Suppressors of cytokine signaling 2 and 3 diametrically control macrophage polarization.

Suppressors of cytokine signaling (SOCS) are important regulators of lipopolysaccharide (LPS) and cytokine responses but their role in macrophage polarization is unknown. We have shown here that myeloid-restricted Socs3 deletion (Socs3(Lyz2cre)) resulted in resistance to LPS-induced endotoxic shock, whereas Socs2(-/-) mice were highly susceptible. We observed striking bias toward M2-like macrophages in Socs3(Lyz2cre) mice, whereas the M1-like population was enriched in Socs2(-/-) mice. Adoptive transfer experiments showed that responses to endotoxic shock and polymicrobial sepsis were transferable and macrophage dependent. Critically, this dichotomous response was associated with enhanced regulatory T (Treg) cell recruitment by Socs3(Lyz2cre) cells, whereas Treg cell recruitment was absent in the presence of Socs2(-/-) macrophages. In addition, altered polarization coincided with enhanced interferon-gamma (IFN-γ)-induced signal transducer and activator of transcription-1 (STAT1) activation in Socs2(-/-) macrophages and enhanced interleukin-4 (IL-4) plus IL-13-induced STAT6 phosphorylation in Socs3(Lyz2cre) macrophages. SOCS, therefore, are essential controllers of macrophage polarization, regulating inflammatory responses.

Obtaining Aromatic Extracts from Portuguese Thymus mastichina L. by Hydrodistillation and Supercritical Fluid Extraction with CO2 as Potential Flavouring Additives for Food Applications.

Humans often respond to sensory impulses provided by aromas, and current trends have generated interest in natural sources of fragrances rather than the commonly used synthetic additives. For the first time, the resulting aroma of a selected culture of Thymus mastichina L. was studied as a potential food ingredient. In this context, dried (DR) and fresh (FR) samples were submitted to carbon dioxide (CO2) supercritical extraction (SFE) and hydrodistillation (HD) methods. The extracts were characterised according to their volatile composition by GC-MS, cytotoxicity against a non-tumour cell culture, and sensory attributes (odour threshold and olfactive descriptors). The most abundant aromas were quantified, and the analysis performed by GC-MS revealed an abundance of terpenoids such as thymol chemotype, followed by the precursors α-terpinene and p-cymene. DR and FR extracts (EX) obtained from SFE-CO2 show the highest content of thymol, achieving 52.7% and 72.5% of the isolated volatile fraction. The DR essential oil (EO) contained the highest amount of terpenoids, but it was also the most cytotoxic extract. In contrast, SFE-CO2 products showed the lowest cytotoxic potential. Regarding FR-OE, it had the lowest extraction yield and composition in aroma volatiles. Additionally, all samples were described as having green, fresh and floral sensory notes, with no significant statistical differences regarding the odour detection threshold (ODT) values. Finally, FR-EX of T. mastichina obtained by SFE-CO2 presented the most promising results regarding food application.

Putting the mouth back in the head: HEENT to HEENOT.

Improving oral health is a leading population health goal; however, curricula preparing health professionals have a dearth of oral health content and clinical experiences. We detail an educational and clinical innovation transitioning the traditional head, ears, eyes, nose, and throat (HEENT) examination to the addition of the teeth, gums, mucosa, tongue, and palate examination (HEENOT) for assessment, diagnosis, and treatment of oral-systemic health. Many New York University nursing, dental, and medical faculty and students have been exposed to interprofessional oral health HEENOT classroom, simulation, and clinical experiences. This was associated with increased dental-primary care referrals. This innovation has potential to build interprofessional oral health workforce capacity that addresses a significant public health issue, increases oral health care access, and improves oral-systemic health across the lifespan.

The potential of almonds, hazelnuts, and walnuts SFE-CO2 extracts as sources of bread flavouring ingredients.

