Perceived stress modulates the activity between the amygdala and the cortex.

The significant link between stress and psychiatric disorders has prompted research on stress's impact on the brain. Interestingly, previous studies on healthy subjects have demonstrated an association between perceived stress and amygdala volume, although the mechanisms by which perceived stress can affect brain function remain unknown. To better understand what this association entails at a functional level, herein, we explore the association of perceived stress, measured by the PSS10 questionnaire, with disseminated functional connectivity between brain areas. Using resting-state fMRI from 252 healthy subjects spanning a broad age range, we performed both a seed-based amygdala connectivity analysis (static connectivity, with spatial resolution but no temporal definition) and a whole-brain data-driven approach to detect altered patterns of phase interactions between brain areas (dynamic connectivity with spatiotemporal information). Results show that increased perceived stress is directly associated with increased amygdala connectivity with frontal cortical regions, which is driven by a reduced occurrence of an activity pattern where the signals in the amygdala and the hippocampus evolve in opposite directions with respect to the rest of the brain. Overall, these results not only reinforce the pathological effect of in-phase synchronicity between subcortical and cortical brain areas but also demonstrate the protective effect of counterbalanced (i.e., phase-shifted) activity between brain subsystems, which are otherwise missed with correlation-based functional connectivity analysis.

Surgical approaches to colonic and rectal anastomosis: systematic review and meta-analysis.

PURPOSE: Postoperative complications after a colonic and rectal surgery are of significant concern to the surgical community. Although there are different techniques to perform anastomosis (i.e., handsewn, stapled, or compression), there is still no consensus on which technique provides the least number of postoperative problems. The objective of this study is to compare the different anastomotic techniques regarding the occurrence or duration of postoperative outcomes such as anastomotic dehiscence, mortality, reoperation, bleeding and stricture (as primary outcomes), and wound infection, intra-abdominal abscess, duration of surgery, and hospital stay (as secondary outcomes). METHODS: Clinical trials published between January 1, 2010, and December 31, 2021, reporting anastomotic complications with any of the anastomotic technique were identified using the MEDLINE database. Only articles that clearly defined the anastomotic technique used, and report at least two of the outcomes defined were included. RESULTS: This meta-analysis included 16 studies whose differences were related to the need of reoperation (p < 0.01) and the duration of surgery (p = 0.02), while for the anastomotic dehiscence, mortality, bleeding, stricture, wound infection, intra-abdominal abscess, and hospital stay, no significant differences were found. Compression anastomosis reported the lowest reoperation rate (3.64%) and the handsewn anastomosis the highest (9.49%). Despite this, more time to perform the surgery was required in compression anastomosis (183.47 min), with the handsewn being the fastest technique (139.92 min). CONCLUSIONS: The evidence found was not sufficient to demonstrate which technique is most suitable to perform colonic and rectal anastomosis, since the postoperative complications were similar between the handsewn, stapled, or compression techniques.

A suggestive approach for assessing item quality, usability and validity of Automatic Item Generation.

Automatic Item Generation (AIG) refers to the process of using cognitive models to generate test items using computer modules. It is a new but rapidly evolving research area where cognitive and psychometric theory are combined into digital framework. However, assessment of the item quality, usability and validity of AIG relative to traditional item development methods lacks clarification. This paper takes a top-down strong theory approach to evaluate AIG in medical education. Two studies were conducted: Study I-participants with different levels of clinical knowledge and item writing experience developed medical test items both manually and through AIG. Both item types were compared in terms of quality and usability (efficiency and learnability); Study II-Automatically generated items were included in a summative exam in the content area of surgery. A psychometric analysis based on Item Response Theory inspected the validity and quality of the AIG-items. Items generated by AIG presented quality, evidences of validity and were adequate for testing student's knowledge. The time spent developing the contents for item generation (cognitive models) and the number of items generated did not vary considering the participants' item writing experience or clinical knowledge. AIG produces numerous high-quality items in a fast, economical and easy to learn process, even for inexperienced and without clinical training item writers. Medical schools may benefit from a substantial improvement in cost-efficiency in developing test items by using AIG. Item writing flaws can be significantly reduced thanks to the application of AIG's models, thus generating test items capable of accurately gauging students' knowledge.

