Search

Abstract Purpose Bariatric surgery (BS), an effective treatment for severe obesity and its comorbidities, may result in micronutrient and vitamin deficiencies. This monocentric prospective observational study aimed at evaluating the efficacy of a specifically designed vitamin/mineral formula (Bariatrifast, BIOITALIA S.r.l., Italy) for preventing and treating micronutrient deficiencies in patients submitted to BS. Methods Twenty patients with severe obesity (mean weight and BMI: 123.5 kg (range 88–174) and 43.3 kg/m2 (range 37–54) respectively) underwent BS (10 vertical sleeve gastrectomy VSG, 10 Roux-en-Y gastric bypass, RYGB). The mean age was 49.9 years (range 27–68). After a presurgical visit (V0), follow-up visits were performed at 1, 3, 6 and 12 months after surgery (V1–V4). Recorded data included weight, height and BMI. A complete blood count, measurement of ferritin, folic acid, vitamin B12, ionized calcium, 25 OH vitamin D, parathyroid hormone (PTH) were obtained. Following BS, patients started the daily oral multivitamin and mineral supplement. Results All patients achieved a significant weight loss (mean − 34.7 ± 11.8 kg). No deficiencies of various vitamins/micronutrients were detected during the entire study period. The serum concentrations of vitamin B12, 25-OH Vitamin D and folic acid increased over the follow-up period compared with V0 (mean increase 243 ng/L, 23 µg /L, 8 µg/L, respectively). Compared to RYGB, patients who underwent sleeve gastrectomy showed higher levels of 25-OH vitamin D at V2, V3 and V4 (all p

Pluvial flash flooding (PFF) is a growing hazard facing cities around the world as a result of rapid urbanization and more intense precipitation from global warming, particularly for low-resourced settings in developing countries. We present collaborative modeling (CM) as an iterative process to meet diverse decision-making needs related to PFF through the co-production of flood hazard models and maps. CM resulted in a set of flood hazard maps accessible through an online viewer that end-users found useful and useable for understanding PFF threats, including debris blockages and barriers to mobility and evacuation. End-users of information included individuals concerned with general flood awareness and preparedness, and involved in infrastructure and emergency management, planning, and policy. CM also showed that rain-on-grid hydrodynamic modeling is needed to depict PFF threats in ways that are intuitive to end-users. These outcomes evidence the importance and transferability of public health rationale for community-based research and principles used here including recognizing community as a unit of identity, building on strengths of the community, and integrating knowledge for the benefit of all partners.

Existing needs to manage flood risk in the United States are underserved by available flood hazard information. This contributes to an alarming escalation of flood impacts amounting to hundreds of billions of dollars per year and countless disrupted lives and affected communities. Making information about flood hazards useful for the range of decisions that dictate the consequences of flooding poses many challenges. Here, we describe collaborative flood modeling, whereby researchers and end-users at two coastal sites co-develop fine-resolution flood hazard models and maps responsive to decision-making needs. We find, first of all, that resident perception and awareness of flooding are enhanced more by fine-resolution depth contour maps than Federal Emergency Management Agency (FEMA) flood hazard classification maps and that viewing fine-resolution depth contour maps helps to minimize differences in flood perception across subgroups within the community, generating a shared understanding. We also find that collaborative flood modeling supports the engagement of a wide range of end-users in contemplating the risks of flooding and provides strong evidence that the co-produced knowledge can be readily adopted and applied for Flood Risk Management (FRM). Overall, collaborative flood modeling advances FRM by providing multiple points of entry for diverse groups of end-users to contemplate the spatial extent, intensity, timing, chance, and consequences of flooding, thus enabling the web of decision-making related to flooding to be better informed with the best available science. This transdisciplinary approach emphasizes vulnerability reduction and is complementary to FEMA Flood Insurance Rate Maps used for flood insurance administration.

Introduction: Medullary thyroid cancer (MTC) is a rare endocrine tumor, which can be sporadic or familial, as a component of multiple endocrine neoplasia 2 (MEN2). Overall, 10% of MTC cases have already developed at presentation or will develop metastasis during follow-up. Testicular metastases are exceptional and only one case of unilateral testis involvement by metastatic MTC has been already reported in literature. We described the first known case of asymptomatic bilateral testicu lar MTC metastases, discovered incidentally at testicular ultrasound (US) performed for unrelated reasons. Case presentation: A Latin American 32-year-old man with MEN 2A syndrome and metastatic MTC underwent andrological and urological examination due to premature ejaculation. US imaging showed two symmetrical hypoechoic lesions involving both testes. Suspecting a bilateral testicular cancer, the patient underwent excision biopsy of both testicular lesions. Histopathology and immunohistochemical examinations documented metastatic MTC of both testicular lesions. Conclusion: Beyond its rarity, testis should be considered as a potential metastatic site of MTC, especially in patients with advanced disease.

