Rejected

Despite 50 years of clinical use and experimental endeavor the anesthetic, analgesic, and psychomimetic effects of ketamine remain to be fully elucidated. While NMDA receptor antagonism has been long held as ketamine's fundamental molecular action, interrogation of bespoke ketamine analogs with known absent NMDA binding, yet profound anesthetic and analgesia fingerprints, suggests alternative targets are responsible for these effects. Herein we describe experimental findings utilizing such analogs as probes to explore ketamine-based analgesic molecular targets. We have focused on two-pore potassium leak channels, identifying TWIK channels as a rational target to pursue further. While the totality of ketamine's mechanistic action is yet to be fully determined, these investigations raise the intriguing prospect of separating out analgesia and anesthetic effects from ketamine's undesirable psychomimesis-and development of more specific analgesic medications.

Intraneural ganglia are benign mucinous cysts located within the epineurium of a peripheral nerve. The pathogenesis and formation of intraneural ganglia are controversial. The main theories described in the literature are of degenerative, synovial or de novo occurrence. We present the case of a 14-year-old boy who presented in our outpatient clinic with a complaint of interdigital neuralgia between hallux and second toe, as well as left foot drop. MRI examination showed a hyperintense cystic distension of the common peroneal nerve measuring 130 mm × 5 mm extending from the poplitea to the anterior compartment of the leg. We performed microscopic decompression and neurolysis surgery. The cyst showed a sac-like distension at its distal end with connection to the tibiofibular joint and was resected. After 8 weeks, postoperatively, the boy claimed to be pain-free and slight recovery of the superficial peroneal nerve was noticed. At 6 months postoperative, the patient showed a continuous improvement of motor function, demonstrating foot eversion with 3/5 muscle strength and foot extension with 2/5 muscle strength. Intraneural ganglia reported for pediatric patients represent a very rare entity. To the best of our knowledge, less than 15 cases have been described within the English-speaking literature.

Patients were found to experience more pain during their second eye cataract surgery compared with their first eye surgery. This study aimed to explore the inflammatory alterations along time in the fellow eye after the first eye surgery and to reveal the underlying mechanism. Eighty patients with bilateral cataracts were recruited and were divided into four groups based on the time of having the second eye surgery. The second eye aqueous humor samples were collected just before surgery and analyzed by mass spectrometry and PCR array. Cytokine activity was enriched in the aqueous humor of the contralateral eye with granulocyte colony-stimulating factor CSF3 significantly upregulated at both gene and protein levels. Rabbits with or without superior cervical ganglionectomy (SCGx) were subjected to lensectomy to mimic human situations. In both human and rabbit models, the fellow eye CSF3 peaked at 1 week post the first eye surgery. Consistently, more neutrophils were recruited to the contralateral eye aqueous humor. Corneal sensitivity and trigeminal electrophysiology were recorded to imply the pain severity in rats receiving capsulorrhexis with or without SCGx. A more intense pulse was detected in the contralateral trigeminal ganglion after the rat received one eye surgery. SCGx could effectively reduce the fellow corneal sensitivity and trigeminal nerve pain. These alterations were under direct regulation of the sympathetic nerves on the surgical eye side. Our results suggest that CSF3 and sympathetic activity could serve as potential analgesic targets during ocular surgeries.

We describe a case of post-coronavirus disease 2019 (COVID-19) multisystem inflammatory syndrome in children (MIS-C). The 12-year-old child presented with appendicitis-like symptoms in the form of gradually worsening abdominal pain localizing over the right iliac fossa, fever, and vomiting. After an appendectomy, the abdominal pain did not resolve. He later developed orthopnea, bilateral lower limb pitting edema, and bilateral fine basal crepitations. This pointed to MIS-C. We should be mindful of multisystem inflammatory syndrome in children in children with a recent history of COVID-19.

