Homotopic contralesional excitation suppresses spontaneous circuit repair and global network reconnections following ischemic stroke.

Understanding circuit-level manipulations that affect the brain's capacity for plasticity will inform the design of targeted interventions that enhance recovery after stroke. Following stroke, increased contralesional activity (e.g. use of the unaffected limb) can negatively influence recovery, but it is unknown which specific neural connections exert this influence, and to what extent increased contralesional activity affects systems- and molecular-level biomarkers of recovery. Here, we combine optogenetic photostimulation with optical intrinsic signal imaging to examine how contralesional excitatory activity affects cortical remodeling after stroke in mice. Following photothrombosis of left primary somatosensory forepaw (S1FP) cortex, mice either recovered spontaneously or received chronic optogenetic excitation of right S1FP over the course of 4 weeks. Contralesional excitation suppressed perilesional S1FP remapping and was associated with abnormal patterns of stimulus-evoked activity in the unaffected limb. This maneuver also prevented the restoration of resting-state functional connectivity (RSFC) within the S1FP network, RSFC in several networks functionally distinct from somatomotor regions, and resulted in persistent limb-use asymmetry. In stimulated mice, perilesional tissue exhibited transcriptional changes in several genes relevant for recovery. Our results suggest that contralesional excitation impedes local and global circuit reconnection through suppression of cortical activity and several neuroplasticity-related genes after stroke, and highlight the importance of site selection for targeted therapeutic interventions after focal ischemia.

Pediatric Radial Neck Fractures: Which Ones Can Be Successfully Closed Reduced in the Emergency Department?

BACKGROUND: The purpose of this study is to examine pediatric patients with a radial neck fracture and determine the factors associated with a failed closed reduction (CR) in the emergency department (ED). METHODS: A total of 70 patients with acute radial neck fractures were retrospectively reviewed. Inclusion criteria were: age 18 years or younger at time of injury, diagnosis of radial neck fracture without other associated elbow fractures, an attempt at CR with manipulation in the ED or immediate surgery, open proximal radial physis, and appropriate imaging to categorize the injury. Charts were reviewed and demographic data was obtained. Initial injury films were reviewed and the Judet classification was used to define fracture types/categories. RESULTS: CR was attempted on 41 patients. Twenty-nine patients went straight to surgery without a CR attempt. Compared with patients that had an attempted CR in the ED, patients that went straight to surgery had longer mean time from injury to ED presentation (5.6 d; P=0.0001), greater mean fracture angulation (55.0 degrees; P=0.001), and greater fracture translation (46.2%; P=0.001). When analyzing the patients that had a CR attempted in the ED, univariate statistical analysis demonstrated that ≥Judet 4 classification (P=0.03), greater amounts of fracture angulation (P=0.003), and a treatment delayed >24 hours from injury (P=0.007) were significant risk factors for failure of CR in the ED. Zero (0/10) patients with fracture angulation ≥60 degrees had a successful CR. Only 1/14 patients presenting >24 hours after injury had a successful CR in the ED. CONCLUSIONS: Circumventing sedation in the ED, and instead splinting for a planned surgical intervention may be a more efficient treatment method for pediatric radial neck fractures that present to the ED>24 hours after injury and/or have angulations ≥60 degrees. Adopting this new strategy may save time, reduce costs, and avoid possible harm/complications associated with sedation in the ED. LEVEL OF EVIDENCE: Level III-prognostic.

Chronic Rhinosinusitis: Potential Role of Microbial Dysbiosis and Recommendations for Sampling Sites.

Chronic rhinosinusitis (CRS) is an inflammatory condition that affects up to 12% of the human population in developed countries. Previous studies examining the potential role of the sinus bacterial microbiota within CRS infections have found inconsistent results, possibly because of inconsistencies in sampling strategies. The aim of this study was to determine whether the sinus microbiome is altered in CRS and additionally if the middle meatus is a suitable representative site for sampling the sinus microbiome. Swab samples were collected from 12 healthy controls and 21 CRS patients, including all eight sinuses for CRS patients and between one and five sinuses for control subjects. The left and right middle meatus and nostril swabs were also collected. Significant differences in the sinus microbiomes between CRS and control samples were revealed using high-throughput 16S rRNA gene sequencing. The genus Escherichia was over-represented in CRS sinuses, and associations between control patients and Corynebacterium and Dolosigranulum were also identified. Comparisons of the middle meatuses between groups did not reflect these differences, and the abundance of the genus Escherichia was significantly lower at this location. Additionally, intra-patient variation was lower between sinuses than between sinus and middle meatus, which together with the above results suggests that the middle meatus is not an effective representative sampling site.

Giant Primary Schwannoma of the Left Nasal Cavity and Ethmoid Sinus.

A unilateral tumour in the nasal cavity or paranasal sinuses is commonly caused by polyps, cysts, and mucoceles, as well as invasive tumours such as papillomas and squamous cell carcinomas. Schwannomas, in contrast, are rare lesions in this area (Minhas et al., 2013). We present a case of a 52-year-old female who presented with a 4-year progressive history of mucous hypersecretion, nasal obstruction, pain, and fullness. Imaging of the paranasal sinuses showed complete opacification of the entire left nasal cavity and sinuses by a tumour causing subsequent obstruction of the frontal and maxillary sinuses. The tumour was completely excised endoscopically. Histopathology was consistent with that of a schwannoma.

Principles for Predicting RNA Secondary Structure Design Difficulty.

