Surgery was undertaken at 125 days gestation for implantation of fetal catheters and placement of a silastic cuff around the umbilical cord. At 132 days gestation (0.89 term), the cuff was inflated to induce umbilical cord occlusion (UCO), or sham (control). Fetal arterial blood samples were collected for assessment of fetal wellbeing and the pregnancy continued until birth. At birth, behavioral milestones for newborn lambs were recorded over 24 h, after which the lambs were euthanased for brain collection and histopathology assessments. After birth, UCO lambs displayed significant latencies to (i) use all four legs, (ii) attain a standing position, (iii) find the udder, and (iv) successfully suckle - compared to control lambs. Brains of UCO lambs showed widespread pathologies including cell death, white matter disruption, intra-parenchymal hemorrhage and inflammation, which were not observed in full term control brains. UCO resulted in some preterm births, but comparison with age-matched preterm non-UCO control lambs showed that prematurity per se was not responsible for the behavioral delays and brain structural abnormalities resulting from the in utero asphyxia. These results demonstrate that a single, brief fetal asphyxic episode in late gestation results in significant grey and white matter disruption in the developing brain, and causes significant behavioral delay in newborn lambs. These data are consistent with clinical observations that antenatal asphyxia is causal in the development of neonatal encephalopathy and provide an experimental model to advance our understanding of neuroprotective therapies.Brief but severe asphyxia in late gestation or at the time of birth may lead to neonatal hypoxic ischemic encephalopathy and is associated with long-term neurodevelopmental impairment. We undertook this study to examine the consequences of transient  We have also observed cerebral hypoperfusion and disruption of cortical activity for up to 24 h following umbilical cord occlusion (UCO) We in utero compensate for this damage prior to birth. For example, erythropoietin (EPO) and its receptor in utero asphyxia produced by UCO, and administration of EPO has been suggested as a treatment for perinatal brain damage The first objective of this study was to determine the effects on lamb survival and behavior of a brief asphyxial insult produced by occluding the umbilical cord at 132 days gestation - considerably before the expected time of parturition (∼147 days). Thus, we chose this gestational age in order to extend our previous work All experimental procedures had received prior approval from the Monash University School of Biomedical Sciences Animal Ethics Committee, in accordance with the Australian Code of Practice Guidelines for the Care and Use of Animals for Scientific Purposes.In Vivo Metric, Healdsburg, USA) was secured around the umbilical cord. Immediately before placing the cuff around the umbilical cord, the volume of water needed to fully inflate the cuff and occlude the blood vessels was determined. In the other 7 fetuses the cord was manipulated at surgery but the cuff was not placed around the cord. The fetuses were then replaced in the uterus, the membranes and uterine incision repaired, and the catheters externalized through a small incision in the ewe’s flank. A fetal arterial blood sample (0.5 ml) was collected each day to measure PO2, PCO2, pH, O2 saturation and blood lactate  and after 7 days recovery the experiment was commenced.Fourteen pregnant Merino-Border Leicester multiparous 4–6 year-old ewes carrying a single fetus (n = 13 ewes) and one twin pregnancy (full term control) were used in this study. Gestational length was known to within 24 h from the mating records. At 125 days gestation (term is ∼147 days), ewes were given prophylactic antibiotics  and general anesthesia was induced by a bolus i.v injection of 20 ml thiopentone sodium , and anaesthesia was maintained with isoflurane  in oxygen/nitrous oxide through an endotracheal tube. Under aseptic conditions, the uterus was identified through a midline incision, and the fetal rump exposed. A polyvinyl catheter  filled with heparin-saline was inserted into one femoral artery and advanced approximately 7.5 cm towards the heart; this catheter was used to obtain arterial blood samples and to record fetal arterial pressure. A second, larger bore catheter was secured onto the fetal skin to measure amniotic fluid pressure. In 7 fetuses an inflatable silastic cuff . At 132 days gestation, UCO was undertaken in the 7 fetuses where the umbilical cuff had been implanted, with injection of a volume of sterile water (2–3 ml) into the cuff to inflate it sufficiently to cause complete cessation of blood flow in the umbilical cord. The duration of the occlusion was set at 10 min, but if mean fetal arterial pressure fell to <20 mmHg the cuff was released and the duration of occlusion was recorded. Fetal arterial blood samples (2–3 ml) were taken at −60, −5, 5, 10, 30, 60, 120, 240, 480, and 720 minutes relative to the onset of the cord occlusion at time 0. Fetal heart rate and arterial pressure were recorded before, during and for 24 h after the cord occlusion, after which the ewe was moved to a large ‘lambing pen’ until the onset of labor. Where no cuff had been implanted, the ewes were also moved to the lambing pen on day 133 of gestation. Fetal blood samples (1–1.5 ml) were taken each day to monitor the condition of the fetuses.Because occlusion of the umbilical cord resulted in early delivery in 5 of the 7 UCO lambs compared to the sham-occluded group (see Results), a further group of 3 (one singleton and two twin) ewes was introduced to the study where labor was induced by intramuscular injection of betamethasone  at 12∶00 h, followed by Epostane (50 mg in 2 ml ethanol) at 17∶00 h on day 136 of gestation. This led to the onset of premature labor 36–48 h following the Epostane injection Four closed-circuit cameras  with infrared night vision were mounted on the ceiling directly above each lambing pen and were used to continuously monitor the ewe for signs of labor, birth and lamb behavior. At the onset of the final stages of labor when membranes were visible at the vulva and/or there was loss of amniotic fluid, at least two investigators were present to assist the ewe if necessary, to cut and secure the catheters when the lamb was delivered and to remove the umbilical cuff immediately after the lamb was clear of the birth canal.We utilised a neurobehavioral assessment based on observations previously conducted in sheep to monitor their wellbeing following birth The brain was removed and cut sagittally into left and right hemispheres and each half was cut coronally into approx. 5 mm thick blocks. . All blocks were immersion-fixed in 4% paraformaldehyde for 48 h, and then immersed in 70% ethanol for 3 to 4 h, cleared in sulphur-free xylene and paraffin embedded. Sections of forebrain were cut at 10 µm thickness and stained for morphological changes with hematoxylin and eosin (H&E). Luxol Fast Blue was used to assess myelin organization and Mallory trichrome staining was used to assess the presence of brain hemorrhage and micro-bleeds, using criteria published elsewhere Examination and scoring of neuropathology outcomes were carried out by an investigator blinded to the treatment (MCM). The brain regions of interest included the frontal cortex, parasagittal cortex and lateral ventricle, subcortical and periventricular white matter, hippocampus and basal ganglia/thalamus. Photomicrographs were taken under light microscopy  at 400x magnification and examined under light microscopy. Neuropathologies were noted, scored and/or counted using a 3 point scoring system based on previously published criteria p<0.05.A Shapiro-Wilks test for normality and Levene’s test for homogeneity of variance were run on all data. Physiological parameters  were analyzed by SPSS software using a repeated measures one-way ANOVA, with a ‘Contrast (simple)’ post hoc test to compare to pre-UCO values. Body and organ weights were analyzed using a one-way ANOVA, and a Tukey’s post hoc test. Behavioral data for lambs in the three study groups  were analyzed using a Kruskal Wallis one-way ANOVA and if significant differences were present, a post hoc analysis using a Mann-Whitney U test was done. Caspase-3 and CNPase data were analysed using a one-way ANOVA and if significant, a student newman keul post hoc test was run. Neuropathological scores were analysed using Kruskal-Wallis test followed by a Dunn’s multiple comparisons post hoc test. All statistical analyses were conducted using SPSS (v18 for Windows). Values are shown as mean ± standard error (SEM). Significance was set at 2, O2 saturation, PCO2, and pH had recovered and were not different from the pre-occlusion values. The increase in plasma lactate concentrations returned to normal values more slowly; by 4 h after UCO the base excess was not different from the control value, and the fetal arterial blood lactate concentration remained slightly but significantly higher than the pre-occlusion value until 24 h after the UCO . After injection of Epostane to induce labor, preterm control lambs were all born at 138–139 days, with a mean birth weight of 3.74±0.13 kg (p = 0.6 vs UCO lambs and p<0.05 vs full-term control lambs). Organ weights relative to body weight were not different between the 3 groups, except adrenal gland relative to body weight was significantly increased in UCO lambs compared to control full-term and preterm control lambs (Control lambs were born between 147 and 151 days gestation (147.5±0.9 days), whereas UCO lambs delivered between 134 and 147 days  in UCO brains, compared to both full-term and preterm controls  were found in the brain only in UCO lambs 24 h after birth, consistent with CNS inflammation. This is of particular importance as neutrophils are typically the first to infiltrate the brain following hypoxia-ischemia, followed by macrophages and lymphocytes Parenchymal abnormalities such as vacuolization were also observed in the post-UCO brains, but not in either the full-term or preterm control lambs. These abnormalities were relatively widespread in cortical gray and white matter. This is consistent with cranial ultrasound and MRI findings in human infants showing parenchymal injuries and lesions to these brain regions at term A striking histopathological finding was the presence of bleeds in the brains of UCO lambs, particularly in the thalamus. Although micro-bleeds were seen both in preterm and full-term control brains – thus suggesting that birth itself might induce a certain amount of intra-parenchymal haemorrhage – these were only observed around small blood