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Multiple myeloma (MM) is a plasma cell neoplasia commonly treated with proteasome inhibitors such as bortezomib. Although bortezomib has demonstrated enhanced survival benefit, some patients relapse and subsequently develop resistance to such therapy. Here, we investigate the mechanisms underlying relapse and refractory MM following bortezomib treatment. We show that bortezomib-exposed proinflammatory macrophages promote an enrichment of MM-tumor-initiating cells (MM-TIC) both in vitro and in vivo. These effects are regulated in part by IL1β, as blocking the IL1β axis by a pharmacologic or genetic approach abolishes bortezomib-induced MM-TIC enrichment. In MM patients treated with bortezomib, high proinflammatory macrophages in the bone marrow negatively correlate with survival rates (HR, 1.722; 95% CI, 1.138–2.608). Furthermore, a positive correlation between proinflammatory macrophages and TICs in the bone marrow was also found. Overall, our results uncover a protumorigenic cross-talk involving proinflammatory macrophages and MM cells in response to bortezomib therapy, a process that enriches the MM-TIC population.Implications:Our findings suggest that proinflammatory macrophages in bone marrow biopsies represent a potential prognostic biomarker for acquired MM resistance to bortezomib therapy.

Figure S1. Bone marrow-derived macrophages enrich MM TICs. Figure S2. IL-1β promotes MM-TIC enrichment. Figure S3. Reduced survival in MM patients with high levels of M1 pro-inflammatory macrophages and TICs. Table S1: Patient characteristics and treatment description Table S2. Panel of antibodies and isotype conjugates used in CyTOF.

The current meta-analysis investigates the efficacy of psychotherapy during psychiatric hospitalization and examines the moderating role of diagnosis and therapeutic approach.We conducted systematic searches in literature databases, including PubMed, PsycInfo, and Google Scholar. In total, 37 samples were included for the meta-analysis with a total of 4,443 patients. The primary outcome was the standardized mean differences in clinical status measured by symptomatic and functional measures.The meta-analysis of 22 samples without a control group resulted in the upper end of the medium effect size for the overall effect of treatment during psychiatric hospitalization that included psychotherapy (k = 22, Cohen's d = 0.70, and 95% Cl 0.36 to 1.04). The meta-analysis of 15 samples with a control group resulted in the upper end of the low effect size for the contribution of psychotherapy to the improvement of patients' clinical status measured by symptomatic and functional measures (k = 15, Cohen's d = 0.43, and 95% CI 0.06 to 0.81). No significant effects were uncovered for psychotherapy orientation. Diagnosis was found to moderate the contribution of psychotherapy in an inpatient setting to the improvement of patients' clinical condition.Psychotherapy during psychiatric hospitalization may be an effective treatment. Across the various samples, psychotherapy has a moderate effect on the reduction of psychiatric symptoms beyond the overall effect of ward treatment.

Purpose In 2012, the Israeli Ministry of Education and its Testing and Evaluation Department introduced a new tool to evaluate the quality of kindergarten teachers’ work. This paper aims to identify how kindergarten teachers perceive the new multiple domains performance tool. Design/methodology/approach The study applied a qualitative paradigm of data collection and analysis. Data collection consisted of semi-structured in-depth interviews conducted with 36 kindergarten teachers. Findings Findings indicated that most kindergarten teachers perceive their work plan and the kindergarten climate as the most important evaluation domains, while perceiving involving parents as the least important and even an unnecessary domain. One-third of them indicated that an innovation domain should be added. Also, the kindergarten teachers perceived the use of the KT-MDPT as both positive and negative. Originality/value There is a clear dearth in scholarly literature dealing with the evaluation of the quality of kindergarten teachers’ work. This study is the first to reveal Israeli kindergarten teachers' attitudes regarding this new tool for work quality evaluation.

In this work, we present biocompatible nanocarriers based on modified polysaccharides capable of transporting insulin macromolecules through human skin without any auxiliary techniques.

