Comparison of different measuring methods in the assessment of the ISNT rule and its variants in a normal population: A cross-sectional study.

PURPOSE: The aim of this study was to compare five different neuroretinal rim (NRR) measurement methods, based on quadrants and NRR widths, in the assessment of the ISNT (inferior (I) > superior (S) > nasal (N) > temporal (T)) rule, and its variants IST (inferior (I) > superior (S) > temporal (S)) rule, IS (inferior (I) > superior (S)) rule and T (temporal is the thinnest) rule in a normal population. Factors influencing compliance with this rule and its variants were also evaluated. METHODS: Stereoscopic fundus images were analysed through a dichoptic viewing system. Two graders labelled the optic disc and cup, as well as the fovea. Custom-made software automatically determined the limits of the optic disc and cup and examined the ISNT rule and its variants using several NRR measurement methods. RESULTS: Sixty-nine subjects with normal eyes were enrolled. For the various NRR measuring methods, the percentage of eyes following the rules, that is, validity ranges were 0.0%-15.9% for the ISNT rule, 31.9%-59.4% for the IST rule, 46.4%-59.4% for the IS rule and 50.7%-100.0% for the T rule. Significant intra-measurement agreement ranges were IST (κ = 0.50-0.85), IS (κ = 0.68-1.00) and T (κ = 0.24-0.77). Only the IST and IS rules achieved significant inter-measurement agreement (κ = 0.47-1.00). After multivariate and receiver operating characteristic (ROC) curve analyses, the vertical cup position cupy (area under the ROC curve (AUROC) = 0.60-0.96; cut-off = |0.005|) was the most important predictor for virtually all NRR measurement agreements for the ISNT, IST and IS rules. The horizontal cup position (AUROC = 0.50-0.92; cut-off = -0.028 to 0.05) was the most important predictive factor for the majority of the NRR measurement agreements for the T rule. CONCLUSIONS: Only the IST and IS rules are valid for the same normal subjects. The most important factor affecting the validity of the ISNT rule and its variants was the anatomical cup position. NRR measurement agreements based on NRR quadrants exhibited larger validity and better agreement. The IST and IS rules can be combined with the alternative SIT (superior (S) > inferior (I) > temporal (T)) and SI (superior (S) > inferior (I)) rules to detect almost all normal subjects.

Rare Case of Rickettsiosis Caused by Rickettsia monacensis, Portugal, 2021.

We report a case of rickettsiosis caused by Rickettsia monacensis in an immunocompetent 67-year-old man in Portugal who had eschar, erythematous rash, and an attached Ixodes ricinus tick. Seroconversion and eschar biopsy led to confirmed diagnosis by PCR. Physicians should be aware of this rare rickettsiosis, especially in geographic regions with the vector.

The conscious experience of color constancy and neural responses to subliminal deviations - A behavioral and EEG/ERP oddball study.

INTRODUCTION: Color constancy, a property of conscious color experience, maintains object color appearance across illuminant changes. We investigated the neural correlates of subliminal vs. conscious stimulus deviations of color constancy manipulations. METHODS: Behavioral and Oddball EEG/ERP experiments were conducted (n = 20). Psychophysical illuminant variation discrimination thresholds were first estimated, to establish individual perceptual awareness ranges, allowing for simulation of natural daylight spectral and spatial variations on colored surfaces, at different ambiguity levels. RESULTS: Behavioral results validated illuminant choice. ERPs showed a significant modulation of posterior P1 component specifically for the subliminal global uniform deviation condition, respecting color constancy. Neural correlates of conscious percepts were identified at posterior N2-P3 latencies, parietal (P3b) and frontal regions. CONCLUSIONS: We identified an early subliminal correlate of low-level illuminant change, which reflects automatic unconscious detection of global color constancy deviations. Its suppression under conscious perception is probably due to top-down suppression according to prediction error models.

Sequence variation at KLK and WFDC clusters and its association to semen hyperviscosity and other male infertility phenotypes.

