Comparison of Levels of Nasal, Salivary, and Plasma Antibody to Severe Acute Respiratory Syndrome Coronavirus 2 During Natural Infection and After Vaccination.

BACKGROUND: Most studies of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) measure antibody or cellular responses in blood; however, the virus infects mucosal surfaces in the nose and conjunctivae and infectious virus is rarely if ever present in the blood. METHODS: We used luciferase immunoprecipitation assays to measure SARS-CoV-2 antibody levels in the plasma, nose, and saliva of infected persons and vaccine recipients. These assays measure antibody that can precipitate the SAR-CoV-2 spike and nucleocapsid proteins. RESULTS: Levels of plasma anti-spike antibody declined less rapidly than levels of anti-nucleocapsid antibody in infected persons. SARS-CoV-2 anti-spike antibody levels in the nose declined more rapidly than antibody levels in the blood after vaccination of infected persons. Vaccination of previously infected persons boosted anti-spike antibody in plasma more than in the nose or saliva. Nasal and saliva anti-spike antibody levels were significantly correlated with plasma antibody in infected persons who had not been vaccinated and after vaccination of uninfected persons. CONCLUSIONS: Persistently elevated SARS-CoV-2 antibody in plasma may not indicate persistence of antibody at mucosal sites such as the nose. The strong correlation of SARS-CoV-2 antibody in the nose and saliva with that in the blood suggests that mucosal antibodies are derived primarily from transudation from the blood rather than local production. While SARS-CoV-2 vaccine given peripherally boosted mucosal immune responses in infected persons, the increase in antibody titers was higher in plasma than at mucosal sites. Taken together, these observations indicate the need for development of mucosal vaccines to induce potent immune responses at sites where SARS-CoV-2 infection occurs. CLINICAL TRIALS REGISTRATION: NCT01306084.

Effect of Presenting Survival Information as Text or Pictograph During Periviable Birth Counseling: A Randomized, Controlled Trial.

OBJECTIVES: To examine whether presenting a 30% or a 60% chance of survival in different survival information formats would influence hypothetical periviable birth treatment choice and whether treatment choice would be associated with participants' recall or their intuitive beliefs about the chances of survival. STUDY DESIGN: An internet sample of women (n = 1052) were randomized to view a vignette with either a 30% or 60% chance of survival with intensive care during the periviable period. Participants were randomized to survival information presented as text-only, in a static pictograph, or in an iterative pictograph. Participants chose intensive care or palliative care and reported their recall of the chance of survival and their intuitive beliefs about their infant's chance of survival. RESULTS: There was no difference in treatment choice by presentation with a 30% vs 60% chance of survival (P = .48), by survival information format (P = .80), or their interaction (P = .18). However, participants' intuitive beliefs about chance of survival significantly predicted treatment choice (P < .001) and had the most explanatory power of any participant characteristic. Intuitive beliefs were optimistic and did not differ by presentation of a 30% or 60% chance of survival (P = .65), even among those with accurate recall of the chance of survival (P = .09). CONCLUSIONS: Physicians should recognize that parents may use more than outcome data to make treatment choices and in forming their own, often-optimistic, intuitive beliefs about their infant's chance of survival. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04859114.

Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines.

Vaccinations are effective in preventing infections; however, it is unknown if patients with chronic lymphocytic leukemia (CLL) who are treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitors (BTKi's) respond to novel adjuvanted vaccines. Understanding the effect of BTKi's on humoral immunity is timely because BTKi's are widely used and vaccination against coronavirus disease 2019 is urgently needed. In 2 open-label, single-arm clinical trials, we measured the effect of BTKi's on de novo immune response against recombinant hepatitis B vaccine (HepB-CpG) and recall response against recombinant zoster vaccine (RZV) in CLL patients who were TN or on BTKi. The primary end point was serologic response to HepB-CpG (anti-hepatitis B surface antibodies ≥10 mIU/mL) and RZV (≥fourfold increase in anti-glycoprotein E). The response rate to HepB-CpG was lower in patients on BTKi (3.8%; 95% confidence interval [CI], 0.7-18.9) than patients who were TN (28.1%; 95% CI, 15.6-45.4; P = .017). In contrast, the response rate to RZV did not differ significantly between the BTKi (41.5%; 95% CI, 27.8-56.6) and TN cohorts (59.1%; 95% CI, 38.7-76.7; P = .2). BTKi's were associated with a decreased de novo immune response following HepB-CpG, whereas recall immune response following RZV was not significantly affected by BTKi therapy. These trials were registered at www.clinicaltrials.gov as #NCT03685708 (Hep-CpG) and #NCT03702231 (RZV).

