Influence of environmental variability and Emiliania huxleyi ecotypes on alkenone-derived temperature reconstructions in the subantarctic Southern Ocean.

Long-chain unsaturated alkenones produced by haptophyte algae are widely used as paleotemperature indicators. The unsaturation relationship to temperature is linear at mid-latitudes, however, non-linear responses detected in subpolar regions of both hemispheres have suggested complicating factors in these environments. To assess the influence of biotic and abiotic factors in alkenone production and preservation in the Subantarctic Zone, alkenone fluxes were quantified in three vertically-moored sediment traps deployed at the SOTS observatory (140°E, 47°S) during a year. Alkenone fluxes were compared with coccolithophore assemblages, satellite measurements and surface-water properties obtained by sensors at SOTS. Alkenone-based temperature reconstructions generally mirrored the seasonal variations of SSTs, except for late winter when significant deviations were observed (3-10 °C). Annual flux-weighted averages in the 3800 m trap returned alkenone-derived temperatures ~1.5 °C warmer than those derived from the 1000 m trap, a distortion attributed to surface production and signal preservation during its transit through the water column. Notably, changes in the relative abundance of E. huxleyi var. huxleyi were positively correlated with temperature deviations between the alkenone-derived temperatures and in situ SSTs (r = 0.6 and 0.7 at 1000 and 2000 m, respectively), while E. huxleyi var. aurorae, displayed an opposite trend. Our results suggest that E. huxleyi var. aurorae produces a higher proportion of C37:3 relative to C37:2 compared to its counterparts. Therefore, the dominance of var. aurorae south of the Subtropical Front could be at least partially responsible for the less accurate alkenone-based SST reconstructions in the Southern Ocean using global calibrations. However, the observed correlations were largely influenced by the samples collected during winter, a period characterized by low particle fluxes and slow sinking rates. Thus, it is likely that other factors such as selective degradation of the most unsaturated alkenones could also account for the deviations of the alkenone paleothermometer.

Cholelithiasis and associated complications in pediatric patients. / Colelitiasis y complicaciones asociadas en pacientes pediátricos.

OBJECTIVE: To review the clinical characteristics and complications associated with cholelithiasis in pediatric patients by identifying risk factors and assessing surgical management and results. METHODS: Retrospective study in patients under 18 years of age undergoing cholelithiasis surgery. The following data were analyzed: age, sex, body mass index (BMI), associated comorbidities, clinical presentation, symptom duration, surgical treatment, pathological report, postoperative complications, and hospital stay. RESULTS: 135 cholelithiasis patients underwent surgery from 2013 to 2018, with an increasing trend in the annual number of cholecystectomies. Most patients were adolescents (86.7%) and female (72.6%), and they had cholesterol gallstones (86.6%) and >85 BMI (33%). Mean symptom duration was 85 days (SD: 148). Symptomatic cholelithiasis was present in 131 cases (97%). CL associated complications were recorded in 64.4% of patients, with cholecystitis, pancreatitis, and choledocholithiasis being the most frequent ones. All patients underwent laparoscopic cholecystectomy; 4 (2.9%) required conversion to open surgery, and 6 (4.4%) had postoperative complications. Mean hospital stay and postoperative follow-up were 5.7 days (SD: 4) and 2.3 months (SD: 1.9), respectively. CONCLUSIONS: Non-hemolytic cholelithiasis in the pediatric population is more frequent in female overweight and obese adolescents. Symptomatic cholelithiasis is associated with higher risk of complications such as cholecystitis, pancreatitis, or choledocholithiasis, which supports early surgical management.

