A genetic cluster of patients with variant xeroderma pigmentosum with two different founder mutations.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare human syndrome associated with hypersensitivity to sunlight and a high frequency of skin tumours at an early age. We identified a community in the state of Goias (central Brazil), a sunny and tropical region, with a high incidence of XP (17 patients among approximately 1000 inhabitants). OBJECTIVES: To identify gene mutations in the affected community and map the distribution of the affected alleles, correlating the mutations with clinical phenotypes. METHODS: Functional analyses of DNA repair capacity and cell-cycle responses after ultraviolet exposure were investigated in cells from local patients with XP, allowing the identification of the mutated gene, which was then sequenced to locate the mutations. A specific assay was designed for mapping the distribution of these mutations in the community. RESULTS: Skin primary fibroblasts showed normal DNA damage removal but abnormal DNA synthesis after ultraviolet irradiation and deficient expression of the Polη protein, which is encoded by POLH. We detected two different POLH mutations: one at the splice donor site of intron 6 (c.764 +1 G>A), and the other in exon 8 (c.907 C>T, p.Arg303X). The mutation at intron 6 is novel, whereas the mutation at exon 8 has been previously described in Europe. Thus, these mutations were likely brought to the community long ago, suggesting two founder effects for this rare disease. CONCLUSIONS: This work describes a genetic cluster involving POLH, and, particularly unexpected, with two independent founder mutations, including one that likely originated in Europe.

Influence of different anaesthetic protocols over the sperm quality on the fresh, chilled (4°C) and frozen-thawed epididymal sperm samples in domestic dogs.

This study assessed the influence of three different anaesthetic protocols on semen quality obtained from the epididymis. Sixty male dogs undergoing to routine sterilization were assigned to three anaesthetic protocols: thiopental group (TG, n = 20), propofol group (PG, n = 20) and ketamine-dexmedetomidine group (KDG, n = 20). Immediately after orchidectomy, the cauda epididymides and vas deferent ducts were isolated and then a retrograde flushing was performed to collect spermatozoa. In experiment 1, after the initial evaluation of the semen (sperm concentration, sperm motility and the percentages of live spermatozoa, abnormal spermatozoa and acrosome membrane integrity), semen samples were diluted in Tris-glucose-egg yolk extender and chilled for 48 hr, and the sperm motility was assessed at 6, 24 and 48 hr. In experiment 2, semen samples were diluted in Tris-glucose-egg yolk extender and chilled for 24 hr, and then samples were frozen in two extenders with different glycerol concentrations, to reach a final concentration of 50-100 × 10(6) spermatozoa ml(-1) , 20% egg yolk, 0.5% Equex and 4% and 5% glycerol, respectively. Mean values of total sperm concentration, sperm viability and the percentages of intact acrosome and abnormal spermatozoa were not significantly different between experimental groups, and therefore, the anaesthetic protocols assessed did not affect sperm parameters mentioned above. However, our study confirmed a detrimental effect of the use of thiopental (TG) over the total sperm motility (p < 0.05) and progressive sperm motility (p < 0.05) of the fresh and chilled epididymal sperm samples. The anaesthetic protocols including the application of propofol or ketamine-dexmedetomidine can be used to recover sperm in domestic canids without significant changes in sperm quality compared when semen is collected routinely and these techniques could be applicable to endangered wild canids.

HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence.

Prevalence and variables associated with solitary pulmonary nodules in a routine clinic-based population: a cross-sectional study.

OBJECTIVE: To determine the prevalence of solitary pulmonary nodules (SPNs) in chest radiology studies and patient's features associated with malignancy in a non-high-risk clinical population. METHODS: Patients ≥35 years were referred for thoracic imaging in two hospitals (2010-2011). Eight radiologists determined the presence and characteristics of SPN. Selected variables were collected from radiological register and medical records. Observer agreement in the diagnosis of SPN was assessed. RESULTS: 25,529 patients were included: 23,102 (90.5%) underwent chest radiograph and 2,497 (9.5%) a CT. The prevalence of SPN was 2.1% (95% CI 1.9 - 2.3) in radiographs and 17.0% (95% CI 15.5 - 18.5) in CT. In patients undergoing chest radiograph, detection of SPN with an irregular border was more frequent among smokers. In patients who had a CT, larger SPNs appeared to be associated with 60 years of age or over, diagnosis of a respiratory illness, or male gender. In addition, an irregular border was also more common among men. CONCLUSIONS: The prevalence of SPNs detected by both radiograph and CT was lower than that shown in screening studies. Patient characteristics such as age, sex, respiratory disease, or smoking habit were associated with nodule characteristics that are known to be related with malignancy. KEY POINTS: There is a lower SPN prevalence in the clinical population than in screening studies. SPN prevalence is associated with some patient characteristics: sex, age, imaging test. Nodule characteristics related to malignancy were associated with some patient characteristics.

