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PURPOSE: Violence is a leading cause of death for adolescents in inner-city settings. This article describes violent behaviors in relation to other risk behaviors (e.g., substance use) among adolescents screened in an urban emergency department (ED). METHODS: Patients aged 14-18 years were approached to self-administer a computerized survey assessing violent behaviors (i.e., physical aggression), substance use (cigarettes, alcohol, marijuana), and weapon carriage. RESULTS: A total of 1128 adolescents (83.8% participation rate; 45.9% male; 58.0% African-American) were surveyed. In the past year, 75.3% of adolescents reported peer violence, 27.6% reported dating violence, and 23.5% reported carrying a weapon. In the past year, 28.0% drank alcohol, 14.4% binge drank, 5.7% reported alcohol-related fighting, and 36.9% smoked marijuana. Logistic regression analyses predicting violent behaviors were significant. Teens reporting peer violence were more likely to be younger, African-American, on public assistance, carry a weapon, binge drink, and smoke marijuana. Teens reporting dating violence were more likely to be female, African-American, carry a weapon, binge drink, screen positive for alcohol problems, and smoke marijuana. Teens reporting alcohol-related fighting were more likely to carry a weapon, binge drink, screen positive for alcohol problems, and smoke marijuana. CONCLUSIONS: Adolescents presenting to an urban ED have elevated rates of violent behaviors. Substance use (i.e., binge drinking and smoking marijuana) is an important risk factor for violent behaviors among urban adolescents. Universal screening and intervention protocols to address multiple risk behaviors, including violent behaviors and substance use, may be useful to prevent injury among adolescents presenting to the urban ED. [ABSTRACT FROM AUTHOR]

Abstract Background Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB), normal differentiated squamous epithelium (ND), and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA) were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and molecular pathways mediating ESCC development and provide information potentially useful in designing novel therapeutic interventions for this tumor type.

Abstract Background Genomic instability plays an important role in human cancers. We previously characterized genomic instability in esophageal squamous cell carcinomas (ESCC) in terms of loss of heterozygosity (LOH) and copy number (CN) changes in tumors using the Affymetrix GeneChip Human Mapping 500K array in 30 cases from a high-risk region of China. In the current study we focused on copy number neutral (CN = 2) LOH (CNNLOH) and its relation to gene expression in ESCC. Results Overall we found that 70% of all LOH observed was CNNLOH. Ninety percent of ESCCs showed CNNLOH (median frequency in cases = 60%) and this was the most common type of LOH in two-thirds of cases. CNNLOH occurred on all 39 autosomal chromosome arms, with highest frequencies on 19p (100%), 5p (96%), 2p (95%), and 20q (95%). In contrast, LOH with CN loss represented 19% of all LOH, occurred in just half of ESCCs (median frequency in cases = 0%), and was most frequent on 3p (56%), 5q (47%), and 21q (41%). LOH with CN gain was 11% of all LOH, occurred in 93% of ESCCs (median frequency in cases = 13%), and was most common on 20p (82%), 8q (74%), and 3q (42%). To examine the effect of genomic instability on gene expression, we evaluated RNA profiles from 17 pairs of matched normal and tumor samples (a subset of the 30 ESCCs) using Affymetrix U133A 2.0 arrays. In CN neutral regions, expression of 168 genes (containing 1976 SNPs) differed significantly in tumors with LOH versus tumors without LOH, including 101 genes that were up-regulated and 67 that were down-regulated. Conclusion Our results indicate that CNNLOH has a profound impact on gene expression in ESCC, which in turn may affect tumor development.

Abstract Background Esophageal squamous cell carcinomas (ESCC) are usually asymptomatic and go undetected until they are incurable. Cytological screening is one strategy to detect ESCC at an early stage and has shown promise in previous studies, although improvement in sensitivity and specificity are needed. Proteases modulate cancer progression by facilitating tumor invasion and metastasis. In the current study, matrix metalloproteinases (MMPs) were studied in a search for new early detection markers for ESCC. Methods Protein expression levels of MMPs were measured using zymography in 24 cases of paired normal esophagus and ESCC, and in the tumor-associated stroma and tumor epithelium in one sample after laser capture microdissection (LCM). MMP-3 and MMP-10 transcripts in both the epithelium and stroma in five cases were further analyzed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Results Gelatin zymography showed bands corresponding in size to MMP-2, MMP-3, MMP-9, and MMP-10 enzymes in each of the 24 cancer cases. MMP levels tended to be higher in tumors than paired normal tissue; however, only the 45 kDa band that corresponds to the activated form of MMP-3 and MMP-10 was strongly expressed in all 24 tumors with little or no expression in the paired normal foci. LCM-based analysis showed the 45 kDA band to be present in both the stromal and epithelial components of the tumor microenvironment, and that MMP-3 and MMP-10 mRNA levels were higher in tumors than paired normal tissues for each compartment. Conclusions Increased levels of MMPs occur in ESCC suggesting their up-regulation is important in esophageal tumorigenesis. The up-regulated gene products have the potential to serve as early detection markers in the clinic.

