Round ligament management during minimally invasive groin hernia repair in women: a systematic review and meta-analysis.

BACKGROUND: Female sex has been associated with worse outcomes after groin hernia repair (GHR), including a higher rate of chronic pain and recurrence. Most of the studies in GHR are performed in males, and the recommendations for females extrapolate from these studies, even though females have anatomy intricacies. The round ligament of the uterus (RLU) is associated with pelvic stabilization and plays a role in sensory function. Transection of the RLU during GHR is controversial as it can allow easier mesh placement but can favor genitourinary complications and chronic pain. As no previous meta-analysis compared preserving versus transecting the RLU during minimally invasive (MIS) GHR, we aim to perform a systematic review and meta-analysis evaluating surgical outcomes comparing the approaches. METHODS: Cochrane Central, Embase, and PubMed databases were systematically searched for studies comparing transection versus preservation of the RLU in MIS groin hernia surgeries. Outcomes assessed were operative time, bleeding, surgical site events, hospital stay, chronic pain, paresthesia, recurrence rates, and genital prolapse rates. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics. A review protocol for this meta-analysis was registered at PROSPERO (CRD 42023467146). RESULTS: 1738 studies were screened. A total of six studies, comprising 1131 women, were included, of whom 652 (57.6%) had preservation of the RLU during MIS groin hernia repair. We found no statistical difference regarding chronic pain, paresthesia, recurrence rates, and postoperative complications. We found a longer operative time for the preservation group (MD 6.84 min; 95% CI 3.0-10.68; P = 0.0005; I2 = 74%). CONCLUSION: Transecting the RLU reduces the operative time during MIS GHR with no difference regarding postoperative complication rates. Although transection appears safe, further prospective randomized studies with long-term follow-up and patient-reported outcomes are necessary to define the optimal management of RLU during MIS GHR.

Transinguinal preperitoneal (TIPP) versus Lichtenstein for inguinal hernia repair: a systematic review and meta-analysis.

PURPOSE: We aimed to perform a systematic review and meta-analysis comparing postoperative outcomes in inguinal hernia repair with TIPP versus Lichtenstein technique. METHODS: Cochrane Central, Scopus, and PubMed were systematically searched for studies comparing TIPP and Lichtenstein´s technique for inguinal hernia repair. Outcomes assessed were operative time, bleeding, surgical site events, hospital stay, the Visual Analogue Pain Score, chronic pain, paresthesia rates, and recurrence. Statistical analysis was performed using RevMan 5.4.1. Heterogeneity was assessed with I2 statistics and random-risk effect was used if I2 > 25%. RESULTS: 790 studies were screened and 44 were thoroughly reviewed. A total of nine studies, comprising 8428 patients were included, of whom 4185 (49.7%) received TIPP and 4243 (50.3%) received Lichtenstein. We found that TIPP presented less chronic pain (OR 0.43; 95% CI 0.20-0.93 P = 0.03; I2 = 84%) and paresthesia rates (OR 0.27; 95% CI 0.07-0.99; P = 0.05; I2 = 63%) than Lichtenstein group. In addition, TIPP was associated with a lower VAS pain score at 14 postoperative day (MD - 0.93; 95% CI - 1.48 to - 0.39; P = 0.0007; I2 = 99%). The data showed a lower operative time with the TIPP technique (MD - 7.18; 95% CI - 12.50, - 1.87; P = 0.008; I2 = 94%). We found no statistical difference between groups regarding the other outcomes analyzed. CONCLUSION: TIPP may be a valuable technique for inguinal hernias. It was associated with lower chronic pain, and paresthesia when compared to Lichtenstein technique. Further long-term randomized studies are necessary to confirm our findings. Study registration A review protocol for this meta-analysis was registered at PROSPERO (CRD42023434909).

Changes in motor activity level in individuals with frontotemporal dementia.

