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Knockdown of the insulator factor CCCTC binding factor (CTCF), which binds XL9, an intergenic element located between HLA-DRB1 and HLA-DQA1, was found to diminish expression of these genes. The mechanism involved interactions between CTCF and class II transactivator (CIITA), the master regulator of major histocompatibility complex class II (MHC-II) gene expression, and the formation of long-distance chromatin loops between XL9 and the proximal promoter regions of these MHC-II genes. The interactions were inducible and dependent on the activity of CIITA, regulatory factor X, and CTCF. RNA fluorescence in situ hybridizations show that both genes can be expressed simultaneously from the same chromosome. Collectively, the results suggest a model whereby both HLA-DRB1 and HLA-DQA1 loci can interact simultaneously with XL9, and describe a new regulatory mechanism for these MHC-II genes involving the alteration of the general chromatin conformation of the region and their regulation by CTCF.
In response to the substantial clinical and economic burden of diseases caused by Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) in Tunisia, the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was recently introduced into the national immunization program. However, there has yet to be a full-scale health economic analysis comparing currently available pneumococcal conjugate vaccines (PCVs) in Tunisia.
The primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for ST-segment elevation myocardial infarction (STEMI). The pharmacoinvasive strategy (PIs) is a reasonable alternative when prompt PPCI is not possible, especially in resource-limited regions. We aimed to compare PPCI versus PIs outcomes in Peru.
Road-traffic injuries are a key cause of death and disability in low-income and middle-income countries, but the effect of city characteristics on road-traffic mortality is unknown in these countries. The aim of this study was to determine associations between city-level built environment factors and road-traffic mortality in large Latin American cities.
The CardioMEMS® sensor is a wireless pulmonary artery pressure device used for monitoring symptomatic heart failure (HF). The use of CardioMEMS was associated with a reduction of hospitalizations of HF patients, but the acquisition cost could be high in low-and-middle income countries. Evidence of cost-effectiveness is needed to help decision-makers to allocate resources according to "value for money". This study is aimed at estimating the cost-effectiveness of CardioMEMS used in HF patients from the third-party payer perspective -Social Security (SS) and Private Sector (PS)- in Argentina.
: The progressive death of dopamine producing neurons in the substantia nigra pars compacta is the principal cause of symptoms of Parkinson's disease (PD). Stem cells have potential therapeutic use in replacing these cells and restoring function. To facilitate development of this approach, we sought to establish a preclinical model based on a large nonhuman primate for testing the efficacy and safety of stem cell-based transplantation. To this end, we differentiated baboon fibroblast-derived induced pluripotent stem cells (biPSCs) into dopaminergic neurons with the application of specific morphogens and growth factors. We confirmed that biPSC-derived dopaminergic neurons resemble those found in the human midbrain based on cell type-specific expression of dopamine markers TH and GIRK2. Using the reverse transcriptase quantitative polymerase chain reaction, we also showed that biPSC-derived dopaminergic neurons express PAX6, FOXA2, LMX1A, NURR1, and TH genes characteristic of this cell type in vivo. We used perforated patch-clamp electrophysiology to demonstrate that biPSC-derived dopaminergic neurons fired spontaneous rhythmic action potentials and high-frequency action potentials with spike frequency adaption upon injection of depolarizing current. Finally, we showed that biPSC-derived neurons released catecholamines in response to electrical stimulation. These results demonstrate the utility of the baboon model for testing and optimizing the efficacy and safety of stem cell-based therapeutic approaches for the treatment of PD.
Myocardial infarction (MI) is the most prevalent cardiovascular disease globally and is considered a public health problem. In Peru, MI is the second leading cause of death at the national level, with a mortality rate that exceeds 10% in the hospital setting. The study aims to determine the clinical and epidemiological characteristics of ST-segment elevation myocardial infarction (STEMI) in tertiary care facilities belonging to the Peruvian public health system.
Selective serotonin reuptake inhibitors (SSRIs) are less efficacious in treating depression in children than in adults. SSRIs block serotonin uptake via the high-affinity, low-capacity serotonin transporter. However, the low-affinity, high-capacity organic cation transporter 3 (OCT3) and plasma membrane monoamine transporter (PMAT) are emerging as important players in serotonin uptake. We hypothesized that OCT3 and/or PMAT are functionally upregulated in juveniles, thereby buffering SSRIs' ability to enhance serotonergic neurotransmission. Unlike in adult mice, we found the OCT/PMAT blocker, decynium-22, to have standalone antidepressant-like effects in juveniles. Using in vivo high-speed chronoamperometry, we found that juveniles clear serotonin from the CA3 region of the hippocampus ~2-fold faster than adult mice. Cell density did not differ between ages, suggesting that faster serotonin clearance in juveniles is unrelated to faster diffusion through the extracellular matrix. Western blot and immunohistochemistry showed that juvenile mice have modestly greater expression of PMAT than adults, whereas OCT3 expression in the CA3 region of the hippocampus was similar between ages. Together, these data suggest that faster serotonin clearance and antidepressant-like effects of decynium-22 in juvenile mice may be due to functionally upregulated PMAT. Faster serotonin clearance via PMAT in juveniles may contribute to reduced therapeutic efficacy of SSRIs in children relative to adults.
