Efficacy of a combined anti-seizure treatment against cholinergic established status epilepticus following a sarin nerve agent insult in rats.

The development of refractory status epilepticus (SE) following sarin intoxication presents a therapeutic challenge. Here, we evaluated the efficacy of delayed combined double or triple treatment in reducing abnormal epileptiform seizure activity (ESA) and the ensuing long-term neuronal insult. SE was induced in rats by exposure to 1.2 LD50 sarin followed by treatment with atropine and TMB4 (TA) 1 min later. Double treatment with ketamine and midazolam or triple treatment with ketamine, midazolam and levetiracetam was administered 30 min post-exposure, and the results were compared to those of single treatment with midazolam alone or triple treatment with ketamine, midazolam, and valproate, which was previously shown to ameliorate this neurological insult. Toxicity and electrocorticogram activity were monitored during the first week, and behavioral evaluations were performed 2 weeks post-exposure, followed by biochemical and immunohistopathological analyses. Both double and triple treatment reduced mortality and enhanced weight recovery compared to TA-only treatment. Triple treatment and, to a lesser extent, double treatment significantly ameliorated the ESA duration. Compared to the TA-only or the TA+ midazolam treatment, both double and triple treatment reduced the sarin-induced increase in the neuroinflammatory marker PGE2 and the brain damage marker TSPO and decreased gliosis, astrocytosis and neuronal damage. Finally, both double and triple treatment prevented a change in behavior, as measured in the open field test. No significant difference was observed between the efficacies of the two triple treatments, and both triple combinations completely prevented brain injury (no differences from the naïve rats). Delayed double and, to a greater extent, triple treatment may serve as an efficacious delayed therapy, preventing brain insult propagation following sarin-induced refractory SE.

Predicting clinical outcome of sulfur mustard induced ocular injury using machine learning model.

The sight-threatening sulfur mustard (SM) induced ocular injury presents specific symptoms in each clinical stage. The acute injury develops in all exposed eyes and may heal or deteriorate into chronic late pathology. Early detection of eyes at risk of developing late pathology may assist in providing unique monitoring and specific treatments only to relevant cases. In this study, we evaluated a machine-learning (ML) model for predicting the development of SM-induced late pathology based on clinical data of the acute phase in the rabbit model. Clinical data from 166 rabbit eyes exposed to SM vapor was used retrospectively. The data included a comprehensive clinical evaluation of the cornea, eyelids and conjunctiva using a semi-quantitative clinical score. A random forest classifier ML model, was trained to predict the development of corneal neovascularization four weeks post-ocular exposure to SM vapor using clinical scores recorded three weeks earlier. The overall accuracy in predicting the clinical outcome of SM-induced ocular injury was 73%. The accuracy in identifying eyes at risk of developing corneal neovascularization and future healed eyes was 75% and 59%, respectively. The most important parameters for accurate prediction were conjunctival secretion and corneal opacity at 1w and corneal erosions at 72 h post-exposure. Predicting the clinical outcome of SM-induced ocular injury based on the acute injury parameters using ML is demonstrated for the first time. Although the prediction accuracy was limited, probably due to the small dataset, it pointed out towards various parameters during the acute injury that are important for predicting SM-induced late pathology and revealing possible pathological mechanisms.

Coping with emotional dysregulation among young adults with ADHD: A mixed-method study of self-awareness and strategies in daily life.

BACKGROUND: Emotional dysregulation (ED) impacts functional outcomes among individuals with attention-deficit hyperactivity disorder (ADHD). Self-awareness and strategies may enhance coping with ED yet are rarely studied in ADHD. OBJECTIVES: To explore ED-related self-awareness and strategies in daily life of adults with ADHD, and to examine the interrelations between them and their association with symptoms. METHODS: Sixty young adults with ADHD participated in a mixed-method study. At baseline, self-awareness and strategies were assessed using the Self-Regulation Skills Interview (SRSI); ADHD symptoms were self-rated using the ASRS symptom checklist. Then, symptoms were rated over 5-days using ecological momentary assessment (EMA). RESULTS: Significant challenges in self-awareness and strategies were demonstrated quantitatively and qualitatively. Awareness of ED was associated with variability of ADHD symptoms on EMA yet not with symptom severity. Qualitative content analysis revealed a range of self-awareness levels, which were related to noticing ED-related cues and understanding contextual factors predictive of ED. Self-awareness and strategies were significantly associated. Strategies varied regarding effort, individual preference and temporality. CONCLUSIONS: Variability of ADHD symptoms was negatively associated with self-awareness of ED. Strategy selection in daily-life among adults with ADHD may be affected by self-awareness and by a possible trade-off between short-term effort and long-term effectiveness.