STUDY QUESTION: Are kallikreins (KLKs), the whey-acidic-protein four-disulfide core domain (WFDCs) and their neighbors, semenogelins (SEMGs), known to play a role in the cascade of semen coagulation and liquefaction, associated with male infertility? SUMMARY ANSWER: Several KLK and SEMG variants are overrepresented among hyperviscosity, asthenozoospermia and oligozoospermia, supporting an effect of abnormal semen liquefaction on the loss of semen quality and in lowering male reproductive fitness. WHAT IS KNOWN ALREADY: In the cascade of semen coagulation and liquefaction the spermatozoa coated by EPPIN (a protease inhibitor of the WFDC family) are entrapped in a cross-linked matrix established by SEMGs. After ejaculation, the SEMG matrix is hydrolyzed by KLK3/2 in a fine-tuned process regulated by other KLKs that allows the spermatozoa to increase motility. STUDY DESIGN SIZE, DURATION: This study includes a cohort of 238 infertility-related cases and 91 controls with normal spermiogram analysis. The remaining 126 controls are healthy males with unknown semen parameters. Sample collection was carried out from June 2011 to January 2015 and variant screening from May 2013 to August 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: We performed a screening by massive parallel sequencing in a pooled sample (N = 222) covering approximately 93 kb of KLK (19q13.3-13.4) and WFDC (20q13) clusters, followed by the genotyping of most promising variants in the full cohort. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 160 common and 296 low-frequency variants passed the quality control filtering. Statistical tests disclosed an association with hyperviscosity of a KLK7 regulatory variant (P = 0.0035), and unveiled a higher burden of deleterious mutations in KLKs than expected by chance (P = 0.0106). KLK variants found to be overrepresented in cases included two substitutions likely affecting the substrate binding pocket, two nonsynonymous variants overlapping in the three-dimensional structure and two mutations mapping in consecutive N-terminal residues. Other variants identified in SEMGs possibly contributing to hyperviscosity and asthenozoospermia consisted of three replacements predicted to modify targets of proteolysis (P = 0.0442 for SEMG1 p.Gly400Asp) and a copy number variation associated with a reduced risk of oligozoospermia (P = 0.0293). LARGE SCALE DATA: Not applicable. LIMITATIONS REASONS FOR CAUTION: The sampling of a few hundred individuals has limited power to detected associations with low-frequency variants and only a small set of variants was prioritized for genotyping. Other susceptibility variants for male infertility may remain unidentified. WIDER IMPLICATIONS OF THE FINDINGS: We provide important evidence for an effect of KLKs and SEMGs variability on semen quality and for modifications in the process of semen liquefaction as a possible cause for male infertility. STUDY FUNDING/COMPETING INTERESTS: This work was funded through the Portuguese Foundation for Science and Technology (FCT) and FEDER through COMPETE and QREN. The authors have no conflict of interest to declare.

Assessing the effects of dynamic luminance contrast noise masking on a color discrimination task.

The aim of this work was to assess the influence of dynamic luminance contrast noise masking (LCNM) on color discrimination for color normal and anomalous trichromats. The stimulus was a colored target on a background presented on a calibrated CRT display. In the static LCNM condition, the background and target consisted of packed circles with variable size and static random luminance. In the dynamic LCNM condition, a 10 Hz square luminance signal was added to each circle. The phase of this signal was randomized across circles. Discrimination thresholds were estimated along 20 hue directions concurrent at the color of the background. Six observers with normal color vision, six deuteranomalous observers, and three protanomalous observers performed the test in both conditions. With dynamic LCNM, thresholds were significantly lower for anomalous observers but not for normal observers, suggesting a facilitation effect of the masking for anomalous trichromats.

Epidemiological and Clinical Aspects of Cutaneous and Mucosal Leishmaniases in Portugal: Retrospective Analysis of Cases Diagnosed in Public Hospitals and Reported in the Literature between 2010 and 2020.

