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3-Tetrazolyl-ß-carbolines were prepared by the Pictet-Spengler approach using a tryptophan analogue as building block, in which the carboxylic acid was replaced by the bioisosteric tetrazole group. Knowing that ß-carbolines are often associated with psychopharmacological effects, the study of the 3-tetrazolyl-ß-carbolines as potential neuroprotective agents against Parkinson's disease was investigated. The evaluation of neuroprotective effects against 1-methyl-4-phenylpyridin-1-ium (MPP+)-induced cytotoxicity allowed to identify compounds with relevant neuroprotective activity. One derivative, 3-(1-benzyl-1H-tetrazol-5-yl)-1-(p-dimethylaminophenyl)-ß-carboline, stood out for its low cytotoxicity and excellent performance, preventing cell death induced by this neurotoxin. The most promising compounds were also evaluated for their neuroprotective properties against iron (III)-induced cytotoxicity. However, only one 3-tetrazolyl-ß-carboline derivative slightly reduced iron-induced cytotoxicity. Overall, the neuroprotective properties of 3-tetrazolyl-ß-carbolines have been demonstrated and this finding may contribute to the development of new therapies for Parkinson's disease.
Subject(s)
Carbolines , Neuroprotective Agents , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/chemical synthesis , Carbolines/chemistry , Carbolines/pharmacology , Carbolines/chemical synthesis , Structure-Activity Relationship , Humans , Molecular Structure , Cell Survival/drug effects , Tetrazoles/chemistry , Tetrazoles/pharmacology , Tetrazoles/chemical synthesis , Dose-Response Relationship, Drug , AnimalsABSTRACT
PURPOSE: Malignant melanoma is an aggressive cancer, and there is a notable dearth on epidemiology, clinical and treatment characterization within the Portuguese population. We performed a scoping review to identify real-world evidence studies focused in Portuguese adult patients with malignant melanoma. METHODS: A comprehensive search was conducted. After screening, we described the studies by design, sample size, geographics, setting, population, and outcomes reported. RESULTS: The search yielded 54 studies, mainly retrospective (79.6%). The population assessed was heterogeneous varying from patients with melanoma in general to specific types of melanoma, or even more restricted to patients with specific conditions. The evidence found was mostly concerning clinical outcomes (n=46), patients' clinical profile (n=44) and demographic characterization (n=48). Treatment information was described in 30 studies whereas only 18 reported epidemiological parameters. Studies were mainly performed by the major oncology centers in Lisbon, Oporto and Coimbra, and only two evaluated the entire Portuguese population. To allow comparability, only studies including patients with cutaneous malignant melanoma were considered (13 of the 54) for outcomes evaluation analysis. Median OS varied from 18 to 36 months, assessed after melanoma treatment. Incidence was the most reported epidemiological parameter, confirming the increasing number of cutaneous malignant melanoma patients over the years. Only one study reported prevalence and four reported mortality rates. CONCLUSIONS: The evidence found confirms the lack of information about malignant melanoma in Portugal, highlighting the need of real-world studies to assess melanoma prevalence and incidence rates, current treatment approaches, and clinical characterization of these patients.
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Mycoses are one of the major causes of morbidity/mortality among immunocompromised individuals. Considering the importance of these infections, the World Health Organization (WHO) defined a priority list of fungi for health in 2022 that include Candida albicans as belonging to the critical priority group and Pichia kudriavzevii (Candida krusei) to the medium priority group. The existence of few available antifungal drugs, their high toxicity, the acquired fungal resistance, and the appearance of new species with a broader spectrum of resistance, points out the need for searching for new antifungals, preferably with new and multiple mechanisms of action. The cyclam salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 was previously tested against several fungi and revealed an interesting activity, with minimal inhibitory concentration (MIC) values of 8 µg/mL for C. krusei and of 128 µg/mL for C. albicans. The main objective of the present work was to deeply understand the mechanisms involved in its antifungal activity. The effects of the cyclam salt on yeast metabolic viability (resazurin reduction assay), yeast mitochondrial function (JC-1 probe), production of reactive oxygen species (DCFH-DA probe) and on intracellular ATP levels (luciferin/luciferase assay) were evaluated. H4[H2(4-CF3PhCH2)2Cyclam]Cl4 induced a significant decrease in the metabolic activity of both C. albicans and C. krusei, an increase in Reactive Oxygen Species (ROS) production, and an impaired mitochondrial function. The latter was observed by the depolarization of the mitochondrial membrane and decrease in ATP intracellular levels, mechanisms that seems to be involved in the antifungal activity of H4[H2(4-CF3PhCH2)2Cyclam]Cl4. The interference of the cyclam salt with human cells revealed a CC50 value against HEK-293 embryonic kidney cells of 1.1 µg/mL and a HC10 value against human red blood cells of 0.8 µg/mL.
