What is the safest mode of birth for extremely preterm breech singleton infants who are actively resuscitated? A systematic review and meta-analyses.

BACKGROUND: The safest delivery mode of extremely preterm breech singletons is unknown. OBJECTIVES: To determine safest delivery mode of actively resuscitated extremely preterm breech singletons. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov from January 1994 to May 2017. SELECTION CRITERIA: We included studies comparing outcomes by delivery mode in actively resuscitated breech infants between 23+0 and 27+6 weeks. DATA COLLECTION AND ANALYSIS: We synthesised data using random effects, generated odds ratios, 95% confidence intervals and number-needed-to-treat (NNT). Our primary outcomes were death (neonatal, before discharge, or by 6 months) and severe intraventricular haemorrhage (grades III/IV), stratified by gestational age (23+0 -24+6 , 25+0 -26+6 , 27+0 -27+6 weeks). MAIN RESULTS: We included 15 studies with 12 335 infants. We found that caesarean section was associated with a 41% decrease in odds of death between 23+0 and 27+6 weeks [odds ratio (OR) 0.59, 95% CI 0.36-0.95, NNT 8], with the greatest decrease at 23+0 -24+6 weeks (OR 0.58, 95% CI 0.44-0.75, NNT 7). The OR at 25+0 -26+6 and 27+0 -27+6 weeks were 0.72 (95% CI 0.34-1.52) and 2.04 (95% CI 0.20-20.62), respectively. We found that caesarean section was associated with 49% decrease in odds of severe intraventricular haemorrhage between 23+0 and 27+6 weeks (OR 0.51, 95% CI 0.29-0.91, NNT 12), whereas the OR at 25+0 -26+6 and 27+0 -27+6 was 0.29 (95% CI 0.07-1.12) and 0.91 (95% CI 0.27-3.05), respectively. CONCLUSIONS: Caesarean section was associated with reductions in the odds of death by 41% and of severe intraventricular haemorrhage by 49% in actively resuscitated breech singletons < 28 weeks of gestation. The data are mostly observational, which may be inherently biased, and scarce on other morbidities, necessitating thorough discussion between parents and clinicians. TWEETABLE ABSTRACT: Caesarean section associated with lower odds of death and severe intraventricular haemorrhage in actively resuscitated breech singletons <28 weeks.

Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Direct oral anticoagulants (DOACs) are widely used as an alternative for warfarin. However, the impact of DOACs on mortality outcomes compared with warfarin remains unclear. OBJECTIVE: To estimate the mortality outcomes in patients treated with DOACs vs. warfarin (or another vitamin K antagonist). METHODS: MEDLINE, EMBASE and CENTRAL databases (inception to September 2014), conference abstracts and www.clinicaltrials.gov, were searched, without language restriction. Studies were selected if there were phase III, randomized trials comparing DOACs with warfarin in patients with non-valvular atrial fibrillation or venous thromboembolism. RESULTS: Thirteen randomized controlled trials involving 102 707 adult patients were included in the analysis. The case-fatality rate of major bleeding was 7.57% (95% CI, 6.53-8.68; I(2) = 0%) in patients taking DOACs and 11.04% (95% CI, 9.16-13.07; I(2) = 33.3%) in patients taking warfarin. The rate of fatal bleeding in adult patients receiving DOACs was 0.16 per 100 patient-years (95% CI, 0.12-0.20; I(2) = 36.5%). When compared with warfarin, DOACs were associated with significant reductions in fatal bleeding (RR, 0.53; 95% CI, 0.43-0.64; I(2) = 0%), cardiovascular mortality (RR, 0.88; 95% CI, 0.82-0.94; I(2) = 0%) and all-cause mortality (RR, 0.91; 95% CI, 0.87-0.96; I(2) = 0%). CONCLUSIONS: The use of DOACs compared with warfarin is associated with a lower rate of fatal bleeding, case-fatality rate of major bleeding, cardiovascular mortality and all-cause mortality.

