Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1, encoding a serine/threonine protein kinase, as a novel schizophrenia susceptibility gene.

BACKGROUND: Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes. METHODS: Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects. RESULTS: We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers. CONCLUSIONS: These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia.     

Acute pulmonary embolism in elderly: clinical characteristics and outcome

OBJECTIVE: To evaluate the clinical characteristics and outcome of acute pulmonary embolism in elderly in comparison to the younger patients. METHODS: Study population consisted of 136 patients with a confirmed diagnosis of acute pulmonary embolism. Clinical characteristics and thromboembolic risk factors were analyzed between the elderly (> or =65 years of age) and the younger (<65 years of age) patients. In-hospital mortality was used as a measure of outcome. RESULTS: Elderly group consisted of 70 patients (age 76.4+/-8.3 years, range 65-96 years; females 58%) and younger group of 66 patients (age 48.5+/-12 years, range 18-64 years, females 59%). Syncope was more frequent in elderly group (19% vs. 6%, P=0.03) but the symptoms of shortness of breath and pleuritic chest pain were not significantly different between groups. Malignancy was the most common risk factor for thrombo-embolism, but immobilization predominated among patients in elderly group (21% vs. 6%, P=0.01). Tachycardia was common in younger patients compared to the elderly. Ventilation-perfusion scan was used more commonly in younger patients (76% vs. 57%, P=0.02), whereas, helical computed-tomography scan was used equally in both groups. Most of the patients had lower extremity duplex study (97% in each group). Inferior vena cava filter placement was common and thrombolytic therapy rare among elderly patients. Patients in elderly group had higher in-hospital mortality (17% vs. 5%, P=0.02). CONCLUSIONS: Syncope is a more frequent presenting symptom and immobilization a common risk factor in elderly patients with acute pulmonary embolism. In addition, they have higher in-hospital mortality.     

Diffusion of responsibility attenuates altruistic punishment: A functional magnetic resonance imaging effective connectivity study

Humans altruistically punish violators of social norms to enforce cooperation and pro‐social behaviors. However, such altruistic behaviors diminish when others are present, due to a diffusion of responsibility. We investigated the neural signatures underlying the modulations of diffusion of responsibility on altruistic punishment, conjoining a third‐party punishment task with event‐related functional magnetic resonance imaging and multivariate Granger causality mapping. In our study, participants acted as impartial third‐party decision‐makers and decided how to punish norm violations under two different social contexts: alone (i.e., full responsibility) or in the presence of putative other third‐party decision makers (i.e., diffused responsibility). Our behavioral results demonstrated that the diffusion of responsibility served as a mediator of context‐dependent punishment. In the presence of putative others, participants who felt less responsible also punished less severely in response to norm violations. Our neural results revealed that underlying this behavioral effect was a network of interconnected brain regions. For unfair relative to fair splits, the presence of others led to attenuated responses in brain regions implicated in signaling norm violations (e.g., AI) and to increased responses in brain regions implicated in calculating values of norm violations (e.g., vmPFC, precuneus) and mentalizing about others (dmPFC). The dmPFC acted as the driver of the punishment network, modulating target regions, such as AI, vmPFC, and precuneus, to adjust altruistic punishment behavior. Our results uncovered the neural basis of the influence of diffusion of responsibility on altruistic punishment and highlighted the role of the mentalizing network in this important phenomenon. Hum Brain Mapp 37:663–677, 2016. © 2015 Wiley Periodicals, Inc .     

Quinine hepatotoxicity. An underrecognized or rare phenomenon?

Quinine-induced hepatic injury has been reported very rarely. We report a case involving a patient with an apparent hypersensitivity to quinine, manifested by a clinical syndrome mimicking a viral illness and a mixed hepatocellular-cholestatic liver injury pattern. We briefly review the unusual literature on this topic, which features many cases of hypersensitivity to the optical isomer of quinine, quinidine; yet, to our knowledge, there has only been one prior report of quinine hepatotoxicity.     

Criteria for management of calcific metamorphosis: review with a case report.

Calcific metamorphosis is seen commonly in the dental pulp after traumatic tooth injuries and is characterized by deposition of hard tissue within the root canal space. Opinion differs among practitioners as to whether to treat these cases upon early detection of calcific metamorphosis or to observe them until symptoms or radiographic signs of pulpal necrosis are detected. In this article, the clinical, radiographic, and histopathologic appearance of calcific metamorphosis is described; a review of the literature is presented to address these issues in an attempt to establish sound rationale for treatment. Approximately 3.8% to 24% of traumatized teeth develop varying degrees of calcific metamorphosis. Studies indicate that of these, approximately 1% to 16% will develop pulpal necrosis. Most of the literature does not support endodontic intervention unless periradicular pathoses is detected or the involved tooth becomes syptomatic. It may be advisable to manage cases demonstrating calcific metamorphosis through observation and periodic examination. A report of a case where in non-surgical endodontic intervention was successfully carried out a patient suffering from calcific metamorphosis with periapical pathoses is also presented.     

