Regulation of cell turnover in the livers of tumour-bearing rats: occurrence of apoptosis

Growth of a highly-deviated ascites hepatoma (Yoshida AH-130) in rats caused initial hyperplastic enlargement of the liver, followed by progressive reduction to a size lower than that seen in controls. The time-course of this biphasic change in liver weight roughly corresponded to the exponential and stationary phases of tumour growth. Histologically, scattered small foci of perilobular necrosis were observed during the hyperplastic phase and these were consistently associated with a moderate elevation of glutamate-pyruvate transaminase (GPT) activity in the blood plasma. By contrast, signs of necrosis were absent and plasma GTP levels had returned to normal during the phase of hepatic involution, which was characterized by enhanced apoptosis, a type of single-cell death known to be involved in the regulation of tissue size under both normal and pathological conditions. Biochemically, alterations in liver protein mass resulted from changed rates of tissue protein degradation. The apoptotic bodies could either be lost from the liver via blood, lymph and bile, or phagocytosed and degraded by adjacent cells. Disposal of the apoptotic bodies is likely to account, at least in part, for the enhanced rates of liver protein turnover that characterize hepatic involution.     

Field evaluation of cycled coupled movements of hand and foot in older individuals

BACKGROUND: Age-related deterioration of motor performance has been investigated, often associated to behavioral slowing and to modification in the quality of movement coordination. However, the complexity of laboratory settings restrains sound quantitative evaluation of inter-limb coordination in large-scale clinical assessments, and no information regarding test stability has been provided. OBJECTIVE: The aims of the present study were to verify in homolateral hand and foot coordination field performances: (1) acceptable test-retest reliability criteria for older adults, and (2) the effects of coordination mode and test velocity at different ages across lifespan. METHODS: Seventy-seven individuals, ranging in age from 10 to 87 years, performed simultaneous flexions and extensions of the homolateral wrist and ankle in the sagittal plane with a 1:1 ratio. Two homolateral conditions (preferred and non-preferred limbs) were tested in two coordination modes: in-phase (isodirectional) and anti-phase (nonisodirectional) at three test frequencies (80, 120 and 180 bpm, respectively). Time of correct execution within a maximum of 60 s was recorded for each test condition. Older adults (n = 36) performed the test and the retest with a week interval. RESULTS: High ICCs (range 0.72-0.98) and acceptable limits of agreement were found for the subsample of older adults. Main effects and significant interactions were found for age, coordination mode, and execution frequency. Time of correct execution was longest in younger adults and shortest in older individuals. At all ages, it was longer for the in-phase than in the anti-phase condition and decreased with increasing execution frequency. However, the amplitude of the differences between execution frequencies varied as a function of age and coordination mode. CONCLUSIONS: The high test-retest stability coefficients confirm that the present field test represents a reliable tool to quantify older individual's performance on cyclic coupled movements of hand and foot allowing large-scale evaluations with an inexpensive apparatus. Aging generally harms homolateral inter-limb coordination performance, but a more complex pattern of effects emerges when coordination mode, and frequency of execution are manipulated. In fact, age-related performance impairments were most pronounced during anti-phase movements, that need increased monitoring and attentional allocation in order to inhibit the natural in-phase mode, and at high execution frequencies, that are strongly affected by age-related muscle weakness, prolonged reaction times, and changes in stretch reflexes.     

Sporadic ALS is not associated with VAPB gene mutations in Southern Italy

There is evidence that multiple sclerosis (MS) may associated with cognitive impairment in 25 to 40% of cases. The gene encoding myeloperoxidase (MPO) is involved in molecular pathways leading to β-amyloid deposition. We investigated a functional biallelic (G/A) polymorphism in the promoter region (-463) of the MPO gene in 465 patients affected by MS, divided into 204 cognitively normal and 261 impaired. We did not find significant differences in allele or genotype distributions between impaired and preserved MS patients. Our findings suggest that MPO polymorphism is not a risk factor for cognitive impairment in MS.     

Resting-state brain connectivity in patients with Parkinson's disease and freezing of gait

BackgroundFreezing of gait is a common cause of disability and falls in patients with Parkinson's disease. We studied brain functional connectivity, by means of resting-state functional magnetic resonance imaging, in patients with Parkinson's disease and freezing of gait.MethodsResting-state functional magnetic resonance imaging at 3 T was collected in 29 patients with Parkinson's disease, of whom 16 presented with freezing of gait as determined by a validated freezing of gait questionnaire, and 15 matched healthy controls. Single-subject and group-level independent component analysis was used to identify the main resting-state networks differing between Parkinson's disease patients with and without freezing of gait. Statistical analysis was performed using BrainVoyager QX.ResultsBetween-group differences in resting-state networks revealed that patients with freezing of gait exhibit significantly reduced functional connectivity within both “executive-attention” (in the right middle frontal gyrus and in the angular gyrus) and visual networks (in the right occipito-temporal gyrus) [p < 0.05 corrected for multiple comparisons]. Freezing of gait clinical severity was significantly correlated with decreased connectivity within the two networks. Consistent with their “executive-attention” network impairment, patients with freezing of gait scored lower on tests of frontal lobe functions (phonemic verbal fluency: p = 0.005; frontal assessment battery: p < 0.001; ten point clock test: p = 0.04).ConclusionsOur findings suggest that a resting-state functional connectivity disruption of “executive-attention” and visual neural networks may be associated with the development of freezing of gait in patients with Parkinson's disease.     