Heel movement in horses: comparison between glued and nailed horse shoes at different speeds.

REASONS FOR PERFORMING STUDY: It has been suggested that the heel of the horse's hoof expands in the stance phase and this reduces the concussion at impact and helps pump blood into the hoof. Therefore, farriers usually leave a gap in the heel region when using the traditional nailed shoe. Recently glued shoes which are attached firmly to the heel have been developed and these could restrict heel movement. OBJECTIVE: To compare the degree of mediolateral heel movement between glued and nailed shoes. METHODS: Seven Thoroughbreds were used. Either their fore- or hind hooves were shod with plain aluminium shoes, attached first with glue and later with nails. Measurements were collected continuously with a displacement sensor fixed between the medial and lateral hoof walls at the heel. The horses ran on a treadmill at a walk (1.8 m/s), trot (3.5 m/s), canter (8 m/s) and gallop (12 m/s). The mediolateral heel movement in a nonweightbearing position was set at zero for each hoof and thus positive and negative numbers represented expansion and contraction, respectively. Average values of 10 consecutive strides at each speed were compared between the 2 shoeing methods by paired t test. RESULTS: At all running speeds, the heels expanded in the first 70-80% of the stance phase and contracted at breakover. The total heel movement calculated as the sum of the maximum expansion and contraction value was less with glued shoeing than with nailed shoeing for walking (all limbs), trotting (all limbs), cantering (leading forelimb and both hindlimbs) and galloping (both hindlimbs). CONCLUSIONS: Glueing restricted heel movement, suggesting possible interference with shock absorption and blood pumping in the hoof. Further study is needed to evaluate the influence of glued shoeing on hoof mechanics.

An accessory chromophore in red vision.

In the absence of a red-sensitive visual pigment, some deep-sea fish use a chlorophyll derivative in their green-sensitive rod cells in order to see deep-red light. Here we show that living rods extracted from a salamander can also accumulate an exogenous chlorophyll derivative, chlorin e6, that renders them as sensitive to red light as they are to green. This vision enhancement by an unbleachable chlorophyll derivative might therefore be a general phenomenon in vertebrate photoreception.

Differences in the pharmacological activation of visual opsins.

Opsins, like many other G-protein-coupled receptors, sustain constitutive activity in the absence of ligand. In partially bleached rods and cones, opsin's activity closes cGMP-gated channels and produces a state of "pigment adaptation" with reduced sensitivity to light and accelerated flash response kinetics. The truncated retinal analogue, beta-ionone, further desensitizes partially bleached green-sensitive salamander rods, but enables partially bleached red-sensitive cones to recover dark-adapted physiology. Structural differences between rod and cone opsins were proposed to explain the effect. Rods and cones, however, also contain different transducins, raising the possibility that G-protein type determines the photoreceptor-specific effects of beta-ionone. To test the two hypotheses, we applied beta-ionone to partially bleached blue-sensitive rods and cones of salamander, two cells that couple the same cone-like opsin to either rod or cone transducin, respectively. Immunocytochemistry confirmed that all salamander rods contain one form of transducin, whereas all cones contain another. beta-Ionone enhanced pigment adaptation in blue-sensitive rods, but it also did so in blue- and UV-sensitive cones. Furthermore, all recombinant salamander rod and cone opsins, with the exception of the red-sensitive cone opsin, activated rod transducin upon the addition of beta-ionone. Thus opsin structure determines the identity of beta-ionone as an agonist or an inverse agonist and in that respect distinguishes the red-sensitive cone opsin from all others.

A visual pigment expressed in both rod and cone photoreceptors.

Rods and cones contain closely related but distinct G protein-coupled receptors, opsins, which have diverged to meet the differing requirements of night and day vision. Here, we provide evidence for an exception to that rule. Results from immunohistochemistry, spectrophotometry, and single-cell RT-PCR demonstrate that, in the tiger salamander, the green rods and blue-sensitive cones contain the same opsin. In contrast, the two cells express distinct G protein transducin alpha subunits: rod alpha transducin in green rods and cone alpha transducin in blue-sensitive cones. The different transducins do not appear to markedly affect photon sensitivity or response kinetics in the green rod and blue-sensitive cone. This suggests that neither the cell topology or the transducin is sufficient to differentiate the rod and the cone response.

