Determinants of weight, psychological status, food contemplation and lifestyle changes in patients with obesity during the COVID-19 lockdown: a nationwide survey using multiple correspondence analysis.

INTRODUCTION: The corona virus disease 2019 (COVID-19) pandemic forced most of the Italian population into lockdown from 11 March to 18 May 2020. A nationwide survey of Italian Clinical Nutrition and Dietetic Services (Obesity Centers or OCs) was carried out to assess the impact of lockdown restrictions on the physical and mental wellbeing of patients with obesity (PWO) who had follow-up appointments postponed due to lockdown restrictions and to compare determinants of weight gain before and after the pandemic. METHODS: We designed a structured 77-item questionnaire covering employment status, diet, physical activity and psychological aspects, that was disseminated through follow-up calls and online between 2 May and 25 June 2020. Data were analyzed by multiple correspondence analysis (MCA) and multiple linear regression. RESULTS: A total of 1,232 PWO from 26 OCs completed the questionnaires (72% female, mean age 50.2 ± 14.2 years; mean BMI 34.7 ± 7.6 kg/m2; 41% obesity class II to III). During the lockdown, 48.8% gained, 27.1% lost, while the remainder (24.1%) maintained their weight. The mean weight change was +2.3 ± 4.8 kg (in weight gainers: +4.0 ± 2.4 kg; +4.2% ± 5.4%). Approximately 37% of participants experienced increased emotional difficulties, mostly fear and dissatisfaction. Sixty-one percent reduced their physical activity (PA) and 55% experienced a change in sleep quality/quantity. The lack of online contact (37.5%) with the OC during lockdown strongly correlated with weight gain (p < 0.001). Using MCA, two main clusters were identified: those with unchanged or even improved lifestyles during lockdown (Cluster 1) and those with worse lifestyles during the same time (Cluster 2). The latter includes unemployed people experiencing depression, boredom, dissatisfaction and increased food contemplation and weight gain. Within Cluster 2, homemakers reported gaining weight and experiencing anger due to home confinement. CONCLUSIONS: Among Italian PWO, work status, emotional dysregulation, and lack of online communication with OCs were determinants of weight gain during the lockdown period.

Population data for Y-chromosome STR haplotypes from Piedmont (Italy).

Eight Y-chromosome STR loci (DYS19, DYS389-I, DYS389-II, DYS390, DYS391, DYS392, DYS393 and DYS385) were analysed in a sample of 236 unrelated males from four towns of Piedmont (Trino, Biella, Cavaglià, Postua). One hundred and fifty six different haplotypes were observed and 55 of them were not previously observed in the Y-STR Haplotype Reference Database (http://www.ystr.org/).

Monoallelic expression of mutant thyroid peroxidase allele causing total iodide organification defect.

Mutations in the thyroid peroxidase (TPO) gene lead to severe congenital hypothyroidism due to total iodide organification defect (TIOD). According to the recessive mode of inheritance, patients are homozygous or compound heterozygous for gene mutations. However, about 17% of cases with typical phenotype harbor a single TPO-mutated allele. We present a TIOD family in which the three affected siblings had a single genomic TPO mutation (R693W) inherited from the unaffected father. Other mutations were not found, although all TPO coding exons and exon/intron boundaries were sequenced. Eleven different polymorphisms were found in hetero- or homozygosity in all family members. On the contrary, using retrotranscribed thyroid tissue RNA, all heterozygous polymorphisms and the mutation were homozygous. The distribution of the polymorphisms indicated that only the mutant paternal allele is transcribed at the thyroid tissue level. We excluded the presence of major deletions involving the maternal chromosome at 2p25 and of maternal imprinting or mutations in part of the regulatory regions of the gene. In summary, we report one family with TIOD due to monoallelic expression of a mutant TPO allele in the thyroid. This mechanism might be generally involved in TIOD cases with a single TPO-mutated allele.

Molecular analysis of the Pendred's syndrome gene and magnetic resonance imaging studies of the inner ear are essential for the diagnosis of true Pendred's syndrome.

