Requirements and expectations of high-quality biomarkers for atopic dermatitis and psoriasis in 2021-a two-round Delphi survey among international experts.

BACKGROUND: Chronic inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis (PSO) present major challenges in health care. Thus, biomarkers to identify disease trajectories and response to treatments to improve the lives of affected individuals warrant great research consideration. The requirements that these biomarkers must fulfil for use as practical clinical tools have not yet been adequately investigated. AIM: To identify the core elements of high-quality AD and PSO biomarkers to prepare recommendations for current biomarker research. METHOD: A cross-sectional two-round Delphi survey was conducted from August to October 2019 and October to November 2020. All participants were members of the BIOMAP project, an EU-funded consortium of clinicians, researchers, patient organizations and pharmaceutical industry partners. The first round consisted of three open-ended questions. Responses were qualitatively analysed, and 26 closed statements were developed. For the second round, 'agreement' was assumed when the responses of ≥70% of the participants were ≥5 points on a 7-point Likert scale for each statement. Priority classification was based on mean scores (<20th percentile = low, 20th to 60th percentile = medium, >60th percentile = high). RESULTS: Twenty-one and twenty-six individuals participated in rounds one and two, respectively. From 26 statements that were included in round 2, 18 achieved agreement (8 concerning the performance, 8 for the purpose and 2 on current obstacles). Seven statements were classified as high priority, e.g. those concerning reliability, clinical validity, a high positive predictive value, prediction of the therapeutic response and disease progression. Another seven statements were assigned medium priority, e.g. those about analytical validity, prediction of comorbidities and therapeutic algorithm. Low priority included four statements, like those concerning cost effectiveness and prediction of disease flares. CONCLUSION: The core requirements that experts agreed on being essential for high-quality AD and PSO biomarkers require rapid validation. Biomarkers can therefore be assessed based on these prioritized requirements.

Feature set optimization in biomarker discovery from genome-scale data.

MOTIVATION: Omics technologies have the potential to facilitate the discovery of new biomarkers. However, only few omics-derived biomarkers have been successfully translated into clinical applications to date. Feature selection is a crucial step in this process that identifies small sets of features with high predictive power. Models consisting of a limited number of features are not only more robust in analytical terms, but also ensure cost effectiveness and clinical translatability of new biomarker panels. Here we introduce GARBO, a novel multi-island adaptive genetic algorithm to simultaneously optimize accuracy and set size in omics-driven biomarker discovery problems. RESULTS: Compared to existing methods, GARBO enables the identification of biomarker sets that best optimize the trade-off between classification accuracy and number of biomarkers. We tested GARBO and six alternative selection methods with two high relevant topics in precision medicine: cancer patient stratification and drug sensitivity prediction. We found multivariate biomarker models from different omics data types such as mRNA, miRNA, copy number variation, mutation and DNA methylation. The top performing models were evaluated by using two different strategies: the Pareto-based selection, and the weighted sum between accuracy and set size (w = 0.5). Pareto-based preferences show the ability of the proposed algorithm to search minimal subsets of relevant features that can be used to model accurate random forest-based classification systems. Moreover, GARBO systematically identified, on larger omics data types, such as gene expression and DNA methylation, biomarker panels exhibiting higher classification accuracy or employing a number of features much lower than those discovered with other methods. These results were confirmed on independent datasets. AVAILABILITY AND IMPLEMENTATION: github.com/Greco-Lab/GARBO. CONTACT: dario.greco@tuni.fi. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Vitamin D replacement ameliorates serum lipoprotein functions, adipokine profile and subclinical atherosclerosis in pre-menopausal women.

