Hip extensor mechanics and the evolution of walking and climbing capabilities in humans, apes, and fossil hominins.

The evolutionary emergence of humans' remarkably economical walking gait remains a focus of research and debate, but experimentally validated approaches linking locomotor capability to postcranial anatomy are limited. In this study, we integrated 3D morphometrics of hominoid pelvic shape with experimental measurements of hip kinematics and kinetics during walking and climbing, hamstring activity, and passive range of hip extension in humans, apes, and other primates to assess arboreal-terrestrial trade-offs in ischium morphology among living taxa. We show that hamstring-powered hip extension during habitual walking and climbing in living apes and humans is strongly predicted, and likely constrained, by the relative length and orientation of the ischium. Ape pelves permit greater extensor moments at the hip, enhancing climbing capability, but limit their range of hip extension, resulting in a crouched gait. Human pelves reduce hip extensor moments but permit a greater degree of hip extension, which greatly improves walking economy (i.e., distance traveled/energy consumed). Applying these results to fossil pelves suggests that early hominins differed from both humans and extant apes in having an economical walking gait without sacrificing climbing capability. Ardipithecus was capable of nearly human-like hip extension during bipedal walking, but retained the capacity for powerful, ape-like hip extension during vertical climbing. Hip extension capability was essentially human-like in Australopithecus afarensis and Australopithecus africanus, suggesting an economical walking gait but reduced mechanical advantage for powered hip extension during climbing.

The structure and competitive substrate inhibition of dihydrofolate reductase from Enterococcus faecalis reveal restrictions to cofactor docking.

We are addressing bacterial resistance to antibiotics by repurposing a well-established classic antimicrobial target, the dihydrofolate reductase (DHFR) enzyme. In this work, we have focused on Enterococcus faecalis, a nosocomial pathogen that frequently harbors antibiotic resistance determinants leading to complicated and difficult-to-treat infections. An inhibitor series with a hydrophobic dihydrophthalazine heterocycle was designed from the anti-folate trimethoprim. We have examined the potency of this inhibitor series based on inhibition of DHFR enzyme activity and bacterial growth, including in the presence of the exogenous product analogue folinic acid. The resulting preferences were rationalized using a cocrystal structure of the DHFR from this organism with a propyl-bearing series member (RAB-propyl). In a companion apo structure, we identify four buried waters that act as placeholders for a conserved hydrogen-bonding network to the substrate and indicate an important role in protein stability during catalytic cycling. In these structures, the nicotinamide of the nicotinamide adenine dinucleotide phosphate cofactor is visualized outside of its binding pocket, which is exacerbated by RAB-propyl binding. Finally, homology models of the TMP(R) sequences dfrK and dfrF were constructed. While the dfrK-encoded protein shows clear sequence changes that would be detrimental to inhibitor binding, the dfrF-encoded protein model suggests the protein would be relatively unstable. These data suggest a utility for anti-DHFR compounds for treating infections arising from E. faecalis. They also highlight a role for water in stabilizing the DHFR substrate pocket and for competitive substrate inhibitors that may gain advantages in potency by the perturbation of cofactor dynamics.

Metric and geometric morphometric analysis of new hominin fossils from Maba (Guangdong, China).

We present an analysis of a set of previously unreported hominin fossils from Maba (Guangdong, China), a cave site that is best known for the presence of a partial hominin cranium currently assigned as mid-Pleistocene Homo and that has been traditionally dated to around the Middle-Late Pleistocene transition. A more recent set of Uranium series dates indicate that the Maba travertine may date to >237 ka (thousands of years ago), as opposed to the original U-series date, which placed Maba at 135-129 ka. The fossils under study include five upper first and second molars and a partial left mandible with a socketed m3, all recovered from different parts of the site than the cranium or the dated sediments. The results of our metric and 2D geometric morphometric ('GM') study suggest that the upper first molars are likely from modern humans, suggesting a more recent origin. The upper second molars align more closely with modern humans, though the minimum spanning tree from the 2D GM analysis also connects Maba to Homo neanderthalensis. The patterning in the M2s is not as clear as with the M1s. The m3 and partial mandible are morphometrically intermediate between Holocene modern humans and older Homo sapiens. However, a minimum spanning tree indicates that both the partial mandible and m3 align most closely with Holocene modern humans, and they also may be substantially younger than the cranium. Because questions exist regarding the context and the relationship of the dated travertine with the hominin fossils, we suggest caution is warranted in interpreting the Maba specimens.

