This concept analysis aims to analyze the concept of sleep disturbance (SD) in the context of heart failure (HF) to guide the development of a clearly defined definition.

The term „sleep disturbance” has been used in the literature to describe sleep problems and sleep disorders among individuals with HF. Environmental, physical, psychological, behavioral, and developmental factors complicate the phenomenon of SD in HF.

Walker and Avant’s method was used for this concept analysis.

Published literature from 2000 to 2020 was identified from electronic health profession-related databases. The current definition and usages of SD were abstracted from empirical work and electronic databases.

A focused review of abstracts and full text relating to SD in HF was performed. Studies featuring original data and peer-reviewed articles written in English were included to investigate the multifactorial contextual meaning of the concept.

SD in HF can be described as a condition in which individuals experience difficulty initiating and maintaining sleep, and difficulty continuing or resuming sleep due to frequent nocturnal arousals due to HF symptoms, sleep-disordered breathing, insomnia, and psychological burdens.

To evaluate SD in HF, clinicians must examine the underlying causes to provide the contextual meaning of the concept. A clearly defined and distinguishable concept of SD in HF provides a possibility for accurate measurements of sleep quality, exploring interventions, and evaluating outcomes.

To evaluate SD in HF, clinicians must examine the underlying causes to provide the contextual meaning of the concept. A clearly defined and distinguishable concept of SD in HF provides a possibility for accurate measurements of sleep quality, exploring interventions, and evaluating outcomes.The calcifuge habit of plants is commonly explained in terms of high soil pH and its effects on nutrient availability, particularly that of phosphorus (P). However, most Proteaceae that occur on nutrient-impoverished soils in south-western Australia are calcifuge, despite their ability to produce cluster-roots, which effectively mobilize soil P and micronutrients. We hypothesize that the mechanism explaining the calcifuge habit in Proteaceae is their sensitivity to P and calcium (Ca), and that soil-indifferent species are less sensitive to the interaction of these nutrients. In this study, we analyzed growth, gas-exchange rate, and chlorophyll fluorescence of two soil-indifferent and four calcifuge Hakea and Banksia (Proteaceae) species from south-western Australia, across a range of P and Ca concentrations in hydroponic solution. We observed Ca-enhanced P toxicity in all analyzed species, but to different extents depending on distribution type and genus. Increasing P supply enhanced plant growth, leaf biomass, and photosynthetic rates of soil-indifferent species in a pattern largely independent of Ca supply. In contrast, positive physiological responses to increasing [P] in calcifuges were either absent or limited to low Ca supply, indicating that calcifuges were far more sensitive to Ca-enhanced P toxicity. In calcifuge Hakeas, we attributed this to higher leaf [P], and in calcifuge Banksias to lower leaf zinc concentration. These differences help to explain these species’ contrasting sensitivity to Ca-enhanced P toxicity and account for the exclusion of most Proteaceae from calcareous habitats. We surmise that Ca-enhanced P toxicity is a major factor explaining the calcifuge habit of Proteaceae, and, possibly, other P-sensitive plants.

The mother-friendly care model and mother-friendly programmes are powerful responses to solve problems in maternity care services including high rates of caesarean section, low breastfeeding rates, and women’s rights issues.

This paper describes the development and implementation of the mother-friendly hospital programme of Turkey.

The Ministry of Health initiated the mother-friendly hospital programme in 2010. National mother-friendly hospital standards, guidelines and evaluation tools were developed. Implementation began in 2015.

Training activities were carried out to enable health care workers (e.g. physicians, midwives, nurses) to train staff of hospitals applying to the programme, and to evaluate and monitor their maternity services; 455 health care workers were trained. Participation in the programme is voluntary and hospitals apply for certification. To apply, the hospital’s caesarean section rate must be lower than the country average. As of January 2020, 73 hospitals have been certified as mother-friendly hospitals.

As a practical implementation of the mother-friendly approach, Turkey’s experience may be useful to other health systems.

As a practical implementation of the mother-friendly approach, Turkey’s experience may be useful to other health systems.

According to the World Health Organization, the ideal caesarean section rate is 10-15% but rates have increased worldwide over the past few decades. Data on caesarean section rates across all Jordanian health sectors over a long period, including recent data that could guide future healthcare policy and interventions, are currently unavailable.

To investigate caesarean sections trends and identify indications (medical and sociodemographic) associated with caesarean sections in Jordanian health sectors.

Medical records of 2.8 million births in Jordan in 1982-2017 were retrieved and analysed. CS trends were compared across health sectors (governmental, university, private, and military hospitals) and with trends in England, Lebanon and Islamic Republic of Iran. CS indications were established from retrospective data, based on 3799 CS births, in 2 hospitals (governmental and private).

The CS rate in Jordan increased over the study period from 5.8 (±1.9)% in 1982-1987 to 31.0 (±0.7)% in 2015-2017. The caesarean sections rate in Jordan was initially lower (1983-2006) then became comparable (2007-2014) to that in England, but lower compared to that in Lebanon (2011-2016). In 2015-2017, caesarean sections rates in Jordanian health sectors were 40.4 (±2.6)% (university), 39.1 (±1.8)% (private), 36.1 (±0.2)% (military) and 27.4 (±0.7)% (governmental). Previous CS (33.6%), abnormal presentation (20.3%), and patient request (16%) were the most common indications.

The CS rate in Jordan is on an alarming upward trend. Urgent action is needed to prevent further increase in CS rate, including provision of clear information, advice, and counselling to pregnant women, as well as strict adherence to high-quality medical guidelines.

