Association between lung function and dyspnoea and its variation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Dyspnoea is a common symptom of respiratory disease. However, data on its prevalence in general populations and its association with lung function are limited and are mainly from high-income countries. The aims of this study were to estimate the prevalence of dyspnoea across several world regions, and to investigate the association of dyspnoea with lung function. METHODS: Dyspnoea was assessed, and lung function measured in 25,806 adult participants of the multinational Burden of Obstructive Lung Disease study. Dyspnoea was defined as ≥2 on the modified Medical Research Council (mMRC) dyspnoea scale. The prevalence of dyspnoea was estimated for each of the study sites and compared across countries and world regions. Multivariable logistic regression was used to assess the association of dyspnoea with lung function in each site. Results were then pooled using random-effects meta-analysis. RESULTS: The prevalence of dyspnoea varied widely across sites without a clear geographical pattern. The mean prevalence of dyspnoea was 13.7 % (SD=8.2 %), ranging from 0 % in Mysore (India) to 28.8 % in Nampicuan-Talugtug (Philippines). Dyspnoea was strongly associated with both spirometry restriction (FVC

First evidence of late-acting self-incompatibility in the Aristolochiaceae.

Most Aristolochiaceae species studied so far are from temperate regions, bearing self-compatible protogynous trap flowers. Although self-incompatibility has been suggested for tropical species, the causes of self-sterility in this family remain unknown. To fill this gap, we studied the pollination of the tropical Aristolochia esperanzae, including the physical and physiological anti-selfing mechanisms. Floral visitors trapped inside flowers were collected to determine the pollinators. Protogyny was characterized by observing the temporal expression of sexual phases and stigmatic receptivity tests. The breeding system was investigated using hand-pollination treatments. Pollen tube growth was observed using epifluorescence to identify the self-incompatibility mechanism. Flies were the most frequent visitors found inside A. esperanzae trap flowers, with individuals from the family Ulidiidae being potential pollinators since they carried pollen. The characteristic flower odour and presence of larvae indicate that A. esperanzae deceives flies through oviposition-site mimicry. Although this species showed incomplete protogyny, stigmatic receptivity decreased during the male phase, avoiding self-pollination. Fruits developed only after cross- and open pollination, indicating that the population is non-autonomous, non-apomictic, and self-sterile. This occurred through a delay in the growth of geitonogamous pollen tubes to the ovary and lower ovule penetration, indicating a late-acting self-incompatibility mechanism. Our findings expand the number of families in which late-acting self-incompatibility has been reported, demonstrating that it is more widespread than previously thought, especially when considering less-studied tropical species among the basal angiosperms.

Investigating the longstanding mystery of stigma length differences between morphs of distylous plants.

Longer stigmas in short-styled morphs of distylous plants have been considered an adaptive characteristic that increases intermorph pollen deposition. The greater pollen deposition in short-styled stigmas may be a by-product of their longer length, making deposition effectiveness comparison between morphs unfeasible. Thus, investigating which morph has the relatively most efficient stigma (i.e., pollen deposition per unit length) can boost our understanding of the adaptive significance of longer stigmas. Here, we compared pollen deposition between morphs relative to stigma length and assessed whether short-styled stigmas are more, less, or equally effective in receiving pollen grains per unit length. We reviewed the literature to characterize the extent of sigma length differences between morphs using the two most speciose distylous genera as model systems: Palicourea and Psychotria (Rubiaceae). Then, we conducted a between-morph comparison of raw and relative pollen depositions in a Palicourea rigida population. We confirmed that short-styled stigmas were longer than long-styled stigmas in both Palicourea (194.31% longer) and Psychotria (52.59% longer) flowers. Furthermore, in the focal Pal. rigida, although short-styled stigmas were 268.04% longer and received 97.04% more pollen grains than long-styled stigmas, the relative pollen deposition had a reverse pattern, with short-styled stigmas being two-times less efficient in receiving pollen. Our results indicate that the longer length of the short-styled stigmas may have a compensatory effect, increasing the chances of pollen grains reaching the stigma and probably maintaining disassortative intermorph pollination in distylous plants.

