Validity and reliability of the Intelligibility in Context Scale: European Portuguese version.

The purpose of the study was to evaluate the validity, reliability, sensitivity and specificity of the European-Portuguese version of the Intelligibility in Context Scale (ICS-EP). Seventy-six children (age: M = 60.6, SD = 8.1 months), 25 having a parent or teacher concern about how they talked and 51 with no concern, were assessed with the phonetic-phonological test (TFF-ALPE) to calculate the following severity measures: percentage of phonemes correct (PPC), percentage of consonants correct (PCC), and percentage of vowels correct (PVC). Parents also filled out a questionnaire about their child's development (e.g. concern about how the child talks). The ICS was then completed by parents to estimate their children's intelligibility with different communicative partners. The results showed that item-level scores were different according to communicative partners. The mean ICS score for the whole sample was 4.5 (SD = 0.6), showing that children were "usually" to "always" intelligible. The ICS had excellent internal consistency (α = 0.96). Children with parental concern about their speech presented significantly lower mean scores (M = 3.91, SD = 0.59) than children without parental concerns (M = 4.78, SD = 0.36). There was a positive correlation between the ICS scores and PPC (r = .655), PCC (r = .654), and PVC (r = .588). A simple linear model was also obtained between the ICS mean score and the severity measures analyzed. High values were obtained for sensitivity (0.80) and specificity (0.84), using a cut-off point of 4.36. We conclude that the ICS-EP has good psychometric properties, suggesting it to be a valid tool for estimating children's intelligibility when talking with different communicative partners. Therefore, this version of the ICS can be used as a screening measure for children's speech intelligibility.

Surgical Management Of Congenital Thoracic Disorders: A 15-Year Center Experience.

INTRODUCTION: Congenital thoracic disorders represent a spectrum of fetal lung bud development abnormalities, which may affect breathing capacity and quality of life. We aim to evaluate the impact of surgery in the treatment of 4 major congenital conditions. MATERIALS AND METHODS: We performed a retrospective cohort analysis of patients who underwent surgical treatment in our tertiary center, from 2007 to 2022. RESULTS: Over the 15-year period, we treated 33 patients, with a male predominance of 55%. 22 patients (67%) were asymptomatic. When symptomatic, the recurrence of respiratory infections was the most common clinical presentation (18%). In 13 patients (39%), diagnosis was achieved through fetal ultrasonography. This study encompassed 13 patients with pulmonary sequestration (39%), 11 patients with bronchogenic cysts (33%), 7 patients with congenital pulmonary airway malformation (21%) and 2 patients with congenital lobar emphysema (6%). Considering solely lung malformation conditions, we accounted 22 patients with a median age of 3 [1-67] years-old. Surgery comprised bilobectomy (9%), lobectomy (77%), lobectomy with wedge resection (5%), segmentectomy (5%) and wedge resection (5%). Concerning bronchogenic cysts, we treated 11 patients with a median age of 19 [14-66] years-old. We identified 1 hilar, 1 intrapulmonary and 9 mediastinal lesions, of which 4 were paraesophageal, 4 were subcarinal and 1 was miscellaneous. Overall, surgery was conducted by thoracotomy in 61% of patients, VATS in 33% and RATS in 6%. The median drainage time was 3 [1-40] days and median hospital stay was 4 [1-41] days. There were no cases of mortality. Ensuing, 94% of patients experienced clinical improvement after surgery. CONCLUSION: Early diagnosis of congenital thoracic malformations increased considerably with the improvement in imaging technology and prenatal screening. Treatment may include expectant conservative treatment. However, in selected cases, surgery may play an important role in symptomatic control and prevention of disease progression.

The Clinical Spectrum of Adrenoleukodystrophy at a Portuguese Tertiary Hospital: Case Series and Review of Literature.

