Adapting the Primary Care PTSD Screener for firefighters.

BACKGROUND: By the nature of their work, first responders are at risk for post-traumatic stress disorder (PTSD). Efficient screening instruments are useful to identify at-risk first responders and connect them to services. AIMS: The current study aimed to (i) evaluate the diagnostic properties of the Primary Care PTSD for DSM-5 (PC-PTSD-5) scale among firefighters, (ii) explore the use of an adapted PC-PTSD-5 on a five-point Likert-type scale and (iii) examine sensitivity and specificity of the adapted instrument in this population. METHODS: Pooled data were analysed among firefighters (N = 92) from a treatment-seeking sample (n = 36) and a population health screening sample (n = 56). Participants completed an adapted version of the PC-PTSD-5 and the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). Receiver operating characteristic curve analyses were performed, referencing PCL-5 cut-off/probable diagnostic threshold scores. RESULTS: The PC-PTSD-5 demonstrated excellent operating characteristics overall. A threshold of 3 was optimal for discriminating probable PTSD using a proxy for the original PC-PTSD-5 (range: 0-5), whereas a score of 9 was identified for the PC-PTSD-5 permutation that allowed for more response variability (range: 0-20). CONCLUSIONS: Our preliminary data suggest the PC-PTSD-5 may be a useful tool for brief firefighter screening, with suggested cut-offs that require further replication and expanded investigation.

Racial Diversity Among American Cardiologists: Implications for the Past, Present, and Future.

In the United States, race-based disparities in cardiovascular disease care have proven to be pervasive, deadly, and expensive. African American/Black, Hispanic/Latinx, and Native/Indigenous American individuals are at an increased risk of cardiovascular disease and are less likely to receive high-quality, evidence-based medical care as compared with their White American counterparts. Although the United States population is diverse, the cardiovascular workforce that provides its much-needed care lacks diversity. The available data show that care provided by physicians from racially diverse backgrounds is associated with better quality, both for minoritized patients and for majority patients. Not only is cardiovascular workforce diversity associated with improvements in health care quality, but racial diversity among academic teams and research scientists is linked with research quality. We outline documented barriers to achieving workforce diversity and suggest evidence-based strategies to overcome these barriers. Key strategies to enhance racial diversity in cardiology include improving recruitment and retention of racially diverse members of the cardiology workforce and focusing on cardiovascular health equity for patients. This review draws attention to academic institutions, but the implications should be considered relevant for nonacademic and community settings as well.

I22: SAXS/WAXS beamline at Diamond Light Source - an overview of 10 years operation.

Beamline I22 at Diamond Light Source is dedicated to the study of soft-matter systems from both biological and materials science. The beamline can operate in the range 3.7 keV to 22 keV for transmission SAXS and 14 keV to 20 keV for microfocus SAXS with beam sizes of 240 µm × 60 µm [full width half-maximum (FWHM) horizontal (H) × vertical (V)] at the sample for the main beamline, and approximately 10 µm × 10 µm for the dedicated microfocusing platform. There is a versatile sample platform for accommodating a range of facilities and user-developed sample environments. The high brilliance of the insertion device source on I22 allows structural investigation of materials under extreme environments (for example, fluid flow at high pressures and temperatures). I22 provides reliable access to millisecond data acquisition timescales, essential to understanding kinetic processes such as protein folding or structural evolution in polymers and colloids.

The molecular landscape and associated clinical experience in infant medulloblastoma: prognostic significance of second-generation subtypes.

AIMS: Biomarker-driven therapies have not been developed for infant medulloblastoma (iMB). We sought to robustly sub-classify iMB, and proffer strategies for personalized, risk-adapted therapies. METHODS: We characterized the iMB molecular landscape, including second-generation subtyping, and the associated retrospective clinical experience, using large independent discovery/validation cohorts (n = 387). RESULTS: iMBGrp3 (42%) and iMBSHH (40%) subgroups predominated. iMBGrp3 harboured second-generation subtypes II/III/IV. Subtype II strongly associated with large-cell/anaplastic pathology (LCA; 23%) and MYC amplification (19%), defining a very-high-risk group (0% 10yr overall survival (OS)), which progressed rapidly on all therapies; novel approaches are urgently required. Subtype VII (predominant within iMBGrp4 ) and subtype IV tumours were standard risk (80% OS) using upfront CSI-based therapies; randomized-controlled trials of upfront radiation-sparing and/or second-line radiotherapy should be considered. Seventy-five per cent of iMBSHH showed DN/MBEN histopathology in discovery and validation cohorts (P < 0.0001); central pathology review determined diagnosis of histological variants to WHO standards. In multivariable models, non-DN/MBEN pathology was associated significantly with worse outcomes within iMBSHH . iMBSHH harboured two distinct subtypes (iMBSHH-I/II ). Within the discriminated favourable-risk iMBSHH DN/MBEN patient group, iMBSHH-II had significantly better progression-free survival than iMBSHH-I , offering opportunities for risk-adapted stratification of upfront therapies. Both iMBSHH-I and iMBSHH-II showed notable rescue rates (56% combined post-relapse survival), further supporting delay of irradiation. Survival models and risk factors described were reproducible in independent cohorts, strongly supporting their further investigation and development. CONCLUSIONS: Investigations of large, retrospective cohorts have enabled the comprehensive and robust characterization of molecular heterogeneity within iMB. Novel subtypes are clinically significant and subgroup-dependent survival models highlight opportunities for biomarker-directed therapies.