Abstract Background Family history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse. Methods 600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regressions, and hazard ratios (HRs) from Cox proportional hazard regressions were estimated. Results Increased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.39–2.12), FH of any UGI cancer (OR = 2.28, 95%CI = 1.77–2.95) and FH of esophageal cancer (OR = 2.84, 95%CI = 2.09–3.86), but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.01–3.29). Conclusion These data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis.

Abstract Background A subset of cutaneous malignant melanoma and dysplastic nevi (CMM/DN) families is linked to 1p36. To date, no CMM/DN susceptibility gene has been identified at this locus. Data from mouse studies identified chromodomain helicase DNA binding protein 5 (CHD5) as a tumor suppressor affecting cellular proliferation and apoptosis via the CDKN2A/p53 pathway. Based on these findings, we felt it was important to screen CHD5 as a familial CMM/DN susceptibility gene. Methods Eight unrelated CMM/DN families showing prior evidence of linkage to the 1p36 locus were identified for CHD5 mutation screening. One CMM/DN affected and one unaffected individual from each family were selected for sequencing of the CHD5 coding exons and their respective intron-exon boundaries. CHD5 variants that were identified solely among affecteds in the screening panel were further assessed by sequencing additional affected and unaffected members of these families to determine if the variant co-segregated with the CMM/DN phenotype. Results Single nucleotide polymorphisms in the CHD5 intronic and coding regions were identified among affecteds in the screening panel. None of these variants completely co-segregated with CMM/DN affection status among these eight families. Conclusion There is no evidence to support CHD5 as a major melanoma susceptibility gene among the eight CMM/DN families screened.

Abstract Background Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease. Methods/Design We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing. Discussion EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.

Abstract Background The melanocortin 1 receptor gene (MC1R) is responsible for normal pigment variation in humans and is highly polymorphic with numerous population-specific alleles. Some MC1R variants have been associated with skin cancer risk. Results Allele frequency data were compiled on 55 single nucleotide polymorphisms from seven geographically distinct human populations (n = 2306 individuals). MC1R nucleotide diversity, π, was much higher (10.1 × 10-4) than in other genes for all subjects. A large degree of population differentiation, determined by FST, was also present, particularly between Asia and all other populations, due to the p.R163Q (c.488 G>A) polymorphism. The least amount of differentiation was between the United States, Northern Europe, and Southern Europe. Tajima's D statistic suggested the presence of positive selection in individuals from Europe. Conclusion This study further quantifies the degree of population-specific genetic variation and suggests that positive selection may be present in European populations in MC1R.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease. Results Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP) array, including loss of heterozygosity (LOH) and copy number alterations (CNA), for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods – using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT) software – and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q), including 20 novel LOH regions (10 kb to 4.26 Mb). Fifteen CNA-loss regions (200 kb to 4.3 Mb) and 36 CNA-gain regions (200 kb to 9.3 Mb) were also identified. Conclusion These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors and typically presents at an advanced and rapidly fatal stage. To better understand the role of genetics in the etiology and prevention of ESCC and to identify potential susceptibility genes as well as early detection markers, we previously compared tumor and matched normal tissues from ESCC patients from a high-risk area of China using cDNA expression microarrays and identified 41 differentially-expressed genes (13 over-expressed and 28 under-expressed). Methods In the current study, we validated and quantitated differential mRNA expression in a sample of nine of these 41 genes, including four that were over-expressed (SPARC, FADD, Fascin, COL7A1), and five that were under-expressed (CK4, TGM3, ECM1, PPL, EVPL), in 75 new ESCC patients using quantitative Real-time RT-PCR and the 2-ΔΔCT method to examine both tumor and matched normal tissue. In addition, we examined expression patterns for these genes by selected demographic and clinical characteristics. Results Four previously over-expressed (tumor ≥2-fold normal) genes were all increased in the majority of new ESCC patients: SPARC was increased in 71% of patients, Fascin in 70%, FADD in 63%, and COL7A1 in 57%. Five previously under-expressed (tumor ≤0.5-fold normal) genes similarly showed decreased mRNA expression in two-thirds or more of patients: CK4 was decreased in 83% of patients, TGM3 in 77%, ECM1 in 73%, and PPL and EVPL in 67% each. In subset analyses, associations with age (for COL7A1), family history (for PPL and ECM1), and alcohol use (for SPARC and Fascin) were also noted. Conclusion These data indicate that these nine genes have consistent differential mRNA expression, validating results of our previous cDNA array results, and affirming their potential role in the early detection of ESCC.

