Displacement ventilation to avoid COVID-19 transmission through offices.

Respiratory infections such as COVID-19 can be spread by respiratory droplets with a diameter larger than 5-10 µ m or by droplet nuclei with a diameter smaller than 5 µ m . Besides wearing masks, fresh air should be supplied frequently in closed rooms to avoid infections. Constructing and operating new isolation rooms require time, money, and maintenance cost, which are scarce in the current pandemic and in many communities. Displacement ventilation may be a feasible and secure option in temporary hospitals and other buildings to control the disease. This paper investigates using CFD simulations how displacement ventilation systems can deliver high air quality, and thermal comfort and minimize the risk of COVID-19 infection in enclosed spaces.

Fouling resistance investigations of seaweed products.

Any solid, unprotected, and undefended surface in the aquatic environment will be fouled. Fouling, on the other hand, can affect a wide range of species that can tolerate some epibiosis. Several others, on the other hand, aggressively keep the epibionts off their body surface (antifouling). Antifouling defenses are built into marine plants like seaweed and seagrass. They do have a distinctive surface structure with tightly packed needle-like peaks and antifouling coverings, which may hinder settling bacteria's ability to cling. Chemical antifouling resistance is most probably a biological reaction to epibiosis' ecological drawbacks, especially for organisms capable of performing photosynthesis. The goal of this study was to see how effective natural compounds derived from littoral seaweeds were in preventing fouling. The brown mussel, an important fouling organism, was evaluated in laboratory bioassays against fifty-one populations' crude organic extracts including fort-two macroalgae species. Antifouling activity, exhibited a distinct phylogenetic pattern, with red macroalgae having the largest share of active species, subsequently brown macroalgae. Antifouling action in green seaweeds has never been significant. Seven species showed some level of induced antifouling defense. Our findings appear to back up previous findings about secondary metabolite synthesis in seaweeds, indicating that in the hunt for novel antifoulants, researchers should concentrate their efforts on tropical red macroalgae.

Breast Tumor Detection, Sizing and Localization Using a 24-Element Antenna Array.

This paper proposes a simple and novel design for breast cancer detection, sizing and localization. A miniature-sized antenna of volume 10 × 10 × 1.6 mm3 is designed at an optimized frequency of 7.98 GHz with a positive gain using the fractal theory; it is based on two nested folds connected to each other using repeated lines, discs and circles. It exhibits a reflection coefficient of -39 dB over a simulated bandwidth of 340 MHz; it has a gain of 1.04 dB and an efficiency of around 70%. This prototype is fabricated and its S11 is measured to get an operational frequency of 8.08 GHz with same S11 and bandwidth values. The insertion of slots in the antenna design improved its performance to get a higher [Formula: see text] of 8.21 GHz and an improved gain of 2.43 dB. The SAR value of the antenna is found to be around 1.4 W/Kg at a safe separation distance of 60 mm from the breast. As an array, it proved its ability to detect the presence of the tumor, its size and position. This is simply achieved by plotting the propagating E-field that is induced inside the breast. The main advantage of this system lies in the fact that it does not require any long-time complicated image processing. By observing E-field plots, it is seen that the | Ex | decreased from 8.37 V/m to 1.91 V/m. As for the | Ey |, it increased from 2.72 V/m to 4.12 V/m; both comparisons made between healthy and cancerous tissues, respectively. Simulations are conducted in HFSS; the antenna proved to be a good candidate for breast tumor detection, sizing and localization systems.

Wearable Blood Pressure Sensing Based on Transmission Coefficient Scattering for Microstrip Patch Antennas.

