DNA glycosylases provide antiviral defence in prokaryotes.

Bacteria have adapted to phage predation by evolving a vast assortment of defence systems1. Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data2. Here, to overcome this limitation, we infected Escherichia coli carrying a soil metagenomic DNA library3 with the lytic coliphage T4 to isolate clones carrying protective genes. Following this approach, we identified Brig1, a DNA glycosylase that excises α-glucosyl-hydroxymethylcytosine nucleobases from the bacteriophage T4 genome to generate abasic sites and inhibit viral replication. Brig1 homologues that provide immunity against T-even phages are present in multiple phage defence loci across distinct clades of bacteria. Our study highlights the benefits of screening unsequenced DNA and reveals prokaryotic DNA glycosylases as important players in the bacteria-phage arms race.

Erratum to 'Low gestational weight gain (+2.0 to 4.9 kg) for singleton-term gestations associated with favorable perinatal outcomes for all prepregnancy obesity classes' [AJOG Global Reports 3 (2023) 100246].

[This corrects the article DOI: 10.1016/j.xagr.2023.100246.].

Low gestational weight gain (+2.0 to 4.9 kg) for singleton-term gestations associated with favorable perinatal outcomes for all prepregnancy obesity classes.

BACKGROUND: Previous studies that evaluated low gestational weight gain or weight loss among prepregnancy obesity classes have not determined the amount of gestational weight gain associated with the lowest risk of adverse perinatal outcomes and neonatal morbidity among singleton term births. OBJECTIVE: This study aimed to evaluate the relationship of specific gestational weight gain categories of weight loss, stable weight, and low gain considered below the 2009 Institute of Medicine guidelines to perinatal outcomes and neonatal morbidity for singleton, term live births among prepregnancy obesity classes. STUDY DESIGN: This was a retrospective cohort study of 18,476 women among 3 classes of prepregnancy obesity, based on measured prepregnancy weight, and delivering a live singleton pregnancy at ≥37 weeks of gestation at a Kaiser Permanente Northern California hospital (2009-2012). Variables from electronic medical records included perinatal outcomes, sociodemographics, and measured prepregnancy and delivery weights to calculate total gestational weight gain, used to define 5 gestational weight gain categories: weight loss (<-2.0 kg), stable weight (-2.0 to +1.9 kg), low gain (+2.0 to 4.9 kg), gain within guidelines (+5.0 to 9.1 kg; referent), and gain above guidelines (>9.1 kg). Logistic regression models estimated adjusted odds ratios and 95% confidence intervals of maternal and newborn perinatal outcomes (hypertensive disorders, cesarean delivery, size for gestational age, length of stay, neonatal intensive care unit admission) associated with gestational weight gain categories stratified by prepregnancy obesity classes 1, 2, and 3. RESULTS: Low gain occurred in 8%, 12%, and 13% of women in obesity class 1 (body mass index, 30.0-34.9), class 2 (body mass index, 35.0-39.9), and class 3 (body mass index, ≥40), respectively. Compared with gestational weight gain within Institute of Medicine guidelines, low gain was associated with similar or improved maternal and newborn perinatal outcomes for all obesity classes without increased odds of neonatal intensive care unit admission, neonatal length of stay ≥3 days, or small for gestational age. The percentages of small for gestational age for the low gain category were 4.4%, 3.0%, and 4.3% among prepregnancy obesity classes 1, 2, and 3, respectively, and comparable with the gestational weight gain within the guideline category (P>.05). The adjusted odds ratios of small-for-gestational age were not statistically significant for all obesity classes; class 1 (1.16; 95% confidence interval, 0.79-1.71) , class 2 (1.05; 95% confidence interval 0.58-1.93), and class 3 (2.03; 95% confidence interval 0.97-4.27). CONCLUSION: Lower gestational weight gain of +2.0 to 4.9 kg showed the most favorable perinatal outcomes, without higher small for gestational age or neonatal morbidity for all obesity classes.

Thirty-year follow-up of the NICHD Study of Early Child Care and Youth Development (SECCYD): the challenges and triumphs of conducting in-person research at a distance.