Aneuploidy, an abnormal chromosome composition, results in a stoichiometric imbalance of protein complexes, which jeopardizes the fitness of aneuploid cells. Aneuploid cells thus need to compensate for the imbalanced DNA levels by regulating their RNA and protein levels, a phenomenon known as dosage compensation. However, the molecular mechanisms involved in dosage compensation in human cells – and whether they can be targeted to selectively kill aneuploid cancer cells – remain unknown. Here, we addressed this question via molecular dissection of multiple diploid vs. aneuploid cell models. Using genomic and functional profiling of a novel isogenic system of RPE1-hTERT cells with various degrees of aneuploidy, we found that aneuploid cells cope with both transcriptional burden and proteotoxic stress. At the mRNA level, aneuploid cells increased RNA synthesis, but concomitantly elevated several RNA degradation pathways, in particular the nonsense-mediated decay (NMD) and the microRNA-mediated mRNA silencing pathways. Consequently, aneuploid cells were more sensitive to the genetic or chemical perturbation of several key components of these RNA degradation pathways. At the protein level, aneuploid cells experienced proteotoxic stress, resulting in reduced translation and increased protein degradation, rendering them more sensitive to proteasome inhibition. These findings were recapitulated across hundreds of human cancer cell lines and primary tumors, confirming that both non-transformed and transformed cells alter their RNA and protein metabolism in order to adapt to the aneuploid state. Our results reveal that aneuploid cells are dependent on the over- or under-activation of several nodes along the gene expression process, identifying these pathways as clinically-actionable vulnerabilities of aneuploid cells.

Aneuploidy is a hallmark of human cancer, yet the cellular mechanisms that allow cells to cope with aneuploidy-induced cellular stresses remain largely unknown. Such coping mechanisms may present cellular vulnerabilities that can be harnessed for targeting cancer cells. Here, we induced aneuploidy in non-transformed RPE1-hTERT cells and derived multiple stable clones with various degrees of chromosome imbalances. We performed an unbiased genomic profiling of 6 isogenic clones, using whole-exome and RNA sequencing. We then functionally interrogated their cellular dependency landscapes, using genome-wide CRISPR/Cas9 screens and large-scale drug screens. We found that aneuploid clones activated the DNA damage response (DDR), and were consequently more resistant to further DNA damage induction. Interestingly, aneuploid cells also exhibited elevated RAF/MEK/ERK pathway activity, and were more sensitive to several clinically-relevant drugs targeting this pathway, and in particular to genetic and chemical CRAF inhibition. CRAF activity was functionally linked to the resistance to DNA damage induction, as CRAF inhibition sensitized aneuploid cells to DNA damage-inducing chemotherapies. The association between aneuploidy, RAF/MEK/ERK signaling, and DDR was independent of p53. The increased activity and dependency of aneuploid cells on the RAF/MEK/ERK pathway was validated in another isogenic aneuploid system, and across hundreds of human cancer cell lines, confirming their relevance to human cancer. Overall, our study provides a comprehensive resource for genetically-matched karyotypically-stable cells of various aneuploidy states, and reveals a novel therapeutically-relevant cellular dependency of aneuploid cells.