Nuts have been part of the human diet since our early ancestors, and their use goes beyond nutritional purposes, for example, as aromatic sources for dairy products. This work explores the potential of almond (Prunus dulcis (Mill.) DA Webb), hazelnut (Corylus avellana L.), and walnut (Juglans regia L.) extracts as sources of food flavouring agents, suggesting a new added-value application for lower quality or excess production fruits. The extracts were obtained by supercritical fluid extraction with carbon dioxide and characterized by: quantification of the volatile fraction by HS-SPME GC-MS; sensory perception and description; and cytotoxicity against Vero cells. All extracts revealed potential as flavouring ingredients due to terpene abundance. No significant differences were observed for the minimal sensory perception, in which the odour threshold values ranged from 8.3 × 10-4 to 6.9 × 10-3 µg·mL-1 for walnuts and almonds extracts, respectively. In contrast, the cytotoxic potential differed significantly among the extracts, and P. dulcis extract presented lower cytotoxicity. Notes as woody, fresh, and green were identified in the volatile intensifiers obtained from the P. dulcis extract. Thus, almond extract was identified as the most promising ingredient to increase the sensory value of food products, namely bread. This potential was verified by an increase in the odour perception of bread after adding 4 µL of extract to each 100 g of bread dough. The quantified eucalyptol and d-limonene terpenes - found in the P. dulcis extract - have improved the release of the pleasant and natural volatile compounds from bread crust and crumb compared to the control bread chemical and sensory profiles.

Improving global virologic surveillance for measles and rubella.

An important aspect of laboratory surveillance for measles and rubella is the genetic characterization of circulating wild-type viruses to support molecular epidemiologic studies and to track transmission pathways. Virologic surveillance that is sufficient to document the interruption of transmission of measles and rubella viruses will be an essential criterion for verification of elimination. Laboratories in the World Health Organization (WHO) Measles and Rubella Laboratory Network have worked to improve and expand virologic surveillance as many regions move toward elimination of measles and rubella/congenital rubella syndrome. As countries approach elimination, it will be necessary to obtain genetic information from as many chains of transmission as possible. In addition, baseline virologic surveillance, especially for rubella, needs to be improved in many countries. This report contains a summary of recent improvements to the methods used for virologic surveillance.

The Effect of the Frequently Used Cinacalcet for pHPT during the COVID-19 Pandemic on Perioperative Decrease in Parathyroid Hormone.

Background: Cinacalcet is a calcimimetic drug that has increasingly been used as a bridging therapy for primary hyperparathyroidism (pHPT), especially during the COVID-19 pandemic. The aim of our study was to investigate if preoperative cinacalcet therapy affects intraoperative parathyroid hormone (IOPTH) monitoring during parathyroidectomy, which is an important indicator for the success of surgery. Methods: In this single-center retrospective analysis, we studied the outcomes of 72 patients who underwent surgery for pHPT. We evaluated two groups: those with cinacalcet therapy before operation­the cinacalcet group (CG)­and those without medical therapy preoperatively (non-CG). In order to perform a between-group comparison of time trends, we fit a linear mixed-effects model with PTH as the response variable and predictors PTH levels preoperatively, group (cinacalcet yes/no), time, the group-by-time interaction, and a random intercept (per subject). Results: Our cohort included 51 (71%) women and 21 (29%) men, who were operated upon for pHPT in the period from January 2018 until August 2021. All patients were diagnosed with pHPT and 54% of the cohort were symptomatic for hypercalcemia. Moreover, 30% of the patients were treated with cinacalcet as a bridging therapy preoperatively, and this increased during the COVID-19 pandemic, as 64% of this group were treated in the last two years. Calcium values were significantly different before (p < 0.001) and after (p = 0.0089) surgery, but calcium level change did not differ significantly between the CG and non-CG. Parathyroid hormone (PTH) levels dropped significantly in both groups during 10 min IOPTH monitoring (p < 0.001), but there was no significant difference between the two groups (p = 0.212). Conclusions: In the examined patient cohort, the use of cinacalcet did not affect the value of IOPTH monitoring during surgery for pHPT.

Chemical and organoleptic properties of bread enriched with Rosmarinus officinalis L.: The potential of natural extracts obtained through green extraction methodologies as food ingredients.

The potential of R. officinalis L. (RO) extracts as a source of aromas was accessed by hydrodistillation (HD) and supercritical fluid extraction using carbon dioxide (SFE-CO2), followed by a series of analysis: quantification by GC-MS, sensory perception and description, and cytotoxicity against Vero cells. The extracts shown abundancy of α-pinene, eucalyptol, S-verbenone and camphor, contributing for the green, fresh, citric, and woody as main sensory notes. The odour threshold (ODT) value (less than 3.0 × 10-3 µg·mL-1) and the cytotoxic potential (ca. 220 µg∙mL-1) defined the concentration range for food application. The most promising extract was added to bread doughs and the final volatile profile was characterised by GC-MS through HS-SPME over time. Among the 34 compounds found, furfural showed an evident contribution in the bread crust aroma, which persisted over four hours of storage, contributing to a pleasant bread fragrance according to the evaluators. This study aims to represent a stepping stone for the use of natural aromas as ingredients for the development of innovative food products.

