Epigenetic disruption of the RARγ complex impairs its function to bookmark AR enhancer interactions required for enzalutamide sensitivity in prostate cancer.

The current study in prostate cancer (PCa) focused on the genomic mechanisms at the cross-roads of pro-differentiation signals and the emergence of lineage plasticity. We explored an understudied cistromic mechanism involving RARγ's ability to govern AR cistrome-transcriptome relationships, including those associated with more aggressive PCa features. The RARγ complex in PCa cell models was enriched for canonical cofactors, as well as proteins involved in RNA processing and bookmarking. Identifying the repertoire of miR-96 bound and regulated gene targets, including those recognition elements marked by m6A, revealed their significant enrichment in the RARγ complex. RARγ significantly enhanced the AR cistrome, particularly in active enhancers and super-enhancers, and overlapped with the binding of bookmarking factors. Furthermore, RARγ expression led to nucleosome-free chromatin enriched with H3K27ac, and significantly enhanced the AR cistrome in G2/M cells. RARγ functions also antagonized the transcriptional actions of the lineage master regulator ONECUT2. Similarly, gene programs regulated by either miR-96 or antagonized by RARγ were enriched in alternative lineages and more aggressive PCa phenotypes. Together these findings reveal an under-investigated role for RARγ, modulated by miR-96, to bookmark enhancer sites during mitosis. These sites are required by the AR to promote transcriptional competence, and emphasize luminal differentiation, while antagonizing ONECUT2.

The MYC axis in advanced prostate cancer is impacted through concurrent targeting of ERß and AR using a novel ERß-selective ligand alongside Enzalutamide.

We have dissected the role of Estrogen receptor beta (ERß) in prostate cancer (PCa) with a novel ERß ligand, OSU-ERb-12. Drug screens revealed additive interactions between OSU-ERB-12 and either epigenetic inhibitors or the androgen receptor antagonist, Enzalutamide (Enza). Clonogenic and cell biolody studies supported the potent additive effects of OSU-ERB-12 (100nM) and Enza (1µM). The cooperative behavior was in PCa cell lines treated with either OSU-ERB-12 plus Enza or combinations involving 17ß-estradiol (E2). OSU-ERb-12 plus Enza uniquely impacted the transcriptiome, accessible chromatin, and the AR, MYC and H3K27ac cistromes. This included skewed transcriptional responses including suppression of the androgen and MYC transcriptomes, and repressed MYC protein. OSU-ERb-12 plus Enza uniquely impacted chromatin accessibility at approximately 3000 nucleosome-free sites, enriched at enhancers, enriched for basic Helix-Loop-Helix motifs. CUT&RUN experiments revealed combination treatment targeting of MYC, AR, and H3K27ac again shaping enhancer accessibility. Specifically, it repressed MYC interactions at enhancer regions enriched for bHLH motifs, and overlapped with publicly-available bHLH cistromes. Finally, cistrome-transcriptome analyses identified ~200 genes that distinguished advanced PCa tumors in the SU2C cohort with high androgen and low neuroendocrine scores.

African American Prostate Cancer Displays Quantitatively Distinct Vitamin D Receptor Cistrome-transcriptome Relationships Regulated by BAZ1A.

