mRNA and protein expression for novel GABAA receptors θ and ρ2 are altered in schizophrenia and mood disorders; relevance to FMRP-mGluR5 signaling pathway

Fragile X mental retardation protein (FMRP) is an RNA-binding protein that targets ∼5% of all mRNAs expressed in the brain. Previous work by our laboratory demonstrated significantly lower protein levels for FMRP in lateral cerebella of subjects with schizophrenia, bipolar disorder and major depression when compared with controls. Absence of FMRP expression in animal models of fragile X syndrome (FXS) has been shown to reduce expression of gamma-aminobutyric acid A (GABA_A) receptor mRNAs. Previous work by our laboratory has found reduced expression of FMRP, as well as multiple GABA_A and GABA_B receptor subunits in subjects with autism. Less is known about levels for GABA_A subunit protein expression in brains of subjects with schizophrenia and mood disorders. In the current study, we have expanded our previous studies to examine the protein and mRNA expression of two novel GABA_A receptors, theta (GABRθ) and rho 2 (GABRρ2) as well as FMRP, and metabotropic glutamate receptor 5 (mGluR5) in lateral cerebella of subjects with schizophrenia, bipolar disorder, major depression and healthy controls, and in superior frontal cortex (Brodmann Area 9 (BA9)) of subjects with schizophrenia, bipolar disorder and healthy controls. We observed multiple statistically significant mRNA and protein changes in levels of GABRθ, GABRρ2, mGluR5 and FMRP molecules including concordant reductions in mRNA and proteins for GABRθ and mGluR5 in lateral cerebella of subjects with schizophrenia; for increased mRNA and protein for GABRρ2 in lateral cerebella of subjects with bipolar disorder; and for reduced mRNA and protein for mGluR5 in BA9 of subjects with bipolar disorder. There were no significant effects of confounds on any of the results.     

Association of platelet collagen receptor polymorphisms with premature acute myocardial infarction

The impact of platelet collagen receptor polymorphisms in the pathogenesis of myocardial infarction at young age remains unknown. To determine whether either of the two platelet collagen receptor polymorphisms (GP VI T13254C and GP Ia C807T) was associated with premature acute myocardial infarction. One hundred patients with premature acute myocardial infarction and 100 age-matched controls with normal coronary angiograms were studied. Genotyping was done using PCR followed by restriction fragment length polymorphism (RFLP). GP Ia C807T polymorphism was more frequent in the patient group (65%) than in the control group (53%). However, there was no association between this polymorphism and premature acute myocardial infarction (P?=?0.08). The prevalence of T13254C polymorphism did not differ between patients (38%) and controls (33%), and this polymorphism was not associated with premature acute myocardial infarction (P?=?0.46). Logistic regression analysis also indicated no association between these polymorphisms and premature acute myocardial infarction (C807T with P?=?0.51 and T13254C with P?=?0.20). There is no association between GP VI T13254C or GP Ia C807T polymorphisms and premature acute myocardial infarction.     

股骨近端锁定加压钢板治疗股骨转子间骨折

目的 探讨股骨近端锁定加压钢板（LCP）内固定治疗股骨转子间骨折的临床疗效.方法 采用股骨近端LCP治疗23例股骨转子间骨折的患者.随访观察骨折愈合时间,按Harris评分标准评价疗效.结果 23例均获随访,时间6~12（9±1.4）个月.骨折愈合时间14~20（17±1.7）周.髋关节Harris评分：优13例,良9例,一般1例.结论 股骨近端LCP内固定治疗股骨转子间骨折创伤小、出血少、对骨膜影响小,符合解剖形态,临床疗效满意.     

Interfacial fracture toughness of different resin cements bonded to a lithium disilicate glass ceramic

Objectives

To evaluate the effect of HF acid etching and silane treatment on the interfacial fracture toughness of a self-adhesive and two conventional resin-based cements bonded to a lithium disilicate glass ceramic.

Methods

Lithium disilicate glass ceramic discs were prepared with two different surface preparations consisting of gritblasted with aluminium oxide, and gritblasted and etched with hydrofluoric acid. Ceramic surfaces with a chevron shaped circular hole were treated by an optimized silane treatment followed by an unfilled resin and then three different resin cements (Variolink II, Panavia F2, and Multilink Sprint). Specimens were kept in distilled water at 37 °C for 24 h and then subjected to thermocycling. The interfacial fracture toughness was measured and mode of failures was also examined. Data were analysed using analysis of variance followed by T-test analysis.

Results

No statistically significant difference in the mean fracture toughness values between the gritblasted and gritblasted and etched surfaces for Variolink II resin cement was found (P > 0.05). For the gritblasted ceramic surfaces, no significant difference in the mean fracture toughness values between Panavia F2 and Variolink II was observed (P > 0.05). For the gritblasted and etched ceramic surfaces, a significantly higher fracture toughness for Panavia F2 than the other cements was found (P < 0.05).

