The biomechanical role of the lacertus fibrosus of the biceps brachii Muscle.

PURPOSE: The lacertus fibrosus (LF) is involved in various surgeries. However, the biomechanical contribution of the LF remains unclear. The aim of this study was to determine the role of the lacertus fibrosus on the elbow and forearm kinematics and on the biceps brachii muscle lever arms. METHODS: This biomechanical study was performed on seven fresh-frozen upper limbs of cadavers. Elbow flexion, forearm supination, and biceps brachii muscle lever arms were analyzed in the intact conditions (I) and after superficial (R) and deep part (R2) of the lacertus fibrosus release, respectively. RESULTS: Elbow flexion shows a significant difference (p < 0.0001) between I, R, R2. Abduction/adduction shows a significant difference between I-R (p < 0.0001) and I-R2 (p < 0.0001). Supination does not show a significant difference in mean maximum amplitude, but between 40 and 70%, there are significant differences. There is a significant mean decrease of lever arm in flexion (28%) and supination (50%) after superficial and deep part of the lacertus fibrosus release. CONCLUSION: The results of this study show that the lacertus fibrosus increases the lever arm during flexion and supination. It limits the flexion and abduction of the elbow and supination of the forearm. Lacertus fibrosus maintains the rhythmicity between the elbow flexion and supination of the forearm. LEVEL OF EVIDENCE: Basic science study, biomechanics.

Digenic Inheritance of Mutations in Homologous Recombination Genes in Cancer Patients.

BACKGROUND/OBJECTIVES: BRCA1, BRCA2, ATM, and CHEK2 are known cancer predisposition genes (CPGs), but tumor risk in patients with simultaneous pathogenic variants (PVs) in CPGs remains largely unknown. In this study, we describe six patients from five families with multiple cancers who coinherited a combination of PVs in these genes. METHODS: PVs were identified using NGS DNA sequencing and were confirmed by Sanger. RESULTS: Families 1, 2, and 3 presented PVs in BRCA2 and ATM, family 4 in BRCA2 and BRCA1, and family 5 in BRCA2 and CHEK2. PVs were identified using NGS DNA sequencing and were confirmed by Sanger. The first family included patients with kidney, prostate, and breast cancer, in addition to pancreatic adenocarcinomas. In the second family, a female had breast cancer, while a male from the third family had prostate, gastric, and pancreatic cancer. The fourth family included a male with pancreatic cancer, and the fifth family a female with breast cancer. CONCLUSIONS: The early age of diagnosis and the development of multiple cancers in the reported patients indicate a very high risk of cancer in double-heterozygous patients associated with PVs in HR-related CPGs. Therefore, in families with patients who differ from other family members in terms of phenotype, age of diagnosis, or type of cancer, the cascade testing needs to include the study of other CPGs.

Constitutional mismatch repair deficiency mimicking Lynch syndrome is associated with hypomorphic mismatch repair gene variants.

Lynch syndrome (LS) and constitutional mismatch repair deficiency (CMMRD) are distinct cancer syndromes caused, respectively, by mono- and bi-allelic germline mismatch repair (MMR) variants. LS predisposes to mainly gastrointestinal and genitourinary cancers in adulthood. CMMRD predisposes to brain, haematological, and LS-spectrum cancers from childhood. Two suspected LS patients with first cancer diagnosis aged 27 or 38 years were found to be homozygous for an MMR (likely) pathogenic variant, MSH6 c.3226C>T (p.(Arg1076Cys)), or variant of uncertain significance (VUS), MLH1 c.306G>A (p.(Glu102=)). MLH1 c.306G>A was shown to cause leaky exon 3 skipping. The apparent genotype-phenotype conflict was resolved by detection of constitutional microsatellite instability in both patients, a hallmark feature of CMMRD. A hypomorphic effect of these and other variants found in additional late onset CMMRD cases, identified by literature review, likely explains a LS-like phenotype. CMMRD testing in carriers of compound heterozygous or homozygous MMR VUS may find similar cases and novel hypomorphic variants. Individualised management of mono- and bi-allelic carriers of hypomorphic MMR variants is needed until we better characterise the associated phenotypes.

