BACKGROUND

Data on readmission as well as the potential impact of length of stay (LOS) after colectomy for colon cancer remain poorly defined. The objective of the current study was to evaluate risk factors associated with readmission among a nationwide cohort of patients after colorectal surgery.

METHODS

We identified 149,622 unique individuals from the Surveillance, Epidemiology, and End Results-Medicare dataset with a diagnosis of primary colorectal cancer who underwent colectomy between 1986 and 2005. In-hospital morbidity, mortality, LOS, and 30-day readmission were examined using univariate and multivariate logistic regression models.

RESULTS

Primary surgical treatment consisted of right (37.4%), transverse (4.9%), left (10.5%), sigmoid (22.8%), abdominoperineal resection (7.3%), low anterior resection (5.6%), total colectomy (1.2%), or other/unspecified (10.3%). Mean patient age was 76.5 years and more patients were female (52.9%). The number of patients with multiple preoperative comorbidities increased over time (Charlson comorbidity score ≥3: 1986 to 1990, 52.5% vs 2001 to 2005, 63.1%; p < 0.001). Mean LOS was 11.7 days and morbidity and mortality were 36.5% and 4.2%, respectively. LOS decreased over time (1986 to 1990, 14.0 days; 1991 to 1995, 12.0 days; 1996 to 2000, 10.4 days; 2001 to 2005, 10.6 days; p < 0.001). In contrast, 30-day readmission rates increased (1986 to 1990, 10.2%; 1991 to 1995, 10.9%; 1996 to 2000, 12.4%; 2001 to 2005, 13.7%; p < 0.001). Factors associated with increased risk of readmission included LOS (odds ratio = 1.02), Charlson comorbidities ≥3 (odds ratio = 1.27), and postoperative complications (odds ratio = 1.17) (all p < 0.01).

CONCLUSIONS

Readmission rates after colectomies have increased during the past 2 decades and mean LOS after this operation has declined. More research is needed to understand the balance and possible trade off between these hospital performance measures for all surgical procedures.

Reactive nitrogen species derived from nitric oxide are potent oxidants formed during inflammation that can oxidize membrane and lipoprotein lipids in vivo. Herein, it is demonstrated that several of these species react with unsaturated fatty acid to yield nitrated oxidation products. Using HPLC coupled with both UV detection and electrospray ionization mass spectrometry, products of reaction of ONOO- with linoleic acid displayed mass/charge (m/z) characteristics of LNO2 (at least three products at m/z 324, negative ion mode). Further analysis by MS/MS gave a major fragment at m/z 46. Addition of a NO2 group was confirmed using [15N]ONOO- which gave a product at m/z 325, fragmenting to form a daughter ion at m/z 47. Formation of nitrated lipids was inhibited by bicarbonate, superoxide dismutase (SOD), and Fe3+-EDTA, while the yield of oxidation products was decreased by bicarbonate and SOD, but not by Fe3+-EDTA. Reaction of linoleic acid with both nitrogen dioxide (*NO2) or nitronium tetrafluoroborate (NO2BF4) also yielded nitrated lipid products (m/z 324), with HPLC retention times and MS/MS fragmentation patterns identical to the m/z 324 species formed by reaction of ONOO- with linoleic acid. Finally, reaction of HPODE, but not linoleate, with nitrous acid (HONO) or isobutyl nitrite (BuiONO) yielded a product at m/z 340, or 341 upon reacting with [15N]HONO. MS/MS analysis gave an NO2- fragment, and 15N NMR indicated that the product contained a nitro (RNO2) functional group, suggesting that the product was nitroepoxylinoleic acid [L(O)NO2]. This species could form via homolytic dissociation of LOONO to LO* and *NO2 and rearrangement of LO* to an epoxyallylic radical L(O)* followed by recombination of L(O)* with *NO2. Since unsaturated lipids of membranes and lipoproteins are critical targets of reactive oxygen and nitrogen species, these pathways lend insight into mechanisms for the formation of novel nitrogen-containing lipid products in vivo and provide synthetic strategies for further structural and functional studies.

Three genes involved in biosynthesis of the lipooligosaccharide (LOS) core of Campylobacter jejuni MSC57360, the type strain of the HS:1 serotype, whose structure mimics GM(2) ganglioside, have been cloned and characterized. Mutation of genes encoding proteins with homology to a sialyl transferase (cstII) and a putative N-acetylmannosamine synthetase (neuC1), part of the biosynthetic pathway of N-acetylneuraminic acid (NeuNAc), have identical phenotypes. The LOS cores of these mutants display identical changes in electrophoretic mobility, loss of reactivity with cholera toxin (CT), and enhanced immunoreactivity with a hyperimmune polyclonal antiserum generated against whole cells of C. jejuni MSC57360. Loss of sialic acid in the core of the neuC1 mutant was confirmed by fast atom bombardment mass spectrometry. Mutation of a gene encoding a putative beta-1,4-N-acetylgalactosaminyltransferase (Cgt) resulted in LOS cores intermediate in electrophoretic mobility between that of wild type and the mutants lacking NeuNAc, loss of reactivity with CT, and a reduced immunoreactivity with hyperimmune antiserum. Chemical analyses confirmed the loss of N-acetylgalactosamine (GalNAc) and the presence of NeuNAc in the cgt mutant. These data suggest that the Cgt enzyme is capable of transferring GalNAc to an acceptor with or without NeuNAc and that the Cst enzyme is capable of transferring NeuNAc to an acceptor with or without GalNAc. A mutant with a nonsialylated LOS core is more sensitive to the bactericidal effects of human sera than the wild type or the mutant lacking GalNAc.

