Effects of mindfulness-based interventions on symptoms and interoception in trauma-related disorders and exposure to traumatic events: Systematic review and meta-analysis.

Interoception is defined as the sense of the internal state of the body. Dysfunctions in interoception are found in several mental disorders, including trauma-related conditions. Mindfulness-Based Interventions (MBIs) have been shown to influence interoceptive processes. Randomised controlled trials (RCTs) have investigated whether MBIs impact symptoms and interoception in patients with trauma-related disorders. We undertook a systematic review and meta-analysis to synthesize these data. We included RCTs with an MBI arm which enrolled adult patients with trauma related-disorders or exposure to a traumatic experience, and addressed changes in interoception and trauma-related symptoms. A random-effects multivariate meta-analytic model was performed to quantify group differences in score change from baseline to follow-up. Twelve studies were included in the systematic review, and eleven in the meta-analysis. Overall, MBIs showed small to moderate positive effects on both interoception and symptoms. Despite a high heterogeneity in results, sensitivity analyses confirmed the robustness of the findings. We conclude that the efficacy of MBIs on trauma-related symptoms and interoception is supported by randomised evidence. However, further research is needed to understand whether changes in interoception might underpin the effectiveness of MBIs in trauma-related disorders.

HER2-positive metastatic breast cancer: a changing scenario.

Adjuvant trastuzumab (AT) dramatically improved HER2-positive breast cancer prognosis. Relapsed disease after AT has different patterns and information is available from observational studies. In this Review Chemotherapy regimens combined to anti-HER2 blockade are discussed, focusing in particular the role of anthracyclines, taxanes and capecitabine. The use of trastuzumab beyond progression and the role of other anti-HER2 agents like lapatinib, pertuzumab and T-DM1 are explored, as also dual blockade and in trastuzumab resistant Patients. Metastatic "de novo" HER2 Luminal (co-expression of HER2 and hormone receptors) Patients are eligible for anastrozole and trastuzumab but if pretreated with trastuzumab they are also eligible for lapatinib and letrozole. In any case endocrine treatment plays a complementary role to chemotherapy which remains pivotal. The last topic explored is treatment options for patients with brain metastases where both trastuzumab given concurrent with radiotherapy or lapatinib and capecitabine appear as potentially active.

Reciprocal translocations in cattle: frequency estimation.

Chromosomal anomalies, like Robertsonian and reciprocal translocations, represent a big problem in cattle breeding as their presence induces, in the carrier subjects, a well-documented fertility reduction. In cattle, reciprocal translocations (RCPs, a chromosome abnormality caused by an exchange of material between non-homologous chromosomes) are considered rare as to date only 19 reciprocal translocations have been described. In cattle, it is common knowledge that the Robertsonian translocations represent the most common cytogenetic anomalies, and this is probably due to the existence of the endemic 1;29 Robertsonian translocation. However, these considerations are based on data obtained using techniques that are unable to identify all reciprocal translocations, and thus, their frequency is clearly underestimated. The purpose of this work is to provide a first realistic estimate of the impact of RCPs in the cattle population studied, trying to eliminate the factors that have caused an underestimation of their frequency so far. We performed this work using a mathematical as well as a simulation approach and, as biological data, we considered the cytogenetic results obtained in the last 15 years. The results obtained show that only 16% of reciprocal translocations can be detected using simple Giemsa techniques, and consequently, they could be present in no <0.14% of cattle subjects, a frequency five times higher than that shown by de novo Robertsonian translocations. This data is useful to open a debate about the need to introduce a more efficient method to identify RCP in cattle.

FISH mapping in cattle (Bos taurus L.) is not yet out of fashion.

Physical mapping of genes by fluorescence in situ hybridization (FISH) seems to be out of fashion in species whose assembled genome sequences are available. However, in this work we evidence the existence of errors in gene location in the Btau_4.0 assembly. We show that DFNA5 and CHCHD6 genes are located on BTA4 and BTA22, respectively, instead of BTA10 and BTA3, as displayed by Btau_4.0. This report emphasizes the need to verify the data on physical localization of genes in the cattle genome (at least by taking into account comparative data reported in available papers) and the need to improve the cattle genome assembly. Our results indicate that FISH mapping in cattle is still useful.

Chromosomal assignment of R-spondin genes in the donkey (Equus asinus, 2n = 62).

