3He MRI in mouse models of asthma.

In the study of asthma, a vital role is played by mouse models, because knockout or transgenic methods can be used to alter disease pathways and identify therapeutic targets that affect lung function. Assessment of lung function in rodents by available methods is insensitive because these techniques lack regional specificity. A more sensitive method for evaluating lung function in human asthma patients uses hyperpolarized (HP) (3)He MRI before and after bronchoconstriction induced by methacholine (MCh). We now report the ability to perform such (3)He imaging of MCh response in mice, where voxels must be approximately 3000 times smaller than in humans and (3)He diffusion becomes an impediment to resolving the airways. We show three-dimensional (3D) images that reveal airway structure down to the fifth branching and visualize ventilation at a resolution of 125 x 125 x 1000 microm(3). Images of ovalbumin (OVA)-sensitized mice acquired after MCh show both airway closure and ventilation loss. To also observe the MCh response in naive mice, we developed a non-slice-selective 2D protocol with 187 x 187 microm(2) resolution that was fast enough to record the MCh response and recovery with 12-s temporal resolution. The extension of (3)He MRI to mouse models should make it a valuable translational tool in asthma research.     

CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer.

Intestinal metaplasia is a key event in multistep gastric carcinogenesis. CDX2, a master regulator of intestinal phenotype, was shown to play a tumor-suppressive role in colon cancer. However, it was reported to be expressed in nearly all gastric intestinal metaplasia and many gastric cancers. As CDX2 is differentially expressed in normal stomach and intestine, we sought to relate the CDX2 expression to gastrointestinal differentiation along gastric carcinogenesis. The expression of CDX2 protein in gastric intestinal metaplasia, dysplasia and cancer was examined and related to their gastrointestinal differentiation. CDX2 expression was significantly decreased in incomplete intestinal metaplasia, which expresses both gastric mucins (MUC5AC and MUC6) and intestinal mucin (MUC2), compared with complete intestinal metaplasia, which expresses intestinal mucin (MUC2) only. Although incomplete intestinal metaplasia morphologically resembles colon, its CDX2 expression was apparently lower than that in the normal colon. Moreover, CDX2 expression was progressively reduced in gastric dysplasia and cancer. The CDX2 expression in gastric cancer was also inversely correlated with the expression of gastric mucins. As incomplete intestinal metaplasia is associated with higher risk of gastric cancer, its lower CDX2 expression compared with that in complete intestinal metaplasia and normal colon epithelium resolved the current contradiction between the tumor-suppressive role of CDX2 in the colon and the high prevalence of CDX2 in intestinal metaplasia. Further decrease of CDX2 expression in gastric dysplasia and cancer suggests that CDX2 plays a similar anticarcinogenic role in intestinal metaplasia as it does in colon. Intestinal metaplasia or dysplasia with low expression of CDX2 may serve as predictive markers for gastric cancer.     

Baseline Serum Prolactin in Drug-naive, First-episode Schizophrenia and Outcome at Five Years: Is it a Predictive Factor?

Objective: Serum prolactin is influenced by antipsychotic use but its relationships with psychopathology and general functioning are not clear. This study aimed to assess these relationships.Design: Serum prolactin levels were measured in patients with schizophrenia before being treated with antipsychotics and at various follow-up points.Setting: The study was conducted in a nongovernmental psychiatric treatment center in Mumbai, India.Participants: The participants included 30 male and 30 female drug-na?ve patients with schizophrenia and 31 control participants.Measurements: The severity of psychopathology at baseline, three weeks, six weeks, and five years following treatment was assessed using a modified Brief Psychiatric Rating Scale. The Global Assessment of Functioning questionnaire was used at baseline and five years follow up.Results: Contrary to our hypotheses, prolactin levels in male but not female patients at baseline were twice those of control volunteers. Correlations between prolactin, Brief Psychiatric Rating Scale, and Global Assessment of Functioning measurements were not significant for any time point up to six weeks, but were only significant at the five-year follow-up appointments, indicating that those patients with higher levels of serum prolactin had a better outcome at five years.Conclusion: Baseline serum prolactin levels in drug-naive patients with schizophrenia may be used for long-term prognosis, but are not reliable indicators of psychopathology and prognosis in the short term. Future research is needed to conclude with confidence whether or not prolactin can be used as a biomarker of psychopathological and overall functioning in schizophrenia.     

Stitch retractor—simple and easy technique to retract brain

BackgroundSelf-retaining brain retractors are commonly used during intracranial surgery, and they are indispensable during microneurosurgery. There is a common severe complication due to the use of self-held retractors, that is, formation of a hemorrhagic infarct area in the brain region exposed to traction. All the more, present retractor systems are fixed and rigid and obstruct surgeons during surgery. Sometimes these retractors create glare in the microscope that distracts the surgeon. We hereby propose a simple and easy method of retraction of brain especially the temporal lobe using the transsylvian approach and vermis using the transvermian approach.MethodsThis is retrospective analysis of 47 patients in 4 years in which we have used our stitch retractor. We have analyzed their outcome, postoperative scan, and ease of performing surgery.ResultsIn 47 patients, there was only 1 postoperative contusion, and the longest period it was kept for is 6 hours. The other advantage was that it does not obstruct in any way while doing dissections and surgery. There was no glare while operating under a microscope.ConclusionWe hereby propose a simple and easy method of retraction of brain especially the temporal lobe using the transsylvian approach and vermis using the transvermian approach. It is minimally traumatic, reducing insult to the brain. It allows the surgeon to dissect without any obstruction and glare in the way. The biggest advantage of the present stitch retractor is that it is very cheap and simple to use.     

Meta-analysis of telomere length in 19?713 subjects reveals high heritability,stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10⁻⁶¹) than father–offspring correlation (r=0.33; P-value=7.01 × 10⁻⁵), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10⁻⁵). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10⁻³⁰) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10⁻²³) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10⁻¹⁰). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.     

Surgical management of pygopagus conjoined twins with spinal bifida

Purpose

Conjoined twins are a rare complication of 9 monozygotic twins and are associated with high perinatal mortality. Pygopagus are one of the rare types of conjoined twins with only a handful of cases reported in the literature.

Case summary

We present the case of one-and-half month-old male pygopagus conjoined twins, who were joined together dorsally in lower lumbar and sacral region and had spina bifida and shared a single thecal sac with combined weight of 6.14 kg. Spinal cord was separated at the level of the conus followed by duraplasty. They had uneventful recovery with normal 15 months follow-up.

Conclusion

Separation of conjoined twins is recommended in where this is feasible with the anticipated survival of both or one infant.

     

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10⁻⁵) and diastolic BP (P=7.61×10⁻³) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10⁻³). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.