Rejected

Coeliac disease (CD) is characterised by diverse clinical symptoms, which may cause diagnostic problems and reduce the patients' quality of life. A study conducted in the United Kingdom (UK) revealed that the mean time between the onset of coeliac symptoms and being diagnosed was above 13 years. This study aimed to analyse the diagnostic process of CD in Poland and evaluate the quality of life of patients before and after CD diagnosis. In addition, results were compared to the results of the original study conducted in the UK.

Idiopatic trigeminal neuralgia purely paroxysmal (ITNp) distributed in the supraorbital and suprathrochlear dermatomes (SSd), refractory to conventional treatments have been linked to the hyperactivity of the corrugator supercilii muscle (CSM). In these patients, the inactivation of the CSM via botulinum toxin type A (BTA) injections has been proven to be safe and effective in reducing migraine burden. The main limitation of BTA is the need of repetitive injections and relative high costs. Based on the study of the motor innervation of the CSM, we describe here an alternative approach to improve these type of migraines, based on a minimally invasive denervation of the CSM.

A adenosine receptors were found to have a role in different pathological states, such as glaucoma, renal fibrosis, neuropathic pain and cancer. Consequently, it is important to utilize any molecular tool which could help to study these conditions. In the present study we continue our search for potent A adenosine receptor ligands which could be successively conjugated to other molecules with the aim of obtaining more potent ( allosteric ligand conjugation) or detectable ligands ( fluorescent molecule or biotin conjugation). Specifically, different aminoester moieties were introduced at the 5 position of the pyrazolo[4,3-]-1,2,4-triazolo[1,5-]pyrimidine core. The ester functionalization represents the candidate for the subsequent conjugation. All the reported compounds are potent hA adenosine receptor antagonists and some of them exhibited high selectivity against the other adenosine receptors. The main structural terms of ligand recognition and selectivity were disclosed by molecular modelling studies. Molecular docking results led to the characterization of an alternative binding mode for antagonists at the orthosteric binding site of the hA adenosine receptor, evaluated and assessed by classical molecular dynamics simulations.

Bonebridge® is a novel active bone-anchored hearing implant. The purpose of this study was to evaluate the ease of implantation, the hearing performances, and the patient-reported benefit.

Extra lateral interbody fusion (XLIF) has been established in recent years as an effective approach to address degenerative lumbar disc disease (DLDD). Although neurological and vascular complications during XLIF have been reported, to our knowledge, a combination of simultaneous vascular and neurovascular complication during XLIF has not been reported to date. A 72-year-old female patient was admitted to our orthopaedic department because of back pain associated with severe neuropathic radicular pain to her both lower extremities, incomplete paraplegia and low back fistula with serous secretion for several weeks. She had been wheel-chair bound since nine years before her admission in our department when she had her initial XLIF operation in another institution. Intraoperatively, an aorta lesion occurred, which was emergently addressed, along with lumbar plexus injury. Since then, she had an extensive history of subsequent operations that ended with a T10-S1 posterior lumbar fusion, with no improvement of her neurological condition, complicated by hardware-induced infection. She underwent her last operation in our department; removal of the posterior lumbar construct and extensive debridement of the posterior lumbar spine. We present this rare case and we perform an extensive literature review. Although XLIF has been established in recent years, the report of major vascular injuries, although rare, has questioned its safety profile. Spine surgeons should be aware of catastrophic major neurovascular complications associated with this procedure and be prepared to address them.

Mu-opioid receptor (MOR) signaling regulates multiple neuronal pathways, including those involved in pain, reward, and respiration. To advance the understanding of MOR's roles in pain modulation, there is a need for high-throughput screening methods of opioids in vitro and high-resolution mapping of opioids in the brain. To fill this need, we designed and characterized a genetically-encoded fluorescent reporter, called S ingle-chain P rotein-based O pioid T ransmission I ndicator T ool for M OR (M-SPOTIT). M-SPOTIT represents a new and unique mechanism for fluorescent reporter design and can detect MOR activation, leaving a persistent green fluorescence mark for image analysis. M-SPOTIT shows an opioid-dependent fluorescence turn-on up to 12.5-fold and is able to detect as fast as a 30-second opioid exposure in cell culture. Additionally, it showed an opioid-dependent fluorescence turn-on up to 4.2-fold in neuronal culture and can detect fentanyl with an EC 50 of 15 nM. M-SPOTIT will be useful for high-throughput detection of opioids in cell cultures and potentially a cellular-resolution detection of opioids in vivo. M-SPOTIT's novel mechanism can be used as a platform to design other G-protein coupled receptor-based sensors.

Cerebral venous sinus thrombosis (CVST) is an uncommon manifestation in patients with the human immunodeficiency virus (HIV) due to the virus's prothrombotic state. Our case involves a 41-year-old Hispanic male with a past medical history of HIV on bictegravir/emtricitabine/tenofovir/alafenamide (Biktarvy), hyperlipidemia, post-traumatic stress disorder, hypogonadism with the cessation of testosterone injections one month prior, and generalized anxiety disorder who presented with retro-orbital headache, intermittent bilateral blurry vision, and flashing lights in the lower lateral left eye for one week. Vitals signs and laboratory studies were within normal limits aside from new iron deficiency anemia. Neurological exam was unremarkable. Computed tomography (CT) of the head showed evidence of a subacute cerebral infarct with hemorrhagic transformation in the right superior parietal lobe. Magnetic resonance imaging (MRI) of the brain with contrast revealed a small thrombosed cortical vein with surrounding hemorrhage and edema in the same location, in addition to a partial thrombosis of the adjacent superior sagittal sinus, which was confirmed by magnetic resonance venogram (MRV). Although cerebral angiography was performed, no intervention was attempted for the partially occluded sagittal sinus. HIV viral load was undetectable with a robust cluster of differentiation (CD) 4 count on therapy. The patient was treated with strict blood pressure control, a statin, and a heparin drip. He remained stable and was discharged on enoxaparin injections with bridging to warfarin. In summary, appropriate lab testing, imaging, and high clinical suspicion are required for proper diagnosis and treatment of venous thromboembolism (VTE) or CVST in an HIV-positive patient.

Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit.

Cutaneous autoimmune and inflammatory diseases are a major burden of global disease and many lack effective treatments that can derive in different dermatoses like atopic dermatitis. Despite the increase prevalence and the high health-care costs worldwide, the heterogeniety and multifactoriality of these diseases mean that effective treatment options are scarce. Plasma rich in growth factors (PRGF) technology could be an alternative approach that may help in the management of this cutaneous condition. The aim of this study was to assess the effect of two different PRGF formulations (just activated and autologous topical serum (ATS)) for the management of skin inflammation. Additionally, ATS was assessed over two patients suffering from radiotherapy induced dermatitis. Human organotypic skin explant cultures (hOSECs) were used as human skin models. To induce atopic dermatitis-like conditions, skin explants were treated with both interleukin-4 (IL-4) and interleukin-13 (IL-13). PRGF and ATS were intradermally and topically applied, respectively. Metabolic activity, reactive oxigen species (ROS), necrosis and inflammatory cytokine production were determined. Both PRGF formulations increased tissue viability and significantly reduced the excessive free radical accumulation and the cutaneous cytokine production such as TNF-α and IL-1β. Case reports showed a positive response after ATS treatment in terms of skin quality improvement, local erythema decrease and burning and itching amelioration. The oedema, swelling and desquamation caused by radiation induced dermatitis was also reduced and the patients referred ceased pruritus and pain. This preliminary study suggests that PRGF might aid in the management of inflammatory skin conditions.