Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study.

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.

A call to create integrated services to better address the needs of migrants who use drugs in Europe.

Each year, thousands of migrants enter the EU. Data on drug use in migrant populations are scarce and inconclusive. However, several risk factors make them particularly vulnerable to engaging in problematic drug use. In this perspective, we summarize the limited information that is available on migrants who use drugs and make a case as to why it is essential to improve access to health and social services, including harm reduction services, for this population. With this aim, we call for the co-creation of integrated services that better address the needs of migrants who use drugs in Europe.

Histone Acetyltransferases p300 and CBP Coordinate Distinct Chromatin Remodeling Programs in Vascular Smooth Muscle Plasticity.

BACKGROUND: Vascular smooth muscle cell (VSMC) phenotypic switching contributes to cardiovascular diseases. Epigenetic regulation is emerging as a key regulatory mechanism, with the methylcytosine dioxygenase TET2 acting as a master regulator of smooth muscle cell phenotype. The histone acetyl-transferases p300 and CREB-binding protein (CBP) are highly homologous and often considered to be interchangeable, and their roles in smooth muscle cell phenotypic regulation are not known. METHODS: We assessed the roles of p300 and CBP in human VSMC with knockdown, in inducible smooth muscle-specific knockout mice (inducible knockout [iKO]; p300iKO or CBPiKO), and in samples of human intimal hyperplasia. RESULTS: P300, CBP, and histone acetylation were differently regulated in VSMCs undergoing phenotypic switching and in vessel remodeling after vascular injury. Medial p300 expression and activity were repressed by injury, but CBP and histone acetylation were induced in neointima. Knockdown experiments revealed opposing effects of p300 and CBP in the VSMC phenotype: p300 promoted contractile protein expression and inhibited migration, but CBP inhibited contractile genes and enhanced migration. p300iKO mice exhibited severe intimal hyperplasia after arterial injury compared with controls, whereas CBPiKO mice were entirely protected. In normal aorta, p300iKO reduced, but CBPiKO enhanced, contractile protein expression and contractility compared with controls. Mechanistically, we found that these histone acetyl-transferases oppositely regulate histone acetylation, DNA hydroxymethylation, and PolII (RNA polymerase II) binding to promoters of differentiation-specific contractile genes. Our data indicate that p300 and TET2 function together, because p300 was required for TET2-dependent hydroxymethylation of contractile promoters, and TET2 was required for p300-dependent acetylation of these loci. TET2 coimmunoprecipitated with p300, and this interaction was enhanced by rapamycin but repressed by platelet-derived growth factor (PDGF) treatment, with p300 promoting TET2 protein stability. CBP did not associate with TET2, but instead facilitated recruitment of histone deacetylases (HDAC2, HDAC5) to contractile protein promoters. Furthermore, CBP inhibited TET2 mRNA levels. Immunostaining of cardiac allograft vasculopathy samples revealed that p300 expression is repressed but CBP is induced in human intimal hyperplasia. CONCLUSIONS: This work reveals that p300 and CBP serve nonredundant and opposing functions in VSMC phenotypic switching and coordinately regulate chromatin modifications through distinct functional interactions with TET2 or HDACs. Targeting specific histone acetyl-transferases may hold therapeutic promise for cardiovascular diseases.

Sex differences in Cardiorenal Syndrome: Insights from CARDIOREN Registry.

