Genital Research Articles

Effect of Comprehensive HIV Prevention Information Package on Syphilis Infection Levels Among Youths in Kakamega and Kericho Counties, Kenya

The world's biggest threat to development and public health is HIV. Youth in sub-Saharan Africa are primarily affected by the HIV epidemic. Despite the availability of HIV prevention options, new infections among youth in Kenya only reduced by 56% between 2015 and 2021. Various HIV prevention interventions have been implemented among youth with little or no assessment of their effectiveness in reducing new HIV infections. The objective of the study was to evaluate the effect comprehensive HIV prevention information package of the package on syphilis infections levels among the youths in Kakamega and Kericho counties, Kenya. A non-randomized control trial was conducted with Kakamega as intervention and Kericho as Comparison County. The pretest questionnaire was administered in both intervention and control counties in December 2001. The posttest questionnaire was administered in both intervention and control counties after nine months of providing HIV prevention information package. Quantitative data was analyzed using descriptive and inferential statistics. Qualitative data was transcribed and analyzed thematically. There was significant increase in knowledge of sexually transmitted infections in intervention county (t = 3.340, P = 0.021). There was significant number of youth in Kakamega county who reported unusual sores in genital area at endline (t = 2.035, P = 0.043). Similarly, more youths sought treatment after experiencing the syphilis symptoms (t = 1.931, P = 0.054) at endline in Kakamega county. There were no significant differences in the number of youths in Kericho county at endline who experienced unusual symptoms, sought treatment and informed their sexual partners (P > 0.05). The findings from the study will inform national rollout of the intervention to contribute to safer sexual behaviors among youth.

Male genitalia, hierarchical homology, and the anatomy of the bullet ant (Paraponera clavata; Hymenoptera, Formicidae).

The male genitalia of insects are among the most variable, complex, and informative character systems for evolutionary analysis and taxonomic purposes. Because of these general properties, many generations of systematists have struggled to develop a theory of homology and alignment of parts. This struggle continues to the present day, where fundamentally different models and nomenclatures for the male genitalia of Hymenoptera, for example, are applied. Here, we take a multimodal approach to digitalize and comprehensively document the genital skeletomuscular anatomy of the bullet ant (Paraponera clavata; Hymenoptera: Formicidae), including hand dissection, synchrotron radiation microcomputed tomography, microphotography, scanning electron microscopy,confocal laser scanning microscopy,and 3D-printing. Through this work, we generate several new concepts for the structure and form of the male genitalia of Hymenoptera, such as for the endophallic sclerite (=fibula ducti), which we were able to evaluate in detail for the first time for any species. Based on this phenomic anatomical study and comparison with other Holometabola and Hexapoda, we reconsider the homologies of insect genitalia more broadly, and propose a series of clarifications in support of the penis-gonopod theory of male genital identity. Specifically, we use the male genitalia of Paraponera and insects more broadly as an empirical case for hierarchical homology by applying and refining the 5-category classification of serial homologs from DiFriscoet al.(2023) (DLW23) to all of our formalized concepts. Through this, we find that: (1) geometry is a critical attribute to account for in ontology, especially as all individually identifiable attributes are positionally indexed hence can be recognized as homomorphic; (2) the definition of "structure" proposed by DLW23 is difficult to apply, and likely heterogeneous; and (3) formative elements, or spatially defined foldings or in- or evaginations of the epidermis and cuticle, are an important yet overlooked class of homomorphs. We propose a morphogenetic model for male and female insect genitalia, and a model analogous to gene-tree species-tree mappings for the hierarchical homology of male genitalia specifically. For all of the structures evaluated in the present study, we provide 3D-printable models - with and without musculature, and in various states of digital dissection - to facilitate the development of a tactile understanding. Our treatment of the male genitalia of P. clavata serves as a basic template for future phenomic studies of male insect genitalia, which will be substantially improved with the development of automation and collections-based data processing pipelines, that is,collectomics. The Hymenoptera Anatomy Ontology will be a critical resource to include in this effort, and in best practice concepts should be linked.

Characterization of urethra closure in female neonatal mice at histological and molecular levels.

