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Marine Drugs Sep 2019The a-Conotoxins are peptide toxins that are found in the venom of marine cone snails and they are potent antagonists of various subtypes of nicotinic acetylcholine...
The a-Conotoxins are peptide toxins that are found in the venom of marine cone snails and they are potent antagonists of various subtypes of nicotinic acetylcholine receptors (nAChRs). Because nAChRs have an important role in regulating transmitter release, cell excitability, and neuronal integration, nAChR dysfunctions have been implicated in a variety of severe pathologies. We describe the isolation and characterization of α-conotoxin MilIA, the first conopeptide from the venom of The peptide was characterized by electrophysiological screening against several types of cloned nAChRs that were expressed in oocytes. MilIA, which is a member of the α3/5 family, is an antagonist of muscle type nAChRs with a high selectivity for muscle versus neuronal subtype nAChRs. Several analogues were designed and investigated for their activity in order to determine the key epitopes of MilIA. Native MilIA and analogues both showed activity at the fetal muscle type nAChR. Two single mutations (Met9 and Asn10) allowed for MilIA to strongly discriminate between the two types of muscle nAChRs. Moreover, one analogue, MilIA [∆1,M2R, M9G, N10K, H11K], displayed a remarkable enhanced potency when compared to native peptide. The key residues that are responsible for switching between muscle and neuronal nAChRs preference were elucidated. Interestingly, the same analogue showed a preference for α9α10 nAChRs among the neuronal types.
Topics: Amino Acid Sequence; Animals; Conotoxins; Conus Snail; Mutation; Neurotoxins; Nicotinic Antagonists; Oocytes; Patch-Clamp Techniques; Peptides; Receptors, Nicotinic; Recombinant Proteins; Structure-Activity Relationship; Xenopus laevis
PubMed: 31527432
DOI: 10.3390/md17090535 -
Frontiers in Public Health 2023The Innovation for Gender Equality in Academia (IGEA) project is focused on the analysis of the gender composition in academia, on the identification of the health needs...
The Innovation for Gender Equality in Academia (IGEA) project is focused on the analysis of the gender composition in academia, on the identification of the health needs of the academic population and on the assessment of their organizational wellbeing, in order to promote equal working conditions and opportunities. The study, focused on the identification of health needs, involved the construction of an questionnaire in order to collect the socio-demographic characteristics and the perception of working environment of the participants. Differences between males and females were evaluated by the Mann-Whitney test, and Pearson Chi-Square or Fisher exact tests as appropriate, highlighting significant differences between genders regarding the occurrence of anxiety, panic, irritation and annoyance related to work activities. A multivariate logistic regression analysis was performed to identify factors associated with the perception of work-related anxiety/panic, showing a direct association with the difficulty in work performance and the work-related stress during the pandemic period, whereas, an indirect association was found with job satisfaction and the feeling of being appreciated by colleagues. Occupational stress can increase the risk of developing physical and mental conditions, also affecting work performance and absenteeism. It is therefore fundamental to plan targeted interventions, implement policies and specific actions, in order to avoid and reduce any differences related to gender.
Topics: Humans; Male; Female; Gender Equity; Occupational Stress; Job Satisfaction; Working Conditions; Work Performance
PubMed: 36895683
DOI: 10.3389/fpubh.2023.1125496 -
Neurological Sciences : Official... Feb 2024A new national survey has been carried out by the Italian Centers for Cognitive Disorders and Dementias (CCDDs). The aim of this new national survey is to provide a...
INTRODUCTION
A new national survey has been carried out by the Italian Centers for Cognitive Disorders and Dementias (CCDDs). The aim of this new national survey is to provide a comprehensive description of the characteristics, organizational aspects of the CCDDs, and experiences during the COVID-19 pandemic.
METHODS
A list of all national CCDDs was requested from the delegates of each Italian region. The online questionnaire is divided in two main sections: a profile section, containing information on location and accessibility, and a data collection form covering organization, services, treatments, activities, and any service interruptions caused by the COVID-19 outbreak.