Changes in motor activity are common in individuals with Frontotemporal dementia (FTD). Yet, it remains unclear why some individuals become motorically hyperactive, while others hypoactive even in early stages of the disease. This study aimed to examine the relationship between motor activity level and (1) FTD clinical subtype, and (2) cortical thickness and subcortical volumes. Eighty-two charts were retrospectively reviewed from patients meeting consensus criteria for one of the three main clinical subtypes of FTD: probable bvFTD, semantic variant Primary Progressive Aphasia (PPA), or non-fluent variant PPA. Participants were assigned to one of three groups: (1) hyperactive, (2) hypoactive, or (3) no record of change. Hyperactivity was prevalent among bvFTD (58.5%) and semantic PPA (68.8%) subtypes while hypoactivity was less common in both subtypes (29.3% and 18.8%, respectively). The majority of patients with non-fluent PPA showed no record of change in motor activity (66.7%). The analysis of cortical thickness and subcortical volumes did not identify significant associations with motor activity levels. In conclusion, increased motor activity is highly prevalent among individuals with FTD, especially bvFTD and svPPA subtypes. These findings may inform prognosis and prediction of changes in motor activity, and allow planning for appropriate environmental and behavioural interventions. Future studies with prospective, standardized longitudinal collection of information regarding the type and level of change in motor activity, including wearable measures of actigraphy, may help to further delineate the onset and progression of abnormal motor behaviours and determine neuroanatomic associations in FTD.

Field efficacy of Metarhizium anisopliae oil formulations against Rhipicephalus microplus ticks using a cattle spray race.

Rhipicephalus microplus tick is the main ectoparasite of cattle in Brazil. The exhaustive use of chemical acaricides to control this tick has favored the selection of resistant tick populations. Entomopathogenic fungi, as Metarhizium anisopliae, has been described as a potential biocontroller of ticks. Therefore, the aim of this study was to evaluate the in vivo efficacy of two oil based formulations of M. anisopliae for the control of the cattle tick R. microplus under field conditions using a cattle spray race as a method of treatment. Initially, in vitro assays were carried out with an aqueous suspension of M. anisopliae, using mineral oil and/or silicon oil. A potential synergism between oils and fungus conidia for tick control was demonstrated. Additionally, the usefulness of silicon oil in order to reduce mineral oil concentration, while improving formulation efficacy was illustrated. Based on the in vitro results, two formulations were selected for use in the field trial: MaO1 (107 conidia/mL plus 5% mineral oil) and MaO2 (107 conidia/mL plus 2.5% mineral oil and 0.01% silicon oil). The adjuvants concentrations (mineral and silicon oils) were chosen since preliminary data indicate that higher concentrations caused significant mortality in adult ticks. For this, 30 naturally infested heifers were divided into three groups based on previous tick counts. The control group did not receive treatment. The selected formulations were applied on animals using a cattle spray race. Subsequently, tick load was evaluated weekly by counting. The MaO1 treatment significantly reduced the tick count only on day +21, reaching approximately 55% efficacy. On the other hand, MaO2 showed significantly lower tick counts on days +7, +14, and +21 after treatment, with weekly efficacy achieving 66%. The results showed a substantial reduction of tick infestation, up to day +28, using a novel formulation of M. anisopliae based in the mixture of two oils. Moreover, we have shown, for the first time, the feasibility of employing formulations of M. anisopliae for large-scale treatment methods, such as a cattle spray race, which in turn, may increase the use and adhesion to biological control tools among farmers.

Epidemiological and clinicopathological findings in 15 fatal outbreaks of salmonellosis in dairy calves and virulence genes in the causative Salmonella enterica Typhimurium and Dublin strains.

Salmonella enterica is a major food-borne pathogen that affects cattle-rearing systems worldwide. Little information is available on the epidemiology and pathology of salmonellosis and the virulence genes (VGs) carried by Salmonella in spontaneous outbreaks in cattle. We describe epidemiological findings in 15 fatal outbreaks of salmonellosis in Uruguayan dairy farms and the age, clinical signs, and pathology in 20 affected calves. We also describe the serotypes and frequencies of 17 VGs in the causative Salmonella strains and explore their associations with epidemiological, clinical, and pathological findings. Salmonella Typhimurium and Dublin were identified in 11/15 and 4/15 outbreaks, respectively. The most frequent reason for consultation was digestive disease (8 outbreaks caused by S. Typhimurium), followed by sudden death (4 outbreaks, 3 caused by S. Dublin). Morbidity, mortality, and lethality ranged 4.8-100%, 3.8-78.9%, and 10-100%, without significant differences between serotypes. Diarrhea, the most common clinical sign (14 cases), was associated with the Typhimurium serotype (OR = 26.95), especially in ≤ 30-day-old calves with fibrinous enteritis as the main autopsy finding. The Dublin serotype affected ≥ 50-day-old calves and was associated with fibrinosuppurative splenitis (p = 0.01) and tubulointerstitial nephritis (OR = 48.95). The chances of the Dublin serotype increased significantly with age. There was low variability of VG across serotypes. The pefA gene was associated with the Typhimurium serotype (OR = 21.95), macroscopic enteritis (p = 0.03), and microscopic fibrinosuppurative splenitis (p = 0.04). Understanding the epidemiology, pathology, and virulence of S. enterica at the farm level is key to delineating prevention and control strategies to mitigate its impact on animal and human health.