Monocytes and macrophages play active roles in atherosclerosis, a chronic inflammatory disease that is a leading cause of death in the developed world. The prevailing paradigm states that, during human atherogenesis, monocytes accumulate in the arterial intima and differentiate into macrophages, which then ingest oxidized lipoproteins, secrete a diverse array of proinflammatory mediators, and eventually become foam cells, the key constituents of a vulnerable plaque. Yet monocytes are heterogeneous. In the mouse, one subset (Ly-6C(hi)) promotes inflammation, expands in hypercholesterolemic conditions, and selectively gives rise to macrophages in atheromata. A different subset (Ly-6C(lo)) attenuates inflammation and promotes angiogenesis and granulation tissue formation in models of tissue injury, but its role in atherosclerosis is largely unknown. In the human, monocyte heterogeneity is preserved but it is still unresolved how subsets correspond functionally. The contradistinctive properties of these cells suggest commitment for specific function before infiltrating tissue. Such commitment argues for discriminate targeting of deleterious subsets while sparing host defense and repair mechanisms. In addition to advancing our understanding of atherosclerosis, the ability to target and image monocyte subsets would allow us to evaluate drugs designed to selectively inhibit monocyte subset recruitment or function, and to stratify patients at risk for developing complications such as myocardial infarction or stroke. In this review we summarize recent advances of our understanding of the behavioral heterogeneity of monocytes during disease progression and outline emerging molecular imaging approaches to address key questions in the field.

The exclusive human pathogen Neisseria meningitidis expresses lipooligosaccharide (LOS), an endotoxin that is structurally distinct from the lipopolysaccharides (LPS) of enteric Gram-negative bacilli. Differences that appear to be biologically important occur in the composition and attachment of acyl chains to lipid A, phosphorylation patterns of lipid A, and the incorporation and phosphorylation of sugar residues in the LOS inner core. Further, unlike most enteric LPS, only two to five sugar residues are attached to the meningococcal LOS inner core, and there are no multiple repeating units of O-antigens. In contrast to Escherichia coli, where the LPS biosynthesis genes are organized as large operons, the meningococcal LOS biosynthesis genes are organized into small operons or are located individually in the chromosome. Some of these genetic loci in meningococci and gonococci display polymorphisms caused by localized chromosomal rearrangements. One mechanism of antigenic variation of meningococci LOS is the regulation of glycosyltransferase activity by slipped strand mispairing of homopolymeric tracts within the 5' end of the genes encoding these enzymes, resulting in the addition of different sugar residues to the LOS molecule. Meningococcal LOS is a critical virulence factor in N. meningitidis infections and is involved in many aspects of pathogenesis, including the colonization of the human nasopharynx, survival after bloodstream invasion, and the inflammation associated with the morbidity and mortality of meningococcemia and meningitis. Meningococcal LOS, which is a component of serogroup B meningococcal vaccines currently in clinical trials, has been proposed as a candidate for a new generation of meningococcal vaccines. The rapidly expanding knowledge of the genetic basis for biosynthesis, structure, and regulation of meningococcal LOS provides insights into unique endotoxin structures and the precise role of LOS in the pathogenesis of meningococcal disease.

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2, encoding methyl-CpG-binding protein 2 (MeCP2). Although MECP2 is ubiquitously transcribed, MeCP2 expression is developmentally regulated and heterogeneous in neuronal subpopulations, defined as MeCP2(lo) and MeCP2(hi). To test the hypothesis that pathways affecting MeCP2 expression changes may be defective in RTT, autism and other neurodevelopmental disorders without MECP2 mutations, a high-throughput quantitation of MeCP2 expression was performed on a tissue microarray containing frontal cortex samples from 28 different patients with neurodevelopmental disorders and age-matched controls. Combined quantitative analyses of MeCP2 protein and alternatively polyadenylated transcript levels were performed by laser scanning cytometry and tested for significant differences from age-matched controls. Normal cerebral samples showed an increase in total MeCP2 expression and the percentage of MeCP2(hi) cells with age that could be explained by increased MECP2 transcription within the MeCP2(hi) population. A significant decrease in the relative usage of the long transcript in the MeCP2(lo) population was observed in postnatal compared to fetal brain, but alternate polyadenylation did not correlate with MeCP2 expression changes at the single cell level. Brain samples from several related neurodevelopmental disorders, including autism, pervasive developmental disorder, Prader-Willi and Angelman syndromes showed significant differences in MeCP2 expression from age-matched controls by apparently different transcriptional and post-transcriptional mechanisms. These results suggest that multiple pathways regulate the complex developmental expression of MeCP2 and are defective in autism-spectrum disorders in addition to RTT.

BACKGROUND

Sedatives and analgesics, in doses that alter consciousness in the intensive care unit (ICU), contribute to delirium and mortality. Pain, agitation, and delirium can be monitored in ICU patients. These symptoms were noted before (PRE) and after (POST) a protocol to alleviate undesirable symptoms. Analgesia and sedation levels, the incidence of coma, delirium, length of stay (LOS), discharge location, and mortality were then compared. We hypothesized that the likely reduction in iatrogenic coma would result in less delirium, because these 2 morbid conditions seem to be linked.

METHODS

All patients were consecutively admitted to an ICU PRE-protocol (August 2003 to February 2004, 610 patients) and POST-protocol (April 2005 to November 2005, 604 patients). Between February 2004 and April 2005, we piloted and taught individualized nonpharmacologic strategies and titration of analgesics, sedatives, and antipsychotics based on sedation, analgesia, and delirium scores. We measured the following outcomes: coma, delirium, LOS, mortality, and discharge location.

RESULTS

The POST group benefited from better analgesia, received less opiates (90.72 + or - 207.45 vs 22.93 + or - 40.36 morphine equivalents/d, P = <0.0001), and, despite comparable sedation, had shorter duration of mechanical ventilation. Medication-induced coma rates (18.1%vs 7.2%, P < 0.0001), ICU and hospital LOS, and dependency at discharge were lower in the POST-protocol group. Subsyndromal delirium was significantly reduced; delirium was similar. The 30-day mortality risk in the PRE cohort was 29.4% vs 22.9% in the POST cohort (log-rank test, P = 0.009).

CONCLUSIONS

Educational initiatives incorporating systematic management protocols with nonpharmacologic measures and individualized titration of sedation, analgesia, and delirium therapies are associated with better outcomes.

