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BackgroundPositive psychological constructs have been associated with reduced suicidal ideation, and interventions to cultivate positive feelings have the potential to reduce suicide risk. This study compares the efficacy of a 6-week, telephone-based positive psychology (PP) intervention against a cognition-focused (CF) control intervention among patients recently hospitalized for depression and suicidal ideation or behavior.MethodA total of 65 adults with a current major depressive episode reporting suicidal ideation or a recent suicide attempt were enrolled from participating in-patient psychiatric units. Prior to discharge, participants were randomized to the PP (n = 32) or CF (n = 33) intervention. In both interventions, participants received a treatment manual, performed weekly PP (e.g. gratitude letter) or CF (e.g. recalling daily events) exercises, and completed weekly one-on-one telephone sessions over 6 weeks. Between-group differences in hopelessness (primary outcome), depression, suicidality and positive psychological constructs at 6 and 12 weeks were tested using mixed-effects models accounting for intensity of post-hospitalization psychiatric treatment.ResultsCompared with PP, the CF intervention was associated with significantly greater improvements in hopelessness at 6 weeks (β = −3.15, 95% confidence interval −6.18 to −0.12, effect size = −0.84, p = 0.04), but not 12 weeks. Similarly, the CF intervention led to greater improvements in depression, suicidal ideation, optimism and gratitude at 6 and 12 weeks.ConclusionsContrary to our hypothesis, the CF intervention was superior to PP in improving hopelessness, other suicide risk factors and positive psychological constructs during a key post-discharge period among suicidal patients with depression. Further study of this CF intervention is warranted in populations at high suicide risk. [ABSTRACT FROM PUBLISHER]

Objectives: We aimed to characterize the effects of COVID-19 Pandemic on 2 h plasma glucose (2 h PG) values after an OGTT postulating a correlation between 2 h PG spectrum and the decline of β-cell function. Particularly, we tried to evaluate the effects on the risk of showing 2 h plasma glucose values in the highest range of normal values in children and adolescent with obesity during COVID-19 Pandemic compared to those evaluated during the 13 years before., Subjects/methods: Data from 532 children and adolescents with obesity and overweight (before COVID-19 Pandemic, 209M/262F, 2008-2019; during COVID-19 Pandemic, 40M/21F, 2020-2021) who had undergone a complete evaluation and had performed an OGTT were analyzed. The two groups were further divided into three sub-groups based on the 2 h PG, group 1 (2 h PG < 5.55 mmol/L), group 2 (5.56 < 2 h PG < 6.60 mmol/L), group 3 (6.61 < 2h PG < 7.72 mmol/L), respectively. The prevalence of 2 h PG values distribution in children was evaluated between before and during COVID-19 Pandemic period and the main differences between the two groups 3 of each period were analyzed., Results: A significant difference (P = 0.01) in terms of distribution of the prevalence of 2h PG values was documented between the group before COVID-19 (35.6%, 45.9% and 18.5%) and the group during COVID-19 Pandemic (31.1%, 31.1% and 37.8%). A roughly doble higher prevalence of subjects with pre-IGT was documented in the COVID-19 group. In addition, group 3 of COVID-19 time showed significantly higher values for waist circumference (WC), Waist/Height ratio (WtHR), fasting glucose and HOMA-IR compared to the group 3 of the period before COVID-19 Pandemic (all P < 0.05)., Conclusions: During COVID-19 time a higher percentage of children are in the highest range of normal 2 h PG values which is known to be associated with a significant impairment of β-cell function and insulin sensitivity and have higher risk of developing IGT., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Linear growth during childhood is the result of the synergic contribution of different factors. The best growth determinant system during each period of life is represented by the growth hormone-insulin-like growth factor axis (GH-IGF), even if several other factors are involved in normal growth. Within the broad spectrum of growth disorders, an increased importance has been placed on growth hormone insensitivity (GHI). GHI was reported for the first time by Laron as a syndrome characterized by short stature due to GH receptor (GHR) mutation. To date, it is recognized that GHI represents a wide diagnostic category, including a broad spectrum of defects. The peculiar characteristic of GHI is the low IGF-1 levels associated with normal or elevated GH levels and the lack of IGF-1 response after GH administration. Recombinant IGF-1 preparations may be used in the treatment of these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mastromauro, Giannini and Chiarelli.)