OBJETIVO: Revisión de las características clínicas y complicaciones asociadas de los pacientes pediátricos con colelitiasis, mediante la identificación de factores de riesgo, la evaluación del manejo quirúrgico y sus resultados. METODOS: Estudio retrospectivo en pacientes menores de 18 años, intervenidos quirúrgicamente por colelitiasis. Se analizaron datos como edad, género, índice de masa corporal (IMC), comorbilidades asociadas, presentación clínica, tiempo de los síntomas, tratamiento quirúrgico, reporte de patología, complicaciones posoperatorias y estancia hospitalaria. RESULTADOS: Se intervinieron quirúrgicamente 135 pacientes con colelitiasis entre los años 2013 a 2018, con una tendencia ascendente en el número de colecistectomías realizadas anualmente. La mayoría fueron pacientes adolescentes (86,7%), con cálculos de colesterol (86,6%), de género femenino (72,6%) y con IMC > 85 (33%). El tiempo de los síntomas en promedio fue de 85 días (DE 148). Colelitiasis sintomática se presentó en 131 casos (97%). Complicaciones asociadas a CL se registraron en 64,4% pacientes, siendo las más frecuentes colecistitis, pancreatitis y coledocolitiasis. En todos los pacientes se realizó colecistectomía laparoscópica, 4 (2,9%) requirieron conversión a cirugía abierta y 6 (4,4%) presentaron complicaciones postoperatorias. La estancia hospitalaria y el seguimiento posoperatorio fueron en promedio 5,7 días (DE 4) y 2,3 meses (DE 1,9), respectivamentea. CONCLUSIONES: La colelitiasis no hemolítica en la población pediátrica, es más frecuente en pacientes adolescentes de género femenino con sobrepeso u obesidad. La colelitiasis sintomática está asociada con mayor riesgo de complicaciones como colecistitis, pancreatitis o coledocolitiasis, en consecuencia, se justifica una intervención quirúrgica temprana.

Nutritional and non-nutritional agents that stimulate white adipose tissue browning.

Obesity is a public health problem present in both developed and developing countries. The white adipose tissue (WAT) is the main deposit of lipids when there is an excess of energy. Its pathological growth is directly linked to the development of obesity and to a wide number of comorbidities, such as insulin-resistance, cardiovascular disease, among others. In this scenario, it becomes imperative to develop new approaches to the treatment and prevention of obesity and its comorbidities. It has been documented that the browning of WAT could be a suitable strategy to tackle the obesity epidemic that is developing worldwide. Currently there is an intense search for bioactive compounds with anti-obesity properties, which present the particular ability to generate thermogenesis in the brown adipose tissue (BAT) or beige. The present study provide recent information of the bioactive nutritional compounds capable of inducing thermogenesis and therefore capable of generate positive effects on health.

Brain microbleeds: Epidemiology and clinical implications. / Microhemorragias cerebrales: epidemiología e implicaciones clínicas.

INTRODUCTION: Brain microbleeds (BMB) are haemosiderin deposits contained within macrophages, which are displayed as hypointense images in some T2-weighted magnetic resonance imaging sequences. There are still many questions to be answered about the pathophysiology and clinical relevance of BMB. DEVELOPMENT: We conducted a literature review of the main epidemiological, clinical, and anatomical pathology studies of BMB performed in the general population, in patients at risk of or already suffering from a vascular disease, and in patients with cognitive impairment. We analysed the prevalence of BMB, risk factors, and potential pathophysiological mechanisms and clinical implications. CONCLUSIONS: The prevalence of BMB is highly variable (3%-27% in the general population, 6%-80% in patients with vascular risk factors or vascular disease, and 16%-45% in patients with cognitive impairment). BMB are associated with ageing, Alzheimer disease (AD), and in particular haemorrhagic or ischaemic cerebrovascular disease. The pathological substrate of BMB is either lipohyalinosis (subcortical BMB) or cerebral amyloid angiopathy (lobar BMB). BMB exacerbate cognitive impairment, possibly through cortical-subcortical and intracortical disconnection, and increase the risk of death, mostly due to vascular causes. BMB also increase the risk of cerebral haemorrhage, particularly in patients with multiple lobar BMB (probable erebral amyloid angiopathy). Therefore, anticoagulant treatment may be contraindicated in these patients. In patients with lower risk of bleeding, the new oral anticoagulants and the combination of clinical and magnetic resonance imaging follow-up could be helpful in the decision-making process.

