Rejected

Transdermal drug delivery (TDD) has recently emerged as an effective alternative to oral and injection administration because of its less invasiveness, low rejection rate, and excellent ease of administration. TDD has made an important contribution to medical practice such as diabetes, hemorrhoids, arthritis, migraine, and schizophrenia treatment, but has yet to fully achieve its potential in the treatment of obesity. Obesity has reached epidemic proportions globally and posed a significant threat to human health. Various approaches, including oral and injection administration have widely been used in clinical setting for obesity treatment. However, these traditional options remain ineffective and inconvenient, and carry risks of adverse effects. Therefore, alternative and advanced drug delivery strategies with higher efficacy and less toxicity such as TDD are urgently required for obesity treatment. This review summarizes current TDD technology, and the main anti-obesity drug delivery system. This review also provides insights into various anti-obesity drugs under study with a focus on the recent developments of TDD system for enhanced anti-obesity drug delivery. Although most of presented studies stay in animal stage, the application of TDD in anti-obesity drugs would have a significant impact on bringing safe and effective therapies to obese patients in the future.

We report a case of a 59-year-old man with hypertrophic pachymeningitis (HP), initially presenting as a tumefactive lesion that disappeared spontaneously. He developed headache and left abducens nerve palsy 2 years before admission, and cerebral magnetic resonance imaging (MRI) revealed a round mass lesion. Meningioma was initially considered, but the lesion disappeared spontaneously along with the symptoms. However, 6 months before admission, left abducens nerve palsy reappeared. Repeated MRI revealed multiple intracranial tumefactive lesions. HP was diagnosed based on the pathological analysis of the biopsied specimen. HP can appear as a vanishing tumor, and pathological evaluation is essential for a precise diagnosis. If spontaneous disappearance of tumefactive intracranial lesions is encountered, the possibility of HP should be considered.

Treatment with medical cannabis (MC) in the United States tends to be patient-driven in nature despite evidence that suggests that patients have remarkably poor knowledge on the medical use of this treatment modality.

Frozen shoulder (FS) is a poorly understood condition resulting in substantial shoulder pain and mobility deficits. The mechanisms behind FS are not yet fully understood, but, similar to other persistent pain states, central pain mechanisms may contribute to ongoing symptoms in this population. The objective of this research was to investigate conditioned pain modulation (CPM) in people with FS compared with pain-free individuals. A total of 64 individuals with FS and 64 healthy volunteers participated in this cross-sectional study. CPM was assessed by using the pressure pain threshold (PPT) and an occlusion cuff (tourniquet test) as the test and conditioning stimulus, respectively. The absolute and percentage of change in PPT (CPM effect) as well as pain profiles (pro-nociceptive vs. anti-nociceptive) of individuals with FS and healthy controls were calculated. No significant differences in the absolute change in the PPT or CPM effect were found in people with FS compared to pain-free controls. Moreover, no between-group differences in the percentage of subjects with pro-nociceptive and anti-nociceptive pain profiles were observed. These results suggest that endogenous pain inhibition is normally functioning in people with FS. Altered central pain-processing mechanisms may thus not be a characteristic of this population.

-To perform a Randomized Controlled Trial (RCT) Disclusion Time Reduction (DTR) study at five Dental Colleges, using intraoral sensors and muscular electrodes. -One hundred students were randomly assigned to a treatment group to receive the ICAGD coronoplasty, or a control group that received tooth polishing. All subjects answered symptom questionnaires: Beck Depression Inventory-II, Functional Restrictions, and Chronic Pain Symptom and Frequency. Subjects self-reported after ICAGD or placebo at 1 week, 1 month, 3 months, and 6 months. The Student's t-Test analyzed the measured data. The Mann-Whitney U Test analyzed the subjective data (Alpha = 0.05). -The Disclusion Times, BDI-II scores, and Symptom Scales were similar between groups prior to treatment ( > 0.05). At 1 week, all three measures reduced in the treatment group, continuing to decline over 6 months ( < 0.05), but not for the controls ( > 0.05). Symptom Frequency, Functional Restrictions, and Pain Frequencies were higher in the treated group ( < 0.05), but declined after ICAGD compared to the control group ( < 0.05). -ICAGD reduced Pain, Functional Restrictions, Symptom Frequency, and Emotional Depression within 1 week, which continued for 6 months. The tooth polishing did not initiate a placebo response.

