Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

DSM-IV defined conduct disorder and oppositional defiant disorder: an investigation of shared liability in female twins.

BACKGROUND: DSM-IV specifies a hierarchal diagnostic structure such that an oppositional defiant disorder (ODD) diagnosis is applied only if criteria are not met for conduct disorder (CD). Genetic studies of ODD and CD support a combination of shared genetic and environmental influences but largely ignore the imposed diagnostic structure. METHOD: We examined whether ODD and CD share an underlying etiology while accounting for DSM-IV diagnostic specifications. Data from 1446 female twin pairs, aged 11-19 years, were fitted to two-stage models adhering to the DSM-IV diagnostic hierarchy. RESULTS: The models suggested that DSM-IV ODD-CD covariation is attributed largely to shared genetic influences. CONCLUSIONS: This is the first study, to our knowledge, to examine genetic and environmental overlap among these disorders while maintaining a DSM-IV hierarchical structure. The findings reflect primarily shared genetic influences and specific (i.e. uncorrelated) shared/familial environmental effects on these DSM-IV-defined behaviors. These results have implications for how best to define CD and ODD for future genetically informed analyses.

Closed central slip injuries--a missed diagnosis?

The extensor apparatus of the finger is a complex structure and injury can lead to significant digital dysfunction. Closed central slip injuries may be missed or diagnosis delayed because of lack of an open wound and often no radiographic abnormality, and can result in boutonniere deformities if untreated. This study aimed to quantify the number of patients attending with closed central slip injuries and to ascertain if the initial diagnosis was correct. The number of patients presenting to us over a 6 month period was recorded. The original diagnosis, time to diagnosis of central slip injury and the presence/absence of a boutonniere deformity were recorded. Ten patients were included in the study. Seven (70%) injuries were due to sport. Eight (80%) had a delayed diagnosis of central slip injury. Six (60%) had previously presented to general practitioners or emergency departments. Seven (70%) had boutonniere deformities. Closed central slip injuries can be missed. Simple clinical tests can diagnose central slip disruption.

An unusual presentation of a glomus tumour.

Glomus tumours are benign, soft tissue tumours, usually of fingertips. Classically they present with severe pain, temperature sensitivity and localised tenderness. The diagnosis is often delayed due to sometimes non-specific symptoms and rarity of the disorder. While usually a clinical diagnosis, imaging may be necessary for diagnosis and localisation. We present a case of glomus tumour of the fingertip with an unusual history.

Carotenoid biosynthesis in Rhodospirillum rubrum: effect of pteridine inhibitor.

A known inhibitor of pteridine utilization (4-phenoxy,2,6-diamino pyridine) blocks the synthesis of colored carotenoids in the photosynthetic bacterium Rhodospirillum rubrum. In many ways the effect is similar to the inhibition of the synthesis of colored carotenoids by diphenylamine. This inhibition is probably independent of other effects of pteridine on photosynthetic electron transport since it is not as readily reversible as the total inhibition of photosynthetic activity by pteridine analogs.

Skeletal muscle calcium metabolism and contractile force in vitamin D-deficient chicks.

