled a multi-chimera subunit vaccine candidate against H. pylori by screening its secretory/outer membrane proteins. We identified B-cell, MHC-II and IFN-γ-inducing epitopes within these proteins. The population coverage, antigenicity, physiochemical properties and secondary structure were evaluated using different in-silico tools, which showed it can be a good and effective vaccine candidate. The 3-D construct was predicted, refined, validated and docked with TLRs. Finally, we performed the molecular docking/simulation and immune simulation studies to validate the stability of interaction and in-silico cloned the epitope sequences into a pET28b(+) plasmid vector. Conclusion The multiepitope-constructed vaccine contains T- cells, B-cells along with IFN-γ inducing epitopes that have the property to generate good cell-mediated immunity and humoral response. This vaccine can protect most of the world’s population. The docking study and immune simulation revealed a good binding with TLRs and cell-mediated and humoral immune responses, respectively. Overall, we attempted to design a multiepitope vaccine and expect this vaccine will show an encouraging result against H. pylori infection in in-vivo use

Imaging features of rhinosporidiosis on contrast CT

Context: Rhinosporidiosis is a chronic granulomatous disease endemic in certain regions of India. Computed tomography (CT) imaging appearances of rhinosporidiosis have not been previously described in the literature. Aims: To study imaging features in rhinosporidiosis with contrast-enhanced CT and elucidate its role in the evaluation of this disease. Materials and Methods: Sixteen patients with pathologically proven rhinosporidiosis were included in the study. Contrast-enhanced CT images were analyzed retrospectively and imaging findings were correlated with surgical and histopathologic findings. Results: A total of 29 lesions were found and evaluated. On contrast-enhanced CT, rhinosporidiosis was seen as moderately enhancing lobulated or irregular soft tissue mass lesions in the nasal cavity (n = 13), lesions arising in nasal cavity and extending through choana into nasopharynx (n = 5), pedunculated polypoidal lesions arising from the nasopharyngeal wall (n = 5), oropharyngeal wall (n = 2), larynx (n = 1), bronchus (n = 1), skin and subcutaneous tissue (n = 2). The inferior nasal cavity comprising nasal floor, inferior turbinate, and inferior meatus was the most common site of involvement (n = 13). Surrounding bone involvement was seen in the form of rarefaction (n = 6), partial (n = 3) or complete erosion (n = 3) of inferior turbinate, thinning of medial maxillary wall (n = 2), and septal erosion (n = 2). Nasolacrimal duct involvement was seen in four cases. Conclusions: Contrast-enhanced CT has an important role in delineating the site and extent of the disease, as well as the involvement of surrounding bone, nasolacrimal duct and tracheobronchial tree. This provides a useful roadmap prior to surgery

Additional file 1 of Designing and development of multi-epitope chimeric vaccine against Helicobacter pylori by exploring its entire immunogenic epitopes: an immunoinformatic approach

Additional file 1. Supplementary figures and tables