Prevention and control of OQDS (olive quick decline syndrome) outbreaks caused by Xylella fastidiosa.

In Southern Italy, since 2013, there has been an ongoing Olive Quick Decline Syndrome (OQDS) outbreak, due to the bacterium Xylella fastidiosa, which has caused a dramatic impact from both socio-economic and environmental points of view. The main players involved in OQDS are represented by the insect vector, Philaenus spumarius, its host plants (olive trees and weeds) and the bacterium, X. fastidiosa. Current agronomic practices are mainly based on uprooting the sick olive trees and their surrounding ones, with later installment of olive cultivars more resistant to the bacterium infection. Unfortunately, both of these practices are having an undesirable impact on the environment (most of these olive trees were monumental ones) and on the economy. Based on a mathematical model expressed in terms of a nontrivial system of ordinary differential equations, our analysis has provided a clear picture of all possible steady states (feasible equilibria) and their stability properties, corresponding to a variety of different parameter scenarios; all of this has been illustrated by a set of computational experiments. A significant original contribution of this paper is the proof of the global asymptotic stability of each of the feasible equilibria under its existence assumptions, a fact that excludes multiple equilibria under the given conditions. It has emerged that the removal of a suitable amount of weed biomass (host plants of the juvenile stages of the insect vector of X. fastidiosa) from olive orchards and surrounding areas leads to the eradication of the epidemic, without requiring neither the removal nor the substitution of the existing olive trees.

Intraoperative parathyroid hormone testing in primary hyperparathyroidism surgery: time for giving up?

PURPOSE: Intraoperative PTH testing (IOPTH) in treatment of primary hyperparathyroidism (PH) is debated. Some authors advise against IOPTH in patients with concordant preoperative imaging undergoing focused parathyroidectomy. This study aims to compare focused parathyroidectomy success rates with and without IOPTH in patients with concordant preoperative imaging. METHODS: Retrospective cohort study involving 599 consecutive patients underwent surgery for PH from 2012 to 2017. Patients with discordant preoperative imaging were excluded. 426 patients underwent focused parathyroidectomy (214 patients without IOPTH and 212 with IOPTH) and were considered for the statistical analysis. In case of insufficient IOPTH decay (less than 50%), a bilateral exploration was carried out. RESULTS: The IOPTH group and the non-IOPTH group were similar for demographics and preoperative PTH and calcaemia. 413 patients were cured and disease persistence rates between groups were not significantly different (p > 0.05). CONCLUSIONS: Although further testing and randomized-controlled trials are required to validate our findings, our data show that IOPTH does not seem to improve the outcome in patients with concordant preoperative imaging undergoing focused parathyroidectomy.

The aberrantly expressed miR-372 partly impairs sensitivity to apoptosis in parathyroid tumor cells.

Parathyroid tumors deregulate microRNAs belonging to the two clusters on the chromosome 19, the C19MC and miR-371-373 clusters. Here, we report that the embryonic miR-372 is aberrantly expressed in half of parathyroid adenomas (PAds) in most of atypical adenomas and carcinomas (n = 15). Through in situ hybridization, we identified that miR-372-positive parathyroid tumor cells were scattered throughout the tumor parenchyma. In PAd-derived cells, ectopic miR-372 inhibited the expression of its targets CDKN1A/p21 and LATS2 at both mRNA and protein levels. Although the viability of parathyroid cells was not affected by miR-372 overexpression, the miRNA blunted camptothecin-induced apoptosis in primary PAd-derived cultures. miR-372 overexpression in parathyroid tumor cells increased parathormone (PTH) mRNA levels, and it positively correlated in vivo with circulating PTH levels. Conversely, the parathyroid-specific genes TBX1 and GCM2 were not affected by miR-372 mimic transfection. Finally, miR-372 dampened the Wnt pathway in parathyroid tumor cells through DKK1 upregulation. In conclusion, miR-372 is a novel mechanism exploited by a subset of parathyroid tumor cells to partially decrease sensitivity to apoptosis, to increase PTH synthesis and to deregulate Wnt signaling.

A mathematical model for malaria transmission with asymptomatic carriers and two age groups in the human population.

