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Background Work-related stress, anxiety and depression (WRSAD) are common, overlapping mental health problems burdened with major medical, occupational, institutional and societal implications. Current occupational health (OH) management of WRSAD is based on clinical and managerial guidelines and individual risk assessment. Aims The study sought to identify patterns of OH advice in WRSAD and the relationships between the OH advice, available evidence, experience and expertise of the OH doctors (OHDs). Methods A retrospective cross-sectional analysis of 101 first-time OH consultations for WRSAD by nine OHDs. Results The three most common OH interventions included follow-up OH consultations, adjusted duties and referrals for counselling. All OHDs preferred a light-touch approach but the less experienced and qualified OHDs were more proactive and prescriptive. Conclusions In the absence of a specific occupational medical guideline for the management of WRSAD, the OH interventions may be guided by clinical guidelines, individual risk assessment, the client’s circumstances or the experience, expertise and preferences of the OHDs. In the study group, OH interventions were under-utilized and not consistently applied. Our findings support the argument for OH guideline for WRSAD to improve the consistency and effectiveness of OH interventions. This is important given the scale of the problem and the recent increase in WRSAD during the COVID-19 pandemic.

Molecular dynamics (MD) computer simulations are used to investigate material ejection and fragment formation during keV C60 and Arm (m = 60, 101, 205, 366, 872 and 2953) bombardment of organic solids composed from octane and β-carotene molecules at 0° and 45° impact angle. Both systems are found to sputter efficiently. For the octane system, material removal occurs predominantly by ejection of intact molecules, while fragment emission is a significant ejection channel for β-carotene. A difference in the molecular dimensions is proposed to explain this observation. It has been shown that the dependence of the sputtering yield Y on the primary kinetic energy E and the cluster size n can be expressed in a simplified form if represented in reduced units. A linear and nonlinear dependence of the Y/n on the E/n are identified and the position of the transition point from the linear to nonlinear regions depends on the size of the cluster projectile. The impact angle has a minor influence on the shape of the simplified representation.

Large-scale molecular dynamics computer simulations are used to investigate the dynamics of material ejection during high-energy Ar_{n} cluster bombardment of Ag(111) at normal incidence. The silver sample containing 7 million atoms is bombarded with Ar_{n} projectiles (n=45-30000) with kinetic energy spanning from a few keV up to 1 MeV. Such a wide range of projectile parameters allows probing processes taking place during low-density collision cascade as well as during high-density events characteristic of micrometeorite bombardment in space. The material modifications and total sputtering yield of ejected particles are investigated. While at low-energy impacts, ejection of individual silver atoms is the main emission channel, the ejection of large clusters from the corona of the created crater dominates for the high-energy impacts.

Background: Stem cells isolated from amniotic fluid are known to be able to differentiate into different cells types, being thus considered as a potential tool for cellular therapy of different human diseases. In the present study, we report a nove! single step protocol for the osteoblastic differentiation of human arrmiotic fluid cells. Results: The described protocol is able to previde osteoblastic cells producing nodules of calcium mineralization within 18 days from withdrawal of amniotic fluid sarnples. These cells display a full expression of markers of osteogenic differentiation (COLl, OC, OPN, OCN, OPG, BSP, Runx2) within 30 days from withdrawal. In arder to test the ability of these cells to proliferate on surfaces commonly used in oral osteointegrated implantology, we carried out cultures onto different test disks, narnely smooth copper, machined titanium and Sandblasted and Acid Etching titanium (SLA titanium). Electron microscopy analysis evidenced the best celi gro'Nth on this latter surface. Conclusions: The described protocol provides an efficient and time-saving tool for the production of osteogenic cells from amniotic fluid that in the future could be used in ora! osteointegrated implantology.

We report the isolation and characterization of novel expressed sequences from the spinal muscular atrophy (SMA) region on human chromosome 5q13. Based on the sequence homology studies these cDNAs were grouped in four classes, one of which shows extensive homologies with the β-glucuronidase (BG) gene, differing in exon arrangement. The other cDNAs do not show any strong homology with known DNA sequences.

Deficit of the short stature homeobox containing gene (SHOX) accounts for 2.15% of cases of idiopathic short stature (ISS) and 50-100% of cases of Leri-Weill dyschondrosteosis (LWD). It has been demonstrated that patients with SHOX deficit show a good response to treatment with GH. Thus, the early identification of SHOX alterations is a crucial point in order to choose the best treatment for ISS and LWD patients. In this study, we analyze the most commonly used molecular techniques for the detection of SHOX gene alterations. multiple ligation-dependent probe amplification analysis appears to represent the gold standard for the detection of deletion involving the SHOX gene or the enhancer region, being able to show both alterations in a single assay.

