Proteogenomics Research Institute for Systems Medicine

BackgroundGlobally, multiple SARS-CoV-2 vaccines received emergency authorization, primarily based on adenoviral vector, mRNA, or inactivated virus platforms. Among them, Covaxin, an inactivated vaccine, was widely used in India and several Southeast Asian countries. Due to their emergency rollout in 2021, the long-term immunogenicity data to assess the impact of these vaccinations have been limited. This study investigated the prolonged immune responses induced by Covaxin, an inactivated virus-based COVID-19 vaccine, in 250 individuals monitored for 2 years.MethodsThis longitudinal study (January 2021–January 2023) tracked 250 participants, collecting blood at seven time points. We measured SARS-CoV-2 spike RBD IgG and neutralizing antibodies using ECLIA and surrogate virus neutralization tests, respectively. We also assessed cellular immunity in a subset of Covaxin recipients through flow cytometry of spike protein-stimulated lymphocytes.ResultsAnti-RBD IgG levels declined rapidly post-vaccination. A significant rise was observed following Omicron infection, with sustained high antibody titers and high virus neutralization capacity. Covaxin recipients demonstrated high CD4+ T-cell activity during the Omicron wave, correlating with mild or asymptomatic infections. These findings suggest that Omicron exposure may have served as a natural booster and hold potential for next-generation vaccine development for COVID. Enhanced T-cell responses, particularly after the third dose, further underscored the vaccine’s ability to maintain cellular immunity. Compared with Covishield, Covaxin elicited milder immune responses, possibly contributing to its favorable safety profile.ConclusionsOverall, this study provides one of the first longitudinal analyses of the humoral and T-cell responses to Covaxin, a vaccine widely administered in India and neighboring Southeast Asian countries.

Lymphoplasmacytic oral mucosal inflammation (stomatitis) in canine patients is common and non-specific. Contact lesions (CL) secondary to periodontal disease are particularly common. Dogs with CL may or may not have canine chronic ulcerative stomatitis (CCUS), yet clinicians are often faced with making treatment decisions without a clear diagnosis. Some may expect canine patients to be treated similarly to feline chronic gingivostomatitis patients, for whom partial- to full-mouth extractions remain the primary intervention. Because this assumption may lead to inappropriate care, clear recommendations for surgical management are needed for canine patients. This retrospective review (2012–2022) evaluated 42 dogs with lymphoplasmacytic stomatitis treated surgically at a dental specialty service. We hypothesized that only a minority of these patients require full-mouth exodontia. Patients were initially stratified as CL or CCUS based on lesion distribution and radiographic findings and reclassified based on treatment response. Clinical outcomes were categorized as complete, partial, or absent response to treatment(s), including COHAT, salvage exodontia, rescue medical management, chronic immunosuppression, and home oral hygiene. Associations between demographic and clinical variables with surgical and clinical endpoints were evaluated using descriptive statistics and chi-square analyses. Small breeds (median 5.4 kg) predominated and were significantly more likely to reach edentulism for any reason. Buccal lesions adjacent to maxillary canine and fourth premolar teeth were most common, but over 60% of cases had mucosal changes beyond the classic paradental lesions. Ultimately, 31% were confirmed as CL and 50% as CCUS. Only 24% underwent salvage exodontia, and 17% were rendered edentulous for mucosal disease management. Achieving edentulism was more common in CL cases (54%) compared to CCUS cases (33%). Most dogs (81%) achieved complete resolution, primarily through treatment of periodontal disease (62%). CL cases showed high response rates to periodontal therapy (83%), while a subset of CCUS patients underwent salvage exodontia (20%) or immunosuppression (5%). The majority of dogs with lymphoplasmacytic stomatitis, including many diagnosed as CCUS, respond to periodontal disease management without full-mouth extractions. These findings support a conservative, staged treatment approach and underscore the need for standardized diagnostic criteria in canine oral inflammatory disease.

