FOOT PRONATION AND STRESS FRACTURES OF THE FEMUR AND TIBIA: A PROSPECTIVE BIOMECHANICAL STUDY

The relation between foot pronation and stress fractures has been suggested. However, evidence based literature is lacking and contradictory. The purpose of this study was to examine whether dynamic parameters of foot pronation are related to the development of stress fractures of the femur and tibia. 2 weeks prior to beginning of 14 weeks of basic military training, 473 infantry recruits were inrolled into the study. 2D analysis was performed to measure foot pronation during treadmill walking. The soldiers were examined during the training course at two weeks intervals for stress fractures. The odds ratio was calculated for each dynamic pronation parameter in relation to the stress fractures. 10% of the 405 soldiers who finished the training were diagnosed with stress fractures of the femur and tibia. Longer pronation time was related to risk reduction for the development of stress fractures and may have a protective effect during an extended period of training

Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds”

Use of the dioxin toxic equivalency factor (TEF) approach in human risk assessments assumes that the combined effects of dioxin-like compounds in a mixture can be predicted based on a potency-adjusted dose-additive combination of constituents of the mixture. In this study, we evaluated the TEF approach in experimental 2-year rodent cancer bioassays with female Harlan Sprague-Dawley rats receiving 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of the three compounds. Statistically based dose–response modeling indicated that the shape of the dose–response curves for hepatic, lung, and oral mucosal neoplasms was the same in studies of the three individual chemicals and the mixture. In addition, the dose response for the mixture could be predicted from a combination of the potency-adjusted doses of the individual compounds. Finally, we showed that use of the current World Health Organization dioxin TEF values adequately predicted the increased incidence of liver tumors (hepatocellular adenoma and cholangiocarcinoma) induced by exposure to the mixture. These data support the use of the TEF approach for dioxin cancer risk assessments

Distribution and correlates of plantar hyperkeratotic lesions in older people

<p>Abstract</p> <p>Background</p> <p>Plantar hyperkeratotic lesions are common in older people and are associated with pain, mobility impairment and functional limitations. However, little has been documented in relation to the frequency or distribution of these lesions. The aim of this study was to document the occurrence of plantar hyperkeratotic lesions and the patterns in which they occur in a random sample of older people.</p> <p>Methods</p> <p>A medical history questionnaire was administered to a random sample of 301 people living independently in the community (117 men, 184 women) aged between 70 and 95 years (mean 77.2, SD 4.9), who also underwent a clinical assessment of foot problems, including the documentation of plantar lesion locations, toe deformities and the presence and severity of hallux valgus.</p> <p>Results</p> <p>Of the 301 participants, 180 (60%) had at least one plantar hyperkeratotic lesion. Those with plantar lesions were more likely to be female (χ²= 18.75, <it>p </it>< 0.01; OR = 2.86), have moderate to severe hallux valgus (χ²= 6.15, <it>p </it>< 0.02; OR = 2.95), a larger dorsiflexion range of motion at the ankle (39.4 ± 9.3 <it>vs </it>36.3 ± 8.4°; <it>t </it>= 2.68, <it>df </it>= 286, <it>p </it>< 0.01), and spent more time on their feet at home (5.1 ± 1.0 <it>vs </it>4.8 ± 1.3 hours, <it>t </it>= -2.46, <it>df </it>= 299, <it>p </it>= 0.01). No associations were found between the presence of plantar lesions and body mass index, obesity, foot posture, dominant foot or forefoot pain. A total of 53 different lesions patterns were observed, with the most common lesion pattern being "roll-off" hyperkeratosis on the medial aspect of the 1^stmetatarsophalangeal joint (MPJ), accounting for 12% of all lesion patterns. "Roll-off" lesions under the 1^stMPJ and interphalangeal joint were significantly associated with moderate to severe hallux valgus (<it>p </it>< 0.05), whereas lesions under the central MPJs were significantly associated with deformity of the corresponding lesser toe (<it>p </it>< 0.05). Factor analysis indicated that 62% of lesion patterns could be grouped under three broad categories, relating to medial, central and lateral locations.</p> <p>Conclusion</p> <p>Plantar hyperkeratotic lesions affect 60% of older people and are associated with female gender, hallux valgus, toe deformity, increased ankle flexibility and time spent on feet, but are not associated with obesity, limb dominance, forefoot pain or foot posture. Although there are a wide range of lesion distribution patterns, most can be classified into medial, central or lateral groups. Further research is required to determine whether these patterns are related to the dynamic function of the foot or other factors such as foot pathology or morphology.</p

COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models

The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax—a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein receptor-binding domain (RBD)—induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function, and lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started

Gastrointestinal Hyperplasia with Altered Expression of DNA Polymerase β

Background: Altered expression of DNA polymerase β (Pol β) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol β over-expression has not yet been evaluated in a mouse model. Methodology/Principal Findings: We have recently developed a novel transgenic mouse model that over-expresses Pol β. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner's gland and mucosal hyperplasia in the duodenum. In addition, osteogenic tumors in mice tails, such as osteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol β over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol β expression. We observed elevated expression of Pol β in stomach adenomas and thyroid follicular carcinomas, but reduced Pol β expression in esophageal adenocarcinomas and squamous carcinomas. Conclusions/Significance: These data support the hypothesis that balanced and proficient base excision repair protein expression and base excision repair capacity is required for genome stability and protection from hyperplasia and tumor formation

Understanding acute ankle ligamentous sprain injury in sports

This paper summarizes the current understanding on acute ankle sprain injury, which is the most common acute sport trauma, accounting for about 14% of all sport-related injuries. Among, 80% are ligamentous sprains caused by explosive inversion or supination. The injury motion often happens at the subtalar joint and tears the anterior talofibular ligament (ATFL) which possesses the lowest ultimate load among the lateral ligaments at the ankle. For extrinsic risk factors to ankle sprain injury, prescribing orthosis decreases the risk while increased exercise intensity in soccer raises the risk. For intrinsic factors, a foot size with increased width, an increased ankle eversion to inversion strength, plantarflexion strength and ratio between dorsiflexion and plantarflexion strength, and limb dominance could increase the ankle sprain injury risk. Players with a previous sprain history, players wearing shoes with air cells, players who do not stretch before exercising, players with inferior single leg balance, and overweight players are 4.9, 4.3, 2.6, 2.4 and 3.9 times more likely to sustain an ankle sprain injury. The aetiology of most ankle sprain injuries is incorrect foot positioning at landing – a medially-deviated vertical ground reaction force causes an explosive supination or inversion moment at the subtalar joint in a short time (about 50 ms). Another aetiology is the delayed reaction time of the peroneal muscles at the lateral aspect of the ankle (60–90 ms). The failure supination or inversion torque is about 41–45 Nm to cause ligamentous rupture in simulated spraining tests on cadaver. A previous case report revealed that the ankle joint reached 48 degrees inversion and 10 degrees internal rotation during an accidental grade I ankle ligamentous sprain injury during a dynamic cutting trial in laboratory. Diagnosis techniques and grading systems vary, but the management of ankle ligamentous sprain injury is mainly conservative. Immobilization should not be used as it results in joint stiffness, muscle atrophy and loss of proprioception. Traditional Chinese medicine such as herbs, massage and acupuncture were well applied in China in managing sports injuries, and was reported to be effective in relieving pain, reducing swelling and edema, and restoring normal ankle function. Finally, the best practice of sports medicine would be to prevent the injury. Different previous approaches, including designing prophylactice devices, introducing functional interventions, as well as change of games rules were highlighted. This paper allows the readers to catch up with the previous researches on ankle sprain injury, and facilitate the future research idea on sport-related ankle sprain injury