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Gene therapy is a particularly useful treatment for nervous system genetic diseases, including those induced especially by infectious organisms and antigens, and is being utilized to treat Hodgkin's disease (HD). Due to the possible clonal relationship between both disorders, immunotherapy directed against CD20 positive cells may be a more effective treatment in patients with persistent HD and NHL. HL growth can be inhibited both in vitro and in vivo by AdsIL-13Ralpha2. High-dose treatment combined with stem cell transplantation has been effective in treating HIV-negative lymphoma that has progressed to high-risk or relapsed disease. For therapy, LMP2-specific CTL will be used. Furthermore, it is possible to view the cytotoxicity of genetically modified adenoviruses that express proteins such as p27Kip1, p21Waf1, and p16INK4A as a foundational element for (2,5)-derived ALCL genetic treatment for Hodgkin's disease.
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Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Humanos , Doença de Hodgkin/genética , Doença de Hodgkin/terapia , ImunoterapiaRESUMO
Destruction of the tumor (cancerous) cells may be caused by live viruses, which have replicative ability and replicate selectively in tumor cells, known as oncolytic virotherapy. In comparison of conservative cancer therapy, tumor-selective replicating viruses have more advantages. These viruses have introduced new methodologies for the human cancer treatment. Numerous strategies are used in development of virotherapeutics. Virotherapy is not unusual concept, but modern advances in technology of genetic modification of oncolytic viruses have improved the ability of targeting tumor cells more specifically, it triggered the development of novel ammunition to fight cancer. An effective virotherapeutic approach with oncolytic viruses exhibits the feasibility and safety under clinical approach. New strategies are being explored to overcome basic obstacles and challenges in virotherapy. Administration of oncolytic viruses, logically, will successfully augment new treatments against many kinds of tumors. Some encouraging antitumor responses shown by combination therapy are provoking strong immunity against established cancer. Chief developments in oncolytic virotherapy have seen in past several years. Significant understandings have been provided by findings on the interface among immune comebacks and viruses, whereas potential results have shown in clinical trials.
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Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Terapia Viral Oncolítica/métodos , Neoplasias/terapia , Vírus Oncolíticos/genética , Terapia CombinadaRESUMO
In this review, there is a complete description of the classes of arboviruses, their evolutionary process, virus characterization, disease transmission methods; it also describes about the vectors involved in transmission and their mood of transmission, both biologically as well as non-biologically and, about host, the resistance mechanism in host, and artificial methods of preventing those viral transmissions. Arboviruses transmitted to hosts by some vectors such as mosquitoes, ticks, etc. The virus replicates in the host can be prevented by some host resistance mechanisms like RNA interference (RNAi), which degrade virus RNA by its antiviral activity, insect repellents, IGRs, and PI technology.
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Arbovírus , Humanos , Animais , Arbovírus/genética , Replicação Viral , Interferência de RNA , Evolução Biológica , Mosquitos VetoresRESUMO
Neuroblastoma is a malignant tumor of neuroblasts, immature nerve cells found in several areas of the body. It usually affects children under age of 5. As usual, the tumor has ability to grow rapidly and to expand vastly which ultimately leads to death. Mostly, management decisions can be drawn by the prediction of the stage of the disease as well as age at the time of its diagnosis. There are four main stages of neuroblastoma, and treatment is according to the low and high risk of the disease. Several cytotoxic agents along with other therapies (antibody therapy, gene therapy, and even immunological therapies, antiangiogenic therapy, etc.) are used. Immunotherapy also has an important treatment option used nowadays for neuroblastoma. The discovery of major neuroblastoma-predisposition gene anaplastic lymphoma kinase cause somatic transformation or gene strengthening in diagnosed neuroblastoma. Promising new antiangiogenic strategies have also been introduced for the treatment of neuroblastoma with multiple mylomas. To manage numerous myelomas and cancers, including neuroblastoma, bone marrow transplantation and peripheral blood stem cell transplantation may be used.
