Rejected

Coracoid transfer is a reliable method for managing anterior shoulder instability in athletes who play contact sports; however, differences between the Bristow and Latarjet procedures are unclear.

Cryptococcal meningoencephalitis is mainly caused by Cryptococcus neoformans and accounts for 90% of fungal meningitis cases in Japan. Cryptococcal meningoencephalitis is a rare disease, and similar to tuberculosis meningitis. It often exhibits subacute or chronic progression symptoms such as headache, fever, coma, personality changes, and memory disturbance. Cryptococcal meningoencephalitis often develops in immunosuppressed hosts, but can sometimes occur in healthy individuals, and the mortality rate is 10-25%, indicating a poor prognosis. For the treatment of cryptococcal meningoencephalitis, introduction therapy using a combination of liposomal amphotericin B and flucytosine is recommended. However, in practice, cryptococcal meningoencephalitis is refractory and often requires prolonged treatment; therefore, it is the most difficult to treat among the central nervous system infections. We discuss the following 11 issues: I. Sustainability of first-line treatments, II. Treatment options in case of decreased renal function, III. Association with increased intracranial pressure IV. Causes of visual impairment, V. Necessary steps when symptoms/laboratory findings worsen during antifungal treatment, VI. Cerebral infarction, VII. Difficulty in controlling underlying and comorbid diseases, VIII. Indications for lumbar and ventricular drainage (Ommaya reservoir placement), IX. Pros and cons of concomitant use of corticosteroids, X. Treatment evaluation index: usefulness of head MRI, and XI. Determining the end of treatment and the need for preventive medication.

Gulf War Illness (GWI) afflicts ~30% of the US military personnel who served in the 1990-91 Persian Gulf War. Symptoms include cognitive deficits, muscle pain, weakness, exercise intolerance and fatigue which are still present after 30 years in war Veterans. Suspect causal agents include exposure to the compounds pyridostigmine (PB), permetrim (PM) and N,N-diethyl-m-toluamide (DEET) which were used as protectants against nerve gases (PB) and insects. We previously reported a study to model GWI in which young male rats were provided PB, PM and DEET at equivalent human doses and physical restraint (to induce stress) for 3 weeks. In GWI animals, skeletal muscle weight was 35% lower vs. controls, which correlated with decreases in myofiber area, limb strength and treadmill time/distance. In a follow up study, we reported on the beneficial effects of the cacao flavanol (-)-epicatechin (epi) provided for 2 weeks by oral gavage on skeletal muscle atrophy and loss of function. In the current study, we wished to explore the potential of Epi to beneficially impact neurological measures of memory including multiple markers of hippocampus structure and function. Male Wistar rats underwent 3 weeks of exposure to either vehicles or DEET, PM, PB and stress. Subgroups of GWI rats (n=7/subgroup) received 15 days of either water (vehicle) or 1 mg/kg/day of Epi treatment by oral gavage and were compared to normal control (n=7). Object recognition tasks were performed to assess effects on memory and hippocampus samples were collected for histological and biochemical analysis. Results demonstrate that Epi treatment yields significant improvements in short and long-term memory vs. GWI rats yielding values similar to those of controls. The assessment of hippocampus oxidative stress (protein carbonylation) and pro-inflammatory cytokines levels (ELISA) of IL-1β, TNF-α and IFN-γ (figure) yielded significant increases with GWI that were fully normalized with Epi to become comparable to controls. Significant increases in markers of hippocampus neuroinflammation (Iba1 and GFAP) and cell death (caspase activity) were noted with GWI and were significantly reduced with Epi. The neuronal survival signaling pathways (TREM2, PI3K and AKT) were adversely impacted by GWI and were partially or fully restored by Epi. Multiple markers of mitochondrial function (citrate synthase activity and ATP levels) adversely impacted by GWI and were fully restored by Epi. Thus, in an animal model of GWI, Epi beneficially impacted markers of hippocampus neuroinflammation, oxidative stress, cell survival, neurotoxicity and mitochondrial function. Such effects translated into improvements in functional endpoints associated with memory centers. As per the recognized safety profile of Epi clinical studies are warranted to explore the effects of treatment in Gulf War Veterans.