Physical activity trajectories from childhood to late adolescence and their implications for health in young adulthood.

Physical activity has been associated with physical and mental health across the life course, yet few studies have used group-based trajectory modeling to examine the effect of longitudinal patterns of physical activity during childhood and adolescence on adult health outcomes. The Raine Study data from Gen2 follow-ups at 8, 10, 14, 17, 20, and 22 years collected between 1998 and 2014 were used. Latent class analysis identified trajectories using parent-reported physical activity for ages 8 to 17. Associations between trajectories and physical and mental health outcomes at ages 20 and 22 were explored, adjusting for current physical activity and considering sex interactions. Analysis in 2019 identified three trajectories: low (13%), mid (65%) and high (22%) physical activity (n = 1628). Compared to the low-activity trajectory, those in the high-activity trajectory had lower adiposity, insulin, HOMA-IR and fewer diagnosed disorders, higher HDL-cholesterol, and faster cognitive processing. For example, those in the high-activity trajectory had lower percent body fat at age 20 compared to those in the mid-activity (-4.2%, 95%CI: -5.8, -2.7) and low-activity (-9.5%, 95%CI: -11.7, -7.2) trajectories. Physical activity trajectories showed different associations between sexes for self-reported physical and mental health, BMI, systolic blood pressure, and depression symptoms. Being in the high- or mid-activity trajectory was associated with a more favorable cardiometabolic and mental health profile in young adulthood. Strategies are needed to help less active children to increase physical activity throughout childhood and adolescence to improve young adult health outcomes.

Dissecting dentine-pulp injury and wound healing responses: consequences for regenerative endodontics.

A thorough understanding of the biology of the dentine-pulp complex is essential to underpin new treatment approaches and maximize clinical impact for regenerative endodontics and minimally invasive vital pulp treatment (VPT) strategies. Following traumatic and carious injury to dentine-pulp, a complex interplay between infection, inflammation and the host defence responses will occur, which is critical to tissue outcomes. Diagnostic procedures aim to inform treatment planning; however, these remain clinically subjective and have considerable limitations. As a consequence, significant effort has focussed on identification of diagnostic biomarkers, although these are also problematic due to difficulties in identifying appropriate diagnostic fluid sources and selecting reproducible biomarkers. This is further compounded by the link between inflammation and repair as many of the molecules involved exhibit significant multifunctionality. The tertiary dentine formed in response to dental injury has been purposefully termed reactionary and reparative dentine to enable focus on associated biological processes. Whilst reactionary dentine produced in response to milder injury is generated from surviving primary odontoblasts, reparative dentine, in response to more intense injury, requires the differentiation of new odontoblast-like cells derived from progenitor/stem cells recruited to the injury site. These two diverse processes result in very different outcomes in terms of the tertiary dentine produced and reflect the intensity rather than specific nature (nonexposure versus exposure) of the injury. The subsequent identification of the odontoblast-like cell phenotype remains challenging due to lack of unique molecular or morphological markers. Furthermore, the cells ultimately lining the newly deposited dentine provide only a snapshot of events. The specific source and plasticity of the progenitor cells giving rise to the odontoblast-like cell phenotype are also of significant debate. It is likely that improved characterization of tertiary dentine may better clarify the influence of cell derivation for odontoblast-like cells and their diversity. The field of regenerative endodontics offers exciting new treatment opportunities, and to maximize outcomes, we propose that the term regenerative endodontics should embrace the repair, replacement and regeneration of dentine-pulp.

A panting score index for sheep.