Understanding the impact of digital, interactive flood hazard maps and flood control systems on public flood risk perception could enhance risk communication and management. This study analyzed a survey of residents living near California’s Newport Bay Estuary and found that self-rated nonspatial perceptions of dread or concern over future flood impacts were positively associated with spatial awareness of flood-prone areas. Trust in flood control systems was associated with greater spatial flood hazard awareness but weaker nonspatial dread or concern, suggesting residents who witnessed and trust flood control systems developed a confident sense of flood-prone areas and that this confidence reduced the overall nonspatial sense of flood dread and concern. Viewing a flood hazard map eliminated differences in spatial hazard awareness between subgroups that existed prior to viewing a map, and viewing a map with estimated flood depth and greater spatial differentiation was associated with higher levels of postmap spatial awareness.

Thyroid cancer is the most common malignancy of the endocrine system. Fine-needle aspiration (FNA) biopsy of thyroid nodules has become the gold standard procedure, in terms of cost and efficacy, for guiding clinicians towards appropriate patients’ management. One challenge for cytopathologists is to accurately classify cytological specimens as benign or malignant based on cytomorphological features. In fact, with a frequency ranging from 10% to 30%, nodules are diagnosed as indeterminate. In recent years, the mutational landscape of thyroid tumors has been extensively described, and two molecular profiles have been identified: RAS-like (NRAS, HRAS, and KRAS mutations; EIF1AX mutations; BRAF K601E mutation; and PPARG and THADA fusions) and BRAFV600E-like (including BRAFV600E mutation and RET and BRAF fusions). The purpose of this review is to discuss the latest molecular findings in the context of indeterminate thyroid nodules, highlighting the role of molecular tests in patients’ management.

Objectives: This study is aimed to report a case of SV-related gastritis and the results of a systematic literature review of SV infections. Methods: Following a case presentation, we systematically searched different databases (MEDLINE, PubMed, Scopus, Web of Science, EMBASE, google scholar) for the items “sarcina,” “ventriculi,” “clostridium” with AND/OR. Results: A total of 55 articles reporting 65 cases of Sarcina Ventriculi were found. Thus, 66 patients, including our case, were reviewed. The median age was 51 years (IQR: 0-87 years). Females accounted for 51% of cases. 68% of patients had one or more comorbidities. SV was isolated in the gastrointestinal tract (88%), respiratory (5%), urine (4%), and bloodstream (3%) systems. Upper endoscopy was performed in 52 patients (79%). Biopsies were obtained in all 52 cases and were normal in 23%. Surgery was warranted in 15 patients (23%), and specific antimicrobial therapy was delivered in 34 (52%) patients. Mortality was 14%. At follow-up, 88% of patients showed complete eradication of the SV infection. Conclusions: Upper gastrointestinal biopsy positive for SV should prompt an evaluation of the clinical conditions, considering the risk of gastric perforation is not negligible. Antibiotic therapy may eradicate the infection and prevent complications. Emergency surgery is required in case of source control.

Flood hazard mapping in the United States (US) is deeply tied to the National Flood Insurance Program (NFIP). Consequently, publicly available flood maps provide essential information for insurance purposes, but they do not necessarily provide relevant information for non-insurance aspects of flood risk management (FRM) such as public education and emergency planning. Recent calls for flood hazard maps that support a wider variety of FRM tasks highlight the need to deepen our understanding about the factors that make flood maps useful and understandable for local end users. In this study, social scientists and engineers explore opportunities for improving the utility and relevance of flood hazard maps through the co-production of maps responsive to end users' FRM needs. Specifically, two-dimensional flood modeling produced a set of baseline hazard maps for stakeholders of the Tijuana River valley, US, and Los Laureles Canyon in Tijuana, Mexico. Focus groups with natural resource managers, city planners, emergency managers, academia, non-profit, and community leaders refined the baseline hazard maps by triggering additional modeling scenarios and map revisions. Several important end user preferences emerged, such as (1) legends that frame flood intensity both qualitatively and quantitatively, and (2) flood scenario descriptions that report flood magnitude in terms of rainfall, streamflow, and its relation to an historic event. Regarding desired hazard map content, end users' requests revealed general consistency with mapping needs reported in European studies and guidelines published in Australia. However, requested map content that is not commonly produced included (1) standing water depths following the flood, (2) the erosive potential of flowing water, and (3) pluvial flood hazards, or flooding caused directly by rainfall. We conclude that the relevance and utility of commonly produced flood hazard maps can be most improved by illustrating pluvial flood hazards and by using concrete reference points to describe flooding scenarios rather than exceedance probabilities or frequencies.

