Tropomyosin is required for cardiac morphogenesis,myofibril assembly,and formation of adherens junctions in the developing mouse embryo

BACKGROUND: We explored a function for tropomyosin (TM) in mammalian myofibril assembly and cardiac development by analyzing a deletion in the mouse TPM1 gene targeting αTM1, the major striated muscle TM isoform. RESULTS: Mice lacking αTM1 are embryonic lethal at E9.5 with enlarged, misshapen, and non‐beating hearts characterized by an abnormally thin myocardium and reduced trabeculae. αTM1‐deficient cardiomyocytes do not assemble striated myofibrils, instead displaying aberrant non‐striated F‐actin fibrils with α‐actinin puncta dispersed irregularly along their lengths. αTM1's binding partner, tropomodulin1 (Tmod1), is also disorganized, and both myomesin‐containing thick filaments as well as titin Z1Z2 fail to assemble in a striated pattern. Adherens junctions are reduced in size in αTM1‐deficient cardiomyocytes, α‐actinin/F‐actin adherens belts fail to assemble at apical cell–cell contacts, and cell contours are highly irregular, resulting in abnormal cell shapes and a highly folded cardiac surface. In addition, Tmod1‐deficient cardiomyocytes exhibit failure of α‐actinin/F‐actin adherens belt assembly. CONCLUSIONS: Absence of αTM1 resulting in unstable F‐actin may preclude sarcomere formation and/or lead to degeneration of partially assembled sarcomeres due to unregulated actomyosin interactions. Our data also identify a novel αTM1/Tmod1‐based pathway stabilizing F‐actin at cell–cell junctions, which may be required for maintenance of cell shapes during embryonic cardiac morphogenesis. Developmental Dynamics 243:800–817, 2014. © 2014 Wiley Periodicals, Inc.     

Intra-hospital Transport of Brain-Injured Patients: A Prospective, Observational Study

Introduction

Discrepant data exist regarding the incidence and severity of clinical problems related to intra-hospital transport of brain-injured patients and no consensus exists whether modern-day intra-hospital transport represents a safe or potentially problematic environment for neurointensive care unit (NICU) patients.

Methods

We examined the incidence of clinical complications and physiological derangements that occurred in 160 neurologically injured patients (90 males, 70 females, mean age 57 ± 17 years) who underwent intra-hospital transport (288 cases, 237 scheduled, 51 unscheduled) for computed tomography scans.

Results

Our findings indicate that (1) at least one significant complication (predominantly hemodynamic) occurred in over one-third (36 %) of all transports (p = n.s scheduled vs. unscheduled) necessitating the deployment of interventions designed to treat changes in arterial pressure (2) despite the presence of trained medical personnel and availability of specialized equipment, intra-cranial pressure was not adequately monitored during transports (especially in patients with intra-cranial hypertension prior to transport) (3) intra-hospital transfer was associated with minor but statistically significant clinical changes, including a reduction in arterial partial pressure of oxygen ( $ {\text{Pa}}_{{{\text{O}}_{ 2} }} $ )/inspired oxygen fraction ( $ {\text{Fi}}_{{{\text{O}}_{ 2} }} $ ) (only in the scheduled transport population), decreased arterial lactate levels (scheduled transport population), lowered body temperature (scheduled transport population), and increased arterial partial pressure of carbon dioxide ( $ {\text{Pa}}_{{{\text{CO}}_{ 2} }} $ ) (scheduled transport population).

Conclusions

Intra-hospital transport of brain-injured NICU patients may present some hazards even if performed by skilled personnel with specialized equipment. In Trauma Centers such as ours, an improvement in the frequency of neuromonitoring [intra-cranial pressure (ICP) and end-tidal CO₂ ( $ {\text{ET}}_{{{\text{CO}}_{ 2} }} $ )] during transport is recommended.     

Opinion paper: Stimulation of complement amplification or activation of the alternative pathway of complement?

In this opinion paper, we suggest that the scheme of the complement system should be redrawn in order to better illustrate its potencies. This can be achieved by putting the amplification loop of the alternative complement pathway at the center of the complement system. This arrangement emphasizes that C3b molecules, generated by any pathway, can stimulate complement amplification. Furthermore, it allows one to differentiate between this type of stimulation of amplification and that driven by those immune complexes that capture dimeric C3b molecules, which are more potent C3 convertase precursors than C3b. Schemes similar to the one drawn may help to better illustrate the interplay of the pathways and convey a clearer comprehension of the mechanics of the complement system.     

A comparison of vaginal, laparoscopic-assisted vaginal, and minilaparotomy hysterectomies for enlarged myomatous uteri

Objective

To compare the operative data and early postoperative outcome of vaginal hysterectomy (VH), laparoscopic-assisted vaginal hysterectomy (LAVH), and minilaparotomy hysterectomy (MiniLPT).

Methods

A total of 150 women who required hysterectomy for enlarged myomatous uteri were randomly allocated into 3 treatment groups: VH (n = 50), LAVH (n = 50), and MiniLPT (n = 50). The primary outcome was hospital discharge time. The secondary outcomes were operative time, blood loss, paralytic ileus, postoperative pain, and intraoperative and early postoperative complications.

Results

Mean hospital discharge time was longest with MiniLPT, and shortest with VH (P < 0.01). VH was the fastest operating technique, was associated with less blood loss, and resulted in shortest duration of paralytic ileus (P < 0.01). No intraoperative complications occurred.

Conclusion

VH should be the preferred surgical approach in patients with enlarged myomatous uteri. When VH is not feasible, LAVH should be considered an alternative to MiniLPT. Further controlled prospective studies are required to confirm these results.     

Prospective evaluation of oral mucositis in acute leukemia patients receiving chemotherapy

Purpose  

Knowledge of oral mucositis (OM) in patients with acute leukemia (AL) and chemotherapy (CT) has remained limited. Thus, a prospective, longitudinal study was undertaken to characterize clinical features, associated risk factors, and behavior of OM in a cohort of AL patients starting CT.