Circadian disruption promotes tumor-immune microenvironment remodeling favoring tumor cell proliferation.

Circadian disruption negatively affects physiology, posing a global health threat that manifests in proliferative, metabolic, and immune diseases, among others. Because outputs of the circadian clock regulate daily fluctuations in the immune response, we determined whether circadian disruption results in tumor-associated immune cell remodeling, facilitating tumor growth. Our findings show that tumor growth rate increased and latency decreased under circadian disruption conditions compared to normal light-dark (LD) schedules in a murine melanoma model. Circadian disruption induced the loss or inversion of daily patterns of M1 (proinflammatory) and M2 (anti-inflammatory) macrophages and cytokine levels in spleen and tumor tissues. Circadian disruption also induced (i) deregulation of rhythmic expression of clock genes and (ii) of cyclin genes in the liver, (iii) increased CcnA2 levels in the tumor, and (iv) dampened expression of the cell cycle inhibitor p21WAF/CIP1 , all of which contribute to a proliferative phenotype.

Rare labial ulcer related to the use of all-trans retinoic acid in a patient with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML). All-trans retinoic acid (ATRA) is the first-choice therapy for the treatment of this disease, but has been associated with side effects, the most serious of which is retinoic acid syndrome (RAS). RAS is characterized by unexplained fever, dyspnea, pulmonary infiltrate, leukocytosis and nephropathy. Genital ulcers have been described in some cases, but only two cases of oral ulcers related to this syndrome have been described in the literature. This paper describes the third case of oral ulceration related to ATRA in a 32-year-old white man with diagnosis of APL. Clinicians should know the side effects of ATRA and identify oral ulcers resulting from this therapy. The prompt identification of these ulcers enables the institution of appropriate treatment and can therefore contribute to continuation of the patient's cancer treatment.

[Contribution of chromosomal microarray analysis by a multidisciplinary prenatal diagnosis center]. / Apport de l'analyse chromosomique par puce à ADN dans un centre de diagnostic prénatal pluridisciplinaire.

OBJECTIVE: Chromosomal analysis by array CGH is a cytogenetic technique that has opened its application to prenatal diagnosis in recent years. The main objective of the study was to analyze the contribution for couples using chromosomal analysis by array CGH in a CPDPN. METHODS: A retrospective cohort study was conducted in 2015 in a CPDPN. All the patients with array CGH analysis were included in the study. The analysis indications were CN≥3.5mm, ultrasound signs, intra-uterine growth retardation and fetal deaths. Data were collected in the prenatal diagnosis and genetic records. RESULTS: In total, 155 patients underwent analysis by array CGH, which corresponds to 36% of patients with invasive sampling indication. Fifteen CGH analysis were positive which represents 9.6% of indications. None of those diagnoses was possible with standard karyotype. These positive results have changed the outcome of pregnancy and what to do for a future pregnancy in 54% of cases. CONCLUSION: Array CGH enables a diagnostic gain despite a delicate interpretation and changes taking care of patients in future pregnancies. These results should be confirmed in a prospective multicenter study.

Motor activity rhythms of forced desynchronized rats subjected to restricted feeding.

Although light is the strongest zeitgeber for the circadian pacemaker, other stimuli can also produce entrainment. In the rat, periodic restricted feeding (RF) is a weak stimulus that may act as a zeitgeber. We tested the effect of RF on the motor activity rhythms of rats subjected to forced dissociation. In this situation two components, supposed to be related with the ventrolateral and dorsomedial areas of the suprachiasmatic nucleus, are detected in their motor activity. One component is entrained to the external light-dark cycle (Light Dependent Component, LDC) and thus has the same period, while the other has a period longer than 24 h (Non-Light Dependent Component, NLDC). This experiment examined whether RF can act on one or both of these two rhythms. Rats were maintained under the light-dark cycles of 22 h (T22) or 23 h (T23) for 44 days with food available for four hours per day. Afterwards the rats received food ad libitum, to test the effect of the previous RF condition. Results show that RF modifies the manifestation of the two initial rhythms, being this effect stronger under T23 than under T22. However RF does not affect the NLDC period. The results reveal that the animal can manifest simultaneously several rhythmic patterns.

[Early or late umbilical cord clamping? A systematic review of the literature]. / 'Pinzamiento precoz o tardío del cordón umbilical? Una revisión sistemática de la literatura médica.