Background: Canada has one of the highest prevalence of cannabis use globally, particularly among young adults aged 20-24 (50%) and youth aged 16-19 (37%). In 2018, Canada legalized recreational cannabis with the aim of protecting youth by restricting their access and raising public awareness of health risks. However, there has been limited qualitative research on the perceptions of harms associated with youth cannabis use since legalization, which is crucial for developing effective harm reduction strategies. This qualitative study examined perceptions of cannabis use among youth from the perspectives of youth, parents, and service providers. We explored how participants described the perceived risks or harms associated with youth cannabis use, as well as how they described their own and others' approaches to reducing cannabis-related risks and harms., Methods: This qualitative study used a community-based participatory research approach in partnership with Families for Addiction Recovery (FAR), a national charity founded by parents of youth and young adults with addiction issues. Virtual semi-structured interviews were conducted, and the data were analyzed using thematic analysis., Results: The study included 88 participants from three key groups (n = 31 youth, n = 26 parents, n = 31 service providers). Two main themes emerged regarding perceived risks or harms associated with cannabis use: (1) concerns about cannabis-related risks and harms, including addiction, brain development, impact on family, and various adverse effects on areas such as motivation, concentration, finances, employment, education, physical and mental health; and (2) minimization of risks and harms, featuring conflicting messages, normalization, and perceptions of cannabis being less harmful than other substances. Additionally, two themes related to harm reduction approaches were identified: (1) implementation of harm reduction, and (2) challenges in implementing a harm reduction approach. Specific challenges for each participant group were noted, along with structural barriers such as unavailable and inaccessible services, easy access to cannabis, inadequate public education, and insufficient information on lower-risk cannabis use guidelines., Conclusions: Youth cannabis use is a significant public health concern that requires a multi-pronged approach. Developing youth-centered harm reduction strategies that recognize the developmental needs and vulnerabilities of youth, as well as the important role of families, is imperative., (© 2024. The Author(s).)

Background/objectives: Childhood maltreatment has been linked to numerous adverse outcomes in adulthood, including problem substance use. However, not all individuals exposed to childhood maltreatment develop substance use problems, indicating the role of other factors in influencing this outcome. Past work suggests that adverse early life experiences, including childhood maltreatment, lead to neurobiological changes in frontolimbic functions that, in turn, result in altered stress and reward responses, heightened impulsivity, affect dysregulation, and, ultimately, increased risk for maladaptive behaviors such as substance use. The aim of this preliminary investigation using cross-sectional data was to test associations between these factors in the relationship between childhood maltreatment and alcohol use problems in a sample of emerging adults., Methods: Emerging adults (18-30 years old) who identified as regular drinkers (i.e., drinking at least 2-4 times in the past month) were recruited from a crowd-sourcing platform (Prolific) as well as community samples. Participants completed online standardized questionnaires assessing reward sensitivity and responsiveness, impulsivity, emotion regulation, and alcohol consequences., Results: Path analyses demonstrated good fit for the data (SRMR = 0.057, RMSEA = 0.096, 90% CI [0.055, 0.142], CFI = 0.957). Childhood maltreatment was associated with reward responsiveness (β = -0.026, Z = -4.222, p < 0.001) and emotion dysregulation (β = 0.669, Z = 9.633, p < 0.001), which in turn was associated with urgency and, subsequently, alcohol consequences (β = 0.758, Z = 7.870, p < 0.001)., Conclusions: Although these findings are preliminary, the current study is one of the first to test a comprehensive model addressing the relationship between childhood maltreatment and alcohol use problems. The findings have the potential to inform treatment strategies that target motivation and goal-directed action for reducing and managing consequences associated with childhood maltreatment. Future research should test the model using longitudinal data to address the limitations of a cross-sectional study and assess temporal associations between constructs.

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection that has a high mortality rate. Proprotein convertase subtilisin kexin 9 (PCSK9) is a serine protease secreted by the liver. Its binding to the low-density lipoprotein (LDL) receptor enhances its degradation, causing an increase in LDL levels in the blood. Objectives : Administering a PCSK9 inhibitor leading to an increase in lipid uptake by the liver may positively affect septic patients due to the increased removal of endotoxins. Methods : This preliminary study aimed to examine the safety of PCSK9 inhibitor use in septic and septic shock patients. We treated five septic patients in the intensive care unit with 300 mg of alirocumab following serious adverse events for 28 days. Results : Four of our patients did not experience any adverse events, and all of them survived. One patient died after discharge from the intensive care unit, and this death was presumably not related to the study drug. The patients rapidly recovered from the inflammatory stage of sepsis. Conclusions : Alirocumab appears safe in severe sepsis and septic shock patients. The outcome data are promising. Only a basic safety profile can be assessed based on this pilot study. Further study with a PCSK-9 inhibitor in septic or septic shock patients is required to further determine its benefit in ICU patients.

Background and Objectives: The incidence of proximal femoral fractures (PFFs) is rising, causing significant morbidity and mortality. Regional anesthesia (RA)'s benefits include the avoidance of intubation and mechanical ventilation, decreased blood loss, and improved analgesia. General anesthesia (GA) offers improved hemodynamic stability. This study examines the in-hospital post-surgical morbidity and mortality seen in PFFs in a cohort of the elderly undergoing GA or RA. Materials and Methods: This is a retrospective cohort study of 319 PFF patients older than 65 years over a single year. Results: In total, 73.7% of patients underwent GA. The patient characteristics were identical between groups, except for smoking. Hypertension was the most frequent comorbidity, followed by hyperlipidemia, NIDDM, and IHD. The overall patient complication rate was 11.4%. Pneumonia was the most common complication (5.1% in GA, 8.4% in RA). A total of 0.9% of patients required ICU admission. Overall, the in-hospital mortality rate was 2.3%, with no statistically significant difference between GA and RA. The GA and RA cohorts were similar in terms of their patient demographics, medical history, and preoperative parameters. In total, 73% of surgeries were under GA. No statistically significant differences were found in total anesthesia time or complication rates. Conclusions: We did not find a difference between general and spinal anesthesia regarding complication rates, anesthesia time, or morbidity. General anesthesia remains best suited for patients receiving anticoagulation treatment and undergoing semi-urgent surgery, but, other than that, the mode of anesthesia administered remains up to the anesthesiologist's preference.

