Collective cell migration of the nephric duct requires FGF signaling

Background : During the course of development, the vertebrate nephric duct (ND) extends and migrates from the place of its initial formation, adjacent to the anterior somites, until it inserts into the bladder or cloaca in the posterior region of the embryo. The molecular mechanisms that guide ND migration are poorly understood. Results : A novel Gata3‐enhancer‐Gfp‐based chick embryo live imaging system was developed that permits documentation of ND migration at the individual cell level for the first time. FGF Receptors and FGF response genes are expressed in the ND, and FGF ligands are expressed in surrounding tissues. FGF receptor inhibition blocked nephric duct migration. Individual inhibitors of the Erk, p38, or Jnk pathways did not affect duct migration, but inhibition of all three pathways together did inhibit migration of the duct. A localized source of FGF8 placed adjacent to the nephric duct did not affect the duct migration path. Conclusions : FGF signaling acts as a “motor” that is required for duct migration, but other signals are needed to determine the directionality of the duct migration pathway. Developmental Dynamics 244:157–167, 2015. © 2014 Wiley Periodicals, Inc.     

Surrogate versus couple therapy in vaginismus

IntroductionWomen who do not have a cooperative partner cannot complete the usual therapeutic process in the treatment of vaginismus, because they cannot progress to the stage of practicing the insertion of the man partner's fingers and the insertion of a penis.AimTo compare traditional couple therapy with therapy utilizing a surrogate partner.MethodsThe study was controlled and retrospective. Data were obtained from the treatment charts of patients who had come to the clinic for treatment of vaginismus. Sixteen vaginismus patients who were treated with a man surrogate partner were compared with 16 vaginismus patients who were treated with their own partners.Main Outcome MeasuresSuccessful pain-free intercourse upon completion of therapy.ResultsOne hundred percent of the surrogate patients succeeded in penile–vaginal intercourse compared with 75% in the couples group (P = 0.1). All surrogate patients ended the therapy because it was fully successful, compared with 69% in the couples group. Twelve percent of the couples group ended the therapy because it failed, and 19% because the couples decided to separate.ConclusionsTreating vaginismus with a man surrogate partner was at least as effective as couple therapy. Surrogate therapy may be considered for vaginismus patients who have no cooperative partner. Ben-Zion I, Rothschild S, Chudakov B, and Aloni R. Surrogate vs. couple therapy in vaginismus.     

Mucormycosis infection following intravenous access in the forearm

Mucormycosis is an opportunistic infection that is often fatal, requiring aggressive local control as well as systemic therapy. A rare case of a forearm infection originating in a traumatic intravenous access portal is described in the present study. The Mucor species infection prevented liver transplant, and the patient passed away. In the present case, it was decided to limit the resection to the skin and subcutaneous tissue based on a frozen section and the viability of the biopsied tissue. With consistently rising numbers of immunocompromised patients, awareness and familiarity with mucormycosis in the extremities is important. Knowing that a minimal traumatic event may precede the infection could assist in prevention and early diagnosis. Guidelines for pathological and clinical diagnosis and treatment need to be further clarified.     

Age-dependent changes in Na current magnitude and TTX-sensitivity in the canine sinoatrial node

In rabbit, sodium current (I_Na) contributes to newborn sinoatrial node (SAN) automaticity but is absent in adult SAN, where heart rate is slower. In contrast, heart rate is high and I_Na is functional in adult mouse SAN. Given the slower heart rates of large mammals, we asked if I_Na is functionally active in SAN of newborn or adult canine heart. SAN cells were isolated from newborn (6-10 days), young (40-43 days) and adult mongrels. I_Na was observed in > 80% of cells from each age. However, current density was markedly greater in newborn, decreasing with age. At all ages, I_Na was sensitive to nanomolar tetrodotoxin (TTX); 100 nmol/L inhibited I_Na by 46.7%, 59.9% and 90.7% in newborn, young and adult cells, respectively. While high TTX sensitivity suggested the presence of non-cardiac isoforms, steady-state inactivation was relatively negative (midpoints − 89.7 ± 0.7 mV, − 95.1 ± 1.2 mV and − 93.4 ± 1.9 mV from newborn to adult). Consequently, I_Na should be unavailable at physiological potentials under normal conditions, and 100 nmol/L TTX did not change cycle length or action potential parameters of spontaneous adult SAN cells. However, computer modeling predicts the large newborn I_Na protects against excess rate slowing from strong vagal stimulation. The results show that canine SAN cells have TTX-sensitive I_Na which decreases with post-natal age. The current does not contribute to normal automaticity in isolated adult cells but can be recruited to sustain excitability if nodal cells are hyperpolarized. This is particularly relevant in newborn, where I_Na is large and parasympathetic/sympathetic balance favors vagal tone.     

Heparanase Levels Are Elevated in the Plasma of Pediatric Cancer Patients and Correlate with Response to Anticancer Treatment

Heparanase is an endoglycosidase that specifically cleaves heparan sulfate (HS) side chains of heparan sulfate proteoglycans, the major proteoglycan in the extracellular matrix (ECM) and cell surfaces. Heparanase upregulation was documented in an increasing number of primary human tumors, correlating with reduced postoperative survival rate and enhanced tumor angiogenesis. The purpose of the current study was to determine heparanase levels in blood samples collected from pediatric cancer patients using an ELISA method. Heparanase levels were elevated four-fold in the plasma of cancer patients compared with healthy controls (664 ± 143 vs 163 ± 18 pg/ml, respectively). Evaluating plasma samples following anticancer therapy revealed reduced heparanase levels (664 ± 143 vs 429 ± 82 pg/ml), differences that are statistically highly significant (P = .0048). Of the 55 patients with complete remission (CR) or very good partial remission (VGPR) at restaging, 41 (74.5%) had lower heparanase amounts, whereas 14 patients (25.5%) had similar or higher amounts of plasma heparanase. All nine patients with stable or advancing disease had similar or elevated levels of heparanase on restaging. The results show that heparanase levels are elevated in the plasma of pediatric cancer patients and closely correlate with treatment responsiveness, indicating that heparanase levels can be used to diagnose and monitor patient''s response to anticancer treatment.