Severe Deficits Research Articles

A prospective study to evaluate the prevelance of chemobrain (CB) in patients (pts) receiving adjuvant treatment.

e23174 Background: Although adjuvant chemotherapy (CT) significantly improves the clinical outcome of pts with early-stage (ES) cancer, it is also known to cause side-effects. CT-induced cognitive impairment or CB refers to a clinical condition characterized by lack of mental sharpness, memory and concentration impairment and difficulty in processing information and executing simple tasks. Prospective data regarding the emergence of CB are limited. We aimed to explore the prevalence and predictors for CB among pts receiving adjuvant CT and to evaluate its impact on their quality of life (QoL). Methods: This was a prospective cohort study conducted at the University Hospital of Larissa. Pts who were recently diagnosed with ES breast (BC) or colorectal (CRC) cancer and were about to receive adjuvant CT containing doxorubicin (D) or oxaliplatin (O), respectively, were eligible for this study (C1). The first control group (C2) consisted of ES cancer pts that were not eligible for adjuvant CT and the second group (C3) was recruited from a pool of healthy controls (HCs). All participants (pcs) met the following inclusion criteria: age > 50 years old, ability to speak and write in Greek. Pts with pre-existing dementia/anxiety disorder and severe anemia were excluded from the study. Pts in C1 were assessed before receiving CT and 3 months after CT initiation. All subjects in C2 and C3 were assessed in 3 months intervals as well. After completion of the informed consent process, all pts and age-matched noncancer controls completed the Greek Version of Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) to specifically assess CB. QoL was measured using the EORTC QLQ-C30. Results: Overall, 82 pts (53 with BC and 29 with CRC) were included in C1, 36 pts (24 with BC and 12 with CRC) in C2 and 15 pcs in C3. At baseline, pts in C1 and C2 had significantly lower FACT-Cog scores than healthy controls in C3 (p: 0.028 and p:0.038, respectively), indicating a higher prevalence of self-reported cognitive impairment among pts with cancer after a curative surgery compared to age-matched HCs. However, after 3 months of CT the majority of pts in C1 (59/82, 72%) demonstrated a decline in their cognitive performance (35/53, 66% in BC pts receiving D and 24/29, 82% in CRC pts receiving O). Pts with CRC receiving O experienced more severe cognitive deficits. On the contrary, 55% of the pts in C2 (20/36, 16 with BC and 4 with CRC) demonstrated an improvement. The presence of CB (decline in cognitive functioning in the absence of severe anemia) was associated with decreased QoL (p = 0.004). Pts were mostly frustrated by the difficulty in executing simple tasks. Conclusions: As demonstrated in one of the largest cohorts of pts with ES cancer, CB is a common problem among pts receiving adjuvant CT and is associated with detrimental impact on daily life. Creating awareness is crucial to offer cancer survivors the best care directed at improving QoL.

THEORISING GENDERED MOTIVATIONS TO STREET VENDING: A STUDY OF WOMEN VENDORS IN DELHI, INDIA

The informal economy is characterised by severe decent work deficits that disproportionately impact women (ILO, 2002a, 2013c). This research identifies multiple dimensions of gendered segmentation within the street vending sector in Delhi arising from an interplay of structural factors experienced differently by women across the life course. Analysis of 105 semi-structured interviews with vendors in Delhi highlights the role of patriarchal norms in public and private spheres in structuring womens entry into street vending. Key issues to access jobs in the formal sector include the patriarchal norms, stigmatisation and societal expectations that limit womens access to education, their ability to work and the type of work they engage in, thus creating segmentation in the labour market. This study concludes that the structural conditions lead to transitions, life events and turning points in womens lives, determining their access to employment in the formal or informal sector.

