Life Gets Better: Important Resilience Factors When Growing Up With ADHD.

OBJECTIVE: To explore emerging adults' descriptions of important resilience factors when growing up with ADHD. METHOD: Individual interviews with 10 emerging adults (21-24 years) who participated in a 10-year follow-up study, analyzed using thematic analysis. RESULTS: The main theme was that "life gets better." Resilience factors contributing to this positive development were strategies to regulate ADHD, valuable relationships, acceptance, seeing positive attributes of ADHD, receiving tailored, non-stigmatizing support, and participating in meaningful activities. CONCLUSION: Growing up with ADHD was associated with both challenges and positives, but the main resilience theme was that life gets better. A variety of resilience factors contributed to this, but relational and environmental factors seemed particularly important. Acceptance, both from society and self-acceptance, were related to all resilience factors in various ways indicating that better knowledge of ADHD might foster better understanding and acceptance of children and adolescents with ADHD.

Characterizing Pediatric Hand Grasps During Activities of Daily Living to Inform Robotic Rehabilitation and Assistive Technologies.

Hand function plays a critical role in how we interact with our physical environment. Hand motor impairments in children can compromise many facets of their daily life including physical independence and social interactions. For adults, there has been an emergence of mechatronic rehabilitation systems to improve hand mobility, strength, and dexterity; assistive technologies such as exoskeletons to drive impaired digits; and highly dexterous upper limb prostheses. Although similar devices are on the clinical horizon for children, childhood play, motor development, and daily activities mean they use their hands in fundamentally different ways than adults. It is imperative that devices for this population facilitate their unique needs; yet it is not completely known which hand movements may be of the highest priority during daily tasks or rehabilitation to best foster functional independence. Here, we evaluated and categorized the hand activity of two children in their home environments. Small wearable video cameras were attached to the children as they performed daily tasks and the video footage was analyzed to obtain the frequency and duration of their hand grasp movements. It was found that 7 common grasps accounted for 90% or greater of the children's hand activity in duration and frequency. This suggests, that like adults, a repertoire of common hand grasps may be prioritized by rehabilitative or assistive devices to ensure effective outcomes in performing daily activities.

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future.

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe.

Complete Genome Sequences of Two Vibrio natriegens Bacteriophages.

Vibrio natriegens, a fast-growing Gram-negative bacterium, is gaining interest as a platform for rapid biotechnology applications and metabolic engineering. Only a few bacteriophages that infect this bacterium have been identified. Here, we describe the isolation and characterization of two V. natriegens bacteriophages isolated from Hatches Creek, Wellfleet, Massachusetts.

Association of combined PD-L1 expression and tumour-infiltrating lymphocyte features with survival and treatment outcomes in patients with metastatic melanoma.

BACKGROUND: Recent advances obtained with immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1) protein have significantly improved the outcome of patients with metastatic melanoma. The PD-L1 expression in tumour cells as detected by immunohistochemistry is a predictive biomarker in some solid tumours, but appears insufficient as prognostic or predictive factor of response to ICIs in metastatic melanomas. OBJECTIVES: We investigated whether the presence and the features of pretreatment CD8+ tumour-infiltrating T lymphocytes (TILs) could be a complementary prognostic or predictive biomarker in patients with metastatic melanoma. METHODS: In this retrospective study, we evaluated the association of PD-L1 expression ≥5% of tumour cells combined with TIL features (CD8, CD28, Ki67) with the overall survival (OS) among 51 patients treated with ICIs and 54 patients treated with other treatment options (non-ICIs). RESULTS: PD-L1 positivity was observed in 33% and 39% of primary melanomas and matched metastases, respectively, with, however, poor concordance between the primary and the matched metastatic site (κ = 0.283). No significant association was noted between PD-L1 expression and CD8+ TIL profile analysed as single markers and OS or response to immunotherapy. Instead, their combined analysis in primary melanoma samples showed that the PD-L1-/CD8+ status was significantly associated with prolonged OS in the whole population (P = 0.04) and in the subgroup treated with non-ICIs (P = 0.009). Conversely, the PD-L1+/CD8+ status was a good prognostic factor in patients treated with ICIs (P = 0.022), whereas was significantly associated with poor prognosis in patients treated with non-ICIs (P = 0.014). While the expression of CD28 was not related to outcome, the Ki67 expression was significantly associated with poor OS in the subgroup CD8+ TIL+/PD-L1- (P = 0.02). CONCLUSIONS: The pretreatment combination of PD-L1 expression with the level of CD8+ TILs could better assess OS and predict therapeutic response of patients with metastatic melanoma treated by either immunotherapy or other treatment regimens.