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Neuroblastoma , Humanos , Neuroblastoma/genética , Neuroblastoma/terapia , Neuroblastoma/patologiaRESUMO
Tetanus remains a considerable cause of mortality among undervaccinated mothers and their infants following unhygienic deliveries, especially in low-income countries. Strategies of the maternal and neonatal tetanus elimination (MNTE) initiative, which targets 59 priority countries, include strengthening antenatal immunization of pregnant women with tetanus toxoid-containing vaccines (TTCVs); conducting TTCV supplementary immunization activities among women of reproductive age in high-risk districts; optimizing access to skilled birth attendants to ensure clean deliveries and umbilical cord care practices; and identifying and investigating suspected neonatal tetanus cases. This report updates a previous report and describes progress toward MNTE during 2000-2022. By December 2022, 47 (80%) of 59 priority countries were validated to have achieved MNTE. In 2022, among the 50 countries that reported coverage with ≥2 doses of TTCV among pregnant women, 16 (32%) reported coverage of ≥80%. In 2022, among 47 validated countries, 26 (55%) reported that ≥70% of births were assisted by skilled birth attendants. Reported neonatal tetanus cases worldwide decreased 89%, from 17,935 in 2000 to 1,995 in 2021; estimated neonatal tetanus deaths decreased 84%, from 46,898 to 7,719. However, the global disruption of routine immunization caused by the COVID-19 pandemic impeded MNTE progress. Since 2020, reported neonatal tetanus cases have increased in 18 (31%) priority countries. Integration of MNTE strategies into priority countries' national postpandemic immunization recovery activities is needed to achieve and sustain global elimination.
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Erradicação de Doenças , Saúde Global , Toxoide Tetânico , Tétano , Humanos , Tétano/prevenção & controle , Tétano/epidemiologia , Tétano/mortalidade , Feminino , Gravidez , Recém-Nascido , Saúde Global/estatística & dados numéricos , Toxoide Tetânico/administração & dosagem , Programas de Imunização , Mortalidade Infantil/tendênciasRESUMO
In contemporary times, geopolitical risk, and natural resources prices are susceptible due to the Russian-Ukraine conflict. In the meantime, emerging economies are struggling to explore the factors that could reduce ecological challenges and enhance environmental management. This research aims to analyze several economic, environmental, political, and institutional variables to ascertain their influence on greenhouse gas emissions in China. Covering the latest period from 1990 to 2022, various time series tests, including normality, stationarity, and cointegration tests. The results confirm that the variables studied have a stable pattern over time and are connected in the long run. The non-normal distribution of variables leads to opt novel moment quantile regression, where the results are tested for robustness via parametric approaches. The empirical results asserted that economic growth, natural resource prices, and trade significantly enhance ecological challenges (emissions). However, globalization, geopolitical risk, and institutional quality significantly reduce such environmental challenges. The results are robust, and both unidirectional and bidirectional causal associations confirm the importance of these variables in environmental management. Based on the results, this study recommends engagement in environmentally-friendly trading, investment in clean and green energy, and strengthening institutional quality for the region's environmental recovery.
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Dióxido de Carbono , Conservação dos Recursos Naturais , Ucrânia , Dióxido de Carbono/análise , Desenvolvimento Econômico , China , Federação Russa , Energia RenovávelRESUMO
Livestock production significantly contributes to greenhouse gas (GHG) emissions particularly methane (CH4) emissions thereby influencing climate change. To address this issue further, it is crucial to establish strategies that simultaneously increase ruminant productivity while minimizing GHG emissions, particularly from cattle, sheep, and goats. Recent advancements have revealed the potential for modulating the rumen microbial ecosystem through genetic selection to reduce methane (CH4) production, and by microbial genome editing including CRISPR/Cas9, TALENs (Transcription Activator-Like Effector Nucleases), ZFNs (Zinc Finger Nucleases), RNA interference (RNAi), Pime editing, Base editing and double-stranded break-free (DSB-free). These technologies enable precise genetic modifications, offering opportunities to enhance traits that reduce environmental impact and optimize metabolic pathways. Additionally, various nutrition-related measures have shown promise in mitigating methane emissions to varying extents. This review aims to present a future-oriented viewpoint on reducing methane emissions from ruminants by leveraging CRISPR/Cas9 technology to engineer the microbial consortia within the rumen. The ultimate objective is to develop sustainable livestock production methods that effectively decrease methane emissions, while maintaining animal health and productivity.