Predicting lever press in a vibrotactile yes/no detection task from S1 cortex of freely behaving rats by µECoG arrays

Aim of the Study Brain-computer interfaces (BCIs) may help patients with severe neurological deficits communicate with the external world. Based on microelectrocorticography (µECoG) data recorded from the primary somatosensory cortex (S1) of unrestrained behaving rats, this study attempts to decode lever presses in a psychophysical detection task by using machine learning algorithms. Materials and Methods 16-channel Pt-Ir microelectrode arrays were implanted on the S1 of two rats, and µECoG was recorded during a vibrotactile yes/no detection task. For this task, the rats were trained to press the right lever when they detected the vibrotactile stimulus and the left lever when they did not. The multichannel µECoG data was analysed offline by time-frequency methods and its features were used for binary classification of the lever press at each trial. Several machine learning algorithms were tested as such. Results The psychophysical sensitivities (A') were similar and low for both rats (0.58). Rat 2 (B'': −0.11) had higher bias for the right lever than Rat 1 (B'': − 0.01). The lever presses could be predicted with accuracies over 66% with all the tested algorithms, and the highest average accuracy (78%) was with the support vector machine. Conclusion According to the recent studies, sensory feedback increases the benefit of the BCIs. The current proof-of-concept study shows that lever presses can be decoded from the S1; therefore, this area may be utilised for a bidirectional BCI in the future.

Recovery of optimal vitamin D improves responsiveness to phosphodiesterase-5 inhibitors therapy in pulmonary arterial hypertension

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): R.A. has received funding from the European Union’s Horizon 2020 research and innovation programme under Marie-Curie grant agreement Nº 847635. Introduction Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We demonstrated that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH. Also, recent evidence suggests that vitD deficiency may cause insufficient response to phosphodiesterase-5 inhibitors (PDE5i), such as sildenafil, in some patients with PAH. Thus, in this study, we hypothesize that the recovery of optimal vitD levels in experimental PAH might help to improve responsiveness to PDE5i therapy. Methods Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and divided into two groups: (a) daily tadalafil therapy (oral;10mg/kg) + continued vitD-free diet (n=9) or (b) daily tadalafil therapy (oral;10mg/kg) + single oral dose of 50,000 IU/Kg of vitD plus standard diet (n=9) for four weeks. Animals were then used for exercise capacity evaluation, invasive haemodynamic, pulmonary vascular analysis, and sample collection. Evolution of cardiac (dys)function was assessed by echocardiography. Results Recovering optimal vitD levels improved pulmonary endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the vasodilator response to sildenafil. Moreover, pulmonary small artery (<55 µm) remodeling was decreased in vitD-restored group, as measured by a decline in mean lumen/total ratio and mean medial thickness. In a morphometric analysis, vitD treatment attenuated increases in both right ventricle (RV) and right atrial hypertrophy, as well as the fulton index. VitD supplementation also improved the exercise capacity with increases seen in distance run, evaluated by endurance tests in a treadmill set. RV catheterization showed that vitD did not decreased the RV dysfunction, evaluated by end-systolic and end-diastolic pressure. Similar to the RV, no alterations were observed in pulmonary artery pressures. However, echocardiographic analysis revealed an improved pulmonary flow in the vitD-restored group, where pulmonary artery acceleration time normalized to ejection time ratio and pulmonary artery velocity-time integral were increased. It also improved tricuspid annular plane systolic excursion (TAPSE). Conclusion Altogether, these data suggest that in animals with PAH treated with tadalafil, restoring vitD levels to an optimal range improves some pathophysiological features of PAH. Therefore, in addition to recovery of optimal vitD status being indicated to restore calcium homeostasis in those PAH patients with severe deficiency, it might help to improve responsiveness to PDE5i.

