Abstract Neuroprotection is a therapeutic approach for the management of neurodegenerative diseases. Experimental thiamine deficiency (TD) in rats provides a model for selective neurodegeneration ...accompanied by chronic oxidative deficits. Rats exhibit neurological and cognitive impairments, which can be partially reversed by thiamine administration, enabling the study of mechanisms of neurodegeneration as well as neuroprotection. In this magnetic resonance (MR) study we used various techniques to characterize the neuroprotective effects of rasagiline, a selective MAO-B inhibitor. TD was induced by a thiamine-deficient diet and daily injections of the central thiamine antagonist, pyrithiamine. Daily injections of either saline or rasagiline (3mg/kg) were also administered to untreated-TD rats and rasagiline-treated TD rats respectively. With the appearance of neurological symptoms, all injections were terminated and thiamine was restored. MRI scans were performed before induction of TD (control values), on days 10, 12 (before symptoms appear), 14 (symptomatic stage) and during the recuperation period. Both groups were assessed using in-vivo serial T2-weighted imaging and diffusion tensor imaging (DTI), from which apparent diffusion coefficient (ADC) and fractional anisotropy (FA) maps were calculated. A histopathological evaluation was correlated with the MRI analysis. Thalamic hyperintensities were significantly smaller and less severe in the rasagiline-treated TD rats. Enlargement of the lateral ventricles was significantly less pronounced in the rasagiline-treated TD group. FA values of the untreated-TD group decreased significantly in the thalamic on days 12 and 14 and in the corpus callosum on day 14. These results demonstrate significant neuroprotection by rasagiline which could have implications for clinical neurodegenerative disorders.
Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are ...considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years.
Case series.
We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022.
The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis.
Retrospective uncontrolled study, small number of kidney biopsies.
This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.
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In muscular dystrophies (MD) the loss of muscle and its ability to function are associated with fibrosis. We evaluated the efficacy of halofuginone in reducing fibrosis in the dy2J/dy2J mouse model ...of congenital MD. Mice were injected intraperitoneally with 5 μg of halofuginone 3 times a week for 5 or 15 weeks, starting at the age of 3 weeks. Halofuginone caused a reduction in collagen synthesis in hindlimb muscles. This was associated with reductions in the degenerated area, in cell proliferation, in the number of myofibers with central nuclei, with increased myofiber diameter, and with enhanced motor coordination and balance. Halofuginone caused a reduction in infiltrating fibroblasts that were located close to centrally nucleated myofibers. Our results suggest that halofuginone reduced the deleterious effects of fibrosis, thus improving muscle integrity. Halofuginone meets the criteria for a novel antifibrotic therapy for MD patients. Muscle Nerve, 2010
Abstract Selective neurodegeneration accompanied by mitochondrial dysfunction characterizes neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Thiamine deficiency (TD) in rats ...is a model for the study of cellular and molecular mechanisms that lead to selective neuronal loss caused by chronic oxidative deficits. Neurodegeneration in TD-rats develops over a period of 12 to 14 days and can be partially reversed by thiamine administration. The aim of this study was to characterize the in-vivo progression of neurodegeneration and the neuronal rescue processes in TD using T2 magnetic resonance mapping and diffusion tensor imaging (DTI). Each rat was scanned prior to TD induction (day 0), before the appearance of neurological symptoms (day 10), during the symptomatic stage (days 12 and 14) and during the recuperation period (days 31 and 87). Time-dependent lesions were revealed mainly in the thalamus and the inferior colliculi. Early decrease in the fractional anisotropy (FA) was found on day 10 in the inferior colliculi and to a lesser degree in the thalamus, while the earliest detectable changes in the T2 parameter occurred only on day 12. FA values in the thalamus remained significantly low after thiamine restoration, suggesting irreversible disarrangement and replacement of neuronal structures. While T2 values in the frontal cortex demonstrated no lesions, FA values significantly increased on days 14 and 31. An enlargement of the lateral ventricles was observed and persevered during the recovery period. This longitudinal MRI study demonstrated that in TD MRI can detect neurodegeneration and neuronal recovery. DTI is more sensitive than T2 mapping in the early detection of TD lesions.