Incomplete resupination during floral development leads to pollination failure in a slipper orchid.

In many families, plants undergo floral resupination by twisting through approximately 180° during floral development so that the flower is effectively positioned upside down. In most orchids, resupination results in the median petal (i.e., the labellum) becoming lowermost, which plays a crucial role in pollination by serving as a landing platform or as a trapping device, or both. Incomplete resupination is predicted to lead to reduced pollination, although tests of this assumption are still lacking. We investigated the effect of resupination using Phragmipedium vittatum, a rare lady's slipper orchid whose specialized labellum forms a trapping device. First, we surveyed the natural occurrence of incomplete resupination. Then we manipulated flowers into non- (≈0°), half- (≈90°), and fully resupinate (≈180°) positions to test the effect of orientation on pollen smear removal and deposition by pollinators (female hoverflies). We found that ca. 10% of flowers in the natural population were not fully resupinate, being either non- (upward, 0-60°) or half-resupinate (sideward, 60-120°). The change in orientation prevented the effectiveness of pollination by hoverflies since no pollen smear removal or deposition were found in flowers from non- and half-resupinate treatments. Although these flowers still attracted hoverflies, they were not trapped effectively. As this orchid is incapable of autonomous self-pollination, flowers that do not resupinate fail to set fruits. These results highlight the importance of correct floral orientation provided by resupination to ensure pollination in orchids and other resupinate flowers.

First Dark Matter Search with Nuclear Recoils from the XENONnT Experiment.

We report on the first search for nuclear recoils from dark matter in the form of weakly interacting massive particles (WIMPs) with the XENONnT experiment, which is based on a two-phase time projection chamber with a sensitive liquid xenon mass of 5.9 ton. During the (1.09±0.03) ton yr exposure used for this search, the intrinsic ^{85}Kr and ^{222}Rn concentrations in the liquid target are reduced to unprecedentedly low levels, giving an electronic recoil background rate of (15.8±1.3) events/ton yr keV in the region of interest. A blind analysis of nuclear recoil events with energies between 3.3 and 60.5 keV finds no significant excess. This leads to a minimum upper limit on the spin-independent WIMP-nucleon cross section of 2.58×10^{-47} cm^{2} for a WIMP mass of 28 GeV/c^{2} at 90% confidence level. Limits for spin-dependent interactions are also provided. Both the limit and the sensitivity for the full range of WIMP masses analyzed here improve on previous results obtained with the XENON1T experiment for the same exposure.

SUBUNGUAL HEMATOMA OVERLAPPING WITH SUBUNGUAL LOCATED FOCAL MELANOCYTIC HYPERPLASIA: DERMATOSURGICAL APPROACH AS OPTIMAL TREATMENT CHOICE.

Subungual lesions present a serious challenge for clinicians. The following factors can cause certain problems in interpreting the data: 1) Changes in lesion morphology over time: It may indicate the presence of a malignant lesion (increased pigmentation over time and lack of distal growth) but may actually be a benign lesion (chronic persistent subungual hematoma). 2) Patient's medical history can be misleading or difficult to verify, especially in problematic patients, or those with mental health problems or communication disorders (e.g., Asperger's syndrome, autism, schizoid psychosis, etc.). 3) The morphology of the lesion itself can be difficult to determine in the presence of simultaneously overlapping lesions. These patient dilemmas primarily concern the differentiation between subungual hematomas from subungual melanomas. The clinicians's concerns are based on the potential for metastasis and the risk of significantly worse prognosis for patients affected by nail biopsy. We present a 19-year-old patient with a subungual pigmented lesion with a clinical/dermatoscopic suspicion for subungual melanoma. Primary complaints for about 3-4 months. Intensified pigmentation and increase in size within two months led to a partial surgical resection of the nail plate and nail bed, followed by adaptation of the wound edges with single interrupted sutures. The histopathological finding was indicative of a subungual hematoma located above a focal melanocytic hyperplasia of the nail bed, clear resection lines. After a literature review, we believe that this is the first case of a patient with simultaneously present subungual benign focal melanocytic hyperplasia overlapping with a chronic persistent subungual hematoma.