[Decorative elements in the medical imaging area improve patients' perception of pleasantness]. / Los elementos decorativos ambientales en el Área de Imagen Médica mejoran la percepción de agradabilidad del paciente.

OBJECTIVES: To evaluate the sensation of pleasantness perceived by patients attended in the radiology department in response to decorative elements hung on the walls in the waiting rooms and in the hallways of the imaging area. MATERIAL AND METHODS: The material resources comprised works of art in the form of "magic windows" representing scenes from nature installed on the ceilings and walls of the waiting area and hallways of the imaging area. Patients were given a brief questionnaire with general data and questions (sadness-cheerfulness, coldness-warmth, darkness-light, and pessimism-optimism) about their perception of the decorative elements. RESULTS: Of the 150 questionnaires collected, 142 were filled out correctly. The overall health of these patients was good in 84 (56%), not bad in 58 (39%), and poor in 8 (5%). The idea seemed very good to 70 patients (47%), good to 58 (39%), not bad to 8 (5%), indifferent to 11 (7%), bad to 1 (1%), and very bad to 2 (1%). As far a patients' mobility, 119 patients (79%) walked into the department, 18 (12%) were wheeled in on beds, and 13 (9%) needed wheelchairs. CONCLUSIONS: We found a high level of satisfaction with the decorative elements.

Cross-sectional area of the tendons of the tarsal region in Standardbred trotter horses.

REASONS FOR PERFORMING STUDY: The assessment of a normal range for cross-sectional area (CSA) of tendons in the tarsal region is important in order to use them as reference values in the identification of pathological changes of dimensions. OBJECTIVES: To provide normal reference values for the CSA of the tendons of the tarsus of Standardbred trotter horses (STH) by means of ultrasonography. METHODS: Transverse echographic images of the tendons were obtained at different levels proximodistally; these images were digitised and CSA values (mean ± s.d.) were obtained for each structure. RESULTS: The largest structure corresponded with the lateral digital flexor/caudal tibial tendon complex at Level 1 and the smallest was the medial digital flexor tendon at Level 4. Almost all tendons showed a slight decreasing in their CSA when crossing the tarsus. CONCLUSIONS: The normal CSA values of tendinous structures in the tarsal region of the STH are reported. These data could be used as anatomical references. POTENTIAL RELEVANCE: The establishment of reference values could serve as a tool to discriminate between normal and abnormal dimensions of tarsal tendons in STH. Other horse breeds should need their own reference values.

Induction of parturition with aglepristone in the Majorera goat.

This study assessed the efficacy of aglepristone at inducing parturition in pregnant goats. Six experimental groups were defined: group A-5 (n = 12), group A-3.3 (n = 12), group A-2.5 (n = 12) and group A-1.5 (n = 12) in which goats were injected SC once with 5.0, 3.3, 2.5 and 1.5 mg of aglepristone per kg body weight of goat, respectively, group L (n = 11), which was treated IM with 3.75 mg of luprostiol; and group Ct (n = 11), which was injected SC with 1 ml of saline solution. Different parameters associated with parturition were thereafter investigated. In addition, plasma progesterone concentrations were defined after treatments till parturition. Aglepristone effectively induced parturition in all of the goats. In the A-5, A-3.3 and A-2.5 groups, the time to parturition was around 30-34 h, and the majority of goats (97.2%, 35/36) started kidding between 25 and 40 h after the aglepristone injection. However, the goats in group A-1.5 showed a significantly (p < 0.01) higher time to parturition (mean: 46.8 h). Overall, the incidence of dystocia registered in aglepristone-induced goats (20.8%, 10/48) and luprostiol-induced goats was not different from that observed after a spontaneous parturition. The percentage of live kids was very similar between A-5, A-3.3, A.2.5 and L groups (95.7, 95.3, 95.0 and 96.3%, respectively) but was higher that observed in the control (83.4%) and A-1.5 (81.2%) groups. In addition, no maternal mortality was registered in any groups. No changes in plasma progesterone were observed during the first 24 h after treatment, and high plasma progesterone concentrations were present at kidding (6.7, 5.5, 4.5 and 3.6 ng/ml for groups A-5, A-3.3, A-2.5 and A-1.5, respectively), confirming that aglepristone does not induce parturition via luteolysis. This study demonstrates that aglepristone can be used to induce parturition in goats with satisfactory efficacy, inducing pregnancy termination without direct or immediate modifications of luteal function.

