Polyhydramnios with bidirectional fetal ductus arteriosus flow in a fetus with congenital diaphragmatic hernia: case report

The etiology of polyhydramnios may be attributed to either increased production of amniotic fluid (fetal polyuria or high-output cardiac failure) or decreased fetal swallowing (obstruction or neurological impairment). Although idiopathic polyhydramnios occurs in nearly half of all cases, it is often associated with fetal abnormalities. Fetal ductus arteriosus flow is normally from right to left. We report a case of antenatally detected bidirectional fetal ductus arteriosus flow diagnosed concomitantly with polyhydramnios. Amnioreduction was performed due to severe maternal symptoms, which resulted in correction of the fetal ductus arteriosus flow. Postnatal diagnosis of a Morgagni diaphragmatic hernia indicates that our sonographic findings collectively may have been a diagnostic clue.     

Assessing Documentation of Critical Imaging Result Follow-up Recommendations in Emergency Department Discharge Instructions

To facilitate follow-up of critical test results across transitions in patient care settings, we implemented an electronic discharge module that enabled care providers to include follow-up recommendations in the discharge instructions. We assessed the impact of this module on documentation of follow-up recommendations for critical imaging findings in Emergency Department (ED) discharge instructions. We studied 240 patients with critical imaging findings discharged from the ED before (n?=?80) and after (n?=?160) implementation of the module. We manually reviewed hand-written forms and electronic discharge instructions to determine if follow-up recommendations were documented. Follow-up recommendations in ED discharge instructions increased from 60.0% (48/80) to 73.8% (118/160) post-module implementation (p?=?0.03), a relative increase of 23%. There was no significant change in the rate of documented critical imaging findings in the discharge instructions (77.5% [62/80] before the intervention and 76.9% [123/160] after the intervention; p?=?0.91). Implementation of a discharge module was associated with increased documentation of critical imaging finding follow-up recommendations in ED discharge instructions. However, one in four patients still did not receive adequate follow-up recommendations, suggesting further opportunities for performance improvement exist.     

Signaling for lymphangiogenesis via VEGFR-3 is required for the early events of metastasis

Metastasis to regional lymph nodes is an important and early event in many tumors. Vascular endothelial growth factor-C (VEGF-C), VEGF-D and their receptor VEGFR-3, play a role in tumor spread via the lymphatics, although the timing of their involvement is not understood. In contrast, VEGFR-2, activated by VEGF-A, VEGF-C and VEGF-D, is a mediator of angiogenesis and drives primary tumor growth. We demonstrate the critical role for VEGFR-3, but not VEGFR-2, in the early events of metastasis. In a tumor model exhibiting both VEGF-D-dependent angiogenesis and lymphangiogenesis, an antibody to VEGFR-2 (DC101) was capable of inhibiting angiogenesis (79 % reduction in PECAM + blood vessels) and growth (93 % reduction in tumor volume). However, unlike an anti-VEGFR-3 Mab (mF4-31C1), DC101 was not capable of eliminating either tumor lymphangiogenesis or lymphogenous metastasis (60 % reduction of lymph node metastasis by DC101 vs 95 % by mF4-31C1). Early excision of the primary tumors demonstrated that VEGF-D-mediated tumor spread precedes angiogenesis-induced growth. Small but highly metastatic primary human breast cancers had significantly higher lymphatic vessel density (23.1 vessels/mm²) than size-matched (11.7) or larger non-metastatic tumors (12.4) thus supporting the importance of lymphatic vessels, as opposed to angiogenesis-mediated primary tumor growth, for nodal metastasis. These results suggest that lymphangiogenesis via VEGF-D is more critical than angiogenesis for nodal metastasis.     

The Production and Characterization of Novel Heavy-Chain Antibodies Against the Tandem Repeat Region of MUC1 Mucin

Camelidae are known to produce immunoglobulins (Igs) devoid of light chains and constant heavy-chain domains (CH₁). Antigen-specific fragments of these heavy-chain IgGs (VHH) are of great interest in biotechnology applications. This paper describes the first example of successfully raised heavy-chain antibodies in Camelus dromedarius (single-humped camel) and Camelus bactrianus (two-humped camel) against a MUC1 related peptide that is found to be an important epitope expressed in cancerous tissue. Camels were immunized against a synthetic peptide corresponding to the tandem repeat region of MUC1 mucin and cancerous tissue preparation obtained from patients suffering from breast carcinoma. Three IgG subclasses with different binding properties to protein A and G were purified by affinity chromatography. Both conventional and heavy-chain IgG antibodies were produced in response to MUC1-related peptide. The elicited antibodies could react specifically with the tandem repeat region of MUC1 mucin in an enzyme linked immunosorbant assay (ELISA). Anti-peptide antibodies were purified after passing antiserum over two affinity chromatography columns. Using ELISA, immunocytochemistry and Western blotting, the interaction of purified antibodies with different antigens was evaluated. The antibodies were observed to be selectively bound to antigens namely: MUC1 peptide (tandem repeat region), human milk fat globule membrane (HMFG), deglycosylated human milk fat globule membrane (D-HMFG), homogenized cancerous breast tissue and a native MUC1 purified from ascitic fluid. K_a values of specific polyclonal anti-peptide antibodies were estimated in C. dromedarius and C. bactrianus, as 7 × 10¹⁰ M^{? 1} and 1.4 × 10¹⁰ M^{? 1} respectively.     