Replication and reliability of Parkinson's disease clinical subtypes

BackgroundWe recently identified three distinct Parkinson's disease subtypes: “motor only” (predominant motor deficits with intact cognition and psychiatric function); “psychiatric & motor” (prominent psychiatric symptoms and moderate motor deficits); “cognitive & motor” (cognitive and motor deficits). ObjectiveWe used an independent cohort to replicate and assess reliability of these Parkinson's disease subtypes. MethodsWe tested our original subtype classification with an independent cohort (N = 100) of Parkinson's disease participants without dementia and the same comprehensive evaluations assessing motor, cognitive, and psychiatric function. Next, we combined the original (N = 162) and replication (N = 100) datasets to test the classification model with the full combined dataset (N = 262). We also generated 10 random split-half samples of the combined dataset to establish the reliability of the subtype classifications. Latent class analyses were applied to the replication, combined, and split-half samples to determine subtype classification. ResultsFirst, LCA supported the three-class solution – Motor Only, Psychiatric & Motor, and Cognitive & Motor– in the replication sample. Next, using the larger, combined sample, LCA again supported the three subtype groups, with the emergence of a potential fourth group defined by more severe motor deficits. Finally, split-half analyses showed that the three-class model also had the best fit in 13/20 (65%) split-half samples; two-class and four-class solutions provided the best model fit in five (25%) and two (10%) split-half replications, respectively. ConclusionsThese results support the reproducibility and reliability of the Parkinson's disease behavioral subtypes of motor only, psychiatric & motor, and cognitive & motor groups.

Alterations of tactile and anatomical spatial representations of the hand after stroke

Stroke often causes long-term motor and somatosensory impairments. Motor planning and tactile perception rely on spatial body representations. However, the link between altered spatial body representations, motor deficit and tactile spatial coding remains unclear. This study investigates the relationship between motor deficits and alterations of anatomical (body) and tactile spatial representations of the hand in 20 post-stroke patients with upper limb hemiparesis. Anatomical and tactile spatial representations were assessed from 10 targets (nails and knuckles) respectively cued verbally by their anatomical name or using tactile stimulations. Two distance metrics (hand width and finger length) and two structural measures (relative organization of targets positions and angular deviation of fingers from their physical posture) were computed and compared to clinical assessments, normative data and lesions sites. Over half of the patients had altered anatomical and/or tactile spatial representations. Metrics of tactile and anatomical representations showed common variations, where a wider hand representation was linked to more severe motor deficits. In contrast, alterations in structural measures were not concomitantly observed in tactile and anatomical representations and did not correlate with clinical assessments. Finally, a preliminary analysis showed that specific alterations in tactile structural measures were associated with dorsolateral prefrontal stroke lesions. This study reveals shared and distinct characteristics of anatomical and tactile hand spatial representations, reflecting different mechanisms that can be affected differently after stroke: metrics and location of tactile and anatomical representations were partially shared while the structural measures of tactile and anatomical representations had distinct characteristics.

X-ray endovascular surgery for in-hospital acute ischemic stroke

The OBJECTIVE was to determine the efficacy of endovascular surgery for in-hospital acute ischemic stroke (AIS) and to identify predictors of unfavorable AIS outcome.METHODS AND MATERIALS. We performed 42 endovascular thrombectomies for in-hospital AIS in patients treated in the hospital for another pathology. Neurological defiCIT was determined by NIHSS scale, thrombectomy efficacy was evaluated by the degree of cerebral revascularization by mTICI scale, functional outcome was determined by Rankin scale (mRS). Multivariate analysis with evaluation of clinical and laboratory, neuroimaging data, and analysis of surgical technique was performed to identify factors contributing to adverse stroke outcome.RESULTS. The mean age of patients was 73.8±11.8 years old. Neurological defiCIT before surgery was 12.8±6.7 points by to NIHSS. Thrombolytic therapy was used in one third of cases, thrombectomy in 92.9 %, and carotid artery stent ing in 2 cases. Successful revascularization (mTICI2b-3) was achieved in 83.3 % of cases. The significant reduction in neurological defiCIT after surgery was achieved to NIHSS 6.0±5.9 points, mRS 2.7±2.1. The mortality rate amounted to 16.7 % of cases. Poor functional outcome (mRS3-5) was significantly associated with: female gender, older age, presence of cardiovascular pathology, recurrent stroke, postoperative tachycardia, low renal tubular filtration rate, hypocoagulation, low cardiac ejection fraction, low aortic valve opening amplitude, high pulmonary hypertension, large left atrial volume, initial severe neurological defiCIT, poor collaterals in the area of cerebral ischemia, proximal internal carotid artery occlusion, hemorrhagic saturation, increased operation time, low degree of revascularization (mTICI0-2a).CONCLUSION. Endovascular surgery has demonstrated its safety and high efficacy in the treatment of in-hospital AIS in surgical hospitalized patients. Endovascular thrombectomies allow to significantly reduce neurological defiCIT and decrease mortality in the severe category of patients with cardioembolic AIS. clinical, laboratory, hemodynamic and neuroimaging factors influencing on poor functional outcome of in-hospital AIS have been determined.

