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.

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.

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.

"Falling snowflakes," an ultrasound sign of hydatid sand.

It has been claimed that the distinction between a simple cyst and a simple noncomplicated hydatid cyst cannot be made by ultrasound examination. It is very important to make this distinction before attempting a diagnostic or therapeutic puncture of a cyst, at least in geographic areas where echinococcosis is endemic. The authors report an ultrasound sign that makes this differential diagnosis possible.

Celiac disease: case report with an associated arthropathy.

A case is presented of a patient with biopsy documented celiac disease who presented with an acute arthropathy along with symptoms of malabsorption. The etiology of the arthropathy could not be determined; however, the temporal relationship of the presenting manifestations (i.e., malabsorption and the arthropathy) as well as lack of further gastrointestinal of joint symptoms after 2 yr of follow-up suggest that in this case the arthropathy was related to the patient's celiac disease. Possible pathogenetic mechanisms for this heretofore unreported relationship are also presented.

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.

Penile thrombophlebitis as a presenting manifestation of pancreatic carcinoma.

Peyronie's disease of the penis is a condition in which there are plaques of fibrous tissue surrounding the corpus cavernosum causing deformity and painful erection. We describe a patient with pancreatic carcinoma who presented with Peyronie-like features. This pseudo-Peyronie's disease was actually an unusual superficial thrombophlebitis of the dorsal penile vein. The literature regarding neoplasm-associated thrombophlebitis is reviewed.

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.

The effect of upper gastrointestinal endoscopy on arterial O2 tension in smokers and nonsmokers with and without premedication.

Fiberoptic upper gastrointestinal endoscopy has become an accepted procedure with recognized and acceptable complication rates. Recently, significant hypoxemia during upper gastrointestinal endoscopy has been identified. This report evaluates changes in arterial blood gases and investigates the effects of drugs, smoking, and length of procedure. Upper gastrointestinal endoscopy was performed on 60 patients--15 patients in four different groups. Group I and II were smokers and nonsmokers who received sedation; groups III and IV were smokers and nonsmokers who received no sedation. A significant drop in PaO2 was noted in each group. Sedation, length of procedure, or smoking did not affect the PaO2 levels significantly. No significant change in PaCO2 was noted in any of the four groups. A V/Q mismatch related to vasospasm and/or bronchospasm is proposed as the main reason for the hypoxemia.