The myopathy associated with vitamin D deficiency has not been well characterized, and it is not known if weakness is a result of a specific effect of vitamin D deficiency on skeletal muscle. Chicks were raised from hatching on a vitamin D-deficient diet, and by 3 wk of age were hypocalcemic and appeared weak. Tension generated by triceps surae during repetitive stimulation of posterior tibial nerve was significantly less than that developed by chicks given vitamin D(3) supplements (309 g tension/g wet weight of triceps surae, SD 60, for vitamin D-deficient chicks; 470, SD 77, for vitamin D(3)-treated chicks, P < 0.01). Histochemical and electron microscopic examination of skeletal muscles of these chicks showed no abnormalities, and there were no electrophysiologic evidences of motor nerve or neuromuscular junction dysfunction. The concentration of ATP in skeletal muscle of the vitamin D-deficient chicks (5.75 mumol/g wet weight, SD 0.17) was not significantly different from that in vitamin D-treated chicks (5.60, SD 0.50). There was no correlation between strength and serum calcium, serum inorganic phosphate, or skeletal muscle inorganic phosphate. Relaxation of tension after tetanic stimulation was slowed in the vitamin D-deficient chicks (20.6 ms, SD 1.7, vs. 15.4, SD 1.3, in vitamin D-treated chicks and 15.3, SD 1.0, in normal control chicks), and in vitro (45)Ca(++) transport by sarcoplasmic reticulum from the vitamin D-deficient chicks was reduced. Calcium content of mitochondria prepared from leg muscles of vitamin D-deficient chicks (24 nmol/mg mitochondrial protein, SD 6) was considerably lower than that of mitochondria from normal control chicks (45, SD 8) or from chicks treated with vitamin D for 2 wk or more (66-100, depending upon level and duration of therapy). Treatment of the vitamin D-deficient chicks from hatching with sufficient dietary calcium to produce hypercalcemia did not significantly raise skeletal muscle mitochondrial calcium content (31 nmol/mg mitochondrial protein, SD 7) and did not prevent weakness. These studies demonstrate objective weakness as a result of myopathy in vitamin D-deficient chicks, and provide evidence that vitamin D deficiency has effects on skeletal muscle calcium metabolism not secondary to altered plasma concentrations of calcium and phosphate.

Low incidence of retained common bile duct stones using a selective policy of biliary imaging.

AIM: Biliary imaging has decreased since the advent of laparoscopic cholecystectomy. This study aimed to examine the incidence of retained common bile duct (CBD) stones, using a selective policy of biliary imaging. METHODS: A prospective computerised database was used to study patients who underwent laparoscopic cholecystectomy by one surgeon over 36 months. Two hundred and thirty-five patients (191 female, 44 male) were operated on. Ages ranged from 15 to 82 years (mean 47 years). Follow-up periods ranged from six to 39 months (mean 23.3 months). Selection for pre-operative endoscopic retrograde cholangiopacreatogram (ERCP), intraoperative cholangiography (IOC) or neither depended on liver function tests (LFTs) and CBD diameter on ultrasound prior to surgery. If LFTs were persistently raised and/or the CBD was dilated on ultrasound, patients underwent pre-operative ERCP. If LFTs were raised, and returned to normal promptly, IOC was performed. RESULTS: Of 235 patients, 26 had pre-operative ERCP, 62 had IOC and 157 had neither. Ten patients had both ERCP and IOC. To date, one patient (0.43%) has radiologically-proven unsuspected retained CBD stones; these were successfully treated with ERCP. CONCLUSION: Selective biliary imaging in patients undergoing laparoscopic cholecystectomy is safe. This process identifies the majority of patients with ductal calculi and minimises the need for unnecessary ERCP and peroperative cholangiography.

The cloning of the human follicle stimulating hormone receptor and its expression in COS-7, CHO, and Y-1 cells.

Follicle stimulating hormone (FSH) receptor clones were isolated from a human testis cDNA library. Characterization of the cDNA clones showed that the DNA and predicted amino acid sequences of the long open reading frame differed from a previously published human ovarian FSH receptor sequence (Minegish et al. (1991) Biochem. Biophys. Res. Commun. 175, 1125-1130) by seven nucleotides and five amino acids. A human FSH receptor splice variant was also identified and characterized. A full-length human FSH receptor cDNA was engineered for expression in COS-7, CHO, and Y-1 cells. In transient transfections of COS-7 cells and stable transfections of Y-1 cells, efficient FSH receptor mRNA accumulation and isolation of FSH-responsive cell lines occurred only when an intron was included in the 5' untranslated region of the FSH receptor transcription unit. Y-1 cells stably transfected with the FSH receptor responded to FSH treatment by rounding up and by synthesizing increased amounts of progesterone. Stably transfected CHO cell lines, which responded to FSH by synthesizing increased amounts of cAMP, were isolated irrespective of the presence of the heterologous intron. The FSH-responsive CHO and Y-1 cell lines may be suitable for the development of better in vitro FSH bioassays. These cells also constitute a convenient source of human FSH receptor protein for use in radioreceptor assays and in studies of receptor-ligand interactions.

