Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement.

Measurements of health indicators are rarely available for every population and period of interest, and available data may not be comparable. The Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) define best reporting practices for studies that calculate health estimates for multiple populations (in time or space) using multiple information sources. Health estimates that fall within the scope of GATHER include all quantitative population-level estimates (including global, regional, national, or subnational estimates) of health indicators, including indicators of health status, incidence and prevalence of diseases, injuries, and disability and functioning; and indicators of health determinants, including health behaviours and health exposures. GATHER comprises a checklist of 18 items that are essential for best reporting practice. A more detailed explanation and elaboration document, describing the interpretation and rationale of each reporting item along with examples of good reporting, is available on the GATHER website.

Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement.

Gretchen Stevens and colleagues present the GATHER statement, which seeks to promote good practice in the reporting of global health estimates.

Correction: Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER statement.

[This corrects the article DOI: 10.1371/journal.pmed.1002056.].

Aberrant 3' oligoadenylation of spliceosomal U6 small nuclear RNA in poikiloderma with neutropenia.

The recessive disorder poikiloderma with neutropenia (PN) is caused by mutations in the C16orf57 gene that encodes the highly conserved USB1 protein. Here, we present the 1.1 Å resolution crystal structure of human USB1, defining it as a member of the LigT-like superfamily of 2H phosphoesterases. We show that human USB1 is a distributive 3'-5' exoribonuclease that posttranscriptionally removes uridine and adenosine nucleosides from the 3' end of spliceosomal U6 small nuclear RNA (snRNA), directly catalyzing terminal 2', 3' cyclic phosphate formation. USB1 measures the appropriate length of the U6 oligo(U) tail by reading the position of a key adenine nucleotide (A102) and pausing 5 uridine residues downstream.We show that the 3' ends of U6 snRNA in PN patient lymphoblasts are elongated and unexpectedly carry nontemplated 3' oligo(A) tails that are characteristic of nuclear RNA surveillance targets. Thus, our study reveals a novel quality control pathway in which posttranscriptional 3'-end processing by USB1 protects U6 snRNA from targeting and destruction by the nuclear exosome. Our data implicate aberrant oligoadenylation of U6 snRNA in the pathogenesis of the leukemia predisposition disorder PN.

Surgical outcomes in adults with benign and malignant sacrococcygeal teratoma: a single-institution experience of 26 cases.

BACKGROUND: Adult sacrococcygeal teratomas are rare, and limited data exist on their management and outcomes following surgery. OBJECTIVE: The aim of this study was to review the outcomes in adult patients undergoing surgery for sacrococcygeal teratomas. DESIGN: A retrospective review of our prospectively maintained surgical pathology and tumor registries was conducted. SETTING: This study was conducted at the Mayo Clinic in Rochester. Information was collected on patients treated between 1980 and 2013. PATIENTS: A total of 26 patients with sacrococcygeal teratoma were identified (19 female), with a median age of 37.5 years. Malignancy was seen in 5 patients. MAIN OUTCOME MEASURES: Data on demographics, clinical presentation, tumor pathology, adjuvant therapy, surgical approach, surgical margins, use of preoperative biopsy, radiological investigations, morbidity, mortality, and local recurrence was collected. Complications were assessed by using the Clavien-Dindo system of classification. RESULTS: Patients most commonly presented with pelvic pain (n = 16) and/or a palpable mass (n = 15). On radiology, 8 lesions were purely cystic, 14 were mixed, and 4 were solid; teratoma was suspected as a diagnosis in 8 patients. Preoperative biopsy (13 patients) had 100% concordance with final pathology. Median tumor size was 6 cm, and the surgical approach was posterior only (n = 15), anterior only (n = 5), and combined anterior-posterior (n = 6). Of 5 patients with malignancy, 3 died of recurrent disease. LIMITATIONS: Limitations of this study include the small number of patients, the long study period, and the heterogeneous nature of these tumors. CONCLUSION: Presacral teratomas require multidisciplinary management and have a risk of malignant transformation. They are more common in females, and the majority are intrapelvic in location in adults. We recommend clinical evaluation, radiological investigation, and image-guided biopsy in all suspicious presacral lesions. A treatment algorithm has been designed to improve the management of these rare tumors.

Systemic Capillary Leak Syndrome Secondary to Coronavirus Disease 2019.