Background: Fluid and insulin treatments are the cornerstones of DKA management and indications on dosages are available. However, according to possible confounding factors, relevant data are still required to explain the different insulin dosages adopted at diabetes onset, particularly based upon insulin sensitivity., Objective: We aimed to explore whether DKA severity is related to different insulin sensitivity states, thus resulting in different insulin requirement at diabetes onset., Methods: Retrospective data from hospital records of 62 newly diagnosed children with type 1 diabetes with DKA were analyzed. The population was divided into three groups: severe, moderate, and mild DKA. Anthropometric, laboratory test, insulin, and glucose administration data were analyzed. The Glucose Infusion Rate (GIR), Insulin Infusion Rate (IIR), and GIR/IIR were calculated and used as indexes of insulin sensitivity. The area under the curve (AUC) for insulin and glucose infusion was calculated., Results: Moving among the three groups, IIR decreased while GIR and GIR/IIR increased from severe to mild DKA group (all p < 0.01). A similar trend was documented for AUC-insulin and AUC-glucose as well as AUC-glucose/AUC-insulin ratio. The Spearman correlation showed a negative correlation between pH and both IIR and AUC-Insulin as well as a positive correlation between pH and both GIR/IIR and AUC-glucose/AUC-insulin ratio., Conclusions: Subjects with severe DKA have a higher insulin requirement compared to those with less severe DKA. Significant differences in terms of insulin sensitivity might be documented according to the severity of DKA, which might result in tailored insulin pH requirement in children with new onset type 1 diabetes., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Bile acids (BAs) are amphipathic molecules synthetized in the liver. They are primarily involved in the digestion of nutrients. Apart from their role in dietary lipid absorption, BAs have progressively emerged as key regulators of systemic metabolism and inflammation. In the last decade, it became evident that BAs are particularly important for the regulation of glucose, lipid, and energy metabolism. Indeed, the interest in role of BA in metabolism homeostasis is further increased due to the global public health increase in obesity and related complications and a large number of research postulating that there is a close mutual relationship between BA and metabolic disorders. This strong relationship seems to derive from the role of BAs as signaling molecules involved in the regulation of a wide spectrum of metabolic pathways. These actions are mediated by different receptors, particularly nuclear farnesoid X receptor (FXR) and Takeda G protein coupled receptor 5 (TGR5), which are probably the major effectors of BA actions. These receptors activate transcriptional networks and signaling cascades controlling the expression and activity of genes involved in BA, lipid and carbohydrate metabolism, energy expenditure, and inflammation. The large correlation between BAs and metabolic disorders offers the possibility that modulation of BAs could be used as a therapeutic approach for the treatment of metabolic diseases, including obesity itself. The aim of this review is to describe the main physiological and metabolic actions of BA, focusing on its signaling pathways, which are important in the regulation of metabolism and might provide new BA -based treatments for metabolic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Giannini, Mastromauro, Scapaticci, Gentile and Chiarelli.)

