Efficacy of cognitive behaviour therapy versus anxiety management for body dysmorphic disorder: a randomised controlled trial

Background: The evidence base for the effectiveness of cognitive behaviour therapy (CBT) for treating Body Dysmorphic Disorder (BDD) is weak. Aims: To determine if CBT is more effective than anxiety management (AM) in an out-patient setting. Method: A single blind, stratified parallel-group randomized controlled trial. The primary endpoint was at 12 weeks, and the Yale Brown Obsessive Compulsive Scale for BDD (BDD-YBOCS) was the primary outcome measure. Secondary measures for BDD included the Brown Assessment of Beliefs (BABS), the Appearance Anxiety Inventory (AAI) and the Body Image Quality of Life Inventory (BIQLI). The outcome measures were collected at baseline and week 12. The CBT group, unlike the AM group, had 4 further weekly sessions that were analysed for their added value. Both groups then completed measures at their 1-month follow-up. Forty-six participants, with DSM-IV diagnosis of BDD including those with a delusional BDD were randomly allocated to either CBT or AM. Results: At 12 weeks, CBT was found to be significantly superior to AM on the BDD-YBOCS ( = -7.19, S.E. () = 2.61, p < .01, C.I. = -12.31, -2.07, d 0.99) as well as the secondary outcome measures of the BABS, AAI and BIQL. Further benefits occurred by Week 16 within the CBT group. There were no differences in outcome for those with delusional BDD or depression. Conclusions: CBT is an effective intervention for people with BDD even with delusional beliefs or depression and is more effective than anxiety management over 12 weeks

Anti-PSMA CAR-engineered NK-92 Cells: An Off-the-shelf Cell Therapy for Prostate Cancer

Prostate cancer (PCa) has become the most common cancer among males in Europe and the USA. Adoptive immunotherapy appears a promising strategy to control the advanced stages of the disease by specifically targeting the tumor, in particular through chimeric antigen receptor T (CAR-T) cell therapy. Despite the advancements of CAR-T technology in the treatment of hematological malignancies, solid tumors still represent a challenge. To overcome current limits, other cellular effectors than T lymphocytes are under study as possible candidates for CAR-engineered cancer immunotherapy. A novel approach involves the NK-92 cell line, which mediates strong cytotoxic responses against a variety of tumor cells but has no effect on non-malignant healthy counterparts. Here, we report a novel therapeutic approach against PCa based on engineering of NK-92 cells with a CAR recognizing the human prostate-specific membrane antigen (PSMA), which is overexpressed in prostatic neoplastic cells. More importantly, the potential utility of NK-92/CAR cells to treat PCa has not yet been explored. Upon CAR transduction, NK-92/CAR cells acquired high and specific lytic activity against PSMA-expressing prostate cancer cells in vitro, and also underwent degranulation and produced high levels of IFN-\u3b3 in response to antigen recognition. Lethal irradiation of the effectors, a safety measure requested for the clinical application of retargeted NK-92 cells, fully abrogated replication but did not impact on phenotype and short-term functionality. PSMA-specific recognition and antitumor activity were retained in vivo, as adoptive transfer of irradiated NK-92/CAR cells in prostate cancer-bearing mice restrained tumor growth and improved survival. Anti-PSMA CAR-modified NK-92 cells represent a universal, off-the-shelf, renewable, and cost-effective product endowed with relevant potentialities as a therapeutic approach for PCa immunotherapy

Risk factors for septic arthritis in patients with joint disease: A prospective study

Objective. To quantify potential risk factors for septic arthritis, in order to identify a basis for prevention. Methods. The occurrence of potential risk factors for septic arthritis in patients with joint diseases attending a rheumatic disease clinic was prospectively monitored at 3-m onth intervals over a period of 3 years. Potential risk factors investigated were type of joint disease, comorbidity, medication, joint prosthesis, infections, and invasive procedures. The frequencies of risk factors in patients with and those without septic arthritis were compared using multiple logistic regression analysis. Results. There were 37 patients with and 4,870 without septic arthritis. Risk factors for developing septic arthritis were age ≥80 years (odds ratio [OR] = 3.5, 95% confidence interval [95% CI] 1.4–8.6), diabetes mellitus (OR = 3.3, 95% CI 1.1–10.1), rheumatoid arthritis (OR = 4.0, 95% CI 1.9–8.3), hip and/or knee prosthesis (OR = 15, 95% CI 4.1–54.3), joint surgery (OR = 5.1, 95% CI 2.2–11.9), and skin infection (OR = 27.2, 95% CI 7.6–97.1) Conclusion. These findings indicate that preventive measures against septic arthritis in patients with joint diseases should mainly be directed at those with joint prostheses and/or skin infection

Adoptive cell therapy of triple negative breast cancer with redirected cytokine-induced killer cells

