Aortic root enlargement in patients undergoing double valve replacement for rheumatic etiology–preliminary results

Introduction  

Combined aortic and mitral valve disease is usually of rheumatic origin. In these patients we often encounter problem of small valve annuli particularly with aortic annulus. It is still debated whether a small prosthesis should be used or aortic root should be enlarged to prevent Patient Prosthesis Mismatch (PPM). This study was undertaken to review our strategy and feasibility of Aortic Root Enlargement (ARE) in patient undergo Double Valve Replacement (DVR) to avoid mismatch without increase in cost of treatment, morbidity or mortality.     

The slow-aging growth hormone receptor/binding protein gene-disrupted (GHR-KO) mouse is protected from aging-resultant neuromusculoskeletal frailty

Neuromusculoskeletal (physical) frailty is an aging-attributable biomedical issue of extremely high import, from both public health and individual perspectives. Yet, it is rarely studied in nonhuman research subjects and very rarely studied in animals with extended longevity. In an effort to address this relatively neglected area, we have conducted a longitudinal investigation of the neuromusculoskeletal healthspan in mice with two senescence-slowing interventions: growth hormone (GH) resistance, produced by GH receptor “knockout” (GHR-KO), and caloric restriction (CR). We report marked improvements in the retention of strength, balance, and motor coordination by the longevity-conferring GHR/BP gene disruption, CR regimen, or a combination of the two. Specifically, GHR-KO mice exhibit superior grip strength, balance, and motor coordination at middle age, and CR mice display superior grip strength at middle age. The advantageous effects established by middle-age are more pronounced in old-age, and these robust alterations are, generally, not gender-specific. Thus, we show that genetic and/or dietary interventions that engender longevity are also beneficial for the retention of neuromusculoskeletal health and functionality. The translational knowledge to be gained from subsequent molecular or histological investigations of these models of preserved functionality and decelerated senescence is potentially relevant to the efforts to reduce the specter of fear, falls, fracture, and frailty in the elderly.     

Mutational analysis of N-Bak reveals different structural requirements for antiapoptotic activity in neurons and proapoptotic activity in nonneuronal cells

N-Bak, a neuron-specific BH3-only splice variant of Bak, is proapoptotic when overexpressed in nonneuronal cells, but antiapoptotic in NGF-deprived sympathetic neurons. We generated mutants of N-Bak and compared their activities in COS-7 or Neuro2A cells to those in NGF-deprived sympathetic neurons. A C-terminal deletion shortly after the BH3 domain of N-Bak compromised its neuroprotective activity but had little effect on its cytotoxic activity in nonneuronal cells. Amino acid changes in the BH3 domain of N-Bak differently affected its function in nonneuronal cells and in neurons. The same changes in the BH3 domain of longer Bak isoform affected its function similarly in nonneuronal cells and neurons. C-terminally truncated Bax, a structural analogue of N-Bak, was also neuroprotective, whereas Blk, a different BH3-only protein was apoptotic in neurons. Thus, neuron-specific antiapoptotic interactions require a "N-Bak-type" conformation, not just a BH3 domain, whereas the presence of a BH3 domain in the Bak protein is sufficient to kill nonneuronal cells.     

Microfluidic compartmentalized co-culture platform for CNS axon myelination research

This paper presents a circular microfluidic compartmentalized co-culture platform that can be used for central nervous system (CNS) axon myelination research. The microfluidic platform is composed of a soma compartment and an axon/glia compartment connected through arrays of axon-guiding microchannels. Myelin-producing glia, oligodendrocytes (OLs), placed in the axon/glia compartment, interact with only axons but not with neuronal somata confined to the soma compartment, reminiscent to in vivo situation where many axon fibres are myelinated by OLs at distance away from neuronal cell bodies. Primary forebrain neurons from embryonic day 16–18 rats were cultured inside the soma compartment for two weeks to allow them to mature and form extensive axon networks. OL progenitors, isolated from postnatal day 1-2 rat brains, were then added to the axon/glia compartment and co-cultured with neurons for an additional two weeks. The microdevice showed fluidic isolation between the two compartments and successfully isolated neuronal cell bodies and dendrites from axons growing through the arrays of axon-guiding microchannels into the axon/glia compartment. The circular co-culture device developed here showed excellent cell loading characteristics where significant numbers of cells were positioned near the axon-guiding microchannels. This significantly increased the probability of axons crossing these microchannels as demonstrated by the more than 51 % of the area of the axon/glia compartment covered with axons two weeks after cell seeding. OL progenitors co-cultured with axons inside the axon/glia compartment successfully differentiated into mature OLs. These results indicate that this device can be used as an excellent in vitro co-culture platform for studying localized axon-glia interaction and signalling.     

Cecal volvulus in children

Volvulus of the cecum is very uncommon in children. Of 189 children operated upon from 1970–1977 for acute intestinal obstruction, in only six children, was cecal volvulus the cause. The etiology and treatment and factors affecting mortality are discussed.