Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development.

Therapeutic use of psilocybin has become a focus of recent international research, with preliminary data showing promise to address a range of treatment-resistant mental health conditions. However, use of psilocybin as a healing entheogen has a long history through traditional consumption of mushrooms from the genus Psilocybe. The forthcoming adoption of new psilocybin-assisted therapeutic practices necessitates identification of preferred sources of psilocybin; consequently, comprehensive understanding of psilocybin-containing fungi is fundamental to consumer safety. Here we examine psilocybin producing fungi, discuss their biology, diversity, and ethnomycological uses. We also review recent work focused on elucidation of psilocybin biosynthetic production pathways, especially those from the genus Psilocybe, and their evolutionary history. Current research on psilocybin therapies is discussed, and recommendations for necessary future mycological research are outlined.

Real-world effectiveness of adalimumab in patients with moderate-to-severe hidradenitis suppurativa: the 1-year SOLACE study.

BACKGROUND: Long-term, real-word data are needed to help manage patients with hidradenitis suppurativa (HS) through this recurrent, painful and debilitating disease. OBJECTIVES: To primarily measure real-world effectiveness of adalimumab in HS and to secondarily observe clinical course of HS in the light of patients' response. METHODS: In SOLACE, adults with moderate-to-severe HS in need for change in ongoing therapy were treated with adalimumab for up to 52 weeks as per physician's medical practice. Treatment effectiveness was measured by Hidradenitis Suppurativa Clinical Response (HiSCR). Inflammatory nodules, abscesses and draining fistulas were counted, Hurley stage was assessed, and disease severity was rated using the International HS Severity Scoring System (IHS4). A post hoc analysis further explored the HiSCR response by abscess and inflammatory nodule (AN) count at baseline (low, medium and high) and gender. Spontaneously reported safety events were collected. RESULTS: From 23 Canadian centres, 69% of the 138 patients achieved HiSCR at week 24, which increased to 82% and 75% at week 52 in patients with medium and high AN counts, respectively. Gender (4 times the odds for female) and age at HS onset (5% decrease with each additional year) had an effect on achieving HiSCR. Treatment with adalimumab led to an important decrease in number of lesions in responders, with most gains observed in inflammatory nodules, more frequently in the lower body area of patients in the high AN count group. The IHS4 scores of responders were substantially lowered, with a larger decrease in patients of the high AN count group. No new safety signal was detected. CONCLUSIONS: The effectiveness of adalimumab was maintained during this 1-year period, and an optimal gain was documented for patients with medium and high AN counts. These real-world data support a prompt treatment of HS patients and the use of IHS4 to monitor treatment.

Fungi Associated with and Influence of Moisture on Development of Kernel Mold of Hazelnut.

Kernel mold on hazelnuts is defined by the United States Department of Agriculture, U.S.A., as any visible fungal growth either on the outside or inside of the kernel. Only one yeast and one filamentous fungus have been associated with kernel mold of hazelnut in Oregon. In this report, fungi were isolated from kernels with mold and identified using morphological and molecular characters. Penicillium spp. were isolated most often from kernels with mold, but species of Aspergillus and Cladosporium and Diaporthe rudis were also frequently isolated. Additional fungi from three other genera were also isolated. All of the same fungi were also isolated from symptomless kernels. Eremothecium coryli or Ramularia sp. previously associated with kernel defects in Oregon were not found associated with symptoms of kernel mold. Incidence of mold was the highest when nuts were incubated in moist chambers on wet, nonautoclaved orchard soil and was significantly higher than kernel mold found in nuts incubated on either air-dried soil or wet, autoclaved soil. Preventing hazelnuts from coming in contact with wet soil in the field using elevated wire screens resulted in significantly less mold development in two out of three years evaluated. Nuts on screens had a greater chance to dry out between rainstorms as measured by significantly lower nut moisture levels at harvest.

Effects of steeped or fermented distillers dried grains with solubles on growth performance in weanling pigs.