PURPOSE OF THE WORK: Although sex-specific differences in heart failure (HF) or kidney disease (KD) have been analyzed separately, the predominant cardiorenal phenotype by sex has not been described. This study aims to explore the sex-related differences in cardiorenal syndrome (CRS) in a contemporary cohort of outpatients with HF. FINDINGS: An analysis of the Cardiorenal Spanish registry (CARDIOREN) was performed. CARDIOREN Registry is a prospective multicenter observational registry including 1107 chronic ambulatory HF patients (37% females) from 13 Spanish HF clinics. Estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73 m2 was present in 59.1% of the overall HF population, being this prevalence higher in the female population (63.2% vs. 56.6%, p = 0.032, median age: 81 years old, IQR:74-86). Among those with kidney dysfunction, women displayed higher odds of showing HF with preserved ejection fraction (HFpEF) (odds ratio [OR] = 4.07; confidence interval [CI] 95%: 2.65-6.25, p < 0.001), prior valvular heart disease (OR = 1.76; CI 95%:1.13-2.75, p = 0.014), anemia (OR: 2.02; CI 95%:1.30-3.14, p = 0.002), more advanced kidney disease (OR for CKD stage 3: 1.81; CI 95%:1.04-3.13, p = 0.034; OR for CKD stage 4: 2.49, CI 95%:1.31-4.70, p = 0.004) and clinical features of congestion (OR:1.51; CI 95%: 1.02-2.25, p = 0.039). On the contrary, males with cardiorenal disease showed higher odds of presenting HF with reduced ejection fraction (HFrEF) (OR:3.13; CI 95%: 1.90-5.16, p < 0.005), ischemic cardiomyopathy (OR:2.17; CI 95%: 1.31-3.61, p = 0.003), hypertension (OR = 2.11; CI 95%:1.18-3.78, p = 0.009), atrial fibrillation (OR:1.71; CI 95%: 1.06-2.75, p = 0.025), and hyperkalemia (OR:2.43, CI 95%: 1.31-4.50, p = 0.005). In this contemporary registry of chronic ambulatory HF patients, we observed sex-related differences in patients with combined heart and kidney disease. The emerging cardiorenal phenotype characterized by advanced CKD, congestion, and HFpEF was predominantly observed in women, whereas HFrEF, ischemic etiology, hypertension, hyperkalemia, and atrial fibrillation were more frequently observed in men.

Pressure release technique versus placebo applied to cervical and masticatory muscles in patients with chronic painful myofascial temporomandibular disorder: A randomised clinical trial.

BACKGROUND: The therapeutic approach to myofascial TMD should focus on pain relief and rehabilitation of function. OBJECTIVE: This study investigated whether pressure release technique (PRT) is effective for reducing pain in people with chronic myofascial temporomandibular disorders (TMD). METHODS: A single-blinded randomised parallel-group trial, with 3 months follow-up was conducted. A total of 72 patients were randomly allocated to receive PRT or sham PRT. Primary outcome was pain assessed with a visual analogue scale (VAS). Secondary outcomes included pressure pain thresholds (PPTs), range of opening of the mouth (ROM), Neck Disability Index (NDI), Pain Catastrophizing Scale (PCS), Tampa Scale for Kinesiophobia (TSK-11), State-Trait Anxiety Index (STAI) and State-Trait Depression Index (ST-DEP). All parameters were assessed at baseline, at the end of the treatment and at 3 months follow-up. Statistical analysis was performed by ANOVA. RESULTS: There were significant main effects of time, group and interaction between time and group (F ≥ 21.92; p < .001) on VAS pain. Post hoc tests showed a significant reduction in VAS pain scores in the PRT group (≥31.9%; p < .001). Effect sizes were moderate in the PRT group at all follow-up periods (≥1.25 Cohen's d). Also, there were significant effects of time in secondary outcomes (F ≥ 9.65; p < .001), and there were also interactions between time and group (F ≥ 3.82; p < .002) with better effects in the PRT group. CONCLUSIONS: The inclusion of PRT to conventional management with occlusal splints and self-care management appears to be effective to improve self-reported levels of pain in patients with chronic myofascial TMD pain. Retrospectively registered (ClinicalTrials.gov: NCT03619889).

Clinical phenotypes and outcomes of SARS-CoV-2, influenza, RSV and seven other respiratory viruses: a retrospective study using complete hospital data.

