VPS13D-based disease: Expansion of the clinical phenotype in two brothers and mutation diversity in the Turkish population.

VPS13D is a recently described gene. Worldwide, only 15 families with 23 affected individuals have been reported with a VPS13D-based disease. Mutated VPS13D causes a complex phenotype with a hyperkinetic movement disorder and ataxia, especially in childhood onset disease. The clinical phenotype of the rare adult-onset cases consists of cerebellar ataxia and/or spastic paraplegia. Here, we report the extensive clinical, laboratory and genetic findings of two offspring from consanguineous parents, with ages of disease onset at 57 and 49 with VPS13D-based ataxia. Although conventional magnetic resonance imaging showed mild cerebellar and cerebral atrophy, diffusion tensor imaging, applied for the first time for VPS13D patients, revealed prominent atrophy in U fibers and cerebellopontine tracts. Whole exome sequencing analysis revealed a biallelic Ala4210Val mutation in the VPS13D, reported only once in the literature. Complementary screening of our in-house database consisting of 295 ataxia and hereditary spastic paraplegia patients revealed two further ataxia patients with novel VPS13D variants. Screening the control cohort for VPS13D variants revealed one asymptomatic individual carrying a novel VPS13D variant. In this study, the phenotypic spectrum of VPS13D-based disease is expanded with the description of pre-senile onset predominant ataxia. Further, with the additional novel mutations described, the report is expected to contribute to the understanding of the yet elusive phenotype-genotype correlations in the rare VPS13D-based movement disorder.

Co-infection relationship with Epstein-Barr virus in gastroduodenal diseases with Helicobacter Pylori. Quantitative PCR and EBNA-1 gene-based approach.

Objective: Helicobacter pylori (Hp) and Epstein-Barr virus (EBV) are involved in gastric cancer (GC) etiology. EBV/Hp co- infection was thought synergistically increase gastroduodenal disease occurence. We aimed to determine the presence of EBV/Hp co-infection in gastroduodenal diseases. Methods: The study group had 68 Hp (+) cases [25 GC, 13 IM (intestinal metaplasia), 30 PU (peptic ulcer)], and the control group had 40 NUD (non-ulcer dyspepsia) cases [20 Hp+, 20 Hp-]. EBV-DNA was detected by non-polymorphic EBNA-1 gene-based qPCR. EBV/EBNA-1 IgG levels were determined by quantitative and qualitative ELISA methods, respectively. Results: EBV-DNA positivity was 32% (8/25), 6.6% (2/30) and 5% (1/20) in GC, PU and NUD Hp (+) cases, respectively. There was a significant difference (p = 0.001) between GC (32%) and NUD Hp (+) (5%) cases in terms of EBV-DNA positivity. Mean EBV-DNA copy numbers were 6568.54 ± 20351, 30.60 ± 159.88 and 13.85 ± 61.93 for GC, PU, and NUD, respectively. In terms of the mean EBV-DNA copy number, a significant difference was found between the groups (p = 0.005). In terms of EBV/EBNA-1 IgG antibody positivity, no significant difference was found between GC and NUD cases (p = 0.248). EBV DNA positivity was found to be significant (odds ration [OR] = 26.71 (p=0.009, %95CI 2.286- 312.041) in multivariate logistic regression. Conclusioin: Although we had a small number of GC cases, it can be suggested that the estimated risk created by the synergistic effect based on the addition of EBV increased 26 times in the presence of Hp in GC.

Noninvasive ventilation with nursing perspective: Impacts on patient tolerance, short-term adverse effects, and nursing workload.

