Enthesopathies (lesions of muscular insertions) as indicators of the activities of neolithic Saharan populations

Enthesopathies are bony lesions involving the sites of insertion of muscles or ligaments. Those caused by hyperactivity of the relevant muscles may be distinguished clearly from those of metabolic or inflammatory origin. Observations from sporting and occupational medicine indicate that specific enthesopathies are correlated with different activities. Examination of the enthesopathies present on two groups of well-preserved neolithic skeletons from separate regions of the Sahara with different paleoenvironments show that overall 20% of the skeletons presented lesions. Three different forms of enthesopathy involved the arm, principally the elbow, and may be tentatively correlated with javelin throwing, wood cutting, and archery. Two types of lesion involving the foot were observed in skeletons from a hunter-gatherer population and may be correlated with much walking or running over hard ground. I suggest that the analysis of such lesions on ancient skeletons may, in concert with other archaeological data, throw light on the activities of ancient people.     

COVID-19 plasma proteome reveals novel temporal and cell-specific signatures for disease severity and high-precision disease management

Coronavirus disease 2019 (COVID-19) is a systemic inflammatory condition with high mortality that may benefit from personalized medicine and high-precision approaches. COVID-19 patient plasma was analysed with targeted proteomics of 1161 proteins. Patients were monitored from Days 1 to 10 of their intensive care unit (ICU) stay. Age- and gender-matched COVID-19-negative sepsis ICU patients and healthy subjects were examined as controls. Proteomic data were resolved using both cell-specific annotation and deep-analysis for functional enrichment. COVID-19 caused extensive remodelling of the plasma microenvironment associated with a relative immunosuppressive milieu between ICU Days 3–7, and characterized by extensive organ damage. COVID-19 resulted in (1) reduced antigen presentation and B/T-cell function, (2) increased repurposed neutrophils and M1-type macrophages, (3) relatively immature or disrupted endothelia and fibroblasts with a defined secretome, and (4) reactive myeloid lines. Extracellular matrix changes identified in COVID-19 plasma could represent impaired immune cell homing and programmed cell death. The major functional modules disrupted in COVID-19 were exaggerated in patients with fatal outcome. Taken together, these findings provide systems-level insight into the mechanisms of COVID-19 inflammation and identify potential prognostic biomarkers. Therapeutic strategies could be tailored to the immune response of severely ill patients.     

Effect of High-Intensity Interval Training on Cardiac Apoptosis Markers in Methamphetamine-Dependent Rats

Chronic methamphetamine use increases apoptosis, leading to heart failure and sudden cardiac death. Previous studies have shown the importance of high-intensity interval training (HIIT) in reducing indices of cardiac tissue apoptosis in different patients, but in the field of sports science, the molecular mechanisms of apoptosis in methamphetamine-dependent rats are still unclear. The present article aimed to investigate the changes in cardiac apoptosis markers in methamphetamine-dependent rats in response to HIIT. Left ventricular tissue was used to evaluate caspase-3, melusin, FAK, and IQGAP1 gene expression. Rats were divided into four groups: sham, methamphetamine (METH), METH-control, and METH-HIIT. METH was injected for 21 days and then the METH-HIIT group performed HIIT for 8 weeks at 5 sessions per week. The METH groups showed increased caspase-3 gene expression and decreased melusin, FAK, and IQGAP1 when compared to the sham group. METH-HIIT showed decreased caspase-3 and increased melusin and FAK gene expression compared with the METH and METH-control groups. The IQGAP1 gene was higher in METH-HIIT when compared with METH, while no difference was observed between METH-HIIT and METH-control. Twenty-one days of METH exposure increased apoptosis markers in rat cardiac tissue; however, HIIT might have a protective effect, as shown by the apoptosis markers.     

健脾化瘀中药提高胞嘧啶脱氨酶/单纯疱疹病毒胸苷激酶基因治疗肝细胞癌的实验研究

目的:观察健脾化瘀中药提高胞嘧啶脱氨酶/单纯疱疹病毒胸苷激酶基因治疗肝细胞癌的作用。方法:脂质体lipofectamine将含有双自杀基因的腺病毒载体pAd-CD/TK导人293细胞,收集病毒上清转染人肝癌细胞BEL7402,MTT法测定BEL7402细胞存活率。裸鼠人肝癌模型转染CD/TK双自杀基因后,给予5-FC500mg/kg,GCV 100mg/kg腹腔注射,同时予健脾化瘀中药960复方灌胃。观察肿瘤生长情况。结果:给予前体药物5-FC和GCV后,CD/TK转染细胞被杀死。并表现出较强的旁观者效应。转染细胞比例达到10%即表现出较强的杀伤作用(P<0.01)。健脾化瘀中药960复方具有提高旁观者效应作用,1.67ml/kg和2.5ml/kg960复方含药血清组细胞存活率显著低于对照组(P<0.01)。转染基因组应用5-FC和GCV治疗后,裸鼠肝癌的生长明显受到抑制(P<0.05),抑瘤率39.42%,单用中药组抑瘤率18.04%,中药与CD/TK 5-FC/GCV联合运用组,较单纯CD/5-FC/HSV-tk/GCV对裸鼠肿瘤模型的生长抑制作用更加明显(P<0.05),抑瘤率55.10%。结伦:腺病毒介导CD/TK自杀基因可有效地杀死人肝癌BEL7402细胞,健脾化瘀中药960复方具有显著提高CD/TK双自杀基因对人肝癌细胞的抑杀作用。     