Limbal stem cell deficiency (LSCD) in rats and mice following whole body exposure to sulfur mustard (SM) vapor.

Ocular injuries following sulfur mustard (SM) exposure are characterized by an acute phase expressed by corneal erosions and inflammation of the anterior segment that after a clinically silent period may be followed by irreversible corneal injuries. The latter includes epithelial defects, chronic inflammation and neovascularization (NV), and were defined in rabbits and in humans as Limbal Stem Cell Deficiency (LSCD), that derived from a delayed loss of corneal epithelial stem cells (ESC), due to secondary processes most likely in the epithelial stem cell (SC) niche. The present study expands our research on SM-induced ocular injury to rodents (rats and mice) following whole body vapor exposure, aiming to define whether the delayed development of LSCD is a general characteristic of SM ocular toxicity. Freely moving rats and mice were exposed to SM vapor (155 µg/l, 10 min). Clinical examination was carried out in rats and included a slit-lamp bio-microscopy, up to 6 months. Eyes were taken for histology at different time points following exposure and evaluation included hematoxylin and eosin (H&E) staining for general morphology, PAS for identification of goblet cells and p63 immunohistochemistry for progenitor epithelial cells. Whole body exposure to SM vapor in rats and mice resulted in acute ocular injury characterized by corneal erosions and ocular inflammation. Following a brief recovery period, 80-90% of the exposed eyes developed corneal NV associated with abnormal corneal epithelium, stromal inflammation and endothelial damage. The late injury was accompanied by migration of conjunctival goblet cells to the cornea and a loss of limbal epithelial progenitor cells, indicating LSCD. The long-term ocular injury shown hereby in rats and mice was consistent with the lesions described in rabbits and in human casualties and demonstrated the general phenomenon of limbal epithelial stem cells deficiency in SM ocular toxicity. The delayed manifestation of this pathology points towards a therapeutic window for the development of medical countermeasures in small animals following exposure in a real life scenario.

Emotional dysregulation and health related quality of life in young adults with ADHD: a cross sectional study.

OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD) is associated with emotional dysregulation (ED) and impaired health related quality of life (HRQoL). However, the role of ED in explaining the relationship between ADHD and HRQoL is unclear. The purpose of the present study was to do so in a sample of non-referred young adults with and without ADHD. METHOD: The study design was cross-sectional. A non-clinical sample of 63 young adults with ADHD (mean age = 24.86 years, SD = 3.25, 78% university students) and 69 gender-matched controls (mean age = 23.84 years, SD = 2.59, 89% university students) were recruited. The Adult ADHD Quality-of-Life scale was used to measure HRQoL; The Self-Report Wender-Reimherr Adult Attention Deficit Disorder Scale and the Difficulties in Emotion Regulation Scale were used to measure ED. Group differences on all measures were tested using univariate and multivariate analyses of covariance, while controlling for age. Finally, a moderation analysis was used in order to examine the impact of ED on HRQoL beyond that accounted for by ADHD symptoms. RESULTS: Both HRQoL and ED were significantly worse for the ADHD group compared to the control group. The medication status of the ADHD group participants had no significant effect on the level of ADHD symptoms, ED or HRQoL. ED moderated the effect of ADHD symptoms on HRQoL for the ADHD group. CONCLUSION: The findings support the centrality of ED in ADHD and its crucial influence on HRQoL. Young adults with ADHD and high levels of ED are at risk for aversive impact on their well-being regardless of their ADHD symptoms level.