A woman in her mid-30s presented to our 30-bed healthcare centre with extensive burns, hours after falling into a shallow pit of burning dried tea leaves. On arrival, there was no evidence of airway compromise. She was fully conscious but had signs of shock and hypovolemia. Forty-five per cent of the total body surface area was burned, including the face, neck, thorax, abdomen, upper limbs and thighs. The family refused referral to a burns centre and insisted on continuing treatment at our facility. Our hospital, not equipped to manage burns, was adapted to deliver effective, immediate care. After initial stabilisation, the patient was unwilling to remain hospitalised because of her husband's employment commitment. Subsequently, we were notified that the patient died within 1 month of discharge. This article highlights the importance of burns care facilities in rural India and the impact of a failure to access quality health on outcomes., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Research on exposure to stressors and nonsuicidal self-injury (NSSI) in daily life has been lacking, particularly among emerging adults (aged 18-25 years). The aim of this study was to determine whether daily stressors predicted same-day and next-day NSSI thoughts and engagement, and whether emotion dysregulation moderated this relation. Participants included 160 emerging adults (83% female, M age  = 19.75, SD = 1.8, 44% White, 22% East Asian, 11% South Asian, and 23% other) who completed a baseline assessment and 14 days of daily diary entries which resulted in 1982 daily assessments (median compliance = 86%; IQR = 12-14). It was found that daily stressors significantly predicted same-day, but not next-day, NSSI thoughts and engagement and this relation was more pronounced for individuals with greater emotion dysregulation. The present study provides new insight into when individuals may be most at risk for NSSI, as well as which individuals may be most vulnerable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Major abdominal wall defects remain a highly morbid complication. Occasionally a fascial defect is encountered, that despite all surgical efforts, is unable to completely approximate at the midline. Here we describe our method and outcomes of using a bridging mesh when the posterior fascia was unable to be approximated during the repair of large postoperative ventral hernias using the modified Rives-Stoppa technique., Methods: A retrospective review was conducted looking at all the open abdominal wall hernia repairs between 2014 and 2020. The cohort of patients who had a bridge placed in addition to the traditional open modified Rives-Stoppa repair were used for this study., Results: Nineteen patients had a mesh inlay bridge placed in addition to a modified Rives-Stoppa repair with a sublay (retrorectus) Ultrapro mesh. For the inlay mesh 13 Symbotex composite meshes were placed and 6 Vicryl meshes used. The average surface area of the defect was 358.1 cm^2. The average length of hospitalization was 8.8 days with a range of 3-24 days. During the immediate postoperative course there were 6 minor complications. During the follow-up period there were 2 recurrences., Discussion: The use of inlay mesh bridge as an adjuvant to a modified Rives-Stoppa repair with a sublay ultrapro mesh is an effective technique for difficult abdominal wall repairs where the posterior fascia is unable to be approximated without tension., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In 2018, Canada legalized recreational cannabis use with the purpose of protecting youth and restricting access. However, concerns have been raised that this objective has not been met as rates of cannabis use among youth aged 16-24 have not declined. Youth cannabis use is associated with various adverse effects including psychosis, anxiety, depression, suicidality, respiratory distress, cannabinoid hyperemesis syndrome, and intoxications. Service providers play a crucial role in addressing youth cannabis use. This study aimed to understand Ontario service providers' perceptions, practices, and recommendations on youth cannabis use., Methods: This mixed method study included a survey and two focus groups. The survey was distributed to mental health service providers serving youth aged 16-24 across Ontario who were given the option to participate in a focus group. The survey included closed and open-ended questions regarding perceptions, practices, and recommendations, while the focus groups explored these categories in greater depth. Descriptive statistics were used to analyze close-ended questions and interpretative content analysis was applied for open-ended questions. Focus group data were analyzed using thematic analysis., Results: The survey was completed by 160 service providers and 12 participated in two focus groups. Regarding perceptions, 60% of survey participants agreed with legalization, 26% had a strong understanding of medical versus recreational cannabis, 84% believed that cannabis has physical and mental health risks, and 49% perceived stigmatization. Less than half of the survey participants reported screening or assessing cannabis use, 16% stated they are highly familiar with treating cannabis use, and 67% reported that they rarely work with families. Subthemes identified in the focus groups under perceptions included normalization and stigmatization, harms for youth, and stigma, racism, and discrimination. Subthemes under practice included cannabis not being the primary focus, challenges with screening, assessment, and intervention, and referral to specialized services. Both the survey and focus group participants recommended increasing public education, enhancing service provider training, improving regulation and policies, reducing stigma and minimization, improving service access, and providing more culturally responsive services., Conclusion: Youth cannabis use in Canada remains a significant public health concern, necessitating a more comprehensive plan to protect Ontario youth and reduce associated harms., (© 2023. Crown.)

