Narrative therapy and family therapy in genetic counseling: A scoping review.

Genetic counseling facilitates psychological and social adaptation in clients and families. Two psychotherapeutic approaches, narrative and family therapy foster client adaptation to adverse situations and may enhance the genetic counseling process. This scoping review aimed to describe the applications of narrative therapy and family therapy in genetic counseling, and to document the actual and perceived value of these approaches in a genetic counseling setting. Nine original research articles and six commentary articles met the study inclusion criteria. Original articles reported on positive client attitudes when these approaches were applied to hereditary cancer and Huntington disease settings. Five studies applied either approach in group sessions, where safety was key to positive outcomes, including sharing lived experiences and coping strategies. Balanced utilization of structured and open elements in group sessions maximized a sense of control, while also allowing for opportunity to self-disclose. Narrative therapy interventions were time efficient and were reported to foster connection with others and shape a new adaptive narrative centered around strengths. Family therapy approaches, based on experiential family therapy, the intersystem model, object relations family therapy, and the social ecology model, required a greater time commitment, but promoted disclosure of complex feelings and diffused tension. Family therapy genogram tools were feasible in practice, easy to implement, and effective at identifying communication barriers. Commentary articles highlighted the alignment of both approaches with genetic counseling goals and their potential value in practice. Utilization of psychotherapeutic approaches can improve counselors' ability to shape sessions, enhance insight and optimize efficacy, and flexibility in moving between models can maximize impact. This review highlights the paucity of studies investigating the efficacy of these psychotherapeutic approaches in the genetic counseling context and the need for more outcomes-based research on the utilization of narrative or family therapy in genetic counseling practice.

Genetic testing for familial melanoma.

While the average lifetime risk of melanoma worldwide is approximately 3%, those with inherited high-penetrance mutations face an increased lifetime risk of 52-84%. In countries of low melanoma incidence, such as in Southern Europe, familial melanoma genetic testing may be warranted when there are two first degree relatives with a melanoma diagnosis. Testing criteria for high incidence countries such as USA, or with very-high incidence, such as Australia and New Zealand, would require a threshold of 3 to 4 affected family members. A mutation in the most common gene associated with familial melanoma, CDKN2A, is identified in approximately 10-40% of those meeting testing criteria. However, the use of multi-gene panels covering additional less common risk genes can significantly increase the diagnostic yield. Currently, genetic testing for familial melanoma is typically conducted by qualified genetic counsellors, however with increasing demand on testing services and high incidence rate in certain countries, a mainstream model should be considered. With appropriate training, dermatologists are well placed to identify high risk individuals and offer melanoma genetic test in dermatology clinics. Genetic testing should be given in conjunction with pre- and post-test consultation. Informed patient consent should cover possible results, the limitations and implications of testing including inconclusive results, and potential for genetic discrimination. Previous studies reporting on participant outcomes of genetic testing for familial melanoma have found significant improvements in both sun protective behavior and screening frequency in mutation carriers.

MITF E318K: A rare homozygous case with multiple primary melanoma.

MITF E318K moderates melanoma risk. Only five MITF E318K homozygous cases have been reported to date, one in association with melanoma. This novel report uses 3D total-body-photography (TBP) to describe the dermatological phenotype of a homozygous MITF E318K individual. The case, a 32-year-old male, was diagnosed with his first of six primary melanomas at 26 years of age. Five melanomas were located on the back and one in the groin. Two were superficial spreading. Three arose from pre-existing naevi and one was a rare naevoid melanoma. 3D-TBP revealed a high naevus count (n = 162) with pigmentation varying from light to dark. Most naevi generally (n = 90), and large (>5 mm diameter) and clinically atypical naevi specifically were located on the back where sun damage was mild. In contrast, naevi count was low (n = 25 total) on the head/neck and lower limbs where sun damage was severe. Thus, melanoma location correlated with naevi density, rather than degree of sun damage. In addition to the MITF E318K homozygosity, there was heterozygosity for four other moderate-risk variants, which may contribute to melanoma risk. Further research is warranted to explore whether melanomas in E318K heterozygous and other homozygotes coincide with regions of high naevi density as opposed to sun damage. This could inform future melanoma screening/surveillance.