When exposed to hot conditions, heat dissipation via an increase in respiration rate (RR) is an important thermoregulatory mechanism for sheep. However, evaluating RR under field conditions is difficult. In cattle, a viable alternative has been to assess panting score (PS); therefore, the objective of this study was to evaluate the relationship between RR and PS to determine if a PS index can be used to evaluate heat load in sheep. One hundred and forty-four Merino wethers (44.02 ± 0.32 kg) were used within a climate-controlled study. The study was replicated twice over 29 days, where each replicate consisted of two treatments: (1) thermoneutral (TN) and (2) hot (HOT). Ambient temperature (TA) and relative humidity (RH) were maintained between 18 and 20 °C and 60 and 70% respectively for the TN treatment. For the HOT treatment, heat load increased steadily over the 29 days. Minimum TA was 22.5 °C and maximum was 38.5 °C, while RH decreased (60 to 30%) as TA increased in the HOT treatment. A comprehensive PS classification was developed by enhancing the current sheep PS index and aligning the descriptors with the current PS index utilized in beef cattle studies. Respiration rate and PS were obtained for each animal at 3-h intervals between 0800 h and 1700 h daily. These data were used to determine the mean RR for each PS, across the study and within the TN and HOT treatments. The relationship between PS and RR was evaluated using a Pearson's correlation coefficient. Data were also analyzed using a general linear model to determine the impact of PS, posture and animal identification (animal ID) on RR within each PS. Unsurprisingly, RR increased as PS increased, and PS, 0 and RR, 2.5 were 30.7 ± 0.59 and 246.8 ± 12.20 bpm respectively. There was a strong relationship between RR and PS (r = 0.71; P < 0.0001). As RR increased, sheep were more likely to be observed standing (P < 0.001). Mean PS of sheep within the HOT treatment (1.49 ± 0.02) were greater (P = 0.0085) when compared to the TN (1.17 ± 0.02) sheep. Individual animal ID accounted for approximately 7-37% of the variation observed for RR across PS, indicating that animal ID and climatic conditions were influencing RR and PS. These results suggest that the comprehensive PS index described here can be used as a visual appraisal of the heat load status of sheep.

Vaccine-Associated Maintenance of Epithelial Integrity Correlated With Protection Against Virus Entry.

To identify the mechanisms by which human immunodeficiency virus type 1 (HIV-1) might penetrate the epithelial barrier during sexual transmission to women and the mechanisms of vaccine-associated protection against entry, we characterized early epithelial responses to vaginal inoculation of simian immunodeficiency virus strain mac251 (SIVmac251) in naive or SIVmac239Δnef-vaccinated rhesus macaques. Vaginal inoculation induced an early stress response in the cervicovaginal epithelium, which was associated with impaired epithelial integrity, damaged barrier function, and virus and bacterial translocation. In vaccinated animals, early stress responses were suppressed, and the maintenance of epithelial barrier integrity correlated with prevention of virus entry. These vaccine-protective effects were associated with a previously described mucosal system for locally producing and concentrating trimeric gp41 antibodies at the mucosal interface and with formation of SIV-specific immune complexes that block the stress responses via binding to the epithelial receptor FCGR2B and subsequent inhibitory signaling. Thus, blocking virus entry may be one protective mechanism by which locally concentrated non-neutralizing Ab might prevent HIV sexual transmission to women.

[Series: Communication in the dental practice. Low levels of literacy and limited health literacy]. / Serie: Communicatie in de tandartspraktijk. Laaggeletterdheid en beperkte gezondheidsvaardigheden.

Approximately 36% of the Dutch population has insufficient or limited health literacy. This disproportionately concerns patients with low socioeconomic status (SES), the elderly and migrants, but also highly-educated patients. Dentists are often unaware of this. A patient with limited health literacy might have trouble with a dentist's explanation or with reading written information. A dentist may not immediately notice this, but can be aware of signals indicating it. Such signals can vary from not completely filling out a questionnaire to wrongly interpreting instructions or systematically not showing up to appointments. The dentist needs to take this into account in his use of language and adapt any informational matter to make it understandable for everyone. Co-workers such as receptionists also need to be informed about signs indicating limited health literacy and how best to communicate with these patients.

[Series: Communication in the dental practice. Communicating in a culturally competent manner]. / Serie: Communicatie in de tandartspraktijk. Cultureel competent communiceren.

Dentists will increasingly have to treat patients with a variety of cultural backgrounds. They will consequently have to deal with various preconceptions about health and how people ought to behave with each other. In order to develop a good dentist-patient relationship and provide appropriate care, the dentist will have to learn to communicate in a culturally competent manner. That requires an open, empathetic attitude and an awareness of one's own norms, values and views. The dentist will have to consider how they differ from those of people from another (sub) culture. With the help of a number of examples, this article will provide an impulse to do that.

[Series: Communication in the dental practice. Motivating change in behaviour]. / Serie: Communicatie in de tandartspraktijk. Motiveren tot gedragsverandering.

Why people display certain behaviour is determined by a number of factors. If a dentist wants to change behaviour harmful to the patient's health, he will have to identify the factors determining this behaviour, taking into account factors like social acceptability. The dentist can then counsel the patient to change his or her behaviour using motivational interviewing techniques fitting the patient's motivational phase. A lot of frustration over non-compliance with (failing to follow-up on) recommended advice couldbe avoided this way.

