Treatment of post-radioactive iodine relapse of hyperthyroidism: comparison of long-term methimazole and radioactive iodine treatment.

BACKGROUND: This study aimed to compare the time to achieve euthyroidism and sustained control of hyperthyroidism after treatment with radioactive iodine (RAI) or long-term methimazole (LT-MMI) in patients with post-RAI relapsed hyperthyroidism. METHODS: Sixty four patients with recurrence of hyperthyroidism after RAI treatment were randomly assigned to either RAI or LT-MMI treatment. Both groups were followed every 1-3 months in the first year and then every 6 months for a total of 60 months. RESULTS: In RAI and LT-MMI groups, mean age was 49.0 ± 12.1 and 50.1 ± 14.6 years and time of relapse of hyperthyroidism after previous RAI treatment was 23.2 ± 18.8 and 20.8 ± 17.1 months, respectively. At the end of study, in the LT-MMI group, 31 (97%) and 1 (3%) were euthyroid and hypothyroid, respectively; in the RAI group, 8 (25%) patients were euthyroid, whereas 18 (56%), 3 (9.5%) and 3 (9.5%) had overt hypothyroidism, subclinical hypothyroidism and hyperthyroidism, respectively. Mean time to euthyroidism was 9.4 ± 5.0 months in the RAI group and 3.5 ± 2.8 months in the LT-MMI group (p < 0.001). Patients in the RAI group spent 77.7 ± 14.0 percent and those in the LT-MMI group spent 95.2 ± 5.9 percent of 60 months in the euthyroid state (p < 0.001). CONCLUSION: In patients with post-RAI relapse of hyperthyroidism, LT-MMI treatment was superior to radioiodine because of faster achievement of euthyroidism and more sustained control of hyperthyroidism during 60 months of follow-up.

Appropriate duration of antithyroid drug treatment as a predictor for relapse of Graves' disease: a systematic scoping review.

BACKGROUND: Following the conventional 12-18 month antithyroid drug (ATD) treatment in Graves' disease (GD), 50% of patients experience relapse of hyperthyroidism. OBJECTIVE: The aim of this systematic scoping review was critical appraisal of duration of ATD therapy in the last 80 years. METHODS: Articles were identified through the search of PubMed from January 1, 1941 to April 30, 2021. All study types were included. Articles were eligible if they reported data on the length of ATD treatment, particularly thyroid hormones and TSH receptor antibodies (TRAb) concentrations and specifically those with data on the remission and/or relapse rates. RESULTS: We described major progress regarding the duration of ATD therapy and related outcomes at every 20 years. Articles of 1941-1960 were mainly concerned with determination of favorable treatment, minimal effective dose, side effects and rate of remission after < 12-month ATD therapy. Studies with larger number of patients and longer follow-ups appeared in 1961-1980; higher remission rate after 18-24 months versus 6 months of ATD therapy was reported. Articles of 1981-2000 focused on identification of factors associated with high relapse rates after discontinuation of ATD. In 2001-2021, ATD became the first choice of treatment in many countries. However, 12-18 months of ATD therapy was arbitrarily chosen as the appropriate option. According to recent studies, persistent normalization of TRAb occurs after 5 years of methimazole therapy and ATD treatment of > 60 months could offer a 4-year remission rate of 85%. CONCLUSION: Long-term ATD treatment for more than 60 months is safe and effective, has the highest remission rate and cures most patients with GD; hence, it should be considered as the most appropriate duration for ATD therapy in these patients.

Natural history of subclinical hypothyroidism and prognostic factors for the development of overt hypothyroidism: Tehran Thyroid Study (TTS).