Obstetrical Constraints and the Origin of Extended Postnatal Brain Maturation in Hominin Evolution.

The origin of difficult birth is still a matter of debate in obstetrics. Recent studies hypothesized that early hominins already experienced obstructed labor even with reduced neonatal head sizes. The aim of this work is to test this hypothesis using an extant obstetrical sample with known delivery outcomes. Three delivery outcomes (i.e., instrument-assisted, Caesarean section, and vaginal birth) were evaluated using a discriminant analysis based on 131 mother-baby dyads and 36 feto-pelvic variables. This obstetrical sample was compared with 20 australopithecine "dyads" generated from the combination of six pelvic reconstructions (three for Australopithecus afarensis, two for A. africanus, and one for A. sediba) and three fetal head size estimations. The obstetrical analysis revealed that dystocic births can be predicted by pelvic features such as an anteroposteriorly flattened pelvic inlet. Australopithecines shared these pelvic morphologies with humans and had eutocic birth only for infants of 110 g brain size or smaller, equaling a human-like neonatal/adult brain size ratio of 25-28%. Although birth mechanism cannot be deduced, the newborn/adult brain size ratio was likely more human-like than previously thought, suggesting that australopithecines were secondarily altricial to circumvent instances of obstructed labor and subsequently require a prolonged postnatal brain growth period, implying some aspects of life history pattern similar to modern humans.

Take it to the limit: The limitations of energetic explanations for birth timing in humans.

A hallmark of modern humans is that our newborns are neurologically immature compared to other primates. It is disputed whether this so-called secondary altriciality evolved due to remodelling of the pelvis associated with bipedal locomotion, as suggested by the obstetrical dilemma hypothesis, or from maternal energetic limitations during pregnancy. Specifically, the 'Energetics of Gestation and Growth' (EGG) hypothesis posits that birth is initiated when foetal energy requirements exceed the maximum sustained maternal metabolic rate during pregnancy at around 2.1 × basal metabolic rate (BMR) of the non-pregnant, non-lactating condition (NPNL). However, the metabolic threshold argued under the EGG framework is derived from one study with a small sample size of only 12 women from the UK. Accordingly, we performed a meta-analysis of all published studies on metabolic scopes during pregnancy to better account for variability. After excluding 3 studies with methodological issues, a total of 12 studies with 303 women from 5 high- and 3 low-income countries were analysed. On average, pregnancy was found to be less metabolically challenging than previously suggested. The studies revealed substantial variation in metabolic scope during pregnancy, which was not reflected by variation in birth timing. Further, in a third of the studies, the metabolic rates exceeded 2.1 × BMRNPNL. Our simulation of foetal energy requirements demonstrated that this metabolic threshold of 2.1 × BMRNPNL cannot realistically be crossed by the foetus around the time of birth. These findings imply that metabolic constraints are not the main limiting factor dictating gestation length.

Integrated approaches to prevent exposure risks related to latex-derived products.

Natural rubber latex is a widely used industrial raw material to produce many consumer and commercial products. Chronic exposures to latex allergenic proteins residual in the finished products can promote hypersensitive immune responses, which affects millions of workers and the general public worldwide. Research has shown the average prevalence of latex allergy worldwide remains approximately 10% among healthcare workers, 7% among susceptible patients, and 4% among general population. Although most effective in preventing latex allergy, completely avoiding contact to latex-derived products is extremely challenging, given the fact that millions of products possibly contain latex, but few are regulated and properly labeled. Due to the difficulty to assure a product completely absent of latex allergens, the United States Food and Drug Administration has recommended to stop using labels like "latex-free" or "does not contain latex." Here we evaluate published data, industrial standards and regulations, identify possible countermeasures, and propose an integrated strategy, including some more practicable approaches (e.g., education/training, product labeling, the use of proper personal protective equipment, occupational selection, and searchable product database) and novel medical treatments (e.g., immunotherapy) to help decreasing latex allergy prevalence.

