Podocyte and glomerular research is center stage for the development of improved preventive and therapeutic strategies for chronic progressive kidney diseases. Held April 3-6, 2016, the 11th ...International Podocyte Conference took place in Haifa and Jerusalem, Israel, where participants from all over the world presented their work on new developments in podocyte research. In this review, we briefly highlight the advances made in characterizing the mechanisms involved in podocyte development, metabolism, acquired injury, and repair, including progress in determining the roles of genetic variants and microRNA in particular, as well as the advances made in diagnostic techniques and therapeutics.
Adherents to the Jewish faith have resided in numerous geographic locations over the course of three millennia. Progressively more detailed population genetic analysis carried out independently by ...multiple research groups over the past two decades has revealed a pattern for the population genetic architecture of contemporary Jews descendant from globally dispersed Diaspora communities. This pattern is consistent with a major, but variable component of shared Near East ancestry, together with variable degrees of admixture and introgression from the corresponding host Diaspora populations. By combining analysis of monoallelic markers with recent genome-wide variation analysis of simple tandem repeats, copy number variations, and single-nucleotide polymorphisms at high density, it has been possible to determine the relative contribution of sex-specific migration and introgression to map founder events and to suggest demographic histories corresponding to western and eastern Diaspora migrations, as well as subsequent microevolutionary events. These patterns have been congruous with the inferences of many, but not of all historians using more traditional tools such as archeology, archival records, linguistics, comparative analysis of religious narrative, liturgy and practices. Importantly, the population genetic architecture of Jews helps to explain the observed patterns of health and disease-relevant mutations and phenotypes which continue to be carefully studied and catalogued, and represent an important resource for human medical genetics research. The current review attempts to provide a succinct update of the more recent developments in a historical and human health context.
The long-term risk associated with childhood kidney disease that had not progressed to chronic kidney disease in childhood is unclear. We aimed to estimate the risk of future end-stage renal disease ...(ESRD) among adolescents who had normal renal function and a history of childhood kidney disease.
We conducted a nationwide, population-based, historical cohort study of 1,521,501 Israeli adolescents who were examined before compulsory military service in 1967 through 1997; data were linked to the Israeli ESRD registry. Kidney diseases in childhood included congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease; all participants included in the primary analysis had normal renal function and no hypertension in adolescence. Cox proportional-hazards models were used to estimate the hazard ratio for ESRD associated with a history of childhood kidney disease.
During 30 years of follow-up, ESRD developed in 2490 persons. A history of any childhood kidney disease was associated with a hazard ratio for ESRD of 4.19 (95% confidence interval CI, 3.52 to 4.99). The associations between each diagnosis of kidney disease in childhood (congenital anomalies of the kidney and urinary tract, pyelonephritis, and glomerular disease) and the risk of ESRD in adulthood were similar in magnitude (multivariable-adjusted hazard ratios of 5.19 95% CI, 3.41 to 7.90, 4.03 95% CI, 3.16 to 5.14, and 3.85 95% CI, 2.77 to 5.36, respectively). A history of kidney disease in childhood was associated with younger age at the onset of ESRD (hazard ratio for ESRD among adults <40 years of age, 10.40 95% CI, 7.96 to 13.59).
A history of clinically evident kidney disease in childhood, even if renal function was apparently normal in adolescence, was associated with a significantly increased risk of ESRD, which suggests that kidney injury or structural abnormality in childhood has long-term consequences.