Heterogeneity in Reported Outcome Measures after Surgery in Superior Canal Dehiscence Syndrome-A Systematic Literature Review.

BACKGROUND: Superior canal dehiscence syndrome (SCDS) can be treated surgically in patients with incapacitating symptoms. However, the ideal treatment has not been determined. OBJECTIVES: This systematic literature review aims to assess available evidence on the comparative effectiveness and risks of different surgical treatments regarding: (1) symptom improvement; (2) objectively measurable auditory and vestibular function; (3) adverse effects, and (4) length of hospitalization. SEARCH METHOD AND DATA SOURCES: A systematic database search according to PRISMA statement was conducted on Pubmed, Embase, and Cochrane library. In addition, reference lists were searched. No correspondence with the authors was established. The last search was conducted on June 9, 2017. STUDY ELIGIBILITY CRITERIA: Retrospective and prospective cohort studies were held applicable under the condition that they investigated the association between a surgical treatment method and the relief of vestibular and/or auditory symptoms. Only studies including quantitative assessment of the pre- to postoperative success rate of a surgical treatment method were included. Case reports, reviews, meta-analysis, and studies not published in English, Dutch, or German were excluded. DATA COLLECTION AND ANALYSIS: The first author searched literature and extracted data; the first and last analyzed the data. MAIN RESULTS: Seventeen studies (354 participants, 367 dehiscences) met the eligibility criteria and were grouped according to surgical approach. Seven combinations of surgical approaches and methods for addressing the dehiscence were identified: plugging, resurfacing, or a combination of both through the middle fossa (middle fossa approach); plugging, resurfacing, or a combination of both through the mastoid (transmastoid approach); round window reinforcement through the ear canal (transcanal approach). Several studies showed high internal validity, but quality was often downgraded due to study design (1). Outcome measures and timing of postsurgical assessment varied among studies, making it unfeasible to pool data to perform a meta-analysis. CONCLUSION: A standardized protocol including outcome measures and timeframes is needed to compare the effectiveness and safety SCDS treatments. It should include symptom severity assessments and changes in vestibular and auditory function before and after treatment.

Chemokine Receptor Signaling and the Hallmarks of Cancer.

The chemokines are a family of chemotactic cytokines that mediate their activity by acting on seven-transmembrane-spanning G protein-coupled receptors. Both the ability of the chemokines and their receptors to form homo- and heterodimers and the promiscuity of the chemokine-chemokine receptor interaction endow this protein family with enormous signaling plasticity and complexity that are not fully understood at present. Chemokines were initially identified as essential regulators of homeostatic and inflammatory trafficking of innate and adaptive leucocytes from lymphoid organs to tissues. Chemokines also mediate the host response to cancer. Nevertheless, chemokine function in this response is not limited to regulating leucocyte infiltration into the tumor microenvironment. It is now known that chemokines and their receptors influence most-if not all-hallmark processes of cancer; they act on both neoplastic and untransformed cells in the tumor microenvironment, including fibroblasts, endothelial cells (blood and lymphatic), bone marrow-derived stem cells, and, obviously, infiltrating leucocytes. This review begins with an overview of chemokine and chemokine receptor structure, to better define how chemokines affect the proliferation, survival, stemness, and metastatic potential of neoplastic cells. We also examine the main mechanisms by which chemokines regulate tumor angiogenesis and immune cell infiltration, emphasizing the pro- and antitumorigenic activity of this protein superfamily in these interrelated processes.

Comano thermal water inhalations in the treatment of allergic rhinitis: preliminary results.

