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This Report Updates Previous Cdc Guidelines and Recommendations on Preferred Prevention and Treatment Regimens Regarding Naturally Occurring Anthrax. Also Provided Are a Wide Range of Alternative Regimens to First-Line Antimicrobial Drugs for Use If Patients Have Contraindications or Intolerances or After a Wide-Area Aerosol Release of: Bacillus anthracis spores if resources become limited or a multidrug-resistant B. anthracis strain is used (Hendricks KA, Wright ME, Shadomy SV, et al.; Workgroup on Anthrax Clinical Guidelines. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis 2014;20:e130687; Meaney-Delman D, Rasmussen SA, Beigi RH, et al. Prophylaxis and treatment of anthrax in pregnant women. Obstet Gynecol 2013;122:885-900; Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics 2014;133:e1411-36). Specifically, this report updates antimicrobial drug and antitoxin use for both postexposure prophylaxis (PEP) and treatment from these previous guidelines best practices and is based on systematic reviews of the literature regarding 1) in vitro antimicrobial drug activity against B. anthracis; 2) in vivo antimicrobial drug efficacy for PEP and treatment; 3) in vivo and human antitoxin efficacy for PEP, treatment, or both; and 4) human survival after antimicrobial drug PEP and treatment of localized anthrax, systemic anthrax, and anthrax meningitis., Changes From Previous Cdc Guidelines and Recommendations Include an Expanded List of Alternative Antimicrobial Drugs to Use When First-Line Antimicrobial Drugs Are Contraindicated or Not Tolerated or After a Bioterrorism Event When First-Line Antimicrobial Drugs Are Depleted or Ineffective Against a Genetically Engineered Resistant: B. anthracis strain. In addition, these updated guidelines include new recommendations regarding special considerations for the diagnosis and treatment of anthrax meningitis, including comorbid, social, and clinical predictors of anthrax meningitis. The previously published CDC guidelines and recommendations described potentially beneficial critical care measures and clinical assessment tools and procedures for persons with anthrax, which have not changed and are not addressed in this update. In addition, no changes were made to the Advisory Committee on Immunization Practices recommendations for use of anthrax vaccine (Bower WA, Schiffer J, Atmar RL, et al. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices, 2019. MMWR Recomm Rep 2019;68[No. RR-4]:1-14). The updated guidelines in this report can be used by health care providers to prevent and treat anthrax and guide emergency preparedness officials and planners as they develop and update plans for a wide-area aerosol release of B. anthracis., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. CDC and contributors to this work disclose that they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services, or commercial supporters that would unfairly influence these CDC recommendations with the following exceptions: Arthur Friedlander reports funding from the U.S. Department of Defense Threat Reduction Agency for research on anthrax vaccines and therapeutics. However, none of the vaccines or therapeutics were discussed for inclusion in the guidelines. Adolf W. Karchmer receives an honorarium for service on the data and safety monitoring board (tofacitinib) for Pfizer. Todd Semla’s spouse owns stock in Abbott. Both Pfizer and Abbott manufacture antimicrobial drugs included in the guidelines. No other potential conflicts of interest were disclosed.

Introduction: Workplace microaggressions are prevalent in clinical settings and contribute to poorer mental health outcomes, as well as to higher rates of burnout for physicians and students experiencing them. While bystander workshops customarily provide guidance on direct interventions to a general audience, the literature does not yet address workshops in an academic setting that consider the individual's motivations and behavior patterns. We implemented a psychologically informed approach to microaggression training to increase participants' understanding and willingness to undergo behavioral change., Methods: We created a survey that included 10 distinct scenarios of discrimination in the clinical setting. Participants' willingness to intervene was assessed on a Likert scale prior to, then following, a 1-hour active bystander intervention workshop conducted virtually. The workshop outlined the role of culture and conflict management style in willingness to intervene. Four modes of intervention were outlined, including direct and indirect methods., Results: A total of 78 medical students, graduate students, residents, and faculty members participated in the workshop. Of those, we compared 68 individuals' pre- and postworkshop responses to our questionnaire. We then focused on the 54 participants with no previous training in psychiatry or psychology. Utilizing a Wilcoxon signed rank test, we compared the average pre/post scores of willingness to intervene and found scores to have improved following workshop attendance ( Z = -6.339, p < .001)., Discussion: Our findings suggest that a psychiatrically informed and culturally sensitive approach to active bystander intervention workshops may promote upstanding more effectively in academic medicine., (© 2023 Stephens et al.)