Purpose of Review: The aim of this review is to present the new definition of the disease, defining the epidemiology, risk factors with a particular attention to the role of insulin resistance (IR) and to define the main treatments explored., Recent Findings: Nonalcoholic fatty liver disease (NAFLD) was previously considered a primary liver disease, but it would be more correct to consider it a component of the metabolic syndrome (MetS) in which IR might play a key role. Based on these findings, it has been recently proposed to modify the classic term of NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) that better reflects the pathophysiology of this complex disease., Summary: Currently, no treatments approved in childhood are available, thus the only recommended approach is the prevention and correction of the known risk factors, and particularly of IR. However, further studies are needed to better clarify the pathogenetic mechanisms of NAFLD in order to establish more tailored therapies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Short stature is a common reason for consulting a growth specialist during childhood. Normal height is a polygenic trait involving a complex interaction between hormonal, nutritional and psychosocial components. Genetic factors are becoming very important in the understanding of short stature. After exclusion of the most frequent causes of growth failure, clinicians need to evaluate whether a genetic cause might be taken into consideration. In fact, genetic causes of short stature are probably misdiagnosed during clinical practice and the underlying cause of short stature frequently remains unknown, thus classifying children as having idiopathic short stature (ISS). However, over the past decade, novel genetic techniques have led to the discovery of novel genes associated with linear growth and thus to the ability to define new possible aetiologies of short stature. In fact, thanks to the newer genetic advances, it is possible to properly re-classify about 25-40% of children previously diagnosed with ISS. The purpose of this article is to describe the main monogenic causes of short stature, which, thanks to advances in molecular genetics, are assuming an increasingly important role in the clinical approach to short children., Competing Interests: Disclosures: Concetta Mastromauro and Francesco Chiarelli have no financial or non-financial relationships or activities to declare in relation to this article., (© Touch Medical Media 2022.)

Background: The COVID-19 pandemic period is having a strong impact on the management of diabetes as well as other chronic diseases as shown by the most severe clinical presentation at onset. The aim of this study was to evaluate the severity of diabetic ketoacidosis (DKA) in youth with newly diagnosed type 1 diabetes in "Santissima Annunziata Hospital" (Chieti, Italy) during COVID-19 pandemic in comparison to the five previous years., Methods: A retrospective population-based incidence study was performed. Data were obtained from hospital records of 172 patients with new onset type 1 diabetes divided into two groups according to the diagnosis: Group I, between January 2015 and February 2020; Group II, between March 2020 and April 2021. Data regarding anthropometric, socio-economic and laboratory test were analyzed. DKA (pH < 7.30) and different severity of the disease (severe pH < 7.10; moderate pH < 7.20, mild pH < 7.30) were evaluated. A Spearman correlation between pH values and the main variables of interest was performed., Results: DKA frequency was increased by 19 percentage in Group II compared to Group I (55% vs 36%; P = 0.03) with a significant increased risk of severe DKA cases compared to the previous five years (severe DKA 22.5% vs. 8.4%, P = 0.01). pH values were significantly related with HbA1c, blood glucose and c-peptide values in all groups. In addition, in Group II but not in Group I, pH values correlated with Triglycerides and TG/HDL cholesterol ratio., Conclusions: During COVID-19 pandemic the risk of more severe clinical presentation of type 1 diabetes at onset is increased. The correlation with lipid profile might suppose an additional effect of lifestyle changes beside the delay in the diagnosis. Modifications of health care system need to be implemented during this peculiar situation in order to avoid such a relevant complication at onset., (© 2022. The Author(s).)

Introduction: Obesity, dyslipidemia, hypertension, and insulin resistance are components of the metabolic syndrome and in adults are positively affected by growth hormone (GH) treatment. Few data are available on youth, especially evaluating the improvement of metabolic features after starting GH treatment. The aim of this study was to evaluate changes in metabolic profile in GHD children across tertiles of h-SDS changes after at least 20 months of GH therapy., Methods: Data from 51 normal-weight children and adolescents with GHD (age: 11.4 ± 2.3 years; h-SDS: -2.25 ± -1.94) who had performed a complete metabolic profile including IGF-1, lipid profile (total cholesterol, triglycerides, HDL cholesterol), glucose metabolism (fasting glycemia, insulin, hemoglobin A1c levels), and insulin resistance indices (HOMA, TG/HDL ratio) before and after start GH treatment were analyzed. Subjects who had received GH therapy for at least 20 months were eligible. Delta changes were calculated for each variable. Subjects were divided according to tertiles of delta changes of h-SDS (1st tertile, 2nd tertile, 3rd tertile) before and after a period of GH treatment., Results: In each tertile group, a significant increase in height SDS was documented. Delta changes in glucose metabolism, lipid profile, and insulin resistance indices significantly improved across tertiles groups, showing the highest tertile a better metabolic pattern., Discussion/conclusions: GH therapy is associated with improvement of metabolic profile. Delta changes seem to be more evident in those children with a higher tertile of delta h-SDS after starting GH therapy. A tailored therapy aimed to reach a proper goal in h-SDS after GH treatment might be necessary in order to reduce cardiovascular risk in GHD children., (© 2022 S. Karger AG, Basel.)