Geriatric Oncology in the Instagram Era: Feasibility and Acceptability Randomised Controlled Trial on Adopting PhotoVoice to Enable Empowerment, Patient-Centred Care, and Shared Decision Making-Study Protocol.

Geriatric assessment (GA) is fundamental to optimising cancer care in older adults, yet implementing comprehensive GA tools in real-world clinical settings remains a challenge. This study aims to assess the feasibility and acceptability of integrating information from patient-derived photographs (PhotoVoice) into enhanced supportive care (ESC) for older adults with cancer. A feasibility randomised controlled trial will be conducted at a regional cancer care centre in Australia. Participants aged 70 and above will be randomised into two groups: PhotoVoice plus ESC or usual care (ESC) alone. In the PhotoVoice group, participants will provide four photographs for deduction of representations of different aspects of their lives using photo-elicitation techniques. ESC will be conducted for both groups, incorporating PhotoVoice analysis in the intervention group. PhotoVoice may improve patient-centred care outcomes, including enhanced communication, shared decision making, and identification of patient priorities and barriers. Findings will provide insights into implementing PhotoVoice in geriatric assessment and guide future trials in cancer among older adults.

Echocardiographic and clinical outcomes following beating heart NeoChord DS1000 mitral valve repair: a single centre case series.

Background: The NeoChord DS1000 system implants artificial neochords transapically, through a left mini-thoracotomy to treat degenerative mitral valve regurgitation (MR). Performed without cardiopulmonary bypass, neochord implantation and length adjustment is guided by transesophageal echocardiography. We describe imaging and clinical outcomes for a single center case series using this innovative device platform. Methods: In this prospective series, all study patients had degenerative MR and were considered for conventional mitral valve surgery. Moderate to high-risk candidates were screened for NeoChord DS1000 eligibility based on echocardiographic criteria. Study criteria included isolated posterior leaflet prolapse, leaflet-to-annulus index greater than 1.2, and coaptation length index greater than 5 mm. Patients with bileaflet prolapse, mitral annular calcification, and ischemic MR were excluded from our early experience. Results: Ten patients underwent the procedure, including 6 males and 4 females, with a mean age of 76 ± 9.5 years. All patients had severe chronic MR and normal left ventricular function. One patient required conversion to an open procedure for failure to deploy neochords with the device transapically. The median number of NeoChord sets was 3 (IQR 2.3-3.8). Immediate post-procedure (POD#0) degree of MR on echocardiography ranged from mild or less, and on postoperative day 1 (POD#1) from moderate or less. Average length of coaptation was 0.85 ± 0.21 cm and average depth of coaptation was 0.72 ± 0.15 cm. At 1-month follow-up echocardiography, MR was graded from trivial to moderate and left ventricular inner diameter dimensions decreased from an average of 5.4 ± 0.4 cm to 4.6 ± 0.3 cm. None of the patients who had successful NeoChord implantation required blood products. There was 1 perioperative stroke with no residual deficits. There were no device-related complications or serious adverse events. The median length of hospital stay was 3 (IQR 2.3-10) days. 30-day and 6-weeks postoperative mortality and readmission rates were 0%. Conclusion: We report the first Canadian case series using the NeoChord DS1000 system for off-pump, transapical, beating heart mitral valve repair, through a left mini-thoracotomy. The early surgical outcomes suggest this approach is feasible, safe, and effective in reducing MR. This novel procedure has the advantage of offering a minimally invasive, off-pump option for select patients with high surgical risk.

Perspectives of Health Care Personnel on the Benefits of Bronchiolitis Interventions.

OBJECTIVES: Many interventions in bronchiolitis are low-value or poorly studied. Inpatient bronchiolitis management is multidisciplinary, with varying degrees of registered nurse (RN) and respiratory therapist (RT) autonomy. Understanding the perceived benefit of interventions for frontline health care personnel may facilitate deimplementation efforts. Our objective was to examine perceptions surrounding the benefit of common inpatient bronchiolitis interventions. METHODS: We conducted a cross-sectional survey of inpatient pediatric RNs, RTs, and physicians/licensed practitioners (P/LPs) (eg, advanced-practice practitioners) from May to December of 2021 at 9 university-affiliated and 2 community hospitals. A clinical vignette preceded a series of inpatient bronchiolitis management questions. RESULTS: A total of 331 surveys were analyzed with a completion rate of 71.9%: 76.5% for RNs, 57.4% for RTs, and 71.2% for P/LPs. Approximately 54% of RNs and 45% of RTs compared with 2% of P/LPs believe albuterol would be "extremely or somewhat likely" to improve work of breathing (P < .001). Similarly, 52% of RNs, 32% of RTs, and 23% of P/LPs thought initiating or escalating oxygen in the absence of hypoxemia was likely to improve work of breathing (P < .001). Similar differences in perceived benefit were observed for steroids, nebulized hypertonic saline, and deep suctioning, but not superficial nasal suctioning. Hospital type (community versus university-affiliated) did not impact the magnitude of these differences. CONCLUSIONS: Variation exists in the perceived benefit of several low-value or poorly studied bronchiolitis interventions among health care personnel, with RNs/RTs generally perceiving higher benefit. Deimplementation, educational, and quality improvement efforts should be designed with an interprofessional framework.

Perioperative Optimization of the Cardiac Surgical Patient.

Perioperative optimization of cardiac surgical patients is imperative to reduce complications, utilize health care resources efficiently, and improve patient recovery and quality of life. Standardized application of evidence-based best practices can lead to better outcomes. Although many practices should be applied universally to all patients, there are also opportunities along the surgical journey to identify patients who will benefit from additional interventions that will further ameliorate their recovery. Enhanced recovery programs aim to bundle several process elements in a standardized fashion to optimize outcomes after cardiac surgery. A foundational concept of enhanced recovery is attaining a better postsurgical end point for patients, in less time, through achievement and maintenance in their greatest possible physiologic, functional, and psychological state. Perioperative optimization is a broad topic, spanning multiple phases of care and involving a variety of medical specialties and nonphysician health care providers. In this review we highlight a variety of perioperative care topics, in which a comprehensive approach to patient care can lead to improved results for patients, providers, and the health care system. A particular focus on patient-centred care is included. Although existing evidence supports all of the elements reviewed, most require further improvements in implementation, as well as additional research, before their full potential and usefulness can be determined.

Sex classification using the human sacrum: Geometric morphometrics versus conventional approaches.

The human pelvis shows marked sexual dimorphism that stems from the conflicting selective pressures of bipedal locomotion and parturition. The sacrum is thought to reflect this dimorphism as it makes up a significant portion of the pelvic girdle. However, reported sexual classification accuracies vary considerably depending on the method and reference sample (54%-98%). We aim to explore this inconsistency by quantifying sexual dimorphism and sex classification accuracies in a geographically heterogeneous sample by comparing 3D geometric morphometrics with the more commonly employed linear metric and qualitative assessments. Our sample included 164 modern humans from Africa, Europe, Asia, and America. The geometric morphometric analysis was based on 44 landmarks and 56 semilandmarks. Linear dimensions included sacral width, corpus depth and width, and the corresponding indices. The qualitative inspection relied on traditional macroscopic features such as proportions between the corpus of the first sacral vertebrae and the alae, and sagittal and coronal curvature of the sacrum. Classification accuracy was determined using linear discriminant function analysis for the entire sample and for the largest subsamples (i.e., Europeans and Africans). Male and female sacral shapes extensively overlapped in the geometric morphometric investigation, leading to a classification accuracy of 72%. Anteroposterior corpus depth was the most powerful discriminating linear parameter (83%), followed by the corpus-area index (78%). Qualitative inspection yielded lower accuracies (64-76%). Classification accuracy was higher for the Central European subsample and diminished with increasing geographical heterogeneity of the subgroups. Although the sacrum forms an integral part of the birth canal, our results suggest that its sex-related variation is surprisingly low. Morphological variation thus seems to be driven also by other factors, including body size, and sacrum shape is therefore likely under stronger biomechanical rather than obstetric selection.

Sex determination accuracy using the human sacrum in a Central European sample.