Background: The clinical presentation of acute appendicitis in the youngest age lacks specific signs and symptoms, and it is difficult to obtain an accurate clinical diagnosis. Once the diagnosis is made, it is necessary to determine if the appendicitis is simple and able to be managed non-surgically, or complicated, therefore requiring surgery. Together with the clinical picture and imaging, routine laboratory values play a vital role in this decision. The aim of this study is to evaluate routine blood in their ability to differentiate between complicated and uncomplicated acute appendicitis., Method: A retrospective analysis was conducted from a single pediatric surgery department of all children 5 years of age or younger who underwent surgery for acute appendicitis between the years 2010-2020., Results: 728 children were diagnosed with acute appendicitis, and 42 children were under the age of 5 years. There was a significant difference in the C-reactive protein, white blood cell count, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio in the complicated group versus the uncomplicated group. The value of these together for prediction complicated appendicitis were 84.8% sensitivity, 80.9% specificity, 82.8% positive predictive value, and 72.8% negative predictive value. These values were all higher than both the Alvarado score and the PAS ( P   <  .05)., Conclusions: C-reactive protein, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio are simple laboratory parameters that can help identify complicated versus uncomplicated appendicitis in children 5 years old or younger. These universal parameters may help guide the treatment and decision to operate on a difficult to diagnose population.

The recent COVID-19 pandemic has catalyzed the attention of the scientific community to the long-standing issue of lower respiratory tract infections. The myriad of airborne bacterial, viral and fungal agents to which humans are constantly exposed represents a constant threat to susceptible individuals and bears the potential to reach a catastrophic scale when the ease of inter-individual transmission couples with a severe pathogenicity. While we might be past the threat of COVID-19, the risk of future outbreaks of respiratory infections is tangible and argues for a comprehensive assessment of the pathogenic mechanisms shared by airborne pathogens. On this regard, it is clear that the immune system play a major role in dictating the clinical course of the infection. A balanced immune response is required not only to disarm the pathogens, but also to prevent collateral tissue damage, thus moving at the interface between resistance to infection and tolerance. Thymosin alpha1 (Tα1), an endogenous thymic peptide, is increasingly being recognized for its ability to work as an immunoregulatory molecule able to balance a derailed immune response, working as immune stimulatory or immune suppressive in a context-dependent manner. In this review, we will take advantage from the recent work on the COVID-19 pandemic to reassess the role of Tα1 as a potential therapeutic molecule in lung infections caused by either defective or exaggerated immune responses. The elucidation of the immune regulatory mechanisms of Tα1 might open a new window of opportunity for the clinical translation of this enigmatic molecule and a potential new weapon in our arsenal against lung infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Canadian youth (aged 16-24) have the highest rates of mental health and addiction concerns across all age groups and the most unmet health care needs. There are many structural barriers that contribute to the unmet mental health care needs of youth including lack of available and appropriate services, high costs, long wait times, fragmented and siloed services, lack of smooth transition between child and adult services, stigma, racism, and discrimination, as well as lack of culturally appropriate treatments. Levesque et al. (2013) developed a framework to better understand health care access and this framework conceptualizes accessibility across five dimensions: (1) approachability, (2) availability, (3) affordability, (4) appropriateness, and (5) acceptability. The purpose of this study was to explore access to addiction and mental health services for youth in Ontario, Canada from the perspectives of youth, parents, and service providers., Methods: This qualitative study was a university-community partnership exploring the experiences of youth with mental health concerns and their families from the perspectives of youth, caregivers, and service providers. We conducted semi-structured interviews and used thematic analysis to analyze data., Results: The study involved 25 participants (n = 11 parents, n = 4 youth, n = 10 service providers). We identified six themes related to structural barriers impacting access to youth mental health and services: (1) "The biggest barrier in accessing mental health support is where to look," (2) "There's always going to be a waitlist," (3) "I have to have money to be healthy," (4) "They weren't really listening to my issues," (5) "Having more of a welcoming and inclusive system," and (6) "Health laws aren't doing what they need to do.", Conclusion: Our study identified five structural barriers that map onto the Levesque et al. healthcare access conceptual framework and a sixth structural barrier that is not adequately captured by this model which focuses on policies, procedures, and laws. The findings have implications for policies and service provisions, and underline the urgent need for a mental health strategy that will increase access to care, improve mental health in youth, decrease burden on parents, and reduce inequities in mental health policies and services., (© 2023. The Author(s).)

