Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions.

Endothelial cell responses to fluid shear stress from blood flow are crucial for vascular development, function, and disease. A complex of PECAM-1, VE-cadherin, VEGF receptors (VEGFRs), and Plexin D1 located at cell-cell junctions mediates many of these events. However, available evidence suggests that another mechanosensor upstream of PECAM-1 initiates signaling. Hypothesizing that GPCR and Gα proteins may serve this role, we performed siRNA screening of Gα subunits and found that Gαi2 and Gαq/11 are required for activation of the junctional complex. We then developed a new activation assay, which showed that these G proteins are activated by flow. We next mapped the Gα residues required for activation and developed an affinity purification method that used this information to identify latrophilin-2 (Lphn2/ADGRL2) as the upstream GPCR. Latrophilin-2 is required for all PECAM-1 downstream events tested. In both mice and zebrafish, latrophilin-2 is required for flow-dependent angiogenesis and artery remodeling. Furthermore, endothelial-specific knockout demonstrates that latrophilin plays a role in flow-dependent artery remodeling. Human genetic data reveal a correlation between the latrophilin-2-encoding Adgrl2 gene and cardiovascular disease. Together, these results define a pathway that connects latrophilin-dependent G protein activation to subsequent endothelial signaling, vascular physiology, and disease.

FN (Fibronectin)-Integrin α5 Signaling Promotes Thoracic Aortic Aneurysm in a Mouse Model of Marfan Syndrome.

BACKGROUND: Marfan syndrome, caused by mutations in the gene for fibrillin-1, leads to thoracic aortic aneurysms (TAAs). Phenotypic modulation of vascular smooth muscle cells (SMCs) and ECM (extracellular matrix) remodeling are characteristic of both nonsyndromic and Marfan aneurysms. The ECM protein FN (fibronectin) is elevated in the tunica media of TAAs and amplifies inflammatory signaling in endothelial and SMCs through its main receptor, integrin α5ß1. We investigated the role of integrin α5-specific signals in Marfan mice in which the cytoplasmic domain of integrin α5 was replaced with that of integrin α2 (denoted α5/2 chimera). METHODS: We crossed α5/2 chimeric mice with Fbn1mgR/mgR mice (mgR model of Marfan syndrome) to evaluate the survival rate and pathogenesis of TAAs among wild-type, α5/2, mgR, and α5/2 mgR mice. Further biochemical and microscopic analysis of porcine and mouse aortic SMCs investigated molecular mechanisms by which FN affects SMCs and subsequent development of TAAs. RESULTS: FN was elevated in the thoracic aortas from Marfan patients, in nonsyndromic aneurysms, and in mgR mice. The α5/2 mutation greatly prolonged survival of Marfan mice, with improved elastic fiber integrity, mechanical properties, SMC density, and SMC contractile gene expression. Furthermore, plating of wild-type SMCs on FN decreased contractile gene expression and activated inflammatory pathways whereas α5/2 SMCs were resistant. These effects correlated with increased NF-kB activation in cultured SMCs and mgR aortas, which was alleviated by the α5/2 mutation or NF-kB inhibition. CONCLUSIONS: FN-integrin α5 signaling is a significant driver of TAA in the mgR mouse model. This pathway thus warrants further investigation as a therapeutic target.

The outcome of closure of inguinal hernia with laparoscopic percutaneous extraperitoneal closure in young adults.

BACKGROUND: Hernioplasty is one of the most commonly performed surgeries. However, the optimal procedure for young adults has not been defined yet. Our study compared the outcomes of laparoscopic percutaneous extraperitoneal closure (LPEC) in young adults with outcomes in children. MATERIAL AND METHODS: We retrospectively reviewed patients aged 0-30 years who underwent LPEC. Data regarding age, sex, hernia type, surgical time, pre-intraoperative laterality, contralateral patent processus vaginalis (CPPV), and complications were analyzed. RESULTS: LPEC was performed on 2642 patients in our hospital. Of these, 51 patients were young adults (aged 15-30 years). Asymptomatic CPPV in unilateral patients was frequent in the <15-year age group (50.2%) compared to the 15-30-year age group (15.9%). The median surgical time was shorter in the <15-year age group (19 min, interquartile range [IQR]: 24-33) compared to that of the 15-30-year age group (33 min, IQR: 23.3-40.8). CONCLUSIONS: This is the first report on the outcomes in young adult patients who underwent LPEC. The median surgical time was longer in the 15-30-year age group than in the <15-year age group. The median follow-up was 4.7 years with no intra-postoperative complications, such as postoperative bleeding, infection, persistent pain, and recurrence. LPEC is an effective, cosmetic, and safe surgical treatment in young adults and children.