Systemic capillary leak syndrome is a rare disorder characterized by dysfunctional inflammatory response, endothelial dysfunction, and extravasation of fluid from the vascular space to the interstitial space leading to shock, hemoconcentration, hypoalbuminemia, and subsequent organ failure. The condition may be idiopathic or secondary to an underlying cause, which can include viral infections. Here we describe a patient with acute coronavirus disease 2019 (COVID-19) infection who presented with hemoconcentration, shock, and hypoalbuminemia. The patient subsequently developed rhabdomyolysis and compartment syndrome of all four extremities, requiring fasciotomies. This is the first reported case of systemic capillary leak syndrome associated with COVID-19 infection. This case adds to the evolving spectrum of inflammatory effects associated with this viral infection.

[Guidelines for Accurate and Transparent Health Estimates Reporting: the GATHER Statement]. / Diretrizes para o relato preciso e transparente de estimativas de saúde: a Declaração GATHER.

Measurements of health indicators are rarely available for every population and period of interest, and available data may not be comparable. The Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER) define best reporting practices for studies that calculate health estimates for multiple populations (in time or space) using multiple information sources. Health estimates that fall within the scope of GATHER include all quantitative population-level estimates (including global, regional, national, or subnational estimates) of health indicators, including indicators of health status, incidence and prevalence of diseases, injuries, and disability and functioning; and indicators of health determinants, including health behaviours and health exposures. GATHER comprises a checklist of 18 items that are essential for best reporting practice. A more detailed explanation and elaboration document, describing the interpretation and rationale of each reporting item along with examples of good reporting, is available on the GATHER website (http://gather-statement.org).

Milk-derived bioactive peptides inhibit human endothelial-monocyte interactions via PPAR-γ dependent regulation of NF-κB.

BACKGROUND: Milk-derived bioactive peptides retain many biological properties and have therapeutic effects in cardiovascular disorders such as atherosclerosis. Under inflammatory conditions the expression of endothelial cells adhesion molecules is induced, increasing monocyte adhesion to human vessel wall, a critical step in the pathogenesis of atherosclerosis. In the present work we explored the effects of milk-derived bioactive peptides on the expression of the inflammatory phenotype of human endothelial cells and their effects on monocyte adherence to endothelial cells. RESULTS: Treatment of endothelial cells with milk-derived hydrolysate inhibited their production of inflammatory proteins MCP-1 and IL-8 and expression of VCAM-1, ICAM-1 and E-selectin. Milk derived hydrolysate also attenuated the adhesion of human monocytes to activated endothelial cells. The effect was similar to that obtained in endothelial cells treated with troglitazone, a ligand of peroxisome proliferators-activator receptor-gamma (PPAR-γ). PPAR-γ is a transcription factor which when activated antagonises the pro-inflammatory capability of nuclear factor κB (NF-κB). We further examined whether the effects of milk-derived hydrolysates on endothelial cells may be mediated through NF-κB activation via a PPAR-γ dependent mechanism. The specific PPAR-γ inhibitor, GW9662 blocked the effects of the hydrolysate on the NF-κB-mediated chemokines and adhesion molecules expression in endothelial cells. CONCLUSIONS: These results suggest that milk-derived bioactive peptides work as anti-atherogenic agents through the inhibition of endothelial-dependent adhesive interactions with monocytes by inhibiting the NF-κB pathway through a PPAR-γ dependent mechanism.

Surgical site infections (SSIs) after stoma reversal (SR): risk factors, implications, and protective strategies.

BACKGROUND: Stoma reversals (SRs) are commonly performed with potentially significant postoperative complications including surgical site infections (SSIs). Our aim was to determine the incidence and risk factors for SSIs in a large cohort of SR patients. DESIGN: We reviewed our institutional 2006-2011 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database for 30-day SSIs in patients undergoing SR. Records were additionally reviewed for 10 non-ACS-NSQIP variables. The primary outcome was SSI after SR. Secondary outcomes were additional 30-day postoperative complications and length-of-stay. Predictors of SSIs were identified using multivariable logistic regression. RESULTS: From 528 SR patients, 36 patients developed a SSI (6.8 %). Most patients underwent SR for loop ileostomies (76.5 %) after index operations for ulcerative colitis (38.6 %) and colorectal cancer (27.8 %). SSI patients had fewer subcutaneous drains compared to patients with no SSI and had significantly higher rates of smoking, ASA 3-4 classification and laparotomies at SR (p < 0.05). Patients with SSI had increased length-of-stay and 30-day morbidities including sepsis and returns to the operating room (p < 0.05) compared to no-SSI patients. On multivariable analysis, subcutaneous drain placement was suggestive of SSI protection (odds ratio [OR] 0.52, 95 % confidence interval [CI] 0.2-1.1), but only smoking was significantly associated with an increased risk for SSI (OR 2.4, 95 % CI 1.1-5.4). CONCLUSIONS: Smoking increased the risk of SR SSIs in patients by over twofold, and SR SSIs are associated with additional significant morbidities. Smoking cessation should be an important part of any SSI risk-reduction strategy.