Pendred's syndrome is a combination of congenital sensorineural hearing loss and iodine organification defect leading to a positive perchlorate test and goiter. Although it is the commonest form of syndromic hearing loss, the variable clinical presentation contributes to the difficulty in securing a diagnosis. The identification of the disease gene (PDS) prompts the need to reevaluate the syndrome to identify possible clues for the diagnosis. To this purpose, in three Italian families presenting with the clinical features of Pendred's syndrome, the molecular analysis was accompanied by full clinical, biochemical, and radiological examination. A correlation between genotype and phenotype was found in the only patient with enlargement of vestibular aqueduct and endolymphatic duct and sac at magnetic resonance imaging. This subject was a compound heterozygote for a deletion in PDS exon 10 (1197delT, FS400) and a novel insertion in exon 19 (2182-2183insG, Y728X). The present study demonstrates for the first time the value of the combination of clinical/radiological and genetic studies in the diagnosis of Pendred's syndrome. The positivity of a perchlorate discharge test and the malformations of membranous labyrinth fit well with the recent achievements on the role of pendrin in thyroid hormonogenesis and the maintenance of endolymph homeostasis.

The role of pendrin in iodide regulation.

Recent advances in human genetics have catalyzed the attention on Pendred's syndrome and its disease-gene, PDS. Studies on the expression of the PDS gene and on the function of its encoded protein, which has been named pendrin, are currently in progress. Consistent with the Pendred's syndrome phenotype, which is characterized by thyroid dysfunction associated to deafness, PDS expression has been demonstrated in the thyroid and in the inner ear. Despite its high homology to known sulfate transporters, pendrin has been shown to transport iodide and chloride, but not sulfate. Thus, it is probably devoted to regulate, at the apical membrane where it has been immunolocalized, the flux of iodide from the thyroid cell to the colloid space. The function of pendrin in the inner ear is not well understood, but it seems to function also at this level as an anion transporter. Indeed, a pronounced PDS expression has been detected in structures of the inner ear, such as the membranous labyrinth and the endolymphatic duct and sac. At this level, the possible role of pendrin could be the maintenance of the appropriate ionic composition of the endolymph. Although many questions remain to be answered, these recent achievements concerning the putative role of pendrin aid to better understand the genetic basis of the peculiar phenotype of Pendred's syndrome, which associate the dysfunction of two so different organs such as the thyroid and the inner ear.

Nephelometry in the clinical assessment of glomerular proteinuria and tubular function in diabetic nephropathy.

Urinary excretion rate and total clearances of albumin, IgG, IgA and alpha 1-microglobulin, together with selectivity index and proteinuria, were determined by computerized nephelometry in 187 IDDM and NIDDM diabetic out-patients and in 39 healthy subjects in order to perform a prompt clinical assessment of diabetic nephropathy. Significant correlations between nephelometric and RIA procedures were demonstrated for the urinary excretion of albumin (p < 0.001) and total IgG (p < 0.001) in diabetic patients and healthy subjects. Nephelometry allowed us to classify diabetic patients in different stages of nephropathy: non nephropathic, normoalbuminuric with hyperfiltration, with incipient (microalbuminuric) and overt nephropathy (macroalbuminuric). Thirty consecutive subjects were analyzed within 1 h from the beginning of the procedure. A normal tubular function was demonstrated in non nephropathic, hyperfiltering and in 34% of microalbuminuric diabetic patients. On the contrary, in 66% of microalbuminuric and in 93% of macroalbuminuric patients alpha 1-microglobulin urinary levels were found above the upper normal limit. Urinary excretion of IgA was significantly increased only in macroalbuminuric diabetic patients (p < 0.001); this marker might therefore characterise the stage of overt nephropathy. Computerized nephelometry can be considered as a prompt, reproducible and high sensitive approach in the clinical evaluation of proteinuria and tubular function in diabetic renal disease.

Retrospective analysis of long-term hemorheologic effects of pentoxifylline in diabetic patients with angiopathic complications.