Ultra-High-Field Neuroimaging Reveals Fine-Scale Processing for 3D Perception.

Binocular disparity provides critical information about three-dimensional (3D) structures to support perception and action. In the past decade significant progress has been made in uncovering human brain areas engaged in the processing of binocular disparity signals. Yet, the fine-scale brain processing underlying 3D perception remains unknown. Here, we use ultra-high-field (7T) functional imaging at submillimeter resolution to examine fine-scale BOLD fMRI signals involved in 3D perception. In particular, we sought to interrogate the local circuitry involved in disparity processing by sampling fMRI responses at different positions relative to the cortical surface (i.e., across cortical depths corresponding to layers). We tested for representations related to 3D perception by presenting participants (male and female, N = 8) with stimuli that enable stable stereoscopic perception [i.e., correlated random dot stereograms (RDS)] versus those that do not (i.e., anticorrelated RDS). Using multivoxel pattern analysis (MVPA), we demonstrate cortical depth-specific representations in areas V3A and V7 as indicated by stronger pattern responses for correlated than for anticorrelated stimuli in upper rather than deeper layers. Examining informational connectivity, we find higher feedforward layer-to-layer connectivity for correlated than anticorrelated stimuli between V3A and V7. Further, we observe disparity-specific feedback from V3A to V1 and from V7 to V3A. Our findings provide evidence for the role of V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures.SIGNIFICANCE STATEMENT Binocular vision plays a significant role in supporting our interactions with the surrounding environment. The fine-scale neural mechanisms that underlie the brain's skill in extracting 3D structures from binocular signals are poorly understood. Here, we capitalize on recent advances in ultra-high-field functional imaging to interrogate human brain circuits involved in 3D perception at submillimeter resolution. We provide evidence for the role of area V3A as a key nexus for disparity processing, which is implicated in feedforward and feedback signals related to the perceptual estimation of 3D structures from binocular signals. These fine-scale measurements help bridge the gap between animal neurophysiology and human fMRI studies investigating cross-scale circuits, from micro circuits to global brain networks for 3D perception.

Unraveling the Pivotal Role of Atropisomerism for Cellular Internalization.

The intrinsic challenge of large molecules to cross the cell membrane and reach intracellular targets is a major obstacle for the development of new medicines. We report how rotation along a single C-C bond, between atropisomers of a drug in clinical trials, improves cell uptake and therapeutic efficacy. The atropisomers of redaporfin (a fluorinated sulfonamide bacteriochlorin photosensitizer of 1135 Da) are separable and display orders of magnitude differences in photodynamic efficacy that are directly related to their differential cellular uptake. We show that redaporfin atropisomer uptake is passive and only marginally affected by ATP depletion, plasma proteins, or formulation in micelles. The α4 atropisomer, where meso-phenyl sulfonamide substituents are on the same side of the tetrapyrrole macrocycle, exhibits the highest cellular uptake and phototoxicity. This is the most amphipathic atropisomer with a conformation that optimizes hydrogen bonding (H-bonding) with polar head groups of membrane phospholipids. Consequently, α4 binds to the phospholipids on the surface of the membrane, flips into the membrane to adopt the orientation of a surfactant, and eventually diffuses to the interior of the cell (bind-flip mechanism). We observed increased α4 internalization by cells of the tumor microenvironment in vivo and correlated this to the response of photodynamic therapy when tumor illumination was performed 24 h after α4 administration. These results show that properly orientated aryl sulfonamide groups can be incorporated into drug design as efficient cell-penetrating motifs in vivo and reveal the unexpected biological consequences of atropisomerism.

Association of amygdala size with stress perception: Findings of a transversal study across the lifespan.

Daily routines are getting increasingly stressful. Interestingly, associations between stress perception and amygdala volume, a brain region implicated in emotional behaviour, have been observed in both younger and older adults. Life stress, on the other hand, has become pervasive and is no longer restricted to a specific age group or life stage. As a result, it is vital to consider stress as a continuum across the lifespan. In this study, we investigated the relationship between perceived stress and amygdala size in 272 healthy participants with a broad age range. Participants were submitted to a structural magnetic resonance imaging (MRI) to extract amygdala volume, and the Perceived Stress Scale (PSS) scores were used as the independent variable in volumetric regressions. We found that perceived stress is positively associated with the right amygdala volume throughout life.