Young adults with Attention Deficit Hyperactivity Disorder (ADHD) struggle with poor quality of life (QoL). Emotional regulation is one's ability to modify their emotional state to promote adaptive, goal-oriented behaviors. Emotional dysregulation is a common yet neglected feature of people with ADHD. Our results show that young adults with ADHD are twice more likely to suffer from emotional dysregulation then their peers. Moreover, higher levels of emotional dysregulation predicted lower levels of QoL. These findings support the centrality of ED in ADHD and their crucial influence on everyday QoL. These findings are important not only on the theoretical level, but may also contribute to the design of interventions that aim to promote quality of life.

A comprehensive analysis of corneal mRNA levels during sulfur mustard induced ocular late pathology in the rabbit model using RNA sequencing.

Exposure to sulfur mustard (SM) may result in severe ocular injuries. While some of the eyes show a clinical resolution of the injury (defined as clinically non-impaired), part of the eyes develop irreversible late ocular pathologies (defined as clinically impaired) that may lead to corneal blindness. Understanding the pathological mechanisms underlying the development of the late pathology may lead to improved treatment options. Therefore, this study aimed to investigate the mRNA expression profiles of corneas from clinically impaired, clinically non-impaired and naïve eyes. Rabbit eyes were exposed to SM vapor and a clinical follow-up was carried out up to 4 weeks using a slit lamp microscope. At this time point, corneal tissues from clinically impaired, clinically non-impaired and naïve eyes were processed for RNA sequencing (RNA-seq) and differential expression analyses. The differential expression profiles were further subjected to pathway enrichment analysis using Ingenuity Pathway Analysis (IPA). Real-time PCR was used for RNA-seq validation. The late pathology developed in 54%-80% of the eyes following ocular exposure to SM, clinically manifested by inflammation, corneal opacity and neovascularization. RNA-seq results showed significant differences in mRNA levels of hundreds of genes between clinically impaired, clinically non-impaired and naïve corneas. Pathway enrichment analysis showed common pathways that were activated in all of the exposed eyes, such as Th1 and Th2 activation pathway, in addition to pathways that were activated only in the clinically impaired eyes compared to the clinically non-impaired eyes, such as IL-6 and ERK5 signaling. Corneal mRNA expression profiles for the clinically impaired, clinically non-impaired and naïve eyes generated a comprehensive database that revealed new factors and pathways, which for the first time were shown to be involved in SM-induced late pathology. Our data may contribute to the research on both the pathological mechanisms that are involved in the development of the late pathology and the protective pathways that are activated in the clinically non-impaired eyes and may point out towards novel therapeutic strategies for this severe ocular injury.

Whole body exposure of rats to sulfur mustard vapor.

Sulfur mustard (SM) is an incapacitating chemical warfare agent used in numerous conflicts around the world and it is still a major threat for both, army troops and civilians. To evaluate its multiple targets effects in experimental setup, a model of whole body exposure (WBE) to SM vapor was established in rats and its simultaneous effects on lungs and eyes as well as on general wellbeing were examined. Rats were exposed to SM vapor. Evaluation (up to 10 weeks post-exposure) included body weight, general observation, blood counts and histological analysis. Results showed that following a latency-period of several hours, rats typical symptoms developed over a period of more than one week. The initial symptoms, characterized by swollen and erythematic nose, deteriorated into extensive rhinorrhea, eye closure, excessive lacrimation as well as rhonchi, wheezing and breathing difficulties. Alopecia and behavioral abnormality were also recorded. A weight loss of up to 40% was measured within one week with spontaneous recovery to baseline level within three weeks after exposure. Blood counts revealed leukopenia during the first three days post-exposure. Histological evaluation revealed a long lasting damage to the trachea, lungs and eyes. Thus, WBE to SM, was found to closely mimic the deleterious effects of SM on the sensitive tissues previously described in human victims during WWI and the Iran-Iraq war. The use of this animal model will enable comprehensive characterization of changes in biological processes that may lead to the development of therapeutic measures to ameliorate SM induced multi-system injuries.

Successful single treatment with ziv-aflibercept for existing corneal neovascularization following ocular chemical insult in the rabbit model.