Growth monitoring is a fundamental approach to evaluate a child's health and it is part of preventive programs to timely identify and treat a possible disease. Height and weight measurements, calculation of height velocity over time are main instruments to discover pathological deviations. Short stature is defined as a height that is greater than or equal 2 standard deviations (SDS) below the mean height for reference children comparable for sex and age. According to the International Classification of Pediatric Endocrine Diagnosis (ICPED) the possible causes of short stature could be divided into three groups: primary growth disorders (intrinsic diseases of the growth plate), secondary growth disorders (diseases that interfere on the growth plate setting) and the idiopathic short stature in which no possible cause is identified. The etiology of short stature is not always a disease, but it could be a variant of normal growth. Furthermore, to date there are new advances in the genetic causes of short stature. A detailed evaluation of a child with growth impairment should include an accurate history, a standardize physical examination, general and specific laboratory evaluations, radiologic investigations and genetic testing. Short stature could represent an important threat for physical and psychological health in a child, so a prompt identification of abnormal growth deviations offers the possibility to early treat the possible cause of shortness. This review aimed to discuss a practical approach to a child with short stature on the bases of the most recent scientific evidence.

One of the priorities of personalized medicine regards the role of early integration of palliative care with cancer-directed treatments, called simultaneous care. This article, written by the Italian Association of Medical Oncology (AIOM) Simultaneous and Continuous Care Task Force, represents the position of Italian medical oncologists about simultaneous care, and is the result of a 2-step project: a Web-based survey among medical oncologists and a consensus conference. We present the opinion of more than 600 oncologists who helped formulate these recommendations. This document covers 4 main aspects of simultaneous care: 1) ethical, cultural, and relational aspects of cancer and implications for patient communication; 2) training of medical oncologists in palliative medicine; 3) research on the integration between cancer treatments and palliative care; and 4) organizational and management models for the realization of simultaneous care. The resulting recommendations highlight the role of skills and competence in palliative care along with implementation of adequate organizational models to accomplish simultaneous care, which is considered a high priority of AIOM in order to grant the best quality of life for cancer patients and their families.

Background: Early integration of palliative care in oncology practice ("simultaneous care", SC) has been shown to provide better care resulting in improved quality-of-life and also survival. We evaluated the opinions of Italian Association of Medical Oncology (AIOM) members., Patients and Methods: A 37-item questionnaire was delivered to 1119 AIOM members. Main areas covered were: social, ethical, relational aspects of disease and communication, training, research, organizational and management models in SC. Three open questions explored the definition of Quality of Life, Medical Oncologist and Palliative Care., Results: Four hundred and forty-nine (40.1%) medical oncologists returned the questionnaires. Forty-nine percent stated they address non-curability when giving a diagnosis of metastatic tumor, and 43% give the information only to patients who clearly ask for it. Fifty-five percent say the main formative activity in palliative medicine came from attending meetings and 90% agree that specific palliative care training should be part of the core curriculum in oncology. Twenty-two percent stated they consulted guidelines for symptom management, 45% relied upon personal experience and 26% make a referral to a palliative care specialist. Seventy-four percent were in favor of more research in palliative medicine. An integration between Units of Oncology and Palliative Care Services early in the course of advanced disease was advocated by 86%. Diverse and multifaceted definitions were given for the concepts of Quality of Life, Palliative Care and Medical Oncologist., Conclusion: SC is felt as an important task, as well as training of medical oncologists in symptom management and research in this field., Competing Interests: The authors have declared no conflicts of interest.