The rice cold-responsive calcium-dependent protein kinase OsCPK17 is regulated by alternative splicing and post-translational modifications.

Plant calcium-dependent protein kinases (CDPKs) are key proteins implicated in calcium-mediated signaling pathways of a wide range of biological events in the organism. The action of each particular CDPK is strictly regulated by many mechanisms in order to ensure an accurate signal translation and the activation of the adequate response processes. In this work, we investigated the regulation of a CDPK involved in rice cold stress response, OsCPK17, to better understand its mode of action. We identified two new alternative splicing (AS) mRNA forms of OsCPK17 encoding truncated versions of the protein, missing the CDPK activation domain. We analyzed the expression patterns of all AS variants in rice tissues and examined their subcellular localization in onion epidermal cells. The results indicate that the AS of OsCPK17 putatively originates truncated forms of the protein with distinct functions, and different subcellular and tissue distributions. Additionally, we addressed the regulation of OsCPK17 by post-translational modifications in several in vitro experiments. Our analysis indicated that OsCPK17 activity depends on its structural rearrangement induced by calcium binding, and that the protein can be autophosphorylated. The identified phosphorylation sites mostly populate the OsCPK17 N-terminal domain. Exceptions are phosphosites T107 and S136 in the kinase domain and S558 in the C-terminal domain. These phosphosites seem conserved in CDPKs and may reflect a common regulatory mechanism for this protein family.

Mixed-polarity random-dot stereograms alter GABA and Glx concentration in the early visual cortex.

The offset between images projected onto the left and right retina (binocular disparity) provides a powerful cue to the three-dimensional structure of the environment. It was previously shown that depth judgements are better when images comprise both light and dark features, rather than only light or only dark elements. Since Harris and Parker (Nature 374: 808-811, 1995) discovered the "mixed-polarity benefit," there has been limited evidence supporting their hypothesis that the benefit is due to separate bright and dark channels. Goncalves and Welchman (Curr Biol 27: 1403-1412, 2017) observed that single- and mixed-polarity stereograms evoke different levels of positive and negative activity in a deep neural network trained on natural images to make depth judgements, which also showed the mixed-polarity benefit. Motivated by this discovery, we seek to test the potential for changes in the balance of excitation and inhibition that are produced by viewing these stimuli. In particular, we use magnetic resonance spectroscopy to measure Glx and GABA concentrations in the early visual cortex of adult humans during viewing of single- and mixed-polarity random-dot stereograms (RDS). We find that participants' Glx concentration is significantly higher, whereas GABA concentration is significantly lower, when mixed-polarity RDS are viewed than when single-polarity RDS are viewed. These results indicate that excitation and inhibition facilitate processing of single- and mixed-polarity stereograms in the early visual cortex to different extents, consistent with recent theoretical work (Goncalves NR, Welchman AE. Curr Biol 27: 1403-1412, 2017).NEW & NOTEWORTHY Depth judgements are better when images comprise both light and dark features, rather than only light or only dark elements. Using magnetic resonance spectroscopy, we show that adult human participants' Glx concentration is significantly higher whereas GABA concentration is significantly lower in the early visual cortex when participants view mixed-polarity random-dot stereograms (RDS) compared with single-polarity RDS. These results indicate that excitation and inhibition facilitate processing of single- and mixed-polarity stereograms in the early visual cortex to different extents.

Clinical and Microbiological Profile of Bacterial Microbial Keratitis in a Portuguese Tertiary Referral Center-Where Are We in 2015?