Background During the last decade, hospital-acquired carbapenem-resistant Acinetobacter baumannii (HA-CRAB) have become endemic in acute care facilities in Israel. Despite the increasing rates CRAB carriage among hospitalized patients in endemic settings, the role of active surveillance cultures (ASC) is still debated. The aim of the study was to evaluate the impact of different components of control measures conducted in an endemic acute care hospital Methods The study consisted of a 12-month baseline period (1 January 2019–31 December 2019; period 1), 12-month 1st intervention period (1 January 2020- December 2020; period 2); 6-month 2nd intervention period (1 January 2021-30 June 2021; period 3) and a 9-month follow-up period (1 June 2021–31 March 2022; period 4). During period 1, basic infection-control measures were implemented including contact precautions for CRAB carriers. During period 2, all CRAB carries were cohorted in a single ward and managed by dedicated health care workers. Enhanced environmental cleaning was conducted by a dedicated team. During periods 3 and 4, high-risk patients were screened on admission; weekly cultures were obtained in high-risk units. The incidence density rate (IDR) of HA-CRAB was defined as the per-patient number of first CRAB isolate from clinical specimens. Incidence rates ratios (IRR) were compared between the study periods. Results During the baseline period, IDR of HA-CRAB was 4.9/10,000 patient days (PD). During period 2, no significant decrease was observed (IDR 3.9/10,000 PD, IRR 0.7 95% CI 0.49-1.16, p=0.15). In response to ongoing transmission in several wards, ASC program was initiated in January 2021. IDR during period 3 was 5.3/10,000 PD (IRR 1.1, 95% CI 0.74- 1.56, p=0.64). Since January 2021, 2.1% (78/3799) were found to be colonized on admission and 5.5% (100/1809) were detected by weekly screening. Among the 291 patients who were detected with CRAB during this period, 70.9% were identified by ASC. During period 4, IDR was 3.1/10,000 PD (IRR 0.60, 95% CI 0.40-0.88, p=0.007). Conclusion The comprehensive intervention that combined intensified control measures with routine ASC was effective in reducing the incidence of HA-CRAB in endemic setting. Disclosures Yasmin Maor, MD, MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Honoraria.

This paper reports one-step synthesis of polysaccharide-based nanovehicles, capable of transporting ionic zinc via plant cuticle without auxiliary stimulation. Delivery of highly hydrophilic nutritive microelements via the hydrophobic cuticle of plant foliage is one of the major challenges in modern agriculture. In traditional nutrition via roots, up to 80% of microelements permeate to soil and get wasted; therefore, foliar treatment is an environmentally and economically preferable alternative. Carboxymethyl cellulose (CMC) was modified to amphiphilic N-octylamide-derivative (CMC-8), which spontaneously self-assemble to nanovehicles. It was found that hydrophobic substituents endow a biopolymer with unexpected affinity toward a hydrophilic payload. CMC-8 nanovehicles effectively encapsulated ionic zinc (ZnSO4) and delivered it upon foliar application to pepper (Capsicum annuum) and tomato (Solanum lycopersicum) plants. Zinc uptake and translocation in plants were monitored by SEM-EDS and fluorescence microscopic methods. In planta monitoring of the carrier was done by labeling nanovehicles with fluorescent carbon dots. Three-dimensional (3-D) structural modeling and conformational dynamics explained the CMC-8 self-assembly mechanism and zinc coordination phenomenon upon introduction of hydrophobic substituents.

To investigate the effects of mental stress stimulus on intraocular pressure (IOP) measurement and visual field (VF) testing. Patients with open angle glaucoma underwent a baseline IOP measurement and VF testing. Afterwards, they completed a computerized mental stress test (Stroop test) which is a known standardized method to induce mental stress. After test completion, patients underwent a second IOP measurement and VF testing. Seventy-two eyes of 36 patients were enrolled. Mean age was 67.0 ± 9.5 years (range 47–84 years). The mean baseline IOP was 15.0 mmHg, and after the Stroop mental stress test, IOP increased to 16.0 mm Hg (P

Metacognitive reflection and insight therapy (MERIT) is an integrative form of psychotherapy which seeks to help adults with serious mental illness make sense of the psychosocial challenges and possibilities they face and decide how to respond to them and direct their own recovery. In this article, we present an adaptation of MERIT to the context of an inpatient ward with an accompanied case illustration. Specifically, we describe how this approach is supported by a broad intersubjective framework, followed by a presentation of processes and contents of the treatment. Special attention is given to the concurrent improvements in reflective abilities and overall well-being of the patient. The unique role that psychotherapy in general, and approaches that emphasize reflective processes in particular, play during acute crises in an inpatient setting is discussed.