Coproduct feeding value may be improved by enzyme and microbial inoculant treatment in liquid diets. Three experiments were conducted to assess growth performance in newly weaned 20-d-old pigs fed corn- and soybean meal-based diets with untreated, steeped, or partially fermented distillers dried grains with solubles (DDGS) from day of weaning. In Exp. 1, conventionally dry fed diets with untreated DDGS (DDGS) or without DDGS (Control) were fed. In Exp. 2, liquid diets (25% DM [75% moisture]) were fed with enzymes (ß-glucanase and xylanase at 67.2 and 51.4 U/g DDGS, respectively) added to dry DDGS at the time of liquid feeding (UNSTP) or steeped with DDGS and added to liquid feed from d 5 to 12 of each batch prior to liquid feeding (STP). In Exp. 1 and 2 DDGS inclusion levels were 7.5% in phase 1 (d 0 to 7) and 25% in phase 2 (d 7 to 21) and phase 3 (d 21 to 35). In Exp. 3 liquid diets were fed with the Exp. 2 enzymes and silage inoculant (360,000 combined cfu and /g DDGS) added to dry DDGS at the time of liquid feeding (UNFER) or fermented with DDGS and added to liquid feed from d 1 to 7 of each batch before liquid feeding (FER). The inclusion levels of DDGS were 7.5% in phase 1 (d 0 to 7), 16.25% in phase 2 (d 7 to 21), and 25% in phase 3 (d 21 to 42 or 48). Experiment 3 diets were fed to light (LBW; 5.8 ± 0.6 kg) or heavy (HBW; 7.6 ± 0.8 kg) BW pigs at weaning, and results were analyzed separately. Pig BW and ADFI were measured weekly in each experiment. In Exp. 1, feeding diets with DDGS depressed ( < 0.05) ADFI on d 7 to 21 (491 vs. 375 ± 21 g DM/pig) and d 0 to 35 (456 vs. 405 ± 13 g DM/pig). In Exp. 2 growth performance was not affected. In Exp. 3 ADFI of HBW pigs was not affected. The HBW pigs fed FER had lower ( < 0.05) ADG and G:F on d 7 to 21 (323 vs. 264 ± 15 g/pig and 0.86 vs. 0.72 ± 0.02 g:g, respectively) and lower ( < 0.05) BW on d 21 (12.4 vs. 11.6 ± 0.2 kg) compared with HBW pigs fed UNFER. The LBW pigs fed FER had lower ( < 0.05) ADFI on d 0 to 7 and 7 to 21 (190 vs. 168 ± 3 and 318 vs. 273 ± 13 g DM/pig, respectively) and had greater ( < 0.05) ADG on d 42 to 48 (773 vs. 941 ± 60 g/pig) and BW on d 48 (24.5 vs. 25.8 ± 0.5 kg) compared with LBW pigs fed UNFER. Results show that up to 25% DDGS inclusion in weaning pig diets did not affect overall growth performance. Liquid-fed partially fermented DDGS had an influence on the growth performance of weanling pigs, particularly during the extended nursery period of pigs of light weaning weight in this study.

A New Postharvest Fruit Rot in Apple and Pear Caused by Phacidium lacerum.

During surveys for postharvest diseases of apple and pear, an unknown postharvest fruit rot was observed in Washington State. The disease appeared to originate from infection of the stem and calyx tissue of the fruit or wounds on the fruit. An unknown pycnidial fungus was consistently isolated from the decayed fruit. Isolates from apple and pear were characterized and identified by molecular phylogenetic analysis and morphology. Pathogenicity of representative isolates on apple and pear fruit was tested under laboratory or field conditions. A BLAST search in GenBank showed that isolates differed from Phacidium lacerum and its synonym, Ceuthospora pinastri, by only 0 to 4 bp in sequences within part of the combined large ribosomal subunit + internal transcribed spacer + small ribosomal subunit regions. The phylogenetic analysis confirmed the taxonomic placement of the unknown fungus in the genus Phacidium, with the highest match being C. pinastri (formerly anamorphic P. lacerum) and with closely related taxa from GenBank forming congeneric clades. The fungus grew at 0 to 30°C and formed unilocular to multilocular pycnidial conidiomata on artificial media after approximately 5 to 7 days at room temperature. On potato dextrose agar incubated for a 12-h photoperiod, semi-immersed globose to subglobose pycnidial conidiomata were 250 to 1,000 µm in diameter (mean = 350), with 1 to 3 nonpapillate to slightly papillate ostioles and a buff conidial matrix. Conidia produced on phialides were 8 to 13 by 1.5 to 2.5 µm, hyaline, aseptate, cylindrical, with an abruptly tapered, typically slightly protuberant base, 2 to 3 guttules, and sometimes with a mucilaginous, flexuous, unbranched appendage which is attached to the apex of the conidium and disappears with age. Conidiogenous cells were flask shaped and 6 to 15 ×1.5 to 3 µm. Colony characteristics included felt-like aerial white mycelium, gray olivaceous at the center becoming greenish to colorless toward the margin, in concentric rings, with pycnidia forming in 5 to 7 days originating from the center of the plate. Morphological characteristics of the fungus had the greatest conformity with the description for C. pinastri. Based on molecular and morphological data, the fungus is identified as P. lacerum. 'Fuji' apple fruit and 'd'Anjou' pear fruit that were wounded, inoculated with representative isolates, and incubated at 0°C yielded the same symptoms as seen on decayed fruit collected from commercial fruit packinghouses. Stem-end rot, calyx-end rot, and wound-associated rot developed on fruit inoculated in the orchard after 3 months of cold storage. The fungus was reisolated from the diseased fruit. This is the first report of a fruit rot in apple and pear caused by P. lacerum. We propose Phacidium rot as the name of this disease.