Adrenoleukodystrophy, a rare genetic disease associated with the X chromosome (X-ALD - X-linked adrenoleukodystrophy), predominantly affects males and stems from mutations in the ABCD1 gene, responsible for transporting very long chain fatty acids (VLCFA) into peroxisomes. It leads to adrenal insufficiency (AI) and axonal demyelination. In males, the phenotype varies from isolated adrenocortical insufficiency and progressive myelopathy to cerebral adrenoleukodystrophy (CALD). The aim of this case series is to characterize patients with different clinical presentations of X-ALD with follow-up at a tertiary Portuguese hospital. All four patients were males, and the median age at the diagnosis was 5 years. Three patients were diagnosed through family screening, with the oldest already displaying hyperpigmentation. Two distinct forms were identified: adolescent CALD (25%) and isolated primary adrenal insufficiency (75%). Analytical studies revealed elevated plasma VLCFA levels in all cases, and genetic analysis demonstrated two different mutations in the ABCD1 gene. This disorder requires early diagnosis for improved prognosis. Screening male children with primary AIfor X-ALD using a VLCFA panel should be considered, particularly after ruling out the most common causes or when learning difficulties are evident. Genetic confirmation of the diagnosis is essential, enabling genetic counseling, family planning, and preimplantation genetic diagnosis.

Lobar Lung Transplantation: A Single-Center 10-Year Experience.

BACKGROUND: The shortage of donors for lung transplants is the main limitation of the preceding. Lobar transplantation is an alternative especially useful in patients with short stature and small thoracic cavities. The aim of this study was to perform a descriptive analysis of Portuguese patients who underwent lobar lung transplantation. METHODS: A retrospective study was conducted, and patients submitted to lobar lung transplantation from January 2012 to December 2023 were evaluated. A descriptive analysis was made, including demographic data, lung diseases, waiting list dynamics, pre-transplant evaluations, and post-transplant outcomes. RESULTS: Sixteen lobar transplants were performed with a predominance of female patients and a median age of 47 years. Most patients had interstitial lung disease or bronchiectasis either due to cystic fibrosis or non-cystic fibrosis. The median predicted total lung capacity (pTLC) ratio was 0.73. The median waiting list time was 6 months with 9 urgent transplants and 1 emergent lobar retransplant. Extracorporeal membrane oxygenation (ECMO) was used in pre-, intra-, and postoperative periods. Most transplanted lobes were the median lobe (ML) + right upper lobe (RUL) and left upper lobe (LUL). The median length of stay was 58 days, with complications such as PDG grade 3, bronchial tree ischemia, and concentrical stenosis of bronchial anastomosis. Six patients died in this period, 1 in the immediate postoperative period and 5 during the post-transplant hospitalization, with a median survival of 20.7 months and a 1-year and 5-year survival rate of 60%. CONCLUSION: Our results show a population with an increased waiting list converging in many urgent cases, with an early mortality and high primary graft dysfunction rate. Nevertheless, mid- and long-term survival are promising.

Lung Transplantation in Pulmonary Arterial Hypertension: The Portuguese Experience.

BACKGROUND: In patients with pulmonary arterial hypertension (PAH), refractory to medical therapy, lung transplantation emerges as an option. This study describes the outcomes of 8 PAH patients who underwent lung transplantation. METHODS: A retrospective, single-center study was conducted among patients with PAH who underwent lung transplantation in our center. RESULTS: Patients had a median age of 46 years, with female sex predominance (75%). Causes of HAP were pulmonary veno-occlusive disease (n = 5, 62.5%), idiopathic PAH (n = 2, 25%), and heritable PAH (n = 1, 12.5%). Pre-transplant hemodynamics revealed a median mean pulmonary artery pressure of 58.5 mm Hg (48-86). All patients received bilateral lung transplants with extracorporeal membrane oxygenation support, displaying immediate post-transplant hemodynamic improvement. Primary graft dysfunction grade 3 (PGD 3) was observed in 75% of patients. Five patients (62.5%) died, with a 72.9% survival at 12 months and 29.2% at 24 months post-transplantation. CONCLUSION: Our study reveals the complexity and challenges of lung transplants in patients with PAH. Despite notable immediate hemodynamic improvements, high rates of PGD 3 and the survival rate remain a concern. Further research to define optimal peri and post-transplant management to improve survival is required.

MAJOR PULMONARY SURGERY IN PATIENTS WITH COMPROMISED LUNG FUNCTION.