Cytokine-Induced Killer (CIK) cells share several functional and phenotypical properties of both T and natural killer (NK) cells. They represent an attractive approach for cell-based immunotherapy, as they do not require antigen-specific priming for tumor cell recognition, and can be rapidly expanded in vitro. Their relevant expression of Fc\u3b3RIIIa (CD16a) can be exploited in combination with clinical-grade monoclonal antibodies (mAbs) to redirect their lytic activity in an antigen-specific manner. Here, we report the efficacy of this combined approach against triple negative breast cancer (TNBC), an aggressive tumor that still requires therapeutic options. Different primitive and metastatic TNBC cancer mouse models were established in NSG mice, either by implanting patient-derived TNBC samples or injecting MDA-MB-231 cells orthotopically or intravenously. The combined treatment consisted in the repeated intratumoral or intravenous injection of CIK cells and cetuximab. Tumor growth and metastasis were monitored by bioluminescence or immunohistochemistry, and survival was recorded. CIK cells plus cetuximab significantly restrained primitive tumor growth in mice, either in patient-derived tumor xenografts or MDA-MB-231 cell line models. Moreover, this approach almost completely abolished metastasis spreading and dramatically improved survival. The antigen-specific mAb favored tumor and metastasis tissue infiltration by CIK cells, and led to an enrichment of the CD16a+ subset. Data highlight the potentiality of this novel immunotherapy strategy where a nonspecific cytotoxic cell population can be converted into tumor-specific effectors with clinical-grade antibodies, thus providing not only a therapeutic option for TNBC but also a valid alternative to more complex approaches based on chimeric antigen receptor-engineered cells. List of abbreviations: ACT, Adoptive Cell Transfer; ADCC, Antibody-Dependent Cell-mediated Cytotoxicity; ADP, Adenosine diphosphate; BLI, Bioluminescence Imaging; CAR, Chimeric Antigen Receptor; CIK, Cytokine Induced Killer cells; CTX, Cetuximab; DMEM, Dulbecco\u2019s Modified Eagle Medium; EGFR, Human Epidermal Growth Factor 1; ER, Estrogen; FBS, Fetal Bovine Serum; FFPE, Formalin-Fixed Paraffin-Embedded; GMP, Good Manufacturing Practices; GVHD, Graft Versus Host Disease; HER2, Human Epidermal Growth Factor 2; HRP, Horseradish Peroxidase; IFN-\u3b3, Interferon-\u3b3; IHC, Immunohistochemistry; IL-2, Interleukin-2; ISO, Irrelevant antibody; i.t., intratumoral; i.v., intravenous, mAbs, Monoclonal Antibodies; mIHC, Multiplex Fluorescence Immunohistochemistry; MHC, Major Histocompatibility Complex; NK, Natural Killer; NKG2D, Natural-Killer group 2 member D; NSG, NOD/SCID common \u3b3 chain knockout; PARP, Poly ADP-ribose polymerase; PBMCs, Peripheral Blood Mononuclear Cells; PBS, Phosphate-buffered saline; PDX, Patient-derived xenograft; PR, Progesterone; rhIFN-\u3b3, Recombinant Human Interferon-\u3b3; RPMI, Roswell Park Memorial Institute; STR, Short tandem Repeat; TCR, T Cell Receptor; TNBC, Triple Negative Breast Cancer; TSA, Tyramide Signal Amplification

Comparison of speech intelligibility in quiet and in noise after hearing aid fitting according to a purely prescriptive and a comparative fitting procedure

We compared two different types of hearing-aid fitting procedures in a double-blind randomized clinical study. Hearing aid fittings based on a purely prescriptive procedure (the NAL-RP formula) were compared to a comparative fitting procedure based on optimizing speech intelligibility scores. Main outcome measures were improvement of speech intelligibility scores in quiet and in noise. Data were related to the real-ear insertion responses that were measured after fitting. For analysis purposes subgroups were composed according to degree of hearing loss, characterized by unaided speech intelligibility in quiet, previous experience with hearing aids, unilateral or bilateral fittings and type of hearing aid. We found equal improvement of speech intelligibility in quiet, while fitting according to the prescriptive formula resulted in a somewhat better performance as expressed by the speech-to-noise ratio in comparison to the comparative procedure. Both procedures resulted in comparable real-ear insertion responses

Author Correction: School grades and educational attainments of adolescents and young adults born preterm

The original version of this Article contained an error in Figures 2, 3, 4 and 5, where the legend for the visual cues incorrectly states ‘Model 2’ for the black square. The correct legends now read: (Figure presented.) The original Figures 2, 3, 4 and 5 and their respective accompanying legend appear below. The original Article has been corrected

School Grades and Educational Attainments of Adolescents and Young Adults Born Preterm

