While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation.
In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself.
An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance.
These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.
Surgical correction of severe proximal hypospadias represents a significant surgical challenge and single-stage corrections are often associated with complications and reoperations. Bracka two-stage repair is an attractive alternative surgical procedure with superior, reliable, and reproducible results.
To study the feasibility and applicability of Bracka two-stage repair for the severe proximal hypospadias and to analyze the outcomes and complications of this surgical technique.
Materials and Methods:
This prospective study was conducted from January 2011 to December 2013. Bracka two-stage repair was performed using inner preputial skin as a free graft in subjects with proximal hypospadias in whom severe degree of chordee and/or poor urethral plate was present. Only primary cases were included in this study. All subjects received three doses of intra-muscular testosterone 3 weeks apart before first stage. Second stage was performed 6 months after the first stage. Follow-up ranged from 6 months to 24 months.
A total of 43 patients operated for Bracka repair, out of which 30 patients completed two-stage repair. Mean age of the patients was 4 years and 8 months. We achieved 100% graft uptake and no revision was required. Three patients developed fistula, while two had metal stenosis. Glans dehiscence, urethral stricture and the residual chordee were not found during follow-up and satisfactory cosmetic results with good urinary stream were achieved in all cases.
The Bracka two-stage repair is a safe and reliable approach in select patients in whom it is impractical to maintain the axial integrity of the urethral plate, and, therefore, a full circumference urethral reconstruction become necessary. This gives good results both in terms of restoration of normal function with minimal complication.
Bracka repair; proximal hypospadias; two-stage repair
The transgenerational consequences of environmental contaminant exposures of aquatic vertebrates have the potential for broad ecological impacts, yet are largely uninvestigated. Bisphenol A (BPA) and 17α-ethinylestradiol (EE2) are two ubiquitous estrogenic chemicals present in aquatic environments throughout the United States and many other countries. Aquatic organisms, including fish, are exposed to varying concentrations of these chemicals at various stages of their life history. Here, we tested the ability of embryonic exposure to BPA or EE2 to cause adverse health outcomes at later life stages and transgenerational abnormalities in medaka fish. Exposures of F0 medaka to either BPA (100 μg/L) or EE2 (0.05 μg/L) during the first 7 days of embryonic development, when germ cells are differentiating, did not cause any apparent phenotypic abnormalities in F0 or F1 generations, but led to a significant reduction in the fertilization rate in offspring two generations later (F2) as well as a reduction of embryo survival in offspring three generations later (F3). Our present observations suggest that BPA or EE2 exposure during development induces transgenerational phenotypes of reproductive impairment and compromised embryonic survival in fish of subsequent generations. These adverse outcomes may have negative impacts on populations of fish inhabiting contaminated aquatic environments.
The transformation of macrophages into lipid-loaded foam cells is a critical early event in the pathogenesis of atherosclerosis. Both receptor-mediated uptake of modified LDL, mediated primarily by scavenger receptors-A (SR-A) and CD36 along with other proteins such as lipoprotein lipase (LPL), and macropinocytosis contribute to macrophage foam cell formation. The signaling pathways that are involved in the control of foam cell formation are not fully understood. In this study, we have investigated the role of phosphoinositide 3-kinase (PI3K) in relation to foam cell formation in human macrophages. The pan PI3K inhibitor LY294002 attenuated the uptake of modified LDL and macropinocytosis, as measured by Lucifer Yellow uptake, by human macrophages. In addition, the expression of SR-A, CD36 and LPL was attenuated by LY294002. The use of isoform-selective PI3K inhibitors showed that PI3K-β, -γ and -δ were all required for the expression of SR-A and CD36 whereas only PI3K-γ was necessary in the case of LPL. These studies reveal a pivotal role of PI3K in the control of macrophage foam cell formation and provide further evidence for their potential as therapeutic target against atherosclerosis.
Electronic supplementary material
The online version of this article (doi:10.1007/s11745-015-3993-0) contains supplementary material, which is available to authorized users.
Atherosclerosis; Foam cell; Cholesterol; Macrophage; Phosphoinositide 3-kinase
Various therapeutic modalities, which are available for treating plantar wart, have not been successful every time.
To evaluate topical adapalene under occlusion in the treatment of plantar warts and compare it with cryo-therapy.