BACKGROUND: The success of noninvasive ventilation (NIV) treatment is closely related to high levels of clinical support. AIMS: In this study, we sought to analyze patient mask compliance and minor side effects and to evaluate additional nursing workload needed for the NIV care. MATERIALS AND METHODS: The study was designed as a prospective and observational. The data were collected from an intensive care unit. Clinical and physiological data, patient tolerance and adverse effects, subjects' complaints about their experience, and additional nursing workload associated with NIV treatment were assessed. RESULTS: Statistically significant improvements were obtained in arterial blood gas analysis, respiratory rate, and heart rate during treatment. In the first 2 h, 65% of subjects had poor mask compliance, patients' comfort scores were poor, and incompliance was associated with discomfort. The ratio of skin problems was 15% in the first 24 h and reached 60% at 48 h. The pain rate due to mask ties was 80% and then increased to 90% at 48 h. There was a significant relationship between the problems detected by the nurses and problems described by the subjects. Additional nursing workload was found as 110 min for 0-6 h. CONCLUSIONS: We observed that the mask compliance and comfort levels of the subjects were poor. Skin breakdowns increased depending on the duration of treatment. Treatment would require continuous nursing support in seven areas. NIV treatment generated a significant amount of workload for nurses. Additional nursing workforce planning is required for NIV units for successful NIV treatment.

Multiparametric MRI of rectal cancer-repeatability of quantitative data: a feasibility study.

PURPOSE: In this study, we aimed to analyze the repeatability of quantitative multiparametric rectal magnetic resonance imaging (MRI) parameters with different measurement techniques. METHODS: All examinations were performed with 3 T MRI system. In addition to routine sequences for rectal cancer imaging protocol, small field-of-view diffusion-weighted imaging and perfusion sequences were acquired in each patient. Apparent diffusion coefficient (ADC) was used for diffusion analysis and ktrans was used for perfusion analysis. Three different methods were used in measurement of these parameters; measurements were performed twice by one radiologist for intraobserver and separately by three radiologists for interobserver variability analysis. ADC was measured by the lowest value, the value at maximum wall thickness, and freehand techniques. Ktrans was measured at the slice with maximum wall thickness, by freehand drawn region of interest (ROI), and at the dark red spot with maximum value. RESULTS: A total of 30 patients with biopsy-proven rectal adenocarcinoma were included in the study. The mean values of the parameters measured by the first radiologist on the first and second measurements were as follows: mean lowest ADC, 721.31±147.18 mm2/s and 718.96±135.71 mm2/s; mean ADC value on the slice with maximum wall thickness, 829.90±144.24 mm2/s and 829.48±149.23 mm2/s; mean ADC value measured by freehand ROI on the slice with maximum wall thickness, 846.56±136.31 mm2/s and 848.23±144.15 mm2/s; mean ktrans value on the slice with maximum wall thickness, 0.219±0.080 and 0.214±0.074; mean ktrans by freehand ROI technique (including as much tumoral tissue as possible), 0.208±0.074 and 0.207±0.069; mean ktrans measured from the dark red foci, 0.308±0.109 and 0.311±0.105. Intraobserver agreement was very good among diffusion and perfusion parameters obtained with all three measurement techniques. Interobserver agreement was very good, except for one of the measurement techniques. As far as interobserver variability is considered, only ADC value measured on the slice with maximum wall thickness differed significantly. CONCLUSION: Multiparametric MRI of rectum, using ADC as the diffusion and ktrans as the perfusion parameter is a repeatable technique. This technique may potentially be used in prediction and evaluation of neoadjuvant treatment response. New studies with larger patient groups are needed to validate the role of multiparametric MRI.

Cerebellar cognitive-affective syndrome preceding ataxia associated with complex extrapyramidal features in a Turkish SCA48 family.