Female hypospadias is a little-known and poorly studied birth defect. This research establishes an anatomical and molecular foundation for future research to investigate the origins of this defect. Hypospadias is a congenital anomaly of the external genitalia where the urethra does not properly close. In humans, hypospadias is mostly reported in male newborns, whereas in females hypospadias is rare, although it is generally considered to be under-reported. Improper urethra closure in the female genitalia can cause recurrent genitourinary tract infections and infertility. In mice, female hypospadias was induced by exposure to exogenous estrogenic compounds. Aside from the link between estrogen exposure and female hypospadias, the process of female urethra closure is largely unstudied, with the precise timing of urethra closure and associated molecular mechanisms remaining poorly understood. To address this gap, we determined when urethra closure occurs and identified gene expression patterns during the process of urethra closure in female neonatal mice from postnatal day (PND) 5 to 10. Using whole mount imaging and histology, we discovered that the initiation of urethra closure begins at PND7, and urethra closure is fully completed by PND10. To identify the genes associated with urethra closure, we conducted bulk RNA sequencing on female external genitalia prior to and after urethra closure. Gene ontology analyses revealed an increase in steroidogenic gene expression (Star, Hsd3b6, and Cyp17a1) during urethra closure, suggesting that the female genitalia locally produce steroids which could facilitate steroid signaling within the genitalia. With this study, we establish an anatomical timeline of female urethra closure and hypothesize a paracrine steroid signaling mechanism of urethra closure. These observations provide entry points to aid in further understanding external genital abnormalities, like hypospadias, in females.

Two new and unusual species of Tibelloides Mello-Leitão, 1939 (Araneae: Philodromidae)

Tibelloides Mello-Leitão, 1939 currently comprises four species of Neotropical grass-dwelling spiders. Herein, we describe and illustrate Tibelloides castelo sp. nov. with few records from Brazil (Minas Gerais, Piauí, Rio de Janeiro), and Tibelloides juatuba sp. nov., with records from Brazil (Minas Gerais, Pará, Paraná, Rondônia) and Paraguay (San Pedro). These two new species differ from the previously described ones by having body and legs conspicuously longer and thinner, male pedipalp without retrolateral marginal conductor, and female genitalia with compound copulatory ducts tubular and elongated.

A Phenomenon: What Are the Minuscule Grey Moths Abundant in the Dry Season in the Tropical Dry Forests of the Pacific Coast of Honduras?

Our investigation centered on the tropical dry forests along the Pacific coast of Honduras, aiming to elucidate the presence and abundance of minuscule grey moths during the dry season. Through specimen dissections and the taxonomic identification of the collected material, we have described three new species: Acalyptris podenasi sp. nov., A. palpiformis sp. nov., and A. tortoris sp. nov. Additionally, we documented two species previously known from neighboring countries, A. lascuevella Puplesis & Robinson and A. basicornis Remeikis & Stonis. The females of A. lascuevella were previously unknown and are documented here for the first time. Morphological examinations were complemented by DNA barcoding, particularly highlighting variation in A. lascuevella. The paper's primary significance lies not only in the description of new species but also in uncovering their taxonomic, morphological, and molecular importance. We found that these species are unique and indicative of the previously unstudied dry forests as a distinct ecosystem. Our findings revealed several novel atypical morphological traits within the studied Nepticulidae, including unusually large signum cells in the female genitalia, a dorso-ventrally divided uncus, and asymmetrical valvae in the male genitalia. These discoveries underscore the morphological diversity of Acalyptris Meyrick and their significance in evolutionary biology. Consequently, the paper addresses a previously unknown phenomenon of the occurrence and astonishing abundance of minuscule plant-mining micromoths in dry deciduous forests during the peak of the dry season. We hope that this paper will encourage Lepidoptera taxonomists to explore micromoths in other tropical dry forests, which, while limited in distribution, hold global importance. The paper is extensively illustrated with photographs of Acalyptris adults and their genitalia, along with maps, habitats, and molecular phylogenetic trees.

Two new species of the genus Parabitecta Hering in Draeseke from Southwestern China (Lepidoptera: Arctiinae: Lithosiini)

The footman moth genus Parabitecta Hering in Draeseke, 1926 is re-characterised and compared to the genera Tortrilema Volynkin, 2021 and Tortribitecta Volynkin, 2024. Two new species are described from Southwestern China (Yunnan Province): Parabitecta yanmena sp. n. and Parabitecta baoshana sp. n. Parabitecta secunda Volynkin & Saldaitis, 2020 is reported from Myanmar for the first time. Adults as well as male and female genitalia are illustrated.