Materials and Methods:
50 patients with 424 plantar warts were included in this single center, two arm, prospective, randomized, control, open study. Patients were allocated randomly into two groups consisting of 25 patients each. Group A patients having 299 plantar warts were treated using adapalene gel 0.1% under occlusion while Group B patients having 125 warts were treated using cryo-therapy. All the patients were evaluated weekly till the clearance of all the warts and the results compared.
All the warts of 25 patients of Group A that were treated using adapalene gel 0.1% cleared in 36.71 ± 19.24 (55.95-17.47) days except those in one patient. In Group B, warts in all except one treated by cryo-therapy cleared in 52.17 ± 30.06 (82.23-22.11) days. There were no side effects like scar formation, irritation, erythema, or infections with adapalene group while in the cryo group scar was seen in 2 patients, pain in 24, erythema in 10, and infection in 3 patients.
Adapalene gel 0.1% under occlusion is an effective, safe and easy to use treatment for plantar warts and may help clear lesions faster than cryo-therapy.
Adapalene; cryo-therapy; occlusion; plantar wart
Although the exact prevalence of hepatitis C virus (HCV) infection in Canada is unknown, previous studies and anecdotal evidence suggest that the burden of HCV disease, including cirrhosis and hepatocellular carcinoma, is increasing. Recent modelling studies investigating disease burden, however, have reported results that are discordant with actual outcomes. Although likely due to varying methodology, these discrepancies prompted the authors of this study to develop a more refined disease progression model that could describe the future burden of disease and cost of HCV infection. The results may facilitate disease forecasting, resource planning and the development of new management strategies.
Chronic infection with hepatitis C virus (HCV) is a major cause of cirrhosis, hepatocellular carcinoma and liver transplantation.
To estimate the burden of HCV-related disease and costs from a Canadian perspective.
Using a system dynamic framework, the authors quantified the HCV-infected population, disease progression and costs in Canada between 1950 and 2035. Specifically, 36 hypothetical, ageand sex-defined cohorts were tracked to define HCV prevalence, complications and direct medical costs (excluding the cost of antivirals). Model assumptions and costs were extracted from the literature with an emphasis on Canadian data. No incremental increase in antiviral treatment over current levels was assumed, despite the future availability of potent antivirals.
The estimated prevalence of viremic hepatitis C cases peaked in 2003 at 260,000 individuals (uncertainty interval 192,460 to 319,880), reached 251,990 (uncertainty interval 177,890 to 314,800) by 2013 and is expected to decline to 188,190 (uncertainty interval 124,330 to 247,200) in 2035. However, the prevalence of advanced liver disease is increasing. The peak annual number of patients with compensated cirrhosis (n=36,210), decompensated cirrhosis (n=3380), hepatocellular carcinoma (n=2220) and liver-related deaths (n=1880) are expected to occur between 2031 and 2035. During this interval, an estimated 32,460 HCV-infected individuals will die of liver-related causes. Total health care costs associated with HCV (excluding treatment) are expected to increase by 60% from 2013 until the peak in 2032, with the majority attributable to cirrhosis and its complications (81% in 2032 versus 56% in 2013). The lifetime cost for an individual with HCV infection in 2013 was estimated to be $64,694.
Although the prevalence of HCV in Canada is decreasing, cases of advanced liver disease and health care costs continue to rise. These results will facilitate disease forecasting, resource planning and the development of rational management strategies for HCV in Canada.
Cirrhosis; Hepatitis C; Hepatocellular carcinoma; Mortality; Outcomes; Treatment
A 56-year-old male developed an ulcer on his glans penis and mucosae of upper and lower lips 3 days after taking ofloxacin, cephalexin, and ornidazole. Clinically, a provisional diagnosis of fixed drug eruption was made. The causative drug was confirmed by an oral provocation test which triggered a reactivation of all lesions only with ornidazole.