OBJECTIVES: To study the microbial profile, antibiotic susceptibility pattern, risk factors, therapeutic trends, and clinical outcomes for microbial keratitis (MK) in a tertiary health care center. METHODS: All cases with suspected bacterial keratitis that were followed at consultation from September 2007 to August 2015 were included. Microbial cultures were obtained and patients were managed following an internal protocol. RESULTS: Two hundred thirty-five patients were included, with a mean age of 50.01±20.73 years. We obtained a 38.4% culture-positive rate, with higher proportion of gram-positives (70.8%). The commonest agents were Staphylococcus aureus (23.1%), Corynebacterium macginleyi (20.0%), and Pseudomonas aeruginosa (13.8%). Fluoroquinolone susceptibility was 97%, with no trend toward its decrease. A total of 95.7% had local risk factors, being trauma and contact lens wear the most common (28.9% each), with different age and pathogens distributions (P<0.001). Topical fluoroquinolones were first-line treatment in 99%, in association with aminoglycosides in 81.6%. Good initial response was registered in 95.9%, but 4.1% needed to step up treatment to fortified antibiotics, mainly if Pseudomonas (P=0.021). Good outcome was achieved in 81.8%, negatively affected by exposure and herpetic keratitis (P<0.001), central location (P=0.01), presence of Tyndall (P<0.001), corneal edema (P<0.001), and worse initial best-corrected visual acuity (P<0.001), but not Pseudomonas isolate (P=0.724). CONCLUSIONS: Gram-positives are the most frequent pathogens and shifting trends in the isolate distribution or emergence of resistant strains were not demonstrated. The susceptibility to first-line antibiotic agents remained high. We suggest a more aggressive approach to P. aeruginosa cases or MK presenting with poor outcome variables.

Ultrafast Dynamics of Manganese(III), Manganese(II), and Free-Base Bacteriochlorin: Is There Time for Photochemistry?

Manganese(III) and manganese(II) complexes of halogenated sulfonamide tetraphenylbacteriochlorins were prepared for the first time via a transmetalation reaction and shown to be stable at room temperature. The behavior of the electronic states of the paramagnetic complexes is remarkably different from those of the metal-free bacteriochlorins or diamagnetic metallobacteriochlorins. The Mn3+ complex exhibits eight electronic transitions between different states from 300 to 1100 nm, with a very prominent band (molar absorption coefficient of ca. 50000 M-1 cm-1) at 829 nm. Ultrafast transient absorption showed the formation of an excited singquintet state that decays to a tripquintet state with a femtosecond lifetime. The tripquintet state decays in 5 ps, yielding a tripseptet state with a 570 ps lifetime. The electronic absorption of the Mn2+ complex more closely resembles those of diamagnetic metallobacteriochlorins, but the longest decay lifetime is only ca. 8 ps. The intense photoacoustic waves generated with near-infrared excitation suggest the use of these complexes in photoacoustic tomography.

7 tesla FMRI reveals systematic functional organization for binocular disparity in dorsal visual cortex.

The binocular disparity between the views of the world registered by the left and right eyes provides a powerful signal about the depth structure of the environment. Despite increasing knowledge of the cortical areas that process disparity from animal models, comparatively little is known about the local architecture of stereoscopic processing in the human brain. Here, we take advantage of the high spatial specificity and image contrast offered by 7 tesla fMRI to test for systematic organization of disparity representations in the human brain. Participants viewed random dot stereogram stimuli depicting different depth positions while we recorded fMRI responses from dorsomedial visual cortex. We repeated measurements across three separate imaging sessions. Using a series of computational modeling approaches, we report three main advances in understanding disparity organization in the human brain. First, we show that disparity preferences are clustered and that this organization persists across imaging sessions, particularly in area V3A. Second, we observe differences between the local distribution of voxel responses in early and dorsomedial visual areas, suggesting different cortical organization. Third, using modeling of voxel responses, we show that higher dorsal areas (V3A, V3B/KO) have properties that are characteristic of human depth judgments: a simple model that uses tuning parameters estimated from fMRI data captures known variations in human psychophysical performance. Together, these findings indicate that human dorsal visual cortex contains selective cortical structures for disparity that may support the neural computations that underlie depth perception.

Comparison of topical dorzolamide and ketorolac treatment for cystoid macular edema in retinitis pigmentosa and Usher's syndrome.