BACKGROUND: Comano thermal water, well known for its activity in the treatment of dermatological diseases, has been successfully employed in the treatment of upper airways disorders. OBJECTIVE: The present preliminary study aimed to evaluate whether Comano thermal water may be able to improve nasal symptoms severity in patients with allergic rhinitis (AR). METHODS: 30 AR patients were enrolled (mean age 40.9 years; 13 males) and treated with inhalation of Comano thermal water for 15 days. Total symptom score (TSS) and visual analogue scale (VAS) for patient's perception of nasal patency were assessed at baseline, after treatment, and after a 2-week follow-up. RESULTS: TSS significantly decreased after treatment as well as VAS significantly increased. The effects were partially long-lasting. CONCLUSION: Comano thermal water inhalation as monotherapy for AR was able to relieve nasal symptoms and patient's perception of nasal patency.

Comparative study of the PD-L1 status between surgically resected specimens and matched biopsies of NSCLC patients reveal major discordances: a potential issue for anti-PD-L1 therapeutic strategies.

BACKGROUND: High expression of programmed death ligand-1 (PD-L1) on tumor cells (TC) and/or on tumor-infiltrating immune cells (IC) is associated with a high response rate in patients with advanced nonsmall-cell lung cancer (NSCLC) treated with PD-L1 inhibitors. The use of a PD-L1 immunohistochemical (IHC) test in determining the responsiveness to immunotherapy has raised the question of the reliability and reproducibility of its evaluation in lung biopsies compared with corresponding resected surgical specimens. PATIENTS AND METHODS: PD-L1 expression in TC and IC was assessed in 160 patients with operable NSCLC on both whole surgical tissue sections and matched lung biopsies, by using a highly sensitive SP142 IHC assay. The specimens were scored as TC 0-3 and IC 0-3 based on increasing PD-L1 expression. RESULTS: PD-L1 expression was frequently discordant between surgical resected and matched biopsy specimens (the overall discordance rate = 48%; 95% confidence interval 4.64-13.24) and κ value was equal to 0.218 (poor agreement). In all cases, the biopsy specimens underestimated the PD-L1 status observed on the whole tissue sample. PD-L1-positive IC tumors were more common than PD-L1-positive TC tumors on resected specimens. The discrepancies were mainly related to the lack of a PD-L1-positive IC component in matched biopsies. CONCLUSIONS: Our results indicate relatively poor association of the PD-L1 expression in TC and IC between lung biopsies and corresponding resected tumors. Although these results need to be further validated in larger cohorts, they indicate that the daily routine evaluation of the PD-L1 expression in diagnostic biopsies can be misleading in defining the sensitivity to treatment with PD-L1 targeted therapy.

Reflectance confocal microscopy features of acral lentiginous melanoma: a comparative study with acral nevi.

BACKGROUND: Acral lentiginous melanoma (ALM) can be difficult to differentiate from acral nevus. Reflectance confocal microscopy (RCM) is widely used for the diagnosis of melanocytic tumours, but the RCM features of ALM and acral nevus have not been described yet. OBJECTIVE: To determine the RCM features of ALM and acral nevus, and their correlation with clinical and histological characteristics. METHODS: Retrospective study of 17 cases of ALM and 26 acral nevi. RESULTS: Pagetoid cells were present in all ALMs with a visible epidermis and in three nevi. A proliferation of atypical melanocytes at the dermal-epidermal junction (DEJ) and/or in the dermis was visible in nine ALMs but not in nevi. The histopathological examination of initial skin biopsies was unable to diagnose ALM in four cases, differing from RCM that could identify malignant tumour cells by exploring the whole lesions. CONCLUSION: Reflectance confocal microscopy can help in the differentiation of ALM and acral nevus, and to guide the biopsy.

Discrepancies between FISH and immunohistochemistry for assessment of the ALK status are associated with ALK 'borderline'-positive rearrangements or a high copy number: a potential major issue for anti-ALK therapeutic strategies.