Uterine Weight and Perioperative Morbidity in Robotic-Assisted versus Conventional Laparoscopic Hysterectomy.

Background and Objectives: Minimally invasive approaches to benign hysterectomy are the current standard of care when feasible. Use of robotic-assisted laparoscopic hysterectomy (RA-LH) has been increasing; however, direct comparative data that accounts for uterine weight in conventional laparoscopic hysterectomy (CLH) and RA-LH is limited. We sought to examine the impact of uterine weight on immediate perioperative morbidity in CLH versus RA-LH. The primary outcome was a composite of complications including visceral injuries, conversions to abdominal procedures, and transfusions. Methods: A retrospective cohort study of patients who underwent a minimally invasive laparoscopic hysterectomy (CLH and RA-LH) in a single hospital system between January 1, 2014 and December 31, 2017 as identified by Current Procedural Terminology codes. The primary exposure was CLH or RA-LH. Uterine weight was categorized into four groups: <150 g, 150 to < 250 g, 250 to < 450 g, and ≥ 450 g. Results: A total of 1506 patients were included; 539 underwent CLH and 967 underwent RA-LH. Median uterine weight was higher in patients who underwent CLH (161.0 g) compared to RA-LH (147.0 g), P = .001. The odds of the composite of complications in CLH was 4.43 (2.84 - 6.92) higher than the odds of the composite in RA-LH. When stratified by the uterine weight, the odds of complications was significantly higher in CLH in the following categories: <150 g, 250 to < 450 g, and ≥ 450 g (OR: 4.41, 3.28, and 7.81, respectively). Conclusion: Surgical morbidity was lower in RA-LH across the spectrum of uterine weights compared to CLH. Patients may particularly benefit from RA-LH at higher uterine weights.

Digital wrist tomosynthesis (DWT)-based finite element analysis of ultra-distal radius differentiates patients with and without a history of osteoporotic fracture.

Despite effective therapies for those at risk of osteoporotic fracture, low adherence to screening guidelines and limited accuracy of bone mineral density (BMD) in predicting fracture risk preclude identification of those at risk. Because of high adherence to routine mammography, bone health screening at the time of mammography using a digital breast tomosynthesis (DBT) scanner has been suggested as a potential solution. BMD and bone microstructure can be measured from the wrist using a DBT scanner. However, the extent to which biomechanical variables can be derived from digital wrist tomosynthesis (DWT) has not been explored. Accordingly, we measured stiffness from a DWT based finite element (DWT-FE) model of the ultra-distal (UD) radius and ulna, and correlate these to reference microcomputed tomography image based FE (µCT-FE) from five cadaveric forearms. Further, this method is implemented to determine in vivo reproducibility of FE derived stiffness of UD radius and demonstrate the in vivo utility of DWT-FE in bone quality assessment by comparing two groups of postmenopausal women with and without a history of an osteoporotic fracture (Fx; n = 15, NFx; n = 51). Stiffness obtained from DWT and µCT had a strong correlation (R2 = 0.87, p < 0.001). In vivo repeatability error was <5 %. The NFx and Fx groups were not significantly different in DXA derived minimum T-scores (p > 0.3), but stiffness of the UD radius was lower for the Fx group (p < 0.007). Logistic regression models of fracture status with stiffness of the nondominant arm as the predictor were significant (p < 0.01). In conclusion this study demonstrates the feasibility of fracture risk assessment in mammography settings using DWT imaging and FE modeling in vivo. Using this approach, bone and breast screening can be performed in a single visit, with the potential to improve both the prevalence of bone health screening and the accuracy of fracture risk assessment.

Development and evaluation of a novel educational program for providers on the use of polygenic risk scores.