The CS rate in Jordan is on an alarming upward trend. Urgent action is needed to prevent further increase in CS rate, including provision of clear information, advice, and counselling to pregnant women, as well as strict adherence to high-quality medical guidelines.

Intimate partner violence against women is a significant problem in Pakistan associated with an alarming set of mental health issues.

To identify the prevalence of intimate partner violence in Pakistan and the causes, health effects and coping strategies used by women.

A comprehensive search based on the identified keywords was conducted using Google Scholar and PubMed. Relevant literature was also searched and included. Abstracts were then shortlisted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and 25 studies were selected. Quantitative studies on intimate partner violence were included in the review. The review comprises only reports published in English from 2008 to 2018.

The review accounts for the overall prevalence of violence and its various subtypes against women in Pakistan psychological 31.3-83.6%, physical 10.0-98.5%, sexual 2.5-77.0%, physical and sexual combined 1.0-68.0% and any other type 6.9-90.0%.

The evidence generated will help notify policy-makers and health officials about the determinants and effects of intimate partner violence, making it easier to address these issues and identify victims as early as possible. It also sheds light on the limitations of this study tools used by the published studies not specifically designed for Pakistan and there is no standardized definition of violence against women. This calls for more studies to be conducted to help find a solution.

The evidence generated will help notify policy-makers and health officials about the determinants and effects of intimate partner violence, making it easier to address these issues and identify victims as early as possible. It also sheds light on the limitations of this study tools used by the published studies not specifically designed for Pakistan and there is no standardized definition of violence against women. This calls for more studies to be conducted to help find a solution.

A reliable and valid tool to assess hearing health literacy in Iranian young people is lacking.

This study aimed to develop a tool to assess the hearing health literacy of young people in the Islamic Republic of Iran and to use the tool to determine the hearing health literacy of a sample of Iranians aged 12-25 years.

A questionnaire was designed with three skill sections obtaining health information, evaluating this information and applying it to benefit health. The validity and reliability of the tool were determined. Cluster sampling was used to select 50 urban clusters across the country from which 5000 Iranians aged between 12-25 years old were selected to complete the questionnaire.

The final questionnaire had 22 items with scores ranging from 22 to 44. The Cronbach alpha was 0.65, and content validity ratio and index were 0.92 and 0.82, respectively. Of the 5000 questionnaires completed, 4890 were included in the analysis. The mean (standard deviation (SD)) age of the participants was 17 (SD 3) years and 45.9% were males. The mean score on the tool was 30.81 (SD 3.75), indicating inadequate health literacy (score 22-36). Only 137 (2.8%) participants had adequate health literacy (score 37-44). Statistically significant differences in mean hearing health literacy were seen for sex, age, years of education, occupation, marital status and income (P < 0.05).

Given the low level of hearing health literacy in Iranian young people, programmes to improve the ear and hearing health literacy are urgently needed.

Given the low level of hearing health literacy in Iranian young people, programmes to improve the ear and hearing health literacy are urgently needed.

Quality and patient safety are essential for the provision of effective health care services. Research on these aspects is lacking in settings of extreme adversity.

This study aimed to explore the perception of health care stakeholders working in extreme adversity settings of the quality of health care and patient safety.

This was a qualitative study conducted through semistructured interviews with 26 health care stakeholders from seven countries of the World Health Organization’s Eastern Mediterranean Region which are experiencing emergencies. The interviews explored the respondents’ perspectives of four aspects of quality and patient safety definition of the quality of health care, challenges to the provision of good quality health care in emergency settings, priority health services and populations in emergency settings, and interventions to improve health care quality and patient safety.

The participants emphasized that saving lives was the main priority in extreme adversity settings. While all people living in emergency situations were vulnerable and at risk, the respondents considered women and children, poor and disabled people, and those living in hard-to-reach areas the priority populations to be targeted by improvement interventions. The challenges to quality of health care were financing problems, service inaccessibility, insecurity of health workers, break down in health systems, and inadequate infrastructure. Respondents proposed interventions to improve quality, however, their effective implementation remains challenging in these exceptional settings.

The interventions identified can serve as a basis for improvements in health care quality that could be adapted to extreme adversity settings.

The interventions identified can serve as a basis for improvements in health care quality that could be adapted to extreme adversity settings.

The exact burden of varicella is not well quantified in Jordan.

This study aimed to estimate the varicella burden in paediatric patients in Jordan who sought care in a hospital-based setting.

This was a multicentre, retrospective review of medical records of patients aged 0-14 years with a primary varicella diagnosis in Jordan between 2013 and 2018. The data assessed were use of health care resources for varicella (outpatient and inpatient visits, tests and procedures, and medication use), and clinical complications of the infection. Estimated costs were based on health care resources used (direct costs) and lost revenue to the child’s caregiver (indirect costs) for outpatients and inpatients.

In total, 140 children with varicella were included 78 outpatients, mean age (standard deviation) 4.4 (3.2) years, and 62 inpatients, mean age 4.0 (3.8) years. No outpatients had varicella-related complications, while 32 (52%) inpatients had ≥ 1 complication. The use of health care resources was higher for inpatients than outpatients, including prescription medication use – 94% of inpatients versus 6% of outpatients. Total costs of varicella were estimated at US$ 66.1 (95% CI 64.1-68.1) per outpatient and US$ 914.7 (95% CI 455.6-1373.9) per inpatient.