Fixed drug eruption; ornidazole; provocation test
Background and Objectives. This is a prospective nested cohort study conducted over a period of 3 years. 2644 women were recruited, out of which final analysis was done for 1884 women. Methods. Cervicovaginal and blood samples were collected for all recruited women. Out of these, 137 women who delivered before 35 weeks were treated as cases and equal number of matched controls were chosen. Analysis of samples for serum G-CSF, AFP, ferritin, and cervicovaginal interleukin-6 and IGFBP-1 was done. Results. Poor orodental hygiene, which can be a social marker, was significantly more common in women who delivered preterm (P = 0.008). Serum alkaline phosphatase and serum ferritin were found to be significantly associated with preterm deliveries. The 90th percentile value of these parameters was considered as cut-off as there is no specific cut-off. Conclusions. Our study did not prove usefulness of any predictive marker. Serum ferritin and alkaline phosphatase were found to have correlation but their values are affected in many conditions and need to be elucidated with caution. Larger studies are needed for predicting preterm labour in asymptomatic women.
Cirrhosis of liver is an important cause of morbidity and mortality and if associated with peripheral neuropathy (PN) it also poses a huge financial, psychological burden for the patients and their families.
The aim of the present study was to study the magnitude of PN among subjects with cirrhosis of liver presenting to tertiary care teaching hospital in central rural India.
Settings and Design:
A cross-sectional study was performed in a tertiary care teaching hospital.
Materials and Methods:
In all patients of cirrhosis of liver irrespective of etiology, aged 15 and above, undergone clinical assessment for peripheral nervous systems damage and confirmed by nerve conduction studies.
Statistical Analysis Used:
We used chi square test to study associations. P value ≤0.05 was considered as significant. Crude odds ratios were computed to assess the strength of association between independent variables and dependent variables along with their 95% confidence intervals.
We included 207 of cirrhosis of liver patients admitted in medicine department from November 2010 through November 2013. Nearly 83% patients were male and 63.2% patients were under the age of 45 years. Common features in these patients were ascites (71%) splenomegaly (63.3%) pedal edema (61.4%) icterus (46.4%) tingling (44.9%) gastrointestinal bleeding(39.1%), ataxia (26.6%), numbness(26.6%), distal motor weakness (21.7%) and paresthesia(20.8%). Among the manifestation of peripheral nerve involvement, loss of ankle reflex was the most common feature in 51.7%, followed by loss of temperature sense 29.5%, loss of vibration sense 20.8%, loss of touch 16.4%, loss of position sense 14.5% and loss of pain in 6.3% of the patients. Peripheral neuropathy was found in 53.6% [95% CI: 46.58- 60.56] study subjects on electrophysiological study.
Analysis of electrophysiological study shows that the PN is very common in study subjects with cirrhosis of liver, especially in male subjects, during the middle age group.
Chronic liver disease; cirrhosis of liver; nerve conduction studies; peripheral neuropathy
The aim of this study was to find whether the visual evoked potential (VEP) latencies and amplitude are altered with different visual angles in healthy adult volunteers or not and to determine the visual angle which is the optimum and most appropriate among a wide range of check sizes for the reliable interpretation of pattern reversal VEPs (PRVEPs).
Materials and Methods:
The present study was conducted on 40 healthy volunteers. The subjects were divided into two groups. One group consisted of 20 individuals (nine males and 11 females) in the age range of 25-57 years and they were exposed to checks subtending a visual angle of 90, 120, and 180 minutes of arc. Another group comprised of 20 individuals (10 males and 10 females) in the age range of 36-60 years and they were subjected to checks subtending a visual angle of 15, 30, and 120 minutes of arc. The stimulus configuration comprised of the transient pattern reversal method in which a black and white checker board is generated (full field) on a VEP Monitor by an Evoked Potential Recorder (RMS EMG. EPMARK II). The statistical analysis was done by One Way Analysis of Variance (ANOVA) using EPI INFO 6.
In Group I, the maximum (max.) P100 latency of 98.8 ± 4.7 and the max. P100 amplitude of 10.05 ± 3.1 μV was obtained with checks of 90 minutes. In Group II, the max. P100 latency of 105.19 ± 4.75 msec as well as the max. P100 amplitude of 8.23 ± 3.30 μV was obtained with 15 minutes. The min. P100 latency in both the groups was obtained with checks of 120 minutes while the min. P100 amplitude was obtained with 180 minutes. A statistically significant difference was derived between means of P100 latency for 15 and 30 minutes with reference to its value for 120 minutes and between the mean value of P100 amplitude for 120 minutes and that of 90 and 180 minutes.