The sacrum is often used for sex estimation of human remains. However, reported sexual classification accuracies based on the sacrum produce highly discrepant estimates ranging from 54% to 98% depending on the method and reference sample. Here, we therefore aim to evaluate the sacrum's efficacy in differentiating males from females by comparing three different approaches in a homogeneous Central European sample (n = 58, 27 males and 31 females) obtained from the 19th century Weisbach collection. Specifically, we investigated the sacrum by 1) a qualitative visual inspection, 2) traditional linear metrics, namely, sacral width, corpus width, and the associated corporo-basal index, and 3) geometric morphometrics (GM) using a 3D configuration of 100 landmarks and semilandmarks. Classification accuracies for the qualitative approach ranged from 69% to 81%. The investigated quantitative methods based on linear dimensions led to comparable classification accuracies of 62% for sacral width and 78% for the corporo-basal index. However, absolute corpus width had a stronger discriminative power (86%), similar to the PC scores from shape space (87%). Unexpectedly, the GM approach, which considered the shape of the entire sacrum, did not classify better than linear variables. This was exceeded only when sacrum shape was combined with corpus width or another measure of size, like the natural logarithm of the centroid size, yielding a classification accuracy of 95%. The male and female group means differed mainly in the general height-to-width relationship and corpus-to-alae proportions, corroborating patterns previously described in the literature. Our results suggest that the sacrum is markedly less effective than the hipbone for sex determination, which is at odds with its central position within the pelvic girdle and thus its supposed obstetric relevance.

The morphological consequences of segmentation anomalies in the human sacrum.

OBJECTIVES: Despite the high frequency of segmentation anomalies in the human sacrum, their evolutionary and clinical implications remain controversial. Specifically, inconsistencies involving the classification and counting methods obscure accurate assessment of lumbosacral transitional vertebrae. Therefore, we aim to establish more reliable morphological and morphometric methods for differentiating between sacralizations and lumbarizations in clinical and paleontological contexts. MATERIALS AND METHODS: Using clinical CT data from 145 individuals aged 14-47 years, vertebral counts and the spatial relationship between the sacrum and adjoining bony structures were assessed, while the morphological variation of the sacrum was assessed using geometric morphometrics based on varied landmark configurations. RESULTS: The prevalence of lumbosacral and sacrococcygeal segmentation anomalies was 40%. Lumbarizations and sacralizations were reliably distinguishable based on the spatial relationship between the iliac crest and the upward or downward trajectory of the linea terminalis on the sacrum. Different craniocaudal orientations of the alae relative to the corpus of the first sacral vertebra were also reflected in the geometric morphometric analyses. The fusion of the coccyx (32%) was frequently coupled with lumbarizations, suggesting that the six-element sacra more often incorporate the coccyx rather than the fifth lumbar vertebra. CONCLUSIONS: Our approach allowed the consistent identification of segmentation anomalies even in isolated sacra. Additionally, our outcomes either suggest that homeotic border shifts often affect multiple spinal regions in a unidirectional way, or that sacrum length is highly conserved perhaps due to functional constraints. Our results elucidate the potential clinical, biomechanical, and evolutionary significance of lumbosacral transitional vertebrae.

Dynamic finite-element simulations reveal early origin of complex human birth pattern.

Human infants are born neurologically immature, potentially owing to conflicting selection pressures between bipedal locomotion and encephalization as suggested by the obstetrical dilemma hypothesis. Australopithecines are ideal for investigating this trade-off, having a bipedally adapted pelvis, yet relatively small brains. Our finite-element birth simulations indicate that rotational birth cannot be inferred from bony morphology alone. Based on a range of pelvic reconstructions and fetal head sizes, our simulations further imply that australopithecines, like humans, gave birth to immature, secondary altricial newborns with head sizes smaller than those predicted for non-human primates of the same body size especially when soft tissue thickness is adequately approximated. We conclude that australopithecines required cooperative breeding to care for their secondary altricial infants. These prerequisites for advanced cognitive development therefore seem to have been corollary to skeletal adaptations for bipedal locomotion that preceded the appearance of the genus Homo and the increase in encephalization.

Characteristics of Hospitalized Children Positive for SARS-CoV-2: Experience of a Large Center.