In this paper a conceptual mathematical model of malaria transmission proposed in a previous paper has been analyzed in a deeper detail. Among its key epidemiological features of this model, two-age-classes (child and adult) and asymptomatic carriers have been included. The extra mortality of mosquitoes due to the use of long-lasting treated mosquito nets (LLINs) and Indoor Residual Spraying (IRS) has been included too. By taking advantage of the natural double time scale of the parasite and the human populations, it has been possible to provide interesting threshold results. In particular it has been shown that key parameters can be identified such that below a threshold level, built on these parameters, the epidemic tends to extinction, while above another threshold level it tends to a nontrivial endemic state, for which an interval estimate has been provided. Numerical simulations confirm the analytical results.

Expression, function, and regulation of the embryonic transcription factor TBX1 in parathyroid tumors.

Transcription factors active in embryonic parathyroid cells can be maintained in adult parathyroids and be involved in tumorigenesis. TBX1, the candidate gene of 22q11.2-DiGeorge syndrome, which includes congenital hypoparathyroidism, is involved in parathyroid embryogenesis. The study aimed to investigate expression, function, and regulation of the parathyroid embryonic transcription factor TBX1 in human parathyroid adult normal and tumor tissues. TBX1 transcripts were detected in normal parathyroids and were deregulated in parathyroid tumors. Using immunohistochemistry, TBX1 protein was detected, mainly at the nuclear level, in a consistent proportion of cells in normal adult parathyroids, whereas TBX1 immunoreactivity was absent in fetal parathyroids. TBX1-expressing cells were markedly reduced in about a half of adenomas (PAds) and two-thirds of carcinomas and the proportion of TBX1-expressing cells negatively correlated with the serum albumin-corrected calcium levels in the analyzed tumors. Moreover, a subset of TBX1-expressing tumor cells coexpressed PTH. TBX1 silencing in HEK293 cells, expressing endogenous TBX1, increased the proportion of cells in the G0/G1 phase of cell cycle; concomitantly, CDKN1A/p21 and CDKN2A/p16 transcripts increased and ID1 mRNA levels decreased. TBX1 silencing exerted similar effects in PAd-derived cells, suggesting cell cycle arrest. Moreover, in PAd-derived cells GCM2 and PTH mRNA levels were unaffected by TBX1 deficiency, whereas it was associated with reduction of WNT5A, an antagonist of canonical WNT/ß-catenin pathway. WNT/ß-catenin activation by lithium chloride inhibited TBX1 expression levels both in HEK293 and PAd-derived cells. In conclusion, TBX1 is expressed in adult parathyroid cells and deregulated in parathyroid tumors, where TBX1 deficiency may potentially contribute to the low proliferative nature of parathyroid tumors.

Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid tumors.

Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca2+]o). [Ca2+]o activates calcium-sensing receptor (CASR), which interacts with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1) the FLNA expression in human parathyroid tumors, (2) its effects on the CASR mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that FLNA localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous FLNA reduced CASR mRNA levels and total and membrane-associated CASR proteins. In agreement, FLNA mRNA levels positively correlated with CASR expression in a series of 74 PAds; however, any significant correlation with primary hyperparathyroidism severity could be detected and FLNA transcript levels did not differ between PAds harboring 990R or 990G CASR variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca2+]o in the absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and parallels the CASR expression levels. Loss of FLNA reduces CASR mRNA and protein expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants.

Discrete or distributed delay? Effects on stability of population growth.

The growth of a population subject to maturation delay is modeled by using either a discrete delay or a delay continuously distributed over the population. The occurrence of stability switches (stable-unstable-stable) of the positive equilibrium as the delay increases is investigated in both cases. Necessary and sufficient conditions are provided by analyzing the relevant characteristic equations. It is shown that for any choice of parameter values for which the discrete delay model presents stability switches there exists a maximum delay variance beyond which no switch occurs for the continuous delay model: the delay variance has a stabilizing effect. Moreover, it is illustrated how, in the presence of switches, the unstable delay domain is as larger as lower is the ratio between the juveniles and the adults mortality rates.

Global stability for epidemic model with constant latency and infectious periods.

