The secretome from human-derived mesenchymal stem cells augments the activity of antitumor plant extracts in vitro.

Cancer is understood as a multifactorial disease that involve multiple cell types and phenotypes in the tumor microenvironment (TME). The components of the TME can interact directly or via soluble factors (cytokines, chemokines, growth factors, extracellular vesicles, etc.). Among the cells composing the TME, mesenchymal stem cells (MSCs) appear as a population with debated properties since it has been seen that they can both promote or attenuate tumor progression. For various authors, the main mechanism of interaction of MSCs is through their secretome, the set of molecules secreted into the extracellular milieu, recruiting, and influencing the behavior of other cells in inflammatory environments where they normally reside, such as wounds and tumors. Natural products have been studied as possible cancer treatments, appealing to synergisms between the molecules in their composition; thus, extracts obtained from Petiveria alliacea (Anamu-SC) and Caesalpinia spinosa (P2Et) have been produced and studied previously on different models, showing promising results. The effect of plant extracts on the MSC secretome has been poorly studied, especially in the context of the TME. Here, we studied the effect of Anamu-SC and P2Et extracts in the human adipose-derived MSC (hAMSC)-tumor cell interaction as a TME model. We also investigated the influence of the hAMSC secretome, in combination with these natural products, on tumor cell hallmarks such as viability, clonogenicity, and migration. In addition, hAMSC gene expression and protein synthesis were evaluated for some key factors in tumor progression in the presence of the extracts by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Multiplex, respectively. It was found that the presence of the hAMSC secretome did not affect the cytotoxic or clonogenicity-reducing activities of the natural extracts on cancer cells, and even this secretome can inhibit the migration of these tumor cells, in addition to the fact that the profile of molecules can be modified by natural products. Overall, our findings demonstrate that hAMSC secretome participation in TME interactions can favor the antitumor activities of natural products.

The Envirome Web Service: Patient context at the point of care.

Patient context - the "envirome" - can have a significant impact on patient health. While envirome indicators are available through large scale public data sources, they are not provided in a format that can be easily accessed and interpreted at the point of care by healthcare providers with limited time during a patient encounter. We developed a clinical decision support tool to bring envirome indicators to the point of care in a large pediatric hospital system in the Kansas City region. The Envirome Web Service (EWS) securely geocodes patient addresses in real time to link their records with publicly available context data. End-users guided the design of the EWS, which presents summaries of patient context data in the electronic health record (EHR) without disrupting the provider workflow. Through surveys, focus groups, and a formal review by hospital staff, the EWS was deployed into production use, integrating publicly available data on food access with the hospital EHR. Evaluation of EWS usage during the 2020 calendar year shows that 1,034 providers viewed the EWS, with a total of 29,165 sessions. This suggests that the EWS was successfully integrated with the EHR and is highly visible. The results also indicate that 63 (6.1%) of the providers are regular users that opt to maintain the EWS in their custom workflows, logging more than 100 EWS sessions during the year. The vendor agnostic design of the EWS supports interoperability and makes it accessible to health systems with disparate EHR vendors.

Bacteriological and histopathological analysis of Penaeus vannamei experimentally infected with Vibrio parahaemolyticus-AHPND strains.

Vibrio parahaemolyticus strains have been identified as the causative agent of acute hepatopancreas necrosis disease (Vp AHPND+) in shrimp. In the present work, a highly virulent (M0904) and less virulent (M0607) strain of Vp AHPND+ were used in experimental infections of Penaeus vannamei. Throughout the experiment, histopathological analyses were conducted on shrimp tissues, and samples from the bottom (B) and water column (WC) of each aquarium were taken to estimate bacterial growth. The first deaths of shrimp challenged with Vp M0904 occurred 4 h post-infection (hpi), reached 50% mortality at 17 hpi, and showed more acute pathological progression associated with AHPND despite both strains having similar bacterial densities from 0-4 hpi. The first deaths of shrimp inoculated with Vp M0607 occurred at 13 hpi, a difference of 9 h. These shrimps displayed reduction of reserve vacuoles in R and B cells of the hepatopancreas, and reached 50% mortality at 27 hpi. As bacterial growth in the WC and B in the first hours was similar for both strains, bacterial density was not a significant factor in Vp virulence. Since pirAB toxin is the causative agent of AHPND, it is possible that there is a threshold level at which the toxin damages hepatopancreatic tissues, so production or secretion of the toxin can be dependent of the Vp strain. We propose new AHPND stage: remission with 3 main routes for the disease outcome after the remission stage (re-infection, chronic effect and recuperation). Hepatopancreatic embryonic cells can be used as a biological indicator of this stage.