Effects of Warm Compresses on the Perineal Area During the Active Phase of Labor: A Quasi-Experimental Study.

Background A perineal tear refers to any injury to the female genitalia during labor, which can occur spontaneously or with the use of instruments. An episiotomy, a surgical procedure, is sometimes performed to enlarge the vaginal orifice to facilitate delivery. Ineffective management of labor pain can result in negative physiological and psychosocial outcomes. Objective This study aims to investigate the effect of warm compresses on the perineal area during active labor. Methods This quasi-experimental study utilized a convenience sample, dividing 80 mothers into intervention and control groups. Participants were randomly assigned to groups after meeting the inclusion criteria and signing consent forms. The inclusion criteria encompassed pregnant women aged 18 years or older with a healthy singleton pregnancy, a cephalic presentation, and a gestational age of 37 weeks or more. The women were in the active phase of the first stage of labor (6-7 cm cervical dilation). In Part I, a data collection tool was developed to gather sociodemographic data, obstetrical history, and initial assessment information. Part II assessed perineal pain using the Visual Analogue Scale. Part III collected data on the perineal status post-delivery, and Part IV gathered information about the newborns. The research was conducted in the labor unit at East Jeddah Hospital, with data collection occurring from November 2022 to February 2023. Results The results of this study revealed that the mean second-stage labor pain score was 9.73 for the control group and 8.68 for the intervention group. In the third stage of labor, the mean pain score was 4.52 for the control group and 2.75 for the intervention group. During the fourth stage of labor, the mean pain score for the control group was 2.90, compared to 1.50 for the intervention group. In terms of perineal outcomes, 17 participants (42.5%) in the intervention group had an intact perineum, compared to 11 participants (27.5%) in the control group. However, there was no significant difference in the episiotomy rate between the two groups. Conclusions The findings of this study indicate that applying a warm compress to the perineal area during active labor can enhance perineal intactness and significantly reduce perineal pain. Future research could explore the challenges nurses encounter when applying warm compresses to the perineum during labor.

Long-term outcomes of infliximab treatment in neuro-Behcet syndrome: A single-center retrospective study.

Behcet's syndrome is a rare inflammatory disorder characterized by oral and genital ulcers, skin lesions, and uveitis. It exhibits a higher prevalence along the historic Silk Road. Neuro-Behcet syndrome (NBS) affects the central nervous system and poses significant morbidity and mortality risks. Infliximab, a TNF-alpha antagonist, has shown potential in NBS management, although the current evidence is mainly derived from case series due to the lack of randomized controlled trials. This retrospective study aimed to evaluate the disease outcomes during the first and second years following infliximab treatment in NBS patients experiencing attacks despite prior conventional immunosuppressive therapy. The study also sought to investigate the safety profile and adverse effects associated with infliximab. Fifty-three NBS patients were examined, with 22 receiving infliximab as either monotherapy or in combination with other therapies. Retrospective analysis was conducted on demographic data, clinical characteristics, and treatment responses. Treatment efficacy was measured using the Expanded Disability Status Scale (EDSS) modified for NBS. The study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist guidelines. Among the study cohort, 60.4% had parenchymal NBS, and 39.6% had nonparenchymal NBS. Treatment with infliximab resulted in remission or disease stabilization in 95% of patients after one year and 68.7% after 2years. Relapse rates were 4.5% at 1year and 18.7% at 2years, with disease progression observed in two cases. Adverse effects were primarily mild to moderate, with no reports of serious adverse events. Infliximab exhibited efficacy in achieving remission or stabilization in NBS patients, maintaining a favorable safety profile. The timing of infliximab treatment may prevent the accumulation of disability and hinder disease progression. Nonetheless, future prospective studies are necessary to confirm these findings and refine treatment strategies for this complex condition.