Tear fluid and complement activation products in tears after ocular surgery.

PURPOSE: Due to technological advancements, surgical invasiveness has been reduced. However, cataract surgery has been implicated in causing postoperative inflammation, including dry eye syndrome. The innate immune system may be involved in postoperative inflammation, and complement activation could potentially play a crucial role in defense against pathogens, homeostasis, and wound healing. To investigate changes in the tear film complement activation products (CAPs) and ocular surface after vitrectomy combined with cataract surgery. METHODS: Forty-three patients (23 women; median age, 69 years) were enrolled in this prospective study and underwent phacoemulsification and vitrectomy. We measured Schirmer's test (ST) and CAPs in the tears at baseline (the day before surgery), 4 days and 1 month after the surgery. Tears were collected in microtubes. The CAPs in the tear fluid were analyzed by cytometric bead array. RESULTS: The median ST (8.5 mm) at baseline increased to 16 mm at 4 days ( P < 0.001) and 10 mm at 1 month (P = 0.44). The C3a levels (1202 pg/ml) at baseline increased to 2753 pg/ml at 4 days (P < 0.001), and 1763 pg/ml at 1 month (P = 0.049). The C4a levels (476 pg/ml) at baseline increased to 880 pg/ml at 4 days (P < 0.001), and 657 pg/ml at 1 month (P = 0.013). The C5a levels (22.6 pg/ml) at baseline increased to 470.9 pg/ml at 4 days (P < 0.001), and 38.3 pg/ml at 1 month (P = 0.0048). The surgical eyes were divided into the short ST group (≦ 10 mm, n = 22) and long ST group (> 10 mm, n = 21) based on the preoperative ST values. At 1 month postoperatively, the C3a levels were 2194 pg/ml in the preoperative short ST group and 1391 pg/ml in the long ST group, with significantly higher C3a concentrations in the short ST group (P < 0.001). CONCLUSIONS: The CAPs levels in tears increased after vitrectomy combined with cataract surgery. A preoperative deficit in tear secretion might induce prolonged complement activation and delayed recovery of ocular surface parameters postoperatively.

Testicular appendage torsion in children.

BACKGROUND: Testicular appendage torsion (TAT) is a medical emergency that presents as an acute scrotum, usually in children and preadolescents. In previous reports of TAT, most cases have been treated conservatively, but some necessitate surgical treatment. Our aim was to examine the incidence, clinical examination findings, etiology, and treatment of TAT. METHODS: We retrospectively reviewed records of all patients with TAT (aged ≤15 years) treated at the Juntendo University Urayasu Hospital between January 2012 and September 2020. Surgical treatment was performed when a diagnosis of testicular torsion could not be completely ruled out or if pain recurred after conservative treatment. Patients with a hard scrotum or scrotal erythema were hospitalized for conservative treatment. Data regarding age, diagnosis, blood test results, and clinical findings were analyzed. RESULTS: Among 101 boys with TAT, the median age was 10 years. The incidence of TAT varied significantly according to age and was highest among patients aged 8-11 years. Sixty-seven boys (66.3%) underwent inpatient surgical treatment, 10 boys (9.9%) received inpatient conservative treatment, and 24 boys (23.8%) received outpatient conservative treatment. The median duration of hospitalization was significantly shorter among those who underwent surgery (2.0 days) than among those who received inpatient conservative treatment group (3.5 days). CONCLUSIONS: Operations were short, uncomplicated, and safe; they shortened the hospital stay; and they would certainly prevent recurrence of TAT and testicular torsion on one side. Furthermore, we recommended that TAT patients presenting with signs of severe inflammation, such as hard scrotum or scrotal erythema, receive early surgical treatment to minimize duration of hospitalization.