BACKGROUND

Road traffic crash is of growing public health importance worldwide contributing significantly to the global disease burden. There is paucity of published data on road traffic crashes in our local environment. This study was carried out to describe the injury characteristics and outcome of road traffic crash victims in our local setting and provide baseline data for establishment of prevention strategies as well as treatment protocols.

METHODS

This was a prospective hospital based study of road traffic crash victims carried out at Bugando Medical Centre in Northwestern Tanzania between March 2010 and February 2011. After informed consent to participate in the study, all patients were consecutively enrolled into the study. Data were collected using a pre-tested questionnaire and analyzed using SPSS computer software version 15.0.

RESULTS

A total of 1678 road traffic crash victims were studied. Their male to female ratio was of 2.1:1. The patients ages ranged from 3 to 78 years with the mean and median of 29.45 (± 24.22) and 26.12 years respectively. The modal age group was 21-30 years, accounting for 52.1% patients. Students (58.8%) and businessmen (35.9%) were the majority of road traffic crash victims. Motorcycle (58.8%) was responsible for the majority of road traffic crashes. Musculoskeletal (60.5%) and the head (52.1%) were the most common body region injured. Open wounds (65.9%) and fractures (26.3%) were the most common type of injuries sustained. The majority of patients (80.3%) were treated surgically. Wound debridement was the most common procedure performed in 81.2% of the patients. The complication rate was 23.7%. The overall average length of hospital stay (LOS) was 23.5 ± 12.3 days. Mortality rate was 17.5%. According to multivariate logistic regression analysis, patients who had severe trauma (Kampala Trauma Score II ≤ 6) and those with long bone fractures stayed longer in the hospital and this was significant (P < 0.001) whereas the age of the patient, severe trauma (Kampala Trauma Score II ≤ 6), admission Systolic Blood Pressure < 90 mmHg and severe head injury (Glasgow Coma Score = 3-8) significantly influenced mortality (P < 0.001).

CONCLUSIONS

Road traffic crashes constitute a major public health problem in our setting and contribute significantly to unacceptably high morbidity and mortality. Urgent preventive measures targeting at reducing the occurrence of road traffic crashes is necessary to reduce the morbidity and mortality resulting from these injuries. Early recognition and prompt treatment of road traffic injuries is essential for optimal patient outcome.

We previously reported reduced sperm concentration and motility in fertile men in a U.S. agrarian area (Columbia, MO) relative to men from U.S. urban centers (Minneapolis, MN; Los Angeles, CA; New York, NY). In the present study we address the hypothesis that pesticides currently used in agriculture in the Midwest contributed to these differences in semen quality. We selected men in whom all semen parameters (concentration, percentage sperm with normal morphology, and percentage motile sperm) were low (cases) and men in whom all semen parameters were within normal limits (controls) within Missouri and Minnesota (sample sizes of 50 and 36, respectively) and measured metabolites of eight current-use pesticides in urine samples provided at the time of semen collection. All pesticide analyses were conducted blind with respect to center and case-control status. Pesticide metabolite levels were elevated in Missouri cases, compared with controls, for the herbicides alachlor and atrazine and for the insecticide diazinon [2-isopropoxy-4-methyl-pyrimidinol (IMPY)]; for Wilcoxon rank test, p = 0.0007, 0.012, and 0.0004 for alachlor, atrazine, and IMPY, respectively. Men from Missouri with high levels of alachlor or IMPY were significantly more likely to be cases than were men with low levels [odds ratios (ORs) = 30.0 and 16.7 for alachlor and IMPY, respectively], as were men with atrazine levels higher than the limit of detection (OR = 11.3). The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid) and metolachlor were also associated with poor semen quality in some analyses, whereas acetochlor levels were lower in cases than in controls (p = 0.04). No significant associations were seen for any pesticides within Minnesota, where levels of agricultural pesticides were low, or for the insect repellent DEET (N,N-diethyl-m-toluamide) or the malathion metabolite malathion dicarboxylic acid. These associations between current-use pesticides and reduced semen quality suggest that agricultural chemicals may have contributed to the reduction in semen quality in fertile men from mid-Missouri we reported previously.

Interstitial pneumonia (IP) is a severe organ manifestation of cytomegalovirus (CMV) disease in the immunocompromised host, in particular in recipients of bone marrow transplantation (BMT). Diagnostic criteria for the definition of CMV-IP include clinical evidence of pneumonia together with CMV detected in bronchoalveolar lavage or lung biopsy. We have used the model of syngeneic BMT and simultaneous infection of BALB/c mice with murine CMV for studying the pathogenesis of CMV-IP by controlled longitudinal analysis. A disseminated cytopathic infection of the lungs with fatal outcome was observed only when reconstituting CD8 T cells were depleted. Neither CD8 nor CD4 T cells mediated an immunopathogenesis of acute CMV-IP. By contrast, after efficient hematolymphopoietic reconstitution, viral replication in the lungs was moderate and focal. The histopathological picture was dominated by preferential infiltration of CD8 T cells confining viral replication to inflammatory foci. Notably, after clearance of acute infection, CD62L(lo) and CD62L(hi) subsets of CD44(+) memory CD8 T cells were found to persist in lung tissue. One can thus operationally distinguish an early CMV-positive IP (phase 1) and a late CMV-negative IP (phase 2). According to the definition, phase 2 histopathology would not be diagnosed as a CMV-IP and could instead be misinterpreted as a CMV-induced immunopathology. We document here that phase 1 as well as phase 2 pulmonary CD8 T cells are capable of exerting effector functions and are effectual in protecting against productive infection. We propose that antiviral "stand-by" memory-effector T cells persist in the lungs to prevent virus recurrence from latency.

OBJECTIVE

This study was conducted to assess the accuracy of self-reported hepatitis C virus (HCV) antibody (anti-HCV) serostatus in injection drug users (IDUs), and examine whether self-reported anti-HCV serostatus was associated with recent injection risk behavior.