Painless, cuffless and continuous blood pressure monitoring sensors provide a more dynamic measure of blood pressure for critical diagnosis or continuous monitoring of hypertensive patients compared to current cuff-based options. To this end, a novel flexible, wearable and miniaturized microstrip patch antenna topology is proposed to measure dynamic blood pressure (BP). The methodology was implemented on a simulated five-layer human tissue arm model created and designed in High-Frequency Simulation Software "HFSS". The electrical properties of the five-layer human tissue were set at the frequency range (2−3) GHz to comply with clinical/engineering standards. The fabricated patch incorporated on a 0.4 mm epoxy substrate achieved consistency between the simulated and measured reflection coefficient results at flat and bent conditions over the frequency range of 2.3−2.6 GHz. Simulations for a 10 g average specific absorption rate (SAR) based on IEEE-Standard for a human arm at different input powers were also carried out. The safest input power was 50 mW with an acceptable SAR value of 3.89 W/Kg < 4W/Kg. This study also explored a novel method to obtain the pulse transit time (PTT) as an option to measure BP. Pulse transmit time is based on obtaining the time difference between the transmission coefficient scattering waveforms measured between the two pairs of metallic sensors underlying the assumption that brachial arterial geometries are dynamic. Consequently, the proposed model is validated by comparing it to the standard nonlinear Moens and Korteweg model over different artery thickness-radius ratios, showing excellent correlation between 0.76 ± 0.03 and 0.81 ± 0.03 with the systolic and diastolic BP results. The absolute risk of arterial blood pressure increased with the increase in brachial artery thickness-radius ratio. The results of both methods successfully demonstrate how the radius estimates, PTT and pulse wave velocity (PWV), along with electromagnetic (EM) antenna transmission propagation characteristics, can be used to estimate continuous BP non-invasively.

Covid-19 Social Distancing, Lifestyle and Health Outcomes Among Persons Living with HIV (PLWH): A Web-based Survey.

We investigated changes in lifestyle, depressive symptoms, self-perception of health, and body weight changes of persons living with HIV (PLWH) during the COVID-19 social distancing (SD). In a Web-based cross-sectional survey, participants (n = 406) were questioned about lifestyle and health status before and during SD. Most responders were men, 50 + years old, high education level; 49.8% had their income reduced during SD. About 9% were diagnosed with COVID-19, of whom 13.5% required hospitalization. During SD: - most participants did not change their food intake, although 25% replaced healthy foods with unhealthy ones; -more than half mentioned poor sleep quality; -about 50% increased their sedentary behavior. Depressive symptoms (reported by 70.9%) were associated with sedentary behavior, poor sleep quality, and reduced income. About one-third had a negative perception of their health status, which was inversely associated with practicing physical exercises and positively associated with sedentarism and poor sleep quality. More than half increased their body weight, which was associated with a lower intake of vegetables. The older age reduced the odds of the three outcomes. Carefully monitoring PLWH regarding SD will enable early interventions toward health.

RESUMEN: En este trabajo investigamos los cambios en el estilo de vida, síntomas depresivos, autopercepción de salud y cambios en el peso corporal de las personas que viven con el VIH (PVCV) durante el distanciamiento social (DS) de COVID-19. En una encuesta transversal en línea, se preguntó a los participantes (n = 406) sobre el estilo de vida y el estado de salud antes y durante el DS. La mayoría de los encuestados eran hombres, mayores de 50 años, con alto nivel educativo. El 49,8% tuvo una disminución en sus ingresos durante el DS. El 9,1% fue diagnosticados con COVID-19, de los cuales 13,5% requirió hospitalización. Durante el DS: - la mayoría de los participantes no cambió su ingesta de alimentos, aunque el 25% reemplazó los alimentos saludables por los no saludables; más de la mitad mencionó mala calidad del sueño; cerca del 50% aumentó su comportamiento sedentario. Los síntomas depresivos (referidos por el 70,9%), fueron incrementados por el sedentarismo, la mala calidad del sueño y reducción de la renta. Cerca de un tercio tenía una percepción negativa de su estado de salud, que se redujo con la práctica de ejercicio físico y aumentó con el sedentarismo y la mala calidad del sueño. Más de la mitad aumentó su peso corporal, lo que se asoció con una menor ingesta de vegetales. Una edad más avanzada redujo las probabilidades de los tres desenlaces. El monitoreo cuidadoso de las PVCV con respecto al DS permitirá intervenciones tempranas para la salud.

Headspace Volatile Organic Compound Profiling of Pleural Mesothelioma and Lung Cancer Cell Lines as Translational Bridge for Breath Research.