BACKGROUND: Patients with advanced lung adenocarcinomas expressing ALK rearrangements are highly responsive to crizotinib, a dual ALK/c-MET inhibitor. Immunohistochemistry (IHC) is an easy clinically and routinely applicable cost-effective assay for ALK, c-MET and ROS1 protein expression for potential treatment with crizotinib. The purpose of this study was to evaluate the percentage and the pattern of ALK-rearranged cells, the variation in the native ALK copy number, as well as ALK, c-MET and ROS1 protein expression, and their significance on outcome of crizotinib-treated lung adenocarcinoma patients. PATIENTS AND METHODS: Consecutive lung adenocarcinoma specimens (n = 176) 'double-negative' (wild-type EGFR and KRAS) were tested for ALK rearrangements/copy number alterations and for ALK, c-MET and ROS1 protein expression using automated standardized protocols. Preliminary data on the outcome of crizotinib-treated patients were recorded. RESULTS: FISH analysis identified 26/176 (15%) cases with ALK rearrangements. Seven cases had discordant results between the ALK FISH and IHC. Five cases with discordant FISH-positive/IHC-negative revealed FISH 'borderline' positivity (15%-20%). Three cases overexpressed c-MET and responded to crizotinib, and two cases with ALK-'borderline' rearranged cells only, not associated with c-MET expression, progressed under crizotinib. Two cases with discordant FISH-negative/IHC-positive revealed ALK gene amplification without associated c-MET or ROS1 protein expression. CONCLUSIONS: The discrepancies observed between the IHC and FISH data revealed unexpected biological events, rather than technical issues, which potentially can have a strong impact on the therapeutic strategy with crizotinib.

Current progresses on nanodelivery systems for the treatment of neuropsychiatric diseases: Alzheimer's and schizophrenia.

Currently Alzheimer's disease and schizophrenia are both well-established neuropsychiatric diseases. Nonetheless, the treatment of these disorders is not unanimous and fully effective. As a consequence, several approaches have been studied to improve patient's conditions. In this context, the development of new drug nanodelivery systems to increase drug bioavailability and reduce adverse effects has been claimed as a good option. Among these systems we focus on the ones that seem to be most promising, such as lipidbased systems (e.g. liposomes, nanoemulsions and lipid nanoparticles), drug nanocrystals, polymeric nanoparticles and micelles. Moreover, the application of these systems by means of alternative administration routes is also discussed. Regardless of the satisfactory results and the associated progresses that have been done in the last years, more studies are required to quickly licence the application of drug nanodelivery systems in human medicines.

A novel lipid nanocarrier for insulin delivery: production, characterization and toxicity testing.

A novel nanocarrier based on solid lipid nanoparticles (SLNs) was developed for insulin delivery using a novel double emulsion method. Physical stability of particles was assessed by size analysis using dynamic light scattering (DLS), matrix crystallinity by differential scanning calorimetry (DSC) and toxicity analysis by Drosophila melanogaster testing. Insulin-SLNs were composed of Softisan®100 1.25% wt, Lutrol®F68 1% wt, soybean lecithin 0.125% wt, and loaded with 0.73-0.58 mg/mL peptide. Placebo-SLNs (insulin-free) also contained 0.025% wt Tween®80. Mean particle sizes of placebo-SLN and insulin-SLN were 958 ± 9.5 and 978 ± 8.3 nm, respectively. The polydispersity index (PI) was 0.28 ± 0.018 and 0.29 ± 0.013, respectively. Polarized light microscopy analysis depicted no aggregation of developed particles. DSC analysis allowed characterizing SLN with 43-51% matrix crystallinity. Using Drosophila melanogaster test, no toxicity was reported for SLN and for the bulk lipid. This study shows that SLNs are promising and helpful to overcome conventional insulin therapy, in particular for their lack of toxicity for oral delivery.

Legacy effects of drought on plant growth and the soil food web.

Soils deliver important ecosystem services, such as nutrient provision for plants and the storage of carbon (C) and nitrogen (N), which are greatly impacted by drought. Both plants and soil biota affect soil C and N availability, which might in turn affect their response to drought, offering the potential to feed back on each other's performance. In a greenhouse experiment, we compared legacy effects of repeated drought on plant growth and the soil food web in two contrasting land-use systems: extensively managed grassland, rich in C and with a fungal-based food web, and intensively managed wheat lower in C and with a bacterial-based food web. Moreover, we assessed the effect of plant presence on the recovery of the soil food web after drought. Drought legacy effects increased plant growth in both systems, and a plant strongly reduced N leaching. Fungi, bacteria, and their predators were more resilient after drought in the grassland soil than in the wheat soil. The presence of a plant strongly affected the composition of the soil food web, and alleviated the effects of drought for most trophic groups, regardless of the system. This effect was stronger for the bottom trophic levels, whose resilience was positively correlated to soil available C. Our results show that plant belowground inputs have the potential to affect the recovery of belowground communities after drought, with implications for the functions they perform, such as C and N cycling.