BACKGROUND AND AIMS: Low vitamin D (vitD) has been linked to increased cardiovascular (CV) risk, but the effects of vitD supplementation are not clarified. We evaluated the impact of vitD normalization on HDL cholesterol efflux capacity (CEC), which inversely correlates with CV risk, the proatherogenic serum cholesterol loading capacity (CLC), adipokine profile and subclinical atherosclerosis. METHODS AND RESULTS: Healthy premenopausal women with vitD deficiency (n = 31) underwent supplementation. Subclinical atherosclerosis was evaluated by flow-mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AIx), measured with standard techniques. HDL CEC and serum CLC were measured by a radioisotopic and fluorimetric assay, respectively. Malondialdehyde (MDA) in HDL was quantified by the TBARS assay. Pre-ß HDL was assessed by 2D-electrophoresis. Serum adipokines were measured by ELISA. VitD replacement restored normal levels of serum 25-hydroxyvitamin D (25OHD) and significantly improved FMD (+4%; p < 0.001), PWV (-4.1%: p < 0.001) and AIx (-16.1%; p < 0.001). Total CEC was significantly improved (+19.5%; p = 0.003), with a specific increase in the ABCA1-mediated CEC (+70.8%; p < 0.001). HDL-MDA slightly but significantly decreased (-9.6%; p = 0.027), while no difference was detected in pre-ß HDL. No change was observed in aqueous diffusion nor in the ABCG1-mediated CEC. Serum CLC was significantly reduced (-13.3%; p = 0.026). Levels of adiponectin were increased (+50.6%; p < 0.0001) and resistin levels were decreased (-24.3%; p < 0.0001). After vitD replacement, an inverse relationship was found linking the ABCA1-mediated CEC with pre-ß HDL (r2 = 0.346; p < 0.001) and resistin (r2 = 0.220; p = 0.009). CONCLUSION: Our data support vitD supplementation for CV risk prevention.

Nasal mucosa and blood cell transcriptome profiles do not reflect respiratory symptoms associated with moisture damage.

Upper and lower respiratory symptoms and asthma are adverse health effects associated with moisture-damaged buildings. Quantitative measures to detect adverse health effects related to exposure to dampness and mold are needed. Here, we investigate differences in gene expression between occupants of moisture-damaged and reference buildings. Moisture-damaged (N = 11) and control (N = 5) buildings were evaluated for dampness and mold by trained inspectors. The transcriptomics cohort consisted of nasal brushings and peripheral blood mononuclear cells (PBMCs) from 86 teachers, with/without self-perceived respiratory symptoms. Subject categories comprised reference (R) and damaged (D) buildings with (S) or without (NS) symptoms, that is, R-S, R-NS, DS, and D-NS. Component analyses and k-means clustering of transcriptome profiles did not distinguish building status (R/D) or presence of respiratory symptoms (S/NS). Only one nasal mucosa gene (YBX3P1) exhibited a significant change in expression between D-S and D-NS. Nine other nasal mucosa genes were differentially expressed between R-S and D-S teachers. No differentially expressed genes were identified in PBMCs. We conclude that the observed mRNA differences provide very weak biological evidence for adverse health effects associated with subject occupancy of the specified moisture-damaged buildings. This emphasizes the need to evaluate all potential factors (including those not related to toxicity) influencing perceived/self-reported ill health in moisture-damaged buildings.

Normal pregnancy outcome after first-trimester exposure to liraglutide in a woman with Type 2 diabetes.

BACKGROUND: Data from animal studies suggest that glucagon-like peptide-1 analogues should not be used in pregnancy, but there have been no reports to date of their effects in human pregnancy. The aim of the present report was to describe a case of exposure to liraglutide during the first trimester of pregnancy in a patient with Type 2 diabetes mellitus. CASE REPORT: A 37-year-old woman with Type 2 diabetes mellitus who had been taking liraglutide for 2 years was admitted in the 13(th) week of gestation. Liraglutide was immediately discontinued and intensive insulin therapy instituted. The woman gave birth to a healthy child after completing an uneventful gestation period. CONCLUSION: Although the present normal pregnancy outcome does not mean that glucagon-like peptide-1 analogues are safe to use in pregnancy, this report contributes to the limited knowledge regarding human exposure to these drugs during pregnancy in women with diabetes.

Whooping cough, twenty years from acellular vaccines introduction.

Clinical pertussis resulting from infection with B. pertussis is a significant medical and public health problem, despite the huge success of vaccination that has greatly reduced its incidence. The whole cell vaccine had an undeniable success over the last 50 years, but its acceptance was strongly inhibited by fear, only partially justified, of severe side effects, but also, in the Western world, by the difficulty to enter in combination with other vaccines: today multi-vaccine formulations are essential to maintain a high vaccination coverage. The advent of acellular vaccines was greeted with enthusiasm by the public health world: in the Nineties, several controlled vaccine trials were carried out: they demonstrated a high safety and good efficacy of new vaccines. In fact, in the Western world, the acellular vaccines completely replaced the whole cells ones. In the last years, ample evidence on the variety of protection of these vaccines linked to the presence of different antigens of Bordetella pertussis was collected. It also became clear that the protection provided, on average around 80%, leaves every year a significant cohort of vaccinated susceptible even in countries with a vaccination coverage of 95%, such as Italy. Finally, it was shown that, as for the pertussis disease, protection decreases over time, to leave a proportion of adolescents and adults unprotected. Waiting for improved pertussis vaccines, the disease control today requires a different strategy that includes a booster at 5 years for infants, but also boosters for teenagers and young adults, re-vaccination of health care personnel, and possibly of pregnant women and of those who are in contact with infants (cocooning). Finally, the quest for better vaccines inevitably tends towards pertussis acellular vaccines with at least three components, which have demonstrated superior effectiveness and have been largely in use in Italy for fifteen years.