INTRODUCTION: There is wide variability in clinical practice in the moment of clamping the umbilical cord. Opinions in the medical community differ on the harm and/or benefits, both for the mother and for the newborn, of early versus late cord clamping. Currently, the debate among those who defend and/or criticize one or other of these practices continues. The aim of this study was to evaluate the effects of early versus late clamping of the umbilical cord in full-term newborns on maternal and neonatal outcomes. MATERIAL AND METHODS: A literature search of randomized clinical trials was carried out in the Cochrane Library, MEDLINE and Lilacs. It was completed with a hand search of references in relevant articles. All randomized controlled clinical trials of good methodological quality that compared early versus late cord clamping in term newborns were selected. RESULTS: Of seven identified studies, four had the required characteristics for inclusion in this systematic review. Comparison of early versus late clamping in these studies revealed that late clamping could diminish the prevalence of children with low iron reserves at 3 months of age by 50%, but this result comes from a study that lost more than 40% of the patients during follow-up. The results concerning anemia at 3 months of age showed statistical heterogeneity since the two studies that analyzed this outcome had opposite results. For other outcomes such as birth weight, Apgar < 5, and tachypnea the studies were too small for significant differences to be detected. CONCLUSIONS: This review shows that there is no clear evidence for defending any of the modalities of cord clamping in full-term newborns. Further research is needed to identify the best moment for cord clamping.

¿Pinzamiento precoz o tardío del cordón umbilical? Una revisión sistemática de la literatura médica / Early or late umbilical cord clamping? A systematic review of the literature

Introducción. Existe una gran variabilidad en la práctica clínica en cuanto al momento de pinzar el cordón umbilical. La comunidad médica manifiesta diferentes opiniones acerca de los daños y/o beneficios, tanto para la madre como para el recién nacido, del pinzamiento precoz frente al tardío. Actualmente continúa el debate entre los que defienden y/o critican cualquiera de estas prácticas. El objetivo de este estudio es evaluar los efectos maternos y neonatales del pinzamiento precoz del cordón umbilical comparado con el pinzamiento tardío en recién nacidos a término. Material y métodos. Se realizó la búsqueda bibliográfica en PubMed, la biblioteca Cochrane (Registro de estudios controlados), Lilacs y búsqueda manual de citas bibliográficas en artículos relevantes. Se seleccionaron todas las investigaciones clínicas controladas aleatorizadas de buena calidad metodológica que compararan el pinzamiento precoz del cordón con el pinzamiento tardío en el recién nacido a término. Resultados. De siete estudios identificados cuatro de ellos reunieron las características para ser seleccionados para su inclusión. Al comparar el pinzamiento precoz comparado con el tardío la revisión de los estudios mostró que el pinzamiento tardío podría disminuir la prevalencia de niños con bajas reservas de hierro a los 3 meses en el 50 %; sin embargo, estos resultados provinieron de un estudio que perdió más del 40 % de los pacientes durante el seguimiento. Para el resultado de anemia a los 3 meses, hubo heterogeneidad estadística en los resultados ya que los dos estudios mostraron efectos opuestos. Para los resultados de peso al nacimiento, Apgar inferior a 5 y taquipnea los estudios fueron muy pequeños para poder detectar diferencias significativas. Conclusiones. Esta revisión muestra que no existe clara evidencia para propiciar ninguna de las dos maneras de pinzamiento del cordón. Se requieren investigaciones que permitan establecer directrices sobre la conducta que se debe seguir

Introduction. There is wide variability in clinical practice in the moment of clamping the umbilical cord. Opinions in the medical community differ on the harm and/or benefits, both for the mother and for the newborn, of early versus late cord clamping. Currently, the debate among those who defend and/or criticize one or other of these practices continues. The aim of this study was to evaluate the effects of early versus late clamping of the umbilical cord in full-term newborns on maternal and neonatal outcomes. Material and methods. A literature search of randomized clinical trials was carried out in the Cochrane Library, MEDLINE and Lilacs. It was completed with a hand search of references in relevant articles. All randomized controlled clinical trials of good methodological quality that compared early versus late cord clamping in term newborns were selected. Results. Of seven identified studies, four had the required characteristics for inclusion in this systematic review. Comparison of early versus late clamping in these studies revealed that late clamping could diminish the prevalence of children with low iron reserves at 3 months of age by 50 %, but this result comes from a study that lost more than 40 % of the patients during follow-up. The results concerning anemia at 3 months of age showed statistical heterogeneity since the two studies that analyzed this outcome had opposite results. For other outcomes such as birth weight, Apgar < 5, and tachypnea the studies were too small for significant differences to be detected. Conclusions. This review shows that there is no clear evidence for defending any of the modalities of cord clamping in full-term newborns. Further research is needed to identify the best moment for cord clamping

French multi-centric study of 2000 amniotic fluid interphase FISH analyses from high-risk pregnancies and review of the literature.

