Large-scale migration into Britain during the Middle to Late Bronze Age.

Present-day people from England and Wales have more ancestry derived from early European farmers (EEF) than did people of the Early Bronze Age. To understand this, here we generated genome-wide data from 793 individuals, increasing data from the Middle to the Late Bronze Age and Iron Age in Britain by 12-fold, and western and central Europe by 3.5-fold.

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival.

Real-Time Monitoring of Levetiracetam Effect on the Electrophysiology of an Heterogenous Human iPSC-Derived Neuronal Cell Culture Using Microelectrode Array Technology.

Levetiracetam (LEV) is a broad-spectrum and widely used antiepileptic drug that also has neuroprotective effects in different neurological conditions. Given its complex interaction with neuronal physiology, a better comprehension of LEV effects on neurons activity is needed. Microelectrode arrays (MEAs) represent an advanced technology for the non-invasive study of electrophysiological activity of neuronal cell cultures.

Levosimendan in Europe and China: An Appraisal of Evidence and Context.

The calcium sensitiser levosimendan (SIMDAX; Orion Pharma) has been in clinical use for the management of acute heart failure and a range of related syndromes in many countries around the world for two decades. More recently, levosimendan has become available in China. The authors have examined the profile of levosimendan in clinical trials conducted inside and outside China and grouped the findings under six headings: effects on haemodynamics, effects on natriuretic peptides, effect on symptoms of heart failure, renal effects, effect on survival, and safety profile.

Growth of Neanderthal infants from Krapina (120-130 ka), Croatia.

Modern humans have a slow and extended period of childhood growth, but to what extent this ontogenetic pathway was present in Neanderthals is debated. Dental development, linked to the duration of somatic growth across modern primates, is the main source for information about growth and development in a variety of fossil primates, including humans. Studies of Neanderthal permanent teeth report a pace of development either similar to recent humans or relatively accelerated.

The role of direct peritoneal resuscitation in the treatment of hemorrhagic shock after trauma and in emergency acute care surgery: a systematic review.

Purpose: Direct peritoneal resuscitation (DPR) has been used to help preserve microcirculation by reversing vasoconstriction and hypoperfusion associated with the pathophysiological process of shock, which can occur despite appropriate intravenous resuscitation. This approach depends on infusing a hyperosmolar solution intraperitoneally via a percutaneous catheter with the tip ending near the pelvis or the root of the mesentery. The abdomen is usually left open with a negative pressure abdominal dressing to continuously evacuate the infused dialysate.

Magnetic resonance imaging before breast cancer surgery: results of an observational multicenter international prospective analysis (MIPA).

Objectives: Preoperative breast magnetic resonance imaging (MRI) can inform surgical planning but might cause overtreatment by increasing the mastectomy rate. The Multicenter International Prospective Analysis (MIPA) study investigated this controversial issue.

Methods: This observational study enrolled women aged 18-80 years with biopsy-proven breast cancer, who underwent MRI in addition to conventional imaging (mammography and/or breast ultrasonography) or conventional imaging alone before surgery as routine practice at 27 centers.

Fear of COVID-19 among Healthcare Workers: The Role of Neuroticism and Fearful Attachment.

Fear of becoming infected is an important factor of the complex suite of emotional reactions triggered by the COVID-19 pandemic. Among healthcare workers (HWs), fear of infection can put at risk their psychological well-being and occupational efficiency. The aim of this study was to analyze the role of personality (i.

A systematic review of the rates of depression in autistic children and adolescents without intellectual disability.

Objectives: Increasing evidence suggests that major depressive disorder (MDD) is highly prevalent in autism spectrum disorder (ASD). The current study is a systematic review of rates of depression in autistic children and adolescents, without intellectual disability.

Design: Adhering to PRISMA guidelines, a total of 14,557 studies were identified through five databases (MEDLINE, EMBASE, Cinahl, ERIC, PsycINFO, and Web of Science).

Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study.

Purpose: Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer.

Methods: It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection.

Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion.

Background And Purpose: Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread.

Methods: Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included.

