Spanish Academy of Dermatology and Venereology (AEDV) expert recommendations for the management of sexual transmitted parasitosis. Scabies, and pediculosis pubis. / Recomendaciones de expertos de la Academia Española de Dermatología (AEDV) para el manejo de las ectoparasitosis de transmisión sexual. Escabiosis y pediculosis púbica.

Sexually transmitted infections are communicable diseases where the pathogen is transmitted through sexual contact. The Sexually Transmitted Infections Working Group of the Spanish Academy of Dermatology and Venereology (AEDV) is engaged in the drafting of documents to guide dermatologists and health care personnel who treat Spanish patients with these infections. This document analyzes the epidemiological, clinical, therapeutic, and control characteristics of 2 sexually transmitted parasitosis: scabies due to Sarcoptes scabiei var. hominis, and pubic pediculosis due to Phthirus pubis. Both parasitoses share a sort of mixed spread through sexual and community transmission regardless of the route through which the infection was initially acquired. This specific feature creates particularities in the management and control of the infestation.

SARS-CoV-2 systemic infection in a kidney transplant recipient: sequence analysis in clinical specimens.

OBJECTIVE: Herein we report clinical and virological data in a patient with COVID-19 infection and a prior history of kidney transplantation who had a good clinical recovery despite systemic infection. PATIENTS AND METHODS: Reverse transcriptase quantitative PCR analysis for the RdRp, N and E target genes detected viral RNA in different types of biological specimens. Whole viral genome sequences were obtained and analyzed from respiratory tract, feces and blood. RESULTS: Viral sequences showed high (~99.9%) homology with the Wuhan seafood market pneumonia virus. Phylogenetic analysis assigned of the SARS-CoV-2 strains to clade G. A rare variant in the orf1ab gene was present in both sequences, while a missense variant was detected only in viral RNA from stool. CONCLUSIONS: The evolution of the COVID-19 systemic infection in the patient presented here was favorable to the hypothesis that immunosuppressive therapy in organ transplant recipients might be involved in viral dissemination. A missense mutation was present in only one specimen from the same patient implying the occurrence of a mutational event in viral RNA, which is suggestive for the presence of an active virus, even though viral isolation is necessary to demonstrate infectivity.

[Utility of Pediatric Appendicitis Score and abdominal ultrasound in the diagnostic process of acute appendicitis]. / Utilidad del Pediatric Appendicitis Score y la ecografía abdominal en el proceso diagnóstico de apendicitis aguda.

INTRODUCTION: Pain in the right iliac fossa is a frequent reason for consultation and the diagnosis of appendicitis remains a challenge. The Pediatric Appendicitis Score (PAS) stratifies the risk of suffering appendicitis, and abdominal ultrasound provides information without irradiation. This study aims to correlate the score and the ultrasound with the screening of appendicitis and evaluate its efficiency. PATIENTS AND METHODS: Prospective study of cases and controls, analytical, observational and longitudinal. Patients <15 years of age, treated for suspected appendicitis in the emergency department of a II level center, were evaluated for 6 months. The data were analyzed univariate and bivariate, using nonparametric and parametric tests according to the distribution. RESULTS: 68 patients with pain in the right iliac fossa were included: 26 appendicitis (cases) (38.2%) and 42 (61.7%) other diagnoses (controls). The PAS in appendicitis was 7.5±1.8 and in other diagnoses 5.4±1.8 (p <0.01). At 70.5% with PAS ≥4 an ultrasound was performed (diagnosis of appendicitis 58.1%, discarded 25.6% and inconclusive 16.3%). Sensitivity and specificity were calculated by PAS groups only, and including ultrasound. The best result was for PAS ≥4 with ultrasound with a sensitivity of 96.2%, specificity 94.1%, PPV 96.1% and NPV 94.1%. CONCLUSIONS: PAS is a good screening tool for the diagnosis of appendicitis. Ultrasound presents a high efficiency for the diagnosis of appendicitis. This efficiency improves when performed in the group of patients with PAS ≥4.

