Navigating an unexpected diagnosis - experience of a tertiary referral centre with two cases of intraplacental choriocarcinoma.

Intraplacental choriocarcinoma is a rare tumour, with approximately 62 reported cases. It may manifest as a spectrum of disease ranging from an incidental lesion diagnosed on routine placental examination to disseminated maternal and/or neonatal disease. In this case series, we presented two rare cases of intraplacental choriocarcinoma with extremely varied clinical presentations. The extremely varied clinical presentations of both patients described in the case series complicated the process of arriving at the diagnosis. In both cases, subsequent investigations showed no maternal or neonatal metastasis, and maternal serum beta-hCG levels downtrended with conservative management. We aim to highlight the importance of performing a detailed physical examination and evaluation of the patient and multidisciplinary management with oncology opinion. A detailed examination of the placenta should also be considered when faced with obstetric complications so that early diagnosis and the required management can be executed in a prompt fashion.

CYP2D6 rs35742686 and rs3892097 Gene Polymorphisms and Childhood Acute Lymphoblastic Leukemia: Relation to Disease Susceptibility in Kashmiri Children.

CYP2D6 is one of the most widely investigated CYPs in relation to gene polymorphism. This study analyzed the relationship between CYP2D6 rs35742686 and rs3892097 single-nucleotide polymorphisms (SNPs) and potential risk factors in the development of acute lymphoblastic leukemia (ALL) in Kashmiri children. We recruited 300 cases and 600 controls for genotyping and risk factors assessment. Genotypes of rs35742686 and rs3892097 were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. CYP2D6 expression analysis was done by quantitative reverse transcription polymerase chain reaction in ALL cases. Conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). High risk of ALL was observed in cases who carried the mutant genotypes of rs35742686 (OR = 18.15; 95% CI = 4.13-79.66, p < 0.0001) or rs3892097 (OR = 24.06; 95% CI = 10.23-56.53, p < 0.0001). Significant interaction was observed between rs35742686 and rs3892097 SNPs (P interaction = 0.001). The risk associated with the variant genotypes of rs35742686 and rs3892097 was retained in the cases whose fathers were smokers or had maternal X-ray exposure ( p < 0.001). Relative messenger ribonucleic acid expression across genotypes was significantly decreased in cases carrying rs35742686 3 (*3/*3) ( n -fold = 0.37 ± 0.156, p < 0.0079) and rs3892097 SNPs (*4/*4) ( n -fold = 0.02 ± 0.0075, p < 0.0001) suggesting these two events are independent in ALL cases. The study concluded that rs35742686 and rs3892097 SNPs are significantly associated with ALL risk in Kashmiri children.

Migrated and Impacted Foreign Body of Retropharyngeal Space: A Case Report.

Foreign body upper aerodigestive tract is a common presentation but foreign body migrating into retropharyngeal space is not only uncommon, but its management also differs and is challenging too. Here we present a case of a foreign body migrating into the retropharyngeal space which was removed intraorally. A 28- year old male patient presented with complaints of pain while swallowing following consumption of sausage and pork two days earlier to the onset of symptoms. X-Ray Neck AP and lateral view were done which revealed a thin metallic foreign body at the level of the T4 vertebra. Upper gastrointestinal endoscopy and rigid esophagoscopy were done in which a foreign body was not visualized in the esophageal lumen. NCCT neck was done which gave precise location and was removed intraorally with the patient in Rose position. A repeat x-ray was done on the 5th day which revealed no foreign body, the patient was discharged on the 7th day. Although the upper aerodigestive tract foreign body is common, foreign body migrating to the posterior pharyngeal wall or into the retropharyngeal space is not common and it is difficult to remove a migrated foreign body many cases requiring open procedures, thoracoscopy, thoracotomy.

Neuroaxial Infantile Hemangiomas: Imaging Manifestations and Association with Hemangioma Syndromes.

