The role of the World Health Organization in male contraceptive development.

The World Health Organization has been involved in male contraceptive development for over 50 years. In line with its functions and mandate, World Health Organization works with diverse stakeholders to support research, develop norms and standards, engage member states, facilitate prequalification, introduction and scale up, measurement, and tracking of contraceptives. World Health Organization has a key role in galvanizing global efforts to ensure universal access to contraception services irrespective of income group. Regarding male contraceptive development, World Health Organization has provided technical leadership, supported early research, created and supported research centers, built research capacity in various countries, and standardized semen analysis procedures. In this paper, a detailed description is provided with examples across the various stages of male contraceptive development. Limited funding to World Health Organization is a key challenge.

The association between gynecologic healthcare providers' sexual health and their comfort discussing their patients' sexual function.

OBJECTIVE: Stigma surrounding discussions of sexuality can prevent patients from discussing sexual health issues with their healthcare providers. Clinicians may also experience similar stigma, compounding the problem if also reticent to assess their patients' sexual health. We explored the association of healthcare providers' personal sexual experience and health with their comfort with and frequency of optimizing their patients' sexual function and satisfaction. METHODS: We conducted an anonymous online survey of gynecologic care providers and their comfort with and frequency of addressing their patients' sexual function. Covariates examined via bivariate analysis included: socio-demographics, training level, prior sexual experiences and education, history of sexual trauma, and current sexual problems and satisfaction. RESULTS: Most respondents (N = 189) identified as sexually active (82.5 %), heterosexual (90.5 %), female (85.7 %) medical trainees (63.5 %). A quarter (23.8 %) reported currently having at least 1 sexual problem and 27.0 % reported a history of sexual trauma. Notably, 91.0 % of respondents had never been asked about their own sexual health by a healthcare provider. Less than half (43.9 %) reported frequently bringing up sexual health issues with their patients, while about half (50.8 %) reported being comfortable optimizing patients' sexual function, which was significantly correlated (p < 0.05) with practicing at the attending level, being comfortable talking about their own sexuality, the absence of sexual problems, reported sexual satisfaction, and prior education in a greater number of sexual healthcare topics. CONCLUSION: Variation in how gynecologic healthcare providers manage their patients' sexual function may be linked to their own sexual experiences and well-being.

"Hate has chipped away at my sense of security": A survey study of the impacts of anti-Asian hate on the health of older Asians.

BACKGROUND: Since the beginning of the COVID-19 pandemic, older Asians have experienced a rise in racism and discrimination based on their race and ethnicity. This study examines how anti-Asian hate impacts older Asians' mental, social, and physical health. METHODS: From March 18, 2022 to January 24, 2023, we conducted a cross-sectional survey study of community-dwelling Asian/Asian American adults aged ≥50 years from the San Francisco Bay Area. Measures included perceptions of anti-Asian hate; direct encounters with hate incidents; indirect experiences with hate incidents (e.g. knowing a friend who was a victim); reports of anxiety, depression, loneliness, and changes in daily activities; ways to address these issues; and discussions with clinicians about hate incidents. RESULTS: Of the 293 older Asians, 158 (54%) were Vietnamese and 97 (33%) Chinese. Eighty-five (29%) participants were direct victims of anti-Asian hate, 112 (38%) reported anxiety, 105 (36%) reported depression, 161 (55%) reported loneliness, and 142 (48%) reported decreased daily activities. Compared with those who were "not-at-all" to "moderately" worried about hate incidents, participants who were "very" to "extremely" worried experienced heightened anxiety (42% versus 16%), loneliness (30% versus 14%), and changes in daily activities (66% versus 31%), p < 0.01 for all. Most participants (72%) felt comfortable discussing hate incidents with clinicians; however, only 31 (11%) reported that a clinician had talked with them about these incidents. CONCLUSION: Both directly and indirectly, anti-Asian hate negatively impacts older Asians' mental, social, and physical health. Clinicians have a role in addressing the health impacts of anti-Asian hate.

Mucosal vaccination in a murine gnotobiotic model of Giardia lamblia infection.