Leishmania infantum, a zoonotic vector-born parasite, is endemic in the Mediterranean region, presenting mostly as visceral (VL), but also as cutaneous (CL) and mucosal leishmaniasis (ML). This study aimed to describe the epidemiological and clinical aspects of the CL and ML cases diagnosed in mainland Portugal between 2010 and 2020. Collaboration was requested from every hospital of the Portuguese National Health System. Cases were screened through a search of diagnostic discharge codes or positive laboratory results for Leishmania infection. Simultaneously, a comprehensive literature search was performed. Descriptive statistics and hypothesis testing were performed using IBM® SPSS® Statistics. A total of 43 CL and 7 ML cases were identified, with a predominance of autochthonous cases (86%). In CL, immunosuppressed individuals constituted a significant proportion of patients (48%), and in this group, disseminated CL (22%) and simultaneous VL (54%) were common. In autochthonous cases, lesions, mostly papules/nodules (62%), were frequently observed on the head (48%). The approach to treatment was very heterogeneous. ML cases were all autochthonous, were diagnosed primarily in older immunosuppressed individuals, and were generally treated with liposomal amphotericin B. The findings suggest a need for enhanced surveillance and reporting, clinical awareness, and diagnostic capacity of these forms of leishmaniasis to mitigate underdiagnosis and improve patient outcomes. A holistic One Health approach is advocated to address the multifaceted challenges posed by leishmaniases in Portugal and beyond.

Reasons for admission to a general medical hospital for patients taking clozapine.

Background: Clozapine is associated with a diverse range of side effects. In addition, patients prescribed clozapine commonly suffer with medical comorbidities. Objectives: This study aimed to characterise patients prescribed clozapine who required medical admission, understand reasons for admission, identify areas for interventions to prevent future admission and describe clozapine management during the inpatient stay. Design: We conducted a retrospective analysis of patients prescribed clozapine who were admitted to a general medical hospital in a 12-month period. Method: Data were collected using electronic drug charts and notes. Results: In total, 114 clozapine patients were hospitalised. Twenty-eight patients (25%) were admitted because of infection, 12 (11%) were elective admissions and 12 (11%) had gastrointestinal problems. Most patients admitted were Black (54%) and half were female. Few changes were made to clozapine dosing on admission or during the inpatient stay. Most patients had been taking clozapine for many years at the point of admission, the majority were able to continue taking it for the duration of their medical treatment and were discharged on the same dose they were taking prior to admission. Clozapine plasma concentrations were not consistently measured with only 18 (16%) patients having one or more plasma concentrations determined during their admission. The median clozapine plasma concentration on admission was 0.48 mg/L (nor-clozapine 0.21 mg/L), with a range of 0.09 to 3.9 mg/L. Three patients were admitted to the intensive care unit during their admission; all were discharged on clozapine. Four patients died; one from lung adenocarcinoma, one bowel obstruction, one cardiac arrest and one chest sepsis. In total, 27 patients (23%) had their clozapine stopped on admission, 6 (22% of this group) unintentionally. Conclusions: Our study found that the most common reason for admission for patients taking clozapine was infection. Plasma concentrations were not measured routinely despite clozapine having a narrow therapeutic index and enhanced potential for toxicity in the medically unwell patient.

Effectiveness of a video-based education on fertility awareness: a randomized controlled trial with partnered women.

Fertility awareness (FA) among young people is low. Fertility awareness interventions have been found to contribute to increase FA in the short-term. The long-term effectiveness of FA interventions on childless and presumed fertile people, committed in a heterosexual relationship and wishing to have children in the near future is not known. In a double-blind parallel randomized controlled trial conducted between 2016 and 2018, 652 childless partnered women were randomized to either watch a 5-min video about fertility (IG: 'Intervention Group') or to not receive any intervention (CG: 'Control Group'). Participants filled out an online questionnaire at the start of the study (and in the IG group immediately before intervention). They then completed the questionnaire after 1 month, 6 months and 1 year. The questionnaire assessed FA and intentions to adopt fertility-protective behaviours. In the IG, FA levels were found to increase at 1 month post-intervention. However, significant interaction effects between group and time were only found for four out of the seven FA variables at the 6-month and 1-year follow-up. No effects were found for: (i) intentions to adopt fertility-protective behaviours; or (ii) desired timing of pregnancy. These results suggest that the fertility video intervention seems to partially increase FA in the long term. Future studies should investigate the effectiveness of different intervention formats with a focus on overcoming high attrition rates.

Clinical and Epidemiological Features of Hospitalized and Ambulatory Patients with Human Monkeypox Infection: A Retrospective Observational Study in Portugal.