INTRODUCCION: El dolor en fosa ilíaca derecha es un motivo frecuente de consulta y el diagnóstico de apendicitis sigue siendo un reto. El Pediatric Appendicitis Score (PAS) estratifica el riesgo de padecer apendicitis, y la ecografía abdominal aporta información sin irradiación. Este estudio pretende correlacionar su puntuación y la ecografía con el despistaje de apendicitis y valorar su rendimiento. MATERIAL Y METODOS: Estudio prospectivo de casos y controles, analítico, observacional y longitudinal. Se evaluó a los pacientes <15 años, atendidos por sospecha de apendicitis en urgencias de un centro de II nivel, durante 6 meses. Se analizaron los datos de forma univariante y bivariante, utilizando pruebas no paramétricas y paramétricas según la distribución. RESULTADOS: Se incluyeron 68 pacientes con dolor en fosa ilíaca derecha: 26 apendicitis (casos) (38,2%) y 42 (61,7%) otros diagnósticos (controles). El PAS en apendicitis fue de 7,5±1,8 y en otros diagnósticos de 5,4±1,8 (p <0,01). Al 70,5% con PAS ≥4 se les realizó una ecografía (diagnósticas de apendicitis 58,1%, descartaron 25,6% y no concluyentes 16,3%). Se calculó la sensibilidad y especificidad por grupos de PAS solamente, e incluyendo la ecografía. El mejor resultado fue para PAS ≥4 con realización de ecografía con una sensibilidad 96,2%, especificidad 94,1%, VPP 96,1% y VPN 94,1%. CONCLUSIONES: El PAS es una buena herramienta de cribado para el diagnóstico de apendicitis. La ecografía presenta un alto rendimiento para el diagnóstico de apendicitis. Este rendimiento mejora al realizarla en el grupo de pacientes con PAS ≥4.

Down-regulation of bcl-2 by p53 in breast cancer cells.

bcl-2 and p53 gene products have been both linked to programmed cell death pathways. We have analyzed several human breast cancer cell lines for the expression of bcl-2 and p53. We found an inverse correlation between the expression of the two proteins. The result suggested that mutant p53 could substitute for bcl-2 function in breast cancer cells and that could also down-regulate bcl-2 expression. We found, indeed, that overexpression of a mutant p53 (mut 175) in MCF-7 cells could induce down-regulation of bcl-2 both at protein and mRNA level. However, the promoter region of the human bcl-2 gene does not contain the negative regulatory element responsible for the down-regulation. If this mechanism will be proved also for the wild-type p53 allele, it may disclose a possible mechanism for p53-induced apoptosis: down-regulation of bcl-2.

Molecular characterization of prostate-specific antigen messenger RNA expressed in breast tumors.

Prostate-specific antigen (PSA) is considered a highly specific biochemical marker of the prostate gland and is currently used for prostate cancer diagnosis and monitoring of patients with prostate adenocarcinoma. We recently demonstrated, however, that about 30% of female breast tumors produce a M(r) 33,000 protein that has striking similarities to seminal PSA. In this study we characterized the presence of PSA in 6 breast tumors and in the testosterone-stimulated T47D breast cancer cell line at the mRNA level. Using reverse transcriptase-polymerase chain reaction and DNA sequencing techniques we identified PSA mRNA in immunoreactive PSA-positive breast tumors but not in immunoreactive PSA-negative breast tumors. The sequence of the generated polymerase chain reaction products was identical to the sequence of the PSA complementary DNA derived from prostate tissue. The data presented here support the notion that breast tumors produce a M(r) 33,000 protein which is identical to PSA produced by the prostate gland. Our study suggests that the presence of PSA in breast tumors may be used as a new additional biochemical marker for breast cancer prognosis, for the spreading of hematogenous micrometastases, and/or for response to adjuvant treatment.

