Using non-invasive behavioral and physiological data to measure biological age in wild baboons.

Biological aging is near-ubiquitous in the animal kingdom, but its timing and pace vary between individuals and over lifespans. Prospective, individual-based studies of wild animals-especially non-human primates-help identify the social and environmental drivers of this variation by indicating the conditions and exposure windows that affect aging processes. However, measuring individual biological age in wild primates is challenging because several of the most promising methods require invasive sampling. Here, we leverage observational data on behavior and physiology, collected non-invasively from 319 wild female baboons across 2402 female-years of study, to develop a composite predictor of age: the non-invasive physiology and behavior (NPB) clock. We found that age predictions from the NPB clock explained 51% of the variation in females' known ages. Further, deviations from the clock's age predictions predicted female survival: females predicted to be older than their known ages had higher adult mortality. Finally, females who experienced harsh early-life conditions were predicted to be about 6 months older than those who grew up in more benign conditions. While the relationship between early adversity and NPB age is noisy, this estimate translates to a predicted 2-3 year reduction in mean adult lifespan in our model. A constraint of our clock is that it is tailored to data collection approaches implemented in our study population. However, many of the clock's components have analogs in other populations, suggesting that non-invasive data can provide broadly applicable insight into heterogeneity in biological age in natural populations.

Analysis of Major and Minor Pedicles in Flap Perfusion by Computational Fluid Dynamics.

Background: Type 2 muscle flaps are characterized by major and minor pedicles, such that the minor pedicle is unreliable, and the major pedicle is a requirement for the success of the flap. The role of the minor pedicle, beyond the decreased caliber and decreased vascular territory in comparison to the major pedicle, is poorly understood. We sought to model the fluid dynamics of a model flap containing a major and minor pedicle to understand differences between the pedicles and the implications on perfusion. Methods: We first generated a computer-assisted design model of a type 2 flap with a major and minor pedicle. We then performed computational fluid dynamics to analyze velocities and flow within the pedicles and flap. Results: In our investigation, we found that the flow velocity within the major pedicle was higher than the minor pedicle, indicative of decreased resistance to flow. Concomitantly, we found decreased pressures within the major pedicle, reflecting decreasing resistance to flow. Interestingly, we found increased kinematic viscosity in flap areas supplied by the minor pedicle, suggesting decreased flow rates and increased resistance. Conclusions: We identified that the major pedicle has increased flow velocity, decreased resistance, and decreased kinematic viscosity, suggesting its dominance in maintaining flap perfusion. Our study also identifies computational fluid dynamics as a powerful tool in studying flap perfusion dynamics.

Modulation of Cellular Stemness for Enhanced Fat Grafting.

Low volumetric retention limits the utility of fat grafting. Although inclusion of stem cells and platelet-rich plasma have been proposed to enhance graft retention, accumulating evidence has failed to show a clear benefit. Here, we propose a strategy to pharmacologically enhance stemness of stem and progenitor cell populations in fat grafts to promote increased volume retention and tissue health. We also propose how to integrate stemness-promoting and differentiation-promoting therapies such as platelet-rich plasma, and viability promoting therapies within the common fat grafting workflow to achieve optimal fat grafting results.

[SGLT2 inhibitors, also in frail older adults?] / SGLT2-remmers, ook bij kwetsbare ouderen?

Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) have gained prominence in the treatment of diabetes mellitus type 2, heart failure, and chronic kidney disease. However, concerns arise for frail older adults, given their underrepresentation in trials and heightened susceptibility to adverse drug events. This review summarizes the clinical effects of SGLT2 inhibitors in older adults with frailty. SGLT2 inhibitors seem to exhibit consistent cardiovascular benefits irrespective of age. As such, these drugs can be beneficial for older adults with 'cardiovascular frailty': in other words, cardiovascular multimorbidity. However, in the current data there is a lack of focus on the broader definition of frailty, which also includes functional status and self-dependence. Also, some research suggest that adverse events, such as volume depletion and genitourinary infections, are more common in the frail older population. Therefore, until more data is available, SGLT2 inhibitors should be prescribed with caution in older adults living with frailty.

Nasal Soft Tissue Triangle Large Composite Graft Take With Postoperative Hyperbaric Oxygen Therapy: A Case Report.

Background: Auricular composite grafts hold great potential for reconstructing the nasal soft tissue triangle with desired aesthetic results because there is ample tissue available for sufficient nasal ala projection and the natural curvature of the helical rim matches that of the alar rim. The use of auricular composite grafts also results in positive functional outcomes because of the cartilaginous airway support provided to widen the external nasal valve. Composite graft survival is highly dependent on graft size, as larger sized grafts have a higher metabolic demand.To improve graft viability and reliability, hyperbaric oxygen therapy can be employed to accommodate the increased metabolic demand seen with larger composite grafts. Conclusions: This report presents the survival of a large skin and cartilage composite graft for nasal soft tissue triangle reconstruction in conjunction with hyperbaric oxygen therapy to improve graft viability.

