Clock gene homologs lin-42 and kin-20 regulate circadian rhythms in C. elegans.

Circadian rhythms are endogenous oscillations in nearly all organisms, from prokaryotes to humans, allowing them to adapt to cyclical environments for close to 24 h. Circadian rhythms are regulated by a central clock, based on a transcription-translation feedback loop. One important protein in the central loop in metazoan clocks is PERIOD, which is regulated in part by Casein kinase 1ε/δ (CK1ε/δ) phosphorylation. In the nematode Caenorhabditis elegans, period and casein kinase 1ε/δ are conserved as lin-42 and kin-20, respectively. Here, we studied the involvement of lin-42 and kin-20 in the circadian rhythms of the adult nematode using a bioluminescence-based circadian transcriptional reporter. We show that mutations of lin-42 and kin-20 generate a significantly longer endogenous period, suggesting a role for both genes in the nematode circadian clock, as in other organisms. These phenotypes can be partially rescued by overexpression of either gene under their native promoter. Both proteins are expressed in neurons and epidermal seam cells, as well as in other cells. Depletion of LIN-42 and KIN-20, specifically in neuronal cells after development, was sufficient to lengthen the period of oscillating sur-5 expression. Therefore, we conclude that LIN-42 and KIN-20 are critical regulators of the adult nematode circadian clock through neuronal cells.

Regulation of the circadian clock in C. elegans by clock gene homologs kin-20 and lin-42.

Circadian rhythms are endogenous oscillations present in nearly all organisms from prokaryotes to humans, allowing them to adapt to cyclical environments close to 24 hours. Circadian rhythms are regulated by a central clock, which is based on a transcription-translation feedback loop. One important protein in the central loop in metazoan clocks is PERIOD, which is regulated in part by Casein kinase 1 ε/δ (CK1 ε/δ ) phosphorylation. In the nematode Caenorhabditis elegans , period and casein kinase 1ε/δ are conserved as lin-42 and kin-20 , respectively. Here we studied the involvement of lin-42 and kin-20 in circadian rhythms of the adult nematode using a bioluminescence-based circadian transcriptional reporter. We show that mutations of lin-42 and kin-20 generate a significantly longer endogenous period, suggesting a role for both genes in the nematode circadian clock, as in other organisms. These phenotypes can be partially rescued by overexpression of either gene under their native promoter. Both proteins are expressed in neurons and seam cells, a population of epidermal stem cells in C. elegans that undergo multiple divisions during development. Depletion of LIN-42 and KIN-20 specifically in neuronal cells after development was sufficient to lengthen the period of oscillating sur-5 expression. Therefore, we conclude that LIN-42 and KIN-20 are critical regulators of the adult nematode circadian clock through neuronal cells.

Timing of umbilical cord occlusion, delayed vs early, in preterm babies: A randomized controlled trial (CODE-P Trial).

INTRODUCTION: Our hypothesis was that delayed cord clamping (DCC) (not earlier than 30 s; at 30-60 s) in premature neonates (born between 26.0 and 32.6 weeks of gestation), as compared with the usual early cord clamping (ECC), significantly reduces the need for blood transfusions and incidence of intraventricular haemorrhage (IVH) without an increased rate of maternal postpartum haemorrhage. MATERIAL AND METHODS: A prospective, open-label, randomized, controlled trial was conducted at Vall d'Hebron Hospital from July 2014 to December 2018. All pregnant women at risk of impending preterm birth (≥26.0-<33.0 weeks of gestation) who were admitted to the obstetrics emergency department were evaluated for eligibility. If they met the eligibility criteria, they were invited to participate in the study and, if they agreed, they signed an informed consent. Patients were randomly assigned to one of two groups: ECC group and DCC group. RESULTS: Our study included a total of 57 patients: 30 in the ECC group and 27 in the DCC group. Due to a lack of funding and low recruitment rates, the study was discontinued in 2018. Maternal characteristics and obstetric outcomes were similar between both groups. The intention-to-treat analysis did not reveal any differences between groups for neonatal red blood cell transfusions, neonatal IVH or maternal postpartum haemorrhage. There were no differences for secondary outcomes. Similarly, no differences were observed in the as-treated analysis. CONCLUSION: The primary and secondary outcomes of our study were not achieved. Therefore, more meta-analysis and trials are needed to evaluate the appropriate timing of cord clamping in preterm birth.

