HyperColorization: propagating spatially sparse noisy spectral clues for reconstructing hyperspectral images.

Hyperspectral cameras face challenging spatial-spectral resolution trade-offs and are more affected by shot noise than RGB photos taken over the same total exposure time. Here, we present a colorization algorithm to reconstruct hyperspectral images from a grayscale guide image and spatially sparse spectral clues. We demonstrate that our algorithm generalizes to varying spectral dimensions for hyperspectral images, and show that colorizing in a low-rank space reduces compute time and the impact of shot noise. To enhance robustness, we incorporate guided sampling, edge-aware filtering, and dimensionality estimation techniques. Our method surpasses previous algorithms in various performance metrics, including SSIM, PSNR, GFC, and EMD, which we analyze as metrics for characterizing hyperspectral image quality. Collectively, these findings provide a promising avenue for overcoming the time-space-wavelength resolution trade-off by reconstructing a dense hyperspectral image from samples obtained by whisk or push broom scanners, as well as hybrid spatial-spectral computational imaging systems.

Drosophila germ granules are assembled from protein components through different modes of competing interactions with the multi-domain Tudor protein.

Membraneless organelles are RNA-protein assemblies which have been implicated in post-transcriptional control. Germ cells form membraneless organelles referred to as germ granules, which contain conserved proteins including Tudor domain-containing scaffold polypeptides and their partner proteins that interact with Tudor domains. Here, we show that in Drosophila, different germ granule proteins associate with the multi-domain Tudor protein using different numbers of Tudor domains. Furthermore, these proteins compete for interaction with Tudor in vitro and, surprisingly, partition to distinct and poorly overlapping clusters in germ granules in vivo. This partition results in minimization of the competition. Our data suggest that Tudor forms structurally different configurations with different partner proteins which dictate different biophysical properties and phase separation parameters within the same granule.

Mini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement.

There are 3 physiological waves of central hypothalamic-pituitary-gonadal (HPG) axis activity over the lifetime. The first occurs during fetal life, the second-termed "mini-puberty"-in the first months after birth, and the third at puberty. After adolescence, the axis remains active all through adulthood. Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by a deficiency in hypothalamic gonadotropin-releasing hormone (GnRH) secretion or action. In cases of severe CHH, all 3 waves of GnRH pulsatility are absent. The absence of fetal HPG axis activation manifests in around 50% of male newborns with micropenis and/or undescended testes (cryptorchidism). In these boys, the lack of the mini-puberty phase accentuates testicular immaturity. This is characterized by a low number of Sertoli cells, which are important for future reproductive capacity. Thus, absent mini-puberty will have detrimental effects on later fertility in these males. The diagnosis of CHH is often missed in infants, and even if recognized, there is no consensus on optimal therapeutic management. Here we review physiological mini-puberty and consequences of central HPG axis disorders; provide a diagnostic approach to allow for early identification of these conditions; and review current treatment options for replacement of mini-puberty in male infants with CHH. There is evidence from small case series that replacement with gonadotropins to mimic "mini-puberty" in males could have beneficial outcomes not only regarding testis descent, but also normalization of testis and penile sizes. Moreover, such therapeutic replacement regimens in disordered mini-puberty could address both reproductive and nonreproductive implications.

Photophysical properties of DAPI in PVA films. Possibility of room temperature phosphorescence.

We studied the spectral properties of 4'-6-diamidino-2-phenylindole (DAPI) in poly (vinyl alcohol) (PVA) films. Absorption and fluorescence spectra, emission and excitation spectra, quantum yield, and fluorescence lifetime have been characterized. An efficient room temperature phosphorescence (RTP) of DAPI has been observed with UV and blue light excitations. A few hundred millisecond phosphorescence lifetime enables a gated detection with sufficient background reduction. We found the phosphorescent Quantum Yield of DAPI in PVA Film to be 0.0009.

Discussion of an approach to starting a JEDI inventory in a College of Pharmacy.

