Cultivation of filamentous fungi to produce sustainable, nutrient rich meat replacements has recently attracted significant commercial and research interest. Here, we report evidence for the safety ...and nutritional value of Neurospora crassa mycoprotein, a whole mycelium food ingredient produced by fermentation and minimal downstream processing. N. crassa has a long history of human use in fermented foods and in molecular biology research. A survey of studies that used N. crassa in animal feed revealed no adverse effects to the health of the animals. Furthermore, a review of the literature found no reports of confirmed allergenicity or toxicity in humans involving N. crassa. Genomic toxigenicity analysis and in vitro testing did not identify any toxins in N. crassa mycoprotein. Two independent genomic allergenicity studies did not identify proteins that would be considered a particular risk for allergenic potential. Furthermore, nutritional analysis demonstrated that N. crassa mycoprotein is a good source of complete protein and is rich in fiber, potassium, and iron. Taken together, the presented data and the history of human use without evidence of human or animal harm indicate that foods containing N. crassa can generally be regarded as safe.
Intergroup dialogue (IGD) is a small group intervention that allows for sustained communication between people across social identity groups. It aims to foster intergroup relationships, develop ...critical consciousness, and increase capacities for promoting social justice. A decade after Dessel and Rogge published their review of the empirical research on IGD from 1997 to 2006, we reviewed the empirical IGD research from 2006 to 2017. We explore research that has examined IGD outcomes, processes, and facilitation, seeking to understand the current state of the research and practice of IGD. We discuss advances and new approaches to IGD, assess growth since Dessel and Rogge’s review, and discuss future directions. We provide five key recommendations for future research on IGD, and five key recommendations for future practice of IGD.
Acute gastrointestinal infections with transient mucosal inflammation frequently precede the onset of functional GI disorders with altered visceral sensory function. We hypothesized that an acute ...inflammation of the mucosa is linked to long-lasting alterations of afferent visceral pathways. Utilizing abdominal wall electromyography, we tested the visceromotor response to tonic rectal distension (60 mm Hg/3 min) in fasted, conscious, male Lewis rats (n = 40) with a barostat device before and 2, 4, 15, and 17 weeks after rectal instillation of saline or trinitrobenzenesulfonic acid plus ethanol. Tissue samples from paired controls were obtained to assess histologic tissue alterations. Inflammatory changes were present up to 2 weeks after acid/ethanol instillation but not after saline instillation. Compared to baseline measurements, the visceromotor response to colorectal distension increased significantly and reached a maximum 17 weeks (P < 0.001) after induction of colitis, while it decreased in control experiments (P < 0.05). In conclusion, these data suggest that an acute inflammation has long-term effects on somatosensory functioning.
The RING finger protein CNOT4 is a component of the CCR4–NOT complex. This complex is implicated in repression of RNA polymerase II transcription. Here we demonstrate that CNOT4 functions as a ...ubiquitin–protein ligase (E3). We show that the unique C4C4 RING domain of CNOT4 interacts with a subset of ubiquitin‐conjugating enzymes (E2s). Using NMR spectroscopy, we detail the interaction of CNOT4 with UbcH5B and characterize RING residues that are critical for this interaction. CNOT4 acts as a potent E3 ligase in vitro. Mutations that destabilize the E2–E3 interface abolish this activity. Based on these results, we present a model of how E3 ligase function within the CCR4–NOT complex relates to transcriptional regulation.
The NOT4 protein is a component of the CCR4.NOT complex, a global regulator of RNA polymerase II transcription. Human NOT4 (hNOT4) contains a RING finger motif of the C(4)C(4) type. We expressed and ...purified the N-terminal region of hNOT4 (residues 1-78) encompassing the RING finger motif and determined the solution structure by heteronuclear NMR. NMR experiments using a (113)Cd-substituted hNOT4 RING finger showed that two metal ions are bound through cysteine residues in a cross-brace manner. The three-dimensional structure of the hNOT4 RING finger was refined with root mean square deviation values of 0.58 +/- 0.13 A for the backbone atoms and 1.08 +/- 0.12 A for heavy atoms. The hNOT4 RING finger consists of an alpha-helix and three long loops that are stabilized by zinc coordination. The overall folding of the hNOT4 RING finger is similar to that of the C(3)HC(4) RING fingers. The relative orientation of the two zinc-chelating loops and the alpha-helix is well conserved. However, for the other regions, the secondary structural elements are distinct.