Conclusions

The interfacial fracture toughness for the lithium disilicate glass ceramic system was affected by the surface treatment and the type of luting agent. Dual-cured resin cements demonstrated a better bonding efficacy to the lithium disilicate glass ceramic compared to the self-adhesive resin cement.

Clinical significance

The lithium disilicate glass ceramic surfaces should be gritblasted and etched to get the best bond when used with Panavia F2 and Multilink Sprint resin cements, whereas for the Variolink II only gritblasting is required. The best bond overall is achieved with Panavia F2.     

Single embryo transfer in preimplantation genetic diagnosis cycles for women <36 years does not reduce delivery rate

BACKGROUND: The Belgian legislation imposes single embryo transfer (SET) on women of <36 years in their first treatment cycle to avoid multiple pregnancies. The aim of this study is to assess the impact of this legislation on the outcome of preimplantation genetic diagnosis (PGD) for inherited diseases in young women undergoing SET. METHODS: A retrospective analysis of PGD cycles for monogenic disorders and translocations in women <36 years on their first treatment cycle. Two groups of patients were defined according to the implementation of the Belgian legislation: (i) double embryo transfer (DET), January 2001-June 2003 (ii) SET, July 2003-June 2005. The primary and secondary outcome measures were delivery per embryo transfer and multiple pregnancy rates, respectively. A subgroup analysis for monogenic disorders and translocations was performed. RESULTS: 62 cycles were included in the DET group and 73 cycles in the SET group. The mean age, number of cumulus-oocyte complexes, number of fertilized oocytes, number of biopsied and cryopreserved embryos were comparable between both groups. There was no significant difference in the delivery rates between the DET and the SET groups (33.9% versus 27.4%, respectively). Multiple pregnancies were avoided when SET was performed. When monogenic disorders and chromosomal translocations were separately evaluated, no significant difference in the delivery rate after SET was observed. CONCLUSIONS: The implementation of a SET policy in young women undergoing PGD for monogenic disorders and translocations enables a significant reduction of multiple pregnancies without significantly affecting the delivery rate.     

Effect of oral administration of dydrogestrone versus vaginal administration of natural micronized progesterone on the secretory transformation of endometrium and luteal endocrine profile in patients with premature ovarian failure: a proof of concept

BACKGROUND: We aimed to explore the endometrial histology and endocrine profiles on day 21 of an artificial cycle in patients with premature ovarian failure (POF) treated with oral dydrogesterone (DG) or vaginal micronized progesterone. METHODS: The study was designed as a prospective pilot study at an academic reproductive medicine unit. Six POF patients were included in the study. After estrogen endometrial priming, patients were randomized to receive DG or progesterone in two subsequent cycles. The main outcome measure was the endometrial histology and the endocrine profiles on day 21 of the cycle. RESULTS: Development of endometrial glands corresponded to an early secretory phase in five out of six cases supplemented with DG (out-phase). In contrast, five out of six cases treated with micronized progesterone showed an endometrium corresponding to a mid-luteal phase (in-phase) (P = 0.021 versus DG). There was a significant difference in the mean progesterone value [8.6 versus 0.3 microg l(-1) (P = 0.013)], the mean LH value [12.9 versus 22.5 IU l(-1) (P = 0.049)] and the mean FSH value [13.0 versus 23.9 IU l(-1) (P = 0.047)] between the progesterone and DG group, respectively, on day 21 of the cycle. CONCLUSIONS: After estrogen endometrial priming in POF patients, exogenous vaginal micronized progesterone is more effective than oral DG in creating an 'in-phase' secretory endometrium and induces significantly higher progesterone and lower LH and FSH serum concentrations on day 21 of the cycle.     

Clinical evaluation of desferrioxamine (DFO) for removal of thallium ions in rat

An investigation was conducted to evaluate the ability of DFO following the administration of thallium salt in male Wistar rats. Thallium was introduced to several groups of weanling male Wistar rats via different means, through drink, food and intraperitoneal injection. A control group was fed on a diet containing a normal level of iron. After a period of 30 days, all the rats administered thallium were severely anemic and showed toxicity symptoms through loss of hair, an increase in thallium and a decrease in iron levels in the blood. Chelation therapy was carried out to remove the toxic element from the body. The ability of desferrioxamine (DFO) in removing thallium was investigated by injection of this chelator for one week to the remaining rats of similar groups. The results showed that the thallium level present in the blood was significantly reduced and, at the same time, the iron concentration returned to the normal level. It was concluded that DFO chelator is able to remove thallium from the body and could be used for the treatment of complications and eradication of symptoms of thallium intoxication.     