PURPOSE: The purpose of the current study, The National Institute of Child Health and Human Development (NICHD) Study of Health in Early and Adult Life (SHINE), was to build on the landmark Study of Early Child Care and Youth Development (SECCYD), a longitudinal birth cohort initiated in 1991, by conducting a health-focused follow-up of the now adult participants. This effort has produced an invaluable resource for the pursuit of life course research examining links between early life risk and resilience factors and adulthood health and disease risk. PARTICIPANTS: Of the 927 NICHD SECCYD participants available for recruitment in the current study, 705 (76.1%) participated in the study. Participants were between 26 and 31 years and living in diverse geographic locations throughout the USA. FINDINGS TO DATE: In descriptive analyses, the sample exhibited risk on health status indicators, especially related to obesity, hypertension and diabetes. Of particular concern, the prevalence of hypertension (29.4%) and diabetes (25.8%) exceeded national estimates in similar-age individuals. Health behaviour indicators generally tracked with the parameters of poor health status, showing a pattern of poor diet, low activity and disrupted sleep. The juxtaposition of the sample's relatively young age (mean=28.6 years) and high educational status (55.6% college educated or greater) with its poor health status is noteworthy, suggesting a dissociation between health and factors that are typically health protective. This is consistent with observed population health trends, which show a worsening of cardiometabolic health status in younger generations of Americans. FUTURE PLANS: The current study, SHINE, lays the groundwork for future analyses in which the uniquely robust measures collected as a part of the original NICHD SECCYD will be leveraged to pinpoint specific early life risk and resilience factors as well as the correlates and potential mechanisms accounting for variability in health and disease risk indicators in young adulthood.

Baseline Sequencing Surveillance of Public Clinical Testing, Hospitals, and Community Wastewater Reveals Rapid Emergence of SARS-CoV-2 Omicron Variant of Concern in Arizona, USA.

The adaptive evolution of SARS-CoV-2 variants is driven by selection for increased viral fitness in transmissibility and immune evasion. Understanding the dynamics of how an emergent variant sweeps across populations can better inform public health response preparedness for future variants. Here, we investigated the state-level genomic epidemiology of SARS-CoV-2 through baseline genomic sequencing surveillance of 27,071 public testing specimens and 1,125 hospital inpatient specimens diagnosed between November 1, 2021, and January 31, 2022, in Arizona. We found that the Omicron variant rapidly displaced Delta variant in December 2021, leading to an "Omicron surge" of COVID-19 cases in early 2022. Wastewater sequencing surveillance of 370 samples supported the synchronous sweep of Omicron in the community. Hospital inpatient COVID-19 cases of Omicron variant presented to three major hospitals 10.51 days after its detection from public clinical testing. Nonsynonymous mutations in nsp3, nsp12, and nsp13 genes were significantly associated with Omicron hospital cases compared to community cases. To model SARS-CoV-2 transmissions across the state population, we developed a scalable sequence network methodology and showed that the Omicron variant spread through intracounty and intercounty transmissions. Finally, we demonstrated that the temporal emergence of Omicron BA.1 to become the dominant variant (17.02 days) was 2.3 times faster than the prior Delta variant (40.70 days) or subsequent Omicron sublineages BA.2 (39.65 days) and BA.5 (35.38 days). Our results demonstrate the uniquely rapid sweep of Omicron BA.1. These findings highlight how integrated public health surveillance can be used to enhance preparedness and response to future variants. IMPORTANCE SARS-CoV-2 continues to evolve new variants throughout the pandemic. However, the temporal dynamics of how SARS-CoV-2 variants emerge to become the dominant circulating variant is not precisely known. Genomic sequencing surveillance offers unique insights into how SARS-CoV-2 spreads in communities and the lead-up to hospital cases during a surge. Specifically, baseline sequencing surveillance through random selection of positive diagnostic specimens provides a representative outlook of the virus lineages circulating in a geographic region. Here, we investigated the emergence of the Omicron variant of concern in Arizona by leveraging baseline genomic sequence surveillance of public clinical testing, hospitals, and community wastewater. We tracked the spread and evolution of the Omicron variant as it first emerged in the general public, and its rapid shift in hospital admissions in the state health system. This study demonstrates the timescale of public health preparedness needed to respond to an antigenic shift in SARS-CoV-2.

SARS-CoV-2 Delta Variant N Gene Mutations Reduce Sensitivity to the TaqPath COVID-19 Multiplex Molecular Diagnostic Assay.

