Surgical repair of congenitally corrected transposition of the great arteries: Results and follow-up

Eighteen patients with congenitally corrected transposition of the great arteries had open heart repair for intracardiac associated defects. Fourteen patients (78%) are alive during the follow-up period (mean 4.5 years). Seventeen (94%) of the 18 patients had ventricular septal defect closure, and 12 (66%) insertion of a pulmonary artery conduit. Surgical repair of the tricuspid valve was required in 6 patients (33%) during the first operation and in 3 additional patients during a second operation (total 50%). When hemodynamic overload or cardiac compromise was detected after surgery it was directly related to identifiable residual defects such as atrioventricular valvular insufficiency, residual ventricular septal defect, or pulmonary conduit stenosis. Repeat open heart operation for residual defects was common during the follow-up period (8 of 18 patients, 44%). No patient showed primary systemic or pulmonary ventricular dysfunction during the follow-up period. None of the last 11 patients developed complete heart block. Postoperative intraventricular conduction defects were common and are presumably caused by surgical injury of the bundle branches.Our observations suggest that surgical repair of congenitally corrected transposition of the great arteries can be currently achieved with acceptable risk. Improved knowledge of the precise location of the specialized conduction system resulted in a marked decrease in the Incidence of atrioventricular (A-V) block in patients with congenitally corrected transposition of the great arteries undergoing intracardiac repair. In the absence of postoperative residual defects it can be expected that longevity and quality of life will improve considerably, but many of these patients may require a repeat operation.     

A fluorescent probe designed for studying protein conformational change

The usefulness of fluorescence in studying protein motions derives from its sensitivity, kinetic resolution, and compatibility with both live cells and physiological assays. Recent advances in microscopy and membrane protein purification have permitted the observation of fluorescence changes that accompany the functional transitions of complex eukaryotic membrane proteins. These techniques rely on probes that can clearly report the environmental changes of specific residues, but most commonly available side-chain-reactive probes are not well suited for this purpose. Here, we introduce a red Cys-reactive probe, aminophenoxazone maleimide (APM), designed with improved chemical and spectral properties for reporting protein conformational change. APM is compact, uncharged, and has a short linker between probe and protein, all of which ensure that it can closely track the motions of the side chain to which it is attached. It undergoes large polarity-dependent changes in Stokes shift, as well as large bathochromic shifts in both excitation maximum (from 521 nm in toluene to 598 nm in water) and emission maximum (580 nm to 633 nm). These polarity-dependent spectral changes offer a potentially simple means of relating fluorescence to local structure and motion, although they are partially offset by some complicating factors in APM fluorescence. We find that, like a rhodamine maleimide, APM senses the conformational changes underlying voltage sensing in the Shaker potassium channel, and it is superior at a site that shows limited reactivity to the rhodamine. The spectral characteristics of APM can also report subtle differences between aqueous positions in purified preparations of the beta2 adrenergic receptor.     

Cat scratch disease encephalopathy in an immunocompetent patient

Cat scratch disease (CSD) is typically a self-limited regional lymphadenopathy in children and young adults that is caused by Bartonella henselae. The majority of CSD cases resolve spontaneously; however, many systemic complications have been described. We report an unusual case of CSD presenting as an epitrochlear arm mass and complicated by encephalopathy. Identification of B. henselae DNA in the affected lymph node and cerebrospinal fluid confirmed the diagnosis of CSD. Systemic antibiotic therapy was administered and the patient improved without any neurological deficit.     

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

BACKGROUNDThe significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODSA multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTSThe BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSIONAntenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDINGIsrael Science Foundation and the Weizmann Institute Fondazione Henry Krenter.     

Cellular senescence-like features of lung fibroblasts derived from idiopathic pulmonary fibrosis patients

Idiopathic pulmonary fibrosis (IPF) is an age-related fatal disease with unknown etiology and no effective treatment. In this study, we show that primary cultures of fibroblasts derived from lung biopsies of IPF patients exhibited (i) accelerated replicative cellular senescence (CS); (ii) high resistance to oxidative-stress-induced cytotoxicity or CS; (iii) a CS-like morphology (even at the proliferative phase); and (iv) rapid accumulation of senescent cells expressing the myofibroblast marker α-SMA. Our findings suggest that CS could serve as a bridge connecting lung aging and its quite frequent outcome -- pulmonary fibrosis, and be an important player in the disease progression. Consequently, targeting senescent cells offers the potential of being a promising therapeutic approach.