SCA48 is a novel spinocerebellar ataxia (SCA) originally and recently characterized by prominent cerebellar cognitive-affective syndrome (CCAS) and late-onset ataxia caused by mutations on the STUB1 gene. Here, we report the first SCA48 case from Turkey with novel clinical features and diffusion tensor imaging (DTI) findings, used for the first time to evaluate a SCA48 patient. A 65-year-old female patient with slowly progressive cerebellar ataxia, cognitive impairment, behavioral changes, and a vertical family history was evaluated. Following the exclusion of repeat expansion ataxias, whole exome sequencing (WES) was performed. Brain magnetic resonance imaging (MRI), including DTI, and single-photon emission computed tomography (SPECT) were used to study the primarily affected tracts and regions. WES revealed the previously reported heterozygous truncating mutation in ubiquitin ligase domain of STUB1 (ENST00000219548:c.823_824delCT, ENSP00000219548:p.L275Dfs*16) leading to a frameshift. Patient's cognitive status was compatible with CCAS. Novel clinical features different from the original report include later onset chorea, dystonia, general slowness of movements, apraxia, and palilalia, some of which have been recently reported in two families with different STUB1 mutations. CCAS is a prominent and often early feature of SCA48 which may be followed years after the onset of the disease by other complex neurological signs and symptoms. DTI may be helpful for demonstrating the cerebello-frontal tracts, involved in CCAS-associated SCA48, the differential diagnosis of which may be challenging especially in its early years.

Using a clinical linac to determine the energy levels of (92m)Nb via the photonuclear reaction.

The bremsstrahlung photons of 18MeV end-point energy produced by a clinical linear accelerator were used to irradiate (93)Nb, producing (92m)Nb via the photonuclear reaction. The gamma-ray spectrum emitted by the excited nucleus was measured with high purity germanium detector. For analysis of the energy transitions, both gf3 and ROOT spectrum analysis programs were applied. The results were shown to be comparable with the literature values, demonstrating the ability to use a clinical liner accelerator in nuclear physics measurements.

Spectroscopic analysis of Ahlat stone (ignimbrite) and pumice formed by volcanic activity.

Natural materials such as ignimbrites are preferred commonly not only in historical places but also in houses or in different kind of buildings all over the world especially around Ahlat in Bitlis-Turkey. Durability, lightness and good-insulation are the significative properties of these stones. Also, pumice is an another preferred material because of its advantages in construction industry. In this paper, four kinds of ignimbrite (light-yellow, yellow, black and white) and pumice from Ahlat region have been investigated by EPR method to determine magnetic properties of them. The results obtained by EPR, EDS and XRD methods are evaluated together. SEM technique is also used to understand the surface morphology of the samples.

Prenatal detection of Pai syndrome without cleft lip and palate: a case report.

Pai syndrome is a rarely encountered disease characterized by findings of median cleft lip, facial skin polyps, nasal mucosal polyps and midline central nervous system lipoma. We report a case with prenatal detection of a pericallosal lipoma and a skin tag on the forehead. After delivery, the diagnosis was confirmed as a case of Pai syndrome.

Platelet-derived CD154: ultrastructural localization and clinical correlation in organ transplantation.

CD154 is an immunostimulatory ligand for CD40 that markedly influences alloimmunity. Its presence in platelets suggests that its release and subsequent immune effects are driven by trauma and thus could be relevant following organ transplantation. However, the release of platelet derived CD154 and its consequences have not been investigated in a clinical transplant setting. To better characterize the relationship between platelet activation and CD154 release, we investigated CD154 release by platelets obtained from normal individuals, and patients with two genetic defects that influence platelet granule development. Using these unique patient populations and immune-electron microscopy, we confirmed that CD154 was an alpha granule and not a cell surface protein, and thereafter optimized the methods for its in vivo measurement in humans. We then investigated plasma CD154 levels in kidney and liver transplant recipients and found no evidence that CD154 levels fluctuated systemically as a result of kidney or liver transplant procedures. Paradoxically, we found that kidney transplant patients had significantly lower systemic CD154 levels during episodes of rejection. These data suggest that the immune effects of CD154 are likely mediated through local and not systemic mechanisms, and discourage the use of CD154 as a peripheral biomarker in organ transplantation.

Primary diffuse choroid plexus T-cell lymphoma: case report.

We present here a case of primary choroid plexus T-cell lymphoma with no evidence of immunodeficiency or immunological disease. As ventricular T-cell lymphoma is extremely rare, there is only limited information on the radiological findings of ventricular T-cell lymphoma. In this report, we also include some unusual MRI findings in this case that have never been described before.

