POTENSI KOMBINASI INDUCED PLURIPOTENT STEM CELL-DERIVED NEURAL PROGENITOR CELL (IPSC-NPC) DENGAN HIDROGEL CHONDROITIN SULFATE SCAFFOLDS YANG MEMEDIASI BASIC FIBROBLAST GROWTH FACTOR (BFGF) SEBAGAI INOVASI TERAPI TERBARU STROKE ISKEMIK

Stroke iskemik adalah jenis stroke yang paling umum terjadi dan merupakan penyakit dengan angka kematian dan kecacatan tertinggi di dunia. Terapi yang ada saat ini dalam menangani stroke masih menyisakan tantangan bagi para peneliti karena belum ditemukannya perawatan yang dapat meregenerasi jaringan otak yang hilang akibat infark. Penggunaan Neural Progenitor Cell (NPC) turunan induced Pluripotent Stem Cell (iPSC) merupakan studi yang berada paling depan dalam tahapan uji praklinis karena diketahui dapat menjadi dan menggantikan neuron serta mempromosikan mekanisme pemulihan endogen seperti angiogenesis. Namun, terdapat hambatan dari penggunaan NPC utamanya pada patofisiologi stroke yang menyebabkan adanya resistensi terhadap terapi seluler. Oleh karena itu, diperlukan kombinasi NPC dengan Scaffold menggunakan Chondroitin sulfate-A (CS-A) berbasis hidrogel yang dapat meningkatkan aliran darah ke inti stroke serta meningkatkan afinitas neurotropik. Kombinasi ini menghasilkan sinergitas terapi yang sangat baik dengan efek utamanya dimediasi oleh basic Fibroblast Growth Factor (bFGF) yang akan memperbaiki kerusakan jaringan di daerah infark. Untuk mengetahui potensi kombinasi NPC dengan Hidrogel CS-A dalam pengobatan stroke iskemik. Literature Review ini disusun menggunakan metode studi pustaka dengan mengumpulkan jurnal yang valid berdasarkan kriteria inklusi dan eksklusi khusus. Kombinasi NPC dengan Hidrogel CS-A secara signifikan meningkatkan perbaikan vaskular, aliran darah kortikal dan hasil perilaku sensorimotor setelah stroke. Peningkatan yang terjadi dimediasi melalui stimulasi pengeluaran bFGF yang mendorong perbaikan jaringan. Efektivitas pemberian NPC secara signifikan dapat ditingkatkan dengan kombinasi Hidrogel CS-A dan telah terbukti dalam berbagai pengujian sehingga diharapkan dapat menjadi upaya terbaru dalam terapi stroke iskemik.

The THREAT-ARREST Cyber-Security Training Platform

Cyber security is always a main concern for critical infrastructures and nation-wide safety and sustainability. Thus, advanced cyber ranges and security training is becoming imperative for the involved organizations. This paper presets a cyber security training platform, called THREAT-ARREST. The various platform modules can analyze an organization’s system, identify the most critical threats, and tailor a training program to its personnel needs. Then, different training programmes are created based on the trainee types (i.e. administrator, simple operator, etc.), providing several teaching procedures and accomplishing diverse learning goals. One of the main novelties of THREAT-ARREST is the modelling of these programmes along with the runtime monitoring, management, and evaluation operations. The platform is generic. Nevertheless, its applicability in a smart energy case study is detailed

Reassessing the role of mitochondrial DNA mutations in autism spectrum disorder

<p>Abstract</p> <p>Background</p> <p>There is increasing evidence that impairment of mitochondrial energy metabolism plays an important role in the pathophysiology of autism spectrum disorders (ASD; OMIM number: 209850). A significant proportion of ASD cases display biochemical alterations suggestive of mitochondrial dysfunction and several studies have reported that mutations in the mitochondrial DNA (mtDNA) molecule could be involved in the disease phenotype.</p> <p>Methods</p> <p>We analysed a cohort of 148 patients with idiopathic ASD for a number of mutations proposed in the literature as pathogenic in ASD. We also carried out a case control association study for the most common European haplogroups (hgs) and their diagnostic single nucleotide polymorphisms (SNPs) by comparing cases with 753 healthy and ethnically matched controls.</p> <p>Results</p> <p>We did not find statistical support for an association between mtDNA mutations or polymorphisms and ASD.</p> <p>Conclusions</p> <p>Our results are compatible with the idea that mtDNA mutations are not a relevant cause of ASD and the frequent observation of concomitant mitochondrial dysfunction and ASD could be due to nuclear factors influencing mitochondrion functions or to a more complex interplay between the nucleus and the mitochondrion/mtDNA.</p

Minisequencing mitochondrial DNA pathogenic mutations

<p>Abstract</p> <p>Background</p> <p>There are a number of well-known mutations responsible of common mitochondrial DNA (mtDNA) diseases. In order to overcome technical problems related to the analysis of complete mtDNA genomes, a variety of different techniques have been proposed that allow the screening of coding region pathogenic mutations.</p> <p>Methods</p> <p>We here propose a minisequencing assay for the analysis of mtDNA mutations. In a single reaction, we interrogate a total of 25 pathogenic mutations distributed all around the whole mtDNA genome in a sample of patients suspected for mtDNA disease.</p> <p>Results</p> <p>We have detected 11 causal homoplasmic mutations in patients suspected for Leber disease, which were further confirmed by standard automatic sequencing. Mutations m.11778G>A and m.14484T>C occur at higher frequency than expected by change in the Galician (northwest Spain) patients carrying haplogroup J lineages (Fisher's Exact test, <it>P</it>-value < 0.01). The assay performs well in mixture experiments of wild:mutant DNAs that emulate heteroplasmic conditions in mtDNA diseases.</p> <p>Conclusion</p> <p>We here developed a minisequencing genotyping method for the screening of the most common pathogenic mtDNA mutations which is simple, fast, and low-cost. The technique is robust and reproducible and can easily be implemented in standard clinical laboratories. </p