Problem description\The University of Nebraska College of Pharmacy is interested in conducting and learning from an inventory of Justice, Equity, Diversity, and Inclusion (JEDI) within the college. QUALITY IMPROVEMENT METHODS: An extensive literature review was undertaken to define the terms included in JEDI and to craft a listing of ideal inventory components. RESULTS OF CQI INQUIRY: The terms used in JEDI were defined and a list of 148 ideal inventory components was created. This list is further segmented by the JEDI components themselves and by five assessment factors including: representation, curriculum & education, policies & procedures, support & resources, and college climate. INTERPRETATION AND DISCUSSION: The attempt to create an ideal listing of JEDI inventory components resulted in an unusably large number of potential items. This occurred intentionally to allow the next steps in the longitudinal creation of a workable, quantifiable, and evaluative JEDI inventory process. Describing these preliminary efforts are important in the ultimate acceptance of the results of the JEDI inventory. CONCLUSION: Deliberate and extensive listing of initial aspirations for a JEDI inventory of a College of Pharmacy or any institution allows for sufficient input and breadth to help assure that no significant factor is overlooked as the process is refined.

Epoprostenol (Prostacyclin Analog) as a Sole Anticoagulant in Continuous Renal Replacement Therapy for Critically Ill Children With Liver Disease: Single-Center Retrospective Study, 2010-2019.

OBJECTIVES: Despite deranged coagulation, children with liver disease undergoing continuous renal replacement therapy (CRRT) are prone to circuit clotting. Commonly used anticoagulants (i.e., heparin and citrate) can have side effects. The aim of this study was to describe our experience of using epoprostenol (a synthetic prostacyclin analog) as a sole anticoagulant during CRRT in children with liver disease. DESIGN: Single-center, retrospective study, 2010-2019. SETTING: Sixteen-bedded PICU within a United Kingdom supra-regional center for pediatric hepatology. PATIENTS: Children with liver disease admitted to PICU who underwent CRRT anticoagulation with epoprostenol. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Regarding CRRT, we assessed filter life duration, effective 60-hour filter survival, and effective solute clearance. We also assessed the frequency of major or minor bleeding episodes per 1,000 hours of CRRT, the use of platelet and RBC transfusions, and the frequency of hypotensive episodes per 1,000 hours of CRRT. In the 10 years 2010-2019, we used epoprostenol anticoagulation during 353 filter episodes of CRRT, lasting 18,508 hours, in 96 patients (over 108 admissions). Median (interquartile range [IQR]) filter life was 48 (IQR 32-72) hours, and 22.9% of filters clotted. Effective 60-hour filter survival was 60.5%.We identified that 5.9% of filters were complicated by major bleeding (1.13 episodes per 1,000 hr of CRRT), 5.1% (0.97 per 1,000 hr) by minor bleeding, and 11.6% (2.22 per 1,000 hr) by hypotension. There were no differences in filter life or clotting between patients with acute liver failure and other liver diseases; there were no differences in rates of bleeding, hypotension, or transfusion when comparing patients with initial platelets of ≤ 50 × 109 per liter to those with a higher initial count. CONCLUSIONS: Epoprostenol, or prostacyclin, as the sole anticoagulant for children with liver disease receiving CRRT in PICU, results in a good circuit life, and complications such as bleeding and hypotension are similar to reports using other anticoagulants, despite concerns about coagulopathy in this cohort.

Transformations of sensory information in the brain suggest changing criteria for optimality.

Neurons throughout the brain modulate their firing rate lawfully in response to sensory input. Theories of neural computation posit that these modulations reflect the outcome of a constrained optimization in which neurons aim to robustly and efficiently represent sensory information. Our understanding of how this optimization varies across different areas in the brain, however, is still in its infancy. Here, we show that neural sensory responses transform along the dorsal stream of the visual system in a manner consistent with a transition from optimizing for information preservation towards optimizing for perceptual discrimination. Focusing on the representation of binocular disparities-the slight differences in the retinal images of the two eyes-we re-analyze measurements characterizing neuronal tuning curves in brain areas V1, V2, and MT (middle temporal) in the macaque monkey. We compare these to measurements of the statistics of binocular disparity typically encountered during natural behaviors using a Fisher Information framework. The differences in tuning curve characteristics across areas are consistent with a shift in optimization goals: V1 and V2 population-level responses are more consistent with maximizing the information encoded about naturally occurring binocular disparities, while MT responses shift towards maximizing the ability to support disparity discrimination. We find that a change towards tuning curves preferring larger disparities is a key driver of this shift. These results provide new insight into previously-identified differences between disparity-selective areas of cortex and suggest these differences play an important role in supporting visually-guided behavior. Our findings emphasize the need to consider not just information preservation and neural resources, but also relevance to behavior, when assessing the optimality of neural codes.