Uric acid and diabetes mellitus: an update.

The relationship between diabetes mellitus (DM) and high serum uric acid is complex and controversial. Many epidemiological studies have reported a positive association, whereas others have reported an inverse association or none. In the pathogenesis of DM it is the intracellular urate that is more important than the extracellular and dissociation between the two is possible. Evidence suggests that high serum uric acid induces insulin resistance and beta cell failure in animal models. Reduction of intracellular uric acid can be achieved by dietary measures such as reducing fructose and salt intake, and uric acid-lowering drugs. We suggest that in the Western diet, these elements play a crucial role in pathogenesis of DM. To determine the precise and exact interrelationship between intracellular and extracellular uric acid, well-designed studies are required. Besides this, clinical trials are needed to determine whether intracellular and extracellular urate reduction will provide benefit in prevention and treatment of DM and complications associated with it.

Nectin-1 Is an Entry Mediator for Varicella-Zoster Virus Infection of Human Neurons.

Varicella-zoster virus (VZV) maintains lifelong latency in neurons following initial infection and can subsequently be reactivated to result in herpes zoster or severe neurological manifestations such as encephalitis. Mechanisms of VZV neuropathogenesis have been challenging to study due to the strict human tropism of the virus. Although neuronal entry mediators of other herpesviruses, including herpes simplex virus, have been identified, little is known regarding how VZV enters neurons. Here, we utilize a human stem cell-based neuronal model to characterize cellular factors that mediate entry. Through transcriptional profiling of infected cells, we identify the cell adhesion molecule nectin-1 as a candidate mediator of VZV entry. Nectin-1 is highly expressed in the cell bodies and axons of neurons. Either knockdown of endogenous nectin-1 or incubation with soluble forms of nectin-1 produced in mammalian cells results in a marked decrease in infectivity of neurons. Notably, while addition of soluble nectin-1 during viral infection inhibits infectivity, addition after infection has no effect on infectivity. Ectopic expression of human nectin-1 in a cell line resistant to productive VZV infection confers susceptibility to infection. In summary, we have identified nectin-1 as a neuronal entry mediator of VZV. IMPORTANCE Varicella-zoster virus (VZV) causes chickenpox, gains access to neurons during primary infection where it resides lifelong, and can later be reactivated. Reactivation is associated with shingles and postherpetic neuralgia, as well as with severe neurologic complications, including vasculitis and encephalitis. Although the varicella vaccine substantially decreases morbidity and mortality associated with primary infection, the vaccine cannot prevent the development of neuronal latency, and vaccinated populations are still at risk for reactivation. Furthermore, immunocompromised individuals are at higher risk for VZV reactivation and associated complications. Little is known regarding how VZV enters neurons. Here, we identify nectin-1 as an entry mediator of VZV in human neurons. Identification of nectin-1 as a neuronal VZV entry mediator could lead to improved treatments and preventative measures to reduce VZV related morbidity and mortality.

Differential Overlap in Human and Animal Fecal Microbiomes and Resistomes in Rural versus Urban Bangladesh.