The objective of the present study was to estimate the prevalence of the different pathological conditions causing clinically evident androgen excess and to document the degree of long-term success of suppressive and/or antiandrogen hormonal therapy in a large consecutive population of patients. All patients presenting for evaluation of symptoms potentially related to androgen excess between October 1987 and June 2002 were evaluated, and the data were maintained prospectively in a computerized database. For the assessment of therapeutic response, a retrospective review of the medical chart was performed, after the exclusion of those patients seeking fertility therapy only, or with inadequate follow-up or poor compliance. A total of 1281 consecutive patients were seen during the study period. Excluded from analysis were 408 patients in whom we were unable to evaluate hormonal status, determine ovulatory status, or find any evidence of androgen excess. In the remaining population of 873 patients, the unbiased prevalence of androgen-secreting neoplasms was 0.2%, 21-hydroxylase-deficient classic adrenal hyperplasia (CAH) was 0.6%, 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH) was 1.6%, hyperandrogenic insulin-resistant acanthosis nigricans (HAIRAN) syndrome was 3.1%, idiopathic hirsutism was 4.7%, and polycystic ovary syndrome (PCOS) was 82.0%. Fifty-nine (6.75%) patients had elevated androgen levels and hirsutism but normal ovulation. A total of 257 patients were included in the assessment of the response to hormonal therapy. The mean duration of follow-up was 33.5 months (range, 6-155). Hirsutism improved in 86%, menstrual dysfunction in 80%, acne in 81%, and hair loss in 33% of patients. The major side effects noted were irregular vaginal bleeding (16.1%), nausea (13.0%), and headaches (12.6%); only 36.6% of patients never complained of side effects. In this large study of consecutive patients presenting with clinically evident androgen excess, specific identifiable disorders (NCAH, CAH, HAIRAN syndrome, and androgen-secreting neoplasms) were observed in approximately 7% of subjects, whereas functional androgen excess, principally PCOS, was observed in the remainder. Hirsutism, menstrual dysfunction, or acne, but not alopecia, improved in the majority of patients treated with a combination suppressive therapy; although more than 60% experienced side effects.

In women, >80% of malignant ovarian tumors are of epithelial origin. Early detection of these tumors is very challenging,and extensive i.p. dissemination is common by the time of diagnosis. The lack of adequate geneticmouse models of ovarian carcinomas significantly delays advances in early detection and treatment. We report that female transgenic mice expressing the transforming region of SV40 under control of the Mullerian inhibitory substance type II receptor gene promoter develop bilateral ovarian tumors in approximately 50% of cases. Histologically, these tumors are poorly differentiated carcinomas with occasional cysts and papillary structures present at the surface of the ovary. These tumors disseminate i.p., invade omentum, and form ascites as do human ovarian carcinomas. The epithelial origin of these tumors is supported by detection of cytokeratins 8 and 19, and the absence of alpha-inhibin, a protein characteristically expressed in normal granulosa cells and most granulosa cell tumors. Cell lines derived from the ascites exhibit the properties of epithelial ovarian cancer, such as anchorage-independent growth, tumorigenicity in immunocompromised mice, expression of epithelial cell markers, and organotropic implantation. The availability of a transgenic mouse model of disseminated ovarian carcinoma and respective cell lines should advance our understanding of this neoplasm, and serve as a useful tool for the evaluation of emerging detection and treatment strategies.

In developing Rana catesbeiana tadpoles, the timing of the thyroid hormone (TH)-dependent metamorphic responses varies markedly among tissues. Yet at any one time these tissues are exposed to the same plasma concentration of TH, suggesting that TH action is regulated in part at the level of the peripheral tissues. A major factor in TH action is the intracellular level of the active TH, T3. This level is dependent not only on the plasma concentration of TH (mostly T4) but also on the intracellular activities of the type 2 5'-deiodinase (D2) and the type 3 5-deiodinase (D3), which are responsible, respectively, for generating and degrading T3. (D1 is not present in this species.) To determine whether differential expression of D2 and D3 among tissues could be a significant factor in the coordination of metamorphic events, the ontogenic profiles of the two enzyme activities and corresponding messenger RNA levels in most tissues of R. catesbeiana tadpoles have been documented. The profiles of D2 expression in tail, hindlimb, forelimb, intestine, skin, and eye differed markedly at both activity and messenger RNA levels, but it was notable that expression was invariably highest in a given tissue at the time of its major metamorphic change. D2 expression was very low in brain and heart and did not vary during development. D2 was not expressed in liver, kidney, or red blood cells. With the exception of red blood cells, D3 expression was detected in all tissues studied. Furthermore, it was evident that in tissues that expressed both deiodinase genes, the two expression profiles were comparable, indicating a potential for tight control of intracellular T3 levels. Direct evidence of the importance of the intracellular conversion of T4 to T3 for TH-dependent metamorphic events was obtained in tadpoles in which endogenous TH synthesis was blocked with methimazole, and the activities of D2 and D3 were inhibited by iopanoic acid. This treatment inhibited metamorphosis. The inhibition could be overcome by the concomitant administration of replacement levels of T3, but not T4. These results strongly support the view that coordinated development in amphibia depends in part on the tissue-specific expression patterns of the D2 and D3 genes, which ensure that the requisite level of intracellular T3 is attained in a given tissue, regardless of the current level of circulating TH, at the appropriate stage of metamorphosis.