Simulador de bajo costo para el entrenamiento en la colocación de accesos vasculares periféricos (AVP) en pediatría / Low-cost simulator for the training of peripheral venous access (PVA) placement in pediatrics

Introducción: El entrenamiento en simuladores permite aprender procedimientos en un marco controlado que protege la seguridad de los pacientes pediátricos y que se integra como una instancia de aprendizaje previa a la realidad con el paciente. En el Centro de Simulación del Hospital de Pediatría Juan P. Garrahan se diseñan y validan simuladores de bajo costo artesanales que permiten contar con recursos propios y de reposición inmediata. Objetivo: Describir el diseño de un simulador de bajo costo para la colocación de accesos vasculares periféricos y reportar la experiencia inicial de validación. Métodos: Se diseñó un simulador artesanal inanimado de punción venosa periférica (parte de miembro superior de un niño de edad aproximada de 8 años) con materiales de bajo costo. En una segunda fase y con el propósito de validarlo, se solicitó la colocación del acceso vascular -en el modelo simulado- a enfermeros del hospital que trabajan en el área de internación (usuarios expertos). Al final de cada experiencia, cada operador reportó su opinión sobre el realismo del modelo y utilidad de la experiencia en forma anónima. Resultados Participaron 43 enfermeros; entre el 75 a 90% de las veces, las repuestas fueron "se parece mucho" o "es igual" a la experiencia real de colocación de un acceso venoso a un niño. El 85% expresó que esta práctica permitía mejorar la destreza, y el 100% que el modelo puede ayudar a enseñarla en forma efectiva. Conclusiones El desarrollo de modelos de simuladores de bajo costo para usos específicos, de baja tecnología, resulta importante para el entrenamiento de habilidades. La aceptación por parte de los usuarios calificados y expertos fue muy buena, encontrando en un alto porcentaje similitud con la realidad (AU)

Introduction: Training on simulators allows for the learning of procedures within a controlled framework that protects the safety of pediatric patients and provides a learning moment previous to working with a real patient. In the Simulation Center at Hospital de Pediatría Juan P. Garrahan low-cost simulators are designed and validated that allow for proper resources and immediate replacement. Aim: To describe the design of a low-cost simulator for the placement of peripheral vascular Access and to report the initial experience with the validation of the device. Methods: An inanimate simulator for peripheral puncture (the upper limb of a child of approximately 8 years of age) was designed using lowcost materials. In a second phase with the purpose of validating the device, nurses of the hospital working in the inpatient area (expert users) were asked to insert a venous catheter in the simulation model. At the end of each procedure, each operator was asked to anonymously give their opinion. Results: 43 nurses participated; between 75 and 90% of times, the answers were "it is very similar "or "it is the same as the experience of placing a real venous catheter in a child. Overall, 85% felt that the training improved their skills and 100% considered that the model may be effective in the teaching process. Conclusions: The development of low-cost, low-technology simulation models is important in the training of skills. Acceptance by qualified users and experts was very good. A high degree of similarity with reality was reported (AU)

Seguridad en el traslado intrahospitalario de pacientes críticos en pediatría / Safety of interhospital transfers of critical care patients in pediatrics

La unidad de cuidados intensivos (UCI) es el ámbito más seguro para la atención de pacientes críticamente enfermos. Sin embargo, hay situaciones en las que el paciente debe ser trasladado a algún otro lugar del hospital, pudiendo incrementar el riesgo para eventos adversos. El objetivo es describir la implementación de un programa de capacitación y realizar un relevamiento de los traslados de pacientes de UCI. Estudio descriptivo y prospectivo. Se incluyeron todos los pacientes trasladados desde las UCI 44-45-72 y 65 durante el periodo de Julio 2012 a Junio 2013. Se diseñó una lista de chequeo, con datos de cada paciente, material para el traslado y registro de efectos adversos. Se agruparon por gravedad en Grupo I: Sin requerimientos de inotrópicos y sin asistencia respiratoria mecánica (ARM) y Grupo II: Requerimientos de ARM y/o inotrópicos (A Estables, B Inestable). Se realizó capacitación del personal encargado de los traslados para completar las listas de chequeo y recomendaciones sobre traslado seguro. Se documentaron 104 traslados y se distribuyeron en Grupo IA 32%, 2A 61% y 2B 11%. Se pesquisó un total de 61 (58.65%) eventos adversos. Se registraron eventos adversos en 58.65% de los traslados y solo 47.11% de los traslados fueron realizados en condiciones adecuadas (AU)