Altering the size of stimulus (visual angle) has an effect on the PRVEP parameters. Our study found that the 120 is the appropriate (and optimal) check size that can be used for accurate interpretation of PRVEPs. This will help in better assessment of the optic nerve function and integrity of anterior visual pathways.
Pattern reversal; P100 latency; P100 amplitude; VEP; visual angle
Objective: To Evaluate I, II, III, IV, V wave latencies and I-III, III-V, I-V inter-peak latencies and V/I wave amplitude ratio in Normal subjects in Central India.
Methods: We recorded BAEP from 50 healthy normal subjects from the community of same sex and geographical setup. The absolute, interpeak and wave V/I amplitude ratio were measurement and recording was done using RMS EMG EP MARK II machine manufactured by RMS recorders and Medicare system, Chandigarh.
Result: Absolute, interpeak and wave V/I amplitude ratio were measured in normal subjects and compared with other previous studies.
Conclusion: This study was conducted as exploratory pilot study only on male healthy controls. Since, the study conducted in different regions, there are some differences in the latencies and interpeak latencies and amplitude ratio but they are within range, so reference range of this study can be used for future studies in this Wardha region of Central India.
Conductive deafness; Inter-peak latency; Peak latency; Sensory-neural hearing loss
Multiple intestinal atresias are rare and its treatment is challenging. Here, we present a case of multiple gastro-intestinal atresia associated with choledochal cyst posing us a surgical challenge.
Multiple intestinal atresia; Choledochal cyst; Polyhydramnios
To survey gastroenterologists in British Columbia and Alberta with regard to awareness of chronic hepatitis C virus (HCV) management and practice patterns among physicians who treat and do not treat HCV-infected patients.
An anonymous two-page mail survey was distributed to actively practicing adult gastroenterologists in British Columbia and Alberta. Among physicians who treated HCV patients, respondents answered assessment of fibrosis pretreatment, measurement of rapid virological response, prescription of protease inhibitors (PIs), barriers to using these agents and referral patterns. For those who did not treat HCV, referral of patients for treatment and to whom was assessed.
Seventy-seven of 166 individuals completed the survey (46% response rate). Most (49%) practiced in academic or large community (42%) settings. Chronic liver disease comprised <25% of individual practice in 71%. Forty-eight (62%) treated HCV and two-thirds prescribed a PI. Barriers to prescription included unfamiliarity (six of 16), lack of allied health (five of 16) and few suitable patients (seven of 16). Pretreatment liver biopsy was performed by 33% (16 of 48) and 69% (33 of 48) used noninvasive measures. Rapid virological response was measured in 83% (40 of 48). Referral patterns changed in 46% (22 of 48) of physicians who treated HCV. All respondents who did not treat HCV referred patients for consideration, with 90% (26 of 29) made to hepatologists.
Chronic liver disease comprised <25% of practice in the majority of surveyed respondents. Among those who treated HCV, one-third have not prescribed a PI. Barriers to prescription and referral pattern changes are noted by those currently treating patients with HCV infection.
Barriers; Guidelines; HCV; Practice; Rapid virological response; Referral; Survey
Validity of Friedewald formula (FF) in patients with serum triglycerides (TGs) <400 mg/dl is unclear.
Materials and Methods:
We compared low-density lipoprotein (LDL)-cholesterol calculated by FF to directly measured LDL in a laboratory database of 14,620 lipid profile samples from south India.
LDL by FF correlated with directly measured LDL with correlation coefficient of 0.89 with the best correlation seen in TG levels 100-150. Higher level of TG (>200) underestimates the LDL calculated by FF particularly at LDL values <70 mg/dl. On the other hand, LDL is overestimated by FF in more than 70% of cases at LDL levels >130 mg/dl.
We suggest repeating the LDL by direct assay techniques particularly in patients with TG >200 and when LDL <70 or >130. This helps in correctly stratifying the coronary artery diseases’ (CADs’) risk and goals of treatment.
Friedewald formula; LDL cholesterol; triglyceride
To validate the pharyngeal findings in sleep nasopharyngoscopy (SNP) of children with snoring - sleep disordered breathing (S-SDB).
Prospective agreement diagnostic study on retrospective data.