African American (AA) prostate cancer associates with vitamin D3 deficiency, but vitamin D receptor (VDR) genomic actions have not been investigated in this context. We undertook VDR proteogenomic analyses in European American (EA) and AA prostate cell lines and four clinical cohorts. Rapid immunoprecipitation mass spectrometry of endogenous protein (RIME) analyses revealed that nonmalignant AA RC43N prostate cells displayed the greatest dynamic protein content in the VDR complex. Likewise, in AA cells, Assay for Transposase-Accessible Chromatin using sequencing established greater 1α,25(OH)2D3-regulated chromatin accessibility, chromatin immunoprecipitation sequencing revealed significant enhancer-enriched VDR cistrome, and RNA sequencing identified the largest 1α,25(OH)2D3-dependent transcriptome. These VDR functions were significantly corrupted in the isogenic AA RC43T prostate cancer cells, and significantly distinct from EA cell models. We identified reduced expression of the chromatin remodeler, BAZ1A, in three AA prostate cancer cohorts as well as RC43T compared with RC43N. Restored BAZ1A expression significantly increased 1α,25(OH)2D3-regulated VDR-dependent gene expression in RC43T, but not HPr1AR or LNCaP cells. The clinical impact of VDR cistrome-transcriptome relationships were tested in three different clinical prostate cancer cohorts. Strikingly, only in AA patients with prostate cancer, the genes bound by VDR and/or associated with 1α,25(OH)2D3-dependent open chromatin (i) predicted progression from high-grade prostatic intraepithelial neoplasia to prostate cancer; (ii) responded to vitamin D3 supplementation in prostate cancer tumors; (iii) differentially responded to 25(OH)D3 serum levels. Finally, partial correlation analyses established that BAZ1A and components of the VDR complex identified by RIME significantly strengthened the correlation between VDR and target genes in AA prostate cancer only. Therefore, VDR transcriptional control is most potent in AA prostate cells and distorted through a BAZ1A-dependent control of VDR function. Significance: Our study identified that genomic ancestry drives the VDR complex composition, genomic distribution, and transcriptional function, and is disrupted by BAZ1A and illustrates a novel driver for AA prostate cancer.

Genomic Insights into Non-steroidal Nuclear Receptors in Prostate and Breast Cancer.

Alterations in transcriptional programs are a fundamental feature of prostate (PCa) and breast cancer (BrCa), and frequently target the actions of the principal steroidal nuclear receptors (NRs), namely the androgen receptor (AR) and the estrogen receptor alpha (ERα), respectively. Indeed, the functions of AR and ERα are central to both prostate and mammary gland biology. The genomic interactions of these NRs become highly distorted in part by changing how they functionally interact with a cohort of non-steroidal Type II NRs, which are by contrast relatively understudied compared to their steroidal cousins. For example, the AR cistrome overlaps with cistromes of different Type II NRs, which suggests a high potential for integrated NR functions to tailor transcriptional signals. Over recent years the cistromes of these Type II NRs, including HNF4s, RARs, PPARs and VDR, have been studied in PCa and BrCa revealing convergence and functional consequences, and are reviewed in the current chapter.

Climate warming-driven phenological shifts are species-specific in woody plants: evidence from twig experiment in Kashmir Himalaya.

Experimental evidences in support of climate warming-driven phenological shifts are still scarce, particularly from the developing world. Here, we investigated the effect of experimental warming on flowering phenology of selected woody plants in Kashmir Himalaya. We selected the twigs of four congeneric pairs of temperate woody species (Prunus, Populus, Ulmus, Viburnum)-typical spring-flowering plants in the region. Using randomised block design, we monitored these winter dormant twigs in controlled growth chambers to study the effect of different temperature regimes (9, 17, 20 and 23 °C) and species identity on the patterns of phenological shifts. We observed a significant phenological shift in all the species showing preponement in the first flower out and senescence phases ranging from 0.56 to 3.0 and 0.77 to 4.04 days per degree increase in temperature, respectively. The duration of flowering phase in all the species showed a corresponding decrease along the gradient of increasing temperature, which was more driven by preponement of the flower senescence than the start of flowering. The patterns of phenological shifts were highly species-specific, and the magnitude of these shifts significantly varied in all the four pairs of congeneric species despite their phylogenetic similarity. Our study provides experimental support to the previous long-term observation and herbarium-based studies showing that the patterns of phenological shifts in response to global climate warming are likely to vary between species, even those belonging to same evolutionary stock. Our findings highlight that a one-size-fits-all strategy to manage the likely impacts of climate warming-induced phenological shifts will seldom succeed, and should instead be designed for the specific phenological responses of species and regions.