Objective: To use data from a randomized trial to determine the cost-effectiveness of a collaborative care (CC) depression and anxiety treatment program and to assess effects of the CC program on health care utilization., Methods: The CC intervention's impact on health-related quality of life, depression-free days (DFDs), and anxiety-free days (AFDs) over the 24-week postdischarge period was calculated and compared with the enhanced usual care (EUC) condition using independent samples t tests and random-effects regression models. Costs for both the CC and EUC conditions were calculated on the basis of staff time, overhead expenses, and treatment materials. Using this information, incremental cost-effectiveness ratios were calculated. A cost-effectiveness acceptability plot was created using nonparametric bootstrapping with 10,000 replications, and the likelihood of the CC intervention's cost-effectiveness was assessed using standard cutoffs. As a secondary analysis, we determined whether the CC intervention led to reductions in postdischarge health care utilization and costs., Results: The CC intervention was more costly than the EUC intervention ($209.86 vs. $34.59; z = -11.71; P < 0.001), but was associated with significantly greater increases in quality-adjusted life-years (t = -2.49; P = 0.01) and DFDs (t = -2.13; P = 0.03), but not AFDs (t = -1.92; P = 0.057). This translated into an incremental cost-effectiveness ratio of $3337.06 per quality-adjusted life-year saved, $13.36 per DFD, and $13.74 per AFD. Compared with the EUC intervention, the CC intervention was also associated with fewer emergency department visits but no differences in overall costs., Conclusions: This CC intervention was associated with clinically relevant improvements, was cost-effective, and was associated with fewer emergency department visits in the 24 weeks after discharge., (Copyright © 2016. Published by Elsevier Inc.)

Background: Depression and anxiety in patients with cardiac disease are common and independently associated with morbidity and mortality. We aimed to explore the use of a 3-step approach to identify inpatients with cardiac disease with depression, generalized anxiety disorder (GAD), or panic disorder; understand the predictive value of individual screening items in identifying these disorders; and assess the relative prevalence of these disorders in this cohort., Methods and Results: To identify depression and anxiety disorders in inpatients with cardiac disease as part of a care management trial, an iterative 3-step screening procedure was used. This included an existing 4-item (Coping Screen) tool in nursing data sets, a 5-item screen for positive Coping Screen patients (Patient Health Questionnaire-2 [PHQ-2], GAD-2, and an item about panic attacks), and a diagnostic evaluation using PHQ-9 and the Primary Care Evaluation of Mental Disorders anxiety disorder modules. Overall, 6210 inpatients received the Coping Screen, 581 completed portions of all 3 evaluation steps, and 210 received a diagnosis (143 depression, 129 GAD, 30 panic disorder). Controlling for age, sex, and the other screening items, PHQ-2 items independently predicted depression (little interest/pleasure: odds ratio [OR]=6.65, P<0.001; depression: OR=5.24, P=0.001), GAD-2 items predicted GAD (anxious: OR=4.09, P=0.003; unable to control worrying: OR=10.46, P<0.001), and the panic item predicted panic disorder (OR=49.61, P<0.001)., Conclusions: GAD was nearly as prevalent as depression in this cohort, and GAD-2 was an effective screening tool; however, panic disorder was rare. These results support the use of 2-step screening for depression and GAD beginning with a 4-item scale (GAD-2 plus PHQ-2)., Clinical Trial Registration: Unique Identifier: NCT01201967. URL: http://www.clinicaltrials.gov/ct2/show/NCT01201967.

