RESUMEN
This study challenges the conventional psycholinguistic view that the distinction between nouns and verbs is pivotal in understanding language impairments in neurological disorders. Traditional views link frontal brain region damage with verb processing deficits and posterior temporoparietal damage with noun difficulties. However, this perspective is contested by findings from patients with Alzheimer's disease (pwAD), who show impairments in both word classes despite their typical temporoparietal atrophy. Notably, pwAD tend to use semantically lighter verbs in their speech than healthy individuals. By examining English-speaking pwAD and comparing them with Persian-speaking pwAD, this research aims to demonstrate that language impairments in Alzheimer's disease (AD) stem from the distributional properties of words within a language rather than distinct neural processing networks for nouns and verbs. We propose that the primary deficit in AD language production is an overreliance on high-frequency words. English has a set of particularly high-frequency verbs that surpass most nouns in usage frequency. Since pwAD tend to use high-frequency words, the byproduct of this word distribution in the English language would be an over-usage of high-frequency verbs. In contrast, Persian features complex verbs with an overall distribution lacking extremely high-frequency verbs like those found in English. As a result, we hypothesize that Persian-speaking pwAD would not have a bias toward the overuse of high-frequency verbs. We analyzed language samples from 95 English-speaking pwAD and 91 healthy controls, along with 27 Persian-speaking pwAD and 27 healthy controls. Employing uniform automated natural language processing methods, we measured the usage rates of nouns, verbs, and word frequencies across both cohorts. Our findings showed that English-speaking pwAD use higher-frequency verbs than healthy individuals, a pattern not mirrored by Persian-speaking pwAD. Crucially, we found a significant interaction between the frequencies of verbs used by English and Persian speakers with and without AD. Moreover, regression models that treated noun and verb frequencies as separate predictors did not outperform models that considered overall word frequency alone in classifying AD. In conclusion, this study suggests that language abnormalities among English-speaking pwAD reflect the unique distributional properties of words in English rather than a universal noun-verb class distinction. Beyond offering a new understanding of language abnormalities in AD, the study highlights the critical need for further investigation across diverse languages to deepen our insight into the mechanisms of language impairments in neurological disorders.
RESUMEN
BACKGROUND: Ifosfamide (IFO) is an alkylating agent administered against different types of malignancies. Several cases of renal injury and serum electrolytes disturbances have been reported in IFO-treated patients. Oxidative stress and mitochondrial dysfunction are suspected of being involved in the mechanism of IFO nephrotoxicity. Carnosine is a dipeptide which its antioxidant and mitochondria protecting properties have been mentioned in different experimental models. The current study aimed to evaluate the nephroprotective properties of carnosine against IFO-induced renal injury. METHODS: Rats were treated with IFO (50 mg/kg, i.p) alone or in combination with carnosine. Serum and urine biomarkers of renal injury in addition to kidney markers of oxidative stress were evaluated. Moreover, kidney mitochondria were isolated, and some mitochondrial indices were assessed. RESULTS: Elevated serum creatinine and BUN, hypokalemia, and hypophosphatemia, in addition, to an increase in urine glucose, protein, γ-GT, and alkaline phosphatase (ALP), were evident in IFO-treated animals. IFO also caused an increase in kidney reactive oxygen species (ROS) and lipid peroxidation (LPO). Renal GSH levels and antioxidant capacity were also depleted with IFO therapy. Mitochondrial dehydrogenase activity, GSH level, membrane potential, and ATP content were decreased while mitochondrial LPO and permeabilization were increased in IFO group. Carnosine (250 and 500 mg/kg, i.p) mitigated IFO-induced oxidative stress and mitochondrial impairment in renal tissue. CONCLUSION: Our data suggest mitochondrial dysfunction and oxidative stress as fundamental mechanisms of renal injury induced by IFO. On the other hand, carnosine supplementation protected kidneys against IFO-induced injury through regulating mitochondrial function and mitigating oxidative stress.