Our previous study verified a sex difference of anti-hyperalgesia in rats and anti-allodynia in mice induced by intrathecal oxytocin (OT). In the model of intraplantar carrageenan-induced inflammatory hyperalgesia, intrathecal OT injection induced a substantial anti-hyperalgesia in male rats even at a low dose (0.125 nmol). In contrast, female rats only responded to an extremely high dose (1.25 nmol). This sex difference concurs with a lower expression of OT receptors and higher expression of insulin-regulated aminopeptidase (IRAP; OT degrading enzyme) in the spinal cords of female rats. In this study, we further determined the role of female hormones in this sex difference by using ovariectomized rats. Our results show that a low dose of intrathecal OT caused a significant anti-hyperalgesia effect in ovariectomized female rats, similar to that seen in male rats. Ovariectomy did not cause any change of paw edema except at the late stage of convalescence when compared with the sham-operated group. Ovariectomy-induced faster recovery from edema but did not affect the severity of hyperalgesia. Moreover, there was a similar amount of IRAP expression in ovariectomized and sham rats. When estradiol (E2) was given together with OT, OT-induced anti-hyperalgesia was abolished at the developmental stage of hyperalgesia in ovariectomized rats. These results show an inhibitory role of female hormones generated from ovaries (mainly estrogen) in the sex difference of anti-hyperalgesia induced by OT. This study suggests the feasibility of a novel OT-based remedy to treat hyperalgesia in men and in menopausal women no receiving hormonal supplements.

The aim of this study was to determine the relationship between surgeon opioid prescribing intensity and subsequent persistent opioid use among patients undergoing surgery.

Prognosis of metastatic neuroblastoma is very poor. Its treatment includes induction chemotherapy, surgery, high-dose chemotherapy, radiotherapy, and maintenance with retinoic acid, associated with the anti-GD2 monoclonal antibody (ch14.18) dinutuximab. Immunotherapy determined a significant improvement in survival rate and is also utilized in relapsed and resistant neuroblastoma patients. Five courses of dinutuximab 100 mg/m are usually administered as a 10-day continuous infusion or over 5 consecutive days every 5 weeks. Dinutuximab targets the disialoganglioside GD2, which is highly expressed on neuroblastoma cells and minimally present on the surface of normal human neurons, peripheral pain fibers, and skin melanocytes. Anti GD2 antibodies bind to surface GD2 and determine the lysis of neuroblastoma cells induced by immune response via the antibody-dependent cellular cytotoxicity and the complement-dependent cytotoxicity. Dinutuximab has significant side effects, including neuropathic pain, peripheral neuropathy, hypersensitivity reactions, capillary leak syndrome, photophobia, and hypotension. The most important side effect is neuropathic pain, which is triggered by the same antibody-antigen immune response, but generates ectopic activity in axons, which results in hyperalgesia and spontaneous pain. Pain can be severe especially in the first courses of dinutuximab infusion, and requires the administration of gabapentin and continuous morphine infusion. This paper will focus on the incidence, mechanisms, characteristics, and treatment of neuropathic pain and peripheral neuropathy due to dinutuximab administration in neuroblastoma patients.

The aim of this study was to determine the rate of persistent pain following total TMJ replacement and to identify potential predictive risk factors. A retrospective review of case notes treated by a single surgeon in a tertiary unit was performed. For each patient a number of variables were recorded including visual analog pain scores (0 to 10) and opioid usage pre surgery and at 12 months or last follow up beyond 12 months. Persistent pain scores of 5 to 7 were regarded as moderate and 8 to 10 as severe. The mean pain score at last follow-up was significantly lower than preoperatively (2.1 vs. 6.3, p < 0.001) with a mean follow-up time of 40.1 months (range 12-44). 16.4% of the patients reported moderate to severe pain and 13.7% were still on regular opioids at the last follow-up. Therefore 15 patients (20.5%) suffered from chronic postoperative pain after TMJ replacement surgery. Patients reporting severe preoperative pain scores (p = 0.04), regular opioid use (p = 0.001) or multiple previous open TMJ surgeries (p = 0.03) were more likely to suffer from chronic persistent pain and these should be regarded as predictive risk factors. The identification of these factors allows for better risk stratification of patients, informed consent and the agreement of expected outcomes. Patients with true articular disease and a single failed surgery should be considered for early total TMJ replacement to minimize multifactorial persistent pain.

In December 2019 a novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic. Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease. Typical symptoms of the initial phase include fever and cough, with possible progression to acute respiratory distress syndrome. Gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2. The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses. Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations, such as fatigue and psychological impairment. To date, there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection. Since COVID-19 can directly or indirectly affect the gut physiology in different ways, it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations (dysbiosis, disruption of the intestinal barrier, mucosal microinflammation, post-infectious states, immune dysregulation and psychological stress). In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms.