Interaction of RECQ4 and MCM10 is important for efficient DNA replication origin firing in human cells

DNA replication is a highly coordinated process that is initiated at multiple replication origins in eukaryotes. These origins are bound by the origin recognition complex (ORC), which subsequently recruits the Mcm2-7 replicative helicase in a Cdt1/Cdc6-dependent manner. In budding yeast, two essential replication factors, Sld2 and Mcm10, are then important for the activation of replication origins. In humans, the putative Sld2 homolog, RECQ4, interacts with MCM10. Here, we have identified two mutants of human RECQ4 that are deficient in binding to MCM10. We show that these RECQ4 variants are able to complement the lethality of an avian cell RECQ4 deletion mutant, indicating that the essential function of RECQ4 in vertebrates is unlikely to require binding to MCM10. Nevertheless, we show that the RECQ4-MCM10 interaction is important for efficient replication origin firing.     

A case report of rapid spontaneous redistribution of acute supratentorial subdural hematoma to the entire spinal subdural space presenting as a Pourfour du Petit Syndrome and review of the literature

Objective

This report illustrates the rare rapid spontaneous redistribution of an acute intracranial supratentorial subdural hematoma (AISSDH) to the entire spinal subdural space (SSS). The study is also unique in that the spinal subdural hematoma (SSH) manifested by the extremely rare Pourfour du Petit Syndrome (PPS).

Methods

A 66-year-old man sustained blunt head trauma. On admission to the regional hospital, he scored 6 on GCS and his pupils were of equal size reacting to light. Initial computed tomography (CT) scan showed a unilateral AISSDH. The patient was referred to our department and arrived 16 h following the accident, at which time a repeat CT scan revealed almost complete resolution of the AISSDH without clinical improvement. On the 9th postinjury day transient anisocoria and tachycardia without spinal symptomatology developed. Since neither neurological examination nor follow-up CT scans showed intracranial pathology explaining the anisocoria, the patient was treated further conservatively. During the next 3 days circulatory instability developed and the patient succumbed to primary traumatic injury. Autopsy revealed a SSH occupying the entire SSS.

Conclusion

This case calls attention to the unique combination of the displacement of an AISSDH to the SSS and the presentation of this clinical entity by the PPS.     

Intraoperative reversal of neuromuscular block with sugammadex or neostigmine during extreme lateral interbody fusion, a novel technique for spine surgery

Purpose  

Extreme lateral interbody fusion (XLIF) is a method for stabilization of the lumbar spine. Intraoperatively, the surgeon identifies the lumbar nerve roots with a stimulator to prevent their injury. The objective of this study was to determine the extent to which shallow rocuronium-induced neuromuscular block must be intraoperatively reversed for reliable identification of nerve roots.     

Is a learning curve for arterial switch operation in small countries still acceptable? Model for cooperation in Europe.

OBJECTIVES: To assess the results of a cooperative arrangement between Slovakia and Slovenia for neonatal cardiac surgery. The aim of the study was to analyze the performance of this approach for complete transposition of the great arteries (D-TGA). METHODS: Due to the overall small number of new patients with D-TGA in Slovenia a decision was made to avoid a prolonged learning curve by centralizing the experience of two countries at one center. Since 1995 the center in Slovakia has become the only referral center for Slovenia. Between February 1993 and June 2002 in this center, 147 patients with D-TGA underwent arterial switch operation (ASO). The median age at operation was 11 days, with 110 patients from Slovakia and 37 patients from Slovenia. RESULTS: Overall hospital mortality was 4.8% (seven patients). The 1, 2, 3, 4 and 5 year survival rate was 95% with the mean follow-up of 4 years. Operation before 1997 (P=0.0001) was identified as a risk predictor for death by multivariate analysis. There are no deaths among the 90 patients operated on after 1996. All patients are without medication with normal left ventricular function. Stenosis (gradient >30 mmHg) was noted in the pulmonary artery reconstruction in seven patients (5%). More than mild aortic regurgitation was noted in five patients (4%). The incidence of redo or reintervention was 5% at 5 years of follow-up. CONCLUSIONS: In the current era a prolonged learning curve for ASO is not acceptable to most European countries and their patients. The risk of surgery can be minimized by concentrating surgical experience as part of the quality control of congenital heart programs. If the number of new patients is small due to the birth rate and size of the population, institutions should merge activity. Such centralization amplifies the experience to the benefit of the patient.     

Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis

Helicobacter pylori (H. pylori) is an infectious agent influencing as much as 50% of the world’s population. It is the causative agent for several diseases, most especially gastric and duodenal peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach. A number of other, extragastric manifestations also are associated with H. pylori infection. These include neurological disorders, such as Alzheimer’s disease, demyelinating multiple sclerosis and Parkinson’s disease. There is also evidence for a relationship between H. pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma. Generally little is known about the relationship between H. pylori infection and diseases of the pancreas. Most evidence about H. pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis. There is data (albeit not fully consistent) indicating modestly increased pancreatic cancer risk in H. pylori-positive patients. The pathogenetic mechanism of this increase is not yet fully elucidated, but several theories have been proposed. Reduction of antral D-cells in H. pylori-positive patients causes a suppression of somatostatin secretion that, in turn, stimulates increased secretin secretion. That stimulates pancreatic growth and thus increases the risk of carcinogenesis. Alternatively, H. pylori, as a part of microbiome dysbiosis and the so-called oncobiome, is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation. The role of H. pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins (mostly enzymes) of H. pylori and pancreatic tissue. Patients with autoimmune pancreatitis often show positivity for antibodies against H. pylori proteins. H. pylori, as a part of microbiome dysbiosis, also is viewed as a potential trigger of autoimmune inflammation of the pancreas. It is precisely these relationships (and associated equivocal conclusions) that constitute a center of attention among pancreatologists, immunologists and pathologists. In order to obtain clear and valid results, more studies on sufficiently large cohorts of patients are needed. The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research. Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer.     