OBJECTIVE: The significance of subclinical hypothyroidism (SCH) is largely due to its potential risk for developing overt hypothyroidism (OH). Investigations are still exploring predictive factors contributing to the progression of SCH to OH, particularly in patients with mildly elevated serum thyrotropin (TSH). We aimed to clarify the natural history of SCH and the predictive factors of its progression, based on the grade of SCH severity. METHODS: This study was conducted within the framework of the Tehran Thyroid Study (TTS), in which 5783 individuals aged ≥ 20 years were followed. After applying exclusion criteria, data of 270 SCH subjects remained for the analysis. Thyroid function tests were assessed at baseline and every 3 years. RESULTS: Of 270 participants with SCH, 239 (88.5%) had TSH level between 5.06 and 10 mU/L, and 31 (11.4%) had TSH ≥ 10 mU/L. During a median follow-up of 10 years, 40% had TSH within the reference range, 44% maintained elevated TSH, and 16% had added low T4 to the elevated TSH. The annual incidence rate of progression to OH was 22.3 (16.5-101.9) per 1000 person-years [18 (12.6-25.6) for those with TSH 5.07-9.9 mU/L and 57.8 (22.8-101.9) for patients with TSH ≥ 10 mU/L per 1000 person-years (P = 0.001)]. After adjusting age, sex, body mass index (BMI), thyroid peroxidase antibody (TPOAb), and serum TSH, only TPOAb positivity (HR: 2.31; 95% CI 1.10-4.83, P = 0.026) and baseline TSH level ≥ 10 mU/L (HR: 5.14; 95% CI 2.14-12.3, P < 0.001) remained as predictors for development of OH. In patients with TSH 5.07-9.9 mU/L, TPOAb positivity was associated with an increased risk of OH (HR: 2.41; 95% CI 1.10-5.30, P = 0.027). However, in patients with TSH ≥ 10 mU/L, TPOAb positivity was not a predictor (P = 0.49). CONCLUSION: TPOAb and not TSH are associated with the development of OH in individuals with serum TSH below 10 mU/L, and follow-up at regular intervals is recommended in TPOAb-positive individuals with TSH between 5 and 10 mU/L.

TTY2 genes deletions as genetic risk factor of male infertility.

Y chromosome has a number of genes that are expressed in testis and have a role in spermatogenesis. TTY2L12A and TTY2L2A are the members of testis transcript Y2 (TTY2) that are Y linked multi-copy gene families, located on Yp11 and Yq11 loci respectively. The aim of this study was to investigate frequency of TTY2L12A and TTY2L2A deletions in azoospermic patients compared with fertile males. This study was performed on 45 infertile males with idiopathic azoospermia without any AZF micro deletions (group A), 33 infertile males with azoospermia which do not screened for AZF micro deletions (group B) and 65 fertile males (group C), from October 2013 to April 2015 in west of Iran. Polymerase chain reaction (PCR) method was used for detection of TTY2L12A and TTY2L2A gene deletions in studied groups. No deletions were detected in normal fertile males of group C. 1 out of 45 azoospermic males of group A (2.22%) and 3 out of 33 azoospermic males of group B (9.09%) had TTY2L2A deletion (p= 0.409 and p= 0.036 respectively), also 1 out of 45 azoospermic males of group A (2.22%) and 4 out of 33 azoospermic males of group B (12.12%) had TTY2L12A deletion (p= 0.409 and p= 0.011 respectively).  None of azoospermic males in Group A and B had deletions in both genes. Our data showed significant correlation between non-obstructive azoospermia and TTY2L12A and TTY2L2A deletions. Thus, it seems that TTY2L12A and TTY2L2A deletions can consider as one of the genetic risk factors for non-obstructive azoospermia.

Effect of Different Doses of Oral Cholecalciferol on Serum 1,25(OH)2D in Vitamin D Deficient Schoolchildren.