Low- and middle-income countries (LMICs) bear the largest mortality burden of antibiotic-resistant infections. Small-scale animal production and free-roaming domestic animals are common in many LMICs, yet data on zoonotic exchange of gut bacteria and antibiotic resistance genes (ARGs) in low-income communities are sparse. Differences between rural and urban communities with regard to population density, antibiotic use, and cohabitation with animals likely influence the frequency of transmission of gut bacterial communities and ARGs between humans and animals. Here, we determined the similarity in gut microbiomes, using 16S rRNA gene amplicon sequencing, and resistomes, using long-read metagenomics, between humans, chickens, and goats in a rural community compared to an urban community in Bangladesh. Gut microbiomes were more similar between humans and chickens in the rural (where cohabitation is more common) than the urban community, but there was no difference for humans and goats in the rural versus the urban community. Human and goat resistomes were more similar in the urban community, and ARG abundance was higher in urban animals than rural animals. We identified substantial overlap of ARG alleles in humans and animals in both settings. Humans and chickens had more overlapping ARG alleles than humans and goats. All fecal hosts from the urban community and rural humans carried ARGs on chromosomal contigs classified as potentially pathogenic bacteria, including Escherichia coli, Campylobacter jejuni, Clostridioides difficile, and Klebsiella pneumoniae. These findings provide insight into the breadth of ARGs circulating within human and animal populations in a rural compared to urban community in Bangladesh. IMPORTANCE While the development of antibiotic resistance in animal gut microbiomes and subsequent transmission to humans has been demonstrated in intensive farming environments and high-income countries, evidence of zoonotic exchange of antibiotic resistance in LMIC communities is lacking. This research provides genomic evidence of overlap of antibiotic resistance genes between humans and animals, especially in urban communities, and highlights chickens as important reservoirs of antibiotic resistance. Chicken and human gut microbiomes were more similar in rural Bangladesh, where cohabitation is more common. Incorporation of long-read metagenomics enabled characterization of bacterial hosts of resistance genes, which has not been possible in previous culture-independent studies using only short-read sequencing. These findings highlight the importance of developing strategies for combatting antibiotic resistance that account for chickens being reservoirs of ARGs in community environments, especially in urban areas.

Evaluation of metabolic and oxidative profile in ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of disease.

This study was conducted on ewes with pregnancy toxemia (PT) with an attempt to evaluate metabolic and oxidative profile in subclinical and clinical ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of the disease. A total of 20 ewes having beta-hydroxy butyric acid (ß-HBA) > 2.5 mmol/L and proven clinical sings of PT, categorized as clinical PT (CPT); 12 ewes having ß-HBA 0.8-2.5 mmol/L and no clinical signs of PT, categorized at subclinical PT (SPT); and 10 ewes having ß-HBA ≤ 0.8 mmol/L, categorized as healthy control (CON) were enrolled. Among 20 CPT ewes, 11 had negative outcomes (non-survivors), six ewes had positive outcomes (survivors), and three were lost during follow-up. A significant increase in non-esterified fatty acid, ß-HBA, triglycerides, gamma-glutamyl transferase, lactate dehydrogenase, and malondialdehyde levels and a significant decrease in fructosamine were observed in CPT and SPT compared to CON. A significant increase in cholesterol, aspartate amino transferase, and creatinine kinase and a significant decrease in albumin, potassium, calcium, superoxide dismutase, and catalase were observed in CPT only. Glucose was significantly decreased in SPT only. The highest area under the curve (AUC) was observed for fructosamine (89.7% and 87.5% for CPT and SPT, respectively) with the optimum cutoff point calculated on the basis of maximum sensitivity (SE) and specificity (SP) being 0.607 mmol/L (SE: 89.3% and SP: 72.2%) and 1.005 mmol/L (SE: 90.0% and SP: 75.3%) for CPT and SPT, respectively. At the cutoff limit of 0.607 mmol/L and 1.005 mmol/L, the odds ratio was 10.8 and 8.0 for CPT and SPT, respectively. A significant decrease in fructosamine and potassium and a significant increase in creatinine, lactate dehydrogenase, and malondialdehyde were observed in non-survivors compared to survivors. It was thus concluded that fructosamine was the best diagnostic indicator of both CPT and SPT followed by non-esterified fatty acid. Fructosamine, creatinine, potassium, lactate dehydrogenase, and malondialdehyde were the best prognostic indicators of PT.

Serum and Cervicovaginal Fluid Antibody Profiling in Herpes Simplex Virus-Seronegative Recipients of the HSV529 Vaccine.