[Therapeutic restraint management in Intensive Care Units: Phenomenological approach to nursing reality]. / Manejo de la inmovilización terapéutica en Unidades de Cuidados Críticos: aproximación fenomenológica a la realidad enfermera.

AIMS: To identify nursing experience on physical restraint management in Critical Care Units. To analyse similarities and differences in nursing experience on physical restraint management according to the clinical context that they are involved in. METHOD: A multicentre phenomenological study was carried out including 14 Critical Care Units in Madrid, classified according to physical restraint use: Common/systematic use, lacking/personalised use, and mixed use. Five focus groups (23 participants were selected following purposeful sampling) were convened, concluding in data saturation. Data analysis was focused on thematic content analysis following Colaizzi's method. FINDINGS: Six main themes: Physical restraint meaning in Critical Care Units, safety (self-retreat vital devices), contribution factors, feelings, alternatives, and pending issues. Although some themes are common to the 3 Critical Care Unit types, discourse differences are found as regards to indication, feelings, systematic use of pain and sedation measurement tools. CONCLUSIONS: In order to achieve real physical restraint reduction in Critical Care Units, it is necessary to have a deep understanding of restraints use in the specific clinical context. As self-retreat vital devices emerge as central concept, some interventions proposed in other settings could not be effective, requiring alternatives for critical care patients. Discourse variations laid out in the different Critical Care Unit types could highlight key items that determine the use and different attitudes towards physical restraint.

Economic recession, illicit drug use and the young population: a systematic literature review and meta-analysis.

AIMS: Economic recessions impact on drug use through different channels, with potential conflicting outcomes. Previous studies have reached mixed outcomes, and a clear and comprehensive picture is difficult to depict. METHODS: We use a systematic review of literature - conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines - and a hierarchical mixed-effects meta-analysis to provide a comprehensive quantitative assessment of the relationship between business cycle and the use of drugs by young populations. The heterogeneity of studies was assessed by the I2 statistic, and the publication bias was evaluated with contour-enhanced funnel plots. RESULTS: We identify 25 studies, published over the period 2008-2020. These articles carried out an empirical analysis of the impact of the business cycle on illegal drug consumption in Organisation for Economic Co-operation Development (OECD) countries. Most of the studies (17 studies) covered the 2007 financial crisis. Among the outcomes, 9 studies traced a countercyclical relationship between economic recessions and drug use, 3 showed a procyclical relationship and 13 studies found mixed results. Unemployment was the most widely used variable to assess macroeconomic conditions in most of the studies (21 studies). The meta-analysis shows a partial correlation of .03 (95% confidence interval (CI): .0147-.0453) between the unemployment rate and drug use among young individuals. Therefore, we conclude that, on average, recessions tend to boost drug use. This impact is more marked with cannabis use than it is with cocaine, opioids or other drugs. CONCLUSION: This study provides robust evidence that in periods of economic downturns, the young populations tend to increase the use of illegal drugs, with cannabis as their main preference. Therefore, in periods of economic severity, society may particularly benefit from implementing widely reaching public prevention programmes and demand reduction interventions, targeting this subgroup of the population.

Clinical and genetic characterization of classical forms of familial adenomatous polyposis: a Spanish population study.

BACKGROUND: Classical familial adenomatous polyposis (FAP) is characterized by the appearance of >100 colorectal adenomas. PATIENTS AND METHODS: We screened the APC and MUTYH genes for mutations and evaluated the genotype-phenotype correlation in 136 Spanish classical FAP families. RESULTS: APC/MUTYH mutations were detected in 107 families. Sixty-four distinct APC point mutations were detected in 95 families of which all were truncating mutations. A significant proportion (39.6%) had not been previously reported. Mutations were spread over the entire coding region and great rearrangements were identified in six families. Another six families exhibited biallelic MUTYH mutations. No APC or MUTYH mutations were detected in 29 families. These APC/MUTYH-negative families showed clinical differences with the APC-positive families. A poor correlation between phenotype and mutation site was observed. CONCLUSIONS: Our results highlight that a broad approach in the genetic study must be considered for classical FAP due to involvement of both APC and MUTYH and the heterogeneous spectrum of APC mutations observed in this Spanish population. The scarcely consistent genotype-phenotype correlation does not allow making specific recommendations regarding screening and management. Differences observed in APC/MUTYH-negative families may reflect a genetic basis other than mutations in APC and MUTYH genes for FAP predisposition.