Specific features of ex‐obese patients significantly influence the functional cell properties of adipose‐derived stromal cells

Adipose‐derived stromal cells (ADSC) are increasingly used in clinical applications due to their regenerative capabilities. However, ADSC therapies show variable results. This study analysed the effects of specific factors of ex‐obese patients on ADSC functions. ADSC were harvested from abdominal tissues (N = 20) after massive weight loss. Patients were grouped according to age, sex, current and maximum body mass index (BMI), BMI difference, weight loss method, smoking and infection at the surgical site. ADSC surface markers, viability, migration, transmigration, sprouting, differentiation potential, cytokine secretion, telomere length and mtDNA copy number were analysed. All ADSC expressed CD73, CD90, CD105, while functional properties differed significantly among patients. A high BMI difference due to massive weight loss was negatively correlated with ADSC proliferation, migration and transmigration, while age, sex or weight loss method had a smaller effect. ADSC from female and younger donors and individuals after weight loss by increase of exercise and diet change had a higher activity. Telomere length, mtDNA copy number, differentiation potential and the secretome did not correlate with patient factors or cell function. Therefore, we suggest that factors such as age, sex, increase of exercise and especially weight loss should be considered for patient selection and planning of regenerative therapies.     

Hypoxic alterations of cortisol circadian rhythm in man after simulation of a long duration flight

Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurisation may be involved in this effect through disruption of circadian rhythms, independently of the number of time zones crossed. In this controlled crossover study, we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the circadian rhythm of plasma cortisol, a marker of the circadian time structure. Sixteen healthy young male volunteers (23-39 years) were exposed in a hypobaric chamber for 8 h (08:00-16:00 h) to 8000 ft, followed 4 weeks later to 12,000 ft. Plasma cortisol was assayed during two 24-h cycles (control and hypoxic exposure) every 2h in all subjects. We found a significant change in the pattern of cortisol secretion during both hypoxic exposures, with an initial fall in cortisol followed by a transient rebound, whereas the phase and the 24-h mean level remained unchanged. The change in cortisol pattern followed the alterations in autonomic balance assessed by heart rate variability (HRV) spectral analysis. The normalised high frequencies and the low-to-high frequencies ratio showed a significant shift toward sympathetic dominance with some differences in time course for both altitudes studied. HRV analysis improved the interpretation of cortisol 24-h profiles. Our data, which strongly suggest that prolonged mild hypoxia alters the expression of cortisol circadian rhythm, should be taken into account to interpret secretory rhythm changes after transmeridian flights.     

Mother-infant bonding

A study of the research on postpartum mother-infant bonding shows that results from poorly constructed research programs were published in major journals and became a part of hospital policy because the bonding concept was politically useful in the struggle between advocates of natural childbirth and managers of the medical model of birth. The concept was also uncritically accepted because it was consistent with a longstanding ideology of motherhood that sees women as the prime architects of their children’s personalities. Diane Eyer earned her Ph.D. in developmental psychology from the University of Pennsylvania. She is currently writing a book on the ways in which the concepts of bonding and attachment have affected our understanding of appropriate early childcare.     

Molecular medicine: Molecular diagnostics, preventive medicine, and gene therapy

New trends in molecular medicine that have emerged owing to the success of the national Human Genome program are characterized. The major attention is paid to molecular diagnostics, preventive medicine, and gene therapy. Preventive medicine is a product of synthesis of the current notions on genetics and biochemistry of human diseases; it comprises pharmacogenetics, presymptomatic diagnosis, and testing of genes of predisposition to the most frequent multifactor diseases. In the Gene Therapy section, advantages and drawbacks of the main methods of delivery of nucleic acids into the cells are considered; diseases that are attempted to be rectified using gene therapy are listed. Exemplified with Duchenne myodystrophy, the problems encountered in correction of a genetic defect with the aid of foreign genes are considered. Results are summarized for assessing the efficiency of various methods of introduction of dystrophin cDNA (gene gun, liposomes, microspheres, viral oligopeptides, and lactoferrin) conducted on the Duchenne myodystrophy model, mdx mice.