In recent years many delay epidemiological models have been proposed to study at which stage of the epidemics the delays can destabilize the disease free equilibrium, or the endemic equilibrium, giving rise to stability switches. One of these models is the SEIR model with constant latency time and infectious periods [2], for which the authors have proved that the two delays are harmless in inducing stability switches. However, it is left open the problem of the global asymptotic stability of the endemic equilibrium whenever it exists. Even the Lyapunov functions approach, recently proposed by Huang and Takeuchi to study many delay epidemiological models, fails to work on this model. In this paper, an age-infection model is presented for the delay SEIR epidemic model, such that the properties of global asymptotic stability of the equilibria of the age-infection model imply the same properties for the original delay-differential epidemic model. By introducing suitable Lyapunov functions to study the global stability of the disease free equilibrium (when R0 ≤ 1) and of the endemic equilibria (whenever R0 > 1) of the age-infection model, we can infer the corresponding global properties for the equilibria of the delay SEIR model in [2], thus proving that the endemic equilibrium in [2] is globally asymptotically stable whenever it exists.

Surgical management of pediatric Graves' disease: an effective definitive treatment.

PURPOSE: The optimal treatment for pediatric Graves' disease (GD) is controversial. Antithyroid drugs are often used initially, but they are associated with a high failure rate. Therefore alternative therapies have become important. In the present study, we analyze our institution's experience regarding the safety and efficacy of thyroid surgery among pediatric patients with GD. METHODS: This is a retrospective chart review of 27 pediatric patients (age ≤ 18 years) with GD who underwent thyroid surgery between 1991 and 2009 at a single academic Institution. We recorded preoperative, intraoperative, and short-term postoperative data. RESULTS: All 27 patients were initially treated with thionamides. The high rate of hyperthyroidism relapse after discontinuation of medical treatment, age < 5 years, adverse reaction to medical therapy, severe ophthalmopathy, and patient preference justified the final decision to proceed with surgery as definitive therapy. All patients underwent total thyroidectomy. We had no mortality; surgical complications were rare: 4 (14.8 %) cases of transient hypocalcemia, 1 (3.7 %) of permanent hypocalcemia, 3 (11.1 %) of transient RLN neuropraxia, and 2 (7 %) of keloid scar. No bleeding, permanent RLN palsy or relapse hyperthyroidism were reported. CONCLUSIONS: Surgical therapy for pediatric GD performed by experienced thyroid surgeons is a safe, definitive and cost-effective treatment.

Plasma cell granuloma of the thyroid gland: a challenging diagnostic problem.

This study reports a case of plasma cell granuloma of the thyroid gland in a 47-year-old woman, presenting with a right subhyoid mass and a previous diagnosis of Hashimoto thyroiditis dating back to 1988, which was made on a subtotal thyroidectomy. Plasma cell granuloma preferentially involves the lung, with only 18 cases of thyroid gland involvement having been reported to date in the English literature. Thyroid plasma cell granuloma preferentially affects women and classically shows a prominent plasma cell infiltrate embedded in a variable degree of fibrous stroma: only 2 of the reported cases exhibited the morphologic features of inflammatory myofibroblastic tumor. These morphologic features may raise problems in the differential diagnosis with other plasma cell-rich disorders, including infectious diseases and auto(dys)immune conditions, including the recently described "IgG4-related sclerosing disease." In view of these considerations, a contemporary diagnostic approach to thyroid plasma cell granuloma is therefore discussed here.

An SEIR epidemic model with constant latency time and infectious period.

We present a two delays SEIR epidemic model with a saturation incidence rate. One delay is the time taken by the infected individuals to become infectious (i.e. capable to infect a susceptible individual), the second delay is the time taken by an infectious individual to be removed from the infection. By iterative schemes and the comparison principle, we provide global attractivity results for both the equilibria, i.e. the disease-free equilibrium E0 and the positive equilibrium E+, which exists iff the basic reproduction number R0 is larger than one. If R0 > 1 we also provide a permanence result for the model solutions. Finally we prove that the two delays are harmless in the sense that, by the analysis of the characteristic equations, which result to be polynomial trascendental equations with polynomial coefficients dependent upon both delays, we confirm all the standard properties of an epidemic model: E0 is locally asymptotically stable for R and unstable for R0 > 1 , while if R0 > 1 then E+ is always asymptotically stable.