Peningkatan Pengetahuan dan Deteksi Dini Keputihan (Leukhorrea) pada Wanita Usia Subur di Desa Margorejo Pati

Vaginal discharge is one of the reproductive health problems that often arise in adolescents which can be an early symptom of cervical cancer. Vaginal discharge is the discharge of white fluid or mucus that comes out of the genital organs that is not in the form of blood. Vaginal discharge is a complaint that often attacks women and does not know age (Sulistianingsih, 2014). Vaginal discharge is still considered not a serious thing so that in maintaining cleanliness, especially the genetic organs in women, are still lacking. This can be seen from the use of underwear that is not made of cotton. Even though it is possible that vaginal discharge can be caused by underwear made of synthetic fibers (nylon). (Kusmiran, 2019) The World Health Organization (WHO) in Suryandari and Rufaida (2019) stated that almost all women and adolescent girls have experienced vaginal discharge, 60% in adolescents (15-22 years old) and 40% in women (23-45 years old), if left vaginal discharge can cause adverse health effects, one of which is cervical cancer. Meanwhile, according to Wulandari (2015), as many as 75% of women who have experienced vaginal discharge at least 1 time in their lifetime with 50% in adolescents and 25% in women of childbearing age (WUS) out of 95% of cervical cancer cases that occur in women in Indonesia are characterized by vaginal discharge (3, 4). One of the effects of pathological vaginal discharge is cervical cancer. Every year, as many as 8,000 women in Indonesia die from cervical cancer. This means that almost every hour, an Indonesian woman dies because she is gnawed by cervical cancer. Cervical cancer attacks and kills women at the productive age of 20-25 years, but can appear in women at a younger age (5). Lack of proper knowledge and information about the health of the reproductive organs can cause a lack of attention to the health of the reproductive organs in terms of vaginal discharge.

Cellular angiofibroma of the female pelvic cavity: a case report

BackgroundCellular angiofibroma is a rare benign mesenchymal tumor that mostly occurs in the genital area. Its occurrence outside this region, particularly in the pelvis, is extremely rare. To our knowledge, this study reports the first case of cellular angiofibroma occurring in the pelvic cavity, except for one case reported in the retroperitoneum.Case presentationA 25-year-old female patient with chronic, intermittent, dull pain in the lower abdomen that lasted for several months was referred to our clinic. Imaging studies revealed a tumor in the pelvic cavity anterior to the bladder. The radiographic characteristics of this tumor indicated a hypervascular nature, suggesting the possibility of a pheochromocytoma or a neuroendocrine tumor. The patient underwent surgical excision of the lesion. To date, no recurrence has been observed four months after excision.ConclusionsCellular angiofibroma, although rare in the pelvic cavity, should be considered in the differential diagnosis of hypervascular pelvic space-occupying lesions. Immunohistochemical staining can help confirm the diagnosis of this condition. Treatment is generally straightforward, involving local excision of the tumor followed by postoperative monitoring.

A new species of Tapajosa Melichar from Curaçao, Lesser Antilles (Hemiptera: Cicadellidae: Proconiini)

A new species of the Neotropical genus Tapajosa Melichar 1924 from Curaçao is proposed, described, and illustrated. Tapajosa arawaka sp. nov. differs from other species of the genus mainly in the shape of male genitalia. Its close morphological affinity with Tapajosa spinata Young, 1968 suggests that ancestors of the new species migrated from mainland Venezuela.

First record of Scotocampa sheljuzhkoi Gyulai & L. Ronkay (Lepidoptera: Noctuidae: Noctuinae) from Kazakhstan

The little-known Noctuidae species Scotocampa sheljuzhkoi Gyulai & L. Ronkay, 2002 is reported from Kazakhstan for the first time. The species was previously considered as endemic to South and Southwest Mongolia and the new distribution data increase its known range by over 750 km to the west. Adults, male genitalia and the habitats of S. sheljuzhkoi and its allopatric sister species Scotocampa indigesta Staudinger, 1888 occurring in the Ili River Valley (SE Kazakhstan) are illustrated. The photograph of the female genitalia of the holotype of Scotocampa crassipuncta (Püngeler, 1905) known from Tarim Basin is illustrated for the first time.