Handwriting difficulties of children with Charcot‐Marie‐Tooth disease type 1A

Hand weakness and impaired manual dexterity have been reported in children with Charcot‐Marie‐Tooth disease type 1A (CMT1A). This early onset of upper limb involvement might explain frequent clinical referrals for assessment and treatment of impaired handwriting performance. The aim of this study was to examine the impact of CMT1A on handwriting speed and legibility, and identify demographic, anthropometric, and physical measures that might relate to handwriting performance. Handwriting speed (Handwriting Speed Test), handwriting legibility (Evaluation Tool of Children's Handwriting‐Cursive), and hand strength (hand‐held dynamometry of tip pinch, lateral pinch and grip) were assessed in 30 children with CMT1A (aged 8–17 years) and 30 age‐ and sex‐matched controls. Children with CMT1A exhibited 34% slower handwriting speed (p < 0.0001) with 4% reduced legibility (p = 0.001) and 37–48% lower hand strength (p < 0.0001). All measures of strength, age, height, and weight were positively associated with handwriting speed (r = 0.39–0.79, p < 0.01). None of these factors related to handwriting legibility (p > 0.05). Regression modelling identified a diagnosis of CMT1A, lateral pinch weakness and younger age as significant independent predictors of slower handwriting speed, explaining 78% of the variance. Children with CMT1A have considerable handwriting difficulties, primarily with speed, and substantial associated hand and finger weakness. Understanding the cause–effect relationship between strength and function might provide modifiable targets for upper limb intervention.     

Results of modified Norwood's operation for hypoplastic left heart syndrome.

OBJECTIVE: The aim of the study was to analyze intermediate results of treatment of the hypoplastic left heart syndrome based on selective indication criteria. METHODS: Between February 1997 and May 1999 38 patients with hypoplastic left heart syndrome (n=35), or with functional variant of hypoplastic left heart syndrome (n=3) were admitted to our department. Contraindications for surgery were birth weight <2500 g, diameter of ascending aorta <2 mm, severe tricuspid regurgitation persisting after initial stabilization, pulmonary regurgitation more than mild, dysfunction of the systemic right ventricle and failure to effectively resuscitate circulation before surgery. RESULTS: Based on these criteria surgery was not indicated in 17 patients. Twenty-one infants were operated on by modified Norwood's procedure using only autologous great vessel tissue for reconstruction of systemic outflow. Overall hospital mortality was 14% (three patients). Eighteen survivors (86%) were discharged with well-balanced circulation. There was one late death (5%). Thirteen patients had already undergone the second stage (bi-directional Glenn) with no death. The mean follow-up was 13. 2+/-9.1 months (range 4-32 months). Considering both early and late events the probability of survival for the whole group (n=21) from the time of surgery was 86% at 1 month, 80% at 12 months, and it remained unchanged at 18 and 24 months of follow-up. CONCLUSIONS: Only a limited number of European countries offer surgical treatment of hypoplastic left heart syndrome. Promising intermediate results (80% survival rate after stage I and II) achieved at our department do not only reflect overcoming the learning curve but also a selective approach to indication for surgery as well. In a country with limited resources selective approach to the patients with hypoplastic left heart syndrome is justified.     

Ultrasound in the diagnosis of diaphragmatic paralysis after operation for congenital heart disease.

Phrenic nerve palsy is a recognised complication of operation for congenital heart disease in children. The accuracy of ultrasound in assessing diaphragmatic motion was prospectively compared with fluoroscopy in 16 patients in whom phrenic nerve palsy was suspected. Ultrasound successfully identified the five patients with phrenic nerve palsy; there were no false positive or false negative diagnoses. Ultrasound was as effective as fluoroscopy in the diagnosis of abnormalities of diaphragmatic motion.     

Intermediate results with correction of tetralogy of Fallot with absent pulmonary valve using a new approach.

OBJECTIVE: The intermediate results achieved with a new technique for primary repair of tetralogy of Fallot with absent pulmonary valve syndrome are reported. METHOD: Apart from correction of tetralogy of Fallot, this approach includes translocation of the pulmonary artery anterior to the aorta and away from the tracheobronchial tree. Since November 1998 this technique has been employed in three symptomatic newborns and three infants with a diagnosis of tetralogy of Fallot with absent pulmonary valve. The median age at surgery was 37 days (range 14-256 days). The median weight at operation was 3.4 kg (range 2.9-4 kg). All patients had severe respiratory problems and congestive heart failure with cyanosis. RESULTS: There was no early or late death during the follow-up (median 27 months). One patient required redo due to failure to thrive as a consequence of right ventricle volume overload. Valved conduit was inserted to pulmonary position. Respiratory symptoms disappeared or were significantly reduced in all patients. Postoperative computed tomographic scan showed no compression of trachea and main bronchi, pulmonary artery was away from tracheobronchial tree in all patients. Patients are doing well with adequate growth. CONCLUSIONS: The new technique described here has a potential to reduce or eliminate bronchial compression by pulmonary artery. Translocation of pulmonary artery anterior to the aorta takes the dilated pulmonary artery away from the trachea and bronchial tree. This approach was found to be technically feasible and can be useful especially in symptomatic newborns and infants.