The fibularis (peroneus) quartus is a variant muscle found within the lateral leg compartment in ~11.5% of cadaveric specimens, though recent studies have shown a higher prevalence of ~20.9 – 21.9%. The proximal muscular attachments can originate from the fibula, fibularis brevis, fibularis longus, and/or the intermuscular septi that form the boundaries of the lateral leg compartment, but it then descends to reside posterior to the lateral malleolus of the fibula. The distal attachment of the fibularis quartus varies greatly, and fibularis quartus muscular variants are often named according to location of its distal attachment. The most common distal insertion site of a fibularis quartus muscle is the lateral surface of the calcaneus into either the fibular trochlea or the retrotrochlear eminence. Therefore, this variant of the fibularis quartus inserting into the lateral surface of the calcaneus is called the fibulocalcaneus externum. During routine cadaveric dissection of a 79-year-old Caucasian male, a rare and novel variation of the fibularis quartus muscle was discovered. Although this variant is seen arising from the fibula, fibularis brevis, and the posterior intermuscular septum, descending posterior to the lateral malleolus, and attaching distally to the lateral surface of the calcaneus, it is unique in that the muscle is inverted, with the tendonous part being more proximal and the muscular portion arising distally. This novel muscle was found unilaterally in the left leg via dissection initially with its distal head inserting on the fibular trochlea of the calcaneus, but ultrasonographic imaging verified its bilateral presence. The subsequent dissection of the right leg revealed a similar inverted muscle, but this variation split into two distal muscle bellies inserting into the retrotrochlear eminence posteriorly and the fibular trochlear anteriorly. Given its anatomy, we have named this rare fibularis quartus variant the fibulocalcaneus externum invertus muscle. Like most fibularis quartus variants, the fibulocalcaneus externum invertus muscle can cause ankle instability, ankle locking, chronic lateral ankle pain, and peroneal compartment syndrome, especially due to acting as a space-occupying lesion within the superior peroneal tunnel due to its distal muscle belly/bellies. While it is unknown if this person had any clinical signs and/or symptoms, clinicians, surgeons, and/or radiologists should be aware of the fibulocalcaneus externum invertus when assessing radiological imaging or preparing for ankle surgeries in and around the lateral leg compartment.

Opioids are extensively used for their analgesic properties but present a variety of unwanted side effects, including tolerance, dependence and respiratory depression. The analgesic effect of opioids is due to activation of µ-opioid receptors (MOR) in the central nervous system and no treatments are currently available to prevent respiratory depression without reducing their analgesic properties. The neural circuits and mechanisms regulating respiratory depression, sedation, and analgesia by opioids often overlap, therefore making challenging the identification of the mechanisms regulating respiratory depression. Neurons expressing tachykinin precursor 1 peptide (Tac1) located in the pre-Bötzinger complex (preBötC) also co-express neurokinin-1 receptors (NK1R) and MORs. NK1R neurons are preferentially inhibited by opioids and play an essential role in mediating opioid-induced respiratory depression.

Cybersickness is an array of symptoms associated with exposure to three-dimensional visualization technology (3DVT) environments, such as virtual reality (VR). It is thought that cybersickness is a type of motion sickness caused by a mismatch in sensory and vestibular input when using these modalities. Symptoms of cybersickness are often akin to those of traditional motion sickness, such as headache and nausea. In the literature, as many as 40-60% of VR users report symptoms of cybersickness, though in our laboratory approximately 20% of users report symptoms of cybersickness. Our past research has shown that the physical environment is often preferred by students, and more effective for learning anatomy, compared to 3DVT environments. We hypothesize that the preference for, and effectiveness of, the physical environment over 3DVT may be a result of cybersickness due to the isolation of the learner from the physical environment. However, no direct measurements of cybersickness or comparisons between 3DVT environments in anatomy are available.