The impact of socioeconomic position on non-communicable diseases: what do we know about it?

AIMS: Non-communicable diseases (NCDs) have become a primary health concern for most countries around the world. The aim of this research is to analyze the relevant evidence that determines the effect of socioeconomic position (SEP) on the incidence and prevalence of NCDs. METHODS: A systematic literature search was performed using PubMed, Cochrane Library, and Web of Science to identify evidence regarding the relationship between income inequalities and NCDs, between 2005 and 2015. The final selection of papers was based on applied studies focusing on Organisation for Economic Co-operation and Development (OECD) countries and articles referring to three main groups of chronic diseases: cardiovascular and heart diseases, cancer, and diabetes. RESULTS: A final set of 47 selected studies were fully taken into account in this review. Despite significant heterogeneity in exposure and outcomes measures, overall the evidence suggests that having low SEP increases the risk of developing cardiovascular diseases (CVDs), lung and breast cancer, and type 2 diabetes. SEP is also associated with multiple NCD risk factors such as smoking and physical inactivity. CONCLUSION: Low socioeconomic status appears to have a significant consistent impact on mortality and morbidity caused by NCDs in OECD countries. Social and economic disadvantages are associated with health inequalities in terms of access to care, increased incident risk of NCDs, and early death. These findings point to the need for public health strategies and research to address socioeconomic status disparity among individuals.

Physical restraint in critical care units from the experience of doctors and nursing assistants: In search of an interdisciplinary interpretation. / La contención mecánica en unidades de cuidados críticos desde la experiencia de los médicos y técnicos en cuidados auxiliares de enfermería: buscando una lectura interdisciplinar.

OBJECTIVES: The study aim was to explore the experience of doctors and nursing assistants in the management of physical restraint (PR) in critical care units. METHOD: A multicentre phenomenological study that included 14 critical care units (CCU) in Madrid (Spain). The CCU were stratified according to their use of physical restraint: "frequently used" versus "seldom used". Three focus groups were formed: the first comprised nursing assistants from CCUs that frequently used physical restraint, the second comprised nursing assistants from CCUs that seldom used physical constraint, and the final group comprised doctors from both CCU subtypes. Sampling method: purposive. DATA ANALYSIS: thematic content analysis. Data saturation was achieved. RESULTS: Four principle themes emerged: 1) concept of safety and risk (patient safety versus the safety of the professional), 2) types of restraint, 3) professional responsibilities (prescription, recording, and professional roles) and 4) "zero restraint" paradigm. The conceptualisation regarding the use of physical contentions shows differences in some of the principal themes, depending on the type of CCU, in terms of policies, use and management of physical constraint (frequently used versus seldom used). CONCLUSIONS: The real reduction in the use of physical restraint in CCU must be based on one crucial point: acceptance of the complexity of the phenomenon. The use of physical restraint observed in the different CCU is influenced by individual, group and organisational factors. These factors will determine how doctors and nursing assistants interpret safety and risk, the centre of care (patient or professional-centred care), the concept of restraint, professional responsibilities and interventions, interactions of the team and the leadership.

Isolation of new toluene-tolerant marine strains of bacteria and characterization of their solvent-tolerance properties.

AIMS: To isolate and characterize new marine bacteria capable of tolerating high concentrations of organic solvents, and to understand the toxic effects of these chemicals on marine bacteria. METHODS AND RESULTS: Five marine bacteria able to tolerate 0.1% (v/v) toluene were isolated and characterized on the basis of their growth and survival rates in the presence of different organic solvents. The toluene-tolerant marine bacteria identified in this study could not grow in the presence of 0.1% (v/v) of several organic solvents with a log P(ow) higher than that of the toluene (which in theory should be less toxic than toluene). The mechanisms underlying solvent tolerance were explored. CONCLUSIONS: Isolates of four different genera were identified as toluene-tolerant. Toxicity of a second phase of an organic solvent toward these isolates could not be predicted on the basis of the solvents' log P(ow). SIGNIFICANCE AND IMPACT OF THE STUDY: To improve the biodegradation rate of some water-insoluble compounds, double-phase bioreactors can be used. This type of bioreactor will require strains able to grow in a salt-containing environment and able to tolerate a second phase of an organic solvent.

