THE PRESENT STATUS OF THE GERM-CELL PROBLEM IN VERTEBRATES

(i) Morphological studies relating to the origin and differentiation of the definitive germ cells in vertebrates have, as indicated, resulted in conflicting views. In many instances two or more competent investigators who have studied the same form have reached different conclusions. (2) Some contend that the germ cells are set aside from the soma during the early stages of embryonic development, and that these alone serve as the progenitors of the functional sex cells. (3) Others recognize an early differentiation of sex cells but hold that these are supplemented by others produced from the somatic epithelium of the gonad in late embryonic or post-embryonic stages. (4) Another group recognizes the early differentiated cells as germ cells but contend that these all degenerate and that the definitive ones are formed from the germinal epithelium. These degenerating germ cells are believed by certain authors to be a phylogenetic recapitulation of the condition in lower forms. (5) Finally, yet another group contends that the so-called primordial germ cells are not germ cells at all but are enlarged cells in some stage of mitosis or in some specific metabolic phase. This group believes that all germ cells are derived from the somatic cells of the germinal epithelium. (6) Experimental work supports the view that the primordial germ cells, which are recognized early, are the progenitors of the definitive sex cells. When these primordial germ cells are prevented from reaching the site of the developing gonad the individual fails to develop sex cells, although a sterile gonad and its associated structures may develop. (7) I suggest that the observed proliferation of germ cells from the germinal epithelium, reported by numerous investigators, can be interpreted in another way by a thorough study of the enlarged germ cells in relation to the epithelium. It seems probable that the cells of the epithelium, which form functional sex elements, are not and never were a part of the mesothelial covering, but are cells which were segregated early, and are merely stored in the epithelium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74677/1/j.1469-185X.1945.tb00313.x.pd

Meeting the International Health Regulations (2005) surveillance core capacity requirements at the subnational level in Europe: the added value of syndromic surveillance

BACKGROUND: The revised World Health Organization's International Health Regulations (2005) request a timely and all-hazard approach towards surveillance, especially at the subnational level. We discuss three questions of syndromic surveillance application in the European context for assessing public health emergencies of international concern: (i) can syndromic surveillance support countries, especially the subnational level, to meet the International Health Regulations (2005) core surveillance capacity requirements, (ii) are European syndromic surveillance systems comparable to enable cross-border surveillance, and (iii) at which administrative level should syndromic surveillance best be applied? DISCUSSION: Despite the ongoing criticism on the usefulness of syndromic surveillance which is related to its clinically nonspecific output, we demonstrate that it was a suitable supplement for timely assessment of the impact of three different public health emergencies affecting Europe. Subnational syndromic surveillance analysis in some cases proved to be of advantage for detecting an event earlier compared to national level analysis. However, in many cases, syndromic surveillance did not detect local events with only a small number of cases. The European Commission envisions comparability of surveillance output to enable cross-border surveillance. Evaluated against European infectious disease case definitions, syndromic surveillance can contribute to identify cases that might fulfil the clinical case definition but the approach is too unspecific to comply to complete clinical definitions. Syndromic surveillance results still seem feasible for comparable cross-border surveillance as similarly defined syndromes are analysed. We suggest a new model of implementing syndromic surveillance at the subnational level. In this model, syndromic surveillance systems are fine-tuned to their local context and integrated into the existing subnational surveillance and reporting structure. By enhancing population coverage, events covering several jurisdictions can be identified at higher levels. However, the setup of decentralised and locally adjusted syndromic surveillance systems is more complex compared to the setup of one national or local system. SUMMARY: We conclude that syndromic surveillance if implemented with large population coverage at the subnational level can help detect and assess the local and regional effect of different types of public health emergencies in a timely manner as required by the International Health Regulations (2005)

Association of Nutritional Support With Clinical Outcomes Among Medical Inpatients Who Are Malnourished or at Nutritional Risk: An Updated Systematic Review and Meta-analysis.

