Twórczość plastyczna jako forma wspierania rozwoju osób niewidomych i głuchoniewidomych

Twórczość plastyczna wydaje się być niedocenianym przez tyflopedagogów obszarem aktywności dzieci, młodzieży oraz dorosłych osób niewidomych i głuchoniewidomych. Tymczasem osoby te warto angażować w wiele form plastycznej kreacji, dodatkowo kierując się zasadą „im wcześniej, tym lepiej”. Tego typu doświadczenia mogą wspierać rozwój poznawczy, emocjonalny i społeczny osób z poważną dysfunkcją wzroku. Zostanie to wykazane na podstawie analizy literatury przedmiotu oraz poprzez przytoczenie studiów przypadków głuchoniewidomych uczestników plenerów rzeźbiarskich w Orońsku.Udostępnienie publikacji Wydawnictwa Uniwersytetu Łódzkiego finansowane w ramach projektu „Doskonałość naukowa kluczem do doskonałości kształcenia”. Projekt realizowany jest ze środków Europejskiego Funduszu Społecznego w ramach Programu Operacyjnego Wiedza Edukacja Rozwój; nr umowy: POWER.03.05.00-00-Z092/17-00

A Compact Dual Band-Notched Circular Ring Printed Monopole Antenna for Super wideband Applications

In this article, a simple and compact dual band-notched (DBN) super wideband (SWB) printed monopole antenna (PMA) has been proposed. The proposed antenna composed of a circular PMA, which is connected through a 50-Ω triangular tapered microstrip fed line (TTMFL) and a round-cornered finite ground plane (RCFGP). It exhibits a very wide frequency band from 1.6–25 GHz (ratio band¬width of 15.63:1) with a voltage standing wave ratio (VSWR) ≤ 2. By employing a U-shaped parasitic element (USPE) near the RCFGP and a T-shaped protruded stub (TSPS) inside the radiating patch, a single band-notched (SBN) characteristic in the frequency band of 3.2–4.4 GHz (WiMAX/C-band) is generated. In order to realize the sec¬ond band-notched function for X-band satellite communication systems (7.2–8.4 GHz), a U-shaped slot (USS) has been inserted in the RCFGP. The overall dimension of the proposed antenna is 24x30x0.787 mm3 and occupies a relatively small space compared to the existing DBN an¬tennas. Good agreement has been attained between pre¬dicted and measured results

Isolation and screening of Streptomyces in soil of protected forest areas from the states of Assam and Tripura, India, for antimicribial metabolites

Objective. — To study the antimicrobial of Antinomycets, isolated from Northeast India. Material and methods. — A total of 110 actinomycetes strains were isolated from the soil samples collected from the protected forest soil from two States in Northeast India These were then characterized by conventional methods and assessed for their antagonistic activity preliminary against test microorganisms. Results. — Amongthe110isolates,65(59.09%)strainsshowedantibacterialactivity,47(42.72%) strains showed antifungal activity and 33 (30%) strains exhibited a broad-spectrum activity against both test bacteria and fungi. The production of nonpolyenic antifungal substances by promising isolates was investigated using several criteria: antibacterial activity, ergosterol inhibition, and UV—vis spectra of active extracts. Conclusion. — These results indicate that the protected areas of Northeast India’s soil microorganisms could be an interesting source of antibacterial and antifungal bioactive substances. # 2007 Elsevier Masson SAS. All rights reserved

Food spectrum dynamics of anadromous Hilsa, Tenualosa ilisha (Hamilton, 1822) inhabiting River Brahmaputra, India curtailing apprehension of food selectivity: An insight into its domestication

Food and feeding habits of Tenualosa ilisha collected from two sampling locations in Brahmaputra River, Assam, India for a period of 12 months from May 2018 to April 2019 were studied. Index of preponderance revealed semi-digested animal matter (25.92 %) as the most dominant food item followed by Bacillariophyta (23.32 %). 31 genera of phytoplankton and 15 genera of zooplankton were observed in the gut of the species. Major groups of zooplankton include cladocerans, copepods, followed by rotifers, while diatoms, green algae and blue green algae were dominant phytoplankton groups. The anadromous tropical shad is planktivorous by nature and has a preference for zooplankton in smaller size groups (< 250 mm) and phytoplankton in larger size groups (> 250 mm). GaSI values (mean±SE) ranged from 1.50±0.14 to 6.93±0.89 and HSI values from 0.58±0.06 to 1.54±0.15. Index of fullness was found to range from 7.08±0.42 to 1.81±0.40. Feeding intensity, GaSI, HSI values showed seasonal variation, found to be low during October to December and high during February to June. Size group-wise analysis of feeding intensity showed high feeding intensity in lower size groups (< 250 mm) and comparatively low feeding intensity and high percentage of empty stomachs in higher size groups (> 250 mm). RLG values ranged from 1.181±0.028 to 1.450±0.052. Monthly average RLG values were found to be highest during November and in the size group of 351 – 400 mm. Changes in food composition were noticed in both months and as well as size groups

