INCIDENTALLY VS. NON-INCIDENTALLY DIAGNOSED PAPILLARY THYROID CARCINOMA: ARE THERE DIFFERENCES?

Thyroid carcinoma (TC) incidence increased over the past 50 years. The explanation for this is not consensual. OBJECTIVE: Compare incidental vs. non-incidental TC (ITC vs. NITC) regarding demographic, clinical, histological data and 5-year clinical outcomes. DESIGN: Retrospective analysis of 225 papillary TC (PTC) cases that completed a 5-year follow-up. METHODS: Created 2 groups: ITC (including the incidentalomas) and NITC (cases of palpable or visible nodules or with thyroid compressive complaints). RESULTS: Included 225 PTC (122 were ITC). There were 95 women in ITC and 78 in NITC. ITC patients were significantly older (53.3±14.8 vs 47.2±17.7, p=0.006). Groups had no differences in family history of TC. ITC mean tumour size was smaller (19.1±9.2 vs 28.6±16.2, p<0.01). Tumours >20mm comprised 36.1% of ITC and 58.2% of NITC. We found no differences in tumour multifocality, histological thyroiditis, aggressive PTC subtypes, capsule or lymph-vascular invasion and gross extrathyroidal extension. There were no differences regarding the number of patients submitted to RAI or in RAI activity. pTMN staging showed higher prevalence of T3a and T4 cases (p<0.01), and M1 status (p=0.025) in NITC. There were no differences in the rates of persistence of disease. Logistic regression showed that the diagnostic modality had no impact on the 5-year clinical outcome. CONCLUSIONS: ITC patients were older and had smaller tumours. NITC showed no worst histological features or 5-year clinical outcome. Approximately, one third of ITC had diameters >20mm. As even large tumours can be ITC, overdiagnosis can be the most likely cause for the TC increasing incidence.

Head and neck cancer patient journey's health literacy: a multidisciplinary team perspective. VOICE study.

PURPOSE: Health literacy is a current Public Health priority in Portugal. The participation of well-informed patients in their care and shared decision making are essential, especially in chronic aggressive and debilitating pathologies such as recurrent or metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC). AIMS: This study aimed to characterize R/M HNSCC patients' and caregivers' information needs identified by healthcare professionals (HCPs). METHODS: Two online Focus Groups, one with only medical doctors and the other with other HCPs involved in the treatment of R/M HNSCC patients, were conducted, using a modified Metaplan, Lean or adapted PDCA methodology. The discussions were audio recorded in full and content analysis was performed using ATLAS.ti qualitative data analysis software. RESULTS: Topics addressed were diagnosis, treatment, quality of life, and global evaluation. In general, all experts agreed that only essential information should be cautiously given, according to patients' and caregivers' wishes. It was consensual that patients are given the necessary information to adhere to treatment. Two main barriers were identified: one barrier was associated with verbal communication due to the lack of health literacy of these patients, and the other barrier regarded healthcare access. It was also considered important to remind patients of the daily and social activities that they could and should maintain, as well as providing sufficient social resources and problem-solving training to caregivers. CONCLUSIONS: This qualitative study highlights the complexity of R/M HNSCC patients' care. Immediate availability of psychologists and psychiatrists should be implemented in all centers that treat HNSCC patients. The differences found between the physicians' Focus Group and other HCPs' Focus Group in some of the addressed topics emphasize the importance of a multidisciplinary and holistic approach, in a biomedical model integrated with a biopsychosocial model.

Clinical and molecular characterization of parathyroid carcinoma in multiple endocrine neoplasia type 1.

Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg/dL (8.4-10.2) and 472 pg/mL (12-65), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the MEN1 gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C>A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic MEN1 variant in the MEN1 gene, which is consistent with MEN1 tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of CDC73, GCM2, TP53, RB1, AKT1, MTOR, PIK3CA and CCND1 genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the MEN1 gene.

Ectopic Cushing's Syndrome Secondary to Acinic Cell Carcinoma of the Parotid Gland: A Case Report.

We present a case report of a patient with a rare high-grade transformation of an acinic cell carcinoma (ACC) of the parotid gland, who developed Cushing's syndrome (CS) as a result of ectopic secretion of adrenocorticotropic hormone by the tumour. The hypercortisolism was successfully treated with metyrapone, and the ACC was treated with local radiotherapy and a combined six cycles of gemcitabine and cisplatin, having achieved a partial response to the tumour. A multidisciplinary approach and combined medical treatment with radiotherapy and were essential for disease control and CS management. ACC should be considered in the differential diagnosis of ectopic CS.