Umbilical microflora and pediatric surgery.

INTRODUCTION: In pediatric surgery, the umbilicus with humid environment prone to bacterial colonization has become the most common site of entrance into the peritoneum. However, the umbilical flora in children has never been reported. This study aimed to describe the characteristics of umbilical microflora in children before antiseptic skin preparation. PATIENTS AND METHODS: We prospectively reviewed all children (age, ≤ 15 years) undergoing surgical procedures using umbilical access between April 2020 and June 2021. Before antiseptic skin preparation, culture swabs were taken from the umbilicus. Data on age, sex, and surgical procedure as well as microflora results and clinical findings were analyzed. RESULTS: Overall, data on 123 children aged between 9 days and 15 years (median: 3 years) were obtained. In the umbilicus, the most frequent colonizing bacteria were coagulase-negative Staphylococcus species and Corynebacterium. The isolation of intestinal bacteria from children aged ≤ 3 years was significantly increased (P = 0.03). The results of the multidrug resistance test revealed that the bacteria from the umbilicus exhibited a high frequency of cefazolin (CEZ) resistance (46.1%). No postoperative surgical site infection was recorded in our study. CONCLUSIONS: This prospective study is the first report to investigate the umbilical microflora in over 100 children. In this study, a large spectrum of both resident and transient microflora was cultured from the umbilicus. This umbilical microflora was similar to previous reports of adult microflora except in children aged ≤ 3 years. Our data suggest that in children ≤ 3 years, preoperative and postoperative antibiotics should be chosen by considering CEZ resistance and intestinal bacteria. The result of umbilical microflora would be useful to select the antibiotics for treatment of surgical site infection (SSI), and the culture swabs from the umbilicus before the operation for the children at high risk for SSI are highly recommended.

Japan's comprehensive undescended testis screening program: incidence of ascending testis after screening.

PURPOSE: Screening for undescended testis (UDT) in Japan is performed as a neonate, then at 1, 3, 10, and 18 months old, and 3 years old. Incidence of ascending testis (AT) after screening was reviewed. METHODS: All orchiopexy/orchiectomy at a single institute between July 2005 and June 2022 were reviewed retrospectively. RESULTS: 376 boys had 422 procedures; 54/422 (12.8%) were in 48 boys ≥ 4 years old (mean age: 6.7 years; range: 4-13); testes were normal (n = 22; 40.7%), small (n = 25; 46.2%), or atrophied (n = 7; 1.3%). There were 47 orchiopexies and 7 orchiectomies for atrophy. Incidence of AT in boys ≥ 4 years old was 24/422 (5.7%). Of these, 16/422 (3.8%) developed after normal descent and 8/422 (1.9%) were associated with retractile testis (AT + RET). Other indications included delayed treatment for UDT (n = 13), late referral by pediatricians (n = 10), and iatrogenic UDT (n = 6). Surgical intervention in boys ≥ 4 years old (12.8%) was less than that reported in the West (range: 30-50%) as was AT: (5.7% versus 15.4%) and AT + RET (1.9% versus 13.8%). CONCLUSIONS: Comprehensive UDT screening probably contributed to the lower incidence of surgery and AT (especially AT + RET) in boys ≥ 4 years old.

Syndecan 4 controls lymphatic vasculature remodeling during mouse embryonic development.

The role of fluid shear stress in vasculature development and remodeling is well appreciated. However, the mechanisms regulating these effects remain elusive. We show that abnormal flow sensing in lymphatic endothelial cells (LECs) caused by Sdc4 or Pecam1 deletion in mice results in impaired lymphatic vessel remodeling, including abnormal valve morphogenesis. Ablation of either gene leads to the formation of irregular, enlarged and excessively branched lymphatic vessels. In both cases, lymphatic valve-forming endothelial cells are randomly oriented, resulting in the formation of abnormal valves. These abnormalities are much more pronounced in Sdc4-/-; Pecam1-/- double-knockout mice, which develop severe edema. In vitro, SDC4 knockdown human LECs fail to align under flow and exhibit high expression of the planar cell polarity protein VANGL2. Reducing VANGL2 levels in SDC4 knockdown LECs restores their alignment under flow, while VANGL2 overexpression in wild-type LECs mimics the flow alignment abnormalities seen in SDC4 knockdown LECs. SDC4 thus controls flow-induced LEC polarization via regulation of VANGL2 expression.