Feasibility and effectiveness of primary umbilical hernia repair with biologic graft: preliminary study.

BACKGROUND: In this prospective non-randomized observational cohort study we evaluated: the feasibility and effectiveness of primary umbilical hernia repair with open tension-free and sutureless technique using a porcine small intestinal submucosa (Surgisis) prosthesis, the quality of the treatment in terms of reduction of postoperative discomfort and the complications at early and long-term follow-up. METHODS: Thirty-six consecutive patients, mean age 45.25 +/- 12.19 years, affected by primary umbilical uncomplicated hernia with a defect size < or = 3 cm, were treated in a day-surgery setting. A tailored flat Surgisis graft was used to ensure an overlap of at least 2 cm; in all patients the mesh was fixed by fibrin glue. Collected data included: visual analogic scale (VAS) pain scores at 24 hours, 72 hours, and 7, 15, and 30 days and number of analgesic medications after operation, complications rate, the quality of life measured by Short Form 36 health survey questionnaire (SF-36) before the operation and at long term follow-up. RESULTS: The mean follow-up time was 5.6 +/- 1.4 years. Postoperative pain was low: the mean visual analogic scale (VAS) scores were 2.8 at 24 h, 1.8 at 72 h, and 0.9, 0.3, and 0.04 at 7, 15, and 30 days, respectively. 77.8% of the patients (28/36) did not use any analgesic drugs. Seroma was reported in 13.8% of the patients (5/36); there were no hematomas, infection, chronic pain and no major complications or mortality (< or = 30 days). Recurrence rate was 2.8% (1/36). Patient satisfaction showed a significant improvement in all SF-36 domain scores (P < 0.001). CONCLUSIONS: The biologic mesh seems to be a safe and reliable device for repairing primary umbilical hernia with high patient comfort, even if not yet an alternative to synthetic mesh.

Transcriptomic profiling reveals differential cellular response to copper oxide nanoparticles and polystyrene nanoplastics in perfused human placenta.

The growing nanoparticulate pollution (e.g. engineered nanoparticles (NPs) or nanoplastics) has been shown to pose potential threats to human health. In particular, sensitive populations such as pregnant women and their unborn children need to be protected from harmful environmental exposures. However, developmental toxicity from prenatal exposure to pollution particles is not yet well studied despite evidence of particle accumulation in human placenta. Our study aimed to investigate how copper oxide NPs (CuO NPs; 10-20 nm) and polystyrene nanoplastics (PS NPs; 70 nm) impact on gene expression in ex vivo perfused human placental tissue. Whole genome microarray analysis revealed changes in global gene expression profile after 6 h of perfusion with sub-cytotoxic concentrations of CuO (10 µg/mL) and PS NPs (25 µg/mL). Pathway and gene ontology enrichment analysis of the differentially expressed genes suggested that CuO and PS NPs trigger distinct cellular response in placental tissue. While CuO NPs induced pathways related to angiogenesis, protein misfolding and heat shock responses, PS NPs affected the expression of genes related to inflammation and iron homeostasis. The observed effects on protein misfolding, cytokine signaling, and hormones were corroborated by western blot (accumulation of polyubiquitinated proteins) or qPCR analysis. Overall, the results of the present study revealed extensive and material-specific interference of CuO and PS NPs with placental gene expression from a single short-term exposure which deserves increasing attention. In addition, the placenta, which is often neglected in developmental toxicity studies, should be a key focus in the future safety assessment of NPs in pregnancy.

An ancestral molecular response to nanomaterial particulates.

The varied transcriptomic response to nanoparticles has hampered the understanding of the mechanism of action. Here, by performing a meta-analysis of a large collection of transcriptomics data from various engineered nanoparticle exposure studies, we identify common patterns of gene regulation that impact the transcriptomic response. Analysis identifies deregulation of immune functions as a prominent response across different exposure studies. Looking at the promoter regions of these genes, a set of binding sites for zinc finger transcription factors C2H2, involved in cell stress responses, protein misfolding and chromatin remodelling and immunomodulation, is identified. The model can be used to explain the outcomes of mechanism of action and is observed across a range of species indicating this is a conserved part of the innate immune system.