Introduction: Malignant pleural mesothelioma (MPM) is a lethal cancer for which early-stage diagnosis remains a major challenge. Volatile organic compounds (VOCs) in breath proved to be potential biomarkers for MPM diagnosis, but translational studies are needed to elucidate which VOCs originate from the tumor itself and thus are specifically related to MPM cell metabolism. Methods: An in vitro model was set-up to characterize the headspace VOC profiles of six MPM and two lung cancer cell lines using thermal desorption-gas chromatography-mass spectrometry. A comparative analysis was carried out to identify VOCs that could discriminate between MPM and lung cancer, as well as between the histological subtypes within MPM (epithelioid, sarcomatoid and biphasic). Results: VOC profiles were identified capable of distinguishing MPM (subtypes) and lung cancer cells with high accuracy. Alkanes, aldehydes, ketones and alcohols represented many of the discriminating VOCs. Discrepancies with clinical findings were observed, supporting the need for studies examining breath and tumor cells of the same patients and studying metabolization and kinetics of in vitro discovered VOCs in a clinical setting. Conclusion: While the relationship between in vitro and in vivo VOCs is yet to be established, both could complement each other in generating a clinically useful breath model for MPM.

Safety and immunogenicity of CoronaVac in people living with HIV: a prospective cohort study.

BACKGROUND: People living with HIV might have a poor or delayed response to vaccines, mainly when CD4 cell counts are low, and data concerning COVID-19 vaccines in this population are scarce. This prospective cohort study assessed the safety and immunogenicity of the inactivated SARS-CoV-2 vaccine CoronaVac in people with HIV compared with people with no known immunosuppression. METHODS: In this prospective cohort study, adults (aged ≥18 years) living with HIV who were regularly followed up at the University of Sao Paulo HIV/AIDS outpatient clinic in Sao Paulo, Brazil, were included in the study. Eligibility for people with HIV was independent of antiretroviral use, HIV viral load, or CD4 cell count. Adults with no known immunosuppression with CoronaVac vaccination history were included as a control group. CoronaVac was given intramuscularly in a two-dose regimen, 28 days apart. Blood was collected before vaccine administration and 6 weeks after the second dose (day 69). Immunogenicity was assessed at baseline (day 0), before second vaccine (day 28), and 6 weeks after second vaccine dose (day 69) through SARS-CoV-2 IgG titre and seroconversion, neutralising antibody (NAb) positivity and percentage activity, and factor increase in IgG geometric mean titres (FI-GMT). We investigated whether HIV status and CD4 count (<500 or ≥500 cells per µL) were associated with CoronaVac immunogenicity by use of multivariable models adjusted for age and sex. FINDINGS: Between Feb 9, 2021, and March 4, 2021, 776 participants were recruited. Of 511 participants included, 215 (42%) were people with HIV and 296 (58%) were people with no known immunosuppression. At 6 weeks after the second vaccine dose (day 69), 185 (91%) of 204 participants with HIV and 265 (97%) of 274 participants with no known immunosuppression had seroconversion (p=0·0055). 143 (71%) of 202 participants with HIV were NAb positive compared with 229 (84%) of 274 participants with no known immunosuppression (p=0·0008). Median IgG titres were 48·7 AU/mL (IQR 26·6-88·2) in people with HIV compared with 75·2 AU/mL (50·3-112·0) in people with no known immunosuppression (p<0·0001); and median NAb activity was 46·2% (26·9-69·7) compared with 60·8% (39·8-79·9; p<0·0001). In people with HIV who had CD4 counts less than 500 cells per µL seroconversion rates, NAb positivity, and NAb activity were lower than in those with CD4 counts of at least 500 cells per µL. In multivariable models for seroconversion, NAb positivity, IgG concentration, and NAb activity after a complete two-dose regimen, adjusted for age and sex, people with HIV who had CD4 counts of at least 500 cells per µL and people with no known immunosuppression had higher immunogenicity than did people with HIV with CD4 counts less than 500 cells per µL. No serious adverse reactions were reported during the study. INTERPRETATION: Immunogenicity following CoronaVac in people with HIV seems strong but reduced compared with people with no known immunosuppression. Our findings highlight the need for strategies to improve vaccine immunogenicity in people with HIV. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and B3-Bolsa de Valores do Brasil.

Presence of Escherichia coli O157:H7 in Dairy Farms located in Najaf, Baghdad, Kirkuk, and Erbil, Iraq.