R-spondins constitute a recently discovered small family of growth factors, and the evidence of their role in several developmental pathways is growing fast. In this work we describe the chromosomal location of the four RSPO genes in the donkey. Using horse BACs, we localized RSPO1 on EAS 5q23, RSPO2 on EAS 12q13, RSPO3 on EAS 24q26, and RSPO4 on EAS 15p13. Moreover, RSPO2, RSPO3, and RSPO4 are the first genes mapped on donkey chromosomes 12, 24, and 15, respectively.

X trisomy in a sterile mare.

This report concerns the cytogenetic analysis, using both C-banding and fluorescence in situ hybridisation techniques, of a sterile mare. Results obtained revealed a 2n = 65, XXX condition with no sign of mosaicism. The work supports the suggestion that X trisomy, rare in horse, causes infertility in mares and is not associated to other clearly visible phenotypic features.

Reciprocal translocation t(4;7)(q14;q28) in cattle: molecular characterization.

Cytogenetic analysis of a phenotypically normal young bull from the Marchigiana breed revealed the presence of an abnormal chromosome. The finding of one oversize chromosome in all metaphases, associated with a 2n = 60, XY karyotype, suggested that a reciprocal translocation had occurred. RBG-banding and FISH analyses, using specific bovine BAC probes, identified a de novo reciprocal translocation t(4;7)(q14;q28). The presence of rcp(4;7) was confirmed by FISH experiments using BTA4 and BTA7 whole chromosome probes. An array-CGH analysis (Agilent 244A) using a bovine custom design was performed to investigate if the translocation was associated with loss or gain of genetic material. The absence of a concomitant deletion or duplication at the break points allowed the balanced state of the translocation to establish. The analysis also revealed the presence of several CNVs throughout the genome. To our knowledge this is the first time the balanced condition of a cattle RCP has been ascertained using the array-CGH approach.

Thyrotropin-secreting pituitary adenomas: biological and molecular features, diagnosis and therapy.

Central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma is a rare cause of hyperthyroidism, representing 0.5-1.0% of all pituitary adenomas. The etiopathogenesis of TSH-secreting-adenomas is unknown and no definite role for various oncogenes has been proven. Patients with TSH-secreting adenoma usually present with signs and symptoms of hyperthyroidism milder than those in patients with hyperthyroidism of thyroid origin, in addition to symptoms secondary to mass effects of the pituitary tumour. Mixed pituitary tumours co-secrete growth hormone and prolactin. The characteristic biochemical abnormalities are normal or high serum TSH concentrations in the presence of elevated total and/or free thyroid hormones concentrations. Measurement of markers of peripheral thyroid hormone action and dynamic tests may aid in the differential diagnosis with the syndrome of resistance to thyroid hormone. Neuroimaging is fundamental to visualize the pituitary tumor. Therapy of TSH-secreting adenomas can be accomplished by surgery, radiation therapies, and medical treatment with somatostatin analogs or dopamine agonists. Nowadays, and in contrast with the first reports on this rare disease, most patients are well controlled by current therapies.

Mutations in the RSPO1 coding region are not the main cause of canine SRY-negative XX sex reversal in several breeds.

This report details a case of SRY-negative XX sex reversal in a mixed breed dog and surveys affected dogs of several breeds for mutations in RSPO1 coding regions. Genomic DNA from the mixed breed case was evaluated for mutations in candidate genes. Sequencing identified a homozygous G to A transition in RSPO1 exon 4 that changes a highly conserved amino acid codon in the thrombospondin domain. The possibility that this was a single nucleotide polymorphism (SNP) could not be excluded by genotyping family members. Therefore, the coding region of RSPO1 was sequenced in a survey of affected dogs, which identified a T to C transition (exon 3) in some, the above G to A transition (exon 4) in others, and no change in the remaining affected dogs. Genotypes at these base pair positions were not uniquely associated with the affected phenotype in any breed, indicating the identified transitions are most likely SNPs, not causative mutations for this canine disorder. However, the possibility that polymorphisms play a modifier role, such as changing threshold or severity of phenotypic expression in a mixed breed dog, cannot be excluded. This study emphasizes the importance of canine pedigree, breed, and population studies in evaluating candidate mutations.

Cytogenetic screening of livestock populations in Europe: an overview.

