Leishmania Uses Mincle to Target an Inhibitory ITAM Signaling Pathway in Dendritic Cells that Dampens Adaptive Immunity to Infection.

C-type lectin receptors sense a diversity of endogenous and exogenous ligands that may trigger differential responses. Here, we have found that human and mouse Mincle bind to a ligand released by Leishmania, a eukaryote parasite that evades an effective immune response. Mincle-deficient mice had milder dermal pathology and a tenth of the parasite burden compared to wild-type mice after Leishmania major intradermal ear infection. Mincle deficiency enhanced adaptive immunity against the parasite, correlating with increased activation, migration, and priming by Mincle-deficient dendritic cells (DCs). Leishmania triggered a Mincle-dependent inhibitory axis characterized by SHP1 coupling to the FcRγ chain. Selective loss of SHP1 in CD11c+ cells phenocopies enhanced adaptive immunity to Leishmania. In conclusion, Leishmania shifts Mincle to an inhibitory ITAM (ITAMi) configuration that impairs DC activation. Thus, ITAMi can be exploited for immune evasion by a pathogen and may represent a paradigm for ITAM-coupled receptors sensing self and non-self.

Type of goals set and progress towards these goals, as part of a behaviour change intervention, in people with mild cognitive impairment: a secondary analysis.

BACKGROUND: Mild cognitive impairment (MCI) affects 5-20% of older people in the UK, but often goes undiagnosed and is associated with increased risk of dementia. Targeting risk factors such as physical inactivity and social isolation through behaviour-change interventions could reduce this risk. However, it is unclear how MCI impacts engagement with these interventions. We aimed to explore how MCI affects goal-setting priorities and progress towards these goals in a behaviour-change intervention (HomeHealth). METHODS: This was a secondary analysis of a completed randomised controlled trial, HomeHealth, which started in January 2021 and recruited 386 participants aged 65 years and older with mild frailty according to the Clinical Frailty Scale from general practices and the community in England. Participants were randomly assigned (1:1) to receive either the HomeHealth intervention (n=195) or treatment as usual (n=191) for 6 months. An evidence-based behaviour change intervention supported older people to work on goals to maintain independence, addressing factors affecting capability, opportunity, and motivation. Goal setting and progress information was available for 167 (86%) of 195 participants who received the intervention. The type of goal set and goal progress (scale 0-2) were compared between participants with healthy cognition, those with potential MCI, and those with probable dementia (rated with Montreal Cognitive Assessment [MoCA]). Qualitative semi-structured interviews were conducted between Aug 16, 2022, and May 18, 2023, with 29 people with MCI who received the intervention, to explore the perceived impact of MCI on goal setting, progress, and maintenance. Data were analysed using codebook thematic analysis. FINDINGS: The mean age of participants was 80·8 years, 105 (63%) of 167 were women and 158 (95%) were white. 54 (32%) of 167 participants had healthy cognition, 94 (56%) had potential MCI, and 19 (11%) probable dementia. Distribution of goal type was similar across the three groups, with most participants setting mobility goals. Progress towards goals (scale 0-2) was similar in people with healthy cognition and potential MCI (1·24 and 1·18, respectively) but lower in those with probable dementia (0·76). However, all met the moderate progress cutoff (0·66-1·32). People with MCI recognised their cognition was getting worse but did not feel the HomeHealth intervention could help. Rather than setting new goals, people with MCI built on existing behaviours. Many did not initially understand the intervention and felt they would have benefitted from contact in between sessions or from more sessions to help goal progress. Once the sessions ended, less than a quarter of participants maintained the goal progress. INTERPRETATION: Interventions to help older adults age well can be successfully delivered in people with MCI, to help them set and make progress towards goals. However, to maintain changes, more intense support is needed. FUNDING: National Institute for Health and Care Research (NIHR) School for Primary Care Research, NIHR Health Technology Assessment.

Goal setting as part of a holistic intervention to promote independence in older people with mild frailty: a process evaluation alongside a randomised controlled trial.