It has been approved that one of the most dangerous foodborne pathogenic bacteria is E. coli O157:H7, which is responsible for several infection and death cases worldwide. It is well documented that in the developing countries E. coli O157:H7 is considered the main causative pathogen of human gastrointestinal infections. Therefore, the current research was aimed to evaluate the prevalence of E. coli O157:H7 in dairy cattle's milk using a rapid method, in Iraq (Najaf, Baghdad, Kirkuk, and Erbil). Over a period of 6 months (During hot months) samples were obtained and investigated by culturing on selective media (CT-SMAC). The multiplex PCR (m-PCR) also used for milk sample direct investigation. Using biochemical tests the recorded data showed that, 2 recognized isolates were E. coli, while the recorded data obtained from m-PCR assay revealed that none of the isolated E. coli was toxigenic E.coli O157:H7. The results of m-PCR on the milk samples revealed that 45 milk samples contained at least one of the following genes: O157, H7, stx1, stx2 genes. Also the results of the m-PCR revealed that 2 samples (raw milk) were toxigenic O157:H7 positive. In conclusion, to the best of authors' knowledge, this investigation was the first report on the prevalence of E. coli O157:H7 in the raw milk samples in Iraq. The results showed that the proportion of contaminated milk samples contaminated with E. coli O157:H7 identified in the current survey were similar to that the results of the previously published research from different dairy products across different countries in the Middle East region.

The Influence of Rumen-Protected Choline and α-tocopherol Supplementation on Early Lactating Dairy Cows Metabolism.

It is well documented that choline is known as one of the essential ingredients of phospholipids. Choline acts as a determinative element for appropriate cell membrane functions. On the other hand α-tocopherol (Vit E) is a fat-soluble vitamin. This vitamin acts as a strong antioxidant in the living body's defense system against oxidative stress. Lipid peroxidation in peripartum and early lactating cows is significantly increased while the level of serum Vit E is decreases dramatically. These concomitant physiological changes demonstrate a higher level of oxidative stress subsequently leads to serious health issues in dairy cows. Therefore, the present research was designed to investigate the following items in dairy cattle: 1) evaluation of the possible changes in serum protein fractions, and 2) comparing the oxidative status of orally RPC and vitamin E supplementation in dairy cows in early lactation period. In the current study 30 early lactating primiparous and multiparous Holstein cows (body condition score (BCS)=2.51 ± 0.10) were used beginning five weeks postpartum. All the animals were randomly divided in to three groups (n=10) (number of lactation=2.61). The animals were randomly assigned to receive one of the following treatments. Group 1 served as control group were not received any supplement. The second group was supplemented with 90 g/d of RPC (Reashre Choline, Balchem, USA). The third group was administrated 4400 IU/d vitamin E (Roche, Vitamins Ltd; Switzerland). In the current study, serum protein electrophoresis showed four main fractions as follows: albumin, α-globulin, ß-globulin, and γ-globulin. The recorded data showed that the percentages of albumin and γ-globulin fractions were higher in treated groups compared to the control group. In the animals supplementing with RPC and vitamin E the percentages of serum albumin increased to the value of 37. 70±1.63 and 38.21±1.28 respectively compare to the control group (34.69±1.21), which were significant (P<0.05).

British Society for Immunology/United Kingdom Primary Immunodeficiency Network consensus statement on managing non-infectious complications of common variable immunodeficiency disorders.

Common variable immunodeficiency (CVID) represents a heterogeneous group of rare disorders. There is considerable morbidity and mortality as a result of non-infectious complications, and this presents clinicians with management challenges. Clinical guidelines to support the management of CVID are urgently required. The UK Primary Immunodeficiency Network and the British Society for Immunology funded a joint project to address this. A modified Delphi Survey was conducted for the assessment, diagnosis and treatment of the non-infectious blood, respiratory, gut and liver complications of CVID. A steering group of 10 consultant immunologists and one nurse specialist developed and reviewed the survey statements and agreed the final recommendations. In total, 22 recommendations and three areas for research were developed.

A systematic review of adult tetanus-diphtheria-acellular (Tdap) coverage among healthcare workers.