Safety guidelines for radiolocalised sentinel node resection.

BACKGROUND: Sentinel node radiolocalisation procedures are associated with low levels of radiation exposure. Radioactive material is present in the operating theatre and pathology laboratory. In most hospitals there are no official regulations in place for sentinel node radiation exposure. AIM: To establish guidelines on the safety of sentinel node mapping with emphasis on the management of radioisotopes. METHODS: The current literature regarding sentinel node procedures and radiation safety was reviewed. EU and US radiation safety regulations were scrutinised. RESULTS: Personnel involved in sentinel node procedures are exposed to low levels of radiation. These levels are not high enough to require designated radiation workers in the theatre and pathology laboratory. Awareness of radiation safety and certain precautions during the procedure and processing of the specimen can further reduce levels of exposure. CONCLUSION: Although low levels of radiation exposure are associated with sentinel node procedures, awareness of radiation safety and adherence to regulations, along with close interdepartmental co-operation, are recommended for further reduction in radiation exposure and safe application of this technique.

Effects of low doses of caffeine on aggressive behavior of male rats.

To date, the effect of low doses of caffeine on aggression has not been systematically examined. Doses of caffeine greater than 30 mg/kg appear to reduce social interaction and aggression in all species studied. In a double blind study of the effects of low doses of caffeine on aggression, rats were housed four per cage, and aggressive behavior against an intruder was recorded during baseline and following administration of 2.5, 5, 10, and 20 mg/kg caffeine. Aggressive behavior was significantly increased following administration of the higher doses of caffeine. Doses of 5, 10, and 20 mg/kg caffeine all were effective in increasing pushing behavior, whereas doses of 5 and 10 mg/kg were most effective in increasing boxing behavior, and a dose of 10 mg/kg was significantly more effective than other doses in increasing chasing and roll-tumble-bite behaviors. Based on these results and other published reports, the inverted-U shaped dose-dependent effect of caffeine on aggression appears to apply, with aggressive behavior being most elevated following doses of 5-20 mg/kg caffeine, less elevated following 2.5 mg/kg or 30 mg/kg, and significantly reduced with doses above 40 mg/kg and at doses below 2.5 mg/kg.

The medial sural artery perforator flap and its application in electrical injury to the hand.

We describe the use of a free medial sural artery perforator flap to reconstruct a complex composite defect to the dorsum of the right index finger following a low voltage electrical injury. The resulting defect was a 3.5 × 5 cm full thickness wound, with segmental tendon loss and loss of underlying periosteum. Due to both size and local vascular injury related to the mechanism, free tissue transfer was felt to be the most reliable option to resurface the composite defect in a single stage. The medial sural artery perforator flap, for reasons outlined below, was felt to be the best option: 1. Thin profile. 2. Vascularised fascia can be taken as a tongue, adjacent to the skin paddle: a gliding surface to prevent the tendon graft sticking to exposed bone. 3. Long pedicle: micro-anastomosis away from zone of injury. 4. Little donor site morbidity: can be closed directly (if <6 cm wide) and does not require sacrifice of any major blood vessel. 5. Can be harvested with nerve and tendon from the same wound. 6. Can include as little or as much tissue required and compared to other fasciocutaneous flaps matches the texture and thickness of the hand most closely. We describe the reconstruction of the composite defect on day 42 post-injury, following one prior debridement. This case highlights the versatility and suitability of the medial sural artery flap in the reconstruction of complex hand burns with resulting composite defects.

Reconstruction of the pelvis and perineum with a free latissimus dorsi myocutaneous flap: a case report.