Wound healing involves a rapid response to the injury by circulating cells, followed by inflammation with an influx of inflammatory cells that release various factors. Soon after, cellular proliferation begins to replace the damaged cells and extracellular matrix, and then tissue remodeling restores normal tissue function. Various factors can lead to pathological wound healing when excessive and irreversible connective tissue/extracellular matrix deposition occurs, resulting in fibrosis. The process is initiated when immune cells, such as macrophages, release soluble factors that stimulate fibroblasts. TGFβ is the most well-characterized macrophage derived pro-fibrotic mediator. Other soluble mediators of fibrosis include connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), and interleukin 10 (IL-10). Thymosin β4 (Tβ4) has shown therapeutic benefit in preventing fibrosis/scarring in various animal models of fibrosis/scarring. The mechanism of action of Tβ4 appears related, in part, to a reduction in the inflammatory response, including a reduction in macrophage infiltration, decreased levels of TGFβ and IL-10, and reduced CTGF activation, resulting in both prevention of fibroblast conversion to myofibroblasts and production of normally aligned collagen fibers. The amino N-terminal end of Tβ4, SDKP (serine-aspartate-lysine-proline), appears to contain the majority of anti-fibrotic activity and has shown excellent efficacy in many animal models of fibrosis, including liver, lung, heart, and kidney fibrosis. Ac-SDKP not only prevents fibrosis but can reverse fibrosis. Unanswered questions and future directions will be presented with regard to therapeutic uses alone and in combination with already approved drugs for fibrosis., (Copyright © 2022.)

The Novel Coronavirus Disease (COVID-19) pandemic has had profound effects on physical and mental health worldwide. Students transitioning out of high school were uniquely impacted at the onset of the pandemic, having missed the opportunity to properly mark the end of their final year in the K-12 school system. The adverse effects of this loss on this population are still unknown. The purpose of the current study was to examine stress, wellbeing, and affect in a sample of 168 students ( N = 168; M age = 17.0, SD = 0.46; 60% female; 40% male) who were completing their final year of high school during the early stages of the pandemic when emergency stay-at-home orders were in place. Participants completed an online survey assessing the impact of COVID-19 on their life satisfaction (pre-COVID19, during COVID-19, and anticipated five years from now), stress, positive affect, and negative affect. Latent class analysis (LCA) was used to create classes of participants based on their responses to the pandemic. A two-subgroup solution provided the best model for the life satisfaction outcome variable. Subgroup 1, optimists , comprised 24% ( N = 40) of the sample and reported high life satisfaction ratings one year prior to COVID-19 and a slight decrease in life satisfaction during COVID-19, and they anticipated an increase in life satisfaction 5 years from now. This group was characterized by low stress, low negative affect, and high positive affect during the pandemic. Subgroup 2, realists , comprised 76% of the population ( N = 128) and experienced similarly high retrospective ratings of pre-COVID life satisfaction but a larger decrease in life satisfaction during the pandemic and a smaller increase in five years. The realist group was characterized by low positive affect, high stress, and high negative affect during the pandemic. The findings suggest that during the pandemic, certain subsamples of adolescents had greater difficulty in managing this transitional period and experienced changes in mood and well-being (i.e., affect, stress) as compared to other adolescents (i.e., optimists ). Future research should investigate the characteristics and coping mechanisms that are instrumental for increasing life satisfaction and positive affect while lowering stress in this population., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Perceived parental criticism is an important measure of the family emotional environment, linked to a variety of psychological difficulties in emerging adults (EAs) and traditionally assessed at a single timepoint. Our study is the first to examine perceived parental criticism as a dynamic construct that fluctuates and interacts with emerging adult (EA) affect across daily life. EAs ( N = 141; ages 18-22; M age = 19.94, 84.5% women) completed a measure of baseline depression symptoms and daily assessments of perceived parental criticism, anger, anxiety, shame, sadness, and happiness across 30 days. Within-person results revealed that previous day perceived parental criticism predicted subsequent day EA anger (but not vice versa). This cross-lagged association only emerged for anger and not other emotions. Additionally, depression moderated this association, with higher depression symptoms increasing the strength of the association. Between-person results revealed that parental criticism was positively associated with mean/trait anger, anxiety, shame, sadness, but not happiness, as well as affect reactivity (innovation variance) for anger. Associations with affect inertia were not significant. Together, these findings suggest parental criticism is more strongly related to negative than positive emotions, is proximally associated with anger in particular, especially among EAs with increased depression, and may be related to aspects of emotion dysregulation. Family interventions aiming to target negative emotionality in EAs should focus on mitigating criticism or educating parents on the importance of considering psychological health such as depression symptomology when providing critical feedback to minimize heightened negative affect or decrease the likelihood of emotional dysfunction in EAs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objectives: There have been concerns about the adverse effects of the COVID-19 pandemic on Canadian youth (aged 16-24) as they have the highest rates of mental health concerns. The objectives of the present study were to explore the experiences of youth with mental health and/or addiction concerns and their families during the pandemic, and to examine how adequate and equitable mental health services have been for youth and families from the perspectives of youth, parents, and service providers., Methods: Using a descriptive qualitative research design and a university-community partnership, we conducted individual interviews with youth, parents, and service providers. The study involved a total of 25 participants (n=15 service users, n=10 service providers). Among the service users, 11 participants were parents and four were youth. We used thematic analysis to analyze interview data., Results: The thematic analysis identified three themes in the data: (1) youth mental health concerns have increased, whereas supports have decreased, (2) families end up being the treatment team with increased burden, little support, and lack of recognition, and (3) inadequate and inequitable mental health services for youth and families are amplified during the pandemic., Conclusion: At a time when mental health needs were higher, the mental health care system offered less support to youth and their families. For a more equitable response to the pandemic, we need an accessible and integrated mental health care system that shows a commitment to addressing social determinants and reducing health disparities and inequities in access to mental health services., (© 2022. The Author(s).)