Designing RNAs that form specific secondary structures is enabling better understanding and control of living systems through RNA-guided silencing, genome editing and protein organization. Little is known, however, about which RNA secondary structures might be tractable for downstream sequence design, increasing the time and expense of design efforts due to inefficient secondary structure choices. Here, we present insights into specific structural features that increase the difficulty of finding sequences that fold into a target RNA secondary structure, summarizing the design efforts of tens of thousands of human participants and three automated algorithms (RNAInverse, INFO-RNA and RNA-SSD) in the Eterna massive open laboratory. Subsequent tests through three independent RNA design algorithms (NUPACK, DSS-Opt and MODENA) confirmed the hypothesized importance of several features in determining design difficulty, including sequence length, mean stem length, symmetry and specific difficult-to-design motifs such as zigzags. Based on these results, we have compiled an Eterna100 benchmark of 100 secondary structure design challenges that span a large range in design difficulty to help test future efforts. Our in silico results suggest new routes for improving computational RNA design methods and for extending these insights to assess "designability" of single RNA structures, as well as of switches for in vitro and in vivo applications.

Streptococcus milleri head and neck abscesses: a case series.

Streptococcus milleri infections and abscesses in the head and neck region have been previously reported, but there is still a dearth of clinical literature on this topic. To add to the available reports and to promote a better understanding and awareness of this clinically important entity, we present this retrospective review of 7 cases of head and neck abscess caused by S milleri infection. We have placed particular emphasis on antibiotic sensitivity patterns. These patients-6 men and 1 woman, aged 28 to 73 years (mean: 42.7)-had been seen at a district general hospital in Gosford, Australia, over a 6-month period. All patients had undergone surgical intervention and had been treated with intravenous antibiotics. All the S milleri cultures were sensitive to penicillin G, cephalexin, and erythromycin. Six of these patients experienced a resolution of their abscess, while 1 patient died from overwhelming sepsis. We believe that the initiation of penicillin G, cephalexin, or erythromycin is a good starting point for empiric therapy. S milleri should be considered as a causative organism in a patient who presents with a head and neck abscess, especially in the presence of a dental infection. Such a patient should be monitored closely for airway obstruction and distal infective sequelae. Also in this article, we compare our findings with those reported in two other published series.

Pancreatoduodenectomy: role of drain fluid analysis in the management of pancreatic fistula.

BACKGROUND: Pancreatic fistula remains an important cause of death following pancreatoduodenectomy. There is still uncertainty regarding the use of drains following pancreatoduodenectomy with recent reports suggesting that it might be harmful with increased complications. We evaluated the use of drain fluid analysis in the management of patients following pancreatoduodenectomy. METHODS: A prospective study was conducted on all patients undergoing pancreatoduodenectomy at two hospitals between April 2004 and August 2006. Drain fluid analysis was carried out from day 3 to day 5. These data were collected with the clinical pictures of the patients and with subsequent radiological assessment. RESULTS: Fifty consecutive patients underwent modified extended pancreatoduodenectomy for a periampullary tumour. In patients with no clinical evidence of a fistula, the mean postoperative drain fluid amylase levels were as follows: on postoperative day 3 it was 262 U/mL (standard error of mean 69), on postoperative day 4 it was 112 U/mL (standard error of mean 47) and on postoperative day 5 it was 125 U/mL (standard error of mean 64). Only three (6/6, 50%) of these patients had clinical features suggestive of a leak and were found to have a pancreatic fistula on subsequent imaging. There was no correlation between the total or mean volumes of drainage and development of a pancreatic fistula. CONCLUSION: The drain fluid analysis did not provide additional information that was not already evident from the clinical picture of the patient. Drain fluid analysis had no effect on patients with a biochemical leak only. Patients who had a significant disruption of their pancreatic anastamosis did not need biochemical analysis as the character, that is, turbidity of the drain fluid was an equally reliable indicator of the underlying pathology.

Laparoscopic bile duct exploration: results of 160 consecutive cases with 2-year follow up.

BACKGROUND: Despite numerous reports showing the advantages of laparoscopic common bile duct exploration (LCBDE), many general surgeons, particularly those working outside of nonspecialist units, continue to rely heavily on endoscopic retrograde cholangiography with sphincterotomy (ERCP) to manage bile duct stones (BDS). This article investigates the performance of LCBDE when adopted as the preferred first-line management of both suspected and incidental BDS by general surgeons in a regional setting. METHODS: A retrospective review was conducted of all patients in whom LCBDE was attempted by a regional general surgical unit. The unit policy was to preferentially treat all incidental and suspected BDS (except in ascending cholangitis or severe pancreatitis) by LCBDE, with ERCP used only if unsuccessful. In addition to chart review, formal prospective follow up by telephone interview was carried out. RESULTS: A total of 160 consecutive patients with BDS (mean age 66.9 years, 65% suspected and 35% incidental) underwent attempted LCBDE between January 2000 and July 2005. Successful clearance was achieved in 84.3% according to chart review. However, four additional cases of retained choledocholithiasis shown by late telephone interview (median interval 2.5 years) yielded a more accurate clearance rate of 81.8%. Major morbidity occurred in 13.8%, including biliary leak in 7.5% and one late biliary stricture (0.6%). Median length of hospital stay was 4.8 days. In-hospital mortality was 0.6%. CONCLUSION: Laparoscopic common bile duct exploration remains an effective, efficient and safe first-line treatment of BDS even when carried out in regional nonspecialist units. In spite of the wide availability of ERCP, general surgeons should be encouraged to continue performing LCBDE in order to optimise patient care and maintain important surgical skills.