Blood rheology alterations have often been reported in diabetic patients and may be associated with an increased risk for diabetic vascular disease. In this light a hemorheologic approach with pentoxifylline has been suggested in diabetic patients with hemorheological changes in order to improve the hemorheology approach and to evaluate the long-term effects of this treatment on the other clinical and metabolic variables. The study concerned a 10-year retrospective analysis of diabetic patients with hemorheologic alterations and angiopathic complications. Pentoxifylline (Trental 400) significantly reduced blood and plasma viscosity (at high and low shear-rates), fibrinogen and erythrocyte aggregation, and increased erythrocyte filterability throughout the study. The improvement of the hemorheologic pattern was obtained independently of the variation in glycometabolic control and body weight changes, whereas concomitant reductions of arterial blood pressure levels and of urinary excretion of albumin and total proteins was observed during the treatment. Pentoxifylline might therefore be successfully employed for long-term periods in the treatment of hemorheologic disorders in diabetic patients without effects on the metabolic pattern.

Analysis of Y-chromosomal SNP haplogroups and STR haplotypes in an Algerian population sample.

The distribution of Y-chromosomal single nucleotide polymorphism (SNP) haplogroups and short tandem repeat (STR) haplotypes was determined in a sample of 102 unrelated men of Arab origin from northwestern Algeria (Oran area). A total of nine different haplogroups were identified by a panel of 22 binary markers. The most common haplogroups observed in the Algerian population were E3b2 (45.1%) and J1 (22.5%). Y-STR typing by a 17-loci multiplex system allowed 93 haplotypes to be defined (88 were unique). Striking differences in the allele distribution and gene diversity of Y-STR markers between haplogroups could be found. In particular, intermediate alleles at locus DYS458 specifically characterized the haplotypes of individuals carrying haplogroup J1. All the intermediate alleles shared a common repeat sequence structure, supporting the hypothesis that the variant originated from a single mutational event.

Use of the amplification refractory mutation system (ARMS) in the study of HbS in predynastic Egyptian remains.

We conducted a molecular investigation of the presence of sicklemia in six predynastic Egyptian mummies (about 3200 BC) from the Anthropological and Ethnographic Museum of Turin. Previous studies of these remains showed the presence of severe anemia, while histological preparations of mummified tissues revealed hemolytic disorders. DNA was extracted from dental samples with a silica-gel method specific for ancient DNA. A modification of the polymerase chain reaction (PCR), called amplification refractory mutation system (ARMS) was then applied. ARMS is based on specific priming of the PCR and it permits diagnosis of single nucleotide mutations. In this method, amplification can occur only in the presence of the specific mutation being studied. The amplified DNA was analyzed by electrophoresis. In samples of three individuals, there was a band at the level of the HbS mutated fragment, indicating that they were affected by sicklemia. On the basis of our results, we discuss the possible uses of new molecular investigation systems in paleopathological diagnoses of genetic diseases and viral, bacterial and fungal infections.

Immunological investigation of malaria and new perspectives in paleopathological studies.

We applied a paleoimmunological investigation, using an immunoenzymatic assay revealing trophozoite derived Plasmodium falciparum histidine rich protein-2 antigen (PfHRP-2). The investigation was carried out on skin, muscle and bone samples. We examined predynastic egyptian mummies (3200 B.C.) from Gebelen, belonging to the Marro's Collection of the Anthropological and Ethnographic Museum of Turin, to assay the presence of malaria. The results obtained suggest an incidence of malaria of about 40% in the mummies of Gebelen group. Data are compatible with other observations effected on populations living in similar ecological conditions of malarial areas.

Genetic analyses and evaluation of peripheral parameters of thyroid hormone action for the differential diagnosis of RTH. A novel heterozygous missense mutation (M334T) discovered.