The intensive care unit (ICU) is the safest environment for the care of critically ill patients. Nevertheless, in certain settings the patients have to be transferred to other sectors of the hospital, which may increase the risk of adverse events. With the aim to describe the implementation of a training program and to assess the transfer of ICU patients a descriptive and prospective study was conducted. All patients transferred from ICUs 44-45,72, and 65 over the period July 2012 to June 2013 were included. A checklist was developed with patient data, materials included in the transfer, and recording of adverse events. Patients were categorized according to severity into Group I: No need for inotropics and mechanical ventilation (MV) and Group II: Need for MV and/or inotropics (A Stable, B Unstable). Personnel in charge of the transfers were trained in the filling out of the checklists and recommendations for safe transfers. One hundred and four transfers were registered; 32% of the patients were in Group IA, 61% in Group 2A, and 11% in 2B. A total of 61 (58.65%) adverse events were observed. Adverse events were registered in 58.65% of the transfers and only 47.11% of the transfers were performed under adequate conditions (AU)

Seasonal and spatial variation of organic tracers for biomass burning in PM1 aerosols from highly insolated urban areas.

PM1 aerosol characterization on organic tracers for biomass burning (levoglucosan and its isomers and dehydroabietic acid) was conducted within the AERTRANS project. PM1 filters (N = 90) were sampled from 2010 to 2012 in busy streets in the urban centre of Madrid and Barcelona (Spain) at ground-level and at roof sites. In both urban areas, biomass burning was not expected to be an important local emission source, but regional emissions from wildfires, residential heating or biomass removal may influence the air quality in the cities. Although both areas are under influence of high solar radiation, Madrid is situated in the centre of the Iberian Peninsula, while Barcelona is located at the Mediterranean Coast and under influence of marine atmospheres. Two extraction methods were applied, i.e. Soxhlet and ASE, which showed equivalent results after GC-MS analyses. The ambient air concentrations of the organic tracers for biomass burning increased by an order of magnitude at both sites during winter compared to summer. An exception was observed during a PM event in summer 2012, when the atmosphere in Barcelona was directly affected by regional wildfire smoke and levels were four times higher as those observed in winter. Overall, there was little variation between the street and roof sites in both cities, suggesting that regional biomass burning sources influence the urban areas after atmospheric transport. Despite the different atmospheric characteristics in terms of air relative humidity, Madrid and Barcelona exhibit very similar composition and concentrations of biomass burning organic tracers. Nevertheless, levoglucosan and its isomers seem to be more suitable for source apportionment purposes than dehydroabietic acid. In both urban areas, biomass burning contributions to PM were generally low (2 %) in summer, except on the day when wildfire smoke arrive to the urban area. In the colder periods the contribution increase to around 30 %, indicating that regional biomass burning has a substantial influence on the urban air quality.

Relationship between mesiodistal crown diameters of permanent first molars and deciduous second molars.

AIM: To determine whether there is a relationship between the mesiodistal crown diameters of permanent first molars and deciduous second molars, and to update their odontometric values for the Spanish population. MATERIALS AND METHODS: A cross-sectional descriptive study was performed of a sample of molars in 101 children (46 boys and 55 girls) of Spanish parents.The measurements were performed on cast dental models using a fine-tipped caliper with accuracy of ± 0.05 mm. RESULTS: Statistically significant differences were detected between sexes both for the permanent first molars and for the deciduous second molars. However, no differences were detected between antimeric teeth. The size of the deciduous second molars was related to the size of the permanent first molar, and this relationship was statistically significant. CONCLUSION: As a correlation was found between the mesiodistal crown diameters of permanent first molars and deciduous second molars, the findings of this study may be used as a predictive factor for tooth-jaw size disharmony, and therefore for possible crowding of the permanent dentition.

Measurement of intracellular gamma-interferon, interleukin-4, and interleukin-10 levels in patients following laparoscopic cholecystectomy.