Expression of the prostate-specific antigen gene by a primary ovarian carcinoma.

We describe a patient with primary ovarian carcinoma that developed after liver transplantation whose tumor was highly positive for prostate-specific antigen (PSA). PSA in tumor tissue was characterized by two immunoassays, HPLC, immunohistochemistry, reverse transcription-PCR, Southern blotting, and DNA sequencing. PSA in the ovarian tumor was present as free, M(r) 33,000 protein (> 90%) and as PSA bound to alpha 1-antichymotrypsin (M(r) 100,000; < 10%). Immunohistochemistry localized PSA in the cytoplasm of epithelial cells of the tumor. Two separate reverse transcription-PCRs for PSA amplified the expected products which hybridized specifically to a PSA cDNA probe on Southern blots. Sequencing of the PCR products, representing the whole coding sequence of the PSA gene, revealed identity with the sequence of PSA cDNA from prostate tissue. These data suggest that the PSA produced by the ovarian tumor was identical in molecular weight and sequence to prostatic PSA. Based on data of tissue culture experiments with breast carcinoma cell lines, we speculate that the PSA gene in the tumor of this patient was up-regulated by the therapeutically administered glucocorticoids after liver transplantation.

Detection of hematogenous micrometastasis in patients with prostate cancer.

The goal of this study was to determine if patients with stage D0-3 prostatic adenocarcinoma have detectable hematogenous micrometastasis. Polymerase chain reaction amplification of prostate-specific antigen mRNA, which is exclusively expressed by prostatic epithelial cells, was used to detect circulating prostatic cells. Peripheral venous blood was obtained from 17 control and 12 prostate cancer patients with stage D0-3 prostatic adenocarcinoma. Of the 12 cancer cases, four patients (stage D1-3) tested positive for prostate-specific antigen RNA, indicating the presence of circulating micrometastasis. The 17 negative controls all tested negative. Contrary to a long held hypothesis, these data point to the possibility that hematogenous metastasis may be a relatively early event in the natural history of human prostate cancer. These findings may have an important impact on our understanding and treatment of prostate cancer.

Formation of helical hairpins during membrane protein integration into the endoplasmic reticulum membrane. Role of the N and C-terminal flanking regions.

The helical hairpin, two closely spaced transmembrane helices separated by a short turn, is a common structural element in integral membrane proteins. Previous studies on the sequence determinants of helical hairpin formation have focussed on the role of polar and charged residues placed centrally in a long stretch of hydrophobic residues, and have yielded a "propensity scale" for the relative efficiency with which different residues promote the formation of helical hairpins. In this study, we shift our attention to the role of charged residues flanking the hydrophobic stretch. Clusters of charged residues are known to hinder membrane translocation, and thus flanking charged residues may conceivably force a long hydrophobic segment to form a helical hairpin even if there are no or only weakly turn-promoting residues in the hydrophobic stretch. We indeed find that Lys and, more surprisingly, Asp residues strongly affect helical hairpin formation when placed next to a poly-Leu-based transmembrane segment. We also find that a cluster of four consecutive Lys residues can affect the efficiency of helical hairpin formation even when placed approximately 30 residues downstream of the hydrophobic stretch. These observations have interesting implications for the way we picture membrane protein topogenesis within the context of the endoplasmic reticulum (ER) translocon.

A turn propensity scale for transmembrane helices.

Using a model protein with a 40 residue hydrophobic transmembrane segment, we have measured the ability of all the 20 naturally occurring amino acids to form a tight turn when placed in the middle of the hydrophobic segment. Turn propensities in a transmembrane helix are found to be markedly different from those of globular proteins, and in most cases correlate closely with the hydrophobicity of the residue. The turn propensity scale may be used to improve current methods for membrane protein topology prediction.

Positively and negatively charged residues have different effects on the position in the membrane of a model transmembrane helix.