Reconstruction of the perineum and pelvic cavity in continuity is an uncommon and difficult challenge. This case describes a 66-year-old man who presented following recurrence of a Dukes' B rectosigmoid adenocarcinoma that had been treated nine years previously by anterior resection, 5-fluorouracil and radiotherapy. His recurrent disease was treated with radical pelvic exenteration with formation of an end colostomy and urinary ileal conduit. A post-operative pelvic collection necessitated incisional drainage via the perineum. This resulted in a perineal defect in continuity with the pelvic cavity, neither of which healed in spite of alternate day packing with antiseptic dressings. The perineum and cavity were reconstructed successfully with a microvascular transfer of the latissimus dorsi using the primary gracilis pedicle as recipient donor vessels.

Paediatric ride-on mower related injuries and plastic surgical management.

Lawnmower related injuries cause significant morbidity in children and young teenagers. The 'ride-on' mowers which are more powerful than the 'walk behind' mowers are becoming increasingly popular. The incidence and severity of injuries from either type of lawnmower appears to be steadily rising as is the burden placed on local plastic surgical and emergency services in managing the care of these patients. The aims of the study were to demonstrate changing trends in lawnmower-related injuries to children presenting to a single unit over a ten-year period and to identify any association between injury severity and machine subtype ('ride-on' versus 'walk-behind'). Hospital databases, theatre records and medical case notes were reviewed retrospectively of all patients under the age of 16 treated for lawnmower related injuries over a 10 year period from July 1998 to June 2008. Data gathered included patient demographics, injury site and severity, management (type and number of surgical procedures), length of hospital stay and outcome. Injury severity score was also calculated for each case. Controlling for estimated regional population changes, there was a significant increase in the number of ride-on mower related accidents in the time period 2003-2008, compared to the time period 1998-2003. Ride-on injuries had significantly higher injury severity scores, longer hospital stays and were more likely to involve amputations as compared with walk-behind injuries. Children can sustain significant injuries with unsafe lawnmower use. The current study demonstrates the increasing incidence of ride-on mower related injuries in children and identifies a greater morbidity associated with such injuries. Such presentations place intense demands on local plastic surgical services.

22q11 chromosome abnormalities and the cleft service.

Deletion of chromosome 22q11 gives rise to a spectrum of anomalies, including cleft palate. These are grouped together as the DiGeorge or velocardiofacial syndrome. Patients with this chromosomal abnormality account for a small, but noteworthy proportion of patients attending our cleft service. They frequently have other significant comorbidities consistent with their diagnosis. Over a ten-year period, 16 patients within our cleft service have been diagnosed, using chromosome analysis, as having deletions at 22q11. All had either a cleft palate and/or velopharyngeal incompetence, for which they underwent repair of the cleft palate or pharyngoplasty. Several have required secondary palate surgery following initial palate surgery. Poor quality of speech was the indication for secondary procedures in the majority of cases. Fourteen of the 16 have other comorbidities, ranging from congenital heart disease to ocular abnormalities. In addition, 15 of the 16 have developmental delays and/or learning difficulties. Other specialties, such as ENT, cardiology, genetics and ophthalmology have been involved in the care of all these patients. Although comprising only a small proportion of patients attending a cleft team, the diagnosis of this chromosomal abnormality is significant, as these patients may require substantial input of resources and the expertise of several specialties. Early recognition of features of this entity and diagnosis can aid more efficient intervention.

Pteridines and the function of the photosynthetic reaction center.

The photoreduction and interaction with the photosynthetic "reaction center" of 2-amino,4-hydroxy-6-substituted pteridine indicates that these low-potential ( approximately -0.7 v), naturally occurring compounds play a primary role in photosynthetic electron transport. These unconjugated pteridines, which occur in association with the photosynthetic apparatus of green plants and photosynthetic bacteria, can be reduced by light in the presence of a bacterial chromatophore fraction from the dihydro form to the tetrahydro form. 6,7-Dimethyl-tetrahydropteridine readily reduces spinach ferredoxin. This compound also specifically interacts with reaction-center chlorophyll and bacteriochlorophyll and produces spectral shifts similar to those produced by light. It is proposed that the electron produced by excited-state chlorophyll is captured and separated by a pteridine at -0.67 v at the photosynthetic reaction center.