Mapping regions in Ste5 that support Msn5-dependent and -independent nuclear export.

Careful control of the available pool of the MAPK scaffold Ste5 is important for mating-pathway activation and the prevention of inappropriate mating differentiation in haploid Saccharomyces cerevisiae. Ste5 shuttles constitutively through the nucleus, where it is degraded by a ubiquitin-dependent mechanism triggered by G1 CDK phosphorylation. Here we narrow-down regions of Ste5 that mediate nuclear export. Four regions in Ste5 relocalize SV40-TAgNLS-GFP-GFP from nucleus to cytoplasm. One region is N-terminal, dependent on exportin Msn5/Ste21/Kap142, and interacts with Msn5 in 2 hybrid assays independently of mating pheromone, Fus3, Kss1, Ptc1, the NLS/PM, and RING-H2. A second region overlaps the PH domain and Ste11 binding site and 2 others are on the vWA domain and include residues essential for MAPK activation. We find no evidence for dependence on Crm1/Xpo1, despite numerous potential nuclear export sequences (NESs) detected by LocNES and NetNES1.1 predictors. Thus, Msn5 (homolog of human Exportin-5) and one or more exportins or adaptor molecules besides Crm1/Xpo1 may regulate Ste5 through multiple recognition sites.

Mucocutaneous manifestations of helminth infections: Nematodes.

In the 21st century, despite increased globalization through international travel for business, medical volunteerism, pleasure, and immigration/refugees into the United States, there is little published in the dermatology literature regarding the cutaneous manifestations of helminth infections. Approximately 17% of travelers seek medical care because of cutaneous disorders, many related to infectious etiologies. This review will focus on the cutaneous manifestations of helminth infections and is divided into 2 parts: part I focuses on nematode infections, and part II focuses on trematode and cestode infections. This review highlights the clinical manifestations, transmission, diagnosis, and treatment of helminth infections. Nematodes are roundworms that cause diseases with cutaneous manifestations, such as cutaneous larval migrans, onchocerciasis, filariasis, gnathostomiasis, loiasis, dracunculiasis, strongyloidiasis, ascariasis, streptocerciasis, dirofilariasis, and trichinosis. Tremadotes, also known as flukes, cause schistosomiasis, paragonimiasis, and fascioliasis. Cestodes (tapeworms) are flat, hermaphroditic parasites that cause diseases such as sparganosis, cysticercosis, and echinococcus.

Possible association of lower rate of postherpetic neuralgia in patients on anti-tumor necrosis factor-α.

Recently, a study of patients with rheumatoid arthritis who developed herpes zoster while taking a tumor necrosis factor (TNF)-α inhibitor reported a decreased incidence of postherpetic neuralgia. The objective of this study was to investigate whether patients on TNF-α inhibitors who developed herpes zoster have a lower incidence of subsequent development of postherpetic neuralgia. A retrospective review of herpes zoster patients on TNF-α inhibitors (infliximab, etanercept, or adalimumab) was conducted in 12 dermatology clinics. Medical records of such patients were reviewed thoroughly to confirm herpes zoster and TNF-α inhibitors and any subsequent development of postherpetic neuralgia (pain score ≥ 3 out of 10 after 90 days of shingles onset) was noted. A total of 206 cases were reviewed, of which only 2 cases (<1%) developed postherpetic neuralgia, a considerably lower incidence rate than noted in the literature. Increasing age is a known risk factor in the development of postherpetic neuralgia. However, of the 58 (28.1%) cases ≥ 70 years of age, only 1 patient (1.7%) developed neuralgia compared to approximately 50% of patients who develop postherpetic neuralgia in this age group as reported in the literature. Treatment with TNF-α inhibitors may be associated with a lower incidence of postherpetic neuralgia but further prospective large-scale studies are needed to confirm this data.

HPV vaccine update: new indications and controversies.

Human papillomavirus (HPV) has a predilection for infecting epidermal and mucosal surfaces such as those of the anogenital region. HPV causes substantial pre-malignant, malignant, and benign disease in both women and men, ranging from cervical, vulvar, penile, and anal cancers to condyloma acuminata (genital warts). Although HPV vaccination is becoming more common, infection rates remain high in both genders. Perception of HPV vaccine has largely centered on its ability to prevent cervical cancer in women, though indication for its use in men is expanding. The benefits to men include prevention of genital warts and, more recently, regulatory approval was expanded in the US for prevention of anal cancer. Herein, we review HPV vaccine with a focus on its new indication in men and existing controversies.