Surgical treatment of intrathyroid metastases: preliminary results of a multicentric study.

BACKGROUND: Intrathyroid metastases (ITM) are rare and usually have a dismal prognosis. The aim of this study was to detect which neoplasms metastasize most often to the thyroid gland, their clinical features and treatment options. MATERIALS AND METHODS: Retrospective analysis of clinical files of 17,122 patients submitted to surgery for thyroid disease between 1995 and 2005. Twenty-five patients (median age 61 years) were affected by ITM. RESULTS: The site of the primary tumor was: kidney (15), lung (4), colon (3), breast (1), melanoma (1), and unknown in 1 patient. Ten patients (40%) complained of preoperative symptoms, in the others, thyroid involvement was incidentally discovered during the follow-up for the primary cancer. Twenty patients (80%) underwent total thyroidectomy, 3 received thyroid lobectomy and 2 palliative procedures. Morbidity was 16%, mortality was nil. The median follow-up was 24 months. CONCLUSION: ITM should always be suspected in any patient with a previous history of malignancy. Fine-needle agobiopsy (FNAB) with immunohistochemical stains may help in preoperative workup. A long delay between the primary tumor and the recurrence warrants surgery and total thyroidectomy seems to be the treatment of choice because of the multifocality of metastasis to the thyroid gland.

The role of delays in innate and adaptive immunity to intracellular bacterial infection.

The immune response in humans is complex and multi-fold. Initially an innate response attempts to clear any invasion by microbes. If it fails to clear or contain the pathogen, an adaptive response follows that is specific for the microbe and in most cases is successful at eliminating the pathogen. In previous work we developed a delay differential equations (DDEs) model of the innate and adaptive immune response to intracellular bacteria infection. We addressed the relevance of known delays in each of these responses by exploring different kernel and delay functions and tested how each affected infection out come. Our results indicated how local stability properties for the two infection outcomes, namely a boundary equilibrium and an interior positive equilibrium, were completely dependent on the delays for innate immunity and independent of the delays for adaptive immunity. In the present work we have three goals. The first is to extend the previous model to account for direct bacterial killing by adaptive immunity. This reflects, for example, active killing by a class of cells known as macrophages, and will allow us to determine the relevance of delays for adaptive immunity. We present analytical results in this setting. Second, we implement a heuristic argument to investigate the existence of stability switches for the positive equilibrium in the manifold defined by the two delays. Third, we apply a novel analysis in the setting of DDEs knows as uncertainty and sensitivity analysis. This allows us to evaluate completely the role of all parameters in the model. This includes identifying effects of stability switch parameters on infection outcome.

An allelopathic competition model with quorum sensing and delayed toxicant production.

The dynamics of a differential functional equation system representing an allelopathic competition is analyzed. The delayed allelochemical production process is represented by means of a distributed delay term in a linear quorum-sensing model. Sufficient conditions for local asymptotic stability properties of biologically meaningful steady-state solutions are given in terms of the parameters of the system. A global asymptotic stability result is also proved by constructing a suitable Lyapunov functional. Some simulations confirm the analytical results.

A report of six cases of familial papillary thyroid cancer.

AIMS: Familial occurrence of papillary thyroid cancer is uncommon. The purpose of this study was review our own experience in a series of 267 papillary thyroid cancers. METHODS: We analysed the clinical records of 267 consecutive patients operated on for papillary thyroid cancer (PTC) in our hospital between June 1980-March 2000. RESULTS: We identified a family history in three families (6 patients), which results in a 2.25% familial papillary thyroid carcinoma (FPTC) rate. Pathology findings revealed that the tumour was multifocal and bilateral in 2 patients. Lymph-node metastases were found in 4 patients. They are all alive with a mean time of follow-up of 74.3 months (range 2-120). CONCLUSIONS: We recommend that patients with familial disease should be treated according to the disease stage and other risk factors, similar to those with sporadic differentiated papillary thyroid cancer. We encourage the further reporting and pedigree analysis to identify patients affected by FPTC.