PURPOSE: To investigate the topical effect of dorzolamide versus ketorolac on retinitis pigmentosa (RP) and Usher's syndrome (US) macular edema. METHODS: Prospective, randomized and interventional study. A total of 28 eyes of 18 patients were included. Five eyes had US, 23 had RP. Fifteen eyes were allocated to ketorolac tromethamine 0.5% (4 drops daily regimen) and 13 eyes to dorzolamide hydrochloride 2% (3 drops daily regimen) treatment groups. Snellen's best-corrected visual acuity (BCVA), foveal thickness (FT) and foveal zone thickness (FZT) measured by Stratus® optical coherence tomography (OCT) were evaluated at baseline, 1, 3, 6 and 12 months after treatment. RESULTS: Patients assigned to ketorolac had a baseline BCVA of 0.37 ± 0.17 logMAR which improved at the end of 1 year to 0.28 ± 0.16 (p = 0.02). Three eyes (20%) of 2 patients improved by 7 letters or more. Mean FT and FZT did not change significantly during the study follow-up. After 1 year of treatment, 4 eyes (27%) of 3 patients showed an improvement of at least 16% of FT and 11% of FZT. Patients assigned to dorzolamide had a baseline BCVA of 0.48 ± 0.34 logMAR which improved in the first 6 months (0.40 ± 0.30; p = 0.01), with a decrease at 1 year (0.42 ± 0.27; p = 0.20). Seven eyes (54%) of 5 patients had an improvement of 7 letters or more. Mean FT and FZT did not change significantly either. After 1 year of treatment, 3 eyes (23%) of 2 patients showed an improvement of at least 16% on FT and 11% on FZT. CONCLUSIONS: RESULTS suggest that dorzolamide and ketorolac might improve visual acuity and therefore be of interest in selected cases. No relationship between retinal thickness fluctuation and visual acuity was found. Sample size was a limitation to the study.

Towards obtaining spatiotemporally precise responses to continuous sensory stimuli in humans: a general linear modeling approach to EEG.

Noninvasive investigation of human sensory processing with high temporal resolution typically involves repeatedly presenting discrete stimuli and extracting an average event-related response from scalp recorded neuroelectric or neuromagnetic signals. While this approach is and has been extremely useful, it suffers from two drawbacks: a lack of naturalness in terms of the stimulus and a lack of precision in terms of the cortical response generators. Here we show that a linear modeling approach that exploits functional specialization in sensory systems can be used to rapidly obtain spatiotemporally precise responses to complex sensory stimuli using electroencephalography (EEG). We demonstrate the method by example through the controlled modulation of the contrast and coherent motion of visual stimuli. Regressing the data against these modulation signals produces spatially focal, highly temporally resolved response measures that are suggestive of specific activation of visual areas V1 and V6, respectively, based on their onset latency, their topographic distribution and the estimated location of their sources. We discuss our approach by comparing it with fMRI/MRI informed source analysis methods and, in doing so, we provide novel information on the timing of coherent motion processing in human V6. Generalizing such an approach has the potential to facilitate the rapid, inexpensive spatiotemporal localization of higher perceptual functions in behaving humans.

The impact of methylene blue in colorectal cancer: Systematic review and meta-analysis study.

PURPOSE: In patients with colorectal cancer (CRC), the most important factor to decide the need of adjuvant chemotherapy is the histological lymph node (LN) evaluation. Our work aimed to give a broad view over the use of methylene blue and its consequences in the number of lymph node harvest. METHODS: PUBMED, WEB OF SCIENCE and EMBASE databases were consulted, retrieving clinical trials, which mentioned the used of intra-arterial methylene blue in patients with colorectal cancer. RESULTS: Eighteen clinical trials analyzing the use of intra-arterial methylene blue in specimens of colorectal cancer were selected. The articles show a statistical difference between the use of methylene blue and the classical dissection in both variable at study. The results of the statistical analysis of the lymph node harvest variable demonstrate a significant statistical difference between the group that received methylene blue injection and the group that underwent conventional dissection. There is a significant statistical difference between the experimental and control groups for the ideal lymph node harvest (lymph node harvest count greater than 12). CONCLUSION: The use of intra-arterial methylene blue revealed a high potential for the quantification of lymph nodes, considering the increase of lymph node harvest and the higher percentage of cases with more than 12 lymph nodes count, albeit the high heterogeneity between the studies in terms of reported results. Future investigations with controlled double blinded studies obtaining better categorized results should be conducted in order to better evaluate this technique and compare it to the current paradigm.