Emerging drugs for complicated skin and skin-structure infections.

UNLABELLED: IMPORTANCE OF THE FILED: With the worldwide surge of MRSA, skin and skin-structure infection (SSTI) treatment has become a challenge for physicians. Cultures and antibiotic susceptibility tests for SSTIs are the rule due to the implication in morbidity and mortality rates associated with MRSA infections. The need for new antibiotics is evident and the effort to decrease antibiotic resistance is a world priority. AREAS COVERED IN THIS REVIEW: This manuscript accesses the actual treatments and the developing of antibiotics for MRSA SSTIs. WHAT THE READER WILL GAIN: This is a review of the data on the available and emerging treatments for MRSA SSTIs. TAKE HOME MESSAGE: There is an unmet medical need for new antibiotics in the new millennium. As physicians, we must assure all appropriate procedures are completed in order to reduce the bacterial resistance, especially for MRSA.

Human papillomavirus vaccines.

Cervical and other cancers linked to the human papillomavirus (HPV) are a cause of significant morbidity and mortality. Since the discovery of HPV as a cause of these cancers, there has been much research and development in the field of HPV vaccination. Two current prophylactic vaccines have proved highly effective in preventing disease because of the vaccine types. Recent advances in prophylactic and therapeutic vaccines are discussed.

Existing antiviral vaccines.

The innovation of vaccines has allowed for one of the greatest advancements in the history of public health. The first of the vaccines have been the antiviral vaccines, in particular the smallpox vaccine that was first developed by Edward Jenner in 1796. This article will review vaccination for the following viral diseases: measles, mumps, rubella, polio, hepatitis A, hepatitis B, influenza, rotavirus, rabies, monkeypox, smallpox, Japanese encephalitis, and yellow fever.

HIV vaccines under study.

Human immunodeficiency virus (HIV) infection is a worldwide epidemic, with over 42 million people currently infected. Since the discovery of HIV as the causative agent of the acquired immune deficiency syndrome (AIDS), many potential vaccines have been created. The first of these vaccines presented disappointing results; however, that has not deterred researchers from continuing to develop more potential HIV vaccines. This article will review the various current HIV vaccine candidates under study.

Filariasis: diagnosis and treatment.

Filariasis is an infectious disease of the lymphatics and subcutaneous tissues caused by nematodes or filariae. Carried by mosquito vectors, this disease causes millions of people to suffer from lymphedema and elephantiasis, characteristics of filariasis infection. This disease can be diagnosed through the identification of microfilariae in blood or skin samples, antigen detection, radiographic imaging, or polymerase chain reaction. Mass drug administration by the World Health Organization has helped to diminish the incidence of filariasis. However, continued research on new drugs and vaccinations will be needed to control and reduce the microfilarial levels in the human population.

Existing antibacterial vaccines.

There are countless bacterial pathogens that cause disease in humans. Many of these bacterial infections not only cause significant morbidity and mortality in the human population but also cause a significant economic impact on society. Vaccines allow for reduction and potential eradication of such diseases. This article will review the currently approved antibacterial vaccines, which are vaccines for pertussis, tetanus, diphtheria, meningococcus, pneumococcus, Haemophilus influenza, cholera, typhoid, and anthrax.

Mucocutaneous manifestations of Epstein-Barr virus infection.

This review focuses on Epstein-Barr virus (EBV) infection, diagnosis, and current treatment, with emphasis on EBV-associated mucocutaneous manifestations in primary infections, acute EBV-associated syndromes, chronic infections, lymphoproliferative disorders, and lymphomas. In primary infection, EBV infects B cells and can cause mucocutaneous manifestations in infectious mononucleosis or acute EBV-associated syndromes such as Gianotti-Crosti syndrome and hemophagocytic syndrome. EBV then persists in the majority of humans generally without causing disease. In some cases, however, latent EBV infection may result in diseases such as hydroa vacciniforme, hypersensitivity to mosquito bites, and lymphoproliferative disorders such as plasmablastic lymphoma, oral hairy leukoplakia, and post-transplant lymphoproliferative disorders, particularly in immunocompromised patients. Latent EBV infection has also been implicated in a variety of malignant conditions such as Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and Kikuchi histocytic necrotizing lymphadenitis. Since the immune system is critical in preventing the progression of EBV disease, the immunologic status of the patient plays a crucial role in the subsequent development of pathologies.

Etanercept: an overview of its role in the treatment of psoriasis.