Tumor location and nature of lymphatic vessels are key determinants of cancer metastasis

Tumor metastasis to lymph nodes is a key indicator of patient survival, and is enhanced by the neo-lymphatics induced by tumor-secreted VEGF-C or VEGF-D, acting via VEGFR-3 signalling. These targets constitute important avenues for anti-metastatic treatment. Despite this new understanding, clinical observations linking metastasis with tumor depth or location suggest that lymphangiogenic growth factors are not the sole determinants of metastasis. Here we explored the influence of tumor proximity to lymphatics capable of responding to growth factors on nodal metastasis in a murine VEGF-D over-expression tumor model. We found that primary tumor location profoundly influenced VEGF-D-mediated lymph node metastasis: 89 % of tumors associated with the flank skin metastasised, in contrast with only 19 % of tumors located more deeply on the body wall (p < 0.01). Lymphatics in metastatic tumors arose from small lymphatics, and displayed distinct molecular and morphological profiles compared with those found in normal lymphatics. Smaller lymphatic subtypes were more abundant in skin (2.5-fold, p < 0.01) than in body wall, providing a richer source of lymphatics for VEGF-D⁺ skin tumors, a phenomenon also confirmed in human samples. This study shows that the proximity of a VEGF-D⁺ primary tumor to small lymphatics is an important determinant of metastasis. These observations may explain why tumor location relative to the lymphatic network is prognostically important for some human cancers.     

Immunohistochemical analysis of survivin expression in thyroid follicular adenoma and carcinoma.

Survivin is one of the 8 members of human inhibitor of apoptosis , which is differentially expressed in cancerous/transformed cells versus normal differentiated tissues. This retrospective study of thyroid histologic samples aimed to assess the clinical usefulness of survivin immunostaining for discrimination between follicular adenoma and carcinoma of thyroid. Immunohistochemical staining for survivin was performed on 41 lesions from patients who had undergone surgery for either follicular adenoma or carcinoma of thyroid. Survivin expression was significantly (P < 0.005) higher in the cases that received a diagnosis of carcinoma in comparison with follicular adenomas cases. Odds ratio of follicular carcinoma for survivin expression was 21.375 (95% CI: 3.283 to 139.177). Our results showed potential value of survivin in discrimination between follicular thyroid adenoma and follicular thyroid carcinoma. We conclude that survivin is a potential candidate for further investigation in the proper histologic diagnosis of thyroid cancers.     

Evaluating the Prevalence of PTSD among Children and Adolescents after Earthquakes and Floods: a Systematic Review and Meta-Analysis

Psychiatric Quarterly - Our study systematically reviews articles about the prevalence of Post-traumatic Stress Disorder (PTSD) among children and adolescents, aiming to evaluate its prevalence...     

Significance of abnormal myocardial perfusion scintigraphy in young adult patients with SLE

Objectives  

Detection of subclinical coronary artery disease (CAD) is a potential challenge in patients with systemic lupus erythematosus (SLE) and it is suggested that myocardial perfusion single photon emission computerized tomography (SPECT) is more sensitive than exercise test in this setting. However, the significance of perfusion abnormalities in SLE patients is not well known. In this study, we evaluated the prognostic significance of myocardial perfusion defects in patients with SLE.     

Diffusion Entropy: A Potential Neuroimaging Biomarker of Bipolar Disorder in the Temporal Pole

Despite much research, bipolar depression remains poorly understood, with no clinically useful biomarkers for its diagnosis. The paralimbic system has become a target for biomarker research, with paralimbic structural connectivity commonly reported to distinguish bipolar patients from controls in tractography‐based diffusion MRI studies, despite inconsistent findings in voxel‐based studies. The purpose of this analysis was to validate existing findings with traditional diffusion MRI metrics and investigate the utility of a novel diffusion MRI metric, entropy of diffusion, in the search for bipolar depression biomarkers. We performed group‐level analysis on 9 un‐medicated (6 medication‐naïve; 3 medication‐free for at least 33 days) bipolar patients in a major depressive episode and 9 matched healthy controls to compare: (1) average mean diffusivity (MD) and fractional anisotropy (FA) and; (2) MD and FA histogram entropy—a statistical measure of distribution homogeneity—in the amygdala, hippocampus, orbitofrontal cortex and temporal pole. We also conducted classification analyses with leave‐one‐out and separate testing dataset (N = 11) approaches. We did not observe statistically significant differences in average MD or FA between the groups in any region. However, in the temporal pole, we observed significantly lower MD entropy in bipolar patients; this finding suggests a regional difference in MD distributions in the absence of an average difference. This metric allowed us to accurately characterize bipolar patients from controls in leave‐one‐out (accuracy = 83%) and prediction (accuracy = 73%) analyses. This novel application of diffusion MRI yielded not only an interesting separation between bipolar patients and healthy controls, but also accurately classified bipolar patients from controls.