Tolerance to lipopolysaccharide promotes an enhanced neutrophil extracellular traps formation leading to a more efficient bacterial clearance in mice.

Tolerance to lipopolysaccharide (LPS) constitutes a stress adaptation, in which a primary contact with LPS results in a minimal response when a second exposure with the same stimulus occurs. However, active important defence mechanisms are mounted during the tolerant state. Our aim was to assess the contribution of polymorphonuclear neutrophils (PMN) in the clearance of bacterial infection in a mouse model of tolerance to LPS. After tolerance was developed, we investigated in vivo different mechanisms of bacterial clearance. The elimination of a locally induced polymicrobial challenge was more efficient in tolerant mice both in the presence or absence of local macrophages. This was related to a higher number of PMN migrating to the infectious site as a result of an increased number of PMN from the marginal pool with higher chemotactic capacity, not because of differences in their phagocytic activity or reactive species production. In vivo, neutrophils extracellular trap (NET) destruction by nuclease treatment abolished the observed increased clearance in tolerant but not in control mice. In line with this finding, in vitro NETs formation was higher in PMN from tolerant animals. These results indicate that the higher chemotactic response from an increased PMN marginal pool and the NETs enhanced forming capacity are the main mechanisms mediating bacterial clearance in tolerant mice. To sum up, far from being a lack of response, tolerance to LPS causes PMN priming effects which favour distant and local anti-infectious responses.

Clinical characteristics and associated comorbidities in diabetic patients with cranial nerve palsies.

BACKGROUND: Cranial mononeuropathy is one of the not so common forms of diabetic neuropathy that often appears to be a serious problem from a diagnostic and therapeutic point of view. AIM: Objective of this study was to determine the incidence, the clinical characteristics, and risk factors associated with cranial nerve palsies among persons with diabetes. METHODS: We have performed a retrospective study of all diabetic patients with cranial nerve palsies who were hospitalized in a metabolic department over a 12-yr period. RESULTS: During the period of the survey, a total of 8150 diabetic subjects were hospitalized and cranial nerve palsies were identified in 61 patients (0.75%). Isolated III nerve palsies accounted for the majority of patients (0.35%), with VII nerve palsies (0.21%) occurring more frequently than VI (0.15%) and multiple palsies (0.04%). Peripheral neuropathy was present in only 24% of patients. Patients with VII nerve palsies showed a tendency toward a lower coexistence of diabetic complications and cardiovascular risk factors than those with III and VI nerve palsies. CONCLUSIONS: Cranial nerve palsies are a not common problem among patients with diabetes; diagnosis of diabetic mononeuropathy should be considered even in the absence of peripheral neuropathy; the oculomotor nerve was most frequently affected in our case report. The coexistence of diabetic complications and cardiovascular risk factors was slightly lower in patients with VII nerve palsy: this fact is compatible with the hypotesis that this event is less closely related to diabetes and metabolic factors in its pathogenesis.

The prevalence and antibiotics susceptibility pattern of Neisseria gonorrhoeae in patients attending OPD clinics at St. Mary's Hospital Lacor Uganda.

INTRODUCTION: Gonorrhea is one of the most common sexually transmitted infections (STls) in developing countries, and the emergence of resistance to antimicrobial agents in Neisseria gonorrhoeae is a major obstacle in the control of gonorrhoea. Periodical determination of the prevalence and monitoring of antimicrobial susceptibility of N. gonorrhoeae is essential for the early detection of emergence of drug resistance. METHODS: A total of 640 consecutive patients who attended the Outpatient Department (OPD) Clinics at St. Mary's Hospital Lacor between Jan 2007-Dec 2011, with gonococcal urethriris symptoms and whose urethral swabs and high vagina swabs (HVS) were cultured, were involved in the study. Two hundred and fifty six (256) patients had positive pus swab culture, of which 151 (23.6%) showed growth of Neisseria gonorrhoeae. All the isolates were tested for antimicrobial susceptibility using the Kirby Bauer-disc diffusion techniques. RESULTS: Gonococcal isolates showed rapid decrease in susceptibility to the antimicrobials especially to ampicillin, tetracycline and erythomycin, ciprofloxacin, and intermediate to chloramphenicol, however, gentamicin and cefotaxime have remained as a single dose sensitive treatment for Neisseria gonorrhoeae. Sensitization on drug use and adopting preventive measures and continuous education on safer sexual behavior through health care authorities would lead to reduction in the prevalence of Neisseria gonorrhoeae and resistance to antimicrobial. DISCUSSION: Gonorrhea is one of the most common sexually transmitted infections (STIs) in developing countries, and the emergence of resistance to antimicrobial agents in Neisseria gonorrhoeae is a major obstacle in the control of gonorrhea. Periodical monitoring of antimicrobial susceptibility of N. gonorrhea is essential for the early detection of emergence of drug resistance.

