Unique Usages of Dehydrated Human Amnion Chorion Membrane Allografts in Dermatology.

Dehydrated human amnion chorion membrane (dHACM) allografts are synthetic skin substitutes derived from placental tissue. dHACM allografts are used for replacing lost or damaged dermal tissue, as they contain many of the components found within the extracellular matrix that are beneficial in wound healing. Common uses of dHACM allografts include the healing of diabetic and non-diabetic foot and leg ulcers, decubitus ulcers, and wounds following debridement. While these grafts have been proven to be beneficial in other disciplines of medicine, their potential for use in the field of dermatology is emerging. Current clinical cases and research have shown dHACM allografts to be beneficial in repairing damaged tissue due to dermatologic conditions. They could play a role in the treatment of conditions causing chronic wounds, including dermal scarring or loss, and the repair of fragile skin. Examples of dHACM allograft use in dermatology include cases of pyoderma gangrenosum, Netherton syndrome, and wound healing with Mohs micrographic surgery. This literature review explores the efficacy of using dHACM allografts for the treatment of healing wounds within the field of dermatology. J Drugs Dermatol. 2023;22(12):1228-1231. doi:10.36849/JDD.7115.

Evidence of non-economic indicators as markers of success for youth in youth employability programs: Insights from a South African study.

Evaluation studies of youth employment programs prioritize employment and earnings outcomes and use these indicators to determine what labor market interventions are most successful. Evidence from pre and post data of a cluster randomized controlled longitudinal study, consisting of 1 892 youth between 18 and 25 years who participated in Youth Employability Programs (YEPs) in South Africa, confirms the importance of the inclusion of non-economic indicators to measure success for youth. This study provides evidence that non-economic markers of success such as job-search resilience, self-esteem, self-efficacy and future orientation are potentially important in the transition to employment in the longer term and points to the need for more evaluations that use these markers to predict youth's success in employment. The findings further suggest that these non-economic outcomes, which were conceptualized as intermediary outcomes, can influence how young people manage the increasingly protracted and difficult transition to work. The study enlarges our understanding of the non-linear and protracted pathways of youth transitions to work in a development context, and how to best support youth in this transition period. These findings have implications for rethinking YEP evaluation outcomes that could lead to adaptive programming and management of interventions.

Peptide-based systems analysis of inflammation induced myeloid-derived suppressor cells reveals diverse signaling pathways.

A better understanding of molecular signaling between myeloid-derived suppressor cells (MDSC), tumor cells, T-cells, and inflammatory mediators is expected to contribute to more effective cancer immunotherapies. We focus on plasma membrane associated proteins, which are critical in signaling and intercellular communication, and investigate changes in their abundance in MDSC of tumor-bearing mice subject to heightened versus basal inflammatory conditions. Using spectral counting, we observed statistically significant differential abundances for 35 proteins associated with the plasma membrane, most notably the pro-inflammatory proteins S100A8 and S100A9 which induce MDSC and promote their migration. We also tested whether the peptides associated with canonical pathways showed a statistically significant increase or decrease subject to heightened versus basal inflammatory conditions. Collectively, these studies used bottom-up proteomic analysis to identify plasma membrane associated pro-inflammatory molecules and pathways that drive MDSC accumulation, migration, and suppressive potency.

'I am a mother': young women's negotiation of femininity and risk in the transition to adulthood.

In studies of sexual risk behaviour among youth, the role of dominant conceptions of masculinity and femininity has received increasing attention. However, where research has sought to explore femininity, it has predominantly focused on adolescent girls. This paper departs from previous research by offering insights into how young women negotiate their femininity as they transition from adolescence to adulthood and encounter changing social contexts. Drawing on data from ethnographic enquiry, it argues that as young women transition out of school and into emerging adulthood, their options for negotiating different types of femininity become constrained, with consequences for engagement in sexual risk behaviours. This may to some extent explain why in some South African contexts older young women are more vulnerable to HIV infection than adolescent girls. The paper offer insights into future prospects for youth development programming seeking to reduce young women's vulnerability to risk.

Anodization control for barrier-oxide thinning and 3D interconnected pores and direct electrodeposition of nanowire networks on native aluminium substrates.