Data regarding 1,25-dihydroxycholecalciferol in adolescents are limited. We aimed to determine serum levels of this active metabolite of vitamin D and the effects of different doses of vitamin D on its concentration in schoolchildren with high prevalence of vitamin D deficiency. In a previously published randomized double-blind, placebo-controlled trial, 210 subjects, aged 14-20 years, were assigned to 3 regimens of vitamin D treatment: group A (n=70) received 50 000 U oral cholecalciferol monthly, group B (n=70), 50 000 U bimonthly, and group C (n=70), placebo. Serum 25(OH)D, calcium, parathyroid hormone, and bone markers were measured at baseline and after 2 and 5 months of treatment. In the present study, serum levels of 1,25(OH)2D were measured in 97 boys and 95 girls. At baseline, girls had significantly higher concentrations of 1,25(OH)2D than boys (36, IQR: 24, 63 vs. 30, IQR: 15, 57.5 pmol/l; p<0.01). There was no significant correlation between serum levels of 25(OH)D and 1,25(OH)2D in the total population (Spearman rho=- 0.111; p=0.126), boys (Spearman rho=0.008; p=0.941), and girls (Spearman rho=0.036; p=0.729). Also, 1,25(OH)2D values did not change over time in different study groups. Moreover, total and sex-stratified analysis did not show any significant difference between different groups at different times of the study period. In an adolescent population with high prevalence of hypovitaminosis D especially in girls, 1,25(OH)2D values were higher in girls than boys. There was no significant change in 1,25(OH)2D concentrations with different doses of vitamin D.

Balancing risk and benefit of extended pelvic lymph node dissection in patients undergoing radical cystectomy.

PURPOSE: The optimal extent of pelvic lymph node dissection (PLND) during radical cystectomy (RC) in patients with urothelial carcinoma of the bladder (UCB) is the subject of ongoing debate. In this study, we compared local recurrence-free and overall survival, in addition to complication rates, after extended PLND (ePLND) compared to standard PLND (sPLND). METHODS: We reviewed the charts of 314 patients who underwent RC for UCB between 2008 and 2013. ePLND was performed in 105 patients, and 105 matched patients who underwent standard PLND (sPLND) were selected based on clinical parameters. Local recurrence-free and overall survival rates were assessed using Kaplan-Meier survival analysis, and Cox proportional hazards models were used to assess potential determinants of these outcomes. Complications were assessed at 30 and 90 days using the Clavien-Dindo reporting system. RESULTS: More lymph nodes were removed by ePLND (median 21) compared to sPLND (median 9; P < 0.001), but the rate of nodal involvement was not different. In multivariable analysis, ePLND was associated with a better local recurrence-free survival (HR = 0.63, P = 0.005), but was not an independent predictor of overall survival (HR = 1.06, P = 0.84). Estimated blood loss was greater with ePLND (1047.3 vs. 584.5 ml P < 0.001), but there was no significant difference in complications. CONCLUSIONS: Extended PLND appears to reduce the risk of local recurrence, but was not an independent predictor of overall survival in this cohort. ePLND was associated with greater blood loss compared to sPLND, but not with other perioperative complications.

Steam inhalation: More harm than good? Perspective from a UK burns centre.

INTRODUCTION: Steam inhalation is common practice in UK households for coryzal symptoms in adults and children. Steam inhalation has the potential to and has caused significant scald injuries, predominantly due to unintentional contact with the hot water used. METHODS: The authors used electronic health records to retrospectively identify all patients admitted with scald injuries secondary to steam inhalation over a 2-year period from January 2018-December 2019 at Chelsea and Westminster Hospital, a regional burns centre. Data collected included patient demographics, mechanism of burn, as well as burn size, depth, treatment and any associated complications. An International Burns Injury Database enquiry assessed the national prevalence steam inhalation scalds over the same time period. RESULTS: 19 adult and paediatric patients were identified in our centre over a 2-year period, with an age range of 2 weeks to 91 years old. The majority (16/19, 84%) of patients received burns to their lower body, with three patients receiving burns to their chest and/or upper limbs. Six patients underwent surgery, 98 clinic appointments were utilised and the total length of hospital stay was 83 days. The estimated total cost of treating these 19 patients was over £31,872. Nationally, 201 cases were identified between Jan 2018-Dec 2019. CONCLUSIONS: Scald injuries secondary to steam inhalation have a significant impact both in terms of hospital stay and cost. Since this study captured only patients admitted to hospital, the true negative impact of steam inhalation is likely to be much higher than calculated. Better public awareness on the risks of steam inhalation and primary prevention policies could reduce the frequency of such injuries.