As the SARS-CoV-2 virus evolves, mutations may result in diminished sensitivity to qRT-PCR diagnostic assays. We investigated four polymorphisms circulating in the SARS-CoV-2 Delta lineage that result in N gene target failure (NGTF) on the TaqPath COVID-19 Combo Kit. These mutations were detected from the SARS-CoV-2 genome sequences that matched with the diagnostic assay results of saliva specimens. Full length N genes from the samples displaying NGTF were cloned into plasmids and assayed using three SARS-CoV-2 qRT-PCR assays. These constructs resulted in reduced sensitivity to the TaqPath COVID-19 Combo Kit compared to the controls (mean Ct differences of 3.06, 7.70, 12.46, and 14.12), but were detected equivalently on the TaqPath COVID-19 Fast PCR Combo 2.0 or CDC 2019_nCoV_N2 assays. This work highlights the importance of genomic sequencing to monitor circulating mutations and provide guidance in improving diagnostic assays.

Disparities in COVID-19-related stressful life events in the United States: Understanding who is most impacted.

Impacts of the COVID-19 pandemic in the United States have been exacerbated by pre-existing inequities in resources and opportunities, leaving the most vulnerable to face a multitude of hardships. The goal of the current study was to characterise COVID-19-related stressful life events in specific life domains and to identify the sociodemographic characteristics of individuals who are more likely to experience such events. Participants (n = 372, 57% female) in a follow-up study of the NICHD Study of Early Child Care and Youth Development completed the Epidemic-Pandemic Impacts Inventory (June-August 2020) to assess COVID-19-related stressors. Sociodemographic factors (gender, race/ethnicity, socioeconomic status and wealth) were examined simultaneously as predictors of the number of stressful life events in separate categories of work/finances, home life, social activity, health and healthcare, adjusted for covariates (household size, community COVID-19 transmission risk). In negative binomial regression analyses, being female (vs. male) predicted a 31%, 64%, 13% and 94% increase in the number of stressful life events in domains of work/finances, home life, social activity and healthcare, respectively, whereas each one standard deviation increase in wealth predicted a 17%, 16% and 21% reduction in the number of stressful life events in domains of work/finances, COVID-19 infection and healthcare, respectively. Findings highlight the pronounced and far-reaching impacts of the COVID-19 pandemic on women as well as the unique role wealth may play in lessening such impacts. This new knowledge may be leveraged to develop intervention and policy-related strategies to remediate impacts of COVID-19-related stressors on those most vulnerable.

Early life predictors of positive change during the coronavirus disease pandemic.

BACKGROUND: The COVID-19 pandemic is a crisis unprecedented in its size and scope. Yet studies of resilience suggest most individuals will successfully negotiate this challenge and some may even experience growth and positive change. Some evidence suggests that the capacity to enact positive change in the face of adversity may be shaped by early life experiences. METHODS: In a subset of 374 participants (57% female, mean age = 29 years) in the Study of Early Child Care and Youth Development (SECCYD), a longitudinal, birth cohort, prospective models were tested to determine whether early life adversities in family and neighborhood contexts predict positive change events in response to the COVID-19 pandemic. Childhood family and neighborhood contexts were assessed using a combination of self-report questionnaires and US Census data. Adulthood positive change events (e.g., becoming more appreciative of things usually taken for granted) were assessed using the Epidemic-Pandemic Impacts Inventory (EPII). RESULTS: In regression analyses, neighborhood disadvantage in childhood, measured both by objective and subjective assessments, predicted a higher number of positive change events in response to the COVID-19 pandemic (ß = .18, p = .004 and ß = .15, p = .006, respectively). Examination of the positive change event subscales showed neighborhood disadvantage in childhood predicted increases in events related to 'perspective taking and charitable giving' (ß = .20, p = .022 and ß = .17, p = .002, respectively) and improved 'social relationships' (ß = .18, p = .004 and ß = .13, p = .020, respectively), but not to positive 'health behaviors' (ps > .05). All associations were independent of sociodemographic factors and childhood family dysfunction. CONCLUSIONS: Findings suggest that neighborhood disadvantage in childhood may shape prosocial responses to stress in adulthood, potentially through early life adaptions to stress that are protective when facing adversity. There are several notable implications of the study findings. Although adversity in early life has clear negative impacts, it is possible that adversity experiences may also provide opportunities to develop adaptive strategies that foster resilience and growth when facing stress. Intervention efforts should consider leveraging such stress-adapted strengths to reduce the many negative impacts of early life adversity.

Preexisting Executive Function Deficits and Change in Health Behaviors During the COVID-19 Pandemic.