Supernumerary ring chromosomes in dermatofibrosarcoma protuberans may contain sequences from 8q11.2-qter and 17q21-qter: a combined cytogenetic and comparative genomic hybridization study.

Dermatofibrosarcoma protuberans (DFSP) presents with characteristic cytogenetic features such as reciprocal t(17;22)(q22;q13) or, more commonly, supernumerary ring chromosomes containing sequences from chromosomes 17 and 22. Here, we report the identification of a novel abnormality in a 43-year-old woman with DFSP. Cytogenetic analysis of tumor cells showed the presence of a supernumerary ring chromosome as the sole anomaly. Amplification of 8q11.2 approximately qter and 17q21 approximately qter sequences was confirmed by comparative genomic hybridization (CGH); the present case apparently lacked amplification of chromosome 22. To our knowledge, this is the first case indicating that the ring chromosome in DFSP is possibly associated with amplified material from chromosomes 8 and 17.

Identification of syt-ssx fusion transcripts in both epithelial and spindle cell components of biphasic synovial sarcoma in small tissue samples isolated by membrane-based laser microdissection.

In order to confirm the presence of SYT-SSX fusion gene in epithelial and spindle cell components of synovial sarcoma, we performed a nested reverse transcriptase-polymerase chain reaction (RT-PCR) using microbeam microdissection of membrane-mounted native tissue (MOMeNT) technique applied on formalin-fixed, paraffin-embedded tumor specimens from two biphasic synovial sarcomas and a control tissue of adamantinoma. Small targeted portions of either an epithelial or spindle cell component of the tumor tissue were microdissected together with the supporter membrane, by using an ultraviolet (337-nm) pulsed laser microbeam coupled into a robot-stage microscope with infinity optics. The SYT-SSX fusion transcript was detected in epithelial and spindle cell components of both biphasic synovial sarcomas, but not in the control tissue. Southern blot analysis also confirmed that the detected messages were derived from the SYT-SSX fusion gene. In conclusion, the microbeam MOMeNT is a useful method for isolating selected small portions from tissue sections. The SYT-SSX fusion gene is present in both cellular components of biphasic synovial sarcoma and is involved in oncogenesis of the synovial sarcoma rather than in morphologic epithelial differentiation. Therefore, in spite of the variable proportions of each component, our results confirm that the synovial sarcoma is of monoclonal origin.

Tumoral calcium pyrophosphate dihydrate crystal deposition disease. A clinicopathologic analysis of five cases.

We describe five cases of tumoral calcium pyrophosphate dihydrate crystal deposition disease (CPPDCD) and discuss the clinical, radiological and pathological features. Patients included 4 males and 1 female, ranging in age from 49 to 70 years (median, 63 yrs). The wrist was involved in two patients. The thumb, palmar aspect of the proximal phalanx of the middle finger and dorsum of the carpal bone of the hand were involved in one patient each. In one patient, a preoperative diagnosis of chondrosarcoma had been made. Macroscopically, the lesion was a circumscribed whitish-gray mass with a more or less chalky appearance, measuring between 1.0 to 6.2 cm (median, 2.5 cm). Histologically, all five lesions contained areas of calcification with crystal deposits and chondroid metaplasia. The majority of crystals were rhomboid in shape, characteristic of CPPD, but some needle-shaped crystals were also identified, which resembled urate crystals. A review of the 54 reported cases of tumoral CPPDCD including our series indicated that they could be divided into two categories based on anatomic location: central (head and neck) type (n = 33) and distal (extremity) type (n = 21). Patients of these two groups were not different with respect to age and gender, but those with the central type often presented with a painful mass (15 patients, 46%), or neurological disturbances (11 patients, 33%). Patients with the distal type presented with a painless mass or swelling (12 patients, 57%), but none had neurological signs, although 8 (38.1%) presented with acute attack similar to tophaceous gout. Tumoral CP-PDCD should be differentiated from tophaceous gout, tumoral calcinosis, and malignant or benign tumors.