Monkeypox, a neglected and re-emergent zoonotic disease caused by monkeypox virus (MPXV) infection, has been endemic in Central and Western Africa for decades. More recently, an outbreak has spread to a global level, occurring in sites with no previous reported cases and being clustered among men who have sex with men, suggesting new modes of transmission. There is an urgent need for research for a better understanding of the genomic evolution and changing epidemiology of the Orthopoxvirus group. Our work aimed to characterize the clinical and epidemiological features of a cohort of patients with MPXV infection in a Portuguese hospital, admitted between 5 May and 26 July 2022. In this retrospective observational study, aggregate data of a case series on the presentation, clinical course, and outcomes of confirmed MPXV infections are reported. The study included 40 men and 1 woman, with a mean age of 37.2 years old; 92.7% identified as men who have sex with men, 90.2% had unprotected sex or sex with multiple or anonymous partners in the previous month, and 39.0% reported to have had sex with an MPXV-confirmed case; 59.5% had previously known human immunodeficiency virus (HIV) infection, all of whom were under antiretroviral therapy, and no patients had acquired immunodeficiency syndrome (AIDS) criteria. About a quarter of patients were observed only a week after symptom onset. All patients had skin or mucosal lesions and the anogenital region was the most frequent lesion site. There were no statistically significant clinical differences between HIV-positive and negative individuals. Four patients were admitted to the inpatient clinic, two of whom had proctitis with difficult-to-manage anal pain. There were no reported deaths. Our findings suggest the sexual route as a relevant mode of transmission of MPXV and confirm the mostly benign presentation of this disease.

Direct and indirect effects of perceived social support on women's infertility-related stress.

BACKGROUND: Social support can be a critical component of how a woman adjusts to infertility, yet few studies have investigated its impact on infertility-related coping and stress. We examined relationships between social support contexts and infertility stress domains, and tested if they were mediated by infertility-related coping strategies in a sample of infertile women. METHODS: The Multidimensional Scale of Perceived Social Support, the Copenhagen Multi-centre Psychosocial Infertility coping scales and the Fertility Problem Inventory were completed by 252 women seeking treatment. Structural equation modeling analysis was used to test the hypothesized multiple mediation model. RESULTS: The final model revealed negative effects from perceived partner support to relationship concern (ß = -0.47), sexual concern (ß = -0.20) and rejection of childfree lifestyle through meaning-based coping (ß = -0.04). Perceived friend support had a negative effect on social concern through active-confronting coping (ß = -0.04). Finally, besides a direct negative association with social concern (ß = -0.30), perceived family support was indirectly and negatively related with all infertility stress domains (ß from -0.04 to -0.13) through a positive effect of active-avoidance coping. The model explained between 12 and 66% of the variance of outcomes. CONCLUSIONS: Despite being limited by a convenience sampling and cross-sectional design, results highlight the importance of social support contexts in helping women deal with infertility treatment. Health professionals should explore the quality of social networks and encourage seeking positive support from family and partners. Findings suggest it might prove useful for counselors to use coping skills training interventions, by retraining active-avoidance coping into meaning-based and active-confronting strategies.

Dual use of Diff-Quik-like stains for the simultaneous evaluation of human sperm morphology and chromatin status.

BACKGROUND: Sperm chromatin status and nuclear DNA damage can be detected using well-established assays. However, most techniques are time-consuming and/or involve elaborate protocols and equipment. We have recently developed a simple and fast method to monitor sperm chromatin status in field conditions using the Diff-Quik assay which is employed in fertility clinics to assess sperm morphology with standard bright field microscopy. In the present study, we demonstrate that any Diff-Quik-like stain can easily, reproducibly and routinely monitor human sperm chromatin status as well. METHODS: Different Diff-Quik-like stains were used to assess sperm morphology and the presence of abnormal dark nuclear staining in human sperm from four ART centres. The TUNEL assay was performed in the same samples, and fertility outcomes were assessed. RESULTS: A significant correlation was found between TUNEL-positive sperm and dark sperm nuclei. Moreover, associations were also found between the percentage of dark sperm nuclei and seminal parameters, embryo development rate, embryo quality and clinical pregnancy, as well as with cryptorchidism, and there was a tendency towards an association with age. A value of 32% abnormal staining is suggested as a predictive threshold for embryo development and pregnancy. CONCLUSIONS: Our results show that any Diff-Quik-like stain, already implemented in most laboratories to assess sperm morphology, can be adapted as an indicator for chromatin status in human sperm.

The colors of natural scenes benefit dichromats.