Systematic review of the ingestion of fructooligosaccharides on the absorption of minerals and trace elements versus control groups.

BACKGROUND & AIMS: Fructooligosaccharides (FOS) are non-caloric and unconventional sugars that are not metabolized by the human body, but can be fermented by the colonic microbiota, leading to some beneficial effects on the absorption of minerals and trace elements. There is, however, a lack of research that describes the continued consumption of FOS in the diet between healthy and ill individuals and their impact. The objective of this systematic review was to evaluate the evidence behind the role of FOS in the absorption of minerals and trace elements in the human body. METHODS: The bibliographic research covered the period from January 2000 to August 2020. Four databases were investigated. We follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA). The systematic review protocol was recorded in PROSPERO (139621). Two reviewers examined and extracted data from qualitative and quantitative studies published in the main databases, through a careful analysis. The risk of bias was assessed by four reviewers. RESULTS: Of a total of 1494 texts, 30 complete articles composed this review. Two overarching categories represented the results: animal models and human models (randomized crossover design). Regarding human models, the results showed an improvement in minerals, especially the absorption of calcium, magnesium and iron after the ingestion of FOS, and specifically the absorption of minerals and trace elements in postmenopausal women was improved. CONCLUSIONS: The use of FOS to improve the absorption of minerals and trace elements seems to be beneficial with evidence corroborating both in human and animal studies. However, the literature lacks articles exploring the daily dose and duration for FOS benefits, as well as long-term side effects in healthy or unhealthy subjects. Future research should focus on addressing the extent of the functional effect of this fiber and identifying the impact on overall health.

Early syphilis mimicking tuberculous meningoencephalitis in an HIV-positive patient.

A man previously treated for tuberculous arthritis presented with acute meningoencephalitis. Cerebrospinal fluid tests suggested infection with Mycobacterium tuberculosis, but a diagnosis of early neurosyphilis was subsequently made.

Retrospective review of Pneumocystis jirovecii pneumonia over two decades.

The aim of the study was to compare a retrospective case note review of all cases of Pneumocystis carinii (now Pneumocystis jirovecii) pneumonia (PJP) over the period 1997-2004 at North Manchester General Hospital with a previous audit covering the years 1986-1995. During 1986-1995, 777 patients were diagnosed with HIV. One hundred and eighty-one were also diagnosed with PJP. Of these, 11 patients required ventilation with a mortality rate of 100%. For the current review during 1997-2004, 210 patients were diagnosed with PJP, and 64 with severe PJP. Median age was 39 years (interquartile range [IQR] 22-61). Twenty-four patients had a prior diagnosis of HIV (median 43 months, IQR 6-72 months), and for 38 patients this was the presenting diagnosis of HIV. Median CD4 was 34 cells/L (IQR of 12-80 cells/L). Median viral load was 3.5 x 10(5) copies/mL (IQR 1-5.8 x 10(5) copies/mL). Eighteen patients required intubation during this period. Nine (50%) were alive at 30 days postextubation. We believe that the 50% reduction in mortality seen between 1997-2004 in intubated patients with severe PJP is due to the improvement in intensive care management of severe respiratory failure rather than changes in the specific management of PJP. The necessity of ventilation in HIV patients is no longer a mandatory death sentence.

Antimutagenicity protection of Ginkgo biloba extract (Egb 761) against mitomycin C and cyclophosphamide in mouse bone marrow.

Ginkgo biloba (Egb 761) extract, the most prescribed phytomedicine in Europe for the treatment of cerebral insufficiency and vascular diseases, was tested for its possible protective effects against mitomycin C (MMC)- and cyclophosphamide (CP)-induced mutagenicity using the micronucleus test in mouse bone marrow. The extract was co-administered to mice at doses of 50, 100 and 200 mg/kg (po) with 4 mg/kg (ip) MMC or 24 mg/kg (ip) CP. All doses of Egb 761 were significantly (P < 0.05) effective in reducing the frequency of micronucleated polychromatic erythrocytes, when compared with MMC or CP alone. Based on these results, we suggest that Egb 761 possesses both direct and indirect antimutagenic potential.