Spatio-temporal feature extraction in sensory electroneurographic signals.

The recording and analysis of peripheral neural signal can provide insight for various prosthetic and bioelectronics medicine applications. However, there are few studies that investigate how informative features can be extracted from population activity electroneurographic (ENG) signals. In this study, five feature extraction frameworks were implemented on sensory ENG datasets and their classification performance was compared. The datasets were collected in acute rat experiments where multi-channel nerve cuffs recorded from the sciatic nerve in response to proprioceptive stimulation of the hindlimb. A novel feature extraction framework, which incorporates spatio-temporal focus and dynamic time warping, achieved classification accuracies above 90% while keeping a low computational cost. This framework outperformed the remaining frameworks tested in this study and has improved the discrimination accuracy of the sensory signals. Thus, this study has extended the tools available to extract features from sensory population activity ENG signals. This article is part of the theme issue 'Advanced neurotechnologies: translating innovation for health and well-being'.

Resistance of Soybean Genotypes to Anticarsia gemmatalis (Lepidoptera: Erebidae): Antixenosis and Antibiosis Characterization.

Injury by herbivores is a major biotic stress that limits soybean [Glycine max (L.) Merrill] crop production. Among the main soybean insect pests, Anticarsia gemmatalis Hübner is responsible for causing significant economic damage in soybean. The primary management strategy for this insect is chemical control and use of Bt transgenic soybean. Alternative strategies, such as host plant resistance, are considered an efficient and less-aggressive method, especially in association with other strategies as part of an integrated pest management (IPM) approach. In this study, we evaluated 30 soybean genotypes to verify antixenosis expression through oviposition, attractiveness, and food consumption tests. From this, we selected 13 promising genotypes to verify the possible presence of antibiosis. Our results suggest that antixenosis was found in genotypes 'TMG 133' RR, 'TMG 1179' RR, 'IAC 19', 'IAC 17', 'IAC 100', D75-10169, and IAC 78-2318. By influence on behavior and negative impact on larval viability, antixenosis and antibiosis were indicated for the genotypes IAC 74-2832, 'IAC 19', 'IAC 17', 'IAC 100', and PI 274454. 'TMG 7062' IPRO was found to provide antibiosis resistance by negatively affecting larval development and viability. Because of reduced food consumption by larvae, antixenosis was indicated for 'IAC 24'. These genotypes should be considered in soybean breeding programs focusing on soybean resistance to A. gemmatalis.

Calcium homeostasis behavior and cardiac function on left ventricular remodeling by pressure overload.

Sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and sarcolemmal Na+/Ca2+ exchanger (NCX1) structures are involved in heart cell Ca2+ homeostasis. Previous studies have shown discrepancies in their function and expression in heart failure. The goal of this study was to evaluate heart function and hypertrophied muscle Ca2+-handling protein behavior under pressure overload. Twenty male Wistar rats were divided into two groups: Aortic stenosis (AoS), induced by a clip placed at the beginning of the aorta, and Control (Sham). After 18 weeks, heart function and structure were evaluated by echocardiogram. Myocardial function was analyzed by isolated papillary muscle (IPM) at basal condition and Ca2+ protein functions were evaluated after post-pause contraction and blockage with cyclopiazonic acid in IPM. Ca2+-handling protein expression was studied by western blot (WB). Echocardiogram showed that AoS caused concentric hypertrophy with enhanced ejection fraction and diastolic dysfunction inferred by dilated left atrium and increased relative wall thickness. IPM study showed developed tension was the same in both groups. AoS showed increased stiffness revealed by enhanced resting tension, and changes in Ca2+ homeostasis shown by calcium elevation and SERCA2a blockage maneuvers. WB revealed decreased NCX1, SERCA2a, and phosphorylated phospholambam (PLB) on serine-16 in AoS. AoS had left ventricular hypertrophy and diastolic dysfunction compared to Sham; this could be related to our findings regarding calcium homeostasis behavior: deficit in NCX1, SERCA2a, and phosphorylated PLB on serine-16.