Sweet basil (Ocimum basilicum) is an annual herb crop that is harvested several times each season. Botrytis cinerea infects the fresh wounds that are created at harvest and grey mould also develops ...on harvested shoots. The aim was to characterize grey mould epidemics and to develop cultural means of controlling sweet basil grey mould in commercial plantings and postharvest. Two annual surveys at 82 sites revealed that grey mould epidemics are polycyclic in nature. The incidence of grey mould was found to be unaffected by the planting date or crop age, but related to weather conditions (i.e., rain events outside the greenhouse) and the limiting factor for grey mould development was the need for a high level of humidity in the greenhouse. Higher planting density, restricted aeration and the use of narrower walk-in tunnels or greenhouse structures with lower ceilings all contribute to epidemics. Latent infection was found in the leaves of harvested shoots as determined by B. cinerea-specific molecular probes. The effectiveness of plant spacing, soil mulch, thermal screens, greenhouse aeration, floating covers and combinations of some of these practices was tested under semi-commercial conditions for four years. A planting density that was half that of the common practice suppressed grey mould incidence in the field experiments with no significant yield losses. This effect can be attributed to the reduced amount of receptive host tissue and better aeration within the canopy at the initial stages of growth. The shoots harvested from the lower-density plots were less susceptible to B. cinerea infection. Floating covers and thermal screens were ineffective in reducing the incidence of grey mould in the field experiments and increased the susceptibility of harvested shoots of sweet basil to rot development. Polyethylene soil cover reduced grey mould in sweet basil planted in soil whereas the same mulch failed to control the disease on plants growing in a detached medium. The combination of increased plant spacing and the use of a polyethylene soil cover synergistically improved the yield of sweet basil shoots. Aeration of the tunnels decreased grey mould intensity and this positive effect was enhanced when the aeration treatment was applied in combination with lower planting density. In conclusion, cultural measures are capable of grey mould suppression in sweet basil and result in reduced susceptibility of the host tissues.
•The limiting factor for basil grey mould development is a high level of relative humidity in the greenhouse.•Cultural methods surveyed and tested for Botrytis cinerea suppression were found effective.•Lowering planting density reduced disease incidence in the field with no significant yield losses.•This is attributed to reduced amount of receptive host tissue and canopy aeration at the initial stages of growth.•Also, the shoots from the lower-density plots were less susceptible to B. cinerea infection.
•An avocado cDNA encoding a putative ICK/KRP protein was isolated.•Expression analysis links PaKRP with the exit from the fruit cell cycle.•Our data suggest an inhibitory role for PaKRP following ...induction by ABA.
Previous studies using ‘Hass’ avocado cultivar showed that its small-fruit (SF) phenotype is limited by cell number. To explore the molecular components affecting avocado cell production, we isolated four cDNAs encoding: an ICK/KRP protein, known to play cell cycle-regulating roles through modulation of CDK function; two CDK proteins and a D-type cyclin, and monitored their expression patterns, comparing NF (normal fruit) versus SF profiles. The accumulation of PaKRP gradually deceased during growth in both fruit populations. Despite these similarities, SF exhibited higher levels of PaKRP accumulation at early stages of growth. Moreover, in NF, augmented PaKRP expression coincided with a decrease in CDK and PaCYCD1 levels, whereas in SF, enhanced PaKPR expression was coupled with an earlier decline of CDK and PaCYCD1 levels. For both NF and SF, enhanced mesocarp PaKRP transcript accumulation, was associated with elevated abscisic acid (ABA) and ABA catabolites content. Nevertheless, the collective ABA levels, including catabolites, were substantially higher in SF tissues, as compared with NF tissues. Finally, additional expression analysis revealed that in cultured cells, PaKRP could be induced by ABA. Together, our data links PaKRP with exit from the fruit cell cycle and suggest a role for ABA in controlling its expression.