Body mass index and risk of over 100 cancer forms and subtypes in 4.1 million individuals in Sweden: the Obesity and Disease Development Sweden (ODDS) pooled cohort study

Obesity, assessed by body mass index (BMI), is an established risk factor for 13 cancers. We aimed to identify further potential obesity-related cancers and to quantify their association with BMI relative to that of established obesity-related cancers. Using Cox regression models on 4,142,349 individuals in Sweden (mean age 27.1 years at weight measurement), we calculated hazard ratios (HRs) for the association between BMI and the risk of 122 cancers and cancer subtypes, grouped by topography and morphology. Cancers with a positive association (i.e., HR>1) at an α-level of 0.05 for obesity (BMI ≥30kg/m2) vs. normal weight (BMI 18.5-24.9kg/m2) or per 5kg/m2 higher BMI, for which obesity is not an established risk factor, were considered potentially obesity related. After 100.2 million person-years of follow-up, 332,501 incident cancer cases were recorded. We identified 15 cancers in men and 16 in women as potentially obesity related. These were cancers of the head and neck, gastrointestinal tract, malignant melanoma, genital organs, endocrine organs, connective tissue, and haematological malignancies. Among these, there was evidence of differential associations with BMI between subtypes of gastric cancer, small intestine cancer, cervical cancer, and lymphoid neoplasms (P values for heterogeneity in HRs <0.05). The HR (95% confidence interval) per 5kg/m2 higher BMI was 1.17 (1.15-1.20) in men and 1.13 (1.11-1.15) in women for potential obesity-related cancers (51,690 cases), and 1.24 (1.22-1.26) in men and 1.12 (1.11-1.13) in women for established obesity-related cancers (84,384 cases). This study suggests a large number of potential obesity-related cancers could be added to already established ones. Importantly, the magnitudes of the associations were largely comparable to those of the already established obesity-related cancers. We also provide evidence of specific cancer subtypes driving some associations with BMI. Studies accounting for cancer-specific confounders are needed to confirm these findings. Swedish Research Council, Swedish Cancer Society, Mrs. Berta Kamprad's Cancer Foundation, Crafoord Foundation, Cancer Research Foundation at the Department of Oncology, Malmö University Hospital, and China Scholarship Council.

Taxonomic review of the Thysanoptyx Hampson generic complex (Lepidoptera: Erebidae: Arctiinae: Lithosiini). I. The genus Collitoptyx Volynkin with descriptions of two new genera, two new subgenera and six new species

The Asiatic footman moth genus Collitoptyx Volynkin, 2023 is reviewed. Two new genera, two new subgenera and six new species are described: Medioptyx gen. n., Caliginoptyx gen. n., Collitoptyx (Insolitoptyx) subgen. n., Collitoptyx (Confusoptyx) subgen. n., Collitoptyx (Collitoptyx) fraterna sp. n. (China and northern Mainland Southeast Asia), Collitoptyx (Collitoptyx) annamia sp. n. (Central Vietnam), Collitoptyx (Insolitoptyx) meghalaya sp. n. (Northeast India), Collitoptyx (Confusoptyx) duplex sp. n. (Northeast India and northern Mainland Southeast Asia), Medioptyx kishidai sp. n. (East China), and Caliginoptyx vientiana sp. n. (northern Laos). A new combination is established: Caliginoptyx zofera (Volynkin, 2023), comb. n. A lectotype is designated for Teulisna sordida Butler, 1881. A new synonym is introduced: Collitoptyx (Collitoptyx) sordida (Butler, 1881) = Thysanoptyx manganensis N. Singh &amp; Joshi, 2017, syn. n. Adults as well as male and female genitalia are illustrated.

Reassessment and phylogenetic position of the overlooked limacoid land snail Trochomorpha sculpticarina Martens, 1883 (Eupulmonata, Ariophantidae), with the description of a new genus