BACKGROUND: Psoriasis is a chronic and disabling disease affecting patients' quality of life. OBJECTIVES: Over the past decade, there has been significant growth in the knowledge of the proinflammatory pathways involved in psoriasis, including the role of increased levels of TNF. This knowledge has led to the increased use of biologic therapy, with such drugs as etanercept, a soluble TNF receptor fusion protein, aimed at inhibiting the actions of TNF. The goal of biologic generation is to provide selectively targeted therapy with fewer adverse events than traditional therapies. METHODS: Etanercept has been studied extensively and Phase III studies have been completed. CONCLUSION: Clinical data reviewed for etanercept-treated moderate to severe psoriasis have shown good efficacy, tolerability and a low adverse event profile.

Effects of gonadal steroid withdrawal on serum phosphate and FGF-23 levels in men.

INTRODUCTION: Fibroblast growth factor (FGF-23) is a novel phosphaturic factor. Current data suggest that serum phosphate, dietary phosphate and 1,25 dihydroxyvitamin D regulate circulating FGF-23 levels in vivo. We examined if hypogonadism-induced increases in serum phosphate are associated with increases in circulating FGF-23 in healthy men in the absence of dietary manipulation. MATERIALS AND METHODS: 25 healthy men were administered goserelin acetate (GnRH analog) 3.6 mg subcutaneously every 4 weeks for 12 weeks to induce acute testosterone and estrogen deficiency. Subjects consumed an ad libitum diet. Morning fasting blood and urine samples were collected to measure serum phosphate, serum intact FGF-23, PTH, and the maximum tubular reabsorption of phosphate (T(m)P/GFR) at baseline, weeks 4 and 12. The changes in serum FGF-23 and phosphate at weeks 4 and 12 were compared to baseline using paired t-tests. RESULTS: Goserelin therapy decreased mean serum testosterone levels from 543+/-160 ng/dL to 33+/-15 ng/dL at week 4 (p<0.001), and to 20+/-10 ng/dL at week 12 (p<0.001). Serum phosphate increased significantly from 3.4+/-0.6 mg/dL to 3.9+/-0.4 mg/dL at week 4 (p=0.002), and to 4.3+/-0.4 mg/dL at week 12 (p<0.001). T(m)P/GFR increased significantly from 3.2+/-0.6 mg/dL to 3.6+/-0.5 mg/dL at week 4 (p<0.004), and to 4.1+/-0.6 mg/dL at week 12 (p<0.001). FGF-23 levels, however, did not change during the 12-week study. CONCLUSIONS: Gonadal steroid deprivation increased serum phosphate levels in men but did not affect serum FGF-23 concentrations. The absence of any change in circulating FGF-23 suggests that supraphysiologic levels of serum phosphate may be required to stimulate circulating FGF-23 or that FGF-23 production is primarily sensitive to changes in dietary phosphate or 1,25 dihydroxyvitamin D within this physiologic serum phosphate range.

Histopathologic findings in uteri and ovaries collected from clinically healthy dogs at elective ovariohysterectomy: a cross-sectional study.

Opinions on ovariohysterectomy (OHE) of bitches vary depending on region and country. In this descriptive, prospective cross-sectional study, uterine tracts and ovaries exhibiting gross pathologic findings (n = 76) were collected post-surgery from a reference population of 3,600 bitches (2.11% incidence) that underwent elective OHE during September to November 2013 and evaluated by histopathology examination. Data were evaluated by using descriptive statistics and chi-squared tests. Bitches were of crossbred background with average age 5 years (range 0.6-8.0 years) and most were nulliparous (69.7%) with no anamnesis of reproductive diseases (81.6%). Frequencies of proestrus, estrus, and diestrus were 42.1%, 6.6%, and 19.7%, respectively. The presence of mammary gland masses (5.3%) significantly correlated with histopathologic findings in ovaries and age of the bitch (p ＜ 0.05). Predominant uterine histopathologies included cystic endometrial hyperplasia, periglandular fibrosis, lymphoplasmocytary endometritis, and adenomyosis (19.7%, 14.5%, 4.0%, and 2.6%, respectively). In ovaries, hyperplasia of rete ovarii, follicular cysts, oophoritis, adenoma of the rete ovarii, cysts of superficial structures, and granulosa cell tumors (10.5%, 10.5%, 7.9%, 4.0%, 2.6%, and 2.6%, respectively) were observed. The results reveal the presence of subclinical pathologies in healthy bitches, suggesting that OHE at an early age is beneficial for prevention of reproductive pathologies.

Dermatology residency program characteristics that correlate with graduates selecting an academic dermatology career.