Giardia lamblia is an important protozoan cause of diarrheal disease worldwide, delayed development and cognitive impairment in children in low- and middle-income countries, and protracted post-infectious syndromes in developed regions. G. lamblia resides in the lumen and at the epithelial surface of the proximal small intestine but is not mucosa invasive. The protozoan parasite is genetically diverse with significant genome differences across strains and assemblages. Animal models, particularly murine models, have been instrumental in defining mechanisms of host defense against G. lamblia, but mice cannot be readily infected with most human pathogenic strains. Antibiotic pretreatment can increase susceptibility, suggesting that the normal microbiota plays a role in controlling G. lamblia infection in mice, but the broader implications on susceptibility to diverse strains are not known. Here, we have used gnotobiotic mice to demonstrate that robust intestinal infection can be achieved for a broad set of human-pathogenic strains of the genetic assemblages A and B. Furthermore, gnotobiotic mice were able to eradicate infection with a similar kinetics to conventional mice after trophozoite challenge. Germ-free mice could also be effectively immunized by the mucosal route with a protective antigen, α1-giardin, in a manner dependent on CD4 T cells. These results indicate that the gnotobiotic mouse model is powerful for investigating acquired host defenses in giardiasis, as the mice are broadly susceptible to diverse G. lamblia strains yet display no apparent defects in mucosal immunity needed for controlling and eradicating this lumen-dwelling pathogen.

ß-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer's disease.

Introduction: The study of the pathophysiology study of Alzheimer's disease (AD) has been hampered by lack animal models that recapitulate the major AD pathologies, including extracellular -amyloid (A) deposition, intracellular aggregation of microtubule associated protein tau (MAPT), inflammation and neurodegeneration. Methods: The humanized APPNL-G-F knock-in mouse line was crossed to the PS19 MAPTP301S, over-expression mouse line to create the dual APPNL-G-F/PS19 MAPTP301S line. The resulting pathologies were characterized by immunochemical methods and PCR. Results: We now report on a double transgenic APPNL-G-F/PS19 MAPTP301S mouse that at 6 months of age exhibits robust A plaque accumulation, intense MAPT pathology, strong inflammation and extensive neurodegeneration. The presence of A pathology potentiated the other major pathologies, including MAPT pathology, inflammation and neurodegeneration. MAPT pathology neither changed levels of amyloid precursor protein nor potentiated A accumulation. Interestingly, study of immunofluorescence in cleared brains indicates that microglial inflammation was generally stronger in the hippocampus, dentate gyrus and entorhinal cortex, which are regions with predominant MAPT pathology. The APPNL-G-F/MAPTP301S mouse model also showed strong accumulation of N6-methyladenosine (m6A), which was recently shown to be elevated in the AD brain. m6A primarily accumulated in neuronal soma, but also co-localized with a subset of astrocytes and microglia. The accumulation of m6A corresponded with increases in METTL3 and decreases in ALKBH5, which are enzymes that add or remove m6A from mRNA, respectively. Discussion: Our understanding of the pathophysiology of Alzheimer's disease (AD) has been hampered by lack animal models that recapitulate the major AD pathologies, including extracellular -amyloid (A) deposition, intracellular aggregation of microtubule associated protein tau (MAPT), inflammation and neurodegeneration. The APPNL-G-F/MAPTP301S mouse recapitulates many features of AD pathology beginning at 6 months of aging, and thus represents a useful new mouse model for the field.

Complete sequence of the closed circular extrachromosomal element of Naegleria pringsheimi De Jonckheere (strain Singh).

The DNA encoding the ribosomal RNA in Naegleria is encoded on closed circular extrachromosomal ribosomal DNA-containing elements (CERE) in the nucleolus. In this report, we describe the sequence of the CERE of Naegleria pringsheimi De Jonckheere (strain Singh).

The demand for male contraception: Estimating the potential market for users of novel male contraceptive methods using United States National Survey of Family Growth data.

