Identification of fifty-seven novel loci for abdominal wall hernia development and their biological and clinical implications: results from the UK Biobank.

PURPOSE: Familial aggregation is known for both hernia development and recurrence. To date, only one genome-wide association study (GWAS) limited to inguinal hernia has been reported that identified four risk-associated loci. We aim to investigate polygenic architecture of abdominal wall hernia development and recurrence. METHODS: A GWAS was performed in 367,394 subjects from the UK Biobank to investigate the polygenic architecture of abdominal wall hernia subtypes (inguinal, femoral, umbilical, ventral) and identify specific single nucleotide polymorphisms (SNPs) that are associated with their risk. Expression quantitative trait loci (eQTL) analysis was performed to identify genes whose expression levels are associated with these SNPs. A genetic risk score (GRS) was used to assess the cumulative effect of multiple independent risk-associated SNPs on hernia development and recurrence in independent subjects (n = 82,064). RESULTS: Heritability (h2) was 0.12, 0.06, 0.16, and 0.07 for inguinal, femoral, umbilical, and ventral hernias, respectively. A high-level of genetic correlation (rg) was found among these subtypes of hernia. We confirmed the aforementioned four loci and identified 57 novel loci (P < 5 × 10-8), including 55, 3, 5, and 3 loci for inguinal, femoral, umbilical, and ventral hernias, respectively. Significantly different expression levels between risk/reference alleles of SNPs were found for 145 genes, including TGF-ß2 and AIG1 for inguinal hernia risk and CALD1 for umbilical hernia risk. Finally, higher GRS deciles were significantly associated with increased risk for hernia development (Ptrend = 3.33 × 10-38) and recurrent hernia repair surgery (Ptrend = 3.64 × 10-14). CONCLUSION: These novel results have potential biological and clinical implications for hernia management in high-risk patients.

New horizons in cytoskeletal dynamics: transport of intermediate filaments along microtubule tracks.

Until recently, the dynamic properties of intermediate filaments (IF) were attributed primarily to the exchange of subunits between a disassembled pool and polymerized 10nm filaments. During interphase, this subunit exchange process was thought to produce local modifications in IF structure. During cell division, shifts in the equilibrium between subunits and polymers were thought to lead to either the global or regional disassembly of IF networks, thereby facilitating their distribution into daughter cells. Recently, novel structural forms of IF that undergo rapid and directed transport in several cell types were revealed. Time-lapse observations of motile IF structures in different cell systems have also revealed novel insights into the mechanisms underlying the transport of cytoskeletal components throughout the cytoplasm and the molecular basis of the 'crosstalk' between different cytoskeletal systems.

Comparison of patients undergoing laser vaporization of the prostate versus TURP using the ACS-NSQIP database.

BACKGROUND: The introduction of laser therapies for the management of bladder outlet obstruction in men with BPH has challenged the gold standard treatment, TURP. We sought to compare the changing clinical characteristics of patients undergoing TURP and laser vaporization of the prostate (LVP) over time. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for men who underwent TURP and LVP from 2007 to 2012. Patient demographics, clinical and intraoperative characteristics and 30-day postoperative outcomes were analyzed. RESULTS: In all, 12,645 men met inclusion criteria, of whom 65% underwent TURP and 35% underwent LVP. Overall, men undergoing TURP were more likely to be scheduled as an emergency (3% vs. 1%, P<0.001), have shorter operative times (53 vs. 56 min, P<0.001), longer hospital stays (2.4 vs 1.0 days, P<0.001), more frequent blood transfusions (2.1% vs. 0.6%, P<0.001) and more postoperative complications including: pneumonia (0.5% vs. 0.3%, P=0.02), septic shock (0.3% vs. 0.1%, P=0.045), and reoperation within 30 days (2.2% vs. 1.4%, P=0.06). However, between 2007 and 2012, there was a significant trend for men undergoing TURP to have increased functional independence (93-96%, P<0.01) and American Society of Anesthesiology (ASA) Physical Class I categorization (0.6-5.1%, P<0.001). In contrast, over the same time period, there was a trend for men undergoing LVP to be significantly older (71-73 years, P<0.001) and have an increased hospital stay (0.50 days to 1.30 days, P=0.03). CONCLUSIONS: Statistically significant differences in clinical characteristics of patients undergoing TURP and LVP have historically existed. However, since 2007, the characteristics of patients undergoing LVP and TURP have changed significantly. Further studies are required to compare these patient characteristics with specific urologic variables and to evaluate clinically significant changes in these cohorts.