PURPOSE: This study aimed to develop an online educational program for using polygenic risk score (PRS) for breast and ovarian cancer risk assessments and to evaluate the impact on the attitudes, confidence, knowledge, and preparedness of genetic health care providers (GHPs). METHODS: The educational program comprises an online module that covers the theoretical aspects of PRS and a facilitated virtual workshop with prerecorded role-plays and case discussions. Data were collected in pre- and posteducation surveys. Eligible participants were GHPs working in Australian familial cancer clinics registered to recruit patients for a breast and ovarian cancer PRS clinical trial (n = 12). RESULTS: A total of 124 GHPs completed the PRS education, of whom 80 (64%) and 67 (41%) completed the pre- and posteducation surveys, respectively. Before education, GHPs reported limited experience, confidence, and preparedness using PRS, but they recognized its potential benefits. After education, GHPs indicated improved attitudes (P ≤ .001), confidence (P ≤ .001), knowledge (P ≤ .001), and preparedness (P ≤ .001) to use PRS. Most GHPs thought that the program entirely met their learning needs (73%) and was completely relevant to their clinical practice (88%). GHPs identified PRS implementation barriers, including limited funding models, diversity issues, and need for clinical guidelines. CONCLUSION: Our education program improved GHP attitudes, confidence, knowledge, and preparedness for using PRS/personalized risk and provides a framework for the development of future programs.

Health Care Utilization During the COVID-19 Pandemic Among Individuals Born Preterm.

Importance: Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm. Objective: To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term. Design, Setting, and Participants: In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022. Exposures: Premature birth (<37 weeks' gestation). Main Outcomes and Measures: The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (≥37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs ≥37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion. Results: Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78). Conclusions and Relevance: These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models.

Pilot imaging of the colony stimulating factor 1 receptor in the brains of virally-suppressed individuals with HIV.

OBJECTIVE: Neuroimmune activation is a putative driver of cognitive impairment in people with HIV (PWH), even in the age of modern antiretroviral therapy. Nevertheless, imaging of the microglial marker, the 18 kDa translocator protein (TSPO), with positron emission tomography (PET) in treated PWH has yielded inconclusive findings. One potential reason for the varied TSPO results is a lack of cell-type specificity of the TSPO target. DESIGN: [ 11 C]CPPC, 5-cyano- N -(4-(4-[ 11 C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl) furan-2-carboxaminde, is a radiotracer for use with PET to image the colony stimulating factor 1 receptor (CSF1R). The CSF1R is expressed on microglia and central nervous system macrophages, with little expression on other cell types. We used [ 11 C]CPPC PET in virally-suppressed- (VS)-PWH and HIV-uninfected individuals to estimate the effect sizes of higher CSF1R in the brains of VS-PWH. METHODS: Sixteen VS-PWH and 15 HIV-uninfected individuals completed [ 11 C]CPPC PET. [ 11 C]CPPC binding (V T ) in nine regions was estimated using a one-tissue compartmental model with a metabolite-corrected arterial input function, and compared between groups. RESULTS: Regional [ 11 C]CPPC V T did not significantly differ between groups after age- and sex- adjustment [unstandardized beta coefficient ( B ) = 1.84, standard error (SE) = 1.18, P  = 0.13]. The effect size was moderate [Cohen's d  = 0.56, 95% confidence interval (CI) -0.16, 1.28), with strongest trend of higher V T in VS-PWH in striatum and parietal cortex (each P  = 0.04; Cohen's d  = 0.71 and 0.72, respectively). CONCLUSIONS: A group difference in [ 11 C]CPPC V T was not observed between VS-PWH and HIV-uninfected individuals in this pilot, although the observed effect sizes suggest the study was underpowered to detect regional group differences in binding.

The MC1R r allele does not increase melanoma risk in MITF E318K carriers.

BACKGROUND: Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored. OBJECTIVES: To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K- individuals. MATERIALS AND METHODS: Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/- cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank). RESULTS: The cohort comprised 1165 MITF E318K- and 322 E318K+ individuals. In E318K- cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P < 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P < 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67-2.49); P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54-1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20-1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P < 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ individuals. CONCLUSIONS: RHC alleles/genotypes modify melanoma risk differently in MITF E318K- and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K- individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ individuals.