INTRODUCTION: The risk stratification of lung resection is fundamentally based on the results of pulmonary function tests. In patients considered to be at risk, major surgery is generally denied, opting for potentially less curative therapies. OBJECTIVE: To evaluate the postoperative outcomes of major lung surgery in a group of patients deemed high risk. METHODS: We performed a retrospective review of clinical records of all patients submitted to lobectomy, bilobectomy or pneumonectomy in a 3-year period in a reference Thoracic Surgery Unit. The patients were then divided in two groups: group A composed of patients with normal preoperative pulmonary function and group B which included patients with impaired lung function, defined as FEV1 and/or DLCO ≤60%. RESULTS: A total of 234 patients were included, 181 (77.4%) in group A and 53 (22.6%) in group B. In group B, patients had more smoking habits, were more often associated with chronic obstructive pulmonary disease and were also more frequently submitted to thoracotomy. When surgery was motivated by primary lung cancer this group had a more advanced clinical stage of the disease. In the postoperative period, these patients had longer hospital stay, longer chest drainage time and greater need for oxygen therapy at home, however, no statistically significant difference was noted in morbidity or mortality. CONCLUSIONS: Major thoracic surgery can be safely performed in selected patients considered to be high risk for resection by pulmonary function tests. A potentially curative surgery should not be denied based on respiratory function tests alone.

Phenolic and lipophilic metabolite adjustments in Olea europaea (olive) trees during drought stress and recovery.

The frequency of combined stress events is increasing due to climate change and represents a new threat to olive (Olea europaea) culture. How olive plants modulate their profile of metabolites under multiple stressing agents remains to unveil, although several metabolites affect plants' resilience, and olive production and quality. Young olive plants were exposed to a water deficit (WD) for 30 days and then exposed to a shock of heat and high UVB-radiation (WDHS+UVB treatment) for 2 days. Then, plants were re-watered and grown under optimal conditions (recovery) for 30 days. Leaves were collected after stress and recovery, analysed by liquid and gas chromatography, and the lipophilic and phenolic profiles were characterized. Except for the oleuropein derivatives, the qualitative metabolite profile was similar during stress and recovery. Metabolite increases or decreases in response to stress were stronger when WD was followed by WDHS+UVB treatment. Phenolic compounds (luteolin-7-O-glucoside, quercetin-3-O-rutinoside, apigenin-7-O-glucoside, chrysoeriol-7-O-glucoside, kaempferol derivatives, oleuropein, and lucidumoside C) were the most involved after WD and WDHS+UVB, possibly acting as reactive oxygen species (ROS) scavengers. Lipophilic compounds were more relevant during the recovery period. The catabolism of fatty acids and carbohydrates may provide the necessary energy for plant performance reestablishment, and sterols, long-chain alkanes, and terpenes metabolic pathways may be shifted for the production of compounds with a more important stress protection role. This work highlights for the first time that tolerance mechanisms activated by WD in olive plants are related to metabolite changes, that are adjusted when other stressors are overlapped (WDHS+UVB), and also help the plants recover. This metabolites' plasticity represents an essential contribution to understanding how dry-farming olive orchards may deal with drought combined with high UV-B or heat.

Absence of methicillin-resistant Staphylococcus aureus colonization among immunocompetent healthy adults: Insights from a longitudinal study.

Methicillin-resistant Staphylococcus aureus (MRSA) has long been known as a major cause of hospital-acquired (HA-MRSA) infections worldwide. For the past twenty years, an increasing number of studies have described its emergence in the community as well. In Portugal, a country with a high-prevalence of HA-MRSA, there are only limited data available on the epidemiology of MRSA in the community. We studied the prevalence of S. aureus and MRSA colonization among healthy adults in Portugal. Between February 2015 and December 2016, a longitudinal study was conducted in which 87 adults aged 25-50 years old were followed for six months. For each participant nasopharyngeal, oropharyngeal and saliva samples were obtained monthly and, in some cases, weekly. A total of 1,578 samples (n = 526 for each sampling site) were examined for the presence of S. aureus and MRSA by classical culture-based methods. Fifty-seven adults (65.5%) carried S. aureus at least once during the six months period of the study: 19.5% were persistent S. aureus carriers and 46.0% were intermittent carriers. Carriage rates per sampling site were 20.5% in nasopharynx, 18.3% in oropharynx, and 13.5% in saliva. Simultaneous screening of the three sampling sites increased detection of S. aureus, which overall occurred in 34.4% of the 526 sampling time-points. No MRSA were isolated. In conclusion, this study adds novel information about the MRSA scenario in the Portuguese community. Our results indicate that, in Portugal, MRSA does not seem to circulate among healthy adults without risk factors and therefore this age group does not constitute, at the current time, a reservoir of MRSA in the community.

