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TV Guide magazine rates the 50 best television programs of all time. 'Seinfeld' is rated as the top show, followed by the 'I Love Lucy' show, 'The Honeymooners,' and 'All in the Family.'

Sexualisierte Gewalt gegen Kinder ist verborgen, aber sie findet mitten in der Gesellschaft statt. Der Schutz der Kinder und ein achtsamer Umgang mit Betroffenen ist die Aufgabe aller. Das Ziel des Artikels ist es, das Ausmaß und die Formen der sexualisierten Gewalt in der Gesellschaft wahrzunehmen. Dies ist die Grundlage dafür, ihr vorzubeugen und gegen sie einzuschreiten. Der Artikel legt Erkenntnisse zu den Vorgehensweisen von Tätern und zu Erfahrungs- und Verarbeitungsweisen von Betroffenen dar. Vor diesem Hintergrund zeigt er christliche Potentiale von achtsamer Begegnung und von biblischen Erzählungen zur Bewältigung von Gewalterfahrung auf.

Common images from erotic dreams are described and analysed for their hidden meanings. Seven images such as sex with a handsome stranger and parental interruption are presented.

Hutchinson–Gilford progeria syndrome (HGPS) is a rare, invariably fatal childhood premature aging disorder caused by a pre-messenger RNA (mRNA) splicing defect in the LMNAgene. We used combined in vitro screening and in vivo validation to systematically explore the effects of target sequence, backbone chemistry and mechanism of action to identify optimized antisense oligonucleotides (ASOs) for therapeutic use in HGPS. In a library of 198 ASOs, the most potent ASOs targeted the LMNAexon 12 junction and acted via non-RNase H-mediated mechanisms. Treatment with an optimized lead candidate resulted in extension of lifespan in a mouse model of HGPS. Progerin mRNA levels were robustly reduced in vivo, but the extent of progerin protein reduction differed between tissues, suggesting a long half-life and tissue-specific turnover of progerin in vivo. These results identify a novel therapeutic agent for HGPS and provide insight into the HGPS disease mechanism.

AbstractAimsPrimary axillary hyperhidrosis (PAHH) is a condition characterized by excessive sweating that negatively impacts health-related quality of life, with significant psychological and social impacts. Glycopyrronium tosylate (GT) is a topical anticholinergic approved in the United States for treatment of PAHH in patients 9 years of age and older. Our objective was to assess the cost-effectiveness of GT as first-line topical therapy compared to topical aluminum chloride from a United States commercial perspective.Materials and methodsA Markov model was developed consisting of four health states based on the Hyperhidrosis Disease Severity Scale (HDSS) over a time horizon of 5 years with discount rates of 3% for both costs and outcomes. Transitions between health states were driven by HDSS response, defined as an improvement of ≥2 points. Non-responders and those who discontinue could switch to later line treatments or no treatment. Health utility scores were based on HDSS scores, supported by published literature.ResultsOver 5 years, GT yielded 0.12 greater QALYs and 0.93 greater LYs with response compared to treatment with prescription aluminum chloride at an incremental cost of $10,584. Relative to prescription aluminum chloride, GT resulted in an incremental cost-effectiveness ratio (ICER) of $87,238 per QALY gained, $11,349 per LY with response. The ICER fell below $100,000 for 66% of probabilistic sensitivity analysis simulations and below $150,000 for 82% of simulations.LimitationsThis analysis represents a simplified scenario of a hypothetical PAHH patient. Due to sparse data, assumptions were required for treatment patterns, efficacy, and persistence.ConclusionBased on the analysis of incremental cost per QALY gained, GT may be cost-effective relative to prescription aluminum chloride at commonly accepted willingness to pay thresholds.