Importance Malnutrition affects a considerable proportion of the medical inpatient population. There is uncertainty regarding whether use of nutritional support during hospitalization in these patients positively alters their clinical outcomes. Objective To assess the association of nutritional support with clinical outcomes in medical inpatients who are malnourished or at nutritional risk. Data Sources For this updated systematic review and meta-analysis, a search of the Cochrane Library, MEDLINE, and Embase was conducted from January 1, 2015, to April 30, 2019; the included studies were published between 1982 and 2019. Study Selection A prespecified Cochrane protocol was followed to identify trials comparing oral and enteral nutritional support interventions with usual care and the association of these treatments with clinical outcomes in non-critically ill medical inpatients who were malnourished. Data Extraction and Synthesis Two reviewers independently extracted data and assessed risk of bias; data were pooled using a random-effects model. Main Outcomes and Measures The primary outcome was mortality. The secondary outcomes included nonelective hospital readmissions, length of hospital stay, infections, functional outcome, daily caloric and protein intake, and weight change. Results A total of 27 trials (n = 6803 patients) were included, of which 5 (n = 3067 patients) were published between 2015 and 2019. Patients receiving nutritional support compared with patients in the control group had significantly lower rates of mortality (230 of 2758 [8.3%] vs 307 of 2787 [11.0%]; odds ratio [OR], 0.73; 95% CI, 0.56-0.97). A sensitivity analysis suggested a more pronounced reduction in the risk of mortality in recent trials (2015 or later) (OR, 0.47; 95% CI, 0.28-0.79) compared with that in older studies (OR, 0.94; 95% CI, 0.72-1.22), in patients with established malnutrition (OR, 0.52; 95% CI, 0.34-0.80) compared with that in patients at nutritional risk (OR, 0.85; 95% CI, 0.62-1.18), and in trials with high protocol adherence (OR, 0.67; 95% CI, 0.54-0.84) compared with that in trials with low protocol adherence (OR, 0.88; 95% CI, 0.44-1.76). Nutritional support was also associated with a reduction in nonelective hospital readmissions (14.7% vs 18.0%; risk ratio, 0.76; 95% CI, 0.60-0.96), higher energy intake (mean difference, 365 kcal; 95% CI, 272-458 kcal) and protein intake (mean difference, 17.7 g; 95% CI, 12.1-23.3 g), and weight increase (0.73 kg; 95% CI, 0.32-1.13 kg). No significant differences were observed in rates of infections (OR, 0.86; 95% CI, 0.64-1.16), functional outcome (mean difference, 0.32; 95% CI, -0.51 to 1.15), and length of hospital stay (mean difference, -0.24; 95% CI, -0.58 to 0.09). Conclusions and Relevance This study's findings suggest that despite heterogeneity and varying methodological quality among trials, nutritional support was associated with improved survival and nonelective hospital readmission rates among medical inpatients who were malnourished and should therefore be considered when treating this population

Nutritional Support and Outcomes in Malnourished Medical Inpatients: A Systematic Review and Meta-analysis

IMPORTANCE: During acute illness, nutritional therapy is widely used for medical inpatients with malnutrition or at risk for malnutrition. Yet, to our knowledge, no comprehensive trial has demonstrated that this approach is effective and beneficial for patients. OBJECTIVE: To assess the effects of nutritional support on outcomes of medical inpatients with malnutrition or at risk for malnutrition in a systematic review of randomized clinical trials (RCTs). DATA SOURCES: The Cochrane Library, MEDLINE, and EMBASE. The study dates were October 5, 1982, to April 30, 2014, in various (mostly European) countries. The dates of our analysis were March 10, 2015, to September 16, 2015. STUDY SELECTION: Based on a prespecified Cochrane protocol, we systematically searched RCTs investigating the effects of nutritional support (including counseling and oral and enteral feeding) in medical inpatients compared with a control group. DATA EXTRACTION: Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus. MAIN OUTCOMES AND MEASURES: The primary study outcome was mortality. Secondary outcomes included hospital-acquired infections, nonelective readmissions, functional outcome, length of hospital stay, daily caloric and protein intake, and weight change. RESULTS: We included 22 RCTs with a total of 3736 participants. Heterogeneity across RCTs was high, with overall low study quality and mostly unclear risk of bias. Intervention group patients significantly increased their weight (mean difference, 0.72 kg; 95% CI, 0.23-1.21 kg), caloric intake (mean difference, 397 kcal; 95% CI, 279-515 kcal), and protein intake (mean difference, 20.0 g/d; 95% CI, 12.5-27.1 g/d) compared with control group patients. No differences between intervention group patients and control group patients were found with respect to mortality (9.8% vs 10.3%; odds ratio [OR], 0.96; 95% CI, 0.72-1.27), hospital-acquired infections (overall, 6.0% vs 7.6%; OR, 0.75; 95% CI, 0.50-1.11), functional outcome (mean Barthel index difference, 0.33 point; 95% CI, -0.88 to 1.55 points), or length of hospital stay (mean difference, -0.42 days; 95% CI, -1.09 to 0.24 days). Nonelective readmissions were significantly decreased by the intervention (20.5% vs 29.6%; risk ratio, 0.71; 95% CI, 0.57-0.87). CONCLUSIONS AND RELEVANCE: In medical inpatients, nutritional support increases caloric and protein intake and body weight. However, there is little effect on clinical outcomes overall except for nonelective readmissions. High-quality RCTs are needed to fill this gap

Revisiting nutritional support for allogeneic hematologic stem cell transplantation-a systematic review.

In 2009, the American Society of Parenteral and Enteral Nutrition and its European counterpart (Euopean Society for Parenteral and Enteral Nutrition) published guidelines regarding nutritional support of patients with hematologic stem cell transplantation. Our aim was to do an up-to-date literature review regarding benefit of nutritional interventions and treatment recommendations. We searched MEDLINE, EMBASE and Cochrane Library for interventional and observational clinical studies. We extracted data based on a predefined case report form and assessed bias. Out of 459 potential abstracts, 13 studies of mostly moderate quality with a total of 18 167 patients were included. Two very large trials reported negative associations of malnutrition and survival, transplant-related mortality and relapse risk. Some trials found enteral nutrition (EN) to be as effective as parenteral nutrition (PN) with lower complication rates. In addition, EN was associated with better survival, less acute GvHD and faster neutrophil recovery. A neutropenic diet was not superior regarding overall survival, but in contrast resulted in higher infection risk. Current moderate quality studies show negative associations of malnutrition and clinical outcomes, with EN being superior to PN. There was no benefit of neutropenic diets. Large, randomized controlled studies are needed to better understand optimal nutritional support in this patient population