Potential drug-drug interactions in males living with HIV who use drugs to treat lower urinary tract symptoms.

OBJECTIVE: Lower urinary tract symptoms (LUTS) are becoming more prevalent in the ageing population of males living with HIV. Drugs to treat LUTS are known for both their potential role as victims in drug-drug interactions (DDIs) and their side effects. We aimed to evaluate the current use of drugs to treat LUTS and to assess potential DDIs in our cohort of adult males living with HIV. DESIGN: This was a retrospective review of pharmacy records. METHODS: We recorded the combination antiretroviral therapy (cART) regimen and any use of drugs to treat LUTS (anatomical therapeutic chemical codes G04CA/CB/CX and G04BD). Potential DDIs were assessed using the interaction checker developed by the University of Liverpool (https://www.hiv-druginteractions.org/checker). RESULTS: A total of 411 adult males living with HIV were included in this analysis. The median (interquartile range [IQR]) age was 53 (41-62) years. Nineteen (4.6%) patients used one or more drugs to treat LUTS. As expected, older patients were more likely to be receiving treatment for LUTS: Q1 (20-40 years) = 0%; Q2 (41-52 years) = 2%; Q3 (53-61 years) = 7%; Q4 (62-79 years) = 10%. Seven potential DDIs between cART and LUTS treatment were noted in six of the 19 (32%) patients. Following medication reviews of these six patients, the following interventions were proposed: evaluate safe use of alpha-blocker (n = 4), change in cART (n = 2), and dose reduction of the anticholinergic agent (n = 1). CONCLUSION: Treatment for LUTS coincided with cART in 7%-10% of patients aged above the median age of 53 years in our cohort. Improvements in DDI management appeared to be possible in this growing cohort of males living with HIV and with LUTS.

Universal gut microbial relationships in the gut microbiome of wild baboons.

Ecological relationships between bacteria mediate the services that gut microbiomes provide to their hosts. Knowing the overall direction and strength of these relationships is essential to learn how ecology scales up to affect microbiome assembly, dynamics, and host health. However, whether bacterial relationships are generalizable across hosts or personalized to individual hosts is debated. Here, we apply a robust, multinomial logistic-normal modeling framework to extensive time series data (5534 samples from 56 baboon hosts over 13 years) to infer thousands of correlations in bacterial abundance in individual baboons and test the degree to which bacterial abundance correlations are 'universal'. We also compare these patterns to two human data sets. We find that, most bacterial correlations are weak, negative, and universal across hosts, such that shared correlation patterns dominate over host-specific correlations by almost twofold. Further, taxon pairs that had inconsistent correlation signs (either positive or negative) in different hosts always had weak correlations within hosts. From the host perspective, host pairs with the most similar bacterial correlation patterns also had similar microbiome taxonomic compositions and tended to be genetic relatives. Compared to humans, universality in baboons was similar to that in human infants, and stronger than one data set from human adults. Bacterial families that showed universal correlations in human infants were often universal in baboons. Together, our work contributes new tools for analyzing the universality of bacterial associations across hosts, with implications for microbiome personalization, community assembly, and stability, and for designing microbiome interventions to improve host health.

Communities of bacteria living in the guts of humans and other animals perform essential services for their hosts such as digesting food, degrading toxins, or fighting viruses and other bacteria that cause disease. These services emerge from so-called 'ecological' relationships between different species of bacteria. One species, for example, may break down a molecule in human food into another compound that is, in turn, digested by another species into a small molecule that the human gut can absorb and use. The bacteria involved in such a process may become more or less common together in their host. In other situations, some bacteria may have opposing roles to each other, meaning that if one species becomes more abundant it may reduce the level of the other. However, it is not known if relationships between different bacteria are consistent across hosts (i.e., universal) or unique to each host (personalized). In other words, if a pair of bacteria increase and decrease in abundance together in one host, do they do the same in other hosts? Microbes often swap genes with each other to gain new traits; as each host harbors a distinctive set of gut microbes, it may be possible for microbial relationships to change depending on the bacterial species present in a specific environment. To investigate, Roche et al. studied the bacteria in thousands of samples of feces collected from 56 baboons over a 13-year period. These samples came from a long-term research project in Amboseli, Kenya which has been studying a population of wild baboons continuously since 1971. Roche et al. measured the abundance of hundreds of gut bacteria in the feces to understand the relationships between pairs. This revealed that connections between species were largely universal rather than personalized to each baboon. Furthermore, the pairs of bacteria with the strongest positive or negative associations had the most consistent relationships across the baboons. Microbial relationships that have strong effects on the microbiome's composition might therefore be especially universal. Further analyses measuring gut bacteria in human babies also found that relationships between pairs of bacteria were largely universal. Hence, individual species of bacteria may fill similar ecological roles in each host across humans and other primates, and perhaps also in other mammals. These findings suggest that it may be possible to leverage the ecological relationships between bacteria to develop universal therapies for human diseases associated with gut bacteria, such as inflammatory bowel disease or Clostridium difficile infection.