Corrigendum to 'Dental pathology of the wild Iberian wolf (Canis lupus signatus): the study of a 20th century Portuguese museum collection': Veterinary and animal science 9 (2020) 100100.

[This corrects the article DOI: 10.1016/j.vas.2020.100100.].

Nano-targeting lessons from the SARS-CoV-2.

The lack of targeting efficacy has frequently led functionalized nanoparticles to accumulate in unwanted cells and tissues while boosting toxicity-related effects. Conversely, viruses are natural nanoparticles that precisely and responsively interact with the biological machinery through an effective-driven fashion. This interaction is enhanced by a meticulous spatial arrangement which results in a quasi-crystalline distribution of proteins on the viruses' surface. Amidst the COVID-19 pandemic, we propose to look at the SARS-CoV-2 nanoscale viral scaffold as an example of a highly-ordered architecture that must inspire and tailor the production of targeted synthetic nanoparticles.

Practical and Simple Systems for Food Intake Studies on Phloem-Sucking Insects.

Studies of insect feeding behavior are useful in different areas of entomology such as plant resistance, biology, and insecticide efficacy. For chewing insects, this kind of technique is well established, but for sap-sucking insects, especially tiny ones such as whiteflies, aphids, and psyllids, these tests can be laborious. Manipulation is difficult and can damage the plant, affecting the results. We describe here three types of cages for tests with small insects, one for seedlings in pots, a second for larger plants or plants in the field, and a third for caging insects on part of a leaf. These cages have been useful for different types of studies in addition to feeding behavior and can facilitate research with small phytophagous sucking insects.

Calcium homeostasis behavior and cardiac function on left ventricular remodeling by pressure overload

Sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) and sarcolemmal Na+/Ca2+ exchanger (NCX1) structures are involved in heart cell Ca2+ homeostasis. Previous studies have shown discrepancies in their function and expression in heart failure. The goal of this study was to evaluate heart function and hypertrophied muscle Ca2+-handling protein behavior under pressure overload. Twenty male Wistar rats were divided into two groups: Aortic stenosis (AoS), induced by a clip placed at the beginning of the aorta, and Control (Sham). After 18 weeks, heart function and structure were evaluated by echocardiogram. Myocardial function was analyzed by isolated papillary muscle (IPM) at basal condition and Ca2+ protein functions were evaluated after post-pause contraction and blockage with cyclopiazonic acid in IPM. Ca2+-handling protein expression was studied by western blot (WB). Echocardiogram showed that AoS caused concentric hypertrophy with enhanced ejection fraction and diastolic dysfunction inferred by dilated left atrium and increased relative wall thickness. IPM study showed developed tension was the same in both groups. AoS showed increased stiffness revealed by enhanced resting tension, and changes in Ca2+ homeostasis shown by calcium elevation and SERCA2a blockage maneuvers. WB revealed decreased NCX1, SERCA2a, and phosphorylated phospholambam (PLB) on serine-16 in AoS. AoS had left ventricular hypertrophy and diastolic dysfunction compared to Sham; this could be related to our findings regarding calcium homeostasis behavior: deficit in NCX1, SERCA2a, and phosphorylated PLB on serine-16.

Dental pathology of the wild Iberian wolf (Canis lupus signatus): The study of a 20th century Portuguese museum collection.

For some wild canids, such as the Iberian wolf, there is a lack of in-depth knowledge about dental pathology. We aimed to evaluate it, in a standardized manner, in specimens from a Portuguese museum collection. Sixty-five deceased specimens of wild Iberian wolves, 61 complete skulls and 4 mandibles, collected in Portugal between 1977 and 1995, were analyzed. Sample comprised 18 females, 24 males and 23 individuals of undetermined sex. Teeth were evaluated by visual observation and dental radiography for tooth wear, periodontitis, fractures and other dental lesions. We have found several causes for teeth absence: artefactual, secondary to periodontitis and agenesia. About 30% of the teeth showed signs of wear. Only a small (<13%) fraction of maxillary and mandibular teeth did not show periodontitis. The tooth 308 showed periodontitis in all males (p = 0.017) and the tooth 104 was significantly affected by this condition in females (p = 0.020). A significant relationship was found between females and tooth wear in three teeth. Periodontitis showed a significant association with tooth wear (p < 0.001) and fractures (p = 0.027). Tooth fractures were more frequent in the maxilla than in the mandible. Seven periapical lesions, seven root fusions and three specimens with malocclusion were identified in the collection. Results are discussed integrating information from diet, habitat, genetic and spatial behavior. Dental radiography is here proposed as an approach for the age estimation in archaeological canids. This research contributes to the knowledge of the dental disease in the largest wolf population in Western Europe, a target subspecies of multiple conservation measures.