Borderline micropapillary serous tumor of the ovary detected during a cesarean section due to a transabdominal cervico-isthmic cerclage in a patient with congenital cervical hypoplasia: a rare case.

A young woman with polycystic ovary syndrome and congenital cervical hypoplasia conceived with clomifen citrate treatment after placement of a transabdominal cervico-isthmic cerclage. Her pregnancy successfully reached term and cesarean section was performed to preserve the cerclage for the next pregnancy; when the ovaries were explored an irregular structure was detected on the left ovary. A wedge biopsy was done and the pathological assessment of the specimen was borderline micropapillary serous tumor of the ovary. The patient wanted to preserve her fertility, therefore a fertility-sparing staging surgery was performed six months after the cesarean section. There was no residual tumor in the left ovary, but there was a borderline tumor in the right ovarian biopsy specimen (frozen section was negative). Two months after staging surgery the patient conceived with IVF and delivered twins at the 33rd week of pregnancy with cesarean section. At her second cesarean section the right ovary and abdomen appeared normal on inspection, but the cerclage tape was in the endocervical canal and was thus removed. To our knowledge this is the second reported case of transabdominal cerclage tape migration into the endocervical canal. The patient is clinically disease-free 18 months after her second cesarean section. The clinical findings, treatment modalities, management and prognosis are discussed together with a literature review of a patient with a serous borderline ovarian tumor and congenital cervical hypoplasia.

A study on the mean free path and half value layer at various alloys for different photon energies.

The mean free path (mfp) and half value layer (x_1 / 2) values of binary and ternary alloys consist of 3d transition metals have been have been calculated at photon energies 22.1, 25.0, 59.5 and 88.0 keV. The experimental linear attenuation coefficients (µ) for present photon energies have been used to obtain the values of mfp and (x_1 / 2) . The experimental mfp and (x_1 / 2) results have compared with the theoretically calculated results based on attenuation coefficients obtained from WinXCom program. A good correspondence has been observed among the present results and the theoretical results.

The α-granule proteome: novel proteins in normal and ghost granules in gray platelet syndrome.

BACKGROUND: Deficiencies in granule-bound substances in platelets cause congenital bleeding disorders known as storage pool deficiencies. For disorders such as gray platelet syndrome (GPS), in which thrombocytopenia, enlarged platelets and a paucity of α-granules are observed, only the clinical and histologic states have been defined. OBJECTIVES: In order to understand the molecular defect in GPS, the α-granule fraction protein composition from a normal individual was compared with that of a GPS patient by mass spectrometry (MS). METHODS: Platelet organelles were separated by sucrose gradient ultracentrifugation. Proteins from sedimented fractions were separated by sodium dodecylsulfate polyacrylamide gel electrophoresis, reduced, alkylated, and digested with trypsin. Peptides were analyzed by liquid chromatography-tandem MS. Mascot was used for peptide/protein identification and to determine peptide false-positive rates. MassSieve was used to generate and compare parsimonious lists of proteins. RESULTS: As compared with control, the normalized peptide hits (NPHs) from soluble, biosynthetic α-granule proteins were markedly decreased or undetected in GPS platelets, whereas the NPHs from soluble, endocytosed α-granule proteins were only moderately affected. The NPHs from membrane-bound α-granule proteins were similar in normal platelets and GPS platelets, although P-selectin and Glut3 were slightly decreased, consistent with immunoelectron microscopy findings in resting platelets. We also identified proteins not previously known to be decreased in GPS, including latent transforming growth factor-ß-binding protein 1(LTBP1), a component of the transforming growth factor-ß (TGF-ß) complex. CONCLUSIONS: Our results support the existence of 'ghost granules' in GPS, point to the basic defect in GPS as failure to incorporate endogenously synthesized megakaryocytic proteins into α-granules, and identify specific new proteins as α-granule inhabitants.

Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis).