Background: Despite interest in transdiagnostic dimensional approaches to psychopathology, little is known about the dynamic interplay of affecting and internalizing symptoms that cut across diverse mental health disorders. We examined within-person reciprocal effects of negative and positive affect (NA, PA) and symptoms (depression and anxiety), and their between-person associations with affective dynamics (i.e., affect inertia)., Methods: Individuals currently receiving treatment for psychological disorders (N = 776) completed daily assessments of affect and symptoms across 14 treatment days (average). We used dynamic structural equation modeling to examine daily affect-symptom dynamics., Results: Within-person results indicated NA-symptom reciprocal effects; PA only predicted subsequent depression symptoms. After accounting for changes in mean symptoms and affect over time, NA-anxiety and PA-depression relations remained particularly robust. Between-person correlations indicated NA inertia was positively associated with NA-symptom effects; PA inertia was negatively associated with PA-symptoms effects., Conclusions: Results suggest that transdiagnostic affective treatment approaches may be more useful for reducing internalizing symptoms by decreasing NA compared to increasing PA. Individual differences in resistance to shifting out of affective states (i.e., high NA vs. PA inertia) may be a useful marker for developing tailored interventions., (© 2022 Wiley Periodicals LLC.)

Introduction: The minimally invasive surgical repair of combined inguinal and ventral hernias often requires shifting from one approach or plane to another. The traditional enhanced-view totally extraperitoneal Rives-Stoppa repair consists of a large retro muscular dissection that is unjustified for small ventral hernias. Here we describe a modification to the minimally invasive Rives-Stoppa repair using a limited retro muscular dissection based on the ventral defect size for small/medium-sized hernias, with or without combined inguinal hernias., Methods: From a single surgical team, a retrospective study was performed over a 1-year period. Demographics, hernia characteristics, surgical techniques, intraoperative/postoperative complications, and outcomes were all analyzed and reported. We also included detailed surgical steps, landmarks, pitfalls, and personal tips for this technique., Results: Twenty-four patients underwent a laparoscopic limited retromuscular dissection ventral hernia repair utilizing the eTEP access technique. Eighteen were primary umbilical hernias and six postoperative incisional hernias, and nine were combined ventral and inguinal hernia repairs. Eight of the primary umbilical hernias were EHS classified as medium size, 11 small, and for the incisional hernias, three were classified as M3W1 and two as M3W2. One procedure was converted to TAPP. There were no intraoperative complications. The mean length of stay was 1.25 days (range 1-3). There was one postoperative retromuscular hematoma and no recurrence during the follow-up period., Conclusion: eTEP with limited dissection offers a good and safe solution for small to medium size hernias; it provides an efficient solution when an inguinal hernia is to be addressed as well., (© 2022. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Obesity is associated with short term perinatal risks, causing increased risks in pre- and post-term birth, small and large for gestational (SGA/LGA), congenital anomalies, and perinatal mortality., Objective: This study evaluate maternal and neonatal outcomes of women with morbid obesity who delivered before BS as compared to their counterparts who delivered after BS., Design: A retrospective analysis in a single institute., Settings: We use the data according to the ICD-9 code and were extracted from hospital archive., Patients: Patients were divided int0 two groups consisted of those of who conceived after BS and those who conceived before BS., Interventions: All women who underwent any BS and retrieved their obstetric files before or after the surgery., Main Outcomes Measures: The pregnancy, delivery data and obstetric factors were collected, clinical variables, background data and surgical bariatric procedures, operating time, length of hospital stay., Results: 149 morbidly obese women, of which 45 delivered after BS (group I) and 104 delivered prior to BS (group II). The most frequent comorbidity was diabetes mellitus, found in 67% of the women who delivered before BS. Time to delivery was longer in the women before BS, (P = 0.015) for the after BS group. Women who delivered before BS compared to women who delivered after BS had higher rates of anemia (p = 0.038), gestational diabetes (p = 0.064), and preeclampsia (p = 0.043). Women with deliveries before BS were characterized by higher birth weight in the neonates, (p < 0.001), more cases of premature membrane rupture, (14%, p < 0.018) and relatively high number of SGAs. A multivariate analysis of the data imply correlation to age and not causation., Limitations: This study was a small retrospective study and selection bias can occur which may reduce the accuracy of the results., Conclusions: There are clear health benefits of weight loss for morbidly obese women of reproductive age, and BS has an important role to play in this population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Evidence suggests that post-secondary students without pre-existing mental health concerns may have experienced worsening mental health during the COVID-19 pandemic, relative to students with pre-existing mental health concerns. To clarify the psychological impacts of the pandemic, and elucidate why differences may exist among students, 20 interviews were conducted with emerging adults enrolled in university. Using directed content analysis, eight themes were identified: three more common among students with pre-existing mental health concerns, three more common among students without pre-existing mental health concerns, and two shared. Although all students experienced novel stressors during the pandemic, students without pre-existing mental health concerns reported greater increases in social and academic isolation, relative to students with pre-existing mental health concerns. Students with pre-existing mental health concerns also leveraged existing coping repertoires, which further supported their ability to manage pandemic-related challenges. Findings highlight how postsecondary institutions can bolster student well-being., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the the Social Sciences and Humanities Research Council (SSHRC) to conduct this research (grant number: 435-2018-0961)., (© 2022 Society for the Study of Emerging Adulthood and SAGE Publishing.)