Variations in signal-to-noise characteristics of tissue-equivalent attenuators for mammographic automatic exposure control system performance evaluation.

PURPOSE: This work investigates the impact of tissue-equivalent attenuator choice on measured signal-to-noise ratio (SNR) for automatic exposure control (AEC) performance evaluation in digital mammography. It also investigates how the SNR changes for each material when used to evaluate AEC performance across different mammography systems. METHODS: AEC performance was evaluated for four mammography systems using seven attenuator sets at two thicknesses (4 and 8 cm). All systems were evaluated in 2D imaging mode, and one system was evaluated in digital breast tomosynthesis (DBT) mode. The methodology followed the 2018 ACR digital mammography quality control (DMQC) manual. Each system-attenuator-thickness combination was evaluated using For Processing images in ImageJ with standard ROI size and location. The closest annual physicist testing results were used to explore the impact of varying measured AEC performance on image quality. RESULTS: The measured SNR varied by 44%-54% within each system across all attenuators at 4 cm thickness in 2D mode. The variation appeared to be largely due to changes in measured noise, with variations of 46%-67% within each system across all attenuators at 4 cm thickness in 2D mode. Two systems had failing SNR levels for two of the materials using the minimum SNR criterion specified in the ACR DMQC manual. Similar trends were seen in DBT mode and at 8 cm thickness. Within each material, there was 115%-131% variation at 4 cm and 82%-114% variation at 8 cm in the measured SNR across the four imaging systems. Variation in SNR did not correlate with system operating level based on visual image quality and average glandular dose (AGD). CONCLUSION: Choice of tissue-equivalent attenuator for AEC performance evaluation affects measured SNR values. Depending on the material, the difference may be enough to result in failure following the longitudinal and absolute thresholds specified in the ACR DMQC manual.

The First Hybrid International Educational Comprehensive Cleft Care Workshop.

OBJECTIVE: Describe the first hybrid global simulation-based comprehensive cleft care workshop, evaluate impact on participants, and compare experiences based on in-person versus virtual attendance. DESIGN: Cross-sectional survey-based evaluation. SETTING: International comprehensive cleft care workshop. PARTICIPANTS: Total of 489 participants. INTERVENTIONS: Three-day simulation-based hybrid comprehensive cleft care workshop. MAIN OUTCOME MEASURES: Participant demographic data, perceived barriers and interventions needed for global comprehensive cleft care delivery, participant workshop satisfaction, and perceived short-term impact on practice stratified by in-person versus virtual attendance. RESULTS: The workshop included 489 participants from 5 continents. The response rate was 39.9%. Participants perceived financial factors (30.3%) the most significant barrier and improvement in training (39.8%) as the most important intervention to overcome barriers facing cleft care delivery in low to middle-income countries. All participants reported a high level of satisfaction with the workshop and a strong positive perceived short-term impact on their practice. Importantly, while this was true for both in-person and virtual attendees, in-person attendees reported a significantly higher satisfaction with the workshop (28.63 ± 3.08 vs 27.63 ± 3.93; P = .04) and perceived impact on their clinical practice (22.37 ± 3.42 vs 21.02 ± 3.45 P = .01). CONCLUSION: Hybrid simulation-based educational comprehensive cleft care workshops are overall well received by participants and have a positive perceived impact on their clinical practices. In-person attendance is associated with significantly higher satisfaction and perceived impact on practice. Considering that financial and health constraints may limit live meeting attendance, future efforts will focus on making in-person and virtual attendance more comparable.

The PilT retraction ATPase promotes both extension and retraction of the MSHA type IVa pilus in Vibrio cholerae.