This article examines how municipal planning contexts can shape urban land use dynamics by investigating the parcel-level land use changes in a five-county Southern California metropolitan area between 1990 and 2005. An analysis, based on a multinomial logit model, shows that land use change patterns significantly vary by municipalities that were situated in heterogeneous planning contexts. More specifically, cities with limited ability to expand their jurisdictional boundaries are found to provide more recreational areas and urban open spaces, while restricting nonconventional land uses. However, no evidence of a shift from single-family to multifamily residential development is detected for such cities.

In molecular pathology, predictive biomarkers identify which patients are likely to respond to targeted drugs. These therapeutic agents block specific molecules directly involved in cancer growth, dedifferentiation and progression. Until few years ago, the only targeted drugs available for advanced thyroid cancer included multi-tyrosine kinase inhibitors, mainly targeting the MAPK pathway and the angiogenic signaling. The administration of these drugs does not necessarily require a molecular characterization of tumors to assess the presence of predictive alterations. However, the availability of new selective targeted drugs for thyroid cancer patients is changing the diagnostic strategies for the molecular characterization of these tumors. The search for targetable alterations can be performed directly on tumor tissue by using a variety of methodologies, depending also on the number and type of alterations to test (i.e. single nucleotide variation or gene rearrangement). Herein, a comprehensive review of the currently available targeted treatments for thyroid cancer, related predictive markers and testing methodologies is provided.

Abstract On January 2020, the WHO Director General declared that the outbreak constitutes a Public Health Emergency of International Concern. The world has faced a worldwide spread crisis and is still dealing with it. The present paper represents a white paper concerning the tough lessons we have learned from the COVID-19 pandemic. Thus, an international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making. With the present paper, international and heterogenous multidisciplinary panel of very differentiated people would like to share global experiences and lessons with all interested and especially those responsible for future healthcare decision making.

Abstract. Flood hazard mapping in the United States (US) is deeply tied to the National Flood Insurance Program (NFIP). Consequently, publicly available flood maps provide essential information for insurance purposes, but do not necessarily provide relevant information for non-insurance aspects of flood risk management (FRM) such as public education and emergency planning. Recent calls for flood hazard maps that support a wider variety of FRM tasks highlight the need to deepen our understanding about the factors that make flood maps useful and understandable for local end-users. In this study, social scientists and engineers explore opportunities for improving the utility and relevance of flood hazard maps through the co-production of maps responsive to end-users' FRM needs. Specifically, two-dimensional flood modeling produced a set of baseline hazard maps for stakeholders of the Tijuana River Valley, US, and Los Laureles Canyon in Tijuana, Mexico. Focus groups with natural resource managers, city planners, emergency managers, academia, non-profit, and community leaders refined the baseline hazard maps by triggering additional modeling scenarios and map revisions. Several important end-user preferences emerged, such as (1) legends that frame flood intensity both qualitatively and quantitatively, and (2) flood scenario descriptions that report flood magnitude in terms of rainfall, streamflow, and its relation to an historic event. Regarding desired hazard map content, end-users' requests revealed general consistency with mapping needs reported in European studies and guidelines published in Australia. However, requested map content that is not commonly produced included: (1) standing water depths following the flood, (2) the erosive potential of flowing water, and (3) pluvial flood hazards, or flooding caused directly by rainfall. We conclude that the relevance and utility of commonly produced flood hazard maps can be most improved by illustrating pluvial flood hazards and by using concrete reference points to describe flooding scenarios rather than exceedance probabilities or frequencies.

Background/objectivesIn animal models, a role in the regulation of energy expenditure (EE) has been ascribed to sphingolipids, active components of cell membranes participating in cellular signaling. In humans, it is unknown whether sphingolipids have a role in the modulation of EE and, consequently, influence weight gain. The present study investigated the putative association of EE and weight gain with sphingolipid levels in the human skeletal muscle, a component of fat-free mass (the strongest determinant of EE), in adipose tissue and plasma.Subjects/methodsTwenty-four-hour EE, sleeping metabolic rate (SMR) and resting metabolic rate (RMR) were assessed in 35 healthy Native Americans of Southwestern heritage (24 male; 30.2±7.73 years). Sphingolipid (ceramide, C; sphingomyelin, SM) concentrations were measured in skeletal muscle tissue, subcutaneous adipose tissue and plasma samples. After 6.68 years (0.26-12.4 years), follow-up weights were determined in 16 participants (4 females).ResultsConcentrations of C24:0, SM18:1/26:1 and SM18:0/24:1 in muscle were associated with 24-h EE (r=-0.47, P=0.01), SMR (r=-0.59, P=0.0008) and RMR (r=-0.44, P=0.01), respectively. Certain muscle sphingomyelins also predicted weight gain (for example, SM18:1/23:1, r=0.74, P=0.004). For specific muscle sphingomyelins that correlated with weight gain and EE (SM18:1/23:0, SM18:1/23:1 and SMR, r=-0.51, r=-0.41, respectively, all P