There is increasing interest in the use of induction chemotherapy before concurrent chemotherapy and radiotherapy in the treatment of locally advanced head and neck cancer. A modest but significant improvement in survival has been observed with cisplatin and 5-fluorouracil (PF) induction before radiotherapy over that seen with radiotherapy alone. The addition of docetaxel to the PF regimen (TPF) appears to provide further survival benefits. The phase II part of a phase II/III trial compared three cycles of TPF induction chemotherapy before concomitant PF chemoradiotherapy with PF chemoradiotherapy alone in 101 patients with locally advanced stage III-IV head and neck cancer. The incidences of hematologic and nonhematologic toxicities during concurrent chemoradiotherapy were not higher in the TPF plus chemoradiotherapy group, and the feasibility of chemoradiotherapy was not compromised. Radiologically evaluated complete response rates at 6-8 weeks from the end of chemoradiotherapy (the primary endpoint) were 21% (95% confidence interval [CI], 11%-36%) with chemoradiotherapy alone and 50% (95% CI, 35%-65%; p = .004) with TPF plus chemoradiotherapy. A median overall survival time of 33.3 months and a 1-year survival rate of 78% were observed with chemoradiotherapy alone, whereas the median survival time was 39.6 months in the TPF plus chemoradiotherapy group, with a 1-year survival rate of 86%. To conclude, increasing evidence suggests that TPF induction chemotherapy improves clinical response and does not compromise subsequent chemoradiotherapy. The results of the ongoing phase III part of the phase II/III study should provide further information about the efficacy and safety of this approach for patients with locally advanced head and neck cancer.

Purpose: To determine the feasibility of neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by concurrent chemoradiotherapy (CHT-RT) compared with the same CHT-RT regimen alone in locally advanced head-and-neck squamous cell carcinoma., Methods and Materials: We treated 24 patients (20 men and 4 women) who had Stage III-IVM0 squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, or hypopharynx. The median patient age was 59 years (range, 41-73 years). The stage distribution was as follows: Stage II, 1 patient; Stage III, 6 patients; and Stage IV, 17; 18 patients had a performance status of 0 and 6 had a performance status of 1. None had undergone previous CHT or RT. Group 1 underwent three cycles of CHT (carboplatin area under the curve 1.5 on Days 1-4 and 5-fluorouracil 600 mg/m(2)/d continuous infusion for 96 h) starting on Days 1, 22, and 43 during RT (one daily fraction, 66-70 Gy within 33-35 fractions). Group 2 underwent three cycles of neoadjuvant TPF (docetaxel 75 mg/m(2), cisplatin 80 mg/m(2), 5-fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) followed by the same CHT-RT regimen., Results: After the first 16 patients, 8 in Group 1 and 8 in Group 2, the concomitant CHT-RT schedule was modified. The limiting toxicity observed during concomitant CHT-RT was similar in Groups 1 and 2, independent of neoadjuvant TPF administration. An excess of G3-G4 mucositis and other relevant toxicity that did not allowing completion of CHT-RT without interruption occurred in 44% of the patients. A reduction of at least one cycle of concurrent CHT was required in 31% of patients. On the basis of these data, the next 8 patients (Group 3) received three cycles of neoadjuvant TPF followed by two cycles only of CHT (cisplatin 20 mg/m(2) on Days 1-4 and 5-fluorouracil 800 mg/m(2)/d continuous infusion for 96 h) (PF) during Weeks 1 and 6 of the planned 7 weeks of RT. In Group 3, 25% of the patients developed World Health Organization G3-G4 mucositis. No World Health Organization hematologic G3-G4 toxicity was seen. RT interruption was required for 2 patients (25%). In 1 patient (12%), one cycle of CHT was omitted. During neoadjuvant TPF (Groups 2 and 3), the principal toxicities were G3-G4 neutropenia (37.5%) and G2 mucositis (44%). At the end of therapy, the CR rate was 62.5% for CHT-RT alone (Group 1) and 80% for neoadjuvant TPF followed by CHT-RT (Groups 2 and 3)., Conclusion: Three cycles of neoadjuvant TPF followed by two cycles of PF during RT are feasible without limiting toxicity. Three cycles of TPF were well tolerated and did not compromise subsequent concomitant CHT-RT. A randomized multicenter Phase III study has been started with the aim of comparing two cycles of PF during RT as standard treatment vs. the experimental arm with three cycles of neoadjuvant TPF followed by two cycles of PF during RT.

