Diffuse malignant pleural mesothelioma in an urban hospital: clinical spectrum and trend in incidence over time

This retrospective analysis reviews the clinical experience of a major urban referral hospital with diffuse malignant pleural mesothelioma during the 14-year period from 1973 through 1986. Seventy-five cases of definite or equivocal mesothelioma were identified. There were four cases of primary malignant peritoneal mesothelioma, seven cases of benign fibrous mesothelioma, and 64 cases of diffuse malignant pleural mesothelioma. In 43 cases (67%) of diffuse malignant pleural mesothelioma, there was historic evidence of asbestos exposure. In 21 cases (33%), there was no known history of asbestos exposure. An increase in annual incidence of diffuse malignant pleural mesothelioma was observed over the study period, from three cases in 1973 to ten cases in 1986. Despite greater awareness of this disease, the diagnosis remains a difficult one to establish given the nonspecific symptoms, signs and radiographic appearance, variable histologic appearance, and poor diagnostic sensitivity and specificity of thoracentesis and closed pleural biopsy. Thoracotomy, thoracoscopy, and CT-guided needle biopsies gave higher yields and are the diagnostic measures of choice when diffuse malignant pleural mesothelioma is suspected.     

Sympathetic skin response (SSR) in erythromelalgia

BACKGROUND: Erythromelalgia (EM) is characterized by severe pain associated with local redness and hotness in the extremities. When the extremity is lowered, or heat is applied, the pain is intensified and when coldness is applied, or the extremity is elevated the pain is decreased. OBJECTIVE: To evaluate if there is any sympathetic nervous system involvement in erythromelalgia, sympathetic skin response (SSR) test was done. SETTING: This study was conducted during the years 1998-2000 in the Department of Physical medicine and Rehabilitation, Shiraz University of Medical Sciences. METHODS: SSR study was done on 22 patients with erythromelalgia and 22 normal subjects were matched for age and sex for comparison. RESULTS: There is a significant difference between the patients and controls especially in the lower extremity findings (P = 0.000). More than 72.7% of the patients had abnormal SSR. CONCLUSION: It is concluded that sympathetic peripheral fibers (C fibers) are involved in erythromelalgia and it is probably the pathogenesis of the disease.     

Epstein-Barr virus-associated smooth muscle tumors in immunocompromised patients: Six case reports

BACKGROUNDEpstein-Barr virus associated smooth muscle tumor (EBV-SMT) is a rare oncological entity. However, there is an increasing incidence of EBV-SMTs, as the frequency of organ transplantation and immunosuppression grows. EBV-SMT diagnosis relies on histopathology and immunochemical staining to distinguish it from post-transplant lymphoproliferative disorder (PTLD). There is no clear consensus on the treatment of EBV-SMTs. However, surgical resection, chemotherapy, radiation therapy, and immunosuppression reduction have been explored with varying degrees of success. CASE SUMMARYOur case series includes six cases of EBV-SMTs across different age groups, with different treatment modalities, adding to the limited existing literature on this rare tumor. The median latency time between immunosuppression and disease diagnosis is four years. EBV-SMTs present with variable degrees of aggressiveness and seem to have worse clinical outcomes in patients with tumor multiplicity and worse immunocompetency.CONCLUSIONIt is imperative to continue building on this knowledge and keeping EBV-SMTs on the differential in immunocompromised individuals.     

Vacancy impacts on electronic and mechanical properties of MX2 (M = Mo,W and X = S,Se) monolayers

Monolayers of transition metal dichalcogenides (TMD) exhibit excellent mechanical and electrical characteristics. Previous studies have shown that vacancies are frequently created during the synthesis, which can alter the physicochemical characteristics of TMDs. Even though the properties of pristine TMD structures are well studied, the effects of vacancies on the electrical and mechanical properties have received far less attention. In this paper, we applied first-principles density functional theory (DFT) to comparatively investigate the properties of defective TMD monolayers including molybdenum disulfide (MoS₂), molybdenum diselenide (MoSe₂), tungsten disulfide (WS₂), and tungsten diselenide (WSe₂). The impacts of six types of anion or metal complex vacancies were studied. According to our findings, the electronic and mechanical properties are slightly impacted by anion vacancy defects. In contrast, vacancies in metal complexes considerably affect their electronic and mechanical properties. Additionally, the mechanical properties of TMDs are significantly influenced by both their structural phases and anions. Specifically, defective diselenides become more mechanically unstable due to the comparatively poor bonding strength between Se and metal based on the analysis of the crystal orbital Hamilton population (COHP). The outcomes of this study may provide the theoretical knowledge base to boost more applications of the TMD systems through defect engineering.

The impacts of six different types of vacancies on the electronic and mechanical properties of MX2 (M = Mo, W and X = S, Se) monolayers have been theoretically revealed.     