vessels, and serious bleeds with parenchymal involvement were seen only in the brains of lambs from the UCO cohort. While intra-ventricular hemorrhage (IVH) is relatively uncommon in full-term neonates, it has been noted to occur with maternal abdominal compression, birth trauma and perinatal asphyxia Several limitations of this study need to be acknowledged. Firstly, the behavioural observations made only up to 24 h after birth may not fully assess the consequence for the lamb of the asphyxial insult sustained at 132 days gestation. While there were no obvious signs of seizure in the UCO lambs, we cannot exclude that this did not occur; the EEG was not measured as this would have meant connecting the lamb to recording apparatus which would have interfered with lamb behaviour and lamb-ewe interactions. In other respects, the particular behaviours that we monitored, which reflect the ability of the lamb to resuscitate and feed itself, are as close as possible to those that would be made by neonatologists in their immediate assessment of the health of the newborn infant. Similar behavioural milestones have been used in previous studies to monitor lamb well-being in utero asphyxia.Secondly, we were not able to determine the true length of labour, which might have contributed to some of the variability observed between the UCO lambs. Delivery of the lambs by caesarean section would have removed this limitation, but the necessary use of an anaesthetic agent  and the need to resuscitate the neonatal lamb would have prevented examination of the normal process of spontaneous recovery of the lamb at birth, and removed the opportunity to examine ewe-lamb interaction that leads ultimately to the lamb managing to find the teat and begin to suckle. Indeed, our main aim was to see to what extent the capacity for normal behaviour in lambs at birth had been restricted by the preceding event of brief Thirdly, the fetuses in the UCO group were subjected to frequent blood sampling before and after occlusion of the umbilical cord whereas the full-term and preterm control lambs were not. The 10 arterial blood samples (2–3 ml) taken over 12 h (see Methods for details of times), and further samples at 24 and 48 h after UCO, represent a blood loss of up to 7.3%, based on the birth weight of 3.52 kg for these fetuses, and assuming a blood volume of 140 ml/kg fetal brain have been studied. While our results support that a in utero asphyxic episode delivered some time (approx. 15 days) before the expected time of delivery was strongly associated with behavioral deficiencies and brain pathology in the neonate, it has not been possible to differentiate between: (i) the severity of injury caused at the time of insult; (ii) additional injury that may arise at birth as a legacy of the original insult; and (iii) cellular responses that are initiated to repair the damaged fetal brain. This may explain some of the variability we observed in the lambs brains at 24 h after birth. UCO in fetal sheep has been shown to increase expression of EPO In pursuit of a relevant animal model of perinatal hypoxic-ischemic brain injury, the present sheep study can be added to those which use the pregnant macaque monkey in utero asphyxia in sheep has consequences that include preterm birth, neuro-functional deficits, and neuropathology that persist until after birth. These findings have important implications for the quest to find clinically useful and relevant treatments that protect the fetal and neonatal brain.In conclusion, the present study provides evidence that a brief, ‘sentinel’ event incorporating global fetal hypoxia, hypercapnia and acidemia in late gestation results in brain damage and neurodevelopmental delays at birth, and may be associated with premature birth. Our data also shows that preterm birth accounts for some of the delay in achieving some of these milestones. The neuropathology observed in the brains of UCO lambs 24 hours after birth corresponds with some of the anatomical and pathological abnormalities reported in cerebral palsy, and is consistent with the ’typical’ morphological changes seen in acute brain inflammation and demyelination. These results inform us that brief


Prostatic utricle cyst is a rare midline cystic lesion between the urinary bladder and the rectum, commonly associated with hypospadias. Along with its rarity, it presents a challenge in its diagnosis and proper management. We report a case of large prostatic utricle cyst that was managed conservatively. Cystic enlargement of prostatic utricle, a vestigial remnant of mullerian duct, is a rare condition in males. It is present in up to 4% and 1% in newborns and adults respectively [1]. In some cases, prostatic utricle is markedly enlarged and present as a cystic lesion in perineum or in pelvic cavity posing diagnostic dilemma. We present a case of large prostatic utricle cyst associated with urethral stricture.A 15-year-old boy presented with dysuria for the last 3 months. He had mid penile hypospadias that was repaired in early childhood. The meatus was at ventral surface of glans and of adequate calibre. His laboratory investigations were within normal limits. Uroflowmetry confirmed poor flow while ultrasonography suggested 30 gm prostate with a midline hypoechoic cyst extending posterior to bladder into pelvic cavity. Bladder had normal wall thickness but had 40 ml as residual urine. Retrograde and voiding urethrography showed dilated penile urethra and distal bulbar urethral stricture with contrast filling in a blind ending tubular structure posterior to the bladder, arising at the level of prostatic urethra and extending beyond the level of bladder neck . This was not palpable per abdomen. Cystourethroscopy revealed a passable stricture in distal bulbar urethra and an opening at the verumontanum ending into a blind cavity. Dorsal onlay buccal mucosa graft (BMG) urethroplasty done for the strictured segment but no treatment was offered for the prostatic utricle cyst. After urethroplasty alone, flow improved, post-void residual urine decreased and patient improved symptomatically. Patient kept on regular follow-up foe last two years and planned for surgical excision of utricle in future only if it becomes symptomatic. Prostatic utricle is a remnant of mullerian duct in males which often present as a sac with a slit like orifice at the apex of verumontanum that projects upward and backward into the substance of the prostate [2]. The incidence of prostatic utricle cyst is 11% to 14% in association with hypospadias or intersex anomalies and up to 50% in the presence of perineal hypospadias [5]. A prostatic utricle cyst can have varied presentation ranging from asymptomatic to recurrent UTI, epididymitis, hematuria, pyuria, urinary incontinence, oligospermia, retention or constipation . Rarely it may enlarge and present as an abnormal lower abdominal or pelvic mass or observed during pelvic or trans-rectal ultrasonography as a fluid filled cavity between bladder and rectum . Though MRI can easily identify these cysts by virtue of their high signal on T2-weighted images [7], simpler radiological studies like retrograde urethro¬graphy can equally differentiate utricle cysts from other prostatic and periprosatic cysts demonstrating it location and connection with posterior urethra [8]. Endoscopic cannulation of the utricular opening with contrast material infusion into the cyst is another method to accurately demonstrate the communication of the urethra with the mass, and can determine the anatomical relationship with surrounding structures [1]. Because these conditions are usually managed conservatively, pathologic proof is not possible in all cases, and the diagnosis is often made on the basis of clinical features and imaging appearance [7].Differential diagnoses include mullerian duct cysts, bladder diverticulum, teratoma, seminal vesicle cyst, epididymal cyst and Wolffian duct cyst . Mullerian duct cyst though may be connected to the verumontanum by a stalk; it does not communicate with the posterior urethra, present late in life and is not associated with genitourinary anomalies . Seminal vesicle and Wolffian duct cysts are located off the midline and contain sperms [1]. Seminal vesicle cysts result from congenital atresia of the ejaculatory duct and are often associated with ipsilateral renal agenesis [7].Surgical management of prostatic utricle cyst remains challenging, because of the rarity of this disorder and due to the close proximity of these lesions to the ejaculatory ducts, pelvic nerves, rectum, vas deferens and ureters [1]. Schuhrke et al, reported endoscopic transurethral cyst catheterization and aspiration, cyst orifice dilatation, incision, or unroofing that suits for small prostatic utricle cysts but recurrence rates were high [3]. Open excision is the better definitive treatment but the problem is the location of cyst which is considered too high to be approached through the perineum or too low to be approached through the abdomen. Several approaches have been described. However, all require extensive dissection, sometimes having two stages and often result in poor exposure. The efforts sometimes ended in incomplete excision, and complicated dissection often needed the excision of one or both seminal vesicles, vas, and portions of the prostate .Surgical treatment should be reserved for symptomatic utricle cysts only. Clinical dilemma arises when a patient presents with symptoms. Concomitant presence of other pathologies may produce similar symptoms and treatment of primary pathology should be done first. Chances of associated infer¬tility and incontinence must be explained to the patient before intervention [8]. In our case, the prostatic utricle was asymptomatic and the presenting symptoms were due to the bulbar urethral stricture. Thus surgical treatment should be individualised and offered to those with persistent symptoms where other causes of similar symptoms have been are treated. Source of Support: NilConflict of Interest: None declared


