Is gender primacy universal?

Emerging evidence suggests that gender is a defining feature of personhood. Studies show that gender is the primary social category individuals use to perceive humanness and the social category most strongly related to seeing someone-or something-as human. However, the universality of gender's primacy in social perception and its precedence over other social categories like race and age have been debated. We examined the primacy of gender perception in the Mayangna community of Nicaragua, a population with minimal exposure to Western influences, to test whether the primacy of gender categorization in humanization is more likely to be a culturally specific construct or a cross-cultural and potentially universal phenomenon. Consistent with findings from North American populations [A. E. Martin, M. F. Mason, J. Pers. Soc. Psychol. 123, 292-315 (2022)], the Mayangna ascribed gender to nonhuman objects more strongly than any other social category-including age, race, sexual orientation, disability, and religion-and gender was the only social category that uniquely predicted perceived humanness (i.e., the extent to which a nonhuman entity was seen as "human"). This pattern persisted even in the most isolated subgroup of the sample, who had no exposure to Western culture or media. The present results thus suggest that gender's primacy in social cognition is a widely generalizable, and potentially universal, phenomenon.

Matrixed CDR grafting: A neoclassical framework for antibody humanization and developability.

Discovery and optimization of a biotherapeutic monoclonal antibody requires a careful balance of target engagement and physicochemical developability properties. To take full advantage of the sequence diversity provided by different antibody discovery platforms, a rapid and reliable process for humanization of antibodies from nonhuman sources is required. Canonically, maximizing homology of the human variable region (V-region) to the original germline was believed to result in preservation of binding, often without much consideration for inherent molecular properties. We expand on this approach by grafting the complementary determining regions (CDRs) of a mouse anti-LAG3 antibody into an extensive matrix of human variable heavy chain (VH) and variable light chain (VL) framework regions with substantially broader sequence homology to assess the impact on complementary determining region-framework compatibility through progressive evaluation of expression, affinity, biophysical developability, and function. Specific VH and VL framework sequences were associated with major expression and purification phenotypes. Greater VL sequence conservation was correlated with retained or improved affinity. Analysis of grafts that bound the target demonstrated that initial developability criteria were significantly impacted by VH, but not VL. In contrast, cell binding and functional characteristics were significantly impacted by VL, but not VH. Principal component analysis of all factors identified multiple grafts that exhibited more favorable antibody properties, notably with nonoptimal sequence conservation. Overall, this study demonstrates that modern throughput systems enable a more thorough, customizable, and systematic analysis of graft-framework combinations, resulting in humanized antibodies with improved global properties that may progress through development more quickly and with a greater probability of success.

Engineering a human P2X2 receptor with altered ligand selectivity in yeast.

P2X receptors are a family of ligand gated ion channels found in a range of eukaryotic species including humans but are not naturally present in the yeast Saccharomyces cerevisiae. We demonstrate the first recombinant expression and functional gating of the P2X2 receptor in baker's yeast. We leverage the yeast host for facile genetic screens of mutant P2X2 by performing site saturation mutagenesis at residues of interest, including SNPs implicated in deafness and at residues involved in native binding. Deep mutational analysis and rounds of genetic engineering yield mutant P2X2 F303Y A304W, which has altered ligand selectivity toward the ATP analog AMP-PNP. The F303Y A304W variant shows over 100-fold increased intracellular calcium amplitudes with AMP-PNP compared to the WT receptor and has a much lower desensitization rate. Since AMP-PNP does not naturally activate P2X receptors, the F303Y A304W P2X2 may be a starting point for downstream applications in chemogenetic cellular control. Interestingly, the A304W mutation selectively destabilizes the desensitized state, which may provide a mechanistic basis for receptor opening with suboptimal agonists. The yeast system represents an inexpensive, scalable platform for ion channel characterization and engineering by circumventing the more expensive and time-consuming methodologies involving mammalian hosts.

The Moral Psychology of Artificial Intelligence.