Patterns of floristic and functional diversity in two treeline ecotone sites of Kashmir Himalaya.

Globally, the treelines at higher elevations in mountains are reported to be advancing up-slope in response to recent climate warming. However, little is known about the treeline advancement in the Himalaya due to paucity of baseline vegetation data with which to compare, thus making their assessment and monitoring challenging. To fill this knowledge gap, the present study documented floristic and functional diversity of two treeline ecotone sites in Kashmir Himalaya. At each site, we conducted field sampling by laying five 20-m2 plots, with one at the highest limit (T0 plot), two plots below and two above the treeline and two nested subplots of 5-m2 for shrubs and five 1-m2 for herbs in each plot. We recorded 97 plant species belonging to 33 families from the two sites. We observed a considerable difference in species composition and distribution along the treeline ecotone. Majority of the species reported were perennial herbs. We observed a significant association of growth forms with the particular plots along the treeline ecotone. At both the sites, we recorded highest species richness at the T0 plot which was correlated well with the functional traits, thus indicating convergence of floristic and functional diversity at this transition zone. Interestingly, the T0 plot at both the sites showed maximum overlap of species with the plots above and below the treeline. In an era of climate warming, our study provides crucial baseline data that will facilitate assessment and monitoring of the Himalayan treelines.

Epigenomic alterations in cancer: mechanisms and therapeutic potential.

The human cell requires ways to specify its transcriptome without altering the essential sequence of DNA; this is achieved through mechanisms which govern the epigenetic state of DNA and epitranscriptomic state of RNA. These alterations can be found as modified histone proteins, cytosine DNA methylation, non-coding RNAs, and mRNA modifications, such as N6-methyladenosine (m6A). The different aspects of epigenomic and epitranscriptomic modifications require protein complexes to write, read, and erase these chemical alterations. Reflecting these important roles, many of these reader/writer/eraser proteins are either frequently mutated or differentially expressed in cancer. The disruption of epigenetic regulation in the cell can both contribute to cancer initiation and progression, and increase the likelihood of developing resistance to chemotherapies. Development of therapeutics to target proteins involved in epigenomic/epitranscriptomic modifications has been intensive, but further refinement is necessary to achieve ideal treatment outcomes without too many off-target effects for cancer patients. Therefore, further integration of clinical outcomes combined with large-scale genomic analyses is imperative for furthering understanding of epigenomic mechanisms in cancer.

Reduced NCOR2 expression accelerates androgen deprivation therapy failure in prostate cancer.

This study addresses the roles of nuclear receptor corepressor 2 (NCOR2) in prostate cancer (PC) progression in response to androgen deprivation therapy (ADT). Reduced NCOR2 expression significantly associates with shorter disease-free survival in patients with PC receiving adjuvant ADT. Utilizing the CWR22 xenograft model, we demonstrate that stably reduced NCOR2 expression accelerates disease recurrence following ADT, associates with gene expression patterns that include neuroendocrine features, and induces DNA hypermethylation. Stably reduced NCOR2 expression in isogenic LNCaP (androgen-sensitive) and LNCaP-C4-2 (androgen-independent) cells revealed that NCOR2 reduction phenocopies the impact of androgen treatment and induces global DNA hypermethylation patterns. NCOR2 genomic binding is greatest in LNCaP-C4-2 cells and most clearly associates with forkhead box (FOX) transcription factor FOXA1 binding. NCOR2 binding significantly associates with transcriptional regulation most when in active enhancer regions. These studies reveal robust roles for NCOR2 in regulating the PC transcriptome and epigenome and underscore recent mutational studies linking NCOR2 loss of function to PC disease progression.

Substantial shifts in flowering phenology of Sternbergia vernalis in the Himalaya: Supplementing decadal field records with historical and experimental evidences.