Comparative study of ankle arthrodesis using cross screw fixation versus anterior contoured plate plus cross screw fixation

Arthrodesis of the ankle joint is still the traditional treatment for symptomatic osteoarthritis. This comparative study was done to assess the functional outcome of open ankle fusion using either cross screw fixation (group A) or anterior contoured plate and cross screw fixation (group B) in a consecutive series of 22 patients. All the patients had the same inclusion criteria. All the patients in both groups underwent the same operative technique and were operated by the same surgeon. Mean follow-up was 26.8 months. The mean time to fusion was 18.8 weeks in group A and 16.8 weeks in group B (p = 0.046). The mean American Orthopaedic Foot and Ankle Society (AOFAS) Ankle and Hind foot score at the final follow-up was 79 in group A and 86 in group B (p = 0.23). Two patients in group A that went to non-union required re-arthrodesis using contoured plate and cross screw fixation; both attained eventual union. We conclude that anterior contoured plate plus cross screw fixation is a simple and reproducible technique for ankle arthrodesis that gives stable internal fixation and excellent clinical results.     

Fatal re-expansion pulmonary oedema in a mechanically ventilated patient

Fatal course of re-expansion pulmonary oedema (REPO) is infrequent and very rarely documented in mechanically ventilated patients. We report a case of fatal REPO following tube thoracostomy for a right-sided pneumothorax in an elderly patient of chronic obstructive pulmonary disease (COPD) with respiratory failure on mechanical ventilation.     

Comparison of coconut water, propolis, HBSS, and milk on PDL cell survival

Coconut water is biologically pure and sterile, with a rich presence of amino acids, proteins, vitamins, and minerals. The purpose of this study was to use a collagenase-dispase assay to investigate the potential of a new storage medium, coconut water, in comparison with propolis, Hank's balanced salt solution (HBSS), and milk in maintaining viable periodontal ligament (PDL) cells on simulated avulsed teeth. Seventy freshly extracted human teeth were divided into 4 experimental groups and 2 control groups. The positive and negative controls corresponded to 0-minute and 8-hour dry times, respectively. The experimental teeth were stored dry for 30 minutes and then immersed in 1 of the 4 media (coconut water, propolis, HBSS, and milk). The teeth were then treated with dispase grade II and collagenase for 30 minutes. The number of viable PDL cells was counted with a hemocytometer and analyzed. Statistical analysis showed that coconut water kept significantly more PDL cells viable compared with propolis, HBSS, or milk. Coconut water can be used as a superior transport medium for avulsed teeth.     

Effective connectivity of brain regions underlying third-party punishment: Functional MRI and Granger causality evidence

Third-party punishment (TPP) for norm violations is an essential deterrent in large-scale human societies, and builds on two essential cognitive functions: evaluating legal responsibility and determining appropriate punishment. Despite converging evidence that TPP is mediated by a specific set of brain regions, little is known about their effective connectivity (direction and strength of connections). Applying parametric event-related functional MRI in conjunction with multivariate Granger causality analysis, we asked healthy participants to estimate how much punishment a hypothetical perpetrator deserves for intentionally committing criminal offenses varying in levels of harm. Our results confirmed that TPP legal decisions are based on two domain-general networks: the mentalizing network for evaluating legal responsibility and the central-executive network for determining appropriate punishment. Further, temporal pole (TP) and dorsomedial prefrontal cortex (PFC) emerged as hubs of the mentalizing network, uniquely generating converging output connections to ventromedial PFC, temporo-parietal junction, and posterior cingulate. In particular, dorsomedial PFC received inputs only from TP and both its activation and its connectivity to dorsolateral PFC correlated with degree of punishment. This supports the hypothesis that dorsomedial PFC acts as the driver of the TPP activation pattern, leading to the decision on the appropriate punishment. In conclusion, these results advance our understanding of the organizational elements of the TPP brain networks and provide better insights into the mental states of judges and jurors tasked with blaming and punishing legal wrongs.     

In vitro fertilization

Assisted reproduction techniques (ART) have become the ultimate treatment for different types of infertility as it circumvents many natural barriers to conception. Evolution of ART has not only included its indications but also the methods of ovarian stimulation, ovarian monitoring, gamete selection, fertilization techniques, embryo selection and culture and embryo storage. This article reviews the currently agreed and controversial indications of assisted reproduction and the preparatory steps before starting treatment. It also summarizes the basic concepts of pituitary down regulation and various protocols to achieve it, the main clinical and laboratory aspects of treatment cycle and complications of treatment.