BACKGROUND AND PURPOSE: Infantile hemangiomas are common lesions in the pediatric population; in rare cases, an infantile hemangioma can be detected along the neural axis. The purposes of our study included determination of the incidence, location, and imaging appearance of neuroaxial infantile hemangiomas and their syndromic association. We also assessed additional features of cerebral and cardiovascular anomalies that may be associated with neuroaxial lesions. MATERIALS AND METHODS: A retrospective cohort study was performed, searching the radiology database for patients with segmental infantile hemangiomas referred for assessment of possible hemangioma syndromes. We retrospectively reviewed brain and spine MR imaging studies, with particular attention paid to neuroaxial vascular lesions, as well as the relevant clinical data. Neuroaxial hemangioma imaging findings were described, and comparison of segmental cutaneous infantile hemangioma location with the imaging findings was performed in patients with confirmed hemangioma syndromes and in patients with isolated skin infantile hemangioma. RESULTS: Ninety-five patients with segmental infantile hemangioma were included in the study, 42 of whom had a hemangioma syndrome; of those, 41 had posterior fossa brain malformations, hemangioma, arterial lesions, cardiac abnormalities, and eye abnormalities (PHACE) syndrome and 1 had diffuse neonatal hemangiomatosis. Neuroaxial involvement was detected in 20/42 patients (48%) with hemangioma syndromes and in no subjects with isolated segmental infantile hemangioma (P < .001). The most common intracranial hemangioma location was within the ipsilateral internal auditory canal (83%). CONCLUSIONS: Many pediatric patients with segmental infantile hemangioma in the setting of hemangioma syndromes, especially those with PHACE, had neuroaxial hemangiomas. This finding may potentially lead to requiring additional clinical evaluation and management of these patients.

Possible role of miR-2909 RNomics in arsenic mediated pancreatic ß-cell dysfunction.

Chronic exposure of humans to inorganic arsenic as a potential risk for the incidence of diabetes has received wide attention. However, the biological mechanism through which arsenic plays a role in the development of diabetes is still being evaluated. One of the hallmark of diabetes is the ß-cell dysfunction followed by the changes in the insulin secretion. Pancreatic duodenal homeobox 1 (PDX1) has been widely recognized to play crucial role in the ß-cell development, survival and its regulation of insulin gene expression. Many of the arsenic mediated cellular affects have been shown to be regulated by miR-2909 in vitro. Our present study provides evidence to reveal that arsenic affects miR-2909 expression in the pancreatic ß-cell and this novel miRNA regulates PDX1 transcriptional expression indirectly through genes coding for c-Jun, MafA, PI3K and directly at the translational level by targeting the PDX1 mRNA. We provide further evidence for this miR-2909 RNomics in pancreatic tissue obtained from NOD mice where the expression of miR-2909 was high compared to the control mice. Keeping in view the fact that arsenic is known to cause ß-cell dysfunction and most of the cellular effects of arsenic have been shown to be mediated through miR-2909 RNomics, our study revealed that arsenic employs miR-2909 (at low doses) and c-Jun (at high doses) to down regulate PDX1 in order to cause ß-cell dysfunction leading to diabetic state.

Urinary-exosomal miR-2909: A novel pathognomonic trait of prostate cancer severity.

The global occurrence of prostate cancer with a range of patient outcome has prompted various investigators to explore novel molecular biomarkers that can precisely detect and track this type of cancer severity. Several studies suggest that micro-RNAs have emerged to act as a new largely unexplored class of biomarkers because of their inherent stability, resilience and recruitment into exosomes present in various human body fluids. With this study, we aim to reveal the nature of urinary-exosomal miR-2909 & miR-615-3p recruitment in patients suffering from either prostate cancer (n=90) or bladder cancer (n=60) as compared to that in either prostate disease-control subjects having benign prostate hyperplasia (n=10) or healthy subjects (n=50). Unlike miR-615-3p, the urinary- exosomal miR-2909 recruitment was not only observed conspicuously in subjects having prostate cancer in comparison to bladder cancer but also the extent of urinary exosomal miR-2909 recruitment showed characteristic variation as a function of prostate cancer aggressiveness as compared to that of either urinary- exosomal miR-615-3p level or existing widely recognised serum prostate specifics antigen (PSA) biomarker of this cancer. In summary, we propose that the extent of urinary exosomal miR-2909 recruitment may provide a potential non-invasive candidate diagnostic marker for the detection of prostate cancer and its aggressiveness.