Chemical and Biological Molecules Involved in Differentiation, Maturation, and Survival of Dopaminergic Neurons in Health and Parkinson's Disease: Physiological Aspects and Clinical Implications.

Parkinson's disease (PD) is one of the most common neurodegenerative disease characterized by a specific and progressive loss of dopaminergic (DA) neurons and dopamine, causing motor dysfunctions and impaired movements. Unfortunately, available therapies can partially treat the motor symptoms, but they have no effect on non-motor features. In addition, the therapeutic effect reduces gradually, and the prolonged use of drugs leads to a significative increase in the number of adverse events.

Arachnoid Cysts of the Internal Auditory Canal: Multiplanar Magnetic Resonance Imaging With Audio-Vestibular Correlates.

Objectives/hypothesis: To investigate prevalence, radiological characteristics, and functional correlates of arachnoid cysts (AC) of the internal auditory canal (IAC) region, including associations of nerve compression with auditory/vestibular symptoms and asymmetrical audiogram or vestibular testing.

Study Design: Retrospective study.

Methods: T2-weighted magnetic resonance imaging (MRI) studies of IACs were retrospectively analyzed from 1247 patients with asymmetric auditory or vestibular symptoms.

Is Gastric Involvement by Strongyloides stercoralis in an Immunocompetent Patient a Common Finding? A Case Report and Review of the Literature.

Purpose: Gastric infection with Strongyloides stercoralis (SS) usually occurs in immunocompromised patients. The unexpected observation of this parasite in an otherwise healthy young lady who had undergone upper endoscopy and biopsy sampling of the gastro-duodenal mucosa, prompted us to review the literature to ascertain the conditions favouring gastric colonization by SS.

Methods: Pathology files of gastroduodenal biopsies received at St.

Diabetic Complications and Oxidative Stress: A 20-Year Voyage Back in Time and Back to the Future.

Twenty years have passed since Brownlee and colleagues proposed a single unifying mechanism for diabetic complications, introducing a turning point in this field of research. For the first time, reactive oxygen species (ROS) were identified as the causal link between hyperglycemia and four seemingly independent pathways that are involved in the pathogenesis of diabetes-associated vascular disease. Before and after this milestone in diabetes research, hundreds of articles describe a role for ROS, but the failure of clinical trials to demonstrate antioxidant benefits and some recent experimental studies showing that ROS are dispensable for the pathogenesis of diabetic complications call for time to reflect.

Propelling Healthcare with Advanced Therapy Medicinal Products: A Policy Discussion.

Recent advances in biomedicine are opening the door to new approaches, and treatment and prevention are being transformed by novel medicines based on genetic engineering, innovative cell-based therapies and tissue-engineered products, and combinations of a medical device with embedded cell or tissue components. These advanced therapy medicinal products (ATMPs) hold one of the keys to making a reality of genuinely personalised medicine. There are an estimated 450 companies across the globe working on the development of gene therapies and more than 1,000 clinical trials underway worldwide, and some 20-30 new ATMPs filings are expected in Europe annually over the next 5 years.

Adult phenotype of encephalopathy.

Background: Pathogenic variants are a frequent cause of developmental and epileptic encephalopathy.

Methods: We recruited 13 adults (between 18 years and 45 years of age) with encephalopathy and reviewed their clinical, EEG, neuroimaging and treatment history.

Results: While most patients had daily seizures at seizure onset, seizure frequency declined or remitted during childhood and adulthood.

Mathematical Modeling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation.

New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts ("waves") of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice.

Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial.

Background: Riociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality.

Incidence of male breast carcinoma in North Uganda: A survey at Lacor Hospital, Gulu, during 2009-2016.

Background: Little information is available on male breast cancer (MBC) incidence from sub-Saharan Africa.

Objective: This is a retrospective study on MBC in rural North Uganda, based on the pathology records of a private, non-profit, missionary hospital.

Methods: All male patients that had histological diagnosis of breast carcinoma from January 2009 to December 2016 were included in this study.

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

Background: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases.