Forensic neuropsychological assessment.

With its firm establishment as a neuropsychology subspecialty, forensic neuropsychological assessment is integral to many criminal and civil forensic evaluations. In addition to evaluating cognitive deficits, forensic neuropsychologists can provide reliable information regarding symptom magnification, malingering, and other neurocognitive and psychological issues that may impact the outcome of a particular legal case. This article is an overview and introduction to neuropsychological assessment in the forensic mental health context. Major issues impacting the current practice of forensic neuropsychology are summarized, and several examples from case law are highlighted.

CHRNB1-associated congenital myasthenia syndrome: Expanding the clinical spectrum.

CHRNB1 encodes the ß subunit of the acetylcholine receptor (AChR) at the neuromuscular junction. Inherited defects in the neuromuscular junction can lead to congenital myasthenia syndrome (CMS), a clinically and genetically heterogeneous group of disorders which includes fetal akinesia deformation sequence (FADS) on the severe end of the spectrum. Here, we report two unrelated families with biallelic CHRNB1 variants, and in each family, one child presented with lethal FADS. We contrast the diagnostic odysseys in the two families, one of which lasted 16 years while the other, utilizing rapid exome sequencing, led to specific treatment in the first 2 weeks of life. Furthermore, we note that CHRNB1 variants may be under-recognized because in both families, one of the variants is a single exon deletion that has been previously described but may not easily be detected in clinically available genetic testing.

Endophytic Paraconiothyrium sp. from Zingiber officinale Rosc. Displays Broad-Spectrum Antimicrobial Activity by Production of Danthron.

The bioactivity spectrum of fungal endophytes isolated from Zingiber officinale was analyzed against clinical pathogens and against the phytopathogen Pythium myriotylum, which causes Pythium rot in ginger. One of the isolates GFM13 showed broad bioactivity against various pathogens tested including P. myriotylum. The spore suspension as well as the culture filtrate of the endophytic fungal isolate was found to effectively protect ginger rhizomes from Pythium rot. By molecular identification, the fungal endophyte was identified as Paraconiothyrium sp. The bioactive compound produced by the isolate was separated by bioactivity-guided fractionation and was identified by GC-MS as danthron, an anthraquinone derivative. PCR amplification showed the presence of non-reducing polyketide synthase gene (NR-PKS) in the endophyte GFM13, which is reported to be responsible for the synthesis of anthraquinones in fungi. This is the first report of danthron being produced as the biologically active component of Paraconiothyrium sp. Danthron is reported to have wide pharmaceutical and agronomic applications which include its use as a fungicide in agriculture. The broad-spectrum antimicrobial activity of danthron and the endophytic origin of Paraconiothyrium sp. offer immense applications of the study.

Metabolite analysis of endophytic fungi from cultivars of Zingiber officinale Rosc. identifies myriad of bioactive compounds including tyrosol.

Endophytic fungi associated with rhizomes of four cultivars of Zingiber officinale were identified by molecular and morphological methods and evaluated for their activity against soft rot pathogen Pythium myriotylum and clinical pathogens. The volatile bioactive metabolites produced by these isolates were identified by GC-MS analysis of the fungal crude extracts. Understanding of the metabolites produced by endophytes is also important in the context of raw consumption of ginger as medicine and spice. A total of fifteen isolates were identified from the four varieties studied. The various genera identified were Acremonium sp., Gliocladiopsis sp., Fusarium sp., Colletotrichum sp., Aspergillus sp., Phlebia sp., Earliella sp., and Pseudolagarobasidium sp. The endophytic community was unique to each variety, which could be due to the varying host genotype. Fungi from phylum Basidiomycota were identified for the first time from ginger. Seven isolates showed activity against Pythium, while only two showed antibacterial activity. The bioactive metabolites identified in the fungal crude extracts include tyrosol, benzene acetic acid, ergone, dehydromevalonic lactone, N-aminopyrrolidine, and many bioactive fatty acids and their derivatives which included linoleic acid, oleic acid, myristic acid, n-hexadecanoic acid, palmitic acid methyl ester, and methyl linoleate. The presence of these varying bioactive endophytic fungi may be one of the reasons for the differences in the performance of the different ginger varieties.

Gliotoxin-producing endophytic Acremonium sp. from Zingiber officinale found antagonistic to soft rot pathogen Pythium myriotylum.

Soft rot caused by Pythium sp. is a major cause of economic loss in ginger cultivation. Endophytic fungi isolated from Zingiber officinale were screened for its activity against the soft rot pathogen Pythium myriotylum. Among the isolates screened, an endophytic fungus which was identified as Acremonium sp. showed promising activity against the phytopathogen in dual culture. The selected fungus was cultured in large scale on solid rice media and was extracted with ethyl acetate. The crude extract was subjected to column chromatography and preparative HPLC to obtain the fraction with the antifungal activity. LC-QTOF-MS/MS analysis of this fraction done using water-acetonitrile gradient identified a mass of m/z 327 (M + H) corresponding to gliotoxin with specific fragments m/z 263, 245, 227, and 111. The result was reconfirmed in negative mode ionization. Gliotoxin is the major antagonistic peptide produced by the commercially used biocontrol agent, Trichoderma sp., which shows high antagonism against Pythium sp. The gliotoxin production by the isolated endophytic Acremonium sp. of Z. officinale shows the possible natural biocontrol potential of this endophytic fungus.

LC-MS/MS based identification of piperine production by endophytic Mycosphaerella sp. PF13 from Piper nigrum.

Piper nigrum is very remarkable for its medicinal properties due to the presence of metabolites like piperine. Emerging understanding on the biosynthetic potential of endophytic fungi suggests the possibility to have piperine producing fungi in P. nigrum. In the current study, endophytic fungi isolated from P. nigrum were screened for the presence of piperine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This resulted in the identification of a Mycosphaerella sp. with the ability to produce piperine extracellularly. The biosynthesis of piperine (C17H19NO3) by the endophytic fungal isolate was confirmed by the presence of m/z 286.1 (M + H(+)) in the LC-MS/MS analysis using positive mode ionization. This was further supported by the presence of specific fragment ions with masses 135, 143, 171 and 201 formed due to the fragmentation of piperine present in the fungal extract.

Phenazine carboxylic acid production and rhizome protective effect of endophytic Pseudomonas aeruginosa isolated from Zingiber officinale.

Ginger (Zingiber officinale) is cultivated commercially in most parts of the world especially in India for its culinary and medicinal applications. One of the major challenges that limit the yield of ginger is rhizome rot disease caused by organisms including Pythium myriotylum. A feasible ecofriendly method is yet to be devised to prevent the plant from this threatening disease. Recent studies on plant microbiome show the possibility of having endophytic organisms with plant protective characteristics associated with the plants. Because of the uniquely evolved underground nature of the ginger rhizome and its peculiar survival in soil for a long time, many interesting endophytic microbes with plant protective characters can be well expected from it. In the current study, previously isolated endophytic Pseudomonas aeruginosa from ginger was investigated in detail for its effect on Pythium myriotylum. The rhizome protective effect of the organism was also studied by co-inoculation studies, which confirmed that Pseudomonas aeruginosa has very potent inhibitory effect on Pythium myriotylum. On further studies, the active antifungal compound was identified as phenazine 1-carboxylic acid.