The antioxidative capacity of four different kraft lignins (KL) and one additional organosolv lignin (OSL) was studied using the Folin–Ciocalteu (FC) assay. To do so, the corresponding FC assay procedure was adapted and optimized to be appropriate for lignin analysis. Different solvents were tested, and DMSO and saturated sodium carbonate (Na2CO3) for pH adjustment showed the best results. The absorption wavelength of 740 nm was chosen due to highest determination coefficients. Continuous calibration is recommended on a daily basis to guarantee accuracy. The antioxidant capacity and related radical scavenging activity of various lignins were correlated with the biomass nature (soft wood vs grasses) and pulping methods (kraft vs organosolv). The results show higher antioxidant activity for kraft vs organosolv lignins. First lignin-derived polyurethane coatings were prepared using the unmodified kraft lignin. The films, prepared via spin coating, show a high flexibility and transparency.

Antisense oligonucleotides (ASOs) are a novel therapeutic approach to target difficult-to-drug protein classes by targeting their corresponding mRNAs. Significantly enhanced ASO activity has been achieved by the targeted delivery of ASOs to selected tissues. One example is the targeted delivery of ASOs to hepatocytes, achieved with N-acetylgalactosamine (GalNAc) conjugation to ASO, which results in selective uptake by asialoglycoprotein receptor (ASGR). Here we have evaluated the potential of GalNAc-conjugated ASOs as a therapeutic approach to targeting difficult-to-drug pathways in hepatocellular carcinoma (HCC). The activity of GalNAc-conjugated ASOs was superior to that of the unconjugated parental ASO in ASGR (+) human HCC cells in vitro, but not in ASGR (−) cells. Both human- and mouse-derived HCC displayed reduced levels of ASGR, however, despite this, GalNAc-conjugated ASOs showed a 5- to 10-fold increase in potency in tumors. Systemically administered GalNAc-conjugated ASOs demonstrated both enhanced antisense activity and antitumor activity in the diethylnitrosamine-induced HCC tumor model. Finally, GalNAc conjugation enhanced ASO activity in human circulating tumor cells from HCC patients, demonstrating the potential of this approach in primary human HCC tumor cells. Taken together, these results provide a strong rationale for a potential therapeutic use of GalNAc-conjugated ASOs for the treatment of HCC.

Multicomponent skin cancer preventive interventions for adolescents that aim to decrease ultraviolet radiation (UVR) exposure and sunburns are particularly needed given their intentional tanning and infrequent use of sun protection. The purpose of this study was to conduct an early-phase study within the Multiphase Optimization Strategy framework that experimentally tested four unique intervention components targeting high school students' skin cancer prevention behaviors. Schools (11 total, N = 1,573 students) were assigned to receive one of four interventions: skin cancer education (control), education plus a sunscreen activity (to illustrate sunscreen's UVR-blocking properties), or behavior change worksheet (sun protection goal setting and planning) or receipt of a personalized UV damage photograph (photograph of facial damage). Sun protection, sunburn, and tanning outcomes were assessed before intervention and at 1-month follow-up. Within- and between-intervention changes in outcomes were examined using generalized estimating equation modeling. All interventions were associated with significant improvements in sun protection. The photograph was superior in controlling intentional tanning and sunburn when compared to the behavior change worksheet (ps < .05). In contrast, the worksheet was associated with greater increases in sun protection use when compared with the photograph (ps < .05). In this experiment testing four skin cancer preventive intervention components that varied in approach, content, and interactivity, the behavior change worksheet was superior in improving sun protection use whereas the UV photograph was superior in controlling intentional tanning and sunburn. Future randomized trials to test combinations of these intervention components are needed, and could identify mechanisms underlying improved effects and demographic or behavioral moderators of intervention effects.

Hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease is becoming more common globally. The incidence of HCC due to nonalcoholic steatohepatitis in comparison to other etiologies is increasing. This is due to the pandemic of obesity and diabetes mellitus, two important risk factors for HCC. HCC arising in this context occurs in about 40% of the cases in a liver which is not yet cirrhotic. This has implications regarding the population which should be enrolled in an HCC surveillance program and regarding the treatment options. Surgery is more frequently contemplated in patients with HCC and no cirrhosis. However, patients with nonalcoholic steatohepatitis-induced HCC have frequent co-morbidities which have to be taken into account when developing a management strategy. Interestingly, these patients are frequently on medications which have been suggested to decrease the risk to develop HCC.