OBJECTIVE: To identify genetic causes of COACH syndrome BACKGROUND: COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/mental retardation), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). METHODS: In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. Diagnostic criteria for JSRD were clinical findings (intellectual impairment, hypotonia, ataxia) plus supportive brain imaging findings (MTS or cerebellar vermis hypoplasia). MKS3/TMEM67 was sequenced in all subjects for whom DNA was available. In COACH subjects without MKS3 mutations, CC2D2A, RPGRIP1L and CEP290 were also sequenced. RESULTS: 19/23 families (83%) with COACH syndrome carried MKS3 mutations, compared to 2/209 (1%) with JSRD but no liver disease. Two other families with COACH carried CC2D2A mutations, one family carried RPGRIP1L mutations, and one lacked mutations in MKS3, CC2D2A, RPGRIP1L and CEP290. Liver biopsies from three subjects, each with mutations in one of the three genes, revealed changes within the congenital hepatic fibrosis/ductal plate malformation spectrum. In JSRD with and without liver disease, MKS3 mutations account for 21/232 families (9%). CONCLUSIONS: Mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L; therefore, MKS3 should be the first gene tested in patients with JSRD plus liver disease and/or coloboma, followed by CC2D2A and RPGRIP1L.

The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria.

BACKGROUND: Prader-Willi syndrome (PWS) is a complex, multisystem disorder. Its major clinical features include neonatal hypotonia, developmental delay, short stature, behavioral abnormalities, childhood-onset obesity, hypothalamic hypogonadism, and characteristic appearance. The genetic basis of PWS is also complex. It is caused by absence of expression of the paternally active genes in the PWS critical region on 15q11-q13. In approximately 70% of cases this is the result of deletion of this region from the paternal chromosome 15. In approximately 28%, it is attributable to maternal uniparental disomy (UPD; inheritance of 2 copies of a chromosome from the mother and no copies from the father, as opposed to the normal 1 copy from each parent) of chromosome 15, and in <2%, it is the result of a mutation, deletion, or other defect in the imprinting center. Clinical diagnostic criteria were established by consensus in 1993. Subsequently, definitive molecular genetic testing became available for laboratory diagnosis of PWS. However, identification of appropriate patients for testing remains a challenge for most practitioners because many features of the disorder are nonspecific and others can be subtle or evolve over time. For example, hypotonic infants who are still in the failure to thrive phase of the disorder often do not have sufficient features for recognition of PWS and often are not tested. Initial screening with these diagnostic criteria can increase the yield of molecular testing for older children and adults with nonspecific obesity and mental retardation. Therefore, the purpose of clinical diagnostic criteria has shifted from assisting in making the definitive diagnosis to raising diagnostic suspicion, thereby prompting testing. We conducted a retrospective review of patients with PWS confirmed with genetic testing to assess the validity and sensitivity of clinical diagnostic criteria published before the widespread availability of testing for all affected patients and recommend revised clinical criteria. METHODS: Charts of all 90 patients with laboratory-confirmed PWS were reviewed. For each patient, the presence or absence of the major, minor, and supportive features listed in the published diagnostic criteria was recorded. The sensitivity of each criterion, mean of the total number of major and minor criteria, and mean total score for each patient were calculated. RESULTS: There were 68 patients with a deletion (del 15q11-q13), 21 with maternal UPD of chromosome 15, and 1 with a presumed imprinting defect. Age range at the time of the most recent evaluation was 5 months to 60 years (median: 14.5 years; del median: 14 years; range: 5 months-60 years; UPD median: 18 years; range: 5-42 years). The sensitivities of the major criteria ranged from 49% (characteristic facial features) to 98% (developmental delay). Global developmental delay and neonatal hypotonia were the 2 most consistently positive major criteria and were positive in >97% of the patients. Feeding problems in infancy, excessive weight gain after 1 year, hypogonadism, and hyperphagia were all present in 93% or more of patients. Sensitivities of the minor criteria ranged form 37% (sleep disturbance and apneas) to 93% (speech and articulation defects). Interestingly, the sensitivities of 8 of the minor criteria were higher than the sensitivity of characteristic facial features, which is a major criterion. Fifteen out of 90 patients with molecular diagnosis did not meet the clinical diagnostic criteria retrospectively. CONCLUSION: When definitive diagnostic testing is not available, as was the case for PWS when the 1993 criteria were developed, diagnostic criteria are important to avoid overdiagnosis and to ensure that diagnostic test development is performed on appropriate samples. When diagnostic testing is available, as is now the case for PWS, diagnostic criteria should serve to raise diagnostic suspicion, ensure that all appropriate people are tested, and avoid the expense of testing unnecessarily. Our results indicate that the sensitivities of most of the published criteria are acceptable. However, 16.7% of patients with molecular diagnosis did not meet the 1993 clinical diagnostic criteria retrospectively, suggesting that the published criteria may be too exclusive. A less strict scoring system may ensure that all appropriate people are tested. Accordingly, we suggest revised clinical criteria to help identify the appropriate patients for DNA testing for PWS. The suggested age groupings are based on characteristic phases of the natural history of PWS. Some of the features (eg, neonatal hypotonia, feeding problems in infancy) serve to diagnose the syndrome in the first few years of life, whereas others (eg, excessive eating) are useful during early childhood. Similarly, hypogonadism is most useful during and after adolescence. Some of the features like neonatal hypotonia and infantile feeding problems are less likely to be missed, whereas others such as characteristic facial features and hypogonadism (especially in prepubertal females) may require more careful and/or expert examination. The issue of who should have diagnostic testing is distinct from the determination of features among confirmed patients. Based on the sensitivities of the published criteria and our experience, we suggest testing all newborns/infants with otherwise unexplained hypotonia with poor suck. For children between 2 and 6 years of age, we consider hypotonia with history of poor suck associated with global developmental delay sufficient criteria to prompt testing. Between 6 and 12 years of age, we suggest testing those with hypotonia (or history of hypotonia with poor suck), global developmental delay, and excessive eating with central obesity (if uncontrolled). At the ages of 13 years and above, we recommend testing patients with cognitive impairment, excessive eating with central obesity (if uncontrolled), and hypogonadotropic hypogonadism and/or typical behavior problems (including temper tantrums and obsessive-compulsive features). Thus, we propose a lower threshold to prompt diagnostic DNA testing, leading to a higher likelihood of diagnosis of this disorder in which anticipatory guidance and intervention can significantly influence outcome.