ObjectivePreferences for end-of-life (EoL) care settings is of considerable interest for developing public health policy and EoL care strategies. Culture, the cause of illness, and background characteristics may impact preferences. The present study aimed to explore preferences for EoL care settings: homes, hospitals, and inpatient hospice units among the general healthy population in Israel. Possible associations between the setting preferences and socio-demographic characteristics were also examined.MethodA cross-sectional survey was conducted among 311 healthy adults who were recruited through a representative internet panel of the Israeli population using the Israeli census sampling method. The sex ratio was almost 1:1 with 158 women (50.8%) and 153 men (49.2%). All participants completed self-report measures using an online survey system. The questionnaires assessed sociodemographics and preferences for EoL care settings.ResultsThis survey revealed that 52.1% of the participants expressed preference for being cared for at home rather than in an inpatient hospice unit, 40.8% expressed being cared for at home rather than in a hospital, while 36.7% had no preference regarding being cared for in hospital or in a hospice unit. Among the socio-demographic variables, only age and gender were found to be significantly associated with preferences for EoL care settings.Significance of resultsThe present study highlights the need to be cautious when regarding home as the preferred EoL care setting, as some individuals declared that they would prefer EoL hospice/hospital care. Age and gender should be considered when discussing and tailoring strategies regarding EoL preferences.

Antiviral drugs play a major role in the control of seasonal influenza epidemics and may provide prophylactic and therapeutic benefits during an eventual pandemic. Among the neuraminidase inhibitors, zanamivir has been shown to be a potent inhibitor of influenza viruses, and similarly against emerging resistant strains. Despite its high antiviral efficiency, zanamivir suffers from poor intestinal permeability, therefore administered via inhalation. Enabling oral delivery of zanamivir will augment the available antiviral tools in clinical practice, increase patient compliance and ultimately improve public health. Encapsulation of hydrophilic drugs within double emulsions (DEs), is an efficacious approach to enhance the oral bioavailability of BCS Class III drugs, such as zanamivir. The objective of this research was to increase the intestinal absorption of zanamivir by means of compatible DEs. Two different types of stable DEs were prepared comprising different internal aqueous phases (W

Dissemination of multidrug-resistant (MDR) bacteria with CTX-M-type extended-spectrum β-lactamases (bla

Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T cell (CART) therapy shows remarkable efficacy in patients with relapsed and/or refractory (R/R) multiple myeloma (MM). HBI0101, a novel second generation optimized anti-BCMA CART cell therapy, was developed in an academic setting. We conducted a phase I dose-escalation study of HBI0101 (cohort 1, 150x10^6 CART cells, N=6; cohort 2; 450x10^6 CART cells, N=7 and cohort 3, 800x10^6 CART cells, N=7) (NCT04720313) in 20 heavily pretreated R/R MM patients. Grade 1-2 cytokine release syndrome (CRS) was reported in 18 patients (90%). Neither grade 3-4 CRS, nor neurotoxicity of any grade were observed. No dose-limiting toxicities (DLTs) were observed in any cohort. The overall response rate (ORR), (stringent) complete response (CR/sCR) and very good partial response (VGPR) rates were 75%, 50% and 25%, respectively. Response rates were dose-dependent with 85% ORR, 71% CR and 57% minimal residual disease (MRD) negativity in the high-dose cohort 3. For the entire cohort, the median overall survival (OS) was 308 days (range, 25-466+), with an estimated OS of 55% as of data cutoff June 27th. The median progression-free survival (PFS) was 160 days, with 6 subjects remaining progression free at the time of data cutoff. Our findings demonstrate the manageable safety profile and efficacy of HBI0101. These favorable data are encouraging and support decentralization of CART production at an academic setting, ensuring a sufficient CART supply in the light of the increasing local demand.