BACKGROUND: An understanding of differences in clinical phenotypes and outcomes COVID-19 compared with other respiratory viral infections is important to optimise the management of patients and plan healthcare. Herein we sought to investigate such differences in patients positive for SARS-CoV-2 compared with influenza, respiratory syncytial virus (RSV) and other respiratory viruses. METHODS: We performed a retrospective cohort study of hospitalised adults and children (≤15 years) who tested positive for SARS-CoV-2, influenza virus A/B, RSV, rhinovirus, enterovirus, parainfluenza viruses, metapneumovirus, seasonal coronaviruses, adenovirus or bocavirus in a respiratory sample at admission between 2011 and 2020. RESULTS: A total of 6321 adult (1721 SARS-CoV-2) and 6379 paediatric (101 SARS-CoV-2) healthcare episodes were included in the study. In adults, SARS-CoV-2 positivity was independently associated with younger age, male sex, overweight/obesity, diabetes and hypertension, tachypnoea as well as better haemodynamic measurements, white cell count, platelet count and creatinine values. Furthermore, SARS-CoV-2 was associated with higher 30-day mortality as compared with influenza (adjusted HR (aHR) 4.43, 95% CI 3.51 to 5.59), RSV (aHR 3.81, 95% CI 2.72 to 5.34) and other respiratory viruses (aHR 3.46, 95% CI 2.61 to 4.60), as well as higher 90-day mortality, ICU admission, ICU mortality and pulmonary embolism in adults. In children, patients with SARS-CoV-2 were older and had lower prevalence of chronic cardiac and respiratory diseases compared with other viruses. CONCLUSIONS: SARS-CoV-2 is associated with more severe outcomes compared with other respiratory viruses, and although associated with specific patient and clinical characteristics at admission, a substantial overlap precludes discrimination based on these characteristics.

Per Oral Endoscopic Myotomy for Zenker's Diverticulum: A Novel and Superior Technique Compared With Septotomy?

INTRODUCTION: Endoscopic management of Zenker diverticuli (ZD) has traditionally been via septotomy technique. The recent development of tunneling technique has shown to be both efficacious and safe. The aim of this study is to evaluate the tunneling technique using per oral endoscopic myotomy (Z-POEM) versus septotomy. METHODS: Patients who underwent endoscopic management of ZD either by Z-POEM or septotomy from March 2017 until November 2020 from 9 international academic centers were included. Demographics, clinical data preprocedure and postprocedure, procedure time, adverse events, and hospital length of stay were analyzed. RESULTS: A total of 101 patients (mean age 74.9 y old, 55.4% male) were included: septotomy (n=49), Z-POEM (n=52). Preprocedure Functional Oral Intake Scale score and Eckardt score was 5.3 and 5.4 for the septotomy group and 5.9 and 5.15 for the Z-POEM group. Technical success was achieved in 98% of the Z-POEM group and 100% of the septotomy group. Clinical success was achieved in 84% and 92% in the septotomy versus Z-POEM groups. Adverse events occurred in 30.6% (n=15) in septotomy group versus 9.6% (n=5) in the Z-POEM group (P=0.017). Reintervention for ongoing symptoms occurred in 7 patients in the septotomy group and 3 patients in the Z-POEM group. Mean hospital length of stay was shorter for the Z-POEM group, at 1.5 versus 1.9 days. CONCLUSIONS: A tunneling technique via the Z-POEM procedure is an efficacious and safe endoscopic treatment for ZD. Z-POEM is a safer procedure with a statistically significant reduction in adverse events compared with traditional septotomy technique.

Thromboxane-dependent coronary vasoconstriction in obese mice: Role of peroxynitrite.

Obesity leads to chronic oxidative stress promoting the development of cardiovascular diseases including coronary artery disease and endothelial dysfunction. Increased reactive oxygen species production associated with obesity might lead to endothelial dysfunction through cyclooxygenase (COX) pathway. We evaluated arachidonic acid (AA)-dependent coronary vascular responses and explored COX metabolism in obese C57BL/6 mice. In response to arachidonic acid (AA), isolated hearts from obese mice showed increased vasoconstriction compared with control mice. Released thromboxane (TX) A2 during AA-induced vasoconstriction phase was increased in heart perfusates from obese mice. Indomethacin and 1-benzylimidazole, both reduced vasoconstriction response in control and obese mice. Vasoconstriction response to TXA2 mimetic analog U46619 was 2.7 higher in obese mice. Obesity increased COX-2, TXS and TX receptor protein expression as well as oxidative stress evaluated by nitrotyrosine and peroxynitrite levels, compared with control mice. Obese mice treated with FeTMPyP, a peroxynitrite scavenger, reversed all these parameters to control levels. These data suggest that alterations in COX pathway may be associated with increased generation of free radicals, including peroxynitrite, that result from the oxidative stress observed in obesity.

Genetic analysis of the pX region of bovine leukemia virus genotype 1 in Holstein Friesian cattle with different stages of infection.