Moral psychology was shaped around three categories of agents and patients: humans, other animals, and supernatural beings. Rapid progress in artificial intelligence has introduced a fourth category for our moral psychology to deal with: intelligent machines. Machines can perform as moral agents, making decisions that affect the outcomes of human patients or solving moral dilemmas without human supervision. Machines can be perceived as moral patients, whose outcomes can be affected by human decisions, with important consequences for human-machine cooperation. Machines can be moral proxies that human agents and patients send as their delegates to moral interactions or use as a disguise in these interactions. Here we review the experimental literature on machines as moral agents, moral patients, and moral proxies, with a focus on recent findings and the open questions that they suggest.

Humanization of the antigen-recognition domain does not impinge on the antigen-binding, cytokine secretion, and antitumor reactivity of humanized nanobody-based CD19-redirected CAR-T cells.

BACKGROUND: The immunogenicity of the antigen-recognition domains of chimeric antigen receptor (CAR)-T cells leads to immune responses that may compromise the antitumor effects of the adoptively transferred T cells. Herein, we attempt to humanize a CD19-specific VHH (named H85) using in silico techniques and investigate the impact of antigen-recognition domain humanization on CAR expression and density, cytokine secretion, and cytolytic reactivity of CAR-T cells based on the humanized VHH. METHODS: H85 was humanized (named HuH85), and then HuH85 was compared with H85 in terms of conformational structure, physicochemical properties, antigenicity and immunogenicity, solubility, flexibility, stability, and CD19-binding capacity using in silico techniques. Next, H85CAR-T cells and HuH85CAR-T cells were developed and CAR expression and surface density were assessed via flow cytometry. Ultimately, the antitumor reactivity and secreted levels of IFN-γ, IL-2, and TNF-α were assessed following the co-cultivation of the CAR-T cells with Ramos, Namalwa, and K562 cells. RESULTS: In silico findings demonstrated no negative impacts on HuH85 as a result of humanization. Ultimately, H85CAR and HuH85CAR could be surface-expressed on transduced T cells at comparable levels as assessed via mean fluorescence intensity. Moreover, H85CAR-T cells and HuH85CAR-T cells mediated comparable antitumor effects against Ramos and Namalwa cells and secreted comparable levels of IFN-γ, IL-2, and TNF-α following co-cultivation. CONCLUSION: HuH85 can be used to develop immunotherapeutics against CD19-associated hematologic malignancies. Moreover, HuH85CAR-T cells must be further investigated in vitro and in preclinical xenograft models of CD19+ leukemias and lymphomas before advancing into clinical trials.

Bridge the gap caused by public health crises: medical humanization and communication skills build a psychological bond that satisfies patients.

BACKGROUND: Patient satisfaction is an important outcome domain of patient-centered care. Medical humanization follows the patient-centered principle and provides a more holistic view to treat patients. The COVID-19 pandemic posed significant barriers to maintaining medical humanization. However, empirical study on the relationship between medical humanization and patient satisfaction is clearly absent. OBJECTIVES: We examined the mediation effects of communication on the relationship between medical humanization and patient satisfaction when faced with a huge public health crisis like the COVID-19 pandemic, and the moderation effect of medical institutional trust on the mediation models. METHODS: A cross-sectional survey study was performed. A final sample size of 1445 patients was surveyed on medical humanization, communication, patient satisfaction and medical institutional trust. RESULTS: All correlations were significantly positive across the main variables (r = 0.35-0.67, p < 0.001 for all) except for medical institutional trust, which was negatively correlated with the medical humanization (r=-0.14, p < 0.001). Moderated mediation analysis showed that the indirect effect of medical humanization on patient satisfaction through communication was significant (b = 0.22, 95% CI: 0.18 ~ 0.25). Medical institutional trust significantly moderated the effect of medical humanization on patient satisfaction (b=-0.09, p < 0.001) and the effect of medical humanization on communication (b= -0.14, p < 0.001). CONCLUSION: Medical humanization positively influence patient satisfaction, communication mediated the association between medical humanization and patient satisfaction, and medical institutional trust negatively moderated the effects of medical humanization on patient satisfaction and communication. These findings suggest that humanistic communication contributes to patient satisfaction in the face of a huge public health crisis, and patients' evaluation of satisfaction is also regulated by rational cognition.