We conducted an inter-and intra-rater agreement study on video documentations of SNP performed on children (non-syndromic, complex, or operated upon) who presented with S-SDB. The videos featured various pharyngeal findings (normal, collapse, mixed or obstruction). Three ‘non-expert’ raters at various stages in their otolaryngological careers rated the videos independently, and on two separate occasions following an instructional session. We calculated both weighted and non-weighted linear kappa.
Each independent observer rated sixty-one videos (2 weeks apart). Intra-observer agreement was 0.64 ± 0.08 (95% CI 0.48-0.81), 0.74 ± 0.07 (95% CI 0.60-0.88), 0.59 ± 0.08 (95% CI 0.43-0.74), for raters 1, two and three. Weighted kappa was 0.6 ± 0.1 (95% CI 0.41-0.79), 0.8 ± 0.06 (95% CI 0.7-0.92), 0.7 ± 0.07 (95% CI 0.57-0.83), respectively. Inter-rater agreements between raters one and two, two and three, three and four were 0.83 ± 0.06 (95% CI 0.71-0.95), 0.52 ± 0.08 (95% CI 0.36-0.70), and 0.53 ± 0.08 (95% CI 0.37-0.69), respectively. Weighted kappa was 0.83 ± 0.073 (95% CI 0.69-0.98), 0.68 ± 0.06 (95% CI 0.56-0.79), and 0.64 ± 0.07 (95% CI 0.49-0.78), respectively.
This is the first validation of pharyngeal findings on SNP in children. It is based on a four types’ classification. Overall reproducibility amongst the three raters and their agreement was moderate to good. Further work should be phase four trials investigating the impact on outcome.
Sleep apnea; Children; Endoscopy; Propofol; Agreement; Diagnosis; Adenotonsillectomy
Deep-sequencing has enabled the identification of large numbers of miRNAs and siRNAs, making the high-throughput target identification a main limiting factor in defining their function. In plants, several tools have been developed to predict targets, majority of them being trained on Arabidopsis datasets. An extensive and systematic evaluation has not been made for their suitability for predicting targets in species other than Arabidopsis. Nor, these have not been evaluated for their suitability for high-throughput target prediction at genome level.
We evaluated the performance of 11 computational tools in identifying genome-wide targets in Arabidopsis and other plants with procedures that optimized score-cutoffs for estimating targets. Targetfinder was most efficient [89% ‘precision’ (accuracy of prediction), 97% ‘recall’ (sensitivity)] in predicting ‘true-positive’ targets in Arabidopsis miRNA-mRNA interactions. In contrast, only 46% of true positive interactions from non-Arabidopsis species were detected, indicating low ‘recall’ values. Score optimizations increased the ‘recall’ to only 70% (corresponding ‘precision’: 65%) for datasets of true miRNA-mRNA interactions in species other than Arabidopsis. Combining the results of Targetfinder and psRNATarget delivers high true positive coverage, whereas the intersection of psRNATarget and Tapirhybrid outputs deliver highly ‘precise’ predictions. The large number of ‘false negative’ predictions delivered from non-Arabidopsis datasets by all the available tools indicate the diversity in miRNAs-mRNA interaction features between Arabidopsis and other species. A subset of miRNA-mRNA interactions differed significantly for features in seed regions as well as the total number of matches/mismatches.
Although, many plant miRNA target prediction tools may be optimized to predict targets with high specificity in Arabidopsis, such optimized thresholds may not be suitable for many targets in non-Arabidopsis species. More importantly, non-conventional features of miRNA-mRNA interaction may exist in plants indicating alternate mode of miRNA target recognition. Incorporation of these divergent features would enable next-generation of algorithms to better identify target interactions.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-348) contains supplementary material, which is available to authorized users.
miRNA; Target prediction; Plants; Deep-sequencing; Non-model plants
Background: Genetic factors cause about 15% of male infertility. Azoospermia factors (AZFa, AZFb, and AZFc) present on Yq are most important for spermatogenesis. We have made an attempt to evaluate the frequencies of microdeletions of AZFa, AZFb, AZFc in idiopathic cases of azoospermia and oligozoospermia from central Indian population.
