Flavivirus–Host Interaction Landscape Visualized through Genome-Wide CRISPR Screens

Flaviviruses comprise several important human pathogens which cause significant morbidity and mortality worldwide. Like any other virus, they are obligate intracellular parasites. Therefore, studying the host cellular factors that promote or restrict their replication and pathogenesis becomes vital. Since inhibiting the host dependency factors or activating the host restriction factors can suppress the viral replication and propagation in the cell, identifying them reveals potential targets for antiviral therapeutics. Clustered regularly interspaced short palindromic repeats (CRISPR) technology has provided an effective means of producing customizable genetic modifications and performing forward genetic screens in a broad spectrum of cell types and organisms. The ease, rapidity, and high reproducibility of CRISPR technology have made it an excellent tool for carrying out genome-wide screens to identify and characterize viral host dependency factors systematically. Here, we review the insights from various Genome-wide CRISPR screens that have advanced our understanding of Flavivirus-Host interactions.     

Entire liver as the only content of hernia of the umbilical cord

Hernia of the umbilical cord is a small omphalocoele with the abdominal defect being less than 4 cm and the small intestine being the usual content. We report a rare case of hernia of the umbilical cord with the whole of the liver herniating through the small defect into the sac as the only content. The pertinent literature is also reviewed.     

Multiple neural tube defects may not be very rare

Background

Multiple neural tube defects (MNTDs) are a rare occurrence. Although the clinical incidence is small, MNTDs raise some interesting embryological queries.

Aim

This study aims to investigate the morphological and clinical variations observed in neonates presenting with multiple neural tube defects and associated central nervous system anomalies.

Materials and methods

This is a prospective study carried out at our institute to assess clinical and morphological variation in patients presenting with multiple neural tube defects.

Results

Among the 263 patients with a neural tube defect, who presented to our outpatient department and emergency departments, only 10 cases of MNTDs were identified. Thus, incidence of MNTDs in the cohort of patients affected with NTD was 0.038 %. Among the 10 patients, 9 had double neural tube defects and 1 patient had three neural tube defects.

Conclusions

Multiple neural tube defects may not be very rare in the general population, especially the populations with high incidence of neural tube defects. Multisite closure theory has the versatility to explain various combinations of neural tube defects, but better insights into the molecular pathways governing this tightly regulated process can provide us the missing link in establishing the pathogenesis of multiple NTDs. It can also provide us with an opportunity to prevent NTDs or treat them in utero by pharmacological modulation of these signaling pathways.     

Retrocaval ureter with stone in the retrocaval segment of the ureter

Retrocaval ureter is abnormal looping of the proximal ureter behind the inferior vena cava. The aberrant anatomy results in the compression of the ureter causing hydronephrosis. This is a very infrequent cause of hydronephrosis in children. Association of retrocaval ureter with a stone in the looping segment of the ureter is extremely rare. We report one such pediatric case which was diagnosed preoperatively with a review of pediatric-only cases reported in last 5 years.     

A study of spontaneous echo contrast in patients with rheumatic mitral stenosis and normal sinus rhythm: an Indian perspective.

OBJECTIVE--To study the incidence of spontaneous echo contrast in left atrium of Indian patients with rheumatic mitral stenosis in normal sinus rhythm and to define its relations. SUBJECTS--Transthoracic and multiplane transoesophageal echocardiographic studies were performed in 89 consecutive patients with rheumatic mitral stenosis who were in normal sinus rhythm. RESULTS--Spontaneous echo contrast in the left atrium was seen in 57.3% of patients on multiplane transoesophageal echocardiography and in only 5.6% on transthoracic echocardiography. The mean mitral valve area was 1.07 (SD 0.33) cm2 and 1.32 (0.45) cm2 (P = 0.004), mean left atrial size was 4.27 (0.67) cm and 3.91 (0.5) cm (P = 0.029), mean diastolic pressure gradient was 12.64 (5.69) mm Hg and 10 (5.5) mm Hg (P = 0.049), and absence of mitral regurgitation was seen in 45% and 23% of patients respectively (P = 0.1). Among patients with spontaneous echo contrast, 31% had either left atrial/appendage thrombus or a history of embolism, upsilon 0% in patients without spontaneous echo contrast (P < 0.0001). CONCLUSIONS--There is a high incidence of spontaneous echo contrast in the left atrium in Indian patients with rheumatic mitral stenosis in normal sinus rhythm on multiplane transoesophageal echocardiography. These patients are likely to embolise or form thrombi in the left atrium. The presence of spontaneous echo contrast is also associated with significantly smaller mitral valve area, larger left atrium, and higher mean diastolic mitral pressure gradient.     

Mycobacterial pulmonary infections after allogeneic bone marrow transplantation

Allogeneic bone marrow transplant recipients are prone to pulmonary infections caused by a wide spectrum of organisms. Nonetheless, the recognition of lung disease caused by Mycobacterium tuberculosis in two patients and Mycobacterium avium-intracellulare in a third patient at the University of Texas M. D. Anderson Hospital represents the first report of these agents occurring in allogeneic marrow recipients. Diagnosis can be difficult due to atypical presentations, initial negative culture results, and the presence of more than one pathogen in these compromised hosts. In the case involving Mycobacterium avium-intracellulare infection, culture of material obtained by bronchoscopy established the diagnosis when repeated sputum samples showed no growth. A vigorous search for mycobacteria is suggested in allogeneic bone marrow transplant recipients with pulmonary infections.     

A novel variant of esophageal atresia with tracheo‐esophageal fistula with a crossed‐over proximal esophageal pouch: a diagnostic dilemma

Diagnosis of esophageal atresia (EA) with tracheo‐esophageal fistula (TEF) can be easily done in newborns with symptoms of excessive salivation and failure to pass infant‐feeding tube (IFT) into the stomach. There are many reports in the literature which describe the diagnostic pitfall of this IFT test. We describe a case of a neonate with EA with TEF in which the upper atretic esophageal pouch had grown long enough to reach up to the level of diaphragm, thus allowing the IFT to go up to significant distance from the alveolus giving the radiograph as if the tube is in the upper part of stomach, thus creating a diagnostic dilemma.     

Laparoscopic port-in-cyst technique for retrieval of hepatic hydatid and review of other techniques used in literature

AimTo describe a technique used for removal of hepatic hydatid cyst laparoscopically.Patients and MethodsThe removal of hydatid membranes was achieved by inserting a 10-mm port right above the cyst. The port is made to enter the cyst, and the membranes are removed without any contact to outer surface, thus avoiding peritoneal spillage.ResultsThe technique was used in 6 patients. Mean age was 3.5 years, range being. 2.5 to 6 years. Three patients had solitary cyst in the right lobe, and 2, in left lobe. One had multiple cyst involving both right and left lobes. Follow-up is of mean 6 months. There is no recurrence or evidence of new cyst owing to peritoneal seeding.ConclusionsSafe extraction of hydatid membranes during laparoscopy can be done by directly placing the port within the decompressed cyst and removing the membranes with minimal use of suction. The port-in-cyst technique excludes any possibility of peritoneal seeding, during hydatid removal which may lead to metachronous recurrence in the peritoneum.