Divertículo de Meckel en el hiato de Winslow como causa extraordinaria de oclusión intestinal / Meckel's diverticulum in the foramen of Winslow as a rare cause of small bowel obstruction

RESUMEN El divertículo de Meckel es la malformación congénita más frecuente del tracto gastrointestinal. Puede permanecer completamente oculto sin dar síntomas o puede ser causa de abdomen agudo quirúrgico en donde se debe descartar patología inflamatoria, infecciosa y/o mecánica. Se presenta un caso excepcional de una obstrucción intestinal producido por una hernia interna generada por un divertículo de Meckel en el hiato de Winslow.

ABSTRACT Meckel's diverticulum is the most common congenital defect of the gastrointestinal tract. It may remain asymptomatic or may cause acute abdomen requiring surgery due to inflammation, infection or mechanical obstruction. We report case of small bowel obstruction produced by an internal hernia generated by a Meckel's diverticulum in the foramen of Winslow.

Adaptation culturally and linguistically to the Chilean population and validation the Dry Eye Questionnaire 5.

BACKGROUND AND OBJECTIVE: There are different methods for evaluating dry eye disease (DID), including questionnaires that analyze different aspects of its symptoms, which are important for its better understanding and therapeutic management. The Dry Eye Questionnaire 5 (DEQ-5), is unique in its kind, because in addition to its simplicity, it measures symptoms in 4 dimensions. The aim of this study is to adapt culturally and linguistically and validate this instrument to the Chilean population. MATERIAL AND METHODS: For the adaptation, the translation and retro-translation of the original version was carried out, its linguistic analysis, the pilot test and the expert panel review (which included a linguistics specialist) were used. For the validation, a psychometric analysis of reliability and validity of the construct was incorporated. The sample in which it was validated was constituted by 205 people with dry eye disease. RESULTS: 141 (69%) of the respondents were women, the mean of age was 48 years ±16,7, and the median of the total score DEQ-5 was 13 points (R.I 8-15 points). The adapted version resulted in a Cronbach alpha of 0.8085, scoring that classified it as good. DISCUSSION: The questionnaire DEQ-5, which was adapted and validated, was a good instrument to be used in populations with similar characteristics of those in the study. More so, the factor analysis enriched comprehension of the way in which people with dry eye disease relate their symptoms and which questions relate more between them, representing in a better way the aspects evaluated of the symptomatology of this disease.

Should phenotype of previous preterm birth influence management of women with short cervix in subsequent pregnancy? Comparison of vaginal progesterone and Arabin pessary.

OBJECTIVE: To investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound. METHODS: This was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery. RESULTS: Between 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth. CONCLUSIONS: Cervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Gallotannin Improves the Photoaged-Related Proteins by Extracellular Signal-Regulated Kinases/c-Jun N-Terminal Kinases Signaling Pathway in Human Epidermal Keratinocyte Cells.

Tannins are a type of polyphenols found in several fruits such as grapes and berries, and nuts such as aronias and acorns. Both hydrolyzable tannins and condensed tannins are referred to as tannins. Among the hydrolyzable tannins, gallotannin has a strong antioxidative property and is known to protect the skin by inhibiting the precursors of elastolytic enzymes. However, its mechanism of protection against ultraviolet B (UVB) damage in human fibroblasts and keratinocytes has not yet been elucidated. In this study, we investigate the antioxidant and antiaging effect of gallotannin on UVB-irradiated human cells by studying its effect on extracellular signal-regulated kinases/c-Jun N-terminal kinases (EKRs/JNKs) signaling related to cell growth and differentiation/stress apoptosis. The results showed that gallotannin improved collagen synthesis, reduced metalloproteinase-1 (MMP-1) expression in a dose-dependent manner, and downregulated MMP-1 levels through the ERK/JNK signaling pathway in UVB-irradiated human cells. Gallotannin also increased glutathione but did not increase transforming growth factor beta 1, which induces fibrosis. We propose that gallotannin is a novel agent for protection against UVB, and acts as an antiaging agent that can be used in food, pharmaceuticals, and cosmetics.