BACKGROUND: Frailty is a condition resulting from a decline in physiological reserves caused by an accumulation of several deficits, which progressively impairs the ability to recover from health adverse events. Following a promising feasibility study, the HomeHealth trial assessed a holistic tailored intervention for older adults with mild frailty to promote independence in their own homes, compared with usual care. We aimed to understand how goal setting worked among older people with mild frailty. METHODS: This study was a process evaluation alongside the HomeHealth randomised trial in older adults with mild frailty. The intervention was delivered at participants' homes, either in person or by telephone or videoconferencing. We carried out semi-structured interviews with older participants who had received the intervention (between three and six appointments), on average 233 days (range 68-465) after their last appointment, purposively sampled according to age, gender, number of sessions attended, adverse events, ethnicity, Index of Multiple Deprivation, Montreal Cognitive Assessment (MoCA) and Barthel scores, research site, and HomeHealth worker. We also conducted interviews with HomeHealth workers who delivered the intervention (n=7). Interviews explored the experience and process of goal setting, benefits and challenges, perceived progress, and behaviour change maintenance after the service had finished. Ethics approval was obtained, and all participants gave informed consent. Interviews were thematically analysed. HomeHealth workers kept formal records of goals set and assessed progress towards goals (0-2 rating scale) during six monthly-sessions, which were descriptively summarised. FINDINGS: 56 interviews were completed between July 15, 2022, and May 18, 2023. Study participants (n=49) had a mean age of 80 years (range 66-94), including 32 (65%) women and 17 (35%) men. Participants self-identified as White (n=42), Asian (n=3), Black (n=2), Mixed (n=1), and other ethnic (n=1) backgrounds. Findings suggested goal setting could be both a challenge and a motivator for older participants with mild frailty. Goal setting worked well when the older person could identify a clear need and set realistic goals linked to functioning, which led to a positive sense of achievement. Challenges occurred when older people were already accessing multiple resources and health services, or where the terminology of "goals" was off-putting due to work or school connotations. Average progress towards goals was 1·15/2. Most participants set goals around improving mobility (or a combination of mobility and another goal type such as socialising), and there was evidence of participants sustaining these behaviour changes after the intervention. INTERPRETATION: Older people with mild frailty can engage well with goal setting to promote independence. The lapse between receiving the intervention and being interviewed limited recall for some participants. However, the acceptability and adherence to the intervention for older people with mild frailty, and their moderate progress towards goals, should encourage further tailored and person-centred practices to promote their independence. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment.

Mineralizing angiopathy as a rare cause of pediatric stroke: review and report of two cases.

In the Indian subcontinent, traumatic brain injury stands as the leading cause of pediatric stroke, whereas in Europe, it is considered a rare or potentially underdiagnosed factor. The etiology of post-traumatic stroke is unknown, although it has been associated with the presence of calcification in the lenticulostriate arteries, a condition known as "mineralizing angiopathy." The theory suggests that calcified lenticulostriate vessels in a brain with inadequate myelination could have an increased vulnerability to mechanical injuries, which may result in their obstruction. This ischemic stroke associated with mineralizing angiopathy usually occurs after mild traumatic brain injury, with an asymptomatic interval following the trauma. The typical age of presentation is between 6 and 24 months. Children with mineralizing lenticulostriate vasculopathy generally experience a favorable outcome after stroke, with the majority achieving complete or nearly complete recovery of their motor functions. Despite aspirin treatment, a small proportion of children may still face stroke recurrence following repeat head trauma. We present the cases of two male patients with clinical features compatible with childhood stroke after a mild traumatic brain injury.

Neurofibromatosis type 1 families with first-degree relatives harbouring distinct NF1 pathogenic variants. Genetic counselling and familial diagnosis: what should be offered?