The aim of this study was to determine the prevalence of psychiatric symptoms among nondemented individuals with memory changes and whether such symptoms predict progression of functional decline or diagnosis of Alzheimer disease (AD). A semi-structured interview was administered at baseline to controls (n = 32) and to nondemented subjects with memory changes (n = 112) and to each subject's collateral source. The interview assessed the impact of cognition on functional abilities in daily life and a variety of psychiatric symptoms, including symptoms of psychosis, depression, and personality change. Participants were followed annually for 3 years to determine who had progressive functional decline and who progressed to meet clinical criteria for AD. Those diagnosed with AD on follow-up had more symptoms of personality change, such as agitation and passivity, at baseline than those who did not progress to meet clinical criteria for AD. Mild depressive symptoms were also more common among individuals at baseline who subsequently 'converted' to AD. Symptoms of personality change were associated with a more rapid increase in functional difficulty over time, whereas depressive symptoms were not. Changes in personality are more common among subjects with memory changes who go on to develop AD. Particular types of personality change, such as agitation and passivity, are related to progression of functional difficulty over time. Depressive symptoms, although common in prodromal AD, are not associated with a more rapid functional decline.

Asymptomatic persons at risk for Huntington's disease (HD) (N = 28) were assessed with neuropsychological, psychiatric, and neurologic tests while undergoing genetic linkage studies to determine their probability of carrying the HD gene. Those participants who were subsequently identified as probable gene carriers did not differ on neurologic or psychiatric examination from those subsequently identified as probable noncarriers. Neuropsychological data are presented for a subset of participants free of other conditions (such as alcoholism) putting them at risk for cognitive deficits. Among these subjects, probable gene carriers were inferior to probable noncarriers on the neuropsychological battery as a whole and on several individual tests involving learning and memory. The results suggest the presence of cognitive decline prior to identifiable motor impairments in HD.

The predictive test for Huntington disease (HD) has allowed those at risk to determine gene status prior to symptoms. The purpose of this research was to understand the motivation and the anticipated reactions of those requesting the test. Forty persons at 50% risk for HD and 31 companions participated in a structured personal interview as part of the predictive test protocol. Reasons for taking the test centered on the reduction of anxiety and uncertainty associated with being at risk and enhanced planning and decision making. Participants also believed that taking the test would produce more positive than negative outcomes. With a favorable result, most anticipated a reduction of anxiety, a more normal future, and relief knowing their children would be at a very low risk. Most also cited benefits as more likely than consequences with an unfavorable result. Making the most of life, easier planning, and reduced uncertainty were rated as more likely than any of the adverse impacts, including short-term depression and becoming frightened. Almost all participants (95%) said they would rather learn that they have the HD gene than remain at 50% risk. The uncertainty, anxiety, and chronic stress associated with being at risk appears to underlie the motivation of many seeking the predictive test for HD.

The availability of high efficiency T-cell cloning techniques recently allowed the identification and characterization of clones derived from the thyroid infiltrate of patients with autoimmune thyroid diseases. Phenotypical and functional analysis of T-cell clones obtained from thyroid infiltrates of patients with Hashimoto's thyroiditis show that most of them are progenies of CD8+ cytolytic T cells with natural killer activity. This phenomenon, of potential importance in tissue damage, is markedly less pronounced in Basedow's disease glands. In both Hashimoto's thyroiditis and Basedow's disease only a minority of clones appear to be specific for autologous thyroid cells and most of them are potent interferon-gamma producers, while increased secretion of tumor necrosis factor-alpha is observed only in Hashimoto's thyroiditis. In contrast with normal lymphoid tissue, only very few T cell clones derived from both BD and HT infiltrates were able to produce detectable amounts of IL-4, suggesting that most of the thyroid-infiltrating T cells represent quite homogeneous populations of Th1-type "inflammatory" T cells. This peculiar potential of lymphokine secretion could play a role in the expression and/or maintenance of thyroid autoimmunity and thyroid functional damage.