Gonadotropins for pubertal induction in males with hypogonadotropic hypogonadism: systematic review and meta-analysis.

OBJECTIVE: Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism. DESIGN: Systematic review and meta-analysis. METHODS: A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713). RESULTS: After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high. CONCLUSIONS: This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.

Home-based arm cycling exercise improves trunk control in persons with incomplete spinal cord injury: an observational study.

Arm cycling is used for cardiorespiratory rehabilitation but its therapeutic effects on the neural control of the trunk after spinal cord injury (SCI) remain unclear. We investigated the effects of single session of arm cycling on corticospinal excitability, and the feasibility of home-based arm cycling exercise training on volitional control of the erector spinae (ES) in individuals with incomplete SCI. Using transcranial magnetic stimulation, we assessed motor evoked potentials (MEPs) in the ES before and after 30 min of arm cycling in 15 individuals with SCI and 15 able-bodied controls (Experiment 1). Both groups showed increased ES MEP size after the arm cycling. The participants with SCI subsequently underwent a 6-week home-based arm cycling exercise training (Experiment 2). MEP amplitudes and activity of the ES, and movements of the trunk during reaching, self-initiated rapid shoulder flexion, and predicted external perturbation tasks were measured. After the training, individuals with SCI reached further and improved trajectory of the trunk during the rapid shoulder flexion task, accompanied by increased ES activity and MEP amplitudes. Exercise adherence was excellent. We demonstrate preserved corticospinal drive after a single arm cycling session and the effects of home-based arm cycling exercise training on trunk function in individuals with SCI.

Teaching in Paediatrics for UK Foundation Doctors: A Cross-Sectional Study.

Background Most doctors will care for children regularly during their careers in settings such as the emergency department, general practice, surgery, or, for a minority, during paediatric specialist training. As such, exposure to topics related to child health ought to be part of the broad curriculum of learning offered to UK Foundation Programme doctors. Objective This study aimed to quantify teaching in paediatrics that is accessed by Foundation doctors. Methods A cross-sectional electronic survey of foundation year one or two (F1/F2) doctors at the end of the 2020-2021 academic year. Ethical approval was granted by the Imperial College London (ICL) Education Ethics Review Process (EERP 2021-082). Results Two-hundred and five Foundation doctors completed the survey, from 16 of the 18 Foundation schools. Respondents attended a median of two hours (interquartile range (IQR) 0-10) of paediatric teaching during the past 12 months, including a median of one hour (IQR 0-2) of core teaching and a median of one hour (IQR 0-9) of non-core teaching. Those who had worked in a paediatric post in the past 12 months, or who were interested in Paediatrics as a career, attended more median hours of teaching. Conclusions Although many doctors will care for children routinely during their later careers, the number of teaching hours in paediatrics experienced by Foundation doctors is low. The UK Foundation Programme should incorporate more teaching in paediatrics to increase exposure to child health amongst newly graduated and as-yet unspecialised doctors.

Effect of annealing on the room temperature luminescence of coumarin 106 in PVA films.