Searching for Heavy Dark Matter near the Planck Mass with XENON1T.

Multiple viable theoretical models predict heavy dark matter particles with a mass close to the Planck mass, a range relatively unexplored by current experimental measurements. We use 219.4 days of data collected with the XENON1T experiment to conduct a blind search for signals from multiply interacting massive particles (MIMPs). Their unique track signature allows a targeted analysis with only 0.05 expected background events from muons. Following unblinding, we observe no signal candidate events. This Letter places strong constraints on spin-independent interactions of dark matter particles with a mass between 1×10^{12} and 2×10^{17} GeV/c^{2}. In addition, we present the first exclusion limits on spin-dependent MIMP-neutron and MIMP-proton cross sections for dark matter particles with masses close to the Planck scale.

CONGRESS REPORT OF THE 5TH NATIONAL CONGRESS OF THE BULGARIAN SOCIETY FOR DERMATOLOGIC SURGERY, SOFIA, 11TH MARCH 2023 WITH MAIN TOPICS: NITROSAMINES AS MOST POWERFUL TRIGGER FOR SKIN CANCER DEVELOPMENT AND PROGRESSION/PERSONALISED ONE STEP MELANOMA SURGERY AS POSSIBLE SKIN CANCER TREATMENT OPTION.

Deciphering the mutational pattern of skin tumours, remains a major challenge for clinicians and researchers. Over 80% of mutations in tumours are acquired, which in practice also means preventable. The surgical treatment of skin cancer and cancer in general is a worldwide, unsolved but at the same time not unsolvable problem. The problem concerning the dilemma of acquired mutations lies in the circumstance of their being allowed and subsequently treated. A more logical solution would be to eliminate the problem by making contact with mutagens in drugs public, clarifying it, studying it in detail and definitively stopping it. At present, there is an alarming and unexplained tendency worldwide : 1) Potential acquired mutations, caused in all probability by contact with known exogenous mutagens- the nitrosamines in most commonly prescribed drugs, are allowed to occur. 2) And subsequently, the diseases generated by them- treated (at a later stage) by multiple surgical interventions and unjustifiably expensive targeted therapy; 3) Mutagens - such as nitrosamines for example, to be in a permissive or possibly permissive availability regime. Moreover, this permissible availability turns out to be ubiquitous and affects the most common medicines worldwide: metformin, ranitidine, propranolol, rifampicin, irbesartan, olmesartan, valsartan, telmisartan, eprosartan, losartan, ACE inhibitors, thiazide diuretics, etc. In certain geographical regions, there is almost no patient taking this type of medication who has not had at least one tumour detected. These significant correlations (nitrosamines/cancer) are labeled by the regulatory institutions as possible, probable, or not currently relevant. But in spite of ˝this inconclusiveness˝, the drugs, containing nitrosamines, are withdrawn from the pharmaceutical market: quickly and quietly, despite the fact that ˝they did not pose a threat˝. The FDA was the only organization and the most important regulatory body worldwide, which lifted the veil from this ominous picture back in 2018: nitrosamines in blood medicines and cancer risk. Unfortunately, at the moment, the problems with this issue are proving to be more than the solutions, and