Rejected

Functional gastrointestinal (GI) disorders (eg irritable bowel syndrome and functional dyspepsia) are very common conditions which are associated with very poor quality of life and high healthcare utilisation. They are caused by disorders of GI functioning, namely altered gut sensitivity, motility, microbiota, immune functioning and central nervous system processing. They cause chronic symptoms throughout the gut (eg pain, dyspepsia and altered bowel habit), all of which are made worse by maladaptive patient behaviours, stress and psychological comorbidity. Management involves a biopsychosocial approach involving changes in lifestyle and diet, addressing coexisting psychological comorbidity and using medication to treat underlying pathophysiology. Pharmacological treatment with antispasmodics, neuromodulators, motility agents and antidepressants is effective. Psychotherapy in motivated individuals is equally effective. Success of treatment is increased by a good doctor-patient relationship and so this needs to be taken into account during the consultation.

Fear of orofacial interventions is a very common problem. Procedural sedation and/or analgesia (PSA) offers added value in reducing anxiety, pain and discomfort. At the Radboud University Medical Centre (Nijmegen, the Netherlands) PSA is conducted under the guidance of physician assistants, resulting in a high degree of patient satisfaction. In this study, the 115 surgeons' satisfaction with PSA procedures for outpatient orofacial surgical interventions was evaluated by means of questionnaires. The study's conclusion is that oral and maxillofacial surgeons are highly satisfied when PSA is administered to very anxious patients. The collaboration with the department of anaestesiology ensures that the outpatient interventions can be performed safely and efficiently by the oral and maxillofacial surgeon.

Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism.

Primary hepatic squamous cell carcinoma (SCC) is a rare malignancy with aggressive clinical features. This is the first case report of a primary hepatic SCC diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), which is a reliable and safe procedure for the histopathological diagnosis of liver lesions, even if the percutaneous approach is difficult due to ascites or hypervascularity at the puncture site. A 52-year-old man presented to the emergency department of a tertiary referral hospital with right upper quadrant abdominal pain and abdominal distention. Given the laboratory data, a diagnosis of spontaneous bacterial peritonitis (SBP) was made. Concurrently, an abdominal computed tomography (CT) scan revealed an 8 cm hypodense mass with delayed peripheral enhancement in the left hepatic lobe and paraaortic and perihepatic lymphadenopathy. As persistent ascites precluded percutaneous liver biopsy, we performed EUS-FNA of the liver mass, and the obtained specimen showed SCC. As otorhinolaryngological consultation and whole-body investigations, including chest CT, upper and lower endoscopy, and positron emission tomography CT, were all unremarkable except for the liver lesion and lymph nodes, a diagnosis of primary hepatic SCC with systemic lymph node metastasis was made. After treatment of SBP with antibiotics, we initiated chemotherapy concurrent with radiation therapy, adapted to his liver function. Radiation and three cycles of chemotherapy were not effective as the disease progressed, as seen on the follow-up CT scan, and the patient died of hepatic failure on the 134th day after diagnosis. In conclusion, EUS-FNA was a reliable method for tissue sampling in liver malignancies, particularly in selected patients with contraindications for percutaneous biopsy.

The yeast (also known as ) has been used for over 30 years to produce thousands of valuable, heterologous proteins, such as insulin to treat diabetes and antibodies to prevent migraine headaches. Despite its success, there are some common, stubborn problems encountered by research scientists when they try to use the yeast to produce their recombinant proteins. In order to provide those working in this field with strategies to overcome these common obstacles, nine experts in protein expression field were interviewed to create a written review and video (https://www.youtube.com/watch?v=Q1oD6k8CdG8). This review describes how each respected scientist addressed a specific challenge, such as identifying high expression strains, improving secretion efficiency and decreasing hyperglycosylation. Their perspective and practical advice can be a tool to help empower others to express challenging proteins in this popular recombinant host.

[This corrects the article DOI: 10.3389/fpain.2021.705345.].