Despite the burden of rheumatic and musculoskeletal diseases (RMDs), these conditions probably deserve more attention from public health authorities in several countries including developed ones. We assessed their contribution to disability.Data on disabilities associated with RMDs were extracted from the national 2008–2009 Disability-Health Survey of 29,931 subjects representative of the population in France. We used the core set of disability categories for RMDs of the World Health Organization's International Classification of Functioning, Disability and Health for analysis. Diagnosis and disabilities were self-reported. We assessed the risk of disability associated with RMDs using odds ratios (ORs) and the societal impact of RMDs using the average attributable fraction (AAF).Overall 27.7% (about 17.3 million people) (95% CI 26.9–28.4%) of the population reported having RMDs. The most prevalent RMDs were low back pain  and osteoarthritis . People reporting osteoarthritis were more disabled in walking  than those without. People reporting inflammatory arthritis were more limited in activities of daily living . From a societal perspective, osteoarthritis was the main contributor to activity limitations . Changing jobs was mainly attributed to neck pain (AAF 13%) and low back pain (11.5%).RMDs are highly prevalent and significantly affect activity limitations and participation restrictions. More effort is needed to improve care and research in this field. Rheumatic and musculoskeletal diseases (RMDs) are a major cause of disability Despite the burden of RMDs and the WHO's Joint and Bone decade initiative extension until 2020 Studies describing disabilities in RMDs are common, but they often focus on one condition, such as rheumatoid arthritis or OA A population-based, self-reported disability survey, the 2008–2009 Disability-Health (DH) Survey, was conducted in France. We previously extracted data from this dataset to assess the respective contribution of chronic conditions to disability in the non-institutionalized population and showed that RMDs, neurological, cardiovascular, and psychiatric disorders were the main contributors This study was planned as a research project. It was performed in collaboration with the French National Institute of Statistics. This study was declared of public interest by the CNIS  and was approved by the CNIL . According to the French law, written informed consent was not required for this type of study.http://www.cmh.ens.fr/greco/enquetes/XML/lil-0459.xml), a cross-sectional population-based survey undertaken by the French National Institute of Statistics and Economic Studies and the French Head Office of Research, Studies, Evaluation and Statistics of the Social Affairs Ministry to describe disabilities. The present work focused on the part of the survey involving the population living in a household  and a low sampling rate for people without daily living restrictions (the largest group). Consequently, the survey respondents were not representative of the French population, but a weighting method, described in the statistic analysis section, allows for estimating representative results at a national level: each of the resulting groups was allocated a specific sampling coefficient that increased with the probability or severity of the presumed handicap. The sampling rate was higher for people living in the geographic areas that were more intensively sampled. From March to July 2008, data were collected for 39 065 subjects across the administrative departments in France. Trained investigators used the computer-assisted interview (CAPI) format to collect data from people in their homes. The questionnaire was 160 pages long and each interview lasted between 2 and 3 hours. A household member or a proxy could answer for identified survey respondents not able to answer alone. The response rate was 76.6%, corresponding to 29 931 subjects with complete data (age range 0–106 years old). Each respondent was assigned a weight reflecting the probability of being investigated and answering the questionnaire, which allowed for estimating representative results at a national level.RMDs were self-reported. Participants were asked to identify their diseases from a list of 52 disorders, which is known to improve the accuracy of self-reporting Table S1), as a numerical variable (number of co-morbidities) or dichotomous variable (co-morbidity represented at least one of these conditions). Data on sex, age, and educational attainment (no diploma represented less than primary school education) were also collected.The survey also collected data on co-morbidities with the same list, which included cardiovascular, neurological, psychiatric, respiratory, sensorial, endocrine, digestive, urologic, dermatologic disorders, and sequelae of injury (Table S2).Disabilities were considered from subjects' reports. With a 160-page questionnaire, respondents were asked about 1) difficulties in performing activities, 2) restrictions in participations, and 3) environmental factors. Experts  provided the linkage between the WHO-ICF core-set categories for musculoskeletal diseases The final weighting factors combined design weights and non-response weights. Design weights were the inverse of the sampling fraction, depending on presumed disability severity and geographic area of residence. Probability of non-response was estimated by logistic regression, with age, sex, type of household, marital status, and questions about health and disability as independent variables. Finally, calibration was based on geographic area of residence, age and sex.For the descriptive analysis, we reported the prevalence of diseases, summarized socio-demographic characteristics and described disabilities by frequencies, means and 95% confidence intervals (95% CIs) estimated using sampling weight.We assessed the contribution of RMDs at both the individual and societal level. To describe the individual risk of disability with a RMD, multiple regression analysis was used to estimate the strength of association between RMDs and disability categories, controlling for age, sex, number of RMDs and co-morbidities, and educational attainment. Results are expressed as odds ratios (ORs) and 95% CIs.To assess the contribution of RMDs at the societal level, we used the average attributable fraction (AAF), defined as the expected proportion of disability preventable by the additional elimination of the condition of interest, after adjustment for a random collection of other disorders (here other RMDs and co-morbidities) Statistical analyses involved use of SAS 9.2 . Sampling weights were accounted for by specific SAS procedures for handling complex sample designs. AAFs were computed with use of the macro developed by Rückinger et al. Table S3). Subjects reporting RMDs were older and had more co-morbidities than those without RMDs , and 59.7% (58.3–61.2%) were women.Overall, 27.7% (95% CI 26.9–28.4%) of the population living in a household reported at least one RMD, corresponding to 17.3 million people. LBP  and OA  were the most prevalent disorders Figure 2Table S4), 21.5% (19.8–23.2%) of subjects reporting OA and 22.5% (19.8–25.3%) reporting inflammatory arthritis had problems walking, compared with 5.3% (4.9–5.7%) of subjects without RMDs. Overall, 16.7% (14.2–19.1%) of subjects reporting inflammatory arthritis had difficulties for shopping (compared with 2.2% (2.1–2.4%) of those without RMD), and 22.3% (19.6–25.1%) for doing housework (compared with 2.6% (2.4–2.8%) of those without RMD). Finally, 49.9% (46.0–53.7%) of subjects reporting osteoporosis had difficulties carrying objects (compared with 15.4% (14.7–16.1%) of those without RMD); 29.8% (26.7–32.9%), needed help from immediate family members (compared with 0.5% (0.4–0.6%) of those without RMD) and 22.7% (19.9–25.4%) from health professionals (compared with 1.8% (1.6–2.0%) of those without RMD). On univariate analysis, subjects with RMDs showed an increased risk of disability in comparison with subjects without (Table S5). On multivariate analysis .Table S6). For subjects ≤20 years old, spine deformity was the main contributor to all disability categories (AAF 15.7% for changing basic body position and 13.8% for moving around). For subjects 21–40 years old, inflammatory arthritis was the main contributor . The impact of LBP on disability categories peaked for subjects 41 to 60 years old . The impact of OA on limitations in activities increased by age up to 80 years old .As expected, the impact of RMDs on disabilities was influenced by age categories  (Table S6). Women were more concerned by OA, inflammatory arthritis  and neck pain , whereas the impact of LBP was greater for men .The overall contribution of RMDs to disability was greater for women than men Click here for additional data file.Table S2Linkage between the core set of disability categories for rheumatic and musculoskeletal diseases (RMDs) in the World Health Organization's International Classification of Functioning, Disability and Health (WHO-ICF) and questions in the 2008–2009 Disability-Health Survey in France.(DOC)Click here for additional data file.Table S3Prevalence of RMDs by sex and age classes from the 2008–2009 Disability-Health Survey in France.(DOC)Click here for additional data file.Table S4Frequency of disability categories of the WHO-ICF core set for RMDs from the 2008–2009 Disability-Health Survey in France.(DOC)Click here for additional data file.Table S5Unadjusted analysis of the association of disability categories of the WHO-ICF core set for rheumatic and musculoskeletal diseases (RMDs) and RMDs from the 2008–2009 Disability-Health Survey in France.(DOC)Click here for additional data file.Table S6Average attributable fraction (AAF) estimates (%) for disability categories of the WHO-ICF core set for RMDs from the 2008–2009 Disability-Health Survey in France by sex and age classes.(DOC)Click here for additional data file.