We studied the effect of annealing on the luminescence of Coumarin 106 (C106) in poly (vinyl alcohol) films (PVA films). The samples and reference polymer films were treated at temperatures between 100 °C and 150 °C (212 F and 302 F) for various times. After cooling and smoothing, the samples and references were measured at room temperature. We observed that the PVA polymer (reference films) changes its optical properties with annealing at higher temperatures, affecting the baselines in absorption and the backgrounds in emission measurements. This requires precise background subtractions and control of the signal-to-noise ratio. Whereas the fluorescence intensity of C106 in PVA films modestly decreases with annealing, the phosphorescence depends dramatically and progressively increases by many folds. The fluorescence quantum yields and lifetimes decrease with the annealing, which suggests an increase in the non-radiative processes in the singlet excited state S1. The increase in the phosphorescence intensities results from increased intersystem crossing (ISC), which also decreases fluorescence. We also studied the effect of annealing on phosphorescence with the directly excited triplet state of C106. In this case, two processes are affected by annealing, S0→T1absorption and T1→S0phosphorescence. The long-wavelength excitation (475 nm) avoids PVA polymer excitation. The phosphorescence lifetime decreases with annealing while the phosphorescence intensity increases. These changes suggest that the radiative rate of T1→ S0increases with annealing.

Safety and efficacy of continuous renal replacement therapy for children less than 10 kg using standard adult machines.

Continuous Renal Replacement Therapy (CRRT) machines are used off-label in patients less than 20 kg. Infant and neonates-dedicated CRRT machines are making their way into current practice, but these machines are available only in select centres. This study assesses the safety and efficacy of CRRT using adult CRRT machines in children ≤ 10 kg and to determines the factors affecting the circuit life in these children. DESIGN: Retrospective cohort study of children ≤ 10 kg who received CRRT (January 2010-January 2018) at a PICU in a tertiary care centre in London, UK. Primary diagnosis, markers for illness severity, CRRT characteristics, length of PICU admission and survival to PICU discharge were collected. Descriptive analysis compared survivors and non-survivors. A subgroup analysis compared children ≤ 5 kg to children 5-10 kg. Fifty-one patients ≤ 10 kg received 10,328 h of CRRT, with median weight of 5 kg. 52.94% survived to hospital discharge. Median circuit life was 44 h (IQR 24-68). Bleeding episodes occurred with 6.7% of sessions and hypotension for 11.9%. Analysis of efficacy showed a reduction in fluid overload at 48 h (P = 0.0002) and serum creatinine at 24 and 48 h (P = 0.001). Blood priming was deemed to be safe as serum potassium decreased at 4 h (P = 0.005); there was no significant change in serum calcium. Survivors had a lower PIM2 score at PICU admission (P < 0.001) and had longer PICU length of stay (P < 0.001).    Conclusion: Pending neonatal and infant dedicated CRRT machines, CRRT can be safely and effectively applied to children weighing ≤ 10 kg using adult-sized CRRT machines. WHAT IS KNOWN: • Continuous Renal Replacement Therapy can be used for a variety of renal and non-renal indications to improve outcomes for children in the paediatric intensive care unit. These include, persistent oliguria, fluid overload, hyperkalaemia, metabolic acidosis, hyperlactatemia, hyperammonaemia, and hepatic encephalopathy. • Young children ≤ 10 kg are most often treated using standard adult machines, off-label. This potentially places them at risk of side effects due to high extracorporeal circuit volumes, relatively higher blood flows, and difficulty in achieving vascular access. WHAT IS NEW: • This study found that standard adult machines were effective in reducing fluid overload and creatinine in children ≤ 10 kg. This study also assessed safety of blood priming in this group and found no evidence of an acute fall in haemoglobin or calcium, and a fall in serum potassium by a median of 0.3 mmol/L. The frequency of bleeding episodes was 6.7%, and hypotension requiring vasopressors or fluid resuscitation occurred with 11.9% of treatment sessions. • These findings suggest that adult CRRT machines are sufficiently safe and efficacious for routine use in PICU for children ≤ 10 kg and suggest that further research is undertaken, regarding the routine rollout of dedicated machines.

Building referral mechanisms for neonatal care in humanitarian emergency settings: A systematic review.