Using Glyphosate on Guarana Seedlings in the Amazon.

The seed yield of guarana (Paullinia cupana H.B.K. var. sorbilis) is affected by weeds. Management is difficult for Amazon farmers and ranchers, owing to the hot and humid climate prevailing in the region, which makes mechanical control inefficient and leads farmers to the decision to use herbicides. Herbicide damage to this species is unknown. The objective of this study was to evaluate glyphosate damage to the development and quality of guarana seedlings. The treatments consisted of glyphosate doses at concentrations of 0, 126, 252, 540, 1080, 2160 and 3240 g a.e. ha-1 and were evaluated for 60 days, in two applications. Analyses were performed for biometrics, seedling development, anthracnose and Injury characteristics. Glyphosate caused symptoms of Injury in all doses applied, but lower doses did not interfere with seedling growth and development. There was a correlation between anthracnose severity and increased glyphosate dose. When applied correctly, glyphosate can be an integrated weed management tool for use in guarana crops.

Differentiated Thyroid Cancer in a Pediatric Population: Estimating the Risk of Recurrence and Evolution Over Time.

Background Differentiated thyroid cancer (DTC) is the most common endocrine cancer during childhood, and the prognosis is usually good. The 2015 American Thyroid Association (ATA) pediatric guidelines for DTC classify patients into three categories (low, intermediate, and high) that represent the risk for persistent/recurrent disease. The "Dynamic Risk Stratification" (DRS) System showed that, in adults, reassessment of disease status during follow-up was a better predictor of disease status at the end of follow-up when compared to ATA risk stratification. This system is still not validated for the pediatric population with DTC. Our aim was to evaluate the usefulness of the DRS system in predicting DTC disease behaviour in this specific population. We also aimed to evaluate potential clinical-pathological factors associated with persistent disease at the end of follow-up. Methods A retrospective analysis of 39 pediatric patients (≤18 years) with DTC was conducted in our institution between 2007 and 2018, including 33 patients who had follow-up ≥ 12 months; these were classified into ATA risk groups and re-stratified according to their response to treatment at 12-24 months of follow-up. The associations between the ordinal variables of the baseline ATA risk group and the disease status re-evaluated 12-24 months after diagnosis (as per the DRS system) and at the end of follow-up were evaluated using a linear-by-linear association test. Gender, age at diagnosis, tumor size, multicentricity, extrathyroid extension, vascular invasion, lymph node metastasis, distant metastasis, and stimulated thyroglobulin (sTg) during the first RAI administration were evaluated as potential factors associated with persistent disease at 27 months after diagnosis using Firth's bias-reduced penalized-likelihood logistic regression. Results In this study, 39 patients were retrospectively analyzed, including 33 patients who had follow-ups ≥ 12 months with a median time of 56 (27-139) months who were classified in ATA risk groups and then re-stratified depending on their response to treatment between 12 and 24 months of follow-up. There was a statistically significant association between ATA risk groups and re-evaluation at 12 and 24 months (p=0.001) and between these two stratifications and the state of disease at final follow-up (p<0.001 for both). Factors with a statistically significant association with persistent disease at 27 months of follow-up were male sex, lymph node metastases at diagnosis, distant metastasis, extrathyroidal extension, and stimulated Tg values. Conclusions The assessment of the response to treatment between 12 and 24 months and at the end of follow-up refines the initial ATA risk stratification, confirming that dynamic risk evaluation is also helpful in the pediatric population.

Clinical significance of papillary thyroid carcinoma with solid/trabecular growth.

OBJECTIVE: The clinical relevance of solid/trabecular (ST) growth in papillary thyroid carcinoma (PTC) is unclear. In this study, we investigated the impact of any amount of ST growth on tumour characteristics and patient outcomes. Furthermore, we evaluated whether ST growth per se affected patients' prognosis in the absence of aggressive features, namely vascular invasion. DESIGN: We analysed 222 PTC patients followed up for more than 5 years in the Department of Endocrinology of the Instituto Português de Oncologia de Lisboa Francisco Gentil from 2002 to 2020. All PTC cases with any percentage of ST growth were included and compared with PTC without ST growth (1:2). Carcinomas with high-grade features were excluded. RESULTS: There were 74 PTC cases with ST growth and 148 without ST growth (median follow-up of 9.3 years). PTC-ST was associated with larger tumour size (p = 0.001) and increased frequency of vascular invasion (p < 0.001) compared with PTC. However, PTC-ST did not exhibit a higher incidence of extrathyroidal extension (p = 1.000) or lymph node metastasis (p = 0.433). Despite the significantly higher prevalence of distant metastasis in PTC-ST compared with PTC (p = 0.043), the significance is lost when the cases with vascular invasion were excluded (p = 0.347). The total radioiodine activity was higher in PTC-ST than in PTC (p = 0.008). Recurrence rates were similar between groups (p = 0.755). The 10-year overall survival and disease-free survival rates for PTC-ST were 94.6% and 98.6%, respectively, similar to the PCT without ST growth (p = 0.097 and p = 0.333, respectively). There was no evidence of an association between the presence of an ST component (p = 0.201) with the risk of death or recurrence, whereas the presence of distant metastasis significantly increased the risk of these events (hazard ratio 10.14, p < 0.001). CONCLUSIONS: The presence of ST growth was associated with several aggressive clinicopathological features. However, the risk of cancer recurrence and death for PTC-ST were similar to PTC. In the absence of vascular invasion, the clinical impact of ST growth alone is negligible.

Endocrine complications after hematopoietic stem cell transplantation during childhood-Results from a close follow-up in a cohort of 152 patients.

CONTEXT: Haematopoietic stem cell transplantation (HSCT) is a therapeutic option for numerous haematologic diseases and solid tumours. Increasing indications for HSCT and reduction in associated mortality have been raising the number of paediatric HSCT survivors and their long-term toxicities. OBJECTIVE: To characterize the endocrine disorders developed after HSCT. DESIGN AND PATIENTS: Retrospective analysis of 152 patients submitted to HSCT in paediatric age with at least 24 months of follow-up at our endocrine late-effects clinics. RESULTS: Patients were followed up for 9.9 (interquartile range [IQR]: 12.2) years. The median age at HSCT was 7.5 (IQR: 9) years. At least one endocrine complication was observed in 65.1% of the patients. Primary hypogonadism was detected in 34.2%. Female gender (p < .001), HSCT > 10 years old (p = .01) and chemotherapy before HSCT (p < .001) were identified as risk factors for developing gonadal dysfunction. Growth hormone deficiency (GHD) occurred in 23.0% with a mean stature Z-score at diagnosis of -1.8 ± 1.4. GHD was associated with cranial (p < .001) and HSCT < 10 years old (p ≤ 0.001). Patients who were exposed to total body irradiation (TBI) were at higher risk for primary hypothyroidism (22.3%) (p = .01), thyroid nodules (17.1%) (p < .001), thyroid carcinoma (5.3%) (p < .001), dyslipidaemia (19.1%) (p < .001) and disturbance of carbohydrate metabolism (19.1%) (p < .001). CONCLUSION: At least one endocrine complication was diagnosed in 65.1% of patients, with gonadal dysfunction being the most prevalent. The conditioning regimen with TBI was a risk factor for the development of several endocrine disorders. This study is one of the largest series evaluating the endocrine disorders among survivors of paediatric HSCT and intends to reinforce the importance of routine follow-up of these patients.

Precocious and accelerated puberty in children with neurofibromatosis type 1: results from a close follow-up of a cohort of 45 patients.

PURPOSE: Central precocious puberty (CPP) in neurofibromatosis type 1 (NF1) occurs mainly in association with optic pathway glioma (OPG), but it can also develop in the absence of OPG. The aim of this study was to analyze the prevalence of puberty disorders in children with NF1 and its association with OPG and its location. METHODS: A retrospective study of 45 children with NF1 (68.9% boys) followed at our center between 2008 and 2020 was conducted. A cerebral MRI scan was performed in all children. We analyzed auxological, laboratory, and imaging data of children with CPP or accelerated puberty (AP). Treatments used for CPP/AP and their effect on height were also evaluated. RESULTS: The prevalence of puberty disorders in our cohort was 17.8% (male to female ratio of 7:1). CPP and AP were diagnosed in 8/45 (17.8%) NF1 children. Among children with puberty disorders, 5/8 (62.5%) had an OPG with chiasm involvement, 1/8 (12.5%) had an isolated optic nerve tumor, and 2/8 (25%) did not have any evidence of OPG on MRI. Fisher's exact test showed an association between CPP/AP and chiasm OPG (p = 0.025). Treatment with triptorrelin was initiated in 5/8 children, of whom four attained final predicted height. CONCLUSION: Our study confirms the higher prevalence of CPP/AP in NF1 patients, as well as an association between chiasm OPG and puberty disorders. However, CPP/AP also occurred in the absence of OPG with an incidence of 9.1%. Comprehensive evaluation of every child with NF1 regardless of the presence of OPG is therefore essential.