Hospital acquired infections in a large north Ugandan hospital.

INTRODUCTION: Hospital care is a precious gift in Uganda, therefore little concern is given to hospital safety and very seldom Hospital Acquired Infection (HAI) risk is evaluated. Within a quality improvement hospital program the Board of Lacor Hospital, a large Missionary Hospital of north Uganda, ordered an HAI control program to be established. The first step of this program was an HAI prevalence survey whose results are presented in this paper. METHODS: A one day prevalence survey was performed on patients admitted at least 48 hours before the survey: short training was offered to qualified nurses and hospital doctors. Lacking a suitable microbiological diagnostic service, clinical definitions of HAI were adopted. Questionnaires were completed by the nurses and data were analyzed and presented to the hospital personnel four days after the survey. A HAI control program was agreed and started soon after. RESULTS: The hospital has 44.000 admissions yearly with 482 beds and main hospital specialties, 410 patients were surveyed Overall HAI prevalence was 28%, more in surgery (47%) and less in pediatrics (21%). Blood stream infections were the most frequent, followed by surgical wound infections and Urinary Tract infections, several lower respiratory tract infections and few gastrointestinal one. HAI prevalence was associated with length of stay in hospital, intravenous cannulas, urinary catheters and emergency surgery. Patients with severe low nutrition status, anemia and complications of the main disease bringing them to hospital experienced higher HAI prevalence. DISCUSSION: This paper shows that HAI can be measured also in absence of microbiological service and that Hospital staff are ready to evaluate this problem. This high HAI prevalence was not expected by the staff and has been a starting point for an hospital HAI control plan.

Coronary heart disease risk assessment in HIV-infected patients: a comparison of Framingham, PROCAM and SCORE risk assessment functions.

OBJECTIVES: The aim of this was to compare the performance of the Framingham, Systematic Coronary Risk Evaluation (SCORE) and Prospective Cardiovascular Munster (PROCAM) scoring systems in the risk assessment of HIV-infected patients with no overt vascular disease. METHODS: A cross-sectional study of 220 HIV-infected patients was conducted at the outpatient clinic of a referral and training centre in infectious and parasitic diseases in Belo Horizonte, Brazil. The Framingham, SCORE and PROCAM equations were calculated. Patients were classified as having low, moderate or high risk, which according to the Framingham and PROCAM equations corresponded to < 10%, 10-20% and > 20% respectively, and according to SCORE corresponded to < 3%, 3-4% and > or = 5% respectively. Cohen's kappa coefficient was used to assess agreement between the methods. RESULTS: Of a total of 220 HIV-infected patients, 56 were antiretroviral (ARV)-naïve while 164 had already been treated with ARV. The prevalence of patients with a high 10-year cardiovascular risk was 3.7%, 2.5% and 1.9% according to the Framingham, PROCAM and SCORE equations respectively. The degree of agreement was moderate between the Framingham and PROCAM risk estimates (kappa = 0.433; p < 0.001), poor-to-fair between the Framingham and SCORE estimates (kappa = 0.220; p < 0.001) and moderate between the PROCAM and SCORE systems (kappa = 0.478; p < 0.001). CONCLUSIONS: There are differences in risk assessment and in the identification of high risk individuals between the three risk functions under evaluation and only a prospective study will be capable of assessing which offers the best current sensitivity, specificity and predictive values for the population under investigation.

Differences in national influenza vaccination policies across the European Union, Norway and Iceland 2008-2009.