Background: Carb-counting is a significant burden for persons with diabetes who require insulin to mitigate postprandial hyperglycemia. A closed-loop (CL) system with auto meal-bolus that eliminates manual mealtime bolusing was studied in adults with T1D. Methods: The system included the MiniMed™ 780G pump and a smartphone-paired smartwatch with the KLUE application that detects eating hand-gestures using motion sensors. A smartphone algorithm converted eating hand-gestures to carb amounts that were relayed to the pump for automatic bolusing. For 6 days, participants (N=17, aged 18-75 years) with T1D used the system with the KLUE app disabled and completed traditional carb-counting and -entry (Baseline) . Thereafter, the KLUE app was enabled for 5 days and carb-counting/carb-entry was prohibited (Study) . Participants were given the same 5 test-meals (one/day) of varying caloric and carb sizes during both periods. Otherwise, they had no other meal restrictions. Results: No significant difference in TIR was observed between periods and time spent at Conclusion: Data suggest that the novel CL system maintains glycemic control similar to that with manual meal bolusing. By eliminating the burden of carb-counting, the new CL system may improve the quality of life in persons with T1D. Disclosure A.Roy: Employee; Medtronic. A.Tirosh: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Merck & Co., Inc., Novo Nordisk, Sanofi, Consultant; Bayer AG, DreaMed Diabetes, Ltd., Research Support; Medtronic, Speaker's Bureau; Eli Lilly and Company. B.Grosman: Employee; Medtronic. D.Miller: Employee; Medtronic. T.Engel: None. O.Cohen: Employee; Medtronic. R.Shalit: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk. S.Shalem: None. M.Laron hirsh: None. Y.Cohen: None.

Introduction For the last three decades, enzyme replacement therapy (ERT) for Gaucher disease (GD) has been available. We aimed to evaluate the effect of ERT on the pregnancy and obstetric outcome in a unique group of multiparous women with type 1 GD (GD1) who had pregnancies with and without ERT. Study design The Gaucher Unit database (1987-2019) was searched for multiparous women who had pregnancies before and after the institution of ERT. Data were collected from the clinic files and study-specific questionnaires. Descriptive, correlation analysis and generalized estimating equations (GEE) were used to study the effect of ERT and confounding variables on study outcomes. Results We identified 19 women with 105 pregnancies, among which 26 (24.7%) terminated in first-trimester miscarriage. The risk for miscarriage was associated with the severity of GD1 genotype and phenotype, but not with ERT usage. Early postpartum hemorrhage (PPH) was reported in 16 (84%) women after 25 deliveries (31.6%, 95% CI 21.6%-43.1%). The risks of early PPH and red blood cell (RBC) transfusions were significantly lower when ERT was used during pregnancy, OR (95% CI) 0.13 (0.03-0.54) and 0.27 (0.08-0.94), respectively, compared to pregnancies without the use of ERT. Conclusion Enzyme replacement therapy during pregnancy is risk reducing for early PPH and RBC transfusions in women with GD1. We suggest considering ERT for the benefit of all pregnant women with GD1, including mild GD1. This article is protected by copyright. All rights reserved.

Bone-resorbing osteoclasts (OCLs) are multinucleated phagocytes, whose central roles in regulating bone formation and homeostasis are critical for normal health and development. OCLs are produced from precursor monocytes in a multistage process that includes initial differentiation, cell-cell fusion, and subsequent functional and morphological maturation; the molecular regulation of osteoclastogenesis is not fully understood. Here, we identify the receptor-type protein tyrosine phosphatase PTPRJ as an essential regulator specifically of OCL maturation. Monocytes from PTPRJ-deficient (JKO) mice differentiate and fuse normally, but their maturation into functional OCLs and their ability to degrade bone are severely inhibited. In agreement, mice lacking PTPRJ throughout their bodies or only in OCLs exhibit increased bone mass due to reduced OCL-mediated bone resorption. We further show that PTPRJ promotes OCL maturation by dephosphorylating the M-CSF receptor (M-CSFR) and Cbl, thus reducing the ubiquitination and degradation of the key osteoclastogenic transcription factor NFATc1. Loss of PTPRJ increases ubiquitination of NFATc1 and reduces its amounts at later stages of osteoclastogenesis, thereby inhibiting OCL maturation. PTPRJ thus fulfills an essential and cell-autonomous role in promoting OCL maturation by balancing between the pro- and anti-osteoclastogenic activities of the M-CSFR and maintaining NFATc1 expression during late osteoclastogenesis.