Wiskott-Aldrich Syndrome (WAS) is characterized by recurrent infections, thrombocytopenia, and eczema. Here, we show that WASp-deficient mice on a BALB/c background have dysregulated cutaneous immune homeostasis with increased leukocyte accumulation in the skin, 1 week after birth. Increased cutaneous inflammation was associated with epithelial abnormalities, namely, altered keratinization, abnormal epidermal tight junctional morphology and increased trans-epidermal water loss; consistent with epidermal barrier dysfunction. Immune and physical barrier disruption was accompanied by progressive skin dysbiosis, highlighting the functional significance of the disrupted cutaneous homeostasis. Interestingly, the dysregulated immunity in the skin preceded the systemic elevation in IgE and lymphocytic infiltration of the colonic lamina propria associated with WASp deficiency. Mechanistically, the enhanced immune cell accumulation in the skin was lymphocyte dependent. Elevated levels of both Type 2 (IL-4, IL-5) and Type 17 (IL-17, IL-22, IL-23) cytokines were present in the skin, as well as the 'itch' factor IL-31. Unexpectedly, the canonical WAS-associated cytokine IL-4 did not play a role in the immune dysfunction. Instead, IL-17 was critical for skin immune infiltration and elevation of both Type 2 and Type 17 cytokines. Our findings reveal a previously unrecognized IL-17-dependent breakdown in immune homeostasis and cutaneous barrier integrity in the absence of WASp, targeting of which may provide new therapeutic possibilities for the treatment of skin pathologies in WAS patients.

Since the outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) in December 2019, there have been some case reports of Coronavirus disease 19 (COVID 19) associated Guillain-Barré Syndrome (GBS). GBS is an inflammatory polyradiculoneuropathy associated with numerous viral and bacterial infections. Here we describe the case of an Ethiopian man with a typical clinical and electrophysiological manifestation of GBS.

Objective To compare the frequency of serum vitamin D levels in patients with and without distal radius fracture. Introduction Hypovitaminosis D is a common problem worldwide. Deficiency of vitamin D is not only associated with musculoskeletal problems, but also with chronic diseases like diabetes mellitus, cardiovascular disease and cancer. Vitamin D deficiency results in bone pain, aggravating osteoporosis and fragility fractures. Distal radius fractures are common upper limb fractures, mostly in the elderly population. Low serum levels of vitamin D have been reported to result in increased risk of distal radius fracture. Methodology This study was conducted at The Indus Hospital Karachi, from 1st March 2020 to 31st August 2020. Consecutive non-probability sampling was done. Patients aged between 20 to 80 years with and without distal radius fractures were enrolled and serum vitamin D levels were compared. Results A total of 130 patients were enrolled in this study, out of which 70 (53.8%) were males. The median (IQR) vitamin D, calcium, alkaline phosphate level, and albumin was 14.8 (9.5-23) ng/ml, 9.2 (8.9-9.5) ng/ml, 91 (77.3-111) U/L, and 4.2 (4-4.5) g/dl, respectively. No significant association between distal radius fracture and vitamin D levels was found in males, whereas a significantly higher proportion of females with no fracture had a mild-moderate deficiency in comparison to females with fracture. Conclusion No significant association was noted between patients with and without distal radius fracture and vitamin D levels, however, we recommend more studies on this topic so that more comprehensive results can be obtained.

This review of commonly prescribed psychotropic drugs aims to update the clinician on possible ophthalmic side effects that may include dry eye, diplopia, mydriasis, and cataracts. This review summarizes our current knowledge of known ocular side effects of psychotropic drugs based on reviews, case reports, case-control studies, a case series, and cross-sectional observational studies reported in the recent literature. The review covers disorders related to depression, anxiety, and stress which are commonly encountered within society and can have debilitating impacts on an individual's quality of life that may require chronic therapeutic management. The main medications used in the treatment and management of these conditions typically target receptors, metabolic enzymes, or transport pumps that alter the pre- and/or post-synaptic levels of neurotransmitters such as serotonin, norepinephrine, dopamine, gamma-aminobutyric acid, and opioids to improve mood and/or relieve pain and anxiety. Novel non-therapeutic options are undergoing clinical trials, and some patients may seek alternative therapies or have associated substance abuse issues to alleviate their symptoms. This review summarizes some of the clinical signs of depression and the main therapeutic options and their reported ocular side effects which may be pertinent today given the rise in use of psychotropic medications used to manage depression, anxiety, and stress.

To observe the main risk factors for pruritic skin evidence complicating type 2 diabetes mellitus (T2DM) and the effectiveness of interventions with comprehensive care measures.

Car sickness is the state of being unhealthy as a result of motions that occur while traveling by vehicles. Passengers traveled by vehicles had experienced car sickness not only as a result of the biological effects but also other associated factors. Therefore, this study aimed to identify sociocultural, individual behavioral factors and situational factors resulting in car sickness of passengers traveling by minibus or bus or both.