PURPOSE: To evaluate the efficacy of ziv-aflibercept as a treatment for established corneal neovascularization (NV) and to compare its efficacy to that of bevacizumab following ocular chemical insult of sulfur mustard (SM) in the rabbit model. METHODS: Chemical SM burn was induced in the right eye of NZW rabbits by vapor exposure. Ziv-aflibercept (2 mg) was applied once to neovascularized eyes by subconjunctival injection while subconjunctival bevacizumab (5 mg) was administered twice a week, for 3 weeks. Non-treated exposed eyes served as a control. A clinical follow-up employed by slit-lamp microscope, was performed up to 12 weeks following exposure and digital photographs of the cornea were taken for measurement of blood vessels length using the image analysis software. Eyes were taken for histological evaluation 2, 4 and 8 weeks following treatment for general morphology and for visualization of NV, using H&E and Masson Trichrome stainings, while conjunctival goblet cell density was determined by PAS staining. RESULTS: Corneal NV developed, starting as early as two weeks after exposure. A single subconjunctival treatment of ziv-aflibercept at 4 weeks post exposure, significantly reduced the extent of existing NV already one week following injection, an effect which lasted for at least 8 weeks following treatment, while NV in the non-treated exposed eyes continued to advance. The extensive reduction in corneal NV in the ziv-aflibercept treated group was confirmed by histological evaluation. Bevacizumab multiple treatment showed a benefit in NV reduction, but to a lesser extent compared to the ziv-aflibercept treatment. Finally, ziv-aflibercept increased the density of conjunctival goblet cells as compared to the exposed non-treated group. CONCLUSIONS: Subconjunctival ziv-aflibercept single treatment presented a highly efficient long-term therapeutic benefit in reducing existing corneal NV, following ocular sulfur mustard exposure. These findings show the robust anti-angiogenic efficacy of ziv-aflibercept and demonstrate the advantage of this treatment over the other anti-angiogenic therapies in ameliorating corneal NV and protecting the ocular surface.

Differential expression of corneal and limbal cytokines and chemokines throughout the clinical course of sulfur mustard induced ocular injury in the rabbit model.

PURPOSE: The sight threatening sulfur mustard (SM) induced ocular injury presents specific symptoms for each clinical stage. The acute injury develops in all of the exposed eyes and is characterized by erosions and severe inflammation. The irreversible late pathology develops only in part of the eyes, and is clinically expressed by chronic inflammation and corneal neovascularization (NV). The mechanisms underlying this injury are still in research and treatment is insufficient. Aiming to shed light on pathological mechanisms and improve the therapeutic measures, we studied the expression pattern of various cytokines and chemokines at different clinical stages of the ocular injury. METHODS: Rabbit right eye was exposed to SM vapor and a clinical follow-up was carried out up to 4 weeks. Corneal and limbal tissues were collected at 48 h, 1w and 4w post exposure and IL-1α, IL-1ß, IL-6, TNFα, macrophage chemotactic protein (MCP)-1 and IL-8 levels were measured by commercial ELISA kits. RESULTS: SM exposed eyes presented an acute injury that was partially resolved within a week in all of the exposed eyes, and was followed by an irreversible late pathology in 50%-80% of the eyes, beginning at 2w. A significant elevation was seen in levels of the studied factors, however each factor presented a unique expression pattern. At the peak of the acute injury, at 48 h, significantly higher levels of corneal IL-1α, IL-8, and TNFα and limbal IL-1α and MCP-1 were found compared to naïve eyes. At 1w, corneal IL-1ß, IL-6, IL-8 and TNFα and limbal IL-8 and MCP-1 levels were significantly higher compared to naïve eyes. During the late pathology, at 4w, elevated levels of corneal IL-1ß, IL-6 and MCP-1 and limbal MCP-1 and IL-8 were found only in eyes presenting NV. CONCLUSIONS: The levels of the studied factors changed throughout the dynamic course of the ocular injury. The prolonged increased levels of limbal MCP-1 and IL-8 may contribute to the continuous recruitment of inflammatory cells, characterizing the symptoms of the late pathology. The significantly elevated IL-1ß and IL-6 at 1w, after the resolution of the acute injury but before the clinical manifestation of the late pathology suggests a therapeutic window for intervention with prevention therapy. Mapping the expression pattern of these cytokines and chemokines points out towards stage-specific therapeutic options.