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Sistemas CRISPR-Cas , Edição de Genes , Gases de Efeito Estufa , Gado , Metano , Rúmen , Metano/metabolismo , Animais , Rúmen/microbiologia , Rúmen/metabolismo , Edição de Genes/métodos , Gases de Efeito Estufa/metabolismo , Bovinos , Cabras , Consórcios Microbianos , Ovinos , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Microbioma Gastrointestinal , Ruminantes/microbiologiaRESUMO
This meta-analysis consolidates various related studies to identify patterns in the impact of feeding algae on performance aspects, including milk fat, milk protein, and carcass yield in several ruminant species, such as cattle, sheep, and goats. The data were collected from 67 articles that examined factors such as the type of algae (macro- and microalgae), algal species, and animal breed. Barki sheep, Moghani sheep, and Zaraibi goats demonstrated an increased average daily gain (P < 0.05) when fed with both macro- and microalgae. Conversely, sheep such as Canadian Arcott and Ile-de-France showed adverse effects on the feed conversion ratio (FCR) (P < 0.05). Elevated FCR values were observed across castrated and young animals (P < 0.05). Algae extract notably increased the hot carcass weight (P < 0.001), particularly among Moghani sheep (P < 0.001). Raw algae significantly reduced the milk fat content (P < 0.001), particularly in cattle and sheep (P < 0.001). A decrease in milk fat was particularly noticeable in lactating females of Assaf sheep, Damascus goats, and Holstein cows (P < 0.001). Overall, algae inclusion tended to decrease the milk protein content (P < 0.05), leading to reduced milk production (P < 0.001) with cumulative algae feeding in Assaf sheep. However, conjugated linoleic acid (CLA; C18:2 c9,t11-CLA and C18:2 c12,t10-CLA) and docosahexaenoic acid (DHA; C22:6n-3) mostly increased in meat and milk from Holstein cow, Assaf sheep, Dorset sheep, and Ile-de-France sheep (P < 0.01). This meta-analysis highlights the necessity for additional research aimed at optimizing the sustainable use of algae in feed for ruminants, despite the demonstrated improvements in performance and the levels of CLA and DHA found in meat and milk.
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Ração Animal , Dieta , Carne , Microalgas , Leite , Alga Marinha , Animais , Microalgas/química , Ração Animal/análise , Leite/química , Leite/metabolismo , Alga Marinha/química , Dieta/veterinária , Carne/análise , Ovinos/fisiologia , Ovinos/crescimento & desenvolvimento , Cabras/fisiologia , Bovinos/fisiologia , Feminino , Fenômenos Fisiológicos da Nutrição AnimalRESUMO
AIDS dementia complex (ADC) is a nervous system disorder that harms the neurons in different parts of the brain. Various features are involved in altering the normal activities of neurons. Neurotoxicity is induced due to HIV viral proteins such as gp120, SDF, Tat, etc. These proteins target macrophages, glial cells, astrocytes, and release neurotoxins. These neurotoxins proved harmful for the neurons, caused apoptotic cell death by raising calcium, glutamate level and by producing various free radicals such as nitric oxide (NO·). Lipid peroxidation and lipids rafts also play a vital role in producing toxicity and apoptotic cell death. Membrane associated oxidative stress, cognitive impairment, and high level of HNE (4-hydroxynonenal); all are involved in ADC pathogenesis.
Assuntos
Complexo AIDS Demência , Síndrome da Imunodeficiência Adquirida , Humanos , Neurotoxinas , Síndrome da Imunodeficiência Adquirida/complicações , Encéfalo , ApoptoseRESUMO
The unique DNA-binding properties of distinct NF-κB dimers influence the selective regulation of NF-κB target genes. To more thoroughly investigate these dimer-specific differences, we combined protein-binding microarrays and surface plasmon resonance to evaluate DNA sites recognized by eight different NF-κB dimers. We observed three distinct binding-specificity classes and clarified mechanisms by which dimers might regulate distinct sets of genes. We identified many new nontraditional NF-κB binding site (κB site) sequences and highlight the plasticity of NF-κB dimers in recognizing κB sites with a single consensus half-site. This study provides a database that can be used in efforts to identify NF-κB target sites and uncover gene regulatory circuitry.