The Prevention of Carboxymethylcellulose on Bowel Adhesions Induced by Talc Peritonitis in Mice.

BACKGROUND: Postoperative bowel adhesions may lead to various disorders, including abdominal pain, bowel obstruction, ischemia, and necrosis. In previous reports, a dose-dependent increase in bowel adhesions was observed in talc-treated animals in comparison with control animals. Although various methods have been devised to prevent peritoneal adhesions, each of these methods has advantages and disadvantages. In this study, we have attempted to reassess the effect of a carboxymethylcellulose (CMC) solution in the reduction of peritoneal adhesions induced by an intraperitoneal injection of a talc suspension in mice. MATERIALS AND METHODS: Mice received an intraperitoneal injection of a talc suspension, followed by an injection of a CMC solution or vehicle. Two weeks after the injection, any adherent bowel mass was removed en bloc, weighed, and histologically observed. RESULTS: The administration of talc induced severe bowel adhesions. CMC treatment was unable to completely inhibit the development of bowel adhesions, but treatment did reduce their weight in a dose-dependent manner. According to a histopathologic analysis, the bowel adhesions were composed of a conglomerate of talc aggregate and granulation tissue. The conglomerate was divided into two zones: the cell-rich marginal zone and the cell-scarce central zone. The injection of CMC specifically reduced the width of the marginal zone and the number of infiltrated cells. CONCLUSIONS: This study demonstrated that CMC inhibited bowel adhesions induced by talc in mice. In addition, this is the first report on the effect of CMC on talc peritonitis accompanied by a detailed histologic examination. Our experimental model is very simple and easy to use. Therefore, it may help in the discovery of new antiadhesive agents and in the analysis of the kinetics of bowel adhesion.

Risk Factors for Incisional Hernia in Children.

BACKGROUND: Incisional hernia (IH) is a major complication of abdominal surgery. Although previous studies reported that the incidence of IH after abdominal surgery in adults was 5-50% and that various independent risk factors were involved, IH in children is still not well known. The objective of our study was to investigate the incidence and risk factors for IH in children. METHODS: We retrospectively reviewed all children who underwent abdominal surgery at the Jikei University Hospitals (Jikei University Hospital, Kashiwa Hospital, Katsushika Medical Center and Daisan Hospital) between January 2001 and December 2016. Abdominal surgery in children was defined as open laparotomy and laparoscopic abdominal surgery in patients ≤ 15 years old. Conventional open repair for inguinal hernias, umbilical hernia repair, congenital abdominal defect repair and orchiopexy were excluded. RESULTS: Overall, 2049 children were performed abdominal surgery. Among them, 14 children (10 males and 4 females) developed IH, and the incidence of IH was 0.68% (14/2049). There is no significant difference between laparotomy and laparoscopic surgery. The statistically significant variables and identified risk factors were operation in neonates, laparoscopic fundoplication and open supraumbilical pyloromyotomy. In all patients who had IH repair, there was no recurrence during the follow-up period 50.4 months (range 1 months-10 years) except two recurrence cases. CONCLUSION: The incidence of IH in children is significantly lower than that in adults, and the above three risk factors were revealed. Before abdominal surgery, we recommend that pediatric surgeons should mention the risk of developing IH when the patient has the above risk factors.

Dynamic control of yeast MAP kinase network by induced association and dissociation between the Ste50 scaffold and the Opy2 membrane anchor.