Acute and long-term ocular effects of acrolein vapor on the eyes and potential therapies.

OBJECTIVE: Acrolein is a potent irritant and a vesicant that was used by the French during WWI as the warfare agent named: "papite". Nowadays, it is produced in large amounts all over the world in the industry for the production of acrylic acid and for agriculture use as herbicide. The aim of this study was to characterize the effects of acute eye exposure to acrolein vapor and to evaluate the efficacy of a topical post-exposure combination treatment with a local anesthetic and a steroid. METHODS: Rabbit eyes were exposed to three doses of acrolein vapor (low, intermediate and high) and treated topically with either 0.4% benoxinate hydrochloride (localin, for 2 h) or dexamethasone (dexamycin, for 6 days) or a combination of both drugs. Clinical follow-up using slit lamp examinations and histological evaluation was performed 4 weeks post-exposure. RESULTS: Acrolein vapor caused immediate eye closure with excess tearing, corneal erosions and severe inflammation of the anterior chamber. This was followed by corneal neovascularization (NV) starting as early as 1 week post-exposure. The damage to the eyes was long lasting, and at 4 weeks following exposure, significant pathological changes were observed. Immediate post-exposure application of the local anesthetic, localin, prevented the eye closure, and the dexamycin treatment reduced significantly the initial inflammation as well as the extent and incidence of corneal NV. CONCLUSIONS: Short-term eye exposure to the irritant acrolein may result in immediate eye closure and long lasting pathologies that could lead to blindness. An anti-inflammatory treatment combined with short-term application of a local anesthetic prevents incapacitation and might minimize significantly the extent of eye injuries.

Beneficial effects of activated macrophages on sulfur mustard-induced cutaneous burns, an in vivo experience.

OBJECTIVE: Macrophages are known to have key functions in almost every stage of wound healing and there is evidence for their beneficial effects in treating decubital ulcers and deep sternal wound infections in human. This study aimed to investigate the efficacy of a treatment with activated macrophages on ameliorating acute and long-term sulfur mustard (SM) induced skin injuries in the hairless guinea pig (HGP) model. METHODS: HGP were exposed to SM vapor and treated with either a single or multiple intra-dermal injections of human activated macrophages in suspension (hAMS) into the wound bed. Clinical and histological evaluations were conducted up to 4 weeks post-exposure. RESULTS: A single treatment with hAMS early after exposure (15 min and 6 h) resulted in a reduction in the number of damaged cells and vesications in the epidermis at 24 h. A substantial increase in cellular infiltration, mostly polymorphonuclears, was taking place in the hAMS-treated animals starting as early as 1 h after exposure. This flow of inflammatory cells continued, in the treated group, for at least 4 weeks, long after the injected macrophages were not detected. Repeated injections of hAMS (15 min, 48 h and 7 d post-exposure) decreased significantly the area of the wounds and improved the integrity of the barrier function as expressed by measuring trans-epidermal water loss up to 10 d. CONCLUSIONS: Our results indicate that the role of macrophages in wound healing is complex; their efficacy may depend on the timing of administration. Further investigation is required to determine whether they are required during the early phase of wound development and/or during the late phase of scar formation and remodeling.

Endothelial cell damage following sulfur mustard exposure in rabbits and its association with the delayed-onset ocular lesions.