Enumeration of probiotic pediococci in animal feed: interlaboratory study.

An enumeration method to be used as official control under Council Directive 70/524/EEC for probiotic pediococci used as feed additives was validated for consideration for adoption as Comitée Européen de Normalisation (CEN) and ISO standards. Seventeen laboratories in 11 European countries carried out an interlaboratory study. A spread plate method following BS ISO 15214:1998 using 4 different agars [MRS, acidified MRS, MRS with triphenyl tetrazolium chloride (TTC), and a newly developed pediococci selective medium (PSM)] was validated. Precision data in terms of repeatability (r) and reproducibility (R) of the method for each medium using different feeding stuffs with a high and a low inoculation level were determined. Pediococci were present in the samples in mixtures with other probiotics. The enumeration of pediococci on all agars showed an RSDr value of 0.4-3.1% and an RSDR of 1.3-4.8%. MRS agar was preferred, followed by acidified MRS and MRS + TTC agar. All 4 media gave similar counts. Depending on the presence and concentration of other probiotic, such as enterococci, lactobacilli, and yeast, acidified MRS or MRS + TTC agar are recommended. The PSM was selective for pediococci and can be used if this species is present at a concentration more than 10-fold lower than other species that can grow on the MRS agars. The methodology with all 4 media is not applicable to mineral feed.

Comparison of equipment management and cleaning protocols for rigid sigmoidoscopy.

BACKGROUND: To provide outcome data relating to cleaning of rigid sigmoidoscopy equipment comparing commonly used techniques, allowing a framework for general guidelines for use in clinical practice. METHODS: A total of 104 rigid sigmoidoscopies were performed in the rooms of two colorectal surgeons using standard techniques. A three-way randomization was performed adopting the following variables: enzymatic washing versus steam sterilization of the light head, disposable versus reusable bellows and use with versus without an air filter. Aerosol from each system was collected on agar plates, and review of colony count numbers was performed. RESULTS: Gross faecal contamination of the rigid sigmoidoscope light head did not occur during any of the procedures. One plate grew a single-gram negative colony; all other contaminated plates showed environmental flora only. Reusable bellows in combination with an air filter showed lower mean colony counts (environmental flora) from the pre-procedure cultures as well as from the bellows' cultures. CONCLUSION: Enteric flora in this study was rarely aerosolized, and the use of an air filter may decrease this likelihood even further. There is no advantage in using disposable insufflation bellows when compared with the reusable type, allowing considerable cost saving. Washing the light head between procedures with enzymatic solution is a safe cheap and effective method of decontamination.

Does the use of nizatidine, as a pro-kinetic agent, improve gastric emptying in patients post-oesophagectomy?

PURPOSE: Delayed gastric emptying following oesophagectomy is common and can often lead to weight loss, malnutrition and a poor quality of life. Animal models have shown that nizatidine, a histamine H2-receptor antagonist, has pro-kinetic properties and can accelerate gastric emptying. Patients post-oesophagectomy require long-term acid suppression medication; if nizatidine can improve gastric emptying, it can be adopted for its dual pharmacological actions. METHODOLOGY: Twenty consecutive patients were prospectively enrolled in this trial following oesophagectomy. All patients were more than 6 months post-surgery and had no evidence of recurrent cancer. A baseline nuclear medicine scan following a radiolabelled meal was conducted and then repeated after 1 week of nizatidine (150 mg bd) treatment. Quality of life and eating comfort data were collected. RESULTS: Oesophagectomy causes a significant delay in gastric emptying. Early satiety (80%) and reflux (65%) were the most common post-operative complaints. The percentage of food remaining in the stomach at 60 min post-meal was significantly more than normal values in both the pre- and post-nizatidine studies. There is no advantage in using nizatidine as a pro-kinetic agent. CONCLUSIONS: Impaired gastric emptying post-surgery causes a change in eating habits. Patients in this study did not lose a significant amount of weight despite all indicating worse eating comfort. Patients required more regular meals or snacks throughout the day and avoid foods that are difficult to swallow. It is likely that gastric motility only plays a small role in the emptying process and gravity combined with appropriate drainage procedures (pyloroplasty/pyloromyotomy) at the time of surgery are more important.

AKR1C isoforms represent a novel cellular target for jasmonates alongside their mitochondrial-mediated effects.