Challenges Experienced by Caregivers in Communicating with Children with Severe to Profound Intellectual Disabilities

<i>Background</i>: Children with severe to profound intellectual disabilities (SPID) may have complex and numerous disabilities, such as intellectual limits and severe deficits in bodily functions. This disorder is typified by issues with speech, language, mobility, agility, and emotional issues providing quality education in appropriate special care centres for children who present with such complex conditions is challenging.<i> Objective</i>: This study explored and described the experiences of caregivers in communicating with children with severe to profound intellectual disabilities in selected special care centres in Gauteng Province.<i> Method</i>: This study followed a qualitative approach and data collection was gathered through in-depth semi-structured interviews, observations in the classroom corroborated children and caregiver`s communication behavior, and document analysis. Eight caregivers were purposively selected to participate in the study. The theory underpinning this study are Ubuntu and Attachment theories. The theories provided the study's foundation and emphasized caring as the central component and influence communication.<i> Result</i>: The thematic analysis revealed the key areas of support needs. The following themes emerged and are as follows: Communication strategies used for children with SPID and, experiences of caregivers in supporting children with SPID. Through these themes the research questions were answered.<i> Conclusion</i>: The study revealed that caregivers' inadequate communication abilities prevent them from responding to the needs of children with SPID. To meet the communication needs of children with SPID, communication requires, relevant communication devices or resources, collaboration with other stakeholders and a qualified trained caregiver.

Intracerebroventricular infusion of secretoneurin inhibits neuronal NLRP3-Apoptosis pathway and preserves learning and memory after cerebral ischemia

Transient global cerebral ischemia (GCI) results in delayed neuronal death, primarily apoptosis, in the hippocampal CA1 subregion, which leads to severe cognitive deficits. While therapeutic hypothermia is an approved treatment for patients following cardiac arrest, it is associated with various adverse effects. Secretoneurin (SN) is an evolutionarily conserved neuropeptide generated in the brain, adrenal medulla and other endocrine tissues. In this study, SN was infused into the rat brain by intracerebroventricular injection 1 day after GCI, and we demonstrated that SN could significantly preserve spatial learning and memory in the Barnes maze tasks examined on days 14–17 after GCI. To further investigate underlying pathways involved, we demonstrated that, on day 5 after GCI, SN could significantly inhibit GCI-induced expression levels of Apoptosis Inducing Factor (AIF) and cleaved-PARP1, as well as neuronal apoptosis and synaptic loss in the hippocampal CA1 region. Additionally, SN could attenuate GCI-induced activation of both caspase-1 and caspase-3, and the levels of pro-inflammatory cytokines IL-1β and IL-18 in the CA1 region. Mechanically, we observed that treatment with SN effectively inhibited NLRP3 protein elevation and the bindings of NLRP3-ASC and ASC-caspase-1 in hippocampal neurons after GCI. In summary, our data indicate that SN could effectively attenuate NLRP3 inflammasome formation, as well as the activation of caspase-1 and -3, the production of pro-inflammatory cytokines, and ultimately the neuronal apoptotic loss induced by GCI. Potential neuronal pyroptosis, or caspase-1-dependent cell death, could also be involved in ischemic neuronal death, which needs further investigation.

MTOR pathway inhibition alters proliferation as well as differentiation of neural stem cells.