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by pathogenic variants in NF1 Recently, NF1 testing has been included as a clinical criterion for NF1 diagnosis. Additionally, preconception genetic counselling in patients with NF1 focuses on a 50% risk of transmitting the familial variant as the risk of having a sporadic NF1 is considered the same as the general population. METHODS: 829 individuals, 583 NF1 sporadic cases and 246 patients with NF1 with documented family history, underwent genetic testing for NF1. Genotyping and segregation analysis of NF1 familial variants was determined by microsatellite analysis and NF1 sequencing. RESULTS: The mutational analysis of NF1 in 154 families with two or more affected cases studied showed the co-occurrence of two different NF1 germline pathogenic variants in four families. The estimated mutation rate in those families was 3.89×10-3, 20 times higher than the NF1 mutation rate (~2×10-4) (p=0.0008). Furthermore, the co-occurrence of two different NF1 germline pathogenic variants in these families was 1:39, 60 times the frequency of sporadic NF1 (1:2500) (p=0.003). In all cases, the de novo NF1 pathogenic variant was present in a descendant of an affected male. In two cases, variants were detected in the inherited paternal wild-type allele. CONCLUSIONS: Our results, together with previous cases reported, suggest that the offspring of male patients with NF1 could have an increased risk of experiencing de novo NF1 pathogenic variants. This observation, if confirmed in additional cohorts, could have relevant implications for NF1 genetic counselling, family planning and NF1 genetic testing.

[Gender-based violence highly vulnerable contexts. Intersectionality: Response adaptation to the diversity of contexts and situations]. / Contextos de especial vulnerabilidad para la violencia de género. Interseccionalidad: adaptando la respuesta a la diversidad de contextos y situaciones.

Addressing gender violence from the health system effectively, still involves addressing numerous challenges. If gender violence is suffered by women with one or more situations of personal and social vulnerability, intervention is surrounded by formidable difficulties. In these heterogeneous situations, early detection is urgent, as well as professional support adapted to each woman with her particular context. The intersectional approach to gender violence provides useful tools for actions in these complex scenarios, full of suffering and fragility. This article mentions the common and specific needs of the most vulnerable women. Recommendations are offered to improve the intervention to be developed from the health system - a privileged space for this - to understand and accompany these women in their diversity, with the most effective services and resources, in coordination with the rest of the social protection systems and entities.

[Teleophthalmology-based diabetic retinopathy screening in a rural health basic area]. / Cribado de la retinopatía diabética mediante teleoftalmología en una zona básica de salud rural.

OBJECTIVE: To investigate the prevalence of diabetic retinopathy in a rural health basic area, and to establish the type, the severity degree and the relationship with sex and with another cardiovascular risk factors. DESIGN: Cross-sectional or prevalence descriptive study. LOCATION: Rural health basic area in Spain. Primary health care level. PARTICIPANTS: 500 patients over 18 years old with diabetes. MAIN MEASUREMENTS: Study of the retina through retinography under mydriasis, according to the Joslin Vision Network protocol, with the incorporation of a diagnostic reading center. Correlation of the existence and severity of the retinopathy with the cardiovascular risk factors -smoking, hypertension and hyperlipidemia- and the characteristics of the diabetes -type, evolution time, treatment, metabolic control and renal function-. RESULTS: The findings showed a 16.4% prevalence, with no significant differences between both sexes. The variables smoking and high blood pressure were related to the existence of retinopathy, and the variable years of diabetes evolution was correlated to both the existence and the severity of the retinopathy. In the study, 9.6% of the affected people were preferentially referred to the ophthalmologists because of sight-threatening retinopathy, and 6.8% of the people studied were referred due to other ophthalmological pathologies. CONCLUSIONS: It is possible to do the ophthalmological follow-up of 82% of the population with diabetes in primary health care, involving its professionals and team-working with the ophthalmologists. It is paramount to consider diabetic retinopathy within the global context of the person with diabetes, relating diabetic retinopathy with the other microvascular complications and cardiovascular diseases.

Trust and inclusion during the Covid-19 pandemic: Perspectives from Black and South Asian people living with dementia and their carers in the UK.