An extensive field study reveals the circulation of new genetic variants of subtype 1a of bovine viral diarrhea virus in Uruguay.

Bovine viral diarrhea virus (BVDV) is a major pathogen worldwide, causing significant economic losses to the livestock sector. In Uruguay, BVDV seroprevalence at the farm level is >80%. In this work, 2546 serum, blood or tissue samples collected from animals suspected of being affected by BVD between 2015 and 2017 were analyzed by reverse transcription PCR and sequencing. Analysis of the BVDV genomic regions 5'UTR/Npro, Npro and E2 revealed that BVDV-1a, 1i and 2b circulate in the country, with BVDV-1a being the most prevalent subtype. Population dynamics studies revealed that BVDV-1a has been circulating in our herds since ~1990. This subtype began to spread and evolve, accumulating point mutations at a rate of 3.48 × 10-3 substitutions/site/year, acquiring specific genetic characteristics that gave rise to two local genetic lineages of BVDV-1a. These lineages are divergent from those circulating worldwide, as well as the vaccine strain currently used in Uruguay. The most notable differences between field and vaccine strains were found in the E2 glycoprotein, suggesting that the amino acid substitutions could result in failure of cross-protection/neutralization after vaccination. This is the first study that compares Uruguayan BVDV field and vaccine strains with other BVDV strains from throughout the world. The results obtained in this study will be very useful for developing a suitable immunization program for BVDV in Uruguay by identifying local field strains as candidates for vaccine development.

Detection of rare and novel EGFR mutations in NSCLC patients: Implications for treatment-decision.

OBJECTIVES: Mutations in the gene that encodes epidermal growth factor receptor (EGFR) are biomarkers that predict how non-small cell lung cancer (NSCLC) patients respond to EGFR-targeted therapies collectively known as tyrosine kinase inhibitors (TKIs). Thus, EGFR genotyping provides crucial information for treatment decision. Both Sanger sequencing and real-time PCR methodologies are used for EGFR genotyping. However, methods based on real-time PCR have limitations, as they may not detect rare or novel mutations. The aim of this study was to determine the prevalence of rare mutations in the tyrosine kinase domain (exons 18-21) of the EGFR gene not targeted by the most frequently used real-time PCR approaches, i.e., the cobas® EGFR Mutation Test, and the Idylla™ EGFR Mutation Assay. METHODS: A total of 1228 NSCLC patients were screened for mutations in exons 18-21 of the EGFR gene using Sanger sequencing. RESULTS: We observed that 252 patients (∼20%) had at least one mutation in the EGFR gene, and 38 (∼3%) carried uncommon genetic alterations that would not be identified by the cobas® or the Idylla™ tests. We further found six new single mutations and seven previously unreported compound mutations. Clinical information and patient outcome are presented for these cases. CONCLUSIONS: This study highlights the value of sequencing-based approaches to identify rare mutations. Our results add to the inventory of known EGFR mutations, thus contributing to improved lung cancer precision treatment.

Effects of Bisphenol A on redox balance in red blood and sperm cells and spermatic quality in zebrafish Danio rerio.

Bisphenol-A (BPA) is a potential endocrine disruptor besides being associated with oxidative damage in several vertebrate classes. In the present study we investigated oxidative effects in erythrocytes and sperm cells as well as spermatic quality in Danio rerio exposed to 14 days at BPA concentrations of 2, 10 and 100 µg/L. Organelles structure, reactive species of oxygen (ROS) and lipoperoxidation (LPO) on erythrocytes and sperm cells were measured by flow cytometry and spermatic parameters were analyzed by the computer-assisted sperm analysis (CASA) system. For both cell types, when compared with control BPA treatment induced a significant increase in ROS and LPO production causing the membrane fluidity disorder, loss of membrane integrity and mitochondrial functionality. Furthermore, it was found a significant increase in DNA fragmentation in erythrocytes of zebrafish BPA exposed. Regarding the spermatic quality, results showed lower sperm motility in animals exposed to BPA, and alterations on velocity parameters of spermatozoa. Thus, the present study concludes that BPA affects the oxidative balance of both cell types, and that can directly affects the reproductive success of the adult Danio rerio. The sensitivity of erythrocytes to oxidative damage induced by BPA was similar to sperm cells, indicating a potential use of blood cells as indicators of oxidative damage present in fish sperm.