Therapeutic options in relapsed refractory (R/R) light-chain (AL) amyloidosis patients are limited. Given the encouraging results in t(11;14) multiple myeloma and the high prevalence of t(11;14) in AL amyloidosis, venetoclax is an attractive treatment option in this setting. We report here the results of a multi-center retrospective study on 26 R/R AL amyloidosis patients treated off-label with venetoclax. The median lines of therapy prior to venetoclax was 3.5 (range 1–7), and 88% of our cohort had t (11;14). Twenty-two patients (85%) were previously treated with daratumumab. The overall hematologic response rate was 88%, 35% achieved a CR, and 35% achieved VGPR. The median event-free survival was 25 months (m) (95% CI 9.7 m-not reached), and the median overall survival was 33 m (95% CI 25.9–39.2 m). Most of the patients in this cohort are in ongoing deep responses and continuing venetoclax therapy. The treatment was relatively safe. One patient died due to infection, and there were two grade 3 infections in our cohort. Tumor lysis syndrome (TLS) was not seen in any patient. Dose reductions were frequent but did not affect the efficacy. These promising results require confirmation in a randomized controlled trial.

To examine personal and organisational factors related to professional functioning of nurses and physicians during the COVID-19 pandemic.Exposure to COVID-19-related stressors has been associated with lower self-reported professional functioning among health care workers.A cross-sectional study among 115 hospital workers during the COVID-19 pandemic in Israel was designed to explore (a) personal professional functioning, (b) clarity of guidelines, (c) work organisation by the management, and (d) health care workers' feeling of contribution to a global effort.A feeling of contribution to a global effort while treating patients with COVID-19 mediated the relationships between work organisation by the management and professional functioning (β = .05, p .05). The clarity of guidelines for routine procedures (β = .21, p .05) and a feeling of β contribution to a global effort (β = .34, p .01) positively predicted professional functioning of nurses and physicians during COVID-19 pandemic (RIn order to achieve optimal functioning of health care workers in an emergency, managers should provide clear guidelines and promote workers' feelings of contribution to a global effort.The provision of clear guidelines and protocols is essential for efficient emergency management. Expressing appreciation for health care workers and providing positive feedback may improve professional functioning.

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease.We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response.A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy.Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).

This qualitative study illuminates the experience of volunteering at sexual assault crisis centers among women survivors of sexual assault. In-depth interviews were conducted with 11 women who had been volunteering at four different sexual assault crisis centers across Israel for 1 to 17 years. The findings reveal three main themes. First, there are five types of motivation to volunteer at such centers, all grounded in the participants’ experience of sexual assault. Second, volunteering fosters recovery by promoting an empowered identity reconstruction and social integration. Third, both challenges and risks to recovery, such as exposure to sexual-assault triggers, arise from the experiences of sexual assault and volunteering at the centers. Moreover, the findings indicate various mechanisms that shape the risks–benefits dynamic involved in volunteering, such as the demands of the volunteering role. Thus, this study shifts the understanding of prosocial behavior by sexual-assault survivors from a binary assessment of “positive” or “negative” to a more comprehensive appraisal at the individual, role, and organizational levels.

This paper reports one-step synthesis of polysaccharide-based nanovehicles, capable of transporting ionic zinc