Anionic polymerization with alkali metals represents one of the most commercially significant and synthetically versatile polymerization methods. However, structural analysis of active alkali metal polymerization catalysts is complicated by aggregation and multicenter reactivity. This work describes discrete dilithium complexes for the anionic polymerization of rac-lactide and o-phthalaldehyde. The reaction of binucleating bis(pyrazolyl)alkane ligands PDRH with two equivalents of LiHMDS (HMDS- = -N(SiMe3)2) gives complexes PDRLi2(HMDS) with a symmetric μ-amide structure, analogous to simple alkali amides. These complexes polymerize rac-lactide by a mechanism analogous to LiHMDS. Notably, PD4-MeLi2(HMDS) gives lower dispersity and better molecular weight control than LiHMDS, consistent with a more well-defined catalyst. In the polymerization of o-phthalaldehyde, PDHLi2(HMDS) and PD4-MeLi2(HMDS) give higher activity and higher selectivity than LiHMDS or butyllithium, commonly used initiators for this reaction, and also give modest stereoselectivity. Our detailed computational analysis of o-phthalaldehyde insertion resulted in a highly cooperative mechanism, with μ-alkoxide bridging of the two metals in the resting state and with back-coordination of the furanyl oxygen. Aldehyde insertion occurs through synchronous nucleophilic addition and migration of the chain end alkoxide, not by aldehyde coordination and insertion. This detailed picture of polymerization by a lithium catalyst will inform mechanistic analysis and catalyst design in anionic polymerization.

Long-acting cabotegravir plus rilpivirine (CAB + RPV LA) administered monthly or every 2 months is recommended by treatment guidelines for maintenance of virologic suppression in people with human immunodeficiency virus type 1 (HIV-1). In clinical trials, CAB + RPV LA demonstrated noninferiority versus United States (US) Food and Drug Administration-approved daily oral therapy, and outcomes in real-world settings can supplement these results. We present month 12 results of BEYOND. BEYOND is an ongoing, 2-year, multicenter, prospective, observational real-world study of adults initiating CAB + RPV LA in the US. Key outcomes included reasons for initiating, virologic outcomes, adherence, and patient-reported outcomes related to treatment satisfaction and treatment challenges at baseline and month 12. In total, 308 participants (median age, 45 years; 83% identified as male; 39% identified as Black) initiated CAB + RPV LA most commonly because of treatment fatigue, adherence anxiety with daily oral therapy, and/or convenience. Of participants with baseline viral load data, 97% (194/200) had a viral load <50 copies/mL for their most recent test reported at month 12. Mean treatment satisfaction scores increased significantly from baseline to month 12 and 97% (223/229) of participants preferred LA versus oral treatment at month 12. Proportions of participants reporting "always" or "often" experiencing challenges related to HIV-1 treatment (fear of disclosure, adherence anxiety, reminder of HIV-1 status, and feeling stigmatized) decreased from baseline to month 12. Month 12 results from the real-world BEYOND study support the effectiveness of CAB + RPV LA for maintenance of virologic suppression and as a preferred treatment option for people with HIV-1.

A scoping review is one of the methods for synthesising evidence, allowing researchers to determine the scope or extent of literature concerning a specific topic. This approach has increasingly become a favoured tool among researchers for its comprehensive examination of literature, identification of existing gaps, clarification of concepts within a domain, and analysis of the methods employed in previous studies. Moreover, it plays a critical role in establishing the framework for a subsequent systematic review, often serving as its foundational phase. However, the initial and extended guidelines for conducting scoping reviews are perceived as lacking in methodological rigour. In response, the Joanna Briggs Institute (JBI) introduced more systematic guidelines to ensure a thorough and rigorous review and reporting process. This article provides a simplified, step-by-step guide for conducting a scoping review in alignment with the JBI recommendations, complemented by practical examples for each step to facilitate a clearer understanding of the process for researchers.