In an age of anthropocene, shifting plant phenology is one of the most striking biological indicators of global environmental change. Majority of the studies reporting shifts in plant phenology are available from the North America and Europe and largely scarce from the developing world, including the Himalaya; and studies integrating multiple methodological approaches to investigate the climate-driven phenological shifts are too rare. Here, we report the shifts in spring flowering phenology of model plant species, Sternbergia vernalis in response to the changing climate in Kashmir Himalaya, by integrating decadal field observational records with long-term herbarium and dated-photograph data, and supported with experimental evidences. Our results revealed a significant increasing trend of 0.038, 0.016 and 0.023 °C/year in the annual mean maximum temperature (Tmax), mean minimum temperature (Tmin) and diurnal temperature range (DTR) respectively; but an insignificant decreasing trend in annual precipitation of -1.24 mm/year over the last four decades (1980-2019) in this Himalayan region. The flowering phenology of S. vernalis has significantly advanced by 11.8 days/°C and 27.8 days/°C increase in Tmax and Tmin respectively, indicating that the climate warming has led to substantial shifts in flowering phenology of the model plant species. We also observed a strong association of seasonal Tmax (December-February) and DTR on the early onset of spring flowering, however precipitation had no significant effect on the timing of flowering. The greenhouse experiment results further supported a significant effect of temperature in triggering the phenological shifts, wherein the model plant grown under different temperature treatments flowered 9-20 days earlier compared to the control. Our study showcases the integrated use of multiple methodological approaches for unravelling the long-term phenological shifts in response to climate change, and contributes in filling the knowledge gaps in the phenological research from the developing world in general and the Himalaya in particular.

Identification of transcription factor co-regulators that drive prostate cancer progression.

In prostate cancer (PCa), and many other hormone-dependent cancers, there is clear evidence for distorted transcriptional control as disease driver mechanisms. Defining which transcription factor (TF) and coregulators are altered and combine to become oncogenic drivers remains a challenge, in part because of the multitude of TFs and coregulators and the diverse genomic space on which they function. The current study was undertaken to identify which TFs and coregulators are commonly altered in PCa. We generated unique lists of TFs (n = 2662), coactivators (COA; n = 766); corepressors (COR; n = 599); mixed function coregulators (MIXED; n = 511), and to address the challenge of defining how these genes are altered we tested how expression, copy number alterations and mutation status varied across seven prostate cancer (PCa) cohorts (three of localized and four advanced disease). Testing of significant changes was undertaken by bootstrapping approaches and the most significant changes were identified. For one commonly and significantly altered gene were stably knocked-down expression and undertook cell biology experiments and RNA-Seq to identify differentially altered gene networks and their association with PCa progression risks. COAS, CORS, MIXED and TFs all displayed significant down-regulated expression (q.value < 0.1) and correlated with protein expression (r 0.4-0.55). In localized PCa, stringent expression filtering identified commonly altered TFs and coregulator genes, including well-established (e.g. ERG) and underexplored (e.g. PPARGC1A, encodes PGC1α). Reduced PPARGC1A expression significantly associated with worse disease-free survival in two cohorts of localized PCa. Stable PGC1α knockdown in LNCaP cells increased growth rates and invasiveness and RNA-Seq revealed a profound basal impact on gene expression (~ 2300 genes; FDR < 0.05, logFC > 1.5), but only modestly impacted PPARγ responses. GSEA analyses of the PGC1α transcriptome revealed that it significantly altered the AR-dependent transcriptome, and was enriched for epigenetic modifiers. PGC1α-dependent genes were overlapped with PGC1α-ChIP-Seq genes and significantly associated in TCGA with higher grade tumors and worse disease-free survival. These methods and data demonstrate an approach to identify cancer-driver coregulators in cancer, and that PGC1α expression is clinically significant yet underexplored coregulator in aggressive early stage PCa.