INTRODUCTION: People from ethnic minority backgrounds living with dementia are more likely to be diagnosed later and have less access to health and social care support than their White counterparts in the United Kingdom (UK). Covid-19 has exacerbated health inequalities and diminished trust from underserved communities in the government and health services. The wider aim of the study was to explore the impact of covid-19 on Black and South-Asian people living with dementia and their carers as well as exploring the experiences of dementia care. The present paper specifically explores their views on trust and mistrust using an ecological model. METHOD: Semi-structured interviews were conducted with 11 family carers and four people living with dementia from South Asian or Black communities living in the community. Thematic analysis was used to analyse data. DESIGN: An exploratory qualiative design was used. RESULTS: Four main themes were developed exploring trust at the structural, organisational, community and individual level. At the structural level, participants discussed the inequity of Covid-19, some lack of trust in the UK Government and confusion in its messaging, and the anxiety sometimes leading to curtailment of media usage. At the organisational level, there was some evidence of a perceived lack of person-centred and culturally sensitive care from healthcare professionals, as well as concerns around care homes as places of safety. At the neighbourhood community level, participants discussed both a distrust as well as a strengthening of relationships and, at the individual level, factors such as knowledge of services, identity, and faith influenced their experience of the pandemic. CONCLUSIONS: People living with dementia need support at all levels and this study highlights how the pandemic impacted each level. Ways to improve trust in the Government and health professionals alongside culturally adapted health messaging should be explored. Alongside this, an examination of how cultural values and norms may influence help-seeking responses to dementia and increase trust in services may be helpful post-pandemic.

Prognostic value of somatosensory-evoked potentials in the newborn with hypoxic-ischemic encephalopathy after the introduction of therapeutic hypothermia.

To establish the ability of somatosensory-evoked potentials (SEPs) to detect neurological damage in neonatal patients with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). Retrospective study including 84 neonates ≥ 36 weeks of gestational age with HIE and TH with SEPs performed in the first 14 days of life. SEPs from the median nerve were performed after completion of TH. Either unilateral or bilateral absence of N20, or unilateral or bilateral latency ≥ 36 ms, was considered pathological. All newborns underwent a cerebral resonance imaging (MRI) at between days 7 and 14 of life and a neurodevelopmental evaluation using the Brunet-Lezine test at two years of age; a global Brunet-Lezine test score < 70 was considered unfavorable. The risk of moderate-to-severe alteration on basal ganglia-thalamic (BGT) and/or white matter areas on MRI for pathological SEPs was as follows: odds ratio 95% IC: 23.1 (6.9-76.9), sensitivity 78.6%, specificity 86.3%, positive predictive value 75.9%, and negative predictive value 88%. The BGT and internal capsule were the areas with the greatest risk of lesion with an altered SEPs: odds ratio 95% IC 93.1 (11.1-777.8). The risk of neurodevelopmental impairment for pathological SEPs was odds ratio 95% IC: 38.5 (4.4-335.3), sensitivity 91.7%, specificity 77.8% positive predictive value 52.4%, and negative predictive value 97.2%. CONCLUSION: The present study demonstrates the good predictive capacity of SEPs performed in the first two weeks of life in newborns with HIE and TH to detect an increased risk of neuroimaging lesions and neurodevelopmental impairment at two years of age. WHAT IS KNOWN: • Bilateral absence of the N20 cortical component of somatosensory evoked potentials has been associated with poor neurological outcome in neonates with hypoxic-ischemic encephalopathy. WHAT IS NEW: • This work confirms the predictive capacity of SEPs by adding two important aspects: the value of latency when interpreting SEPs results and the absence of effect of the hypothermia method used on the results of SEPs.

Two new RHD alleles with deletions spanning multiple exons.

BACKGROUND: The most common large-deletion RHD allele (RHD*01N.01) includes the entire coding sequence, intervening regions and untranslated regions. The rest of large-deletion RHD alleles reported to-date consist of single-exon deletions, such as RHD*01N.67 which includes exon 1. MATERIALS AND METHODS: Samples from two donors with RhD-negative serology yielded unclear or inconclusive results when subject to confirmatory testing on RHD genotyping arrays. To determine their RHD genotypes, genomic DNA was analyzed with a combination of allele-specific PCR, long-range PCR, Sanger sequencing, and next-generation sequencing assays. RESULTS: Allele-specific PCR failed to detect products for RHD exons 1 to 3 in one sample and RHD exons 1 to 5 in the other. A quantitative next-generation sequencing assay confirmed deletion of exons 1 to 3 and 1 to 5 respectively, and detected the absence of an RHD gene in trans in both samples. Long-range PCR and Sanger sequencing enabled identification of the breakpoints for both alleles. Both deletions start within the 5' Rhesus box (upstream of the identity region for the 1-to-3 deletion, downstream of it for the 1-to-5 deletion), and end within introns. CONCLUSIONS: Resolution of unclear or inconclusive results from targeted genotyping arrays often leads to the discovery of new alleles. The 5' Rhesus box may be a hot spot for genetic recombination events, such as the large deletions described in this report.