Previous herpes simplex virus type 2 (HSV-2) vaccines have not prevented genital herpes. Concerns have been raised about the choice of antigen, the type of antibody induced by the vaccine, and whether antibody is present in the genital tract where infection occurs. We reported results of a trial of an HSV-2 replication-defective vaccine, HSV529, that induced serum neutralizing antibody responses in 78% of HSV-1-/HSV-2- vaccine recipients. Here we show that HSV-1-/HSV-2- vaccine recipients developed antibodies to epitopes of several viral proteins; however, fewer antibody epitopes were detected in vaccine recipients compared with naturally infected persons. HSV529 induced antibodies that mediated HSV-2-specific natural killer (NK) cell activation. Depletion of glycoprotein D (gD)-binding antibody from sera reduced neutralizing titers by 62% and NK cell activation by 81%. HSV-2 gD antibody was detected in cervicovaginal fluid at about one-third the level of that in serum. A vaccine that induces potent serum antibodies transported to the genital tract might reduce HSV genital infection.

Information Order for Periviable Counseling: Does It Make a Difference?

OBJECTIVES: To examine whether the order of presenting survival vs disability information, with or without the description of infant neonatal intensive care unit (NICU) experiences would influence treatment choice during hypothetical periviable birth counseling. STUDY DESIGN: An internet sample of childbearing-aged women (n = 839) viewed a pictograph displaying the chances of survival and a pictograph on the chances of disability for a baby resuscitated during the periviable period. The sample was randomized to the order of pictographs and level of description of infant NICU experiences. Participants selected between intensive care or comfort care and reported their personal values. RESULTS: The order of the information influenced treatment choices (P = .02); participants were more likely to choose intensive care if they saw the survival pictograph first (70%) than the disability pictograph first (62%). Level of description of premature infant NICU experiences did not influence treatment choice (P = .92). Participants who valued sanctity of life, autonomy in making decisions, who were more religious, and had adequate health literacy were more likely to choose intensive care. Such participant characteristics had greater explanatory power than the experimental manipulations. CONCLUSIONS: Subtle differences in how information is presented may influence critical decisions. However, even among women with the same values, diversity in treatment choice remains.

Anomalous nucleation of crystals within amorphous germanium nanowires during thermal annealing.

In this work, germanium nanowires rendered fully amorphous via xenon ion irradiation have been annealed within a transmission electron microscope to induce crystallization. During annealing crystallites appeared in some nanowires whilst others remained fully amorphous. Remarkably, even when nucleation occurred, large sections of the nanowires remained amorphous even though the few crystallites embedded in the amorphous phase were formed at a minimum of 200 °C above the temperature for epitaxial growth and 100 °C above the temperature for random nucleation and growth in bulk germanium. Furthermore, the presence of crystallites was observed to depend on the diameter of the nanowire. Indeed, the formation of crystallites occurred at a higher annealing temperature in thin nanowires compared with thicker ones. Additionally, nanowires with a diameter above 55 nm were made entirely crystalline when the annealing was performed at the temperature normally required for crystallization in germanium (i.e. 500 °C). It is proposed that oxygen atoms hinder both the formation and the growth of crystallites. Furthermore, as crystallites must reach a minimum size to survive and grow within the amorphous nanowires, the instability of crystallites may also play a limited role for the thinnest nanowires.

Comparative analysis of prognostic histopathologic parameters in subtypes of epithelioid pleural mesothelioma.