Accuracy of freehand fluoroscopy-guided placement of C1 lateral mass and C2 isthmic screws in atlanto-axial instability

Background  

The C1 lateral mass and C2 isthmic stabilization, as introduced by Goel and Laheri and by Harms and Melcher, is a well-known fixation technique. We present the clinical and radiographic results with freehand fluoroscopy guided C1 lateral mass and C2 isthmic fixation in a consecutive series of 28 patients, evaluating the accuracy of screw placement.     

Topical hemostatic agents in neurosurgery,a comprehensive review: 15 years update

Neurosurgical Review - Hemostasis in neurosurgery is of utmost importance. Bleeding management is one of the crucial steps of each neurosurgical procedure. Several strategies, namely thermal,...     

Leptin expression in colorectal and breast cancer patients

Leptin is a hormone which controls fat metabolism. Leptin plasma levels and adipose tissue mRNA expression were measured in cancer patients. Plasma levels were correlated with TNM staging, cachexia parameters, tumour markers and hormones. Breast and colorectal cancer patients showed blood plasma levels of insulin, TNF-alpha and tumour markers higher than controls. Breast cancer patients, but not colorectal cancer patients, had plasma levels and adipose tissue expression of leptin significantly higher than controls associated with elevated values of estrogen- and progesterone-receptors. These data suggest the possible use of leptin as a clinical marker.     

A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene.

We report a novel case of multiple endocrine neoplasia type 2A (MEN 2A) associated with two mutations of the protooncogene RET. One affects codon 634 and causes a cysteine to arginine substitution; the second at codon 640 causes an alanine to glycine substitution in the transmembrane region. The two mutations were present on the same RET allele and were detected in germline and tumor DNA. Both mutations were de novo, i.e. they were not found in the DNA of the parents or relatives. Immunohistochemical and RT-PCR analysis showed that the pheochromocytoma expressed calcitonin as well as both RET alleles. A cell line established from the tumor and propagated in culture sustained the expression of RET and calcitonin, as did the original pheochromocytoma. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma without parathyroid gland involvement, we speculate that this clinical picture could be correlated with the two RET mutations and to the unusual calcitonin production. This is the first report of a MEN 2A case due to two mutations of the RET gene and associated with a calcitonin-producing pheochromocytoma.     

Disconnectome of the migraine brain: a “connectopathy” model

BackgroundIn the past decades a plethora of studies has been conducted to explore resting-state functional connectivity (RS-FC) of the brain networks in migraine with conflicting results probably due to the variability and susceptibility of signal fluctuations across the course of RS-FC scan. On the other hand, the structural substrates enabling the functional communications among the brain connectome, characterized by higher stability and reproducibility, have not been widely investigated in migraine by means of graph analysis approach. We hypothesize a rearrangement of the brain connectome with an increase of both strength and density of connections between cortical areas specifically involved in pain perception, processing and modulation in migraine patients. Moreover, such connectome rearrangement, inducing an imbalance between the competing parameters of network efficiency and segregation, may underpin a mismatch between energy resources and demand representing the neuronal correlate of the energetically dysfunctional migraine brain.MethodsWe investigated, using diffusion-weighted MRI imaging tractography-based graph analysis, the graph-topological indices of the brain “connectome”, a set of grey matter regions (nodes) structurally connected by white matter paths (edges) in 94 patients with migraine without aura compared to 91 healthy controls.ResultsWe observed in migraine patients compared to healthy controls: i) higher local and global network efficiency (p < 0.001) and ii) higher local and global clustering coefficient (p < 0.001). Moreover, we found changes in the hubs topology in migraine patients with: i) posterior cingulate cortex and inferior parietal lobule (encompassing the so-called neurolimbic-pain network) assuming the hub role and ii) fronto-orbital cortex, involved in emotional aspects, and visual areas, involved in migraine pathophysiology, losing the hub role. Finally, we found higher connection (edges) probability between cortical nodes involved in pain perception and modulation as well as in cognitive and affective attribution of pain experiences, in migraine patients when compared to healthy controls (p < 0.001). No correlations were found between imaging and clinical parameters of disease severity.ConclusionThe imbalance between the need of investing resources to promote network efficiency and the need of minimizing the metabolic cost of wiring probably represents the mechanism underlying migraine patients’ susceptibility to triggers. Such changes in connectome topography suggest an intriguing pathophysiological model of migraine as brain “connectopathy”.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01315-6.