OBJECTIVE: To examine the characteristics of 107 dermatology residency programs to determine which factors are correlated with producing academic dermatologists to help reverse the trend of a growing shortage of academic dermatologists. DESIGN: We collected data ranging from total publications to grant funding. Extensive Internet searches were completed to obtain most of the data. Individual programs were contacted as needed to obtain any missing data that were not found on the program's Web site. SETTING: Dermatology residency programs (departments and divisions) in the United States. MAIN OUTCOME MEASURES: Factors that correlated with producing full-time academic dermatologists. RESULTS: We tabulated and analyzed characteristics of 107 dermatology residency programs. Total full-time faculty members in 2004, total publications in 2004, and total publications from January 1, 2001, to December 31, 2004, were the 3 factors most strongly correlated with producing full-time faculty. National Institutes of Health and Dermatology Foundation grants and American Skin Association grant recipients were the 3 characteristics most strongly inversely correlated with producing full-time faculty. Those who entered academic dermatology tended to stay at the same program where they completed a dermatology residency, especially if this program was considered a "smaller" program. CONCLUSIONS: The programs' characteristics of total publications in 2004 and from 2001 to 2004 were 2 of the 3 factors most strongly positively correlated with dermatology residents entering academic dermatology. Encouraging residents to publish may be a window to motivate them toward a career in academic dermatology.

Effects of high volume saline enemas vs no enema during labour--The N-Ma Randomised Controlled Trial [ISRCTN43153145].

BACKGROUND: Enemas are used during labour in obstetric settings with the belief that they reduce puerperal and neonatal infections, shorten labour duration, and make delivery cleaner for attending personnel. However, a systematic review of the literature found insufficient evidence to support the use of enemas. The objective of this RCT was to address an identified knowledge gap by determining the effect of routine enemas used during the first stage of labour on puerperal and neonatal infection rates. DESIGN: RCT (randomised controlled trial; randomized clinical trial). OUTCOMES: Clinical diagnosis of maternal or neonatal infections, labour duration, delivery types, episiotomy rates, and prescription of antibiotics. SETTING: Tertiary care referral hospital at the Javeriana University (Bogotá, Colombia) that attended 3170 births during study period with a caesarean section rate of 26%. PARTICIPANTS: 443 women admitted for delivery to the obstetrics service (February 1997 to February 1998) and followed for a month after delivery. Inclusion criteria were women with: low risk pregnancy and expected to remain in Bogotá during follow up; gestational age > or = 36 weeks; no pelvic or systemic bacterial infection; intact membranes; cervix dilatation < or = 7 cm. INTERVENTION: 1 litre saline enema, versus no enema, allocated following a block random allocation sequence and using sealed opaque envelopes. RESULTS: Allocation provided balanced groups and 86% of the participants were followed up for one month. The overall infection rate for newborns was 21%, and 18% for women. We found no significant differences in puerperal or neonatal infection rates (Puerperal infection: 41/190 [22%] with enema v 26/182 [14%] without enema; RR 0.66 CI 95%: 0.43 to 1.03; neonatal infection 38/191 [20%] with enema v 40/179 [22%] without enema; RR 1.12, 95% CI 95% 0.76 to 1.66), and median labour time was similar between groups (515 min. with enema v 585 min. without enema; P = 0.24). Enemas didn't significantly change episiorraphy dehiscence rates (21/182 [12%] with enema v 32/190 [17%] without enema; P = 0.30). CONCLUSION: This RCT found no evidence to support routine use of enemas during labour. Although these results cannot rule out a small clinical effect, it seems unlikely that enemas will improve maternal and neonatal outcomes and provide an overall benefit.

Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial.

BACKGROUND: Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant. OBJECTIVE: The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)D(total). DESIGN: This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D ≤20 ng/mL (by immunoassay) and administered 50,000 IU ergocalciferol/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure. RESULTS: On-study 25(OH)D(total) was assessed by liquid chromatography-tandem mass spectrometry. In the treated group, 25(OH)D(total) rose from 18 ± 7 to 43 ± 12 ng/mL (P < 0.001) with no change in the placebo group. Despite this increase, at 12 wk, there were no between-group differences in either insulin response or insulin sensitivity; nor were there differences in any measured secondary endpoints. There was no evidence of effect modification by sex, race, glucose tolerance status, baseline 25(OH)D(total), or BMI. CONCLUSION: In healthy persons with low 25(OH)D(total), ergocalciferol administration for 12 wk normalizes 25(OH)D(total) but does not improve insulin secretion, insulin sensitivity, or other markers of metabolic health.