Ocular Sarcoidosis and Autoimmune Polyglandular Syndrome Type 2: A Case Report.

PURPOSE: to describe a clinical case of ocular sarcoidosis in a patient with Autoimmune Polyglandular Syndrome Type 2 (APS-2). METHODS: an 86-year-old female diagnosed with APS-2 was referred to our uveitis department with rapid visual loss in her left eye during a 3-month period. Her best-corrected visual acuity (BCVA) was counting fingers in her left eye (OS) and 20/40 in her right eye (OD). Slit-lamp biomicroscopy was unremarkable OD but revealed granulomatous keratic precipitates OS. Fundoscopy revealed bilateral optic disc oedema and +2 and 4+ vitritis (SUN classification) in her OD and OS, respectively. RESULTS: the patient underwent chest X-Ray which revealed bilateral hilar lymphadenopathy and fibrosis. On high-resolution computed tomography of the lungs, ground-glass opacities were visible, and a diagnosis of ocular sarcoidosis was presumed. After exclusion of infectious diseases, the patient was treated with methotrexate and oral corticosteroids and there was substantial improvement of the optic nerve oedema and vitritis. At the most recent visit, 2 years later, OS BCVA was 20/50. CONCLUSION: There may be an association between ocular sarcoidosis and APS or other autoimmune disorders.

Encapsulation of the septal cell wall protects Streptococcus pneumoniae from its major peptidoglycan hydrolase and host defenses.

Synthesis of the capsular polysaccharide, a major virulence factor for many pathogenic bacteria, is required for bacterial survival within the infected host. In Streptococcus pneumoniae, Wze, an autophosphorylating tyrosine kinase, and Wzd, a membrane protein required for Wze autophosphorylation, co-localize at the division septum and guarantee the presence of capsule at this subcellular location. To determine how bacteria regulate capsule synthesis, we studied pneumococcal proteins that interact with Wzd and Wze using bacterial two hybrid assays and fluorescence microscopy. We found that Wzd interacts with Wzg, the putative ligase that attaches capsule to the bacterial cell wall, and recruits it to the septal area. This interaction required residue V56 of Wzd and both the transmembrane regions and DNA-PPF domain of Wzg. When compared to the wild type, Wzd null pneumococci lack capsule at midcell, bind the peptidoglycan hydrolase LytA better and are more susceptible to LytA-induced lysis, and are less virulent in a zebrafish embryo infection model. In this manuscript, we propose that the Wzd/Wze pair guarantees full encapsulation of pneumococcal bacteria by recruiting Wzg to the division septum, ensuring that capsule attachment is coordinated with peptidoglycan synthesis. Impairing the encapsulation process, at localized subcellular sites, may facilitate elimination of bacteria by strategies that target the pneumococcal peptidoglycan.

Parathyroid carcinoma: Single centre experience.

OBJECTIVE: Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature. DESIGN: Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021. RESULTS: Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and mean PTH of 1173 pg/ml (276-2500). Hyperparathyroidism-mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5-year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1. CONCLUSION: Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.

Predictive factors for thyroid complications after radiation therapy-data from a cohort of cancer patients closely followed since they were irradiated.