Subject(s)
Antifungal Agents , Candida albicans , Candida , Microbial Sensitivity Tests , Reactive Oxygen Species , Antifungal Agents/pharmacology , Candida albicans/drug effects , Humans , Reactive Oxygen Species/metabolism , Candida/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Membrane Potential, Mitochondrial/drug effects , PichiaABSTRACT
PURPOSE: Despite a rise in clinical use of radiopharmaceutical therapies, the biological effects of radionuclides and their relationship with absorbed radiation dose are poorly understood. Here, we set out to define this relationship for Auger electron emitters [99mTc]TcO4- and [123I]I- and ß--particle emitter [188Re]ReO4-. Studies were carried out using genetically modified cells that permitted direct radionuclide comparisons. METHODS AND MATERIALS: Triple-negative MDA-MB-231 breast cancer cells expressing the human sodium iodide symporter (hNIS) and green fluorescent protein (GFP; MDA-MB-231.hNIS-GFP) were used. In vitro radiotoxicity of [99mTc]TcO4-, [123I]I-, and [188Re]ReO4- was determined using clonogenic assays. Radionuclide uptake, efflux, and subcellular location were used to calculate nuclear absorbed doses using the Medical Internal Radiation Dose (MIRD) formalism. In vivo studies were performed using female NSG mice bearing orthotopic MDA-MB-231.hNIS-GFP tumors and compared with X-ray-treated (12.6-15 Gy) and untreated cohorts. Absorbed dose per unit activity in tumors and sodium iodide symporter-expressing organs was extrapolated to reference human adult models using OLINDA/EXM. RESULTS: [99mTc]TcO4- and [123I]I- reduced the survival fraction only in hNIS-expressing cells, whereas [188Re]ReO4- reduced survival fraction in hNIS-expressing and parental cells. [123I]I- required 2.4- and 1.5-fold lower decays/cell to achieve 37% survival compared with [99mTc]TcO4- and [188Re]ReO4-, respectively, after 72 hours of incubation. Additionally, [99mTc]TcO4-, [123I]I-, and [188Re]ReO4- had superior cell killing effectiveness in vitro compared with X-rays. In vivo, X-ray led to a greater median survival compared with [188Re]ReO4- and [123I]I- (54 days vs 45 and 43 days, respectively). Unlike the X-ray cohort, no metastases were visualized in the radionuclide-treated cohorts. Extrapolated human absorbed doses of [188Re]ReO4- to a 1 g tumor were 13.8- and 11.2-fold greater than for [123I]I- in female and male models, respectively. CONCLUSIONS: This work reports reference dose-effect data using cell and tumor models for [99mTc]TcO4-, [123I]I-, and [188Re]ReO4- for the first time. We further demonstrate the tumor-controlling effects of [123I]I- and [188Re]ReO4- in comparison with external beam radiation therapy.