Gemals, a new drug candidate, extends lifespan and improves electromyographic parameters in a rat model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal disease involving selective and progressive degeneration and death of motor neurons. ALS is a multifactorial disease in which oxidative stress, glutamate excitotoxicity, intracellular aggregates, neurofilamentous disorganization, zinc excitotoxicity, mitochondrial damage, neuroinflammation, abnormalities in growth factors and apoptosis play a role. Any therapeutic approach to delay or stop the evolution of ALS should therefore ideally target these multiple pathways leading to motor neuron death. We have developed a combination therapy (Gemals) composed of functional polypeptides (fatty acids, free radical scavengers and amino acids linked to poly-L-lysine), chosen according to their known potentiality for regeneration or protection of neuronal components such as myelin, axon transport and mitochondria. We found that Gemals significantly extended lifespan and improved electromyographic parameters in a SOD1(G93A) rat model. The use of two drug concentrations indicated a possible dose dependence. These initial findings open the way to further investigation necessary to validate this new drug as a candidate for ALS treatment.

A novel method for in-vivo evaluation of finger kinematics including definition of healthy motion patterns.

BACKGROUND: Despite recent progress in motion capture technology, such as stereophotogrammetry based on the tracking of markers set on the subject, it remains challenging to develop a complete protocol for in-vivo functional evaluation of the hand. The current practical problems regarding small anatomical segments, such as the fingers, are mainly due to the high concentration of markers in a relatively reduced volume. METHODS: This paper proposes a novel procedure for hand functional analysis by analysing finger behaviour along the main displacement plane simultaneously with combined motions. The objective was two-fold. For one thing, a novel data collection protocol was implemented, which includes specific setting of the motion capture system and the development of finger marker clusters. The second purpose of this study was to create a reference database of a healthy sample for further clinical investigation. Twenty healthy volunteers took part in the study. Analytical motions (flexion/extension and abduction/adduction) of all five fingers were recorded. FINDINGS: Results showed good correspondence with the literature. Specific kinematic behaviour of each analysed joint is reported. Statistically significant differences were found between the right and left sides of the subjects for the flexion/extension movement only, between the finger joints and between the fingers for all movements. No significant difference was found between genders. A validation protocol was performed, which proved the validity of the presented methodology. INTERPRETATION: The protocol appears suitable for further use in motion analysis and for musculoskeletal modelling of the hand. It will also be considered for clinical application.

Motion representation of the long fingers: a proposal for the definitions of new anatomical frames.

Despite the availability of the International Society of Biomechanics (ISB) recommendations for the orientation of anatomical frames, no consensus exists about motion representations related to finger kinematics. This paper proposes novel anatomical frames for motion representation of the phalangeal segments of the long fingers. A three-dimensional model of a human forefinger was acquired from a non-pathological fresh-frozen hand. Medical imaging was used to collect phalangeal discrete positions. Data processing was performed using a customized software interface ("lhpFusionBox") to create a specimen-specific model and to reconstruct the discrete motion path. Five examiners virtually palpated two sets of landmarks. These markers were then used to build anatomical frames following two methods: a reference method following ISB recommendations and a newly-developed method based on the mean helical axis (HA). Motion representations were obtained and compared between examiners. Virtual palpation precision was around 1mm, which is comparable to results from the literature. The comparison of the two methods showed that the helical axis method seemed more reproducible between examiners especially for secondary, or accessory, motions. Computed Root Mean Square distances comparing methods showed that the ISB method displayed a variability 10 times higher than the HA method. The HA method seems to be suitable for finger motion representation using discrete positions from medical imaging. Further investigations are required before being able to use the methodology with continuous tracking of markers set on the subject's hand.