BACKGROUND: Executive functions (EF) support engagement in goal-directed behaviors, including several health behaviors. Stressful and cognitively demanding events can disrupt EFs and interfere with health behavior, possibly to a greater extent in those with preexisting EF deficits. This study examined the association between preexisting EF deficits and subsequent negative changes in eating patterns, physical activity, sedentariness, and alcohol/substance use during the COVID-19 pandemic. METHOD: Participants were 374 young adults in a follow-up study of the longitudinal, multisite Study of Early Child Care and Youth Development (SECCYD). Preexisting EF deficits were assessed with the Barkley Deficits in Executive Function Scales-Short Form, and personally impactful negative changes in four health behaviors (physical activity, unhealthy eating, sedentary time, alcohol/substance use) during the COVID-19 pandemic were subsequently assessed with the Epidemic-Pandemic Impacts Inventory. RESULTS: In ordered logistic regression models, higher preexisting total EF deficits were associated with greater negative impactful changes in physical activity and unhealthy eating, independent of sociodemographic variables, obesity, and (as relevant) accelerometer-based physical activity and pre-COVID-19 diet quality. Socioeconomic status moderated the association between total EF deficits and impactful change in alcohol/substance use, with EF deficits linked to greater impactful change in alcohol/substance use only in higher socioeconomic strata. CONCLUSION: Individuals with preexisting EF deficits appear more vulnerable to the negative impact of the COVID-19 pandemic on several key health behaviors. As the pandemic unfolds, strategies may be needed to identify those with EF deficits (e.g., screening tools) and provide them with tailored support for chronic disease risk reduction.

Patterns of Early Life Weight Gain and Female Onset of Puberty.

Context: Prepubertal obesity is a well-established predictor of earlier pubertal onset, which is itself a risk factor for poor health and well-being. Identifying specific patterns of weight gain in early life may help explain differential risk for earlier pubertal onset. Objective: The objective of the study was to examine patterns of weight gain across infancy and early childhood in relation to pubertal onset outcomes. Design Setting and Participants: Participants were 426 girls in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, a longitudinal birth cohort of children and their families followed between birth and adolescence. Main Outcome Measures: Three pubertal onset outcomes were examined, including age at menarche and ages at Tanner stage II for dimensions of breast and pubic hair development. Results: In infancy (birth to 15 months), greater percent weight gain and higher birthweight predicted earlier pubertal onset for all outcomes (Ps < 0.05). In early childhood (24 months to grade 1), body mass index (BMI) trajectories reflecting BMI values that were persistently high or changed from low to high over time (vs BMI values that were stable at median or low levels), predicted younger ages at menarche and the onset of breast (Ps < 0.05), but not pubic hair (Ps > 0.05), development. All associations were independent of breastfeeding, maternal menarcheal age, and race/ethnicity. Conclusions: Distinct patterns of early life weight gain predict differential risk for earlier onset puberty. Focusing on these patterns for earlier and more targeted intervention may help lessen life course linkages between prepubertal obesity, accelerated pubertal development, and negative postpubertal outcomes.

Early Life Adversity and Pubertal Timing: Implications for Cardiometabolic Health.

OBJECTIVE: To identify early life adversity (ELA) risk factors for earlier pubertal timing, itself a risk factor for poor cardiometabolic health, and to determine whether such ELA-related risk may be mediated by pre-pubertal body mass index (BMI). METHODS: Subjects included 426 female participants in a prospective birth cohort study, the NICHD Study of Early Child Care and Youth Development. Survival analysis models were fit to examine ELA exposures, representing childhood socioeconomic status (SES), maternal sensitivity, mother-child attachment, and negative life events, along with child health indicators and covariates, in relation to pubertal timing outcomes, including age at menarche and ages at Tanner stage II for breast and pubic hair development. RESULTS: Higher childhood SES emerged as an independent predictor of older age at menarche, showing each one standard deviation increase in childhood SES corresponded to a 1.3% increase in age at menarche (factor change = 1.013; 1.003-1.022; p < .01), but did not predict breast or pubic hair development (ps > .05). In mediation analyses, indirect (mediated) effects of mother-child attachment on the pubertal timing outcomes, via pre-pubertal BMI, were all statistically significant (ps < .05). CONCLUSIONS: Higher childhood SES predicted directly, and secure (vs. insecure) mother-child attachment predicted indirectly (via pre-pubertal BMI), later pubertal timing, suggesting these factors may protect girls from earlier pubertal development. By extension, clinical implications are that intervention strategies designed to lessen ELA- and pre-pubertal obesity-related risk may be effective in remediating life course pathways linking ELA, accelerated pubertal development, and cardiometabolic risk.