Clinical animal cytogenetics development began in the 1960's, almost at the same time as human cytogenetics. However, the development of the two disciplines has been very different during the last four decades. Clinical animal cytogenetics reached its 'Golden Age' at the end of the 1980's. The majority of the laboratories, as well as the main screening programs in farm animal species, presented in this review, were implemented during that period, under the guidance of some historical leaders, the first of whom was Ingemar Gustavsson. Over the past 40 years, hundreds of scientific publications reporting original chromosomal abnormalities generally associated with clinical disorders (mainly fertility impairment) have been published. Since the 1980's, the number of scientists involved in clinical animal cytogenetics has drastically decreased for different reasons and the activities in that field are now concentrated in only a few laboratories (10 to 15, mainly in Europe), some of which have become highly specialized. Currently between 8,000 and 10,000 chromosomal analyses are carried out each year worldwide, mainly in cattle, pigs, and horses. About half of these analyses are performed in one French laboratory. Accurate estimates of the prevalence of chromosomal abnormalities in some populations are now available. For instance, one phenotypically normal pig in 200 controlled in France carries a structural chromosomal rearrangement. The frequency of the widespread 1;29 Robertsonian translocation in cattle has greatly decreased in most countries, but remains rather high in certain breeds (up to 20-25% in large beef cattle populations, even higher in some local breeds). The continuation, and in some instances the development of the chromosomal screening programs in farm animal populations allowed the implementation of new and original scientific projects, aimed at exploring some basic questions in the fields of chromosome and/or cell biology, thanks to easier access to interesting biological materials (germ cells, gametes, embryos ...).

A new case of rob(14;17) in cattle.

Robertsonian translocations, also called centric fusions, represent the most frequent chromosome anomalies in cattle, and rob(1;29) is the most widespread. However, centric fusions involving other chromosomes have been discovered in different cattle breeds. Here we report the appearance of a new case of rob(14;17) in an Italian cattle breed more than ten years after the first and only case had been observed, and we demonstrate the independent origin of this anomaly from the previous case.

A new case of reciprocal translocation in a young bull: rcp(11;21)(q28;q12).

Routine cytogenetic investigations of the Chianina cattle (BTA) breed revealed the presence of longer and smaller chromosomes than the largest (BTA1) and smallest (BTA29) chromosomes in the cells of a young, normal-looking bull used for reproduction. Application of both RBA-banding and Ag-NOR techniques, as well as the use of the FISH technique and specific molecular markers of both BTA11 (IL1B, ASS and LGB) and BTA21 (SERPINA and D21S45) established that these two abnormal chromosomes were the product of a reciprocal translocation between BTA11 and BTA21. Both der(11) and der(21) were C-band positive and the chromosome regions affected were rcp(11;21)(q28;q12). The young bull had a normal body conformation, including external genitalia, normal levels of testosterone (as in the control) and non-detectable levels of both 17 beta-estradiol and progesterone (as in the control). The animal never showed libido in the presence of both males and females in oestrus. After slaughter at 18 months, histological evaluation revealed normal organized testes, seminiferous tubules and epididymis but with poor proliferative germ cells consisting mainly of spermatogonia, middle pachytene spermatocytes and early spermatids with late spermatids and spermatozoa being very rare.

Characterization of a balanced reciprocal translocation, rcp(9;11)(q27;q11) in cattle.

Cytogenetic analysis of a phenotypically normal young bull from Marchigiana breed revealed the presence of an abnormal karyotype. The observation of longer and smaller chromosomes than BTA1 and BTA29, respectively in all metaphases suggested the presence of a reciprocal translocation. RBG-banding confirmed this hypothesis revealing the involvement of BTA9 and BTA11. FISH analyses using cattle-specific BAC clones (474A12 and 293G09 for BTA9; 035D03 for BTA11) identified rcp(9;11)(q27;q11) in the two regions affected. Moreover analyses performed on both parents established the 'de novo' origin of the anomaly. Comparison with human homologue sequences (HSA6q24.3-->q25.3 for BTA9q27 and HSA2q11.1-->q12.1 for BTA11q11) revealed that both breakpoint regions are gene rich as up to date at least 200 genes have been localized in these regions. Thus, further analyses are required to identify the sequences disrupted by the breakpoints and to verify their consequences on rcp carrier phenotype.

Increased intestinal permeability precedes clinical onset of type 1 diabetes.