METHODS

In five U.S. cities (Baltimore, Chicago, Los Angeles, New York, and Seattle), 3,004 IDUs from 15 to 30 years old were recruited for a baseline interview to determine eligibility for a randomized controlled trial of a behavioral intervention. HIV and HCV antibody testing were performed, and subject data (e.g., demographics, drug and sexual risk behavior, and history of HIV and HCV testing) were collected via audio computer-administered self-interview. Risk behavior during the previous three months was compared to self-reported anti-HCV serostatus.

RESULTS

Anti-HCV prevalence in this sample of young IDUs was 34.1%. Seventy-two percent of anti-HCV-positive and 46% of anti-HCV-negative IDUs in this sample were not aware of their HCV serostatus. Drug treatment or needle exchange use was associated with increased awareness of HCV serostatus. Anti-HCV-negative IDUs who knew their serostatus were less likely than those unaware of their status to inject with a syringe used by another IDU or to share cottons to filter drug solutions. Knowledge of one's positive anti-HCV status was not associated with safer injection practices.

CONCLUSIONS

Few anti-HCV-positive IDUs in this study were aware of their serostatus. Expanded availability of HCV screening with high quality counseling is clearly needed for this population to promote the health of chronically HCV-infected IDUs and to decrease risk among injectors susceptible to acquiring or transmitting HCV.

Tumors can suppress the host immune system by employing a variety of cellular immune modulators, such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). In the peripheral blood of patients with advanced stage melanoma, there is an accumulation of CD14(+)HLA-DR(lo/-) MDSC that suppress autologous T cells ex vivo in a STAT-3-dependent manner. However, a precise mechanistic basis underlying this effect is unclear, particularly with regard to whether the MDSC induction mechanism relies on cell-cell contact of melanoma cells with CD14(+) cells. Here, we show that early-passage human melanoma cells induce phenotypic changes in CD14(+) monocytes, leading them to resemble MDSCs characterized in patients with advanced stage melanoma. These MDSC-like cells potently suppress autologous T-cell proliferation and IFN-γ production. Notably, induction of myeloid-suppressive functions requires contact or close proximity between monocytes and tumor cells. Further, this induction is largely dependent on production of cyclooxygenase-2 (COX-2) because its inhibition in these MDSC-like cells limits their ability to suppress T-cell function. We confirmed our findings with CD14(+) cells isolated from patients with advanced stage melanoma, which inhibited autologous T cells in a manner relying up prostaglandin E2 (PGE2), STAT-3, and superoxide. Indeed, PGE2 was sufficient to confer to monocytes the ability to suppress proliferation and IFN-γ production by autologous T cells ex vivo. In summary, our results reveal how immune suppression by MDSC can be initiated in the tumor microenvironment of human melanoma.

The density of native (preexisting) collaterals and their capacity to enlarge into large conduit arteries in ischemia (arteriogenesis) are major determinants of the severity of tissue injury in occlusive disease. Mechanisms directing arteriogenesis remain unclear. Moreover, nothing is known about how native collaterals form in healthy tissue. Evidence suggests vascular endothelial growth factor (VEGF), which is important in embryonic vascular patterning and ischemic angiogenesis, may contribute to native collateral formation and arteriogenesis. Therefore, we examined mice heterozygous for VEGF receptor-1 (VEGFR-1(+/-)), VEGF receptor-2 (VEGFR-2(+/-)), and overexpressing (VEGF(hi/+)) and underexpressing VEGF-A (VEGF(lo/+)). Recovery from hindlimb ischemia was followed for 21 days after femoral artery ligation. All statements below are P<0.05. Compared to wild-type mice, VEGFR-2(+/-) showed similar: ischemic scores, recovery of hindlimb perfusion, pericollateral leukocytes, collateral enlargement, and angiogenesis. In contrast, VEGFR-1(+/-) showed impaired: perfusion recovery, pericollateral leukocytes, collateral enlargement, worse ischemic scores, and comparable angiogenesis. Compared to wild-type mice, VEGF(lo/+) had 2-fold lower perfusion immediately after ligation (suggesting fewer native collaterals which was confirmed by angiography) and blunted recovery of perfusion. VEGF(hi/+) mice had 3-fold greater perfusion immediately after ligation, more native collaterals, and improved recovery of perfusion. These differences were confirmed in the cerebral pial cortical circulation where, compared to VEGF(hi/+) mice, VEGF(lo/+) formed fewer collaterals during the perinatal period when adult density was established, and had 2-fold larger infarctions after middle cerebral artery ligation. Our findings indicate VEGF and VEGFR-1 are determinants of arteriogenesis. Moreover, we describe the first signaling molecule, VEGF-A, that specifies formation of native collaterals in healthy tissues.

The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. On the basis of the currently available evidence, a group of experts reached a consensus regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counseling should be provided emphasizing the importance of lifestyle, especially weight reduction and exercise in overweight women, smoking, and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotropins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotropins is associated with increased chances for multiple pregnancy, and, therefore, intense monitoring of ovarian response is required. Laparoscopic ovarian surgery alone is usually effective in less than 50% of women, and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC-gonadotropin paradigm) is reported to be highly effective with a cumulative singleton live-birth rate of 72%. Recommended third-line treatment is in vitro fertilization (IVF). More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-line, second-line, or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.

Two sites of the Neandertal-associated Middle Paleolithic of Iberia, dated to as early as approximately 50,000 years ago, yielded perforated and pigment-stained marine shells. At Cueva de los Aviones, three umbo-perforated valves of Acanthocardia and Glycymeris were found alongside lumps of yellow and red colorants, and residues preserved inside a Spondylus shell consist of a red lepidocrocite base mixed with ground, dark red-to-black fragments of hematite and pyrite. A perforated Pecten shell, painted on its external, white side with an orange mix of goethite and hematite, was abandoned after breakage at Cueva Antón, 60 km inland. Comparable early modern human-associated material from Africa and the Near East is widely accepted as evidence for body ornamentation, implying behavioral modernity. The Iberian finds show that European Neandertals were no different from coeval Africans in this regard, countering genetic/cognitive explanations for the emergence of symbolism and strengthening demographic/social ones.

