Outcomes following emergency colorectal cancer presentation in the elderly.

AIM: Colorectal cancer is predominantly a disease of the elderly and up to 30% of these patients will present as an emergency. We compared the outcomes of 'elderly' patients presenting to our unit with a colorectal cancer emergency over a 10-year period with those of a 'younger' cohort. METHODS: A single centre retrospective review of colorectal cancer emergencies between 1 April 2007 and 1 April 2017 was performed. Patients were separated into two cohorts: 'young' (< 75 years) and 'elderly' (≥ 75 years). Data collected included demographics, disease status, treatment and outcomes. RESULTS: A total of 341 patients (< 75 years: n = 154; ≥ 75 years: n = 187) presented as a colorectal cancer emergency. Significantly fewer 'elderly' patients underwent curative surgical procedures (72% vs 49%, P < 0.0001) or received adjuvant chemotherapy (56% vs 21%, P < 0.0001). 'Elderly' patients had significantly more postoperative cardio-respiratory complications (7% vs 36%, P < 0.0001), but despite this there was no significant difference in 30-day mortality (7% vs 12%) and survival rates at 1 year (75% vs 74%) or 3 years (56% vs 49%). Elderly patients treated with best supportive care had a median overall survival of just 62 (range 1-955) days. CONCLUSION: Patients ≥ 75 years presenting as a colorectal cancer emergency were significantly less likely to undergo emergency curative surgery or receive adjuvant chemotherapy than those < 75 years. However, the 30-day mortality, 1- and 3-year survival rates for patients undergoing curative surgery were comparable.

Piezo1 channels are mechanosensors in human fetoplacental endothelial cells.

STUDY QUESTION: Does the shear stress sensing ion channel subunit Piezo1 have an important mechanotransduction role in human fetoplacental endothelium? SUMMARY ANSWER: Piezo1 is present and functionally active in human fetoplacental endothelial cells, and disruption of Piezo1 prevents the normal response to shear stress. WHAT IS KNOWN ALREADY: Shear stress is an important stimulus for maturation and function of placental vasculature but the molecular mechanisms by which the force is detected and transduced are unclear. Piezo1 channels are Ca2+-permeable non-selective cationic channels which are critical for shear stress sensing and maturation of murine embryonic vasculature. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: We investigated the relevance of Piezo1 to placental vasculature by studying human fetoplacental endothelial cells (FpECs) from healthy pregnancies. Endothelial cells were isolated from placental cotyledons and cultured, for the study of tube formation and cell alignment to shear stress. In addition, human placental arterial endothelial cells were isolated and studied immediately by patch-clamp electrophysiology. MAIN RESULTS AND THE ROLE OF CHANCE: The synthetic Piezo1 channel agonist Yoda1 caused strong elevation of the intracellular Ca2+ concentration with a 50% effect occurring at about 5.4 µM. Knockdown of Piezo1 by RNA interference suppressed the Yoda1 response, consistent with it being mediated by Piezo1 channels. Alignment of cells to the direction of shear stress was also suppressed by Piezo1 knockdown without loss of cell viability. Patch-clamp recordings from freshly isolated endothelium showed shear stress-activated single channels which were characteristic of Piezo1. LIMITATIONS, REASONS FOR CAUTION: The in vitro nature of fetoplacental endothelial cell isolation and subsequent culture may affect FpEC characteristics and PIEZO1 expression. In addition to Piezo1, alternative shear stress sensing mechanisms have been suggested in other systems and might also contribute in the placenta. WIDER IMPLICATIONS OF THE FINDINGS: These data suggest that Piezo1 is an important molecular determinant of blood flow sensitivity in the placenta. Establishing and manipulating the molecular mechanisms regulating shear stress sensing could lead to novel therapeutic strategies to improve blood flow in the placenta. LARGE-SCALE DATA: Not applicable. STUDY FUNDING/COMPETING INTEREST(S): LCM was funded by a Clinical Research Training Fellowship from the Medical Research Council and by the Royal College of Obstetricians and Gynaecologists, and has received support from a Wellcome Trust Institutional Strategic Support Fund. JS was supported by the Wellcome Trust and a BHF Intermediate Research Fellowship. HJG, CW, AJH and PJW were supported by PhD Studentships from BHF, BBSRC and the Leeds Teaching Hospitals Charitable Foundation respectively. All authors declare no conflict of interest.