E-cadherin mediated cell-biomaterial interaction reduces migration of keratinocytes in-vitro.

Percutaneous devices suffer from imperfect sealing of the epidermis-implant interphase, the so-called three-phase junction, allowing invading pathogens access to colonize the implant at the tissue interface and potentially cause an infection. In skin, one of the key components of the epidermal barrier is the E-cadherin mediated adherens junctions. We investigated the response of a human keratinocyte cell line (HaCaT) to a titanium substrate functionalized with the extracellular domain of E-cadherin fused to an Fc domain. Polydopamine was used as a binding layer to attach the E-cadherin to the titanium surface in two ways: 1) by attaching protein A to the polydopamine followed by E-cadherin (aligned orientation) or 2) by direct attachment of the E-cadherin to the polydopamine (random orientation). The E-cadherin surface functionalization was stable for up to two months as determined by ELISA. HaCaTs did attach to the surface irrespective of E-cadherin orientation. However, decreased cell proliferation and increased cell size was observed for cells on aligned E-cadherin surfaces as compared to a positive control coated with fibronectin. The adhesion of the HaCaTs to the surface with aligned E-cadherin was more sensitive to cell media Ca2+ depletion. A confluent layer of HaCaTs was almost immobile on the aligned E-cadherin surface, as compared to a surface coated with fibronectin, whereas cell migration was also observed on randomly oriented E-cadherin. The E-cadherin coated surfaces were non-adhesive for primary human dermal fibroblasts, a cell type not expressing E-cadherin. These results show the potential of using E-cadherin as a functional surface at the three-phase junction of percutaneous implants to ensure epidermal attachment, limit epidermal downgrowth and prevent fibroblast adhesion.

Ambroxol as a novel disease-modifying treatment for Parkinson's disease dementia: protocol for a single-centre, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Currently there are no disease-modifying treatments for Parkinson's disease dementia (PDD), a condition linked to aggregation of the protein α-synuclein in subcortical and cortical brain areas. One of the leading genetic risk factors for Parkinson's disease is being a carrier in the gene for ß-Glucocerebrosidase (GCase; gene name GBA1). Studies in cell culture and animal models have shown that raising the levels of GCase can decrease levels of α-synuclein. Ambroxol is a pharmacological chaperone for GCase and is able to raise the levels of GCase and could therefore be a disease-modifying treatment for PDD. The aims of this trial are to determine if Ambroxol is safe and well-tolerated by individuals with PDD and if Ambroxol affects cognitive, biochemical, and neuroimaging measures. METHODS: This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer's disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician's Global Impression of Change (CGIC). Secondary measures will include the Parkinson's disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson's disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes. DISCUSSION: If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.

Ultrasound Measurements of Fetal Thyroid: Reference Ranges from a Cohort of Low-Risk Pregnant Women.

BACKGROUND: Adequate thyroid function is essential for normal growth and development of the fetus. Sonographic recognition of alterations in fetal thyroid dimensions may be the first sign of thyroid dysfunction, permitting early diagnosis and intervention. The main goal of this study was to build curves with reference values for ultrasound measurements of the fetal thyroid from 14 to 40 weeks of gestation. METHODS: This is a prospective longitudinal study of 90 Brazilian pregnant women, complementary to a cohort multicentre study named "WHO multicentre study for the development of growth standards from fetal life to childhood: the fetal component." Pregnant women without any pre-existing conditions that might affect fetal growth received antenatal care from the first trimester until childbirth, undergoing serial ultrasound evaluations of the fetus, including the thyroid. Longitudinal, anteroposterior, and transverse diameters of both thyroid lobes were measured in the fetus. Fetal thyroid lobe volume was also estimated. By quantile regression analysis, reference curves of measurements were fitted according to the gestational age. RESULTS: A reference standard of thyroid growth was defined during pregnancy by fitting curves of its measurements. Reference values for the 10th, 50th, and 90th centiles of fetal thyroid measurements (longitudinal, anteroposterior, transverse diameters, and lobe volume) were defined, from 14 to 40 weeks of gestation. CONCLUSION: We provided a reference curve of optimal thyroid development in a low-risk population that can be used as a standard of comparison to diagnose deviations from the norm. In addition, we demonstrated an alternative and simplified method for early recognition of thyroid morphological alterations by an individualized technique to evaluate the thyroid lobes.