To describe a case of concurrent rhegmatogenous retinal detachment, choroidal detachment, and macular hole (RRD-CD-MH) formation in a patient after uncomplicated cataract extraction and intraocular lens implantation (CEIOL). In addition, we summarize the previously reported cases of RRD-CD-MH in the literature. Interventional case report and literature review. A 71-year-old white man without relevant medical or ocular history underwent an uncomplicated CEIOL. He presented with counting fingers vision and intraocular pressure of 5 mmHg after 3 weeks. On dilated fundus examination, multiple superior tears and total RRD with a serous CD was evident. Intraoperatively, a full-thickness MH was identified. The patient underwent routine RRD and MH repair, with instillation of 1,000 centistoke silicone oil (SiO). The retina successfully re-attached, the CD resolved, and the intraocular pressure normalized; however, the MH did not initially close. The SiO was removed approximately 4 months later and, while the MH remained open, the patient's vision improved to 20/80. Approximately three years after the surgical repair, the MH closed spontaneously, and the vision remained at 20/80. Our patient developed an RRD-CD-MH after uncomplicated CEIOL. The MH displayed delayed closure. The vision improved after surgical repair, and remained stable in the long term.

Objetivo: Reunir as evidências científicas sobre o uso da simulação para o treinamento em medicina de emergência, contemplando os aspectos mais relevantes e atuais no contexto internacional pós-pandemia pela COVID-19. Método: Foi realizada uma revisão integrativa da literatura com publicações entre 01 maio de 2020 e 01 maio de 2022, nas bases PubMed, Web of Science e Embase, utilizando o fluxograma PRISMA. Resultados: Um total de 19 artigos foram incluídos como a amostra final a ser analisada. A maioria dos estudos usaram desenhos transversais (n=12) para avaliar os efeitos da simulação em situações de emergência clínica. Os estudo longitudinais (n=7) focaram em desenvolver currículos de simulação ou avaliar cursos e instrumentos de ensino clínico. As evidências sugerem um foco importante no treinamento e desenvolvimento das interações entre instrutores, docentes, pacientes e estudantes, tanto a partir de habilidades técnicas quanto as comportamentais. Assim, as diversas técnicas de simulação permitem adaptar essa estratégia a diferentes níveis curriculares e com diferentes objetivos de desenvolvimento profissional e competências. Conclusão: O uso da simulação dentro de um ambiente seguro de aprendizagem, voltado ao ensino e treinamento da medicina de emergência têm contribuído como mais uma ferramenta para a melhora da performance dos profissionais da área, promovendo um atendimento mais seguro aos pacientes e de maior de qualidade na assistência à saúde

BackgroundCervical cancer is preventable with vaccination and early detection and treatment programs. However, in order for these programs to work as intended, stigma related to HPV and cervical cancer must be understood and addressed. We explored pre-existing stigma associated with HPV and cervical cancer in the public healthcare system of a low-resource setting prior to implementation of an HPV screen-and-treat program.MethodsThis study conducted thematic analysis of data collected during implementation of a novel HPV screen-and-treat system for cervical cancer early detection and treatment in Iquitos, Peru. We included 35 semi-structured interviews (19 health professionals, 16 women with cervical precancer or cancer), eight focus groups (70 community women), one workshop (14 health professionals), 210 counseling observations (with 20 nurse-midwives), and a document review. We used the Socio-Ecological Model to organize the analysis.ResultsWe identified three main themes: 1. the implication that women are to blame for their HPV infection through characterizations of being easy or promiscuous, 2. the implication that men are to blame for women’s HPV infections through being considered careless or unfaithful, 3. HPV is shameful, embarrassing, and something that should be hidden from others. Consequently, in some cases, women refrained from getting screened for HPV. These themes were seen at the individual level among women, relationship level among women, men, and family members, community level among healthcare staff, and societal level within components of cervical cancer guidelines and male chauvinism.ConclusionsCervical cancer early detection and treatment programs in limited resource settings must address stigma entrenched throughout the entire healthcare system in order to sustainably and successfully implement and scale-up new programs. Interventions to tackle this stigma can incorporate messages about HPV infections and latency to lessen the focus on the influence of sexual behavior on HPV acquisition, and instead, promote screening and treatment as paramount preventative measures.