Resistance to thyroid hormone (RTH) is a rare disease characterized by goiter and elevated free thyroid hormone (TH) levels in the presence of detectable concentrations of TSH. Most RTH patients harbor mutations in the ligand binding domain (LBD) of thyroid hormone receptor beta (TRbeta) gene, without a clear correlation between genotype and phenotype. Clinical, biochemical and genetic analyses were performed in several members of one family, because the index case presented with elevated free TH, measurable TSH and no hyperthyroid manifestations, but with a pituitary lesion at MRI. High free TH levels and TSH concentrations in the normal range were found also in 4 relatives. The presence of euthyroidism in all patients together with peripheral parameters of TH action in the normal range led to the diagnosis of generalized RTH (GRTH). In the five affected members, the genetic analysis revealed a novel heterozygous missense mutation at codon 334 (M334T). A different mutation at codon 334 was previously described in association with selective pituitary resistance to thyroid hormone (PRTH). Therefore, we confirm that substitutions at Methionine 334 are critical for the structural integrity of TRbeta LBD. The association of different phenotypes with substitutions affecting the same codon is another contribution confirming that RTH phenotype does not generally depend upon the site of the mutation in the LBD of TRbeta1.

Decreased immunosuppressive effect of cortisol on natural killer cytotoxic activity in senile dementia of the Alzheimer type.

Former studies have indicated alterations of the cytotoxic activity of natural killer (NK) cells in senile dementia of the Alzheimer type (SDAT). These changes may be related to the increased reactivity of NK cells with cytokines, even if an impairment of the immunosuppressive effect of glucocorticoids cannot be excluded. In the present study we have demonstrated a lower immunosuppressive effect of cortisol on NK cytolytic function in patients with SDAT than in healthy elders and in patients with dementia of multi-infarct origin (MID). This suppression is completely lacking when cortisol is employed at low concentrations (10(-7) M) and is significantly reduced after incubation at physiological (10(-6) M; p < 0.001) and supraphysiological concentrations (10(-5) M; p < 0.001). The addition of IL-2 (50 and 100 IU/ml/cells) significantly antagonizes the effects of cortisol in SDAT, whereas the cortisol-dependent immunosuppression is partially maintained in healthy elders and in patients with MID. Our data indicate that the defect of the immunosuppressive effect of cortisol may play a role in NK dysregulation in SDAT, contributing to the cytokine-mediated NK overactivity in this disease.

Enhanced cytotoxic response of natural killer cells to interleukin-2 in Alzheimer's disease.

Experimental data suggest an involvement of immune cellular components in the development of Alzheimer's disease (AD). Against this background, the spontaneous natural killer (NK) cell activity and the NK-induced cytotoxicity after interleukin-2 (IL-2) were studied in healthy elderly subjects and in patients with dementia of Alzheimer type (SDAT) and multi-infarct type (MID). Higher NK cytotoxicity (expressed as total lysis and percent increase) at different IL-2 concentrations (50 and 100 IU/ml/cells) was demonstrated in patients with SDAT than in healthy elderly subjects (p < 0.001) and MID patients (p < 0.001). NK cell activity of MID patients was similar to that of healthy elderly and healthy young subjects. A negative correlation between the percent increase in NK cytotoxicity after IL-2 and the Mini Mental State Examination Score was also found in SDAT patients (p < 0.01). Alterations of IL-2-mediated NK cytotoxicity may therefore support the neuroimmune hypothesis of AD.

Excitatory pattern of gamma-interferon on natural killer cell activity in senile dementia of the Alzheimer type.

Spontaneous natural killer (NK) cell activity and NK-induced cytotoxicity after interferon-gamma (IFN-gamma) were measured in healthy elderly subjects and in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID). Normal basal and IFN-gamma-stimulated NK cytotoxicity were found in healthy old subjects and in patients with MID. On the contrary higher NK cytotoxicity after IFN-gamma (650 IU) was demonstrated in SDAT patients than in MID and healthy subjects (p < 0.001). A significant inverse correlation between the percent increase of NK cytotoxicity after IFN-gamma and the Mini Mental State Examination score (p < 0.001) was also demonstrated in patients with SDAT. Our data might suggest a cytokine-dependent mechanism of NK activation in SDAT associated with the neuroimmune hypothesis of the disease.

Multigenerational familial medullary thyroid cancer (FMTC): evidence for FMTC phenocopies and association with papillary thyroid cancer.