TWEAK/Fn14 signalling regulates the tissue microenvironment in chronic pancreatitis

Chronic pancreatitis increases the risk of developing pancreatic cancer through the upregulation of pathways favouring proliferation, fibrosis, and sustained inflammation. We established in previous studies that the ligand tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) signals through its cognate receptor fibroblast growth factor-inducible 14 (Fn14) to regulate these underlying cellular processes in the chronic liver injury niche. However, the role of the TWEAK/Fn14 signalling pathway in pancreatic disease is entirely unknown. An analysis of publicly available datasets demonstrated that the TWEAK receptor Fn14 is upregulated in pancreatitis and pancreatic adenocarcinoma, with single cell RNA sequencing revealing pancreatic ductal cells as the main Fn14 producers. We then used choline-deficient, ethionine-supplemented (CDE) diet feeding of wildtype C57BL/6J and Fn14 knockout littermates to (a) confirm CDE treatment as a suitable model of chronic pancreatitis and (b) to investigate the role of the TWEAK/Fn14 signalling pathway in pancreatic ductal proliferation, as well as fibrotic and inflammatory cell dynamics. Our time course data obtained at three days, three months, and six months of CDE treatment reveal that a lack of TWEAK/Fn14 signalling significantly inhibits the establishment and progression of the tissue microenvironment in CDE-induced chronic pancreatitis, thus proposing the TWEAK/Fn14 pathway as a novel therapeutic target

Activity and toxicity of intramuscular 1000 iu/m² polyethylene glycol-E. coli L-asparaginase in the UKALL 2003 and UKALL 2011 clinical trials

In successive UK clinical trials (UKALL 2003, UKALL 2011) for paediatric acute lymphoblastic leukaemia (ALL), polyethylene glycol-conjugated E. coli L-asparaginase (PEG-EcASNase) 1000 iu/m2 was administered intramuscularly with risk-stratified treatment. In induction, patients received two PEG-EcASNase doses, 14 days apart. Post-induction, non-high-risk patients (Regimens A, B) received 1–2 doses in delayed intensification (DI) while high-risk Regimen C patients received 6–10 PEG-EcASNase doses, including two in DI. Trial substudies monitored asparaginase (ASNase) activity, ASNase-related toxicity and ASNase-associated antibodies (total, 1112 patients). Median (interquartile range) trough plasma ASNase activity (14 ± 2 days post dose) following first and second induction doses and first DI dose was respectively 217 iu/l (144–307 iu/l), 265 iu/l (165–401 iu/l) and 292 iu/l (194–386 iu/l); 15% (138/910) samples showed subthreshold ASNase activity (<100 iu/l) at any trough time point. Older age was associated with lower (regression coefficient −9.5; p < 0.0001) and DI time point with higher ASNase activity (regression coefficient 29.9; p < 0.0001). Clinical hypersensitivity was observed in 3.8% (UKALL 2003) and 6% (UKALL 2011) of patients, and in 90% or more in Regimen C. A 7% (10/149) silent inactivation rate was observed in UKALL 2003. PEG-EcASNase schedule in UKALL paediatric trials is associated with low toxicity but wide interpatient variability. Therapeutic drug monitoring potentially permits optimisation through individualised asparaginase dosing

Ethnic differences in SARS-CoV-2 vaccine hesitancy in United Kingdom healthcare workers: Results from the UK-REACH prospective nationwide cohort study