Small bowel obstruction in pregnancy is a complex surgical problem with a high risk of fetal loss.

INTRODUCTION: Small bowel obstruction (SBO) in pregnancy is rare and is most commonly caused by adhesions from previous abdominal surgery. Previous literature reviews have emphasised the need for prompt laparotomy in all cases of SBO because of the significant risks of fetal loss and maternal mortality. We undertook a review of the contemporary literature to determine the optimum management strategy for SBO in pregnancy. METHODS: The MEDLINE® and PubMed databases were searched for cases of SBO in pregnancy between 1992 and 2014. Two cases from our own institution were also reviewed. RESULTS: Forty-six cases of SBO in pregnancy were identified, with adhesions being the most common aetiology (50%). The overall risk of fetal loss was 17% and the maternal mortality rate was 2%. In cases of adhesional SBO, 91% of cases were managed surgically, with 14% fetal loss. Two cases (9%) were managed conservatively with no complications. Magnetic resonance imaging (MRI) was used to diagnose SBO in 11% of cases. CONCLUSIONS: Based on our experience and the contemporary literature, we recommend that urgent MRI of the abdomen should be undertaken to diagnose the aetiology of SBO in pregnancy. In cases of adhesional SBO, conservative treatment may be safely commenced, with a low threshold for laparotomy. In other causes, such as volvulus or internal hernia, laparotomy remains the treatment of choice.

Automatic laser welding and milling with in situ inline coherent imaging.

Although new affordable high-power laser technologies enable many processing applications in science and industry, depth control remains a serious technical challenge. In this Letter we show that inline coherent imaging (ICI), with line rates up to 312 kHz and microsecond-duration capture times, is capable of directly measuring laser penetration depth, in a process as violent as kW-class keyhole welding. We exploit ICI's high speed, high dynamic range, and robustness to interference from other optical sources to achieve automatic, adaptive control of laser welding, as well as ablation, achieving 3D micron-scale sculpting in vastly different heterogeneous biological materials.

Small bowel perforation secondary to accidental dental plate ingestion.

The majority of ingested foreign bodies will pass through the gastrointestinal tract without incident, with less than 1% of cases resulting in complications. Herein we present a case of small bowel perforation secondary to the accidental ingestion of a dental plate. A diagnosis of perforation was made by CT imaging, but the exact cause could only be determined after resection of the affected bowel and histo-pathological examination. We re-iterate the importance of accurate and thorough history taking in patients with possible foreign body ingestion.

Deconvolution of the factors contributing to the increase in global hurricane intensity.

To better understand the change in global hurricane intensity since 1970, we examined the joint distribution of hurricane intensity with variables identified in the literature as contributing to the intensification of hurricanes. We used a methodology based on information theory, isolating the trend from the shorter-term natural modes of variability. The results show that the trend of increasing numbers of category 4 and 5 hurricanes for the period 1970-2004 is directly linked to the trend in sea-surface temperature; other aspects of the tropical environment, although they influence shorter-term variations in hurricane intensity, do not contribute substantially to the observed global trend.

Changes in tropical cyclone number, duration, and intensity in a warming environment.

We examined the number of tropical cyclones and cyclone days as well as tropical cyclone intensity over the past 35 years, in an environment of increasing sea surface temperature. A large increase was seen in the number and proportion of hurricanes reaching categories 4 and 5. The largest increase occurred in the North Pacific, Indian, and Southwest Pacific Oceans, and the smallest percentage increase occurred in the North Atlantic Ocean. These increases have taken place while the number of cyclones and cyclone days has decreased in all basins except the North Atlantic during the past decade.

Coupled ocean-atmosphere dynamics in the Indian Ocean during 1997-98.