Exploring patients and caregivers needs and experiences in oncological physiotherapy: a call for collaborative care.

PURPOSE: This study explores whether the full potential of physiotherapy is reaching cancer patients and their caregivers at all stages of the oncological process, aiming to identify gaps and opportunities for improving care. METHODS: The World Cafe co-design methodology facilitated discussions among cancer patients and caregivers. This dynamic, inclusive, and engaging approach fostered diverse perspectives and deeper insights through collaborative and flexible discussions. Sessions were recorded, transcribed, and qualitatively analyzed. RESULTS: Sixteen participants were involved (eight cancer survivors and eight caregivers). The mean age of cancer survivors was 63.8 years, while the average age of caregivers was 59.3 years. Breast cancer was the most prevalent diagnosis among patients, and most caregivers had lost their family members to cancer. Analysis revealed two primary themes: "feeling cared for" and "the role of physiotherapy in the oncological process." Key findings highlight the need for more humanized healthcare, with professionals providing support through effective communication and empathy. Significant gaps were detected in both systematic referrals to physiotherapists and their integration into care teams. Testimonies highlighted the lack of knowledge about the full potential of physiotherapy in oncology, hindering access. There was also a demand for recognizing specialized oncological physiotherapists. CONCLUSIONS: These findings highlight significant gaps in physiotherapy care for cancer survivors and caregivers, including unmet needs due to the lack of information, resources, and effective communication. Future efforts should focus on increasing the visibility of physiotherapy, integrating specialized physiotherapists into oncology teams, and enhancing the emotional education of healthcare professionals to provide more humanized care.

Implementation feasibility of animal-assisted therapy in a pediatric intensive care unit: effectiveness on reduction of pain, fear, and anxiety.

Animal-assisted therapies are an innovative strategy within health care humanization initiatives, and they could play a role in the reduction of pain or anxiety. The main objective of this work was to evaluate the feasibility of implementing animal-assisted therapy in a pediatric intensive care unit and its effectiveness for the reduction of pain, fear, and anxiety. A prospective, quasi-experimental study of animal-assisted therapy was designed in the pediatric intensive care unit of the Hospital Universitario 12 de Octubre of Madrid, from January 2019 to December 2019. The study sample included patients who had been admitted to the unit and were over 3 years old. Satisfaction surveys were collected from the patients, family, and health personnel involved. Physiological variables and the level of pain (visual analog scale or Wong-Baker scale), fear (Child Medical Fear Scale), and anxiety (modified Yale Preoperatory Anxiety Scale) were evaluated before and after each session. Any existence of adverse events was recorded. A total of 74 therapy sessions were performed on 61 patients. All sessions were completed without any adverse effects. A total of 164 surveys were collected, providing an overall project rating of 9.69 out of a possible 10. The survey comments were found to be positive in most cases. No differences were found in the physiological variables measured before and after each session. There was a statistically significant decrease in pain, fear, and anxiety levels (p < 0.01).   Conclusion: The implementation of an animal-assisted therapy project in a pediatric intensive care unit is feasible and safe and has a high degree of acceptance among both participants and healthcare staff. Animal-assisted therapy is effective for the reduction of pain, fear, and anxiety, and therefore, it could be considered an adjunct to non-pharmacological therapy. What is Known: • Animal assisted therapies (AAT) are an innovative strategy that could be beneficial to help pediatrics patients cope with admission difficulties and could even play a role in reducing pain, anxiety and/or delirium. • To date there are not studies to analyze the effectiveness of AAT in the field of Pediatric Intesive Care. What is New: • Our study confirms the feasibility and effectiveness of the implementation of an AAT in the field of Pediatric Intensive Care with a high degree of acceptance by participants, caregivers and healthcare personnel. • AAT demonstrated a reduction in pain, fear and anxiety in pediatrics patients admitted to Pediatric Intensive Care Unit.