To evaluate costs and effectiveness of ambulatory care provided by specialists, nonspecialists (general internists), and both specialists and nonspecialists (co-care) to patients with knee ...osteoarthritis (OA) and/or chronic low back pain (LBP).
We studied Veterans Health Administration (VHA) outpatients from the Veterans Health Study with LBP and/or OA followed for at least 6 months between August 1993 and December 1995, who completed the Medical Outcomes Study Short Form 36-item (SF-36) functional status questionnaires at both baseline and followup. We obtained costs of VHA outpatient utilization and medications for these patients during the followup period. We compared costs and effectiveness of the ambulatory care provided by specialists, nonspecialists, and co-care. We also compared specialty care with nonspecialty care using an incremental cost effectiveness ratio (ICER) of annualized cost difference divided by annualized SF-36 based Physical Component Summary (PCS) improvement difference. ICER stability was assessed using bootstrap sampling.
Among 398 patients, followed an average of 14 months, 155 received only nonspecialty care, 49 specialty-only care, and 192 co-care. After regression analysis, adjusted for age, disease characteristics, and baseline health status, PCS improvements per year were 1.66 (SD 8.22) for nonspecialty care, 3.48 (SD 7.91) for specialty care, and 0.65 (SD 8.08) for co-care; while costs of care per year were $1099 (SD $1681), $1376 (SD $1503), and $2517 (SD $1644), respectively (all data US dollars). A standardized ICER of $152 per PCS unit indicated specialty care to be cost effective compared with nonspecialty care.
Specialist-only ambulatory care for OA or LBP was associated with improvement in functional status at slightly higher costs compared with nonspecialty care. Co-care, however, was substantially more costly and was associated with little improvement in functional status.
Lymphocytes are widely believed to be responsible for persistent intestinal inflammation in inflammatory bowel diseases. Mycophenolate mofetil (MMF) is a potent immunosuppressant that inhibits ...lymphocyte proliferation and has been shown to be effective in preventing allograft rejection after organ transplantation. The purpose of this study was to assess the modulating effects of MMF on intestinal inflammation in an experimental model of colitis in rats.
Colitis was induced by rectal instillation of trinitrobenzenesulfonic acid (TNBS) in ethanol in male Sprague-Dawley rats. One group of rats (n = 10) was treated with MMF i.p. (25 mg/kg b.w.) daily for 1 week starting 24 h after induction of colitis. A second group of rats (n = 10) was treated with MMF at the same dose 2 days, I day and 1 h prior to induction of colitis. Control animals (n = 10) received vehicle only. After being killed, colonic tissue was macroscopically evaluated for necrosis and microscopically for ulcerations. Sections were stained and examined for the presence of granulocytes.
Administration of MMF after induction of TNBS colitis reduced macroscopic injury by 62% compared to control animals (P = 0.01). Microscopic ulcerations were reduced by 64% compared to controls (P = 0.009). In addition, posttreatment significantly reduced the number of granulocytes. MMF pretreatment did not significantly prevent macroscopic or microscopic tissue damage, or change the number of granulocytes.
Systemic administration of MMF significantly ameliorates tissue damage in a model of experimental colitis in rats suggesting that this compound may play an important role as an immunosuppressant in the therapy of inflammatory bowel diseases.