Four offspring of three different Huntington disease (HD) affected x affected matings were assessed by genetic linkage analysis for possible homozygosity. One individual was found to have a 95% likelihood of being an HD homozygote. The homozygote individual had an age at onset and symptoms which were similar to those of affected HD heterozygote relatives, including some with younger onset. This confirms the observation of Wexler et al. that in HD the homozygote is not more severely afflicted than the heterozygote.

The advent of presymptomatic and prenatal testing in Huntington disease (HD) may change the reproductive behavior of persons at risk for HD. In order to assess future change, an analysis of fertility and reproductive fitness was carried out on 999 affected and 2,253 unaffected offspring from 235 New England families. Ascertainment biases observed for persons born before 1910 and after 1929 reduced the sample to 250 HD cases and 201 unaffected sib controls born between 1910 and 1929. No increase in reproductive rate was found in HD-affected men compared to male control sibs. A small increase in fertility averaging 0.5 child was seen in HD-affected females compared to unaffected females, but this difference was not significant. The increase in mean number of children for HD females is accounted for in part by a small number of affected women who had very large families. No evidence was found to suggest that any increase in reproductive rate for affected persons was related to offspring being born after HD onset. The fitness of both HD-affected and unaffected females was not significantly different from that of the general population of Massachusetts.

One hundred thirty-one individuals at 50% risk of inheriting Huntington disease (HD) responded to a survey to study their attitudes toward taking a genetic test based on the identification of a genetically linked DNA polymorphism. Ninety-six percent of the respondents believe that presymptomatic testing should be available, and 66% say they will use it themselves. Fewer married individuals, in comparison to those single, separated, and divorced, intend to take the test. Many respondents (40%) said their primary reason for wanting to be tested is to end the uncertainty in their lives. Results suggest that there will be self-selection in test use, with many individuals who believe they will be depressed or possibly suicidal with a positive test result deciding not to be tested or unsure about testing. However, 15% of those who want to be tested acknowledge that they may be at risk for suicide if they are probable gene carriers. Only 12% of all respondents say they will be likely to use prenatal testing, suggesting that initial demand may be low in New England. Implementation of presymptomatic testing challenges health care providers to develop strategies to care for otherwise healthy persons who will be given a diagnosis years before the onset of illness.

The probability of carrying the gene for Huntington's disease can in many cases be estimated in the children of affected persons by identifying a specific DNA marker that is genetically linked to the gene. We studied 47 persons at 50 percent risk of inheriting Huntington's disease who requested a presymptomatic or prenatal genetic-linkage test between September 1986 and January 1988. The participants were given pre-test counseling and psychological and neurologic evaluations. Nineteen persons later voluntarily withdrew from the protocol, including one who would have been excluded anyway, and one person was from a family that was too small to allow testing. Three D4S10 restriction-fragment-length polymorphisms produced by the HindIII, EcoRI, and Bg/I enzymes were used for all tests, and the probability that a subject was a Huntington's disease carrier was calculated. The accuracy of the test was compromised by a 4 percent recombination frequency between D4S10 and the Huntington's disease gene. Fifteen presymptomatic tests and one prenatal test were completed. Four yielded positive results, seven yielded negative results, and five were uninformative; seven persons are awaiting test results. All participants with positive tests experienced intermittent depression, but none required hospitalization, and no suicide threats were reported. Five participants received a diagnosis of Huntington's disease on the basis of the neurologic assessment. We conclude that some persons in the early stages of Huntington's disease may seek presymptomatic testing rather than neurologic evaluations.