Revealing new measles virus transmission routes by use of sequence analysis of phosphoprotein and hemagglutinin genes.

With improved measles virus (MV) control, the genetic variability of the MV-nucleoprotein hypervariable region (NP-HVR) decreases. Thus, it becomes increasingly difficult to determine the origin of a virus using only this part of the genome. During outbreaks in Europe and Africa, we found MV strains with identical NP-HVR sequences. However, these strains showed considerable diversity within a larger sequencing window based on concatenated MV phosphoprotein and hemagglutinin genes (P/H pseudogenes). In Belarus, Germany, Russia, and the Democratic Republic of Congo, the P/H pseudogenes provided insights into chains of transmission, whereas identical NP-HVR provided none. In Russia, for instance, the P/H pseudogene identified temporal clusters rather than geographical clusters, demonstrating the circulation and importation of independent variants rather than large local outbreaks lasting for several years, as suggested by NP-HVR. Thus, by extending the sequencing window for molecular epidemiology, a more refined picture of MV circulation was obtained with more clearly defined links between outbreaks and transmission chains. Our results also suggested that in contrast to the P gene, the H gene acquired fixed substitutions that continued to be found in subsequent outbreaks, possibly with consequences for its antigenicity. Thus, a longer sequencing window has true benefits both for the epidemiological surveillance of measles and for the better monitoring of viral evolution.

Partnering to Support Education for Midwives and Nurses in Liberia.

The midwifery and occupational health faculty of a U.S. university were approached by parish and health care leaders from Caldwell, Liberia, for assistance in addressing critical maternal health care needs in their community. Liberia has suffered setbacks in its efforts to improve health care for its people due to recent civil wars and the Ebola epidemic of 2014 to 2016. Initial discussions among international groups centered around realistic ways to help in the face of multiple compelling needs. Grant support for U.S. faculty to conduct exploratory meetings and educational workshops in Liberia was secured. Ethical principles and best practices in partnering across borders guided this partnership and include reciprocity, equity, and empowerment of health care workers, including nurses, midwives, community workers, and health center staff. Here, we describe the preparation for and implementation of these workshops, as well as plans for continuing collaborations that emerged from these workshops.

Improving the Mechanical Strength of Dental Applications and Lattice Structures SLM Processed.

To manufacture custom medical parts or scaffolds with reduced defects and high mechanical characteristics, new research on optimizing the selective laser melting (SLM) parameters are needed. In this work, a biocompatible powder, 316L stainless steel, is characterized to understand the particle size, distribution, shape and flowability. Examination revealed that the 316L particles are smooth, nearly spherical, their mean diameter is 39.09 µm and just 10% of them hold a diameter less than 21.18 µm. SLM parameters under consideration include laser power up to 200 W, 250-1500 mm/s scanning speed, 80 µm hatch spacing, 35 µm layer thickness and a preheated platform. The effect of these on processability is evaluated. More than 100 samples are SLM-manufactured with different process parameters. The tensile results show that is possible to raise the ultimate tensile strength up to 840 MPa, adapting the SLM parameters for a stable processability, avoiding the technological defects caused by residual stress. Correlating with other recent studies on SLM technology, the tensile strength is 20% improved. To validate the SLM parameters and conditions established, complex bioengineering applications such as dental bridges and macro-porous grafts are SLM-processed, demonstrating the potential to manufacture medical products with increased mechanical resistance made of 316L.

Integrating Oral Health Curricula into Midwifery Graduate Programs: Results of a US Survey.

INTRODUCTION: Midwives are a significant segment of the US maternal and primary health care workforce and play a pivotal role in addressing women's oral health care needs during pregnancy and throughout their life span. The purpose of this research was to assess oral health curricular integration in midwifery programs and examine factors that influence integration and satisfaction with graduates' level of oral health competence. METHODS: A cross-sectional, national survey of midwifery programs was conducted using an electronically distributed 19-item, self-administered questionnaire completed by the Directors of Midwifery Education. Data analysis included univariate and bivariate statistics. RESULTS: All of the responding midwifery programs (N = 33) were educating their graduates about oral health; however, less than a quarter (22.6%) of program directors were satisfied with their graduates' competency. Significant factors promoting integration were routine teaching by a dental professional and a formal relationship with a dental school, dental residency, or dental hygiene program. Programs with 4 or more hours of oral health curriculum were more likely to have a faculty oral health champion, use simulation in evaluation of their learners, and include interprofessional oral health education. DISCUSSION: With adequate oral health education, midwives are ideally positioned to integrate oral health in pregnancy care as well as well woman care throughout the life span, thereby expanding access to oral health care.