Hematopoietic stem cells (HSCs) are heterogeneous with respect to their self-renewal, lineage, and reconstitution potentials. Although c-Kit is required for HSC function, gain and loss-of-function c-Kit mutants suggest that even small changes in c-Kit signaling profoundly affect HSC function. Herein, we demonstrate that even the most rigorously defined HSCs can be separated into functionally distinct subsets based on c-Kit activity. Functional and transcriptome studies show HSCs with low levels of surface c-Kit expression (c-Kit(lo)) and signaling exhibit enhanced self-renewal and long-term reconstitution potential compared with c-Kit(hi) HSCs. Furthermore, c-Kit(lo) and c-Kit(hi) HSCs are hierarchically organized, with c-Kit(hi) HSCs arising from c-Kit(lo) HSCs. In addition, whereas c-Kit(hi) HSCs give rise to long-term lymphomyeloid grafts, they exhibit an intrinsic megakaryocytic lineage bias. These functional differences between c-Kit(lo) and c-Kit(hi) HSCs persist even under conditions of stress hematopoiesis induced by 5-fluorouracil. Finally, our studies show that the transition from c-Kit(lo) to c-Kit(hi) HSC is negatively regulated by c-Cbl. Overall, these studies demonstrate that HSCs exhibiting enhanced self-renewal potential can be isolated based on c-Kit expression during both steady state and stress hematopoiesis. Moreover, they provide further evidence that the intrinsic functional heterogeneity previously described for HSCs extends to the megakaryocytic lineage.

OBJECTIVE

We examined the impact of social discrimination and financial hardship on unprotected anal intercourse with a male sex partner of serodiscordant or unknown HIV status in the past 3 months among 1081 Latino and 1154 Black men who have sex with men (MSM; n = 2235) residing in Los Angeles County, California; New York, New York; and Philadelphia, Pennsylvania.

METHODS

We administered HIV testing and a questionnaire assessing 6 explanatory variables. We combined traditional mediation analysis with the results of a path analysis to simultaneously examine the direct, indirect, and total effects of these variables on the outcome variable.

RESULTS

Bivariate analysis showed that homophobia, racism, financial hardship, and lack of social support were associated with unprotected anal intercourse with a serodiscordant or sero-unknown partner. Path analysis determined that these relations were mediated by participation in risky sexual situations and lack of social support. However, paths between the explanatory variable and 2 mediating variables varied by participants' serostatus.

CONCLUSIONS

Future prevention research and program designs should specifically address the differential impact of social discrimination and financial hardship on lack of social support and risky sexual situations among Latino and Black MSM.

BACKGROUND

Traumatic brain injury (TBI) can be compounded by physiologic derangements that produce secondary brain injury. The purpose of this study is to elucidate the frequency with which physiologic factors that are associated with secondary brain injury occur in patients with severe closed head injuries and to determine the impact of these factors on outcome.

METHODS

The records of 81 adult blunt trauma patients with Glasgow Coma Scale scores < or = 8 and transport times < 2 hours to a Level I trauma center were retrospectively reviewed searching for the following 11 secondary brain injury factors (SBIFs) in the first 24 hours postinjury: hypotension, hypoxia, hypercapnia, hypocapnia, hypothermia, hyperthermia, metabolic acidosis, seizures, coagulopathy, hyperglycemia, and intracranial hypertension. We recorded the worst SBIF during six time periods: hours 1, 2, 3, 4, 5 to 14, and 16 to 24. Occurrence of each SBIF was then correlated with outcome.

RESULTS

Hypocapnia, hypotension, and acidosis occurred more frequently than other SBIFs (60-80%). Hypotension, hyperglycemia, and hypothermia were associated with increased mortality rate. Patients with episodes of hypocapnia, acidosis, and hypoxia had significantly longer intensive care unit length of stay (LOS). These three SBIFs and hyperglycemia related to longer hospital LOS as well. Hypotension and acidosis were associated with discharge to a rehabilitation facility rather than home. Finally, multivariate regression analysis revealed that hypotension, hypothermia, and Abbreviated Injury Scale score of the head were independently related to mortality, whereas other SBIFs, age, Injury Severity Score, and Glasgow Coma Scale score were not. Metabolic acidosis and hypoxia were related to longer intensive care unit and hospital LOS.

CONCLUSIONS

Our early management of head-injured patients stresses avoidance and correction of SBIFs at all costs. Nonetheless, SBIFs occur frequently in the first 24 hours after traumatic brain injury. Six of the 11 factors studied are associated with significantly worse outcomes. Hypotension and hypothermia are independently related to mortality. Because these SBIFs are potentially preventable, protocols could be developed to decrease their frequency.

Eicosanoids are essential mediators of the inflammatory response and contribute both to the initiation and the resolution of inflammation. Leukocyte-type 12/15-lipoxygenase (12/15-LO) represents a major enzyme involved in the generation of a subclass of eicosanoids, including the anti-inflammatory lipoxin A(4) (LXA(4)). Nevertheless, the impact of 12/15-LO on chronic inflammatory diseases such as arthritis has remained elusive. By using two experimental models of arthritis, the K/BxN serum-transfer and a TNF transgenic mouse model, we show that deletion of 12/15-LO leads to uncontrolled inflammation and tissue damage. Consistent with these findings, 12/15-LO-deficient mice showed enhanced inflammatory gene expression and decreased levels of LXA(4) within their inflamed synovia. In isolated macrophages, the addition of 12/15-LO-derived eicosanoids blocked both phosphorylation of p38MAPK and expression of a subset of proinflammatory genes. Conversely, 12/15-LO-deficient macrophages displayed significantly reduced levels of LXA(4), which correlated with increased activation of p38MAPK and an enhanced inflammatory gene expression after stimulation with TNF-alpha. Taken together, these results support an anti-inflammatory and tissue-protective role of 12/15-LO and its products during chronic inflammatory disorders such as arthritis.