Right ventricular performance using myocardial deformation imaging in infants with bronchopulmonary dysplasia.

OBJECTIVE: Right ventricular (RV) performance among infants with bronchopulmonary dysplasia (BPD) remains poorly understood. We tested the hypothesis that myocardial deformation imaging (MDI) strain and strain rate would allow for differentiation between infants with severe and milder forms of BPD, independent of tissue Doppler imaging (TDI) and superior to conventional echocardiographic measurements. STUDY DESIGN: Infants with various severities of BPD (11 with none or mild, 13 with moderate and 10 with severe) underwent conventional echocardiography, TDI and MDI assessments at >36 weeks of corrected gestational age. BPD severity grading was determined according to the National Institutes of Child Health and Disease workshop rating scale by physicians blinded to the echocardiogram results. Group data were compared with one-way analysis of variance or Kruskal-Wallis tests, with post hoc multiple comparisons. RESULTS: No differences in traditional echocardiographic parameters or TDI among the three BPD severity groups were observed; none of the infants had evidence of pulmonary hypertension. Using MDI, infants with severe BPD had lower peak global systolic strain than did infants with moderate BPD (P<0.01) or mild/none BPD (P<0.01). Early and late diastolic strain rate measurements were similar across the three groups. CONCLUSIONS: Among infants with severe forms of BPD, evidence of abnormal RV systolic function was detected with MDI, but not traditional echocardiographic or TDI measurements. Infants with severe forms of BPD may represent a particularly high-risk subgroup for decreased RV performance warranting cardiac surveillance. MDI should be considered as a method to quantitate RV function in this population.

A novel mutation in the connexin 46 gene (GJA3) causes autosomal dominant zonular pulverulent cataract in a Hispanic family.

PURPOSE: A five-generation Hispanic pedigree with autosomal dominant zonular pulverulent cataract was studied to identify the causative mutation in connexin 46 (Cx46), a gap junction protein responsible for maintaining lens homeostasis. METHODS: Twenty-six individuals from the family were comprehensively clinically examined. DNA was extracted from their peripheral blood samples. The DNA was used for automated genotyping with fluorescently labeled microsatellite markers and for mutation detection by automated sequencing. RESULTS: A novel D3Y missense mutation in GJA3 segregated with autosomal dominant (AD) zonular pulverulent cataract throughout the family. The mutation was absent in the unaffected individuals in the family and in 230 control chromosomes. CONCLUSIONS: A novel mutation causing AD zonular pulverulent cataract has been identified in a Hispanic Central American family. This is the first report of a mutation in GJA3 causing autosomal dominant congenital cataract (ADCC) in this ethnic group. It is also the first reported cataract-causing mutation in the NH2-terminal region of the Cx46 protein.

Preparedness of pediatric residents for fellowship: a survey of US neonatal-perinatal fellowship program directors.

OBJECTIVE: To evaluate the preparedness of pediatric residents entering accredited neonatal-perinatal medicine (NPM) fellowships in the United States. STUDY DESIGN: A multi-domain, validated survey was distributed to Program Directors (PDs) of US NPM fellowship programs. The 47-item survey explored 5 domains: professionalism, independent practice, psychomotor ability, clinical evaluation, and academia. A systematic, qualitative analysis on free-text comments was also performed. RESULTS: Sixty-one PDs completed the survey, for a response rate of 62% (61/98). For entering fellows, PDs assessed performance in professionalism positively, including 76% as communicating effectively with parents and 90% treating residents/house-staff with respect. In contrast, most PDs rated performance in psychomotor abilities negatively, including 59% and 79% as deficient in bag-and-mask ventilation and neonatal endotracheal intubation, respectively. Although 62% of PDs assessed entering fellows positively for genuine interest in academic projects, fewer than 10% responded positively that entering fellows understood research protocol design, basic statistics, or were capable of writing a cohesive manuscript well. Thematic clustering of qualitative data revealed deficits in psychomotor ability and academia/scholarship. CONCLUSIONS: On the basis of the perspective of front line educators, graduating pediatric residents are underprepared for subspecialty fellowship training in NPM. To provide the best preparation for pediatric graduates who pursue advanced training, changes to residency education to address deficiencies in these important competencies are warranted.

