Enteric defensins are essential regulators of intestinal microbial ecology.

Antimicrobial peptides are important effectors of innate immunity throughout the plant and animal kingdoms. In the mammalian small intestine, Paneth cell alpha-defensins are antimicrobial peptides that contribute to host defense against enteric pathogens. To determine if alpha-defensins also govern intestinal microbial ecology, we analyzed the intestinal microbiota of mice expressing a human alpha-defensin gene (DEFA5) and in mice lacking an enzyme required for the processing of mouse alpha-defensins. In these complementary models, we detected significant alpha-defensin-dependent changes in microbiota composition, but not in total bacterial numbers. Furthermore, DEFA5-expressing mice had striking losses of segmented filamentous bacteria and fewer interleukin 17 (IL-17)-producing lamina propria T cells. Our data ascribe a new homeostatic role to alpha-defensins in regulating the makeup of the commensal microbiota.

Ecological generalism drives hyperdiversity of secondary metabolite gene clusters in xylarialean endophytes.

Although secondary metabolites are typically associated with competitive or pathogenic interactions, the high bioactivity of endophytic fungi in the Xylariales, coupled with their abundance and broad host ranges spanning all lineages of land plants and lichens, suggests that enhanced secondary metabolism might facilitate symbioses with phylogenetically diverse hosts. Here, we examined secondary metabolite gene clusters (SMGCs) across 96 Xylariales genomes in two clades (Xylariaceae s.l. and Hypoxylaceae), including 88 newly sequenced genomes of endophytes and closely related saprotrophs and pathogens. We paired genomic data with extensive metadata on endophyte hosts and substrates, enabling us to examine genomic factors related to the breadth of symbiotic interactions and ecological roles. All genomes contain hyperabundant SMGCs; however, Xylariaceae have increased numbers of gene duplications, horizontal gene transfers (HGTs) and SMGCs. Enhanced metabolic diversity of endophytes is associated with a greater diversity of hosts and increased capacity for lignocellulose decomposition. Our results suggest that, as host and substrate generalists, Xylariaceae endophytes experience greater selection to diversify SMGCs compared with more ecologically specialised Hypoxylaceae species. Overall, our results provide new evidence that SMGCs may facilitate symbiosis with phylogenetically diverse hosts, highlighting the importance of microbial symbioses to drive fungal metabolic diversity.

Sexually Transmitted Infections Diagnosed Among Sexual and Gender Minority Communities During the First 11 Months of the COVID-19 Pandemic in Midwest and Southern Cities in the United States.

BACKGROUND: The COVID-19 pandemic adversely affected sexual health services. Given the burden of sexually transmitted infections (STIs) on sexual and gender minorities (SGMs), we estimated incidence of self-reported STI diagnoses and factors associated with STI diagnoses among SGMs during the pandemic's first year. METHODS: A cohort of 426 SGM persons, 25 years or older, recruited in Chicago, Milwaukee, Detroit, Minneapolis, and Houston completed 5 online surveys from April 2020 to February 2021. Persons self-reported on each survey all health care provider STI diagnoses. Kaplan-Meier was used to estimate the cumulative risk of STI diagnoses, stratified by human immunodeficiency virus (HIV) status. Factors associated with STI diagnoses were assessed with a longitudinal negative binomial regression. RESULTS: Median age was 37 years, and 27.0% were persons living with HIV (PLH). Participants reported 63 STIs for a cumulative incidence for PLH and HIV-negative persons of 0.19 (95% confidence interval [CI], 0.13-0.29) and 0.12 (95% CI, 0.09-0.17), respectively. Regardless of HIV, a younger age and changes in health care use were associated with STI diagnoses. Among HIV-negative persons, the rate of STI diagnoses was higher in Houston than the Midwest cities (adjusted relative risk, 2.37; 95% CI, 1.08-5.20). Among PLH, a decrease in health care use was also associated with STI diagnoses (adjusted relative risk, 3.53; 95% CI, 1.01-12.32 vs no change in health care services), as was Hispanic ethnicity and using a dating app to meet a sex partner. CONCLUSIONS: Factors associated with STI diagnoses during the COVID-19 pandemic generally reflected factors associated with STI incidence before the pandemic like geography, HIV, age, and ethnicity.