OBJECTIVE

Our purpose was to assess the short-term results and describe the technique of arthroscopic repair of irreparable rotator cuff tears by use of a GraftJacket allograft (Wright Medical Technology, Arlington, TN).

METHODS

Between March 2003 and February 2004, 16 patients with massive, contracted, immobile rotator cuff tears were treated with arthroscopic placement of a GraftJacket allograft by a single surgeon. Patients were followed up for 1 to 2 years. All were evaluated preoperatively and postoperatively by use of the modified University of California, Los Angeles scoring system, Constant score, and Simple Shoulder Test. Magnetic resonance imaging was performed postoperatively at 3 months and 1 year.

RESULTS

At a mean follow-up of 26.8 months (range, 12 to 38 months), 15 of 16 patients were satisfied with the procedure. The mean University of California, Los Angeles score increased from 18.4 preoperatively to 30.4 postoperatively (P = .0001). The Constant score increased from 53.8 to 84.0 (P = .0001). Statistically significant improvements were seen in pain, forward flexion, and external rotation strength. Thirteen patients had full incorporation of the graft into the native tissue as documented on magnetic resonance imaging. There were no complications in this cohort of patients.

CONCLUSIONS

Our study supports GraftJacket allograft as a viable solution for surgical salvage in select cases of massive, irreparable rotator cuff pathology. This treatment option may provide patients with decreased pain and increased function despite a previously irreparable rotator cuff tear.

METHODS

Level IV, therapeutic case series.

The forkhead O transcription factors (FOXO) integrate a range of extracellular signals, including growth factor signaling, inflammation, oxidative stress, and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many yet to be unraveled cell type-specific responses. Naive antigen-specific CD8(+) T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure. In addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival. Using lymphocytic choriomeningitis virus Armstrong to probe the response to infection, we found that Foxo1(-/-) CD8(+) T cells expand normally with no defects in effector differentiation, but continue to exhibit characteristics of effector T cells long after antigen clearance. The KLRG1(lo) CD8(+) T cells that are normally enriched for memory-precursor cells retain Granzyme B and CD69 expression, and fail to up-regulate TCF7, EOMES, and other memory signature genes. As a correlate, Foxo1(-/-) CD8(+) T cells were virtually unable to expand upon secondary infection. Collectively, these results demonstrate an intrinsic role for FOXO1 in establishing the post-effector memory program that is essential to forming long-lived memory cells capable of immune reactivation.

Objective: To evaluate the effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome by performing a systematic review of available published literature on pregnancies affected by COVID-19.

Methods: We performed a systematic review to evaluate the effect of COVID-19 on pregnancy, perinatal and neonatal outcome. We conducted a comprehensive literature search using PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure Database and Wan Fang Data up to and including 20 April 2020 (studies were identified through PubMed alert after that date). For the search strategy, combinations of the following keywords and medical subject heading (MeSH) terms were used: 'SARS-CoV-2', 'COVID-19', 'coronavirus disease 2019', 'pregnancy', 'gestation', 'maternal', 'mother', 'vertical transmission', 'maternal-fetal transmission', 'intrauterine transmission', 'neonate', 'infant' and 'delivery'. Eligibility criteria included laboratory-confirmed and/or clinically diagnosed COVID-19, patient being pregnant on admission and availability of clinical characteristics, including at least one maternal, perinatal or neonatal outcome. Exclusion criteria were non-peer-reviewed or unpublished reports, unspecified date and location of the study, suspicion of duplicate reporting and unreported maternal or perinatal outcomes. No language restrictions were applied.

Results: We identified a high number of relevant case reports and case series, but only 24 studies, including a total of 324 pregnant women with COVID-19, met the eligibility criteria and were included in the systematic review. These comprised nine case series (eight consecutive) and 15 case reports. A total of 20 pregnant patients with laboratory-confirmed COVID-19 were included in the case reports. In the combined data from the eight consecutive case series, including 211 (71.5%) cases of laboratory-confirmed and 84 (28.5%) of clinically diagnosed COVID-19, the maternal age ranged from 20 to 44 years and the gestational age on admission ranged from 5 to 41 weeks. The most common symptoms at presentation were fever, cough, dyspnea/shortness of breath, fatigue and myalgia. The rate of severe pneumonia reported amongst the case series ranged from 0% to 14%, with the majority of the cases requiring admission to the intensive care unit. Almost all cases from the case series had positive computed tomography chest findings. All six and 22 cases that had nucleic-acid testing in vaginal mucus and breast milk samples, respectively, were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Only four cases of spontaneous miscarriage or termination were reported. In the consecutive case series, 219/295 women had delivered at the time of reporting and 78% of them had Cesarean section. The gestational age at delivery ranged from 28 to 41 weeks. Apgar scores at both 1 and 5 min ranged from 7 to 10. Only eight neonates had birth weight < 2500 g and nearly one-third of neonates were transferred to the neonatal intensive care unit. There was one case of neonatal asphyxia and death. In 155 neonates that had nucleic-acid testing in throat swab, all, except three cases, were negative for SARS-CoV-2. There were no cases of maternal death in the eight consecutive case series. Seven maternal deaths, four intrauterine fetal deaths (one with twin pregnancy) and two neonatal deaths (twin pregnancy) were reported in a non-consecutive case series of nine cases with severe COVID-19. In the case reports, two maternal deaths, one neonatal death and two cases of neonatal SARS-CoV-2 infection were reported.