AIMS: Malignant pleural mesothelioma (MPM) is a rare malignancy with a dismal prognosis. While the epithelioid type is associated with a more favourable outcome, additional factors are needed to further stratify prognosis and to identify patients who can benefit from multimodal treatment. As epithelioid MPM shows remarkable morphological variability, the prognostic role of the five defined morphologies, the impact of the nuclear grading system and the mitosis-necrosis score were investigated in this study. METHODS AND RESULTS: Tumour specimens of 192 patients with epithelioid MPM from five European centres were histologically subtyped. Nuclear grading and mitosis-necrosis score were determined and correlated with clinicopathological parameters and overall survival (OS). Digital slides of 55 independent cases from The Cancer Genome Atlas (TCGA) database were evaluated for external validation. Histological subtypes were collapsed into three groups based on their overlapping survival curves. The tubulopapillary/microcystic group had a significantly longer OS than the solid/trabecular group (732 days versus 397 days, P = 0.0013). Pleomorphic tumours had the shortest OS (173 days). The solid/trabecular variants showed a significant association with high nuclear grade and mitosis-necrosis score. The mitosis-necrosis score was a robust and independent prognostic factor in our patient cohort. The prognostic significance of all three parameters was externally validated in the TCGA cohort. Patients with tubulopapillary or microcystic tumours showed a greater improvement in OS after receiving multimodal therapy than those with solid or trabecular tumours. CONCLUSIONS: Histological subtypes of epithelioid MPM have a prognostic impact, and might help to select patients for intensive multimodal treatment approaches.

Population structure of Venturia inaequalis, a hemibiotrophic fungus, under different host resistance specificities in the Kashmir valley.

Venturia inaequalis is a notorious fungal pathogen and show classical gene for gene interaction with its apple host. Neutral markers provide clues about history, evolutionary potential, genetic diversity and population structure of V. inaequalis. The genetic diversity and population structure of fungus indicates that the pathogen is highly diverse with the capacity to breach the scab resistance genes. In the present study, we collected 108 V. inaequalis isolates from three apple cultivars differing in Rvi1 resistance gene. Based on the AMOVA, the variation was mostly distributed among the isolates, providing evidence of non-existence of subpopulation in orchards thus founder population is difficult to arise in Kashmir apple orchards. Pair wise genetic differentiation is less due to regular occurrence of gene flow between the populations residing on different orchard as infected material is transported without stringent quarantine measures. Based on principal coordinate analysis and clustering algorithm as implemented in STRUCTURE, we observed admixture between the two subpopulations, which is quite low, suggesting the existence of pre-zygotic and post-zygotic barriers to gene flow and we cannot rule out the existence of other structures shared by accessions belonging to different varieties. Due to the continuous increase in introduction and monoculture of apple varieties, mixed orchard with different host resistance specificities are more suitable for managing the apple scab in Kashmir valley.

Notions of Preprocedural Patient Anxiety in the Realm of IR.

PURPOSE: To determine the views and current practice preferences of interventional radiologists and allied healthcare providers regarding management of preprocedural anxiety. MATERIALS AND METHODS: From March to April 2018, members of the Society of Interventional Radiology were surveyed regarding their opinions in the assessment and management of patient anxiety. Degree of responsibility for the management of anxiety was also queried through the use of a scale (1 = no responsibility; 2 = some responsibility; 3 = major responsibility). RESULTS: Of 1163 respondents (23.8% response rate), most described preprocedural anxiety as somewhat to very important in their practice (n = 961, 82.6%), somewhat to very important to the patients (n = 1087, 93.5%), and at least sometimes interfering with delivery of care (n = 815, 70.1%). Most respondents did not measure preprocedural anxiety directly (n = 953, 81.9%), but would address it if raised by the patient (n = 911, 82.9%). Patient education (n = 921, 79.1%), medications (n = 801, 68.8%), and therapeutic or empathetic interactions (n = 665, 56.4%) were most preferred to manage anxiety. Radiologists, nurses, patients, primary care providers, family members, and psychologists or psychiatrists were all allocated responsibility to reduce anxiety. CONCLUSIONS: Interventional radiologists and other providers are aware of the importance of preprocedural anxiety. Despite the notion that most radiologists did not address anxiety directly, most indicated a willingness to discuss the issue if raised by patients. Patient education, medications, and several other techniques are preferred to manage preprocedural anxiety. Responsibility to reduce anxiety is perceived to be shared among radiologists, nurses, patients, family members, and other health care providers.

Effect of aluminium concentration on phase formation and radiation stability of Cr2Al x C thin film.