Low-Dose Insulin as an Antiscarring Therapy in Breast Surgery: A Randomized Controlled Trial.

BACKGROUND: The role of insulin in expediting wound healing is firmly established within the context of major trauma and burns; however, only limited clinical evidence exists as to its effects on scar formation. This study aims to build on previous laboratory work to examine the potential antiscarring properties of insulin in a clinical environment. METHODS: Ninety-one patients undergoing bilateral aesthetic breast operations were recruited to receive low-dose insulin and placebo injections to the medial 3 cm of their submammary incisions within the context of a randomized, intrapatient, placebo-controlled trial, and scar quality was assessed at 3-, 6-, and 12-month reviews using the Manchester Scar Scale. RESULTS: Across the cohort at 12-month review, the insulin-treated scars had lower scar scores (p = 0.055) compared with placebo. Subgroup analysis of individuals with heavier scars showed that median scar scores were significantly lower for the insulin-treated scars with regard to both scar contour (p = 0.048) and scar distortion (p = 0.045). CONCLUSIONS: Subcutaneous insulin injections reduced the appearance of scarring in this study compared with placebo. The greatest effect was seen in those participants who showed heavier scars and, as such, insulin has a role as an antiscarring therapy in individuals likely to be affected by heavier scarring. Further research is required to more precisely delineate which subjects may benefit most from this treatment. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

[Useful radiological techniques in orthodontics]. / Techniques radiographiques utiles en orthodontie.

Specialists in dento-facial orthopedics have a large range of dental radiological techniques at their disposal to help them in their diagnostic and therapeutic procedures. Peri-apical, occlusal, panoramic, and cephalometric X-Rays are two-dimensional techniques that orthodontists can complement, if necessary, with Multi slices CT scan or Cone Beam Computed Tomography. Orthodontists must apply and respect quality criteria for each type of film in order to derive the best information from every image and to avoid producing artifacts or false images that will reduce their diagnostic value and, accordingly, the service that they render to patients. Practitioners must be willing to spend the few moments it takes to position patients correctly in the radiological apparatus instead of taking multiple views to compensate for failing to scrupulously follow protocols of radiology.

In vitro study of novel collagenase (XIAFLEX®) on Dupuytren's disease fibroblasts displays unique drug related properties.

Dupuytren's disease (DD) is a benign, fibroproliferative disease of the palmar fascia, with excessive extracellular matrix (ECM) deposition and over-production of cytokines and growth factors, resulting in digital fixed flexion contractures limiting hand function and patient quality of life. Surgical fasciectomy is the gold standard treatment but is invasive and has associated morbidity without limiting disease recurrence. Injectable Collagenase Clostridium histolyticum (CCH)--Xiaflex®--is a novel, nonsurgical option with clinically proven in vivo reduction of DD contractures but with limited in vitro data demonstrating its cellular and molecular effects. The aim of this study was to delineate the effects of CCH on primary fibroblasts isolated from DD and non-DD anatomical sites (using RTCA, LDH, WST-1, FACS, qRT-PCR, ELISA and In-Cell Quantitative Western Blotting) to compare the efficacy of varying concentrations of Xiaflex® against a reagent grade Collagenase, Collagenase A. Results demonstrated that DD nodule and cord fibroblasts had greater proliferation than those from fat and skin. Xiaflex® exposure resulted in dose- and time-dependent inhibition of cellular spreading, attachment and proliferation, with cellular recovery after enzyme removal. Unlike Collagenase A, Xiaflex® did not cause apoptosis. Collagen expression patterns were significantly (p<0.05) different in DD fibroblasts across anatomical sites - the highest levels of collagen I and III were detected in DD nodule, with DD cord and fat fibroblasts demonstrating a smaller increase in both collagen expression relative to DD skin. Xiaflex® significantly (p<0.05) down-regulated ECM components, cytokines and growth factors in a dose-dependent manner. An in vitro scratch wound assay model demonstrated that, at low concentrations, Xiaflex® enabled a faster fibroblast reparatory migration into the wound, whereas, at high concentrations, this process was significantly (p<0.05) inhibited. This is the first report elucidating potential mechanisms of action of Xiaflex® on Dupuytren fibroblasts, offering a greater insight and a better understanding of its effect in DD.