Prognostic value of neutrophil-to-lymphocyte ratio in COVID-19 patients: A systematic review and meta-analysis

Background: Neutrophil-to-lymphocyte ratio (NLR) is an accessible and widely used biomarker. NLR may be used as an early marker of poor prognosis in patients with COVID-19. Objective: To evaluate the prognostic value of the NLR in patients diagnosed with COVID-19. Methods: We conducted a systematic review and meta-analysis. Observational studies that reported the association between baseline NLR values (ie, at hospital admission) and severity or all-cause mortality in COVID-19 patients were included. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS). Random effects models and inverse variance method were used for meta-analyses. The effects were expressed as odds ratios (ORs) and their 95% confidence intervals (CIs). Small study effects were assessed with the Egger's test. Results: We analysed 61 studies (n = 15 522 patients), 58 cohorts, and 3 case-control studies. An increase of one unit of NLR was associated with higher odds of severity (OR 6.22; 95%CI 4.93 to 7.84; P <.001) and higher odds of all-cause mortality (OR 12.6; 95%CI 6.88 to 23.06; P <.001). In our sensitivity analysis, we found that 41 studies with low risk of bias and moderate heterogeneity (I2 = 53% and 58%) maintained strong association between NLR values and both outcomes (severity: OR 5.36; 95% CI 4.45 to 6.45; P <.001; mortality: OR 10.42 95% CI 7.73 to 14.06; P =.005). Conclusions: Higher values of NLR were associated with severity and all-cause mortality in hospitalised COVID-19 patients.Revisión por pare

A case of inflammatory pseudotumour of the gallbladder presenting as a big mass of uncertain behavior

Background: Inflammatory pseudotumour has been used to describe an inflammatory or fibrosing tumoral process of an undetermined cause that may involve a variety of organ systems, including the lungs, spleen, liver, lymph nodes, pancreas and extrahepatic bile duct with potential for recurrence and persistent local growth. In this article, we report a patient with a big mass of uncertain nature and behavior.Case presentationA 60-year-old woman presented with a 1-week history of abdominal pain, fever and jaundice. Six months before she had had right upper quadrant pain that was interpreted as biliary colic. A contrast-enhanced CT scan showed a big mass of soft tissue with diffuse infiltration of the gallbladder, displacement of the transverse colon, hepatic flexure and duodenum. For diagnostic distinction between a chronic inflammatory disease or a neoplasm, exploratory laparotomy was required. Intraoperative exploration disclosed a big mass of hard texture involving the gallbladder, with multiple concrements, hepatoduodenal ligament, right and transverse mesocolon, stomach and duodenum.Cholecystectomy was performed, preserving adjacent organs with macroscopic desmoplastic reaction. Histopathologic examination of the gallbladder showed a spindle cell proliferation with diffuse chronic inflammatory infiltrate of lymphocytes, plasma cells and hyalinized fibrous stroma. No vascular invasion or cellular atypia were evident.ConclusionInflammatory pseudotumour is a rare condition and diagnostic distinction from a chronic inflammatory disease or other neoplasm is only possible by histopathologic examination. There is a limited number of case reports in the literature indicating tumor location in the gallbladder

Burden of Parkinsonism and Parkinson\u27s Disease on Health Service Use and Outcomes in Latin America

\ua9 2023 - The authors. Published by IOS Press.Background: Little is known about the burden of parkinsonism and Parkinson\u27s disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis. Objective: The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries. Methods: 12,865 participants aged 65 years and older from the 10/66 population-based cohort study were analysed. Baseline assessments were conducted in 2003-2007 and followed-up 4 years later. Parkinsonism and PD were defined using current clinical criteria or self-reported diagnosis. Logistic regression models assessed the association between parkinsonism/PD with baseline health service use (community-based care or hospitalisation in the last 3 months) and Cox proportional hazards regression models with incident dependency (subjective assessment by interviewer based on informant interview) and mortality. Separate analyses for each country were combined via fixed effect meta-analysis. Results: At baseline, the prevalence of parkinsonism and PD was 7.9% (n = 934) and 2.6% (n = 317), respectively. Only parkinsonism was associated with hospital admission at baseline (OR 1.89, 95% CI 1.30-2.74). Among 7,296 participants without dependency at baseline, parkinsonism (HR 2.34, 95% CI 1.81-3.03) and PD (2.10, 1.37-3.24) were associated with incident dependency. Among 10,315 participants with vital status, parkinsonism (1.73, 1.50-1.99) and PD (1.38, 1.07-1.78) were associated with mortality. The Higgins I2 tests showed low to moderate levels of heterogeneity across countries. Conclusions: Our findings show that older people with parkinsonism or PD living in Latin America have higher risks of developing dependency and mortality but may have limited access to health services

Leg length, skull circumference, and the incidence of dementia in Latin America and China: A 10/66 population-based cohort study

\ua9 2018 Prince et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies. Methods Population-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident dementia, and mortality, three to five years later. Results Of the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66–0.97) and for skull circumference was 1.02 (95% CI, 0.84–1.25), with no heterogeneity of effect between sites (I2 = 0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992–1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHR 0.82, 95% CI 0.67–0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported. However, the effect of skull circumference was modified by gender (M vs F ASHR 0.86, 95% CI 0.75–0.98), but in the opposite direction to that hypothesized with a greater protective effect of larger skull dimensions in men. Conclusions Consistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neu-rodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development