Standards of Care for the Health of Transgender and Gender Diverse People, Version 8.

Background: Transgender healthcare is a rapidly evolving interdisciplinary field. In the last decade, there has been an unprecedented increase in the number and visibility of transgender and gender diverse (TGD) people seeking support and gender-affirming medical treatment in parallel with a significant rise in the scientific literature in this area. The World Professional Association for Transgender Health (WPATH) is an international, multidisciplinary, professional association whose mission is to promote evidence-based care, education, research, public policy, and respect in transgender health. One of the main functions of WPATH is to promote the highest standards of health care for TGD people through the Standards of Care (SOC). The SOC was initially developed in 1979 and the last version (SOC-7) was published in 2012. In view of the increasing scientific evidence, WPATH commissioned a new version of the Standards of Care, the SOC-8. Aim: The overall goal of SOC-8 is to provide health care professionals (HCPs) with clinical guidance to assist TGD people in accessing safe and effective pathways to achieving lasting personal comfort with their gendered selves with the aim of optimizing their overall physical health, psychological well-being, and self-fulfillment. Methods: The SOC-8 is based on the best available science and expert professional consensus in transgender health. International professionals and stakeholders were selected to serve on the SOC-8 committee. Recommendation statements were developed based on data derived from independent systematic literature reviews, where available, background reviews and expert opinions. Grading of recommendations was based on the available evidence supporting interventions, a discussion of risks and harms, as well as the feasibility and acceptability within different contexts and country settings. Results: A total of 18 chapters were developed as part of the SOC-8. They contain recommendations for health care professionals who provide care and treatment for TGD people. Each of the recommendations is followed by explanatory text with relevant references. General areas related to transgender health are covered in the chapters Terminology, Global Applicability, Population Estimates, and Education. The chapters developed for the diverse population of TGD people include Assessment of Adults, Adolescents, Children, Nonbinary, Eunuchs, and Intersex Individuals, and people living in Institutional Environments. Finally, the chapters related to gender-affirming treatment are Hormone Therapy, Surgery and Postoperative Care, Voice and Communication, Primary Care, Reproductive Health, Sexual Health, and Mental Health. Conclusions: The SOC-8 guidelines are intended to be flexible to meet the diverse health care needs of TGD people globally. While adaptable, they offer standards for promoting optimal health care and guidance for the treatment of people experiencing gender incongruence. As in all previous versions of the SOC, the criteria set forth in this document for gender-affirming medical interventions are clinical guidelines; individual health care professionals and programs may modify these in consultation with the TGD person.

Semen characteristics of transwomen referred for sperm banking before sex transition: a case series.

Transwomen (TW) can now turn to cryopreserve spermatozoa before gender reassignment (GR). The objective is to assess semen quality of TW and evaluate adequacy for assisted reproduction technology (ART). Pre-freezing (PF) and post-thaw (PT) semen parameters of 2 and PF data of 27 TW who were referred for sperm banking in Cleveland Clinic/USA and Ghent Center/Belgium, before GR, were retrospectively analysed. The study period was between February, 2003 and October, 2011. We also evaluated adequacy of 24-h PT data for ART. PF data of 29 TW, mean age of 28.9 years, showed high incidence of oligozoospermia (27.58%), asthenozoospermia (31%) and teratozoospermia (31%). Mean sperm concentration was 46.9 × 10(6) /ml, mean per cent motility was 42.9 and mean per cent sperm morphology (Kruger's) was 7.98. The 24-h PT data, for 2 TW, showed mean motility 22.4%, mean total motile sperm count 13.7 × 10(6) and total motile sperm concentration 8.7 × 106/ml. Single patient had used the frozen spermatozoon for intrauterine insemination (IUI) of a surrogate mother resulting in birth of healthy newborn. It is concluded that poor PF and 24-h PT semen quality is frequently seen among TW. As such, considerable proportion of TW should use more expensive method of ART, for example IVF/ICSI rather than inexpensive IUI.

In vitro resistance of Bacillus anthracis Sterne to doxycycline, macrolides and quinolones.