Varicella is associated with considerable use of health care resources in Jordan and may be responsible for annual costs of US$ 11.5 million. These results support universal varicella vaccination in Jordan.

Varicella is associated with considerable use of health care resources in Jordan and may be responsible for annual costs of US$ 11.5 million. These results support universal varicella vaccination in Jordan.

Iodine uptake is a main factor affecting thyroid disease. In Turkey, mandatory salt iodization began in 1999-2000.

This study in 2009 determined the prevalence of thyroid diseases in older people in Mamak district, Ankara after iodization to ascertain if salt iodization alone is sufficient to reach adequate iodine levels in the older population.

All Mamak residents ≥ 65 years were eligible for inclusion in the study. Demographic data and medical history were recorded. All participants had a thyroid ultrasound. Blood samples were taken to assess thyroid function and autoantibodies, and urine samples to assess iodine concentration. Participants with low levels of thyroid stimulating hormone underwent scintigraphy to assess thyroid uptake. Fine-needle aspiration biopsy was done of nodules ≥ 1.5 cm where thyroid stimulating hormone was not suppressed.

Of 1200 eligible residents, 979 were included. Their mean age was 70.9 (standard deviation (SD) 5.7) years; 49.7% were women. Mean urinary iodine concentration was 98 (SD 81.29) μg/L. Goitre was found in 18.2% (89/487) of women and 6.7% (33/492) of men (P < 0.001) and 43.8% (428/979) had nodules. Subclinical hypothyroidism was found in 5.8% (57/979) of the participants, overt hyperthyroidism in 0.8% (8/979), subclinical hyperthyroidism in 2.2% (22/979) and T3 thyrotoxicosis in 0.3% (3/979). Toxic multinodular goitre and toxic adenoma caused 80% of hyperthyroidism cases. Biopsy detected no malignant pathology.

After salt iodization, iodine levels have not yet reached favourable levels in older people. Iodization of salt seems insufficient to achieve these levels in older people; alternative iodine supplementation should be considered.

After salt iodization, iodine levels have not yet reached favourable levels in older people. Iodization of salt seems insufficient to achieve these levels in older people; alternative iodine supplementation should be considered.

The Patient Assessment of Care for Chronic Conditions (PACIC-5As) is a questionnaire developed in English and designed to evaluate the health care experiences of people living with chronic conditions such as diabetes.

This study aimed to translate, culturally adapt and validate the PACIC-5As instrument for the Arab context in a sample of Saudi Arabian people with diabetes.

The PACIC-5As was translated into Arabic using a forward and backward translation process. The Arabic version was then validated with a sample of 557 Saudi Arabians with diabetes who were recruited from tertiary level diabetes centres in Riyadh between January and March 2018. In order to evaluate the psychometric properties of the Arabic version, Cronbach alphas and item correlations were determined and exploratory factor analysis was performed.

The translated PACIC-5As had good psychometric quality. Cronbach alpha was > 0.9 and the inter-item correlation ranged between 0.36 and 0.56. Exploratory factor analysis showed a single-factor structure.

An Arabic version of the PACIC-5As questionnaire is now available to assess the experience of patients with diabetes. The results of this study can be used to improve the quality of the delivery of health care in Arabic-speaking countries.

An Arabic version of the PACIC-5As questionnaire is now available to assess the experience of patients with diabetes. The results of this study can be used to improve the quality of the delivery of health care in Arabic-speaking countries.

During epidemics and pandemics, health systems, and especially hospitals, face many challenges in the management of patients and staff. Hospital preparedness measures are critical for hospitals to respond effectively to the admission and management of COVID-19 patients. Ministry of health policy for pandemics must cover the ability of hospitals to respond to COVID-19.

The aim of this study was to develop a checklist for evaluating the preparedness of hospitals to respond to the COVID-19 pandemic.

We searched for and reviewed available evidence, including the literature and guidelines presented by related organizations. Due to the COVID-19 outbreak, face-to-face interview was not possible so we used telephone and video connections, mobile applications and email for unstructured interviews. Checklist development was carried out by a multidisciplinary panel of experts.

After applying the opinions of the experts, the final checklist had 2 main domains measures at national and measures at hospital level. Preparedness at national level was categorized into 3 aspects that are implemented by the health ministry. Preparedness at hospital level was categorized in 24 subgroups.

Hospital preparedness for admission and management of COVID-19 patients is essential. A checklist for the assessment of hospital preparedness for COVID-19 patient management and hospital management was designed and developed. Our preparedness assessment checklist is an expanded tool that provides clear and practical guidance that can be adapted for any hospital admitting COVID-19 patients.

Hospital preparedness for admission and management of COVID-19 patients is essential. A checklist for the assessment of hospital preparedness for COVID-19 patient management and hospital management was designed and developed. Our preparedness assessment checklist is an expanded tool that provides clear and practical guidance that can be adapted for any hospital admitting COVID-19 patients.

Urinary tract infection is one of the most common infections and its treatment is complicated by the emergence of antibiotic resistance. Resistance patterns of organisms differ between community-acquired and hospital-associated urinary tract infections.

The aim of this study was to determine the most effective antibiotics against uropathogens and if antibiotic resistance differed by setting (inpatient versus outpatient).

This 2016-2017 cross-sectional study examined 300 midstream clean-catch urine samples with positive culture (150 outpatient and 150 inpatient samples) for the uropathogens isolated and the resistance of these pathogens to different antibiotics. Samples were obtained from the laboratory of Baharloo hospital, Tehran. The differences in antibiotic resistance between inpatient and outpatient uropathogens were analysed using the chi-squared test.