OBJECTIVE: To estimate the potential market for novel male contraceptives (NMCs) using United States National Survey of Family Growth (NSFG) data, 2015-2017. STUDY DESIGN: We described the market for NMCs via secondary analysis of the 2015-2017 NSFG's weighted male respondent data, utilizing surrogate markers for contraceptive switching (NSFG) and contraceptive discontinuation data from the Contraceptive CHOICE project. Potential NMC users included men relying on: (1) no methods or less effective methods but who reported that they would be "very upset" if they got someone pregnant, (2) permanent methods but who reported that they might still want more children, (3) a female partner's method that she might discontinue in the next year, (4) a male method even when his partner uses her own contraceptive. RESULTS: Of 3340 respondents-representing 55,890,830 sexually active, reproductive-age men-23.2% used no contraception at last intercourse, 15.8% condoms, 5.1% withdrawal, and 5.1% vasectomy. Among respondents relying solely on condoms, withdrawal, or no method, 19.7%, 3.8%, and 4.4% would be "very upset" if they got someone pregnant. For permanent contraceptive users, 17.3%-20.5% wanted another child. For men reliant on their partner's long-acting reversible or combined hormonal contraceptive, 12-17% and 45-51% of partners might discontinue their method. These data conservatively suggest that 13% or more than 7 million men would potentially use NMCs, rising to 15.5 million with less restrictive contraceptive switching criteria. CONCLUSION: Adjusting for pregnancy attitudes and likelihood of contraceptive switching, a substantial portion (between 7-15.5 million) of reproductive age men in the US are potential NMC users. IMPLICATIONS: The population of potential novel male contraceptive users extends beyond just users of condoms, withdrawal and vasectomy and should include couples practicing dual-partner contraception and female partners using contraceptive methods that they may become dissatisfied with and discontinue.

Iris atrophy following intracameral dexamethasone injection: a report of two pediatric cases.

We report 2 pediatric cases of iris atrophy that developed roughly 1 month after intracameral injection of dexamethasone suspension 9% following unilateral goniotomy and cataract extraction.

Prospective study examining the impact of cerebral angiography on quantitative pupillometer values in the interventional radiology suite.

OBJECTIVES: The purpose of this pilot study was to obtain baseline quantitative pupillometry (QP) measurements before and after catheter-directed cerebral angiography (DCA) to explore the hypothesis that cerebral angiography is an independent predictor of change in pupillary light reflex (PLR) metrics. DESIGN: This was a prospective, observational pilot study of PLR assessments obtained using QP 30 min before and after DCA. All patients had QP measurements performed with the NPi-300 (Neuroptics) pupillometer. SETTING: Recruitment was done at a single-centre, tertiary-care academic hospital and comprehensive stroke centre in Dallas, Texas. PARTICIPANTS: Fifty participants were recruited undergoing elective or emergent angiography. Inclusion criteria were a physician-ordered interventional neuroradiological procedure, at least 18 years of age, no contraindications to PLR assessment with QP, and nursing transport to and from DCA. Patients with a history of eye surgery were excluded. MAIN OUTCOME MEASURES: Difference in PLR metric obtained from QP 30 min before and after DCA. RESULTS: Statistically significant difference was noted in the pre and post left eye readings for the minimum pupil size (a.k.a., pupil diameter on maximum constriction). The mean maximum constriction diameter prior to angiogram of 3.2 (1.1) mm was statistically larger than after angiogram (2.9 (1.0) mm; p<0.05); however, this was not considered clinically significant. Comparisons for all other PLR metrics pre and post angiogram demonstrated no significant difference. Using change in NPi pre and post angiogram (Δpre=0.05 (0.77) vs Δpost=0.08 (0.67); p=0.62), we calculated the effect size as 0.042. Hence, detecting a statistically significant difference in NPi, if a difference exists, would require a sample size of ~6000 patients. CONCLUSIONS: Our study provides supportive data that in an uncomplicated angiogram, even with intervention, there is no effect on the PLR.

The metabolite vanillic acid regulates Acinetobacter baumannii surface attachment.

