Genomic insights into population history and biological adaptation in Oceania.

The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes1. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage genomes of 317 individuals from 20 populations from the Pacific region. We find that the ancestors of Papuan-related ('Near Oceanian') groups underwent a strong bottleneck before the settlement of the region, and separated around 20,000-40,000 years ago. We infer that the East Asian ancestors of Pacific populations may have diverged from Taiwanese Indigenous peoples before the Neolithic expansion, which is thought to have started from Taiwan around 5,000 years ago2-4. Additionally, this dispersal was not followed by an immediate, single admixture event with Near Oceanian populations, but involved recurrent episodes of genetic interactions. Our analyses reveal marked differences in the proportion and nature of Denisovan heritage among Pacific groups, suggesting that independent interbreeding with highly structured archaic populations occurred. Furthermore, whereas introgression of Neanderthal genetic information facilitated the adaptation of modern humans related to multiple phenotypes (for example, metabolism, pigmentation and neuronal development), Denisovan introgression was primarily beneficial for immune-related functions. Finally, we report evidence of selective sweeps and polygenic adaptation associated with pathogen exposure and lipid metabolism in the Pacific region, increasing our understanding of the mechanisms of biological adaptation to island environments.

Measuring the Efficiency of Purging by non-random Mating in Human Populations.

Human populations harbor a high concentration of deleterious genetic variants. Here, we tested the hypothesis that non-random mating practices affect the distribution of these variants, through exposure in the homozygous state, leading to their purging from the population gene pool. To do so, we produced whole-genome sequencing data for two pairs of Asian populations exhibiting different alliance rules and rates of inbreeding, but with similar effective population sizes. The results show that populations with higher rates of inbred matings do not purge deleterious variants more efficiently. Purging therefore has a low efficiency in human populations, and different mating practices lead to a similar mutational load.

Silicone Particles in Capsules Around Breast Implants: An Investigation Into Currently Available Implants in North America.

BACKGROUND: Breast implants have always been composed of a silicone elastomer envelope filled with either silicone gel or saline. Breast implant illness (BII) is a set of symptoms that has previously been linked to the leakage of silicone particles from the implants into the body. OBJECTIVES: Our research aimed to quantify the number of silicone particles present in the capsules of breast implants available in North America. METHODS: Thirty-five periprosthetic capsules were sampled and analyzed, and silicone particles were counted and measured. The capsule surface area was then measured and utilized to calculate particle density and total number of silicone particles. RESULTS: Eighty-five percent of capsules analyzed from silicone gel implants contained silicone, with an average of 62 particles per mm3 of capsular tissue. These implants had approximately 1 million silicone particles per capsule. In contrast, none of the saline implant capsules contained silicone. Capsules from macrotextured tissue expanders contained fewer and larger silicone particles. CONCLUSIONS: Silicone gel implants presented silicone particle bleeding into the periprosthetic capsule, totaling on average 1 million silicone particles per capsule. On the other hand, no silicone particle bleeding was observed from saline breast implants. These data suggest that particle bleeding comes from the inner silicone gel, and not from the smooth outer silicone shell. Previous studies have reported the presence of breast implant illness in patients with both silicone- and saline-filled implants. Therefore, our data suggest that silicone migration is not the sole cause of BII.

Why and when was lactase persistence selected for? Insights from Central Asian herders and ancient DNA.

The genetic adaptation of humans to the consumption of milk from dairying animals is one of the most emblematic cases of recent human evolution. While the phenotypic change under selection, lactase persistence (LP), is known, the evolutionary advantage conferred to persistent individuals remains obscure. One informative but underappreciated observation is that not all populations whose ancestors had access to milk genetically adapted to become lactase persistent. Indeed, Central Asian herders are mostly lactase nonpersistent, despite their significant dietary reliance on dairy products. Investigating the temporal dynamic of the -13.910:C>T Eurasian mutation associated with LP, we found that, after its emergence in Ukraine 5,960 before present (BP), the T allele spread between 4,000 BP and 3,500 BP throughout Eurasia, from Spain to Kazakhstan. The timing and geographical progression of the mutation coincides well with the migration of steppe populations across and outside of Europe. After 3,000 BP, the mutation strongly increased in frequency in Europe, but not in Asia. We propose that Central Asian herders have adapted to milk consumption culturally, by fermentation, and/or by colonic adaptation, rather than genetically. Given the possibility of a nongenetic adaptation to avoid intestinal symptoms when consuming dairy products, the puzzle then becomes this: why has LP been selected for at all?