Matrix metalloproteinase-9 promotes neutrophil and T cell recruitment and migration in the postischemic liver.

Matrix metalloproteinases-2 and -9 (MMP-2/9) are critically involved in degradation of extracellular matrix, and their inhibition is discussed as a promising strategy against hepatic ischemia-reperfusion (I/R) injury. Here, we analyzed the role of MMP-2 and -9 for leukocyte migration and tissue injury in sham-operated mice and in mice after I/R, treated with a MMP-2/9 inhibitor or vehicle. Using zymography, we show that the MMP-2/9 inhibitor abolished I/R-induced MMP-9 activation, whereas MMP-2 activity was not detectable in all groups. As demonstrated by intravital microscopy, MMP-9 inhibition attenuated postischemic rolling and adherence of total leukocytes in hepatic postsinusoidal venules, CD4+ T cell accumulation in sinusoids, and neutrophil transmigration. These effects were associated with reduction of plasma tumor necrosis factor alpha (TNF-alpha) levels and endothelial expression of CD62P. Motility of interstitially migrating leukocytes was assessed by near-infrared reflected light oblique transillumination microscopy in the postischemic cremaster muscle. Upon MMP-9 blockade, leukocyte migration velocity and curve-line and straight-line migration distances were reduced significantly as compared with the vehicle-treated I/R group. Postischemic sinusoidal perfusion failure, hepatocellular apoptosis, and alanine aminotransferase activity were only slightly reduced after MMP-9 inhibition, whereas aspartate aminotransferase activity and mortality were significantly lower. In conclusion, MMP-9 is involved in the early recruitment cascades of neutrophils and CD4+ T cells, promotes neutrophil and T cell transmigration during hepatic I/R, and is required for motility of interstitially migrating leukocytes. MMP-9 blockade is associated with an attenuation of TNF-alpha release and endothelial CD62P expression, weakly protects from early microvascular/hepatocellular I/R damage, but improves postischemic survival.

A Literature Review on Women's Oral Health Across the Life Span.

The importance of women's oral health and its association with overall systemic health cannot be overemphasized. Poor oral health can have several detrimental effects on a woman's health across her life span. This article reviews the literature and describes how nurses, nurse practitioners, and nurse-midwives can incorporate oral cavity examinations into their care of women.

Oral Health in Pregnancy.

Oral health is crucial to overall health. Because of normal physiologic changes, pregnancy is a time of particular vulnerability in terms of oral health. Pregnant women and their providers need more knowledge about the many changes that occur in the oral cavity during pregnancy. In this article we describe the importance of the recognition, prevention, and treatment of oral health problems in pregnant women. We offer educational strategies that integrate interprofessional oral health competencies.

Incorporating a primary care practicum in midwifery education.

INTRODUCTION: There is a shortage of primary care providers in the United States. As more individuals obtain health insurance coverage with the Patient Protection and Affordable Care Act, the number seeking care will increase dramatically. Both the Institute of Medicine and the American College of Nurse-Midwives state that certified nurse-midwives and certified midwives should function at their full scope of practice, which includes primary care services as delineated by the Core Competencies for Basic Midwifery Practice. Nonetheless, the percentage of midwives who self-identify as primary care providers is decreasing. Dedicated primary care educational experiences may increase student confidence and encourage the incorporation of primary care into midwifery practice after graduation. METHODS: Midwifery students in 2 cohorts completed questionnaires before and after a dedicated primary care practicum to study changes in the perceived level of confidence in primary care provision. The students in cohort A participated in 45 hours of primary care clinical time, whereas the students in cohort B participated in 88 hours of primary care clinical time. Postclinical focus groups provided qualitative data on student perceptions and attitudes about the clinical experience. Student responses were coded by cohort and analyzed using qualitative descriptive analysis. RESULTS: Seventeen midwifery students from 2 cohorts completed questionnaires. Students in both cohorts reported increased perceived confidence in almost all primary care domains. DISCUSSION: Participation in a dedicated primary care clinical rotation increased student-perceived confidence in primary care practice. The inclusion of designated primary care clinical education in nurse-midwifery education may contribute to meeting the national need for primary care providers. This article is part of a special series of articles that address midwifery innovations in clinical practice, education, interprofessional collaboration, health policy, and global health.