Investigation of Hospital Pricing Information for Plastic Surgery Procedures Reveals Widespread Violation of the CMS Price Transparency Act.

BACKGROUND: Price transparency allows patients to estimate surgical procedure costs, which can affect where they elect to receive care and should theoretically result in hospitals setting lower and more uniform prices. To elucidate the traditionally opaque nature of health care pricing, the U.S. Centers for Medicare & Medicaid Services has mandated that hospitals publicly release their pricing information. The authors sought to investigate the utility of price transparency for plastic surgery patients, who are uniquely situated to benefit because of the dominance of elective procedures. METHODS: This study included 54 randomly chosen public and private hospitals. Pricing information for 15 common plastic surgery-related procedures was compiled from their websites. RESULTS: One year after the ruling went into effect, only 13% of hospitals were fully compliant with Centers for Medicare & Medicaid Services requirements for reporting standard charges. The most commonly reported plastic surgery procedures were adjacent tissue transfers (CPT codes 14000, 14001, 14301, and 14302), with an average of 32.4% of hospitals listing pricing data. The 25.9% of hospitals reporting the immediate insertion of breast implants (CPT code 19340) pricing presented a wide range of gross prices, from $2346.09 to $29,969.35. Free and pedicled flaps (CPT codes 19364, 19361, 19367, 19368, and 19369) were less commonly reported than autologous tissue transfer or nonflap breast procedures ( P = 0.00). CONCLUSIONS: A comparative analysis of published prices provides a starting point for surgeons to recommend facilities to patients based on price. However, significant variability was observed in data presentation, reported procedures, and listed prices. These inconsistencies in reporting and unrealistic ranges in price render the comparison of plastic surgery prices among hospitals impractical.

Smoking as a Risk Factor for Forehead Flap Wound Outcomes: An Analysis of 1030 Patients.

Background: The forehead flap is a local transposition flap based on a pedicled vessel commonly used to reconstruct facial defects. Often patients requiring reconstructions are smokers, yet the effects of smoking on forehead flaps are not well defined. Our study is aimed to examine smoking as a preoperative risk factor for complications following forehead flaps. Methods: This retrospective cohort study used data collected from the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2019. Multivariate logistic regression models were fitted to evaluate the association between smoking and development of wound complications. Results: A total of 1030 forehead flaps cases were analyzed and separated into 2 cohorts based on current smoking status: 789 (76.6%) nonsmokers versus 241 (23.4%) smokers. No significant differences in rates of wound complications were found for nonsmokers versus smokers (2.7% vs 4.1%; P = .0807), including when adjusted for comorbidities in a multivariate logistic regression model (adjusted odds ratio, 1.297 [95% confidence interval, 0.55-2.9]; P = .5174). Conclusions: Smoking has been demonstrated to be a risk factor for plastic surgery procedures. However, in our review of 1030 forehead flaps, smokers did not have worse outcomes compared with nonsmokers. Although it is still advised to recommend smoking cessation given multiple health benefits, smoking status should not preclude candidacy for facial reconstruction with a forehead flap based on complication risk.

Soft Tissue Expansion in Total Knee Arthroplasty Due to Extensive Scarring and Fibrosis in Multiple-Operated Knee.

Background: Inadequate wound closure is a feared complication following total knee arthroplasty (TKA). A knee with a multiple operative history, excessive scarring, and fibrosed surrounding soft tissue presents a significant challenge. In cases with preoperative uncertainty for sufficient soft tissue coverage because of ischemia and tension on closure, soft tissue expansion (STE) has been reported to be an effective tool for optimizing successful closure. Case Report: For the case in this report, STE was performed on a knee with multiple scars, potential ischemia, fibrosis, and soft tissue contractures prior to TKA. Conclusions: In cases of uncertain soft tissue coverage in TKA, the use of STE can be a useful method in creating adequate wound closure.

Synchrony and idiosyncrasy in the gut microbiome of wild baboons.