Escherichia coli (72.0% of the 300 samples) and Klebsiella spp (13.0%) were the most common uropathogens isolated. A greater proportion of inpatient samples showed resistance to ceftriaxone, cefixime, sulfamethoxazole-trimethoprim, ciprofloxacin and nalidixic acid than the outpatient samples (P < 0.05). The most effective antibiotics for Gram-negative uropathogens were imipenem (only 6.0% of these uropathogens overall were antibiotic-resistant), amikacin (6.3%) and nitrofurantoin (10.3%).

Uropathogen resistant rates in inpatients were higher than outpatient rates. The use of imipenem and amikacin instead of traditional first-line empirical therapy (fluoroquinolone and sulfamethoxazole-trimethoprim) is advised for hospitalized patients with urinary tract infections.

Uropathogen resistant rates in inpatients were higher than outpatient rates. The use of imipenem and amikacin instead of traditional first-line empirical therapy (fluoroquinolone and sulfamethoxazole-trimethoprim) is advised for hospitalized patients with urinary tract infections.

Tobacco is a leading cause of death and illness despite > 50 years of antitobacco efforts.

To establish the determinants of current and former smoking and smokeless tobacco use in Sudan as measured by the STEPwise Survey 2016.

A household-based cross-sectional World Health Organization STEPwise Survey was conducted among 7745 Sudanese citizens aged 18-69 years across 11 states in Sudan. A 4-stage stratified cluster sampling design was implemented. The generic STEPS Instrument (version 3.2) was used and questions were tailored to the Sudanese context.

Among current male smokers, 63.7% were aged ≤ 35 years, 50.7% were illiterate or did not complete primary school, 84.5% were employed and 52.4% were in the lowest 2 quintiles of income. Among male smokeless tobacco users, 54.8% were aged ≤ 35 years, 48.4% were illiterate or did not complete primary school, 89.7% were employed and 52.2% were in the lowest 2 quintiles of income. Using multivariate logistic regression models, current smoking in men was associated with older age, informal education, unemployment and lower income. Smokeless tobacco use was associated with age 18-25 years, informal education, unemployment and lower income.

Both forms of tobacco use were associated with poor socioeconomic status and unemployment. Smokeless tobacco use was associated with age 18-25 years as opposed to smoking tobacco use. These results can inform the target audience of the future tobacco control plans.

Both forms of tobacco use were associated with poor socioeconomic status and unemployment. Smokeless tobacco use was associated with age 18-25 years as opposed to smoking tobacco use. These results can inform the target audience of the future tobacco control plans.On 25 September 2015, the United Nations (UN) General Assembly adopted and committed to a new development agenda „Transforming our world the 2030 Agenda for Sustainable Development”, which translated into 17 Sustainable Development Goals (SDGs). Global commitment to SDGs ushered in renewed calls to improve availability and accessibility of timely and quality information to monitor the progress towards achieving the health-related SDGs globally and in the Eastern Mediterranean Region (EMR). Health-related targets – under SDG 3 and also within other goals – require careful measurement and monitoring in order to track progress and success in policy implementation. SDG targets requires accurate and timely reporting of diseases, risk factors, mortality and causes of deaths (ranging from maternal mortality to death from road traffic accidents) and health care and social determinants of health.Osteoarthritis (OA) is a public health problem that affects 240 million people globally; however, the current treatment options for OA are not effective. Therefore, there is still an urgent need to identify novel strategies to reduce the incidence and progression of OA. The circular RNA hsa_circ_0094742 was reported to be downregulated in patients with OA. However, the underlying mechanism remains unclear. The levels of hsa_circ_0094742 in CHON-001 were detected by reverse transcription quantitative polymerase chain reaction. Moreover, Cell Counting Kit-8 assay and Ki67 staining were used to determine the cell viability. The protein expression of biomarkers was detected by western blot analysis. In addition, the putative downstream target of hsa_circ_0094742 was predicted using the Circinteractome and TargetScan online databases. The putative targeting relationship was verified by dual luciferase reporter assay and fluorescence in situ hybridization. Next, cell apoptosis was determined by Annexin V/PI staining. hsa_circ_0094742 overexpression (OE) inhibited interleukin (IL)-1β-induced decline in the viability of CHON-001 cells and primary human chondrocytes. Furthermore, IL-1β-induced alterations in aggrecan, matrix metallopeptidase 13, X-linked inhibitor of apoptosis protein (XIAP), Bax and active caspase 3 were reversed by hsa_circ_0094742 OE. Luciferase reporter assay indicated that miR-127-5p was the downstream target of hsa_circ_0094742, and latexin was the target of miR-127-5p. hsa_circ_0094742 OE inhibited IL-1β-induced decline in CHON-001 cell viability by targeting miRNA-127-5p. The findings of the present study revealed the biological rational of the use of hsa_circ_0094742 OE as an anti-IL-1β effector in human chondrocytes. These findings may prompt further research on hsa_circ_0094742 as a potent circRNA target for the treatment of OA.

Different immunohistochemical markers to detect amastigotes in cutaneous leishmaniasis have been proposed with variable diagnostic usefulness.

To evaluate the diagnostic usefulness of immunohistochemical amastigotes identification by specific polyclonal anti-Leishmania antibodies and CD1a expression (clone EP3622) in a series of PCR confirmed cutaneous leishmaniasis.