2-[(4-Hydroxyphenyl)iminomethyl]thiophene.

The molecular structure of the title compound, C(11)H(9)NOS, has three planar moieties, two of which are rings, namely the hydroxyphenyl and the thiophene, with an angle of 20.76 (10) degrees between them. The crystal structure is stabilized by an O-H.N hydrogen bond and by C-H.O intermolecular interactions. The C.O intermolecular contact distance is 3.443 (2) A.

Thiophene-2-carbaldehyde N-(2,4-dinitrophenyl)-N-methylhydrazone.

Molecules of the title compound, C12H10N4O4S, are linked through intermolecular hydrogen bonds to form a dimeric structure. The crystal structure of the dimer is stabilized by two intermolecular hydrogen bonds of the C-H...O type. The C...O intermolecular contact distance is 3.339(3) A, and the C=N and N-N distances are 1.279(2) and 1.371(7) A, respectively. One O atom of the 2-nitro group is disordered over two sites.

Camptodactyly, myopia, and fibrosis of the medial rectus of the eye in two sibs born to consanguineous parents: autosomal recessive entity?

Unaffected but consanguineous parents suggest autosomal recessive inheritance of a previously apparently undescribed syndrome of camptodactyly, fibrosis of the medial rectus muscle of the eye, severe myopia, facial anomalies, joint contractures, and mild scoliosis in a 13-year-old Turkish girl and her 11-year-old brother. The girl also had ptosis.