COVID-19 has disrupted the treatment of non-communicable diseases (NCDs). This study conducted a multimorbidity analysis and evaluated hospital admissions and death rates among diabetic patients before and after the implementation of lockdown due to the COVID-19 pandemic in Peru. Data from the Ministry of Health (MINSA) of Peru from January 2017 to December 2020 was used. Hospital death, discharge and the percentage of death/hospital admissions were defined as outcomes of interest. We performed an interrupted time series analysis to assess the aggregate change in the outcomes of interest before and after mandatory lockdown in response to the COVID-19 pandemic in Peru (n = 65,935). Additionally, a network analysis was performed to evaluate the frequency of occurrence of hospital admissions before and after the mandatory lockdown according to demographic characteristics. The average monthly hospital admissions among diabetic patients in Peru decreased by 29% after the implementation of the lockdown. The largest reduction was observed in women (-41%) and for patients 60 years or older (-35%). Furthermore, there was a 92% increase in the average number of monthly deaths. The largest percentage change occurred in men (+113%) and in the group of 40-59 years (+144%). After the implementation of lockdown in Peru, hospital admissions among diabetic patients significantly decreased while in-hospital mortality slightly increased. Our findings shed light on the limitations of the Peruvian health system and the importance of ensuring continued care of NCDs as part of the response strategy during times of crisis.
Dorsal raphe (DR) serotonin neurons provide a major input to the ventral tegmental area (VTA). Here, we show that DR serotonin transporter (SERT) neurons establish both asymmetric and symmetric synapses on VTA dopamine neurons, but most of these synapses are asymmetric. Moreover, the DR-SERT terminals making asymmetric synapses on VTA dopamine neurons coexpress vesicular glutamate transporter 3 (VGluT3; transporter for accumulation of glutamate for its synaptic release), suggesting the excitatory nature of these synapses. VTA photoactivation of DR-SERT fibers promotes conditioned place preference, elicits excitatory currents on mesoaccumbens dopamine neurons, increases their firing, and evokes dopamine release in nucleus accumbens. These effects are blocked by VTA inactivation of glutamate and serotonin receptors, supporting the idea of glutamate release in VTA from dual DR SERT-VGluT3 inputs. Our findings suggest a path-specific input from DR serotonergic neurons to VTA that promotes reward by the release of glutamate and activation of mesoaccumbens dopamine neurons.
This study aimed to estimate the budget impact of the incorporation of venetoclax for the treatment of patients with Acute Myeloid Leukemia (AML) over 75 years of age or those with comorbidities and contraindications for the use of intensive chemotherapy, from the perspective of the social security and the private third-party payers in Argentina.
Evidence on the economic value of rotavirus vaccines in middle-income countries is limited. We aimed to model the implementation of three vaccines (human rotavirus, live, attenuated, oral vaccine [HRV, 2 doses]; rotavirus vaccine, live, oral, pentavalent [HBRV, 3 doses] and rotavirus vaccine, live attenuated oral, freeze-dried [BRV-PV, 3 doses] presented in 1-dose and 2-dose vials) into the South African National Immunisation Programme.
In this article, we examine the research on sofosbuvir with a bibliometric analysis of global research production. The study of sofosbuvir has been a field of intense research in the past few years, with Latin American contributions playing a modest role. With continued drug development and approval of hepatitis C antivirals, research is expected to increase. Our findings will assist scholars and policy makers in their efforts to improve scientific research policies, with the goal of maximizing the access to treatments, especially in low and middle-income countries.
to determine the global offer of Massive Open Online Courses (MOOCs) in health and nursing, and to know the characteristics of its content, for continuing education in nursing professionals in Peru. Exploratory study was carried out on the websites: Coursera, edX, FutureLearn, XuetangX and Udacity, Class Central and MOOC List. The courses were classified according to the five nursing areas recognized by the Peruvian College of Nurses (Colegio de Enfermeros del Perú, CEP). From each course, data was collected on institution and country of origin, hours per week and total duration in weeks, audio and subtitle language.
ST-segment elevation myocardial infarction (STEMI) is the most severe clinical form of acute myocardial infarction, for which the current treatment consists of effective and timely myocardial reperfusion (within 12 hours of symptom onset). However, between 10% and 15% of patients with STEMI arrive at hospital facilities 12 hours after the onset of symptoms (late presentation). Therefore, the objective of the present study will be to determine if late revascularisation (12-72 hours after the onset of symptoms) affects the indicators of cardiovascular mortality, reinfarction, recurrent infarction, hospitalisation for heart failure and post infarction angina compared with no late revascularisation in patients with STEMI.
This study aimed to: (1) estimate the disease burden of herpes zoster (HZ) and (2) assess the potential public health impact of introducing adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination in adults aged ≥50 years in Argentina, Brazil, Mexico, Chile, and Colombia using the ZOster ecoNomic Analysis (ZONA) static multicohort Markov model. The model followed individuals aged ≥50 years from administration of RZV over their remaining lifetime. Inputs were based, most often, on local data. First dose coverage was assumed to be 35%, with 75% second dose compliance. It was predicted that without RZV, there would be 23,558,675 HZ cases, 6,115,981 post-herpetic neuralgia (PHN) cases, and 7,058,779 non-PHN complications in the five countries, but introducing RZV under assumed coverage could avoid 4,583,787 (19%) HZ cases, 1,130,751 (18%) PHN cases, and 1,373,419 (19%) non-PHN complications. Also, 10427,504 (20%) doctor's office visits and 1,630,201 (19%) days of hospitalization could be averted in the three countries (Argentina, Brazil, and Mexico) with available input data. The numbers needed to be vaccinated to avoid one case of HZ were 9-10 across countries, and to avoid one case of PHN, 35-40. One-way sensitivity analyses showed that the input parameters with the largest impact on the estimated number of HZ cases avoided were first dose coverage, initial HZ incidence, and vaccine efficacy waning. In conclusion, the introduction of RZV for older adults in Latin America could greatly reduce the public health burden of HZ and reduce the related doctor visits and hospitalization days.
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