Genome-wide linkage analysis and tumoral characterization reveal heterogeneity in familial colorectal cancer type X.

BACKGROUND: Familial colorectal cancer type X (FCCTX) fulfils clinical criteria defining Lynch syndrome (LS), but is not related to germline mutations in DNA mismatch-repair genes. Its aetiology remains unexplained and there is little evidence of involvement of the common colorectal carcinogenetic pathways. We aimed to identify susceptibility loci and gain insights into carcinogenic pathways involved FCCTX tumour development. METHODS: We performed a linkage analysis in 22 FCCTX families. We also constructed a tissue microarray in order to define an immunohistochemical (IHC) profile for FCCTX tumours (N = 27) by comparing them to three other types of colorectal tumors: LS (N = 18), stable early-onset (N = 31) and other sporadic disease (N = 80). Additionally, we screened for BRAF/KRAS mutations and determined CpG island methylator phenotype (CIMP) status for all FCCTX tumours. RESULTS: We found suggestive evidence of linkage at four chromosomal regions; 2p24.3, 4q13.1, 4q31.21 and 12q21.2-q21.31. We screened genes in 12q21 and ruled out the implication of RASSF9 and NTS, good candidates due to their potential involvement in carcinogenesis and colorectal epithelium development. Based on IHC profiles FCCTX tumours did not form a single, exclusive cluster. They were clearly different from LS, but very similar to stable early onset tumours. The CIMP and chromosomal instability pathways were implicated in one-third and one-quarter of FCCTX cases, respectively. The remaining cases did not have alterations in any known carcinogenic pathways. CONCLUSIONS: Our results highlight the heterogeneity of FCCTX tumours and call into question the utility of using only clinical criteria to identify FCCTX cases.

Experimental infection with a Leptospira hardjo strain isolated from cattle of the eastern plains of Colombia.

The infectivity and pathogenicity of a strain of Leptospira hardjo isolated from the eastern plains of Colombia were evaluated. Ten pregnant heifers were artifically inoculated and monitored during 10 months. During the trial, isolation of leptospires was attempted and antibodies were detected by the microscopic agglutination test. Leptospires were recovered from the urine of six of the inoculated animals up to 6 months after infection. Eight of ten calves born from the inoculated heifers were born weak, and one of them died 12 h after parturition. Three of the weak calves had generalized jaundice of the internal surfaces. Half of the cows developed metritis and had a retained placenta. Serological reactions were seen against serotypes other than L. hardjo. A chronic infection was apparently established in the inoculated heifers with leptospiruria resulting in reinfection of the animals and a secondary rise in antibody levels.

Menopause in normal and uncomplicated NIDDM women: physical and emotional symptoms and hormone profile.

OBJECTIVE: To compare the physical characteristics, emotional symptoms and metabolic conditions of menopausal women with and without non insulin dependent diabetes mellitus (NIDDM). METHODS: We studied 100 menopausal women 45-72 years of age, 51 with and 49 without NIDDM, in a cross-sectional design. Biological characteristics were collected and emotional symptoms were assessed with a modified Hamilton and Bech-Rafaelsen scale, scoring depression, anxiety, non specific symptoms of depression (NSSD) and the empty nest syndrome (ENS). Weight, body mass index (BMI), waist/hip and abdomen/hip ratios and percent of body fat were registered. The sulfoconjugated form of the dehydroepiandrosterone (DHEAS), follicle stimulating hormone (FSH), cortisol and fasting, as well as postprandial insulin/glucose ratios, were measured in blood. RESULTS: Women with NIDDM had earlier mean age for menopause, more central obesity and less peripheral fat; they had also more prevalent emotional symptoms than non diabetic menopausal women. In women with NIDDM, symptoms were associated with years since diagnosis and with BMI. In non diabetic menopausal women schooling and attitudes to sexuality were associated with symptoms. FSH was inversely associated with BMI in both diabetic and non diabetic women; postprandial insulin/glucose ratio was correlated with central obesity in the group without NIDDM and cortisol with sitting systolic blood pressure (SBP) in the group with NIDDM. CONCLUSION: The diagnosis of NIDDM and its metabolic conditions were associated with an increased frequency of some symptoms in menopausal women.

Domestic vectors of Chagas' disease in three rural communities of Nicaragua.