Management of Intussusception in the Era of Ultrasound-Guided Hydrostatic Reduction: A 3-Year Experience from a Tertiary Care Center.

INTRODUCTION: Ultrasound-guided hydrostatic reduction (HSR) is currently the initial management tool in the treatment of intussusception. HSR is, however, confronted with failures besides there are still a number of patients who primarily undergo surgical intervention for the management of intussusception. We undertook this study to assess the efficacy of HSR and also to look for factors demanding the surgical exploration in patients with intussusception. MATERIALS AND METHODS: A total of 215 patients with intussusception from June 2014 to June 2017 were prospectively studied. HSR was carried out in 203 patients, which was successful in 187 and unsuccessful in 16. These two groups were compared using the Student's t-test. Significance was set at P < 0.05. Twelve patients undergoing surgery primarily were also assessed for the factors affecting the decision-making. RESULTS: HSR was successful in 187 and unsuccessful in 16. The failed group was more likely to have symptoms over 24 h, appearance of crescent, and ≥10-cm length on ultrasonography (USG). Two of these patients had ischemic bowel, two had ileoileal intussusception, and eight had pathological lead points, whereas no obvious cause could be identified in the rest of the four patients. Among the 12 patients who were primarily operated, four patients had peritonitis and other four patients were neonates. Laparoscopic reduction was done in four patients. CONCLUSION: HSR is a safe and effective treatment modality for intussusception. However, it is met with higher failure rates in patients with risk factors such as delayed presentation, appearance of crescent on USG, and length >10 cm. The role of HSR is also dubious in situations such as neonatal intussusception, small-bowel intussusception, and multiple intussusceptions and also in preventing the future recurrence. Such patients ought to be managed by laparotomy or where feasible by laparoscopy. Furthermore, before embarking on HSR, peritonitis and bowel ischemia should be ruled out clinically and radiologically. In the suspicious cases of bowel ischemia, USG Doppler may be helpful.

Signature of genome wide gene expression in classical swine fever virus infected macrophages and PBMCs of indigenous vis-a-vis crossbred pigs.

The genetic basis of differential host immune response vis-à-vis transcriptome profile was explored in PBMCs of indigenous (Ghurrah) and crossbred pigs after classical swine fever vaccination and in monocyte derived macrophages (MDMs) challenged with virulent classical swine fever (CSF) virus. The humoral immune response (E2 antibody) was higher (74.87%) in crossbred than indigenous pigs (58.20%) at 21st days post vaccination (21dpv). The rate of reduction of ratio of CD4+/CD8+ was higher in crossbred pigs than indigenous pigs at 7th days post vaccination (7dpv). The immune genes IFIT1, IFIT5, RELA, NFKB2, TNF and LAT2 were up regulated at 7dpv in RNA seq data set and was in concordance during qRT-PCR validation. The Laminin Subunit Beta 1 (LAMB1) was significantly (p ≤ 0.05) down-regulated in MDMs of indigenous pigs and consequently a significantly (p ≤ 0.01) higher copy number of virulent CSF virus was evidenced in macrophages of crossbred pigs than indigenous pigs. Activation of LXR:RXR pathway at 60 h post infection (60hpi) in MDMs of indigenous versus crossbred pigs inhibited nuclear translocation of NF-κB, resulted into transrepression of proinflammatory genes. But it helped in maintenance of HDL level by lowering down cholesterol/LDL level in MDMs of indigenous pigs. The key immune genes (TLR2, TLR4, IL10, IL8, CD86, CD54, CASP1) of TREM1 signaling pathway were upregulated at 7dpv in PBMCs but those genes were downregulated at 60hpi in MDMs indigenous pigs. Using qRT-PCR, the validation of differentially expressed, immunologically important genes (LAMB1, OAS1, TLR 4, TLR8 and CD86) in MDMs revealed that expression of these genes were in concordance with RNA-seq data.

