One of the most exciting events in current biogerontology is the elucidation of environmental control over the rate of aging. Many observations suggest that appropriate external stimuli can ameliorate the state of various biological entities and even rejuvenate them. Recent findings support the possibility that nonpathological aging of cells may be caused solely by external signals and moreover that this aging might be reversible. We have extended this principle to the level of the whole organism. We have suggested that a range of natural environmental conditions exists that corresponds to adequate vital activity within which an organism can maintain optimal functioning, renew itself, and remain ageless. But the environmental mortality of such organisms in natural niches is rather high. To reduce this mortality, the organism requires a milder but less stimulating environment in the presence of which (below some threshold level), the organism's renewal process becomes incomplete and the organism starts to age. Nevertheless, an age-dependent increase in the mortality rate due to senescence can be compensated for by a significant initial reduction in mortality due to environmental causes. The moderate present-day increase of life expectancy is the result of just such an initial mortality reduction. Living in a safe environment along with simulation of natural external positive influences or adequate responses to negative influences can decelerate, stop, and even reverse aging as well as considerably extend mean and extreme life span.
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Seizure
January 2025
University of Adelaide, Adelaide SA 5005, Australia; Flinders University, Bedford Park SA 5042, Australia; Lyell McEwin Hospital, Elizabeth Vale SA 5112, Australia; Department of Neurology and the Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA 02138, USA.
Purpose: Epilepsia partialis continua (EPC) is form of focal motor status epilepticus, with limited guidelines regarding effective pharmacological management. This systematic review aimed to describe previously utilized pharmacological management strategies for EPC, with a focus on patient outcomes.
Methods: A systematic review of the databases PubMed, EMBASE, and SCOPUS was performed from inception to May 2024.
Apolipoprotein E (APOE) has multiple functions in metabolism and immunoregulation. Its common germline variants APOE2, APOE3 and APOE4 give rise to three functionally distinct gene products. Previous studies reported yin-yang roles of APOE2 and APOE4 in immunological processes, but their effects in hematopoietic stem cell transplantation (HSCT) have never been studied.
View Article and Find Full Text PDFN Engl J Med
January 2025
From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine-UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) - both in Pittsburgh; AGO-B and Helios Klinikum Berlin-Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie-Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) - all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-S.H.); Instituto do Câncer do Estado de São Paulo, São Paulo (M.S.M.); Orlando Health Cancer Institute, Orlando, FL (E.P.M.); Hospital Universitario La Paz-Instituto de Investigación del Hospital Universitario La Paz, Madrid (A.R.); L'Institut du Cancer de Montpellier-Val d'Aurelle, Montpellier (V.D.), Institut Bergonié, INSERM Unité 1312, and Université de Bordeaux UFR Sciences Médicales, Bordeaux (H.R.B.) - all in France; Providence Cancer Institute, Portland, OR (A.K.C.); the Department of Surgery, Oncology, and Gastroenterology, University of Padua, and Oncology 2, Istituto Oncologico Veneto IRCCS, Padua (V.G.), and the Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo (E.R.C.) - all in Italy; Stanford University School of Medicine, Stanford, CA (I.L.W.); the National Cancer Institute, Mexico City (C.A.-S.); Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT (M.P.D.); the All-Ireland Cooperative Oncology Research Group (J.P.C.), and the Oncology Unit, Cancer Clinical Trials and Research Unit, Beaumont RCSI Cancer Centre, and Cancer Trials Ireland (B.T.H.) - all in Dublin; Fudan University Shanghai Cancer Center, Shanghai, China (Z.S.); Institute for Oncology and Radiology of Serbia, Belgrade (L.S.); Grupo Médico Ángeles, Guatemala City, Guatemala (H.C.-S.); Roche Products, Welwyn Garden City, United Kingdom (A.K., A.S.); and F. Hoffmann-La Roche, Basel, Switzerland (C.L., T.B., B.N., E.R.).
Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.
Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.
Neurology
February 2025
Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Ontario, Canada.
Pathogenic variants in cause congenital muscular dystrophy through hypoglycosylation of alpha-dystroglycan (OMIM #615350). The established phenotypic spectrum of GMPPB-related disorders includes recurrent rhabdomyolysis, limb-girdle muscular dystrophy, neuromuscular transmission abnormalities, and congenital muscular dystrophy with variable brain and eye anomalies. We report a 9-month-old male infant with congenital muscular dystrophy, infantile spasms, and compound heterozygous pathogenic variants (c.
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