Activation of calcium channels leads to cell injury and proteinuria, while blocking of TRPC5 by novel small molecules (eg, ML204 Merck or AC1903 Cayman Chemical) has been suggested to prevent disease ...progression by preclinical studies, providing new opportunities for future treatment.7 Population disparity in chronic kidney disease has long been a troubling concern. Population-based gene mapping led to the identification of high-frequency variants at the APOL1 genetic locus, which account for much of the disparity in non-diabetic chronic kidney disease of glomerular origin in the African ancestry population.8 This discovery is already impacting day-to-day clinical decision-making regarding kidney donation, and in the assessment of outcomes when transplanting kidneys of high-risk genotype.9 To what extent is this progress decreasing the need for kidney biopsy or transforming the way pathologists examine kidney biopsy samples from pure morphological to molecular analysis? Productive observational global consortia (like PodoNet, the Nephrotic Syndrome Study Network NEPTUNE, the SPOR Canadian Glomerulonephritis Registry and Translational Research Initiative, and others), wherein patient biological samples (kidney biopsy, serum, plasma, and urine) are systematically collected and analysed, are using these investigational platforms.13 Differential transcriptional, proteomic, metabolomic, and epigenomic signatures (such as non-coding RNAs), among others, are being investigated to understand their potential utility in the clinical care of patients with nephrotic syndrome, mainly in terms of identification of novel pathophysiological pathways and molecules, variability of disease progression, prognostic biomarkers, and response to therapy.13 Could this approach lead to mechanism-based interventional clinical trials? A survey of registered clinical trials at ClinicalTrials.gov shows that this is already the case.
Non‐neoplastic stromal cells harvested from patient tumors were identified as tumor‐derived mesenchymal stem cells (MSCs) by their multipotential capacity to differentiate into adipocytes, ...osteoblasts, and chondrocytes and by the expression of MSC specific cell surface markers. These procedures yielded also epithelial cancer cells and their counterpart MSC from gastric carcinoma (GSC1) and lung carcinoma (LC2). While the LC2 cancer cell growth is independent of their LC‐MSC, the GSC1 cancer cell growth is critically dependent on the presence of their counterpart GSC‐MSC or their conditioned medium (CM). The fact that none of the various other tumor‐derived MSCs was able to restore the specific effect of GSC‐MSC on GSC1 cancer cell growth suggests specificity of tumor‐derived MSC, which are specifically recruited and “educated”/reprogrammed by the cancer cells to support tumor growth. Using cytokine array analysis, we were able to demonstrate that GSC1 cell growth is mediated through hepatocyte growth factor (HGF)/c‐MET signaling pathway which is activated exclusively by HGF secreted from GSC‐MSC. An innovative approach demonstrates GSC1‐mediated specific tropism of “naïve” MSC from the adjacent tissue in a tumor specific manner to support tumor progression. The results suggest that specific tumor tropic “naïve” MSC are reprogrammed in a tumor‐specific manner to support gastric tumor progression. Understanding the mechanisms involved in the interactions of the tumor cancer cells and tumor‐derived MSC will constitute the basis for developing multimodal anticancer therapeutic strategies that will also take into account the specific tumor tropism properties of MSC and their reprogramming. Stem Cells 2016;34:1011–1026
Chronic kidney disease (CKD) is a major public health challenge, affecting as much as 8 to 18% of the world population. Identifying childhood risk factors for future CKD may help clinicians make ...early diagnoses and initiation of preventive interventions for CKD and its attendant comorbidities as well as monitoring for complications. The purpose of this review is to describe childhood risk factors that may predict development of overt kidney disease later in life. Currently, there are multiple childhood risk factors associated with future onset and progression of CKD. These risk factors can be grouped into five categories: genetic factors (e.g., monogenic or risk alleles), perinatal factors (e.g., low birth weight and prematurity), childhood kidney diseases (e.g., congenital anomalies, glomerular diseases, and renal cystic ciliopathies), childhood onset of chronic conditions (e.g., cancer, diabetes, hypertension, dyslipidemia, and obesity), and different lifestyle factors (e.g., physical activity, diet, and factors related to socioeconomic status). The available published information suggests that the lifelong risk for CKD can be attributed to multiple factors that appear already during childhood. However, results are conflicting on the effects of childhood physical activity, diet, and dyslipidemia on future renal function. On the other hand, there is consistent evidence to support follow-up of high-risk groups.