Thirty-three skin samples corresponding to PCR confirmed cutaneous leishmaniasis were included in the study. All samples were stained with Hematoxylin-eosin and Giemsa. Moreover, immunohistochemical studies with anti-CD1a and anti-Leishmania antibodies were performed. The patients clinical features and the observed histopathological features were also recorded.

From the selected 33 biopsies, Leishmania spp. amastigotes were detected in 48.4% of cases with conventional Hematoxylin-eosin stain and in 57.5% of cases by Giemsa staining. In 31/33 cases, anti-CD1a allowed us to identify parasitic structures, and in 33/33 cases amastigotes were when the CD1a immunostaining is added to the classical Haematoxylin – eosin and Giemsa staining.In recent years, considerable and growing attention has been given to the application of host-associated microorganisms as a more suitable source of probiotics in aquaculture sector. Herein, we isolated and screened the olive flounder gut microbiota for beneficial bacterial strains that might serve as potential probiotics in a low fishmeal extruded aquafeed. Among the ten identified isolates, Bacillus amyloliquefaciens SK4079 and B. subtilis SK4082 were screened out based on their heat-resistant ability as well as enzymatic and non-hemolytic activities. Although both strains were well able to utilize carboxymethyl cellulose (CMC), xylan, and soybean meal (SBM) as a single carbon source in the minimal nutrient M9 medium, B. subtilis exhibited significantly higher cellulase, xylanase, and protease activities than B. amyloliquefaciens. The two selected strains were well able to degrade the undesirable anti-nutritional component of the SBM, which would limit its utilization as protein source in aquafeed industry. Significantly higher biofilm formation capacity and notably stronger adhesive interactions with the flounder’s skin mucus were detected in B. subtilis than B. amyloliquefaciens. Immobilization of the spores from the selected strains, in a SBM complex carrier, remarkably enhances their thermal resistance at 120 °C for 5 min and different drying conditions. It was also interesting to learn that the B. subtilis spores could survive and remain viable after being sprayed onto extruded low-fish meal feed pellets for as long as 6 months. Overall, the findings of the present study could help the food/feed industries achieve their goal of developing cost-effective yet efficient products.The use of fluoridated dentifrices is recognized as the main reason for the decline of dental caries and its effect is associated with the bioavailability of fluoride (F) in the oral cavity. High-fluoride dentifrice has been indicated for patients at high risk of caries and management of root lesions. This study aimed to evaluate the bioavailability of F in saliva after the use of high-fluoride dentifrice during the nocturnal period. Fifteen healthy adults participated in this is in vivo and crossover study in which the concentration of F in their saliva was determined after brushing with the tested dentifrices a conventional (1450 ppm F) or with high-fluoride concentration (5000 ppm F). Before brushing, the participants collected the non-stimulated saliva (baseline), immediately after brushing (time zero) and after 5min, 2h, 4h, and 8h, during the nocturnal period (between 1000 pm and 0600 am). The salivary F concentration was determined using a specific F ion electrode. Regarding statistical analysis, a paired t-test was used to compare dentifrices with p fixed at 5%. At baseline, there was no significant difference between groups (p>0.001). Immediately after brushing, both dentifrices increased the F salivary concentration, with the highest concentration reached in time zero; however, the use of 5000 ppm F dentifrice maintained the higher F salivary concentration at all times evaluated (p less then 0.001), remaining higher until 8 h after brushing. Furthermore, this treatment showed higher F bioavailability in relation to time, evaluated by the area under the curve (p less then 0.001). Thus, it can be concluded that the high-fluoride dentifrice increased the bioavailability of salivary F during the nocturnal period in comparison with conventional dentifrice.Inhibition of the Alzheimer’s disease associated protein β-site amyloid precursor protein cleaving enzyme-1 (BACE1) remains a potential avenue for treatment of this disease. The cellular thermal shift assay (CETSA) is an attractive method of screening for protein binding molecules due to its ability to detect intracellular binding while avoiding the need to purify the protein in question. Here, the CETSA was carried out using the known BACE1 inhibitor verubecestat, where an increase in Tagg to 53.27 ± 0.89 °C from 49.53 ± 0.69 °C was observed. Three test compounds from the ChemBridge DiverSet compound library, identified to bind BACE1 using differential scanning fluorimetry, were then screened using the CETSA. Only compound C34 yielded a significant increase in Tagg (p value ≤ 0.05), indicative of intracellular binding. This is the first description of the cellular thermal shift assay being used to detect BACE1 binding molecules, with one novel BACE1 binding molecule being validated.Breast cancer (BC) threatened the life health of a tremendous amount of the population, and the estimated number of death is still rising nowadays. We found that stress-induced phosphoprotein 1 (STIP1) is overexpressed in BC tissues compared to non-tumorous breast tissues. Our study is to validate the prognostic value of STIP1 and investigate its biological role in BC. We verified the upregulation of STIP1 in multiple databases, proved that STIP1 is upregulated in BC tissues and cell lines using real-time quantitative PCR (qRT-PCR). We used small interfering RNA to examine the function of STIP1 in BC cell lines (BT-549, MDA-MB-231, Hs-578 T) and explored the mechanism of function of STIP1 in BC cells using Western blotting and qRT-PCR. Analyses of multiple databases indicated that high STIP1 expression is a marker that effectively distinguishes BC patients from healthy control and predicts worse clinical outcomes in BC. The loss-of-function experiments showed that STIP1 silencing results in inhibition of cell proliferation and migration, inducing cell apoptosis, and S-phase arrest in vitro. Our study also showed that STIP1 downregulation inhibited the JAK2/STAT3 pathway and epithelial-mesenchymal transition process. Rescue experiments demonstrated that the oncogenic effect of STIP1 is partially dependent on mediating JAK2 expression. This study verified that STIP1 is an oncogenic gene that promotes BC progression and serves as a valuable diagnostic and outcome-related marker of BC.