Here we report a strategy for combining techniques for pore branching and barrier layer thinning to produce 3D porous anodized aluminum oxide films with direct ohmic contact to the native aluminum. This method provides an example of a rationally designed template which need not be removed from the aluminum, but which is also not constrained to traditional 2D pore geometry. We first demonstrate the barrier layer removal and pore branching techniques independently, and then combine them to produce free standing arrays of interconnected Ni nanostructures. Nickel nanostructures are deposited directly onto the aluminum to demonstrate the success of the structural modification, and showcase the potential for these films to be used as templates. This approach is the first to demonstrate the design and execution of multiple pore modification techniques in the same membrane, and demonstrates the first directly deposited 3D structures on aluminum substrates.

Calreticulin regulates transforming growth factor-ß-stimulated extracellular matrix production.

Endoplasmic reticulum (ER) stress is an emerging factor in fibrotic disease, although precise mechanisms are not clear. Calreticulin (CRT) is an ER chaperone and regulator of Ca(2+) signaling up-regulated by ER stress and in fibrotic tissues. Previously, we showed that ER CRT regulates type I collagen transcript, trafficking, secretion, and processing into the extracellular matrix (ECM). To determine the role of CRT in ECM regulation under fibrotic conditions, we asked whether CRT modified cellular responses to the pro-fibrotic cytokine, TGF-ß. These studies show that CRT-/- mouse embryonic fibroblasts (MEFs) and rat and human idiopathic pulmonary fibrosis lung fibroblasts with siRNA CRT knockdown had impaired TGF-ß stimulation of type I collagen and fibronectin. In contrast, fibroblasts with increased CRT expression had enhanced responses to TGF-ß. The lack of CRT does not impact canonical TGF-ß signaling as TGF-ß was able to stimulate Smad reporter activity in CRT-/- MEFs. CRT regulation of TGF-ß-stimulated Ca(2+) signaling is important for induction of ECM. CRT-/- MEFs failed to increase intracellular Ca(2+) levels in response to TGF-ß. NFAT activity is required for ECM stimulation by TGF-ß. In CRT-/- MEFs, TGF-ß stimulation of NFAT nuclear translocation and reporter activity is impaired. Importantly, CRT is required for TGF-ß stimulation of ECM under conditions of ER stress, as tunicamycin-induced ER stress was insufficient to induce ECM production in TGF-ß stimulated CRT-/- MEFs. Together, these data identify CRT-regulated Ca(2+)-dependent pathways as a critical molecular link between ER stress and TGF-ß fibrotic signaling.

Does amount of weight gain during pregnancy modify the association between obesity and cesarean section delivery?

BACKGROUND: Two-thirds of reproductive-aged women in the United States are overweight or obese and at risk for numerous associated adverse pregnancy outcomes. This study examined whether the amount of weight gained during pregnancy modifies the prepregnancy body mass index (BMI)-cesarean delivery association. METHODS: A total of 2,157 women aged 18-45 who participated in the 2008-2009 North Carolina Pregnancy Risk Assessment Monitoring System had complete information on prepregnancy BMI, maternal weight gain, and mode of delivery on infant birth certificates. Logistic regression was used to obtain odds ratios (ORs) and 95 percent confidence intervals (CIs) to model the association between prepregnancy BMI and cesarean delivery, and a stratified analysis was conducted to determine whether maternal weight gain was an effect modifier of the prepregnancy BMI-cesarean delivery association. RESULTS: Obese women had 1.78 times the odds of cesarean delivery as compared with women with a normal BMI (95% CI: 1.44-2.16). When adjusted for race/ethnicity, live birth order, household income, and education, the association increased in magnitude and remained statistically significant (OR = 2.01, 95% CI: 1.63-2.43). In stratified analyses, the obesity-cesarean delivery association persisted and remained statistically significant among all maternal weight gain categories. CONCLUSIONS: Health care practitioners should stress the importance of achieving a healthy prepregnancy weight and gaining an appropriate amount of weight during pregnancy to reduce the risk of cesarean delivery and other adverse pregnancy outcomes.

A Case of Metastatic Choriocarcinoma-Related Paraneoplastic Thyroid Storm.