Materials and Methods: We have analyzed a total of 156 subjects (95 oligozoospermia and 61 azoospermia) & 50 control subjects. DNA samples were analyzed for microdeletions of Y chromosome by PCR-screening of 18 sequences-tagged-site (STS) markers from different region of the AZF on Yq and SRY on Yp.
Results: Out of 156 cases analyzed, 13 (8.33%) subjects (8 azoospermia and 5 oligozoospermia) showed partial deletion of AZF regions, of which deletion in AZFc region was the most common (84.6%) followed by AZFb (15.4%) and AZFa (15.4%). The sites and sizes of deletions varied among patients. Histological study of the testicular tissue of the available subjects, who showed microdeletions of Y chromosome, showed spermatogenic arrest at different stages. The frequency of Y chromosome microdeletion in our subjects was 8.33%.
Conclusion: Some Indian studies reported low frequencies of microdeletions than that of our result. We suggest that the frequency of deletions may be affected by the involvement of different genetic factors, ethnic population and different geographical regions. PCR based Y chromosome screening for microdeletions will be useful and great help to infertility clinics for genetic counselling and assisted reproduction.
Male Infertility; Y microdeletions; AZF factor
To evaluate whether glaucomatous visual field defect particularly the pattern standard deviation (PSD) of Humphrey visual field could be associated with visual evoked potential (VEP) parameters of patients having primary open angle glaucoma (POAG).
Visual field by Humphrey perimetry and simultaneous recordings of pattern reversal visual evoked potential (PRVEP) were assessed in 100 patients with POAG. The stimulus configuration for VEP recordings consisted of the transient pattern reversal method in which a black and white checker board pattern was generated (full field) and displayed on VEP monitor (colour 14″) by an electronic pattern regenerator inbuilt in an evoked potential recorder (RMS EMG EP MARK II).
The results of our study indicate that there is a highly significant (P<0.001) negative correlation of P100 amplitude and a statistically significant (P<0.05) positive correlation of N70 latency, P100 latency and N155 latency with the PSD of Humphrey visual field in the subjects of POAG in various age groups as evaluated by Student's t-test.
Prolongation of VEP latencies were mirrored by a corresponding increase of PSD values. Conversely, as PSD increases the magnitude of VEP excursions were found to be diminished.
pattern reversal; pattern standard deviation; visual field; P100 latency
We report a case of full term female child having persistent cloaca who was diagnosed to have right lung agenesis on investigations.
Persistent cloaca; Lung agenesis
•Cytokines, and proteases expressed by macrophages play key roles in atherosclerosis.•The proteases ADAMTS-1, -4 and -5 were expressed in human atherosclerotic lesions.•The anti-atherogenic cytokine interleukin-33 (IL-33) inhibited the expression of these ADAMTS proteases in human macrophages.•This action of IL-33 required extracellular signal-regulated kinase, c-Jun N-terminal kinase and phosphoinositide 3-kinase signaling pathways.•These studies reveal novel anti-atherogenic action of IL-33 along with the underlying molecular mechanisms involved.
Atherosclerosis is an inflammatory disorder of the vasculature regulated by cytokines. Amongst the cytokines, IL-33 attenuates the development of atherosclerosis in mouse model systems via several mechanisms, including inhibition of macrophage foam cell formation and promotion of a Th1 to Th2 shift. Proteases produced by macrophages, such as matrix metalloproteinases and members of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, play potential roles in regulating atherosclerotic plaque stability. Despite such importance, the action of IL-33 on the expression of such proteases has not been analyzed. We have therefore investigated the effect of IL-33 on the expression of ADAMTS-1, -4 and -5 in human macrophages. Immunohistochemical analysis showed that these three proteases were expressed in human atherosclerotic lesions, particularly by macrophages and, to a lesser extent, by smooth muscle cells and endothelial cells. The expression of ADAMTS-1, -4 and -5 in human macrophages was specifically inhibited by IL-33. The action of IL-33 on the expression of these ADAMTS members was mediated through its receptor ST2. IL-33 activated ERK1/2, JNK1/2 and c-Jun, but not p38 MAPK or Akt, in human macrophages. RNA interference assays using a combination of adenoviral encoding small hairpin RNA and small interfering RNA showed a requirement of ERK1/2, JNK1/2, c-Jun, PI3Kγ and PI3Kδ, but not p38α, in the IL-33-inhibited expression of these ADAMTS isoforms. These studies provide novel insights into the expression of ADAMTS-1, -4 and -5 in human atherosclerotic lesions and the regulation of their expression in human macrophages by the key anti-atherogenic cytokine IL-33.