Climate variability in the Indian Ocean region seems to be, in some aspects, independent of forcing by external phenomena such as the El Niño/Southern Oscillation. But the extent to which, and how, internal coupled ocean-atmosphere dynamics determine the state of the Indian Ocean system have not been resolved. Here we present a detailed analysis of the strong seasonal anomalies in sea surface temperatures, sea surface heights, precipitation and winds that occurred in the Indian Ocean region in 1997-98, and compare the results with the record of Indian Ocean climate variability over the past 40 years. We conclude that the 1997-98 anomalies--in spite of the coincidence with the strong El Niño/Southern Oscillation event--may primarily be an expression of internal dynamics, rather than a direct response to external influences. We propose a mechanism of ocean-atmosphere interaction governing the 1997-98 event that may represent a characteristic internal mode of the Indian Ocean climate system. In the Pacific Ocean, the identification of such a mode has led to successful predictions of El Niño; if the proposed Indian Ocean internal mode proves to be robust, there may be a similar potential for predictability of climate in the Indian Ocean region.

Translational repressor bruno plays multiple roles in development and is widely conserved.

oskar (osk) mRNA is tightly localized to the posterior pole of the Drosophila oocyte, where the subsequent expression of Osk protein directs abdomen and germ-line formation in the developing embryo. Misplaced expression of Osk protein leads to lethal body patterning defects. The Osk message is translationally repressed before and during the localization process, ensuring that Osk protein is only expressed after the mRNA has reached the posterior. An ovarian protein, Bruno (Bru), has been implicated as a translational repressor of osk mRNA. Here we report the isolation of a cDNA encoding Bru using a novel approach to the expression cloning of an RNA-binding protein, and the identification of previously described mutants in the arrest (aret)-locus as mutants in Bru. The mutant phenotype, along with the binding properties of the protein and its pattern of accumulation within the oocyte, indicate that Bru regulates multiple mRNAs involved in female and male gametogenesis as well as early in embryogenesis. Genetic experiments provide further evidence that Bru functions in the translational repression of osk. Intriguingly, we find that Bru interacts physically with Vasa (Vas), an RNA helicase that is a positive regulator of osk translation. Bru belongs to an evolutionarily conserved family of genes, suggesting that Bru-mediated translational regulation may be widespread. Models for the molecular mechanism of Bru function are discussed.

Drosophila virilis oskar transgenes direct body patterning but not pole cell formation or maintenance of mRNA localization in D. melanogaster.

The Drosophila melanogaster gene oskar is required for both posterior body patterning and germline formation in the early embryo; precisely how oskar functions is unknown. The oskar transcript is localized to the posterior pole of the developing oocyte, and oskar mRNA and protein are maintained at the pole through early embryogenesis. The posterior maintenance of oskar mRNA is dependent upon the presence of oskar protein. We have cloned and characterized the Drosophila virilis oskar homologue, virosk, and examined its activity as a transgene in Drosophila melanogaster flies. We find that the cis-acting mRNA localization signals are conserved, although the virosk transcript also transiently accumulates at novel intermediate sites. The virosk protein, however, shows substantial differences from oskar: while virosk is able to rescue body patterning in a D. melanogaster oskar- background, it is impaired in both mRNA maintenance and pole cell formation. Furthermore, virosk induces a dominant maternal-effect lethality when introduced into a wild-type background, and interferes with the posterior maintenance of the endogenous oskar transcript in early embryogenesis. Our data suggest that virosk protein is unable to anchor at the posterior pole of the early embryo; this defect could account for all of the characteristics of virosk mentioned above. Our observations support a model in which oskar protein functions both by nucleating the factors necessary for the activation of the posterior body patterning determinant and the germ cell determinant, and by anchoring these factors to the posterior pole of the embryo. While the posterior body patterning determinant need not be correctly localized to provide body patterning activity, the germ cell determinant may need to be highly concentrated adjacent to the cortex in order to direct pole cell formation.

Multiple RNA regulatory elements mediate distinct steps in localization of oskar mRNA.

Pattern formation in the early development of many organisms relies on localized cytoplasmic proteins, which can be prelocalized as mRNAs. The Drosophila oskar gene, required both for posterior body patterning and germ cell determination, encodes one such mRNA. Localization of oskar mRNA is an elaborate process involving movement of the transcript first into the oocyte from adjacent interconnected nurse cells and then across the length of the oocyte to its posterior pole. We have mapped RNA regulatory elements that direct this localization. Using a hybrid lacZ/oskar mRNA, we identify several elements within the oskar 3' untranslated region that affect different steps in the process: the early movement into the oocyte, accumulation at the anterior margin of the oocyte and finally localization to the posterior pole. This use of multiple cis-acting elements suggests that localization may be orchestrated in a combinatorial fashion, thereby allowing localized mRNAs with ultimately different destinations to employ common mechanisms for shared intermediate steps.