Thyroid storm due to gestational trophoblastic disease (GTD) with metastatic choriocarcinoma is a rare but potentially life-threatening endocrine emergency. We report on a woman with molar pregnancy and metastatic choriocarcinoma who presented with thyroid storm (Burch-Wartofsky point scale of 45) a few weeks after the evacuation of GTD. She was initially managed with intravenous hydrocortisone, oral propylthiouracil (PTU), and esmolol infusion. After stabilization in the intensive care unit, 10 cycles of chemotherapy with etoposide, methotrexate, leucovorin, dactinomycin, and cyclophosphamide (EMA-CO) were initiated for stage 4 choriocarcinoma with brain and lung metastases. She underwent a hysterectomy soon after completing chemotherapy and received an additional 3 cycles of chemotherapy after the hysterectomy. As human chorionic gonadotropin (hCG) levels normalized, thyroid function reverted to normal as well. At the last follow-up, the patient was asymptomatic, euthyroid (without antithyroid medication), had a normal hCG titer of 1.7 mIU/mL (normal nonpregnant reference is < 5 mIU/mL), and the lung and brain lesions had resolved entirely. Management of thyroid storm in the presence of untreated metastatic choriocarcinoma requires a high index of suspicion and a multidisciplinary team approach to prevent complications and improve survival.

Perinatal Homicide in the United States: A Systematic Literature Review.

This review focused on literature from the United States evaluating homicide during the perinatal period. It was completed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies met the criteria for inclusion, including: describing prevalence and risk factors related to homicide deaths of pregnant or postpartum birthing individuals; being conducted in the United States; and being published in English 2007 or later. This review found that homicide is an important contributor to maternal mortality and is a leading cause of death during pregnancy and the postpartum period, especially if an individual is Black and under the age of 30. Future efforts must be made to standardize data collection efforts and resolve nuanced terminology that results in interpretation challenges. The United States should examine maternal deaths through the entirety of the perinatal period and fully invest in violence prevention efforts.

Long-COVID improves in 50% of patients after a year in a Midwestern cohort.

Background: Many of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of taste and smell, and impaired daily functioning. Research Question: This study aims to better understand the chronology of long-COVID symptoms. Study Design and Methods: We prospectively enrolled 403 adults from the University of Iowa long-COVID clinic (June 2020 to February 2022). Participants provided symptom data during acute illness, symptom progression, and other clinical characteristics. Patients in this registry received a survey containing questions including current symptoms and status since long-COVID diagnosis (sliding status scale, PHQ2, GAD2, MMRC). Those >12 months since acute-COVID diagnosis had chart review done to track their symptomology. Results: Of 403 participants contacted, 129 (32%) responded. The mean age (in years) was 50.17 +/-14.28, with 31.8% male and 68.2% female. Severity of acute covid treatment was stratified by treatment in the outpatient (70.5%), inpatient (16.3%), or ICU (13.2%) settings. 51.2% reported subjective improvement (sliding scale scores of 67-100) since long-COVID onset. Ages 18-29 reported significantly higher subjective status scores. Subjective status scores were unaffected by severity. 102 respondents were >12 months from their initial COVID-19 diagnosis and were tracked for longitudinal symptom persistence. All symptoms tracked had variance (mean fraction 0.58, range 0.34-0.75) in the reported symptoms at the time of long-COVID presentation when compared with patient survey report. 48 reported persistent dyspnea, 23 (48%) had resolved it at time of survey. For fatigue, 44 had persistence, 12 (27%) resolved. Interpretation: Overall, 51.2% respondents improved since their long-COVID began. Pulmonary symptoms were more persistent than neuromuscular symptoms (anosmia, dysgeusia, myalgias). Gender, time since acute COVID infection, and its severity didn't affect subjective status or symptoms. This study highlights recall bias that may be prevalent in other long-COVID research reliant on participant memory.

Discordance between patient report and chart review of risk factors for antimicrobial resistance in ED patients.

OBJECTIVES: The objective of this study is to identify the level of agreement between patient self-report and chart review for presence of antimicrobial resistance (AR) risk factors in emergency department (ED) patients. METHODS: This is a cross-sectional analysis of adult ED patients from July 2010 to January 2011. All ED patients 18 years or older were eligible. Exclusion criteria included pregnant women, prisoners, altered mental status, non-English speakers, traumas, and patients unable to provide consent. Data were obtained by ED patient interview and review of the preceding 3 months of the medical record. We report the difference between patient self-report and chart review of identifying 1 or more AR risk factors using McNemar's χ(2). The test statistic was also calculated for individual risk factors and significance adjusted for multiple comparisons (P < .003). Agreement was calculated using κ with 95% confidence intervals (CIs). Risk factor domains assessed included nursing home residence, recent health care utilization, current indwelling devices, and medical history. RESULTS: Among 289 patients, 1 or more risk factors were reported by 68% (95% CI, 63%-74%) of patients and found in 59% (95% CI, 53%-65%) of charts, a difference of 9.7% (95% CI, 5.3%-14%) (P < .001; κ = 0.72). Patients were more likely to report recent antibiotic use (42% vs 29%; P < .001; κ = 0.52) and recent surgery (17% vs 11%; P < .001; κ = 0.64). CONCLUSIONS: There is disagreement between ED patient self-report and medical record review for many AR risk factors. This could affect both clinical care and results of ED research studies relying on chart reviews. Patient self-report identifies a greater number of AR risk factors than chart review.