Members of the aldo-keto reductase (AKR) superfamily, particularly the AKR1C subfamily, are emerging as important mediators of the pathology of cancer. Agents that inhibit these enzymes may provide novel agents for either the chemoprevention or treatment of diverse malignancies. Recently, jasmonates, a family of plant stress hormones that bear a structural resemblance to prostaglandins, have been shown to elicit anticancer activities both in vitro and in vivo. In this study, we show that jasmonic acid (JA) and methyl jasmonate (MeJ) are capable of inhibiting all four human AKR1C isoforms. Although JA is the more potent inhibitor of recombinant AKR1C proteins, including the in vitro prostaglandin F synthase activity of AKR1C3, MeJ displayed greater potency in cellular systems that was, at least in part, due to increased cellular uptake of MeJ. Moreover, using the acute myelogenous leukemia cell lines HL-60 and KG1a, we found that although both jasmonates were able to induce high levels of reactive oxygen species in a dose-dependent fashion, only MeJ was able to induce high levels of mitochondrial superoxide (MSO), possibly as an epiphenomenon of mitochondrial damage. There was a strong correlation observed between MSO formation at 24 hours and reduced cellularity at day 5. In conclusion, we have identified AKR1C isoforms as a novel target of jasmonates in cancer cells and provide further evidence of the promise of these compounds, or derivatives thereof, as adjunctive therapies in the treatment of cancer.

Characterization of two novel aldo-keto reductases from Arabidopsis: expression patterns, broad substrate specificity, and an open active-site structure suggest a role in toxicant metabolism following stress.

Aldo-keto reductases (AKRs) are widely distributed in nature and play numerous roles in the metabolism of steroids, sugars, and other carbonyls. They have also frequently been implicated in the metabolism of exogenous and endogenous toxicants, including those stimulated by stress. Although the Arabidopsis genome includes at least 21 genes with the AKR signature, very little is known of their functions. In this study, we have screened the Arabidopsis thaliana genomic sequence for genes with significant homology to members of the mammalian AKR1 family and identified four homologues for further study. Following alignment of the predicted protein sequences with representatives from the AKR superfamily, the proteins were ascribed not to the AKR1 family but to the AKR4C subfamily, with the individual designations of AKR4C8, AKR4C9, AKR4C10, and AKR4C11. Expression of two of the genes, AKR4C8 and AKR4C9, has been shown to be coordinately regulated and markedly induced by various forms of stress. The genes have been overexpressed in bacteria, and recombinant proteins have been purified and crystallized. Both enzymes display NADPH-dependent reduction of carbonyl compounds, typical of the superfamily, but will accept a very wide range of substrates, reducing a range of steroids, sugars, and aliphatic and aromatic aldehydes/ketones, although there are distinct differences between the two enzymes. We have obtained high-resolution crystal structures of AKR4C8 (1.4 A) and AKR4C9 (1.25 A) in ternary complexes with NADP(+) and acetate. Three extended loops, present in all AKRs and responsible for defining the cofactor- and substrate-binding sites, are shorter in the 4C subfamily compared to other AKRs. Consequently, the crystal structures reveal open and accommodative substrate-binding sites, which correlates with their broad substrate specificity. It is suggested that the primary role of these enzymes may be to detoxify a range of toxic aldehydes and ketones produced during stress, although the precise nature of the principal natural substrates remains to be determined.

Continuous wound infusion of local anesthetic for the control of pain after elective abdominal colorectal surgery.

PURPOSE: Local anesthetic wound infusion has been investigated in recent years as a potential alternative to standard analgesic regimens after major surgery. This study investigates the efficacy of a continuous wound infusion of ropivacaine in conjunction with best practice postoperative analgesia after midline laparotomy for abdominal colorectal surgery. METHODS: We performed a randomized, participant and outcome assessor-blinded, placebo-controlled trial on patients presenting for major abdominal colorectal surgery at our institution between December 2003 and February 2006. Patients were allocated to receive ropivacaine 0.54 percent or normal saline via a dual catheter Painbuster Soaker (I-Flow Corporation, OH, USA) continuous infusion device into their midline laparotomy wound for 72 hours postoperatively. RESULTS: A total of 310 patients were included in this study. The continuous wound infusion of ropivacaine after abdominal colorectal surgery conveys minimal benefit compared with saline wound infusion. No statistically significant difference could be shown for: pain at rest, morphine usage, length of stay, mobility, nausea, or return of bowel function. There was a small, statistically significant difference in mean pain on movement on Day 1 for the ropivacaine group (adjusted mean difference -0.6 (range, -1.08 to -0.13)). Although this trend continued on Days 2 and 3, the differences between groups were no longer statistically significant. CONCLUSIONS: Management of pain after major abdominal colorectal surgery is best achieved through adopting a multimodal approach to analgesia. Delivery of ropivacaine to midline laparotomy wounds via a Painbuster Soaker device is safe, but we have not demonstrated any significant clinical advantage over current best practice.