Membrane localization of the Ste11 MAPKKK is essential for activation of both the filamentous growth/invasive growth (FG/IG) MAP kinase (MAPK) pathway and the SHO1 branch of the osmoregulatory HOG MAPK pathway, and is mediated by binding of the Ste50 scaffold protein to the Opy2 membrane anchor. We found that Opy2 has two major (CR-A and CR-B), and one minor (CR-D), binding sites for Ste50. CR-A binds Ste50 constitutively and can transmit signals to both the Hog1 and Fus3/Kss1 MAPKs. CR-B, in contrast, binds Ste50 only when Opy2 is phosphorylated by Yck1/Yck2 under glucose-rich conditions and transmits the signal preferentially to the Hog1 MAPK. Ste50 phosphorylation by activated Hog1/Fus3/Kss1 MAPKs downregulates the HOG MAPK pathway by dissociating Ste50 from Opy2. Furthermore, Ste50 phosphorylation, together with MAPK-specific protein phosphatases, reduces the basal activity of the HOG and the mating MAPK pathways. Thus, dynamic regulation of Ste50-Opy2 interaction fine-tunes the MAPK signaling network.

Degradation of host ubiquitin E3 ligase Itch by human cytomegalovirus UL42.

Human cytomegalovirus (HCMV) UL42 is classified as a CMV-specific but function-unknown gene. According to its amino acid sequence, UL42 has a C-terminal hydrophobic domain predicted to be a transmembrane domain and two PPxY (PY) motifs in its N terminus, but no N-terminal signal peptide. These features resemble those of herpes simplex virus (HSV) UL56 and varicella-zoster virus ORF0. HCMV UL42 interacts with Itch, a member of the Nedd4 family of ubiquitin E3 ligases, through its PY motifs as observed in HSV UL56. HCMV UL42 was partially colocalized with the trans-Golgi network and cytoplasmic vesicles in transfected fibroblasts. Itch was colocalized with HCMV UL42 and accumulated in a fine-speckled pattern in the cytoplasm. UL42 induced the ubiquitination and degradation of Itch in HCMV-infected fibroblasts, and was partially colocalized with p62, a ubiquitin-binding protein, and CD63, a marker of lysosome and multivesicular bodies. The electrophoretic pattern of Itch was altered by infection with HCMV and the amount of Itch was increased by the deletion of UL42. Our findings suggest that the regulatory function of the Nedd4 E3 ligase family and the structural features of HCMV UL42 are conserved characteristics in herpesviruses.

Association between the arm-to-choroidal circulation time and clinical profile in patients with polypoidal choroidal vasculopathy.

PURPOSE: To investigate the association between the arm-to-choroidal circulation time (ACT) on indocyanine green angiography (IA) and clinical profile in patients with polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: Single-center retrospective study. METHODS: We included 38 eyes of 38 patients with PCV diagnosed using multimodal imaging and did not undergo previous treatment. All patients were treated with monthly aflibercept injections for 3 months and treat-and-extend regimens for the subsequent 12 months. Posterior vortex vein ACT was assessed on the first visit using Heidelberg IA. The patients were divided into two groups: ACT ≥20 s (L group; eight eyes) and ACT <20 s (S group; 30 eyes). The clinical profiles before and after treatment were analyzed to assess associations with ACT. RESULTS: The mean ACT was 16.39±3.3 s (L group: 21.25±1.49 s, women:men=2:6, mean age: 77.3±6.5 years; S group: 15.10±2.17 s, women:men=7:23, mean age: 75.5±6.9 years). No significant difference was observed in the mean subfoveal choroidal thickness between the L and the S groups (176±75 µm vs. 230±79 µm, P=0.10). However, there were significant differences between the L and S groups in retinal fluid accumulation and hemorrhage recurrence (eight/eight eyes, 100% vs. 13/30 eyes, 43%, P<0.001), mean aflibercept injections (8.8±1.6 vs. 7.0±1.6, P<0.01) during the 12-month period, and the number of polypoidal lesions (1.8±0.7 vs. 1.3±0.5, P<0.05). CONCLUSION: Patients with PCV and ACT >20 s are more likely to experience exudative change recurrence in the retina during treatment because they have more polypoidal lesions.

Laparoscopic herniorrhaphy for inguinal hernia with thanatophoric dysplasia: A case report.