Assuntos
Regulação da Expressão Gênica , NF-kappa B/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Análise por Conglomerados , DNA/química , DNA/genética , Bases de Dados Genéticas , Humanos , Macrófagos/metabolismo , Camundongos , NF-kappa B/genética , Análise Serial de Proteínas , Ligação Proteica , Multimerização ProteicaRESUMO
Food security and environmental pollution are major concerns for the expanding world population, where farm animals are the largest source of dietary proteins and are responsible for producing anthropogenic gases, including methane, especially by cows. We sampled the fecal microbiomes of cows from varying environmental regions of Pakistan to determine the better-performing microbiomes for higher yields and lower methane emissions by applying the shotgun metagenomic approach. We selected managed dairy farms in the Chakwal, Salt Range, and Patoki regions of Pakistan, and also incorporated animals from local farmers. Milk yield and milk fat, and protein contents were measured and correlated with microbiome diversity and function. The average milk protein content from the Salt Range farms was 2.68%, with an average peak milk yield of 45 litters/head/day, compared to 3.68% in Patoki farms with an average peak milk yield of 18 litters/head/day. Salt-range dairy cows prefer S-adenosyl-L-methionine (SAMe) to S-adenosyl-L-homocysteine (SAH) conversion reactions and are responsible for low milk protein content. It is linked to Bacteroides fragilles which account for 10% of the total Bacteroides, compared to 3% in the Patoki region. The solid Non-Fat in the salt range was 8.29%, whereas that in patoki was 6.34%. Moreover, Lactobacillus plantarum high abundance in Salt Range provided propionate as alternate sink to [H], and overcoming a Methanobrevibacter ruminantium high methane emissions in the Salt Range. Furthermore, our results identified ruminant fecal microbiomes that can be used as fecal microbiota transplants (FMT) to high-methane emitters and low-performing herds to increase farm output and reduce the environmental damage caused by anthropogenic gases emitted by dairy cows.
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Microbioma Gastrointestinal , Lactação , Feminino , Bovinos , Animais , Dieta/veterinária , Proteínas do Leite , Gases , Metano/metabolismoRESUMO
OBJECTIVE: Asthma is a heterogeneous and genetically complex respiratory disease, and more than 300 million people are affected worldwide. In this study, frequencies of four SNPs (rs3816470, rs7216389, rs8067378, rs12603332) in chromosome 17q21 region were analyzed and their relationship with the asthma susceptibility, in the Pashtun population of Khyber Pakhtunkhwa province (KPK) of Pakistan were investigated. METHODS: DNA samples from 500 subjects (asthma cases/controls) were genotyped by Sanger sequencing. Chi-square tests, logistic regression analysis, linkage disequilibrium, and haplotype analysis techniques were applied to study the association of the SNPs with asthma. RESULTS: Genetic models, including recessive, dominant, co-dominant, over-dominant, and additive, were tested. The frequencies of alleles T/T at rs3816470 (OR = 1.91; 95%CI = 1.15-3.18; p = .011*) and rs7216389 (OR = 2.14; 95%CI = 1.21-3.79; p = .0076*), A/A at rs 8067378 (OR = 1.89; 95%CI = 1.17-3.06; p = .0081*), C/C at rs12603332 (OR = 1.97; 95%CI = 1.18-3.27; p = .008*), under recessive models, respectively, were significantly (p-values < .0125) associated with asthma susceptibility. The frequencies of T/T genotype in rs3816470 (OR = 6.01; 95%CI = 2.48-14.60; p = .000147*), and rs7216389 (OR = 5.05; 95%CI = 1.79-14.21; p = .003296*), and C/C at rs12603332 (OR = 2.64; 95%CI = 1.11-6.32; p = .019063*), were significantly (p-values < .0125) associated with asthma susceptibility in Pashtun women by stratified analysis based on age and gender. Similarly, three unique haplotypes were found associated with disease development and protective effect in female and male subjects. Linkage disequilibrium analysis presented a strong linkage (≥80%) between SNP variants and predicted their co-inheritance in the studied population. CONCLUSION: The 17q21 variants (rs3816470, rs7216389, rs12603332) were found significantly (p-values < .0125) associated with asthma predisposition in the Pashtun population of KPK exclusively in the female asthmatic cases.Supplemental data for this article can be accessed.