Bacillus anthracis is a potential biological warfare agent. Its ability to develop resistance to antimicrobial agents currently recommended for the treatment of anthrax infection is a major concern. B. anthracis Sterne was grown from a live veterinary vaccine and used it to test for the development of resistance after 21 sequential subcultures in sub-inhibitory concentrations of doxycycline and three quinolones (ciprofloxacin, alatrofloxacin and gatifloxacin) and 15 sequential subcultures in sub-inhibitory concentrations of three macrolides (erythromycin, azithromycin and clarithromycin). After 21 subcultures the minimal inhibitory concentrations (MICs) increased from 0.1 to 1.6 mg/l for ciprofloxacin, from 1.6 to 12.5 mg/l for alatrofloxacin, from 0.025 to 1.6 mg/l for gatifloxacin and from 0.025 to 0.1 mg/l for doxycycline. After 15 passages of sequential subculturing with macrolides, the MICs increased from 12.5 to 12.5 or 50.0 mg/l for azithromycin, from 0.2 to 1.6 or 0.4 mg/l for clarithromycin and from 6.25 to 6.25 or 50 mg/l for erythromycin. After sequential passages with a single quinolone or doxycycline, each isolate was cross-tested for resistance using the other drugs. All isolates selected for resistance to one quinolone were also resistant to the other two quinolones, but not to doxycycline. The doxycycline-resistant isolate was not resistant to any quinolone.

Nuclear, biological, and chemical training in the U.S. Army Reserves: mitigating psychological consequences of weapons of mass destruction.

Weapons of mass destruction (WMD) and their associated delivery systems pose a major threat to the national security of the United States. The Department of Defense is pursuing a number of activities to counter paramilitary and terrorist threats from nuclear, biological, and chemical (NBC) agents. These efforts include supporting, training, and equipping the U.S. Army Reserves (USAR) for the medical management of physical injuries and psychological trauma resulting from the use of NBC weapons both in the United States and overseas. The USAR will play an important role in responding to a WMD incident because most of the Army's support assets are in the USAR. The USAR is training to perform its mission in an NBC-contaminated environment by engaging in realistic WMD exercises using state-of-the-art protective equipment and medical support. Realistic training builds confidence in medical defenses and in NBC protective equipment. This translates into accomplishing the mission while minimizing the psychological and physical casualties in an NBC-contaminated battlefield or in support of a WMD terrorist incident.

Performance decrement after combined exposure to ionizing radiation and Shigella sonnei.

Ionizing radiation could increase morbidity from common bacterial infections in military personnel on the modern battlefield. The combined effects of a sublethal dose of ionizing radiation and the bacterial diarrheal agent Shigella sonnei on body weight and forelimb grip strength in mice were assessed over a 30-day period. Individually housed B6D2F1 female mice were divided into four groups: control, sham irradiation + gavage with saline vehicle; 3 Gy 60Co gamma radiation at 0.4 Gy/min radiation + saline gavage; sham irradiation + 1.3 x 10(8) colony-forming units (CFUs) S. sonnei via gavage, administered 4 days postirradiation; and the combination of 3 Gy 60Co gamma radiation + 1.3 x 10(8) CFUs S. sonnei. Behavioral tests were conducted 3 days preirradiation and on days 9, 14, and 22 postirradiation. Body weight was significantly reduced in the radiation + Shigella group on days 5 to 10 postirradiation. Forelimb grip strength was reduced for mice in the radiation + Shigella group on days 9 and 14 postirradiation. These data demonstrate that an exposure to gamma radiation in combination with the bacterial agent S. sonnei can lead to a synergistic loss of body weight and degradation in performance.

Combined effects of Venezuelan equine encephalitis IIIA virus and gamma irradiation in mice.

The combined effects of injury from exposure to ionizing radiation and the potential biological warfare agent Venezuelan equine encephalitis (VEE) virus remain largely unknown. To study these effects, 4- to 5-week-old B6D2F1/J female mice were given a sublethal whole-body 7 Gy dose of 60Co gamma-photon radiation followed 48 hours later by aerosol or intraperitoneal challenge with enzootic VEE IIIA virus. Survival was observed for 30 days. A single sublethal 7 Gy dose of gamma radiation reduced the LD50/30 of VEE IIIA virus, in intraperitoneal challenged mice by a factor of 10(4) from 1.1 x 10(6) plaque-forming units (pfu) to 1 x 10(2) pfu, and in aerosol challenged mice, by a factor of 5 from 70 pfu to 14 pfu. These findings further confirm there is a combined effect of exposure to ionizing radiation and biological warfare agents, which could be devastating to unprotected populations and thus should be investigated further.

Subtalar joint stability. Talocalcaneal interosseous ligament function studied in cadaver specimens.