Evolutionarily conserved dual lysine motif determines the non-chaperone function of secreted Hsp90alpha in tumour progression.

Both intracellular and extracellular heat shock protein-90 (Hsp90) family proteins (α and ß) have been shown to support tumour progression. The tumour-supporting activity of the intracellular Hsp90 is attributed to their N-terminal ATPase-driven chaperone function. What molecular entity determines the extracellular function of secreted Hsp90 and the distinction between Hsp90α and Hsp90ß was unclear. Here we demonstrate that CRISPR/Case9 knocking out Hsp90α nullifies tumour cells' ability to migrate, invade and metastasize without affecting the cell survival and growth. Knocking out Hsp90ß leads to tumour cell death. Extracellular supplementation with recombinant Hsp90α, but not Hsp90ß, protein recovers tumourigenicity of the Hsp90α-knockout cells. Sequential mutagenesis identifies two evolutionarily conserved lysine residues, lys-270 and lys-277, in the Hsp90α subfamily that determine the extracellular Hsp90α function. Hsp90ß subfamily lacks the dual lysine motif and the extracellular function. Substitutions of gly-262 and thr-269 in Hsp90ß with lysines convert Hsp90ß to a Hsp90α-like protein. Newly constructed monoclonal antibody, 1G6-D7, against the dual lysine region of secreted Hsp90α inhibits both de novo tumour formation and expansion of already formed tumours in mice. This study suggests an alternative therapeutic approach to target Hsp90 in cancer, that is, the tumour-secreted Hsp90α, instead of the intracellular Hsp90α and Hsp90ß.

Immunomodulatory activity of aqueous extract of Nyctanthes arbor-tristis flowers with particular reference to splenocytes proliferation and cytokines induction.

OBJECTIVES: To investigate the immunomodulatory activity of aqueous extract of Nyctanthes arbor-tristis flowers (NAFE) with particular reference to splenocytes proliferation and induction of cytokines. MATERIALS AND METHODS: Antibody titer was determined by tube agglutination and indirect ELISA assay in four groups of mice-control, antigen alone, and NAFE-treated (400 and 800 mg/kg for 21 days) after immunization with Salmonella antigen while cellular immunity was studied in three groups of rats (control and NAFE-treated - 400 and 800 mg/kg) following DNCB application. Splenocytes from untreated and NAFE-treated rats were stimulated using concanavalin-A (Con-A) and optical density (OD) and stimulation index were determined. Splenocytes from control rats were also treated in vitro with NAFE (50-1600 µg/ml) and Con-A to determine the effect on splenocytes proliferation. Interleukin-2 (IL-2) and IL-6 levels in splenocytes supernatant from control and NAFE-treated rats and following in vitro treatment of splenocytes with NAFE (50-1600 µg/ml) were determined using ELISA kits. RESULTS: Marked to a significant increase in antibody titer by both the methods in NAFE-treated mice and a significant increase in skin thickness in rats after challenge with DNCB, respectively suggested humoral and cell-mediated immunostimulant potential of NAFE. Significant increase in OD and stimulation index following e x vivo and in vitro exposure of splenocytes and sensitization with Con-A and significant elevation in IL-2 and IL-6 levels in splenocytes supernantant was also observed after their ex vivo and in vitro exposure to NAFE. CONCLUSION: Humoral and cell-mediated immunostimulant activity of NAFE seems to be mediated through splenocytes proliferation and increased production of cytokines, especially IL-2 and IL-6.

