Paternal mosaicism for a novel PBX1 mutation associated with recurrent perinatal death: Phenotypic expansion of the PBX1‐related syndrome

Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra‐renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one‐day‐old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Further investigation by droplet digital PCR revealed that the mutation had occurred post‐zygotically in the father, with different variant allele frequencies of the mosaic PBX1 mutation in blood (10%) and sperm (20%). Interestingly, the father had subclinical hydronephrosis in childhood. With an expected recurrence risk of one in five, chorionic villus sampling and prenatal diagnosis for the PBX1 mutation identified recurrence in a subsequent pregnancy. The family opted to continue the pregnancy and the second affected sibling was stillborn at 35 weeks, presenting with similar severe bilateral diaphragmatic eventration, microsplenia, and complete sex reversal (46, XY female). This study highlights the importance of follow‐up studies for presumed de novo and low‐level mosaic variants and broadens the phenotypic spectrum of developmental abnormalities caused by PBX1 mutations.     

Mechanoafferent neurons innervating tail of Aplysia. I. Response properties and synaptic connections

Mechanical, chemical, or electrical stimulation of the tail elicits a short-latency (less than 1 s) tail-withdrawal reflex that is graded with the intensity of the stimulus. The tail-withdrawal reflex is not elicited by stimulation of parts of the body outside of the tail region. Mechanoafferent neurons innervating the tail are located in a small subcluster within a large, homogeneous group of medium-size (40-80 micron) cells on the ventrocaudal (VC) surface of each pleural ganglion. The tail sensory neurons within this large VC cluster are activated by tactile pressure or by electrical stimulation of discrete regions of the tail. They adapt slowly to maintained stimulation and sometimes respond to stimulus offset as well. Both mechanical and electrical stimuli produce responses that are graded with the intensity of the stimulus. Cells in the VC cluster appear to be primary mechanoreceptors because they have axons in peripheral nerves (including nerves innervating the tail), they exhibit action potentials lacking prepotentials in response to tactile stimulation, and these action potentials are still produced by cutaneous stimulation when peripheral and central chemical synaptic transmission is blocked. Stimulation of fields all over the body surface evokes synaptically mediated hyperpolarizing responses in individual mechanoafferent neurons that may represent afferent inhibition. Hyperpolarizing responses lasting many seconds can be produced by brief cutaneous stimuli. The mechanoafferent neurons innervating the tail region make strong monosynaptic connections to tail motor neurons in the ipsilateral pedal ganglion, and through these connections this subpopulation of the VC neurons appears to make a substantial contribution to the short-latency tail-withdrawal reflex. In addition, the combined excitatory receptive fields of these mechanoafferents match the excitatory receptive field of the tail-withdrawal reflex. Mechanoafferent neurons in the VC cluster that have receptive fields on other parts of the body (outside the excitatory receptive field of the tail-withdrawal reflex) have not been observed to make monosynaptic connections to the tail motor neurons. The neurons innervating the tail are reliably found in a discrete region within the larger VC cluster. In addition to this gross somatotopic organization, there is evidence of a finer level of somatotopic organization between the position of the excitatory receptive field on the tail and the position of the cell soma in the tail subcluster.(ABSTRACT TRUNCATED AT 400 WORDS)     

Differential Susceptibility of Chlamydiae to Exogenous Fibroblast Interferon

Mouse fibroblasts (L cells) were incubated for 5 h with 1,000 U of murine fibroblast interferon (MuIFN α+ β) per ml and then were infected with either Chlamydia trachomatis (LGV 440), C. psittaci (6BC), or C. psittaci (Cal 10). Intracellular development of C. trachomatis was reduced 90% in interferon-treated cells 24 h after infection when compared with controls, whereas C. psittaci growth was not affected in interferon-treated cells.     

Housing type,housing location and mental health

A number of studies have suggested a connection between the type of dwellings which people occupy and their mental health. People who live in flats are usually shown to be more prone to mental illness than those who live in houses. Those who live in high-rise accommodation are shown to be particularly vulnerable. These conclusions were examined by comparing rates on an indicator of psychological distress, in different dwelling types located in good and bad council housing areas. The results suggest that psychological distress is more closely associated with the location of a dwelling than with dwelling type. High-rise flats located on inner-city problem estates are associated with high levels of psychological distress, while low levels are found in similar dwelling types located in the suburbs. These findings are consistent when the effect of age, health, sex and household class are taken into consideration.     