Assuntos
Asma , Predisposição Genética para Doença , Humanos , Masculino , Feminino , Paquistão/epidemiologia , Asma/epidemiologia , Asma/genética , Estudos de Casos e Controles , Genótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Chromium (Cr) is reported to be hazardous to environmental components and surrounding biota when levels exceed allowable thresholds. As Cr is extensively utilized in different industries, thereby comprehensively studied for its toxicity. Along with Cr, the applications of nano-Cr or chromium oxide nanoparticles (Cr2O3-NPs) are also expanding; however, the literature is scarce or limited on their phytotoxicity. Thereby, the current work investigated the morpho-physiological insights of macro- and nanoparticles of Cr in Hordeum vulgare L. plants. The increased accumulation and translocation of Cr under the exposure of both forms disturbed the cellular metabolism that might have inhibited germination and growth as well as interfered with the photosynthesis of plants. The overall extent of toxicity was noticeably higher under nanoparticles' exposure than macroparticles of Cr. The potential cue for such phytotoxic consequences mediated by Cr nanoparticles could be an increased bioavailability of Cr ions which was also supported by their total content, mobility, and factor toxicity index. Besides, to support further these findings, synchrotron X-ray technique was used to reliably identify Cr-containing compounds in the plant tissues. The X-ray spectra of the near spectral region and the far region of the spectrum of K-edge of Cr were obtained, and it was established that the dominant crystalline phase corresponds to Cr2O3 (eskolaite) from the recorded observations. Thus, the obtained results would allow revealing the mechanism of macro- and nanoparticles of Cr induced impacts on plant at the tissue, cellular- and sub-cellular levels.
Assuntos
Hordeum , Nanopartículas , Cromo/química , Nanopartículas/toxicidade , Nanopartículas/química , Plantas , Raízes de Plantas/metabolismoRESUMO
Despite its widespread prevalence, bullying in educational institutions is not considered a serious social issue in Pakistan. Present study explores the understandings and experiences of college students about bullying and documents the status of anti-bullying interventions in educational institutions. This study is based on in-depth interviews with students and principals of private sector colleges in Pakistan. The study showcases the important aspects of bullying that hurt the educational, personal and social lives of students. The most frequent form of bullying experienced by the students constitutes verbal bullying. Bullying occurs at specific places on campuses which are less supervised by teachers and administration. Although the principals were of the view that they had zero tolerance towards bullying in their premises, they did not have any preventive measures. There is a dire need to develop a policy to address the issue of bullying in educational institutions.
RESUMO
Shigellosis is a serious foodborne diarrheal disease caused by the Shigella species. It is a critical global health issue. In developing countries, shigellosis causes most of the mortality in children below 5 years of age. Globally, around 165 million cases of diarrhea caused by Shigella are reported, which accounts for almost 1 million deaths, in which the majority are recorded in Third World nations. In this study, silver nanoparticles were synthesized using Mangifera indica kernel (MK-AgNPs) seed extracts. The biosynthesized M. indica silver nanoparticles (MK-AgNPs) were characterized using an array of spectroscopic and microscopic tools, such as UV-Vis, scanning electron microscopy, particle size analyzer, Fourier transform infrared spectroscopy, and X-ray diffractometer. The nanoparticles were spherical in shape and the average size was found to be 42.7 nm. The MK-AgNPs exhibited remarkable antibacterial activity against antibiotic-resistant clinical Shigella sp. The minimum inhibitory concentration (MIC) value of the MK-AgNPs was found to be 20 µg/mL against the multi-drug-resistant strain Shigella flexneri. The results clearly demonstrate that MK-AgNPs prepared using M. indica kernel seed extract exhibited significant bactericidal action against pathogenic Shigella species. The biosynthesized nanoparticles from mango kernel could possibly prove therapeutically useful and effective in combating the threat of shigellosis after careful investigation of its toxicity and in vivo efficacy.