Glycemic control and maternal and fetal outcomes in pregnant women with type 1 diabetes according to the type of basal insulin.

OBJECTIVE: To examine the potential role of the type of basal insulin on glycemic control and maternal and foetal outcomes in pregnant women with type 1 diabetes (T1DM). STUDY DESIGN: Retrospective cohort study of pregnancies attended at 18 Spanish tertiary hospitals. INCLUSION CRITERIA: T1DM, singleton pregnancies, delivery between 2002-2010, and use of the same basal and prandial insulin from before pregnancy until delivery. RESULTS: A total of 1534 pregnancies were included. The basal insulin most commonly used was Neutral Protamine Hagedorn (NPH) (51.7%), followed by glargine (23.2%) and continuous subcutaneous insulin infusion (CSII) (21.1%). CSII users had longer diabetes duration. Multiple logistic regression analysis showed that CSII was independently associated with lower doses of insulin, higher glycated haemoglobin (HbA1c) in all trimesters, and higher rates of miscarriage, preterm birth and neonatal hypoglycemia. Glargine was related to a higher risk of preterm birth and a small-for-gestational age infant (SGA). The odds ratios (OR) of the associations between insulin type and clinical outcomes (from 0.642 to 4.894) have a relevant magnitude. CONCLUSIONS: In this observational study of pregnant women with T1DM, the type of basal insulin was independently associated with metabolic variables and foetal outcomes.

Do knowledge of uterine artery resistance in the second trimester and targeted surveillance improve maternal and perinatal outcome? UTOPIA study: a randomized controlled trial.

OBJECTIVES: To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population. METHODS: This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor < 37 weeks' gestation, placental abruption, stillbirth, gestational hypertension, admission to neonatal intensive care unit and neonatal complications. Secondary outcomes were a composite score for maternal complications (disseminated intravascular coagulation, maternal mortality, postpartum hemorrhage, pulmonary edema, pulmonary embolism, sepsis), and medical interventions (for example, corticosteroid administration and induction of labor) in patients developing placenta-related complications. RESULTS: In total, 11 667 women were included in the study. Overall, PE occurred in 348 (3.0%) cases, early-onset PE in 48 (0.4%), IUGR in 722 (6.2%), early-onset IUGR in 93 (0.8%) and early-onset PE with IUGR in 32 (0.3%). UtA mean pulsatility index > 90(th) percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07-1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11)). CONCLUSIONS: Routine second-trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cardiac complications during pregnancy are better predicted with the modified WHO risk score.

BACKGROUND/OBJECTIVE: Several risk scores (RSs) have been used to stratify risk of cardiac complications (CCs) in pregnant patients with heart disease. We aimed to compare and contrast the accuracy of several RSs for predicting CC in this population. METHODS: Prospective inclusion of all consecutive pregnant patients with heart disease, and follow-up until 6 months postpartum. CCs were defined as primary if admission was required due to heart failure, arrhythmia or thromboembolic events, and secondary if the decline in NYHA class compared with baseline was >2 or urgent invasive cardiac procedures were needed. The discriminatory power of each RS was assessed by the area-under-the receiver-operating characteristic (ROC) curve (AUC). RESULTS: 179 patients, mean age: 32 years, accounted for 13.4% of CC (primary 11.7%, secondary 1.7%); the main diagnosis was congenital heart disease (CHD) in 68% followed by valvulopathies in 16%, arrhythmia in 7% and myocardiopathies in 5%. 22% (n=40) were classified as mWHO=1, 59% (n=105) mWHO=2 including subgroup 2-3, 14% (n=26) mWHO=3 and 4%(n=7) mWHO=4; 1 patient was unclassifiable. mWHO showed a better AUC (0.763) than CARPREG (0.67). For the CHD population, ZAHARA RS showed an AUC of 0.74, and Khairy an AUC of 0.632. CONCLUSIONS: mWHO was better at predicting CC than CARPREG; mWHO was also better at predicting CC than the specific CHD RS in the CHD subgroup. PRACTICE: There are an increasing number of pregnant women with HD. IMPLICATIONS: Improved prediction of CC risk during pregnancy can provide better preconception assessment in women with HD.

