Introduction Physical distancing has encouraged the public to utilize the Internet for virtually all daily activities during the COVID-19 pandemic. This study aimed to assess the impact of COVID-19 on Internet addiction (IA) prevalence and analyzed the correlated factors during quarantine and pandemic. Methods An online survey was generated, comprising of a sociodemographic section, Internet Addiction Diagnostic Questionnaire (KDAI), Symptoms Checklist-90, and Pittsburgh Sleep Quality Index. The hyperlink was disseminated through social media, companies, and universities. Overall, 4,734 adults, (mean age 31.84 ± 7.73 years old and 55.2% males) representing all 34 provinces of Indonesia, gave valid responses. Results Point prevalence of IA during the COVID-19 pandemic was 14.4% in Indonesian adults. Online duration increased by 52% compared to before the pandemic. Physical distancing was not established as a risk of IA. Increased daily online duration, specific motivations, types of application, and having confirmed/suspected COVID-19 cases within the household were predictive of IA. All subscales of SCL-90 and PSQI were higher in the group with positive/suspect cases of COVID-19 within households and were correlated to higher scores of IA. Discussion Physical distancing alone was not associated with an increased risk of IA. The prevalence of IA during COVID-19 was higher than the previously proposed rate among Indonesian adults, which might be related to digital activities associated with COVID-19 and the popularity of virtual socializing. Furthermore, psychopathologies and sleep disruptions were related to IA occurrences and especially prevalent in groups with proximity to COVID-19. Fear of COVID-19 contraction and rampant misinformation of COVID-19 probably contributed to these factors, which potentially harbor long-term consequences. Conclusion The current study demonstrated a high point prevalence of IA and identified several preventable factors predictive of IA during home-quarantine and COVID-19, especially in adults with confirmed/suspected COVID-19 cases within the household. However, physical distancing did not increase the odds of IA. Public health agencies should maintain physical distancing advisory while providing adaptive psychiatric education and service.

The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.

The 2-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator (SERM) which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. In vivo structure-activity relationships and molecular modeling studies have indicated that the orientation of the basic amine-containing side chain of 1, relative to the stilbene plane, is an important discriminating factor for the maintenance of tissue selectivity. We have constructed a series of analogues of 1 in which this side chain is held in an orientation which is orthogonal to the stilbene plane, similar to the low-energy conformation predicted for raloxifene. Herein, we report on the synthesis of these compounds and on their activity in a series of in vitro and in vivo biological assays reflective of the SERM profile. In particular, we describe their ability to (1) bind the estrogen receptor, (2) antagonize estrogen-stimulated proliferation of MCF-7 cells in vitro, (3) stimulate TGF-beta3 gene expression in cell culture, (4) inhibit the uterine effects of ethynyl estradiol in immature rats, and (5) potently reduce serum cholesterol and protect against osteopenia in ovariectomized (OVX) rats without estrogen-like stimulation of uterine tissue. These data demonstrate that one of these compounds, LY357489,4, is among the most potent SERMs described to date with in vivo efficacy on bone and cholesterol metabolism in OVX rats at doses as low as 0.01 mg/kg/d.

Introduction: Physical distancing policy during coronavirus disease 2019 (COVID-19) pandemic requires adolescents to spend most of their time at home, thus increasing Internet use duration. Limited social interaction with their peers may lead to loneliness and an increased risk of mental health among adolescents. This study aimed to assess the prevalence of Internet addiction (IA) among adolescents and analyze the influence of psychosocial factors toward the heightened risk of IA during the COVID-19 pandemic.Methods: An online survey comprising sociodemographic questionnaire, Internet Addiction Diagnostic Questionnaire (KDAI), Strengths and Difficulties Questionnaire (SDQ), and Pittsburgh Sleep Quality Index (PSQI) was distributed. Overall, a total of 2,932 adolescents (mean age, 17.38 ± 2.24 years old; female, 78.7%), originating from 33 of 34 provinces in Indonesia, completed the survey.Results: The point prevalence of IA among Indonesian adolescents during the COVID-19 outbreak was 19.3%. Increased Internet use duration, internalization, externalization, low prosocial behavior, and sleep disturbances were found as risk factors of IA, either directly or as mediating variables. Physical distancing, large-scale social restriction (PSBB), and health status were not correlated to IA.Discussion: Physical distancing was not established as a risk of IA. This could be due to other psychological factors such as internalization, externalization, prosocial, and sleep problems that had correlations to IA occurrence among adolescents in the COVID-19 pandemic. Sleep impairment might have resulted from the emotional and behavioral issues and directly contributed to IA development.Conclusion: The present study found the prevalence of IA among Indonesian adolescents to be higher than the adult during the COVID-19 pandemic. Several psychological measures were indicated to increase the risk of IA, while physical distancing did not elevate the risk. Thus, remote schooling is preferable in Indonesia along with proper parental supervision to minimize Internet use for entertainment purposes.