How do people living with dementia perceive eating and drinking difficulties? A qualitative study.

BACKGROUND: Eating and drinking problems are common among people living with later-stage dementia, yet few studies have explored their perspectives. OBJECTIVE: This study aimed to explore how people living with mild dementia understand possible future eating and drinking problems and their perspectives on assistance. DESIGN: Qualitative study using semi-structured interviews. SETTING: Community. METHODS: We conducted semi-structured interviews with 19 people living with mild dementia. Interviews were transcribed verbatim and analysed thematically. RESULTS: Five themes were identified: (i) awareness of eating and drinking problems; (ii) food and drink representing an individual's identity and agency; (iii) delegating later decisions about eating and drinking to family carers; (iv) acceptability of eating and drinking options; and (v) eating and drinking towards the end of life. For people living with mild dementia, possible later eating and drinking problems could feel irrelevant and action may be postponed until they occur. Fears of being a burden to family and of being treated like a child may explain reluctance to discuss such future problems. People living with mild dementia might wish to preserve their agency and maintain good quality of life, rather than be kept alive at later stages by artificial nutrition and hydration. CONCLUSION: For people with mild dementia, eating and drinking problems may seem unrelated to them and so get left undiscussed. Negative connotations regarding eating and drinking problems may hinder the discussion. The optimal time to discuss possible future problems with eating and drinking with people with mild dementia may need an individual approach.

Enteral tube feeding for people with severe dementia.