Conserved classes of homeodomains in Schistosoma mansoni, an early bilateral metazoan.

Genes containing a homeobox can be divided into classes based on the distinctive peptide sequences of their diverged homeodomains. Many of these classes, including Antennapedia, engrailed and paired, are strongly conserved in higher multicellular animals, but have not previously been found in platyhelminths, the flatworms which represent the most primitive bilateral metazoans. We have screened cDNA libraries of the platyhelminth Schistosoma mansoni using a degenerate oligonucleotide derived from the third helix of the homeodomain, and have identified numerous schistosome homeobox-containing sequences, including members of the Antennapedia, engrailed and paired classes. The schistosome homeodomain sequences are more similar to the higher animals sequences in their respective classes than they are to each other, indicating that the establishment of these three distinctive classes is at least as ancient as the flatworms. Our data suggest that the ancestral functions of the Antennapedia, engrailed and paired classes involve fundamental features of all bilateral metazoan development. The putative full-length coding sequence of the S. mansoni en homologue is presented.

The cost of treating small cell lung cancer.

OBJECTIVE: To determine the cost of treating small cell lung cancer (SCLC) and to assess quality-adjusted survival in these patients. DESIGN: Retrospective analysis. SETTING: Westmead Hospital, a tertiary referral institution. PATIENTS: Consecutive sample of 31 patients with histologically proved SCLC, treated between January 1987 and December 1987. MAIN OUTCOME MEASURES: The cost of investigation, hospitalisation, chemotherapy, radiotherapy and follow-up of patients overall and for those with limited and extensive disease respectively. Quality-adjusted survival was based on a Q-TWiST analysis. RESULTS: The median overall cost per patient was $14,413 (range, $1188-$39,598) for all patients and for limited disease and extensive disease was $18,234 (range, $1914-$39,598) and $13,177 (range, $1188-$32,798) respectively. The two major costs were hospitalisation (42%) and chemotherapy (18%). Radiotherapy accounted for 11% of all costs. The Q-TWiST analysis suggests that for patients with limited disease, quality-adjusted survival is similar to absolute survival. CONCLUSIONS: The treatment of SCLC at our institution was expensive but the cost may be reduced by reduction in the duration of hospitalisation, the use of less expensive combination drug regimens, or the use of "true" outpatient chemotherapy. Despite intensive therapy, patients with limited disease maintained a reasonable quality of life.

Tissue effects of an ultrasonic scalpel for clinical surgical use.

The effects of a new ultrasonic scalpel were studied in laboratory animals. Tissue heat conduction from the tip of the ultrasonic blade was measured. Tissue damage was assessed by light microscopy of histochemically stained sections. The ultrasonic scalpel incised nonfibrous tissue effectively, with minimal heat conduction, and the incisions healed with no evidence of fibrosis nor of tissue destruction.

A review of macromolecular transport and secretion at the cellular level.

This is a review of current information concerning mechanisms involved in transport and secretion of macromolecules in exocrine glands. Emphasis has been placed on information available for pancreatic acinar cells. The review was prompted by the availability of considerable amounts of new information developed during the past several years. Exportable proteins in the pancreatic acinar cells are synthesized on ribosomes attached to the endoplasmic reticulum. Following synthesis, nascent proteins are transported from ribosomes attached to the endoplasmic reticulum into intracisternal spaces bound by the endoplasmic reticulum. The proteins are then carried to the Golgi complex by transitional elements. Zymogen granules are formed in the Golgi complex and migrate to the cell apex. Appropriate stimulation leads to fusion of the zymogen granule membrane and apical plasmalemma followed by a break in the membrane and consequent release of the granule content into the ductules. The extact molecular events involved in the process of secretion are not known. The roles of cAMP and cGMP in pancreatic secretion are supported by indirect evidence only. The role of calcium in secretion is apparent, but further investigation is needed to delineate the exact mechanism of its action. Membrane depolarization and associated ionic fluexes seem to play a significant role.