Impact of COVID‐19 on wound care in Germany

Recent studies showed that the COVID‐19 pandemic caused collateral damage in health care in terms of reduced hospital submissions or postponed treatment of other acute or chronic ill patients. An anonymous survey was sent out by mail to patients with chronic wounds in order to evaluate the impact of the pandemic on wound care. Sixty‐three patients returned the survey. In 14%, diagnostic workup or hospitalisation was cancelled or postponed. Thirty‐six percent could not seek consultation by their primary care physician as usual. The use of public transport or long travel time was not related to limited access to medical service (P = .583). In ambulatory care, there was neither a significant difference in the frequency of changing wound dressings (P = .67), nor in the person, who performed wound care (P = .39). There were no significant changes in wound‐specific quality of life (P = .505). No patient used telemedicine in order to avoid face‐to‐face contact or anticipate to pandemic‐related restrictions. The COVID‐19 pandemic impaired access to clinical management of chronic wounds in Germany. It had no significant impact on ambulatory care or wound‐related quality of life. Telemedicine still plays a negligible role in wound care.     

Craniofacial Development: Neural Crest in Molecular Embryology

Craniofacial development, one of the most complex sequences of developmental events in embryology, features a uniquely transient, pluripotent stem cell-like population known as the neural crest (NC). Neural crest cells (NCCs) originate from the dorsal aspect of the neural tube and migrate along pre-determined routes into the developing branchial arches and frontonasal plate. The exceptional rates of proliferation and migration of NCCs enable their diverse contribution to a wide variety of craniofacial structures. Subsequent differentiation of these cells gives rise to cartilage, bones, and a number of mesenchymally-derived tissues. Deficiencies in any stage of differentiation can result in facial clefts and abnormalities associated with craniofacial syndromes. A small number of conserved signaling pathways are involved in controlling NC differentiation and craniofacial development. They are used in a reiterated fashion to help define precise temporospatial cell and tissue formation. Although many aspects of their cellular and molecular control have yet to be described, it is clear that together they form intricately integrated signaling networks required for spatial orientation and developmental stability and plasticity, which are hallmarks of craniofacial development. Mutations that affect the functions of these signaling pathways are often directly or indirectly identified in congenital syndromes. Clinical applications of NC-derived mesenchymal stem/progenitor cells, persistent into adulthood, hold great promise for tissue repair and regeneration. Realization of NCC potential for regenerative therapies motivates understanding of the intricacies of cell communication and differentiation that underlie the complexities of NC-derived tissues.     

Validation of the Mayo Adhesive Probability score as a predictor of adherent perinephric fat and outcomes in open partial nephrectomy

BackgroundAdherent perinephric fat (APF) contributes to surgical complexity and can be associated with adverse perioperative outcomes for partial nephrectomy (PN). The Mayo Adhesive Probability (MAP) score accurately predicts the presence of APF during robotic-assisted partial nephrectomy (RAPN). Our primary aim is to validate MAP score as a predictor of APF in open partial nephrectomy (OPNx).MethodsWe reviewed 105 consecutive OPNx (100 patients) performed by a single surgeon with intraoperative determination of APF. We evaluated the ability of the MAP score to discriminate between those with APF and those without APF by estimating the area under the receiver operating characteristic curve (AUROCC). The association of perioperative outcomes with APF was evaluated as well.ResultsForty-three patients [49%; 95% confidence interval (CI), 39–59%] had intraoperative identification of APF. The MAP score had excellent ability to predict APF in OPNx (AUROCC, 0.82; 95% CI, 0.74–0.92). APF was observed in 6% of patients with a MAP score of 0-1, 27% with score 2, 52% with score 3, 75% with score 4, and 90% with score 5. The presence of APF was associated with longer operative times (P=0.004) and higher estimated blood loss (EBL) (P=0.003). Although not statistically significant, our study did suggest that APF may be associated with postoperative complications and prolonged length of stay (LOS) (>3 days).ConclusionsMAP score accurately predicts the presence of APF in patients undergoing OPNx. APF is associated with longer operative time and higher blood loss in OPNx.     

Bystander CD8 T-cell-mediated demyelination is interferon-gamma-dependent in a coronavirus model of multiple sclerosis

Mice infected with the coronavirus mouse hepatitis virus, strain JHM (JHM) develop a disease that shares many histological characteristics with multiple sclerosis. We previously demonstrated that JHM-infected mice that only have CD8 T cells specific for an epitope not in the virus develop demyelination on specific activation of these cells. Herein we show that this process of bystander T-cell-mediated demyelination is interferon-gamma (IFN-gamma)-dependent. The absence of IFN-gamma abrogated demyelination but did not change T-cell infiltration or expression levels of inflammatory cytokines or chemokines in the spinal cord. These results are consistent with models in which IFN-gamma contributes to CD8 T-cell-mediated demyelination by activation of macrophages/microglia, the final effector cells in the disease process.     