A statistically significant higher prevalence of the RET p.Met918Thr somatic mutation, identified by direct sequencing, was previously reported in MTC > 2 cm than in smaller tumors. Aim of this study was to correlate the full RET and RAS mutation profile, identified by a Next Generation Sequencing approach, with the growth rate, proliferation and tumor size of MTC. Data of 149 sporadic MTC patients were correlated with RET mutations and Ki67 positivity. Eighty-one cases had a somatic RET mutation, 40 had a RAS mutation and 28 were negative. A statistically significant higher prevalence of RET mutations was found in MTC > 2 cm. A higher prevalence of RET more aggressive mutations, higher allelic frequencies and, higher percentage of Ki67 positive cells were found in larger tumors which had also a worse outcome. Our study highlights the predom inant role of RET somatic mutations in MTC tumorigenesis. We demonstrate that RET mutation prevalence and allelic frequency (AF) are significantly higher in larger tumors. Based on these results, we can conclude that RET mutated C-cells’s growth and proliferation are more rapid than those of non-mutated cells and give origin to bigger and more aggressive MTC.

BackgroundLarge thyroid masses, particularly if rapidly growing, are often characterized by compression and infiltration of the vital structures of the neck. Therefore, an early and precise diagnosis, not only of malignancy but also of histotype, is mandatory to set up the right therapy. The aim of this study was to evaluate the diagnostic performance of fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) in this setting.Patients and MethodsWe prospectively evaluated 95 patients with large and rapidly growing thyroid masses admitted to the University Hospital of Pisa between April 2014 and January 2020. All patients were submitted to FNAC and CNB in the same session. The ability of both procedures to diagnose the malignancy of the lesions, particularly the histotype, and to obtain sufficient material to perform molecular analysis was evaluated.ResultsFNAC obtained adequate tumor sample to reach a diagnosis in 76 of 95 (80%) patients, while a higher percentage was obtained with CNB (92/95, 96.8%). FNAC was able to identify the malignancy of the lesion in 74 of 95 (77.9%) cases, but only in 16 of 74 (21.6%) cases was it able to define the histotype. CNB was able to define the malignancy of the lesion in all but three cases (92/95, 96.8%), and in all specimens, the histotype was identified. Moreover, in all cases, the material extracted from CNB was optimal to perform molecular analysis. No surgery-related complications were experienced with both procedures.ConclusionsCNB is a rapid and safe procedure with higher performance compared to FNAC in identifying the histotype of large and rapidly growing thyroid masses. Moreover, adequate material can be obtained to characterize the molecular profile for the treatment of potentially lethal cancers. In the era of precision medicine, CNB should be introduced in routine clinical practice as a key procedure for an early diagnosis and therapy of these diseases.

Papillary thyroid carcinoma (PTC) with hobnail areas above 30% is classified as hobnail variant (HVPTC). Although it is widely accepted that HVPTC has a worse outcome than classical PTC, it is unclear whether PTC with hobnail features below 30% is as aggressive as HVPTC. We gathered the largest mono-institutional series of PTC with hobnail areas and HVPTC to evaluate differences in terms of pathological features of aggressiveness, molecular profile, and treatment outcome. A total of 99 PTC with hobnail features above 5% were retrospectively selected; 34 of them met the criteria for HVPTC (0.4% of all PTC diagnosed at our institution). All tumors showed high rates of extra-thyroidal extension (40.4%), lymph node metastasis (68.1% of patients with lymphadenectomy), and vascular emboli (49.5%), with no differences according to the 30% cutoff. On the other hand, distant metastases were present in HVPTC only (9.4%). Also, advanced age, advanced disease stage, and TERT promoter mutation were associated with HVPTC. More than half of the patients with follow-up had structural or biochemical persistence after 1 year from surgery. Structural persistence was significantly more common in patients with HVPTC (37.5% vs. 8.7%), while no differences were observed considering structural and biochemical persistence together. The presence of hobnail features identifies locally aggressive tumors, and, consequently, it should be always acknowledged in the pathological report. However, tumors with more than 30% hobnail areas frequently present TERT promoter mutations, advanced disease stage, and structural persistence after radioiodine ablation.