Two-Stage Hepatectomy for Bilateral Colorectal Liver Metastases: A Multi-institutional Analysis.

BACKGROUND: Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US). METHODS: A retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM. RESULTS: From December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed using an open technique (n = 194, 99.5%). The median number of tumors was 7 (range 2-33). One-hundred and twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival (OS) was 50 months, with a median follow-up of 28 months (range 2-143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar OS as those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second-stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complication rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). OS was significantly decreased by positive resection margins and increased estimated blood loss (EBL; p = 0.036 and p = 0.05, respectively). CONCLUSION: This is the largest TSH series in the US and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.

Biochemical characterization of Serpula lacrymans iron-reductase enzymes in lignocellulose breakdown.

Putative iron-reductase (IR) genes from Serpula lacrymans with similarity to the conserved iron-binding domains of cellobiose dehydrogenase (CDH) enzymes have been identified. These genes were cloned and expressed to functionally characterize their activity and role in the decomposition of lignocellulose. The results show that IR1 and IR2 recombinant enzymes have the ability to depolymerize both lignin and cellulose, are capable of the reduction of ferric iron to the ferrous form, and are capable of the degradation of nitrated lignin. Expression of these genes during wheat straw solid-state fermentation was shown to correlate with the release of compounds associated with lignin decomposition. The results suggest that both IR enzymes mediate a non-enzymatic depolymerisation of lignocellulose and highlight the potential of chelator-mediated Fenton systems in the industrial pre-treatment of biomass.

Digital Rectal Examination Remains a Key Prognostic Tool for Prostate Cancer: A National Cancer Database Review.

BACKGROUND: Prostate cancer clinical stage T2 (cT2) subclassifications, as determined by digital rectal examination (DRE), are a historic method of staging prostate cancer. However, given the potential discomfort associated with prostate examination and the wide availability of other prognostic tests, the necessity of DRE is uncertain. This study sought to determine the prognostic value of the prostate cancer cT2 subclassifications in a contemporary cohort of patients. METHODS: The National Cancer Database was used to identify a cohort of men with high-risk clinical T2N0M0 prostate cancer treated with external-beam radiotherapy and androgen deprivation therapies ± surgery from 2004 to 2010. We assessed overall survival from a landmark time of 10 months using Kaplan-Meier and log-rank test analysis. A multivariate proportional hazards model was used to estimate the simultaneous effects of multiple factors, including cT2 subclassification and other well-established prognostic indicators of overall survival in prostate cancer. RESULTS: A total of 5,291 men were included in the final analysis, with a median follow-up of 5.4 years. The cT2a, cT2b, and cT2c subclassifications demonstrated increasing hazard ratios of 1.00 (reference), 1.25 (95% CI, 1.07-1.45; P=.0046), and 1.43 (95% CI, 1.25-1.63; P<.0001), respectively, reflecting a higher probability of death with each incremental increase in cT2 subclassification. This finding was independent of other known prognostic variables on multivariate analysis. CONCLUSIONS: Results show that cT2 subclassifications had independent prognostic value in a large and contemporary cohort of men. cT2 classification remains an important, low-cost prognostic tool for men with prostatic adenocarcinoma. The clinical relevance of this test should be appreciated and accounted for by providers treating prostate adenocarcinoma.

Use of Neoadjuvant Chemotherapy in the Treatment of Locally Advanced Rectal Cancer.

BACKGROUND: Current treatment for locally advanced rectal cancer includes neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy. With neoadjuvant chemotherapy (NC), both chemoradiation and chemotherapy are given in the neoadjuvant setting. This study aims to assess patterns of NC utilization and differences in treatment response compared with standard treatment at our institution. MATERIALS AND METHODS: We performed a retrospective review of patients treated for stage II-III rectal cancer at our institution between 2008 and 2018, examining patient demographics, tumor characteristics, and treatment modality. The primary outcome of interest was complete response (CR) to treatment, including both pathologic and clinical CR. RESULTS: Of 184 patients, 134 (72.8%) received standard therapy, and 50 (27.2%) received NC. In the standard treatment group, 70.1% were node positive, and 9.0% had T4-disease, compared with 92.0% and 26.0% in the NC group, respectively (both P < 0.01). NC utilization increased over time, with 3.4% of patients receiving NC between 2008 and 2012, compared with 48.5% in 2013-2018 (P < 0.01). CR was achieved in 19.4% versus 34.0% (P < 0.01) of patients in standard versus NC groups. With multivariate analysis, NC (odds ratio = 3.02 [95% confidence interval 1.37-6.67], P = 0.01) was associated with increased likelihood of achieving CR, whereas higher T-stage was associated with decreased likelihood of CR (for cT4, odds ratio = 0.06 [95% confidence interval 0.01-0.56], P = 0.01). CONCLUSIONS: Use of NC was increasingly used at our institution from 2008 to 2018. Patients who received NC achieved higher rates of CR compared with those undergoing standard therapy, despite having more advanced disease. These data support trends from other institutions and provides rationale for further study regarding use of NC for locally advanced rectal cancer.