The pX genetic region of bovine leukemia virus (BLV) includes four genes with overlapping reading frames that code for the Tax, Rex, R3, and G4 proteins. These proteins are involved in the regulation of transcriptional and post-transcriptional viral expression, as well as having oncogenic potential. Our goal was to investigate the pathogenicity of the pX region of BLV genotype 1 in terms of lymphocytosis, lymphomas, and proviral DNA load. We screened 724 serological samples from mixed-age Holstein Friesian cattle from six states in Mexico. Peripheral blood leukocytes (PBLs) were isolated from whole blood with anticoagulant, and genomic DNA was extracted from the PBLs using a commercial kit. Then, a set of primers that hybridize in conserved regions of the BLV pX region were used, which allowed for PCR standardization to detect proviral DNA in infected cells. Positive amplicons were sequenced using the Sanger method, resulting in 1156-nucleotide-long final sequences that included the four pX region genes. The experimental group consisted of 30 animals. Twelve of these had lymphocytosis, six had lymphoma, and 12 were apparently healthy cattle without any signs of lymphocytosis or lymphoma. The presence of lymphoma was detected in six bovine tumor tissues using histopathology, and the presence of BLV was detected by in situ hybridization. Phylogenetic analysis demonstrated that the 30 sequences were associated with genotype 1, and the genetic distance between the sequences ranged from 0.2% to 2.09%. We identified two sequences in the G4 gene: one with a three-nucleotide deletion resulting in the loss of a leucine (AGU_7488L, in a cow with lymphocytosis), and one with a nine-nucleotide deletion resulting in the loss of leucine, proline, and leucine (AGU_18A, in a cow without lymphocytosis). Analysis of the PX region indicated that positive selection had occurred in the G4, rex, and R3 genes, and we found no difference in proviral DNA load between the studied groups. We were unable to establish an association between variations in the pX region and the development of lymphocytosis, lymphoma, asymptomatic status, or proviral DNA load in BLV-infected cattle.

Exhausted CD4+ T Cells during Malaria Exhibit Reduced mTORc1 Activity Correlated with Loss of T-bet Expression.

CD4+ T cell functional inhibition (exhaustion) is a hallmark of malaria and correlates with impaired parasite control and infection chronicity. However, the mechanisms of CD4+ T cell exhaustion are still poorly understood. In this study, we show that Ag-experienced (Ag-exp) CD4+ T cell exhaustion during Plasmodium yoelii nonlethal infection occurs alongside the reduction in mammalian target of rapamycin (mTOR) activity and restriction in CD4+ T cell glycolytic capacity. We demonstrate that the loss of glycolytic metabolism and mTOR activity within the exhausted Ag-expCD4+ T cell population during infection coincides with reduction in T-bet expression. T-bet was found to directly bind to and control the transcription of various mTOR and metabolism-related genes within effector CD4+ T cells. Consistent with this, Ag-expTh1 cells exhibited significantly higher and sustained mTOR activity than effector T-bet- (non-Th1) Ag-expT cells throughout the course of malaria. We identified mTOR to be redundant for sustaining T-bet expression in activated Th1 cells, whereas mTOR was necessary but not sufficient for maintaining IFN-γ production by Th1 cells. Immunotherapy targeting PD-1, CTLA-4, and IL-27 blocked CD4+ T cell exhaustion during malaria infection and was associated with elevated T-bet expression and a concomitant increased CD4+ T cell glycolytic metabolism. Collectively, our data suggest that mTOR activity is linked to T-bet in Ag-expCD4+ T cells but that reduction in mTOR activity may not directly underpin Ag-expTh1 cell loss and exhaustion during malaria infection. These data have implications for therapeutic reactivation of exhausted CD4+ T cells during malaria infection and other chronic conditions.

SARS-CoV-2 testing in patients with low COVID-19 suspicion at admission to a tertiary care hospital, Stockholm, Sweden, March to September 2020.