Twelve patients with different features of Turner syndrome, and with Xp and Yp rearrangements involving the pseudoautosomal region (PAR1) are described. In all patients, FISH analysis showed loss of one copy of the Short Stature Homeobox (SHOX)-containing gene. Ten patients had short stature and one disproportionate (mesomelic) normal stature, while the last one had normal stature. Skeletal abnormalities, including shortened ulna, were detected in nine subjects, and in six of them Madelung deformity was observed. These clinical data indicated a genotype phenotype correlation between haploinsufficiency of SHOX, and short stature and skeletal abnormalities.

Deletions in distal Yq interval 6 represent the cause of 10-15% of idiopathic severe male infertility and map to a region defined AZFc (azoospermia factor c). The testis-specific gene DAZ is considered a major AZFc candidate, and its deletion has been associated with a severe disruption in spermatogenesis. However, DAZ is actually a multicopy gene family consisting of seven clustered copies spanning about 1 megabase. Only deletions removing the entire DAZ gene cluster together with other genes have been reported in infertile males. Because no case of spermatogenic failure has been traced to intragenic deletions, point mutations, or even deletions not involving all the DAZ copies, the definitive proof for a requirement of DAZ for spermatogenesis is still debatable. Here we report the first case of a partial deletion of the DAZ cluster removing all but one of the copies. This deletion is present in a patient affected with severe oligozoospermia who had a testicular phenotype characterized by a great quantitative reduction of germ cells (severe hypospermatogenesis). The absence of this deletion in the fertile brother of the patient suggests that this de novo mutation indeed caused the spermatogenic failure.

A male patient is reported with a 45,X karyotype and Leri-Weill dyschondrosteosis (LWD). FISH analysis with SHOX and SRY gene probes was carried out. One copy of both SHOX and SRY was detected in interphase nuclei, clarifying the origin of LWD and the male phenotype. Molecular results suggested that the 45,X karyotype arose through two independent events. The first occurred at paternal meiosis leading to an unequal crossing over between the short arms of the X and Y chromosomes. As a consequence, the SRY gene was translocated onto Xp, thereby explaining the male phenotype of the patient. The second event probably occurred at maternal meiosis or at the early stages of the zygote resulting in the loss of the maternal X chromosome. Keywords: 45,X karyotype; Leri-Weill syndrome; SHOX gene

Recent studies have suggested that simvastatin may exert endothelial-protective and anti-ischemic effects via nitric oxide (NO) mechanisms. The aim of this study was to evaluate, in isolated working rat hearts, the effect of acute simvastatin administration on endothelial and inducible NO-synthase (eNOS and iNOS) mRNA and on myocytic apoptosis after ischemia-reperfusion. We used isolated working rat hearts submitted to 15 min global, no-flow, normothermic ischemia and 180 min reperfusion. To detect myocytic apoptosis we used DNA agarose gel electrophoresis and Tunel technique; eNOS and iNOS expression were evaluated by multiplex reverse transcriptase-polymerase chain reaction; glyceraldehyde-3-phosphate dehydrogenase (G3PDH) was used as standard. The eNOS and iNOS mRNAs were expressed as G3PDH/eNOS and G3PDH/iNOS densitometric ratio (BioRad Gel Doc 1000). Hearts were divided into four groups: A) hearts excised and used as histological controls; B) untreated hearts submitted to ischemia and reperfusion; C) actinomicin D-treated (1.5 mg/kg) hearts, perfused with 25 microM simvastatin, subjected to ischemia and reperfusion; D) hearts treated with simvastatin 25 microM and submitted to ischemia and reperfusion. In Group B we evidenced a significant myocytic apoptotic damage, reduced in groups C and D. In Group B an increase in G3PDH/eNOS ratio vs Group A was detected; in Group D a reduction in G3PDH/eNOS ratio vs Group B occurred; no significant changes were observed between groups C and D. As for G3PDH/iNOS ratio, it was significantly increased in Group D with respect to groups A and B. Our data suggest that simvastatin in acute may modulate NO-synthase mRNA expression (induction of eNOS mRNA by means of post-transcriptional mechanisms and inhibition of iNOS postischemic overexpression) and reduce myocytic apoptosis.