The recent surge in coronavirus disease 2019 cases led to the consideration of a booster vaccine in previously vaccinated immunosuppressed individuals. However, the immunogenic effect of a third-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in immunosuppressed patients is still unknown.This was an observational cohort study of 279 previously vaccinated immunosuppressed patients followed at a single tertiary hospital in Israel. Patients were administered a third dose of the Pfizer-BioNTech mRNA vaccine (BNT162b2) between July 14 and July 21, 2021. Levels of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured 3 to 4 weeks after vaccination.Of the cohort of 279 patients, 124 (44.4%) had haematologic malignancies, 57 (20.4%) had rheumatologic diseases, and 98 (35.1%) were solid organ-transplant recipients. Anti-SARS-CoV-2 antibody levels increased in 74.9% of cases. Across the entire cohort, the median absolute antibody levels (expressed in AU/mL) increased from 7 (interquartile range (IQR), 0.1-69) to 243 (IQR, 2-4749) after the booster dose. The response significantly varied across subgroups: The transplant cohort showed the greatest increase in absolute antibody levels (from 52 (IQR, 7.25-184.5) to 1824 (IQR, 161-9686)), followed by the rheumatology (from 22 (IQR, 1-106) to 1291 (IQR, 6-6231)) and haemato-oncology (from 1 (IQR, 0.1-7) to 7.5 (IQR, 0.1-407.5)) cohorts. The χA third dose of BNT162b2 is immunogenic in most immunosuppressed individuals, although antibody response may differ based on the type of disease and immunosuppression. The antibody level that correlates with protection is still unknown; thus, future studies are needed to evaluate clinical outcomes.

How do judges formulate their written decisions when rejecting plaintiffs’ requests in a welfare context? In this paper, based on our thematic analysis, we show how judges construct a nuanced concept of ‘welfare deservingness’ to narratively mitigate their own moral and emotional tensions when making decisions on remedies in public-housing cases. Deploying a notion borrowed from criminology—‘neutralisation techniques’—we discuss the material and symbolic implications of this concept, contributing to the theoretical discussion of both poverty law and legal professionalism. We claim that judges use ‘neutralisation techniques’ to negotiate, justify, and explain their decisions while attempting to avoid or lessen the dilemmas they typically face, given the scarcity of housing resources and their inability to grant material assistance. Employing these techniques, the judges create ‘deservingness spectrum’ that enables them to essentially subvert the binary division of accepted/denied cases. At one end of this spectrum, the denial of the plaintiff's ‘victim’ status is enacted through the negation of symbolic deservingness and, thus, the denial of housing is framed as a warranted sanction on the plaintiff's reproachable character. At the other end, the techniques allow the judges to recognise ‘symbolic deservingness’ while still not providing material aid. Judges are therefore able to preserve their professional status and sense of moral rectitude when making such unenviable housing decisions. More broadly, our analysis offers a novel lens through which to critically understand judicial decision-making in welfare jurisprudence.

Chitosan is a nature-sourced polysaccharide widely used in numerous applications. The antibacterial potential of chitosan has attracted researchers to further develop and utilize this polymer for the formation of biocompatible antibacterial agents for both the food and healthcare industries. The tested hypothesis in this study is that modified N-alkylaminated chitosan nanoparticles (CNPs) have selective binding properties to Gram-negative bacteria strains that result in bacterial aggregation. Various bacterial strains were tested of five Gram-negative bacteria including Erwinia carotovora, Escherichia coli, Pseudomonas aeruginosa, Salmonella, and Serratia marcescens, as well as three Gram-positive bacteria strains including Bacillus licheniformis, Bacillus megaterium, and Bacillus subtilis. The fluorescence microscopy characterization showed that the presence of CNPs caused the aggregation of Escherichia coli bacteria cells, where modified CNPs with a shorter chain length of the substituent caused a higher aggregation effect. Moreover, it was found that the CNPs exhibited a selective binding behavior to Gram-negative as compared to Gram-positive bacteria strains, mainly to Escherichia coli and Salmonella. Also, the scanning electron microscopy characterization showed that CNPs exhibited selective binding to Gram-negative bacteria, which was especially understood when both Gram-negative and Gram-positive bacteria strains were within the same sample. In addition, the bacterial viability assay suggests that CNPs with a lower degree of substitution have a higher inhibitory effect on bacterial growth. CNPs with longer side chains had a less inhibitory effect on the bacterial growth of Gram-negative strains, where a concentration-dependent response pattern was only seen for the cases of Gram-negative strains, and not for the case of Gram-positive strain. To conclude, the further understanding of the selective binding of CNPs to Gram-negative bacteria strains may produce new opportunities for the discovery and characterization of effective antibacterial agents.