This prospective and multi-centric study confirms the accuracy and the limitations of interphase FISH and shows that any cytogenetics laboratory can perform this technique. With regard to the technical approach, we think that slides must be examined by two investigators, because the scoring may be subjective. The main problem with the AneuVysion kit concerns the alpha satellite probes, and especially the chromosome 18 probe, which is sometimes very difficult to interpret because of the high variability of the size of the spots, and this may lead to false negative and uninformative cases. The best solution would be to replace these probes by locus-specific probes. Concerning clinical management, we offer interphase FISH only in very high-risk pregnancies or/and at late gestational age because of the cost of the test. We think that an aberrant FISH result can be used for a clinical decision when it is associated with a corresponding abnormal ultrasound scan. In other cases, most of the time, we prefer to wait for the standard karyotype.

Circadian rhythms in airline pilots submitted to long-haul transmeridian flights.

BACKGROUND: Circadian rhythms shift out of phase after transmeridian flights. Desynchronization between body rhythms and the environment is linked to jet lag, which depends on age, flight direction, and number of time zones crossed. METHODS: To investigate this problem in airline pilots, we performed a multivariate analysis of their circadian systems during Madrid-Mexico-Madrid flights (-7 time zones, n = 12) and Madrid-Tokyo-Madrid flights (+8 time zones, n = 21). Telemetry was used to record pilots' activity, skin temperature, and heart rate, obtaining 6 d of continuous data, including 2 d before the flight, the flights themselves, 2 d at the stopover, and 1 d after the return flight. Time series were analyzed by cosinor, and the resulting parameters of the rhythms were compared by ANOVA and Tukey contrasts in every category formed by the age groups (under and over 50 yr old) and flight direction groups. Subjective time estimation of short, intermediate, and long intervals was recorded. Other psychological variables were measured, including anxiety, tiredness, and performance. RESULTS AND CONCLUSIONS: Activity/rest and heart rate rhythms appeared to be linked to a "weak oscillator." Temperature rhythms manifested a rigid response after the phase shifts of the light/dark cycle, closely related to the biological clock. Subjective time appreciation tended to be overestimated without exhibiting a clear circadian component, but attributable to fatigue and stress. Psychometric evaluation showed that desynchronization affected all the pilots. Some results showed an age-related variability with a more marked influence in younger pilots. No consistent effects regarding flight direction were found.

Diabetes insipidus revealing acute myelogenous leukaemia with a high platelet count, monosomy 7 and abnormalities of chromosome 3: a new entity?

We describe three cases of acute myeloid leukaemia revealed by diabetes insipidus. The patients were 42, 38 and 39 yr old and they had marked hyperleukocytosis, circulating immature granular cells and a normal or elevated platelet count. The leukaemia was type AML-M2 according to the FAB classification. Cytogenetic studies showed inversion of chromosome 3 (q21;q26) in 2 cases and a translocation (3;3)(q21;q29?) in the remaining case, both associated with monosomy 7. All the cerebral CT scans were normal. Complete remission was never achieved, and all three patients survived less than 14 months. Desmopressin therapy was active but treatment could not be reduced. The association of dysmegakaryopoiesis with a chromosome 3 abnormality and diabetes insipidus is probably not fortuitous and could represent a new entity.

Detection of foetal cells in maternal blood and prenatal sex determination by in situ hybridization. Procedure verification.

We describe an enrichment of foetal cells from maternal blood with a combination of double density gradient and Magnetic Activated Cell Sorting (MACS) of CD71, glycophorin A (GPA), CD34 and CD36 antibodies labeled cells followed by fluorescence in situ hybridization (FISH) with chromosome-specific DNA probes for determination of foetal sex.

Pallister-Killian syndrome [i(12p)]: first pre-natal diagnosis using cordocentesis in the second trimester confirmed by in situ hybridization.