Modulation of Host miRNAs Transcriptome in Lung and Spleen of Peste des Petits Ruminants Virus Infected Sheep and Goats.

Peste des petits ruminants (PPR) is one of the highly contagious viral disease, characterized by fever, sore mouth, conjunctivitis, gastroenteritis, and pneumonia, primarily affecting sheep and goats. Reports suggested variable host response in goats and sheep and this host response vis-a-vis the expression of microRNAs (miRNAs) has not been investigated. Here, miRNAs were sequenced and proteomics data were generated to identify the role of differentially expressed miRNA (DEmiRNA) in PPR virus (PPRV) infected lung and spleen tissues of sheep and goats. In lungs, 67 and 37 DEmiRNAs have been identified in goats and sheep, respectively. Similarly, in spleen, 50 and 56 DEmiRNAs were identified in goats and sheep, respectively. A total of 20 and 11 miRNAs were found to be common differentially expressed in both the species in PPRV infected spleen and lung, respectively. Six DEmiRNAs-miR-21-3p, miR-1246, miR-27a-5p, miR-760-3p, miR-320a, and miR-363 were selected based on their role in viral infections, apoptosis, and fold change. The target prediction analysis of these six selected DEmiRNAs from the proteome data generated, revealed involvement of more number of genes in lung and spleen of goats than in sheep. On gene ontology analysis of host target genes these DEmiRNAs were found to regulate several immune response signaling pathways. It was observed that the pathways viz. T cell receptor signaling, Rap1 signaling, Toll-like receptor signaling, and B cell receptor signaling governed by DEmiRNAs were more perturbed in goats than in sheep. The data suggests that PPRV-induced miR-21-3p, miR-320a, and miR-363 might act cooperatively to enhance viral pathogenesis in the lung and spleen of sheep by downregulating several immune response genes. The study gives an important insight into the molecular pathogenesis of PPR by identifying that the PPRV-Izatnagar/94 isolate elicits a strong host response in goats than in sheep.

Use of gastrografin in the management of worm-induced small bowel obstruction in children.

OBJECTIVE: Ascaris-induced small bowel obstruction (SBO) is a common sequel of Ascaris lumbricoides (AL) infestation. Most cases respond to conservative treatment practiced in different centers worldwide. We conceived a prospective randomized trial to compare the conservative treatment with gastrografin administered in addition to the conservative treatment. STUDY DESIGN: This prospective randomized study was conducted between January 2011 and June 2014 at Department of Paediatric and Neonatal Surgery, a tertiary-care hospital. Patients were divided into two groups, one group received conservative treatment and the other received gastrografin in addition to conservative treatment. Forty patients having uncomplicated AL-induced SBO were included in each group. Gastrografin was administered through nasogastric tube and serial clinical and radiological monitoring was performed. The duration of hospital stay, time between admission and first oral feed, passage of worms/flatus were compared in the two groups. Student's t test was used for comparing these variables. RESULTS: Average time for passage of flatus or worms and resolution of abdominal signs and was shorter in gastrografin group as compared to the conservative group. This difference was found to be statistically significant. The average duration of hospital stay in gastrografin group was 25.20 ± 8.01 h whereas it was 61.12 ± 14.64 h in the conservative group (P < 0.001). The difference in the operation rate was statistically insignificant (2 in gastrografin group and 3 in the conservative group).No serious adverse reaction was noted after gastrografin administration. CONCLUSION: Use of gastrografin resulted in faster relief of signs and symptoms of AL-induced SBO, early passage of worms/flatus and return to oral feeds. However, the role of gastrografin role in reducing the likelihood of laparotomy remains inconclusive. Adverse effects of gastrografin can be prevented if it is used in well-hydrated patients.

Pulmonary Sequestration: Early Diagnosis and Management.