Background: In most countries, healthcare workers (HCWs) represent a priority group for vaccination against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) due to their elevated risk of COVID-19 and potential contribution to nosocomial SARS-CoV-2 transmission. Concerns have been raised that HCWs from ethnic minority groups are more likely to be vaccine hesitant (defined by the World Health Organisation as refusing or delaying a vaccination) than those of White ethnicity, but there are limited data on SARS-CoV-2 vaccine hesitancy and its predictors in UK HCWs. Methods: Nationwide prospective cohort study and qualitative study in a multi-ethnic cohort of clinical and non-clinical UK HCWs. We analysed ethnic differences in SARS-CoV-2 vaccine hesitancy adjusting for demographics, vaccine trust, and perceived risk of COVID-19. We explored reasons for hesitancy in qualitative data using a framework analysis. Findings: 11,584 HCWs were included in the cohort analysis. 23% (2704) reported vaccine hesitancy. Compared to White British HCWs (21.3% hesitant), HCWs from Black Caribbean (54.2%), Mixed White and Black Caribbean (38.1%), Black African (34.4%), Chinese (33.1%), Pakistani (30.4%), and White Other (28.7%) ethnic groups were significantly more likely to be hesitant. In adjusted analysis, Black Caribbean (aOR 3.37, 95% CI 2.11 - 5.37), Black African (aOR 2.05, 95% CI 1.49 - 2.82), White Other ethnic groups (aOR 1.48, 95% CI 1.19 - 1.84) were significantly more likely to be hesitant. Other independent predictors of hesitancy were younger age, female sex, higher score on a COVID-19 conspiracy beliefs scale, lower trust in employer, lack of influenza vaccine uptake in the previous season, previous COVID-19, and pregnancy. Qualitative data from 99 participants identified the following contributors to hesitancy: lack of trust in government and employers, safety concerns due to the speed of vaccine development, lack of ethnic diversity in vaccine studies, and confusing and conflicting information. Participants felt uptake in ethnic minority communities might be improved through inclusive communication, involving HCWs in the vaccine rollout, and promoting vaccination through trusted networks. Interpretation: Despite increased risk of COVID-19, HCWs from some ethnic minority groups are more likely to be vaccine hesitant than their White British colleagues. Strategies to build trust and dispel myths surrounding the COVID-19 vaccine in these communities are urgently required. Emphasis should be placed on the safety and benefit of SARS-CoV-2 vaccination in pregnancy and in those with previous COVID-19. Public health communications should be inclusive, non-stigmatising and utilise trusted networks

TWEAK/Fn14 signalling promotes cholangiocarcinoma niche formation and progression.

Background & Aims: Cholangiocarcinoma (CCA) is a cancer of the hepatic bile ducts that is rarely resectable and is associated with poor prognosis. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is known to signal via its receptor fibroblast growth factor-inducible 14 (Fn14) and induce cholangiocyte and myofibroblast proliferation in liver injury. We aimed to characterise its role in CCA. Methods: The expression of the TWEAK ligand and Fn14 receptor was assessed immunohistochemically and by bulk RNA and single cell transcriptomics of human liver tissue. Spatiotemporal dynamics of pathway regulation were comprehensively analysed in rat and mouse models of thioacetamide (TAA)-mediated CCA. Flow cytometry, qPCR and proteomic analyses of CCA cell lines and conditioned medium experiments with primary macrophages were performed to evaluate the downstream functions of TWEAK/Fn14. In vivo pathway manipulation was assessed via TWEAK overexpression in NICD/AKT-induced CCA or genetic Fn14 knockout during TAA-mediated carcinogenesis. Results: Our data reveal TWEAK and Fn14 overexpression in multiple human CCA cohorts, and Fn14 upregulation in early TAA-induced carcinogenesis. TWEAK regulated the secretion of factors from CC-SW-1 and SNU-1079 CCA cells, inducing polarisation of proinflammatory CD206+ macrophages. Pharmacological blocking of the TWEAK downstream target chemokine monocyte chemoattractant protein 1 (MCP-1 or CCL2) significantly reduced CCA xenograft growth, while TWEAK overexpression drove cancer-associated fibroblast proliferation and collagen deposition in the tumour niche. Genetic Fn14 ablation significantly reduced inflammatory, fibrogenic and ductular responses during carcinogenic TAA-mediated injury. Conclusion: These novel data provide evidence for the action of TWEAK/Fn14 on macrophage recruitment and phenotype, and cancer-associated fibroblast proliferation in CCA. Targeting TWEAK/Fn14 and its downstream signals may provide a means to inhibit CCA niche development and tumour growth. Lay summary: Cholangiocarcinoma is an aggressive, chemotherapy-resistant liver cancer. Interactions between tumour cells and cells that form a supportive environment for the tumour to grow are a source of this aggressiveness and resistance to chemotherapy. Herein, we describe interactions between tumour cells and their supportive environment via a chemical messenger, TWEAK and its receptor Fn14. TWEAK/Fn14 alters the recruitment and type of immune cells in tumours, increases the growth of cancer-associated fibroblasts in the tumour environment, and is a potential target to reduce tumour formation

Structure–activity study of N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a bitopic ligand that acts as a negative allosteric modulator of the dopamine D2 receptor

We recently demonstrated that SB269652 (1) engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural deter- minants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric “head” groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R “privileged structures” generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharma- cology. We validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R