Impact of rotavirus vaccination on childhood hospitalizations for seizures: Heterologous or unforeseen direct vaccine effects?

There is a growing interest in the possible relationship between rotavirus (RV) vaccine and hospitalizations due to childhood seizures. We explored variation in hospitalization rates after 9 years of vaccination against pre-vaccination period for children <5 years of age from Galicia (Northwest Spain) before and after the introduction of the RV vaccines. Hospitalization rates for childhood seizures in Galician children were compared before and after RV vaccine introduction (in 2007) using different statistical approaches, including time series analyses. Our study cohort totaled 7,712 children <5 years of age admitted to hospital between 2002 and 2015 for "all kind of childhood seizures". Hospitalization rates decreases steadily with reductions ranging from 22.3% (95% CI: 15.0-29.1) in 2008, to 50.9% (95% CI: 45.5-55.7) in 2014, and significant results were also observed for <1, 1, and 2-year-old children in comparison with pre-vaccination period hospitalization rate. Regression models indicate a negative association between RV vaccination and hospitalizations for all kind of seizures. In addition, time series analyses are consistent with this finding and predict that vaccination coverage will affect hospitalization rates for "all kind of seizures" after 9 months. The results strongly support that RV vaccination has significantly reduced hospitalization rates due to childhood seizures.

Biomechanics in young and adult italian standardbred trotter horses in real racing conditions.

This study was undertaken to characterize and establish the kinematic standards of Italian standardbred trotter horses in real racing conditions. Certain parameters, such as the angles of both front and hind fetlock joints, stride length, stride frequency and average speed in youngs and adults are presented, examinated and compared with statistical tests. The angles and stride length were obtained using ONTRACK software over frames extracted from two CANON MV630i digital videocameras. For the stride frequency, a third identical videocamera filmed the horses to count the number of beats per minute. The average speed was calculated by multiplying the stride frequency by the stride length and transforming the result into kilometers per hour. The data reveal that as speed increases, younger horses have more extended fetlock joints than adults. Contrary to this, at the maximum speed (hereafter referred to as sprint speed) the adults increase both their stride frequency and stride length, while young horses increase stride frequency and decrease stride length. We think that the knowledge of these parameters in competition breeds could have potential relevance as they may reveal early indicators of the development of proper and adequate characteristics in young horses of those breeds.

Assessment of the mutagenic, antimutagenic and cytotoxic activities of ethanolic extract of araticum (Annona crassiflora Mart. 1841) by micronucleus test in mice.

A typical Brazilian plant, araticum (Annona crassiflora Mart.), is widely used in humans as therapeutic medicine to treat several diseases such as diarrhea, rheumatism and syphilis. It contains acetogenins which present cytotoxic, antitumogenic, and antiparasitic properties. In this study, mutagenic, antimutagenic and cytotoxic effects of araticum leaves ethanolic extract were evaluated by micronucleus test in mice. To evaluate the mutagenic activity, animals were treated with ethanolic extract of araticum (EEA) using 10, 20, 50, 100 and 160 mg.kg(-1). For all doses, micronucleated polychromatic erythrocytes (MNPCE) frequency was evaluated at 24, 48 and 72 hours after treatment. To evaluate the antimutagenic activity, animals were treated with 10, 20, 50 and 100 mg.kg(-1) of EEA and 4 mg.kg(-1) of MMC simultaneously. The frequency of MNPCE was evaluated 36 hours after exposure. Cytotoxicity was evaluated by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). In the mutagenicity assessment, all doses of EEA resulted in no significant increase of MNPCE (P > 0.05), compared to solvent- control group. Regarding administration time, no significant difference among three evaluation periods was observed (P > 0.05). Such results indicate that EEA did not exert mutagenic activity. Cytotoxicity was evident in doses of 50, 100 and 160 mg.kg(-1) at 24 and 48 hours after exposure. Concerning antimutagenicity, except the 10 mg.kg(-1) co-administered with 4 mg/kg of MMC, all doses reduced significantly the frequency of MNPCE compared to the positive control group (P < 0.05). These results, therefore, indicate an antimutagenic activity of the EEA. Cytotoxicity was significantly increased (P < 0.01) at 100 mg.kg(-1) EEA doses co-administered with 4 mg.kg(-1) of MMC.