BACKGROUND: The balance of benefits and harms associated with enteral tube feeding for people with severe dementia is not clear. An increasing number of guidelines highlight the lack of evidenced benefit and potential risks of enteral tube feeding. In some areas of the world, the use of enteral tube feeding is decreasing, and in other areas it is increasing. OBJECTIVES: To assess the effectiveness and safety of enteral tube feeding for people with severe dementia who develop problems with eating and swallowing or who have reduced food and fluid intake. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE, Embase, four other databases and two trials registers on 14 April 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs), or controlled non-randomised studies. Our population of interest was adults of any age with a diagnosis of primary degenerative dementia of any cause, with severe cognitive and functional impairment, and poor nutritional intake. Eligible studies evaluated the effectiveness and complications of enteral tube feeding via a nasogastric or gastrostomy tube, or via jejunal post-pyloric feeding, in comparison with standard care or enhanced standard care, such as an intervention to promote oral intake. Our primary outcomes were survival time, quality of life, and pressure ulcers. DATA COLLECTION AND ANALYSIS: Three review authors screened citations and two review authors assessed full texts of potentially eligible studies against inclusion criteria. One review author extracted data, which were then checked independently by a second review author. We used the 'Risk Of Bias In Non-randomised Studies of Interventions' (ROBINS-I) tool to assess the risk of bias in the included studies. Risk of confounding was assessed against a pre-agreed list of key potential confounding variables. Our primary outcomes were survival time, quality of life, and pressure ulcers. Results were not suitable for meta-analysis, so we presented them narratively. We presented results separately for studies of percutaneous endoscopic gastrostomy (PEG) feeding, nasogastric tube feeding and studies using mixed or unspecified enteral tube feeding methods. We used GRADE methods to assess the overall certainty of the evidence related to each outcome for each study. MAIN RESULTS: We found no eligible RCTs. We included fourteen controlled, non-randomised studies. All the included studies compared outcomes between groups of people who had been assigned to enteral tube feeding or oral feeding by prior decision of a healthcare professional. Some studies controlled for a range of confounding factors, but there were high or very high risks of bias due to confounding in all studies, and high or critical risks of selection bias in some studies. Four studies with 36,816 participants assessed the effect of PEG feeding on survival time. None found any evidence of effects on survival time (low-certainty evidence). Three of four studies using mixed or unspecified enteral tube feeding methods in 310 participants (227 enteral tube feeding, 83 no enteral tube feeding) found them to be associated with longer survival time. The fourth study (1386 participants: 135 enteral tube feeding, 1251 no enteral tube feeding) found no evidence of an effect. The certainty of this body of evidence is very low. One study of PEG feeding (4421 participants: 1585 PEG, 2836 no enteral tube feeding) found PEG feeding increased the risk of pressure ulcers (moderate-certainty evidence). Two of three studies reported an increase in the number of pressure ulcers in those receiving mixed or unspecified enteral tube feeding (234 participants: 88 enteral tube feeding, 146 no enteral tube feeding). The third study found no effect (very-low certainty evidence).  Two studies of nasogastric tube feeding did not report data on survival time or pressure ulcers. None of the included studies assessed quality of life. Only one study, using mixed methods of enteral tube feeding, reported on pain and comfort, finding no difference between groups. In the same study, a higher proportion of carers reported very heavy burden in the enteral tube feeding group compared to no enteral tube feeding. Two studies assessed the effect of nasogastric tube feeding on mortality (236 participants: 144 nasogastric group, 92 no enteral tube feeding). One study of 67 participants (14 nasogastric, 53 no enteral tube feeding) found nasogastric feeding was associated with increased mortality risk. The second study found no difference in mortality between groups. The certainty of this evidence is very low. Results on mortality for those using PEG or mixed methods of enteral tube feeding were mixed and the certainty of evidence was very low. There was some evidence from two studies for enteral tube feeding improving nutritional parameters, but this was very low-certainty evidence. Five studies reported a variety of harm-related outcomes with inconsistent results. The balance of evidence suggested increased risk of pneumonia with enteral tube feeding. None of the included studies assessed behavioural and psychological symptoms of dementia. AUTHORS' CONCLUSIONS: We found no evidence that tube feeding improves survival; improves quality of life; reduces pain; reduces mortality; decreases behavioural and psychological symptoms of dementia; leads to better nourishment; improves family or carer outcomes such as depression, anxiety, carer burden, or satisfaction with care; and no indication of harm. We found some evidence that there is a clinically significant risk of pressure ulcers from enteral tube feeding. Future research should focus on better reporting and matching of control and intervention groups, and clearly defined interventions, measuring all the outcomes referred to here.

Frizzled 1 and Wnt1 as new potential therapeutic targets in the traumatically injured spinal cord.

Despite the experimental evidence pointing to a significant role of the Wnt family of proteins in physiological and pathological rodent spinal cord functioning, its potential relevance in the healthy and traumatically injured human spinal cord as well as its therapeutic potential in spinal cord injury (SCI) are still poorly understood. To get further insight into these interesting issues, we first demonstrated by quantitative Real-Time PCR and simple immunohistochemistry that detectable mRNA expression of most Wnt components, as well as protein expression of all known Wnt receptors, can be found in the healthy human spinal cord, supporting its potential involvement in human spinal cord physiology. Moreover, evaluation of Frizzled (Fz) 1 expression by double immunohistochemistry showed that its spatio-temporal and cellular expression pattern in the traumatically injured human spinal cord is equivalent to that observed in a clinically relevant model of rat SCI and suggests its potential involvement in SCI progression/outcome. Accordingly, we found that long-term lentiviral-mediated overexpression of the Fz1 ligand Wnt1 after rat SCI improves motor functional recovery, increases myelin preservation and neuronal survival, and reduces early astroglial reactivity and NG2+ cell accumulation, highlighting the therapeutic potential of Wnt1 in this neuropathological situation.

Craniopharyngiomas: A clinicopathological and molecular study of 52 cases - Experience in the Complejo Hospitalario de Toledo and Hospital Universitario 12 de Octubre (Madrid).