Public participation geographic information systems (PPGIS) have been increasingly used to assess resident spatial knowledge of environmental hazards and to validate and supplement expert estimates of hazardous areas with local knowledge, but few studies have demonstrated methods for directly comparing local and expert knowledge of the spatial distribution of hazards. This study collected PPGIS digital sketch maps of flood-prone areas from 166 residents living adjacent to the Newport Bay Estuary in Southern California to examine variations in spatial knowledge of flood risk. First, we assessed agreement among participants and found that residents of areas with a higher percentage of homeowner, older, and higher income residents had greater agreement regarding areas at risk of flooding. Second, we introduced composite indices to assess the agreement between participant sketches of flood-prone areas with modeled estimates of the distribution of flood hazards, and found that the level of agreement between local and expert knowledge varied by the scale of analysis and by personal and contextual factors. Respondents with higher educational attainment, household income, and homeownership were associated with greater agreement between resident sketch maps and expert estimates of hazardous areas. Results inform spatial aspects of flood risk planning and communication by demonstrating how digital sketch maps can be used to identify potential shortcomings of expert hazard models, as well as hazardous areas where resident risk perception may be weak.

Public participation geographic information systems (PPGIS) have been increasingly used to assess resident spatial knowledge of environmental hazards and to validate and supplement expert estimates of hazardous areas with local knowledge, but few studies have demonstrated methods for directly comparing local and expert knowledge of the spatial distribution of hazards. This study collected PPGIS digital sketch maps of flood-prone areas from 166 residents living adjacent to the Newport Bay Estuary in Southern California to examine variations in spatial knowledge of flood risk. First, we assessed agreement among participants and found that residents of areas with a higher percentage of homeowner, older, and higher income residents had greater agreement regarding areas at risk of flooding. Second, we introduced composite indices to assess the agreement between participant sketches of flood-prone areas with modeled estimates of the distribution of flood hazards, and found that the level of agreement between local and expert knowledge varied by the scale of analysis and by personal and contextual factors. Respondents with higher educational attainment, household income, and homeownership were associated with greater agreement between resident sketch maps and expert estimates of hazardous areas. Results inform spatial aspects of flood risk planning and communication by demonstrating how digital sketch maps can be used to identify potential shortcomings of expert hazard models, as well as hazardous areas where resident risk perception may be weak.

ImportanceAlthough growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.ObjectiveTo evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.Design, setting, and participantsInternational, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.Main outcomes and measuresFrequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.ResultsConsensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.Conclusions and relevanceThyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.

The communication of information about natural hazard risks to the public is a difficult task for decision makers. Research suggests that newer forms of technology present useful options for building disaster resilience. However, how effectively these newer forms of media can be used to inform populations of the potential hazard risks in their community remains unclear. This research uses primary data from an in-person survey of 164 residents of Newport Beach, California during the spring of 2014 to ascertain the current and preferred mechanisms through which individuals receive information on flood risks in their community. Factor analysis of survey data identified two predominant routes of dissemination for risk information: older traditional media and newer social media sources. A logistic regression model was specified to identify predictors for choosing a particular communication route. This analysis revealed that age is the central factor in predicting the sources people use to receive risk information. We follow the analysis by discussing this finding and its policy implications.

The communication of information about natural hazard risks to the public is a difficult task for decision makers. Research suggests that newer forms of technology present useful options for building disaster resilience. However, how effectively these newer forms of media can be used to inform populations of the potential hazard risks in their community remains unclear. This research uses primary data from an in-person survey of 164 residents of Newport Beach, California during the spring of 2014 to ascertain the current and preferred mechanisms through which individuals receive information on flood risks in their community. Factor analysis of survey data identified two predominant routes of dissemination for risk information: older traditional media and newer social media sources. A logistic regression model was specified to identify predictors for choosing a particular communication route. This analysis revealed that age is the central factor in predicting the sources people use to receive risk information. We follow the analysis by discussing this finding and its policy implications.