Antenatal corticosteroids and perinatal outcomes in infants born at 23-25 weeks of gestation.

OBJECTIVES: To evaluate the perinatal results of infants born between 23 and 25.6 weeks of gestation. METHODS: Medical charts of all women giving birth prematurely (23-25.6 w) from January 2005 to December 2011 were retrospectively reviewed. Cases of malformed infants or deliveries elsewhere were excluded. RESULTS: 198 infants were included. Chorioamnionitis occurred in 86 (43.4%) of the whole group: 26 (86.7%) in the 23-week; 35 (53.8%) in the 24-week and 25 (24.3%) in the 25-week groups. Foetal maturation with antenatal corticosteroids was complete in 119 cases (60.1%): 4 (13.3%) in the 23-week; 35 (53.8%) in the 24-week and 80 (77.7%) in the 25-week groups. Foetal death at birth occurred in 22 cases (11%) and 61 newborns (30.8%) died in the neonatal period. Of the 106 survivors with 2 years complete follow-up, 45 infants (42.4%) did not present sequelae; 16 infants (15.1%) had severe sequelae. A 66.6% (4) of infants born at 23 weeks of gestation did not present sequelae compared with a 32.3% (11) at 24 weeks and 45.4% (30) at 25 weeks. CONCLUSIONS: The chorioamnionitis rate was higher when gestational age was lower. The foetal maturation rate was higher when gestational age was higher. A low severe sequelae rate was observed in the whole series, particularly in the 23-week group where the rate was lower than expected; however, these results could have been influenced by the small size of the 23-week group.

2,3,5,6-Tetramethylpyrazine of Ephedra sinica regulates melanogenesis and inflammation in a UVA-induced melanoma/keratinocytes co-culture system.

BACKGROUND: 2,3,5,6-Tetramethylpyrazine (TMP) is known as a composition of Ephedra sinica and it has been used in the treatment of several disorders such as asthma, heart failure, rhinitis, and urinary incontinence. It has been reported that TMP inhibits melanoma metastasis and suppression angiogenesis by VEGF. OBJECTIVE: The inhibitory activity of melanogenic proteins by TMP was confirmed in UVA-induced melanoma/keratinocyte co-culture system in this paper. METHODS: The melanin content, cell viability and cytokines release such as TNFα, IL-1ß, IL-8 and GM-CSF were measured by ELISA assay. In addition, TRP1, MITF and MAPK signaling protein expression were also evaluated by Western blotting analysis. RESULTS: Decreasing melanogenic factors (TRP1, MITF, and MAPK) and factors (TNFα, IL-1ß, IL-8, and GM-CSF) improving skin cancer and inflammation were identified. CONCLUSION: It suggests that TMP can serve as a potent candidate for regulation of melanogenesis.

Expectant management in pregnant women with early and severe preeclampsia and concomitant risk factors.

AIM: The aim of this study was to demonstrate that women with severe early-onset preeclampsia and concomitant risk factors benefit from expectant management. METHODS: This retrospective study was conducted between January 2009 and December 2010. Stable women with severe preeclampsia between 23+6 and 33+6weeks of gestation were admitted to the IOCU for conservative management. They were classified into two groups: those with concomitant risk factors, i.e. associated medical conditions, HELLP syndrome, severe oligohydramnios, fetal growth restriction and multiple pregnancies (group A) and those without (group B). P values lesser than 0.05 were considered statistically significant. RESULTS: No significant differences were found in maternal and perinatal outcomes between groups. Neither were differences observed in pregnancy prolongation (mean: 8.42days (SD±7.462) in group A and 10.5days (SD±8.235) in group B (p=0.391)). At the start of expectant management, 31.8% of fetuses had an abnormal middle cerebral artery Doppler; prior to delivery, this percentage was 77.4%. CONCLUSION: Pregnant women with severe early-onset preeclampsia and associated risk factors benefited from expectant management. During expectant management using a continuous magnesium sulfate regimen, the majority of fetuses showed cerebral vasodilatation. The exact clinical value of this finding should be clarified in further studies.