BackgroundUniversal SARS-CoV-2 testing at hospital admission has been proposed to prevent nosocomial transmission.AimTo investigate SARS-CoV-2 positivity in patients tested with low clinical COVID-19 suspicion at hospital admission.MethodsWe characterised a retrospective cohort of patients admitted to Karolinska University Hospital tested for SARS-CoV-2 by PCR from March to September 2020, supplemented with an in-depth chart review (16 March-12 April). We compared positivity rates in patients with and without clinical COVID-19 suspicion with Spearman's rank correlation coefficient. We used multivariable logistic regression to identify factors associated with test positivity.ResultsFrom March to September 2020, 66.9% (24,245/36,249) admitted patient episodes were tested; of those, 61.2% (14,830/24,245) showed no clinical COVID-19 suspicion, and the positivity rate was 3.2% (469/14,830). There was a strong correlation of SARS-CoV-2 positivity in patients with low vs high COVID-19 suspicion (rho = 0.92; p < 0.001).From 16 March to 12 April, the positivity rate was 3.9% (58/1,482) in individuals with low COVID-19 suspicion, and 3.1% (35/1,114) in asymptomatic patients. Rates were higher in women (5.0%; 45/893) vs men (2.0%; 12/589; p = 0.003), but not significantly different if pregnant women were excluded (3.7% (21/566) vs 2.2% (12/589); p = 0.09). Factors associated with SARS-CoV-2 positivity were testing of pregnant women before delivery (odds ratio (OR): 2.6; 95% confidence interval (CI): 1.3-5.4) and isolated symptoms in adults (OR: 3.3; 95% CI: 1.8-6.3).ConclusionsThis study shows a relatively high SARS-CoV-2 positivity rate in patients with low COVID-19 suspicion upon hospital admission. Universal SARS-CoV-2 testing of pregnant women before delivery should be considered.

Microalgae Bioactive Compounds to Topical Applications Products-A Review.

Microalgae are complex photosynthetic organisms found in marine and freshwater environments that produce valuable metabolites. Microalgae-derived metabolites have gained remarkable attention in different industrial biotechnological processes and pharmaceutical and cosmetic industries due to their multiple properties, including antioxidant, anti-aging, anti-cancer, phycoimmunomodulatory, anti-inflammatory, and antimicrobial activities. These properties are recognized as promising components for state-of-the-art cosmetics and cosmeceutical formulations. Efforts are being made to develop natural, non-toxic, and environmentally friendly products that replace synthetic products. This review summarizes some potential cosmeceutical applications of microalgae-derived biomolecules, their mechanisms of action, and extraction methods.

Photolyase Production and Current Applications: A Review.

The photolyase family consists of flavoproteins with enzyme activity able to repair ultraviolet light radiation damage by photoreactivation. DNA damage by the formation of a cyclobutane pyrimidine dimer (CPD) and a pyrimidine-pyrimidone (6-4) photoproduct can lead to multiple affections such as cellular apoptosis and mutagenesis that can evolve into skin cancer. The development of integrated applications to prevent the negative effects of prolonged sunlight exposure, usually during outdoor activities, is imperative. This study presents the functions, characteristics, and types of photolyases, their therapeutic and cosmetic applications, and additionally explores some photolyase-producing microorganisms and drug delivery systems.

Nanostructures for drug delivery in respiratory diseases therapeutics: Revision of current trends and its comparative analysis.

Respiratory diseases are leading causes of death and disability in developing and developed countries. The burden of acute and chronic respiratory diseases has been rising throughout the world and represents a major problem in the public health system. Acute respiratory diseases include pneumonia, influenza, SARS-CoV-2 and MERS viral infections; while chronic obstructive pulmonary disease (COPD), asthma and, occupational lung diseases (asbestosis, pneumoconiosis) and other parenchymal lung diseases namely lung cancer and tuberculosis are examples of chronic respiratory diseases. Importantly, chronic respiratory diseases are not curable and treatments for acute pathologies are particularly challenging. For that reason, the integration of nanotechnology to existing drugs or for the development of new treatments potentially benefits the therapeutic goals by making drugs more effective and exhibit fewer undesirable side effects to treat these conditions. Moreover, the integration of different nanostructures enables improvement of drug bioavailability, transport and delivery compared to stand-alone drugs in traditional respiratory therapy. Notably, there has been great progress in translating nanotechnology-based cancer therapies and diagnostics into the clinic; however, researchers in recent years have focused on the application of nanostructures in other relevant pulmonary diseases as revealed in our database search. Furthermore, polymeric nanoparticles and micelles are the most studied nanostructures in a wide range of diseases; however, liposomal nanostructures are recognized to be some of the most successful commercial drug delivery systems. In conclusion, this review presents an overview of the recent and relevant research in drug delivery systems for the treatment of different pulmonary diseases and outlines the trends, limitations, importance and application of nanomedicine technology in treatment and diagnosis and future work in this field.