Humanization with CD34-positive hematopoietic stem cells in NOG-EXL mice results in improved long-term survival and less severe myeloid cell hyperactivation phenotype relative to NSG-SGM3 mice.

NSG-SGM3 and NOG-EXL mice combine severe immunodeficiency with transgenic expression of human myeloid stimulatory cytokines, resulting in marked expansion of myeloid populations upon humanization with CD34+ hematopoietic stem cells (HSCs). Humanized NSG-SGM3 mice typically develop a lethal macrophage activation syndrome and mast cell hyperplasia that limit their use in long-term studies (e.g., humanization followed by tumor xenotransplantation). It is currently unclear to what extent humanized NOG-EXL mice suffer from the same condition observed in humanized NSG-SGM3 mice. We compared the effects of human CD34+ HSC engraftment in these two strains in an orthotopic patient-derived glioblastoma model. NSG-SGM3 mice humanized in-house were compared to NOG-EXL mice humanized in-house and commercially available humanized NOG-EXL mice. Mice were euthanized at humane or study endpoints, and complete pathological assessments were performed. A semiquantitative multiparametric clinicopathological scoring system was developed to characterize chimeric myeloid cell hyperactivation (MCH) syndrome. NSG-SGM3 mice were euthanized at 16 weeks after humanization because of severe deterioration of clinical conditions. Humanized NOG-EXL mice survived to the study endpoint at 22 weeks after humanization and showed less-severe MCH phenotypes than NSG-SGM3 mice. Major differences included the lack of mast cell expansion and limited tissue/organ involvement in NOG-EXL mice compared to NSG-SGM3 mice. Engraftment of human lymphocytes, assessed by immunohistochemistry, was similar in the two strains. The longer survival and decreased MCH phenotype severity in NOG-EXL mice enabled their use in a tumor xenotransplantation study. The NOG-EXL model is better suited than the NSG-SGM3 model for immuno-oncology studies requiring long-term survival after humanization.

Eating pigs, not Peppa Pig: The effect of identifiability on children's propensity to humanize, befriend, and consume edible animals.

This research aimed to provide experimental evidence on whether identifying an edible animal by a name and specific preferences encourages children to perceive the animal as more similar to humans, increases their willingness to befriend the animal, and makes them less willing to consume it. In two pre-registered studies involving 208 preschool children, participants were presented with pictures of pigs (Study 1) and chickens (Study 2). In the identifiability condition, one animal was depicted with individual qualities such as a name and personal preferences, while in the non-identifiability condition, animals were portrayed with characteristics representative of the entire species. The children then rated their desire to befriend and consume the animal, while in Study 2, they also rated the animal's similarity to humans. The results revealed that animal identifiability led to higher perceived similarity to humans, increased the desire to befriend it, and reduced inclination to consume the animal. These findings highlight animal identifiability's powerful and robust effect on children's attitudes toward edible animals.

Parents' and nurses' affective perception of a pictorial intervention in a pediatric hospital environment: Quasi-experimental design pre-post-testing.

BACKGROUND/AIM: The humanization of the hospital environment of pediatric departments represents an area of research and intervention on improving the quality of life for hospitalized patients, but also that one of relatives and health professionals. The aim of the study was to test, in a sample of nurses and hospitalized children's parents, whether the pictorial intervention impacted the perceptions of affective qualities of hospital environment. METHODS: This quasi-experimental design study investigated the effects of a pictorial humanization intervention which consisted of some naturalistic and colorful illustrations in the corridor of two pediatric wards of an Italian hospital. A total of 425 parents of hospitalized children and 80 nurses were asked to complete the Italian version of the "Scale of measurement of the affective qualities of places" in two different moments: 1) before the pictorial intervention and 2) three months after its implementation. RESULTS: For all participants (parents and nurses), results showed a significant effect of pictorial intervention with the four positive dimensions investigated (Relaxing, Exciting, Pleasant, and Stimulating) reporting higher scores after being performed it, and with the four negative dimensions (Distressing, Gloomy, Unpleasant, Sleepy) showing lower scores. CONCLUSIONS: Data suggest that the pictorial intervention could be particularly useful to create more welcoming hospital environments, reducing distress levels from hospitalized patients, but also of relatives and healthcare professionals. IMPLICATIONS TO PRACTICE: Pictorial interventions improve the emotional atmosphere in pediatric healthcare settings. Integrating visual elements related to care and healing enhances user experience, creating a more welcoming environment.