Conclusions: Despite the increasing number of published studies on COVID-19 in pregnancy, there are insufficient good-quality data to draw unbiased conclusions with regard to the severity of the disease or specific complications of COVID-19 in pregnant women, as well as vertical transmission, perinatal and neonatal complications. In order to answer specific questions in relation to the impact of COVID-19 on pregnant women and their fetuses, through meaningful good-quality research, we urge researchers and investigators to present complete outcome data and reference previously published cases in their publications, and to record such reporting when the data of a case are entered into one or several registries. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Efecto de la enfermedad coronavirus 2019 (COVID-19) en el resultado materno, perinatal y neonatal: revisión sistemática OBJETIVO: Evaluar el efecto de la enfermedad coronavirus 2019 (COVID-19) en el resultado materno, perinatal y neonatal por medio de una revisión sistemática de la literatura publicada disponible sobre los embarazos afectados por COVID-19. MÉTODOS: Se realizó una revisión sistemática para evaluar el efecto de COVID-19 en el resultado del embarazo, perinatal y neonatal. Se realizó una búsqueda exhaustiva de literatura utilizando PubMed, EMBASE, la Biblioteca Cochrane, la Base de Datos de la Infraestructura Nacional de Conocimiento de China y Wan Fang Data hasta el 20 de abril de 2020 inclusive (los estudios se identificaron mediante el sistema de alertas de PubMed después de esa fecha). Para la estrategia de búsqueda, se utilizaron combinaciones de las siguientes palabras clave y términos (en inglés) de Medical Subject Headings (MeSH): ‘SARS-CoV-2’, ‘COVID-19’, ‘enfermedad coronavirus 2019’, ‘embarazo’, ‘gestación’, ‘materno’, ‘madre’, ‘transmisión vertical’, ‘transmisión materno-fetal’, ‘transmisión intrauterina’, ‘neonato’, ‘bebé’ y ‘parto’. Los criterios de elegibilidad fueron COVID-19 confirmado por laboratorio y/o diagnosticado clínicamente, el hecho de que la paciente estuviera embarazada en el momento del ingreso y la disponibilidad de características clínicas, con al menos un resultado materno, perinatal o neonatal. Los criterios de exclusión fueron los informes no revisados por pares o no publicados, la fecha y el lugar del estudio sin especificar, la sospecha de informes duplicados y los resultados maternos o perinatales no reportados. No se aplicaron restricciones de idioma. RESULTADOS: Se identificó un elevado número de informes de casos y series de casos pertinentes, pero sólo 24 estudios, que incluían un total de 324 mujeres embarazadas con COVID-19, cumplieron los criterios de elegibilidad y se incluyeron en la revisión sistemática. Estos comprendían nueve series de casos (ocho consecutivas) y 15 informes de casos. Los informes de casos se referían a un total de 20 pacientes embarazadas con COVID-19 confirmado por un laboratorio. En los datos combinados de las ocho series de casos consecutivas, que incluían 211 (71,5%) casos de COVID-19 confirmados por laboratorio y 84 (28,5%) casos diagnosticados clínicamente, la edad materna varió entre 20 y 44 años y la edad gestacional en el momento del ingreso fue entre 5 y 41 semanas. Los síntomas más comunes del cuadro clínico inicial fueron fiebre, tos, disnea/dificultad para respirar, fatiga y mialgia. La tasa de neumonía grave reportada en las series de casos varió entre el 0% y el 14%, y la mayoría de los casos requirieron el ingreso en la unidad de cuidados intensivos. Casi todos los casos de la serie de casos tuvieron resultados positivos en la tomografía axial computerizada. Los 6 y 22 casos en que se realizaron pruebas de ácido nucleico en muestras de mucosidad vaginal y leche materna, respectivamente, dieron negativo para el síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2). Sólo se notificaron cuatro casos de aborto o interrupción del embarazo. En la serie de casos consecutivos, 219 de 295 mujeres habían dado a luz en el momento de la presentación del informe y el 78% de ellas lo hicieron mediante cesárea. La edad gestacional en el momento del parto varió entre 28 y 41 semanas. Las puntuaciones de Apgar a 1 minuto y a 5 minutos variaron entre 7 y 10. Sólo ocho recién nacidos pesaron al nacer <2500 g y casi un tercio de los recién nacidos fueron transferidos a la unidad de cuidados intensivos para recién nacidos. Hubo un caso de asfixia y muerte neonatal. Excepto tres casos, el resto de los 155 neonatos a los que se les hicieron pruebas de ácido nucleico en un frotis faríngeo, dieron negativo para el SARS-CoV-2. No hubo casos de muerte materna en las ocho series consecutivas de casos. Se reportaron siete muertes maternas, cuatro muertes fetales intrauterinas (una con embarazo de gemelos) y dos muertes de recién nacidos (embarazo de gemelos) en una serie no consecutiva de nueve casos con COVID-19 grave. En los informes de casos se comunicaron dos muertes maternas, una muerte de recién nacido y dos casos de infección de recién nacidos por SARS-CoV-2. CONCLUSIONES: A pesar del creciente número de estudios publicados sobre COVID-19 en embarazos, no hay suficientes datos de buena calidad para sacar conclusiones no sesgadas con respecto a la gravedad de la enfermedad o a las complicaciones específicas de COVID-19 en las mujeres embarazadas, así como a la transmisión vertical y a las complicaciones perinatales y neonatales. A fin de responder a preguntas específicas en relación con los efectos de COVID-19 en mujeres embarazadas y sus fetos, mediante una investigación significativa de buena calidad, se insta a los investigadores y a los encargados de investigaciones a que presenten en sus publicaciones datos completos sobre los resultados y casos de referencia publicados anteriormente, y a que registren esos informes cuando los datos de un caso se introduzcan en uno o varios registros. © 2020 Los autores. Ultrasonido en Obstetricia y Ginecología publicado por John Wiley & Sons Ltd. en nombre de la Sociedad Internacional de Ultrasonido en Obstetricia y Ginecología.