Can 8-weeks of Training Affect Active Drag in Young Swimmers?

The aim of this study was to assess the effects of 8-weeks of training on active drag in young swimmers of both genders. Eight girls and twelve boys' belonging to the same swimming team and with regular competitive participation in national and regional events for the previous two seasons participated in this study. Active drag measurements were conducted in two different evaluation moments: at the beginning of the season and after 8 weeks of training (6.0 ± 0.15 training units per week, 21.00 ± 3.23 km per week and 3.50 ± 0.23 km per training unit). The maximal swimming velocity at the distance of 13 m, active drag and drag coefficient were measured on both trials by the method of small perturbations with the help of an additional hydrodynamic body. After 8 weeks of training, mean active drag (drag force and drag coefficient) decreased in girls and boys, although no significant differences were found between the two trials. It seems that 8 weeks of swimming training were not sufficient to allow significant improvements on swimming technique. Key pointsThe velocity perturbation method seems to be a good, simple and reliable approach to assess active drag in young swimmers.Eight weeks of swimming training were not sufficient to allow significant improvements on swimming hydrodynamics.There were no differences between boys and girls concerning active drag. A possible explanation may be related to the similar values of body mass and height in boys and girls found in this study.Specific training sets concerning technique correction and improvement in young swimmers might be a main aim during training planning.

Hyperinsulinaemic Hypoglycaemia and Polycystic Kidney Disease - A Rare Case Concerning PMM2 Gene Pleiotropy.

Co-occurrence of hyperinsulinaemic hypoglycaemia and polycystic kidney disease (HIPKD) has been recently described. It is caused by a non-coding variant in the promoter region for phosphomannomutase 2 (PMM2), c.-167G>T, both in homozygous or compound heterozygous variants with deleterious coding. Although PMM2 has been associated with congenital disorder of glycosylation, patients do not present with this phenotype and have normal carbohydrate-deficient transferring testing. The authors present a rare case where specific PMM2 study was performed as a result of clinical suspicions. The patient was a 6-year-old female followed at our clinic due to congenital hyperinsulinism since she was 1 month old. She also presented with bilateral polycystic kidneys, detected in prenatal set, and simple hepatic cysts, for which she was treated with diazoxide and captopril. Initial metabolic and genetic studies were normal. PMM2 gene sequence study revealed the promotor variant c.-167G>T in compound heterozygosity with the previously described pathogenic variant c.422G>A (p.Arg141His), confirming the diagnosis of HIPKD. This is a notable case as it highlights the importance of keeping this diagnostic hypothesis in mind and serves as a reminder to perform proper clinical and genetic investigation. A correct, and early, diagnosis will avoid unnecessary additional investigations and will allow appropriate genetic counselling for this autosomal recessive disorder.

Neuron-microglia crosstalk up-regulates neuronal FGF-2 expression which mediates neuroprotection against excitotoxicity via JNK1/2.

Glial cells and neurons are in constant reciprocal signalling both under physiological and neuropathological conditions. Microglial activation is often associated with neuronal death during inflammation of the CNS, although microglial cells are also known to exert a neuroprotective role. In this work, we investigated the interplay between cerebellar granule neurons (CGN) and microglia in the perspective of CGN survival to an excitotoxic stimulus, quinolinic acid (QA), a catabolite of the tryptophan degradation pathway. We observed that CGN succumb to QA challenge via extracellular signal regulated kinase 1 and 2 (ERK) activation. Our data with transgenic mice expressing the natural inhibitor of calpains, calpastatin, indicate that together with cathepsins they mediate QA-induced toxicity acting downstream of the mitogen-activated protein kinase kinase-ERK pathway. Microglial cells are not only resistant to QA but can rescue neurons from QA-mediated toxicity when they are mixed in culture with neurons or by using mixed culture-conditioned medium (MCCM). This effect is mediated via fibroblast growth factor-2 (FGF-2) present in MCCM. FGF-2 is transcriptionally up-regulated in neurons and secreted in the MCCM as a result of neuron-microglia crosstalk. The neuroprotection is associated with the retention of cathepsins in the lysosomes and with transactivation of inducible heat-shock protein 70 downstream of FGF-2. Furthermore, FGF-2 upon release by neurons activates c-jun N-terminal kinase 1 and 2 pathway which also contributes to neuronal survival. We suggest that FGF-2 plays a pivotal role in neuroprotection against QA as an outcome of neuron-microglia interaction.