Near-stoichiometric and under-stoichiometric Cr2Al x C (x = 0.9 and 0.75) amorphous compositions were deposited onto a silicon substrate at 330 K in a layer-by-layer fashion using magnetron sputtering from elemental targets. The film thickness was found to be 0.9 µm and 1.2 µm for the near- and under-stoichiometric compositions respectively. A transmission electron microscope (TEM) heating holder was used to heat thin sample lamellae prepared using focused ion beam milling. Near-stoichiometric Cr2AlC thin films consisted of nano MAX phase after crystallization at 873 K. Under-stoichiometric Cr2Al x C (x = 0.75) thin films contained MAX phase along with nanocrystalline chromium aluminides after crystallization at 973 K. Irradiations with 320 keV xenon ions was performed at 623 K using a TEM with an in-situ ion irradiation (MIAMI) facility. Nanocrystalline films of near-stoichiometric Cr2AlC irradiated up to 83 displacements per atom (dpa) showed no observable changes. Also, irradiation of under-stoichiometric nanocrystalline thin films up to 138 dpa did not show any observable amorphization, and recrystallization was observed. This radiation resistance of near- and under-stoichiometric thin films is attributed to the known self-healing property of Cr2Al x C compositions further enhanced by nanocrystallinity.

Weighted dimensionality reduction and robust Gaussian mixture model based cancer patient subtyping from gene expression data.

BACKGROUND: The heterogeneous nature of cancer necessitates subtyping of cancer patients into distinct and well separated subgroups. However, computational issues arise because gene expression data is noisy and contains outliers apart from being high dimensional. As such, an attempt to subtype cancer patients from gene expression data leads to highly overlapping Kaplan-Meier (KM) survival plots and thus clear distinction among the discovered subtypes becomes difficult. Here we attempt to achieve a greater separation among the subtypes through a robust clustering pipeline. METHODS: We propose a robust framework to achieve a better separation among the discovered subtypes. Our framework is based on dimensionality reduction of a weighted gene expression matrix using t-distributed Stochastic Neighbor Embedding (t-SNE) and a robust Gaussian mixture model based clustering approach. Every gene is weighted according to the median absolute deviation (MAD) of the gene before dimensionality reduction. The results are quantified by measuring the minimum pairwise separation among the KM plots and minimum hazard ratio among the subtypes. We also introduce a novel method, called cumulative survival separation, to quantify the separation among the discovered subtypes. RESULTS: To validate the proposed methodology we obtained five cancer gene expression datasets from The Cancer Genome Atlas (TCGA) and comparisons with Consensus Clustering (CC), Consensus non-negative matrix factorization (CNMF), fast density-aware spectral clustering (Spectrum) and Neighborhood based Multi-Omics clustering (NEMO) methodologies show that the proposed method is able to achieve a greater separation compared to the aforementioned methods in literature. For instance, the minimum pairwise life expectancy difference (in days) between the discovered subtypes for GBM is 61 days for the proposed methodology with MAD scores, whereas it is approximately 33, 19, 49 and 33 days only for CC, Spectrum, Nemo and CNMF respectively. Comparisons are also shown for the proposed framework with and without using the MAD scores and it is observed that MAD score significantly improves the subtype separation. Hazard ratio analysis also shows that the proposed methodology performs better. Furthermore, pathway over-representation analyses were carried to identify relevant genetic pathways which can be possible targets for treatment. CONCLUSION: The results suggest that the use of median absolute deviation and a robust clustering methodology are helpful in achieving greater separation among the subtypes with better statistical and clinical significance.

A topological approach for cancer subtyping from gene expression data.