During the last decades pertussis incidence raised globally. Several vaccination strategies targeting adults to reduce pertussis among young infants have been proposed, including vaccination of healthcare workers (HCWs). The aim of this study was to analyse, by performing a systematic review of literature, published papers that evaluated Tdap coverage among HCWs, variables associated with vaccine uptake and efforts implemented to raise vaccination rates. We searched the MedLine, Embase, SCOPUS, LILACS, Web of Science and Cochrane for full-text studies that evaluated Tdap coverage in HCW. Two independent reviewers screened the articles and extracted the data.Twenty-eight studies published from 2009 to 2018 were reviewed. Most studies were conducted in the USA. Initial Tdap coverage varied from 6.1% to 63.9%. USA and France are the only two countries with studies evaluating Tdap coverage within HCWs using national data. In the USA, Tdap coverage in HCWs raised from 6.1% to 45.1% from 2007 to 2015. In the analysis of French national data, a Tdap coverage of 63.9% was observed. Five studies used interventions to raise Tdap coverage in HCWs. Two intervention studies implemented mandatory vaccination and three used educational strategies. All of them achieved coverages over 86%. Only eleven studies analysed the association of Tdap vaccination with variables of interest. Previous immunization with other vaccines recommended for HCWs (like influenza, hepatitis B and MMR) was positively associated with Tdap uptake in four studies. In conclusion, overall Tdap coverage among HCWs is low, but seems to increase over the years after the vaccine introduction and with implementation of interventions to increase coverage.

Role of Lock Therapy for Long-Term Catheter-Related Infections by Multidrug-Resistant Bacteria.

The management of long-term central venous catheter (LTCVC) infections by multidrug-resistant (MDR) bacteria in cancer patient is a challenge. The objectives of this study were to analyze outcomes in cancer patients with LTCVC-associated infection, identify risks for unfavorable outcomes, and determine the impact of MDR bacteria and antibiotic lock therapy (ALT) in managing such infections. We evaluated all LTCVC-associated infections treated between January 2009 and December 2016. Infections were reported in accordance with international guidelines for catheter-related infections. The outcome measures were 30-day mortality and treatment failure. We analyzed risk factors by Cox forward-stepwise regression. We identified 296 LTCVC-associated infections; 212 (71.6%) were classified as bloodstream infections (BSIs). The most common agent was Staphylococcus aureus Forty-six (21.7%) infections were due to MDR Gram-negative bacteria. ALT was used in 62 (29.2%) patients, with a 75.9% success rate. Risk factors identified for failure of the initial treatment were having a high sequential organ failure assessment (SOFA) score at diagnosis of infection and being in palliative care; introduction of ALT at the start of treatment was identified as a protective factor. Risk factors identified for 30-day mortality after LTCVC-associated infection were a high SOFA score at diagnosis, infection with MDR bacteria, and palliative care; introduction of ALT at the start of treatment, hematological malignancies, and adherence to an institutional protocol for the management of LTCVC-associated infection were identified as protective factors. Despite the high incidence of infection with MDR bacteria, ALT improves the outcome of LTCVC-associated infection in cancer patients.

Invasive Aspergillosis Mimicking Metastatic Lung Cancer.

In a patient with a medical history of cancer, the most probable diagnosis of an 18FDG-avid pulmonary mass combined with intracranial abnormalities on brain imaging is metastasized cancer. However, sometimes a differential diagnosis with an infectious cause such as aspergillosis can be very challenging as both cancer and infection are sometimes difficult to distinguish. Pulmonary aspergillosis can present as an infectious pseudotumour with clinical and imaging characteristics mimicking lung cancer. Even in the presence of cerebral lesions, radiological appearance of abscesses can look like brain metastasis. These similarities can cause significant diagnostic difficulties with a subsequent therapeutic delay and a potential adverse outcome. Awareness of this infectious disease that can mimic lung cancer, even in an immunocompetent patient, is important. We report a case of a 65-year-old woman with pulmonary aspergillosis disseminated to the brain mimicking metastatic lung cancer.

Biomarkers for early diagnosis of malignant mesothelioma: Do we need another moonshot?

Early diagnosis of malignant pleural mesothelioma (MPM) is a challenge for clinicians. The disease is usually detected in an advanced stage which precludes curative treatment. We assume that only new and non-invasive biomarkers allowing earlier detection will result in better patient management and outcome. Many efforts have already been made to find suitable biomarkers in blood and pleural effusions, but have not yet resulted in a valid and reproducible diagnostic one. In this review, we will highlight the strengths and shortcomings of blood and fluid based biomarkers and highlight the potential of breath analysis as a non-invasive screening tool for MPM. This method seems very promising in the early detection of diverse malignancies, because exhaled breath contains valuable information on cell and tissue metabolism. Research that focuses on breath biomarkers in MPM is in its early days, but the few studies that have been performed show promising results. We believe a breathomics-based biomarker approach should be further explored to improve the follow-up and management of asbestos exposed individuals.