The Malay Peninsula has traditionally been considered to harbour a diverse land-snail fauna, both in terms of a high species richness and a wide variety of conchological traits, especially within the limacoid land snails. A recent survey along the Malay Peninsula of southern Thailand discovered an overlooked limacoid taxon “Trochomorpha” sculpticarina Martens, 1883, previously assigned to genus Trochomorpha of the Trochomorphidae. This genus is herein described as Janbinmorphagen. nov. based on comparative studies of shell morphology, external features, genital anatomy and radular morphology, as well as analyses of partial sequences of two mitochondrial markers, COI and 16S rRNA, and of one nuclear marker, 28S rRNA. This new genus is characterised by a combination of distinct morphological and anatomical features. The most distinguishing features are a depressed trochiform shell with a keeled last whorl, gametolytic organ without a duct, gametolytic sac with two lobes, and proximal epiphallus encircled with a thick sheath and attached by the penial retractor muscle. In addition, an analysis of the differentiation in mitochondrial and nuclear markers confirmed that this new genus, first recognised by morphology, is also genetically distinct. The molecular data also confirm that J. sculpticarinacomb. nov. is a member of the Ariophantidae and has a close evolutionary relationship to Hemiplecta and Maelamaodiscus.

Taxonomic Revision of the Dichotomius mormon (Ljungh, 1799) Species Group (Coleoptera: Scarabaeidae: Scarabaeinae), with a Description of a New Species from Bolivia.

Dichotomius Hope, 1838 (Coleoptera: Scarabaeidae: Scarabaeinae) is a very abundant and diverse genus of dung beetles of the New World ecosystems, with about 190 species, distributed in four subgenera. Luederwaldt (Separata Rev Mus Paul 14: 3-13 1929) proposed the division of subgenera into sections (now species groups) based mainly on characters of external morphology. Based on Luederwaldt's proposal, progress has been made in recent years in the taxonomic revision of the genus; however, inconsistencies have been found in the subgeneric division and species groups proposed by this author. Based on the external morphology and the male genital organ of the all type material and other material deposited in fifteen entomological collections, in this paper, the redefinition and taxonomic revision of the Dichotomius mormon species group is carried out. The new definition of the group and the species key are presented. Five species are included in the group: Dichotomius conicollis (Blanchard, 1846) (Bolivia), Dichotomius larseni sp. nov. (Bolivia), Dichotomius mormon (Ljungh, 1799) (Argentina, Brazil, and Paraguay), Dichotomius ohausi (Luederwaldt, 1923) (Brazil, Colombia, Ecuador, and Peru), and Dichotomius talaus (Erichson, 1847) stat. rev. (Bolivia, and Peru). The lectotypes for D. conicollis, Copris ephialtes Mannerheim, 1829, Copris nasuta Castelnau, 1840, Copris protensus Perty, 1830, D. ohausi, and D. talaus were designated. For each of the species that are included in the group, the following information is presented: taxonomic history, species' citation in published literature, description or redescription of males and females, list of material examined, photographs of the external morphology, illustrations of male genital organ and its endophallites, and distribution map.

Linear Morphometry of Male Genitalia Distinguishes the Ant Genera Monomorium and Syllophopsis (Hymenoptera: Formicidae) in Madagascar.

Morphometric analyses of male genitalia are routinely used to distinguish genera and species in beetles, butterflies, and flies, but are rarely used in ants, where most morphometric analyses focus on the external morphology of the worker caste. In this work, we performed linear morphometric analysis of the male genitalia to distinguish Monomorium and Syllophopsis in Madagascar. For 80 specimens, we measured 10 morphometric characters, especially on the paramere, volsella, and penisvalvae. Three datasets were made from linear measurements: mean (raw data), the ratios of characters (ratio data), and the Removal of Allometric Variance (RAV data). The following quantitative methods were applied to these datasets: hierarchical clustering (Ward's method), unconstrained ordination methods including Principal Component Analysis (PCA), Non-Metric Multidimensional Scaling analyses (NMDS), Linear Discriminant Analysis (LDA), and Conditional Inference Trees (CITs). The results from statistical analysis show that the ratios proved to be the most effective approach for genus-level differentiation. However, the RAV method exhibited overlap between the genera. Meanwhile, the raw data facilitated more nuanced distinctions at the species level compared with the ratios and RAV approaches. The CITs revealed that the ratios of denticle length of the valviceps (SeL) to the paramere height (PaH) effectively distinguished between genera and identified key variables for species-level differentiation. Overall, this study shows that linear morphometric analysis of male genitalia is a useful data source for taxonomic delimitation.

Genomic ascertainment of CHEK2-related cancer predisposition.