We have studied the effects of single charged residues on the position of a model transmembrane helix in the endoplasmic reticulum membrane using the glycosylation mapping technique. Asp and Glu residues cause a re-positioning of the C-terminal end of the transmembrane helix when placed in the one to two C-terminal turns but not when placed more centrally. Arg and Lys residues, in contrast, have little effect when placed in the two C-terminal turn but give rise to a more substantial shift in position when placed 9-11 residues from the helix end. We suggest that this difference between the effects of positively and negatively charged residues can be explained by the so-called snorkel effect, i.e. that the very long side-chains of Arg and Lys can reach up along the transmembrane helix to allow the terminal, charged moiety to reside in the lipid headgroup region while the Calpha of the residue is positioned well below the membrane/water interface.

Turns in transmembrane helices: determination of the minimal length of a "helical hairpin" and derivation of a fine-grained turn propensity scale.

We have recently reported a first experimental turn propensity scale for transmembrane helices. This scale was derived from measurements of how efficiently a given residue placed in the middle of a 40 residue poly(Leu) stretch induces the formation of a "helical hairpin" with two rather than one transmembrane segment. We have now extended these studies, and have determined the minimum length of a poly(Leu) stretch compatible with the formation of a helical hairpin. We have also derived a more fine-grained turn propensity scale by (i) introducing each of the 20 amino acid residues into the middle of the shortest poly(Leu) stretch compatible with helical hairpin formation, and (ii) introducing pairs of residues in the middle of the 40 residue poly(Leu) stretch. The new turn propensities are consistent with the amino acid frequencies found in short hairpin loops in membrane proteins of known 3D structure.

Effects of 'hydrophobic mismatch' on the location of transmembrane helices in the ER membrane.

We have studied the effects of 'hydrophobic mismatch' between a poly-Leu transmembrane helix (TMH) and the ER membrane using a glycosylation mapping approach. The simplest interpretation of our results is that the lumenal end of the TMH is located deeper in the membrane for both short (negative mismatch) and long (positive mismatch) TMHs than for poly-Leu segments of intermediate length. We further find that the position-specific effect of Lys residues on the location of short TMHs in the membrane varies with an apparent helical periodicity when the Lys residue is moved along the poly-Leu stretch. We discuss these findings in the context of models for peptide-lipid interactions during hydrophobic mismatch.

A comparative analysis of prostate-specific antigen gene sequence in benign and malignant prostate tissue.

OBJECTIVES: Different molecular forms of prostate-specific antigen (PSA) appear to be expressed by benign prostatic hyperplasia (BPH) compared with prostate cancer. These differences are not well understood and may arise from aberrant RNA splicing, altered protein glycosylation, or variant PSA complexing to macroglobulins. To our knowledge, a direct comparison of PSA mRNA sequences in BPH versus prostate cancer to account for these differences has not been reported. The purpose of this study was to compare the complete PSA mRNA gene sequences in benign and malignant prostate tissue to determine whether altered PSA phenotypes are a result of gene mutations and to compare the published PSA sequences. METHODS: Total RNA was extracted from 17 prostate specimens from 8 patients, including matched benign and malignant prostate tissue in 6 patients. The samples were subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) of the PSA coding sequence and part of the 3' untranslated region. Directed DNA sequencing was performed on these fragments. RESULTS: The benign and malignant prostate tissue cDNA sequence data of both strands were aligned and a computer analysis revealed 100% match with no evidence of mutation in prostate cancer compared to normal tissue. Sequence analysis did not reveal point mutations or aberrant splicing in any of the samples, including the matched malignant and nonmalignant tissues. Comparison with published sequences revealed infrequent and inconsistent sequence differences. CONCLUSIONS: These findings suggest that the PSA gene expressed in malignant prostate tissue is the wild type. PSA structural alterations previously reported in the literature may occur through post-transitional mechanisms. A detailed understanding of the possible differences in the PSA gene sequence is essential as we develop newer techniques that utilize RT-PCR to perform molecular diagnosis and staging of prostate cancer.