The last revised classification of endometriosis of the American Fertility Society takes the extension of endometriotic lesions and the three macroscopic appearances of this disease into ...consideration. The aim of this study was to determine whether morphometric analyses are able to describe the grade of activity of endometriotic lesions according to their macroscopic-morphological appearances. Endometriotic samples of 45 patients were analyzed morphometrically using a semiautomatical planimeter. Six different parameters were investigated: the cytoplasmic surface of epithelial cells, the nucleus surface of epithelial cells, the nucleus surface of stromal cells, the gland surface, the gland circumference and the gland diameter. No statistically significant differences (p > 0.05) between the macroscopic appearances of the endometriotic lesions and the six analyzed morphometric parameters were found. The majority of the endometriotic lesions showed median values for the cytoplasmic surface of epithelial cells, the nucleus surface of epithelial cells and the gland surface that did not differ from the median values of all tissues, independently of the macroscopic appearances of these lesions and of the corresponding serum hormonal levels of 17 beta-estradiol and progesterone that were measured at the time of biopsy (p > 0.05). Our morphometric data showed that the red and so-called 'active' endometriotic lesions did not exhibit different morphometric characteristics from the so-called 'inactive' black or white lesions. We found that white and black lesions showed in some cases higher morphometric values than the mean values, so that these macroscopic appearances of endometriotic lesions cannot be considered as 'burned-out' endometriotic tissues. Therefore, black or white endometriotic lesions also have to be considered as therapeutically relevant, as they cannot be defined as 'inactive' endometriosis.
Current models of tumorigenesis postulate that testicular germ cell cancer uniformly develops through a preinvasive lesion termed testicular intraepithelial neoplasia (TIN). An open testicular biopsy ...is a simple and highly sensitive method to diagnose TIN, and this procedure constitutes the basis for curative treatment of TIN. Patients with testis cancer carry a significantly increased risk of developing contralateral testicular tumors. Therefore, a contralateral biopsy has been recommended in these patients. A negative biopsy was assumed to exclude the risk of a subsequent germ cell cancer in the testis due to the high sensitivity of the method. Reports on false-negative biopsies gave rise to the idea that TIN is not uniformly distributed throughout the testis. Consequently, double biopsies are thought to increase the diagnostic sensitivity.
A 24-year-old patient with nonseminomatous testis cancer is reported. The patient had TIN-negative double biopsies in the contralateral testis. He received three cycles of standard PEB (cisplatin, etoposide, bleomycin) chemotherapy for visceral metastasis. 1 year after treatment the patient developed a nonseminomatous contralateral testis cancer which was treated by partial orchiectomy and subsequent local radiotherapy with 20 Gy.
The case presented here highlights some clinically important aspects: a) even double biopsies of the testis may fail to detect TIN. b) Systemic cisplatin-based chemotherapy may fail to prevent contralateral testicular germ cell cancer. c) A metachronous contralateral testis cancer may-in contrast to common clinical perception-develop even soon after the diagnosis of the first testis tumor. Furthermore, the case could foster the hypothesis that testicular germ cell tumors may in some cases develop without a preceding stage of TIN.
Acute mucosal inflammation may initiate alterations of visceral sensory function. However, experimental studies on the potential effects of a transient inflammation on visceral sensitivity are ...lacking.
We performed colorectal distensions with a barostat device in fasted, conscious, male Lewis rats (n = 20) and assessed the nociceptive response (visceromotor response; VMR) to tonic colorectal distension (CRD) (60 mmHg/3 min) by abdominal-wall electromyography. Measurements were taken before and 3, 5 and 14 days after induction of a transient and self-limiting colitis by instillation of trinitrobenzenesulphonic acid (TNB)/ethanol (or saline as control). Tissue samples from paired controls were obtained to assess histological tissue alterations.
TNB/ethanol but not saline induced an acute colitis, with most severe histological lesions occurring 5 days after instillation. After 14 days, there was no histological evidence for persisting mucosal alterations. Five days after induction of TNB/ethanol colitis, the VMR to CRD reached a transient increase (P < 0.05 v. baseline), which returned to baseline levels by day 14. In control experiments (rectal saline instillation), the VMR to CRD decreased significantly compared with baseline values (P < 0.05).
Following an acute colitis due to single colorectal instillation of TNB/ethanol, histological changes are associated with an enhanced nociceptive response to CRD.
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