Strategies to Reach Nomadic Children During Polio SIAs: Experience in Dadaab and Fafi Sub-Counties of Kenya after the 2013-2014 Polio Outbreak.

BACKGROUND: Poliomyelitis, often called polio is a viral paralytic disease caused by Polioviruses. Although all susceptible individuals are at risk of getting infected, only about 1% become paralyzed. During the 2013 Polio Outbreak in Garissa County in Kenya, 50% of the confirmed cases were from the nomadic population although it comprises of only less than 20% of the total population in the county. Following concerns from the Horn of Africa Polio Technical Advisory Group (TAG) regarding inadequate vaccine coverage of nomadic population, several strategies were put in place to improve coverage and Acute Flaccid Paralysis case reporting among nomads in the rest of the planned 2014 polio vaccination campaigns. We describe strategies initiated from April 2014 by the Ministry of Health and partners to reach children in nomadic settlement in the two sub-counties of Dadaab and Fafi of Garissa County. METHODS: The strategies involved improving the mapping and tracking of the nomadic population by establishing lists of nomadic settlements obtained from local clan leaders and government administrators, their <5-year-old populations and focal persons. Focal persons were used to mobilise residents in their respective settlements and guide vaccination teams during campaigns. Settlement leaders were sensitised to report cases of Acute Flaccid Paralysis. In remote hamlets, trained community health volunteers were used as vaccinators. In such places drugs for common illness were also provided during the campaigns. A tracking tool to monitor nomadic population movement and special tally sheets to capture data were created. Training of vaccination personnel and intense social mobilisation activities was done. RESULTS AND CONCLUSION: About 2,000 additional children, from both nomadic and non-nomadic areas were reached when the new initiatives were started. For the first time, an actual number of nomadic children accessed was documented. Suspected AFP cases continued to be reported from nomadic settlements, and the number of zero dose children among the nonpolio AFP cases dropped. With modification and improvement, these strategies may be used to take health services such as routine immunisation to nomadic communities and reduce their vulnerability to vaccine preventable disease outbreaks.

The effect of electro-acupuncture on pro-oxidant antioxidant balance values in overweight and obese subjects: a randomized controlled trial study.

Objective To undertake a randomized controlled trial in 196 obese subjects to examine the effect of electro-acupuncture on serum pro-oxidant antioxidant balance (PAB) values. Methods Subjects received authentic acupuncture (cases) or sham acupuncture (controls) for 6 weeks in combination with a low-calorie diet. In the following 6 weeks, they received the low-calorie diet alone. Serum PAB was measured at baseline, and 6 and 12 weeks later. Results We found that serum PAB values decreased significantly in the group receiving the authentic acupuncture compared to the sham treatment (p<0.001) at week 6, and whilst serum PAB increased significantly (p<0.05) in the second phase of the study, a significant difference between two groups remained at 12 weeks (p<0.05). Conclusions Electro-acupuncture in combination with a low-calorie diet was more effective at reducing serum PAB values in obese subjects compared to diet alone. Further work is required to determine the mechanism by which electro-acupuncture has this effect.

Longitudinal changes of structural connectivity in traumatic axonal injury.

OBJECTIVES: To identify structural connectivity change occurring during the first 6 months after traumatic brain injury and to evaluate the utility of diffusion tensor tractography for predicting long-term outcome. METHODS: The participants were 28 patients with mild to severe traumatic axonal injury and 20 age- and sex-matched healthy control subjects. Neuroimaging was obtained 0-9 days postinjury for acute scans and 6-14 months postinjury for chronic scans. Long-term outcome was evaluated on the day of the chronic scan. Twenty-eight fiber regions of 9 major white matter structures were reconstructed, and reliable tractography measurements were determined and used. RESULTS: Although most (23 of 28) patients had severe brain injury, their long-term outcome ranged from good recovery (16 patients) to moderately (5 patients) and severely disabled (7 patients). In concordance with the diverse outcome, the white matter change in patients was heterogeneous, ranging from improved structural connectivity, through no change, to deteriorated connectivity. At the group level, all 9 fiber tracts deteriorated significantly with 7 (corpus callosum, cingulum, angular bundle, cerebral peduncular fibers, uncinate fasciculus, and inferior longitudinal and fronto-occipital fasciculi) showing structural damage acutely and 2 (fornix body and left arcuate fasciculus) chronically. Importantly, the amount of change in tractography measurements correlated with patients' long-term outcome. Acute tractography measurements were able to predict patients' learning and memory performance; chronic measurements also determined performance on processing speed and executive function. CONCLUSIONS: Diffusion tensor tractography is a valuable tool for identifying structural connectivity changes occurring between the acute and chronic stages of traumatic brain injury and for predicting patients' long-term outcome.