AIMS/HYPOTHESIS: Recent observations have shown subclinical intestinal abnormalities in human type 1 diabetes. Whether these are related to the pathogenetic process or secondary to the diabetes remains to be clarified. The aim of this study was to investigate this issue by examining intestinal permeability to sugars in subjects at different stages of type 1 diabetes: preclinical, new-onset and long-term established disease. METHODS: Eighty-one subjects with islet autoimmunity (18 preclinical, 28 new-onset and 35 long-term type 1 diabetes) and 40 healthy control subjects were investigated by a lactulose-mannitol test, consisting of oral administration of the two sugars and measurement of their urinary excretion. RESULTS: All groups of subjects with islet autoimmunity showed an increase in intestinal permeability (p < or = 0.009 vs controls) to the disaccharide lactulose, indicative of a damaged barrier, but a similar permeability to the monosaccharide mannitol (NS vs controls), indicative of an integral surface mucosa; consequently there was an increase in the lactulose:mannitol excretion ratio (p < or = 0.025 vs controls). CONCLUSIONS/INTERPRETATION: These findings indicate the presence of a subclinical enteropathy associated with type 1 diabetes that is already detectable before clinical onset of the disease, and suggest that the small intestine is an organ participating in the pathogenetic process of type 1 diabetes.

Cattle rob(1;29) originating from complex chromosome rearrangements as revealed by both banding and FISH-mapping techniques.

Sixteen carriers of rob(1;29) (one of which was homozygous) from six different breeds (four Italian and two Portuguese), two heterozygous carriers of rob(26;29), three river buffaloes and two sheep were cytogenetically investigated in this study by using banding and FISH-mapping techniques (the latter only in cattle and river buffalo). Single- and dual- colour FISH were used with bovine probes containing both INRA143 (mapping proximally to BTA29) and bovine satellite (SAT) DNA SAT I, SAT III and SAT IV (mapping at the centromeric regions of cattle chromosomes). The combined use of these probes, the comparison of rob(1;29) with the dicentric rob(26;29) and with both river buffalo and sheep chromosomes (biarmed pairs) allowed us to hypothezise that rob(1;29) originated from complex chromosomal rearrangements through at least three sequential events: (a) centric fusion with the formation of a dicentric chromosome; (b) formation of a monocentric chromosome with loss of SAT I from both BTA1 and BTA29, most of SAT IV from BTA29 and, probably, some repeats of SAT III from BTA1; (c) double pericentric inversion or, more probably, a chromosome transposition of a small chromosome segment containing INRA143 from proximal p-arms to proximal q-arm of the translocated chromosome.

Fertility of cryopreserved sperm in three bulls with different Robertsonian translocations.

The fertility of three bulls carrying different Robertsonian translocations (rob(1;29), rob(14;17) and rob(26;29)) was evaluated. Oocytes-cumulus complexes obtained from slaughterhouse-derived ovaries were matured and then fertilised in vitro with frozen/thawed seminal material from the above mentioned subjects, and from control bulls with normal karyotype. An assessment was first made of the concentration, vitality and acrosome integrity of the seminal material to be sure that possible differences in the results of the in vitro fertilisation experiments were not due to seminal material quality. The results of the experiments, evaluated by the percentage of cleaved embryos and blastocysts per cleaved embryo, indicated that the three bulls carrying Robertsonian translocations had similar fertilising power and semen qualitative parameters to the controls. These data suggest that neither gametogenesys impairment nor decreased spermatozoa fertilising capacity is responsible for the reduced fertility in bulls with Robertsonian translocations. What the data do confirm is that the observed in vivo hypofertility for karyologically abnormal bulls is mainly due to early embryonic mortality.

Comparative FISH-mapping of the survival of motor neuron gene (SMN) in domestic bovids.

A comparative fluorescence in situ mapping of the SMN gene was performed on R-banded chromosome preparations of cattle (Bos taurus, BTA, 2n = 60), river buffalo (Bubalus bubalis, BBU, 2n = 50), sheep (Ovis aries, OAR, 2n = 54) and goat (Capra hircus, CHI, 2n = 60), as well as on those of a calf from Piedmont breed affected by arthrogryposis. SMN was located on BTA20q13.1, OAR16q13.1, CHI20q13.1 and BBU19q13. These chromosomes and chromosome bands are believed to be homeologous, confirming the high degree of chromosome homeologies among bovids. The position of SMN was refined in cattle, compared to the two previous localizations, while it is a new gene assignment in the other three bovids. A comparative fiber-FISH performed on extended chromatin of both normal cattle and calf affected by arthrogryposis revealed more extended FITC signals in the calf, compared to the normal cattle (control), suggesting a possible duplication of the SMN gene in the calf affected by arthrogryposis. .