Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient-control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential relevance to frontotemporal dementia genetic etiology. As more causal and risk genes are identified, it has become apparent that affected individuals can carry multiple disease-associated variants. In light of this observation, we discuss the oligogenic architecture of ALS. To end, we highlight emerging key molecular processes and opportunities for therapy.

The meta-analysis does not show an advantage of staple fixation of mesh over fibrin glue fixation in laparoscopic total extraperitoneal inguinal hernia repair. Because fibrin glue mesh fixation with laparoscopic inguinal hernia repair achieves similar hernia recurrence rates compared with staple/tack fixation, but decreased incidence of chronic inguinal pain, it may be the preferred technique.

In this paper we present some results concerning the stability of flow in a circular pipe to small but finite axisymmetric disturbances. The flow is unstable if the amplitude of a disturbance exceeds a critical value, the equilibrium amplitude, which we have calculated for a wide range of wave-numbers and Reynolds numbers. For large values of the Reynolds number, R, and for a real value of the wave-number, α, we indicate that the energy density of a critical disturbance is of order c2i, where −ααci is the damping rate of the associated infinitesimal disturbance. The energy, per unit length of the pipe, of a critical disturbance which is concentrated near the axis of the pipe is of order R−2, and the wave-number α is of order R1/3 For a critical disturbance which is concentrated near the wall of the pipe the energy is of order $R^{-\frac{3}{2}}$ and α is of order R½. This suggests that non-linear instability is most likely to be caused by a ‘centre’ mode rather than by a ‘wall’ mode. The wall mode solution is also essentially the solution for the problem of plane Couette flow when αR is large. We compare it with the true solution.In an appendix Dr A. E. Gill indicates how some of the results of this paper may be inferred from a simple scale analysis.

Mutation screening and phenotypic profiling of 2 amyotrophic lateral sclerosis-(ALS) and frontotemporal dementia-(FTD) associated genes, CHCHD10 and TUBA4A, were performed in a Belgian cohort of 459 FTD, 28 FTD-ALS, and 429 ALS patients. In CHCHD10, we identified a novel nonsense mutation (p.Gln108*) in a patient with atypical clinical FTD and pathology-confirmed Parkinson's disease (1/459, 0.22%) leading to loss of transcript. We further observed 3 previously described missense variants (p.Pro34Ser, p.Pro80Leu, and p.Pro96Thr) that were also present in the matched control series. In TUBA4A, we detected a novel frameshift mutation (p.Arg64Glyfs*90) leading to a truncated protein in 1 FTD patient (1/459 of 0.22%) with family history of Parkinson's disease and cognitive impairment, and a novel missense mutation (p.Thr381Met) in 2 sibs with familial ALS and memory problems (1 index patient/429, 0.23%) in whom we previously identified a pathogenic Chromosome 9 open reading frame 72 repeat expansion mutation. The present study confirms the role of CHCHD10 and TUBA4A in the FTD-ALS spectrum, although genetic variations in these 2 genes are extremely rare in the Belgian population and often associated with symptomatology of related neurodegenerative diseases including Parkinson's disease and Alzheimer's disease.

We evaluated the genetic impact of the amyotrophic lateral sclerosis (ALS) risk gene never in mitosis gene a-related kinase 1 (NEK1) in a Belgian cohort of 278 patients with ALS (n = 245) or ALS with frontotemporal dementia (ALS-FTD, n = 33) and 609 control individuals. We identified 2 ALS patients carrying a loss-of-function (LOF) mutation, p.Leu854Tyrfs*2 and p.Tyr871Valfs*17, that was absent in the control group. A third LOF variant p.Ser1036* was present in 2 sibs with familial ALS but also in an unrelated control person. Missense variants were common in both patients (3.6%) and controls (3.0%). The missense variant, p.Arg261His, which was previously associated with ALS risk, was detected with a minor allele frequency of 0.90% in patients compared to 0.33% in controls. Taken together, NEK1 LOF variants accounted for 1.1% of patients, although interpretation of pathogenicity and penetrance is complicated by the observation of occasional LOF variants in unaffected individuals (0.16%). Furthermore, enrichment of additional ALS gene mutations was observed in NEK1 carriers, suggestive of a "second hit" model were NEK1 variants may modify disease presentation of driving mutations.

Purpose Inguinal hernia repair is a common general surgery procedure with low morbidity. However, postoperative urinary retention (PUR) occurs in up to 22% of patients, resulting in further extraneous treatments. This single institution series investigates whether patient comorbidities, surgical approaches, and anesthesia methods are associated with developing PUR after inguinal hernia repairs. Methods This is a single institution retrospective review of inguinal hernia from 2012 to 2015. PUR was defined as patients without a postoperative urinary catheter who subsequently required bladder decompression due to an inability to void. Univariate and multivariate logistic regressions were performed to quantify the associations between patient, surgical, and anesthetic factors with PUR. Stratification analysis was conducted at age of 50 years. Results 445 patients were included (42.9% laparoscopic and 57.1% open). Overall rate of PUR was 11.2% (12% laparoscopic, 10.6% open, and p = 0.64). In univariate analysis, PUR was significantly associated with patient age >50 and history of benign prostatic hyperplasia (BPH).Risk stratification for age >50 revealed in this cohort a 2.49 times increased PUR risk with lack of intraoperative bladder decompression (p = 0.013). Conclusions At our institution, we found that patient age, history of BPH, and bilateral repair were associated with PUR after inguinal hernia repair. No association was found with PUR and laparoscopic vs open approach. Older males may be at higher risk without intraoperative bladder decompression, and therefore, catheter placement should be considered in this population, regardless of surgical approach.

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Surgical site infections (SSIs) complicate the postoperative course of a significant proportion of general abdominal surgical patients and are associated with excessive health care costs. SSIs increase postoperative morbidity and mortality, and may require hospital admission, intravenous antibiotics, and even surgical reintervention. Risks associated with SSIs are related to both host and perioperative factors. However, a vast majority of these infections are preventable. More recently, quality initiative programs such as American College of Surgeons National Surgical Quality Improvement Program are expanding their roles to help better monitor adherence to improvement measures. Indeed, standardizing preoperative antibiotic prophylaxis timing is perhaps the most persuasive example and this has been integral to reducing postoperative SSI rates. Herein, the authors provide an update on the epidemiology, risk factors, identification, and management of wound infections following abdominal surgery.