Social behavior and kin discrimination in a mixed group of cloned and non cloned heifers (Bos taurus).

For more than ten years, reproductive biotechnologies using somatic cell nuclear transfer have made possible the production of cloned animals in various domestic and laboratory species. The influence of the cloning process on offspring characteristics has been studied in various developmental aspects, however, it has not yet been documented in detail for behavioral traits. Behavioral studies of cloned animals have failed to show clear inter-individual differences associated with the cloning process. Preliminary results showed that clones favor each other's company. Preferential social interactions were observed among cloned heifers from the same donor in a mixed herd that also included cloned heifers and control heifers produced by artificial insemination (AI). These results suggest behavioral differences between cloned and non-cloned animals and similarities between clones from the same donor. The aim of the present study was to replicate and to extend these previous results and to study behavioral and cognitive mechanisms of this preferential grouping. We studied a group composed of five cloned heifers derived from the same donor cow, two cloned heifers derived from another donor cow, and AI heifers. Cloned heifers from the same donor were more spatially associated and interacted more between themselves than with heifers derived from another donor or with the AI individuals. This pattern indicates a possible kin discrimination in clones. To study this process, we performed an experiment (using an instrumental conditioning procedure with food reward) of visual discrimination between images of heads of familiar heifers, either related to the subjects or not. The results showed that all subjects (AI and cloned heifers) discriminated between images of familiar cloned heifers produced from the same donor and images of familiar unrelated heifers. Cattle discriminated well between images and used morphological similarities characteristic of cloned related heifers. Our results suggest similar cognitive capacities of kin and non kin discrimination in AI and cloned animals. Kinship may be a common factor in determining the social grouping within a herd.

Semantic, typicality and odor representation: a cross-cultural study.

This study investigated odor-category organization in three cultures by evaluating (i) the relationship between linguistic and perceptual categorization and (ii) the existence of an internal structure of odor categories. In the first experiment, three groups of 30 participants from American, French and Vietnamese cultures performed a sorting task. The first group sorted 40 odorants on the basis of odor similarity, the second group sorted 40 odor names on the basis of name similarity and the last group sorted 40 odor names on the basis of imagined odor similarity. Results showed that odor categorization was based on perceptual or conceptual similarity and was in part independent of word and imagined categorizations. In the second experiment, another group of 30 participants from each culture rated the typicality of the odorants for 11 odor categories. Results showed that some odorants were rated as more typical than others. Moreover, the typicality gradient predicted the odor space obtained in the odor sorting task in a consensual way among the three cultures. These results suggest that, as for other categories, odor categories are based on perceptual similarities rather than on semantic cues. Moreover odor-category structure might have a core representation which might be common to different cultures with boundaries which might be more culturally dependent.

From rotation to disfiguration: testing a dual-strategy model for recognition of faces across view angles.

A study is reported of the effect of distinctive marks on the recognition of unfamiliar faces across view angles. Subjects were asked to memorize a set of target faces, half of which had distinctive marks. Recognition was assessed by presenting the target faces, either in the same orientation, or after 90 degrees rotation, mixed with an equal number of distractors. Results show that the effect of distinctive marks depends on the view presented during learning. When a frontal view was learned, as predicted by the dual-strategy model [Valentin et al, in press, in Computational, Geometric, and Process Perspectives on Facial Cognition: Context and Challenges Eds T Wenger, J Townsend (Hillsdale, NJ: Lawrence Erlbaum Associates)], distinctive marks improve recognition performance in the 90 degrees condition but not in the 0 degree condition. However, when a profile view was learned, distinctive marks have no effect on recognition performance, even in the 90 degrees condition where a frontal view is tested.