The mRNA expression was analyzed by quantitative polymerase chain reaction (qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to confirm protein synthesis. The cell growth inhibition rate in the combination group was significantly higher compared with those in the asiaticoside and rapamycin groups for human aortic fibroblasts  and human aortic smooth muscle cells . However, for human coronary artery endothelial cells (HCAECs), the cell growth inhibition rates in the combination, asiaticoside and rapamycin groups were 11.09±1.17, 26.22±4.24 and 34.80±2.80%, respectively (P<0.05), as detected by MTT assay. The qPCR assay showed that in the combination group the level of von Willebrand factor (vWF) mRNA was downregulated, while platelet endothelial cell adhesion molecule (PECAM-1) and endothelial nitric oxide synthase (eNOS) mRNAs were upregulated in HCAECs compared with the rapamycin group (P<0.05). Transforming growth factor (TGF)-β1 and TIMP1 mRNAs were downregulated while Smad7 and matrix metalloproteinase 1 (MMP1) mRNAs were upregulated in HAFs compared with the rapamycin and AT groups (P<0.05). The ELISA showed that the type I collagen level was significantly reduced in HASMCs and HAFs (P<0.05). The data suggest that asiaticoside combined with rapamycin may be effective in the reduction of ISR.The aim of this study was to investigate and characterize the efficacy and mechanism of action of asiaticoside in combination with rapamycin in the inhibition of in-stent restenosis (ISR). The effects of asiaticoside combined with rapamycin on cell proliferation  In-stent restenosis (ISR) following vascular intervention affects the long-term curative effect markedly . AlthougCentella asiatica, a plant of the Umbelliferae family, which has been used for the treatment of hypertrophic scars for numerous years and is an ingredient in Chinese traditional herbal medicines. Previous studies have demonstrated that asiaticoside has a variety of biological effects, including anti-inflammatory  belongs to a family of cytokines with a variety of functions relating to fibrosis, growth, differentiation and apoptosis . TGF-β iposition .TGF-β1 promotes synthesis of the ECM by upregulating the α2 (type I) collagen gene, which results in an increase in the synthesis of type I collagen in fibroblasts; the increased ECM contributes to artery remodeling. The Smad signaling pathway is the primary signaling pathway for TGF-β. Among the Smad family, Smad7 is a general antagonist of the TGF-β family. Smad7 regulates TGF-β signaling via a negative feedback loop and mediates the crosstalk between TGF-β and other signaling pathways . Matrix ® II were purchased from Invitrogen Life Technologies . SYBR® Premix Ex Taq™ II  was obtained from Takara Bio, Inc. . ABI PRISM® 7900HT Sequence Detection system was purchased from Invitrogen Life Technologies and the enzyme-linked immunosorbent assay (ELISA) kit for collagen type I was purchased from Shanghai BlueGene Biotech Co., Ltd. .Bare metal stents (BMSs) were purchased from Shanghai MicroPort Medical (Group) Co., Ltd. , asiaticoside was purchased from Guangxi Changzhou Natural Pharmaceutical Co., Ltd., , rapamycin was obtained from Shanghai Gene Biotechnology company , Shandon Excelsior ES™ Tissue Processor was purchased from Thermo Fisher Scientific Inc.  and the EXAKT 310 CP Basic cutting system was purchased from Exakt Technologies, Inc. . Human aortic fibroblasts (HAFs), human aortic smooth muscle cells (HASMCs) and human coronary artery endothelial cells (HCAECs) were purchased from ScienCell Research Laboratories . Trypsin 0.25% (w/v), 0.53 mM EDTA, endothelial cell medium, fibroblast medium, smooth muscle cell medium, 3--2,5-diphenyltetrazolium bromide (MTT), TRIzol and SuperScriptPrimary HCAECs were cultured in EC growth medium (EBM-2) containing 5% fetal bovine serum (FBS) and 1% endothelial cell growth supplement  and 5 ml of penicillin/streptomycin solution , antibiotics and antimycotics in an incubator with 5% carbon dioxide at 37°C. Primary HASMCs were cultured in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% FBS, 100 U/ml penicillin, 100 U/ml streptomycin and 1 mmol/l L-glutamine in an incubator with 5% carbon dioxide at 37°C. Primary HAFs were cultured in fibroblast medium (FM) containing 20% FBS, 1% fibroblast growth supplement (FGS) and 5 ml 1% penicillin/streptomycin solution (P/S) in an incubator with 5% carbon dioxide at 37°C. All assays were performed on cells at 80–100% confluence, between passages 1 and 2, and were repeated at least 3 times.−12, 1×10−13, 1×10−14, 1×10−15 mol/l) and the rapamycin group was treated with various concentrations of rapamycin . The combination group was treated with asiaticoside and rapamycin, in which the rapamycin concentration was 10−9 mol/l and asiaticoside was used in various concentrations . For qPCR and ELISA analysis, the blank group was treated with 1% dimethyl sulfoxide (DMSO), the asiaticoside group was treated with 10−5 mol/l asiaticoside and the rapamycin group was treated with 10−9 mol/l rapamycin. The combination group was treated with 10−5 mol/l asiaticoside and 10−9 mol/l rapamycin. Following treatment with various drugs, the cells were incubated for 48 h at 37°C. The supernatants were harvested and centrifuged for 15 min at 10,656 × g, and then removed and stored at −20°C for ELISA. The cells were harvested for qPCR.The cells were seeded in 96-well plates with 8,000 cells per well and treated with asiaticoside, rapamycin or both drugs (24 wells for each group) and incubated with 5% carbon dioxide at 37°C for 24 h. For cell viability analysis, the blank group was treated with 1% dimethyl sulfoxide (DMSO), the asiaticoside group was treated with various concentrations of asiaticoside (1×10Cell viability was detected using an MTT assay. MTT (5 mg/ml) was added to each well. The cells were incubated for one hour and then made soluble with cytolysis solution . Absorbance was determined at 570 nm by spectrophotometry.® II. For HCAECs, the vWF, PECAM-1 and eNOS mRNAs were detected. For HAFs, the TGF-β1, Smad7, type I collagen, TIMP1 and MMP1 mRNAs were detected. The primer sequences are listed in ® Premix Ex Taq™ II  was used. The PCR reaction was carried out with the ABI PRISM® 7900HT Sequence Detection system. The samples were analyzed in duplicate. β-actin was used as an internal control. PCR products were separated by electrophoresis in a 2% agarose gel. Densitometry values representing gene expression were first normalized to β-actin expression .Briefly, total RNA was isolated using TRIzol according to the manufacturer’s instructions. Reverse transcription-generated cDNA was obtained using SuperscriptThe culture supernatants were collected and stored at −20°C. For HASMCs and HAFs, the type I collagen level was determined using an ELISA kit for collagen type I.The data were processed using SPSS software . The results are presented as the mean ± standard error of the mean (SEM). The differences among experimental groups were compared by one-way analysis of variance (ANOVA), and two sets of isolated sample data were checked using a Student’s t-test. P<0.05 was considered to indicate a statistically significant result.Compared with the blank group, asiaticoside was able to markedly inhibit the proliferation of HASMCs and HAFs (P<0.01). Compared with the asiaticoside and rapamycin groups, the combination group showed a greater inhibition of HASMCs and HAFs. In HASMCs, the inhibitory rates were 33.12±1.35, 26.21±7.59 and 28.27±4.92%, respectively (P<0.05) and in HAFs, they were 63.50±3.83, 53.06±8.10 and 60.34±4.93%, respectively (P<0.05). These results showed a certain synergism between asiaticoside and rapamycin in HASMCs and HAFs. By contrast, the combination group showed a weaker inhibition of HCAECs compared with that observed in the single drug groups; the inhibitory rates were 11.09±1.17, 26.22±4.24 and 34.80±2.80%, respectively (P<0.05). We suggest that asiaticoside may antagonize the inhibitory effect of rapamycin on vascular ECs .The levels of type I collagen, TGF-β1, Smad7, MMP1 and TIMP1 are shown in As shown in in vivo and in vitro. Asiaticoside combined with rapamycin exerted greater effects than asiaticoside or rapamycin alone. Asiaticoside has a good synergism with rapamycin to inhibit vascular smooth muscle cells (VSMSs) and fibroblasts, while it is also antagonistic to ECs, which may protect the vascular endothelium. The qPCR and ELISA results showed that the combination therapy induced the downregulation of vWF, type I collagen, TGF-β1 and TIMP1, and the upregulation of PECAM-1, eNOS, Smad7 and MMP1. This suggests that the combination therapy may function via the TGF-β pathway.The results indicate that asiaticoside is likely to be effective at reducing ISR ISR is a process involving several pathological pathways, in which VSMC and fibroblast proliferation, neointimal formation, negative remodeling of the artery and epithelialization delay play important roles. Rapamycin-eluting stents (RESs) are widely used to treat severe stenosis of the coronary artery. As an immunosuppressant, rapamycin binds to the cytosolic receptor FKBP12, then inhibits mammalian target of rapamycin (mTOR), which leads to inhibition of the down-regulation of the cyclin-dependent kinase inhibitor p27kip1, thereby inhibiting VSMC proliferation and migration . Howeveret al have demonstrated that asiaticoside inhibits scar fibroblast growth via the Smad signal pathway. The Smad7 protein and mRNA levels were reported to be increased in asiaticoside-treated fibroblasts, compared with control fibroblasts (et al observed that asiaticoside enhanced the expression of type I collagen in human periodontal ligament cells (Our study shows that asiaticoside has a synergism with rapamycin in VSMCs and fibroblasts, which results in a greater increase of cell growth inhibition rate than using a single drug. The combination effects are achieved via several mechanisms. Asiaticoside may inhibit the proliferation of VSMCs and fibroblasts, which is consistent with other studies ,20,21. Aroblasts ,21. It int cells , which cnt cells . Our reset al (In ECs, asiaticoside shows significant activity as a rapamycin antagonist, therefore, the inhibition of cell proliferation in the combination group is lower than that in the rapamycin group. There are few studies concerning the effect of asiaticoside on ECs. Zhou et al  establis


Creatine kinase (CK), lactate dehydrogenase (LDH), and amylase levels of preterm infants following long-term tocolysis in pregnant women are limited. The objective of this study was to determine if the tocolytic therapy affects CK, LDH, and amylase levels in the umbilical blood. This study included 215 preterm infants born to women treated with and without ritodrine hydrochloride. CK, LDH, and amylase levels in the umbilical blood at delivery were determined. Infants were divided according to the ritodrine tocolysis, as follows: Group A (n = 91), not exposed to ritodrine; Group B (n = 44), IV ritodrine for <1 week; Group C (n = 80), IV ritodrine for ≥1 week. The CK concentration in cord blood of Group C (198.8 ± 14.2 IU/L) was significantly higher in comparison with Group A . There was no significant difference in LDH and amylase levels in the three groups. The CK significantly correlated with gestational age  and birth weight . LDH and amylase levels did not change with gestational age nor birth weight. In conclusion, long-term ritodrine tocolysis leads to increased umbilical blood CK level. Recently, the incidence of preterm birth has increased, despite rapid advances in maternal-fetal medicine. The beta-adrenergic agent ritodrine hydrochloride is commonly used for the treatment of preterm labor in Japan. Numerous adverse effects have been reported during tocolysis with such drugs, including cardiac, pulmonary, and metabolic effects . AsymptoWe hypothesized that ritodrine hydrochloride would affect the preterm fetuses, thereby adversely affecting escape enzyme levels. Therefore, the aim of this study is to determine if the tocolytic therapy affects CK, LDH, and amylase levels in the umbilical blood of preterm infants.To examine the clinical significance