Polyelectrolyte-Enrobed Cancer Cells in View of Personalized Immune-Therapy.

Targeting the immune system with a personalized vaccine containing cues derived from the patient's malignancy might be a promising approach in the fight against cancer. It includes neo-antigens as well as nonmutated tumor antigens, preferentially leading to an immune response that is directed to a broader range of epitopes compared to strategies involving a single antigen. Here, this paper reports on an elegant method to encapsulate whole cancer cells into polyelectrolyte particles. Porous and nonaggregated microparticles containing dead cancer cells are obtained by admixing mannitol and live cancer cells with oppositely charged polyelectrolytes, dextran sulfate (anionic polysaccharide), and poly-l-arginine (cationic polypeptide) prior to atomization into a hot air stream. It shows that the polyelectrolyte-enrobed cancer cells, upon redispersion in phosphate buffered saline buffer, are stable and do not release cell proteins in the supernatant. In vitro experiments reveal that the particles are nontoxic and strongly increase uptake of cell lysate by dendritic cells. In vitro assessment of antigen presentation by dendritic cells reveal the potential of the polyelectrolyte-enrobed cancer cells as promotors of antigen cross-presentation. Finally, it is demonstrated that the immunogenicity can be enhanced by surface adsorption of a polymer-substituted TLR7-agonist.

The transcriptome of lung tumor-infiltrating dendritic cells reveals a tumor-supporting phenotype and a microRNA signature with negative impact on clinical outcome.

Targeting immunomodulatory pathways has ushered a new era in lung cancer therapy. Further progress requires deeper insights into the biology of immune cells in the lung cancer micro-environment. Dendritic cells (DCs) represent a heterogeneous and highly plastic immune cell system with a central role in controlling immune responses. The intratumoral infiltration and activation status of DCs are emerging as clinically relevant parameters in lung cancer. In this study, we used an orthotopic preclinical model of lung cancer to dissect how the lung tumor micro-environment affects tissue-resident DCs and extract novel biologically and clinically relevant information. Lung tumor-infiltrating leukocytes expressing generic DC markers were found to predominantly consist of CD11b+ cells that, compare with peritumoral lung DC counterparts, strongly overexpress the T-cell inhibitory molecule PD-L1 and acquire classical surface markers of tumor-associated macrophages (TAMs). Transcriptome analysis of these CD11b+ tumor-infiltrating DCs (TIDCs) indicates impaired antitumoral immunogenicity, confirms the skewing toward TAM-related features, and indicates exposure to a hypoxic environment. In parallel, TIDCs display a specific microRNA (miRNA) signature dominated by the prototypical lung cancer oncomir miR-31. In vitro, hypoxia drives intrinsic miR-31 expression in CD11b+ DCs. Conditioned medium of miR-31 overexpressing CD11b+ DCs induces pro-invasive lung cancer cell shape changes and is enriched with pro-metastatic soluble factors. Finally, analysis of TCGA datasets reveals that the TIDC-associated miRNA signature has a negative prognostic impact in non-small cell lung cancer. Together, these data suggest a novel mechanism through which the lung cancer micro-environment exploits the plasticity of the DC system to support tumoral progression.

Screening for depression in hospitalized medical patients.

Depression among hospitalized patients is often unrecognized, undiagnosed, and therefore untreated. Little is known about the feasibility of screening for depression during hospitalization, or whether depression is associated with poorer outcomes, longer hospital stays, and higher readmission rates. We searched PubMed and PsycINFO for published, peer-reviewed articles in English (1990-2016) using search terms designed to capture studies that tested the performance of depression screening tools in inpatient settings and studies that examined associations between depression detected during hospitalization and clinical or utilization outcomes. Two investigators reviewed each full-text article and extracted data. The prevalence of depression ranged from 5% to 60%, with a median of 33%, among hospitalized patients. Several screening tools identified showed high sensitivity and specificity, even when self-administered by patients or when abbreviated versions were administered by individuals without formal training. With regard to outcomes, studies from several individual hospitals found depression to be associated with poorer functional outcomes, worse physical health, and returns to the hospital after discharge. These findings suggest that depression screening may be feasible in the inpatient setting, and that more research is warranted to determine whether screening for and treating depression during hospitalization can improve patient outcomes. Journal of Hospital Medicine 2017;12:118-125.