The nosocomial bacterium Acinetobacter baumannii is protected from antibiotic treatment by acquiring antibiotic resistances and by forming biofilms. Cell attachment, one of the first steps in biofilm formation, is normally induced by environmental metabolites. We hypothesized that vanillic acid (VA), the oxidized form of vanillin and a widely available metabolite, may play a role in A. baumannii cell attachment. We first discovered that A. baumannii actively breaks down VA through the evolutionarily conserved vanABKP genes. These genes are under the control of the repressor VanR, which we show binds directly to VanR binding sites within the vanABKP genes bidirectional promoter. VA in turn counteracts VanR inhibition. We identified a VanR binding site and searched for it throughout the genome, especially in pili encoding promoter genes. We found a VanR binding site in the pilus encoding csu operon promoter and showed that VanR binds specifically to it. As expected, a strain lacking VanR overproduces Csu pili and makes robust biofilms. Our study uncovers the role that VA plays in facilitating the attachment of A. baumannii cells to surfaces, a crucial step in biofilm formation. These findings provide valuable insights into a previously obscure catabolic pathway with significant clinical implications.

Natural Histories and Disease Complications in a Cohort of 151 Children With Gastric or Duodenal Eosinophilia.

INTRODUCTION: Eosinophilic gastritis (EoG) and duodenitis (EoD) are rare conditions that are poorly understood. Our aim was to describe the natural history of children with varying degrees of gastric or duodenal eosinophilia with respect to disease complications and histologic and endoscopic longitudinal trajectories. METHODS: The electronic medical record at a tertiary children's hospital was queried to identify patients with EoG, EoD, or EoG + EoD who were cared for between January 2010 and 2022. Multiple logistic regression was performed to explore associations between baseline features and persistence/recurrence of eosinophilia or complications remote from diagnosis. RESULTS: We identified 151 patients: 92 with EoG, 24 with EoD, 12 with EoG + EoD, and 23 with tissue eosinophilia but did not meet histologic criteria for EoG or EoD (low grade). The average age at diagnosis was 10.6 years, and average follow-up was 5.8 years. Twenty-five percent of patients with EoG or EoD had persistence/recurrence of eosinophilia; this was associated with increases in the EoG Endoscopic Reference Score (adjusted odds ratio [aOR] 1.34, confidence interval [CI] 1.03-1.74) on diagnostic endoscopy. Eighteen percent suffered from disease complications, and development of late complications was associated with presenting with a complication (aOR 9.63, CI 1.09-85.20), severity of duodenal endoscopic abnormalities (aOR 8.74, CI 1.67-45.60), and increases in the EoG Endoscopic Reference Score (aOR 1.70, CI 1.11-2.63). DISCUSSION: Patients with gastric and duodenal eosinophilia should be followed closely to monitor for recurrence and complications, especially those presenting with endoscopic abnormalities or complications.

In vivo delivery of engineered synthetic DNA-encoded SARS-CoV-2 monoclonal antibodies for pre-exposure prophylaxis in non-human primates.

COVID-19 remains a major public health concern. Monoclonal antibodies have received emergency use authorization (EUA) for pre-exposure prophylaxis against COVID-19 among high-risk groups for treatment of mild to moderate COVID-19. In addition to recombinant biologics, engineered synthetic DNA-encoded antibodies (DMAb) are an important strategy for direct in vivo delivery of protective mAb. A DMAb cocktail was synthetically engineered to encode the immunoglobulin heavy and light chains of two different two different Fc-engineered anti-SARS-CoV-2 antibodies. The DMAbs were designed to enhance in vivo expression and delivered intramuscularly to cynomolgus and rhesus macaques with a modified in vivo delivery regimen. Serum levels were detected in macaques, along with specific binding to SARS-CoV-2 spike receptor binding domain protein and neutralization of multiple SARS-CoV-2 variants of concern in pseudovirus and authentic live virus assays. Prophylactic administration was protective in rhesus macaques against signs of SARS-CoV-2 (USA-WA1/2020) associated disease in the lungs. Overall, the data support further study of DNA-encoded antibodies as an additional delivery mode for prevention of COVID-19 severe disease. These data have implications for human translation of gene-encoded mAbs for emerging infectious diseases and low dose mAb delivery against COVID-19.