Memory CD8+ T cells exhibit tissue imprinting and non-stable exposure-dependent reactivation characteristics following blood-stage Plasmodium berghei ANKA infections.

Experimental cerebral malaria (ECM) is a severe complication of Plasmodium berghei ANKA (PbA) infection in mice, characterized by CD8+ T-cell accumulation within the brain. Whilst the dynamics of CD8+ T-cell activation and migration during extant primary PbA infection have been extensively researched, the fate of the parasite-specific CD8+ T cells upon resolution of ECM is not understood. In this study, we show that memory OT-I cells persist systemically within the spleen, lung and brain following recovery from ECM after primary PbA-OVA infection. Whereas memory OT-I cells within the spleen and lung exhibited canonical central memory (Tcm) and effector memory (Tem) phenotypes, respectively, memory OT-I cells within the brain post-PbA-OVA infection displayed an enriched CD69+ CD103- profile and expressed low levels of T-bet. OT-I cells within the brain were excluded from short-term intravascular antibody labelling but were targeted effectively by longer-term systemically administered antibodies. Thus, the memory OT-I cells were extravascular within the brain post-ECM but were potentially not resident memory cells. Importantly, whilst memory OT-I cells exhibited strong reactivation during secondary PbA-OVA infection, preventing activation of new primary effector T cells, they had dampened reactivation during a fourth PbA-OVA infection. Overall, our results demonstrate that memory CD8+ T cells are systemically distributed but exhibit a unique phenotype within the brain post-ECM, and that their reactivation characteristics are shaped by infection history. Our results raise important questions regarding the role of distinct memory CD8+ T-cell populations within the brain and other tissues during repeat Plasmodium infections.

Time to focus on circulating nucleic acids for diagnosis and monitoring of gliomas: A systematic review of their role as biomarkers.

Gliomas are diffusely growing tumours arising from progenitors within the central nervous system. They encompass a range of different molecular types and subtypes, many of which have a well-defined profile of driver mutations, copy number changes and DNA methylation patterns. A majority of gliomas will require surgical intervention to relieve raised intracranial pressure and reduce tumour burden. A proportion of tumours, however, are located in neurologically sensitive areas and a biopsy poses a significant risk of a deficit. A majority of gliomas recur after surgery, and monitoring tumour burden of the recurrence is currently achieved by imaging. However, most imaging modalities have limitations in assessing tumour burden and infiltration into adjacent brain, and sometimes imaging is unable to discriminate between tumour recurrence and pseudo-progression. Liquid biopsies, obtained from body fluids such as cerebrospinal fluid or blood, contain circulating nucleic acids or extracellular vesicles containing tumour-derived components. The studies for this systematic review were selected according to PRISMA criteria, and suggest that the detection of circulating tumour-derived nucleic acids holds great promises as biomarker to aid diagnosis and prognostication by monitoring tumour progression, and thus can be considered a pathway towards personalized medicine.

The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria.

BACKGROUND: Recent genome wide analysis studies have identified a strong association between single nucleotide variations within the human ATP2B4 gene and susceptibility to severe malaria. The ATP2B4 gene encodes the plasma membrane calcium ATPase 4 (PMCA4), which is responsible for controlling the physiological level of intracellular calcium in many cell types, including red blood cells (RBCs). It is, therefore, postulated that genetic differences in the activity or expression level of PMCA4 alters intracellular Ca2+ levels and affects RBC hydration, modulating the invasion and growth of the Plasmodium parasite within its target host cell. METHODS: In this study the course of three different Plasmodium spp. infections were examined in mice with systemic knockout of Pmca4 expression. RESULTS: Ablation of PMCA4 reduced the size of RBCs and their haemoglobin content but did not affect RBC maturation and reticulocyte count. Surprisingly, knockout of PMCA4 did not significantly alter peripheral parasite burdens or the dynamics of blood stage Plasmodium chabaudi infection or reticulocyte-restricted Plasmodium yoelii infection. Interestingly, although ablation of PMCA4 did not affect peripheral parasite levels during Plasmodium berghei infection, it did promote slight protection against experimental cerebral malaria, associated with a minor reduction in antigen-experienced T cell accumulation in the brain. CONCLUSIONS: The finding suggests that PMCA4 may play a minor role in the development of severe malarial complications, but that this appears independent of direct effects on parasite invasion, growth or survival within RBCs.