RESULTS
In total, 511 out of 534 (96%) facilities completed the profile section, while 450 out of 534 (84%) CCDDs also completed the data collection form. Almost half of the CCDDs (55.1%) operated for 3 or fewer days a week. About one-third of the facilities had at least two professional figures among neurologists, geriatricians and psychiatrists. In 2020, only a third of facilities were open all the time, but in 2021, two-thirds of the facilities were open.
CONCLUSION
This paper provides an update on the current status of CCDDs in Italy, which still shows considerable heterogeneity. The survey revealed a modest improvement in the functioning of CCDDs, although substantial efforts are still required to ensure the diagnosis and care of patients with dementia.
Topics: Humans; Pandemics; Cognitive Dysfunction; Cognition Disorders; Surveys and Questionnaires; COVID-19; Dementia; Italy
PubMed: 37592124
DOI: 10.1007/s10072-023-06958-8 -
Behavioral and Psychological Effects of Coronavirus Disease-19 Quarantine in Patients With Dementia.Frontiers in Psychiatry 2020In March 2020, the World Health Organization declared a global pandemic due to the novel coronavirus SARS-CoV-2 and several governments planned a national quarantine in...
BACKGROUND
In March 2020, the World Health Organization declared a global pandemic due to the novel coronavirus SARS-CoV-2 and several governments planned a national quarantine in order to control the virus spread. Acute psychological effects of quarantine in frail elderly subjects with special needs, such as patients with dementia, have been poorly investigated. The aim of this study was to assess modifications of neuropsychiatric symptoms during quarantine in patients with dementia and their caregivers.
METHODS
This is a sub-study of a multicenter nation-wide survey. A structured telephone interview was delivered to family caregivers of patients with diagnosis of Alzheimer disease (AD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and vascular dementia (VD), followed regularly at 87 Italian memory clinics. Variations in behavioral and psychological symptoms (BPSD) were collected after 1 month since quarantine declaration and associations with disease type, severity, gender, and caregiver's stress burden were analyzed.
RESULTS
A total of 4,913 caregivers participated in the survey. Increased BPSD was reported in 59.6% of patients as worsening of preexisting symptoms (51.9%) or as new onset (26%), and requested drug modifications in 27.6% of these cases. Irritability, apathy, agitation, and anxiety were the most frequently reported worsening symptoms and sleep disorder and irritability the most frequent new symptoms. Profile of BPSD varied according to dementia type, disease severity, and patients' gender. Anxiety and depression were associated with a diagnosis of AD (OR 1.35, CI: 1.12-1.62), mild to moderate disease severity and female gender. DLB was significantly associated with a higher risk of worsening hallucinations (OR 5.29, CI 3.66-7.64) and sleep disorder (OR 1.69, CI 1.25-2.29), FTD with wandering (OR 1.62, CI 1.12-2.35), and change of appetite (OR 1.52, CI 1.03-2.25). Stress-related symptoms were experienced by two-thirds of caregivers and were associated with increased patients' neuropsychiatric burden (p<0.0001).
CONCLUSION
Quarantine induces a rapid increase of BPSD in approximately 60% of patients and stress-related symptoms in two-thirds of caregivers. Health services need to plan a post-pandemic strategy in order to address these emerging needs.
PubMed: 33033486
DOI: 10.3389/fpsyt.2020.578015 -
Journal of Dental Anesthesia and Pain... Feb 2021This systematic review aimed to qualitatively and quantitatively evaluate the effectiveness of cryotherapy in the reduction of postendodontic pain. The review question... (Review)
Review
This systematic review aimed to qualitatively and quantitatively evaluate the effectiveness of cryotherapy in the reduction of postendodontic pain. The review question was, "What will be the success rate of cryotherapy technique among human patients with postendodontic pain?". The review protocol was framed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Six studies were included in the review, and quantification of five studies was performed through a meta-analysis. In the forest plot representation of the studies comparing the control and cryotherapy groups in terms of the success rate in the management of postendodontic pain, the combined risk ratio (RR) was 0.80 (95% CI: 0.56 to 1.13) with a P value of 0.20. Based on the quantitative analysis, it can be suggested that intracanal cryotherapy does not play a significant role in reducing postendodontic pain.