Presence of Irritable Bowel Syndrome Symptoms in Quiescent Inflammatory Bowel Disease Is Associated with High Rate of Anxiety and Depression.

BACKGROUND: Inflammatory bowel disease (IBD; Crohn's disease, CD and Ulcerative colitis, UC) and irritable bowel syndrome (IBS) have overlapping symptoms. Few prevalence studies of IBS in quiescent IBD have used colonoscopy with histology to confirm inactive disease. The aims were (1) to determine the percentage of IBD patients in deep remission whose persistent IBS-like symptoms (IBD/IBS+) would cause them to be classified as having active disease, based on the calculation of Harvey Bradshaw Index (HBI) or UC disease activity index (UCDAI); (2) to identify demographic and disease characteristics that are associated with IBD/IBS+. METHODS: This was a prospective study at a single tertiary care IBD center. 96/112 patients with colonoscopy and histology confirmed quiescent disease consented and completed Rome III criteria for IBS Survey, and the hospital anxiety and depression scale (HADS). Other demographic and disease specific data were collected. RESULTS: 36% (28/77) and 37% (7/19) of CD and UC patients, respectively, met diagnostic criteria for IBS. Significantly higher HBI/UCDAI scores (p = 0.005) and low short inflammatory bowel disease questionnaire (SIBDQ) scores (p ≤ 0.0001) were seen in IBD/IBS+ patients. 29% of patients in deep remission were mis-categorized by HBI/UCDAI as having active disease when they fulfilled Rome III criteria for IBS. Psychiatric diagnosis (OR 3.53 95% CI 1.2-10.2) and earlier onset of IBD (OR 1.056 95% CI 1.015-1.096) were associated with IBD/IBS+. Patients fulfilling IBS criteria had higher hospital anxiety and depression scale (HADS). CONCLUSION: IBD/IBS+ affect scoring of IBD disease activity scales and become less useful in guiding treatment plans.

Blockade of interleukin-27 signaling reduces GVHD in mice by augmenting Treg reconstitution and stabilizing Foxp3 expression.

Reestablishment of competent regulatory pathways has emerged as a strategy to reduce the severity of graft-versus-host disease (GVHD), and recalibrate the effector and regulatory arms of the immune system. However, clinically feasible, cost-effective strategies that do not require extensive ex vivo cellular manipulation have remained elusive. In the current study, we demonstrate that inhibition of the interleukin-27p28 (IL-27p28) signaling pathway through antibody blockade or genetic ablation prevented lethal GVHD in multiple murine transplant models. Moreover, protection from GVHD was attributable to augmented global reconstitution of CD4+ natural regulatory T cells (nTregs), CD4+ induced Tregs (iTregs), and CD8+ iTregs, and was more potent than temporally concordant blockade of IL-6 signaling. Inhibition of IL-27p28 also enhanced the suppressive capacity of adoptively transferred CD4+ nTregs by increasing the stability of Foxp3 expression. Notably, blockade of IL-27p28 signaling reduced T-cell-derived-IL-10 production in conventional T cells; however, there was no corresponding effect in CD4+ or CD8+ Tregs, indicating that IL-27 inhibition had differential effects on IL-10 production and preserved a mechanistic pathway by which Tregs are known to suppress GVHD. Targeting of IL-27 therefore represents a novel strategy for the in vivo expansion of Tregs and subsequent prevention of GVHD without the requirement for ex vivo cellular manipulation, and provides additional support for the critical proinflammatory role that members of the IL-6 and IL-12 cytokine families play in GVHD biology.