of the relationship between ritodrine hydrochloride and escape enzymes in the preterm infants, we reviewed all patients who were delivered at less than 36 weeks of gestation with preterm birth in the Perinatal Center of Social Insurance Funabashi Central Hospital between July 1, 2005, and June 30, 2008. Informed consent was obtained from all subjects and all study protocols were approved by the institutional review board before the start of this study. Subjects were included preterm labor, premature rupture of membranes (PROM), and cervical insufficiency. Preterm labor was defined as demonstrated progressive dilation of the cervix with uterine contractions before 36 weeks of gestation. PROM was documented by sterile speculum examination, confirming the pooling of fluid in the posterior vaginal fornix, an alkaline pH, ferning, and direct visualization of fluid leakage from the cervical canal. Cervical insufficiency was defined as premature effacement or dilatation of the cervix in the absence of labor or ultrasonographic evidence of cervical shortening less than 25 mm or funneling. Subjects were excluded if at the time of admission they had intrauterine growth restriction (IUGR), pregnancy-induced hypertension (PIH), multiple pregnancy, abruptio placenta, chromosomal abnormality, or stillbirth. Moreover, pregnant women who did not receive glucocorticosteroids for accelerating fetal organ maturation and decreasing the risk of respiratory distress syndrome (RDS) and intraventricular hemorrhage (IVH) were eligible for this study. Gestational age was estimated based on menstrual dates and an ultrasound examination performed before 20 weeks of gestation. PIH was diagnosed where there was systolic blood pressure higher than 140 mm Hg and/or diastolic blood pressure higher than 90 mm Hg after 20 gestational weeks. IUGR was defined as estimated weight less than the 10th percentile of the Japanese standard . Clinicaμg/min, which was increased by 50 μg/min every 10–20 min until uterine contractions ceased. When control of uterine contractions could not be achieved even with administration of 200 μg/min of ritodrine, magnesium sulfate was added to the regimen. The method of administration was based on that described by Zuspan and Ward [Ritodrine hydrochloride and magnesium sulfate were administered as tocolytic agents for preterm labor and cervical insufficiency . The iniand Ward , with inOn admission and every week thereafter, maternal blood tests including serum CK, LDH, and amylase were performed. Umbilical venous blood was obtained from all infants at delivery. The serum was immediately analyzed for CK, LDH, and amylase, using an automatic analyzer with analysis at 37°C .Neonatal data dealing with gestational age, birth weight, 1 min and 5 min Apgar scores, gender, umbilical cord pH, Kaup index, and neonatal complications  necrotizing enterocolitis, and retinopathy) were recorded.Patients were divided into three groups according to the use of ritodrine hydrochloride during the antepartum period, as follows: Group A, preterm infants who were not exposed to ritodrine hydrochloride in utero, Group B, preterm infants after short-term tocolysis, which means the mothers of these infants were given intravenous infusion of ritodrine hydrochloride for <1 week; Group C, preterm infants after long-term tocolysis by intravenous infusion of ritodrine hydrochloride for ≥1 week. Moreover, two subsets of each group were further evaluated: those with no exposure to magnesium sulfate in utero  and those after tocolysis by intravenous infusion of magnesium sulfate .U test for continuous variables, as well as the chi-square or Fisher's exact test to compare proportions. The relationship between escape enzymes and gestational age or birth weight were studied by regression analysis. Correlations between levels of escape enzymes and gestational age or birth weight was calculated for data from Groups A, B, and C and all infants were combined into a single group. The statistical package used was SPSS, version 21 . Values of P < 0.05 were considered statistically significant.Results are expressed as mean ± standard error of mean (SEM). Clinical characteristics were compared among the groups using a Kruskal-Wallis test, followed by the Mann-Whitney A total of 215 cases were enrolled in this study, with 91 cases in Group A, 44 cases in Group B, and 80 cases in Group C. Clinical background data for the four groups are compared in P < 0.01) and Group B (P < 0.05). The rate of cesarean delivery of Group B was significantly lower than that of Group A (P < 0.01) and Group C (P < 0.01). Moreover, the CK concentration in maternal blood of Group C was significantly higher in comparison with Group B. There was no significant difference in LDH and amylase levels in the three groups. No pregnant women showed any signs of rhabdomyolysis and pancreatitis.No significant differences were identified between all groups in terms of maternal age, gravidity, parity, body mass index at delivery, gestational age at delivery, birth weight, sex male, Apgar score at 1 and 5 min, umbilical arterial pH, Kaup index, and placental weight. The frequency of administration of magnesium sulfate of Group C was significantly higher than that of Group A (P < 0.05). CK concentrations were significantly higher in Groups C1 and C2 than in Groups A1 and A2, respectively (P < 0.05). No significant differences in CK levels were seen between Groups A1 and A2, Groups B1 and B2, or Groups C1 and C2.r = 0.42, P < 0.01) and birth weight . LDH and amylase levels did not change with gestational age  nor birth weight .r = 0.46, P < 0.01; Group B, r = 0.41, P < 0.01; Group C, r = 0.50, P < 0.01) or birth weight  in each group  nor with birth weight  (data not shown).LDH did not change with gestational age  or birth weight . In Group B, positive linear correlations were observed between amylase level and gestational age  or birth weight . In Group C, amylase did not change with gestational age (r = 0.04) nor with birth weight (r = 0.07)  .The purpose of this study was to investigate relationships between ritodrine hydrochloride and escape enzymes in the preterm infants.There is some controversy regarding the optimum duration of tocolysis. In Japan, treatment is expected to prolong pregnancy as much as possible by suppressing uterine contractions enough to delay delivery but, in the US and Canada, it is used to maintain pregnancy by substantial and rapid inhibition of concentrations for a period long enough to enable maturation of fetal lung to be promoted with corticosteroids . Takagi CK and LDH are nonspecific markers of tissue and muscle injury. Preliminary studies suggest that fetal or umbilical cord blood enzymes at delivery reflect the effects of labor and drugs. Adamcová et al. reported that CK level correlated significantly with gestational age or birth weight . Weiner in vitro [Although ritodrine hydrochloride is generally considered fairly safe , no repoin vitro . Second,in vitro .LDH is virtually ubiquitous in the body, and several tissues, such as heart, liver, skeletal muscle, and kidney, show a tissue-serum ratio greater than 1000, and hence raised values are of nonspecific clinical significance. The mechanisms leading to extracellular release of LDH are still poorly understood. Pathological events include ischemia, shock, toxic, and inflammatory conditions and mechanical and physical destruction of tissue . PerkinsRitodrine hydrochloride can induce hyperamylasemia in pregnant women . Takahasβ-adrenergic stimulation, with an absence of desensitization in the neonatal heart. Other immature organs are capable of homologous desensitization in response to β-agonists.Moreover, in control group, negative linear correlations were observed between amylase level and gestational age or birth weight. However, in short-term ritodrine tocolysis, positive linear correlations were observed between amylase level and gestational age or birth weight. As ritodrine hydrochloride freely diffuses across the placenta, this positive linear correlation means that the increased cord amylase level might be due to a direct effect of the ritodrine hydrochloride in infants with higher ritodrine concentration in short-term ritodrine tocolysis. However, in long-term ritodrine tocolysis group, no correlation was found between amylase levels and gestational age or birth weight. There was an inverse relationship between short-term tocolysis and long-term tocolysis. Although the reason for this is unknown, it may be related to desensitization to ritodrine hydrochloride that was suggested by Takahashi et al. . ConcernThe objective of this retrospective analysis was to clarify the variations in escape enzyme levels in umbilical cord blood when ritodrine hydrochloride with or without magnesium sulfate was administered as tocolytic therapy. We found that the CK concentration was significantly higher with long-term ritodrine tocolysis than with no ritodrine administration. In addition, significant differences were seen between all groups in the frequency of concomitant administration of magnesium sulfate. One possibility is that magnesium sulfate may have additive effects on CK levels over those of ritodrine hydrochloride. Subsets with and without magnesium sulfate were thus further evaluated, and we found that CK concentrations in those with long-term ritodrine tocolysis were significantly higher than in those without ritodrine administration.Our results point to another area for future investigation: the potential for differences in mode of delivery to affect fetal responses to tocolytic therapy. Significant differences in the rate of cesarean delivery were apparent among the three groups. Mode of delivery may thus contribute to the levels of escape enzymes in the umbilical blood of preterm infants. Some controversy exists regarding the effects of mode of delivery on escape enzyme levels in umbilical cord blood. Leiserowitz et al. reported that pregnant women having a vaginal delivery show significantly elevated CK and CK-MB levels . ConversAlthough the transfer of CK through the placenta cannot be excluded, because its molecular weight is 82 kDa, our data support the idea that the transfer of CK across the placenta is limited. A major limitation in this study was the relatively small number of patients. Further investigation with a larger number of patients is thus warranted.Long-term tocolysis should be taken into account in the clinical interpretation of CK levels in umbilical blood. Further studies are necessary to confirm the relationship between ritodrine hydrochloride and escape enzymes in the umbilical blood of preterm infants. Further prospective study is needed to confirm findings.