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BACKGROUND: Seroepidemiological studies provide estimates of population-level immunity, prevalence/incidence of infections, and evaluation of vaccination programs. We assessed the seroprevalence of protective antibodies against influenza and evaluated the correlation of seroprevalence with the cumulative annual influenza incidence rate. METHODS: We conducted an annual repeated cross-sectional seroepidemiological survey, during June-August, from 2014 to 2019, in Portugal. A total of 4326 sera from all age groups, sex, and regions was tested by hemagglutination inhibition assay. Seroprevalence and geometric mean titers (GMT) of protective antibodies against influenza were assessed by age group, sex, and vaccine status (65+ years old). The association between summer annual seroprevalence and the difference of influenza incidence rates between one season and the previous one was measured by Pearson correlation coefficient (r). RESULTS: Significant differences in seroprevalence of protective antibodies against influenza were observed in the population. Higher seroprevalence and GMT for A(H1N1)pdm09 and A(H3N2) were observed in children (5-14); influenza B seroprevalence in adults 65+ was 1.6-4.4 times than in children (0-4). Vaccinated participants (65+) showed significant higher seroprevalence/GMT for influenza. A strong negative and significant correlation was found between seroprevalence and ILI incidence rate for A(H1N1)pdm09 in children between 5 and 14 (r = -0.84; 95% CI, -0.98 to -0.07); a weak negative correlation was observed for A(H3N2) and B/Yamagata (r ≤ -0.1). CONCLUSIONS: The study provides new insight into the anti-influenza antibodies seroprevalence measured in summer on the ILI incidence rate in the next season and the need for adjusted preventive health care measures to prevent influenza infection and transmission.
Subject(s)
Antibodies, Viral , Influenza, Human , Humans , Seroepidemiologic Studies , Cross-Sectional Studies , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Influenza, Human/immunology , Female , Male , Adult , Incidence , Antibodies, Viral/blood , Child, Preschool , Child , Middle Aged , Adolescent , Young Adult , Aged , Portugal/epidemiology , Infant , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Hemagglutination Inhibition Tests , Influenza B virus/immunology , Seasons , Infant, Newborn , Aged, 80 and overABSTRACT
In bacteria, intracellular K+ is involved in the regulation of membrane potential, cytosolic pH, and cell turgor as well as in spore germination, environmental adaptation, cell-to-cell communication in biofilms, antibiotic sensitivity, and infectivity. The second messenger cyclic-di-AMP (c-di-AMP) has a central role in modulating the intracellular K+ concentration in many bacterial species, controlling transcription and function of K+ channels and transporters. However, our understanding of how this regulatory network responds to c-di-AMP remains poor. We used the RCK (Regulator of Conductance of K+) proteins that control the activity of Ktr channels in Bacillus subtilis as a model system to analyze the regulatory function of c-di-AMP with a combination of in vivo and in vitro functional and structural characterization. We determined that the two RCK proteins (KtrA and KtrC) are neither physiologically redundant or functionally equivalent. KtrC is the physiologically dominant RCK protein in the regulation of Ktr channel activity. In explaining this hierarchical organization, we found that, unlike KtrA, KtrC is very sensitive to c-di-AMP inactivation and lack of c-di-AMP regulation results in RCK protein toxicity, most likely due to unregulated K+ flux. We also found that KtrC can assemble with KtrA, conferring c-di-AMP regulation to the functional KtrA/KtrC heteromers and potentially compensating KtrA toxicity. Altogether, we propose that the central role of c-di-AMP in the control of the K+ machinery, by modulating protein levels through gene transcription and by regulating protein activity, has determined the evolutionary selection of KtrC as the dominant RCK protein, shaping the hierarchical organization of regulatory components of the K+ machinery.