AIM: During humanitarian emergencies, women and children are particularly vulnerable to health complications and neonatal mortality rates have been shown to rise. Additionally, health cluster partners face challenges in coordinating referrals, both between communities and camps to health facilities and across different levels of health facilities. The purpose of this review was to identify the primary referral needs of neonates during humanitarian emergencies, current gaps and barriers, and effective mechanisms for overcoming these barriers. METHODS: A systematic review was performed using four electronic databases (CINAHL, EMBASE, Medline, and Scopus) between June and August 2019 (PROSPERO registration number CRD42019127705). Title, abstract, and full text screening were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The target population was neonates born during humanitarian emergencies. Studies from high-income countries and prior to 1991 were excluded. The STROBE checklist was used to assess for risk of bias. RESULTS: A total of 11 articles were included in the analysis; these were mainly cross-sectional, field-based studies. The primary needs identified were referrals from homes to health facilities before and during labour, and inter-facility referrals after labour to more specialised services. Some of the main barriers included a lack of roads and infrastructure for transport, staff shortages-especially among more specialised services, and a lack of knowledge among patients for self-referral. Mechanisms for addressing these needs and gaps included providing training for community healthcare workers (CHWs) or traditional birth attendants to identify and address antenatal and post-natal complications; education programmes for pregnant women during the antenatal period; and establishing ambulance services in partnership with local Non-Governmental Organizations. CONCLUSION: This review benefited from a strong consensus among selected studies but was limited in the quality of data and types of data that were reported. Based on the above findings, the following recommendations were compiled: Focus on local capacity-building programmes to address programmes acutely. Recruit CHWs to raise awareness of neonatal complications among pregnant women. Upskill CHWs to provide timely, appropriate and quality care during humanitarian emergencies.

Transformations of sensory information in the brain reflect a changing definition of optimality.

Neurons throughout the brain modulate their firing rate lawfully in response to changes in sensory input. Theories of neural computation posit that these modulations reflect the outcome of a constrained optimization: neurons aim to efficiently and robustly represent sensory information under resource limitations. Our understanding of how this optimization varies across the brain, however, is still in its infancy. Here, we show that neural responses transform along the dorsal stream of the visual system in a manner consistent with a transition from optimizing for information preservation to optimizing for perceptual discrimination. Focusing on binocular disparity - the slight differences in how objects project to the two eyes - we re-analyze measurements from neurons characterizing tuning curves in macaque monkey brain regions V1, V2, and MT, and compare these to measurements of the natural visual statistics of binocular disparity. The changes in tuning curve characteristics are computationally consistent with a shift in optimization goals from maximizing the information encoded about naturally occurring binocular disparities to maximizing the ability to support fine disparity discrimination. We find that a change towards tuning curves preferring larger disparities is a key driver of this shift. These results provide new insight into previously-identified differences between disparity-selective regions of cortex and suggest these differences play an important role in supporting visually-guided behavior. Our findings support a key re-framing of optimal coding in regions of the brain that contain sensory information, emphasizing the need to consider not just information preservation and neural resources, but also relevance to behavior.

Association between caregiver and household alcohol use and child behavior problems in KwaZulu Natal, South Africa.

We explored the association between household alcohol use and behavior problems among South-African children, using data from the Asenze study, a population-based cohort of South African children and their caregivers. Household alcohol use and child behavior were assessed when children were 6-8 years old. To examine the association, we performed linear regressions. The sample included 1383 children with complete data under the care of 1251 adults. Children living in a household where self-reported caregiver alcohol use was scored as hazardous (4.6%) had higher levels of problem behavior (ß = 1.94, 95% CI 0.06-3.82). There were no statistically significant associations between reported hazardous alcohol use by another member of the household (14.5%) and child problem behavior. Hazardous household alcohol use was associated with child problem behavior and this effect appeared to be mainly driven by primary caregiver use.

Standard and Hypofractionated Dose Escalation to Intraprostatic Tumor Nodules in Localized Prostate Cancer: 5-Year Efficacy and Toxicity in the DELINEATE Trial.