INTRODUCTION: Cancer survivors are at an increased risk of adverse outcomes, including thyroid neoplasms, given the high radiosensitivity of this gland. The aim of this study is to assess the incidence and timeframe of thyroid complications in cancer patients, followed systematically since their radiation therapy, and to identify risk factors for the development of hypothyroidism and thyroid cancer. METHODS: We performed a retrospective study, including 282 subjects, who received neck, craniospinal, or total body irradiation (TBI). Patients were grouped into four primary diagnostic clusters: leukaemia, Hodgkin's disease, central nervous system, and head and neck tumours. RESULTS: Hypothyroidism was observed in 56.7% of patients, on average 6.8 ± 5.9 years after the treatment. Neck and craniospinal irradiation presented a 3.5-fold increased risk for the development of hypothyroidism compared to TBI. Papillary thyroid cancer was diagnosed in 8.5% of the patients, on average, 18.5 ± 4.9 years after radiotherapy (RT). Female gender, younger age, and lower irradiation doses were independently associated with thyroid cancer development. CONCLUSION: Our study provides useful information about the risk of hypothyroidism and thyroid cancer after RT, as it was performed in a cohort of patients closely followed since the oncological therapies, and, thus, may give new insights into the follow-up management of these patients.

Flash glucose monitoring and glycemic control in type 1 diabetes with subcutaneous insulin infusion.

AIMS: To analyze the association between scan frequency and glycemic measures in continuous subcutaneous insulin infusion (CSII) treated type 1 diabetes (T1DM) adults. METHODS: This retrospective study included 140 patients (> 18 years) with T1DM who used flash glucose monitoring (FGM). For each patient, we analyzed the Ambulatory Glucose Profile data over a period of 90 days. Data regarding glucose management indicator (GMI), time above, below and within range (TIR) and coefficient of variation (CV) were correlated with the number of daily scans. The effect of each additional test on glucose parameters was also evaluated. RESULTS: Users performed a mean of 8.6 ± 4.4 scans per day. There was an inverse correlation between scanning frequency and GMI (r = - 0.431, p < 0.001), CV (r = - 0.440, p < 0.001), time above and below range (r = - 0.446, p < 0.001 and r = - 0.200, p = 0.018, respectively). The number of daily scans correlated positively with TIR (r = 0.554, p < 0.001). For each additional scan per day, the mean GMI decreased 0.09% and TIR increased 1.60%. CONCLUSIONS: In patients with T1DM and CSII, higher rates of scanning correlated with improved glycemic markers, including reduced GMI and CV and increased TIR. For each test performed, there was a significant effect on the improvement of all glucose parameters.

Mediastinal Thyroid Carcinoma and Graves' Disease: A Rare Presentation.

BACKGROUND: Mediastinal thyroid carcinoma is extremely rare, with few cases reported in the literature. Case Report. A 73-year-old man presented with weight loss for 6 months. Imaging by computed tomography (CT) documented a large mediastinal mass below the thyroid gland and pulmonary metastases. Neck ultrasound found two spongiform nodules in the right thyroid lobe, and fine-needle aspiration citology (FNAC) of these nodules revealed they are benign. Endobronchial ultrasound-guided needle biopsy of the mediastinal mass was compatible with papillary thyroid cancer. A few weeks later, the patient developed overt hyperthyroidism due to Graves' disease, which was treated with antithyroid drugs. 99mPertechnetate scintigraphy showed increased diffuse uptake in the thyroid parenchyma but the absence of uptake in the paratracheal mass and in the lung nodules. The patient was not considered eligible for surgical intervention or therapy with tyrosine kinase inhibitor due to tracheal and mediastinal vessel invasion and was treated with palliative radiotherapy. Two months later, restaging PET-FDG showed an intense uptake in the right lobe of the thyroid gland, lymph nodes, lungs, bone, muscle, myocardial, kidney, and adrenal gland. CONCLUSION: In this case, thyroid carcinoma presented as a mediastinal mass with concurrent hyperthyroidism due to Graves' disease. Although uncommon, the clinicians should be aware of these situations. Obtaining a prompt histological examination of an intrathoracic mass is crucial to ensure an early diagnosis and treatment.

A novel TRPM6 variant (c.3179T>A) causing familial hypomagnesemia with secondary hypocalcemia.