Genomic evidence for MHC disassortative mating in humans.

Although pervasive in many animal species, the evidence for major histocompatibility complex (MHC) disassortative mating in humans remains inconsistent across studies. Here, to revisit this issue, we analyse dense genotype data for 883 European and Middle Eastern couples. To distinguish MHC-specific effects from socio-cultural confounders, the pattern of relatedness between spouses in the MHC region is compared to the rest of the genome. Couples from Israel exhibit no significant pattern of relatedness across the MHC region, whereas across the genome, they are more similar than random pairs of individuals, which may reflect social homogamy and/or cousin marriages. On the other hand, couples from The Netherlands and more generally from Northern Europe are significantly more MHC-dissimilar than random pairs of individuals, and this pattern of dissimilarity is extreme when compared with the rest of the genome. Our findings support the hypothesis that the MHC influences mate choice in humans in a context-dependent way: MHC-driven preferences may exist in all populations but, in some populations, social constraints over mate choice may reduce the ability of individuals to rely on such biological cues when choosing their mates.

In vitro osteodifferentiation of intact human amniotic membrane is not beneficial in the context of bone repair.

The human amniotic membrane (hAM) is an attractive biomaterial for regenerative medicine, as it contains amniotic mesenchymal stromal cells (hAMSC), epithelial cells (hAEC) and growth factors. We examined the potential use of hAM in orthopaedic and maxillofacial bone surgery, integrating the requirements of current regulations regarding advanced therapy medicinal products (ATMP) in the European Union. Previous studies have described the potential osteodifferentiation of intact hAM during whole-tissue culture in osteogenic conditions. The present study aims to determine whether in vitro osteodifferentiation of hAM is needed in the context bone repair, and the influence of this process on tissue structure, cell phenotype and cell function. Different conditions (fresh or cultured hAM; intact or hAM-derived cells) were tested. Phenotypic and functional analyses were performed with standard approaches (cell culture and staining, histological and immunolabelling) as well as original approaches (tissue staining, energy dispersive X-ray and X-ray diffraction). In our study, non-osteodifferentiated hAM (i.e., fresh or native hAM) exhibited innate pre-osteoblastic potential. Osteodifferentiation of fresh hAM induced a change in tissue structure, cell phenotype and function. Therefore, we hypothesize that pre-osteodifferentiation may not be necessary, especially if it induces unwanted changes. To our surprise, in these osteogenic conditions, hAEC had a mesenchymal phenotype with osteocyte function, and even native synthesis of hydroxyapatite, focusing osteogenic potential mainly in this epithelial layer. In conclusion, in vitro osteodifferentiation by tissue culture does not appear to be necessary for hAM to be used as an innovative ATMP for bone repair.

Residence rule flexibility and descent groups dynamics shape uniparental genetic diversities in South East Asia.

OBJECTIVES: Social organization plays a major role in shaping human population genetic diversity. In particular, matrilocal populations tend to exhibit less mitochondrial diversity than patrilocal populations, and the other way around for Y chromosome diversity. However, several studies have not replicated such findings. The objective of this study is to understand the reasons for such inconsistencies and further evaluate the influence of social organization on genetic diversity. MATERIALS AND METHODS: We explored uniparental diversity patterns using mitochondrial HV1 sequences and 17 Y-linked short tandem repeats (STRs) in 12 populations (n = 619) from mainland South-East Asia exhibiting a wide range of social organizations, along with quantitative ethno-demographic information sampled at the individual level. RESULTS: MtDNA diversity was lower in matrilocal than in multilocal and patrilocal populations while Y chromosome diversity was similar among these social organizations. The reasons for such asymmetry at the genetic level were understood by quantifying sex-specific migration rates from our ethno-demographic data: while female migration rates varied between social organizations, male migration rates did not. This unexpected lack of difference in male migrations resulted from a higher flexibility in residence rule in patrilocal than in matrilocal populations. In addition, our data suggested an impact of clan fission process on uniparental genetic patterns. CONCLUSIONS: The observed lack of signature of patrilocality on Y chromosome patterns might be attributed to the higher residence flexibility in the studied patrilocal populations, thus providing a potential explanation for the apparent discrepancies between social and genetic structures. Altogether, this study highlights the need to quantify the actual residence and descent patterns to fit social to genetic structures.