Joey McIntyre, the newest cast member of 'Boston Public, discusses his role on the show, and his career. McIntyre is a former teenage pop singer, who continues to work on his music.

Discusses the benefits of volunteer work to lawyers. Details on pro bono work; Views on social work; Way to attract a client.

This paper provides a framework for conceptualizing and reviewing the literature on the influences of organizational culture and climate on individual creativity. Although often treated interchangeably, culture and climate are distinct constructs operating at different levels of meaning; yet at the same time, they are closely interrelated. Culture is the beliefs and values held by management and communicated to employees through norms, stories, socialization processes, and observations of managerial responses to critical events. The beliefs and values that typify a culture for creativity become manifested in organizational structures, practices, and policies. In turn, these structures, practices, and policies guide and shape individual creativity by creating a climate that communicates both the organization's goals regarding creativity and the means to achieve those goals. The paper concludes with a discussion of issues relating to the development of cultures and climates for creativity and potential new directions for future research.

Background: Sedative-hypnotic (SH) medications are often used to treat chronic insomnia, with potentially serious long-term side effects. The objective of this study is to evaluate an interprofessional SH deprescribing program within a community team-based, primary care practice, with or without cognitive behavioural therapy for insomnia (CBT-I).Methods: Retrospective chart review for patients referred to the team pharmacist for SH deprescribing from February 2016 to June 2019.Results: A total of 121 patients were referred for SH deprescribing, with 111 (92%) patients who attempted deprescribing (average age 69, range 29-97 years) and 22 patients who also received CBT-I. Overall, 36 patients (32%) achieved complete abstinence, and another 36 patients (32%) reduced their dosage by ≥50%. For the 36 patients who achieved complete abstinence, 26 (72%) patients remained abstinent at 6 months (9 patients resumed using SH and 1 patient was lost to follow-up). The proportion of patients achieving complete abstinence or reduced dosage of ≥50% (successful tapering) was higher with CBT-I than without CBT-I but did not reach statistical significance (77% vs 62%, p= 0.22). There were also no statistically significant differences detected in the success between those who took a benzodiazepine and those who took a Z-drug (67% vs 61%, p= 0.55) or for those who took SH daily and those who took them intermittently (67% vs 44%, p= 0.09).Conclusion: Almost two-thirds of patients participating in our pharmacist-led program were able to stop or taper their SH medications by ≥50%. The role of CBT-I in SH deprescribing remains to be further elucidated. Can Pharm J (Ott)2021;154:xx-xx.

AZD4785 is a therapeutic antisense oligonucleotide targeting KRAS mRNA with promising preclinical antitumor activity and a favorable safety profile.

Stimulation of C3crop yield by rising concentrations of atmospheric carbon dioxide ([CO2]) is widely expected to counteract crop losses that are due to greater drought this century. But these expectations come from sparse field trials that have been biased towards mesic growth conditions. This eight-year study used precipitation manipulation and year-to-year variation in weather conditions at a unique open-air field facility to show that the stimulation of soybean yield by elevated [CO2] diminished to zero as drought intensified. Contrary to the prevalent expectation in the literature, rising [CO2] did not counteract the effect of strong drought on photosynthesis and yield because elevated [CO2] interacted with drought to modify stomatal function and canopy energy balance. This new insight from field experimentation under hot and dry conditions, which will become increasingly prevalent in the coming decades, highlights the likelihood of negative impacts from interacting global change factors on a key global commodity crop in its primary region of production.

Relates the story of a woman who is always worried when her partner will attend bachelor parties and sought therapy together with her partner. Her reaction when her partner suggested that they look for a therapist; Details of their sessions with the therapist; View of the therapist on her discomfort with bachelor parties.

Focuses on the disadvantages of using advertisements to explain and describe medical problems and potential treatments. Features of an advertisement for Paxil, a medication for manic depression; Factors that are significant for treating chronic anxiety and depression.

Discusses strategies used by women to achieve goals on health, fitness and relationships. Knowledge of the consequences of sugary or fattening food choices; Reduction of coffee intake and increase of water intake; Improvement of communication with husbands; Social smoking.

Describes how teenage girls in Brazil celebrate and spend their summer seasons.