BACKGROUND: Occurrence in a familial setting is well established for medullary thyroid carcinoma (MTC) and has been more recently reported for papillary thyroid cancer (PTC). Germline mutations or rearrangements of the RET proto-oncogene are the genetic background of the majority of hereditary MTCs and of about 25-40% of PTCs. PATIENTS: A large multigenerational familial medullary thyroid cancer (FMTC) family, comprised of four generations and a total of 60 subjects, has been fully evaluated. Studies on germline RET mutations and polymorphisms, on somatic RET activation and on haplotyping with RET-linked markers, were performed. RESULTS: RET mutational analysis revealed a rare missense point mutation in exon 15 of RET (A891S), associated with FMTC. Haplotype analysis showed a co-segregation between the allelic variant 5 of D10S578 marker (which is tightly linked to the RET locus) and the RET mutation. Two patients, from different branches of the family, did not harbour the point mutation A891S despite histological confirmation of MTC. In these cases, haplotype analysis excluded the involvement of the RET gene itself in the pathogenesis of the MTC. In three patients, the coexistence, in different foci, of medullary and papillary thyroid cancer was documented. The genetic studies did not show ret/PTC rearrangements. The microsatellite analysis excluded co-segregation of RET locus with the MTC/PTC phenotype. CONCLUSIONS: We report a full clinical and molecular analysis of a large FMTC kindred with an uncommon RET mutation. In two family members, phenotype and genotype were not concordant, representing the first evidence of FMTC phenocopies. Furthermore, the association of familial forms of medullary and papillary thyroid cancers has been found in 30% of patients undergoing thyroidectomy for MTC. In these situations, genetic analyses excluded the possible germline involvement of RET. Though FMTC phenocopies are likely to represent an exceptional finding, such a possibility should be taken into account in the genetic counselling for MEN 2 syndromes.

New data on the genetic structure of the population of Sicily: analysis of the Alia population (Palermo, Italy).

The distribution of 13 genetic markers (AB0, Rh, ACP, ADA, AK, ESD, GLO, PGD, PGMl, SOD, GC, TF, and PI) were studied in a sample from the Alia population of Sicily, Italy. A total of 34 alleles were detected. In comparison with other Sicilian populations, Alia always appeared genetically distinctive, either in terms of overall genetic diversity or for the number of unique alleles present. The results are consistent with previous studies that show no genetic uniformity within the island. More specifically, the data support the genetic divergence of the eastern and western halves of the island and highlight genetic boundaries that run through Sicily and divide it into three distinct areas.

Hyperviscosity and microproteinuria in central obesity: relevance to cardiovascular risk.

OBJECTIVES: To investigate the role of blood rheology changes in the occurrence of glomerular proteinuria in obese patients with central fat distribution. SUBJECTS: Fifty-nine obese out-patients (31 with central and 28 with peripheral body fat distribution) and 24 healthy subjects. MEASUREMENTS: Blood and plasma viscosity (Rotational viscometer CV100 HAAKE), erythrocyte deformability (whole-blood filtration time), fibrinogen (nephelometry), urinary excretion rates of albumin, IgG, transferrin and IgA (nephelometry). RESULTS: Higher blood viscosity (at low and high shear-rates), plasma viscosity, fibrinogen, erythrocyte aggregability and lower erythrocyte deformability were found in patients with central obesity than in patients with peripheral obesity (P < 0.01) and in healthy subjects (P < 0.001). Furthermore an increased urinary excretion rate of albumin (P < 0.001), IgG (P < 0.001), transferrin (P < 0.01) and IgA (P < 0.05) was found in patients with central obesity than in the other two groups. Blood hyperviscosity (at shear-rate 1 s-1 and 1/200 ratio) significantly correlated with the amount of urinary excretion of proteins independently of the other clinical and metabolic variables. CONCLUSIONS: The data demonstrated haemorheologic disorders related to pathologic proteinuria in patients with central obesity. The interaction between these two components may increase the risk of widespread cardiovascular disease.