Attendance in special education (SE) is more common among individuals born preterm than among those born at term. Less is known about school grades of those born preterm in mainstream education (ME), and how these grades predict later educational attainment. This population-based register-linkage study assessed (1) attendance in SE, and then focused on those in ME by assessing (2) school grades at 16 year, (3) completed educational level at 25 year, and (4) school grades as predictors for completed education by gestational age (GA) with full-term birth (39-41 completed weeks) as reference. The sample comprised 223,744 individuals (10,521 preterm, 4.7%) born in Finland (1/1987-9/1990). Of the sample, 4.9% attended SE. Those born preterm had up to 5.5-fold rates for SE. In ME, those born extremely preterm (EPT) had marginally lower mathematics grades compared with full-term counterparts, whilst those born late preterm or early term had slightly higher grades. Those born EPT or very preterm had lower physical education grades in ME. However, the minor differences in school grades according to GA appear not to translate into educational differences in young adulthood. The associations between school grades at 16 year and completed education at 25 year did not vary by GA.Peer reviewe

Hyaluronan is a natural and effective immunological adjuvant for protein-based vaccines

One of the main goals of vaccine research is the development of adjuvants that can enhance immune responses and are both safe and biocompatible. We explored the application of the natural polymer hyaluronan (HA) as a promising immunological adjuvant for protein-based vaccines. Chemical conjugation of HA to antigens strongly increased their immunogenicity, reduced booster requirements, and allowed antigen dose sparing. HA-based bioconjugates stimulated robust and long-lasting humoral responses without the addition of other immunostimulatory compounds and proved highly efficient when compared to other adjuvants. Due to its intrinsic biocompatibility, HA allowed the exploitation of different injection routes and did not induce inflammation at the inoculation site. This polymer promoted rapid translocation of the antigen to draining lymph nodes, thus facilitating encounters with antigen-presenting cells. Overall, HA can be regarded as an effective and biocompatible adjuvant to be exploited for the design of a wide variety of vaccines

Improving birth weight measurement and recording practices in Kenya and Tanzania: a prospective intervention study with historical controls

BACKGROUND: Low birth weight (LBW) is a significant public health concern given its association with early-life mortality and other adverse health consequences that can impact the entire life cycle. In many countries, accurate estimates of LBW prevalence are lacking due to inaccuracies in collection and gaps in available data. Our study aimed to determine LBW prevalence among facility-born infants in selected areas of Kenya and Tanzania and to assess whether the introduction of an intervention to improve the accuracy of birth weight measurement would result in a meaningfully different estimate of LBW prevalence than current practice. METHODS: We carried out a historically controlled intervention study in 22 health facilities in Kenya and three health facilities in Tanzania. The intervention included: provision of high-quality digital scales, training of nursing staff on accurate birth weight measurement, recording and scale calibration practices, and quality maintenance support that consisted of enhanced supervision and feedback (prospective arm). The historically controlled data were birth weights from the same facilities recorded in maternity registers for the same calendar months from the previous year measured using routine practices and manual scales. We calculated mean birth weight (95% confidence interval CI), mean difference in LBW prevalence, and respective risk ratio (95% CI) between study arms. RESULTS: Between October 2019 and February 2020, we prospectively collected birth weights from 8441 newborns in Kenya and 4294 in Tanzania. Historical data were available from 9318 newborns in Kenya and 12,007 in Tanzania. In the prospective sample, the prevalence of LBW was 12.6% (95% confidence intervals [CI]: 10.9%-14.4%) in Kenya and 18.2% (12.2%-24.2%) in Tanzania. In the historical sample, the corresponding prevalence estimates were 7.8% (6.5%-9.2%) and 10.0% (8.6%-11.4%). Compared to the retrospective sample, the LBW prevalence in the prospective sample was 4.8% points (3.2%-6.4%) higher in Kenya and 8.2% points (2.3%-14.0%) higher in Tanzania, corresponding to a risk ratio of 1.61 (1.38-1.88) in Kenya and 1.81 (1.30-2.52) in Tanzania. CONCLUSION: Routine birth weight records underestimate the risk of LBW among facility-born infants in Kenya and Tanzania. The quality of birth weight data can be improved by a simple intervention consisting of provision of digital scales and supportive training

Search for New Physics with Jets and Missing Transverse Momentum in pp collisions at sqrt(s) = 7 TeV

A search for new physics is presented based on an event signature of at least three jets accompanied by large missing transverse momentum, using a data sample corresponding to an integrated luminosity of 36 inverse picobarns collected in proton--proton collisions at sqrt(s)=7 TeV with the CMS detector at the LHC. No excess of events is observed above the expected standard model backgrounds, which are all estimated from the data. Exclusion limits are presented for the constrained minimal supersymmetric extension of the standard model. Cross section limits are also presented using simplified models with new particles decaying to an undetected particle and one or two jets