Neural stem cells (NSCs) are essential for both embryonic development and adult neurogenesis, and their dysregulation causes a number of neurodevelopmental disorders, such as epilepsy and autism spectrum disorders. NSC proliferation and differentiation in the developing brain is a complex process controlled by various intrinsic and extrinsic stimuli. The mammalian target of rapamycin (mTOR) regulates proliferation and differentiation, among other cellular functions, and disruption in the mTOR pathway can lead to severe nervous system development deficits. In this study, we investigated the effect of inhibition of the mTOR pathway by rapamycin (Rapa) on NSC proliferation and differentiation. The NSC cultures were treated with Rapa for 1, 2, 6, 24, and 48 h. The effect on cellular functions was assessed by immunofluorescence staining, western blotting, and proliferation/metabolic assays. mTOR inhibition suppressed NSC proliferation/metabolic activity as well as S-Phase entry by as early as 1 h of Rapa treatment and this effect persisted up to 48 h of Rapa treatment. In a separate experiment, NSCs were differentiated for 2 weeks after treatment with Rapa for 24 or 48 h. Regarding the effect on neuronal and glial differentiation (2 weeks post-treatment), this was suppressed in NSCs deficient in mTOR signaling, as evidenced by downregulated expression of NeuN, MAP2, and GFAP. We assume that the prolonged effect of mTOR inhibition is realized due to the effect on cytoskeletal proteins. Here, we demonstrate for the first time that the mTOR pathway not only regulates NSC proliferation but also plays an important role in NSC differentiation into both neuronal and glial lineages.

Drought influences the fungal community structure, diversity, and functionality inhabiting the grapevine xylem and enhances the abundance of Phaeomoniella chlamydospora

Grapevine productivity worldwide is increasingly threatened by global warming, potentially exacerbating water scarcity. This study examines drought's effects on grapevine xylem's fungal communities, particularly regarding Phaeomoniella chlamydospora, linked to esca and Petri diseases. Investigating one-year-old grafted grapevines under varied water regimes, including severe, moderate, and no water deficit, the research assesses how drought influences fungal diversity, structure, and interactions within the xylem. Utilizing ITS high-throughput amplicon sequencing and droplet-digital PCR, the study tracks changes in fungal composition and P. chlamydospora prevalence over two growing seasons. The induced water stress not only altered the diversity and composition of the fungal microbiome in the xylem vessels but also affected co-occurrence networks, resulting in less complex networks with fewer correlations between taxa, potentially increasing grapevine vulnerability to various biotic and abiotic stresses. Severe water deficit significantly reduced microbial diversity, leading to a shift in the abundance of pathotrophs such as P. chlamydospora in the xylem. This underscores the interconnectedness between water stress, microbiome dynamics, and plant health. The combination of compromised plant defenses, altered physiological conditions, and shifts in the surrounding microbial community may create conditions conducive to increased P. chlamydospora abundance in the xylem vessels of young vines following water stress.

Effects of intercropping and regulated deficit irrigation on the yield, water and land resource utilization, and economic benefits of forage maize in arid region of Northwest China

Intercropping has been widely recognized to have great advantages in terms of increasing yield, controlling pests and diseases, and saving land, particularly in developing countries. Regulated deficit irrigation reduces water consumption and improves water productivity (WP). However, it is unclear whether the combination of intercropping and deficit irrigation could improve crop yield and WP simultaneously. In this experiment, three planting modes, including forage maize (Zea mays L.) monoculture (M), lablab bean (Lablab purpureus L.) monoculture (L), and maize-lablab bean intercropping (ML) were used. Six irrigation modes were set for each planting mode, including severe water deficit (W1), late water deficit (W2), alternate water deficit (W3), late moderate water deficit (W4), early moderate water deficit (W5), and full irrigation (W6). Results showed that compared with M, the ML treatment significantly increased the fresh forage yield (9.8%–17.0%), hay yield (9.5%–13.1%), crude protein yield (22.9%–25.9%), and WP (7.8%–8.7%). The W5 treatment achieved similar fresh forage yield, hay yield, and crude protein yield as that of the W6 treatment but reduced irrigation water by 25% and increased the WP (21.9%–24.8%). Intercropping achieved a high-water equivalence ratio (WER;1.52–1.81) and land equivalence ratio (LER;1.56–1.84), indicating its advantages over monocultures. The W6 treatment had the lowest WER and LER, suggesting that excessive irrigation can reduce the efficiency of utilizing land and water resource in maze-based forage production. Among all treatments, ML–W5 achieved the highest net income and output to input ratio. Overall, intercropping of forage maize and lablab bean with moderate deficit irrigation at an early stage could be used as a high-yield and efficient forage production system in the arid areas of northwest China.