Daily,limited access to methamphetamine self-administration during pregnancy leads to increased methamphetamine sensitivity in adult offspring

Methamphetamine use by women, even throughout pregnancy, is common. But there is limited knowledge about the effects in prenatally methamphetamine-exposed children. This study investigated how prenatal methamphetamine exposure in rats, via maternal i.v. self-administration, affected the sensitivity of adult offspring to methamphetamine in comparison with controls. The offspring were generated from dams either self-administering methamphetamine daily under limited-access conditions prior to and throughout pregnancy, or their respective saline-yoked control dams. Spontaneous and methamphetamine-induced locomotor activity was assessed in male and female offspring of both exposure groups after a range of methamphetamine doses. In a separate group of offspring, acquisition of i.v. methamphetamine self-administration, responding under fixed and progressive ratio schedules of methamphetamine reinforcement, and reinstatement of extinguished drug-seeking behavior were assessed. Methamphetamine dose-dependently increased locomotor activity in both exposure groups. However, methamphetamine-exposed males showed significantly enhanced locomotor activity compared with controls at 1 mg/kg, and methamphetamine-exposed females showed significantly enhanced locomotor activity compared with controls at 3.2 mg/kg. Methamphetamine-exposed offspring of both sexes acquired methamphetamine self-administration faster and showed overall higher levels of methamphetamine-induced reinstatement compared with controls. Taken together, these results indicate that prenatal methamphetamine exposure to relatively low levels alters methamphetamine sensitivity in male and female adult offspring.     

Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.     

Modulation by lonidamine on the combined activity of cisplatin and epidoxorubicin in human breast cancer cells

The ability of lonidamine (LND), an energolytic derivativeof indazole-carboxylic acid, to modulate the cytotoxic activityof cisplatin (CDDP) and epidoxorubicin (EPI), singly orin combination, was investigated in two human breastcancer cell lines (MCF7 and T47D). A 72-hrpost-incubation with a non-cytotoxic concentration of LND (75M) increased the activity of a 1-hr CDDPtreatment as well as that of a 1to 16-hr EPI treatment. A different pattern ofinteraction among the drugs and modulator was observedas a function of the sequence of drugtreatment. Specifically, supra-additive or additive effects of thecombination were obtained in the two cell linesaccording to the different treatment schemes. In particular,the maximum potentiation was observed in MCF7 cellssimultaneously exposed to CDDP, EPI and LND for1 hr and then post-incubated with LND for72 hr, and in T47 first exposed toEPI and LND, then to CDDP and LND,and finally post-incubated with LND. Flow cytometric analysisof MCF7 cell distribution in the different cyclephases showed that combined treatment with EPI/CDDP/LND wasable to stabilize cell cycle perturbations (mainly G₂Maccumulation) induced by individual agents. The ability ofLND to potentiate CDDP and EPI cytotoxicity, andthe consideration that LND causes side effects differentfrom those caused by alkylating agents and anthracyclines,make this compound an attractive candidate for multidrugcombination therapy in breast cancer.     

An open-randomized clinical trial of selegiline in amyotrophic lateral sclerosis

Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS.     

Plasma concentrations and renal clearance of orotic acid in argininosuccinic acid synthetase deficiency

Argininosuccinic acid synthetase deficiency (ASD) is a rare disorder of urea cycle metabolism, with pronounced citrullinemia and orotic aciduria being characteristic biochemical features. To further investigate the role of plasma orotic acid and its possible use for monitoring the metabolic status in ASD, we determined plasma orotic acid, amino acid, and ammonium levels in plasma samples collected over a period of 3 years from a patient who is now 8 years of age. Orotic acid plasma concentrations varied widely from less than 1 μmol/l to more than 60 μmol/l. The renal clearance of orotic acid was eightfold the glomerular filtration rate, thus supporting an active mechanism underlying the excretion of this pyrimidine. Data obtained during a metabolic crisis yielded a statistically significant linear correlation of orotic acid plasma levels with those of glutamine and ammonium, which are generally accepted for assessment of the successful treatment of this disorder. Our data revealed no advantage of plasma orotic acid concentrations over the established amino acids (glutamine and arginine) and ammonium for determining acute treatment responses. Since several effects of high levels of orotic acid have been described in mammals, further research is necessary to assess a possible contribution of orotic acid to the pathogenesis of ASD and the use of plasma orotic acid levels in the long-term monitoring of these patients. Received: 3 November 1998 / Revised: 3 May 1999 / Accepted: 3 May 1999     

National Surveillance System and Hib meningitis incidence in Italy

In 1994, the Italian Ministry of Health implemented a National Surveillance System to obtain data on the incidence of bacterial meningitis and its causative agents, including Haemophilus influenzae type b (Hib). As a consequence, case reporting of Hib meningitis is increasing year by year; in 1996, there were 126 notifications, of which 73% were in children under 2 years of age. Although underreporting still exists, parallel prospective or retrospective epidemiological surveys conducted in some Italian Regions allowed for partial correction of the incidence of Hib meningitis (up to 18.5/100,000 population in 1994).