Contemporary cochlear implants with multiple electrode stimulation can produce good speech perception but poor music perception. Hindered by the lack of a gold standard to quantify electric pitch, relatively little is known about the nature and extent of the electric pitch abnormalities and their impact on cochlear implant performance. Here we overcame this obstacle by comparing acoustic and electric pitch perception in 3 unilateral cochlear-implant subjects who had functionally usable acoustic hearing throughout the audiometric frequency range in the non-implant ear. First, to establish a baseline, we measured and found slightly impaired pure tone frequency discrimination and nearly perfect melody recognition in all 3 subjects’ acoustic ear. Second, using pure tones in the acoustic ear to match electric pitch induced by an intra-cochlear electrode, we found that the frequency-electrode function was not only 1–2 octaves lower, but also 2 times more compressed in frequency range than the normal cochlear frequency-place function. Third, we derived frequency difference limens in electric pitch and found that the equivalent electric frequency discrimination was 24 times worse than normal-hearing controls. These 3 abnormalities are likely a result of a combination of broad electric field, distant intra-cochlear electrode placement, and non-uniform spiral ganglion cell distribution and survival, all of which are inherent to the electrode-nerve interface in contemporary cochlear implants. Previous studies emphasized on the “mean” shape of the frequency-electrode function, but the present study indicates that the large “variance” of this function, reflecting poor electric pitch discriminability, is the main factor limiting contemporary cochlear implant performance. Pitch is a fundamental auditory percept that carries not only melodic information in music perception, but also speaker, prosodic or even lexical information in language processing. Pitch may be affected by sound pressure and waveform, but it primarily depends upon sound frequency One design goal for a cochlear implant is to replicate this tonotopic organization and sharp frequency selectivity in a deafened ear. Contemporary multi-electrode cochlear implants have been successful in producing good speech perception in quiet, but fail to produce normal pitch perception Relatively little is known about the discriminability of electric pitch. At best, the implant users could use pulse rates  to judge or produce music intervals Three cochlear-implant subjects who had significant acoustic hearing in the non-implanted ear participated in the present study. All procedures in this study were approved by the University of California Irvine Institutional Review Board. Subjects gave written informed consent before data collection. S2 was a veteran and had fluctuating hearing loss most likely due to Meniere’s disease. He received a Med El implant  and was the subject who had been thoroughly studied by Dorman et al. S3, who worked in finance, suddenly lost her hearing on one side and developed debilitating tinnitus on the same side for unknown reasons. She received a Med El implant to control her tinnitus. In her clinical processor, the pulse rate was 1587 Hz per electrode and the pulse duration was 25.42 µs/phase. She did not use the implant on a daily basis and scored 43% correct, which is a below-average sentence recognition score. She had normal hearing (≤15 dB HL) at all test frequencies.Frequency discrimination. Pure tones were used to measure frequency difference limens. The standard frequencies ranged from 125 to 8000 Hz in octave steps. The duration of each tone was 500 ms with 50-ms cosine-squared ramps. The level of each tone was presented at the individual’s most comfortable loudness. All pure tones were generated digitally and presented monaurally to the subject through a Sennheiser headphone .Frequency-electrode function. Pure tones used to match electric pitch were generated and presented in the same way as for measurement of frequency discrimination in the non-implant ear. All electric stimuli were generated and controlled by a research interface. For S1, electric stimuli were generated by the Bionic Ear Data Collection System software . The stimuli were 500-ms, charge-balanced biphasic pulse trains. The pulse duration was 107.8 µs/phase for the 100-Hz and 200-Hz pulse rates, and 53.9 µs/phase for the 2900-Hz pulse rate. For S2 and S3, electric stimuli were generated by a diagnostic interface box . The stimuli were 500-ms, charge-balanced biphasic pulse trains. The pulse duration was 240.8 µs/phase for the 200-Hz pulse rate, and 24.2 µs/phase for the 1652-Hz and 2941-Hz pulse rates. Except for S1, pulse duration for relatively high rate (>1000 Hz) stimulation was similar to that used in the clinical processor. A much longer pulse duration was needed for low rate (100 or 200 Hz) stimulation to reach sufficient loudness in all subjects. This difference in pulse duration could affect perception between low- and high-rate electric stimulation, but would not affect pitch matching between acoustic and electric stimulation because pulse duration was held constant in each individual comparison. In all cases, the pulse trains were presented at the most comfortable loudness to each electrode in monopolar stimulation mode. Neither acoustic nor electric level was roved.Melody recognition. Twelve familiar melodies were used to assess functional pitch performance Intra-cochlear electrode position. The same method as previously described Frequency discrimination. A 2-alternative, forced-choice (2AFC) adaptive procedure Frequency-electrode function. For S1 and S2, a modified 2AFC double-staircase adaptive procedure For S3, the double-staircase adaptive procedure was not used due to time limitation. Instead, the subject was instructed to adjust the pure-tone frequency so that the pure tone was just higher in pitch than the electric stimulus, and then again so that it was just lower in pitch. The pure-tone frequency was adjusted on an unmarked scale from 20 to 20000 Hz. The point of subjective equality in pitch was the average of the just higher and just lower frequency values. The difference limen was half of the difference between these two values. Despite using a different method, S3 produced results similar to those for S1 and S2.Melody recognition. A 12-alternative, forced-choice method was used to obtain percent correct scores using both the clinical map and the adjusted frequency-electrode function. To produce the adjusted frequency-electrode function, the cut-off frequencies for the bandpass filter in each channel were set to the just lower and just higher pitch matches for the corresponding electrode. The adjusted frequency-electrode function would correct electrode-pitch reversals , but would not eliminate redundant electrodes . Each melody was presented 3 times and the order of presentation was randomized. Melodies consist of well-known tunes such as “Twinkle Twinkle Little Star” and “Old Macdonald” There was great individual variability, but several trends were apparent in the data. First, there was a roughly monotonic trend between frequency and electrode position, with higher frequencies being matched to more basal electrodes. Second, there was a clear effect of pulse rate on the frequency-electrode function. The lower rates (≤200 Hz) produced lower pitches than the higher rates (>1600 Hz) at the same electrode position. Third, all frequency-electrode functions were much lower than the Greenwood function. S1 produced functions that were about 2 octaves below the Greenwood function for high-rate stimulation and even more for low-rate stimulation. The high-rate function also departed from the clinical map for basal electrodes (4 µ15 mm from round window). For S2, high-rate stimulation produced a function that was about 1 octave below the Greenwood function for the most apical electrode and about 2 octaves below for the most basal electrode. The measured function was reasonably close to the clinical map, with the former being slightly higher for apical electrodes and lower for basal electrodes. This high-rate result was similar to the result obtained by Dorman et al. from the same subject The slope of all measured frequency-electrode functions was calculated on a logarithmic frequency vs. linear distance scale. The mean slope of the measured functions was –0.075 , which was much shallower than the –0.154 slope for the Greenwood function. On average, the measured frequency-electrode function was 2 times more compressed in frequency range than the Greenwood function.The bottom panel (labeled S3) shows 6 additional data sets for comparison. Like the present result, 5 previous studies involving 7 similar unilateral cochlear-implant subjects who had contralateral residual acoustic hearing Previous studies The present study suggests that the poor quality of electric pitch perception is mainly responsible for the limited cochlear implant performance. In fact, the 24 times larger Weber fraction for electric stimulation than acoustic stimulation likely represents the best-case scenario. The actual Weber fraction for electric stimulation could be worse than the present estimation because the cochlear implant user could have made lower or higher pitch judgment based on some other subjective quality . Previous studies using a multi-scaling approach came to a similar conclusion that electric stimulation, with either single- or dual-electrode stimulation, produces multi-dimensional percepts that are incompatible with the salient pitch evoked by a pure tone Electric stimulation via contemporary intra-cochlear electrodes can produce a temporally precise neural firing pattern that is phase locked to stimulation at rates well above 1000 Hz Although a cochlear spiral ganglion based map can potentially improve the frequency-electrode function Two other approaches using novel stimulation might be considered as true disruptive technology. Different from diffuse electric stimulation, optical stimulation is focused and can produce a highly selective spatial excitation pattern The present study measured frequency-electrode functions and evaluated their effects on melody recognition for 3 unilateral cochlear implant subjects who had significant acoustic hearing over the entire audiometric frequency range in the non-implant ear. Compared with the Greenwood function, the averaged frequency-electrode function was lower in pitch and compressed in frequency range, particularly at low stimulation rates. Adjusted frequency-electrode functions did not improve cochlear implant melody recognition. The derived Weber fraction for electric pitch was 24 times worse than that for acoustic pitch, indicating that the large variance in electric pitch is the main cause for poor cochlear implant melody recognition.


