Preoperative Versus Postoperative Compensation of the Contralateral Normal Kidney in Patients Treated with Radical Nephrectomy for Renal Cell Carcinoma

Background: We sought to identify the factors affecting renal compensatory processes that occur preoperatively as well as postoperatively in patients treated with radical nephrectomy (RNx) for renal cell carcinoma (RCC). Methods: We retrospectively reviewed the records of 906 patients treated with RNx for RCC. We defined the early compensatory process (process 1) as compensatory adaptation of the contralateral normal kidney (CNK) before RNx. We defined the late compensatory process (process 2) as compensatory adaptation of the CNK after RNx. Total compensation was defined as the combination of these two processes. Multivariable logistic regression analyses were used to identify significant factors associated with processes 1, 2, and total compensation. Results: Mean preoperative, 1-week, and 5-year postoperative estimated glomerular filtration rates (eGFR) were 84.5, 57.6, and 63.7 mL/min/1.73 m2, respectively. Female sex (p < 0.001), lower body mass index (BMI) (p < 0.001), absence of hypertension (p = 0.019), lower preoperative eGFR (p < 0.001), larger tumor volume (p < 0.001), and larger CNK volume (p < 0.001) were significantly associated with process 1. Younger age (p = 0.019), higher BMI (p < 0.001), and absence of diabetes mellitus (DM) (p = 0.033) were significantly associated with process 2. Female sex (p < 0.001), younger age (p < 0.001), absence of DM (p = 0.002), lower preoperative eGFR (p < 0.001), and larger tumor (p = 0.001) and CNK volumes (p < 0.001) were significantly associated with total compensation. Conclusions: Different factors affected each compensatory process. Process 1 made a greater contribution to the entire renal compensatory process than process 2.

Extracellular vesicles – propagators of neuropathology and sources of potential biomarkers and therapeutics for neurodegenerative diseases

ABSTRACTNeurodegenerative diseases are characterised by the irreversible degeneration of neurons in the central or peripheral nervous systems. These include amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD) and prion diseases. Small extracellular vesicles (sEVs), a type of EV involved in cellular communication, have been well documented as propagating neurodegenerative diseases. These sEVs carry cargo, such as proteins and RNA, to recipient cells but are also capable of promoting protein misfolding, thus actively contributing to the progression of these diseases. sEV secretion is also a compensatory process for lysosomal dysfunction in the affected cells, despite inadvertently propagating disease to recipient cells. Despite this, sEV miRNAs have biomarker potential for the early diagnosis of these diseases, while stem cell-derived sEVs and those generated through exogenous assistance demonstrate the greatest therapeutic potential. This Review will highlight novel advancements in the involvement of sEVs as propagators of neuropathology, biomarkers and potential therapeutics in neurodegenerative diseases.

Middle English Open Syllable Lengthening (MEOSL) or Middle English Compensatory Lengthening (MECL)?

This study addresses a controversial aspect of the change traditionally known as Middle English Open Syllable Lengthening (MEOSL): the variable results of lengthening in disyllabic (C)V.CVC stems, the heaven–haven conundrum. It presents a full philological survey of the recoverable monomorphemic input items and their reflexes in Present-day English (PDE). A re-examination of the empirical data reveals a previously unnoticed correlation between lengthening and the sonority of the medial consonant in forms such as paper, rocket, gannet and baron, as well as interplay between that consonant and the σ2 coda. The alignment of disyllabic stems with a medial alveolar stop and a sonorant weak syllable coda (Latin, better, otter) with (C)V.RVR stems (baron, felon, moral) opens up a new perspective on the reconstruction of tapping in English. The results of lengthening in disyllabic forms, including those previously thought of as ‘exceptions’ to the change, are modeled in Classical OT and Maxent OT, prompting an account which reframes MEOSL as a stem-level compensatory process (MECL) for all inputs. We show that OT grammars with conventional constraints can correctly predict variation in the (C)V.TəR stems and categorical lengthening or non-lengthening in other disyllabic stems. Broadening the phonological factors beyond the open-syllable condition for potential stressed σ1 inputs in (C)V.CV(C) stems allows us to apply the same constraints to stems whose input structure does not involve an open syllable and to propose a uniform account of stressed vowel quantity in all late Middle English mono- and di-syllabic stems.

Influence of operative treatment of variсocele on the development of arterial hypertension

Purpose of the research. To assess the incidence of arterial hypertension in men with varicocele and to identify the relationship between increased blood pressure and surgical treatment of varicocele. Material and methods. A survey of 412 men receiving treatment for arterial hypertension, 482 men previously operated on for varicocele and 68 patients with varicocele who had no surgical treatment was conducted. Results. Varicose veins of the spermatic cord in patients with arterial hypertension were detected in 44.6% of cases, which exceeds the incidence of varicocele occurrence in men of a comparable age category by 1.52 times. Surgical treatment of the left spermatic cord varicocele is combined with the development of arterial hypertension in 51.2% of patients, which is three times higher than the incidence of hypertension in men who didnt undergo surgical treatment for varicocele and twice the frequency of hypertension in the general population of men of comparable age. The more frequent occurrence of renal arterial hypertension in patients who underwent surgical treatment for varicocele may indicate an adverse effect of occlusion of the internal spermatic vein on the state of renal venous hemodynamics. Conclusion. Varicocele should be considered as a compensatory process for renal venous hypertension due to obstruction of blood flow through the renal vein, and elimination of compensatory blood flow can lead to renal venous hypertension, hypoxia and the development of arterial hypertension.

Hebbian plasticity requires compensatory processes on multiple timescales

We review a body of theoretical and experimental research on Hebbian and homeostatic plasticity, starting from a puzzling observation: while homeostasis of synapses found in experiments is a slow compensatory process, most mathematical models of synaptic plasticity use rapid compensatory processes (RCPs). Even worse, with the slow homeostatic plasticity reported in experiments, simulations of existing plasticity models cannot maintain network stability unless further control mechanisms are implemented. To solve this paradox, we suggest that in addition to slow forms of homeostatic plasticity there are RCPs which stabilize synaptic plasticity on short timescales. These rapid processes may include heterosynaptic depression triggered by episodes of high postsynaptic firing rate. While slower forms of homeostatic plasticity are not sufficient to stabilize Hebbian plasticity, they are important for fine-tuning neural circuits. Taken together we suggest that learning and memory rely on an intricate interplay of diverse plasticity mechanisms on different timescales which jointly ensure stability and plasticity of neural circuits. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

Morphological Changes in the Suprachiasmatic Nucleus of Aging Female Marmosets (Callithrix jacchus)

The suprachiasmatic nuclei (SCN) are pointed to as the mammals central circadian pacemaker. Aged animals show internal time disruption possibly caused by morphological and neurochemical changes in SCN components. Some studies reported changes of neuronal cells and neuroglia in the SCN of rats and nonhuman primates during aging. The effects of senescence on morphological aspects in SCN are important for understanding some alterations in biological rhythms expression. Therefore, our aim was to perform a comparative study of the morphological aspects of SCN in adult and aged female marmoset. Morphometric analysis of SCN was performed using Nissl staining, NeuN-IR, GFAP-IR, and CB-IR. A significant decrease in the SCN cells staining with Nissl, NeuN, and CB were observed in aged female marmosets compared to adults, while a significant increase in glial cells was found in aged marmosets, thus suggesting compensatory process due to neuronal loss evoked by aging.