PURPOSE: Our purpose was to report 5-year efficacy and toxicity of intraprostatic lesion boosting using standard and hypofractionated radiation therapy. METHODS AND MATERIALS: DELINEATE (ISRCTN 04483921) is a single center phase 2 multicohort study including standardly fractionated (cohort A: 74 Gy/37F to prostate and seminal vesicles [PSV]; cohort C 74 Gy/37F to PSV plus 60 Gy/37F to pelvic lymph nodes) and moderately hypofractionated (cohort B: 60 Gy/20F to PSV) prostate intensity-modulated radiation therapy patients with National Comprehensive Cancer Network intermediate/high-risk disease. Patients received an integrated boost of 82 Gy (cohorts A and C) or 67 Gy (cohort B) to multiparametric magnetic resonance imaging identified lesion(s). Primary endpoint was late Radiation Therapy Oncology Group (RTOG) gastrointestinal (GI) toxicity at 1 year. Secondary endpoints were acute and late toxicity (clinician and patient reported) and freedom from biochemical/clinical failure at 5 years. RESULTS: Two hundred and sixty-five men were recruited and 256 were treated (55 cohort A, 153 cohort B, and 48 cohort C). Median follow-up for each cohort was >5 years. Cumulative late RTOG grade 2+ GI toxicity at 1 year was 3.6% (95% confidence interval [CI], 0.9%-13.8%) (cohort A), 7.2% (95% CI, 4%-12.6%) (cohort B), and 8.4% (95% CI, 3.2%-20.8%) (cohort C). Cumulative late RTOG grade 2+ GI toxicity to 5 years was 12.8% (95% CI, 6.3%-25.1%) (cohort A), 14.6% (95% CI, 9.9%-21.4%) (cohort B), and 20.7% (95% CI, 11.2%-36.2%) (cohort C). Cumulative RTOG grade 2+ genitourinary toxicity to 5 years was 12.9% (95% CI, 6.4%-25.2%) (cohort A), 18.2% (95% CI, 12.8%-25.4%) (cohort B), and 18.2% (95% CI, 9.5%-33.2%) (cohort C). Five-year freedom from biochemical/clinical failure was 98.2% (95% CI, 87.8%-99.7%) (cohort A), 96.7% (95% CI, 91.3%- 98.8%) (cohort B), and 95.1% (95% CI, 81.6-98.7%) (cohort C). CONCLUSIONS: The DELINEATE trial has shown safety, tolerability, and feasibility of focal boosting in 20 or 37 fractions. Efficacy results indicate a low chance of prostate cancer recurrence 5 years after radiation therapy. Evidence from ongoing phase 3 randomized trials is awaited.

Optic flow in the natural habitats of zebrafish supports spatial biases in visual self-motion estimation.

Animals benefit from knowing if and how they are moving. Across the animal kingdom, sensory information in the form of optic flow over the visual field is used to estimate self-motion. However, different species exhibit strong spatial biases in how they use optic flow. Here, we show computationally that noisy natural environments favor visual systems that extract spatially biased samples of optic flow when estimating self-motion. The performance associated with these biases, however, depends on interactions between the environment and the animal's brain and behavior. Using the larval zebrafish as a model, we recorded natural optic flow associated with swimming trajectories in the animal's habitat with an omnidirectional camera mounted on a mechanical arm. An analysis of these flow fields suggests that lateral regions of the lower visual field are most informative about swimming speed. This pattern is consistent with the recent findings that zebrafish optomotor responses are preferentially driven by optic flow in the lateral lower visual field, which we extend with behavioral results from a high-resolution spherical arena. Spatial biases in optic-flow sampling are likely pervasive because they are an effective strategy for determining self-motion in noisy natural environments.

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder: A Randomized Clinical Trial.

Importance: Despite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown. Objective: To test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD. Design, Setting, and Participants: This randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021. Interventions: A 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion. Main Outcomes and Measures: Blood oxygen level-dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli. Results: Of the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007). Kisspeptin's enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects. Conclusions and Relevance: These findings lay the foundations for clinical applications for kisspeptin in women with HSDD. Trial Registration: ISRCTN trial registry identifier: ISRCTN17271094.