Dehumanization in intensive care units and standard wards: A survey for a comparative cross-sectional study.

OBJECTIVES: Dehumanization refers to the practice of treating patients as objects rather than individuals with dignity and respect. METHODS: This study explores dehumanization in healthcare, specifically mechanistic dehumanization and self-dehumanization, which can result in poor care and negative outcomes. A cross-sectional observational study was conducted using a dehumanization questionnaire given to 324 nurses in various departments. The study took place at ANONYMIZED, from September to November 2022. The questionnaire analyzed emotions like anger, impatience, and apathy, identified as key dehumanizing factors. RESULTS: Results indicated that these emotions were prevalent in nurses' perceptions of patients. Interestingly, while Intensive Care nurses often involved families in patient care, leading to higher satisfaction, ward department nurses sometimes viewed patient or family relationships as obstacles. Despite this, 66 % of nurses reported satisfaction with the care provided, while 12 % were indifferent. CONCLUSIONS: The study concludes that the root of dehumanization lies in nurses' inability to feel emotions, the impersonality of care, and the sterility of assistance, leading to self-dehumanization. To combat this, the study suggests strengthening nursing autonomy and education and fostering a positive work environment. The way nurses perceive themselves directly impacts their treatment of patients.

Cultural adaptation and validation of the caring behaviors assessment tool into Spanish.

BACKGROUND: The aim of the research was to translate, culturally adapt and validate the Caring Behaviors Assessment (CBA) tool in Spain, ensuring its appropriateness in the Spanish cultural context. METHODS: Three-phase cross-cultural adaptation and validation study. Phase 1 involved the transculturation process, which included translation of the CBA tool from English to Spanish, back-translation, and refinement of the translated tool based on pilot testing and linguistic and cultural adjustments. Phase 2 involved training research assistants to ensure standardized administration of the instrument. Phase 3 involved administering the transculturally-adapted tool to a non-probabilistic sample of 402 adults who had been hospitalized within the previous 6 months. Statistical analyses were conducted to assess the consistency of the item-scale, demographic differences, validity of the tool, and the importance of various caring behaviors within the Spanish cultural context. R statistical software version 4.3.3 and psych package version 2.4.1 were used for statistical analyses. RESULTS: The overall internal consistency of the CBA tool was high, indicating its reliability for assessing caring behaviors. The subscales within the instrument also demonstrated high internal consistency. Descriptive analysis revealed that Spanish participants prioritized technical and cognitive aspects of care over emotional and existential dimensions. CONCLUSIONS: The new version of the tool proved to be valid, reliable and culturally situated, which will facilitate the provision of objective and reliable data on patients beliefs about what is essential in terms of care behaviors in Spain.

A critical perspective on institutional violence against hospitalized children: Testimonies by health professionals and family members.

The purpose of this study is to understand institutional violence (IV) in the relationships between health professionals, hospitalized children, and family members. This is a qualitative study developed at the pediatric inpatient unit of a university hospital in the city of Salvador, Bahia, Brazil. The research participants consisted of 39 health professionals who specialized in pediatrics and 10 family members of hospitalized children. Semi-structured interviews were the method used for data collection. Using discourse analysis as a basis and taking a Foucauldian perspective, the researchers observed that the expressions of IV could be traced to abusive power relations within the system. We found four discursive forms within the data set: communication problems as IV, violence through inattention and neglect, violence as an action and consequent materialization on the body, and psychological violence as a submission mechanism. Based on these findings, we argue that professionals, managers, the scientific community, and users might be able to better guarantee the safety of children by recognizing IV and effectively intervening in it.