Effective acid mine drainage remediation in fixed bed column using porous red mud/fly ash-containing geopolymer spheres.

Acid mine drainage (AMD) poses a significant threat to water quality worldwide, being amongst the most problematic environmental concerns of the millennium. This work reports for the first time the remediation of real AMD, from a Portuguese abandoned mine, in fixed bed column using porous red mud/fly ash-based geopolymeric spheres. Porous waste-based spheres (2.6 ± 0.2 mm) were obtained by a suspension-solidification method through the addition of optimum foaming agent dosage. The sorbent capacity in removing cations from AMD was evaluated by targeting selected hazardous elements: Zn, Cu, Co, Pb and Ni, based on their occurrence in the effluent and potential hazard. The spheres exhibited a dual mechanism of action, simultaneously neutralizing the acidic sample while removing cations through adsorption achieving removal efficiencies between 51 % and 80 %. Other elements present in high levels, such as iron were efficiently removed (>96 %). The role of precipitation, due to the pH neutralization, and adsorption was determined. The sorbent regeneration and reusability were evaluated for up to five cycles. Moreover, the effectiveness of waste-based geopolymers treating distinct AMD waters due to seasonal variations was also evaluated, further demonstrating the effectiveness of the proposed strategy to address environmental concerns stemming from mining activities.

Influence of root shape on canal complexity at the mandibular molar apical surgical resection level: A micro-CT study.

OBJECTIVES: This study aimed to investigate the relationship between the aspect ratios of mandibular molar roots at the apical 3-mm level and their root canal complexity. DESIGN: This study used micro-CT imaging to analyze 163 two-rooted mandibular molars. The aspect ratios of the roots at the apical 3-mm level were categorized as "< 2.75" or "≥ 2.75" (mesial) and "< 1.75" or "≥ 1.75" (distal). A two-dimensional (2D) analysis focused on four apical axial cross-section levels to determine the presence of main and accessory canals and isthmus. Additionally, a three-dimensional (3D) assessment of the apical 4-mm of both roots examined main and accessory canals, apical foramina, apical deltas, and middle mesial canals. RESULTS: Mesial roots with aspect ratios ≥ 2.75 showed a higher number of main canals at all levels compared to those with aspect ratios < 2.75 at the 3-mm level. Additionally, the ≥ 2.75 group exhibited more accessory canals and a higher average number of accessory canals. The 3D assessment confirmed significantly more accessory canals and apical foramina in the ≥ 2.75 group. The prevalence of roots with apical deltas was nearly double in the ≥ 2.75 group, and middle mesial canals were exclusively found in this group. In the distal root, the ≥ 1.75 group showed a significantly higher number of main canals at all axial levels. No significant differences were observed between groups in terms of accessory canals, apical foramina, or deltas. CONCLUSIONS: A higher root aspect ratio is related to higher anatomical complexity.

From rust to robust disinfectants: How do iron oxides and inorganic oxidants synergize with UVA light towards bacterial inactivation?

Pathogens in drinking water remain a challenge for human health, photo-Fenton process is a promising technique for pathogen inactivation, herein, two common iron oxides, hematite and magnetite mediate persulfate (peroxymonosulfate-PMS - and peroxydisulfate-PDS) involved photo-Fenton-like processes were constructed for E. coli inactivation, and the inactivation performance was investigated and compared with the photo-Fenton process under a low intensity UVA irradiation. Results indicated that with a low dose of iron oxides (1 mg/L) and inorganic peroxides (10 mg/L), PMS-involved photo-Fenton-like process is the best substitute for the photo-Fenton one over pH range of 5-8. In addition, humic acid (HA, one of the important components of natural organic matter) incorporated iron oxide-mediated photo-Fenton-like processes for bacteria inactivation was also studied, and facilitating effect was found in UVA/hematite/PMS and UVA/magnetite/PDS systems. Reactive oxygen species (ROS) exploration experiments revealed that ·OH was the predominant radical in H2O2- and PDS-containing systems, whereas 1O2 was one of the principal reactive species in the PMS systems. In addition to the semiconductor photocatalysis of iron oxides and UVA-activated oxidants, iron-complexes (iron-oxidant complexes and iron-bacteria complexes) mediated ligand-to-metal charge transfer (LMCT) processes also made contribution to bacterial inactivation. Overall, this study demonstrates that it is feasible to replace H2O2 with PMS in a photo-Fenton-like process for water disinfection using a low dose of reagents, mediated by cheap catalysts, such as hematite and magnetite, it is also hoped to provide some insights to practical water treatment.