Are black Hispanics black or Hispanic? Exploring disparities at the intersection of race and ethnicity.

BACKGROUND: Disparities in health among blacks and Hispanics compared to whites individuals exist for a number of health measures; however, the health profile of individuals who are both black and Hispanic is not well known. We sought to determine whether race and ethnicity have synchronous or independent effects on health-related outcomes. METHODS: We combined the National Health Interview Survey for 2000-2007 to identify 896 black Hispanics. We selected health-related outcomes where white Hispanics and non-Hispanic blacks significantly differed. We computed adjusted prevalence estimates for black Hispanics and compared them to determine whether their health-related outcomes more closely resemble white Hispanics or non-Hispanic blacks. All prevalence estimates were adjusted for age, sex, education, marital status, income and survey year. RESULTS: Black Hispanics' health behaviours resembled white Hispanics or were similar to both white Hispanics and non-Hispanic blacks. For health services outcomes, they resembled non-Hispanic blacks. However, their health status was influenced by both race and ethnicity, with black Hispanics resembling both white Hispanic and non-Hispanic black people. CONCLUSION: We conclude that health behaviour interventions incorporating knowledge of Hispanic cultures may be sufficient to reach black Hispanics. However, health services or health status, interventions targeted broadly to Hispanic people may not be sufficient. In some respects black Hispanic people comprise a distinct subgroup that may require targeted attention in public health interventions.

The emerging role of Clostridium histolyticum collagenase in the treatment of Dupuytren disease.

Dupuytren disease (DD) is a common fibroproliferative disease of unknown etiopathogenesis affecting the palmar aponeurosis, causing reduced hand function and resulting in fixed flexion contractures of the digits. Current gold standard treatment for the management of DD is surgical excision involving removal of the affected palmar fascial tissue. However, there are potential complications associated with surgery as it is costly and a positive surgical outcome is often short-lived because the disease tends to recur. Therefore, there is growing interest in nonsurgical, outpatient-based treatments that could be quicker, cheaper, reduce morbidity, show a decreased rate of recurrence, and give DD patients an improved quality of life when compared with traditional surgical management. Of the available nonsurgical options, injectable Clostridium histolyticum collagenase (CHC) has received recent clinical interest. In this article, a brief overview of DD surgical and nonsurgical treatments utilized is given, followed by a detailed examination of the nine papers published to date on the use of CHC in DD (and similar fibrotic disorders). These papers have investigated safe and efficacious doses for the injection of CHC to treat palpable DD cords in adult patients and have shown significant short- to mid-term results for correction to near-full digital extension (≤5° extension) following CHC injection of DD cords. CHC has been shown to target the collagen-based DD cords while sparing surrounding neurovasculature, with a complication profile that appears comparable to that of the surgical methods currently utilized. In conclusion, clostridial collagenase is a novel nonsurgical treatment option of considerable potential in the management of DD when administered by specialist hand surgeons with detailed knowledge of the disease and the relevant anatomy. Nonetheless, there is a need for further data on long-term results, complications, and rate of recurrence with the use of this emerging treatment option.

Novel noninvasive identification of biomarkers by analytical profiling of chronic wounds using volatile organic compounds.

A complex profile of volatile organic compounds ("VOC"s) emanates from human skin, which is altered by changes in the body's metabolic or hormonal state, the external environment, and the bacterial species colonizing the skin surface. The aim of this study was to compare VOC profiles sampled from chronic leg wounds with those from asymptomatic skin. Five participants with chronic arterial leg ulcers were selected. VOC samples were obtained using polydimethylsilicone membranes ("skin-patch method") and analyzed by gas chromatography-ion trap mass spectrometry. Resultant data were analyzed using multivariate analysis and mass spectral matches were compared against the National Institute of Standards and Technology database. Principal component analysis showed differences in profiles obtained from healthy skin and boundary areas and between profiles from healthy skin and lesion samples (p<0.05). Partial least squares for discriminant analysis gave an average prediction accuracy of 73.3% (p<0.05). Mass spectral matching (verified against microbial swab results) identified unique VOCs associated with each sample area, wound bacterial colonization, and ingested medications. This study showcases a reproducible, robust, noninvasive methodology that is applicable in a clinical setting and may offer a new, hitherto unexplored, class of biochemical markers underpinning the metabolism of chronic wounds.