Necrotic neurons enhance microglial neurotoxicity through induction of glutaminase by a MyD88-dependent pathway.

BACKGROUND: Microglia are macrophage-like cells that constantly sense the microenvironment within the central nervous system (CNS). In the event of neuronal stress or injury, microglial cells rapidly react and change their phenotype. This response may lead to a deleterious type of microglial activation, which is often associated with neuroinflammation and neurotoxicity in several neuropathological conditions. We investigated the molecular mechanisms underlying triggering of microglial activation by necrotic neuronal damage. METHODS: Primary cultures of microglia were used to study the effect of necrotic neurons on microglial inflammatory responses and toxicity towards cerebellar granule neurons (CGN). The mouse hippocampal cell line, HT22, was used in this study as the main source of necrotic neurons to stimulate microglia. To identify the signal transduction pathways activated in microglia, primary microglial cultures were obtained from mice deficient in Toll-like receptor (TLR) -2, -4, or in the TLR adapter protein MyD88. RESULTS: Necrotic neurons, but not other necrotic cell types, induced microglial activation which was characterized by up-regulation of: i) MHC class II; ii) co-stimulatory molecules, i.e. CD40 and CD24; iii) beta2 integrin CD11b; iii) pro-inflammatory cytokines, i.e. interleukin 6 (IL-6), IL-12p40 and tumor-necrosis factor (TNF); iv) pro-inflammatory enzymes such as nitric oxide synthase (iNOS, type II NOS), indoleamine 2,3-dioxygenase (IDO) and cyclooxygenase-2 (COX-2) and increased microglial motility. Moreover, microglia-conditioned medium (MCM) obtained from cultures of activated microglia showed increased neurotoxicity mediated through the N-methyl-D-aspartate receptor (NMDAR). The activation of microglia by necrotic neurons was shown to be dependent on the TLR-associated adapter molecule myeloid differentiation primary response gene (MyD88). Furthermore, MyD88 mediated enhanced neurotoxicity by activated microglia through up-regulation of the expression and activity of glutaminase, an enzyme that produces glutamate, which is an NMDAR agonist. CONCLUSION: These results show that necrotic neurons activate in microglia a MyD88-dependent pathway responsible for a pro-inflammatory response that also leads to increased neurotoxic activity through induction of glutaminase. This finding contributes to better understanding the mechanisms causing increased neuroinflammation and microglial neurotoxicity in a neurodegenerative environment.

Prenatal Diagnosis and Management of a Fetal Goiter Hypothyroidism due to Dyshormonogenesis.

Fetal goiter is a rare disorder not expected to be found during a healthy woman's pregnancy. It can be a prenatal manifestation of congenital hypothyroidism due to thyroid dyshormonogenesis and it can lead to serious perinatal complications. A vascularized fetal neck mass was detected at 29 weeks' gestation of a healthy primigravida. Magnetic resonance was suggestive of goiter causing airway deviation without polyhydramnios. Maternal thyroid function was normal and thyroid antibodies were negative. Two intra-amniotic levothyroxine infusions were performed at 32 and 33 weeks. Serial imaging control showed no progression of the mass. Elective caesarean section was performed at 38 weeks. The male newborn was admitted to the intensive care unit due to cardiorespiratory insufficiency with pulmonary hypertension. Hormonal assays revealed primary congenital hypothyroidism and ultrasonography confirmed diffuse goiter. Levothyroxine was started. Currently, he is 6 years old with adequate growth and normal psychomotor development. Genetic study found a heterozygous mutation in the TPO gene.

A case of Protracted Diarrhea in a Newborn: a Diagnostic Challenge.

Congenital diarrhea comprises a broad range of pathologies and often requires a thorough workup and immediate treatment. Although rare, microvillous inclusion disease (MVID) should be included in differential diagnosis of this presentation in the neonate. We report the case of a 36-week newborn who developed signs of severe dehydration and lethargy, requiring fluid resuscitation and total parenteral nutrition. MVID was diagnosed by recognition of profuse secretory diarrhea after an exhaustive etiological investigation, confirmed by DNA analysis.