Rejected

There is vast published literature proposing repetitive transcranial magnetic stimulation (rTMS) technology on the motor cortex (M1) for the treatment of neuropathic pain (NP). Systematic reviews (SRs) focus on a specific problem and do not provide a comprehensive overview of a research area. This study aimed to summarize and analyze the evidence of rTMS on the M1 for NP treatment through a new synthesis method called evidence mapping.

African tick-bite fever (ATBF), caused by , is the main tick-borne rickettsiosis and the second most frequent cause of fever after malaria in travelers returning from sub-Saharan Africa. General descriptions on ATBF were made in the first two decades after recognized as a new infectious entity, and since then, many authors have contributed to the knowledge of the disease by reporting clinical cases in scientific literature. We developed a systematic review that evaluated all available evidence in the literature regarding clinical, epidemiological, and laboratory features of confirmed rickettsiosis cases. We followed the recommendations made by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guide. A total of 48 scientific publications (108 confirmed cases) were analyzed in order to extract data for developing this review. Overall, our results show that rickettsiosis is more frequent in males in the age group of 18-64 years, more than 80% of the cases occurred in European travelers, South Africa was the country where most infections were acquired, and almost 40% of cases occurred in clusters. Clinically, more than 80% of the cases had fever and eschar (55% developed multiple eschars), rash was present in less than the half of cases, and lymphangitis was not a common sign (11%). Headache, myalgia and regional lymphadenopathy were predominant nonspecific clinical manifestation (mean of 60%, 49% and 51%, respectively). Our results show that at least 70% of cases had altered laboratory parameters, most often showing an increase in transaminases and C-reactive protein. Tetracycline-class antibiotics, as monotherapy, were used in most (>90%) of the patients. Overall, only 4% of cases had complications, 12% required hospitalization, and there was a 100% rate of clinical recovery.

Crocin, the main biologically active carotenoid of saffron, generally is derived from the dried trifid stigma of L. Many studies have demonstrated that crocin has several therapeutic effects on biological systems through its anti-oxidant and anti-inflammatory properties. The wide range of crocin activities is believed to be because of its ability to anchor to many proteins, triggering some cellular pathways responsible for cell proliferation and differentiation. It also has therapeutic potentials in arthritis, osteoarthritis, rheumatoid arthritis, and articular pain probably due to its anti-inflammatory properties. Anti-apoptotic effects, as well as osteoclast inhibition effects of crocin, have suggested it as a natural substance to treat osteoporosis and degenerative disease of bone and cartilage. Different mechanisms underlying crocin effects on bone and cartilage repair have been investigated, but remain to be fully elucidated. The present review aims to undertake current knowledge on the effects of crocin on bone and cartilage degenerative diseases with an emphasis on its proliferative and differentiative properties in mesenchymal stem cells.

Perioperative neurocognitive disorders (PNDs) occur commonly in older patients after anesthesia and surgery. Treating astrocytes with general anesthetic drugs stimulates the release of soluble factors that increase the cell-surface expression and function of GABA receptors in neurons. Such crosstalk may contribute to PNDs; however, the receptor targets in astrocytes for anesthetic drugs have not been identified. GABA receptors, which are the major targets of general anesthetic drugs in neurons, are also expressed in astrocytes, raising the possibility that these drugs act on GABA receptors in astrocytes to trigger the release of soluble factors. To date, no study has directly examined the sensitivity of GABA receptors in astrocytes to general anesthetic drugs that are frequently used in clinical practice. Thus, the goal of this study was to determine whether the function of GABA receptors in astrocytes was modulated by the intravenous anesthetic etomidate and the inhaled anesthetic sevoflurane. Whole-cell voltage-clamp recordings were performed in astrocytes in the stratum radiatum of the CA1 region of hippocampal slices isolated from C57BL/6 male mice. Astrocytes were identified by their morphologic and electrophysiologic properties. Focal puff application of GABA (300 μM) was applied with a Picospritzer system to evoke GABA responses. Currents were studied before and during the application of the non-competitive GABA receptor antagonist picrotoxin (0.5 mM), or etomidate (100 μM) or sevoflurane (532 μM). GABA consistently evoked inward currents that were inhibited by picrotoxin. Etomidate increased the amplitude of the peak current by 35.0 ± 24.4% and prolonged the decay time by 27.2 ± 24.3% ( = 7, < 0.05). Sevoflurane prolonged current decay by 28.3 ± 23.1% ( = 7, < 0.05) but did not alter the peak amplitude. Etomidate and sevoflurane increased charge transfer (area) by 71.2 ± 45.9% and 51.8 ± 48.9% ( = 7, < 0.05), respectively. The function of astrocytic GABA receptors in the hippocampus was increased by etomidate and sevoflurane. Future studies will determine whether these general anesthetic drugs act on astrocytic GABA receptors to stimulate the release of soluble factors that may contribute to PNDs.

Arboviruses primarily consist of RNA, which favours greater genetic plasticity, with a higher frequency of mutations that allow the virus to adapt to different hosts. The initial symptomatology is nonspecific, in that the patient can present fever, myalgia, arthralgia, rash and headache. This makes a clinical diagnosis using laboratory tests difficult and time-consuming. In Brazil, the main arboviruses involved in epidemics belong to the family . The patient in this case is from the municipality of São Bernardo do Campo, an area endemic for arboviruses. He presented symptoms of fever, myalgia and headache.