BACKGROUND: Gene expression data contains key information which can be used for subtyping cancer patients. However, computational methods suffer from 'curse of dimensionality' due to very high dimensionality of omics data and therefore are not able to clearly distinguish between the discovered subtypes in terms of separation of survival plots. METHODS: To address this we propose a framework based on Topological Mapper algorithm. The novelty of this work is that we suggest a method for defining the filter function on which the mapper algorithm heavily depends. Survival analysis of the discovered cancer subtypes is carried out and evaluated in terms of minimum pairwise separation between the Kaplan-Meier plots. Furthermore, we present a method to measure the separation between the discovered subtypes based on hazard ratios. RESULTS: Five cancer genomics datasets obtained from The Cancer Genome Atlas portal have been used for comparisons with Robust Sparse Correlation-Otrimle (RSC-Otrimle) algorithm and Similarity Network Fusion(SNF). Comparisons show that the minimum pairwise life expectancy difference (in days) between the discovered subtypes for lung, colon, breast, glioblastoma and kidney cancers is 107, 204, 20, 88 and 425 days, respectively, for the proposed methodology whereas it is only 69, 43, 6, 61 and 282 days for RSC-Otrimle and 9, 95, 18, 60 and 148 days for SNF. Hazard ratio analysis also shows that the proposed methodology performs better in four of the five datasets. A visual inspection of Kaplan-Meier plots reveals that the proposed methodology achieves lesser overlap in Kaplan-Meier plots especially for lung, breast and kidney cases. Furthermore, relevant genetic pathways for each subtype have been obtained and pathways which can be possible targets for treatment have been discussed. CONCLUSION: The significance of this work lies in individualized understanding of cancer from patient to patient which is the backbone of Precision Medicine.

Impact of obesity on adverse in-hospital outcomes in patients undergoing percutaneous mitral valve edge-to-edge repair using MitraClip® procedure - Results from the German nationwide inpatient sample.

BACKGROUND AND AIM: The number of percutaneous edge-to-edge mitral regurgitation (MR) valve repairs with MitraClip® implantations increased exponentially in recent years. Studies have suggested an obesity survival paradox in patients with cardiovascular diseases. We investigated the influence of obesity on adverse in-hospital outcomes in patients with MitraClip® implantation. METHODS AND RESULTS: We analyzed data on characteristics of patients and in-hospital outcomes for all percutaneous mitral valve repairs using the edge-to-edge MitraClip®-technique in Germany 2011-2015 stratified for obesity vs. normal-weight/over-weight. The nationwide inpatient sample comprised 13,563 inpatients undergoing MitraClip® implantations. Among them, 1017 (7.5%) patients were coded with obesity. Obese patients were younger (75 vs.77 years,P < 0.001), more often female (45.4% vs.39.5%,P < 0.001), had more often heart failure (87.1% vs.79.2%,P < 0.001) and renal insufficiency (67.0% vs.56.4%,P < 0.001). Obese and non-obese patients were comparable regarding major adverse cardiac and cerebrovascular events (MACCE) and in-hospital death. The combined endpoint of cardio-pulmonary resuscitation (CPR), mechanical ventilation and death was more often reached in non-obese than in obese patients with a trend towards significance (20.6%vs.18.2%,P = 0.066). Obesity was an independent predictor of reduced events regarding the combined endpoint of CPR, mechanical ventilation and death (OR 0.75, 95%CI 0.64-0.89,P < 0.001), but not for reduced in-hospital mortality (P = 0.355) or reduced MACCE rate (P = 0.108). Obesity class III was associated with an elevated risk for pulmonary embolism (OR 5.66, 95%CI 1.35-23.77,P = 0.018). CONCLUSIONS: We observed an obesity paradox regarding the combined endpoint of CPR, mechanical ventilation and in-hospital death in patients undergoing MitraClip® implantation, but our results failed to confirm an impact of obesity on in-hospital survival or MACCE.

Skin disease profile of Syrian refugees in Jordan: a field-mission assessment.

BACKGROUND: Since the beginning of the Syrian war in 2011, the world has faced the most severe refugee crisis in history and 5.6 million Syrians have sought asylum in neighbouring countries or in Europe. According to recent estimates, more than 650 000 Syrian refugees are displaced in Jordan. OBJECTIVES: This article aims to assess the demographic characteristics and skin disease profile of Syrian displaced people residing in Al Za'atari camp and in communities in Jordan. Furthermore, the authors discuss the barriers to healthcare provision experienced during field missions. METHODS: This is a retrospective analysis of medical records collected during three medical missions in Jordan by an international dermatological team. Data on patient age, gender, country of origin and skin disease diagnoses were recorded both in Al Za'atari camp and Jordanian towns near the Syrian border. RESULTS: A total of 1197 patients were assessed during the field missions, with 67.7% female and 37.1% under the age of 14 years. Dermatitis was the leading dermatological condition in both refugee camp and community healthcare clinics. Infectious diseases were the second most common; however, fungal presentations were more common in the community as opposed to viral in Al Za'atari. CONCLUSIONS: High dermatitis presentations were likely secondary to the environment, living conditions and lack of access to emollients. Infectious diseases were postulated secondary to poor hygiene and sharing of overcrowded spaces. Barriers to health care included limited pharmacological formulary, difficulty in continuity of care and case referrals due to lack of specialized services. Better access to health care, improvement of living conditions and hygiene, and increased availability of medications including emollients and sunscreens are all interventions that should be carried out to reduce skin disease burden. Our findings should further urge the international community to uphold their commitments and uptake engagement in improving health care for Syrian displaced people.