at the same time it remains completely unclear who is to blame for this 'sporadic contamination': the packaging of the drug, the humidity in the rooms where the preparations are stored or the synthesis process itself - the explanations are divergent, the responsibility is blurred. This fuzzy liability does not affect the manufacturers and distributors of the preparations/nitrosamines themselves in the manner required by law for this (mis)act. The Bulgarian Society of Dermatological Surgery remains to be the only organization worldwide that for the 5th consecutive year continues to seek solutions to the above-mentioned problems by: 1) Officialising all cases of skin tumors (but not only) occurring after intake of nitrosamine-contaminated drugs, 2) also officialising a significant number of cases of patients with cutaneous melanomas treated by the one-stage surgical removal method within one surgical session (OSMS). The main priorities of the organization remain: 1) the complete elimination of nitrosamines from drugs worldwide, 2) the optimization of melanoma surgical treatment guidelines with the goal of treatment within 1 surgical session: for thin melanomas, dysplastic nevi and melanoma in situ, a surgical margin of safety of 1 cm in all directions and without detection and removal of the draining sentinel lymph node. Whereas for medium and thick melanomas, the focus should be directed to the following recommendation: 2 cm surgical margin of safety plus detection and removal of the draining lymph node within one surgical session. The indication for the surgical removal of these lesions should be made on the basis of radically different criteria from those used to date by the AJCC/EJC, namely: based on 1) clinical presentation/ clinical morphology, 2) dermatoscopic finding, and if there is a melanoma suspected lesion with possible tumour thickness greater than 1 mm , 3) ultrasonographic measurement for preoperative determination of tumor thickness should be additionally performed. The methodology is applicable in up to 80% of cases, excluding only some rare findings such as: amelanotic cutaneous melanomas, cutaneous melanomas with regression zones or those with localization in the neck and head. However, after careful individual assessment and a subsequent selected approach, even these exceptions could be included in the innovative algorithm for one step surgical removal of cutaneous melanomas. The resulting problems of not resolving these two dilemmas could lead to: 1) Generation of skin cancer (but not only), through the availability of nitrosamines in drugs. 2) Unnecessary and stressful /surgeries for the patients- 2 in number, which not infrequently lead to complication of their status (due to delay of histopathological analysis/ desire for second opinion/ delay regarding the timeframe for the second surgical intervention/ uncertainty regarding the resection lines within the first intervention/ failure to respect the recommended surgical security resection margins already within the first surgical session, etc.). 3) Huge additional costs to health care systems on the order of probably/roughly calculated about $50 billion per year. Resolution of these two dilemmas would likely result in a dramatic drop in cancer incidence worldwide and a significant improvement in the effectiveness/efficiency of surgical treatment for cutaneous melanoma.