Small concentrations, big results: µM addition of photoactive iron oxides with PMS, PDS, or H2O2, leads to enhanced removal of viruses at near-neutral pH.

The photo-Fenton process is effective for pathogen removal, and its low-cost versions can be applied in resource-poor contexts. Herein, a photo-Fenton-like system was proposed using low concentrations of iron oxides (hematite and magnetite) and persulfates (peroxymonosulfate - PMS, and peroxydisulfate - PDS), which exhibited excellent inactivation performance towards MS2 bacteriophages. In the presence of bacteria, MS2 inactivation was inhibited in H2O2 and PDS systems but promoted in PMS-involved systems. The inactivation efficacy of all the proposed systems for mixed bacteria and viruses was greater than that of the sole bacteria, showing potential practical applications. The inactivation performance of humic acid-incorporated iron oxides mediating photo-Fenton-like processes was also studied; except for the PMS-involved system, the inactivation efficacy of the H2O2- and PDS-involved systems was inhibited, but the PDS-involved system was still acceptable (< 2 h). Reactive species exploration experiments indicated that ·OH was the main radical in the H2O2 and PDS systems, whereas 1O2 played a key role in the PMS-involved system. In summary, hematite- and magnetite-mediated persulfate-assisted photo-Fenton-like systems at low concentrations can be used as alternatives to the photo-Fenton process for virus inactivation in sunny areas, providing more possibilities for point-of-use drinking water treatment in developing countries.

Prevalence of undiagnosed rheumatic and musculoskeletal diseases and its association with health-related quality of life and with physical function.

AIM: To estimate the disease specific prevalence of undiagnosed rheumatic and musculoskeletal diseases (RMDs) in Portugal and determine if people with undiagnosed RMDs have worse quality of life, physical function and higher health resources consumption, than people without RMDs. METHODS: A subgroup analysis of EpiReumaPt was made that included all participants≥18 years evaluated by a rheumatologist. Participants were stratified into three groups: undiagnosed RMDs; previously diagnosed RMDs; non-RMDs. A descriptive analysis of the three groups was performed. To estimate the prevalence of undiagnosed RMDs, weighted proportion were computed considering the sample design. The three groups were compared (Undiagnosed RMDs vs non-RMDs; Previously diagnosed RMDs vs non-RMDs) for health related quality of life (HRQoL) (EQ5D), physical function (HAQ), mental health (HADS) and health resources consumption. The effect of being undiagnosed for these outcomes was assessed in multivariable models adjusted for age, gender, geographical region and years of education (reference: non-RMD). RESULTS: A total of 3877 participants were included. The prevalence of undiagnosed RMDs was 29%. Compared to participants without RMDs, undiagnosed participants had lower HRQoL (EQ-5D: ß (95% CI)=-0.07 (-0.103,-0.043)) and physical function (HAQ: ß (95% CI)=0.10 (0.05, 0.15)), more anxiety (OR (95% CI)=2.3 (1.4, 3.7)) and depression symptoms (OR (95% CI)=1.4 (0.8, 2.4)). Undiagnosed RMDs participants were more likely to visit an orthopedist (OR (95% CI)=2.0 (1.1, 3.5)) and had a higher number of orthopedic appointments (IRR (95% CI)=2.5 (1.3, 4.9)) than participants without RMDs. CONCLUSION: Patients with undiagnosed RMDs are frequent in Portugal, have worse HRQoL, physical function and mental health than people without RMDs. Undiagnosed patients are nonetheless consumers of health resources and tend to seek help from specialties other than rheumatology. Increasing the awareness of RMDs might promote their early identification and treatment leading to both personal and societal benefits.