Assuntos
Disenteria Bacilar , Mangifera , Nanopartículas Metálicas , Shigella , Criança , Humanos , Mangifera/química , Nanopartículas Metálicas/química , Prata/farmacologia , Prata/química , Disenteria Bacilar/tratamento farmacológico , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Testes de Sensibilidade Microbiana , Espectroscopia de Infravermelho com Transformada de Fourier , Antibacterianos/farmacologia , Antibacterianos/química , SementesRESUMO
OBJECTIVE: To see if transporting paediatric patents to operation theatres using a battery operated vehicle decreases preoperative anxiety and reduce incidents of postoperative adverse events. METHODS: The study was conducted from May to August 2019 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised paediatric patients aged 3-5 years assessed as American Society of Anaesthesiologists grade I and II who were scheduled to undergo elective intrathecal chemotherapy under general anaesthesia. The subjects were randomised into intervention group A and control group B. Patients in group A were part of an incentive-based game in the holding bay area and were transported to the operation theatre using a battery-operated toy vehicle. Those in group B watched a pre-decided cartoon on television screen in the holding bay and were transported further using wheel chair. Induction of anaesthesia was done in the presence of guardians in both the groups. Patient anxiety was assessed using the modified Yale Preoperative Anxiety Scale in holding bay area T0, prior to induction of anaesthesia T1, and postoperative anaesthesia-related recovery T2. Data was analysed using SPSS 22. RESULTS: Of the 36 patients, 18(50%) were in group A; 12(66.6%) boys and 6(33.3%) girls with mean age 4.01±0.48 years. The remaining 18(50%) subjects were in group B; 13(72.2%) boys and 5(27.8%) girls with mean age 3.96 years. The difference in anxiety between the groups at T0 was non-significant (p=0.73). At T1 and T2, the scores were significantly lower group A compared to group B (p<0.05). Group A patients had better bag mask ventilation compliance at induction and remarkably less incidence of hypoxia, bronchospasm, postoperative agitation and early discharge from PACU. CONCLUSIONS: Incentive-based game therapy decreased anxiety among paediatric patients preoperatively, made them more compliant and improved postoperative recovery.
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Ansiedade , Motivação , Masculino , Feminino , Criança , Humanos , Pré-Escolar , Ansiedade/prevenção & controle , Anestesia Geral , PaquistãoRESUMO
The efficacy of the inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine has not been fully elucidated across the whole spectrum of patients on kidney replacement therapy. We aimed to characterize the long-term antibody response of inactivated SARS-CoV-2 vaccine administered in kidney transplant recipients (KTRs) and hemodialysis (HD) patients. We performed this prospective observational study in 50 HD, 64 KTR, and 41 healthy control groups (HG) given two doses of CoronaVac. We measured anti-Spike antibodies after 28 days of every vaccine dose, 3rd and 6th months after the first dose, and compared them between cohorts. After two doses, an anti-spike immunoglobulin G of ≥50 AU/ml was present in HD, KTR, and HG as 44%, 7.2%, and 58.5%, respectively (p < 0.001). Furthermore, the proportion of antibody titers peaked at 86.5%, 23%, and 97.6% (p < 0.001) at the 3rd month and decreased significantly at the 6th month in most HD and HG participants, whereas this effect was not observed in KTRs from basal until the 6th month (p < 0.001). During the follow-up, the incidence of coronavirus disease 2019 disease was higher (p < 0.003) in KTRs compared to the other groups, but there was no requirement for an intensive care unit and no death was recorded. We found a negative correlation between antibody seroconversion and age (p < 0.016). The antibody response following inactivated vaccine in dialysis patients is almost comparable to controls for 6 months. In contrast, kidney transplant patients have a poor response. These findings reinforce the need to discuss the vaccination strategy in immunocompromised patients, including the third dose with homologous or heterologous vaccines.
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COVID-19 , Transplante de Rim , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Diálise Renal , SARS-CoV-2RESUMO
BACKGROUND: Immune checkpoint inhibitors (ICIs) have been proven to be very effective in the treatment of multiple cancers. They have a unique side-effect profile distinct from conventional chemotherapy that can manifest as immune-related adverse events (irAEs). With expanding ICI use, clinicians will increasingly encounter irAEs, and thus adequate physician knowledge on their recognition and management is crucial. METHODS: To assess physician knowledge of irAEs due to ICIs, an online survey was administered to resident physicians in internal medicine (IM), emergency medicine, and family medicine (FM), as well as to faculty physicians in IM and FM. RESULTS: We sent the survey to 413 physicians and received responses from 155 (38%), of which 110 were residents and 45 were faculty. Pembrolizumab was identified as an ICI by 79% of physicians, nivolumab by 64%, and ipilimumab by 55%. Twenty-five percent incorrectly thought infliximab and adalimumab were ICIs. Most physicians (93%) were able to identify the gastrointestinal tract as an irAE site, whereas only 57% and 67% were able to identify cardiovascular and renal systems as irAE sites, respectively. A total of 59% believed steroids negatively affect efficacy of ICIs and should be used with caution to treat irAEs, 65% incorrectly thought endocrinopathies due to irAEs are usually reversible, and 45% of FM residents considered antibiotics as the mainstay of treatment in ICI-mediated colitis. On a self-rated scale from 0 to 100, the median comfort level for all physicians in recognizing irAEs was 15 and for treatment of irAEs was 10. CONCLUSIONS: Significant knowledge gaps exist among residents and faculty physicians across multiple specialties regarding the recognition and treatment of irAEs due to ICIs. Given that these physicians are usually the first point of contact with patients, physician education on identification and treatment of irAEs is needed. Early detection of these toxicities is critical for their resolution.