The relations of birth weight and maternal body mass index (BMI) to overweight remain unresolved. We prospectively examined the relations of birth weight with various anthropometric measures at age 3 to 6 years, the effect of maternal BMI, and the patterns of these relations in an analysis using 9 birth weight categories.The subjects were 210 172 singleton infants born alive with a gestational age ≥28 weeks between October 1993 and December 1996; the subjects were followed up in 2000. Birth weight, maternal height and weight, and other relevant information were measured or collected prospectively. Overweight and underweight were defined by using National Center for Health Statistics/World Health Organization reference data. Logistic regression models were used to estimate relative risks. Analyses stratified by quartile of maternal BMI were performed to examine the effects of maternal BMI on the associations of birth weight with overweight and underweight.Birth weight was linearly associated with height, weight, and BMI at age 3–6 years. Adjustment for maternal BMI did not alter this association. Birth weight was positively associated with overweight and negatively associated with underweight. The relation curves for both overweight and underweight resembled half of a flat parabolic curve. The associations for overweight and underweight were slightly stronger for the highest and lowest quartiles of maternal BMI, respectively.Higher birth weight is associated with an increased risk for childhood overweight, and lower birth weight with an increased risk for underweight. The associations between birth weight and early childhood anthropometric growth measures could not explained by maternal BMI. This is of great concern, as the number of overweight children is growing worldwide.14 have prospectively examined the relations of birth weight with mean height, weight, and BMI measured before age 7 years. The 1958 British birth cohort13 comprised 10 683 participants and reported that the curve for the relation between birth weight and BMI at age 7 years was weakly linear; however, it was J-shaped for BMI at age 33 years, when birth weight categories were restricted to tertile cut-offs, probably due to small sample size.A few studies15 Simultaneous investigation of the associations of birth weight with overweight and underweight might aid in understanding the relation between birth weight and later growth.The data are limited regarding the relation between birth weight and low anthropometric indices such as childhood underweight. Low anthropometric indices are prevalent in developing countries and are associated with poor cognitive and educational performance in children.Here, we attempted to comprehensively and prospectively assess the relation between birth weight and body growth, after extensive adjustment for potential confounders, in a large Chinese birth cohort followed to age 6 years. We aimed to determine if birth weight was related to underweight, as well as overweight, and if the relations persisted in all strata of maternal BMI. In addition, we generated curves for the associations of birth weight to overweight and underweight by using 9 birth weight groups.16 Women entered the program either at a premarital health assessment or at any stage of pregnancy. Information about demographic and relevant obstetric and pregnancy outcomes was collected at the time of entry, subsequent prenatal visits, or delivery. All singleton children born alive to the enrolled women were followed until March through July 2000. Of the 241 060 children, 3274 children had died, 8620 had moved out of the study area, and 7532 (3.1%) were lost to follow up. After excluding 7026 children with unknown birth weight or sex and 4436 children whose height or weight were not measured at the time of follow-up, 210 172 children remained in the cohort for the primary analyses. The Peking University Health Science Center Institutional Review Board approved this study.The subjects were 241 060 singleton infants born alive with a gestational age ≥28 weeks between October 1993 and December 1996. The mothers of the infants had all participated in a population-based prenatal care program implemented in 26 counties or cities in Zhejiang, Jiangsu, and Hebei province, China.All children were born in hospitals, where birth weight was routinely assessed within 1 hour of birth and recorded. Because of the large sample size, we were able to include 9 birth weight groups  in our investigation of the pattern of the associations between birth weight and overweight/underweight. The birth weight category of 3.00 to 3.24 kg contained the largest number of children, and was thus selected as the reference group.2).Childhood growth measurements included height, weight, BMI, overweight, and underweight. Height and weight were measured by trained local health workers. Weight (kg) and height (cm) were measured in light indoor clothing without shoes, overcoats, or hats. All instruments were calibrated by local experts in quality and technical supervision. BMI was calculated as weight divided by height (kg/mref)/SDref. The term overweight in this study includes both overweight and obese children.Overweight was defined as Z-scores of weight-for-height >2 and underweight as Z-scores of weight-for-age ≤2, which were calculated based on National Center for Health Statistics/World Health Organization reference data using the formula, Z-score = , P25 to <P50 (11.0), P50 to <P75 (14.0), P75 kg). Child factors included sex  and body length at birth (<P5 (43.0 cm), P5 to <P50 (50.0 cm), P50 to <P95 (52.0 cm), ≥P95). We treated all these factors as categorical variables in the analyses.Staff at the prenatal care program recorded information about maternal and infant characteristics, which enabled us to control for various potential confounding factors. Maternal factors included area of residence (northern/southern), age at delivery , occupation (farmer/non-farmer), education , primiparous (yes/no), folic acid supplementation during pregnancy (yes/no), gestational age , pregnancy-induced hypertension (yes/no), and maternal weight gain during pregnancy . The results showed that the effect of maternal BMI, although present, was weak; thus, maternal BMI was evaluated as a confounder.Because maternal BMI might influence the association between birth weight and overweight,19 In a subsequent model, we further adjusted for other potential confounders except maternal BMI. In the third model, we added maternal BMI.We used regression models to assess the associations between birth weight and early childhood growth after adjusting for covariates. In the first model, we adjusted for child residence area, sex, and age at follow-up because these 3 variables were directly and strongly associated with childhood body size in the cohort.P values were 2-sided. A P value <0.05 was considered statistically significant.When marginal means or relative risks were estimated, we treated birth weight and all covariates as indicators. For each birth weight category, marginal means were estimated by using general linear regression models; relative risks of overweight or underweight were estimated using logistic regression models. When testing trends, we assigned the median value or squared median value of each birth weight category as a score and treated this score as a continuous variable. When testing interactions between birth weight and maternal BMI, we included the product term of the 2 variables in a model, where only birth weight was treated as a continuous variable, using the median value of each category as a score. All analyses were performed using SPSS 11.5 . All reported Among the 210 172 children in our cohort, 87.5% lived in a southern area, 51.9% were boys, and mean age (SD) at follow-up was 59.0 (8.2) months (range: 40–79 months). Overall, 99.2% of children were of Han ethnicity, the dominant ethnic group in China. A total of 63% of the mothers of the children in the cohort entered the prenatal care program during premarital health assessment, 19% during the first trimester of pregnancy, 11% during the second trimester, and 7% during the third trimester. As shown in Table The numbers of children (median birth weight) in the 9 birth weight groups were 3911 (2.3 kg), 11 275 (2.6 kg), 19 451 (2.9 kg), 57 885 (3.1 kg), 42 058 (3.4 kg), 46 225 (3.5 kg), 16 451 (3.8 kg), 9868 (4.0 kg), and 3048 (4.4 kg).P for linear trend <0.001). Figure P for linear trend <0.001).We first examined the association of birth weight with mean height, weight, and BMI, where these anthropometric measurements were treated as dependent continuous variables. The children’s area of residence, sex, and age at follow-up were known to be directly associated with their anthropometric measurements. After adjustment for these factors using generalized linear models, birth weight was positively associated with height, weight, and BMI .Due to the positive association of maternal height and weight with childhood growth, we incorporated these variables into a model. The results were not substantially changed Table . When maP for quadratic trend <0.001). The slopes of both curves began to change at a birth weight of approximately 3.4 kg, after which the risk for overweight increased more rapidly with birth weight and decreased more slowly for underweight.We then used logistic regression model to assess relations of birth weight to overweight and underweight. After adjustment for the child’s area of residence, sex, and age at follow-up, birth weight was positively correlated with overweight Figure  and inveP for quadratic trend <0.001) in any stratum.Further adjustment for other maternal or child-related factors, and additional adjustment for maternal height and weight, moderately changed the estimated risks, but the quadratic trend remained unchanged. As compared with a birth weight of 3.00 to 3.24 kg, a birth weight ≥4.25 kg was associated with a relative risk of overweight of 2.17  and a risk of underweight of 0.50  (Table P = 0.016) and underweight (P < 0.001). The associations of birth weight with these 2 outcomes were consistent in all 4 strata of maternal BMI, although the positive association with overweight was stronger for the 4th quartile, and the negative association with underweight was stronger for the 1st quartile.We grouped all subjects by quartiles of maternal BMI, and applied an interaction analysis using a logistic model. We observed significant interaction between maternal BMI and birth weight in the models for overweight , and their interactions.13This was a large population-based prospective cohort study. Approximately 92% of live-born children were located and followed up. All relevant information such as birth weight and maternal height and weight were measured or collected prospectively. The large sample size allowed us to define more birth weight groups to examine the pattern of association between birth weight and childhood growth. In addition, we adjusted for several factors, such as maternal BMI, pregnancy-induced hypertension, maternal weight gain during pregnancy, and child gestational age and body length at birth. These factors had been recognized as potential confounders, but were not fully accounted for in previous studies.19 and was unlikely to substantially affect the results. Another limitation was that information on maternal smoking and alcohol consumption during pregnancy was not collected. National data from China indicate that the prevalences of smoking and heavy alcohol drinking among Chinese women were 3.1%27 and 0.8%,28 respectively, and the values are likely to be lower for pregnant Chinese women. The third limitation in the present study was a digit preference in the recording of birth weight, especially for 100-gram intervals, although this is unlikely to change the overall results, as the digit preference is assumed to be nondifferential over the 9 birth weight groups.One limitation of the present study was that we did not collect data on diet or physical activity. Obtaining affordable food is no longer a problem in China due to rapid economic development. Children’s diets are mainly determined by their mothers’ preferences, as influenced by maternal education and occupation. Physical exercise is mainly associated with adult obesityIn conclusion, our findings suggest that higher birth weight increases the risk of childhood overweight, that lower birth weight increases the risk of childhood underweight, and that these results cannot be explained by maternal BMI. Birth weight is linearly correlated with childhood growth, and the curves of the relations of birth weight to overweight and underweight appear to be quadratic.