Negative pressure wound therapy reduces incidence of postoperative wound infection and dehiscence after long-segment thoracolumbar spinal fusion: a single institutional experience

Background contextWound dehiscence and surgical site infections (SSIs) can have a profound impact on patients as they often require hospital readmission, additional surgical interventions, lengthy intravenous antibiotic administration, and delayed rehabilitation. Negative pressure wound therapy (NPWT) exposes the wound site to negative pressure, resulting in the improvement of blood supply, removal of excess fluid, and stimulation of cellular proliferation of granulation tissue.PurposeTo assess the incidence of wound infection and dehiscence in patients undergoing long-segment thoracolumbar fusion before and after the routine use of NPWT.Study designRetrospective study.Patient sampleOne hundred sixty patients undergoing long-segment thoracolumbar spine fusions were included in this study.Outcome measuresPostoperative incidence of wound infection and dehiscence.MethodsAll adult patients undergoing thoracolumbar fusion for spinal deformity over a 6-year period at Duke University Medical Center by the senior author (CB) were included in this study. In 2012, a categorical change was made by the senior author (CB) that included the postoperative routine use of incisional NPWT devices after primary wound closure in all long-segment spine fusions. Before 2012, NPWT was not used. After primary wound closure, a negative pressure device is contoured to the size of the incision and placed over the incision site for 3 postoperative days. We retrospectively review the first 46 cases in which NPWT was used and compared them with the immediately preceding 114 cases to assess the incidence of wound infection and dehiscence.ResultsOne hundred sixty (NPWT: 46 cases, non-NPWT: 114 cases) long-segment thoracolumbar spine fusions were performed for deformity correction. Baseline characteristics were similar between both cohorts. Compared with the non-NPWT cohort, a 50% decrease in the incidence of wound dehiscence was observed in the NPWT patient cohort (6.38% vs. 12.28%, p=.02). Similarly, compared with the non-NPWT cohort, the incidence of postoperative SSIs was significantly decreased in the NPWT cohort (10.63% vs. 14.91%, p=.04).ConclusionsRoutine use of incisional NPWT was associated with a significant reduction in the incidence of postoperative wound infection and dehiscence.     

Occurrence of respiratory syncytial virus subtypes in hospitalized children in Cleveland, Ohio from 1985 to 1988.

In order to determine the frequency of occurrence of the two respiratory syncytial virus (RSV) subtypes in hospitalized children in Cleveland, Ohio, we analyzed clinical isolates obtained during three consecutive winter epidemic seasons between 1985 and 1988. RSV was recovered from the frozen clinical specimens of 197 patients: 176 subtype A, and 21 subtype B. Subtype A predominated during all three epidemic seasons, ranging from 83 to 94% of isolates. We surveyed the clinical records of 16 children with subtype B, and 101 children with subtype A infections, hospitalized at the University Hospitals of Cleveland during these winter epidemics and found no differences in age, sex, race, or clinical spectrum of severity of disease caused by the two subtypes. In contrast to previously reported data, subtype A predominated in each of the winter seasons studied within this community. We conclude that both subtypes circulate concurrently within the community during the winter. In hospitalized children both subtypes appear to cause a similar spectrum of disease. Both the concurrent circulation of RSV subtypes and the similar spectrum of illness pose for important considerations in the development of effective vaccines against this common respiratory agent in children.     

Detection of the hemoglobin E mutation using the color complementation assay: application to complex genotyping

The color complementation assay (CCA) is a method of allele-specific DNA amplification by which competitive priming and extension of fluorescently labeled oligonucleotide primers determine the color of DNA amplification product. This diagnostic method precludes the need for radioisotopes, electrophoresis, and multiple high-stringency reaction conditions. The multiplicity of mutant globin genes present in Southeast Asians complicates clinical diagnosis and underscores the importance of DNA-based diagnostic methods. We have applied CCA to distinguish beta A and beta E alleles. Competing 15mer primers were a fluorescein-labeled complement to beta A and a rhodamine-labeled complement to beta E, identical except for their central nucleotides. A common unlabeled primer was used to amplify DNA product, the color of which was determined by the perfectly complementary primer. Color photography and spectrofluorometry, as well as a method of black-white photography that we developed to distinguish fluorescein- and rhodamine- labeled DNA, were used to record results. We applied CCA to define the complex genotype of a Thai woman with thalassemia intermedia, 96% HbE, and 4% HbF whose possible genotypes included several permutations of alpha-thalassemia, beta-thalassemia, and beta E genes. zeta-Globin gene mapping of DNA doubly digested with Bg/II and Asp 718 showed the -alpha 3.7/--SEA genotype, and CCA confirmed homozygous beta E/beta E. The CCA is useful for diagnosing the compound hemoglobin genotypes of Southeast Asians and could be applied also to prenatal diagnosis in this population.