Diverse bacterial species use type IVa pili (T4aP) to interact with their environments. The dynamic extension and retraction of T4aP is critical for their function, but the mechanisms that regulate this dynamic activity remain poorly understood. T4aP are typically extended via the activity of a dedicated extension motor ATPase and retracted via the action of an antagonistic retraction motor ATPase called PilT. These motors are generally functionally independent, and loss of PilT commonly results in T4aP hyperpiliation due to undeterred pilus extension. However, for the mannose-sensitive hemagglutinin (MSHA) T4aP of Vibrio cholerae, the loss of PilT unexpectedly results in a loss of surface piliation. Here, we employ a combination of genetic and cell biological approaches to dissect the underlying mechanism. Our results demonstrate that PilT is necessary for MSHA pilus extension in addition to its well-established role in promoting MSHA pilus retraction. Through a suppressor screen, we also provide genetic evidence that the MshA major pilin impacts pilus extension. Together, these findings contribute to our understanding of the factors that regulate pilus extension and describe a previously uncharacterized function for the PilT motor ATPase.

Attitudes of Australian dermatologists on the use of genetic testing: A cross-sectional survey with a focus on melanoma.

Background: Melanoma genetic testing reportedly increases preventative behaviour without causing psychological harm. Genetic testing for familial melanoma risk is now available, yet little is known about dermatologists' perceptions regarding the utility of testing and genetic testing ordering behaviours. Objectives: To survey Australasian Dermatologists on the perceived utility of genetic testing, current use in practice, as well as their confidence and preferences for the delivery of genomics education. Methods: A 37-item survey, based on previously validated instruments, was sent to accredited members of the Australasian College of Dermatologists in March 2021. Quantitative items were analysed statistically, with one open-ended question analysed qualitatively. Results: The response rate was 56% (256/461), with 60% (153/253) of respondents between 11 and 30 years post-graduation. While 44% (112/252) of respondents agreed, or strongly agreed, that genetic testing was relevant to their practice today, relevance to future practice was reported significantly higher at 84% (212/251) (t = -9.82, p < 0.001). Ninety three percent (235/254) of respondents reported rarely or never ordering genetic testing. Dermatologists who viewed genetic testing as relevant to current practice were more likely to have discussed (p < 0.001) and/or offered testing (p < 0.001). Respondents indicated high confidence in discussing family history of melanoma, but lower confidence in ordering genetic tests and interpreting results. Eighty four percent (207/247) believed that genetic testing could negatively impact life insurance, while only 26% (63/244) were aware of the moratorium on using genetic test results in underwriting in Australia. A minority (22%, 55/254) reported prior continuing education in genetics. Face-to-face courses were the preferred learning modality for upskilling. Conclusion: Australian Dermatologists widely recognise the relevance of genetic testing to future practice, yet few currently order genetic tests. Future educational interventions could focus on how to order appropriate genetic tests and interpret results, as well as potential implications on insurance.

The effect of obesity on adipose-derived stromal cells and adipose tissue and their impact on cancer.

The significant increase in the incidence of obesity represents the next global health crisis. As a result, scientific research has focused on gaining deeper insights into obesity and adipose tissue biology. As a result of the excessive accumulation of adipose tissue, obesity results from hyperplasia and hypertrophy within the adipose tissue. The functional alterations in the adipose tissue are a confounding contributing factor to many diseases, including cancer. The increased incidence and aggressiveness of several cancers, including colorectal, postmenopausal breast, endometrial, prostate, esophageal, hematological, malignant melanoma, and renal carcinomas, result from obesity as a contributing factor. The increased morbidity and mortality of obesity-associated cancers are attributable to increased hormones, adipokines, and cytokines produced by the adipose tissue. The increased adipose tissue levels observed in obese patients result in more adipose stromal/stem cells (ASCs) distributed throughout the body. ASCs have been shown to impact cancer progression in vitro and in preclinical animal models. ASCs influence tumor biology via multiple mechanisms, including the increased recruitment of ASCs to the tumor site and increased production of cytokines and growth factors by ASCs and other cells within the tumor stroma. Emerging evidence indicates that obesity induces alterations in the biological properties of ASCs, subsequently leading to enhanced tumorigenesis and metastasis of cancer cells. As the focus of this review is the interaction and impact of ASCs on cancer, the presentation is limited to preclinical data generated on cancers in which there is a demonstrated role for ASCs, such as postmenopausal breast, colorectal, prostate, ovarian, multiple myeloma, osteosarcoma, cervical, bladder, and gastrointestinal cancers. Our group has investigated the interactions between obesity and breast cancer and the mechanisms that regulate ASCs and adipocytes in these different contexts through interactions between cancer cells, immune cells, and other cell types present in the tumor microenvironment (TME) are discussed. The reciprocal and circular feedback loop between obesity and ASCs and the mechanisms by which ASCs from obese patients alter the biology of cancer cells and enhance tumorigenesis will be discussed. At present, the evidence for ASCs directly influencing human tumor growth is somewhat limited, though recent clinical studies suggest there may be some link.

Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

Amelanotic/hypopigmented melanoma in a sibship with oculocutaneous albinism.

Oculocutaneous albinism (OCA) is a rare condition characterized by hypopigmentation. A female proband and her sister, both with primary amelanotic/hypopigmented melanoma, underwent three-dimensional total-body photography and dermoscopy. Both sisters had exome sequencing along with their brother, who had OCA but no history of melanoma. Imaging analysis was consistent with OCA in terms of individual typology angle scores, degree of sun damage, and high naevus counts. Exome data filtered for variants in known OCA and melanoma/naevi susceptibility genes (n = 98) found all siblings were compound heterozygous for TYR mutations (Arg402Ter and Val275Phe), previously reported as causative OCA variants. A rare missense variant in PARP1 (p.Pro377Ser) was solely present in the melanoma-unaffected brother, which is noteworthy as this was previously reported as potentially protective in a familial melanoma pedigree positive for CDKN2A mutations. Evaluation and confirmation of functional impact in larger cohorts could personalize melanoma screening in OCA.

Expression of Novel Kinase MAP3K19 in Various Cancers and Survival Correlations.

Mitogen Activated Protein (MAP) kinases are a category of serine/threonine kinases that have been demonstrated to regulate intracellular events including stress responses, developmental processes, and cancer progression Although many MAP kinases have been extensively studied in various disease processes, MAP3K19 is an understudied kinase whose activities have been linked to lung disease and fibroblast development. In this manuscript, we use bioinformatics databases starBase, GEPIA, and KMPlotter, to establish baseline expressions of MAP3K19 in different tissue types and its correlation with patient survival in different cancers.

GM1 ganglioside modifies microglial and neuroinflammatory responses to α-synuclein in the rat AAV-A53T α-synuclein model of Parkinson's disease.

Among the pathological events associated with the dopaminergic neurodegeneration characteristic of Parkinson's disease (PD) are the accumulation of toxic forms of α-synuclein and microglial activation associated with neuroinflammation. Although numerous other processes may participate in the pathogenesis of PD, the two factors mentioned above may play critical roles in the initiation and progression of dopamine neuron degeneration in PD. In this study, we employed a slowly progressing model of PD using adeno-associated virus-mediated expression of human A53T α-synuclein into the substantia nigra on one side of the brain and examined the microglial response in the striatum on the injected side compared to the non-injected (control) side. We further examined the extent to which administration of the neuroprotective ganglioside GM1 influenced α-synuclein-induced glial responses. Changes in a number of microglial morphological measures (i.e., process length, number of endpoints, fractal dimension, lacunarity, density, and cell perimeter) were indicative of the presence of activated microglial and an inflammatory response on the injected side of the brain, compared to the control side. In GM1-treated animals, no significant differences in microglial morphology were observed between the injected and control striata. Follow-up studies showed that mRNA expression for several inflammation-related genes was increased on the A53T α-synuclein injected side vs. the non-injected side in saline-treated animals and that such changes were not observed in GM1-treated animals. These data show that inhibition of microglial activation and potentially damaging neuroinflammation by GM1 ganglioside administration may be among the many factors that contribute to the neuroprotective effects of GM1 in this model and possibly in human PD.