Vaginal progesterone, cerclage or cervical pessary for preventing preterm birth in asymptomatic singleton pregnant women with a history of preterm birth and a sonographic short cervix.

OBJECTIVE: To compare the outcome of pregnancy in cohorts of women with singleton pregnancy and history of preterm birth and sonographic short cervix managed with different treatment protocols, namely cerclage, vaginal progesterone or cervical pessary. METHODS: This was a comparison of three management protocols for women with singleton pregnancy and a high risk of preterm birth because of a prior spontaneous preterm birth before 34 weeks and a shortened cervical length detected by transvaginal ultrasound. The study included 142 women who were initially treated with cerclage (USA), 59 with vaginal progesterone (UK) and 42 with cervical pessary (Spain). Perinatal outcomes were compared between the three cohorts. RESULTS: There were no statistically significant differences in perinatal losses, neonatal morbidity and preterm births among the three groups, apart from a higher rate of preterm birth before 34 weeks' gestation after treatment with vaginal progesterone in comparison with treatment with cervical pessary (32% vs 12%; relative risk (RR) = 2.70; 95% CI, 1.10-6.67). When only the subgroups of women with cervical length < 25 mm, irrespective of gestational age, were compared, the difference between these two cohorts was not statistically significant (RR = 2.21; 95% CI, 0.83-5.89). CONCLUSION: Cerclage, vaginal progesterone and pessary appear to have similar effectiveness as management strategies in women with singleton pregnancy, previous spontaneous preterm birth and short cervix. Direct randomized comparisons of these strategies, or combinations thereof, are needed to determine optimal management.

First trimester serum angiogenic/anti-angiogenic status in twin pregnancies: relationship with assisted reproduction technology.

BACKGROUND: The risk of pre-eclampsia (PE) increases in twin pregnancies, especially when assisted reproduction technologies (ART) are used. The aim of this study was to assess angiogenic/anti-angiogenic factors in maternal serum in the first trimester of twin pregnancies and establish if the mode of conception influences angiogenic status. METHODS: This prospective study enrolled women with twin (n = 61) and singleton (n = 50) pregnancies. Dichorionic twin pregnancies were divided into two groups according to their mode of conception. Singleton pregnancies were used as the control group. Soluble fms-like tyrosine kinase (sFlt-1), free placental growth factor (PlGF) and soluble endoglin (sEng) concentrations were measured in the first trimester maternal serum. RESULTS: In the first trimester, women with twin pregnancies had higher serum concentrations of the anti-angiogenic factor sFlt-1 than that with singleton pregnancies (3924 ± 250 versus 2426 ± 162 pg/ml, respectively; P < 0.001). Maternal serum PlGF concentrations were lower in singleton pregnancies than those in twin pregnancies (37 ± 3.7 versus 59 ± 5.6, respectively; P < 0.001). Serum concentrations of sFlt-1 were higher in twin pregnancies conceived by ART than those in spontaneous twin pregnancies (4313 ± 389 versus 3522 ± 300 pg/ml, respectively; P < 0.05). No differences between groups were observed for sEng. CONCLUSIONS: In the first trimester, twin pregnancies conceived using ART showed a heightened anti-angiogenic status that could explain the increased risk of PE in these cases.

Sonographic cervical length measurement in pregnant women with a cervical pessary.