ADAMTS; Cytokine action; Cardiovascular disease; Macrophages; Signal transduction; ADAMTS, a disintegrin and metalloproteinase with thrombospondin motifs; apoE, apolipoprotein E; BMDM, bone marrow-derived macrophages; DAB, 3,3′-diaminobenzidine; ECM, extracellular matrix; HMDM, human monocyte-derived macrophages; IHC, immunohistochemistry; MMP, matrix metalloproteinase; RT-qPCR, real-time quantitative PCR; shRNA, small hairpin RNA; siRNA, small interfering RNA
Wilms’ tumour (WT) is seldom seen in a neonate and prenatal diagnosis is rare. We present a case of antenatally diagnosed left sided WT with features of hydrops foetalis in a girl baby. Emergency LSCS was done at 34 weeks of gestation for foetal distress. Patient required mechanical ventilation for birth asphyxia and congestive cardiac failure. After stabilization, gross total resection of the tumour was done on day 4 of life. Histopathology HPE confirmed classical WT (stage I). Unfortunately, the patient died on the second postoperative day despite all supportive measures.
Wilms’ tumour; Hydrops foetalis; Antenatal detection
To assess the impact of being born preterm or small for gestational age (SGA) on several adult outcomes.
We analyzed data for 4518 adult participants in 5 birth cohorts from Brazil, Guatemala, India, the Philippines, and South Africa.
In the study population, 12.8% of males and 11.9% of females were born preterm, and 26.8% of males and 22.4% of females were born term but SGA. Adults born preterm were 1.11 cm shorter (95% CI, 0.57-1.65 cm), and those born term but SGA were 2.35 cm shorter (95% CI, 1.93-2.77 cm) compared with those born at term and appropriate size for gestational age. Blood pressure and blood glucose level did not differ by birth category. Compared with those born term and at appropriate size for gestational age, schooling attainment was 0.44 years lower (95% CI, 0.17-0.71 years) in those born preterm and 0.41 years lower (95% CI, 0.20-0.62 years) in those born term but SGA.
Being born preterm or term but SGA is associated with persistent deficits in adult height and schooling, but is not related to blood pressure or blood glucose level in low- and middle-income settings. Increased postnatal growth is associated with gains in height and schooling regardless of birth status, but not with increases in blood pressure or blood glucose level.
AGA, Appropriate for gestational age; BMI, Body mass index; GA, Gestational age; IFG, Impaired fasting glucose; LGA, Large for gestational age; LMP, Last menstrual period; SGA, Small for gestational age
Male sex determination is initiated through the testis-determining factor SRY that promotes Sertoli cell differentiation and subsequent gonadal development. The basic helix-loop-helix (bHLH) gene Tcf21 was identified as one of the direct downstream targets of SRY. The current study was designed to identify the downstream targets of TCF21 and the potential cascade of bHLH genes that promote Sertoli cell differentiation. A modified ChIP-Chip comparative hybridization analysis identified 121 direct downstream binding targets for TCF21. The gene networks and cellular pathways potentially regulated by these TCF21 targets were identified. One of the main bHLH targets for TCF21 was the bHLH gene scleraxis (Scx). An embryonic ovarian gonadal cell culture was used to examine the functional role of Sry, Tcf21, and Scx to promote an in vitro sex reversal and induction of Sertoli cell differentiation. SRY and TCF21 were found to induce the initial stages of Sertoli cell differentiation, whereas SCX was found to induce the later stages of Sertoli cell differentiation associated with pubertal development using transferrin gene expression as a marker. Therefore, a cascade of SRY followed by TCF21 followed by SCX appears to promote, in part, Sertoli cell fate determination and subsequent differentiation. The current observations help elucidate the initial molecular events involved in the induction of Sertoli cell differentiation and testis development.
The SRY target TCF21 induces a downstream cascade of bHLH genes and the induction of Sertoli cell differentiation.
basic helix-loop-helix; cell differentiation; ChIP-Chip; SRY; scleraxis; Scx; Sertoli cells; sex determination; testis development