OBJECTIVE: Ocular injuries following exposure to the toxic agent sulfur mustard (SM) are characterized by acute corneal erosions and inflammation of the anterior segment that may be followed by delayed corneal injuries, expressed clinically by neovascularization and epithelial defects. The present study aimed to investigate the effects of SM on corneal endothelium (CE) during the acute and delayed phase in relation to the development of the long-term pathology. METHODS: Rabbit eyes were exposed to SM vapor. A clinical follow-up including pachymetry for measurement of corneal thickness were conducted up to 3 months following exposure. In vivo analysis of corneal endothelium in the central and peripheral cornea was carried out, using a contact specular microscopy. Morphometric analysis of cell area and number of cells was performed, to include the acute and delayed phases. Eyes were taken for histology at different time points following exposure (1 h to 3 months). TUNEL staining (Terminal deoxynucleotidyl transferase dUTP nick end labeling) was conducted for detection of apoptosis during the acute phase. RESULTS: SM induced acute corneal erosions and prolonged anterior segment inflammation. Corneal thickness increased within hours, declined after few days but remained higher compared to baseline value for months after the exposure, indicating a chronic edema. Apoptotic alterations were first observed at 6 h resulting in a significant decline in the number of endothelial cells at 24-48 h following exposure. Healing of the endothelium was relatively fast and at one week the Descemet's membrane was resurfaced, yet, the density and morphology of the cells was often abnormal. Moreover, histological evaluation revealed deformation and enlargement of many cells (polymegathism and pleomorphism), thickening and double layered Descemet's membrane. These changes were more pronounced in corneas displaying delayed pathology. DISCUSSION AND CONCLUSIONS: SM induced apoptotic cell death of endothelial cells that was accompanied by corneal edema. The impaired healing of the endothelium, including the decrease in endothelial cell density was associated with the delayed-onset injuries. Since human corneal endothelium is almost amitotic, endothelium toxicity should be taken into consideration when testing potential treatments against ocular injuries following SM exposure.

Archaeometallurgical Analysis of the Provincial Silver Coinage of Judah: More on the Chaîne Opératoire of the Minting Process.

Silver coins were the first coins to be manufactured by mass production in the southern Levant. An assemblage of tiny provincial silver coins of the local (Judahite standard) and (Attic) obol-based denominations from the Persian and Hellenistic period Yehud and dated to the second half of the fourth century BCE were analyzed to determine their material composition. Of the 50 silver coins, 32 are defined as Type 5 (Athena/Owl) of the Persian period Yehud series (ca. 350-333 BCE); 9 are Type 16 (Persian king wearing a jagged crown/Falcon in flight) (ca. 350-333); 3 are Type 24 series (Portrait/Falcon) of the Macedonian period (ca. 333-306 BCE); and 6 are Type 31 (Portrait/Falcon) (ca. 306-302/1 BCE). The coins underwent visual testing, multi-focal light microscope observation, XRF analysis, and SEM-EDS analysis. The metallurgical findings revealed that all the coins from the Type 5, 16, 24, and 31 series are made of high-purity silver with a small percentage of copper. Based on these results, it is suggested that each series was manufactured using a controlled composition of silver-copper alloy. The findings present novel information about the material culture of the southern Levant during the Late Persian period and Macedonian period, as expressed through the production and use of these silver coins.

Everyday Cognitive Control and Emotion Dysregulation in Young Adults With and Without ADHD: An Ecological Momentary Assessment Study.

OBJECTIVE: This study examined the contribution of the temporal dynamics of two cognitive control mechanisms-inhibitory control (IC) and working memory (WM)-to emotion dysregulation (ED) in attention-deficit/hyperactivity disorder (ADHD) in ecological settings. METHOD: One hundred twenty-two participants (age 18-33 years; 60 with ADHD) reported their ED at baseline, followed by a 5-day ecological momentary assessment (EMA) study, with short behavioral IC and WM tasks performed five times/day. RESULTS: For IC, mean and lability of performance over EMA significantly accounted for differences in ED but not baseline performance. For WM, both baseline and mean of EMA, but not EMA lability, accounted for ED variance. ADHD status further contributed to the explained variance of ED. CONCLUSIONS: Our results support the contribution of dynamic IC processes to ED in ADHD, in addition to WM performance level, and highlight the importance of dynamic and ecological investigation of different cognitive control components.

The use of aflibercept (VEGF trap) in mitigating sulfur mustard-induced corneal neovascularization in a rabbit model.