Intralobar sequestration is characterized by aberrant formation of nonfunctional lung tissue that has no communication with the bronchial tree and receives systemic arterial blood supply. Failure of earlier diagnosis can lead to recurrent pneumonia, failure to thrive, multiple hospital admissions, and more morbidity. The aim of this case report is to increase the awareness about the lung sequestration, to diagnose and treat it early, so that it is resected before repeated infection, and prevent the morbidity and mortality.

Antioxidants and its Properties as Affected by Extrusion Process: A Review.

Antioxidants are important for plant and animal's life or health. These are the substances that protect them from the damage produced by unstable molecules called as free radicals. There are various types of antioxidants to be reported both natural as well as synthetic such as melatonin, Vitamin C, glutathione, tocopherols and tocotrienols, BHA and BHT, etc. A new antioxidant 5-O-[6˝-(3- hydroxy-3methyl glutarate) ß-D-glucodise was found while studying bioactive antioxidants from plant foods for nutraceutical product development. Antioxidants have been used for increasing shelf life of various food products including extruded product. Antioxidants, their beneficial advantages and the effect of extrusion on antioxidants were reviewed and found to be effective in increasing the shelf life. This review article discusses recent patents, presents importance of antioxidant, phytochemicals and effect of process of extrusion on antioxidants.

Inguinal Hydatid cyst in a child: A rare case report.

INTRODUCTION: Hydatid disease is a common health problem in developing countries and liver and lungs are the most commonly involved organs. Hydatid cyst in inguinal canal is very rare and no case in children has been reported in literature. PRESENTATION OF CASE: We describe a four year male child with right inguinal swelling with occasional pain and gradually increase in size. The diagnosis of lipoma of the cord was made. Up on inguinal exploration, coincidently Hydatid cyst was detected. Postoperatively histopathological examination (HPE) of the cyst confirmed the diagnosis of Hydatid disease and patient was put on albendazole therapy for three months. DISCUSSION: Hydatid disease is very rare in the inguinal canal and no case in children has been reported. In adults fewer than five cases has been reported and is usually coincidently detected during surgical exploration, as was in our case. Ultrasonography, CT, MRI and other serological tests may help in pre-operative diagnosis. CONCLUSION: In endemic areas, patients with progressive enlarging groin swelling, possibility of Hydatid cyst should be kept in mind and should be operated as early as possible.

Late-presenting congenital diaphragmatic hernia.

BACKGROUND: This study was undertaken to highlight the clinical profile, misdiagnosis, surgical treatment,and prognosis of late-presenting congenital diaphragmatic hernia (CDH) cases in a tertiary level hospital. PATIENTS AND METHODS: This retrospective study included all the babies and children >1 month of age with CDH who were admitted in our Hospital (Sher-i-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India) during the period between January 2008 and December 2013. Babies with age <1 month were excluded from the study. Data regarding clinical profile, operative records, and follow-up was reviewed and analysed statistically. RESULTS: A total of 20 patients were included in this study. The clinical picture ranged from respiratory distress (13 patients) to non-specific gastrointestinal complaints (5 patients). In two patients, CDH was misdiagnosed as pneumothorax and had got chest tube inserted in other hospitals before referral to this tertiary care centre. In 14 patients chest, X-ray revealed the diagnosis of CDH and in remaining five patients (including the two patients with misdiagnosis) further investigations were undertaken to establish the diagnosis. Age ranged from 45 days to 17 years with an average age of 58.9 months. There were 12 male and 8 female patients. In all the 20 patients, surgical procedures were undertaken with the retrieval of herniated contents from the thoracic cavity and repair of the diaphragmatic defect. There was no mortality in our series. All the 20 patients were followed-up for a period ranging from 6 months to 5 years (median 3.1 years). CONCLUSIONS: Late-presenting CDH can have diverse clinical presentation. Late diagnosis and misdiagnosis can result in significant morbidity and potential mortality if these cases are not managed properly at an appropriate stage. Outcome is favourable if these patients are expeditiously identified and surgically repaired.