Rejected

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.

In the field theories in physics, any particular region of the presumed space-time continuum and all interactions between elementary objects therein can be objectively measured and/or accounted for mathematically. Since this does not apply to any of the field theories, or any other neural theory, of consciousness, their explanatory power is limited. As discussed in detail herein, the matter is complicated further by the facts than any scientifically operational definition of consciousness is inevitably partial, and that the phenomenon has no spatial dimensionality. Under the light of insights from research on meditation and expanded consciousness, chronic pain syndrome, healthy aging, and eudaimonic well-being, we may conceive consciousness as a source of potential energy that has no clearly defined spatial dimensionality, but can produce significant changes in others and in the world, observable in terms of changes in time. It is argued that consciousness may have evolved to enable the human species to generate such changes in order to cope with unprecedented and/or unpredictable adversity. Such coping could, ultimately, include the conscious planning of our own extinction when survival on the planet is no longer an acceptable option.

Postoperative headache (POH) is common in clinical practice, however, no studies about POH after Stanford type A acute aortic dissection surgery (AADS) exist. This study aims to describe the incidence, risk factors and outcomes of POH after AADS, and to construct two prediction models. Adults who underwent AADS from 2016 to 2020 in four tertiary hospitals were enrolled. Training and validation sets were randomly assigned according to a 7:3 ratio. Risk factors were identified by univariate and multivariate logistic regression analysis. Nomograms were constructed and validated on the basis of independent predictors. POH developed in 380 of the 1,476 included patients (25.7%). Poorer outcomes were observed in patients with POH. Eight independent predictors for POH after AADS were identified when both preoperative and intraoperative variables were analyzed, including younger age, female sex, smoking history, chronic headache history, cerebrovascular disease, use of deep hypothermic circulatory arrest, more blood transfusion, and longer cardiopulmonary bypass time. White blood cell and platelet count were also identified as significant predictors when intraoperative variables were excluded from the multivariate analysis. A full nomogram and a preoperative nomogram were constructed based on these independent predictors, both demonstrating good discrimination, calibration, clinical usefulness, and were well validated. Risk stratification was performed and three risk intervals were defined based on the full nomogram and clinical practice. POH was common after AADS, portending poorer outcomes. Two nomograms predicting POH were developed and validated, which may have clinical utility in risk evaluation, early prevention, and doctor-patient communication.

The aim of the study was to analyze the results of the use of laser destruction of the articular branch of the obturator nerve in elderly and senile patients with degenerative coxarthrosis. The results of treatment of 34 patients over 65 years of age with symptomatic degenerative diseases of the hip joint (HJD) and somatic contraindications for total hip arthroplasty have been prospectively studied. In the study group, in the period from 2017 to 2019, laser destruction of the articular branch of the obturator nerve (970 nm, frequency 9 Hz and power 3 W in a total dose of 100 J) was carried out. The average follow-up was 12 months. To assess the effectiveness of surgical treatment, the dynamics of the pain syndrome in the hip joint was analyzed according to the visual analogue scale, the quality of life according to the SF-36 questionnaire, the functional state of the hip joint according to the W.H.Harris scale and the presence perioperative surgical complications. As a result, it was found that the use of laser destruction of the articular branch of the obturator nerve in degenerative coxarthrosis in elderly and senile patients (if total hip arthroplasty was not possible) made it possible to significantly reduce the level of preoperative pain syndrome, restore the quality of life and improve the functional state of patients with low risks of surgical complications.

Reactive arthritis (ReA) is a chronic inflammatory disease usually caused by a preceding gastrointestinal or genitourinary bacterial infection. ReA usually occurs in the lower limbs causing joint pain and joint swelling. Physiotherapy-led exercise is recommended to prevent muscle atrophy. The purpose of this case report is to describe the outcome after 12 weeks of low-load blood flow restricted resistance training (BFR-RT) as a rehabilitation method for a young male suffering from ReA. A 17-year-old male suffered from ReA in the both knee joints and the left hip joint. 36 months after the incident, he suffered from another ReA incident in his right knee. Non-steroid anti-inflammatory drugs and a new arthrocentesis added with corticosteroid injection was unsuccessful in treating the ReA. The patient performed 12 weeks of BFR-RT on the right lower limb with a low amount of supervision after the first week of training. Assessment of unilateral 30-sec chair stand test (u30-sec CST), low-thigh circumference above apex patella, The Knee Injury and Osteoarthritis Outcome Score (KOOS), The Forgotten Knee Joint Score (FJS), and Numeric Ranking Scale for pain (NRS) was performed at baseline and after 3,6,9, and 12 weeks of BFR-RT. The patient completed all planned exercise sessions. u30-sec CST improved with 7 repetitions (reps) on the right limb and 5 reps on the left leg. Low-thigh circumference decreased 1.1 cm on the right leg and 1.0 on the left leg. KOOS symptoms, ADL, quality of life and FJS demonstrated a clinically relevant change on 10, 14 and 23 points. The present case study indicates that even with low amounts of supervision BFR-RT could increase functional performance, reduce knee joint swelling and improve key patient-reported outcome.