Subject(s)
Bacillus subtilis , Bacterial Proteins , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Bacillus subtilis/metabolism , Bacillus subtilis/genetics , Potassium/metabolism , Gene Expression Regulation, Bacterial , Dinucleoside Phosphates/metabolism , Potassium Channels/metabolism , Potassium Channels/geneticsABSTRACT
Two heterometallic Cu(II)/Ni(II) coordination polymers, [Cu2(Hbdea)2Ni(CN)4]n (1) and [Cu2(dmea)2Ni(CN)4]n·nH2O (2), were successfully self-assembled in water by reacting Cu(II) nitrate with H2bdea (N-butyldiethanolamine) and Hdmea (N,N-dimethylethanolamine) in the presence of sodium hydroxide and [Ni(CN)4]2-. These new coordination polymers were investigated by single-crystal and powder X-ray diffraction and fully characterized by FT-IR spectroscopy, thermogravimetry, elemental analysis, variable-temperature magnetic susceptibility measurements, and theoretical DFT and CASSCF calculations. Despite differences in crystal systems, in both compounds, each dinuclear building block [Cu2(µ-aminopolyalcoholate)2]2+ is bridged by diamagnetic [Ni(CN)4]2- linkers, resulting in 1D (1) or 2D (2) metal-organic architectures. Experimental magnetic studies show that both compounds display strong antiferromagnetic coupling (J = -602.1 cm-1 for 1 and -151 cm-1 for 2) between Cu(II) ions within the dimers mediated by the µ-O-alkoxo bridges. These results are corroborated by the broken symmetry DFT studies, which also provide further insight into the electronic structures of copper dimeric units. By reporting a facile self-assembly synthetic protocol, this study can be a model to widen a still limited family of heterometallic Cu/Ni coordination polymer materials with different functional properties.
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The misuse of pharmaceuticals has significantly increased in recent decades, becoming a major public health concern. The risks associated with medication misuse are particularly high in cases of overdose, especially when the active substances are chiral, as enantioselectivity plays an important role in toxicity. Promethazine (PMZ) is a chiral antihistamine marketed as a racemate and it is misused in "Purple Drank", a recreational drug beverage, that combines codeine and/or PMZ, with soda or alcohol leading to serious health consequences and fatalities in consumers around the world, particularly among teenagers. Information regarding the enantioselectivity in the toxicity of (R,S)-PMZ and its main metabolites, namely promethazine sulfoxide (PMZSO) and desmonomethyl promethazine (DMPMZ), is unknown. This work reported, for the first time, the enantioseparation, in milligram scale, of (R,S)-PMZ, (R,S)-DMPMZ, (R,S)- PMZSO and the determination of their absolute configurations by electronic circular dichroism (ECD). The enantioseparation of all the six enantiomers was accomplished in a homemade semi-preparative column with amylose tris-3,5-dimethylphenylcarbamate (AD) coated with aminopropyl Nucleosil silica. The enantiomeric purity was evaluated using the analytical Lux® 3⯵m i-Amylose-3 column, yielding enantiomeric purity values ranging between 94.4% and 99.7%. The elution order of all the enantiomers was accomplished combining the ECD results with an optical rotation detector. The elution order of the enantiomers was influenced only by the chiral selector, rather than the mobile phase. The cytotoxicity of the racemates and the isolated enantiomers towards differentiated SH-SY5Y cells was evaluated. (R,S)-DMPMZ exhibited a significantly higher cytotoxicity than (R,S)-PMZ, suggesting the metabolic bioactivation of (R,S)-PMZ. Conversely, no significant cytotoxicity was found for (R,S)-PMZSO, underscoring a metabolic detoxification pathway. Remarkably, enantioselectivity was observed for the cytotoxicity of PMZ; (R)-PMZ was significantly more cytotoxic than (S)-PMZ. The results underscore the importance to isolate the enantiomers in their enantiomerically form and their correct identification for toxicity enantioselectivity studies, which are vital to understand the drug's behaviour and safety, especially in case of overdoses.