Patients with advanced thyroid cancer harboring NTRK rearrangements can be treated with highly effective selective inhibitors. Immunohistochemistry (IHC) analysis, to detect Trk protein expression, represents an appealing screening strategy for NTRK rearrangements, but its efficacy has been poorly explored in thyroid cancer. The aim of this study is to investigate the diagnostic utility of Trk IHC in the identification of NTRK rearrangements. A series of 26 follicular-derived thyroid tumors, positive for NTRK rearrangements, and 28 NTRK fusion-negative controls were retrospectively analyzed by IHC using the pan-Trk monoclonal antibody (clone EPR17341) on the Ventana system. Area under the curve (AUC), sensitivity and specificity were calculated by ROC analysis. Trk expression was detected in 25 samples, including 22 out of the 26 NTRK-rearranged (84.6%) and three out of 28 NTRK-negative samples (10.7%). Four out of twenty-six NTRK-rearranged thyroid tumors were negative for Trk expression (15.4%), all carrying the ETV6/NTRK3 fusion. The AUC, sensitivity and specificity were 0.87, 0.85 and 0.89, respectively. A screening based on IHC analysis showed limited sensitivity and specificity in the identification of NTRK-rearranged tumors. Since falsely negative results could preclude the administration of effective targeted drugs, alternative detection strategies should be considered for thyroid cancer.

Direct evidence in humans for the impact of the microbiome on nutrient absorption is lacking. We conducted an extended inpatient study using two interventions that we hypothesized would alter the gut microbiome and nutrient absorption. In each, stool calorie loss, a direct proxy of nutrient absorption, was measured. The first phase was a randomized cross-over dietary intervention in which all participants underwent in random order 3 d of over- and underfeeding. The second was a randomized, double-blind, placebo-controlled pharmacologic intervention using oral vancomycin or matching placebo ((https://clinicaltrials.gov/ct2/show/NCT02037295)). Twenty-seven volunteers (17 men and 10 women, age 35.1 [plus or minus] 7.3, BMI 32.3 [plus or minus] 8.0), who were healthy other than having impaired glucose tolerance and obesity, were enrolled and 25 completed the entire trial. The primary endpoints were the effects of dietary and pharmacological intervention on stool calorie loss. We hypothesized that stool calories expressed as percentage of caloric intake would increase with underfeeding compared with overfeeding and increase during oral vancomycin treatment. Both primary endpoints were met. Greater stool calorie loss was observed during underfeeding relative to overfeeding and during vancomycin treatment compared with placebo. Key secondary endpoints were to evaluate the changes in gut microbial community structure as evidenced by amplicon sequencing and metagenomics. We observed only a modest perturbation of gut microbial community structure with under- versus overfeeding but a more widespread change in community structure with reduced diversity with oral vancomycin. Increase in Akkermansia muciniphila was common to both interventions that resulted in greater stool calorie loss. These results indicate that nutrient absorption is sensitive to environmental perturbations and support the translational relevance of preclinical models demonstrating a possible causal role for the gut microbiome in dietary energy harvest. A proof-of-concept clinical study shows that perturbations to the gut microbiome affect nutrient absorption in humans., Author(s): Alessio Basolo [sup.1] , Maximilian Hohenadel [sup.1] , Qi Yan Ang [sup.2] , Paolo Piaggi [sup.1] , Sascha Heinitz [sup.1] [sup.3] [sup.4] , Mary Walter [sup.5] , Peter Walter [...]

Summary: Sporadic Medullary Thyroid Carcinoma (sMTC) is a rare but aggressive thyroid tumor. RET and RAS genes are present in about 50%–80% of cases, but most of the remaining cases are still orphan of a genetic driver. We studied the largest series of sMTC by deep sequencing to define the mutational landscape. With this methodology we greatly reduced the number of RET- or RAS-negative cases and we confirmed the central role of RET and RAS mutations. Moreover, we highlighted the bad prognostic role of RET mutations in sMTC and consolidated the favorable prognostic role of RAS mutations. For the first time, we showed that the variant allele frequency represents an additional prognostic marker inside the group of RET-mutated sMTC. : Biological Sciences; Cancer; Genomics Subject Areas: Biological Sciences, Cancer, Genomics

Some housing researchers have criticized the United States housing subsidy scheme referred to as the Low-Income Housing Tax Credit (LIHTC) program for failing to promote better opportunities for low-income persons. In this study, therefore, we examine the socio-economic and built-environment characteristics of LIHTC developments at the neighborhood level. Specifically, we aim to investigate the characteristics associated with LIHTC developments compared to neighborhoods without this kind of development. We focus on California statewide initially and then narrow our focus to examine LIHTC developments in Los Angeles County (LAC). We then compare the results from the two levels of government. We compiled data from several sources including the U.S. Census Bureau, the State of California, the Southern California Association of Governments, and other secondary sources; used Geographic Information Systems (GIS) to aid in creating several location-based indicators; and employed logistic regression for analyses. Our results show that LIHTC developments at the statewide and county levels tend to be in racially/ethnically diverse neighborhoods with higher levels of economic hardship, lower rents, a higher percentage of renters, and spatial clustering of LIHTC developments. With LAC removed from the state-level analysis, economic hardship is not more likely to occur in LIHTC neighborhoods. This finding suggests, except for in LAC, state policies may be having some level of success in locating LIHTC housing outside of hardship areas. Finally, in examining additional built-environment variables in LAC, we find LIHTC developments were more likely to be in a neighborhood with a park than other neighborhoods in the county. We discuss these results further and conclude with a brief recap of results, policy recommendations, and suggestions for future research.