Major surgery suppresses intracellular T-cell cytokine production. Laparoscopic surgery has been reported to have no effect on in vitro lymphocyte reactivity, but its effects on intracellular cytokine production are unknown. This study measured T-cell intracellular gamma-interferon, interleukin-4 (IL-4), and interleukin-10 (IL-10), along with serum interleukin-6 (IL-6) and cortisol levels, immediately before and 1 day after laparoscopic cholecystectomy in a cohort of six Air Force and veteran patients. Stimulated intracellular levels of gamma-interferon were slightly, but not significantly, elevated during the postoperative period in all T-cell subsets. There were no postoperative changes in stimulated IL-4 or IL-10 levels. Postoperative serum IL-6 levels, but not serum cortisol levels, were significantly elevated compared to preoperative values. In conclusion, laparoscopic surgery causes slight trauma but has no effect on T-cell intracellular interferon, IL-4, and IL-10 responses.

An outbreak of fulminant hepatitis delta in the Waorani, an indigenous people of the Amazon basin of Ecuador.

An outbreak of delta hepatitis occurred during 1998 among the Waorani of the Amazon basin of Ecuador. Among 58 people identified with jaundice, 79% lived in four of 22 Waorani communities. Serum hepatitis B surface antigen (HBsAg) was found in the sera of 54% of the jaundiced persons, and 14% of asymptomatic persons. Ninety-five percent of 105 asymptomatic Waorani had hepatitis B core (HBc) IgG antibody, versus 98% of 51 with jaundice. These data confirm that hepatitis B virus (HBV) infection is highly endemic among the Waorani. Sixteen of 23 (70%) HBsAg carriers identified at the onset of the epidemic had serologic markers for hepatitis D virus (HDV) infection. All 16 were jaundiced, where as only two of seven (29%) with negative HDV serology were jaundiced (P = .0006). The delta cases clustered in families, 69% were children and most involved superinfection of people chronically infected with HBV. The data suggest that HDV spread rapidly by a horizontal mode of transmission other than by the sexual route.

Major surgery suppresses maximal production of helper T-cell type 1 cytokines without potentiating the release of helper T-cell type 2 cytokines.

BACKGROUND: Major surgery is known to suppress T-cell function; however, its differential effects on the production of helper T-cell type 1 (T(H)1) and type 2 (T(H)2) cytokines remains unknown. OBJECTIVE: To measure the production patterns of T(H)1 (interleukin 2 [IL-2] and interferon gamma) and T(H)2 (IL-4 and IL-10) cytokines following major surgery. DESIGN, SETTING, AND PATIENTS: A cohort study of patients (both active and former members of the armed forces) at a military hospital. INTERVENTION: Aortic surgery or carotid endarterectomy and measurement of serum IL-6 levels by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Unstimulated and stimulated intracellular levels of IL-2, IL-4, IL-10, and interferon gamma in CD4+, CD8+, and gammadelta+ T cells and serum IL-6 levels immediately before and for 2 days after aortic surgery or carotid endarterectomy. RESULTS: No unstimulated production of T(H) or T(H)2 cytokines was detected. Stimulated intracellular levels of IL-2 and interferon gamma were significantly depressed during the postoperative period in all T-cell subsets in both patient groups. There were no postoperative increases in stimulated IL-4 or IL-10 levels. CONCLUSION: Major surgery suppresses the potential responses of T(H)1 cytokines without enhancing production of T(H)2 cytokines.

Active surveillance for Vibrio cholerae O1 and vibriophages in sewage water as a potential tool to predict cholera outbreaks.

The 1991 Peruvian cholera epidemic has thus far been responsible for 600,000 cholera cases in Peru. In an attempt to design a cholera surveillance program in the capital city of Lima, weekly sewage samples were collected between August 1993 and May 1996 and examined for the presence of Vibrio cholerae O1 bacteria and V. cholerae O1 bacteriophages (i.e., vibriophages). During the 144 weeks of surveillance, 6,323 cases of clinically defined cholera were recorded in Lima. We arbitrarily defined an outbreak as five or more reported cases of cholera in a week. The odds of having an outbreak were 7.6 times greater when V. cholerae O1 was present in sewage water during the four previous weeks compared with when it was not (P < 0.001). Furthermore, the odds of having an outbreak increased as the number of V. cholerae O1 isolations during the previous 4 weeks increased (P < 0.001). The odds of having an outbreak were 2.4 times greater when vibriophages were present in sewage water during the four previous weeks compared with when they were not, but this increase was not statistically significant (P = 0.15). The odds of having an outbreak increased as the number of vibriophage isolations during the previous 4 weeks increased (P < 0.05). The signaling of a potential cholera outbreak 1 month in advance may be a valuable tool for implementation of preventive measures. In Peru, active surveillance for V. cholerae O1 and possibly vibriophages in sewage water appears to be a feasible and effective means of predicting and outbreak of cholera.