Sex-specific genetic diversity is shaped by cultural factors in Inner Asian human populations.

OBJECTIVES: Sex-specific genetic structures have been previously documented worldwide in humans, even though causal factors have not always clearly been identified. In this study, we investigated the impact of ethnicity, geography and social organization on the sex-specific genetic structure in Inner Asia. Furthermore, we explored the process of ethnogenesis in multiple ethnic groups. METHODS: We sampled DNA in Central and Northern Asia from 39 populations of Indo-Iranian and Turkic-Mongolic native speakers. We focused on genetic data of the Y chromosome and mitochondrial DNA. First, we compared the frequencies of haplogroups to South European and East Asian populations. Then, we investigated the genetic differentiation for eight Y-STRs and the HVS1 region, and tested for the effect of geography and ethnicity on such patterns. Finally, we reconstructed the male demographic history, inferred split times and effective population sizes of different ethnic groups. RESULTS: Based on the haplogroup data, we observed that the Indo-Iranian- and Turkic-Mongolic-speaking populations have distinct genetic backgrounds. However, each population showed consistent mtDNA and Y chromosome haplogroups patterns. As expected in patrilocal populations, we found that the Y-STRs were more structured than the HVS1. While ethnicity strongly influenced the genetic diversity on the Y chromosome, geography better explained that of the mtDNA. Furthermore, when looking at various ethnic groups, we systematically found a genetic split time older than historical records, suggesting a cultural rather than biological process of ethnogenesis. CONCLUSIONS: This study highlights that, in Inner Asia, specific cultural behaviors, especially patrilineality and patrilocality, leave a detectable signature on the sex-specific genetic structure.

Patterns of admixture and population structure in native populations of Northwest North America.

The initial contact of European populations with indigenous populations of the Americas produced diverse admixture processes across North, Central, and South America. Recent studies have examined the genetic structure of indigenous populations of Latin America and the Caribbean and their admixed descendants, reporting on the genomic impact of the history of admixture with colonizing populations of European and African ancestry. However, relatively little genomic research has been conducted on admixture in indigenous North American populations. In this study, we analyze genomic data at 475,109 single-nucleotide polymorphisms sampled in indigenous peoples of the Pacific Northwest in British Columbia and Southeast Alaska, populations with a well-documented history of contact with European and Asian traders, fishermen, and contract laborers. We find that the indigenous populations of the Pacific Northwest have higher gene diversity than Latin American indigenous populations. Among the Pacific Northwest populations, interior groups provide more evidence for East Asian admixture, whereas coastal groups have higher levels of European admixture. In contrast with many Latin American indigenous populations, the variance of admixture is high in each of the Pacific Northwest indigenous populations, as expected for recent and ongoing admixture processes. The results reveal some similarities but notable differences between admixture patterns in the Pacific Northwest and those in Latin America, contributing to a more detailed understanding of the genomic consequences of European colonization events throughout the Americas.

Fresh and in vitro osteodifferentiated human amniotic membrane, alone or associated with an additional scaffold, does not induce ectopic bone formation in Balb/c mice.