Given the limited effectiveness of pharmacological treatments for cognitive decline, non-pharmacological interventions have gained increasing attention. Evidence exists on the effectiveness of cognitive rehabilitation in preventing elderly subjects at risk of cognitive decline and in reducing the progression of functional disability in cognitively impaired individuals. In recent years, telerehabilitation has enabled a broader application of cognitive rehabilitation programs. The purpose of this study is to test a computer-based intervention administered according to two different modalities (at the hospital and at home) using the tools CoRe and HomeCoRe, respectively, in participants with Mild or Major Neurocognitive Disorders. Non-inferiority, single-blind randomized controlled trial where 40 participants with Mild or Major Neurocognitive Disorders will be assigned to the intervention group who will receive cognitive telerehabilitation through HomeCoRe or to the control group who will receive in-person cognitive intervention through CoRe, with the therapist administering the same computer-based exercises. The rehabilitative program will last 6 weeks, with 3 sessions/week, each lasting ~45 min. All the participants will be evaluated on an exhaustive neuropsychological battery before (T0) and after (T1) the intervention; follow-up visits will be scheduled after 6 (T2) and 12 months (T3). The results of this study will inform about the comparability (non-inferiority trial) of HomeCoRe with CoRe. Their equivalence would support the use of HomeCoRe for at distance treatment, favoring the continuity of care. This study has been approved by the Local Ethics Committee and registered in https://clinicaltrials.gov (NCT04889560). The dissemination plan includes the scientific community through publication in open-access peer-reviewed scientific journals and presentations at national and international conferences. Clinicaltrials.gov https://clinicaltrials.gov/ct2/show/NCT04889560 (registration date: May 17, 2021).

Brain paracoccidioidomycosis (PCM) or neuroparacoccidioidomycosis (NPCM) is a fungal infection of the central nervous system (CNS) caused by , a dimorphic fungus. The CNS involvement is through bloodstream dissemination. The association between NPCM and systemic lupus erythematous (SLE) is rare. However, SLE patients are under risk of opportunistic infections given their immunosuppression status.

The rise in rates of opioid abuse in recent years in the United States has led to a dramatic increase in the incidence of neonatal abstinence syndrome (NAS). Despite improved understanding of NAS and its acute symptoms, there remains a paucity of information regarding the long-term effects of prenatal exposure to drugs of abuse on neurological development. The primary goal of this study was to investigate the effects of prenatal drug exposure on synaptic connectivity within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway associated with drug abuse and addiction, in a mouse model. Our secondary goal was to examine the role of the Ca channel subunit α2δ-1, known to be involved in key developmental synaptogenic pathways, in mediating these effects. Pregnant mouse dams were treated orally with either the opioid drug buprenorphine (commonly used in medication-assisted treatment for substance use patients), gabapentin (neuropathic pain drug that binds to α2δ-1 and has been increasingly co-abused with opioids), a combination of both drugs, or vehicle daily from gestational day 6 until postnatal day 11. Confocal fluorescence immunohistochemistry (IHC) imaging of the brains of the resulting wild-type (WT) pups at postnatal day 21 revealed a number of significant alterations in excitatory and inhibitory synaptic populations within the anterior cingulate cortex (ACC), nucleus accumbens (NAC), and medial prefrontal cortex (PFC), particularly in the buprenorphine or combinatorial buprenorphine/gabapentin groups. Furthermore, we observed several drug- and region-specific differences in synaptic connectivity between WT and α2δ-1 haploinsufficient mice, indicating that critical α2δ-1-associated synaptogenic pathways are disrupted with early life drug exposure.

To compare complete neuroendoscopic and microscopic microvascular decompression (MVD) in primary trigeminal neuralgia (PTN) and their impacts on the microstructure of the trigeminal nerve.

Large to giant congenital melanocytic nevus (lgCMN) is a benign cutaneous tumor that develops during embryogenesis. A large number of lgCMN patients are ineligible for surgical treatment; hence, there is an urgent need to develop pharmacological treatments. Clinically, tumorigenesis and progression essentially halt after birth, resulting in the homeostasis of growth arrest and survival. Numerous studies have employed whole-genome or whole-exome sequencing to clarify the etiology of lgCMN; however, transcriptome sequencing of lgCMN is still lacking. Through comprehensive transcriptome analysis, this study elucidated the ongoing regulation and homeostasis of lgCMN and identified potential targets for treatment. Transcriptome sequencing, identification of differentially expressed genes and hub genes, protein-protein network construction, functional enrichment, pathway analysis, and gene annotations were performed in this study. Immunohistochemistry, real-time quantitative PCR, immunocytofluorescence, and cell cycle assays were employed for further validation. The results revealed several intriguing phenomena in lgCMN, including -induced cell cycle arrest, antiapoptotic activity, and immune evasion caused by malfunction of tumor antigen processing. The arrested cell cycle in lgCMN is consistent with its phenotype and rare malignant transformation. Antiapoptotic activity and immune evasion might explain how such heterogeneous cells have avoided elimination. Major histocompatibility complex (MHC) class I-mediated tumor antigen processing was the hub pathway that was significantly downregulated in lgCMN, and , , , and were identified as candidate hub genes. In conclusion, our research provides new perspectives for immunotherapy and targeted therapy.