OBJECTIVES: Define the spectrum of disease in pediatric inpatients with a positive SARS-CoV-2 test result in a manner relevant to pediatric hospital medicine. METHODS: Retrospective case series of all patients aged <22 years hospitalized at our institution with a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction test result between May 1, 2020, and September 30, 2020. Demographic, clinical, and outcome data were collected and analyzed. RESULTS: Three distinct presentations were associated with acute SARS-CoV-2 positivity. Patients had incidental infection (40%), were potentially symptomatic (47%), or were significantly symptomatic (14%). The average length of stay differed between the significantly symptomatic group and the incidental and potentially symptomatic groups (P =.002). Average age differed among these groups, with significantly symptomatic patients older by >2 years. Fifty-five percent of incidental and 47% of potentially symptomatic patients had at least 1 identified comorbidity, whereas 90% of significantly symptomatic patients had at least 1 (P = .01). There was a significant relationship between obesity (P = .001) and asthma (P = .004) and severe disease. Additionally, there was a statistically significant difference between groups with respect to fever, hypoxia, supplemental oxygen use, duration of supplemental oxygen, and ICU admission, with a significantly higher percentage of patients in the significantly symptomatic group meeting each of these criteria (P < .001 for all categories). CONCLUSIONS: Pediatric patients hospitalized with SARS-CoV-2 fall into distinct categories, which are critical to understanding the true pathology of SARS-Cov-2 as it relates to hospitalized pediatric patients. Most hospitalized patients who test positive for SARS-CoV-2 are asymptomatic or have a reason for hospitalization other than coronavirus disease 2019.

New insights on hip bone sexual dimorphism in adolescents and adults using deformation-based geometric morphometrics.

Morphological variation of the human pelvis, and particularly the hip bone, mainly results from both female-specific selective pressure related to the give birth of large-headed newborns, and constraints in both sexes for efficient bipedal locomotion, abdominal stability, and adaptation to climate. Hip bone morphology has thus been extensively investigated using several approaches, although the nuances of inter-individual and sex-related variation are still underappreciated, and the effect of sex on ontogenetic patterns is debated. Here, we employ a landmark-free, deformation-based morphometric approach to explore variation in modern human hip bone shape and size from middle adolescence to adulthood. Virtual surface models of the hip bone were obtained from 147 modern human individuals (70 females and 77 males) including adolescents, and young and mature adults. The 3D meshes were registered by rotation, translation, and uniform scaling prior to analysis in Deformetrica. The orientation and amplitude of deviations of individual specimens relative to a global mean were assessed using Principal Component Analysis, while colour maps and vectors were employed for visualisation purposes. Deformation-based morphometrics is a time-efficient and objective method free of observer-dependent biases that allows accurate shape characterisation of general and more subtle morphological variation. Here, we captured nuanced hip bone morphology revealing ontogenetic trends and sex-based variation in arcuate line curvature, greater sciatic notch shape, pubic body and rami length, acetabular expansion, and height-to-width proportions of the ilium. The observed ontogenetic trends showed a higher degree of bone modelling of the lesser pelvis of adolescent females, while male variation was mainly confined to the greater pelvis.

Sacrum morphology supports taxonomic heterogeneity of "Australopithecus africanus" at Sterkfontein Member 4.

The presence of multiple Australopithecus species at Sterkfontein Member 4, South Africa (2.07-2.61 Ma), is highly contentious, and quantitative assessments of craniodental and postcranial variability remain inconclusive. Using geometric morphometrics, we compared the sacrum of the small-bodied, presumed female subadult Australopithecus africanus skeleton Sts 14 to the large, alleged male adult StW 431 against a geographically diverse sample of modern humans, and two species of Pan, Gorilla, and Pongo. The probabilities of sampling morphologies as distinct as Sts 14 and StW 431 from a single species ranged from 1.3 to 2.5% for the human sample, and from 0.0 to 4.5% for the great apes, depending on the species and the analysis. Sexual dimorphism and developmental or geologic age could not adequately explain the differences between StW 431 and Sts 14, suggesting that they are unlikely to be conspecific. This supports earlier claims of taxonomic heterogeneity at Sterkfontein Member 4.