Elbow Extensor Muscles in Humans and Chimpanzees: Adaptations to Different Uses of the Upper Extremity in Hominoid Primates.

The anatomical and functional characteristics of the elbow extensor muscles (triceps brachii and anconeus) have not been widely studied in non-human hominoid primates, despite their great functional importance. In the present study, we have analyzed the muscle architecture and the expression of the myosin heavy chain (MHC) isoforms in the elbow extensors in humans and chimpanzees. Our main objective was to identify differences in these muscles that could be related to the different uses of the upper extremity in the two species. In five humans and five chimpanzees, we have analyzed muscle mass (MM), muscle fascicle length (MFL), and the physiological cross-sectional area (PCSA). In addition, we have assessed the expression of the MHC isoforms by RT-PCR. We have found high MM and PCSA values and higher expression of the MHC-IIx isoform in the triceps brachii of chimpanzees, while in humans, the triceps brachii has high MFL values and a higher expression of the MHC-I and MHC-IIa isoforms. In contrast, there were no significant differences between humans and chimpanzees in any of the values for the anconeus. These findings could be related to the participation of the triceps brachii in the locomotion of chimpanzees and to the use of the upper extremity in manipulative functions in humans. The results obtained in the anconeus support its primary function as a stabilizer of the elbow joint in the two species.

Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials.

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., ß-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5-5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8-25.2 g/day (SUCRA = 0.94) and patiromer 8.4-16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.

The Inhibition of Complement System in Formal and Emerging Indications: Results from Parallel One-Stage Pairwise and Network Meta-Analyses of Clinical Trials and Real-Life Data Studies.

This manuscript presents quantitative findings on the actual effectiveness of terminal complement component 5 (C5) inhibitors and complement component 1 (C1) esterase inhibitors through their formal and common "off-label" (compassionate) indications. The results emanated from pairwise and network meta-analyses to present evidence until September 2019. Clinical trials (CT) and real-life non-randomized studies of the effects of interventions (NRSI) are consistent on the benefits of C5 inhibitors and of the absence of effects of C1 esterase inhibitors (n = 7484): Mathematically, eculizumab (surface under the cumulative ranking area (SUCRA) >0.6) and ravulizumab (SUCRA ≥ 0.7) were similar in terms of their protective effect on hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathy (TMA) in atypical hemolytic uremic syndrome (aHUS), and acute kidney injury (AKI) in aHUS, in comparison to pre-/off-treatment state and/or placebo (SUCRA < 0.01), and eculizumab was efficacious on thrombotic events in PNH (odds ratio (OR)/95% confidence interval (95% CI) in CT and real-life NRSI, 0.07/0.03 to 0.19, 0.24/0.17 to 0.33) and chronic kidney disease (CKD) occurrence/progression in PNH (0.31/0.10 to 0.97, 0.66/0.44 to 0.98). In addition, meta-analysis on clinical trials shows that eculizumab mitigates a refractory generalized myasthenia gravis (rgMG) crisis (0.29/0.13 to 0.61) and prevents new acute antibody-mediated rejection (AMR) episodes in kidney transplant recipients (0.25/0.13 to 0.49). The update of findings from this meta-analysis will be useful to promote a better use of complement inhibitors, and to achieve personalization of treatments with this class of drugs.

Three-dimensional geometric morphometric analysis of the distal radius insertion sites of the palmar radiocarpal ligaments in hominoid primates.

OBJECTIVES: To identify anatomic differences in the insertion sites of the palmar radiocarpal ligaments in different species of hominoid primates that may be related to their different types of locomotion. MATERIALS AND METHODS: We have used three-dimensional geometric morphometrics (3D GM) to analyze the distal radius ligament insertion sites in 31 Homo sapiens, 25 Pan troglodytes, 31 Gorilla gorilla, and 15 Pongo pygmaeus. We have also dissected the radioscaphocapitate (RSC), long radiolunate (LRL) and short radiolunate (SRL) ligaments in six H. sapiens and five P. troglodytes to obtain quantitative values that were then compared with the results of the 3D GM analysis. RESULTS: H. sapiens had a relatively larger insertion site of the RSC + LRL ligament than the other hominoid primates. P. pygmaeus and P. troglodytes had a relatively large SRL ligament insertion site with a palmar orientation. In G. gorilla, the two ligament insertion sites were relatively smaller and the SRL insertion site had an ulnopalmar orientation. DISCUSSION: The morphological differences observed can be related to the types of locomotion used by the different species and to quantitative data obtained from the dissection of ligaments in H. sapiens and P. troglodytes. 3D GM analysis of ligament insertion sites can help in interpreting the types of locomotion used by extinct hominoid primates through the analysis of preserved fossilized fragments of the distal radius.