A screening study performed on 2,803 pregnant women using the "triple test" is reported.Nine hundred and twenty-one had a high prior risk, having35 years while, after the screening, only 201 women had a positive test at risk higher than 1:270, and underwent to amniocentesis. The detection rate (DR) for all abnormalities was 91% while for Down's syndrome (DS) it was 87.5% and for neural tube defects 85.5%. Foetal abnormalities were detected in 20 cases (1:10) while 181 were false positive cases (6.5%), of which 151 for DS (5.4%). False negative were observed only in 2 cases within 2,339 at term pregnancies.The authors retain that high DR is related to the exactness of determination of gestation age calculated by scan and to the homogeneity of the examined population.

Two patients are reported who presented with 4q deletion and r(4), respectively. Cytogenetic and FISH analysis defined the breakpoints respectively at bands 4q33--q35 proximal to the telomere, and 4pter and 4q35.2 qter. Moreover in both cases rearranged chromosomes maintained telomeric sequences. The first patient showed some clinical features of deletion 4q and a pointed 5th finger, a characteristic finding in deletion 4q31--qter. The second patient had mild dysmorphism associated with growth retardation.

Fluorescence in situ hybridization (FISH) and cytogenetic analysis were carried out in 33 transplanted patients suffering from different hematologic disease using probes for X and Y chromosomes and ABL and BCR genes. FISH showed that recipient cells were invariably present during post-transplant follow-up. Stable minimal residual disease was associated with clinical and hematologic remission, while a progressive increase of host cells was strictly related with disease relapse. Cytogenetic investigation on the same samples showed recipient cells only in few cases. It was concluded that FISH analysis is useful for: (1) characterizing cases in which standard cytogenetic analysis has failed; (2) detecting host cells in sex-mismatched transplanted patients; and (3) evaluating Ph-negative CML with the BCR/ABL rearrangement. The possibility of detecting chromosome rearrangements in interphase nuclei using FISH analysis improves diagnosis and prediction of disease evolution and prompts earlier therapeutic approaches.

We report the molecular cytogenetic analysis of a case of Philadelphia (Ph)-negative, BCR-positive chronic myeloid leukemia (CML) which appeared by conventional cytogenetics to have a t(6;9)(p23;q34) as the sole cytogenetic abnormality. Neither conventional nor pulse-field Southern blots detected any rearrangement of the DEK or CAN genes which are often fused in acute myeloid leukemia (AML) with t(6;9)(p23;q34). However, rearrangements of both BCR and ABL genes were detected. The breakpoint in BCR was located in the major translocation cluster region between exons b1 and b3. ABL rearrangements were detected with an ABL exon 1B probe and with a probe located 5' of the entire ABL gene. Comigration between the rearranged fragments obtained with M-bcr-5' and ABL exon 1B probes was observed, implying that the entire ABL gene was fused to the 5' part of the BCR gene. Fluorescence in situ hybridization (FISH) analyses using BCR and ABL probes showed that in 20% of metaphases BCR and ABL signals were present on one chromosome 6 at 6p23, whilst in 80% of metaphases BCR and ABL signals were identified on both copies of chromosome 6. Furthermore, FISH analysis with a whole-chromosome 22 paint demonstrated that chromosome 22 material was present on both copies of chromosome 6. These data indicate a complex Philadelphia translocation involving chromosome band 6p23 and duplication of the whole aberrant chromosome. The nature of the gene locus on 6p23, involved in this rearrangement, remains unknown. A similar translocation has been previously reported in a case of CML, which also lacked DEK and CAN gene rearrangements implying that abnormalities of 6p23 involving genes other than DEK may be a recurrent abnormality in CML.

Two non-familial extra supernumerary abnormal chromosomes (ESAC) were detected in fetuses monitored by midtrimes ter amniocentesis. Characterization of these ESACs was carried out using conventional cytogenetic analysis, fluorescence in situ hybridization, and DNAse I hypersensitivity. Based on these studies it was concluded that the two ESACs were derived respectively from chromosomes 14/22 and isodicentric chromosome 15. Based on cytogenetic results it was argued that unconsistent phenotypic effect was associated with the two aneuploidies. This optimistic view was confirmed at birth of unaffected babies and unremarkable follow up at 6 and 12 months.