OBJECTIVES: The aims of this study were to describe and assess the feasibility of measuring cervical length by standard transvaginal sonography (TVS) and transperineal sonography (TPS) in women with a cervical pessary and compare these measurements with those obtained with a new transvaginal technique. METHODS: Measurement of cervical length by TPS was attempted immediately before measurement using TVS in 48 women with a cervical pessary at between 22 and 23 weeks' gestation. The TVS procedure consisted of two types of measurement: in the first, the probe was placed on the anterior fornix (standard technique) and in the second, the probe was inserted into the pessary to touch the anterior cervical lip (new technique). Two physicians consecutively performed these procedures and compared the measurements obtained. Intraclass correlation coefficients (ICCs) with 95% CI were used to evaluate interobserver reliability, and Bland-Altman analysis was used to assess interobserver agreement. RESULTS: In total, 258 measurements (obtained from 43 women) were analyzed. Interobserver ICCs of the measurements obtained were 0.58 (95% CI, 0.34-0.75) for TPS, 0.65 (95% CI, 0.44-0.79) for the standard TVS technique and 0.97 (95% CI, 0.95-0.98) for the new TVS technique. Bland-Altman analysis showed small mean differences between measurements obtained by two physicians for the three methods, but with narrower limits of agreements (LOA) for the new TVS technique: TPS mean difference - 0.99 mm (95% LOA, - 13.23 to 11.25 mm), standard TVS technique mean difference - 0.23 mm (95% LOA, - 10.90 to 10.44 mm) and new TVS technique mean difference - 0.01 mm (95% LOA, - 2.57 to 2.55 mm). It was apparent from the images obtained that the external os was not visible in 89% of cases when either the TPS or standard TVS technique was used. However, the external os was visible in all cases when the new TVS method was used. CONCLUSIONS: We propose a new technique for measuring and monitoring cervical length in women with a cervical pessary that provides improved visualization of the cervix and increased reliability in comparison to established techniques.

Phylogenetic analysis in a recent controlled outbreak of Crimean-Congo haemorrhagic fever in the south of Iran, December 2008.

Crimean-Congo haemorrhagic fever (CCHF) is a viral zoonotic disease with a high mortality rate in humans. The CCHF virus is transmitted to humans through the bite of Ixodid ticks or contact with blood or tissues of CCHF patients or infected livestock. In December 2008, a re-emerging outbreak of CCHF occurred in the southern part of Iran. Five people were hospitalised with sudden fever and haemorrhaging, and CCHF was confirmed by RT-PCR and serological assays. One of the cases had a fulminant course and died. Livestock was identified as the source of infection; all animals in the incriminated herd were serologically analysed and more than half of them were positive for CCHFV. We demonstrated that two routes of transmission played a role in this outbreak: contact with tissue and blood of infected livestock, and nosocomial transmission. Phylogenetic analyses helped to identify the origin of this transmission. This outbreak should be considered as a warning for the national CCHF surveillance system to avoid further outbreaks through robust prevention and control programmes.

The epidemiology of tick-borne relapsing fever in Iran during 1997-2006.

BACKGROUND: Tick-borne relapsing fever is an acute febrile and endemic disease in Iran. For many reasons, the incidence of disease is on decrease, however tick-borne relapsing fever is still a health issue in the rural areas for travelers. This study was carried out during 1997-2006 to investigate the tick-borne relapsing fever in Iran. METHODS: Based on a cross-sectional, retrospective and descriptive study in all the provinces, the residents in the endemic areas who were febrile and suspicious to tick-borne relapsing fever were enrolled in the study. Tick-borne relapsing fever is a notifiable disease in Iran and the national communicable disease surveillance data were used through questionnaires. The infectivity of Ornithodoros species to Borrelia also was studied in two highly endemic areas including Hamadan and Qazvin provinces. RESULTS: During 1997-2006, a total of 1415 cases have been reported from the entire country. The highest prevalence was observed in year 2002 with the incidence rate of 0.41/100,000 population. Ardabil province is the first ranked infected area (625 out of 1415), followed by Hamadan, Zanjan, Kurdestan and Qazvin provinces sequentially. The disease is recorded during the whole year but its peak occurs during summer and autumn. There have been 87.6% of the cases recorded from June to November. Forty five percent of the infected cases were male and one third of the patients were under 5 years of age. Fifty four percent of the patients comprise the children under 10 years. Ninety two percent of the cases were living in rural areas where their dwellings were close to animal shelters. They were involved mainly with farming and animal husbandry activities. All the febrile patients with confirmed spirochetes in their blood samples were treated according to a national guideline for tick-borne relapsing fever treatment. Only 7% of the patients were hospitalized and 0.8% of them exhibited the Jarisch-Herxheimer reaction. The study of infectivity of Ornithodoros species to Borrelia revealed that Ornithodoros tholozani was infected with Borrelia persica and Ornithodoros erraticus with Borrelia microti. CONCLUSION: Travelers to the rural areas with high prevalence of the disease should be made aware of the risk of tick-borne relapsing fever and use of appropriate control measures. Communicable disease surveillance including tick-borne relapsing fever should be pursued as well.