PubMed: 33585681
DOI: 10.17245/jdapm.2021.21.1.15 -
ACS Pharmacology & Translational Science Apr 2022SARS-CoV-2 infection is still spreading worldwide, and new antiviral therapies are an urgent need to complement the approved vaccine preparations. SARS-CoV-2 nps13...
SARS-CoV-2 infection is still spreading worldwide, and new antiviral therapies are an urgent need to complement the approved vaccine preparations. SARS-CoV-2 nps13 helicase is a validated drug target participating in the viral replication complex and possessing two associated activities: RNA unwinding and 5'-triphosphatase. In the search of SARS-CoV-2 direct antiviral agents, we established biochemical assays for both SARS-CoV-2 nps13-associated enzyme activities and screened both and a small in-house library of natural compounds. Myricetin, quercetin, kaempferol, and flavanone were found to inhibit the SARS-CoV-2 nps13 unwinding activity at nanomolar concentrations, while licoflavone C was shown to block both SARS-CoV-2 nps13 activities at micromolar concentrations. Mode of action studies showed that all compounds are nsp13 noncompetitive inhibitors versus ATP, while computational studies suggested that they can bind both nucleotide and 5'-RNA nsp13 binding sites, with licoflavone C showing a unique pattern of interaction with nsp13 amino acid residues. Overall, we report for the first time natural flavonoids as selective inhibitors of SARS-CoV-2 nps13 helicase with low micromolar activity.
PubMed: 35434533
DOI: 10.1021/acsptsci.1c00253 -
Skin Appendage Disorders Jul 2020Many dermatological conditions require extraction of material from the lesion followed by visualization under a microscope. However, visualization of the extracted...
INTRODUCTION
Many dermatological conditions require extraction of material from the lesion followed by visualization under a microscope. However, visualization of the extracted material can be done using a dermoscope instead. We propose "extraction dermoscopy" as an addition to the already existing treasury that dermoscopy holds.
METHODS
After approval from the institutional ethics committee, a cross-sectional study was carried out in a tertiary care hospital. Polarized and non-polarized versions of in vivo dermoscopy, as well as extraction dermoscopy, were performed on a total of 77 lesions, including 5 eruptive vellus hair cysts, 2 cilia incarnata externum, 10 trichostasis spinulosa, 20 keratosis pilaris, 20 molluscum contagiosum, and 20 lesions of milia. Heine Delta 20T and Dino-Lite Premier AM4113T were employed for dermoscopic examination.
RESULTS
A total of 77 lesions were selected, including 5 eruptive vellus hair cysts, 2 cilia incarnata externum, 10 trichostasis spinulosa, 20 keratosis pilaris, 20 molluscum contagiosum, and 20 lesions of milia. Extraction dermoscopy of the eruptive vellus cysts revealed skin color to brownish colored cysts with a bunch of pigmented hair. Similarly, findings of all other lesions were described and recorded post-extraction.
CONCLUSION
Extraction dermoscopy helps confirm the diagnosis without visualization under a microscope. Its application in recent times makes the explanation of the nature of many disorders to patients easier, and demonstration of extracted lesions may further improve doctor-patient communication.