MULTIFOCAL FIXED DRUG ERUPTION MIMICKING ACQUIRED DERMAL MELANOCYTOSIS.

Fixed drug eruptions (FDEs) are adverse drug reactions manifesting in the skin after exposure to a certain drug. The lesions can manifest as single or multiple eruptions followed by a post-inflammatory hyperpigmentation. The condition is very common among the young adult population and can be located on different parts of the body: the trunk, extremities, face, lips, etc. We report a case of a multifocal FDE following oral intake of Loratadine, Cetirizine dihydrochloride, Ibuprofen and/or Acetylsalicylic acid. Patch testing was recommended but later on declined by the patient. However, a small punch biopsy confirmed the diagnosis of multifocal fixed drug eruption. The lesions are often misdiagnosed or mistaken for other skin conditions. Differential diagnosis with an acquired dermal melanocytosis or other cutaneous eruptions could be done. Therefore, a brief review of the above-mentioned medications in the pathogenesis of the condition will be discussed.

Diagnostic and therapeutic approach of central sleep apnea in heart failure - the role of adaptive servo-ventilation. A statement of the Portuguese society of pulmonology and the Portuguese sleep association.

It is known that patients with heart failure (HF) have an increased risk of developing central sleep apnoea (CSA), with Cheyne-Stokes respiration. The development of servo-ventilation aimed to treat CSA and improve the quality of life (QoL) of these patients. A large randomized clinical study, SERVE-HF, was conducted in order to test this theory in patients with HF and reduced ejection fraction (HFrEF). The results from this trial seemed to indicate that, in these patients, there was no beneficial effect of the assisted ventilation in CSA treatment. More surprisingly, an increased rate of all-cause or cardiovascular mortality was observed. This has led to dramatic changes in clinical practice, with decreased frequency of servo-ventilation prescription across Europe, including Portugal, due to changes in the guidelines. However, SERVE-HF was conducted only in severe systolic HF patients with CSA, and caution must be taken when extrapolating these results to HF patients with preserved ejection fraction or CSA patients without HF. The study also showed poor adherence, methodological and statistical gaps, including study design, patient selection, data collection and analysis, treatment adherence, and group crossovers, which have not been discussed in the trial as potential confounding factors and raise several concerns. Moreover, the adaptive servo-ventilation (ASV) device used in SERVE-HF was unable to lower the minimum support pressure below 3 mm H20, and this has been suggested as one of the probable contributing reasons to the excess mortality observed in this study. This limitation has since been solved, and this ASV device is no longer used. This paper describes the results of a Portuguese Task Force on the treatment of central sleep apnoea in patients with chronic HF.

Teleconsultation in respiratory medicine - A position paper of the Portuguese Pulmonology Society.

The COVID-19 pandemic crisis, among so many social, economic and health problems, also brought new opportunities. The potential of telemedicine to improve health outcomes had already been recognised in the last decades, but the pandemic crisis has accelerated the digital revolution. In 2020, a rapid increase in the use of remote consultations occurred due to the need to reduce attendance and overcrowding in outpatient clinics. However, the benefit of their use extends beyond the pandemic crisis, as an important tool to improve both the efficiency and capacity of future healthcare systems. This article reviews the literature regarding telemedicine and teleconsultation standards and recommendations, collects opinions of Portuguese experts in respiratory medicine and provides guidance in teleconsultation practices for Pulmonologists.

Primary headache with onset in childhood and adolescence: natural history and prognostic factors in a Portuguese population. / Cefaleas primarias con inicio en la infancia y la adolescencia: historia natural y factores pronósticos en una población portuguesa.

INTRODUCTION: Headaches are the most frequent neurological disorder in the pediatric population, with great impact on quality of life. This study aims to characterize a cohort of patients followed at a pediatric neurology unit between January 1st 2013 and December 31st, 2021. MATERIALS AND METHODS: We reviewed medical records and selected patients with primary headaches and a minimum follow-up of 12 months. RESULTS: A total of 226 patients were included, 54.4% female, with an average age at headache onset of 9 ± 3.5 (3.1-16.5) years; 63.5% were prepubertal. A positive family history of headache was identified in 76.6% of cases and triggers in 63.6%. At first clinical assessment, 45.1% were classified as migraine without aura, 10.6% as migraine with aura, 3.5% tension-type, 8% mixed (tension and migraine), 1.3% other type and 31.4% were unclassifiable. The patients had a median follow-up of 2.4 (1.8-3.3) years. The diagnosis of tension-type headaches remained stable in 75% of the patients and resolved in 25%; 13% of the patients with migraine without aura changed into another type of headache and 17.4% resolved; 44.4% of the patients with migraine with aura turned into another type of headache and 11.1% resolved. Of the variables studied, only duration of headache episode had a significant association with headache remission, with odds ratio 0.16 (p = 0.03; 95% confidence interval: 0.032-0.84). CONCLUSIONS: Our study shows that headache type in pediatric population changes over time, especially in those with migraine with aura. The duration of each headache episode was presented as a predictor of headache remission over time.