The human amniotic membrane (hAM) has been successfully used as a natural carrier containing amniotic mesenchymal stromal cells, epithelial cells and growth factors. It has a little or no immunogenicity, and possesses useful anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. It has been used for many years in several indications for soft tissue repair. We previously reported that hAM represents a natural and preformed sheet containing highly potent stem cells, and could thus be used for bone repair. Indeed, native hAM possesses pre-osteoblastic potential that can easily be stimulated, even as far as mineralization, by means of in vitro osteogenic culture. However, cell culture induces damage to the tissue, as well as to cell phenotype and function. The aim of this study was to evaluate new bone formation by fresh and in vitro osteodifferentiated hAM, alone or associated with an additional scaffold presenting osteoinductive properties. Moreover, we also aimed to determine the effect of in vitro hAM pre-osteodifferentiation on its in vivo biocompatibility/tissue degradation. Results showed that neither fresh nor osteodifferentiated hAM induced ectopic bone formation, whether or not it was associated with the osteoinductive scaffold. Secondly, fresh and osteodifferentiated hAM presented similar in vivo tissue degradation, suggesting that in vitro hAM pre-osteodifferentiation did not influence its in vivo biocompatibility.

MHC-dependent mate choice in humans: why genomic patterns from the HapMap European American dataset support the hypothesis.

The role of the major histocompatibility complex (MHC) in mate choice in humans is controversial. Nowadays, the availability of genetic variation data at genomic scales allows for a careful assessment of this question. In 2008, Chaix et al. reported evidence for MHC-dependent mate choice among European American spouses from the HapMap 2 dataset. Recently, Derti et al. suggested that this observation was not robust. Furthermore, when Derti et al. applied similar analyses to the HapMap 3 European American samples, they did not see a significant effect. Although some of the points raised by Derti et al. are relevant, we disagree with the reported absence of evidence for MHC-dependent mate choice within the HapMap samples. More precisely, we show here that the MHC dissimilarity among HapMap 3 European American spouses is still extreme in comparison to the rest of the genome, even after multiple testing correction. This finding supports the hypothesis of MHC-dependent mate choice in some human populations.

Storage and qualification of viable intact human amniotic graft and technology transfer to a tissue bank.

Human amniotic membrane (hAM) is known to have good potential to help the regeneration of tissue. It has been used for over 100 years in many medical disciplines because of its properties, namely a scaffold containing stem cells and growth factors, with low immunogenicity and anti-microbial, anti-inflammatory, anti-fibrotic and analgesic properties. In order to use this "boosted membrane" as an advanced therapeutic medicinal product for bone repair, we aimed to observe the influence of tissue culture and/or cryopreservation on cell viability and tissue structure, and secondly, to adapt to a tissue bank, identify easy processes to store hAM containing viable cells and to verify the quality of the graft before its release for use. To this end, we tested different published culture or cryopreservation storage conditions and cell viability assays. Tissue structure was evaluated by Giemsa staining and was compared to histological analysis. Preliminary results show no dramatic decrease in cell viability in cultured hAM as compared to cryopreserved hAM, but tissue structure alterations were observed with both storage conditions. Histological and immunohistochemical data highlight that tissue damage was associated with significantly modified protein expression, which could lead to a possible loss of differentiation potential. Finally, we report that trypan blue and Giemsa staining could constitute controls that are "materially and easily transferable" to a tissue bank.

Cosmetic male genital surgery: a narrative review.

Background and Objective: Through the centuries the appearance of the male genitalia has always been an important concern for men, symbolizing virility, potency and sexual contentment. Correction of perceived deficiencies and deformities of the male genitalia can be addressed by aesthetic surgery as well as the enhancement its external aspect. If the social acceptance of cosmetic surgery, particularly of women's breasts, dates from the early 1950s, male intimate cosmetic surgery emerged from the shadows about 10 years ago with a medical community still very suspicious and reproachful. The present paper aims to describe and discuss the current state of the art regarding male intimate cosmetic surgery. Methods: A narrative review of the literature was performed using publications from January 2000 to September 2022. The publications were retrieved from the PubMed database using Medical Subject Headings (MeSH) terms and keywords. The authors' goal is to narrate the aesthetic non-surgical and surgical enhancement procedures of the male apparatus. Key Content and Findings: This narrative review examines the diverse procedures associated with male genitalia aesthetics. Conclusions: Aesthetics of the male genitalia is now an unavoidable and important part of aesthetic surgery worldwide with an increasing demand. Nonsurgical and surgical techniques described in the literature should be reviewed.