Subject(s)
Promethazine , Promethazine/chemistry , Stereoisomerism , Humans , Cell Line, Tumor , Circular Dichroism/methods , Cell Survival/drug effects , Chromatography, High Pressure Liquid/methodsABSTRACT
BACKGROUND: The global scale-up of antiretroviral treatment (ART) offers significant health benefits by suppressing HIV-1 replication and increasing CD4 cell counts. However, incomplete viral suppression poses a potential threat for the emergence of drug resistance mutations (DRMs), limiting ART options, and increasing HIV transmission. OBJECTIVE: We investigated the patterns of transmitted drug resistance (TDR) and acquired drug resistance (ADR) among HIV-1 patients in Portugal. METHODS: Data were obtained from 1050 HIV-1 patient samples submitted for HIV drug resistance (HIVDR) testing from January 2022 to June 2023. Evaluation of DRM affecting viral susceptibility to nucleoside/tide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) was performed using an NGS technology, the Vela Diagnostics Sentosa SQ HIV-1 Genotyping Assay. RESULTS: About 71% of patients were ART naïve and 29% were experienced. Overall, 20% presented with any DRM. The prevalence of TDR and ADR was 12.6% and 41.1%, respectively. M184V, T215S, and M41L mutations for NRTI, K103N for NNRTI, and M46I/L for PIs were frequent in naïve and treated patients. E138K and R263K mutations against INSTIs were more frequent in naïve than treated patients. TDR and ADR to INSTIs were 0.3% and 7%, respectively. Patients aged 50 or over (OR: 1.81, p = 0.015), originating from Portuguese-speaking African countries (PALOPs) (OR: 1.55, p = 0.050), HIV-1 subtype G (OR: 1.78, p = 0.010), and with CD4 < 200 cells/mm3 (OR: 1.70, p = 0.043) were more likely to present with DRMs, while the males (OR: 0.63, p = 0.003) with a viral load between 4.1 to 5.0 Log10 (OR: 0.55, p = 0.003) or greater than 5.0 Log10 (OR: 0.52, p < 0.001), had lower chances of presenting with DRMs. CONCLUSIONS: We present the first evidence on TDR and ADR to INSTI regimens in followed up patients presenting for healthcare in Portugal. We observed low levels of TDR to INSTIs among ART-naïve and moderate levels in ART-exposed patients. Regimens containing PIs could be an alternative second line in patients with intermediate or high-level drug resistance, especially against second-generation INSTIs (dolutegravir, bictegravir, and cabotegravir).
Subject(s)
Anti-HIV Agents , Drug Resistance, Viral , HIV Infections , HIV-1 , High-Throughput Nucleotide Sequencing , Mutation , Humans , HIV-1/genetics , HIV-1/drug effects , Portugal/epidemiology , HIV Infections/virology , HIV Infections/drug therapy , HIV Infections/epidemiology , Drug Resistance, Viral/genetics , Male , Female , Middle Aged , Adult , Anti-HIV Agents/pharmacology , Anti-HIV Agents/therapeutic use , Genotype , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , Young Adult , AgedABSTRACT
BACKGROUND: In Europe, up to 70% of visceral leishmaniasis (VL) cases occurring in adults living with HIV. People living with HIV with VL co-infection often display persistent parasitemia, requiring chronic intermittent anti-Leishmania therapies. Consequently, frequent VL relapses and higher mortality rates are common in these individuals. As such, it is of paramount importance to understand the reasons for parasite persistence to improve infection management. METHODS: To outline possible causes for treatment failure in the context of HIV-VL, we followed a person living with HIV-VL co-infection for nine years in a 12-month period. We characterized: HIV-related clinicopathological alterations (CD4+ T counts and viremia) and Leishmania-specific seroreactivity, parasitemia, quantification of pro-inflammatory cytokines upon stimulation and studied a Leishmania clinical isolate recovered during this period. RESULTS: The subject presented controlled viremia and low CD4+ counts. The subject remained PCR positive for Leishmania and also seropositive. The cellular response to parasite antigens was erratic. The isolate was identified as the first Leishmania infantum case with evidence of decreased miltefosine susceptibility in Portugal. CONCLUSION: Treatment failure is a multifactorial process driven by host and parasite determinants. Still, the real-time determination of drug susceptibility profiles in clinical isolates is an unexplored resource in the monitoring of VL.
Subject(s)
Coinfection , HIV Infections , Leishmania infantum , Leishmaniasis, Visceral , Phosphorylcholine/analogs & derivatives , Adult , Humans , Portugal , Coinfection/drug therapy , Parasitemia , Viremia , HIV Infections/complications , HIV Infections/drug therapy , Leishmaniasis, Visceral/complications , Leishmaniasis, Visceral/drug therapyABSTRACT
Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.