Obesity in breast cancer--what is the risk factor?

Environmental factors influence breast cancer incidence and progression. High body mass index (BMI) is associated with increased risk of post-menopausal breast cancer and with poorer outcome in those with a history of breast cancer. High BMI is generally interpreted as excess adiposity (overweight or obesity) and the World Cancer Research Fund judged that the associations between BMI and incidence of breast cancer were due to body fatness. Although BMI is the most common measure used to characterise body composition, it cannot distinguish lean mass from fat mass, or characterise body fat distribution, and so individuals with the same BMI can have different body composition. In particular, the relation between BMI and lean or fat mass may differ between people with or without disease. The question therefore arises as to what aspect or aspects of body composition are causally linked to the poorer outcome of breast cancer patients with high BMI. This question is not addressed in the literature. Most studies have used BMI, without discussion of its shortcomings as a marker of body composition, leading to potentially important misinterpretation. In this article we review the different measurements used to characterise body composition in the literature, and how they relate to breast cancer risk and prognosis. Further research is required to better characterise the relation of body composition to breast cancer.

A Postharvest Fruit Rot of Apple Caused by Lambertella corni-maris in Washington State.

During surveys for postharvest diseases of apple conducted in Washington State, an unknown fruit rot was observed on stored apple fruit collected from commercial fruit packinghouses. This disease was present in 66 of the 179 grower lots sampled, accounting for an average 1 to 3% of the total decayed fruit sampled. The disease appeared to originate from infection of wounds on the fruit skin. Lesions were brown and decayed tissues were spongy. A Lambertella sp. was consistently isolated from the decayed fruit. Sequences of the fungus and those of Lambertella corni-maris in GenBank differed by 0 to 4 bp across the combined small ribosomal subunit + internal transcribed spacer + large ribosomal subunit regions with a maximum identity ranging from 99 to 100%. The fungus grew at 0 to 20°C and formed apothecia on artificial media after 8 to 24 weeks. On potato dextrose agar under a 12-h photoperiod, apothecial dimensions were variable, ranging from 1 to 6 mm in diameter with stipes of 1 to 4 by 0.5 mm. Asci were 76 to 125 by 3.5 to 5.5 µm, inoperculate, eight-spored, clavate, and narrowed at the base. Ascospores were aseptate, 7 to 10 by 2.5 to 4.5 µm, uniseriate to biseriate, and orange-brown at maturity in the ascus. Colony characteristics included little or no aerial mycelium, dark-yellow to gray-black mycelium, gray-black pseudosclerotia, and yellow pigmentation in the agar. Morphological characteristics of the fungus overlapped with the description of L. corni-maris. 'Fuji' apple fruit that were wounded, inoculated with representative isolates, and incubated at 0°C yielded the same symptoms as seen in packinghouses, and the fungus was reisolated from the diseased fruit. This is the first report of a fruit rot in stored apple caused by L. corni-maris in the United States. We propose Lambertella rot as the name of this disease.

Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease that currently lacks genomic and genetic biomarkers to assist in its clinical management. We performed whole-exome sequencing (WES) of three BPDCN cases. Based on these data, we designed a resequencing approach to identify mutations in 38 selected genes in 25 BPDCN samples. WES revealed 37-99 deleterious gene mutations per exome with no common affected genes between patients, but with clear overlap in terms of molecular and disease pathways (hematological and dermatological disease). We identified for the first time deleterious mutations in IKZF3, HOXB9, UBE2G2 and ZEB2 in human leukemia. Target sequencing identified 29 recurring genes, ranging in prevalence from 36% for previously known genes, such as TET2, to 12-16% for newly identified genes, such as IKZF3 or ZEB2. Half of the tumors had mutations affecting either the DNA methylation or chromatin remodeling pathways. The clinical analysis revealed that patients with mutations in DNA methylation pathway had a significantly reduced overall survival (P=0.047). We provide the first mutational profiling of BPDCN. The data support the current WHO classification of the disease as a myeloid disorder and provide a biological rationale for the incorporation of epigenetic therapies for its treatment.