Five patients (age range 7-14 years) received allogeneic bone marrow transplantation (BMT) for Fanconi anemia (FA). All patients showed progressive pancytopenia associated with congenital malformations. Diagnosis was confirmed by studies of cellular hypersensitivity to the clastogenic effect of the DNA crosslinking agent diepoxybutane. The conditioning regimen consisted of low dose cyclophosphamide (5 mg/kg x 4) and fractionated total body irradiation (167 cGy x 3). For graft-versus-host disease prophylaxis one patient was given cyclosporin alone while the remaining four patients received a combination of cyclosporin and two doses of methotrexate. Marrow was given unmanipulated from HLA-identical siblings. All patients are alive 18-67 months after grafting with Karnofsky scores of 100% and normal hemopoiesis of donor origin. Modifications in transplant protocols such as those here described have resulted in a decreased risk of severe transplant-related complications. These results confirm that BMT is a curative therapy in FA patients and should be considered as a first choice treatment if an HLA-identical donor is available.

AluI and HaeIII restriction endonuclease banding patterns were analyzed in Macaca fuscata and Cercopithecus aethiops sabaeus chromosomes. AluI produced C-negative bands in both species of monkeys, while HaeIII induced the appearance of C-negative bands on Macaca chromosomes and of simultaneous G + C bands on Cercopithecus metaphases.

The authors report on a cytogenetic survey of 61 patients with preleukemic syndrome (PLS). Of these, 41 had a myeloproliferative disease (MPD) and 20 a myelodysplastic syndrome (MDS). Clonal chromosome abnormalities appeared in 24 patients (39.3%) at disease onset. Such changes had a frequency of 26.8% in patients with MPD and 65% in those with MDS. The authors stress the usefulness of ethidium bromide high resolution techniques. They allow obtaining a larger number of metaphases and elongated chromosomes with higher banding resolution and could account for the frequent detection of chromosome changes in most groups of MDS patients in the present series. Moreover, they discuss the possible significance of some chromosome aberrations suggesting that patients with MPD may live longer than those with MDS because of their higher frequency of normal karyotypes.

In Down syndrome there is a high incidence of overt or subclinical hypothyroidism as well as some immunological defects, early thymic involution associated to low serum zinc levels. Zinc supplementation to the diet has been reported to transiently improve thymic function; moreover thymic function has been shown to be in relation with the pituitary-thyroid axis. The aim of this study was to evaluate if, in Down patients, zinc therapy could improve also thyroid function, by determining serum levels of total and free thyroid hormones and basal TSH levels. In 52 patients studied, we found a high incidence of subclinical hypothyroidism (30%); in 17 patients treated with zinc sulphate we showed a reduction of FT3. More significantly, we detected 9 patients with low zinc levels in which zinc supplementation improved thyroid function, thus reducing the incidence of subclinical hypothyroidism.

The authors report on the activity of Hinf I restriction endonuclease on human fixed metaphase chromosomes. Experiments performed by digesting chromosomes just after harvesting or after ageing in methanol-acetic acid displayed a different pattern of digestion on metaphases, since only aged preparations showed gaps on heterochromatic regions of chromosomes 1, 9 and 16 and C-like bands on other chromosomes. In this view, the authors suggest that structural modifications of the DNA, induced by acid fixation, can influence Hinf I activity on fixed metaphase chromosomes.

Cytogenetic studies on a group of 140 patients with alterations of sex features (sex uncertainty, gynecomasty, menstrual abnormality and so on) confirmed a high incidence of chromosome abnormalities (25%). Most frequent abnormal kariotypes were X0 and XXY. Furthermore, cytogenetic investigations showed a higher rate of heterochromatic polymorphism in patients (33.7%) than in controls (13.4%), the most frequent being 1qh, 9qh and 16qh. A possible role of heterochromatic polymorphism in determining sex chromosome abnormalities or, directly, sex diseases, and in possibly enhancing neoplastic risk, is suggested.

The authors report haematologic and cytogenetic data from 47 patients with ANLL, demonstrating the usefulness of cytogenetic studies for the classification as well as for the prognosis of this disorder. Chromosome studies also permitted the classification of marrow cellularity in: all diploid metaphases (NN), diploid and aneuploid metaphases (AN), and all aneuploid metaphases (AA). The remission rate for patients in whom only normal metaphases were detected (NN patients) was 83% while the remission rates were 67% and 33% respectively for patients in whom both normal and abnormal metaphases were seen (AN patients) and for those in whom only abnormal metaphases were noted (AA patients). In all FAB subgroups, complete remission was related to chromosomal abnormalities, except for M4 patients who evidenced a large number of complete remissions, although presenting more chromosomal abnormalities. The longer survival in this subgroup may be related to rearrangements of chromosome 16, which is associated with a better prognosis.