Debates on humanization of human-animal brain chimeras - are we putting the cart before the horses?

Research on human-animal chimeras have elicited alarms and prompted debates. Those involving the generation of chimeric brains, in which human brain cells become anatomically and functionally intertwined with their animal counterparts in varying ratios, either via xenografts or embryonic co-development, have been considered the most problematic. The moral issues stem from a potential for "humanization" of the animal brain, as well as speculative changes to the host animals' consciousness or sentience, with consequential alteration in the animal hosts' moral status. However, critical background knowledge appears to be missing to resolve these debates. Firstly, there is no consensus on animal sentience vis-à-vis that of humans, and no established methodology that would allow a wholesome and objective assessment of changes in animal sentience resulting from the introduction of human brain cells. Knowledge in interspecies comparative neuropsychology that could allow effective demarcation of a state of "humanization" is also lacking. Secondly, moral status as a philosophical construct has no scientific and objective points of reference. Either changes in sentience or humanization effects would remain unclear unless there are some neuroscientific research grounding. For a bioethical stance based on moral status of human-animal brain chimera to make meaningful contributions to regulatory policies, it might first need to be adequately informed by, and with its arguments constructed, in a manner that are factually in line with the science. In may be prudent for approved research projects involving the generation of human-animal brain chimera to have a mandatory component of assessing plausible changes in sentience.

[The humanization of medical education: publications review].

The humanization of medical education is targeted at integration of humanitarian values and approaches into system of education of medical personnel to improve their professional and personal training. This process includes education in medical ethics, development of communication skills, stress management and implementation of humanitarian disciplines into the curriculum. The humanization contributes into formation of empathy, responsibility and professionalism in future physicians that helps to better understand and consider psychological, social and emotional needs of patients. The problems of including humanitarian sciences into medical education are associated with lack of systematic approach, adequate curricula and qualified lecturers. To optimize process, it is necessary to focus on education of ideals and beliefs, development of integrated curricula and enhancement of humanitarian component of education.

Generation and characterization of humanized affinity-matured EGFL6 antibodies for ovarian cancer therapy.

OBJECTIVES: Epidermal growth factor EGF-like domain multiple-6 (EGFL6) is highly expressed in high grade serous ovarian cancer and promotes both endothelial cell proliferation/angiogenesis and cancer cell proliferation/metastasis. As such it has been implicated as a therapeutic target. As a secreted factor, EGFL6 is a candidate for antibody therapy. The objectives of this study were to create and validate humanized affinity-matured EGFL6 neutralizing antibodies for clinical development. METHODS: A selected murine EGFL6 antibody was humanized using CDR grafting to create 26 variant humanized antibodies. These were screened and the lead candidate was affinity matured. Seven humanized affinity-matured EGFL6 antibodies were screened for their ability to block EGFL6 activity on cancer cells in vitro, two of which were selected and tested their therapeutic activity in vivo. RESULTS: Humanized affinity matured antibodies demonstrated high affinity for EGFL6 (150 pM to 2.67 nM). We found that several humanized affinity-matured EGFL6 antibodies specifically bound to recombinant, and native human EGFL6. Two lead antibodies were able to inhibit EGFL6-mediated (i) cancer cell migration, (ii) proliferation, and (iii) increase in ERK phosphorylation in cancer cells in vitro. Both lead antibodies restricted growth of an EGFL6 expressing ovarian cancer patient derived xenograft. Analysis of treated human tumor xenografts indicated that anti-EGFL6 therapy suppressed angiogenesis, inhibited tumor cell proliferation, and promoted tumor cell apoptosis. CONCLUSIONS: Our studies confirm the ability of these humanized affinity-matured antibodies to neutralize EGFL6 and acting as a therapeutic to restrict cancer growth. This work supports the development of these antibody for first-in-human clinical trials.