Multifetal reduction increases the risk of preterm delivery and fetal growth restriction in twins: a case-control study.

OBJECTIVE: To compare pregnancy outcome in twin gestations resulting from multifetal reduction to "primary" twin pregnancies derived from either spontaneous conception or infertility therapy. DESIGN: Case-control study. SETTING: University-affiliated tertiary center. PATIENT(S): Multifetal pregnancies (quadruplets or more) reduced to twins (group A) compared with twin gestations conceived either spontaneously (group B) or through infertility therapy (group C). INTERVENTION(S): Multifetal reduction for group A; perinatal care for groups A, B, and C. MAIN OUTCOME MEASURE(S): Comparison of perinatal complications between groups including antepartum bleeding, premature membrane rupture, and preterm labor. Neonatal outcomes compared including gestational age at delivery, birth weight, incidence of fetal growth restriction, and twin discordancy. RESULT(S): A higher incidence of idiopathic preterm labor was noted in group A cases (14/18) compared with either of the control groups (B: 26/54, or C: 24/54). As a consequence, group A had the lowest gestational age at delivery (32.6 +/- 3.9 weeks) compared with groups B (33.6 +/- 4.4 weeks) and C (36.0 +/- 3.4 weeks). Corresponding birth weights of both first- and second-born twins were significantly lower in group A compared with group C, whereas the birth weight comparison between groups A and B showed a nonsignificant difference. The proportion of pregnancies in which one or both twins weighted less than the 10th percentile was greatest in group A pregnancies (A: 5/18 versus C: 5/54). Discordant birth weight among twin pairs was proportionately greater for group A cases at both the 20% and 30% discordance levels. CONCLUSION(S): Twin gestations resulting from multifetal reduction are at increased risk for preterm birth, fetal growth restriction, and discordancy when compared with fertility therapy-derived, nonreduced twins.

Outcomes of lateral retroperitoneal reservoir placement of three-piece penile prosthesis in patients following radical prostatectomy.

While placement of a three-piece inflatable penile prosthesis (IPP) with a midline reservoir can be performed with favorable outcomes after radical prostatectomy (RP), postoperative fascial scarring can introduce surgical complexity, increase intra-operative complications and/or potential obstacles for future inguinal and/or perineal surgeries. We describe the implantation of the IPP with lateral reservoir placement through a separate incision to avoid surgical complications. We obtained clinical characteristics of all patients (1998-2009) who underwent RP before IPP placement with lateral reservoir placement (cases). For comparison, patients who underwent IPP placement with midline reservoir placement were also identified (controls). Thirty-one patients with a history of RP underwent IPP placement using the lateral placement technique without intra-operative or post-operative complications. There were no significant differences in the intra-operative complication rate among 31 control patients. However, at a median follow-up of >2 years, there was a significantly higher rate of post-operative complications in controls, likely reflecting the increased co-morbidities in this group. The results of this study suggest that three-piece IPP with lateral retroperitoneal reservoir implantation is associated with comparable long-term outcomes and can be performed safely in patients who have previously undergone RP.

Fast transport of neurofilament protein along microtubules in squid axoplasm.

Using squid axoplasm as a model system, we have visualized the fast transport of non-filamentous neurofilament protein particles along axonal microtubules. This transport occurs at speeds of 0.5-1.0 microm/second and the majority of neurofilament particles stain with kinesin antibody. These observations demonstrate, for the first time, that fast (0.5-1.0 microm/second) transport of neurofilament proteins occurs along microtubules. In addition, our studies suggest that neurofilament protein can be transported as non-membrane bound, nonfilamentous subunits along axons, and that the transport is kinesin-dependent. Microtubule-based fast transport might therefore provide a mechanism for the distribution and turnover of neurofilament, and perhaps other cytoskeletal proteins, throughout neurons.