Pallister Killian syndrome (PKS) is the most frequent form of partial autosomal tetrasomy 12p in humans. Sufferers have a mosaic of isochromosome 12p [i(12p)]. We report the first pre-natal diagnosis on fetal blood cells after cordocentesis during the second trimester. The extra chromosome was first diagnosed by in situ hybridization. Fluorescence in situ hybridization (FISH) was used to count the interphase and/or metaphase cells containing the isochromosome. A review of the literature identified 27 other reports of PKS diagnosed pre-natally. We showed that the most consistent pre-natal ultrasound findings include hypertelorism, broad neck, shorts limbs, abnormal hands or feet, diaphragmatic hernia and hydramnios. Recognition of this congenital malformation pattern pre-natally may allow utilization of FISH.

Increased prosomal proteins in breast cancer cells and in neighboring normal cells in Parsi and non-Parsi populations.

Monoclonal antibodies were raised against the prosomal proteins p27K, p29K and the prosome-like protein p21K (PLP) from normal breast glandular cells and from benign and malignant tumors. They were used to clarify the involvement of prosomes in tumorigenesis of human breast cells. Immunostaining showed the distribution of prosomes in the cytoplasm and nuclei of cells from European normal women (EN) and Parsi (P) and non-Parsi (NP) benign (B) and malignant (M) tissues. The flow-cytometry studies showed an increased mean percentage of labeled cells, particularly with anti-p27K prosomal protein mAb, in malignant tissue from NP compared to EN. The p21K data indicated an increase in the number of cells labeled by flow-cytometry studies in all groups compared to EN, while p29K-expressing cells were more abundant in NPN, PB, PM and NPM. Intergroup comparison showed that the mean percentage of cells labeled with anti-p27K and anti-p29K was significantly higher in PB than in NPB, as seen by flow cytometry, whereas there was a higher production or accumulation of the p21K (PLP) prosomal protein in NPM than in PM, as seen by immunostaining. By comparison with EN, there were also significantly more normal cells containing the three antigens in the apparently normal tissue in the neighborhood of the tumor in NPM, and more cells containing p21K in PM patients than in EN. As prosomes are involved in the cell differentiation and in the cell cycle control, the changes observed in breast tissues may be related to oncogenic processes. Furthermore, the modified subunit pattern of prosomes in cancer and, possibly, pre-cancer tissue may be of interest for diagnosis purposes.

Dimethyl sulfoxide-induced apoptosis in human leukemic U937 cells.

Dimethyl sulfoxide (DMSO), which induces differentiation of myeloid cells, was found to cause apoptosis in human leukemic U937 cells. Apoptosis was assessed by DNA electrophoresis and flow cytometry. The time needed to induce apoptosis varied from a few hours to 2-3 days, depending on the concentration of DMSO used. The plasma membrane remained intact long after DNA fragmentation had occurred. DMSO-induced apoptosis was inhibited by zinc ions and, to a lesser extent, by the protein kinase C activator: phorbol 12-myristate 13-acetate (PMA). Cycloheximide and actinomycin D did not prevent DMSO-induced apoptosis, showing that U937 cells do not require protein or RNA synthesis to undergo apoptosis. DMSO induced apoptosis despite the expression of the anti-apoptotic Bcl-2 protein in U937 cells. The amount of Bcl-2 remained unchanged during DMSO-induced apoptosis.

Chronic lymphocytic leukemia presenting with massive chylous ascites.

A newly diagnosed patient with chronic lymphocytic leukemia who presented with ascites is described. Paracentesis revealed the presence of massive chylous ascites. Further work-up disclosed leukemic infiltration of the liver and bone marrow. Complications leading to his death included renal failure, gastrointestinal hemorrhage, bacterial peritonitis, and Staphylococcus aureus bacteremia. Chylous ascites is a rarely reported manifestation of chronic lymphocytic leukemia. The case is presented, and a review of the literature is discussed.

Ultrasound scanning as a screening technique for hydatidosis in developing countries.

This study presents new evidence as to the usefulness of ultrasound scanning in field conditions, to screen out hydatidosis in endemic areas, and to compare its detection capability with serological methods. It also intends to demonstrate that for an efficient rural ultrasound screening, neither an experienced ultra sonographer nor expensive and sophisticated equipment is necessary, it can be done by suitably trained personnel (eg, nurse, public health worker), using basic equipment, without public health installations or electricity, thus making it a feasible, simple, fast, and cheap screening method for hydatidosis.