Human gut microbial dynamics are highly individualized, making it challenging to link microbiota to health and to design universal microbiome therapies. This individuality is typically attributed to variation in host genetics, diets, environments and medications but it could also emerge from fundamental ecological forces that shape microbiota more generally. Here, we leverage extensive gut microbial time series from wild baboons-hosts who experience little interindividual dietary and environmental heterogeneity-to test whether gut microbial dynamics are synchronized across hosts or largely idiosyncratic. Despite their shared lifestyles, baboon microbiota were only weakly synchronized. The strongest synchrony occurred among baboons living in the same social group, probably because group members range over the same habitat and simultaneously encounter the same sources of food and water. However, this synchrony was modest compared to each host's personalized dynamics. In support, host-specific factors, especially host identity, explained, on average, more than three times the deviance in longitudinal dynamics compared to factors shared with social group members and ten times the deviance of factors shared across the host population. These results contribute to mounting evidence that highly idiosyncratic gut microbiomes are not an artefact of modern human environments and that synchronizing forces in the gut microbiome (for example, shared environments, diets and microbial dispersal) are not strong enough to overwhelm key drivers of microbiome personalization, such as host genetics, priority effects, horizontal gene transfer and functional redundancy.

Gut microbiome heritability is nearly universal but environmentally contingent.

Relatives have more similar gut microbiomes than nonrelatives, but the degree to which this similarity results from shared genotypes versus shared environments has been controversial. Here, we leveraged 16,234 gut microbiome profiles, collected over 14 years from 585 wild baboons, to reveal that host genetic effects on the gut microbiome are nearly universal. Controlling for diet, age, and socioecological variation, 97% of microbiome phenotypes were significantly heritable, including several reported as heritable in humans. Heritability was typically low (mean = 0.068) but was systematically greater in the dry season, with low diet diversity, and in older hosts. We show that longitudinal profiles and large sample sizes are crucial to quantifying microbiome heritability, and indicate scope for selection on microbiome characteristics as a host phenotype.

A comparison of dominance rank metrics reveals multiple competitive landscapes in an animal society.

Across group-living animals, linear dominance hierarchies lead to disparities in access to resources, health outcomes and reproductive performance. Studies of how dominance rank predicts these traits typically employ one of several dominance rank metrics without examining the assumptions each metric makes about its underlying competitive processes. Here, we compare the ability of two dominance rank metrics-simple ordinal rank and proportional or 'standardized' rank-to predict 20 traits in a wild baboon population in Amboseli, Kenya. We propose that simple ordinal rank best predicts traits when competition is density-dependent, whereas proportional rank best predicts traits when competition is density-independent. We found that for 75% of traits (15/20), one rank metric performed better than the other. Strikingly, all male traits were best predicted by simple ordinal rank, whereas female traits were evenly split between proportional and simple ordinal rank. Hence, male and female traits are shaped by different competitive processes: males are largely driven by density-dependent resource access (e.g. access to oestrous females), whereas females are shaped by both density-independent (e.g. distributed food resources) and density-dependent resource access. This method of comparing how different rank metrics predict traits can be used to distinguish between different competitive processes operating in animal societies.

Towards a "prescribing license" for medical students: development and quality evaluation of an assessment for safe prescribing.

PURPOSE: This report describes the development and validation process of an assessment with national consensus in appropriate and safe pharmacotherapy. METHODS: A question-database on safe prescription based on literature of pharmacotherapy-related harm was developed by an expert group from Dutch medical faculties. Final-year medical students concluded a 2-year education program on appropriate and safe prescription by one of nine assessment variants of 40 multiple-choice questions each. An expert panel of professionals (n = 10) answered all database questions and rated questions on relevance. Questions were selected for revision based on lack of relevance or poor test and item characteristics. RESULTS: A total of 576 final-year medical students of the Radboud University was assessed. There was no significant difference in performance between students and content expert group (p = 0.7), probably due to learning behavior. Out of 165 questions, 59 were selected for revision. CONCLUSION: Joint national effort from a team of experts in prescription and pharmacotherapy is an appropriate way to achieve a valid and reliable last-year student drug prescription assessment.

Costs and drivers of helminth parasite infection in wild female baboons.