To examine the relationship between physical activity (PA) and preterm birth (PTB) within the context of depressive symptoms (DS).

Data are from the Life-course Influences of Fetal Environments (LIFE) Study, a cohort comprised of 1410 Black women, age 18-45 years who delivered a singleton in Metropolitan Detroit, MI. DS were measured with the Center for Epidemiologic Studies Depression Scale (CES-D); a score > 23 indicates severe DS. Traditional leisure time PA (LTPA) and non-LTPA during pregnancy (walking for a purpose, climbing stairs) were both measured. Modified Poisson regression models were used to estimate the association between PTB and PA. Effect modification by severe DS was assessed via stratification.

Approximately 16% of women had a PTB; 20% had CES-D scores > 23. Walking for a purpose was the most frequently reported type of PA (79%), followed by any LTPA (37.7%) and climbing stairs (13.5%). Compared with women who reported no PA, women who reported walking for a purpose (PR = 0.70, 95% CI 0.61, 1.10), partaking in LTPA (PR = 0.67, 95% CI 0.50, 0.90), or climbing stairs (PR = 0.61, 95% CI 0.45, 0.81) were less likely to have PTB. Results stratified by severe DS show the association between LTPA and PTB was more pronounced in women with severe DS, while the non-LTPA relationship with PTB was more heterogeneous.

Women who participated in traditional LTPA (any or walking only) and non-LTPA experienced improved birth outcomes. LTPA may buffer against PTB among pregnant Black women with severe DS as well as none or mild DS.

Women who participated in traditional LTPA (any or walking only) and non-LTPA experienced improved birth outcomes. LTPA may buffer against PTB among pregnant Black women with severe DS as well as none or mild DS.Preterm birth is an important determinant of neonatal morbidity and mortality and intra-amniotic infection (IAI) and inflammation play a causative role. The constitutive proteasome and immunoproteasome are key players in maintenance of proteostasis and their alteration outside pregnancy has been linked to pathogenesis of numerous inflammatory diseases. Our goal was to evaluate the levels, activities, and potential origin of amniotic fluid (AF) proteasome in women with preterm birth induced by infection and/or inflammation. Total proteasome and immunoproteasome concentrations were measured in AF retrieved by trans-abdominal amniocentesis from 155 pregnant women. Proteasome activities were measured with fluorogenic substrates targeting caspase-like (CAS-L), trypsin-like (TRY-L), or chymotrypsin-like (CHE-L) lytic activities. We found that IAI significantly upregulated AF concentrations of total proteasome and of the immunoproteasome (P less then 0.001 for both) with no differences based on gestational age. Based on substrate preference and profile of pharmacologic inhibition, we identified the CHE-L activity of the immunoproteasome as the primary lytic activity upregulated in AF of pregnancies complicated by IAI. When compared with matched maternal blood and cord blood, proteasome activity was by far the highest in AF and this was further elevated in IAI. Western blot confirmed β5 (PSMB5) and β5i (PSMB8) subunits of the constitutive proteasome and immunoproteasome are present in AF and IHC staining of fetal membranes pointed to chorio-decidua as a potential source. In conclusion, IAI is associated with increased AF immunoproteasome activity that by analogy with other inflammatory diseases may generate antigenic oligopeptides and may play a role in triggering preterm birth.The incidence of lung cancer is affected by air pollution, especially in high-density urban areas with heavy road traffic and dense urban form. Several studies have examined the direct relationship between lung cancer incidence and road traffic as well as urban form. However, the results are still inconsistent for high-density urban areas. This study focused on urban form and road traffic, aiming at revealing their relationship with lung cancer incidence in high-density urban areas at the neighborhood level. For this, an ecological study was conducted in downtown Shanghai to identify important indicators and explore quantitative associations. Negative binomial regression was fitted with lung cancer incidence as the dependent variable. The independent variables included indicators for road traffic and urban form, greenness, demographic, and socio-economic factors. The results showed that building coverage, averaged block perimeter area ratio, density of metro station without the glass barrier system, and the percentage of low-quality residential land were positively correlated with lung cancer incidence in the neighborhood, while population density was negatively correlated with lung cancer incidence. This study found a strong self-selection effect of socio-economic factors in the relationship between lung cancer incidence and greenness. These results may be useful for conducting health impact assessments and developing spatial planning interventions for respiratory health in high-density urban areas.

The Internet is increasingly used as a source of information. This study investigates with a multidimensional methodology the quality of information of websites dedicated to obesity treatment and weight-loss interventions. We compared websites in English, a language that it is used for the international scientific divulgation, and in Italian, a popular local language.

Level of Evidence Level I, systematic review search on four largely used search engines. Duplicated and unrelated websites were excluded. We checked popularity with PageRank; technological quality with Nibbler; readability with the Flesch Reading Ease test or the Gulpease readability index; quality of information with the DISCERN scale, the JAMA benchmark criteria, and the adherence to the Health on the Net Code.