SUMMARY: Familial hypomagnesemia with secondary hypocalcemia (FHSH) is a rare autosomal recessive disorder (OMIM# 602014) characterized by profound hypomagnesemia associated with hypocalcemia. It is caused by mutations in the gene encoding transient receptor potential cation channel member 6 (TRPM6). It usually presents with neurological symptoms in the first months of life. We report a case of a neonate presenting with recurrent seizures and severe hypomagnesemia. The genetic testing revealed a novel variant in the TRPM6 gene. The patient has been treated with high-dose magnesium supplementation, remaining asymptomatic and without neurological sequelae until adulthood. Early diagnosis and treatment are important to prevent irreversible neurological damage. LEARNING POINTS: Loss-of-function mutations of TRPM6 are associated with FHSH. FHSH should be considered in any child with refractory hypocalcemic seizures, especially in cases with serum magnesium levels as low as 0.2 mM. Normocalcemia and relief of clinical symptoms can be assured by administration of high doses of magnesium. Untreated, the disorder may be fatal or may result in irreversible neurological damage.

Case Report: Sarcoidosis mimicking head and neck cancer progression.

Several case reports have been published describing the coexistence of sarcoidosis and cancer. In the literature, simultaneous occurrence of head and neck cancer and sarcoidosis is rarely reported. In this paper we present a case of a 42-year-old man with squamous cell carcinoma of the oral cavity, locally advanced, which after surgery and adjuvant radiotherapy developed local persistence and progression in the mediastinal lymph nodes. The patient was submitted to chemotherapy and after a complete response, new suspicious mediastinal and hilar lymph nodes appeared in the thoracic computed tomography (CT) scan and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) scan. To enroll the patient in a clinical trial, the patient underwent mediastinoscopy with mediastinal lymph node dissection. The histopathological findings were consistent with sarcoidosis and no metastatic disease was found. Since the patient had no symptoms and the levels of serum angiotensin converting enzyme were normal, no further pharmacological intervention was done. After 4 years of follow up the patient remains without evidence of cancer. This case shows that although imagological techniques (CT and FDG-PET scan) are extensively used to assess the tumor response, false-positive cases can occur. Whenever it is possible a biopsy of the suspected metastatic site should always be performed.

Mucoadhesive chitosan-coated solid lipid nanoparticles for better management of tuberculosis.

Taking into consideration the potential mucoadhesion properties of systems in lung delivery, this paper describes the preparation and characterization of chitosan-coated solid lipid nanoparticles (C-SLNs) loaded with rifampicin (RIF) as anti-tuberculosis (anti-TB) drug. The process of development and characterization of the NPs in terms of size, surface charge, encapsulation efficiency (EE), morphology, in vitro drug release, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), in vitro assessment of mucoadhesive property, cell viability and permeability studies are documented. Results showed that the SLNs had a smooth spherical shape with a size of ca. 245-344 nm and with a zeta potential around -30 mV for SLNs and +40 mV for C-SLNs. The surface charge variation from negative to positive charge and FTIR analysis demonstrated the successful process of coating the nanoparticles (NPs) surface with chitosan. The DSC thermograms were in agreement with the nanostructure of the SLNs. The EE of drug was found to be higher than 90% and the loading capacity (LC) around 4.5%. C-SLNs show higher in vitro muchoadesive properties and a higher permeability in alveolar epithelial cells A549 than uncoated SLNs, indicating that the developed C-SLNs can be used as a promising carrier for sasfer and efficient management of TB.

Absence of Tau triggers age-dependent sciatic nerve morphofunctional deficits and motor impairment.

Dementia is the cardinal feature of Alzheimer's disease (AD), yet the clinical symptoms of this disorder also include a marked loss of motor function. Tau abnormal hyperphosphorylation and malfunction are well-established key events in AD neuropathology but the impact of the loss of normal Tau function in neuronal degeneration and subsequent behavioral deficits is still debated. While Tau reduction has been increasingly suggested as therapeutic strategy against neurodegeneration, particularly in AD, there is controversial evidence about whether loss of Tau progressively impacts on motor function arguing about damage of CNS motor components. Using a variety of motor-related tests, we herein provide evidence of an age-dependent motor impairment in Tau-/- animals that is accompanied by ultrastructural and functional impairments of the efferent fibers that convey motor-related information. Specifically, we show that the sciatic nerve of old (17-22-months) Tau-/- mice displays increased degenerating myelinated fibers and diminished conduction properties, as compared to age-matched wild-type (Tau+/+) littermates and younger (4-6 months) Tau-/- and Tau+/+ mice. In addition, the sciatic nerves of Tau-/- mice exhibit a progressive hypomyelination (assessed by g-ratio) specifically affecting large-diameter, motor-related axons in old animals. These findings suggest that loss of Tau protein may progressively impact on peripheral motor system.