Cavum velum interpositum cysts in normal and anomalous fetuses in second trimester of pregnancy: Comparison of its size and prevalence

ObjectiveCavum veli interpositi (CVI) is a potential space below the splenium of corpus callosum and sometimes presents as a cyst.Materials and methodsIn this prospective cross-sectional study, 360 fetuses with normal second trimester scan and 152 s trimester fetuses with structural abnormalities were included.ResultsThe CVI cysts were more common in fetuses with brain anomaly compared to normal fetuses and fetuses with extra-central nervous system (CNS) anomalies (23% vs 18.3% and 18% respectively; p value < 0.01). The mean size of cysts in normal fetuses, fetuses with extra-CNS anomalies and fetuses with brain abnormalities was 4.6 mm, 5.8 mm and 9.2 mm respectively. There was a significant difference between cysts size in normal fetuses and fetuses with brain anomalies (p value < 0.01) and the cut-point was 7.1 mm.ConclusionThe prevalence of CVI cysts is more in fetuses with brain anomaly. Fetuses with a cyst size >7.1 mm need a more detailed brain examination.     

Disturbance of zinc and glucose homeostasis by methyl tert-butyl ether (MTBE); evidence for type 2 diabetes

1.?The prevalence of diabetes and the other metabolic disorders has noticeably increased worldwide. A causal link between increasing risk of type 2 diabetes and exposure to environmental pollutants has been reported.

2.?We hypothesized that exposure to methyl tert-butyl ether (MTBE), an oxygenate additive to gasoline would hinder zinc and glucose homeostasis in rats.

3.?Male Sprague–Dawley rats received MTBE in drinking water for 90 days. At the end of the treatment, pancreas and blood samples were collected for biochemical and molecular examinations. Expression of four candidate genes, including Insulin1, Insulin2, MT1A, SLC30A8 by Real-Time Quantitative PCR (Q-PCR) as well as biochemical parameters, including fasting blood glucose (FBS), triglycerides (TG), cholesterol (CHO), low-density lipoprotein (LDL), high-density lipoprotein (HDL), copper (Cu²⁺) and calcium (Ca²⁺) levels as well as High-sensitive C-reactive protein were assessed as endpoints.

4.?This study suggested that MTBE exposure can be associated with disruption in zinc homeostasis and glucose tolerance.     

Rare recombination events generate sequence diversity among balancer chromosomes in Drosophila melanogaster