Prevalence of error-prone abbreviations used in medication prescribing for hospitalised patients: multi-hospital evaluation.

The use of error-prone abbreviations in prescribing is a potential cause of misinterpretation that may lead to medication error. This study determined frequency and type of error-prone abbreviations in inpatient medication prescribing across three Australian hospitals. Three hundred and sixty-nine (76.9%) patients had one or more error-prone abbreviations used in prescribing, with 8.4% of orders containing at least one error-prone abbreviation and 29.6% of these considered to be high risk for causing significant harm.

Questions from the fourth son: a clinician reflects on immunomonitoring, surrogate markers and systems biology.

The fourth son is the one who doesn't even know how to ask a question. Tumor immunology is challenged by the failure to identify reliable surrogate markers in vaccine and other experimental therapies for cancer; perhaps investigators haven't yet asked the right questions. Unlike prophylactic vaccines for infectious disease, where the development of antibody is considered a satisfactory endpoint, no such endpoint exists for human therapeutic vaccines. Why is this? Despite an extensive roster of in vitro assays that correlate immune responses to favorable clinical outcomes, no assay is sufficiently reliable to be usefully predictive for vaccine therapy. The discussion reviews some of the historical developments in tumor immunology and the problem of defining a causal relationship when strong correlations are identified. The development of mathematical models from empirical data may help inform the clinician/scientist about underlying mechanisms and help frame new testable hypotheses.

The culture of articular chondrocytes in hydrogel constructs within a bioreactor enhances cell proliferation and matrix synthesis.

Bovine and human articular chondrocytes were seeded in 2% alginate constructs and cultured for up to 19 days in a rotating-wall-vessel (RWV) and under static conditions. Culture within the RWV enhanced DNA levels for bovine chondrocyte-seeded constructs when compared with static conditions but did not produce enhancement for human cells. There was a significant enhancement of glycosaminoglycans and hydroxyproline synthesis for both bovine and human chondrocytes. In all cases, histological analysis revealed enhanced Safranin-O staining in the peripheral regions of the constructs compared with the central region. There was an overall increase in staining intensity after culture within the RWV compared with static conditions. Type-II collagen was produced by both bovine and human chondrocytes in the peripheral and central regions of the constructs and the staining intensity was enhanced by culture within the RWV. A capsule of flattened cells containing type-I collagen developed around the constructs maintained under static conditions when seeded with either bovine or human chondrocytes, but not when cultured within the RWV bioreactor.

Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial.

BACKGROUND: Insulin sensitizing agents may be useful in treatment of non-alcoholic fatty liver disease. AIM: A pilot study to evaluate the efficacy and safety of metformin in non-alcoholic fatty liver disease. METHODS: In an open labelled study, patients with histologically confirmed non-alcoholic fatty liver disease were given metformin (20 mg/kg) for 1 year. Insulin resistance (by log homeostasis assessment model analysis for insulin resistance and Quantitative Insulin Sensitivity Check Index) and post-treatment hepatic histology were compared with pre-treatment histology. RESULTS: Fifteen patients completed 1 year of treatment. During the initial 3 months, there was improvement in alanine aminotransferase and aspartate aminotransferase (P-value 0.01 and 0.02, respectively) along with improvement in insulin sensitivity. However, after 3 months, there was no further improvement in insulin sensitivity and there was gradual rise in aspartate aminotransferase and alanine aminotransferase back to pre-treatment levels. Among the 10 patients with post-treatment biopsy, three (33%), showed improvement in steatosis, two (20%) showed improvement in inflammation score and one (10%) showed improvement in fibrosis. CONCLUSION: Metformin treatment was associated with only a transient improvement in liver chemistries. A progressive, sustainable reduction in insulin sensitivity was not noted during treatment.

Dynamic compressive strain inhibits nitric oxide synthesis by equine chondrocytes isolated from different areas of the cartilage surface.