Unsatisfactory Neurological Outcome in an Intramedullary Thoracic Intermediate-Grade Melanocytoma-Systematic Review and Illustrative Case.

Intramedullary melanocytomas are exceedingly rare, with only twenty-four cases reported up to now. They present as local invasive tumors despite their benign biological behavior. Attempting a complete safe resection often results in severe post-operative neurological deficits, as in our case presented here. A systematic review was conducted across the PubMed and Scopus databases including studies published till February 2024. A total of 19 studies were included, encompassing 24 cases. A similar distribution between sexes was noted (M:F 13:11), with ages ranging from 19 to 79 years. The thoracic segment was most affected, and intermediate-grade melanocytoma (19 cases) was the most common histotype. Radiographically, intramedullary melanocytomas usually appear as hyperintense hemorrhagic lesions peripheral to the central canal with focal nodular enhancement. Intraoperatively, they are black-reddish to tan and are tenaciously adherent lesions. In the sampled studies, IONM employment was uncommon, and post-operative new-onset neurological deficits were described in 16 cases. Adjuvant RT was used in four cases and its value is debatable. Recurrence is common (10 cases), and adjuvant therapies (RT or repeated surgery) seem to play a palliative role. A 68-year-old woman presented with a three-year history of worsening spastic paraparesis and loss of independence in daily activities (McCormick grade 4). An MRI revealed an intramedullary tumor from Th5 to Th7, characterized by T1-weighted hyperintensity and signs of recent intralesional hemorrhage. Multimodal neuromonitoring, comprising the D-Wave, guided the resection of a black-tan-colored tumor with hyper-vascularization and strong adherence to the white matter. During final dissection of the lesion to obtain gross total resection (GTR), a steep decline in MEPs and D-Wave signals was recorded. Post-operatively, the patient had severe hypoesthesia with Th9 level and segmental motor deficits, with some improvement during neurorehabilitation. Histopathology revealed an intermediate-grade melanocytoma (CNS WHO 2021 classification). A four-month follow-up documented the absence of relapse. This literature review highlights that intramedullary T1 hyperintense hemorrhagic thoracic lesions in an adult patient should raise the suspicion of intramedullary melanocytoma. They present as locally aggressive tumors, due to local invasiveness, which often lead to post-operative neurological deficits, and frequent relapses, which overwhelm therapeutic strategies leading to palliative care after several years.

Manganese and Vanadium Co-Exposure Induces Severe Neurotoxicity in the Olfactory System: Relevance to Metal-Induced Parkinsonism.

Chronic environmental exposure to toxic heavy metals, which often occurs as a mixture through occupational and industrial sources, has been implicated in various neurological disorders, including Parkinsonism. Vanadium pentoxide (V2O5) typically presents along with manganese (Mn), especially in welding rods and high-capacity batteries, including electric vehicle batteries; however, the neurotoxic effects of vanadium (V) and Mn co-exposure are largely unknown. In this study, we investigated the neurotoxic impact of MnCl2, V2O5, and MnCl2-V2O5 co-exposure in an animal model. C57BL/6 mice were intranasally administered either de-ionized water (vehicle), MnCl2 (252 µg) alone, V2O5 (182 µg) alone, or a mixture of MnCl2 (252 µg) and V2O5 (182 µg) three times a week for up to one month. Following exposure, we performed behavioral, neurochemical, and histological studies. Our results revealed dramatic decreases in olfactory bulb (OB) weight and levels of tyrosine hydroxylase, dopamine, and 3,4-dihydroxyphenylacetic acid in the treatment groups compared to the control group, with the Mn/V co-treatment group producing the most significant changes. Interestingly, increased levels of α-synuclein expression were observed in the substantia nigra (SN) of treated animals. Additionally, treatment groups exhibited locomotor deficits and olfactory dysfunction, with the co-treatment group producing the most severe deficits. The treatment groups exhibited increased levels of the oxidative stress marker 4-hydroxynonenal in the striatum and SN, as well as the upregulation of the pro-apoptotic protein PKCδ and accumulation of glomerular astroglia in the OB. The co-exposure of animals to Mn/V resulted in higher levels of these metals compared to other treatment groups. Taken together, our results suggest that co-exposure to Mn/V can adversely affect the olfactory and nigral systems. These results highlight the possible role of environmental metal mixtures in the etiology of Parkinsonism.