RecA levels modulate biofilm development in Acinetobacter baumannii.

Infections caused by Acinetobacter baumannii, a Gram-negative opportunistic pathogen, are difficult to eradicate due to the bacterium's propensity to quickly gain antibiotic resistances and form biofilms, a protective bacterial multicellular community. The A. baumannii DNA damage response (DDR) mediates the antibiotic resistance acquisition and regulates RecA in an atypical fashion; both RecALow and RecAHigh cell types are formed in response to DNA damage. The findings of this study demonstrate that the levels of RecA can influence formation and dispersal of biofilms. RecA loss results in surface attachment and prominent biofilms, while elevated RecA leads to diminished attachment and dispersal. These findings suggest that the challenge to treat A. baumannii infections may be explained by the induction of the DDR, common during infection, as well as the delicate balance between maintaining biofilms in low RecA cells and promoting mutagenesis and dispersal in high RecA cells. This study underscores the importance of understanding the fundamental biology of bacteria to develop more effective treatments for infections.

Descriptive study of the real-world, long-term cost estimates and duration of use for hormonal and nonhormonal intrauterine devices using US commercial insurance claims.

BACKGROUND: Intrauterine devices (IUDs) have comparable efficacy to permanent surgical contraceptive methods; however, long-term costs are infrequently considered. Existing estimates inconsistently account for costs outside of IUD insertion or removal, actual duration of use, or differences between hormonal and nonhormonal IUDs. OBJECTIVE: To describe health care resource utilization and commercial payer costs that arise throughout hormonal and nonhormonal IUD use. METHODS: In this retrospective cohort study, paid claims data (Merative, MarketScan) from a large US commercial claims database were evaluated between 2013 and 2019. Claims were included from individuals aged 12 to 45 years who had an IUD inserted in 2014, continuous insurance coverage for 1 year prior to insertion and throughout follow-up, and no insertion, removal, or reinsertion in the previous year. Procedures and services that could be IUD-related were identified using Current Procedural Terminology and International Classification of Diseases, Ninth and Tenth Edition codes. Duration of IUD use was evaluated by Kaplan-Meier analysis of time to IUD removal. Event rates were determined for identified procedures and services; costs were calculated as the sum of payer reimbursements per enrolled individual. All IUD types available during the study period were described: 2 hormonal IUDs (52-mg and 13.5-mg levonorgestrel-releasing [LNG]) and the nonhormonal (380-mm2 copper) IUD. RESULTS: Of 195,009 individuals meeting the age requirement and receiving an IUD in 2014, 63,386 met the inclusion criteria and 53,744 had their IUD type on record-42,777 (67.5%) 52-mg LNG, 2,932 (4.6%) 13.5-mg LNG, and 8,035 (12.7%) nonhormonal IUD users. Despite differences in their indicated duration (13.5-mg LNG, 3 years; 52-mg LNG, 5 years; and nonhormonal, 10 years), most individuals had their IUD removed before its indicated full duration of use (13.5-mg LNG, 56.1%; 52-mg LNG, 61.3%; nonhormonal [at 5 years], 54.6%). The event rate per 100 individuals during the follow-up period was highest for abnormal uterine bleeding (16.2), ovarian cysts (9.3), and surgical management of uterine perforations (4.5). IUD insertion costs (mean ± SE) per enrolled individual for the 13.5-mg LNG, 52-mg LNG, and nonhormonal IUDs were $931 ± $9, $1,107 ± $4, and $897 ± $6, respectively. Cumulative mean ± SE 5-year postinsertion costs for the 13.5-mg LNG, 52-mg LNG, and nonhormonal IUDs were $2,892 ± $232, $1,514 ± $31, and $1,389 ± $97, respectively, among the remaining enrolled individuals. CONCLUSIONS: In this descriptive study of commercially insured IUD users, at least half had their IUD removed before its indicated duration. IUD improvements that reduce the frequency of abnormal uterine bleeding, ovarian cysts, and uterine perforations may help reduce long-term IUD costs.

Data Equity for Asian American and Native Hawaiian and Other Pacific Islander People in Reproductive Health Research.