Subject(s)
HIV Infections , Sexual and Gender Minorities , Male , Humans , Adult , Homosexuality, Male , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/prevention & control , Portugal/epidemiology , EuropeABSTRACT
Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 and its clinical impact during the fall-winter season of 2021/22. From 19 European countries, 58 institutes reported 10,481 (6.8%) EV-positive samples of which 1,004 (9.6%) were identified as EV-D68 (852 respiratory samples). Clinical data was reported for 969 cases. 78.9% of infections were reported in children (0-5 years); 37.9% of cases were hospitalised. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases with six reported with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of two novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale EV-D68 European upsurge with severe clinical impact and the emergence of B3-derived lineages.
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Adhesive bonding has been increasingly employed in multiple industrial applications. This has led to a large industrial demand for faster, simpler, and cheaper characterization methods that allow engineers to predict the mechanical behavior of an adhesive with numerical models. Currently, these characterization processes feature a wide variety of distinct standards, specimen configurations, and testing procedures and require deep knowhow of complex data-reduction schemes. By suggesting the creation of a new and integrated experimental tool for adhesive characterization, it becomes possible to address this problem in a faster and unified manner. In this work, following a previous numerical study, the mode I and II components of fracture-toughness characterization were validated experimentally in two different configurations, Balanced and Unbalanced. For mode I, it was demonstrated that both configurations presented similar numerical and experimental R-curves. The relative error against standard tests was lower than ±5% for the Balanced specimen; the Unbalanced system showed higher variations, which were predicted by the numerical results. Under mode II, the Balanced specimen displayed plastic deformation due to high deflections. On the contrary, the Unbalanced specimen did not show this effect and presented a relative error of approximately ±2%. Nonetheless, it was proven that this approach to obtain such data by using a single unified specimen is still feasible but needs further development to obtain with similar precision of standard tests. In the end, a conceptual change is proposed to solve the current mode II issues.
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Neonatal jaundice is a frequently observed occurrence in full-term newborns and typically manifests between 48 and 96 hours following birth. Early-onset jaundice is primarily induced by pathological factors, namely sepsis, hemolysis and an excessive accumulation of bilirubin resulting from the breakdown of red blood cells.We present a case involving a full-term newborn with an uneventful perinatal history, who exhibited jaundice within the initial day of life and was subsequently admitted to the neonatal intensive care unit to commence intensive phototherapy. Initial screenings for sepsis and blood group incompatibility yielded negative results. However, despite 6 hours of phototherapy, the bilirubin levels did not decrease, prompting an investigation into central nervous system haemorrhage, which uncovered the presence of a haemorrhagic stroke.After a worsening in neurological status with neonatal crisis and need for phenobarbital, a life-saving craniotomy was performed. Clinical evolution was good with no additional crisis detected after the early neonatal period and improvement in motor function at 2-month-old follow-up.
Subject(s)
Jaundice, Neonatal , Jaundice , Sepsis , Humans , Infant, Newborn , Infant , Jaundice, Neonatal/diagnosis , Jaundice, Neonatal/etiology , Jaundice, Neonatal/therapy , Bilirubin , Intensive Care Units, Neonatal , PhototherapyABSTRACT
Wearables offer a promising solution for simultaneous posture monitoring and/or corrective feedback. The main objective was to identify, synthesise, and characterise the wearables used in the workplace to monitor and postural feedback to workers. The PRISMA-ScR guidelines were followed. Studies were included between 1 January 2000 and 22 March 2023 in Spanish, French, English, and Portuguese without geographical restriction. The databases selected for the research were PubMed®, Web of Science®, Scopus®, and Google Scholar®. Qualitative studies, theses, reviews, and meta-analyses were excluded. Twelve studies were included, involving a total of 304 workers, mostly health professionals (n = 8). The remaining studies covered workers in the industry (n = 2), in the construction (n = 1), and welders (n = 1). For assessment purposes, most studies used one (n = 5) or two sensors (n = 5) characterised as accelerometers (n = 7), sixaxial (n = 2) or nonaxialinertial measurement units (n = 3). The most common source of feedback was the sensor itself (n = 6) or smartphones (n = 4). Haptic feedback was the most prevalent (n = 6), followed by auditory (n = 5) and visual (n = 3). Most studies employed prototype wearables emphasising kinematic variables of human movement. Healthcare professionals were the primary focus of the study along with haptic feedback that proved to be the most common and effective method for correcting posture during work activities.