63 Italian websites and 41 English websites were evaluated. English websites invested more in the technological quality especially for the marketing, experience of the user, and mobile accessibility. Both the Italian and English websites were of poor quality and readability.

These results can inform guidelines for the improvement of health information and help Internet users to achieve a higher level of information. Users must find benefits of treatment, support to the shared decision-making, the sources used, the medical editor’s supervision, and the risk of postponing the treatment.

These results can inform guidelines for the improvement of health information and help Internet users to achieve a higher level of information. Users must find benefits of treatment, support to the shared decision-making, the sources used, the medical editor’s supervision, and the risk of postponing the treatment.This volume has highlighted the many recent advances in tinnitus theory, models, diagnostics, therapies, and therapeutics. But tinnitus knowledge is far from complete. In this chapter, contributors to the Behavioral Neuroscience of Tinnitus consider emerging topics and areas of research needed in light of recent findings. New research avenues and methods to explore are discussed. Issues pertaining to current assessment, treatment, and research methods are outlined, along with recommendations on new avenues to explore with research.

The global SARS-CoV-2 pandemic placed Irish Laboratory Medicine services under sustained and massive strain. Rapid reconfiguration was required to introduce new assays at high capacity for diagnosis and monitoring of COVID-19, while maintaining existing services.

The aim of this national survey was to capture Laboratory Medicine’s response across the Republic of Ireland during the first wave of the COVID-19 pandemic.

An electronic survey developed using Microsoft Forms® was emailed on 5 October 2020 to 53 local representatives of the PeriAnalytic and Laboratory Medicine Society (PALMSoc), reaching 38 separate pathology departments in the country.

A total of 45 responses from 38 laboratories were received (72% response rate) representing a range of departments and disciplines. Most laboratories (63%) introduced new tests, and in a time frame of less than 6weeks (80%). Point-of-care testing (POCT) played a significant role in the response to COVID-19, with almost half of respondents (47%) reporting that additional equipment was introduced. Maintenance of the Quality Management System (QMS) proved challenging, with 60% of respondents indicating that not all aspects were sustained. When asked about changes to staff rostering, 98% of respondents reported that changes were made. All adjustments were made despite staffing challenges; only 18% of respondents described the staffing levels in their department as 100% prior to the onset of the first wave.

This study confirms an agile and resilient response to the COVID-19 pandemic from Ireland’s Laboratory Medicine services despite many economic and staffing challenges.

This study confirms an agile and resilient response to the COVID-19 pandemic from Ireland’s Laboratory Medicine services despite many economic and staffing challenges.

The Wender Utah Rating Scale (WURS) is a widely used retrospective scale in adults presenting for ADHD evaluations which features items relating to childhood symptoms.

The aim of this study is to establish if certain childhood symptoms (including ADHD) as identified by the WURS-61 are associated with specific mental health disorders in adulthood.

Case-control study of N=630 attending Adult Mental Health Services (AMHS) and a control group without mental disorders (N=96).

The mean age of the participants was 39.81 (SD 12.94) of which 387 (53.3%) were females. There were no significant differences between cases and controls in terms of age (t= 1.829, df 724, p=.068) and gender (x

=1.123, df 1, p=.289). Exploratory factor analysis of WURS-61 reveals 5 factors. Using factor scores and after cross-tabulation, we found that The presence of childhood impulsivity, emotional lability and distress in addition to inattention/disorganisation were significantly associated with adult ADHD diagnosis (F90). WURS items which suggests childhood conduct problems were associated with a number of adult diagnoses, when present either on its own (psychoactive substance use, or when present in combination with childhood impulsivity, emotional lability and distress (personality disorders).

There is an association between certain childhood behaviours and risk for later development of personality disorders, and psychoactive substance use. There is overlap of childhood symptoms to those who later diagnosed in adulthood with ADHD, personality disorders, and substance abuse.

There is an association between certain childhood behaviours and risk for later development of personality disorders, and psychoactive substance use. There is overlap of childhood symptoms to those who later diagnosed in adulthood with ADHD, personality disorders, and substance abuse.Abnormal expression of claudin-1 (CLDN1) has important roles in carcinogenesis and metastasis in various cancers. The role of CLDN1 in human oral squamous cell carcinoma (OSCC) remains unknown. Here, we report the functional role of CLDN1 in metastasis of human OSCC, as a potential target regulated by withaferin A. From gene expression profiling with microarray technology, we found that the majority of notable differentially expressed genes were classified into migration/invasion category. Withaferin A impaired the motility of human OSCC cells in vitro and suppressed metastatic nodule formation in an in vivo metastasis model, both associated with reduced CLDN1. CLDN1 overexpression enhanced metastatic nodule formation in vivo, resulting in severe metastatic lesions in lung tissue. Moreover, CLDN1 expression was positively correlated to lymphatic metastasis in OSCC patients. The impaired motility of human OSCC cells upon withaferin A treatment was restored by CLDN1 overexpression. Furthermore, upregulation of let-7a induced by withaferin A was inversely correlated to CLDN1 expression. Overall, these give us an insight into the function of CLDN1 for prognosis and treatment of human OSCC, substantiating further investigation into the use of withaferin A as good anti-metastatic drug candidate.

Sodium-glucose co-transporter2 inhibitors (SGLT2is) are licensed for the treatment of type2 diabetes (T2D) and more recently for heart failure with or without diabetes. They have been shown to be safe (from the cardiovascular (CV) perspective) and effective (in terms of glycaemia, and in some cases, in reducing CV events) in extensive randomised controlled trials (RCTs). However, there remain concerns regarding the generalisability of these findings (to those ineligible for RCT participation) and about non-CV safety. For effectiveness, population-based pharmacoepidemiology studies can confirm and extend the findings of RCTs to broader populations and explore safety, for which RCTs are not usually powered, in more detail.