[Use of mortality probability models (MPM II) in the evaluation of the effectiveness of care of critically ill patients. European and North American Study of Severity Systems]. / Utilización de los modelos probabilísticos de mortalidad (MPM II) para evaluar la efectividad de la atención a pacientes en estado crítico. European and North American Study of Severity Systems.

BACKGROUND: The performance of the Mortality Probability Models (MPM II) has been assessed in Intensive Care Units (ICUs) in Catalonia and the Balearic Islands. The MPM II system has been customized to that geographic area and quality performance has been evaluated in each ICU. METHODS: 1,270 adult critical patients, consecutively admitted in 16 ICUs from Catalonia and 1 from the Balearic Islands have been included. Probability of dying in the hospital has been calculated at admission in the ICU and at 24 hours using the models MPM II0 and MPM II24. Goodness-of-fit of the MPM II system in the overall group of 17 ICUs has been analyzed. Logistic regression has been used to customize the MPM II system to all the ICUs together. A Quality Performance Index (QPI) for each ICU has been obtained by dividing the number of the observed deaths by the number of deaths expected by the MPM II system. RESULTS: The overall QPI was 1.15 when using the MPM II0 and 1.17 when using the MPM II24. The QPI in the 17 ICUs ranged from 0.58 to 2.05. Three ICUs showed excess of mortality and 2 ICUs had less deaths than expected. The process of customization of MPM II to the 17 ICUs as a group improved the estimation of expected mortality. CONCLUSIONS: The use of severity indexes allows to compare the outcome of patients in the ICU and provides an indicator of quality of care. The excess of mortality observed in some ICU should produce a watchful follow-up of outcome. Risk factors for excess of mortality should be studied.

[Mortality and hospital stay adjusted for severity as indicators of effectiveness and efficiency of the care provided to critically ill patients. European and North American Study of Severity Systems]. / Mortalidad y estancia hospitalaria ajustadas por gravedad como indicadores de efectividad y eficiencia de la atención a pacientes en estado crítico. European and North American Study of Severity Systems.

BACKGROUND: Hospital mortality and length of stay, both adjusted for severity of illness, have been used as indicators of effectiveness and efficiency of health care in critical patients. PATIENTS AND METHODS: 1,270 adult critical patients, consecutively admitted in 17 intensive care units (ICU) from Catalonia and the Balearic Islands, Spain, have been included. For each hospital, effectiveness has been assessed with a quality performance index (QOI) obtained by dividing the number of observed deaths by the number of deaths expected according to the MPM system (MPM II0). Efficiency has been assessed with a resource utilization index (RUI) obtained by dividing the number of observed weighted hospital days (WHD) by the number of expected WHD. WHD is a measure of resource use which weights ICU days more heavily than non-ICU days. Expected WHD have been obtained by a regression model including severity of illness and the presence/absence of surgery. RESULTS: Ten of the 17 hospitals life within one standard deviation of the mean on both clinical and economical indices. There are 3 hospitals with optimal values on both indices. There is no evidence of association between effectiveness and resource utilization. CONCLUSIONS: Clinical and economical performance of hospitals can be quantified with simple indicators which allow to compare centers. Hospitals can be effective and efficient at the same time.

[Mortality in Catalonia: description and comparison by age and sex]. / La mortalitat a Catalunya: descripció i comparació per edat i sexe.