Craniopharyngiomas (CPs) are histologically benign tumors that are associated with high levels of morbidity. Two clinicopathological variants - adamantinomatous (ACP) and papillary (PCP) - have been described. They differ in their molecular features, whereby activating mutations in BRAF (V600E) and CTNNB1 genes characterize PCP and ACP, respectively. Recently, both variants have been shown to express elevated PD-L1 protein expression, but ACP also exhibited tumor cell-intrinsic PD-1 expression. In this study we analyze these molecular alterations in 52 cases with a long follow-up and examine their associations with immunohistochemical and clinical characteristics. ACPs comprise 73.1% of cases, while 21.2% are PCPs. Aberrant nuclear immunoreactivity for ß-catenin was observed in all ACPs. BRAF p.V600E mutations were observed in 90.9% of PCPs. Only one ACP case featured both alterations. Both types of CP exhibited strong nuclear staining for p63 with diffuse and basal distribution. ACP and PCP consistently expressed PD-L1, most in a substantial percentage of tumor cells, with a distinctive spatial distribution of expression in each subtype; only ACP demonstrated PD-1 expression. There was no evidence of differences in clinical prognosis between ACPs and PCPs. The identification of hallmark molecular signatures in the two CP variants is useful for sub-categorization in routine histopathology reporting. It is also pertinent to personalized therapy and for the development of improved non-invasive therapeutic strategies in this disease.

Self-efficacy beliefs mediate the association between pain intensity and pain interference in acute/subacute whiplash-associated disorders.

PURPOSE: To evaluate whether a set of pre-accident demographic, accident-related, post-accident treatment and psychosocial factors assessed in people with acute/subacute whiplash-associated disorders (WAD) mediate the association between pain intensity and: (1) pain interference and (2) expectations of recovery, using Bayesian networks (BNs) analyses. This study also explored the potential mediating pathways (if any) between different psychosocial factors. METHODS: This was a cross-sectional study conducted on a sample of 173 participants with acute/subacute WAD. Pain intensity, pain interference, pessimism, expectations of recovery, pain catastrophizing, and self-efficacy beliefs were assessed. BN analyses were conducted to analyse the mediating effects of psychological factors on the association between pain intensity and pain-related outcomes. RESULTS: The results revealed that self-efficacy beliefs partially mediated the association between pain intensity and pain interference. Kinesiophobia partially mediated the association between self-efficacy and pain catastrophizing. Psychological factors did not mediate the association between pain intensity and expectations of recovery. CONCLUSION: These results indicate that individuals with acute/subacute WAD may present with lesser pain interference associated with a determined pain intensity value when they show greater self-efficacy beliefs. As the cross-sectional nature of this study limits firm conclusions on the causal impact, researchers are encouraged to investigate the role that patient's self-efficacy beliefs play in the transition to chronic WAD via longitudinal study designs.

Nutrition and hydration for people living with dementia near the end of life: A qualitative systematic review.

AIMS: To synthesize the qualitative evidence of the views and experiences of people living with dementia, family carers, and practitioners on practice related to nutrition and hydration of people living with dementia who are nearing end of life. DESIGN: Systematic review and narrative synthesis of qualitative studies. DATA SOURCES: MEDLINE, Embase, PsycINFO, CINAHL. REVIEW METHODS: Databases were searched for qualitative studies from January 2000-February 2020. Quantitative studies, or studies reporting on biological mechanisms, assessments, scales or diagnostic tools were excluded. Results were synthesized using a narrative synthesis approach with thematic analysis. RESULTS: Twenty studies were included; 15 explored the views of practitioners working with people living with dementia in long-term care settings or in hospitals. Four themes were developed: challenges of supporting nutrition and hydration; balancing the views of all parties involved with 'the right thing to do'; national context and sociocultural influences; and strategies to support nutrition and hydration near the end of life in dementia. CONCLUSION: The complexity of supporting nutrition and hydration near the end of life for someone living with dementia relates to national context, lack of knowledge, and limited planning while the person can communicate. IMPACT: This review summarizes practitioners and families' experiences and highlights the need to include people living with dementia in studies to help understand their views and preferences about nutrition and hydration near the end of life; and those of their families supporting them in the community. The review findings are relevant to multidisciplinary teams who can learn from strategies to help with nutrition and hydration decisions and support.

Adherence to the Class-Based Component of a Tai Chi Exercise Intervention for People Living With Dementia and Their Informal Carers.