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve.

JOURNAL/nrgr/04.03/01300535-202506000-00029/figure1/v/2024-08-05T133530Z/r/image-tiff Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits (tNGCs). However, the use of tNGCs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects (typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGC would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGCs and compared the various features of these improved silk+ tNGCs with the tubes without holes (silk- tNGCs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk+ tNGCs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk+ group was found compared with autologous nerve transplants and silk-, accompanied by improved axon regeneration at the distal coaptation point compared with the silk- tNGCs at 7 weeks postoperatively. In the 15-mm (critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk+ tNGCs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGCs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimization of the macroscopic holes silk+ tNGC approach containing macroscopic holes might result in improved grafting technology suitable for future clinical use.

Intermittent Metabolic Switching and Vascular Cognitive Impairment.

Intermittent fasting (IF), a dietary pattern alternating between eating and fasting periods within a 24-hour cycle, has garnered recognition for its potential to enhance both healthspan and lifespan in animal models and humans. It also shows promise in alleviating age-related diseases, including neurodegeneration. Vascular cognitive impairment (VCI) spans a severity range from mild cognitive deficits to severe cognitive deficits and loss of function in vascular dementia. Chronic cerebral hypoperfusion has emerged as a significant contributor to VCI, instigating vascular pathologies such as microbleeds, blood-brain barrier dysfunction, neuronal loss, and white matter lesions. Preclinical studies in rodents strongly suggest that IF has the potential to attenuate pathological mechanisms, including excitotoxicity, oxidative stress, inflammation, and cell death pathways in VCI models. Hence, this supports evaluating IF in clinical trials for both existing and at-risk VCI patients. This review compiles existing data supporting IF's potential in treating VCI-related vascular and neuronal pathologies, emphasizing the mechanisms by which IF may mitigate these issues. Hence providing a comprehensive overview of the available data supporting IF's potential in treating VCI by emphasizing the underlying mechanisms that make IF a promising intervention for VCI.

Introduction: A Practical Guide to Central Nervous System Malformations—From Genetics, to Diagnosis and Treatment

AbstractCentral nervous system (CNS) malformations encompass diverse congenital anomalies impacting brain and spinal cord development, profoundly affecting neurological function. They arise from disruptions in embryonic neural tube formation, neuronal migration, and cortical organization. This abstract provides a comprehensive overview of CNS malformations, covering classification, etiology, clinical manifestations, and diagnostic challenges. CNS malformations fall into distinct groups: neural tube defects (e.g., anencephaly, spina bifida), resulting from incomplete neural tube closure; malformations of cortical development (e.g., lissencephaly, polymicrogyria), featuring irregularities in cortical folding; and anomalies affecting structures like the corpus callosum, cerebellum, and CNS vasculature, alongside conditions such as hydrocephalus and Chiari malformations. Genetic factors, including mutations in LIS1, DCX, and RELN, contribute significantly, while environmental factors like maternal folic acid deficiency also play a role. Some malformations occur in genetic syndromes (e.g., tuberous sclerosis, neurofibromatosis). Clinical presentations vary, with neural tube defects typically presenting severe deficits at birth, while cortical malformations manifest as intellectual disabilities, seizures, and motor deficits. Hydrocephalus elevates intracranial pressure, and Chiari malformations cause headaches and neurological symptoms. Diagnosis necessitates a multidisciplinary approach involving clinical evaluation, neuroimaging, genetic testing, and histopathological analysis. Prenatal diagnosis via ultrasound and magnetic resonance imaging is crucial for planning interventions, while postnatal diagnosis relies on clinical and imaging findings.Understanding CNS malformations is vital for early detection, intervention, and comprehensive care provision. Advances in genetics and neuroimaging offer hope for improved outcomes and better quality of life for affected individuals.