We used 6 fresh-frozen foot specimens to evaluate the contribution of the talocalcaneal interosseous ligament (IOL) in stabilizing the subtalar (talocalcaneal) joint. The tibia and ankle joint were secured, and the calcaneus was subjected to a bending and axial force applied circumferentially. The position of the calcaneus relative to the talus was monitored with a magnetic tracking system. Motion was recorded at every half degree in the 0 degree to 360 degrees arc before and after sectioning of the IOL. The results in the intact feet indicated that, with circumferential loading of the subtalar joint, there were two stable zones (supination stable zone, pronation stable zone) during which little displacement occurred and two transition zones during which the supination and pronation movement occurred. There was a greater degree of supination displacement after IOL sectioning (p = 0.008), but no pronation displacement. The IOL contributed substantially to subtalar joint stability, particularly in supination.

The use of topographical landmarks to improve the outcome of Agee endoscopic carpal tunnel release.

A modified approach to endoscopic carpal tunnel release has been developed and tested in 60 cadaveric specimens by three surgeons using the Agee endoscopic carpal tunnel release system. The modified approach, which includes specific localization of the hook of the hamate, flexor retinaculum, and the superficial palmar arch utilizing topographical landmarks, avoids entry into Guyon's canal and injury to the ulnar artery and nerve, median nerve, and common digital nerves. Use of the anatomic approach resulted in significantly superior results. There were fewer incomplete releases, and fewer surgical passes were required, for the inexperienced surgeons. When these anatomic considerations were not included, the learning curve was much steeper. For surgeons planning endoscopic surgical release of the transverse carpal ligament, the described topographical approach improves the technical competence with the procedure and reduces the number of complications and learning curve associated with new procedures. We recommend the use of topographical landmarks and other anatomic considerations during endoscopic carpal tunnel release.

Identification of antigens of pathogenic free-living amoebae by protein immunoblotting with rabbit immune and human sera.

Prominent antigens of pathogenic and nonpathogenic free-living amoebae were identified by using polyclonal rabbit immune sera in immunoblot assays. The intent was to determine if prominent epitopes identified with rabbit immune sera could also be recognized by human sera. With rabbit sera, the development of immunoreactive bands was restricted to molecular masses of greater than 18.5 kDa for Naegleria, Hartmannella, and Vahlkampfia antigens. Two or more broad bands of less than 18.5 kDa were prominent features in three different Acanthamoeba species. Few cross-reactive antibodies could be detected between representative species of the three different subgroups of Acanthamoeba. Naegleria antigen was likewise serologically distinct, as were Hartmannella and Vahlkampfia antigens. The relative lack of cross-reacting antibodies between the pathogenic amoebae suggested that i would be desirable to use a panel of amoebic antigens to represent the range of serologically distinct antigens for assessing reactive antibodies in human sera. In pooled human sera (10 serum specimens per pool), the appearance of minimally reactive bands ranging from 32.5 to 106 kDa was a common feature of all six antigens. A prominent band of less than 18.5 kDa was identified in the Acanthamoeba culbertsoni antigen lane in 2 of the 10 human serum specimen pools. When sera from each of the two groups were tested individually by immunoblotting, the reaction with A. culbertsoni antigen could be associated with one individual. By using a panel of amoebic antigens, this method could prove useful in recognizing undiagnosed amoebic infections by revealing specific reactive antibodies.

Prevalence of sperm bound antibodies in infertile men with varicocele: the effect of varicocele ligation on antibody levels and semen response.

An increased level of antisperm antibodies has been demonstrated in infertile men with varicocele compared with normal fertile men, suggesting a possible cause and effect relationship. To evaluate the possible etiological role of antisperm antibodies in varicocele patients, we performed a prospective study of 32 infertile men undergoing varicocele ligation. Semen analyses and antisperm antibodies as measured by the immunobead test were performed preoperatively and postoperatively at 3 and 6 months. Of the infertile men with varicocele 28% had a positive immunobead test compared with 0% of normal fertile men. The average total motile sperm count was significantly different (p < 0.05, 2-tailed t test) for 9 varicocele patients with sperm-bound antibody (3.2 x 10(6)) compared with 23 without antibody (8.4 x 10(6)). Postoperatively, 68% of all patients exhibited improved semen parameters, with no change in antibody status in either group. Among the antibody positive group 71% showed an increase in motile sperm per ml. of 2.8 x 10(6) to 17.2 x 10(6) (525% increase, p < 0.05), while in the antibody negative group 67% showed an increase of 3.8 x 10(6) to 24.9 x 10(6) (553% increase, p < 0.05). Our study suggests that there is an increased incidence of sperm-bound immunoglobulin in infertile varicocele patients and an apparent adverse effect on semen parameters in these patients. However, the presence of sperm-bound immunoglobulin did not affect the percentage response to surgical correction, nor can we postulate an immunological mechanism as a major etiological factor in varicocele induced infertility.