Advanced Age Does Not Negatively Impact Health-Related Quality of Life in Inflammatory Bowel Disease.

BACKGROUND: Health-related quality of life (HRQoL) is significantly impacted in patients with inflammatory bowel disease (IBD). Many studies have assessed HRQoL in patients of all ages, and few focus on the elderly. AIM: To determine the influence of advanced age (> 65 years) and age at diagnosis on patients with IBD. METHODS: This is a retrospective study of prospectively collected data from a single IBD tertiary referral center. Patients had disease activity indices [Harvey-Bradshaw index (HBI), Ulcerative Colitis Disease Activity Index (UCDAI), and Short Inflammatory Bowel Disease Questionnaire (SIBDQ)] recorded during every clinic visit. Three groups of patients: > 65 years, 41-64 years, and < 40 years with > 5 SIBDQ entries were included. Influence of disease type, disease duration, extent of involvement, and comorbidities such as cardiovascular (CV) disease, pulmonary disease, diabetes mellitus (DM), and psychological disorders were noted as confounders. Statistical analysis was performed using ANOVA, Pearson correlation, and logistic regression model. RESULTS: Disease severity indices significantly affected SIBDQ score in both Crohn's disease (CD) and ulcerative colitis (UC) (p < 0.001 for HBI in CD, p < 0.001 UCDAI in UC). Disease extent (p = 0.011) and psychological disorders (p < 0.001) significantly affected SIBDQ score in CD. Chronological age, age at diagnosis, disease duration, number of clinic visits, CV disease, pulmonary disease, and DM were not significant predictors of SIBDQ score (p > 0.05). CONCLUSIONS: HRQoL was negatively influenced by disease extent and psychological disorders in CD but not in UC patients. Advanced age was not a predictor of poor HRQoL in both CD and UC.

Evaluation of the Pharmacokinetics and Efficacy of a Busulfan Test Dose in Adult Patients Undergoing Myeloablative Hematopoietic Cell Transplantation.

Owing to interpatient variability in busulfan exposure, therapeutic monitoring of busulfan is often used in myeloablative allogeneic transplantation to ensure that patients are near the optimal steady-state goal of 900 ng/mL. One challenge in therapeutic monitoring of busulfan is the brief course of busulfan treatment, requiring prompt analysis and dose adjustments as needed. Pharmacokinetic evaluation of a busulfan test dose before the start of the conditioning regimen would allow for all conditioning regimen doses to be given at the calculated optimized dose. An observational study was completed to evaluate the effects of a busulfan test dose of 0.9 mg/kg administered before the start of a myeloablative intravenous busulfan-based conditioning regimen. Sixty adult patients who received a busulfan conditioning regimen were reviewed, including 30 patients prior to the implementation of the busulfan test dose (pretest dose group) and 30 patients who received the busulfan test dose (posttest dose group). The primary objective was a pharmacokinetic evaluation of the percentage of patients who achieved the desired steady-state goal using the test dose strategy. The safety and efficacy of the busulfan test dose were evaluated as well. The average busulfan steady-state level after the first dose of the conditioning regimen was significantly lower in the pre-test dose group compared with the post-test dose group (660 ng/mL versus 879.9 ng/mL; P < 0.001). Compared with the post-test dose group, significantly fewer patients in the pre-test dose group were within 10% of the busulfan steady-state goal (10% versus 73.3%; P < 0.001) or within 5% of the goal (0% versus 53%; P < 0.001). Requirements for parenteral nutrition and/or patient-controlled analgesia owing to mucositis and rates of veno-occlusive disease were not significantly different between the pre-test dose group and the post-test dose group. The rates of disease relapse, mortality, and acute graft-versus-host disease were similar in the two groups. A pretransplantation busulfan test dose of 0.9 mg/kg improved the patients' ability to reach therapeutic busulfan target levels after the first conditioning dose and resulted in fewer adjustments during conditioning. The use of a busulfan test dose did not significantly increase patients' risk of mucositis or other safety outcomes.

Sucrose Non-Fermenting Related Kinase Expression in Ovarian Cancer and Correlation with Clinical Features.