TITLE: Cefaleas primarias con inicio en la infancia y la adolescencia: historia natural y factores pronósticos en una población portuguesa.Introducción. Las cefaleas son el trastorno neurológico más habitual en la población pediátrica e influyen notablemente en su calidad de vida. La finalidad de este estudio es caracterizar una cohorte de pacientes en seguimiento en una unidad de neurología pediátrica entre el 1 de enero de 2013 y el 31 de diciembre de 2021. Materiales y métodos. Hemos revisado informes médicos y seleccionado a pacientes con dolores de cabeza primarios y un seguimiento mínimo de 12 meses. Resultados. Se incluyó a un total de 226 pacientes, el 54,4% mujeres, con una media de edad al comenzar las cefaleas de 9 ± 3,5 (3,1-16,5) años; el 63,5% eran prepuberales. Se identificó un historial familiar positivo de cefalea en el 76,6% de los casos y factores desencadenantes en el 63,6%. En una primera evaluación clínica, el 45,1% se identificó como migrañas sin aura; el 10,6%, como migrañas con aura; el 3,5%, como cefalea tensional; el 8%, como de tipo mixto (cefalea tensional y migraña); el 1,3%, de otro tipo; y el 31,4% resultó inclasificable. Los pacientes se sometieron a un seguimiento promedio de 2,4 (1,8-3,3) años. El diagnóstico de cefalea tensional se mantuvo estable en el 75% de los pacientes y se solucionó en un 25%; para el 13% de los pacientes con migraña sin aura, el diagnóstico cambió a otro tipo de cefalea, y para el 17,4%, se solucionó; para el 44,4% de los pacientes sin migraña con aura, el diagnóstico cambió por el de otro tipo de cefalea, y para el 11,1%, se resolvió. De las variables estudiadas, sólo la duración del episodio de cefalea tuvo una asociación significativa con la remisión de la cefalea, con una odds ratio de 0,16 (p = 0,03; intervalo de confianza al 95%: 0,032-0,84). Conclusiones. Nuestro estudio muestra que el tipo de cefalea en la población pediátrica cambia con el paso del tiempo, especialmente en los pacientes con migraña con aura. La duración de cada uno de los episodios de cefalea se presentó como un predictor de la remisión de la cefalea con el paso del tiempo.

Host plant intraspecific variation determines gall traits.

Galls display a multiplicity of traits, including colours, which are driven by pigment accumulation. Their conspicuousness has attracted researchers' attention and several hypotheses have been raised. However, plants themselves vary intra-specifically, including in their pigment concentrations. As galls are a result of host tissue development, colours may be a by-product of the host's own traits, being more conspicuous simply because the sites where galls develop already have the predisposition to accumulate more pigment. Here, we call this the host variation hypothesis. We test this hypothesis using the system of galls induced by Palaeomystella oligophaga on Macairea radula host plant. Using spectrophotometry, we calculated the Anthocyanin Reflectance Index (ARI) of gall projections, which are responsible for their characteristic colours. We tested the influence of occupant identity (galling insect or any natural enemy), gall volume, parenchyma thickness, height from the ground, ARI of leaf, ARI of gall surface and ARI of the respective stem. We corroborated the host variation hypothesis since the anthocyanin content in stems and in galls' projections were positively related. Moreover, anthocyanin in galls' projections was positively related to anthocyanin in the gall surface and negatively related to gall volume and parenchyma thickness. This shows that, besides the host specificities, galls' own traits may also be responsible for pigment accumulation, influencing their colours. In this study, using colour as an example, we show that although galls tend to be considered complex expressions of galling insects' stimuli, their traits may be simply influenced by previous and specific attributes of the host organs.

Study on the dose profile in CT-fluoroscopy.

This work aims to contribute to the description of the dose profile in Computed Tomography Fluoroscopy (CTF). Our approach uses a function model to fit the single slice dose profiles (SSDP) for any point inside the gantry of the CT unit, with special attention to points off the rotation axis. The function model was successfully tested with measurements performed using GafChromic film. The parameters of the SSDP at the rotation axis (isocenter) and at 8 cm and 16 cm off the isocenter were determined. The model allows an estimation of the slice thickness at the isocenter and for points at 8 cm and 16 cm off the isocenter. The differences between the slice thicknesses results in overestimation of the Computed Tomography Dose Index, CTDI, by values as high as 20% if the nominal slice thickness instead of the model estimated value is used. The results obtained in this work provided a good description of the dose profiles, which can be used in further studies such as comparisons with measurements performed with phantoms and patients.