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Antineoplásicos Imunológicos , Médicos , Humanos , Antineoplásicos Imunológicos/uso terapêutico , Inibidores de Checkpoint Imunológico , Nivolumabe , Ipilimumab , Estudos RetrospectivosRESUMO
Maternal and neonatal tetanus (MNT)* remains a major cause of neonatal mortality with an 80%-100% case-fatality rate among insufficiently vaccinated mothers after unhygienic deliveries, especially in low-income countries (1). In 1989, the World Health Assembly endorsed elimination of neonatal tetanus; the activity was relaunched in 1999 as the MNT elimination (MNTE)§ initiative, targeting 59¶ priority countries. MNTE strategies include 1) achieving ≥80% coverage with ≥2 doses of tetanus toxoid-containing vaccine (TTCV2+)** among women of reproductive age through routine and supplementary immunization activities (SIAs) in high-risk districts,§§ 2) achieving ≥70% of deliveries by a skilled birth attendant,¶¶ and 3) implementing neonatal tetanus case-based surveillance (2). This report summarizes progress toward achieving and sustaining MNTE during 2000-2020 and updates a previous report (3). By December 2020, 52 (88%) of 59 priority countries had conducted TTCV SIAs. Globally, infants protected at birth*** against tetanus increased from 74% (2000) to 86% (2020), and deliveries assisted by a skilled birth attendant increased from 64% (2000-2006) to 83% (2014-2020). Reported neonatal tetanus cases worldwide decreased by 88%, from 17,935 (2000) to 2,229 (2020), and estimated deaths decreased by 92%, from 170,829 (2000) to 14,230 (2019). By December 2020, 47 (80%) of 59 priority countries were validated to have achieved MNTE, five of which conducted postvalidation assessments.§§§ To achieve elimination in the 12 remaining countries and sustain elimination, innovation is needed, including integrating SIAs to cover multiple vaccine preventable diseases and implementing TTCV life course vaccination.
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Erradicação de Doenças/métodos , Programas de Imunização , Saúde do Lactente , Saúde Materna , Toxoide Tetânico/administração & dosagem , Tétano/prevenção & controle , Adulto , Países em Desenvolvimento/estatística & dados numéricos , Erradicação de Doenças/estatística & dados numéricos , Feminino , Prioridades em Saúde , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Cobertura VacinalRESUMO
BACKGROUND: The literature lacks data on World Health Organization (WHO) class II and III deficient liver donors who underwent right hepatectomy during living donor liver transplantation (LDLT). METHODS: In this prospective cohort study, we compared the perioperative outcomes of 15 glucose-6 phosphate dehydrogenase (G6PD) deficient living liver donors with a matched cohort of 39 nondeficient living liver donors undergoing right lobe donation. RESULTS: Out of 15 G6PD deficient donors, four (26.67%) donors had class II, and 11 (73.34%) had class III G6PD deficiency. The mean postoperative trough hemoglobin level was significantly lower in the deficient group than the nondeficient group (9.38 ± 1.59 g/dL vs. 10.27 ± .91 g/dL, p = .046). The mean peak indirect bilirubin level was significantly higher in the deficient group than the nondeficient group (2.22 ± 1.38 mg/dL vs. 1.40 ± .89 mg/dL, p = .047), and a similar trend was observed in total serum bilirubin (3.99 ± 2.57 mg/dL vs. 2.99 ± 1.46 mg/dL, p = .038). Biochemical evidence of hemolysis was found only in three (20%) deficient donors, but none of them needed a blood transfusion. No mortality was observed in either group. All other parameters, including demographics, operative parameters, graft characteristics, and hospital stay were comparable between both groups (p > .05). CONCLUSION: G6PD deficiency with WHO class II and above should not be considered a contraindication for right lobe donation.