Sucrose non-fermenting related kinase (SNRK) is a serine/threonine kinase known to regulate cellular metabolism and adipocyte inflammation. Since alterations in adipocyte metabolism play a role in ovarian cancer metastasis, we investigated the expression of SNRK in benign and malignant human ovarian tissue using immunohistochemistry and qPCR. The number of SNRK positive (+) nuclei is increased in malignant tissue compared to benign tissue (21.03% versus 14.90%, p < .0431). The most strongly stained malignant SNRK+ nuclei were stage 1 compared to stage 2-4 disease. Differential expression of SNRK in early versus late stage disease suggests specific roles for SNRK in ovarian cancer metastasis.

Hematopoietic Progenitor Cell Mobilization with Ifosfamide, Carboplatin, and Etoposide Chemotherapy versus Plerixafor-Based Strategies in Patients with Hodgkin and Non-Hodgkin Lymphoma.

Studies comparing the efficacy and safety of chemo-mobilization with ifosfamide, carboplatin, and etoposide (ICE) ± rituximab with plerixafor-based approaches in lymphoma patients have not been performed. We analyzed hematopoietic progenitor cell mobilization outcomes in lymphoma patients undergoing chemo-mobilization with ICE (n = 35) compared with either routine plerixafor (n = 30) or "just in time" (JIT) plerixafor-based mobilization (n = 33). Chemo-mobilization provided a significantly higher total CD34(+) cell yield (median collection, 5.35 × 10(6) cells/kg for ICE versus 3.15 × 10(6) cells/kg for routine plerixafor and 3.6 × 10(6) cells/kg for JIT plerixafor, P < .001). The median day 1 yield of CD34(+) cells was not significantly different (median, 2.2 × 10(6) cells/kg in ICE versus 1.9 × 10(6) cells/kg in upfront plerixafor versus 1.7 × 10(6) cells/kg in JIT plerixafor, P = .20). There was no significant difference in the 3 groups in terms of total number of apheresis sessions performed (median, 2 in each group; P = .78). There were no mobilization failures (inability to collect at least 2 × 10(6) cells/kg) in the chemo-mobilization group, whereas 5 patients (16.7%) in the routine plerixafor and 3 patients (9.1%) in JIT group had mobilization failure (P = .04). Mean time to neutrophil engraftment was faster in the chemo-mobilization group, 10.3 days (±1.2) compared with 12.1 days (±3.6) in the routine plerixafor group and 11.6 days (±3.0) in the JIT group (P < .001) and mean time to platelet engraftment was 13.7 days (±.7) in ICE versus 20.3 days (±1.6) in routine plerixafor versus 17.1 days (± .9) in JIT group (P < .001). Red blood cell transfusions were significantly higher in the chemo-mobilization group (34.3% versus 0 versus 3.2% versus 1, P < .001) and so were the platelet transfusions (22.9% versus 0 versus 0, P < .001). Excluding the cost of chemotherapy administration, chemo-mobilization was associated with significantly less mobilization cost (average cost $17,601.76 in ICE versus $28,963.05 in routine and $25,679.81 in JIT, P < .001). Our data suggests that chemo-mobilization with ICE provides a higher total CD34(+) cell yield, lower rates of mobilization failure, faster engraftment, and lower cost compared to plerixafor-based approaches with comparable toxicity profile between the groups, except for higher transfusion requirements with chemo-mobilization.

Outcome of Gleason 3 + 5 = 8 Prostate Cancer Diagnosed on Needle Biopsy: Prognostic Comparison with Gleason 4 + 4 = 8.