Dichromacy impairs color vision and impoverishes the discrimination of surface colors in natural scenes. Computational estimates based on hyperspectral imaging data from natural scenes suggest that dichromats can discriminate only about 10% of the colors discriminated by normal trichromats. These estimates, however, assume that the colors are equally frequent. Yet, pairs of colors confused by dichromats may be rare and thus have small impact on overall perceived chromatic diversity. This study estimated, empirically, how much dichromats are disadvantaged in discriminating surface colors drawn from natural scenes. The stimulus for the experiment was a scene made of real three-dimensional objects painted with matte white paint and illuminated by a spectrally tunable light source. In each trial the observers saw the scene illuminated by two spectra in two successive time intervals and had to indicate whether the colors perceived in the objects in the two intervals were the same or different. The spectra were drawn randomly from hyperspectral data of natural scenes and therefore represented natural spectral statistics. Four normal trichromats and four dichromats carried out the experiment. It was found that the number of pairs that could be discriminated by dichromats was almost 70% of those discriminated by normal trichromats, a proportion much higher than anticipated from estimates of discernible colors. Moreover, data from model simulations show that normal trichromats and dichromats use lightness differences for discrimination in about 40% and 50% of the discriminable pairs, respectively. Together these results suggest that the color distributions of natural scenes benefit the color vision of dichromats.

Characterization of microbiota in male infertility cases uncovers differences in seminal hyperviscosity and oligoasthenoteratozoospermia possibly correlated with increased prevalence of infectious bacteria.

PROBLEM: Sexually transmitted diseases and other infections of male genitourinary tract are thought to negatively impact reproductive health, affecting semen quality. Despite a possible link between bacteria and infertility, few studies attempted to characterize seminal microbiota in healthy and diseased subjects. METHODS OF THE STUDY: A high-throughput sequencing of 16S ribosomal RNA gene was performed in a cohort of infertility-related cases (N = 89) and controls (N = 29) using a pooled sample approach. RESULTS: A global characterization of microbiota was obtained at low cost, without compromising the identification of bacterial taxa. This strategy allowed us to detect changes in the microbiota of infertility-related phenotypes, such as an increment of Proteobacteria in seminal hyperviscosity, and to separate this later group from oligoasthenoteratozoospermia based in bacterial (family/genus) abundances. CONCLUSION: We provide data for a likely contribution of bacteria into seminal hyperviscosity and oligoasthenoteratozoospermia, partially correlated with an increment of Neisseria, Klebsiella, and Pseudomonas pathogens and a reduction in Lactobacillus probiotic agent.

Male psychological adaptation to unsuccessful medically assisted reproduction treatments: a systematic review.

BACKGROUND: Similarly to women, men suffer from engaging in fertility treatments, both physically and psychologically. Although there is a vast body of evidence on the emotional adjustment of women to infertility, there are no systematic reviews focusing on men's psychological adaptation to infertility and related treatments. OBJECTIVE AND RATIONALE: The main research questions addressed in this review were 'Does male psychological adaptation to unsuccessful medically assisted reproduction (MAR) treatment vary over time?' and 'Which psychosocial variables act as protective or risk factors for psychological maladaptation?' SEARCH METHODS: A literature search was conducted from inception to September 2015 on five databases using combinations of MeSH terms and keywords. Eligible studies had to present quantitative prospective designs and samples including men who did not achieve pregnancy or parenthood at follow-up. A narrative synthesis approach was used to conduct the review. OUTCOMES: Twelve studies from three continents were eligible from 2534 records identified in the search. The results revealed that psychological symptoms of maladjustment significantly increased in men 1 year after the first fertility evaluation. No significant differences were found two or more years after the initial consultation. Evidence was found for anxiety, depression, active-avoidance coping, catastrophizing, difficulties in partner communication and the use of avoidance or religious coping from the wife as risk factors for psychological maladjustment. Protective factors were related to the use of coping strategies that involve seeking information and attribution of a positive meaning to infertility, having the support of others and of one's spouse, and engaging in open communication about the infertility problem. WIDER IMPLICATIONS: Our findings recommend an active involvement of men during the treatment process by health care professionals, and the inclusion of coping skills training and couple communication enhancement interventions in counselling. Further prospective large studies with high-quality design and power are warranted.