Israel: health and beyond Skorecki, Karl, Prof; Horton, Richard, Dr
The Lancet (British edition),
06/2017, Letnik:
389, Številka:
10088
Journal Article
Recenzirano
Summary The principle that global human identity and dignity supersede other values is a broadly accepted conviction that guides practice and policies in the realm of human health in most of the ...world. An assessment of the level of success that Israel has achieved in health, in the face of formidable challenges, including rapid population growth, diverse and often divided ethnic affiliations, and existential security threats, leads us to propose that extension of this principle of global human identity and dignity, together with the objective of a decent society, as overriding values beyond health to other domains of human endeavour within Israel and in its relations with neighbouring peoples, represents an entirely achievable imperative. The result will be to further advance Israel's aspiration to serve as a model for societal decency with wide international acceptance and engagement. We have identified several determinants of Israel's advancement in health, including: articulation of a clear vision, national purpose, and long-term commitment that seeks to take the health of its citizens seriously; a multi-ethnic population that brings diversity and energy to national progress; a political democracy, which is characterised by robust debate and discussion about the nation's future; national legislation governing cardinal health-care processes; cultural and religious histories that respect and revere scholarship, learning, research, and charitable donation; an expanding economy, with recent but increasing appreciation of the economic, social, and political underpinnings of health and health inequalities; a strong base of international support from the Diaspora Jewish community; and a strong desire for acceptance by the international community in key arenas, especially science and health. As a result, despite the fewer than seven decades since its establishment, Israel has achieved important milestones in health. Nevertheless, this trajectory of achievement is threatened by several serious challenges, including the capacity to sustain high-quality universal health coverage, especially for an ageing population living with multiple comorbidities in the face of a stagnant level of the percentage of treasury funding to health care at a level that is well below the average of the Organisation for Economic Co-operation and Development; ever-increasing transfer of services and care covered by the mandatory public health services basket to private programmes; insufficient progress in resolving health disparities among and between communities, populations, and regions of the country congruent with disparities in income and employment; gender inequities; a looming increase in the already alarming shortfall in health-care professionals; and failure to match inpatient and acute care facilities to manage growing needs. These challenges within Israel are magnified in the context of health disparities with the neighbouring Palestinian population, a situation in which ongoing—but fragile and limited—health cooperation and training arrangements cannot stand in for a solution that will address Palestinian national aspirations. We come away from this Series with a great sense of optimism, but with specific recommendations that are based on the foregoing challenges. We believe that by increasing the investment in the health sector, which includes investing in the societal, political, educational, and environmental underpinnings of health, far more can be achieved to move Israel to a model international leadership position in health care, education, and research, and turn health into an engine for economic wellbeing and development. Religious leadership in Israel, with its formidable political influence, can be harnessed to promote health initiatives in areas ranging from smoking cessation and healthy diet to organ transplantation, and most of all condemnation of hostility and its replacement by peaceful resolution of even the deepest conflicts. Most of all, this Series showed that there is an enormous opportunity, which Israel can lead, to leverage the universally accepted principles of health as a sanctuary against conflict and inequity, to achieve a brighter future for a deeply troubled region of the world.
COVID-19 is a complex disease with a multifaceted set of disturbances involving several mechanisms of health and disease in the human body. Sex hormones, estrogen, and testosterone, seem to play a ...major role in its pathogenesis, development, spread, severity, and mortalities. Examination of factors such as age, gender, ethnic background, genetic prevalence, and existing co-morbidities, may disclose the mechanisms underlying SARS-CoV-2 infection, morbidity, and mortality, paving the way for COVID-19 amelioration and substantial flattening of the infection curve. In this mini-review, we focus on the role of testosterone through a discussion of the intricate mechanisms of disease development and deterioration. Accumulated evidence suggests that there are links between high level (normal male level) as well as low level (age-related hypogonadism) testosterone in disease progression and expansion, supporting its role as a double-edged sword. Unresolved questions point to the essential need for further targeted studies to substantiate these contrasting mechanisms.
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