Pathological fracture through a C-6 aneurysmal bone cyst. Case report.

The authors describe the case of an 18-year-old man who presented with complaints of weakness and paresis in his arms following an injury. Radiological examination demonstrated an aneurysmal bone cyst of C-6. The patient underwent a two-stage operation. Satisfactory results were obtained after complete resection of the lesion, laminoplasty, and anterior fusion without placement of instrumentation. The authors consider a two-stage operation supplemented by fusion without instrumentation to be the best treatment for young patients with aneurysmal bone cysts occurring at C-6.

Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: a fluorescence in situ hybridization and comparative genomic hybridization analysis.

Cytogenetic analysis of Bednar tumor (pigmented dermatofibrosarcoma protuberans) has not been reported previously. Here, we report the identification of a supernumerary ring chromosome in a Bednar tumor by chromosome painting with fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH). Chromosome painting with FISH demonstrated that the supernumerary ring chromosome was composed of discontinuous, interwoven sequences from chromosomes 17 and 22. Amplification of chromosomes 17 and 22 sequences was confirmed by CGH. These results indicate that Bednar tumor and dermatofibrosarcoma protuberans are characterized by the same chromosomal features. To our knowledge, this is the first report that the ring chromosome in Bednar tumor is composed of amplified material from chromosomes 17 and 22.

Phototransduction in transgenic mice after targeted deletion of the rod transducin alpha -subunit.

Retinal photoreceptors use the heterotrimeric G protein transducin to couple rhodopsin to a biochemical cascade that underlies the electrical photoresponse. Several isoforms of each transducin subunit are present in the retina. Although rods and cones seem to contain distinct transducin subunits, it is not known whether phototransduction in a given cell type depends strictly on a single form of each subunit. To approach this question, we have deleted the gene for the rod transducin alpha-subunit in mice. In hemizygous knockout mice, there was a small reduction in retinal transducin alpha-subunit content but retinal morphology and the physiology of single rods were largely normal. In homozygous knockout mice, a mild retinal degeneration occurred with age. Rod-driven components were absent from the electroretinogram, whereas cone-driven components were retained. Every photoreceptor examined by single-cell recording failed to respond to flashes, with one exception. The solitary responsive cell was insensitive, as expected for a cone, but had a rod-like spectral sensitivity and flash response kinetics that were slow, even for rods. These results indicate that most if not all rods use a single transducin type in phototransduction.

Theta ganglion cell type of cat retina.

We define a new bistratified ganglion cell type of cat retina using intracellular staining in vitro. The theta cell has a small soma, slender axon, and delicate, highly branched dendritic arbor. Dendritic fields are intermediate in size among cat ganglion cells, with diameters typically two to three times those of beta cells. Fields increase in size with distance from the area centralis, ranging in diameter from 70 to 150 microns centrally to a maximum of 700 microns in the periphery. Theta cells have markedly smaller dendritic fields within the nasal visual streak than above or below it and smaller fields nasally than temporally. Dendritic arbors are narrowly bistratified. The outer arbor lies in the lower part of sublamina a (OFF sublayer) of the inner plexiform layer where it costratifies with the dendrites of OFF alpha cells. The inner arbor occupies the upper part of sublamina b (ON sublayer), where it costratifies with ON alpha dendrites. The outer and inner arbors are composed of many relatively short segments and are densely interconnected by branches that traverse the a/b sublaminar border. Experiments combining retrograde labeling with intracellular staining indicate that theta cells project to the superior colliculus and to two components of the dorsal lateral geniculate nucleus (the C laminae and medial interlaminar nucleus). Theta cells project contralaterally from the nasal retina and ipsilaterally from the temporal retina. They apparently correspond to a sluggish transient or phasic W-cell with an ON-OFF receptive field center.