Background: Studies have found that unilateral and bilateral kyphoplasty have comparable clinical outcomes. Only a few studies have compared the radiographic results of using unilateral vs. simultaneous bilateral approaches. We aimed to examine and compare the radiographic results of unilateral (UKP) vs. bilateral simultaneous double-balloon kyphoplasty (DKP) for treating symptomatic vertebral compression fractures (VCF)., Methods: A retrospective cohort of all patients treated for VCF by DKP and UKP over five years in a single medical center. From 2009 to 2012, we routinely performed UKP; from 2012, DKP was the routine due to potential benefits in vertebral realignment. We evaluated pre- and post-surgical fracture characteristics including vertebral height, sagittal and coronal Cobb angle, and fracture reduction. Statistical analysis included a t -test for independent variables and Pearson's correlation., Results: The study cohort consisted of 81 patients (75.8 years ± 10.86) who underwent surgery, with a total of 119 vertebras. We performed 89 UKP on fractured vertebras and 30 DKP on 30 vertebrae. The UKP average fluoroscopy radiation exposure was 15.8 mGy (±11.5) per level compared to 11.2 mGy (±8.7) for DKP, p = 0.03. DKP showed significant fracture reduction, 2.8 degrees of Cobb angle, equaling the patient positioning effect on fracture reduction., Conclusion: DKP results in better fracture reduction than UKP, and equals the effect of patient positioning without increased radiation exposure or adverse events.

Purpose: To evaluate and detail the management of a difficult, long-term, open abdomen in a resource constraint setting with the use of Hydrocolloid dressing., Method: An observational retrospective study was conducted at a single level-1 trauma center. Over a 5-year period, all the open abdomen patients were evaluated and the cohorts who were treated with Hydrocolloid dressings were described in detail from their admission to their discharge., Results: During this period, there were 147 open abdomens. 7.5% (11) patients required long-term open abdomen management, in which Hydrocolloid dressing was utilized. Of this group, there were no entero/colonic-atmospheric fistulas, and there was either de-novo complete skin coverage, successful skin graft placement, or definitive abdominal wall repair in all the patients. De-novo complete skin coverage took an average of 7.4 months. All the patients were discharged home after an average of 107 days hospitalized., Conclusion: Despite not being an optimal management of an open abdomen, there are always a small group of these patients who lose abdominal domain, are critically ill or injured, and have prolonged hospitalization with an open abdomen. In this cohort, and especially in resource constraint settings, Hydrocolloid dressing is a cost-efficient, simple, and effective method to treat the 'long-term' open abdomens., (© 2020. Springer-Verlag France SAS, part of Springer Nature.)

Purpose: Sleeve gastrectomy is one of the most popular bariatric procedures performed. A complication of this surgery is sleeve stenosis, causing significant morbidity and the need for corrective intervention. Endoscopic treatment using pneumatic dilation has evolved as an effective, and minimally invasive, technique to successfully treat this complication. Here we report our experience with endoscopic management of sleeve stenosis at a tertiary bariatric center., Material and Methods: We identified all patients that underwent endoscopic management of sleeve stenosis at a tertiary bariatric center from 2010. We reviewed patient demographics, operative data, interval to endoscopic treatment, and outcomes of pneumatic dilations., Results: Sixty seven patients underwent 130 endoscopic dilations. The majority of these patients were female (71%), and at the time of sleeve gastrectomy average age was 43.3 years (range 18-68 years) and average BMI was 41.5 kg/m 2 (range 31-63 kg/m 2 ). The time interval to first endoscopic procedure was 7.2 months (range 0.75-53 months), with an average of 2 procedures per patient. During the follow-up period, the success rate of endoscopic dilatation was 76.1%, while the remaining 16 patients underwent conversion to gastric bypass. Two patients underwent emergency conversion to gastric bypass for sleeve perforation during the procedure (1.5%). There was a modest weight gain of 3 kg (4.2% total body weight) after sleeve dilatation., Conclusions: Endoscopic management of sleeve stenosis is safe and effective, with a success rate of over 75%. During endoscopic management, there was a 1.5% risk of sleeve perforation requiring emergency surgery. Mild weight regain occurred following endoscopic sleeve dilation., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)