A scoping review of perineural steroids for the treatment of chronic postoperative inguinal pain.

PURPOSE: To review the literature on the efficacy and safety of perineural steroid injections around the ilioinguinal, iliohypogastric, and genitofemoral nerves for chronic postoperative inguinal pain (CPIP). METHODS: A scoping review was performed to find all relevant case reports, case series, prospective or retrospective cohort studies, case-control studies, and randomized controlled trials (RCTs) where a steroid was used for perineural procedures around ilioinguinal, iliohypogastric, and/or genitofemoral nerves for CPIP. Databases searched included Ovid MEDLINE, EMBASE, CINHAL, Cochrane CENTRAL, and Google Scholar. RESULTS: A total of five publications were found-three studies were prospective case series, one a retrospective cohort study, and one a RCT. The most common steroids used were methylprednisolone and triamcinolone. The average methylprednisolone-equivalent dose used per procedure was 46 mg (SD 21.9). Procedural guidance included anatomic landmarks (three studies), nerve stimulation and ultrasound (one study), and computed tomography guidance (one study). Four studies reported analgesic benefit in 55-75 % of included patients, with one study documenting an effect up to 50 months later after steroid perineural injections. The RCT demonstrated no benefit of adding steroid to a local anesthetic in the perioperative setting but it did not enroll patients with existing neuropathic pain. No adverse outcomes of perineural steroids were documented within reviewed studies. CONCLUSIONS: The paucity of data, heterogeneity and lack of appropriate control groups in the available literature precludes firm conclusions on the efficacy and safety of perineural steroids for CPIP. Future adequately powered, high-quality, placebo-controlled studies are needed.

Follow-up (99m)Tc EC renal dynamic scintigraphy and DMSA-III SPECT/CT in unmasking a masqueraded case of Horseshoe kidney.

Hydronephrosis is a common finding in urinary tract outflow obstruction. Chronically obstructed hydronephrotic system may be associated with parenchymal changes. Ultrasound, intravenous urography, micturating cysto-urethrogram and scintigraphy are commonly performed to evaluate the cause of obstruction. In childhood, pelviureteric junction obstruction is a common cause of the hydronephrosis. Hydronephrosis can also be present in horseshoe kidneys due to poor drainage. However, a large sized hydronephrotic cavity may obscure the finding of horseshoe kidney. A case was reported, and it was diagnosed as horseshoe kidney on follow-up renal dynamic scan and confirmed with the help of dimercaptosuccinic acid SPECT/CT.

Indwelling peritoneal catheters in patients with cirrhosis and refractory ascites.

BACKGROUND: The prevalence of spontaneous bacterial peritonitis (SBP) in hospitalised cirrhotics with ascites is 10-30%. Treatment for refractory ascites includes paracenteses, transjugular intrahepatic portosystemic shunt or drain placement; the latter is discouraged due to a perceived infection risk. AIM: This study aimed to evaluate the risk of bacterial peritonitis (BP) with peritoneal drains in patients with Child-Pugh class B or C cirrhosis and determine their impact on survival. METHODS: We conducted a retrospective review of end-stage liver disease (ESLD) patients with non-malignant, refractory ascites who had peritoneal drains placed for ≥3 days at Loyola University between 1999 and 2009. Cell counts were performed at drain placement and within 72 h. BP was defined as ascitic polymorphonuclear neutrophils >250/mm(3) . Univariate analysis assessed the association between demographics, laboratory markers and development of BP. Kaplan-Meier curve estimates by infection were constructed and survival distributions were compared using log-rank statistic. RESULTS: There were 227 drain placements during the study period. Twenty-two per cent were diagnosed with BP (12% had SBP at drain placement; 10% developed BP within 72 h). There was no association between BP and baseline characteristics. Patients who developed BP within 72 h of drain placement had 50% mortality at 5 months compared with 50 months in those without infection (log-rank P ≤ 0.003). CONCLUSION: In ESLD patients who received an indwelling peritoneal catheter, there was 10% risk of developing BP and significant mortality increase. Though placing drains is not the mainstay of treatment for refractory ascites, we confirm the theoretical adverse risk of peritoneal drains on infection and survival in cirrhotics.