Autogenous breast reconstruction for total mastectomies: a narrative review.

Background and Objective: Mastectomies have a significant socio-psychological impact, motivating patients to undergo breast reconstruction. Initially, silicone implants were used to reconstruct the breast. However, breast implants have been the subject of successive crises throughout the years. Indeed, rupture, silicone bleeding, and capsular contracture remain topical. In 2019, the BIOCELL textured breast implants was banned and recalled due to the discovery of the breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). More recently, the breast implant illness has been depicted in the media. To cope with these issues and to respond to some patients' expectations for a natural reconstruction, plastic surgeons have developed autogenous solutions for breast reconstruction. Since Taylor's research on angiosomes, the development of the microsurgery and more recently fat grafting, autogenous breast reconstruction has known a tremendous expansion. Autologous breast reconstruction allows a more natural feeling and texture. This narrative review aims to provide to the readers a comprehensive and updated evidence-based overview of state of the art about autologous breast reconstruction after total mastectomy. Methods: We conducted a narrative review of the literature searching for papers published between January 2010 and December 2022. The MeSH terms with different combinations were used to identify articles for inclusion. After screening article titles and abstracts independently by three authors, 66 papers were included in this review. Key Content and Findings: In this review, the authors describe and discuss the different autogenous techniques in breast reconstruction. Conclusions: Autologous reconstructions provide very satisfactory, durable, and reliable results with relatively low complication rates. Deep inferior epigastric perforator (DIEP) flaps, latissimus dorsi flaps and autologous fat grafting are the most common type of autogenous breast reconstructions.

Anatomical Study of the Penile Suspensory System: A Surgical Application to Micropenis.

Penile enlargement surgery is the second most desired cosmetic procedure in men worldwide. The mainstay of penile lengthening procedures is a partial release of the penile suspensory ligament system. Concerns regarding erect penis stability after this procedure have been raised by the surgical community. This study describes the anatomical features of the penile suspensory ligament system and explores the stability mechanisms of the penis. Methods: This study is subdivided in two parts: an anatomical analysis and a clinical analysis. The anatomical part consists of a dissection of eight male cadavers to describe the anatomy and test the stability after sectioning successively the suspensory ligaments. The clinical part consists of an analysis of 30 patients with micropenis operated on for penile lengthening by a penile suspensory ligament release and lipofilling. Results: The suspensory apparatus consists of four distinct ligamentous structures: fundiform, suspensory, dense vertical, and arcuate ligaments. These different structures are lax superficially but become firm and tense posteriorly. The section of the fundiform and suspensory ligaments did not destabilize the penis. Conclusion: Penile lengthening by way of cautious suspensory ligament release can be performed without erection instability.

A genetic and linguistic analysis of the admixture histories of the islands of Cabo Verde.

From the 15th to the 19th century, the Trans-Atlantic Slave-Trade (TAST) influenced the genetic and cultural diversity of numerous populations. We explore genomic and linguistic data from the nine islands of Cabo Verde, the earliest European colony of the era in Africa, a major Slave-Trade platform between the 16th and 19th centuries, and a previously uninhabited location ideal for investigating early admixture events between Europeans and Africans. Using local-ancestry inference approaches, we find that genetic admixture in Cabo Verde occurred primarily between Iberian and certain Senegambian populations, although forced and voluntary migrations to the archipelago involved numerous other populations. Inter-individual genetic and linguistic variation recapitulates the geographic distribution of individuals' birth-places across Cabo Verdean islands, following an isolation-by-distance model with reduced genetic and linguistic effective dispersals within the archipelago, and suggesting that Kriolu language variants have developed together with genetic divergences at very reduced geographical scales. Furthermore, based on approximate bayesian computation inferences of highly complex admixture histories, we find that admixture occurred early on each island, long before the 18th-century massive TAST deportations triggered by the expansion of the plantation economy in Africa and the Americas, and after this era mostly during the abolition of the TAST and of slavery in European colonial empires. Our results illustrate how shifting socio-cultural relationships between enslaved and non-enslaved communities during and after the TAST, shaped enslaved-African descendants' genomic diversity and structure on both sides of the Atlantic.