Based on global burden of headache reports, migraine is a prevalent disorder that affect approximately 15% of the adult population. Generally migraine attacks are sporadic, however, some individuals develop a chronic disease form. To date, several researches have shown that migraine is associated with some gastrointestinal disorders such as Helicobacter pylori (HP) infection, irritable bowel syndrome (IBS), and celiac disease (CD). However, the mechanisms explaining how the gut and the brain may interact in patients with migraine are not entirely clear. In this study, we aimed to evaluate the role of the short-chain fatty acids (SCFAs), such as sodium propionate (SP) and sodium butyrate (SB) as mediators and modulators of host intestinal microbial ecology, in regulating the pathophysiology of migraine in a mouse model induced by nitroglycerine (NTG).

Eosinophilic Esophagitis (EoE) is a chronic condition characterized by esophageal dysfunction including dysphagia, abdominal pain and eosinophilic inflammation (>15/HPF) of the esophagus. At present, the most commonly used treatment for the management of EoE are steroids, both systemic as well as tropical, and dietary elimination. The advantage of the systemic steroids include ease of administration, rapid response, and very high response rate. However, poor solubility and the adverse effect related to prolonged steroid use are well documented. Moreover, there is a high relapse rate of EoE after the treatment is discontinued which limit the use of oral steroids as a maintenance therapy. Similarly, Ranitidine (Zantac), histamin-2 blocker, used to treat gastrointestinal reflux and heart burns, has been recently withdrawn from the market by FDA due to increased risk of cancer. Digestive Tea has been used at the Traditional Chinese Medicine (TCM) practice to improve gastrointestinal (GI) symptoms such as stomach pain, constipation and abnormal bowel movement. Different versions of Digestion Teas are further developed to address specific clinical GI symptoms. Compound 7, 4 Dihydroxy flavone (DHF) is a flavonoid purified from Glycyrrhiza uralensis from Digestive Tea. Previously our group has shown inhibition of Eotaxin, Th2 cytokines and IgE in-vitrousing DHF. The objective of this study is to reveal potential mechanisms underlying DHF improving symptoms related to EoE using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analyses, and in silico molecular docking. Based on the pathway analyses, the most important targets identified were TNF- α, IL-6, IL1β, MAPK1, MAPK3, AKT1, CASP3 and CCND in AGE-RAGE pathway. We further validated the targets of our computational modeling in human esophagus biopsy sample by ELISA and qRT-PCR. We found significant reduction in levels of TNF-α (p<0.001), IL-6 (p<0.001), IL-8 (p<0.001) and IL1-β (p<0.05) in the supernatant of biopsy sample cultured with DHF. Moreover, gene expression profile showed significant reduction in level of TNF- α (p<0.01), IL1-β (p<0.05), IL-6 (p<0.01) and CCND (p<0.05) in the biopsy sample cultured with DHF. Furthermore, our molecular docking analysis revealed that DHF can directly bind TNF- α with free binding energies of -7.7 kcal/mol. Taken together, the current study may lead to development of DHF as an active therapeutic candidate in treatment of EoE.

Chronic prostatitis (CP) has long been considered one of the common causes of male infertility. The influence of therapy for CP on spermatogenesis is well studied. However, recently, especially in the era of the new coronavirus infection (COVID-19), much attention has been paid to the effects of cytokines on the pathogenesis of the inflammatory process, and their impact on male fertility.

Pain, swelling and joint stiffness are the major problems following arthroscopic ACL reconstruction (ACLR) surgery that restrict early return to sports and athletic activities. The patients often receive prolonged analgesic medications to control the inflammatory response and resume the pre-injury activities. This systematic review aims to evaluate the safety and efficacy of intraarticular (IA) hyaluronic acid (HA) injection following ACLR.