Intramuscular spindle cell hemangioendothelioma.

Spindle cell hemangioendothelioma occurring in skeletal muscle is extremely rare. No reported studies have performed an imaging evaluation of intramuscular spindle cell hemangioendothelioma. We report on such a tumor arising in an unusual site, the right extensor digiti minimi, in a 46-year-old woman. An en bloc resection was performed and the patient has been disease free for 8 years. Radiologic imaging in the present case showed similar findings to those described in intramuscular hemangioma.

The Eta ganglion cell type of cat retina.

We define a morphologic type of ganglion cell in cat retina by using intracellular staining in vitro. The eta cell has a small soma, slender axon, and delicate, highly branched dendritic arbor. Dendritic fields are intermediate in size among cat ganglion cells, with diameters typically two to three times those of beta cells. Fields increase in size as a function of distance from the area centralis, ranging in diameter from 90 microm to 200 microm centrally to a maximum of 600 microm in the periphery. This increase is unusually radially symmetric. By contrast with other cat ganglion cell types, eta cells do not have markedly smaller dendritic fields within the visual streak than above or below it nor much smaller fields nasally than temporally. Dendrites ramify broadly throughout sublamina a (OFF sublayer) of the inner plexiform layer. They arborize most densely in S2, where they costratify with dendrites of OFF alpha cells. There is apparently no matching ON variety of eta cell. Experiments combining retrograde labeling with intracellular staining indicate that eta cells project to the superior colliculus and to two components of the dorsal lateral geniculate nucleus (the C laminae and medial interlaminar nucleus). Eta cells apparently project contralaterally from the nasal retina and ipsilaterally from the temporal retina. The morphology and projection patterns of the eta cell suggest that its physiologic counterpart is a type of sluggish or W-cell with an OFF center, an ON surround, and possibly a transient light response.

Supernumerary ring chromosomes and nuclear blebs in some low-grade malignant soft tissue tumours: atypical lipomatous tumours and dermatofibrosarcoma protuberans.

We investigated the diagnostic significance of supernumerary ring chromosomes in low-grade soft-tissue neoplasms. Chromosome slides were prepared from 123 samples of soft-tissue tumours using the standard trypsin-Giemsa banding technique. Supernumerary ring chromosomes were found in 6 cases of soft tissue tumours: 5 cases of atypical lipomatous tumour (ALT) and 1 case of dermatofibrosarcoma protuberans (DFSP). By chromosome painting with fluorescence in situ hybridization (FISH), the ring chromosome in 1 ALT was painted over its entire length with the chromosome 12 probe. Nuclear blebs and micronuclei, which were observed in each case of ALT, also contained chromosome 12 material; and these structures may represent a topological distribution of ring or giant marker chromosomes in the interphase nuclei. Our findings suggest that supernumerary ring chromosomes are characteristic of some low-grade soft tissue neoplasms including ALT and DFSP.

Epithelioid sarcoma with an 18q aberration.

Epithelioid sarcoma is a peculiar soft-tissue neoplasm of uncertain origin, which is characterized by an epithelioid morphology of tumor cells coexpressing epithelial (keratin) and nonepithelial (vimentin) antigens. We herein report a new cytogenetic abnormality with der(22)t(18;22)(q11;p11.2) in a case of epithelioid sarcoma that occurred in the elbow of a 75-year-old man. Histologically, the tumor demonstrated a multinodular proliferation of epithelioid cells, with positive immunostaining for keratin, epithelial membrane antigen (EMA), and vimentin. Cultured tumor cells obtained from fresh surgical materials were frozen in plastic ampules and stocked in a liquid nitrogen freezer. Six years after surgery, the cells were recovered from the freezer and utilized for both morphologic and cytogenetic analyses. These cultured cells both before and after the freezing exhibited essentially the same epithelioid morphology and immunophenotypes as those of the original tumor. A chromosome analysis, together with fluorescence in situ hybridization (FISH), demonstrated a 61-67 modal population, and a characteristic clonal abnormality with der(22)t(18;22)(q11;p11.2). Other clonal abnormalities included numerical (-3, -4, +7, -13, -14, -16, -18, +20, -22) and structural (8p+, 9p+, 12p+, i(21q)) aberrations. Some variant clones also demonstrated i(18q). Since the breakpoint at 18q11 is similar to that reported in synovial sarcoma, this finding may support the presence of a histogenetic relationship between epithelioid sarcoma and synovial sarcoma. Our study thus indicates that the storage of frozen cells is useful for both morphologic and cytogenetic analyses of soft tissue tumors.