Multiply inverted balancer chromosomes that suppress exchange with their homologs are an essential part of the Drosophila melanogaster genetic toolkit. Despite their widespread use, the organization of balancer chromosomes has not been characterized at the molecular level, and the degree of sequence variation among copies of balancer chromosomes is unknown. To map inversion breakpoints and study potential diversity in descendants of a structurally identical balancer chromosome, we sequenced a panel of laboratory stocks containing the most widely used X chromosome balancer, First Multiple 7 (FM7). We mapped the locations of FM7 breakpoints to precise euchromatic coordinates and identified the flanking sequence of breakpoints in heterochromatic regions. Analysis of SNP variation revealed megabase-scale blocks of sequence divergence among currently used FM7 stocks. We present evidence that this divergence arose through rare double-crossover events that replaced a female-sterile allele of the singed gene (sn^X2) on FM7c with a sequence from balanced chromosomes. We propose that although double-crossover events are rare in individual crosses, many FM7c chromosomes in the Bloomington Drosophila Stock Center have lost sn^X2 by this mechanism on a historical timescale. Finally, we characterize the original allele of the Bar gene (B¹) that is carried on FM7, and validate the hypothesis that the origin and subsequent reversion of the B¹ duplication are mediated by unequal exchange. Our results reject a simple nonrecombining, clonal mode for the laboratory evolution of balancer chromosomes and have implications for how balancer chromosomes should be used in the design and interpretation of genetic experiments in Drosophila.Balancer chromosomes are genetically engineered chromosomes that suppress crossing over with their homologs and are used for many purposes in genetics, including construction of complex genotypes, maintenance of stocks, and estimation of mutation rates. Balancers typically carry multiple inversions that suppress genetic exchange or result in the formation of abnormal meiotic products if crossing over does occur (Fig. 1A); for example, single crossovers inside the inverted segment create acentric or dicentric chromosomes that will fail to segregate properly during meiosis or large deletions or duplications that will likely result in inviable gametes (1, 2). Balancers also often carry recessive lethal or sterile mutations to prevent their propagation as homozygotes as well as dominant markers for easy identification. First developed for use in Drosophila melanogaster, balancer chromosomes remain some of the most powerful tools for genetic analysis in this species (3).Open in a separate windowFig. 1.Consequences of a single or double crossover between a WT X chromosome and an X chromosome carrying a single inversion, In(1)dl-49. Euchromatin is shown in blue, heterochromatin is shown in gray, and centromeres are depicted as circles. Thin white lines mark locations of inversion breakpoints, and yellow crosses/thin lines mark locations of crossover events. (A) A single crossover event within the inverted segment results in the formation of chromosomes with deletions and zero (acentric) centromeres or duplications and two (dicentric) centromeres, neither of which will segregate properly during meiosis. (B) A double crossover within an inverted segment results in intact chromosomes with one centromere that will segregate properly during meiosis.Despite their widespread use, very little is known about the organization of Drosophila balancer chromosomes at the molecular level. Since their original syntheses decades ago, balancers have undergone many manipulations, including the addition or removal of genetic markers. Moreover, rare recombination events can cause spontaneous loss of deleterious alleles on chromosomes kept over balancers in stock, as well as loss of marker alleles on balancer chromosomes themselves (3). Likewise, recent evidence has shown that sequence variants can be exchanged between balancer chromosomes and their wild type (WT) homologs via gene conversion during stock construction or maintenance (4, 5). Thus, substantial variation may exist among structurally identical balancer chromosomes owing to various types of sequence exchange.To gain insight into the structure and evolution of balancer chromosomes, we have undertaken a genomic analysis of the most commonly used X chromosome balancer in D. melanogaster, First Multiple 7 (FM7). We have focused on FM7 because this X chromosome balancer series lacks lethal mutations and thus can be easily sequenced in a hemizygous or homozygous state. In addition, the FM7 chromosome has been shown to pair normally along most of its axis with a standard X chromosome, providing a structural basis for possible exchange events (6). Moreover, although details of how early balancers in D. melanogaster were created are not fully recorded, the synthesis and cytology of the FM7 series is reasonably well documented (3).The earliest chromosome in the FM7 series, FM7a, was constructed using two progenitor X chromosome balancers, FM1 and FM6, to create a chromosome carrying three inversions—In(1)sc⁸, In(1)dl-49, and In(1)FM6—relative to the WT configuration (7, 8) (Fig. 2A). Subsequently, a female-sterile allele of singed (sn^X2) was introduced onto FM7a to create FM7c, which prevents the loss of balanced chromosomes carrying recessive lethal or female-sterile mutations (9). More recently, versions of FM7a and FM7c have been generated that carry transgene insertions that allow the determination of balancer genotypes in embryonic or pupal stages (10–14).Open in a separate windowFig. 2.Structure of the FM7 balancer chromosome. Euchromatin is shown in blue, and heterochromatin is shown in gray. (A) Schematic view of the organization of WT and FM7 X chromosomes. FM7 contains three inversions—In(1)sc⁸, In(1)dl-49, and In(1)FM6—relative to WT. The six breakpoint junctions for the three inversions are numbered 1–6 and are shown in detail in B. (B) Location and organization of inversion breakpoints in FM7. Each inversion has two breakpoints that can be represented as A/B and C/D in the standard WT arrangement and as A/C and B/D in the inverted FM7 arrangement, where A, B, C, and D represent the sequences on either side of the breakpoints. Locations of euchromatic breakpoints are on Release 5 genome coordinates, and the identity of the best BLAST match in FlyBase is shown for heterochromatic sequences. Primers used for PCR amplification are shown above each breakpoint; details are provided in Methods and Datasets S2 and S3. Forward and reverse primers are named with respect to the orientation of the assembled breakpoint contigs, not the orientation of the WT or FM7 X chromosome.To identify the inversion breakpoints in FM7 balancers and to study patterns of sequence variation that may have arisen since the origin of the FM7 series, we sequenced genomes of eight D. melanogaster stocks carrying the FM7 chromosome (four FM7a and four FM7c). We discovered several megabase-scale regions in which FM7c chromosomes differ from one another, which presumably arose via double-crossover (DCO) events from balanced chromosomes (Fig. 1B). These DCOs eliminate the female-sterile sn^X2 allele in the centrally located In(1)dl-49 inversion and are expected to confer a fitness advantage to sn⁺ chromosomes, either by allowing propagation of sn⁺ FM7 as homozygotes in females or by sn⁺ FM7 males outcompeting sn^X2 FM7 males in culture. We found that loss of the sn^X2 allele is common in FM7c chromosomes by screening other FM7c-carrying stocks at the Bloomington Drosophila Stock Center. We also identified the breakpoints of the B¹ duplication carried on FM7, and found direct molecular evidence for the role of unequal exchange in the origin and reversion of the B¹ allele (15–19). Our results provide clear evidence that the common assumption that balancers are fully nonrecombining chromosomes is incorrect on a historical timescale, and that substantial sequence variation exists among balancer chromosomes in circulation today.