Sulfur mustard (SM)-induced ocular injury is characterized by an acute inflammatory response that may become chronic or enter a latent phase with delayed pathology. This study aimed to evaluate the efficacy of ziv-aflibercept and aflibercept in preventing and ameliorating corneal neovascularization (NV), respectively, following chemical eye exposure to SM vapor in a rabbit model. Chemical SM ocular insult was induced in the right eye of rabbits. A single application of ziv-aflibercept was administered 2 h or 9 days post-exposure. A single subconjunctival aflibercept treatment in an ocular formulation was administered 4 weeks after SM vapor exposure and subsequent to an initial 1-week treatment with 0.1 % dexamethasone. Clinical monitoring was performed 5-12 weeks post-exposure, and digital corneal pictures were taken to assess the extent of NV. The rabbits were euthanized and the corneas were processed for histological assessment. Treatment with ziv-aflibercept 2 h and 9 days post-exposure moderately reduced insult severity and partially delayed or prevented corneal NV. Aflibercept application 4 weeks post-exposure significantly reduced the extent of NV for 8 weeks. The substantial decrease in existing corneal NV in this group was confirmed by histology. These results reveal the powerful anti-angiogenic efficacy of the VEGF-trap for ameliorating existing NV as opposed to preventing NV development, revealing the ability of this treatment to mitigate corneal NV.

Characterization of acute and long-term pathologies of superficial and deep dermal sulfur mustard skin lesions in the hairless guinea pig model.

Sulfur mustard induces severe acute and prolonged damage to the skin and only partially effective treatments are available. We have previously validated the use of hairless guinea pigs as an experimental model for skin lesions. The present study aimed to characterize a model of a deep dermal lesion and to compare it with the previously described superficial lesion. Clinical evaluation of the lesions was conducted using reflectance colorimetry, trans-epidermal water loss and wound area measurements. Prostaglandin E(2) content, matrix metalloproteinase-2 and 9 activity, and histopathology were conducted up to 4 weeks post-exposure. Sulfur mustard skin injury, including erythema and edema, impairment of skin barrier and wounds developed in a dose-dependent manner. Prostaglandin E(2) content and matrix metalloproteinase-2 and 9 activities were elevated during the wound development and the healing process. Histological evaluation revealed severe damage to the epidermis and deep dermis and vesications. At 4 weeks postexposure, healing was not completed: significantly impaired stratum corneum, absence of hair follicles, and epidermal hyperplasia were observed. These results confirm the use of the superficial and deep dermal skin injuries in the hairless guinea pigs as suitable models that can be utilized for the investigation of the pathological processes of acute as well as long-term injuries. These models will be further used to develop treatments to improve the healing process and prevent skin damage and long-term effects.

Occupational experiences of college students with ADHD: A qualitative study.

BACKGROUND: College students with attention deficit hyperactivity disorder (ADHD) face difficulties with occupational performance in many functional domains. Despite the broad literature on academic and psychosocial functions, there is a gap in knowledge regarding how these students experience participation in their various daily functions. OBJECTIVE: Gaining a deeper understanding of the occupational experiences of college students with ADHD and exploring factors that facilitate or impede their occupational performance. METHOD: Twenty college students with ADHD were interviewed using the Occupational Performance History Interview (OPHI-II). Qualitative content analysis was employed. RESULTS: Six themes were found in relation to varied occupational domains: (1) Eating and meal preparation: Too little or too much; (2) Sleep: Not enough to 'recharge batteries'; (3) Medication management: Intense ambivalence; (4) Studying: Too hard, too effortful (5) Work: Need it and love it; and (6) Leisure: Desired yet absent. Each theme contained categories related to factors that influenced performance. Impeding factors included occupational demands, ADHD biological attributes, and personal beliefs. Facilitating factors included self-awareness, executive strategies, adaptive routines, and enabling social context. CONCLUSIONS: College students with ADHD experience profound difficulties in occupational performance, yet variation occurs across domains, attributable to occupational, biological, psychological, and social factors. Results can inform tailored interventions supporting occupational performance in this population.

Skin decontamination efficacy of sulfur mustard and VX in the pig model: A comparison between Fuller's earth and RSDL.