Beta-2-adrenoceptor agonists as inhibitors of lung vascular permeability to radiolabelled transferrin in the adult respiratory distress syndrome in man

Increased lung vascular permeability leading to increased plasma protein extravasation and accumulation (PPA) is a characteristic feature of acute lung injury. Using a previously described technique, PPA was monitored in the lungs of patients with the adult respiratory distress syndrome (ARDS) — an extreme example of acute lung injury in man. An external radiation probe detector was used to monitor the pulmonary accumulation of the plasma protein transferrin radiolabelled in-vivo with ^113mIn. Ten patients with ARDS exhibiting increased PPA indices (>1.0x10^-3/min) were given an intravenous infusion of terbutaline (7 g/kg) over 30 min. Of the four patients in whom the post-drug PPA indices remained within the ARDS range, none survived, whilst five of the six patients in whom the post-drug PPA indices were reduced to below 1.0x10^-3/min survived. PPA indices prior to the administration of terbutaline were not significantly different between the survivor (n=5) and non-survivor (n=5) groups. There was a significant decrease in the PPA indices following terbutaline in survivors (p<0.01) but not in non-survivors. Thus beta-2-agonists in therapeutic doses can inhibit increased lung vascular permeability in man. These findings may have prognostic and therapeutic implication for beta-2-agonists in ARDS.     

Former Foster System Youth: Perspectives on Transitional Supports and Programs

The Journal of Behavioral Health Services & Research - Youth aging out of the foster care system have well-documented challenges when transitioning to adulthood. Multiple transition services...     

Direct comparison of reproducibility and reliability in quantitative assessments of burn scar properties

IntroductionDetermining the efficacy of anti-scar technologies can be difficult as qualitative, subjective assessments are often utilized instead of systematic, objective measures. Perceptions regarding the reliability of instruments for quantitative measurements along with their high cost and increased data collection time may discourage their use, leading to use of scar scales which are relatively quick and low-cost. To directly evaluate the reliability of instruments for quantitative measurements of scar properties, instruments and two qualitative scales were compared by assessing a variety of cutaneous scars.MethodsScar height and surface texture were evaluated using a 3D scanner and a mold/cast technique. Scar color was evaluated by using a spectroscopy-based tool, the Mexameter®, and digital photography with image analysis. Scar biomechanics were evaluated using the BTC-2000?, Dermal Torque Meter (DTM®), and ballistometer®. The Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) were used to qualitatively evaluate the same scar properties. Intraclass correlation coefficients (ICC) were used to determine inter- and intra-user reliability (poor, moderate, good, excellent) with all instruments and the kappa reliability statistic was used to asses inter-user reliability (poor, fair, moderate, good, very good) for VSS and POSAS. Time for measurement collection and after collection analysis was also recorded.ResultsThe Mexameter® was the most reliable method for evaluating erythema and pigmentation compared to digital photography and image processing, POSAS and VSS. Digital photography and analysis was more reliable than POSAS and VSS. Assessment of scar height was significantly more reliable when using a 3D scanner versus VSS and POSAS. The 3D scanner and mold-cast techniques also offered an additional benefit of providing an absolute value of scar height relative to the surrounding tissue. Intra-user reliability for all mechanical tests was moderate to good. Inter-user reliability was greater when using the BTC-2000? and ballistometer® versus the DTM®. All quantitative measurements took less than 90 s for collection, with the exception of the mold/cast technique.ConclusionNon-invasive instruments allow scar properties to be quantitatively assessed with high sensitivity and as a function of time and/or treatment without the need for biopsy collection. Overall, the reliability of scar assessments was significantly improved when quantitative instruments were utilized versus scar scales. Quantitative assessment of color and biomechanics were swift, requiring less than 90 s per measurement while assessments of texture and height required additional analysis time after collection. With proper training of clinical staff and well-defined protocols for measurement collection, reliable, quantitative assessments of scar properties can be collected with little disruption to the clinical workflow.