OBJECTIVE: To assess the fit of the parametric mortality laws proposed by Heligman and Pollard to the mortality experience of Catalonia (Spain) with the goal of describing and comparing mortality by age and gender, in the time periods 1985-86 and 1990-91. DATA AND METHODS: The data were obtained from the official mortality Registry and population Census for the respective years. Observed conditional probabilities of dying by age and gender were adjusted using the parametric mortality laws formulated by Heligman and Pollard. These laws provide information about mortality characteristics in childhood, in youth and in adults. Goodness of fit of the models was assessed using chi-square, sign, and Steven's tests. Significant outliners were also determined and considered in the analysis. RESULTS: In Catalonia from 1985-86 to 1990-91 the probability of dying increased among people aged 16 to 40 years, this being higher in males as compared to females. For people older than 40 years of age the probability of dying in males did not change, but decreased for females. In this time period, the probability of dying slightly decreased during childhood. The life expectancy at birth for males decreased from 74.12 years in 1985-86 to 73.85 years in 1990-91. In contrast, the life expectancy at birth for females increased from 80.08 years in 1985-86 to 80.88 in 1990-91, thus widening mortality differences by gender. CONCLUSIONS: Heligman and Pollard laws of mortality are useful in describing mortality by age and gender, as well as in analyzing the evolution of mortality over time. The unfavorable evolution of mortality among young men living in Catalonia has contributed to reversing the trend of life expectancy at birth in the twentieth century.

[Determination of HbA2 by a microchromatographic method. Reliability and simplification of the use of prepared columns]. / Dosaggio della Hb A2 con metodo microcromatografico. Affidabilità e semplificazione d'uso di colonne preconfezionate.

A modified procedure for hemoglobin A2 determination by microchromatography was developed simplifying an easily commercially available column kit method. Blood samples were analyzed simultaneously by means of DE-52 microchromatography described by Huisman et al. (reference 12) to check the reliability of the new modified method. In the Pediatric Clinic of Cagliari University where the original Huisman method was used the values of HbA2 obtained were as follows: Normal subjects (35 cases) 2.470 +/- 0.351, beta-Thalassemia heterozygous subjects (38 cases) 5.142 +/- 0.342. The modified method gave respectively the following results: Normal subjects 2.578 +/- 0.303, beta-Thalassemia heterozygous subjects 5.465 +/- 0.400. No overlap was found between normal and beta-thalassemia trait samples. It is suggested that the simplified method is very reliable and very simple to organize even in laboratories with few facilities and when needs for only few tests per week exist.

[Episiotomy and puerperium at home]. / Episiotomía y puerperio domiciliario.

This article reports on an observational and prospective study by means of a telephone questionnaire carried out between three and six months after childbirth via vaginal delivery among 100 women; its purpose was to discover the differences among episiotomies, large, small and with tears, and their effects during puerperium, in order to make professionals aware of the importance of pain and the consequences of a episiotomy. 82% of the women contacted by telephone responded to this questionnaire. 74.4% of these patients had undergone a right mediolateral episiotomy; 12.2% of these patients had undergone a left mediolateral episiotomy. The delay in starting to have sexual relations was significant among those women who underwent a large episiotomy (> 4 cm) p < 0.001. Another finding was that the duration of dyspareunia increased significantly in relation to the size of the episiotomy, p < 0.0059; as well as the difference in hemoglobin before or intra-birth and postbirth, p < 0.0153 in the skin and 0.026 in the vagina. The relationship among pain, analgesia and size was significant in the skin readings, p < 0.007.

The hepatitis B x antigen anti-apoptotic effector URG7 is localized to the endoplasmic reticulum membrane.

Hepatitis B x antigen up-regulates the liver expression of URG7 that contributes to sustain chronic virus infection and to increase the risk for hepatocellular carcinoma by its anti-apoptotic activity. We have investigated the subcellular localization of URG7 expressed in HepG2 cells and determined its membrane topology by glycosylation mapping in vitro. The results demonstrate that URG7 is N-glycosylated and located to the endoplasmic reticulum membrane with an Nlumen-Ccytosol orientation. The results imply that the anti-apoptotic effect of URG7 could arise from the C-terminal cytosolic tail binding a pro-apoptotic signaling factor and retaining it to the endoplasmic reticulum membrane.