Quantification of Myosin Heavy Chain Isoform mRNA Transcripts in the Supraspinatus Muscle of Vertical Clinger Primates.

Vertical clinging is a specialized form of locomotion characteristic of the primate family Callitrichidae. Vertical clinging requires these pronograde primates to maintain a vertical posture, so the protraction of their forelimbs must resist gravity. Since pronograde primates usually move as horizontal quadrupeds, we hypothesized that the supraspinatus muscle of vertical clingers would present specific characteristics related to the functional requirements imposed on the shoulder area by vertical clinging. To test this hypothesis, we quantified by real-time quantitative polymerase chain reaction the mRNA transcripts of myosin heavy chain (MHC) isoforms in the supraspinatus muscle of 15 species of pronograde primates, including vertical clingers. Our results indicate that the supraspinatus of vertical clingers has a specific expression pattern of the MHC isoforms, with a low expression of the transcripts of the slow MHC-I isoform and a high expression of the transcripts of the fast MHC-II isoforms. We conclude that these differences can be related to the particular functional characteristics of the shoulder in vertical clingers, but also to other anatomical adaptations of these primates, such as their small body size.

The head and neck muscles of the serval and tiger: homologies, evolution, and proposal of a mammalian and a veterinary muscle ontology.

Here we describe the head and neck muscles of members of the two extant felid subfamilies (Leptailurus serval: Felinae; Panthera tigris: Pantherinae) and compare these muscles with those of other felids, other carnivorans (e.g., domestic dogs), other eutherian mammals (e.g., rats, tree-shrews and modern humans), and noneutherian mammals including monotremes. Another major goal of the article is to discuss and help clarify nomenclatural discrepancies found in the Nomina Anatomica Veterinaria and in veterinary atlases and textbooks that use cats and dogs as models to understand the anatomy of domestic mammals and to stress differences with modern humans. We propose a unifying nomenclature that is expanded to all the head and neck muscles and to all mammalian taxa in order to help build veterinary and mammalian muscle ontologies. Our observations and comparisons and the specific use of this nomenclature point out that felids such as tigers and servals and other carnivorans such as dogs have more facial muscle structures related to the mobility of both the auricular and orbital regions than numerous other mammals, including modern humans, which might be the result of an ancient adaptation related to the remarkable predatory capacities of carnivorans. Interestingly, the skeletal differences, mainly concerning the hyoid apparatus, pharynx, and larynx, that are likely associated with the different types of vocalizations seen in the Felinae (mainly purring) and Pantherinae (mainly roaring) are not accompanied by clear differences in the musculature connected to these structures in the feline L. serval and the pantherine P. tigris.

Biometry and statistical analysis of the styloid process.

The hyoid apparatus is made up of three osteocartilaginous elements that go from the base of the cranium to the hyoid bone; the portions, cranially to caudally, are as follow: stylohyal, ceratohyal, and apohyal. Fusion and ossification of these three components will bring about somewhat long stylohyoid processes, whereas the stylohyal portion is the one that gives rise to the authentic stylohyoid process. The variability of the hyoid apparatus may imply associated compressive pathologies, for which an etiological diagnosis is important. A study was undertaken of 835 craniums of a homogeneous male and female adult population, involving a morphometric analysis of the styloid processes in which quantification was made of the following continual descriptive measurements: thickness, length, sagittal angle, transversal angle, and the distance between vertices. Multivariate data analysis techniques were applied to the data set to describe the relationships between these measurements. The main conclusion from the analysis is the existence of two different groups of styloid processes and the derivation of a prediction score.