Gastric per-oral endoscopic myotomy versus pyloromyotomy for gastroparesis: An international comparative study.

BACKGROUND AND AIM: Gastroparesis is a potentially debilitating gastric motility disorder with limited treatment options. Highest efficacy treatments include gastric per-oral endoscopic myotomy (GPOEM) and surgical pyloromyotomy. This study compares the efficacy and safety of GPOEM versus laparoscopic pyloromyotomy for refractory gastroparesis. METHODS: Patients who underwent GPOEM or laparoscopic pyloromyotomy for refractory gastroparesis from four centers across the USA and Latin America were included in a dedicated registry. Data collected included patient demographics, imaging, laboratory values, clinical success, gastroparesis cardinal symptom index, procedure time, pre-op and post-op gastric emptying times, adverse events, and hospital length of stay. RESULTS: A total of 102 patients were included (mean age 47; 32.4% male): GPOEM n = 39, surgical pyloromyotomy n = 63.Technical success was 100% in both groups. Clinical success was 92.3% in the GPOEM group and 82.5% in the surgery group (P = 0.164). The GPOEM group had a significantly higher post-op GSCI score reduction by 1.3 units (P < 0.00001), post-op retention reduction at 2 h by 18% (P < 0.00001), post-op retention reduction at 4 h by 25% (P < 0.00001) and a lower procedure time by 20 min (P < 0.00001) as compared with surgery. GPOEM also had a lower hospital length of stay by 2.8 days (P < 0.00001). Adverse events were significantly fewer in the GPOEM group (13%) compared with surgery group (33.3%; P = 0.021). Mean blood loss in the GPOEM group was only 3.6 mL compared with 866 mL in the surgery group. CONCLUSIONS: The GPOEM may be a less invasive, safer, and more efficacious procedural treatment for refractory gastroparesis as compared with surgical pyloromyotomy.

Splenomegaly: Diagnosis and Management in Adults.

Splenomegaly can be due to several mechanisms but is almost always a sign of a systemic condition. Patient habits, travel, and medical conditions can increase risk of splenomegaly and suggest etiology. Symptoms can suggest infectious, malignant, hepatic, or hematologic causes. Physical examination will typically reveal splenomegaly, but abdominal ultrasonography is recommended for confirmation. Physical examination should also assess for signs of systemic illness, liver disease, and anemia or other hematologic issues. The most common causes of splenomegaly in the United States are liver disease, malignancy, and infection. Except for apparent causes such as infectious mononucleosis, basic laboratory analysis and ultrasonography are the first-line steps in determining etiology. Malaria and schistosomiasis are common in tropical regions, where as many as 80% of people may have splenomegaly. Management of splenomegaly involves treating the underlying disease process. Splenectomies and spleen reduction therapies are sometimes performed. Any patient with limited splenic function requires increased vaccination and prophylactic antibiotics for procedures involving the respiratory tract. Acute infections, anemia, and splenic rupture are the most common complications of splenomegaly, and people with splenomegaly should refrain from participating in contact sports to decrease risk of rupture.

Review of hepatitis C screening programs for immigrants in Spain from endemic countries.

BACKGROUND: hepatitis C virus (HCV) screening strategies in European countries do not usually include the migrant population from endemic countries as a target group for screening. The aim of this study is to describe and to evaluate HCV screening strategies for the migrant population residing in Spain and to compare the differences at a regional level. METHODS: on-line research on every Health Public Department's website of each autonomous community was carried out during 2017 and 2019. RESULTS: Aragon, Cantabria, Catalunya, Canary Islands and Madrid have HCV screening programmes and include migrants from high-endemic countries as a high-risk group that should be targeted in the screening programme. The Valencian Community and the Basque Country have an HCV programme although migrants for high endemic countries are not included as a high-risk group. Finally, the other autonomic communities have no specific programme for HCV in place. Few of them have a screening control system and/or evaluation. CONCLUSION: there is heterogeneity on the different HCV autonomic programs concerning the risk groups that should be targeted. A homogenization of such criteria would be recommended. HCV screening in migrant populations from endemic countries should be extended to the rest of autonomic communities. More measures for control and evaluation should be implemented in autonomic strategies with specific indicators for migrant populations.