Detection of sexually antagonistic transmission distortions in trio datasets.

Sexual dimorphisms are widespread in animals and plants, for morphological as well as physiological traits. Understanding the genetic basis of sexual dimorphism and its evolution is crucial for understanding biological differences between the sexes. Genetic variants with sex-antagonistic effects on fitness are expected to segregate in populations at the early phases of sexual dimorphism emergence. Detecting such variants is notoriously difficult, and the few genome-scan methods employed so far have limited power and little specificity. Here, we propose a new framework to detect a signature of sexually antagonistic (SA) selection. We rely on trio datasets where sex-biased transmission distortions can be directly tracked from parents to offspring, and identify signals of SA transmission distortions in genomic regions. We report the genomic location of six candidate regions detected in human populations as potentially under sexually antagonist selection. We find an enrichment of genes associated with embryonic development within these regions. Last, we highlight two candidate regions for SA selection in humans.

3D planning and patient-specific surgical guides in forearm osteotomy in children: Radiographic accuracy and clinical morbidity.

INTRODUCTION: Three-dimensional (3D) planning and patient-specific surgical guides are increasingly used in the treatment of skeletal deformities. The present study hypothesis was that they are reliable in forearm osteotomy in children, with low morbidity. MATERIAL AND METHODS: Twenty-there children with one or several osteotomies to correct forearm deformities were retrospectively included: 9 (20 osteotomies) with surgical guide (G+), and 14 (28 osteotomies) without (G-). Etiologies comprised 8 cases of Madelung disease (3G+, 5G-) and 15 of post-traumatic malunion (6G+, 9G-). Mean age at surgery was 14.8±1.9 years. The patient-specific 3D-printed polyamide guides were produced from 3D virtual models based on 3D CT reconstruction. Mean follow-up was 22.1±13.6 months. RESULTS: Mean correction error was 5.3°±4.1 and 4.2°±4.1 in the frontal and sagittal planes respectively in G+ (p=0.6). Surgery time was significantly shorter in G+, by a mean 42min (p=0.02). Mean total radiation dose (preoperative CT+intraoperative fluoroscopy) was significantly higher in G+ (p<0.0001). Complications rates were similar between groups. Improvement in PRWE score was significantly greater in G+. CONCLUSION: The present preliminary results were encouraging. 3D planning and patient-specific surgical guides can be used in the treatment of forearm deformity in children. LEVEL OF EVIDENCE: III; retrospective cohort study.

Complex genetic admixture histories reconstructed with Approximate Bayesian Computation.

Admixture is a fundamental evolutionary process that has influenced genetic patterns in numerous species. Maximum-likelihood approaches based on allele frequencies and linkage-disequilibrium have been extensively used to infer admixture processes from genome-wide data sets, mostly in human populations. Nevertheless, complex admixture histories, beyond one or two pulses of admixture, remain methodologically challenging to reconstruct. We developed an Approximate Bayesian Computation (ABC) framework to reconstruct highly complex admixture histories from independent genetic markers. We built the software package MetHis to simulate independent SNPs or microsatellites in a two-way admixed population for scenarios with multiple admixture pulses, monotonically decreasing or increasing recurring admixture, or combinations of these scenarios. MetHis allows users to draw model-parameter values from prior distributions set by the user, and, for each simulation, MetHis can calculate numerous summary statistics describing genetic diversity patterns and moments of the distribution of individual admixture fractions. We coupled MetHis with existing machine-learning ABC algorithms and investigated the admixture history of admixed populations. Results showed that random forest ABC scenario-choice could accurately distinguish among most complex admixture scenarios, and errors were mainly found in regions of the parameter space where scenarios were highly nested, and, thus, biologically similar. We focused on African American and Barbadian populations as two study-cases. We found that neural network ABC posterior parameter estimation was accurate and reasonably conservative under complex admixture scenarios. For both admixed populations, we found that monotonically decreasing contributions over time, from Europe and Africa, explained the observed data more accurately than multiple admixture pulses. This approach will allow for reconstructing detailed admixture histories when maximum-likelihood methods are intractable.