PURPOSE: ISUP (International Society for Urologic Pathology) and WHO adopted prognostic Grade Groups 1 to 5 that simplify prostate cancer grading for prognosis. Grade Group 4 is Gleason score 8 cancer, which is heterogeneous, and it encompasses Gleason score 4 + 4 = 8, 3 + 5 = 8 and 5 + 3 = 8. The comparative prognostic implications of these various Gleason scores had not been studied by urological pathologists after a re-review of slides. MATERIALS AND METHODS: Patients with a highest biopsy Gleason score of 3 + 5 = 8 or 4 + 4 = 8 were included in the study. Controls were cases with a highest Gleason score of 4 + 3 = 7 or 9-10. A total of 423 prostatic biopsy cases accessioned from 2005 to 2013 at 2 institutions were reviewed. Clinicopathological findings and followup (median 33.4 months) were assessed. RESULTS: Among Gleason score 8 cancers the cancer status outcome in 51 men with Gleason score 3 + 5 = 8 was marginally worse than in 114 with Gleason score 4 + 4 = 8 (p = 0.04). This was driven by a persistent nonmetastatic (after radiation/hormone therapy) cancer rate of 37% among Gleason score 3 + 5 = 8 cases vs 24% among Gleason score 4 + 4 = 8 cases. Conversely, cancer specific survival at 36-month followup was 97.8% in 3 + 5 cases vs 92.6% in 4 + 4 cases but this was not significant (p = 0.089). Cancer specific survival in the Gleason score 8 group was dichotomized by the presence of cribriform growth (p = 0.018). All Gleason score categories did not differ in the fraction of biopsy cores positive, clinical presentation or pathological findings, including the frequency of Gleason pattern 5, in 70 patients who underwent prostatectomy. CONCLUSIONS: Using the most current standards of prostate cancer grading the prognosis is not different in Gleason score 3 + 5 = 8 and 4 + 4 = 8 cancers. This justifies including both in Grade Group 4.

Endometrial carcinoma: The perioperative and long-term outcomes of robotic surgery in the morbidly obese.

BACKGROUND AND METHODS: To evaluate surgical and pathologic outcomes of robotic assisted versus open hysterectomy for women with at least class II (BMI >35) and class III (BMI >40) obesity with endometrial cancer. Women with endometrial cancer and class II obesity, treated with open or robotic hysterectomy between 3/2005 and 3/2013 were eligible for inclusion in this retrospective cohort. Patients with class III obesity were reviewed both within the cohort of class II and as a separate subset. Data were collected on demographics, operative statistics, pathology, post-operative complications, and oncologic outcomes. Tests of significance used Chi-square, Fisher's exact test, t-test, and Wilcoxon rank-sum. RESULTS: One hundred and thirty-six women with BMI >35 who underwent hysterectomy (56 robotic and 80 abdominal) were included. Patients undergoing robotic hysterectomies had fewer post-operative complications, shorter hospital stays, and lower blood loss compared to the abdominal group. A subset (83 of 136) with class III obesity had similar findings. Operative times, lymph node dissection rates, and lymph node yield (both pelvic and para-aortic) were similar between open and robotic surgery in both obesity classes. Oncologic outcomes and use of adjuvant treatment was not compromised. CONCLUSIONS: Robotic hysterectomy is a safe and effective option for morbidly obese women with endometrial cancer. J. Surg. Oncol. 2016;114:884-887. © 2016 2016 Wiley Periodicals, Inc.

Viral Agents Causing Brown Cap Mushroom Disease of Agaricus bisporus.

The symptoms of viral infections of fungi range from cryptic to severe, but there is little knowledge of the factors involved in this transition of fungal/viral interactions. Brown cap mushroom disease of the cultivated Agaricus bisporus is economically important and represents a model system to describe this transition. Differentially expressed transcript fragments between mushrooms showing the symptoms of brown cap mushroom disease and control white noninfected mushrooms have been identified and sequenced. Ten of these RNA fragments have been found to be upregulated over 1,000-fold between diseased and nondiseased tissue but are absent from the Agaricus bisporus genome sequence and hybridize to double-stranded RNAs extracted from diseased tissue. We hypothesize that these transcript fragments are viral and represent components of the disease-causing agent, a bipartite virus with similarities to the family Partitiviridae. The virus fragments were found at two distinct levels within infected mushrooms, at raised levels in infected, nonsymptomatic, white mushrooms and at much greater levels (3,500 to 87,000 times greater) in infected mushrooms exhibiting brown coloration. In addition, differential screening revealed 9 upregulated and 32 downregulated host Agaricus bisporus transcripts. Chromametric analysis was able to distinguish color differences between noninfected white mushrooms and white infected mushrooms at an early stage of mushroom growth. This method may be the basis for an "on-farm" disease detection assay.

Genome sequence of the button mushroom Agaricus bisporus reveals mechanisms governing adaptation to a humic-rich ecological niche.