REASONS FOR PERFORMING STUDY: Chondrocytes within articular cartilage respond to the mechanical stresses associated with normal joint loading via a series of signalling pathways. Specific biomolecules, such as nitric oxide (NO), have been implicated in these mechanotransduction processes. It has been shown that the synthesis of NO can be inhibited by dynamic compressive strain of chondrocytes in vitro which, in turn, leads to an up-regulation of specific metabolic parameters. HYPOTHESIS: Chondrocytes isolated from different joint locations and seeded in agarose constructs respond in a distinct manner to the application of dynamic compression. METHODS: Chondrocytes were isolated separately from the equine patella groove and the femoral condyle, representing high loaded areas (HLA) and low loaded areas (LLA), respectively, of 6 specimens of different ages. The cells were seeded in agarose constructs and cultured either in an unstrained state or strained under dynamic loading at 1 Hz for 48 h. The synthesis of nitric oxide (NO), proteoglycan synthesis and chondrocyte proliferation were assessed. RESULTS: Equine chondrocytes were found to synthesise significant basal levels of NO, regardless of topographical origin or age of tissue. Marked differences in both proteoglycan synthesis and cell proliferation were, however, revealed between the 2 chondrocyte subpopulations. Dynamic compression inhibited NO synthesis but significant alterations in proteoglycan synthesis and cell proliferation were apparent in a minority of cases. CONCLUSIONS AND POTENTIAL RELEVANCE: The differential response of the subpopulations of chondrocytes derived from the HLA and LLA provides a potential mechanism which enables the biomechanical demands of differing joint regions to be maintained.

Major differences in the IgG subclass response to Helicobacter pylori in the first and third worlds.

BACKGROUND: Studies in developed countries would suggest that the immune response to Helicobacter pylori infection is a T helper cell I predominant response. Unlike subjects from developed countries, those resident in developing countries are subject to infection with a myriad of gastrointestinal pathogens from early in life. Given that H. pylori is acquired early in life, such infections may alter the immune response to H. pylori. The aim of this study was to compare the immune response to H. pylori in subjects from developed and developing countries. METHODS: Using a previously validated IgG subclass ELISA, the H. pylori specific IgG I/IgG2 subclass ratio (a marker of the T helper cell response) in 58 adult and 21 paediatric symptomatic H. pylori positive Sowetan subjects was compared with that in 64 Australian and 45 German symptomatic H. pylori positive subjects. RESULTS: An IgGI predominant response (IgG1/IgG2 ratio >1) was observed in 81% of Sowetan adults and 90% of children compared with 4.7% of Australians and 4.4% of Germans. The IgG1/IgG2 ratio was significantly higher in Sowetans compared with Australians and Germans (P < 0.001). In Australian and German subjects the IgG1/IgG2 ratio was significantly higher in NUD compared with DU. No significant difference was observed between NUD and other disease states in Sowetans. CONCLUSIONS: This study is the first to provide evidence that the host immune response to H. pylori infection in an African population differs to that observed in subjects from developed countries. Further studies are required to determine if this occurs in other developing countries.

Predictive model for immunotherapy of alopecia areata with diphencyprone.

BACKGROUND: Immunotherapy with diphencyprone (diphenylcyclopropenone) is used in the treatment of alopecia areata (AA). Response rates have varied in the literature. OBJECTIVES: To determine the efficacy of diphencyprone therapy for AA in the largest reported cohort of patients; to identify patient and treatment factors predictive of therapeutic success; and to develop a practical model for predicting patient response. METHODS: The medical records of 148 consecutive patients treated with diphencyprone were reviewed. A clinically significant response to diphencyprone therapy was defined as a cosmetically acceptable response or greater than 75% terminal hair regrowth. Survival analyses using the Kaplan-Meier method and the Cox proportional hazards model were performed to determine significant factors predictive of regrowth and relapse. RESULTS: Using a survival analysis model, the cumulative patient response at 32 months was 77.9% (95% confidence interval, 56.8%-98.9%). Variables independently associated with clinically significant regrowth were age at onset of disease and baseline extent of AA. Older age at onset of AA portended a better prognosis. A cosmetically acceptable end point was obtained in 17.4% of patients with alopecia totalis/universalis, 60.3% with 75% to 99% AA, 88.1% with 50% to 74% AA, and 100% with 25% to 49% AA. A lag of 3 months was present between initiation of therapy and development of significant hair regrowth in the first responders. Relapse after achieving significant regrowth developed in 62.6% of patients. CONCLUSIONS: Response to diphencyprone treatment in AA is affected by baseline extent of AA and age at disease onset. A prolonged treatment course might be necessary. A predictive model has been developed to assist with patient prognostication and counseling.