We report the cytogenetic data of two patients with erythroleukemia showing the chromosome Ph'. In one case the chromosome Ph', as revealed with the GTG band technique was the result of a translocation involving the chromosomes 19 and 22. The aim of this work is to provide more contribution to the knowledge of the origin of the Ph' and to give data in the field of this disease for which few cytogenetic data are available after the introduction of the banding techniques.

One case of Chronic Granulocytic Leukemia is reported, in which the patient showed, during a blastic crisis, an aneupolid cariotype 45, XX, t (9; 22) (q34; q11), -16. This paper emphasizes the rare involvement of the chromosome 16 in Leukemias, and stresses the high frequency of the alterations of the chromosome group E in the course of blastic crisis.

The restriction endonucleases HpaII and MspI both cleave the nucleotide sequence CCGG, but the action of HpaII is inhibited if the internal cytosine is methylated. HpaII and MspI were used on fixed chromosomes from bone marrow cells of individuals suffering from chronic myelogenous leukemia and healthy individuals. We found that MspI acts with the same efficiency on all chromosome samples, whereas HpaII extracts more DNA from the chromosomes of leukemic individuals than from the chromosomes of nonleukemic individuals. We postulate that demethylation of cytosine in the CpG dinucleotide of leukemic cell DNA accounts for our findings.

A cooperative study between clinical and cytogenetic steps in 44 patients with Ph'+ CGL is reported in order to verific the usefulness of the cytogenetic screening for the diagnosis and the right classification of the patients. The study of the clinical steps is carried out on the basis of the parameters suggested by Tura and coll.; in the one of the cytogenetic steps Sandberg classification modified by the Authors is adopted. In 40 cases the comparison shows a marrow correspondence between clinical and cytogenetic steps. In fact the overage survival in the classical true steps of the disease is almost the sance in the 1st and 2nd step. In the 3rd step the survival is strongly reduced meaning that the more chromosome alterations are observed the more survival is reduced.

We report cytogenetic data concerning 9 patients with chronica granulocytic leukemia and eosinophilia at the onset and during the chronic phase of the disease before the blastic crisis. The cariotype analises in the intermediate phases allowed to determine the first changes which could be involved in the evolutionary events of the disease up to the moment in which the typical markers of the blastic crisis can be found.

Experiments were performed on fixed metaphase chromosomes using standard techniques for revealing paracentromeric heterochromatin (C bands) followed by staining with acridine orange with the aim of studying C-banding mechanism. Data obtained suggest that the specific resistance to the chemical-physical treatments of the heterochromatic areas is a consequence of the particular structural conditions that the C-positive material shows only after its early renaturation.

We report on a case of "de novo" interstitial duplication of bands 2p21-22 in a 31-month-old female with mild mental retardation and dysmorphism. Cytogenetic investigations were performed on peripheral blood by adding 5-BrdU and 5-FdU. Measurements of enzymatic activity of malate dehydrogenase, whose gene has been mapped on the band 2p23, added reliability to the identification of bands 2p21-22 as the duplicated segment. The authors suggest that the duplication of this segment is able to cause the clinical picture of the syndrome of partial 2p trisomy.

One case of a patient with Chronic Granulocytic Leukemia showing a double Ph' together with trisomy 17 during blastic crisis is reported. The Ph' chromosome resulting from a standard translocation of the chromosomes 9 and 22 was present in all the 16 mitoses observed, while the trisomy 17 was found in 15. This case is an additional contribution which demonstrates the presence of the alterations of the chromosome group E during the blastic crisis.

In this we report cytogenetic data concerning two patients with Acute Lymphoblastic Leukemia (ALL), submitted to bone marrow transplantation. In one of two patients the chimere was present while in the other case it was absent, since the donor and the acceptor were of the same sex. However even in the latter case, the cytogenetic analysis was useful and led to the identification of endomitosis and endoreduplication phenomena, which are signs for an unlucky prognosis.

Interactions amond DNA, phospholipids, and Cu2+ ions have been investigated by means of thermal denaturation technique. The results indicate that phosphatidylserine and sphingomyelin interact with Cu2+ ions, which are able to prevent the chance of binding of the phospholipids to the double helix. This interaction is strictly dependent upon the concentration of the divalent cation and reduces the capability of the employed phospholipids to modify the thermal stability of DNA.