Bone scan as a stratification variable in advanced prostate cancer.

The serial technetium 99 (99Tc) bone scans of 76 patients with Stage D-2 prostate cancers were reviewed. Sites of metastases in skeletal areas in decreasing order were vertebrae, ribs, pelvis, long bones, and skull. Patients with one or two involved skeletal areas had a significantly longer progression-free interval and survival time than patients with three or more bony areas of uptake. Bone scans might be used as a stratification variable in future prospective clinical trials of Stage D-2 prostate cancer.

Operation Desert Shield: medical aspects of weapons of mass destruction.

Our concern over possible use of weapons of mass destruction against U.S. forces in the Middle East has increased because Iraq has violated the Geneva Protocol of 1925 and the 1972 Biological Weapons Convention, attempted to acquire nuclear capability and delivery systems, and is reported to be developing biological weapons. The Army Medical Department has had no experience, since World War I, in the management and treatment of mass casualties contaminated by chemical agents, and has never treated casualties resulting from the use of nuclear or biological weapons used against our soldiers. Management and diagnosis of casualties will be complicated by their possible exposure to a mixture of chemical warfare and biological warfare agents. Triage is an essential aspect in the management of mass casualties since the number of injured patients will exceed the maximum medical capability to treat each patient on arrival. All levels of medical support must be prepared to protect themselves, their equipment and supplies, and their patients from contamination. In contaminated operations on the integrated battlefield, it will be of utmost importance to incorporate flexibility and innovation to match the medical and tactical situation.

MR imaging in fibromatosis: results in 26 patients with pathologic correlation.

Fibromatoses are a diverse group of soft-tissue lesions that have been inconsistently categorized and treated. The purpose of our study was to establish the range of appearances of fibromatoses on MR images and perform a pathologic correlation to explain the variable signal-intensity patterns. During a 3-year period, 26 patients with deep fibromatoses were examined with MR. The MR images were evaluated for signal-intensity characteristics, and findings were correlated retrospectively with the pathologic diagnoses. The results showed that the MR appearance of fibromatoses is similar to that of other soft-tissue lesions, and the signal intensities vary greatly from lesion to lesion and within lesions themselves. The fibromatoses were either hyperintense, isointense, hypointense, or of mixed signal intensity relative to adjacent skeletal muscle. The hypointense areas appear to be zones of hypocellularity and dense collagen deposition. Microscopically all of the lesions invaded adjacent structures, but the MR appearances of the margins varied and were judged to be well demarcated (n = 14), intermediate (n = 5), or poorly demarcated (n = 6). Our experience shows that fibromatoses have a variable MR appearance no different from that of other soft-tissue lesions, and this variability reflects the composition and cellularity of the lesions.

Post-traumatic osteolysis of the clavicle: MR features.

We present the magnetic resonance findings in a pathologically proven case of post-traumatic osteolysis of the distal clavicle. High signal intensity tissue centered on the acromioclavicular joint was seen on T2-weighted images, consistent with synovial proliferation.

Color Doppler sonographic imaging in the assessment of upper-extremity deep venous thrombosis.

Color Doppler flow imaging with linear-array transducers was performed in 130 extremities in 91 patients with suspected upper-extremity deep venous thrombosis. Thrombi were detected in 39 studies (30%). Eighty-four patients had either imaging examinations (22 studies comprising venography in 20 patients, CT in one, and MR imaging in one) or clinical follow-up (99 studies) for correlation. In studies with imaging correlation, the sensitivity of the Doppler studies was 78% and the specificity was 92%. There were two false-negative examinations in which the proximal subclavian vein either could not be imaged or the anatomy was distorted. There was one false-positive color Doppler diagnosis of deep venous thrombosis in a case of partial obstruction of the subclavian vein caused by extrinsic compression. There were no known additional errors in color Doppler imaging in patients who had clinical follow-up. Four cases of isolated superior vena cava or proximal innominate vein obstruction were missed by color Doppler imaging. Color Doppler flow imaging is an accurate, noninvasive method for the evaluation of upper-extremity deep venous thrombosis. Other imaging tests may be required when the color Doppler study is negative and central venous thrombosis is suspected.