Thanatophoric dysplasia (TD) is a rare and severe type of skeletal dysplasia. Typical clinical findings include macrocephaly, shortening of the four limbs, underdeveloped lungs, and thoracic hypoplasia. Neonates with TD develop severe respiratory problems due to thoracic hypoplasia and require respiratory management for survival. Despite the resolution of respiratory problems, long-term survival cases are rare. Previous studies have reported that surgical procedures in patients with TD are limited to those necessary for survival, including tracheostomy, laminectomy, and ventricular shunt. A 1-year-old boy with TD was treated with laparoscopic herniorrhaphy. To the best of our knowledge, this is the first report of TD treated with laparoscopic procedure.

Intraocular pressure changes during intravitreal aflibercept injection based on treat-and-extend regimen in Japanese patients with neovascular age-related macular degeneration and glaucoma.

PURPOSE: To assess the changes in intraocular pressure (IOP) after intravitreal aflibercept injections in Japanese patients with neovascular age-related macular degeneration (nAMD) complicated by glaucoma. STUDY DESIGN: Retrospective observational study. METHODS: We retrospectively reviewed 27 eyes of 25 Japanese patients diagnosed with nAMD complicated by glaucoma. The patients were treated with 2 mg/0.05 ml of aflibercept and followed for 52 weeks according to a treat-and-extend (TAE) regimen after 3 consecutive monthly injections. The IOP of each eye was measured at each visit using non-contact tonometry. IOP changes as well as additional glaucoma treatments during 52 weeks were recorded. RESULTS: The mean of aflibercept injections was 8.3 ± 1.9. The mean IOP at baseline was 14.0 ± 3.1 mmHg, and the mean IOP after aflibercept therapy was 13.0 ± 2.4 mmHg at the final visit (P = 0.0463). No patients received additional glaucoma treatment of eye drops or surgery. CONCLUSION: Our results suggest that intravitreal aflibercept injections may be beneficial for patients with nAMD complicated by glaucoma.

Complement activation products in tears of dry eye and meibomian gland dysfunction.

Sixty-seven patients (38 woman; median age, 69 years) were enrolled to assess complement activation products (CAPs) in tear fluid with/without dry eye (DE) and with/without meibomian gland dysfunction (MGD). Patients were divided into four groups based on the presence/absence of DE and MGD: group DM had both DE and MGD, group DN had DE without MGD, group NM had MGD without DE, and group NN had neither DE nor MGD. The levels of C3a and C5a in the collected tears were analyzed using a cytometric bead array. The C3a concentrations in the DM, DN, NM, and NN groups were 2326 pg/ml, 1411 pg/ml, 1821 pg/ml, and 978 pg/ml, respectively. The C5a concentrations in the DM, DN, NM, and NN groups were 24.7 pg/ml, 15.3 pg/ml, 24.1 pg/ml, and 12.9 pg/ml, respectively. The concentrations of C3a and C5a in the DM and NM groups were significantly higher than in the NN group (P < 0.05 for both comparisons). The CAPs in the tear fluid in MGD and DE increased. Local dysregulation of the innate immune system can be associated with the development of MGD and DE in elderly patients.

Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions.

Endothelial cell responses to fluid shear stress from blood flow are crucial for vascular development, function and disease. A complex of PECAM-1, VE-cadherin, VEGF receptors (VEGFRs) and PlexinD1 located at cell-cell junctions mediates many of these events. But available evidence suggests that another mechanosensor upstream of PECAM-1 initiates signaling. Hypothesizing that GPCR and Gα proteins may serve this role, we performed siRNA screening of Gα subunits and found that Gαi2 and Gαq/11 are required for activation of the junctional complex. We then developed a new activation assay, which showed that these G proteins are activated by flow. We next mapped the Gα residues required for activation and developed an affinity purification method that used this information to identify latrophilin-2 (Lphn-2/ADGRL2) as the upstream GPCR. Latrophilin-2 is required for all PECAM-1 downstream events tested. In both mice and zebrafish, latrophilin-2 is required for flow-dependent angiogenesis and artery remodeling. Furthermore, endothelial specific knockout demonstrates that latrophilin plays a role in flow-dependent artery remodeling. Human genetic data reveal a correlation between the latrophilin-2-encoding Adgrl2 gene and cardiovascular disease. Together, these results define a pathway that connects latrophilin-dependent G protein activation to subsequent endothelial signaling, vascular physiology and disease.