Parental understanding of crucial medical jargon used in prenatal prematurity counseling.

BACKGROUND: Parent-clinician shared decision making is the recommended model for the care of premature infants; thus, clinicians provide prenatal prematurity counseling to parents in the event of a mother's hospitalization for premature birth. However, parental understanding of medical jargon commonly used during prematurity counseling is unknown. METHODS: Within an overall research agenda to develop and test an educational aid for prenatal prematurity education, we designed the Parental Knowledge of Premature Birth questionnaire. To evaluate parental comprehension of the medical jargon contained within the questionnaire, we conducted cognitive interviews, a formal method for evaluating comprehension and response to questionnaire items. Parents were recruited from a Level IV Neonatal Intensive Care Unit; purposeful recruitment ensured diversity with respect to gender, race, literacy level, and child's gestational age. Data collection and analysis followed standard qualitative methods for cognitive interviewing. We report on the insights gained from these cognitive interviews regarding parental understanding of crucial medical jargon commonly used during prenatal prematurity counseling. RESULTS: Participants included 10 women and 6 men who ranged in age from 23 to 38 years and represented Black/African-American (38%), Asian (6%), and white (56%) backgrounds. Five participants (31%) had less than a high school education or reading level below 9th grade (Wide Range Achievement Test version 4 reading subtest). In the first round of interviews, parents of all education and literacy levels had difficulty with medical jargon commonly used in prematurity counseling. Terms that parents found difficult to understand included "gestational age", "mild or no developmental problems", and "neonatologist". Modified terms tested in a second round of interviews showed improved comprehension. CONCLUSION: Cognitive interviews provided empirical testing of parental understanding of crucial medical jargon and highlighted that language commonly used during prenatal prematurity counseling is not understood by many parents. For parents to participate in shared decision making, plain language should be used to maximize their understanding of medical information.

Giving Voice to Parents in the Development of the Preemie Prep for Parents (P3) Mobile App.

BACKGROUND: Parents at risk for preterm birth frequently receive prematurity education when the mother is hospitalized for premature labor. Parental ability to learn and consider the information is limited because of the stress of the hospitalization. A promising approach is dissemination of information to at-risk parents before the birth hospitalization. PURPOSE: This article describes formative research used to develop smartphone-based prematurity education app for parents at-risk for preterm birth. METHODS: Stakeholders were parents with a prior preterm birth. Using stakeholder meeting transcripts, constant comparative analysis was used to reflect upon the parental voice. RESULTS: The parents named the app, Preemie Prep for Parents (P3). Parent perspectives revealed desire for information in the following 5 categories. (1) Power in knowledge and control: parents want autonomy when learning information that may influence medical decision-making. (2) Content and framing of information: they desire information from a trusted resource that helps promote prenatal health and provides neonatal intensive care information. (3) Displaying content: parents want personalization, push notifications, photographs displaying fetal development, and easy-to-understand statistics. (4) Providing information without causing harm: they desire non-value-laden information, and they do not support "gamifying" the app to enhance utilization. (5) Decision making: parents want information that would benefit their decision making without assuming that parents have a certain outlook on life or particular values. IMPLICATIONS FOR PRACTICE: These findings support the need for the P3 App to aid in decision making when parents experience preterm birth. IMPLICATIONS FOR RESEARCH: The findings highlight the need to study the effects of smartphone-based prematurity education on medical decision-making.