A triatomine survey was conducted in three rural settlements of Nicaragua (Santa Rosa, Quebrada Honda and Poneloya) where Chagas' disease is endemic, to determine rates of house infestation, evaluate the housing condition and to assess the performance of the Maria sensor box in detection of domestic vectors. A total of 184 households were selected and vectors were sought by the methods of timed manual capture and by sensor boxes. The solve vectors species found in this study was Triatoma dimidiata. Of the examined bugs 50, 60 and 33%, in the respective communities, were infected with T. cruzi. The rates of house infestation as determined by manual capture and sensor boxes were respectively, 48.3% and 54.2% in Santa Rosa, 29.8% and 51.2% in Quebrada Honda and in Poneloya 3.8 and 5.9% with significant difference between the methods in Quebrada Honda. When compared with the manual capture, the Maria sensor box detected vectors in 71.4% of positive houses in two of the communities but also was able to detect bugs in 39.3% and 41.1% of houses where manual capture had been negative. Housing condition was evaluated according to three structural parameters, in this way, in the first community 79.2% of houses were classified as bad, 20.8% as regular; in the second one 42.5% were bad and 57.5% regular, whereas in the third 62.5% of the houses were regular. Rates of infestation did not differ greatly between the different housing conditions. Our results show that the sensor box is as efficient as manual capture and could be implemented in our country.

Childhood victimization and violent offending.

The relationship between childhood victimization and violent offending is examined using a prospective cohorts design. Official criminal histories for a large sample of substantiated and validated cases of physical and sexual abuse and neglect (N = 908) from the years 1967 through 1971 were compared to those of a matched control group (N = 667) of individuals with no official record of abuse or neglect. Sex-specific and race-specific effects of childhood victimization and other characteristics of violent offending (chronicity, age of onset, temporal patterns, and continuity) are assessed. Childhood victimization increased overall risk for violet offending and particularly increased risk for males and blacks. In comparison to controls, abused and neglected children began delinquent careers earlier. Temporal patterns of violet offending were examined and childhood victims did not differ in age of arrest for first violent offense, nor were they more likely to continue offending. The findings and their limitations are discussed, as well as directions for future research.

[Percutaneous tracheostomy]. / Traqueostomía percutánea.

Percutaneous tracheostomy using dilatation is a new technique for opening up the trachea whose use has become generalized in intensive care units since this method has numerous advantages over conventional tracheostomy and a lesser number of adverse effects. This article describes a nursing protocol for this technique; it reviews its most frequent complications and it details the nursing care which patients require once they have undergone.

[Antiseptic agents: chlorhexidine]. / Antisépticos. Clorhexidina.

Chlorhexidine is a broad spectrum antiseptic widely used in clinical practice. This antiseptic works rapidly and its effects last for six hours. Since it is not absorbed through the skin nor through mucus, its systematic toxicity is minimum. It keeps on working in contact with organic matter and, since it is transparent, it does not hide the evolution of injuries. In this article, the authors review the properties and indications for this antiseptic; they also comment on some studies having lesser known indications.

Placental transfusion strategies in extremely preterm infants: the next piece of the puzzle.

Evidence is growing on the potential value of enhancing placental-fetal transfusion at birth, with recent endorsement of the practice by the World Health Organization and American College of Gynecologists. However, these recommendations provide clinicians with little guidance on the optimal practice among infants born extremely premature (<28 weeks gestation) and those requiring immediate resuscitation. The goals of this review are to: 1) provide rationale for better outcomes among extremely preterm infants following delayed cord clamping or umbilical cord "milking" than with immediate cord clamping; 2) describe clinical situations that warrant immediate cord clamping following delivery and explore the controversy regarding optimal cord clamping practice among extremely premature infants, including those requiring immediate resuscitation; 3) discuss the quality of evidence in this subgroup of infants; 4) consider areas for future research, with a focus on characterizing if placental-fetal transfusion affects the magnitude or timing of variables associated with physiological transition. The review provided herein suggests that delayed cord clamping or umbilical cord milking can be applied safely to infants born prior to 28 weeks gestation, but the lack of evidence on the best practice among infants born severely depressed and requiring immediate resuscitation, who comprise a greater proportion of infant deliveries at the lowest gestational ages, is recognized. Future studies using well-defined physiologic outcome measures are needed to understand the role of placental transfusion in premature infants' adaptations to extrauterine life.