Incidence of Vibrio cholerae O1 diarrhea in children at the onset of cholera epidemic in periurban Lima, Peru.

OBJECTIVE: To determine the incidence of Vibrio cholerae O1-associated diarrhea in children during the onset of the 1991 cholera epidemic in Peru. METHODS: Stool cultures were obtained from children (mean age, 26 months) participating in a prospective community-based study of diarrhea in a periurban community in Lima between February and May, 1991. RESULTS: Of the 409 diarrheal episodes cultured V. cholerae O1 was isolated in 14 (3.4%) episodes. This represented an incidence of 0.11 episode per child year, higher than previously reported rates in children from endemic cholera areas. Most cases were mild; only 1 case required hospitalization. CONCLUSIONS: Our study indicates that from the beginning of this epidemic, V. cholerae O1 caused diarrhea in children as well as adults and should therefore be considered as one of the possible pathogens when children from a cholera-affected area develop diarrhea.

Comparative effectiveness of co-trimoxazole and tetracycline in the treatment of Cholera.

The purpose of the study reported here was to compare the bactericidal effectiveness of tetracycline and co-trimoxazole (a combination of sulfamethoxazole and trimethoprim) in treating cholera. The study, an open-ended random trial using adult patients with cholera cases confirmed by stool culture, was carried out in March 1993 at the Cholera Treatment Unit (CTU) of the Hospital de Apoyo Departmental María Auxiliadora in Lima, Peru. A total of 107 subjects were divided into two groups (A and B). The 50 in Group A received 500 mg of tetracycline orally every 6 hours for 3 days; the 57 in Group B received co-trimoxazole (160 mg of trimethoprim and 800 mg of sulfamethoxazole) orally every 12 hours for 3 days. The two groups were comparable in terms of age, sex, duration of symptoms prior to hospital admission, time at which antibiotic treatment was initiated, and clinical evolution. Control stool cultures of specimens obtained after treatment showed Vibrio cholerae O-1 present in 2% of the Group A and 12.3% of the Group B patients, and also showed V. cholerae non-O-1 present in 2% of the Group A patients and 3.5% of the Group B patients. Overall, it was concluded that both therapeutic treatment regimens were effective and that the strains of V. cholerae observed in the southern sector of the city of Lima were still susceptible to both antibiotics.

Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16.

Injury to stratified epithelia causes a strong induction of keratins 6 (K6) and 16 (K16) in post-mitotic keratinocytes located at the wound edge. We show that induction of K6 and K16 occurs within 6 h after injury to human epidermis. Their subsequent accumulation in keratinocytes correlates with the profound reorganization of keratin filaments from a pan-cytoplasmic distribution to one in which filaments are aggregated in a juxtanuclear location, opposite to the direction of cell migration. This filament reorganization coincides with additional cytoarchitectural changes and the onset of re-epithelialization after 18 h post-injury. By following the assembly of K6 and K16 in vitro and in cultured cells, we find that relative to K5 and K14, a well-characterized keratin pair that is constitutively expressed in epidermis, K6 and K16 polymerize into short 10-nm filaments that accumulate near the nucleus, a property arising from K16. Forced expression of human K16 in skin keratinocytes of transgenic mice causes a retraction of keratin filaments from the cell periphery, often in a polarized fashion. These results imply that K16 may not have a primary structural function akin to epidermal keratins. Rather, they suggest that in the context of epidermal wound healing, the function of K16 could be to promote a reorganization of the cytoplasmic array of keratin filaments, an event that precedes the onset of keratinocyte migration into the wound site.