A pre-planned and registered ((International PROSPEctive Register Of Systematic Reviews) PROSPERO registration CRD42019160792) systematic review of population-based studies investigating SGLT2i effectiveness and safety, following Meta-analyses Of Observational Studies in Epidemiology (MOOn for GMIs (PER HR 2.08-3.15), and possibly for LLA (PER HR 0.74-2.79) and DKA (PER HR 0.96-2.14), but with considerable uncertainty.

In T2D, SGLT2is appear safe from the CV perspective and may have associated benefit in primary as well as secondary CVD prevention. For safety, they may be associated with an increased risk of GMI, LLA and DKA, although longer follow-up studies are needed.

In T2D, SGLT2is appear safe from the CV perspective and may have associated benefit in primary as well as secondary CVD prevention. For safety, they may be associated with an increased risk of GMI, LLA and DKA, although longer follow-up studies are needed.Depression is one of the most frequent psychiatric comorbidities associated with epilepsy having a major impact on the patient’s quality of life. Several screening tools are available to identify and follow up psychiatric disorders in epilepsy. Out of various psychiatric disorders, people with epilepsy (PWE) are at greater risk of developing depression. This bidirectional relationship further hinders pharmacotherapy of comorbid depression in PWE as some antiepileptic drugs (AEDs) worsen associated depression and coadministration of existing antidepressants (ADs) to alleviate comorbid depression has been reported to worsen seizures. Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs) are first choice of ADs and are considered safe in PWE, but there are no high-quality evidences. Similar to observations in people with depression, PWE also showed pharmacoresistant to available SSRI/SNRIs, which further complicates the disease prognosis. Randomized double-blind placebo-controlled clinical trials are necessary to report efficacy and safety of available ADs in PWE. We should also move beyond ADs, and therefore, we reviewed common pathological mechanisms such as neuroinflammation, dysregulated hypothalamus pituitary adrenal (HPA) axis, altered neurogenesis, and altered tryptophan metabolism responsible for coexistent relationship of epilepsy and depression. Based on these common pertinent pathways involved in the genesis of epilepsy and depression, we suggested novel targets and therapeutic approaches for safe management of comorbid depression in epilepsy.

The incidence of pituitary adenoma (PA) increases with age. Transsphenoidal surgery (TSS) in elderly patients is often considered to have greater risk compared to the younger population. The aim of this study is to compare surgical results, evolution and postoperative complications between elderly and young patients undergoing TSS.

Retrospective review of patients undergoing TSS between 2011 and 2018 in our institution. Patients were divided into two cohorts elderly (≥65 years) and non-elderly (<65 years). Characteristics and outcomes of both groups were compared at diagnosis, before surgery and for an average of 5.9 years of postoperative follow-up.

One hundred and twenty-five patients were included, 53 patients were ≥65 years (42%). The elderly patients were more likely to have non-functioning PA (NFPA) (90.5% vs. 45.8%, p <0.01), a higher proportion of macroadenomas (92.4% vs. 77.8%, p = 0.029) and greater extrasellar extension (88.7% vs. 68.1%, p = 0.007). The elderly group also had more comprSS given that successful results can be achieved if an experienced pituitary team is available.

The study investigated the role of hepatitis B core-related antigen (HBcrAg) in hepatitis B virus (HBV) relapse after stopping tenofovir disoproxil fumarate (TDF) in HBeAg-negative patients.

A total of 185 HBeAg-negative patients without cirrhosis who had stopped TDF treatment for at least 6months were recruited. All patients fulfilled the stopping criteria proposed by the Asian Pacific Association for the Study of the Liver 2012.

The 3-year cumulative incidences of virological relapse, clinical relapse, and hepatitis B surface antigen (HBsAg) loss were 72, 60.1 and 14.5%, respectively. End-of-treatment (EOT) HBsAg level was an independent predictor of virological relapse (hazard ratio (HR) 2.263; 95% confidence interval (CI) 1.779-2.887), clinical relapse (HR 1.773; 95% CI 1.367-2.298), and HBsAg loss (HR 0.179; 95% CI 0.096-0.335). Among patients who had HBsAg < 100 and ≥ 100IU/mL, the 3-year virological relapse rates were 37.4% and 85.3% (p < 0.001), clinical relapse rates were 30.3 and 71.7% (p < 0.001), and HBsAg loss rates were 40.6 and 2.6% (p < 0.001), respectively. Among the 53 patients with EOT HBsAg level < 100IU/mL, the 3-year virological relapse rates in patients with baseline HBcrAg levels < 4.7 and ≥ 4.7 log

U/mL were 20.3 and 60.4% (p = 0.003), and the clinical relapse rates were 10.3 and 59.5% (p < 0.001) respectively. Additionally, the 3-year HBsAg loss rates in patients with baseline HBcrAg ≤ 3 and > 3 log

U/mL were 42.9 and 7.9% (p < 0.001).

The combination of EOT HBsAg and baseline HBcrAg levels could further reduce the risk of HBV relapse after stopping TDF therapy in HBeAg-negative patients.

The combination of EOT HBsAg and baseline HBcrAg levels could further reduce the risk of HBV relapse after stopping TDF therapy in HBeAg-negative patients.