The rhizosphere of a drought-tolerant plant species in Morocco: A refuge of high microbial diversity with no taxon preference.

Arid and semi-arid areas are facing increasingly severe water deficits that are being intensified by global climate changes. Microbes associated with plants native to arid regions provide valuable benefits to plants, especially in water-stressed environments. In this study, we used 16S rDNA metabarcoding analysis to examine the bacterial communities in the bulk soil, rhizosphere and root endosphere of the plant Malva sylvestris L. in Morocco, along a gradient of precipitation. We found that the rhizosphere of M. sylvestris did not show significant differences in beta-diversity compared to bulk soil, although, it did display an increased degree of alpha-diversity. The endosphere was largely dominated by the genus Rhizobium and displayed remarkable variation between plants, which could not be attributed to any of the variables observed in this study. Overall, the effects of precipitation level were relatively weak, which may be related to the intense drought in Morocco at the time of sampling. The dominance of Rhizobium in a non-leguminous plant is particularly noteworthy and may permit the utilization of this bacterial taxon to augment drought tolerance; additionally, the absence of any notable selection of the rhizosphere of M. sylvestris suggests that it is not significatively affecting its soil environment.

Early adversity causes sex-specific deficits in perforant pathway connectivity and contextual memory in adolescent mice

BackgroundEarly life adversity impairs hippocampal development and function across diverse species. While initial evidence indicated potential variations between males and females, further research is required to validate these observations and better understand the underlying mechanisms contributing to these sex differences. Furthermore, most of the preclinical work in rodents was performed in adult males, with only few studies examining sex differences during adolescence when such differences appear more pronounced. To address these concerns, we investigated the impact of limited bedding (LB), a mouse model of early adversity, on hippocampal development in prepubescent and adolescent male and female mice.MethodsRNA sequencing, confocal microscopy, and electron microscopy were used to evaluate the impact of LB and sex on hippocampal development in prepubescent postnatal day 17 (P17) mice. Additional studies were conducted on adolescent mice aged P29-36, which included contextual fear conditioning, retrograde tracing, and ex vivo diffusion magnetic resonance imaging (dMRI).ResultsMore severe deficits in axonal innervation and myelination were found in the perforant pathway of prepubescent and adolescent LB males compared to LB female littermates. These sex differences were due to a failure of reelin-positive neurons located in the lateral entorhinal cortex (LEC) to innervate the dorsal hippocampus via the perforant pathway in males, but not LB females, and were strongly correlated with deficits in contextual fear conditioning.ConclusionsLB impairs the capacity of reelin-positive cells located in the LEC to project and innervate the dorsal hippocampus in LB males but not female LB littermates. Given the critical role that these projections play in supporting normal hippocampal function, a failure to establish proper connectivity between the LEC and the dorsal hippocampus provides a compelling and novel mechanism to explain the more severe deficits in myelination and contextual freezing found in adolescent LB males.

Impact of Iron Supplementation on Children with Severe Attention Deficit Hyperactive Disorder- A Randomized Clinical Trial

Background: Iron acts as a risk factor and psychostimulant modulator in treatment of ADHD with iron deficiency anemia. Objective: To see the impact of iron supplementation on severe ADHD children. Materials and Methods: This randomized controlled trial conducted in the OPD, Pediatric Neurology from July 2019 to January 2020; NINS 50 children of severe ADHD with iron deficiency were enrolled. Participants were randomized into group A (25 cases) given a combination of Methylphenidate and iron, and group B (25 cases) given Methylphenidate alone for 3 months. Conner’s rating scale, CBC and serum ferritin was evaluated after one and three months, severity was compared between treatment groups. Analysis of data was done by SPSS version of 22.0. Result: Combined ADHD, poor academic performance, poor appetite, frequent infection was common features of IDA among the cases. All hematological parameters were increased from baseline to 1 month and 3 months follow up in all cases but significantly improved in Iron receiving groups. the severity of T scores of ADHD index were decreased at 1 month (p=0.047) and 3 months (p= 0.026) after intervention. Conclusion: This study concluded that iron supplementation along with psychostimulant found better response in severe ADHD children BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 48-53