Overexpression of human keratin 16 produces a distinct skin phenotype in transgenic mouse skin.

Human cytokeratin 16 (K16; 48 kDa) is constitutively expressed in postmitotic keratinocytes in a variety of stratified epithelial tissues, but it is best known for the marked enhancement of its expression in stratified squamous epithelia showing hyperproliferation or abnormal differentiation. Of particular interest to us, K16 is strongly induced at the wound edge after injury to the epidermis, and its accumulation correlates spatially and temporally with the onset of reepithelialization. To examine the properties of K16 in its natural cellular context, we introduced a wild-type human K16 gene into the germ line of transgenic mice. Several transgenic lines were established and characterized. Under most conditions, the human K16 transgene is regulated tissue specifically in the skin of transgenic mice. Animals that feature low levels of transgene expression are indistinguishable from controls during the first 6-8 months of life. In contrast, transgenic animals expressing the transgene at higher levels develop skin lesions at 1 week after birth, coinciding with the emergence of fur. At a cellular level, alterations begin with the reorganization of keratin filaments and are first seen at the level of the hair follicle outer root sheath (ORS), where K16 expression is known to occur constitutively. The lesions then progressively spread to involve the proximal epidermis, with which the ORS is contiguous. Elevated transgene expression is associated with a marked thickening of these two epithelia, along with altered keratinocyte cytoarchitecture and aberrant keratinization but no keratinocyte lysis. The implications of this phenotype for epithelial differentiation, human genodermatoses, and wound healing in skin are discussed.

Characterization of the normal progesterone and placental protein 14 responses to human chorionic gonadotropin stimulation in the luteal phase.

OBJECTIVE: To examine whether midluteal phase administration of the luteotrophic hormone hCG can result in higher and more stable serum levels than random sampling of P and placental protein 14 (PP14). DESIGN: Prospective controlled clinical study. SETTING: Normal human volunteers in an academic research environment. PARTICIPANTS: Twenty-six fertile, regularly cycling women. INTERVENTIONS: Blood samples were drawn at 0, 3, 6, 9, 12, 18, and 24 hours and then daily for the next 6 days, after a single IM injection of 5,000 IU hCG or saline given on day 5, 7, or 9 after the LH surge, as detected by rapid plasma assays. MAIN OUTCOME MEASURES: Serum P and PP14 measurements. RESULTS: Peak P and PP14 concentrations occurred at 6 hours and 5 days, respectively, after hCG stimulation on luteal phase day 9. Progesterone but not PP14 levels were significantly higher and less variable after hCG than after saline administration on this day. Progesterone responses exceeded 11.0 ng/mL (35.0 nmol/L) in all women, suggesting that this represents the cutoff limit for normal luteal function. Because PP14 responses were highly variable and inconsistent, it was not possible to determine a threshold for normal endometrial function. CONCLUSIONS: Midluteal phase administration of hCG in normal women induces consistent serum P levels > 11.0 ng/mL (35.0 nmol/L) but highly variable PP14 responses.

Comparative analysis of progesterone and placental protein 14 measurements in the evaluation of luteal function.

OBJECTIVE: Our purpose was to investigate the diagnostic accuracy of single or summed measurements of progesterone and placental protein 14, a progestin-dependent endometrial glycoprotein, in the evaluation of luteal function. STUDY DESIGN: Forty-five healthy women had daily blood measurements of luteinizing hormone, progesterone, and placental protein 14 during one menstrual cycle. RESULTS: Thirty-nine women had normal and six had deficient luteal function on the basis of serial progesterone determinations. Luteal insufficiency was not accurately diagnosed by single progesterone or placental protein 14 values or by integrated placental protein 14 measurements. In contrast, the condition was correctly identified in all but one cycle when the sum of progesterone on days 4 and 7 was < 49 nmol/L (15.4 ng/ml). A poor correlation was found between peak or integrated measurements of progesterone and placental protein 14. CONCLUSION: Measurement of serum progesterone, but not placental protein 14, on 2 days of the midluteal phase provides a convenient and reliable test of luteal function.