The immunophenotypic fingerprint of patients with primary antibody deficiencies is partially present in their asymptomatic first-degree relatives.

The etiology of primary antibody deficiencies is largely unknown. Beside rare monogenic forms, the majority of cases seem to have a more complex genetic basis. Whereas common variable immunodeficiency has been investigated in depth, there are only a few reports on milder primary antibody deficiencies such as idiopathic primary hypogammaglobulinemia and IgG subclass deficiency. We performed flow cytometric immunophenotyping in 33 patients with common variable immunodeficiency, 23 with idiopathic primary hypogammaglobulinemia and 21 with IgG subclass deficiency, as well as in 47 asymptomatic first-degree family members of patients and 101 unrelated healthy controls. All three groups of patients showed decreased memory B- and naïve T-cell subsets and decreased B-cell activating factor receptor expression. In contrast, circulating follicular helper T-cell frequency and expression of inducible T-cell co-stimulator and chemokine receptors were only significantly altered in patients with common variable immunodeficiency. Asymptomatic first-degree family members of patients demonstrated similar, albeit intermediate, alterations in naïve and memory B- and T-cell subsets. About 13% of asymptomatic relatives had an abnormal peripheral B-cell composition. Furthermore, asymptomatic relatives showed decreased levels of CD4+ recent thymic emigrants and increased central memory T cells. Serum IgG and IgM levels were also significantly lower in asymptomatic relatives than in healthy controls. We conclude that, in our cohort, the immunophenotypic landscape of primary antibody deficiencies comprises a spectrum, in which some alterations are shared between all primary antibody deficiencies whereas others are only associated with common variable immunodeficiency. Importantly, asymptomatic first-degree family members of patients were found to have an intermediate phenotype for peripheral B- and T-cell subsets.

Familial Mediterranean fever mutations lift the obligatory requirement for microtubules in Pyrin inflammasome activation.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is caused by mutations in the inflammasome adaptor Pyrin, but how FMF mutations alter signaling in FMF patients is unknown. Herein, we establish Clostridium difficile and its enterotoxin A (TcdA) as Pyrin-activating agents and show that wild-type and FMF Pyrin are differentially controlled by microtubules. Diverse microtubule assembly inhibitors prevented Pyrin-mediated caspase-1 activation and secretion of IL-1ß and IL-18 from mouse macrophages and human peripheral blood mononuclear cells (PBMCs). Remarkably, Pyrin inflammasome activation persisted upon microtubule disassembly in PBMCs of FMF patients but not in cells of patients afflicted with other autoinflammatory diseases. We further demonstrate that microtubules control Pyrin activation downstream of Pyrin dephosphorylation and that FMF mutations enable microtubule-independent assembly of apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) micrometer-sized perinuclear structures (specks). The discovery that Pyrin mutations remove the obligatory requirement for microtubules in inflammasome activation provides a conceptual framework for understanding FMF and enables immunological screening of FMF mutations.

Genes associated with common variable immunodeficiency: one diagnosis to rule them all?

Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by hypogammaglobulinaemia, impaired production of specific antibodies after immunisation and increased susceptibility to infections. CVID shows a considerable phenotypical and genetic heterogeneity. In contrast to many other primary immunodeficiencies, monogenic forms count for only 2-10% of patients with CVID. Genes that have been implicated in monogenic CVID include ICOS, TNFRSF13B (TACI), TNFRSF13C (BAFF-R), TNFSF12 (TWEAK), CD19, CD81, CR2 (CD21), MS4A1 (CD20), TNFRSF7 (CD27), IL21, IL21R, LRBA, CTLA4, PRKCD, PLCG2, NFKB1, NFKB2, PIK3CD, PIK3R1, VAV1, RAC2, BLK, IKZF1 (IKAROS) and IRF2BP2 With the increasing number of disease genes identified in CVID, it has become clear that CVID is an umbrella diagnosis and that many of these genetic defects cause distinct disease entities. Moreover, there is accumulating evidence that at least a subgroup of patients with CVID has a complex rather than a monogenic inheritance. This review aims to discuss current knowledge regarding the molecular genetic basis of CVID with an emphasis on the relationship with the clinical and immunological phenotype.