In 2009 the second cross-sectional web-based survey was undertaken by the Vaccine European New Integrated Collaboration Effort (VENICE) project across 27 European Union (EU) member states (MS), Norway and Iceland (n=29) to determine changes in official national seasonal influenza vaccination policies since a survey undertaken in 2008 and to compare the estimates of vaccination coverage between countries using data obtained from both surveys. Of 27 responding countries, all recommended vaccination against seasonal influenza to the older adult population. Six countries recommended vaccination of children aged between six months and <18 years old. Most countries recommended influenza vaccination for those individuals with chronic medical conditions. Recommendations for vaccination of healthcare workers (HCW) in various settings existed in most, but not all countries. Staff in hospitals and long-term care facilities were recommended vaccination in 23 countries, and staff in out-patient clinics in 22 countries. In the 2009 survey, the reported national estimates on vaccine coverage varied by country and risk group, ranging from 1.1% - 82.6% for the older adult population; to between 32.9% -71.7% for clinical risk groups; and from 13.4% -89.4% for HCW. Many countries that recommend the influenza vaccination do not monitor the coverage in risk groups. In 2008 and 2009 most countries recommended influenza vaccination for the main risk groups. However, despite general consensus and recommendations for vaccination of high risk groups, many countries do not achieve high coverage in these groups. The reported vaccination coverage still needs to be improved in order to achieve EU and World Health Organization goals.

A new semiresorbable mesh for primary inguinal repair: a preliminary observational study on quality of life and safety.

BACKGROUND: A currently unsolved problem of open inguinal hernia repair (IHR) is chronic postoperative inguinal pain (CPIP), which affects 10-12% of patients after IHR. In the present paper, we explored the results of a newly designed partially absorbable mesh made of polypropylene and polylactic acid (HybridMesh®) for open hernia repair and its impact on postoperative safety, efficacy, comfort and pain. METHODS: A prospective multicentric pilot trial was conducted in third-referral centers across Italy (n = 5). Inclusion criteria were unilateral primary inguinal hernia in patients of both genders and BMI < 30 kg/m2. All patients were submitted to elective Lichtenstein mesh hernia repair under local anesthesia with HybridMesh. Primary outcome measure was the evaluation of Carolina Comfort Scale and modifications at 2 years after surgery and its correlation with surgical variables; secondary outcomes were postoperative early and late morbidity, recurrence and postoperative early quality of life. RESULTS: Between 2015 and 2016, 125 (5 female) patients were operated, 2-year follow-up rate was 100%. The surgical site occurrence rate was 28% without the need of procedural interventions. Twenty-four months after surgery, no case of severe CPIP was recorded and altered global CCS score was present in 16 patients (13.0%). At univariate analysis, CCS score was negatively affected by fixation with sutures (OR 3.949; 95% CI 1.334-13.300), with no effect shown on multivariate analysis. Alterations in pain and movement limitations domains of CCS were observed in 9.7% of patients, at univariate analysis; they occurred more frequently when the mesh was sutured (OR 4.437; 95% CI 1.387-17.025) and in patients suffering from SSO (ecchymosis: OR 3.269; 95% CI 1.032-10.405); however, no effect was shown on multivariate analysis. Two recurrences (1.6%) were identified within the first postoperative year. CONCLUSIONS: The results of this study support the safety, efficacy and good tolerability of HybridMesh as a device to treat primary unilateral inguinal hernia during open anterior approach. Further studies are needed to clarify its role in comparison to currently available devices at longer follow-ups.

Structural brain anomalies in Cri-du-Chat syndrome: MRI findings in 14 patients and possible genotype-phenotype correlations.

INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings. PATIENTS AND METHODS: Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution. RESULTS: MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients. CONCLUSIONS: Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.

Drug resistance mutation profile and accumulation kinetics in human immunodeficiency virus-positive individuals infected with subtypes B and F failing highly active antiretroviral therapy are influenced by different viral codon usage patterns.

The major human immunodeficiency virus type 1 subtype circulating in Brazil is B, followed by F and C. We have genotyped 882 samples from Brazilian patients for whom highly active antiretroviral therapy failed, and we found subtype B and the unique recombinant B/F1 forms circulating. Due to codon usage variation, there is a significantly lower incidence of the substitutions L210W, Q151M, and F116Y in subtype F1 isolates than in the subtype B counterparts.

Stapled hemorrhoidopexy: day surgery or one day surgery?

Hemorrhoidal disease is one of the most common anorectal disorders, from 10% to 20% of all patients admitted at a clinical investigation need to undergo surgery, stapled haemorrhoidopexy is gaining wide acceptance as an interesting, safe and less painful technique, but hemorrhage is one of the most serious early complications and is a severe complication in day surgery. In our day surgery proctology, surgical procedures represent about 32%. Of these, 24% are for hemorrhoidal disease, we present our protocol and experience for early and safe discharge, 6h after stapled hemorrhoidopexy surgery.