The objective of this study was to understand the experiences of people living with dementia and their informal carers' taking part together (in dyads) in Tai Chi classes and the aspects influencing their adherence. Dyads' experiences of taking part in Tai Chi classes for 20 weeks within the TACIT Trial were explored through class observations (n = 22 dyads), home-interviews (n = 15 dyads), and feedback. Data were inductively coded following thematic analysis. Tai Chi classes designed for people with dementia and their informal carers were enjoyable and its movements, easy to learn. Facilitators of participants' adherence were the socializing component and their enjoyment of the classes, whereas unexpected health problems were the main barrier. Finding the optimal level of challenge in the class setting might be crucial for people with dementia to feel satisfied with their progression over sessions and enable their continued participation.

Spatio-temporal and Cellular Expression Patterns of PTK7 in the Healthy and Traumatically Injured Rat and Human Spinal Cord.

Despite the emerging role of protein tyrosine kinase 7 (PTK7) as a Wnt co-receptor and the relevant functions of the Wnt family of proteins in spinal cord injury (SCI), the potential involvement of PTK7 in SCI is currently unknown. As a first essential step to shed light on this issue, we evaluated the spatio-temporal and cellular expression patterns of PTK7 in healthy and traumatically injured rat and human spinal cords. In the uninjured rats, PTK7 expression was observed in the ependymal epithelium, endothelial cells, meningeal fibronectin-expressing cells, and specific axonal tracts, but not in microglia, astrocytes, neurons, oligodendrocytes, or NG2+ cells. After rat SCI, the mRNA expression of PTK7 was significantly increased, while its spatio-temporal and cellular protein expression patterns also suffered evident changes in the injured region. Briefly, the expression of PTK7 in the affected areas was observed in axons, reactive astrocytes, NG2+ and fibronectin-expressing cells, and in a subpopulation of reactive microglia/macrophages and blood vessels. Finally, in both healthy and traumatically injured human spinal cords, PTK7 expression pattern was similar to that observed in the rat, although some specific differences were found. In conclusion, we demonstrate for the first time that PTK7 is constitutively expressed in the healthy adult rat and human spinal cord and that its expression pattern clearly varied after rat and human SCI which, to our knowledge, constitutes the first experimental evidence pointing to the potential involvement of this co-receptor in physiological and pathological spinal cord functioning.

Feasibility and Accuracy of Different Methods for Collecting Data on Falls Among Older People With Dementia.

This study compared different methods for collecting data on falls among people with dementia to identify which is most feasible and accurate. Eighty-three dyads, comprised of a community-dwelling person with dementia and their informal carer, participated in the TAi ChI for people with demenTia (TACIT) trial. Falls were collected prospectively over 6 months using monthly calendars, weekly and monthly telephone interviews, and 3-monthly telephone interviews with the carer. Unique falls identified across the reporting methods were combined, and this total was compared against each reporting method in isolation and combinations. A higher frequency of falls indicated greater accuracy. Falls data collection was most feasible with weekly telephone interviews (84%), and most accurate with the combination of weekly telephone interviews with monthly calendars (96%). For the greatest completeness and accuracy of falls data with community-dwelling people with dementia, researchers should use both weekly telephone interviews and monthly calendars.

[The body hurts, and what about social pain? Does it hurts too?] / El cuerpo duele, y el dolor social ¿duele también?

This paper studies the concept of «social pain¼ and its relationship with physical pain. An in-depth review of its physiology has been carried out, including similarities and differences in processing with relation to physical pain, as well as the interactions between both processes. Social pain is defined as an unpleasant emotional experience which is triggered when the individual feels excluded or rejected by people or social groups with whom they wish have a relationship. This perceived situation produces the same feelings of suffering as that of physical pain. This kind of pain is processed in the same brain areas as physical pain in its affective dimension. It may be revived mentally, even though the interpersonal conflictive situation may have ended long ago. Both types of pain are sources of stress. The confluence of both situations in the same individual adds complications and more pressure to that which is already exerted separately by both stressing factors. This circumstance must be taken into account when dealing with patients with chronic pain.