What represents a face? A computational approach for the integration of physiological and psychological data.

Empirical studies of face recognition suggest that faces might be stored in memory by means of a few canonical representations. The nature of these canonical representations is, however, unclear. Although psychological data show a three-quarter-view advantage, physiological studies suggest profile and frontal views are stored in memory. A computational approach to reconcile these findings is proposed. The pattern of results obtained when different views, or combinations of views, are used as the internal representation of a two-stage identification network consisting of an autoassociative memory followed by a radial-basis-function network are compared. Results show that (i) a frontal and a profile view are sufficient to reach the optimal network performance; and (ii) all the different representations produce a three-quarter view advantage, similar to that generally described for human subjects. These results indicate that although three-quarter views yield better recognition than other views, they need not be stored in memory to show this advantage.

Structural aspects of face recognition and the other-race effect.

The other-race effect was examined in a series of experiments and simulations that looked at the relationships among observer ratings of typicality, familiarity, attractiveness, memorability, and the performance variables of d' and criterion. Experiment 1 replicated the other-race effect with our Caucasian and Japanese stimuli for both Caucasian and Asian observers. In Experiment 2, we collected ratings from Caucasian observers on the faces used in the recognition task. A Varimax-rotated principal components analysis on the rating and performance data for the Caucasian faces replicated Vokey and Read's (1992) finding that typicality is composed of two orthogonal components, dissociable via their independent relationships to: (1) attractiveness and familiarity ratings and (2) memorability ratings. For Japanese faces, however, we found that typicality was related only to memorability. Where performance measures were concerned, two additional principal components dominated by criterion and by d' emerged for Caucasian faces. For the Japanese faces, however, the performance measures of d' and criterion merged into a single component that represented a second component of typicality, one orthogonal to the memorability-dominated component. A measure of face representation quality extracted from an autoassociative neural network trained with a majority of Caucasian faces and a minority of Japanese faces was incorporated into the principal components analysis. For both Caucasian and Japanese faces, the neural network measure related both to memorability ratings and to human accuracy measures. Combined, the human data and simulation results indicate that the memorability component of typicality may be related to small, local, distinctive features, whereas the attractiveness/familiarity component may be more related to the global, shape-based properties of the face.

More about the difference between men and women: evidence from linear neural networks and the principal-component approach.

The ability of a statistical/neural network to classify faces by sex by means of a pixel-based representation has not been fully investigated. Simulations with pixel-based codes have provided sex-classification results that are less impressive than those reported for measurement-based codes. In no case, however, have the reported pixel-based simulations been optimized for the task of classifying faces by sex. A series of simulations is described in which four network models were applied to the same pixel-based face code. These simulations involved either a radial basis function network or a perceptron as a classifier, preceded or not by a preprocessing step of eigendecomposition. It is shown that performance comparable to that of the measurement-based models can be achieved with pixel-based input (90%) when the data are preprocessed. The effect of the eigendecomposition preprocessing of the faces is then compared with spatial-frequency analysis of face images and analyzed in terms of the perceptual information it captures. It is shown that such an examination may offer insight into the facial aspects important to the sex-classification process. Finally, the contribution of hair information to the performance of the model is evaluated. It is shown that, although the hair contributes to the sex-classification process, it is not the only important contributor.

Theory-based correlations and their role in children's concepts.

Recent accounts of conceptual development have emphasized the important role intuitive theories play in concept formation; however, it is still not clear exactly how these theories exert their influence. We present evidence that elementary school age children use theories to link together specific features associated with individual concepts. The results of our first experiment indicate that theory-based correlations play a prominent role in typicality judgments and in decisions about category membership. In a second experiment, we demonstrate that children's theories play an important role in determining which attributes will be considered most central to the concept. The results of these studies suggest that feature correlations can serve to link children's concepts with their intuitive theories of the world.