Tamoxifen-loaded liposomal topical formulation arrests hair growth in mice.

BACKGROUND: For several decades, androgens have dominated endocrine research in the domain of hair growth control. However, it has long been known that oestrogens also tend to alter hair follicle (HF) growth and cycling significantly by binding to locally expressed high-affinity oestrogen receptors (ORs). Tamoxifen (TAM) is a selective OR modulator. OBJECTIVES: The current work aims to investigate the effect of topically applied TAM on the hair growth of mice. METHODS: Test formulations were applied once daily on the shaved back area of the mice for a period of 5 weeks. The effect of these formulations was studied by visual and histological examinations. RESULTS: Animals treated with saline and placebo gel formulation showed significant hair growth on the 20th day. The number and length of follicles were also found to be normal. In contrast, no hair growth was observed in the animals treated with TAM gel, even after the termination of treatment. The HFs were found to be arrested in telogen phase with clear signs of follicle dystrophy. CONCLUSIONS: The hair growth-retarding effect of TAM observed in the current study clearly demonstrates its OR agonistic effect on hair growth. This work also provides a distinct lead towards the possible potential of TAM liposomal gel in the treatment of hirsutism.

Evaluation of evidenced-based radioprotective efficacy of Gymnema sylvestre leaves in mice brain.

A Gymnema sylvestre leaves extract (GSE) rich in gymnemic acids was examined for its antioxidant activities through various in vitro assays, along with its radioprotective efficacy in mice brain. The IC(50) values of GSE for 2,2-diphenyl-1-picryl-hydrazyl scavenging assays, superoxide radical scavenging assays, inhibition of in vitro lipid peroxidation assays, and protein carbonyl formation assay were 238, 140, 99.46, and 28.03 microg/mL, respectively. Furthermore, the total phenolic content in GSE was equivalent to 18.06 microg/mL of Gallic acid. The rate of *OH radical scavenging activity of GSE is 0.46 times slower than SCN- derived from nanosecond pulse radiolysis studies. Results of in vivo studies showed that radiation (8 Gy)-induced augmentation in the levels of lipid peroxidation and depletion in glutathione and protein levels in mice brain were significantly ameliorated by GSE pretreatment. Results suggest that the radioprotective efficacy of GSE may be due to its antioxidant properties.

Spinacia oleracea Modulates Radiation-Induced Biochemical Changes in Mice Testis.

The present study is an attempt to investigate the radioprotective efficacy of spinach against radiation induced oxidative stress, since its leaves are rich in antioxidants like carotenoids (beta-carotene, lutein and zeaxanthin) and high content of proteins, minerals, vitamin C. For the experimental study, healthy Swiss mice were selected from an inbred colony and divided into four groups. Group I (normal) it did not receive any treatment. Group II (drug treated) was orally supplemented with extract of spinach extract once daily at the dose of 1100 mg/kg for fifteen consecutive days. Group III (control) received distilled water orally equivalent to spinach extract for fifteen days than exposed to 5 Gy of gamma radiation. Group IV (experimental) was also administered orally with spinach extract for 15 consecutive days once daily. Thereafter, exposed to single dose of 5Gy of gamma radiation. After the exposure mice were than sacrificed at different autopsy intervals viz. 1, 3, 7, 15 and 30 days. Testis was removed for various biochemical estimations viz. LPO, protein, cholesterol and glycogen. Radiation induced augmentation in lipid peroxidation, glycogen and cholesterol values were significantly ameliorated by supplementation of SE extract, whereas radiation induced deficit in protein content could be elevated. This indicates that spinach extract pre - treatment renders protection against various biochemical changes in the mice testis to some extent if taken continuously which might be due to synergistic effect of antioxidant constituents present in the spinach.