Proteome profiling of virus-host interactions of wild type and attenuated measles virus strains.

Quantitative gel-based proteomics (2D DIGE coupled to MALDI-TOF/TOF MS) has been used to investigate the effects of different measles virus (MV) strains on the host cell proteome. A549/hSLAM cells were infected either with wild type MV strains, an attenuated vaccine or a multiple passaged Vero cell adapted strain. By including interferon beta treatment as a control it was possible to distinguish between the classical antiviral response and changes induced specifically by the different strains. Of 38 differentially expressed proteins in total (p-value ≤0.05, fold change ≥2), 18 proteins were uniquely modulated following MV infection with up to 9 proteins specific per individual strain. Interestingly, wt strains displayed distinct protein patterns particularly during the late phase of infection. Proteins were grouped into cytoskeleton, metabolism, transcription/translation, immune response and mitochondrial proteins. Bioinformatics analysis revealed mostly changes in proteins regulating cell death and apoptosis. Surprisingly, wt strains affected the cytokeratin system much stronger than the vaccine strain. To our knowledge, this is the first study on the MV-host proteome addressing interstrain differences. BIOLOGICAL SIGNIFICANCE: In the present study we investigated the host cell proteome upon measles virus (MV) infection. The novelty about this study is the side-by side comparison of different strains from the same virus, which has not been done at the proteome level for any other virus including MV. We used different virus strains including a vaccine strain, wild type isolates derived from MV-infected patients as well as a Vero cell adapted strain, which serves as an intermediate between vaccine and wild type strain. We observed differences between vaccine and wild type strains as well as common features between different wild type strains. Perhaps one of the most surprising findings was that differences did not only occur between wild type and vaccine or Vero cell adapted strains but also between different wild type strains. In fact our study suggests that besides the cytokeratin and the IFN system wild type viruses seem to differ as much among each other than from vaccine strains. Thus our results are suggestive of complex and diverse virus-host interactions which differ considerably between different wild type strains. Our data indicate that interstrain differences are prominent and have so far been neglected by proteomics studies.

Mammary hypoplasia: not every breast can produce sufficient milk.

Breast milk is considered the optimal form of nutrition for newborn infants. Current recommendations are to breastfeed for 6 months. Not all women are able to breastfeed. Mammary hypoplasia is a primary cause of failed lactogenesis II, whereby the mother is unable to produce an adequate milk volume. Women with mammary hypoplasia often have normal hormone levels and innervation but lack sufficient glandular tissue to produce an adequate milk supply to sustain their infant. The etiology of this rare condition is unclear, although there are theories that refer to genetic predisposition and estrogenic environmental exposures in select agricultural environments. Women with mammary hypoplasia may not exhibit the typical breast changes associated with pregnancy and may fail to lactate postpartum. Breasts of women with mammary hypoplasia may be widely spaced (1.5 inches or greater), asymmetric, or tuberous in nature. Awareness of the history and clinical signs of mammary hypoplasia during the prenatal period and immediate postpartum increases the likelihood that women will receive the needed education and physical and emotional support and encouragement. Several medications and herbs demonstrate some efficacy in increasing breast milk production in women with mammary hypoplasia.

Interplay of measles virus with early induced cytokines reveals different wild type phenotypes.

Differential effects of measles virus (MV) on the innate immune response may influence virus spread and severity of disease. Using a representative panel of 22 MV strains including 14 different genotypes, we found that wild-type (wt) differ considerably in their sensitivity to type I interferon (IFN). The wt virus production was 2-47-fold lower in IFN-alpha treated Vero/hSLAM cells, whereas vaccine virus production was reduced only 2-3-fold. Sequence analysis of the MV-P/C/V gene, revealed no obvious amino acid mutations that correlated with the different phenotypes. Strains also widely differed in their ability to induce type I IFN, tumor necrosis factor (TNF) alpha and other cytokines in human A549/hSLAM cells. Some wt strains that were highly sensitive to type I IFN induced only low levels of these and other cytokines. In vitro wt strains that produced the 5' copy-back defective interfering RNAs (5'cb-diRNA) characterized by Shingai et al. (2007), induced high levels of cytokines that otherwise were only reached by vaccine strains. These 5'cb-diRNAs emerged only in virus cultures during multiple passaging and were not detectable in clinical samples of measles patients. These subgenomic RNAs are an important confounding parameter in passaged wt viruses which must be carefully assessed in all in vitro studies. The present data show that MV wt strains differ in their sensitivity and their ability to temper with the innate immune response, which may result in differences in virulence.