In muscular dystrophies (MD) the loss of muscle and its ability to function are associated with fibrosis. We evaluated the efficacy of halofuginone in reducing fibrosis in the dy2J/dy2J mouse model ...of congenital MD. Mice were injected intraperitoneally with 5 μg of halofuginone 3 times a week for 5 or 15 weeks, starting at the age of 3 weeks. Halofuginone caused a reduction in collagen synthesis in hindlimb muscles. This was associated with reductions in the degenerated area, in cell proliferation, in the number of myofibers with central nuclei, with increased myofiber diameter, and with enhanced motor coordination and balance. Halofuginone caused a reduction in infiltrating fibroblasts that were located close to centrally nucleated myofibers. Our results suggest that halofuginone reduced the deleterious effects of fibrosis, thus improving muscle integrity. Halofuginone meets the criteria for a novel antifibrotic therapy for MD patients. Muscle Nerve, 2010 PUBLICATION ABSTRACT
Atrial fibrillation (AF) is the most prevalent heart arrhythmia. AF manifests on the electrocardiogram (ECG) though irregular beat-to-beat time interval variation, the absence of P-wave and the ...presence of fibrillatory waves (f-wave). We hypothesize that a deep learning (DL) approach trained on the raw ECG will enable robust detection of AF events and the estimation of the AF burden (AFB). We further hypothesize that the performance reached leveraging the raw ECG will be superior to previously developed methods using the beat-to-beat interval variation time series. Consequently, we develop a new DL algorithm, denoted ArNet-ECG, to robustly detect AF events and estimate the AFB from the raw ECG and benchmark this algorithms against previous work. Methods: A dataset including 2,247 adult patients and totaling over 53,753 hours of continuous ECG from the University of Virginia (UVAF) was used. Results: ArNet-ECG obtained an F1 of 0.96 and ArNet2 obtained an F1 0.94. Discussion and conclusion: ArNet-ECG outperformed ArNet2 thus demonstrating that using the raw ECG provides added performance over the beat-to-beat interval time series. The main reason found for explaining the higher performance of ArNet-ECG was its high performance on atrial flutter examples versus poor performance on these recordings for ArNet2.
Introduction: Deep learning models for detecting episodes of atrial fibrillation (AF) using rhythm information in long-term, ambulatory ECG recordings have shown high performance. However, the ...rhythm-based approach does not take advantage of the morphological information conveyed by the different ECG waveforms, particularly the f-waves. As a result, the performance of such models may be inherently limited. Methods: To address this limitation, we have developed a deep learning model, named RawECGNet, to detect episodes of AF and atrial flutter (AFl) using the raw, single-lead ECG. We compare the generalization performance of RawECGNet on two external data sets that account for distribution shifts in geography, ethnicity, and lead position. RawECGNet is further benchmarked against a state-of-the-art deep learning model, named ArNet2, which utilizes rhythm information as input. Results: Using RawECGNet, the results for the different leads in the external test sets in terms of the F1 score were 0.91--0.94 in RBDB and 0.93 in SHDB, compared to 0.89--0.91 in RBDB and 0.91 in SHDB for ArNet2. The results highlight RawECGNet as a high-performance, generalizable algorithm for detection of AF and AFl episodes, exploiting information on both rhythm and morphology.
Introduction: Atrial fibrillation (AF) is the most common heart arrhythmia, characterized by the presence of fibrillatory waves (f-waves) in the ECG. We introduce a voting scheme to estimate the ...dominant atrial frequency (DAF) of f-waves. Methods: We analysed a subset of Holter recordings obtained from the University of Virginia AF Database. 100 Holter recordings with manually annotated AF events, resulting in a total 363 AF events lasting more than 1 min. The f-waves were extracted using four different template subtraction (TS) algorithms and the DAF was estimated from the first 1-min window of each AF event. A random forest classifier was used. We hypothesized that better extraction of the f-wave meant better AF/non-AF classification using the DAF as the single input feature of the RF model. Results: Performance on the test set, expressed in terms of AF/non-AF classification, was the best when the DAF was computed computed the three best-performing extraction methods. Using these three algorithms in a voting scheme, the classifier obtained AUC=0.60 and the DAFs were mostly spread around 6 Hz, 5.66 (4.83-7.47). Conclusions: This study has two novel contributions: (1) a method for assessing the performance of f-wave extraction algorithms, and (2) a voting scheme for improved DAF estimation.