Helminth parasites can have wide-ranging, detrimental effects on host reproduction and survival. These effects are best documented in humans and domestic animals, while only a few studies in wild mammals have identified both the forces that drive helminth infection risk and their costs to individual fitness. Working in a well-studied population of wild baboons (Papio cynocephalus) in the Amboseli ecosystem in Kenya, we pursued two goals, to (a) examine the costs of helminth infections in terms of female fertility and glucocorticoid hormone levels and (b) test how processes operating at multiple scales-from individual hosts to social groups and the population at large-work together to predict variation in female infection risk. To accomplish these goals, we measured helminth parasite burdens in 745 faecal samples collected over 5 years from 122 female baboons. We combine these data with detailed observations of host environments, social behaviours, hormone levels and interbirth intervals (IBIs). We found that helminths are costly to female fertility: females infected with more diverse parasite communities (i.e., higher parasite richness) exhibited longer IBIs than females infected by fewer parasite taxa. We also found that females exhibiting high Trichuris trichiura egg counts also had high glucocorticoid levels. Female infection risk was best predicted by factors at the host, social group and population level: females facing the highest risk were old, socially isolated, living in dry conditions and infected with other helminths. Our results provide an unusually holistic understanding of the factors that contribute to inter-individual differences in parasite infection, and they contribute to just a handful of studies linking helminths to host fitness in wild mammals.

Treatment of Breast Animation Deformity in Implant-Based Reconstruction with Selective Nerve Ablation.

Breast animation deformity is a known complication of subpectoral implant placement that is usually corrected by repositioning the implant to the prepectoral position. Other less common treatment options include performing the muscle splitting biplanar technique, triple plane technique, neuromodulator injections, and secondary neurotomies via transection of the pectoral muscle. We report a patient with animation deformity successfully treated with direct identification and ablation of the medial and lateral pectoral nerves using selective bipolar electrocautery. The patient is a woman with a history of invasive ductal carcinoma who underwent bilateral mastectomy and breast reconstruction with subpectoral implant placement and autologous fat grafting. Within 1 year of her breast reconstruction, she developed hyperactive pectoralis muscle contraction with resulting distortion of both breasts. Given the disadvantages of repositioning the implant to the prepectoral position and transecting the pectoralis muscles via secondary neurotomy, we chose to directly identify and selectively ablate distal branches of the medial and lateral pectoral nerves. This offers a novel technique for correcting breast animation deformity without transecting the pectoralis muscles, causing muscle atrophy, and preserving the subpectoral implant position.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .

Neoumbilicoplasty with a Superiorly Based Abdominal Skin Flap.

We propose a neoumbilicoplasty technique that can be applied when the umbilical stalk becomes disrupted during an abdominoplasty. This case used surgical concepts that involved progressive thinning of the flap in a 3-cm radius around the neoumbilicus, with increased thinning toward the neoumbilical position. This was followed with suture tacking of the thinned abdominal flap to create a concavity around the neoumbilicus. A longer "U" shaped incision was created and also sutured down to abdominal wall to recreate an umbilical "floor" with the adjacent skin sutured to the superior-based flap to construct the walls of the neoumbilicus. An aesthetically pleasing umbilicus resulted with high patient satisfaction and a lack of postoperative complications. There were no additional scars extending beyond the umbilical region.

Gauze Impregnated With Quaternary Ammonium Salt Reduces Bacterial Colonization of Surgical Drains After Breast Reconstruction.

Surgical site infection after breast reconstruction is associated with increased length of hospital stay, readmission rates, cost, morbidity, and mortality. Identifying methods to reduce surgical site infection without the use of antibiotics may be beneficial at reducing antimicrobial resistance, reserving the use of antibiotics for more severe cases. Quaternary ammonium salts have previously been shown to be a safe and effective antimicrobial agent in the setting of in vitro and in vivo animal experiments. A retrospective study was conducted to investigate the antimicrobial properties of a quaternary ammonium salt, 3-trimethoxysilyl propyldimethyloctadecyl ammonium chloride (QAS-3PAC; Bio-spear), at reducing surgical drain site colonization and infection after breast reconstruction (deep inferior epigastric perforator flap reconstruction or tissue expander placement). Twenty patients were enrolled, with 14 surgical drains covered with nonimpregnated gauze and 17 surgical drains covered with QAS-3PAC impregnated gauze, for the purposes of investigating bacterial colonization. Antibiotic sensitivity analysis was also conducted when bacterial cultures were positive. The overall incidence of bacterial colonization of surgical drains was lower in the treatment group compared with the control group (17.6% vs 64.3%, respectively; P = 0.008). QAS-3PAC impregnated gauze reduced the incidence of bacterial colonization of surgical drains during the first (0.0% vs 33.3%) and second (33.3% vs 87.5%; P = 0.04) postoperative week. Furthermore, no enhanced antibiotic resistance was noted on drains treated with QAS-3PAC impregnated gauze. The results of this study suggest that QAS-3PAC impregnated gauze applied over surgical drains may be an effective method for reducing the incidence of bacterial colonization.