Though racial and ethnic disparities in sexual and reproductive health outcomes are receiving greater interest and research funding, the experiences of Asian American and Native Hawaiian and Other Pacific Islander (NHPI) people are often combined with those of other racial and ethnic minority groups or excluded from data collection altogether. Such treatment is often rationalized because Asian American and NHPI groups comprise a smaller demographic proportion than other racial or ethnic groups, and the model minority stereotype assumes that these groups have minimal sexual and reproductive health needs. However, Asian American and NHPI people represent the fastest-growing racial-ethnic groups in the United States, and they face disparities in sexual and reproductive health access, quality of care, and outcomes compared with those of other races and ethnicities. Disaggregating further by ethnicity, people from certain Asian American and NHPI subgroups face disproportionately poor reproductive health outcomes that suggest the need for culturally targeted exploration of the unique drivers of these inequities. This commentary highlights the evidence for sexual and reproductive health disparities both in and between Asian American and NHPI groups. We also examine the failures of national data sets and clinical studies to recruit Asian American and NHPI people in proportion to their share of the U.S. population or to consider how the cultural and experiential diversity of Asian American and NHPI people influence sexual and reproductive health. Lastly, we provide recommendations for the equitable inclusion of Asian American and NHPI people to promote and systematize the study and reporting of sexual and reproductive health behaviors and outcomes in these culturally, religiously, and historically diverse groups.

Cerebrospinal fluid as vaginal discharge: ventriculoperitoneal shunt migration following Cesarean section.

Congenital hydrocephalus was once a permanently disabling and even fatal disease. With the advent of ventriculoperitoneal shunts, affected women are now surviving to their reproductive years and beyond. Pregnancy outcomes in this population are generally positive. However due to possible shunt complications, including infection, migration, and organ perforation, perinatal care for pregnant individuals with a ventriculoperitoneal shunt is complex and requires input from both obstetric and neurosurgical providers. We present the case of a 28-year-old G1P1 with a history of congenital hydrocephalus and ventriculoperitoneal shunt who presented to the emergency department at two months postpartum with clear fluid leaking from her vagina. The shunt's distal end had migrated and perforated the uterus causing cerebrospinal fluid to leak into the uterine cavity. Surgical repair was required of both the uterine hysterotomy and ventriculoperitoneal shunt, and the patient's symptoms ultimately resolved. Patients with a history of shunt placement who later undergo abdominal surgery, including cesarean section, are at risk for shunt complications. Shunt-dependent patients presenting in the post-partum period with new neurological or abdominopelvic complaints should undergo evaluation by a multidisciplinary team.

Complete sequence of the closed circular extrachromosomal element (CERE) of Naegleria australiensis De Jonckheere (strain PP 397).

Ribosomal RNA is not encoded in chromosomal DNA in amoebae of the Naegleria genus but the rRNA genes are located on closed circular extrachromosomal ribosomal DNA (rDNA)-containing elements (CERE). In this report, we describe the sequence of the CERE of Naegleria australiensis De Jonckheere (strain PP397).

Expectations for family building, assisted reproduction, and adoption among lesbians in the National Survey of Family Growth, 2017-2019.