Agaricus bisporus is the model fungus for the adaptation, persistence, and growth in the humic-rich leaf-litter environment. Aside from its ecological role, A. bisporus has been an important component of the human diet for over 200 y and worldwide cultivation of the "button mushroom" forms a multibillion dollar industry. We present two A. bisporus genomes, their gene repertoires and transcript profiles on compost and during mushroom formation. The genomes encode a full repertoire of polysaccharide-degrading enzymes similar to that of wood-decayers. Comparative transcriptomics of mycelium grown on defined medium, casing-soil, and compost revealed genes encoding enzymes involved in xylan, cellulose, pectin, and protein degradation are more highly expressed in compost. The striking expansion of heme-thiolate peroxidases and ß-etherases is distinctive from Agaricomycotina wood-decayers and suggests a broad attack on decaying lignin and related metabolites found in humic acid-rich environment. Similarly, up-regulation of these genes together with a lignolytic manganese peroxidase, multiple copper radical oxidases, and cytochrome P450s is consistent with challenges posed by complex humic-rich substrates. The gene repertoire and expression of hydrolytic enzymes in A. bisporus is substantially different from the taxonomically related ectomycorrhizal symbiont Laccaria bicolor. A common promoter motif was also identified in genes very highly expressed in humic-rich substrates. These observations reveal genetic and enzymatic mechanisms governing adaptation to the humic-rich ecological niche formed during plant degradation, further defining the critical role such fungi contribute to soil structure and carbon sequestration in terrestrial ecosystems. Genome sequence will expedite mushroom breeding for improved agronomic characteristics.

Implementation of an Adjunct Strategy to Reduce Blood Pressure in Blacks with Uncontrolled Hypertension: a Pilot Project.

A high prevalence of uncontrolled hypertension among Blacks is a major cause of racial health disparities in the United States. We established a community/academic partnership to improve hypertension control in Blacks receiving medical care at a federally qualified health center in Milwaukee. The defining components of our program included: six group sessions (one/month), based on the American Heart Association's Simple Seven curriculum and designed to motivate and empower patients to manage their blood pressure; active involvement of a community health worker; and ongoing participation of a community advisory board. The study design included a matched control group not exposed to the intervention. Patients in both groups received their usual medical care. Overall, compared to baseline, systolic blood pressure decreased at both 6 and 12 months (P < 0.004); however, the reduction of blood pressure in the intervention and control groups did not differ significantly (P = .62). Based on written responses to a questionnaire and structured focus group interviews after completing the six-month program, participants reported that the intervention was effective. In retrospect, they suggested that more attention might have been given to spirituality and stress reduction. Larger and longer-term studies will be required to evaluate the added value of this type of intervention.

Plerixafor and abbreviated-course granulocyte colony-stimulating factor for mobilizing hematopoietic progenitor cells in light chain amyloidosis.

Cytokine-based mobilization in light chain (AL) amyloidosis is frequently complicated by fluid overload, weight gain, cardiac arrhythmias, and peri-mobilization mortality. We analyzed hematopoietic progenitor cells (HPC) mobilization outcomes in 49 consecutive AL amyloidosis patients at our institution between 2004 and 2013 with granulocyte colony-stimulating factor (G) (10 µg/kg/day) (n = 25) versus an institutional protocol to limit G exposure using plerixafor (P) (.24 mg/kg s.c. starting day 3 of G 10 µg/kg) (n = 24). G+P strategy yielded higher total CD34(+) cells/kg (12.8 × 10(6) versus 6.3 × 10(6); P < .001) and CD34(+) cells/kg collected on day 1 (10.8 × 10(6) versus 4.9 × 10(6), P = .004) compared with the G cohort. More G+P patients collected ≥5 × 10(6) CD34(+) HPCs/kg (22 versus 16, P = .02) and ≥ 10 × 10(6) CD34(+) HPCs/kg (13 versus 5, P = .01). Four patients (16%) had mobilization failure with G; none with G+P. Peri-mobilization weight gain was lower with G+P strategy (median weight gain 1 versus 7 pounds, P = .009). Numbers of apheresis sessions (median, 1 versus 1, P = .52), number of hospitalization days (median, 1.1 versus 1.6, P = .52), transfusions, use of intravenous antibiotics, and cardiac arrhythmias were similar. In conclusion, our study demonstrates that upfront use of G+P as a mobilization strategy results in superior HPC collection, no mobilization failures, and less weight gain than G alone.