Although the function of the sensory system rapidly develops soon after birth in newborn pups, little is known about the mechanisms triggering this functional development of the sensory system.Here we show that the birth of pups plays an active role in the functional development of the sensory system. We first optimized the experimental procedure for suckling behavior using neonatal mouse pups. Using this procedure, we found that preterm birth selectively accelerated the development of suckling behavior in neonatal pups, but not that of motor performance, suggesting that the birth of pups regulates the functional development of the sensory system soon after birth.Taken together with our recent findings that birth itself regulates the initiation of sensory map formation in the somatosensory and visual systems, these results support the idea that the birth of pups actively regulates the anatomical and functional development of the sensory system. The birth of pups is the most drastic environmental change in the entire life of mammals. Before birth, embryos are isolated in the uterus and are kept away from external sensory stimuli. Nutrients and oxygen are automatically supplied by their mothers. In contrast, soon after birth, newborn pups start to receive external sensory stimuli and need to process sensory information from the external world. Using sensory information, newborn pups need to search for nipples actively to obtain milk. Because the environment of pups before and after parturition changes drastically, it is plausible that the nervous system needs to change dynamically during this environmental transition. However, little has been uncovered about the roles of birth in the maturation of the brain.The somatosensory system has been widely used for investigating the influence of extrinsic environmental and intrinsic genetic factors on sensory map formation and developmental plasticity, with profound implications for other circuits in the central nervous system -10. ReceBecause the formation of anatomical sensory maps is regulated by birth, we hypothesized that the functional maturation of the sensory system is also regulated by birth. To test this hypothesis, we focused on suckling behavior, which is the behavior of neonatal pups to find nipples and obtain milk, because suckling behavior is observed soon after birth . When a Here, to examine the role of birth in the development of suckling behavior soon after birth, we determined an optimal experimental procedure for examining suckling behavior in mice. Then, we examined the effect of preterm birth on the development of suckling behavior. We found that the development of suckling behavior, but not that of motor performance, was accelerated by preterm birth. Thus, our results suggest that the birth of pups regulates not only the anatomical development of the sensory system, but also the functional maturation of the sensory system.Previously, suckling behavior has been mainly examined using rats ,18. HoweUnfortunately, however, a half of the pups failed to attach to nipples within a test period 180 sec), and therefore we were unable to measure nipple attachment latency for them (data not shown). We reasoned that the length of separation of pups from their mothers was not enough to fully motivate pups to search for nipples, presumably because some pups were not hungry enough. In fact, milk remaining in their stomachs was observed through the skin in some pups even after the 4-hour separation (data not shown). Consistently, it was reported that it took more than 4 hours for neonatal pups to digest milk [0 sec, anWe then examined nipple attachment latency during development. As reported previously using rats , the perHowever, we noticed that younger pups often failed to find nipples because they completely lost their way and went to the lactating dam’s head or tail, resulting in the failure to find nipples Figure C. This sWe found that nipple attachment latency indeed significantly decreased between P5 and P9  . In contrast, when recovery was extended to 21 hours, we did not find any significant difference in nipple attachment latency between non-treated pups and sham-operated pups, suggesting that 21 hours are enough for operated pups to recover . Thus, we decided to allow operated pups to recover for 21 hours before the suckling behavior test. We then performed ION section, allowed the operated pups to recover for 21 hours, and examined whether pups attached to nipples within 180 sec. Interestingly, we found that ION section completely prevented all pups from finding nipples at both P7 and P10 even though they actively rooted into their mothers’ ventrum , suggesting that pain derived from our surgical procedure did not affect suckling behavior. Taken together, these results suggest that somatosensory inputs are indeed important for suckling behavior.Although it seemed likely that the lack of somatosensory inputs led to the effect of ION section, it also seemed possible that pain caused by ION section resulted in the effect. We believe the latter is unlikely because of the following reasons. First, the activity of ION-sectioned pups was indistinguishable from that of non-treated pups. Even though ION-sectioned pups were unable to attach to nipples, they actively rooted into their mothers’ ventrum and probed around nipples. If the pain of ION section were severe, their behavior would be quite different from that of non-treated pups. Second, the body weight of sham-operated pups increased similarly to that of non-treated pups. We performed sham operation at P7 and measured the body weight one day after recovery. We did not find a significant difference between sham-operated pups and non-treated pups , barrels and intracortical circuits such as barrel nets, are formed in the somatosensory cortex ,10,22-27The birth of pups is one of the most drastic environmental changes in the entire life of mammals. It seems likely that newborn pups have to adapt to this drastic environmental change and have to start using the sensory system to survive soon after birth. Interestingly, we demonstrated that the birth of pups selectively regulates the initiation of sensory map formation in the somatosensory and visual systems during development . AlthougPreviously, experimental procedures for measuring nipple attachment latency were designed for use with animals other than mice -15,18. WIn summary, we demonstrated that the birth of pups regulates brain development not only anatomically but also functionally. We successfully found that preterm birth significantly accelerated the development of suckling behavior, suggesting that birth indeed regulates functional brain development. Interestingly, the development of motor performance was independent of birth, suggesting that birth regulates the development of the sensory system related to suckling behavior.All procedures were performed in accordance with a protocol approved by the University of Tokyo Animal Care Committee and with a protocol approved by Kanazawa University Animal Care Committee. ICR mice  were reared under the normal 12 h light–dark cycle. The day of insemination was designated as 0 dpc. Gestation days were counted in 6-hour increments . To ensure data reflected the precise time of delivery, pregnant mice were monitored using digital video recorders as described previously .Our procedure for examining the suckling behavior of neonatal mice was made by modifying the procedure used for neonatal rats . A lactaBefore starting the test, pups were separated from their mothers and kept on a warm plate with home cage tips for the indicated time period . At the beginning of the suckling behavior test, the pups were placed in close proximity to the nipples on the ventrum of the anesthetized dam without contacting the nipples, and the time until the pups attached to nipples was measured. All tests were videotaped, and the latency between being placed in the cage and attaching to a nipple was recorded for each pup. A few pups failed to reach nipples within 180 sec, and in such cases, we excluded those pups from our analyses.It should be noted that nipple attachment latency seemed to be affected by maturation of the dam’s nipples. It seemed that nipple attachment latency tended to be longer when mothers had small nipples. Therefore, in order to obtain stable and reproducible results for nipple attachment latency, when we compared nipple attachment latency between preterm and full-term pups, we used the same anesthetized mother for different littermates rather than using their biological mothers.To examine the development of the pups’ motor performance, a righting reflex test was performed. Mouse pups often fall on their back and then right themselves onto all four feet, and we measured how much time it took to right themselves onto all four feet as described previously ,21.ION transection was conducted as described previously . Pups atTo induce preterm birth, mifepristone treatment was carried out as described previously with modifications ,30. The t-test, Welch’s t-test, the Mann–Whitney U test and the Kruskal-Wallis test with the Scheffe’s F test. “n” means the number of animals.Statistical analyses were performed using Statcel2 software  and R software. To assess statistical significance, we first performed the Kolmogorov-Smirnov test. P values were determined by an unpaired Student’s ION: Infraorbital nerve.The authors declare that they have no competing interest.TT and HK designed the experiments; TT performed the experiments; TT analyzed the data; TT and HK wrote the paper. Both authors read and approved the final manuscript.Movie S1. Suckling behavior in mouse pups at P6 and P9.Click here for fileMovie S2. Suckling behavior in sham-operated and ION-sectioned pups.Click here for file


The nasopalatine cyst is the most common epithelial and nonodontogenic cyst of the maxilla. The cyst originates from epithelial remnants from the nasopalatine duct. The cells may be activated spontaneously during life or are eventually stimulated by the irritating action of various agents . It is different from a radicular cyst. The definite diagnosis should be based on clinical, radiological, and histopathological findings. The treatment is enucleation of the cystic tissue, and only in rare cases a marsupialisation needs to be performed. A case of a nasopalatine duct cyst in a 35-year-old male is reviewed. The typical radiologic and histological findings are presented. The nasopalatine duct cyst (NPDC) was first ever described by Meyer in 1914 . NasopalNPDCs affect a wide age range; however, most present in the fourth through sixth decades of life, and most studies show a significantly higher frequency in men than woman, with the ratio being 2.5 : 1 . PatientThe present case of NPDC is one such typical pathology with the classical presentation which could have been easily misdiagnosed as a periapical lesion.A 35-year-old male reported to the dental clinic with the chief complaint of painless swelling over the palate and anterior maxilla. The swelling was gradually increasing in size for the past 3 months with associated displacement of maxillary central incisors. There was no associated history of trauma.On examination, a well defined firm nontender swelling was seen on the left side of anterior hard palate and crossing over the midline to the right side. The crown of left central incisor was displaced labially and mesially, overlapping the crown of right central incisor . A proviMaxillary occlusal radiograph showed a well-defined round radiolucency approximately 2.5 cm in size with corticated margins in the midline and between the central incisors which was the typical radiographic feature of NPDC . The lesCT scan also showed a well-defined radiolucency in anterior maxilla in the region of incisive canal, 2.6 cm × 2.8 cm in size. Mesiodistally the radiolucency was causing displacement of the roots of both maxillary central incisors and it was not extending laterally beyond the roots of incisors. Inferiorly it was extending till the crest of interdental bone. Loss of cortication was seen along the buccal and palatal aspects of the lesion in the sagittal sections. The lesion was causing mild elevation of the floor of nasal fossa in the anterior region with deviation of the nasal septum to the right side Figures , and 5. A surgical enucleation was done with intact removal of the cyst  and the NPDCs are usually central or unilateral with no prevalence of side occurrence. Radiographically, they are seen as well-defined round or oval radiolucencies in the midline, although some lesions may appear heart-shaped , either Due to similar signs and symptoms, the NPDC may be easily misdiagnosed by the clinicians as a periapical lesion. This is why many authors believe that its prevalence is actually higher than presented in the literature . AlthougA reported 71.8% of NPDCs have squamous, columnar, cuboidal, or some combination of these epithelial types; respiratory epithelium is seen in only 9.8% , 14, 15.The present case had typical clinical, radiographic, and histopathological features of a nasopalatine duct cyst. The importance of this case is in the diagnosis of such lesions which can easily be misinterpreted as periapical cyst and inadvertent root canal therapy of surrounding vital teeth can be avoided.Nasopalatine duct cysts are the most common nonodontogenic cyst of the oral cavity seen in the general population. NPDCs must be distinguished from other maxillary anterior radiolucencies. Vitality testing of teeth adjacent to or involved with a cyst-like lesion is mandatory and the final diagnosis could only be performed after histological analysis. It is important that practitioners are aware of the features of the NPDC.


Streptococcus group B), treated or not treated during pregnancy or labor, may be cause of serious illness in the newborn. The aim of this study was to observe the evolution of infants exposed to certain risk factors, using the total blood count and the determination of C-reactive protein.Maternal infection is an important cause of morbidity and mortality in newborns. Rupture of membranes more than 18 hours before birth, fever during labor, urinary tract infections or vaginal infections  received prophylactic antibiotics at birth, however, registering changes in blood counts (leukocytosis/leukocytopenia) and/or increased levels of C-reactive protein in 10% of cases (resistance to antibiotics administered anterpartum/intrapartum?).All infants entered into the study were evaluated after at least 12 hours of life, determining the total blood count and C-reactive protein. There have been changes to these tests to a large number of subjects included in the study, and there have been cases in which, though the usual tests were within normal limits, infants developed symptoms, with no altered values of these laboratory tests (up to 72 hours). The infants exposed to certain risk factors (membranes ruptured more than 18 hours before birth and the presence of group B The result of common tests can be used to evaluate the newborn exposed to certain infectious factors, and to specify the correct therapeutic attitude, but in close relation with the clinical outcome, considering their non-specificity and potential false positive or negative results.