miRNApath: a database of miRNAs, target genes and metabolic pathways.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression and hence play important roles in metabolic pathways. Recent studies have evidenced the interrelation of miRNAs with cell proliferation, differentiation, development, and diseases. Since they are involved in gene regulation, they are intrinsically related to metabolic pathways. This leads to questions that are particularly interesting for investigating medical and laboratorial applications. We developed an miRNApath online database that uses miRNA target genes to link miRNAs to metabolic pathways. Currently, databases about miRNA target genes (DIANA miRGen), genomic maps (miRNAMap) and sequences (miRBase) do not provide such correlations. Additionally, miRNApath offers five search services and a download area. For each search, there is a specific type of input, which can be a list of target genes, miRNAs, or metabolic pathways, which results in different views, depending upon the input data, concerning relationships between the target genes, miRNAs and metabolic pathways. There are also internal links that lead to a deeper analysis and cross-links to other databases with more detailed information. miRNApath is being continually updated and is available at http://lgmb.fmrp.usp.br/mirnapath.

Evaluation of clinicians' knowledge and practices regarding medical radiological exposure: findings from a mixed-methods investigation (survey and qualitative study).

OBJECTIVES: To assess the impact of initiatives aiming to increase clinician awareness of radiation exposure; to explore the challenges they face when communicating with patients; to study what they think is the most appropriate way of communicating the long-term potential risks of medical radiological exposure to patients. DESIGN: A quantitative and qualitative evaluation through a survey and focal groups. SETTING: San Juan Hospital and Dr Peset Hospital (Southeast Spain) and clinicians from Spanish scientific societies. PARTICIPANTS: The surveys were answered (a) in person (216: all the radiologists (30), urologists (14) and surgeons (44) working at both participant hospitals; a sample of general practitioners from the catchment area of one hospital (45), and a consecutive sample of radiologists attending a scientific meeting (60)) or (b) electronically through Spanish scientific societies (299: radiologists (45), pneumologists (123), haematologists (75) and surgeons (40)). Clinicians were not randomly selected and thus the results are limited by the diligence of the individuals filling out the survey. PRIMARY AND SECONDARY OUTCOME MEASURES: Clinicians' knowledge and practices regarding medical radiological exposure, and what they considered most appropriate for communicating information to patients. RESULTS: Nearly 80% of the clinicians surveyed had never heard of the European recommendations. Fewer than 20% of the clinicians surveyed identified correctly the radiation equivalence dose of intravenous urography or barium enema. It was reported by 31.7% that they inform patients about the long-term potential risks of ionising radiation. All participants agreed that the most appropriate way to present information is a table with a list of imaging tests and their corresponding radiation equivalence dose in terms of chest X-rays and background radiation exposure. CONCLUSIONS: Medical radiological exposure is frequently underestimated and rarely explained to patients. With a clear understanding of medical radiological exposure and proper communication tools, clinicians will be able to accurately inform patients.

Adverse effects of hyperglycemia on kidney development in rats: in vivo and in vitro studies.

Congenital malformations occur more frequently in the offspring of diabetic mothers. These in vivo and in vitro studies investigate the potential adverse effects of hyperglycemia on kidney development in the rat. Female rats were made hyperglycemic throughout gestation with a single injection of streptozotocin (STZ) on day 0 of gestation, or for a short period encompassing the early stage of renal organogenesis by infusing glucose from gestational days 12-16. Kidney development in the pups was assessed by determining the total number of nephrons formed in the kidney. The number of nephrons was significantly reduced (10-35%) in the pups from STZ-treated dams, as a function of hyperglycemia. There were also fewer nephrons in pups from dams given glucose infusion whose hyperglycemia was transiently higher on day 13 of gestation. The in vitro experiments were done on metanephroi removed from 14-day-old fetuses and grown for 6 days in medium containing 0, 6.9, 13.8, or 27.5 mmol/l glucose. The development of explants grown in 0, 13.8, and 27.5 mmol/l glucose was impaired compared with that of explants grown in the 6.9 mmol/l control medium, showing that the glucose concentration must be closely controlled to ensure optimum in vitro metanephros development. Thus, exposure to hyperglycemia in utero can cause a nephron deficit, which in turn may have renal consequences later in life.