Antibody-resistant mutants of Borrelia burgdorferi: in vitro selection and characterization.

We used polyclonal antisera and monoclonal antibodies (mAbs) to inhibit the growth of clonal populations of two strains of Borrelia burgdorferi, the Lyme disease agent, and thereby select for antibody-resistant mutants. mAbs were directed at the outer membrane proteins, OspA or OspB. Mutants resistant to the growth-inhibiting properties of the antibodies were present in the populations at frequencies ranging from 10(-5) to 10(-2). The several escape variants that were examined were of four classes. Class I mutants were resistant to all mAbs; they lacked OspA and OspB and the linear plasmid that encodes them. Two other proteins were expressed in larger amounts in class I mutants; mAbs to these proteins inhibited the mutant but not the wild-type cells. Class II mutants were resistant to some but not all mAbs; they had truncated OspA and/or OspB proteins. Class III mutants were resistant only to the selecting mAb; they had full-length Osp proteins that were not bound by the selecting antibody in Western blots. In two class III mutants resistant to different anti-OspA mAbs, missense mutations were demonstrated in the ospA genes. Class IV mutants were likewise resistant only to selecting antibody, but in this case the selecting antibody still bound in Western blots

Determining the Contribution of Epidermal Cell Shape to Petal Wettability Using Isogenic Antirrhinum Lines

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De novo mutation in SLC25A22 gene: expansion of the clinical and electroencephalographic phenotype

The SLC25A22 (Solute Carrier Family 25, Member 22) gene encodes for a mitochondrial glutamate/H+ symporter and is involved in the mitochondrial transport of metabolites across the mitochondrial membrane. We hereby report a 12-year-old girl presenting with early-onset epileptic encephalopathy, hypotonia, and global developmental delay. Whole exome sequencing identified a novel homozygous missense mutation in SLC25A22 gene (c.97A>G; p.Lys33Glu), as the likely cause of the disease. The phenotype of our patient and EEG recordings do not completely overlap with the phenotypes previously described, leading to a new and more complex form of disease associated with SLC25A22 variants, characterized by dyskinetic movements and oculogyric crisis

Type Ia Supernovae as Stellar Endpoints and Cosmological Tools

Empirically, Type Ia supernovae are the most useful, precise, and mature tools for determining astronomical distances. Acting as calibrated candles they revealed the presence of dark energy and are being used to measure its properties. However, the nature of the SN Ia explosion, and the progenitors involved, have remained elusive, even after seven decades of research. But now new large surveys are bringing about a paradigm shift --- we can finally compare samples of hundreds of supernovae to isolate critical variables. As a result of this, and advances in modeling, breakthroughs in understanding all aspects of SNe Ia are finally starting to happen.Comment: Invited review for Nature Communications. Final published version. Shortened, update

Prognostic value of discharge heart rate in acute heart failure patients: More relevant in atrial fibrillation?

Aims: The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (admission-discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes. Methods: We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentre, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission. Results: The mean age of the study population was 72+/-12years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one year all-cause mortality (Relative risk (RR)=1.182, confidence interval (CI) 95% 1.024-1.366, p=0.022) in SR. In AF patients discharge HR was associated with one year all cause mortality (RR=1.276, CI 95% 1.115-1.459, p</=0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction. Conclusions: In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Treatment of symptomatic macromastia in a breast unit

BACKGROUND: Patients suffering from symptomatic macromastia are usually underserved, as they have to put up with very long waiting lists and are usually selected under restrictive criteria. The Oncoplastic Breast Surgery subspeciality requires a cross-specialty training, which is difficult, in particular, for trainees who have a background in general surgery, and not easily available. The introduction of reduction mammaplasty into a Breast Cancer Unit as treatment for symptomatic macromastia could have a synergic effect, making the scarce therapeutic offer at present available to these patients, who are usually treated in Plastic Departments, somewhat larger, and accelerating the uptake of oncoplastic training as a whole and, specifically, the oncoplastic breast conserving procedures based on the reduction mammaplasty techniques such as displacement conservative techniques and onco-therapeutic mammaplasty. This is a retrospective study analyzing the outcome of reduction mammaplasty for symptomatic macromastia in our Breast Cancer Unit. METHODS: A cohort study of 56 patients who underwent bilateral reduction mammaplasty at our Breast Unit between 2005 and 2009 were evaluated; morbidity and patient satisfaction were considered as end points. Data were collected by reviewing medical records and interviewing patients. RESULTS: Eight patients (14.28%) presented complications in the early postoperative period, two of them being reoperated on. The physical symptoms disappeared or significantly improved in 88% of patients and the degree of satisfaction with the care process and with the overall outcome were really high. CONCLUSION: Our experience of the introduction of reduction mammaplasty in our Breast Cancer Unit has given good results, enabling us to learn the use of different reduction mammaplasty techniques using several pedicles which made it possible to perform oncoplastic breast conserving surgery. In our opinion, this management policy could bring clear advantages both to patients (large-breasted and those with a breast cancer) and surgeons

ELECTRIC SAND PILLOW EFFECT ON THE SHIVERING LEVEL OF SECTIO CAESAREA PATIENTS WITH SPINAL ANESTHESIA

According to WHO, the rate of delivery by sectio caesarea is quite large, which is around 24%-30% of all childbirth processes, for developed countries such as the Netherlands it is around 9-13%. In Indonesia, the percentage is still large, which is more than 50%. Sectio caesaria surgery can cause physiological changes in the body such as a decrease in body temperature. Hypothermia affects several organ systems initially causing an increase in metabolic rate, tachycardia in the cardiovascular system, peripheral vascular resistance, causing shivering. Based on the preliminary study, 195 patients (75%). Shivering if not treated immediately will cause discomfort, shivering can also develop into serious complications. This study goals to determine the effect of an electric sand pillow on the shivering level of sectio caesarea patients after spinal anesthesia at Budhi Asih Hospital, Jakarta in 2021. The research method used is a quasi- experimentalresearch with a two-group pre-test-post-test design. The sample in this study were some post SC patients at Budhi Asih Hospital as many as 70 people, the sampling technique was purposive sampling. There was a significant difference between before and after giving the electric sand pillow (p=0.000). There is an effect of an electric sand pillow on decreasing the shivering level