新型冠状病毒肺炎(COVID-19)对孕产妇、围产期和新生儿结局的影响:系统性评价 目的: 通过对有关新型冠状病毒肺炎(COVID-19)影响的妊娠的已发表文献进行系统性评价来评估 COVID-19 对孕产妇、围产期和新生儿结局的影响。 方法: 我们进行了系统性评价来评估COVID-19对妊娠、围产期和 新生儿结局的影响。截至 2020 年 4 月 20 日(含)，我们使用 PubMed、EMBASE、Cochrane 图书馆、中国国家知识基础设施数据库和万方数据库 进行了全面文献检索(在 2020 年 4 月 20 日之后通过 PubMed 警报对这些研 究进行了识别)。将以下关键字和医学主题词(MeSH)术语的组合用作搜索策略:“SARS-CoV-2”、“COVID-19”、“新型冠状病毒肺炎”、“妊娠”、“怀孕”、“孕产妇”、“母亲”、“垂直传播”、“母婴传播”、“宫内传播”、“新生儿”、“婴儿”和“分娩”。资格标准包括实验室确认和/或临床诊断的 COVID-19、患者入院时已怀孕以及临床特征的可用性(包括至少一项孕产妇、围产期和新生儿结局)。排除标准为未经同行评议或未发表的报告、未指定研究的日期和地点、怀疑重复的报告以及未报告的母亲或围产期结局。未采用语言限制。 结果: 我们确定了大量相关的病例报告和病例系列，但是只有 24 项研究(包括总共 324 名患有 COVID-19 的孕妇)符合资格标准而被纳入系统性评价中。其中包括 9 个病例系列(8 个连续)和 15 个病例报告。病例报告中，共包括 20 例经实验室确诊患有 COVID-19 的孕妇。在 8 个连续病例系列的合并数据中(包括 211 例(71.5%)实验室确诊病例和 84 例(28.5%)临床确诊的 COVID-19 病例)，孕产妇年龄为 20 至 44 岁，入院时胎儿胎龄为 5 到 41 周。有临床表现时的最常见症状是发烧、咳嗽、呼吸困难/呼吸急促、疲劳和肌痛。在病例系列中，报告的重症肺炎发生率为 0% 到 14%，大多数病例需要 在重症监护室接受治疗。病例系列中的几乎所有病例的计算机断层扫描胸部检查结果均为阳性。6 例和 22 例病例的阴道粘液和母乳样本接受了核酸检测，这些样本的严重急性呼吸系统综合征冠状病毒 2(SARS-CoV-2)结果均为阴性。仅报告了四例自然流产或终止妊娠的病例。在报告时，连续病例系列中，有219/295名孕妇分娩，其中78%接受了剖腹产。分娩时的胎龄范围为 28 至 41 周。1 分钟和 5分钟的阿普加评分范围为 7 到 10。只有八个新生儿的出生体重 <2500 g，并且近三分之一的新生儿被转入新生儿重症监护室。发生一例新生儿窒息死亡事件。接受了咽拭子核酸检测的 155 名新生儿中，只有三例病例的SARS-CoV-2检测结果为阳性。8 个连续病例系列中，没有出现孕产妇死亡病例。在 9 例 COVID-19 非连续重症病例系列中，报告了 7 例孕产妇死亡、4 例宫内胎儿死亡(1 例双胎妊娠)和 2 例新生儿死亡(双胎妊娠)。在病例报告中，报告了 2 例孕产妇死亡、1 例新生儿死亡和 2 例新生儿 SARS-CoV-2 感染。 结论: 尽管有关患有 COVID-19 的孕妇的已发表研究数量不断增加，但是在孕妇中 COVID-19 严重程度或特定并发症、垂直传播、围产期和新生儿并发症方面，尚无足够的高质量数据可用于得出公正的结论。为了通过有意义的高质量研究来回答有关 COVID-19 对孕妇及其胎儿的影响的具体问题，我们敦促研究者提供完整的结局数据并在其发表的研究中引用既往发表的病例，并在一个病例的数据被输入到一个或多个登记表时记录此类报告。© 2020 作者。威利父子公司(John Wiley & Sons Ltd)代表国际妇产科超声学会(ISUOG)出版《国际妇产超声杂志》(Ultrasound in Obstetrics & Gynecology)。.

Keywords: COVID-19; SARS-CoV-2; coronavirus disease 2019; neonatal outcome; pregnancy outcome; vertical transmission.

Object recognition is achieved even in circumstances when only partial information is available to the observer. Perceptual closure processes are essential in enabling such recognitions to occur. We presented successively less fragmented images while recording high-density event-related potentials (ERPs), which permitted us to monitor brain activity during the perceptual closure processes leading up to object recognition. We reveal a bilateral ERP component (N(cl)) that tracks these processes (onsets approximately 230 msec, maximal at approximately 290 msec). Scalp-current density mapping of the N(cl) revealed bilateral occipito-temporal scalp foci, which are consistent with generators in the human ventral visual stream, and specifically the lateral-occipital or LO complex as defined by hemodynamic studies of object recognition.

Monoclonal antibodies (MAb) 3F11 and 06B4 recognize epitopes that are conserved on gonococcal lipooligosaccharides (LOS), present on some meningococcal LOS, and conserved on human erythrocytes. LOS of some group B and C prototype meningococcal LOS strains (LOS serotypes L1 to L8) treated with neuraminidase showed increased expression of the 3F11 and 06B4 MAb-defined epitopes. Neuraminidase-treated LOS separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver stained showed a shift in migration from a component with a mass of approximately 4.8 kDa to a component with a mass of between 4.5 and 4.6 kDa. The same strains grown in medium with excess CMP-N-acetylneuraminic acid had LOS that shifted in migration to a slightly higher component (mass, approximately 4.8 kDa). Chemical analysis of the neuraminidase-digested products from one LOS indicated it contained approximately 1.5% sialic acid. Covalent linkage between sialic acid and the LOS was confirmed by analysis of de-O-acylated and dephosphorylated LOS by liquid secondary ion mass spectrometry. Three studies show that some meningococci contain sialic acid in their LOS, that the sialic acid is cleaved and lost in conventional acetic acid hydrolysis, and that the sialic acid alters the expression of MAb-defined epitopes.