PubMed: 32903886
DOI: 10.1159/000508518 -
Current Oncology (Toronto, Ont.) Apr 2023Despite high incidence rates and severe complications, the management of xerostomia lacks clinical guidelines. The aim of this overview was to summarize the clinical... (Review)
Review
Despite high incidence rates and severe complications, the management of xerostomia lacks clinical guidelines. The aim of this overview was to summarize the clinical experience derived from the last 10 years of treatments and prevention using systemic compounds. Results showed that the cytoprotective drug amifostine, and its antioxidant agents, are the most discussed as preventive agents of xerostomia in head and neck cancer (HNC) patients. In the presence of the disease, the pharmacological treatments have been mainly directed to stimulate secretion of the damaged salivary glands, or to counteract a decreased capacity of the antioxidant system, in view of an increasing of reactive oxygen species (ROS). However, the data demonstrated low ability of the drugs, together with a great number of side effects, which strongly limit their use. Concerning traditional medicine (TM), valid clinical trials are so limited that neither the efficacy nor the absence of interferences to concomitant chemical therapies can be validated. Consequently, the management of xerostomia and its devastating complications remain a very significant void in daily clinical practice.
Topics: Humans; Radiation-Protective Agents; Antioxidants; Xerostomia; Amifostine; Medicine, Traditional
PubMed: 37232794
DOI: 10.3390/curroncol30050336 -
Diagnostics (Basel, Switzerland) Jun 2024Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin... (Review)
Review
Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin A (CgA), pancreatic polypeptide (PP), and neuron-specific enolase (NSE) have limitations in terms of specificity and sensitivity. Specific circulating markers such as serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and various gastrointestinal hormones such as gastrin, glucagon, somatostatin, and vasoactive intestinal peptide (VIP) have a role in identifying functional NENs. Recent advances in molecular and biochemical markers, also accounting for novel genomic and proteomic markers, have significantly improved the landscape for the diagnosis and monitoring of NENs. This review discusses these developments, focusing on both traditional markers such as CgA and NSE, as well as specific hormones like gastrin, insulin, somatostatin, glucagon, and VIP. Additionally, it covers emerging genomic and proteomic markers that are shaping current research. The clinical applicability of these markers is highlighted, and their role in improving diagnostic accuracy, predicting surgical outcomes, and monitoring response to treatment is demonstrated. The review also highlights the need for further research, including validation of these markers in larger studies, development of standardized assays, and integration with imaging techniques. The evolving field of biochemical markers holds promise for improving patient outcomes in the treatment of NENs, although challenges in standardization and validation remain.
PubMed: 38928704
DOI: 10.3390/diagnostics14121289 -
World Journal of Clinical Cases May 2021Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of DEB, characterized by recurrent pruritus of the extremities, pruritus papules, nodules, and...
BACKGROUND
Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare subtype of DEB, characterized by recurrent pruritus of the extremities, pruritus papules, nodules, and mossy-like plaques. To date, fewer than 100 cases have been reported. We report a misdiagnosed 30-year-old man with sporadic late-onset DEB-Pr who responded well to tacrolimus treatment, thereby serving as a guide to correct diagnosis and treatment.
CASE SUMMARY
A 30-year-old man presented with recurrent itching plaques of 1-year duration in the left tibia that aggravated and involved both legs and the back. Examination revealed multiple symmetrical, purple, and hyperpigmented papules and nodules with surface exfoliation involving the tibia and dorsum of the neck with negative Nissl's sign, no abnormalities in the skin, mucosa, hair, or fingernail, and no local lymph node enlargement. Blisters were never reported prior to presentation. Serum immunoglobulin E level was 636 IU/mL. Clinical manifestations suggested DEB-Pr. Histological examination showed subepidermal fissure, scar tissue, and milia. Direct immunofluorescence showed no obvious abnormalities. However, we were unable to perform electron microscopy or genetic research following his choice. We treated him with topical tacrolimus. After 2 wk, the itching alleviated, and the skin lesions began to subside. No adverse reactions were observed during treatment.
CONCLUSION
Topical tacrolimus is a safe treatment option for patients with DEB-Pr and can achieve continuous relief of severe itching.
PubMed: 33969095
DOI: 10.12998/wjcc.v9.i13.3090