[Series: Communication in the dental practice. Delivering bad news]. / Serie: Communicatie in de tandartspraktijk. Het slechtnieuwsgesprek.

In general practice a dentist will from time to time have to convey bad news to his patients. Often they feel burdened by this because of the emotional impact of such a conversation. This article discusses the way in which patients prefer to have bad news relayed to them. Using cases suggestions are made how to structure the bad news conversation.

[Series: Communication in the dental practice. Dealing with conflict and intimidation in the dental practice]. / Serie: Communicatie in de tandarts­praktijk. Omgaan met conflicten en intimidatie in de tandartspraktijk.

In the dental practice, several situations that might lead to conflict are imaginable. How a dentist deals with a conflict depends in part on the importance he places on the content of the conflict in relation to the importance of the relationship with the patient. This article briefly describes 5 conflict management styles. On the basis of case histories, suggestions are made for handling situations when a conflict leads to aggression, you are facing sexual intimidation or a conflict develops with a demanding patient. Finally, some advice is given on how to deal with errors/complications in treatment and dealing with criticism.

[Series: Communication in the dental practice. Building a good dentist-patient relationship with communication]. / Serie: Communicatie in de tandartspraktijk. Met communicatie bouwen aan een goede tandarts-patiëntrelatie.

A good dentist-patient relationship promotes better oral health of the patient. In order to build and maintain such a relationship a dentist should possess good communication skills. First of all, an open, empathic attitude is important, in which the dentist is aware that he can make mistakes interpreting patient behaviour. Good observational skills are necessary to detect (non-)verbal signals indicating how to interpret the patient's story. By demonstrating non-verbal, paralingual and verbal listening behaviour,he can show patients that he is paying attention to them. When discussing findings, it is important for patients to receive a clear explanation and be given the opportunity to ask questions. It is also wise to pay attention to the patient's expectations of the treatment outcome, elaborate on the advantages and disadvantages of the treatment alternatives and to be transparent in case of complications.

[Series: Communication in the dental practice. Dealing with anxiety in the dental office]. / Serie: Communicatie in de tandartspraktijk. Omgaan met angst in de tandartspraktijk.

Dentists frequently have to deal with anxious children and adults. Whether these patients can be treated successfully in a regular dental office depends on the type of fear and its severity. Proper diagnostic procedures are therefore paramount. This article gives an overview of how dental fear develops, is sustained, and can be treated. It elaborates on the communication skills important in reducing anxiety and preventing children from developing dental fear.

[Communication in the dental practice. Communicating with older patients]. / Serie: Communicatie in de tandartspraktijk. Communiceren met de oudere patiënt.

The ageing of the population in the Netherlands and in Belgium and the growing number of older people who still have their own teeth mean that dentists are seeing older patients in their dental practices increasingly often. Loss of cognitive abilities can hinder communication with the patients. Dementia and care-resistant behaviour demand a special patient-centred approach. In addition, frail older people are often dependent on carers or volunteers who actively participate in the conversation when the patient visits the dentist. This article addresses issues dentists should take into account in such cases. It also makes suggestions about how most effectively to direct communications with older patients and/or their companions.

Correction: Development of an optimized AAV2/5 gene therapy vector for Leber congenital amaurosis owing to defects in RPE65.

The authors originally published this article under the incorrect license type; this has now been corrected and is published under the CC-BY license.

Restoration of vision after transplantation of photoreceptors.

Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.

In situ regeneration of retinal pigment epithelium by gene transfer of E2F2: a potential strategy for treatment of macular degenerations.

The retinal pigment epithelium (RPE) interacts closely with photoreceptors to maintain visual function. In degenerative diseases such as Stargardt disease and age-related macular degeneration, the leading cause of blindness in the developed world, RPE cell loss is followed by photoreceptor cell death. RPE cells can proliferate under certain conditions, suggesting an intrinsic regenerative potential, but so far this has not been utilised therapeutically. Here, we used E2F2 to induce RPE cell replication and thereby regeneration. In both young and old (2 and 18 month) wildtype mice, subretinal injection of non-integrating lentiviral vector expressing E2F2 resulted in 47% of examined RPE cells becoming BrdU positive. E2F2 induced an increase in RPE cell density of 17% compared with control vector-treated and 14% compared with untreated eyes. We also tested this approach in an inducible transgenic mouse model of RPE loss, generated through activation of diphtheria toxin-A gene. E2F2 expression resulted in a 10-fold increase in BrdU uptake and a 34% increase in central RPE cell density. Although in mice this localised rescue is insufficiently large to be demonstrable by electroretinography, a measure of massed retinal function, these results provide proof-of-concept for a strategy to induce in situ regeneration of RPE for the treatment of RPE degeneration.