Novel pain management therapies for patients with pemphigus.

Pemphigus is a class of rare autoimmune diseases that causes incredibly painful blistering of the skin and significantly impacts patients' day-to-day lives and well-being. Many strides have been made in treating pemphigus; however, no comprehensive literature exists on how to treat the pain that accompanies the disease. It is important to remember that treating pemphigus involves a two-fold treatment plan assessing both the underlying autoimmune disease and the pain involved with the lesions. This literature review explores novel therapies that have been shown to be effective in treating pain in pemphigus.

Intracellular calreticulin regulates multiple steps in fibrillar collagen expression, trafficking, and processing into the extracellular matrix.

Calreticulin (CRT), a chaperone and Ca(2+) regulator, enhances wound healing, and its expression correlates with fibrosis in animal models, suggesting that CRT regulates production of the extracellular matrix. However, direct regulation of collagen matrix by CRT has not been previously demonstrated. We investigated the role of CRT in the regulation of fibrillar collagen expression, secretion, processing, and deposition in the extracellular matrix by fibroblasts. Mouse embryonic fibroblasts deficient in CRT (CRT(-/-) MEFs) have reduced transcript levels of fibrillar collagen I and III and less soluble collagen as compared with wild type MEFs. Correspondingly, fibroblasts engineered to overexpress CRT have increased collagen type I transcript and protein. Collagen expression appears to be regulated by endoplasmic reticulum (ER) calcium levels and intracellular CRT, because thapsigargin treatment reduced collagen expression, whereas addition of exogenous recombinant CRT had no effect. CRT(-/-) MEFs exhibited increased ER retention of collagen, and collagen and CRT were co-immunoprecipitated from isolated cell lysates, suggesting that CRT is important for trafficking of collagen through the ER. CRT(-/-) MEFs also have reduced type I procollagen processing and deposition into the extracellular matrix. The reduced collagen matrix deposition is partly a consequence of reduced fibronectin matrix formation in the CRT-deficient cells. Together, these data show that CRT complexes with collagen in cells and that CRT plays critical roles at multiple stages of collagen expression and processing. These data identify CRT as an important regulator of collagen and suggest that intracellular CRT signaling plays an important role in tissue remodeling and fibrosis.

The calreticulin-binding sequence of thrombospondin 1 regulates collagen expression and organization during tissue remodeling.

Amino acids 17-35 of the thrombospondin1 (TSP1) N-terminal domain (NTD) bind cell surface calreticulin to signal focal adhesion disassembly, cell migration, and anoikis resistance in vitro. However, the in vivo relevance of this signaling pathway has not been previously determined. We engineered local in vivo expression of the TSP1 calreticulin-binding sequence to determine the role of TSP1 in tissue remodeling. Surgical sponges impregnated with a plasmid encoding the secreted calreticulin-binding sequence [NTD (1-35)-EGFP] or a control sequence [mod NTD (1-35)-EGFP] tagged with enhanced green fluorescent protein were implanted subcutaneously in mice. Sponges expressing NTD (1-35)-EFGP formed a highly organized capsule despite no differences in cellular composition, suggesting stimulation of collagen deposition by the calreticulin-binding sequence of TSP1. TSP1, recombinant NTD, or a peptide of the TSP1 calreticulin-binding sequence (hep I) increased both collagen expression and matrix deposition by fibroblasts in vitro. TSP1 stimulation of collagen was inhibited by a peptide that blocks TSP1 binding to calreticulin, demonstrating the requirement for cell surface calreticulin. Collagen stimulation was independent of TGF-ß activity and Smad phosphorylation but was blocked by an Akt inhibitor, suggesting that signaling through the Akt pathway is important for regulation of collagen through TSP1 binding to calreticulin. These studies identify a novel function for the NTD of TSP1 as a mediator of collagen expression and deposition during tissue remodeling.

Hippocampal lesion effects on occasion setting by contextual and discrete stimuli.