Incertidumbre frente a la enfermedad renal crónica / Uncertainty in chronic kidney disease

RESUMEN ElY objetivo de este estudio es reconocer las incertidumbres más comunes que presentan los pacientes con diagnóstico de enfermedad renal crónica. Se realizó revisión sistemática de la literatura científica de artículos publicados entre 2012 a 2018, en idioma español, portugués e inglés, y accesibles a texto completo. Búsqueda exhaustiva y reproducible de trabajos originales en las bases de datos Scielo, PubMed, Ebschost, Dialnet, Redalyc, con los descriptores (DeCS) "Renal Insufficiency Chronic", "Theory of uncertainty", "Renal Dialysis" y sus equivalentes en español, inglés y portugués, con valoración crítica de la calidad científica de los estudios aplicando lista de chequeo PRISMA (2009). Las incertidumbres fueron analizadas desde la teoría de enfermería de MIshel Merle. Los hallazgos muestran que las más comunes están relacionadas con la ambigüedad y falta de información; en la valoración del proceso se presenta mayormente la inferencia y el enfrentamiento de la enfermedad es visto como un peligro, manifestado con sentimientos de ansiedad y depresión.

ABSTRACT The aim of this study was to recognize the most common uncertainties presented by patients diagnosed with Chronic Kidney Disease. Systematic review was made of the scientific literature of articles published between 2012 to 2018, in Spanish, Portuguese and English, and accessible to text full. Comprehensive and reproducible search of original works in the Scielo, PubMed, Ebschost, Dialnet, Redalyc databases, with the descriptors (DeCS) "Renal Insufficiency Chronic", "Theory of uncertainty", "Renal Dialysis" and their equivalents in Spanish, English, and Portuguese with critical assessment of the scientific quality of the studies applying PRISMA checklist (2009). The uncertainties were analyzed from the nursing theory of MIshel Merle, the findings show that the most common are related to ambiguity and lack of information; Inference of the process, the inference is mostly presented and the confrontation of the disease is seen as a danger manifested with feelings of anxiety and depression.

Relación entre hallazgos radiológicos e inmunofenotipos tumorales de pacientes con cáncer de mama / Relationship between radiological findings and immunophenotyped in breast cancer

Resumen OBJETIVO: Evaluar la relación entre los hallazgos radiológicos e inmunofenotipos tumorales de pacientes con cáncer de mama. MATERIALES Y MÉTODOS: Estudio observacional, retrospectivo y transversal, efectuado en el Hospital ABC de la Ciudad de México, entre 2013 y 2017. Se incluyeron pacientes con diagnóstico de cáncer de mama establecido por biopsia percutánea o escisional, que contaran con estudios de inmunohistoquímica e imagen (mastografía, ultrasonido o ambos). Para evaluar la relación entre las características morfológicas de las lesiones observadas en los estudios radiológicos y el inmunofenotipo se utilizó la prueba de χ2. RESULTADOS: Se registraron 182 pacientes. En cuanto a las características de las lesiones se encontró relación significativa entre las masas de morfología irregular con bordes espiculados y las calcificaciones agrupadas con tumores luminales, y entre las calcificaciones de morfología amorfa con los tumores luminales A y las pleomórficas finas con los tumores luminales B. CONCLUSIÓN: Existe relación entre los hallazgos morfológicos por imagen y el inmunofenotipo de los tumores mamarios. Es importante que el médico radiólogo especialista en imagen mamaria conozca esta relación, con la finalidad de proporcionar información de la inmunohistoquímica al momento del estudio diagnóstico de imagen.

Abstratc OBJECTIVE: Establish if there is a relationship between the radiological findings and the immunophenotype of breast cancer. MATERIALS AND METHODS: An observational, cross-sectional, retrospective study realized at the ABC Medical Center, over a period of 4 years, that included patients diagnosed with breast cancer performed by percutaneous or excisional biopsy, with an immunohistochemical study and images (mammography and/or ultrasound). The relationship between the morphological characteristics of the lesions observed in the radiological studies and the immunophenotyped was studied by means of the χ2 test. RESULTS: We included 182 patients, among the characteristics of the lesions we found a significant relationship between the masses of irregular morphology with spiculate edges and the calcifications grouped with luminal tumors; calcifications of amorphous morphology with luminal A and pleomorphic fine tumors with luminal B. CONCLUSION: The results suggest that there is a relationship between the morphological findings by imaging and the immunophenotype of mammary tumors.