ObjectiveCirculating albumin is negatively associated with adiposity but whether it is associated with increased energy intake, lower energy expenditure or weight gain has not been examined.MethodsIn study 1 (n=238; 146 men), we evaluated whether fasting albumin concentration was associated with 24-h energy expenditure and ad libitum energy intake. In study 2 (n=325;167 men), we evaluated the association between plasma albumin and change in weight and body composition.ResultsAfter adjustment for known determinants of energy intake lower plasma albumin concentration was associated with greater total daily energy intake (β= 89.8 kcal/day per 0.1 g/dl difference in plasma albumin, p=0.0047). No associations were observed between plasma albumin concentrations and 24-h energy expenditure or 24-h respiratory quotient (p>0.2). Over 6 years, volunteers gained on average 7.5 ± 11.7 kg (p

The pathophysiology of gastrointestinal damage in coronavirus disease (COVID-19) is probably multifactorial. It is not clear whether the etiology of intestinal ischemia may be directly related to viral replication or may result from hyper-coagulability following SARS-CoV-2 infection.To confirm a pathogenic role of COVID-19, we retrospectively investigated the presence of SARS-CoV-2 virus in the ischemic bowel of five COVID-19 patients undergoing emergency surgery for intestinal ischemia in the period of March 2020–May 2021. Immunohistochemical positivity with weak intensity was observed in four out of five cases, but only one case was strongly positive both at immunohistochemistry and at molecular analysis. The histological alterations in the intestinal tissue samples showed similarity with the well-known alterations described in typical targetorgans of the virus (e.g., the lung). This observation suggests a similar mechanism of action of the virus. Further larger studies are, thus, required to confirm this preliminary finding. Clinicians should carefully monitor all COVID-19 patients for the possible presence of a SARS-CoV-2 intestinal infection, a potential cause of ischemia and bowel perforation.

A dysregulation between energy intake (EI) and energy expenditure (EE), the two components of the energy balance equation, is one of the mechanisms responsible for the development of obesity. Conservation of energy equilibrium is deemed a dynamic process and alterations of one component (energy intake or energy expenditure) lead to biological and/or behavioral compensatory changes in the counterpart. The interplay between energy demand and caloric intake appears designed to guarantee an adequate fuel supply in variable life contexts. In the past decades, researchers focused their attention on finding efficient strategies to fight the obesity pandemic. The ketogenic or “keto” diet (KD) gained substantial consideration as a potential weight-loss strategy, whereby the concentration of blood ketones (acetoacetate, 3-β-hydroxybutyrate, and acetone) increases as a result of increased fatty acid breakdown and the activity of ketogenic enzymes. It has been hypothesized that during the first phase of KDs when glucose utilization is still prevalent, an increase in EE may occur, due to increased hepatic oxygen consumption for gluconeogenesis and for triglyceride-fatty acid recycling. Later, a decrease in 24-h EE may ensue due to the slowing of gluconeogenesis and increase in fatty acid oxidation, with a reduction of the respiratory quotient and possibly the direct action of additional hormonal signals.

In the last decade, multikinase inhibitors (MKIs) have changed the paradigm of treatment of advanced and progressive thyroid cancer. Compared with the traditional treatment with chemotherapy and radiotherapy, these new drugs have shown a good efficacy in controlling the neoplastic disease, and also a different toxicity profile compared to traditional chemotherapy, milder but still present and involving mainly the nutritional profile. Weight loss, nausea, anorexia, stomatitis, diarrhea may be associated with malnutrition and cancer-related cachexia. The latter is characteristic of the advanced cancer stage and may be present before starting MKIs, or may develop afterwards. Adverse events with nutritional impact may cause a significant impairment of quality of life, often requiring dose reduction and sometimes drug discontinuation, but with a lower efficacy on the neoplastic disease. The aim of this paper was to discuss the role of nutritional therapy in advanced thyroid cancer and the importance of prevention, early recognition and careful management of malnutrition and cachexia during systemic therapy with MKIs.