Three experiments examined the role of the dorsal hippocampus (dHIPP) in occasion setting with diffuse contextual and discrete light stimuli serving as occasion setters in classical fear conditioning with rats. Both sham-operated and dHIPP-lesioned animals readily learned a L→T+, T- serial feature-positive discrimination in which a light (L) "set the occasion" for reinforcement of a tone (T+). dHIPP-lesioned animals were deficient, however, in acquiring a similar discrimination in which different contexts (A and B) served as occasion setters, i.e., A(T+) and B(T-). The lesioned animals also failed to discriminate between a context in which a tone had been partially reinforced and a context in which no conditioning had taken place, whereas sham-operated animals froze more to the tone in the conditioned context than in the novel context. Collectively, the data indicate that the dorsal hippocampus is important in processing information about the signaling value of contextual, but not discrete, stimuli.

Recent updates in oral terbinafine: its use in onychomycosis and tinea capitis in the US.

Onychomycosis and tinea capitis are prevalent fungal diseases that are difficult to cure and usually require systemic treatment. Onychomycosis has high recurrence rates and can significantly affect a patient's quality of life. Oral terbinafine has been approved for onychomycosis for 20 years in Europe and 15 years in the United States. Over these past 20 years, numerous studies show that oral terbinafine is a safe and efficacious treatment for onychomycosis. More recently, oral terbinafine also has been approved for tinea capitis. Once difficult to treat, terbinafine has revolutionised treatment of these fungal diseases. It has minimal side effects and its limited drug interactions make it an excellent treatment option for patients with co-morbidities. This review discusses oral terbinafine and new insights into the treatment of onychomycosis and tinea capitis. Recent publications have enhanced our knowledge of the mechanisms of oral terbinafine and its efficacy in treating onychomycosis. Oral terbinafine vs. other antifungal therapeutic options are reviewed. Overall, terbinafine remains a superior treatment for dermatophyte infections because of its safety, fungicidal profile, once daily dosing, and its ability to penetrate the stratum corneum.

Stress impairs optimal behavior in a water foraging choice task in rats.

Stress is a biologically significant social-environmental factor that plays a pervasive role in influencing human and animal behaviors. While stress effects on various types of memory are well characterized, its effects on other cognitive functions are relatively unknown. Here, we investigated the effects of acute, uncontrollable stress on subsequent decision-making performance in rats, using a computer vision-based water foraging choice task. Experiencing stress significantly impaired the animals' ability to progressively bias (but not maintain) their responses toward the larger reward when transitioning from equal to unequal reward quantities. Temporary inactivation of the amygdala during stress, however, blocked impairing effects on decision making.

Treatment of semantic verb classes in aphasia: acquisition and generalization effects.

Verb retrieval difficulties are common in aphasia; however, few successful treatments have been documented (e.g. Conroy, P., Sage, K., & Lambon Ralph, M. A. (2006) . Towards theory-driven therapies for aphasic verb impairments: A review of current theory and practice. Aphasiology, 20, 1159-1185). This study investigated the efficacy of a novel verb retrieval treatment in two individuals with aphasia who experience verb retrieval difficulty. It involved training verb classes with large (e.g. cut verbs) and limited (e.g. contact verbs) sets of semantic features. Based on action representation theories, semantically based training of cut verbs was predicted to generalize to retrieval of untrained cut and contact verbs. One participant improved on trained verbs whereas the other participant did not. Neither participant demonstrated within nor across-class generalization to untrained verbs. However, both participants significantly improved in verb naming as measured by An Object and Action Naming Battery, and their predominant error pattern changed from noun to verb substitutions. Therefore, both participants improved in overall verb retrieval strategies despite limited success with verbs trained in this treatment. Implications for the design of future treatments are discussed.

Individual Differences in Reward-Based Learning Predict Fluid Reasoning Abilities.

The ability to reason and problem-solve in novel situations, as measured by the Raven's Advanced Progressive Matrices (RAPM), is highly predictive of both cognitive task performance and real-world outcomes. Here we provide evidence that RAPM performance depends on the ability to reallocate attention in response to self-generated feedback about progress. We propose that such an ability is underpinned by the basal ganglia nuclei, which are critically tied to both reward processing and cognitive control. This hypothesis was implemented in a neurocomputational model of the RAPM task, which was used to derive novel predictions at the behavioral and neural levels. These predictions were then verified in one neuroimaging and two behavioral experiments. Furthermore, an effective connectivity analysis of the neuroimaging data confirmed a role for the basal ganglia in modulating attention. Taken together, these results suggest that individual differences in a neural circuit related to reward processing underpin human fluid reasoning abilities.