There is clear evidence that deleterious germline variants in CHEK2 increases risk for breast and prostate cancers; there is limited or conflicting evidence for other cancers. Genomic ascertainment was used to quantify cancer risk in CHEK2 germline pathogenic variant heterozygotes. Germline CHEK2 variants were extracted from two exome-sequenced biobanks linked to the electronic health record: UK Biobank (n= 469,765) and Geisinger MyCode (n=170,503). Variants were classified as per American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) criteria. Heterozygotes harbored a CHEK2 pathogenic/likely pathogenic (P/LP) variant; controls harbored benign/likely benign CHEK2 variation or wildtype CHEK2. Tumor phenotype and demographic data were retrieved; to adjust for relatedness, association analysis was performed with SAIGE-GENE+ with Bonferroni correction. In CHEK2 heterozygotes in both MyCode and UK Biobank, there was a significant excess risk of all cancers tested, including breast cancer (C50; OR=1.54 and 1.84, respectively), male genital organ cancer (C60-C63; OR=1.61 and 1.77 respectively), urinary tract cancer (C64-C68; OR=1.56 and 1.75, respectively) and lymphoid, hematopoietic, and related tissue cancer (C81-C96; OR=1.42 and 2.11, respectively). Compared to controls, age-dependent cancer penetrance in CHEK2 heterozygotes was significantly younger in both cohorts; no significant difference was observed between the penetrance of truncating and missense variants for cancer in either cohort. Overall survival was significantly decreased in CHEK2 heterozygotes in UK Biobank but there was no statistical difference in MyCode. Using genomic ascertainment in two population-scale cohorts, this investigation quantified the prevalence, penetrance, cancer phenotype and survival in CHEK2 heterozygotes. Tailored treatment options and surveillance strategies to manage those risks are warranted.

Boris N. Kholtsov (1861–1940): outstanding urologist, scientist, and teacher. To the 100th anniversary of the start of employment in the Urological Clinic of the Leningrad State Institute for Advanced Training of Doctors

This article is dedicated to outstanding clinical scientist Professor B.N. Kholtsov (1861–1940). The main stages of his scientific, clinical, and teaching activities and his scientific achievements in the development of novel methods for treating diseases of the urinary and male genital organs are presented. He was the first to propose a two-stage adenomectomy technique, an original method of urethral resection in case of stricture, and developed a surgical treatment method for contracture of the bladder neck. The role of Kholtsov in the training of urologists at the Department of Urology of the Leningrad State Institute for Advanced Training of Doctors, which he headed in 1926–1940, is shown. Kholtsov was a talented clinician, scientist, teacher, and innovator, whose main ideas remains in demand today.

Evaluation and comparison of nine growth and development-based measures of pubertal timing

BackgroundPubertal timing is heritable, varies between individuals, and has implications for life-course health. There are many different indicators of pubertal timing, and how they relate to each other is unclear. Our aim was to quantitatively compare nine indicators of pubertal timing.MethodsWe used data from questionnaires and height, weight, and bone measurements from ages 7–17 y in a population-based cohort of 4267 females and 4251 males to compare nine growth and development-based indicators of pubertal timing. We summarise age of each indicator, their phenotypic and genetic correlations, and how they relate to established genetic risk score (GRS) for puberty timing, and phenotypic childhood body composition measures.ResultsWe show that pubic hair in males (mean: 12.6 y) and breasts in females (11.5 y) are early indicators of puberty, and voice breaking (14.2 y) and menarche (12.7 y) are late indicators however, there is substantial variation between individuals in pubertal age. All indicators show evidence of positive phenotypic intercorrelations (e.g., r = 0.49: male genitalia and pubic hair ages), and positive genetic intercorrelations. An age at menarche GRS positively associates with all other pubertal age indicators (e.g., difference in female age at peak height velocity per SD higher GRS: 0.24 y, 95%CI: 0.21 to 0.26), as does an age at voice breaking GRS (e.g., difference in age at male axillary hair: 0.11 y, 0.07 to 0.15). Higher childhood fat mass and lean mass associated with earlier puberty timing.ConclusionsOur findings provide insights into the measurements of the timing of pubertal growth and development and illustrate value of various pubertal timing indicators in life-course research.