Subject(s)
Posture , Wearable Electronic Devices , Humans , Posture/physiology , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Workplace , Feedback , Accelerometry/instrumentationABSTRACT
Numerous pieces of evidence have supported the therapeutic potential of photobiomodulation (PBM) to modulate bone remodeling on mechanically stimulated teeth, proving PBM's ability to be used as a coadjuvant treatment to accelerate orthodontic tooth movement (OTM). However, there are still uncertainty and discourse around the optimal PBM protocols, which hampers its optimal and consolidated clinical applicability. Given the differential expression and metabolic patterns exhibited in the tension and compression sides of orthodontically stressed teeth, it is plausible that different types of irradiation may be applied to each side of the teeth. In this sense, this study aimed to design and implement an optimization protocol to find the most appropriate PBM parameters to stimulate specific bone turnover processes. To this end, three levels of wavelength (655, 810 and 940 nm), two power densities (5 and 10 mW/cm2) and two regimens of single and multiple sessions within three consecutive days were tested. The biological response of osteoblasts and periodontal ligament (PDL) fibroblasts was addressed by monitoring the PBM's impact on the cellular metabolic activity, as well as on key bone remodeling mediators, including alkaline phosphatase (ALP), osteoprotegerin (OPG) and receptor activator of nuclear factor κ-B ligand (RANK-L), each day. The results suggest that daily irradiation of 655 nm delivered at 10 mW/cm2, as well as 810 and 940 nm light at 5 mW/cm2, lead to an increase in ALP and OPG, potentiating bone formation. In addition, irradiation of 810 nm at 5 mW/cm2 delivered for two consecutive days and suspended by the third day promotes a downregulation of OPG expression and a slight non-significant increase in RANK-L expression, being suitable to stimulate bone resorption. Future studies in animal models may clarify the impact of PBM on bone formation and resorption mediators for longer periods and address the possibility of testing different stimulation periodicities. The present in vitro study offers valuable insights into the effectiveness of specific PBM protocols to promote osteogenic and osteoclastogenesis responses and therefore its potential to stimulate bone formation on the tension side and bone resorption on the compression side of orthodontically stressed teeth.
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BACKGROUND: In Europe, psychiatric disorders seem to affect up to 50% of the homeless. In Portugal there were, at a certain time, circa 3,396 homeless people, half living in the capital city, Lisboa. AIMS: The Homeless Outreach Psychiatric Engagement for Lisboa (HOPE 4 Lisboa) was created, in January 1st 2022, as a collaboration including staff from the local state asylum, medical school and town hall in Lisboa, Portugal, in order to provide better treatment for the super difficult cases of psychiatric patients living homeless in Lisboa. METHOD: During 2022, the HOPE 4 team made night rounds, every 15 days on Tuesday's night (20:30 to 23:30) trying to reach, at least, one dozen of homeless psychiatric patients, previously identified. RESULTS: The HOPE 4 Lisboa interviewed 101 patients (53.4%) out of the 189 programed visits. From this group, 72 (72%) had already a previous psychiatric diagnosis. From those 101 patients, reports for 47 (47%) were sent for an eventual compulsory psychiatric assessment. From those 47 only 21 patients (21%) were admitted in the psychiatry ward. Finally we discuss the most super difficult patient we found, as a small case report: a John Doe living in complete Diogenes syndrome. CONCLUSIONS: there are still a few psychiatrists interested in treating homeless people completely or partially out of the classic mental health care systems. Some claim to be doing interstitial psychiatry, others street psychiatry, but we could also call it marontology.