Objective: To characterize the family-building goals and experiences of lesbians compared with those of heterosexual females in the United States. Design: Secondary analysis of nationally representative, cross-sectional survey data. Setting: National Survey of Family Growth 2017-2019. Patients: 159 reproductive-age lesbian respondents and 5,127 reproductive-age heterosexual respondents. Interventions: We characterized family-building goals and the use of assisted reproduction and adoption among lesbians using nationally representative female respondent data from the 2017-2019 National Survey of Family Growth. We performed bivariate analyses examining variations in these outcomes between lesbian and heterosexual individuals. Main Outcome Measures: Wantedness of children, use of assisted reproductive technology, and pursuit of adoption among reproductive-age lesbian and heterosexual participants. Results: We identified 159 reproductive-age lesbian respondents of the National Survey of Family Growth, representing 2.3% or approximately 1.75 million US individuals of reproductive age. The lesbian respondents were younger, less religious, and less likely to have children than heterosexual respondents. These groups did not differ significantly by race/ethnicity, education, or income. More than half of the individuals reported wanting a child in the future, with proportions similar between the lesbian and heterosexual individuals (48% vs. 51%, respectively; P = .52). Accordingly, 18% of both the lesbian and heterosexual individuals reported that they would be greatly bothered if they were unable to have children. Nevertheless, health care providers reportedly asked the lesbians about their desire to get pregnant less frequently than they asked the heterosexual individuals (21% vs. 32%, respectively; P = .04). Only 26% of the lesbians had ever been pregnant compared with 64% of the heterosexual individuals (P<.01). Approximately one third (31%) of lesbians with medical insurance were seeking reproductive services compared with 10% of heterosexual individuals (P = .05). Lesbians were significantly more likely to be seeking adoption than heterosexual individuals (7.0% vs. 1.3%, respectively; P = .01), although they were more likely to report being turned down (17% vs. 10%, respectively; P = .03), not knowing why they were unable to adopt (19% vs. 1%, respectively; P = .02), and quitting because of the adoption process (100% vs. 45%, respectively; P = .04). Conclusions: Approximately half of US females of reproductive age desire to have a child, a proportion that is not different between lesbian and heterosexual individuals. However, fewer lesbians are asked about their desires to get pregnant, and fewer ever become pregnant. Lesbians are significantly more likely to pursue assisted reproductive services when covered by insurance and more likely to seek adoption. Unfortunately, lesbians are more likely to face challenges with adoption.

Competition and reward structures nearly eliminate time-on-task performance decrements: Implications for theories of vigilance and mental effort.

Across four experiments, we manipulated features of a simple reaction time (RT) task to examine the effects of such features on sustained attention. In Experiment 1, we created simple RT "game" that pitted participants against two computerized avatars. In one condition, participants were awarded points, while the other condition did not receive points. Performance in the two conditions did not differ, but both conditions showed shorter RTs and shallower time-on-task performance decrements compared to a standard psychomotor vigilance task. In Experiment 2, we removed the competitive feature but retained the point system. In this case, participants without a point system showed a steeper performance decrement than those with a point system. Experiments 3 and 4 replicated these effects and corroborated their findings with pupillometry. Participants in both conditions of Experiment 3 (competitive task) and the points condition of Experiment 4 showed larger task-evoked pupillary responses than participants in the no-points condition of Experiment 4. These findings challenge the notion that time-on-task performance decrements are caused by resource depletion (Smit et al., 2004) and are better explained by motivational control (Hockey, 2011) or cost-benefit theories (Boksem & Tops, 2008; Kurzban et al., 2013) of mental effort and sustained attention. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Design of Beta-2 Microglobulin Adsorbent Protein Nanoparticles.

Beta-2 microglobulin (B2M) is an immune system protein that is found on the surface of all nucleated human cells. B2M is naturally shed from cell surfaces into the plasma, followed by renal excretion. In patients with impaired renal function, B2M will accumulate in organs and tissues leading to significantly reduced life expectancy and quality of life. While current hemodialysis methods have been successful in managing electrolyte as well as small and large molecule disturbances arising in chronic renal failure, they have shown only modest success in managing plasma levels of B2M and similar sized proteins, while sparing important proteins such as albumin. We describe a systematic protein design effort aimed at adding the ability to selectively remove specific, undesired waste proteins such as B2M from the plasma of chronic renal failure patients. A novel nanoparticle built using a tetrahedral protein assembly as a scaffold that presents 12 copies of a B2M-binding nanobody is described. The designed nanoparticle binds specifically to B2M through protein-protein interactions with nanomolar binding affinity (~4.2 nM). Notably, binding to the nanoparticle increases the effective size of B2M by over 50-fold, offering a potential selective avenue for separation based on size. We present data to support the potential utility of such a nanoparticle for removing B2M from plasma by either size-based filtration or by polyvalent binding to a stationary matrix under blood flow conditions. Such applications could address current shortcomings in the management of problematic mid-sized proteins in chronic renal failure patients.