Mechanosensing through talin 1 contributes to tissue mechanical homeostasis.

It is widely believed that tissue mechanical properties, determined mainly by the extracellular matrix (ECM), are actively maintained. However, despite its broad importance to biology and medicine, tissue mechanical homeostasis is poorly understood. To explore this hypothesis, we developed mutations in the mechanosensitive protein talin1 that alter cellular sensing of ECM stiffness. Mutation of a novel mechanosensitive site between talin1 rod domain helix bundles 1 and 2 (R1 and R2) shifted cellular stiffness sensing curves, enabling cells to spread and exert tension on compliant substrates. Opening of the R1-R2 interface promotes binding of the ARP2/3 complex subunit ARPC5L, which mediates the altered stiffness sensing. Ascending aortas from mice bearing these mutations show increased compliance, less fibrillar collagen, and rupture at lower pressure. Together, these results demonstrate that cellular stiffness sensing regulates ECM mechanical properties. These data thus directly support the mechanical homeostasis hypothesis and identify a novel mechanosensitive interaction within talin that contributes to this mechanism.

Assessment of laparoscopic inguinal hernia repair using the classification for single port laparoscopy in adolescents and young adults.

BACKGROUND: Inguinal hernia repair is one of the most common operations performed worldwide. No consensus currently exists regarding the most appropriate operation for inguinal hernia in adolescent and young adult (AYA) patients. This study aimed to evaluate the outcomes in AYA patients undergoing high ligation or mesh repair under laparoscopy by examining the location and size of the hernia orifice defect. METHODS: We retrospectively reviewed all patients aged 15 to 40 years old who underwent laparoscopic hernia repair. Under single port laparoscopy, we classified the anatomic location (lateral, medial, or femoral) and size of the hernia orifice according to the classification by the European Hernia Society (EHS). A laparoscopic percutaneous extraperitoneal closure (LPEC) was performed on the patients with a lateral hernia with a hernia orifice defect size of ≤1.5 cm (L1). Transabdominal preperitoneal (TAPP) repair was performed on the patients with a lateral hernia with a hernia orifice defect size of >1.5 cm (L2 or 3). RESULTS: Overall, 40 patients underwent the mentioned surgical procedures. We performed LPEC on 22 patients, and TAPP on 18 patients. There were no intraoperative or postoperative complications and recurrences. CONCLUSIONS: This is the first report that evaluated the outcomes of AYA patients who underwent high ligation or mesh repair under laparoscopy by examining the location and size of the hernia orifice defect. Our data indicated that LPEC were effective and safe for AYA patients with small hernia orifice defect.

Risk factors of infection of implanted device after the Nuss procedure.

PURPOSE: The Nuss procedure is a minimally invasive procedure for the correction of pectus excavatum. It involves insertion of a substernal metal bar. A feared complication of any implantation procedure is infection, which often requires removal of the implanted device. This report describes the authors' experience with infectious complications after the Nuss procedure. METHODS: The study included 195 patients diagnosed with pectus excavatum. We performed the Nuss procedure under thoracoscopic control on all the patients. Factors analyzed for all patients included bar infection, sex, age, number of bars, and season of the year during which the operation was performed. RESULTS: Of the 195 study patients, there were 11 patients who suffered postoperative infectious complications, including 7 patients with cellulitis and 4 patients with bar infections. We removed the infected bars from three of the patients with bar infections. Ten of the patients with infected bar had undergone their operations in the summer. Sex, age and number of bars did not differ significantly between patients with or without infections. However, a significantly higher number of infections occurred among patients who underwent the Nuss procedure in the summer compared with the other seasons of the year (P < 0.05, Kruskal-Wallis Test). CONCLUSION: All patients with cellulitis successfully recovered with conservative treatment. However, 75 % of the patients with bar infections required removal of the infected device. Our study results showed that performance of the Nuss procedure during summer is a risk factor for postoperative infection. We recommend that particularly careful technique must be used during summer to prevent postoperative infections following the Nuss procedure.