Conditioned pain modulation (CPM) is a physiological measure thought to reflect an individual's endogenous pain modulation system. CPM varies across individuals and provides insight into chronic pain pathophysiology. There is growing evidence that CPM may help predict individual pain treatment outcome. However, paradigm variabilities and practical issues have impeded widespread clinical adoption of CPM assessment. This study aimed to compare two CPM paradigms in people with chronic pain and healthy individuals. A total of 30 individuals (12 chronic pain, 18 healthy) underwent two CPM paradigms. The heat CPM paradigm acquired pain intensity ratings evoked by a test stimulus (TS) applied before and during the conditioning stimulus (CS). The pressure CPM paradigm acquired continuous pain intensity ratings of a gradually increasing TS, before and during CS. Pain intensity was rated from 0 (no pain) to 100 (worst pain imaginable); Pain50 is the stimulus level for a response rated 50. Heat and pressure CPM were calculated as a change in TS pain intensity ratings at Pain50, where negative CPM scores indicate pain inhibition. We also determined CPM in the pressure paradigm as change in pressure pain detection threshold (PDT). We found that in healthy individuals the CPM effect was significantly more inhibitory using the pressure paradigm than the heat paradigm. The pressure CPM effect was also significantly more inhibitory when based on changes at Pain50 than at PDT. However, in individuals with chronic pain there was no significant difference in pressure CPM compared to heat or PDT CPM. There was no significant correlation between clinical pain measures (painDETECT and Brief Pain Inventory) and paradigm type (heat vs. pressure), although heat-based CPM and painDETECT scores showed a trend. Importantly, the pressure paradigm could be administered in less time than the heat paradigm. Thus, our study indicates that in healthy individuals, interpretation of CPM findings should consider potential modality-dependent effects. However, in individuals with chronic pain, either heat or pressure paradigms can similarly be used to assess CPM. Given the practical advantages of the pressure paradigm (e.g., short test time, ease of use), we propose this approach to be well-suited for clinical adoption.

Corneal neuropathic pain can be difficult to treat, particularly due to its lack of response to standard dry eye therapies. We describe a variety of topical therapeutic options that are available to treat corneal neuropathic pain with a significant or primary peripheral component. We also describe possible mechanisms of action for such topical therapies. Topical corticosteroids and blood-derived tear preparations can be helpful. Newer therapies, including topical lacosamide and low-dose naltrexone are emerging therapeutic options that may also be considered. Corneal neuropathic pain with a significant peripheral component may be managed with a variety of topical therapeutic options.

Ischemic infarction of pituitary apoplexy (PA) is a rare type of pituitary apoplexy. This study aims to characterize ischemic PA via clinical presentations, imaging data, histopathological manifestations, and focus on the management and prognosis of the disease.

Neurological disorders related to neuroinfections are highly prevalent in Sub-Saharan Africa (SSA), constituting a major cause of disability and economic burden for patients and society. These include epilepsy, dementia, motor neuron diseases, headache disorders, sleep disorders, and peripheral neuropathy. The highest prevalence of human immunodeficiency virus (HIV) is in SSA. Consequently, there is a high prevalence of neurological disorders associated with HIV infection such as HIV-associated neurocognitive disorders, motor disorders, chronic headaches, and peripheral neuropathy in the region. The pathogenesis of these neurological disorders involves the direct role of the virus, some antiretroviral treatments, and the dysregulated immune system. Furthermore, the high prevalence of epilepsy in SSA (mainly due to perinatal causes) is exacerbated by infections such as toxoplasmosis, neurocysticercosis, onchocerciasis, malaria, bacterial meningitis, tuberculosis, and the immune reactions they elicit. Sleep disorders are another common problem in the region and have been associated with infectious diseases such as human African trypanosomiasis and HIV and involve the activation of the immune system. While most headache disorders are due to benign primary headaches, some secondary headaches are caused by infections (meningitis, encephalitis, brain abscess). HIV and neurosyphilis, both common in SSA, can trigger long-standing immune activation in the central nervous system (CNS) potentially resulting in dementia. Despite the progress achieved in preventing diseases from the poliovirus and retroviruses, these microbes may cause motor neuron diseases in SSA. The immune mechanisms involved in these neurological disorders include increased cytokine levels, immune cells infiltration into the CNS, and autoantibodies. This review focuses on the major neurological disorders relevant to Africa and neuroinfections highly prevalent in SSA, describes the interplay between neuroinfections, immune system, neuroinflammation, and neurological disorders, and how understanding this can be exploited for the development of novel diagnostics and therapeutics for improved patient care.