Skin decontamination following exposure to chemical agents is a most important component of the individual defense doctrine, removing the agent, ceasing its penetration and preventing secondary contamination of the first responders. The goal of the current study was to compare the efficacy of Reactive Skin Decontaminant Lotion (RSDL) and Fuller's Earth (FE) following exposure to sulfur mustard (SM) and VX, aiming to find the optimal procedure for mass casualty decontamination protocol. Decontamination efficacy was evaluated in pigs by measurement of lesion area and erythema (SM) and cholinesterase inhibition and clinical symptoms (VX). FE and RSDL were highly effective against both agents. Following SM exposure, the two decontaminants demonstrated a significant decrease in lesions' size together with the decrease in exposure duration. Likewise, skin decontamination following exposure to VX with either FE or RSDL resulted in reduction in clinical symptoms and prevention of death. Decontamination was worthwhile even if postponed, up to 30 min (SM) and 2 h (VX). In conclusion, both decontamination products were efficient in ameliorating the toxic effects even though in a different mechanism. Finally, for mass casualty scenario, FE is preferred as a universal decontaminant, considering its safety, ease of use and longer shelf life.

Characterization of acute and long-term sulfur mustard-induced skin injuries in hairless guinea-pigs using non-invasive methods.

BACKGROUND/PURPOSE: Skin exposure to sulfur mustard (HD) results in erythema, edema and severe injury, which take long time to heal and might impose a heavy burden on the health system. Despite many years of research, there is no treatment that prevents the development of the cytotoxic effects of HD causing acute and prolonged damage to the skin. Therefore, it is of great importance to develop treatments that will ameliorate the extent of injury and improve as well as shorten the healing process. The aim of the present study was to establish a small animal model for a long-term HD-induced skin injury using the hairless guinea-pig (HGP) and to further test the efficacy of anti-inflammatories in ameliorating the pathology. METHODS: HGPs were exposed to HD vapor on four sites for various time durations (1, 5, 10, 15 and 30 min). Clinical evaluation was conducted using reflectance colorimetry, transepidermal water loss and wound-area measurements. Biochemical [prostaglandin (PGE) content and metalloproteinase-9 (MMP-9) activity] and histopathological evaluations were conducted up to 2 weeks post-exposure. RESULTS: Typical symptoms of HD skin injury developed including erythema and edema and the extent of injury was closely related to the exposure duration. Histological evaluation revealed severe edema, infiltration of inflammatory cells, damage to basal cells and vesication. By 2 weeks, healing was not completed, impaired basement membrane and epithelial hyperplasia were observed. PGE content and MMP-9 activity increased at 2 h post-exposure; however, while PGE returned to baseline levels within 24 h, MMP-9 remained elevated at least up to 48 h. Furthermore, a short-term, topical, anti-inflammatory post-exposure treatment was effective in reducing the extent of the acute injury. CONCLUSION: These results indicate that the effects of HD on HGP skin are similar to previously shown effects in the pig model and in humans and therefore support the use of the HGP as an animal model for long-term effects of HD on skin injury and for studying the efficacy of anti-inflammatory treatments.

Occupational identity of adolescents with ADHD: A mixed methods study.

BACKGROUND: Occupational identity (OI) is shaped by occupational experiences over time and has been studied among individuals with a variety of health conditions. Adolescents with ADHD face numerous challenges in their occupational performance that may threaten their OI. OBJECTIVE: This study sought to compare the occupational identities of adolescents with and without ADHD and to gain a deeper understanding of the characteristics of OI among adolescents with ADHD. METHODS: Sixty-four adolescents with (n = 21) and without ADHD (n = 43) were interviewed using the Occupational Performance History Interview (OPHI-II). A mixed methodology was applied, using quantitative and subsequent qualitative content analyses of 10 interviews, with a directed approach. RESULTS: OPHI-II OI interval scores and 7/11 items of the OI scale were significantly lower in the ADHD group compared to controls. In the qualitative content analyses, three major themes were found: (i) the meaning of success in academic participation, (ii) the consequences of not succeeding in academic participation and (iii) self-explanations for not succeeding in academic participation. CONCLUSION: Findings demonstrate the presence of OI challenges among adolescents with ADHD. Occupational therapy intervention may be needed in order to promote occupational adaptation.