Subject(s)
Ill-Housed Persons , Mental Disorders , Humans , Mental Disorders/therapy , Portugal , Time Factors , HospitalizationABSTRACT
Regardless of the benefits of fall prevention programs, people with Parkinson's disease (PD) will still fall. Therefore, it is crucial to explore novel therapeutic approaches that are well-accepted and effective for addressing fall risk and the fear of falls among this population. The present study aims to assess the feasibility of the Landing Wise program as a therapeutic intervention for reducing the fear of falling in people with PD. A mixed-methods study will be conducted using convenience sampling to recruit 20 people with PD with a moderate concern of falling from a Parkinson's Patients Association. In addition to usual care, participants will attend 2 days per week, 90 min group sessions for 8 weeks. The intervention combines group cognitive behavioral intervention with the training of safe landing strategies. Feasibility will be assessed by six key domains (recruitment strategy and rates, enrollment, retention, acceptability, reasons for decline/withdrawal, and adverse events). Quantitative data will be analyzed using descriptive statistics to characterize the sample, followed by inferential statistics to evaluate differences in the Short Falls Efficacy Scale-International Scale, Movement Disorder Society Unified Parkinson's Disease Rating Scale, Timed Up Go, 6-Minutes Walking Distance, and fall frequency and severity scores between baseline and final assessment. Qualitative data will be analyzed using an inductive thematic analysis process. There is a growing interest in developing new effective therapeutic approaches for people with PD. If proven program feasibility, this study precedes a randomized controlled trial to establish the effectiveness of the Landing Wise program.
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A 54-year-old female presented with complaints of glare and progressive visual loss OS with a corrected distance visual acuity (CDVA) OS of 20/100. The patient had grade 1 corneal edema with a "beaten bronze" appearance on specularly reflected light, pseudopolycoria, and a nuclear sclerotic cataract. The diagnosis of nuclear cataract and progressive iris atrophy iridocorneal endothelial (ICE) syndrome was made, and the patient underwent uneventful phacoemulsification with capsular bag placement of an AcrySof SA60AT intraocular lens combined with pseudopolycoria repair using an endocapsular Model A REPER artificial iris. Six months later, the patient was submitted to a Descemet's stripping automated endothelial keratoplasty (DSAEK) procedure, and 6 months after that the CDVA was 20/32 with no corneal edema and normal intraocular pressure. This two-step surgical approach, combining phacoemulsification and endocapsular foldable iris prosthesis placement followed by DSAEK, may be considered a promising option to successfully treat progressive iris atrophy ICE syndrome patients.
ABSTRACT
Machado-Joseph disease (MJD/SCA3) is the most frequent dominant ataxia worldwide. It is caused by a (CAG)n expansion. MJD has two major ancestral backgrounds: the Machado lineage, found mainly in Portuguese families; and the Joseph lineage, present in all five continents, probably originating in Asia. MJD has been described in a few African and African-American families, but here we report the first diagnosed in Sudan to our knowledge. The proband presented with gait ataxia at age 24; followed by muscle cramps and spasticity, and dysarthria, by age 26; he was wheel-chair bound at 29 years of age. His brother had gait problems from age 20 years and, by age 21, lost the ability to run, showed dysarthria and muscle cramps. To assess the mutational origin of this family, we genotyped 30 SNPs and 7 STRs flanking the ATXN3_CAG repeat in three siblings and the non-transmitting father. We compared the MJD haplotype segregating in the family with our cohort of MJD families from diverse populations. Unlike all other known families of African origin, the Machado lineage was observed in Sudan, being shared with 86 Portuguese, 2 Spanish and 2 North-American families. The STR-based haplotype of Sudanese patients, however, was distinct, being four steps (2 STR mutations and 2 recombinations) away from the founder haplotype shared by 47 families, all of Portuguese extraction. Based on the phylogenetic network constructed with all MJD families of the Machado lineage, we estimated a common ancestry at 3211 ± 693 years ago.