Immunization against anthrax with aromatic compound-dependent (Aro-) mutants of Bacillus anthracis and with recombinant strains of Bacillus subtilis that produce anthrax protective antigen.

The safety and efficacy of five prototype, live anthrax vaccines were studied in Hartley guinea pigs and CBA/J and A/J mice. Two of the strains, Bacillus anthracis FD111 and FD112, are Aro- mutants derived by Tn916 mutagenesis of B. anthracis UM23-1. Bacillus subtilis PA1 and PA2 contain a recombinant plasmid, pPA101 or pPA102, respectively, that carries the gene from B. anthracis encoding synthesis of protective antigen (PA). The final strain, B. subtilis PA7, was isolated in this study from B. subtilis DB104 transformed with pPA101. All five strains were less virulent in guinea pigs and A/J and CBA/J mice than the toxinogenic, nonencapsulated B. anthracis veterinary vaccine Sterne strain. A/J and CBA/J inbred mice represent strains that are innately susceptible and resistant, respectively, to the Sterne strain. These differences in susceptibility are due to differences in ability to produce complement component 5. In guinea pigs, immunization with PA1 or PA2 vegetative cells or PA7 spores protected greater than or equal to 95% from an intramuscular spore challenge with the virulent, "vaccine-resistant" B. anthracis Ames strain. Strain PA2 vegetative cells and strain PA7 spores were as effective as the Sterne strain in Sterne-resistant CBA/J mice, protecting 70% of the mice from Ames strain spore challenge. Immunization with FD111 or FD112 vegetative cells fully protected guinea pigs from challenge. Immunization with FD111 cells protected up to 100% of CBA/J mice and up to 70% of A/J mice.

Transposon Tn916 mutagenesis in Bacillus anthracis.

Mutagenesis of Bacillus anthracis by the streptococcal tetracycline resistance transposon Tn916 is described. Tn916 was transferred from Streptococcus faecalis DS16C1 to B. anthracis VNR-1 by conjugation in a standard filter mating procedure. Tetracycline-resistant (Tcr) transconjugants were obtained at a frequency of 1.6 X 10(-8) per donor CFU. When donor and recipient cells were treated with nafcillin before conjugation, the frequency was increased nearly 10-fold. Nafcillin pretreatment of donor and recipient strains was used in all subsequent conjugation experiments. S.faecalis CG110, containing multiple chromosomal insertions of Tn916, transferred the transposon to B. anthracis VNR-1 at a frequency of 9.3 x 10(-5). A Tcr B. anthracis transconjugant, strain VNR-1-tet-1, transferred Tn916 to B. anthracis UM23-1 and Bacillus subtilis BST1 at frequencies of 2.1 x 10(-4) and 5.8 X 10(-6), respectively. The transfer of Tn916 occurred only on membrane filters, since no Tcr transconjugants were obtained when strains VNR-1-tet-1 and UM23-1 were mixed and incubated in broth culture. The presence of the Tn916-associated tetM gene in Tcr B. anthracis and B. subtilis transconjugants was confirmed in hybridization experiments by using a 5-kilobase-pair DNA fragment containing the tetM gene as a probe. Of 3,000 B. anthracis UM23-1 Tcr transconjugants tested, 21 were phenylalanine auxotrophs and 2 were auxotrophic for phenylalanine, tyrosine, and tryptophan.

Mechanical transmission of Bacillus anthracis by stable flies (Stomoxys calcitrans) and mosquitoes (Aedes aegypti and Aedes taeniorhynchus).

We evaluated the potential of stable flies, Stomoxys calcitrans, and two species of mosquitoes, Aedes aegypti and Aedes taeniorhynchus, to transmit Bacillus anthracis Vollum 1B mechanically. After probing on Hartley guinea pigs with a bacteremia of ca. 10(8.6) CFU of B. anthracis per ml of blood, individual or pools of two to four stable flies or mosquitoes were allowed to continue feeding on either uninfected guinea pigs or A/J mice. All three insect species transmitted lethal anthrax infections to both guinea pigs and mice. Both stable flies and mosquitoes transmitted anthrax, even when they were held at room temperature for 4 h after exposure to the bacteremic guinea pig before being allowed to continue feeding on the susceptible animals. This study confirms that blood-feeding insects can mechanically transmit anthrax and supports recent anecdotal reports of fly-bite-associated cutaneous human anthrax. The potential for flies to mechanically transmit anthrax suggests that fly control should be considered as part of a program for control of epizootic anthrax.