Robust single trial identification of conscious percepts triggered by sensory events of variable saliency.

The neural correlates of visual awareness are elusive because of its fleeting nature. Here we have addressed this issue by using single trial statistical "brain reading" of neurophysiological event related (ERP) signatures of conscious perception of visual attributes with different levels of saliency. Behavioral reports were taken at every trial in 4 experiments addressing conscious access to color, luminance, and local phase offset cues. We found that single trial neurophysiological signatures of target presence can be observed around 300 ms at central parietal sites. Such signatures are significantly related with conscious perception, and their probability is related to sensory saliency levels. These findings identify a general neural correlate of conscious perception at the single trial level, since conscious perception can be decoded as such independently of stimulus salience and fluctuations of threshold levels. This approach can be generalized to successfully detect target presence in other individuals.

Protective activity of hydroxytyrosol metabolites on erythrocyte oxidative-induced hemolysis.

The capacity of important hydroxytyrosol metabolites (homovanillyl alcohol, hydroxytyrosol acetate, homovanillyl alcohol acetate, hydroxytyrosol 3' and 4'-O-glucuronides, and homovanillyl alcohol 4'-O-glucuronide) to protect red blood cells (RBCs) from oxidative injury induced by the radical initiator 2,2'-azo-bis(2-amidinopropane) dihydrochloride (AAPH) or by the natural radical initiator H2O2 was evaluated. In the presence of AAPH, all compounds showed to protect RBCs from hemolysis in a dose-dependent manner, exccept for the homovanillyl alcohol glucuronide, with the order of activity being at 20 µM hydroxytyrosol > hydroxytyrosol glucuronides = hydroxytyrosol acetate = homovanillyl alcohol = homovanillyl acetate > homovanillyl alcohol glucuronide. At 10 µM, hydroxytyrosol, hydroxytyrosol acetate, and hydroxytyrosol glucuronides still protected hemoglobine from oxidation and from morphological RBC changes. In the presence of H2O2, hydroxytyrosol showed to significantly protect RBCs from oxidative hemolysis in a dose-dependent manner, but the hydroxytyrosol glucuronides showed only a limited protection that was independent of the concentration used.

Effect of scene dimensionality on colour constancy with real three-dimensional scenes and objects.

The effect of scene dimensionality on colour constancy was tested with real scenes and objects. Observers viewed a three-dimensional (3-D) scene, or its two-dimensional (2-D) planar projection, through a large beam-splitter that projected the virtual image of a real test object (a cube or its 2-D projection) so that it appeared part of the scene. Test object and scene could be illuminated independently with high chromatic precision. In each trial, the illuminance of the scene changed abruptly from 25000 K to 6700 K and the illuminant of the test object changed either consistently or inconsistently with it by a variable quantifiable amount. Observers had to decide whether the test object underwent a change in its materials. The extent of constancy obtained in the experiment was not influenced by scene dimensionality and varied significantly with the colour of the test object. These results suggest that color constancy in the conditions tested here may be determined by local spectral quantities.

Perception of illuminant colour changes across real scenes.

In a complex natural scene the colour and intensity of the illumination may vary considerably across the scene. Changes in intensity can easily be detected but the same does not seem to be true of colour changes. We investigated the extent to which chromatic changes of the illuminant are detected and the relation of detection performance with colour constancy and scene interpretation. The stimuli were complex real 3-D scenes rendered with spatial colour gradients of which the extremes had correlated colour temperatures within the range 25000 K-3300 K. Observers' sensitivity to these spatial changes of the illuminant was found to be low and critically dependent on scene composition. Also, even in extreme conditions where colour constancy is known to fail, changes in the color of the illuminant across the scenes could not be perceived. These results suggest that insensitivity to spatial changes of the colour of the illuminant is a strong phenomenon and that it holds regardless of colour constancy.

Effect of scene complexity on colour constancy with real three-dimensional scenes and objects.

The effect of scene complexity on colour constancy was tested with a novel technique in which a virtual image of a real 3-D test object was projected into a real 3-D scene. Observers made discriminations between illuminant and material changes in simple and complex scenes. The extent of colour constancy achieved varied little with either scene structure or test-object colour, suggesting a dominant role of local cues in determining surface-colour judgments.