We assessed the spatial distribution of subsidized housing units provided through 2 federally supported, low-income housing programs in Orange County, California, in relation to neighborhood walkability, transit access, and traffic exposure.We used data from multiple sources to examine land-use and health-related built environment factors near housing subsidized through the Housing Choice Voucher Program and the Low Income Housing Tax Credit (LIHTC) program, and to determine these patterns' associations with traffic exposure.Subsidized projects or units in walkable, poorer neighborhoods were associated with lower traffic exposure; higher traffic exposure was associated with more transit service, a Hispanic majority, and mixed-use areas. Voucher units are more likely than LIHTC projects to be located in high-traffic areas.Housing program design may affect the location of subsidized units, resulting in differential traffic exposure for households by program type. Further research is needed to better understand the relationships among subsidized housing locations, characteristics of the built environment, and health concerns such as traffic exposure, as well as which populations are most affected by these relationships.

Background. Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by RET proto-oncogene mutation. Two different clinical variants of MEN2 are known (MEN2A and MEN2B): medullary thyroid carcinoma (MTC) almost always present and associated with pheochromocytoma (Pheo), and primary hyperparathyroidism (HPTH) in MEN2A and with Pheo and other nonendocrine diseases in MEN2B. Case Report. A 7-year-old girl, previously treated for a pelvic plexiform neurofibroma, arrived at our observation with a peculiar MEN2B syndrome and with HPTH. The neck ultrasound showed bilateral thyroid nodules, local lymph node lesions, and a suspicious left hyperplastic parathyroid. The CT scan showed a megacolon and described the persistence of the pelvic tumor. A new RET germline deletion in exon 11 (c.1892_1899delCGAGCT; p.Glu632_Leu633del) was found. She underwent total thyroidectomy, central compartment and latero-cervical lymph node dissection, and neck exploration for primary HPTH. The histology confirmed bilateral MTC, multiple lymph node metastases, a hyperplastic parathyroid, and a parathyroid adenoma. Conclusions. This is the first case of a complex syndrome characterized by peculiar features of MEN2B, without Pheo but with a pelvic plexiform neurofibroma and with HPTH, which is typical of MEN2A. A “de novo” new germline RET deletion located in exon 11 was found.

Abstract Existing needs to manage flood risk in the United States are underserved by available flood hazard information. This contributes to an alarming escalation of flood impacts amounting to hundreds of billions of dollars per year and countless disrupted lives and affected communities. Making information about flood hazards useful for the range of decisions that dictate the consequences of flooding poses many challenges. Here, we describe collaborative flood modeling, whereby researchers and end‐users at two coastal sites co‐develop fine‐resolution flood hazard models and maps responsive to decision‐making needs. We find, first of all, that resident perception and awareness of flooding are enhanced more by fine‐resolution depth contour maps than Federal Emergency Management Agency (FEMA) flood hazard classification maps and that viewing fine‐resolution depth contour maps helps to minimize differences in flood perception across subgroups within the community, generating a shared understanding. We also find that collaborative flood modeling supports the engagement of a wide range of end‐users in contemplating the risks of flooding and provides strong evidence that the co‐produced knowledge can be readily adopted and applied for Flood Risk Management (FRM). Overall, collaborative flood modeling advances FRM by providing multiple points of entry for diverse groups of end‐users to contemplate the spatial extent, intensity, timing, chance, and consequences of flooding, thus enabling the web of decision‐making related to flooding to be better informed with the best available science. This transdisciplinary approach emphasizes vulnerability reduction and is complementary to FEMA Flood Insurance Rate Maps used for flood insurance administration.

The diagnosis of the primary origin of metastases to the thyroid gland is not easy, in particular in case of concomitant lung adenocarcinoma which shares several immunophenotypical features. Although rare, these tumors should be completely characterized in order to set up specific therapies. This is the case of a 64-years-old woman referred to our institution for a very advanced neoplastic disease diagnosed both as poorly differentiated/anaplastic thyroid cancer (PDTC/ATC) for the huge involvement of the neck and concomitant lung adenocarcinoma (LA). Neither the clinical features and the imaging evaluation nor the tumor markers allowed a well-defined diagnosis. Moreover, the histologic features of the thyroid and lung biopsies confirmed the synchronous occurrence of two different tumors. The molecular analysis showed a c.34G>T (p.G12C) mutation in the codon 12 of K-RAS gene, in both tissues. Since, this mutation is highly prevalent in LA and virtually absent in PDTC/ATC the lung origin of the malignancy was assumed, and the patient was addressed to the correct therapeutic strategy.