Health professionals' perceptions of planned home birth care within the Brazilian health system.

BACKGROUND: The American College of Obstetricians and Gynecologists, in its opinion of the Committee on Midwifery Practice, points out that planned home birth is a woman's and family's right to experience, but also to choose and be informed about, their baby's place of birth. The aim of this study was to understand obstetric nurses' perceptions of planned home childbirth care within the framework of the Brazilian obstetric model. METHOD: A qualitative study, with Snowball Sampling recruitment, totaling 20 obstetric nurses through semi-structured interviews between September 2022 and January 2023, remotely, using the Google Meet application and the recording feature. After the data had been collected, the material was transcribed in full and subjected to content analysis in the thematic modality with the support of ATLAS.ti 8.0 software. RESULTS: Obstetric care at home emerged as a counterpoint to hospital care and the biomedical model, providing care at home based on scientific evidence and humanization, bringing qualified information as a facilitator of access and financial costs as an obstacle to effective home birth. CONCLUSION: Understanding obstetric nurses' perceptions of planned home birth care in the context of the Brazilian obstetric model shows the need for progress as a public policy and for strategies to ensure quality and regulation.

Psychosocial changes during COVID-19 lockdown on nursing home residents, their relatives and clinical staff: a prospective observational study.

BACKGROUND: Previous works have observed an increase of depression and other psychological disorders on nursing home residents as a consequence of coronavirus disease 2019 (COVID-19) lockdown; however, there are few studies that have performed a comprehensive evaluation of all people involved in nursing homes environment. The objective of the work was to analyse the impact of lockdown on psychosocial factors of nursing home residents, relatives and clinical staff and how these variables have influenced residents' survival. METHODS: A prospective study was designed. Evaluations were performed at three different times: a) at the beginning of Spanish confinement, in March 2020; b) just before the second wave of the pandemic, with relaxation of security measures but in lockdown, and c) in January-February 2021, at the end of the second wave, when visits were already allowed. The study was conducted on three different nursing homes. Three hundred and one residents, 119 clinical staff and 51 relatives took part in the study. Anxiety and depression were evaluated in all participants. A scale on the meaning of suffering was also performed. In addition, burnout status was also determined in the clinical staff. RESULTS: All participants showed lower depression during lockdown, while at the beginning and at the end of the confinement, these values were significantly increased. In residents, these changes were dependent of cognitive status (p = 0.012). Anxiety was significantly higher in residents. The evolution of anxiety was similar than with depression, with lower values during confinement, although clinical staff showed higher anxiety levels at the beginning. The feeling of suffering was significantly lower in the clinical staff than in resident and relative groups. Residents' survival was dependent of cognitive status (p = 0.018) and voluntary confinement (p < 0.001). CONCLUSIONS: During the first COVID-19 lockdown, psychological wellbeing of residents cared in nursing homes, their relatives and staff did not seem to be seriously affected. Previous mental health in relatives and staff together with a resilient approach to the adversity might partly be protecting factors. The lack of consequences on residents' anxiety, depression and perception of social support may reflect the special attention and care they received. Finally, as in the current study only data of the first two COVID-19 waves were analysed, its findings might be partly generalized to all the pandemic.

First-in-class humanized FSH blocking antibody targets bone and fat.

Blocking the action of FSH genetically or pharmacologically in mice reduces body fat, lowers serum cholesterol, and increases bone mass, making an anti-FSH agent a potential therapeutic for three global epidemics: obesity, osteoporosis, and hypercholesterolemia. Here, we report the generation, structure, and function of a first-in-class, fully humanized, epitope-specific FSH blocking antibody with a KD of 7 nM. Protein thermal shift, molecular dynamics, and fine mapping of the FSH-FSH receptor interface confirm stable binding of the Fab domain to two of five receptor-interacting residues of the FSHß subunit, which is sufficient to block its interaction with the FSH receptor. In doing so, the humanized antibody profoundly inhibited FSH action in cell-based assays, a prelude to further preclinical and clinical testing.