Ontogeny of preproenkephalin mRNA expression in the rat retina.

Endogenous opioid systems (i.e. opioid peptides and opioid receptors) modulate developmental events in the neonatal mammalian retina. In the present study, the mRNA encoding preproenkephalin A (PPE), the prohormone for the opioid growth factor (OGF), [Met5]-enkephalin, was studied in the developing and the adult retinas of rats. Northern analysis indicated the presence of a 1.4-kb message in the developing and adult retinas corresponding to rat PPE mRNA. Quantitation showed that PPE message was present on postnatal day 1 at 5% of the adult level, and increased during development until the adult quantity was reached by postnatal day 27. In situ hybridization experiments first detected the presence of PPE mRNA in retinal tissues during late gestation. In late prenatal and neonatal retinas, PPE message was associated with areas of the developing retina containing proliferating neuroblasts and postmitotic cells. Later in development, message appeared to be located primarily within the inner retina, with abundant PPE mRNA associated with putative horizontal cells of the inner nuclear layer (INL). The adult retina showed a similar pattern of PPE gene expression in the cells of the INL. These findings document that the gene expression in the retina for PPE begins in the fetus, continues during retinal development, and coincides with the presence of a PPE mRNA derivative ([Met5]-enkephalin) that regulates DNA synthesis during retinal ontogeny. Our results are also the first to show the presence of PPE message in the adult mammalian retina, suggesting transcription of an opioid gene in the mature visual system.

Syndrome of inappropriate secretion of antidiuretic hormone in elderly patients with rheumatoid arthritis associated with infections: report of two cases.

Two rheumatoid arthritis (RA) patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) during the course of infection are herein reported. One patient developed SIADH during the course of a localized cutaneous herpes zoster infection while the other developed SIADH in conjunction with Staphylococcus simulans septicemia. We consider that the development of SIADH was strongly associated with superimposed infections in the underlying RA. This is the first report discussing the association of SIADH and infections in RA patients in which SIADH is diagnosed by measurement of plasma ADH.

Ontogeny of the opioid growth factor, [Met5]-enkephalin, and its binding activity in the rat retina.

The endogenous opioid peptide [Met5]-enkephalin is a tonically active opioid growth factor (OGF) with an inhibitory action on DNA synthesis in the developing rat retina. In this study, the ontogeny of the spatial and temporal expression of OGF and its binding activity was examined. OGF-like immunoreactivity was detected in the retina at gestation day (E) 20, but not at E18, and was localized to ganglion cell and neuroblast layers; immunochemical reaction was no longer seen in the retina by postnatal day 6. Native OGF was further identified and characterized by high-performance liquid chromatography (HPLC) studies and immunodot assays, which revealed that [Met5]-enkephalin was present in the neonatal, but not adult, rat retina. OGF binding activity was detected as early as E18 using [125I]-[Met5]-enkephalin and in vitro receptor autoradiography. Little OGF binding activity was noted for prenatal retinas, but appreciable activity was observed from birth to postnatal day 4; no OGF binding could be detected after postnatal day 5 or in the adult. These results reveal the transient appearance of the OGF, [Met5]-enkephalin, and its receptor binding activity in the developing mammalian retina, and show that their ontogeny coincides with the timetable of DNA synthesis of retinal neuroblasts.