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Mitochondrial diseases are complex disorders caused by nuclear or mitochondrial DNA mutations, leading to oxidative phosphorylation deficiency and excessive production of reactive oxygen species (ROS). While ROS have been well established in the pathogenesis of these diseases, the role of reactive nitrogen species (RNS) remains unclear. In this study, we performed a quantitative analysis of muscle fibers to investigate the relationship between protein nitration and mitochondrial abnormalities (mitochondrial proliferation and cytochrome-c oxidase (COX) deficiency) and factors like genotype, muscle damage, and age. A total of 1961 muscle fibers (303 from 4 controls and 1658 from 29 patients with mitochondrial diseases) were analyzed by immunostaining for nitro-tyrosine. Contrary to previous findings, which identified nitro-tyrosine only in small muscle vessels, we observed a broader distribution affecting the sarcolemma and sarcoplasm. Using multivariate techniques, we identified a significant correlation between protein nitration and mitochondrial proliferation but found no associations with COX deficiency, age, muscle damage, or genotype. These findings suggest that nitrative stress may contribute to mitochondrial dysfunction or play a role in signaling processes that induce mitochondrial biogenesis. Our results provide new insights into the molecular mechanisms of mitochondrial diseases and highlight the potential relevance of protein nitration. [ABSTRACT FROM AUTHOR] more...

Spinal cord injury (SCI) can cause significant motor, sensory, and autonomic dysfunction by disrupting neural connections. As a result, it is a global health challenge that requires innovative interventions to improve outcomes. This review assesses the wide-ranging impacts of SCI and focuses on the laparoscopic implantation of neuroprosthesis (LION) as an emerging and promising rehabilitation technique. The LION technique involves the surgical implantation of electrodes on lumbosacral nerves to stimulate paralyzed muscles. Recent findings have demonstrated significant improvements in mobility, sexual function, and bladder/bowel control in chronic SCI patients following LION therapy. This manuscript revisits the potential physiological mechanisms underlying these results, including neuroplasticity and modulation of autonomic activity. Additionally, we discuss potential future applications and amendments of LION therapy. This study emphasizes the potential of neuromodulation as a complementary approach to traditional rehabilitation, that can provide a beacon of hope for improving functionality and quality of life for individuals with SCI. [ABSTRACT FROM AUTHOR] more...

The Asia‐Pacific Plasma Leaders' Network (APPLN) plays a crucial role in addressing the regional shortage of plasma‐derived medicinal products (PDMPs), particularly in low‐ and middle‐income countries (LMICs). It provides a platform for experts to share their expertise and drive multi‐stakeholder collaborations. While several PDMPs are acknowledged by the World Health Organization (WHO) as life‐saving therapeutics on the Model List of Essential Medicine for treating various chronic and acute life‐threatening diseases, there are still many inadequacies in the availability and affordability of PDMPs. These challenges arise from insufficient domestic supplies of plasma suitable for fractionation, as well as a lack of technical and financial capabilities to implement contract or domestic plasma fractionation programmes. At two separate dialogue forums organized by the APPLN in 2023, experts discussed the unmet needs of PDMPs for individuals living with haemophilia and immunodeficiencies in the region. They also highlighted the limited access to early diagnosis and patient‐centred care in several LMICs. To address these issues, there is an urgent need to increase the availability of high‐quality domestic plasma for fractionation. Adopting a stepwise approach to utilize unused recovered plasma and establishing contract fractionation programmes could be viable strategies to potentially enhance PDMP availability in LMICs. However, achieving this goal requires improving existing domestic infrastructures for blood collection, implementing adequate policy reforms and fostering competent local leadership. Ultimately, there is no 'one‐size‐fits‐all' strategy for securing safe plasma proteins for all patients in need. Collaborative efforts are essential for achieving progressive self‐sufficiency in PDMPs. [ABSTRACT FROM AUTHOR] more...

Background/Objectives: Dopamine dysfunction (DA) is a hallmark of many neurological disorders. In this case, the mechanism of changes in dopamine transmission on behavior remains unclear. This study is a look into the intricate link between disrupted DA signaling, neuronal activity patterns, and behavioral abnormalities in a hyperdopaminergic animal model. Methods: To study the relationship between altered DA levels, neuronal activity, and behavioral deficits, local field potentials (LFPs) were recorded during four different behaviors in dopamine transporter knockout rats (DAT-KO). At the same time, local field potentials were recorded in the striatum and prefrontal cortex. Correlates of LFP and accompanying behavioral patterns in genetically modified (DAT-KO) and control animals were studied. Results: DAT-KO rats exhibited desynchronization between LFPs of the striatum and prefrontal cortex, particularly during exploratory behavior. A suppressive effect of high dopamine levels on the striatum was also observed. Wild-type rats showed greater variability in LFP patterns across certain behaviors, while DAT-KO rats showed more uniform patterns. Conclusions: The decisive role of the synchrony of STR and PFC neurons in the organization of motor acts has been revealed. The greater variability of control animals in certain forms of behavior probably suggests greater adaptability. More uniform patterns in DAT-KO rats, indicating a loss of striatal flexibility when adapting to specific motor tasks. It is likely that hyperdopaminergy in the DAT-KO rat reduces the efficiency of information processing due to less synchronized activity during active behavior. [ABSTRACT FROM AUTHOR] more...

Plasma‐derived medicinal products (PDMPs) are recognized internationally as essential medicines required to treat various acute and chronic conditions including congenital deficiencies of plasma proteins in haemophilia and primary immune deficiency. Global provision of these medicines is dominated by a small number of commercial companies, influencing the price and availability of the products. Achieving a level of strategic independence from this dominance is now seen as a public health priority in many countries. During the Regional Congress of the International Society for Blood Transfusion (ISBT) in Cape Town, South Africa, in November 2023, around 50 delegates from 24 countries participated in a workshop (WS) organized jointly by the International Plasma and Fractionation Association (IPFA) and the ISBT Working Party on Global Blood Safety on pathways towards provision of PDMPs from domestic plasma independent of commercial purchase in the open market. The WS was structured around three themes, each addressed by a separate group:Quality/safety requirements for plasma for fractionation (PfF)Stepwise access for safe plasma proteinsApproaching contract fractionation A synthesis of conclusions from these groups included the following:The need to acquire support from government authorities for a national plasma policy, recognizing the difficulties posed by unstable political and bureaucratic environments.The value of embedding plasma and PDMPs within a patient blood management (PBM) paradigm to promote optimal clinical use of PDMPs.Training of blood/plasma collection personnel in the relevant principles of Good Manufacturing Practice (GMP), coupled with regulatory oversight of plasma product production in the engaged jurisdictions.Appreciation that limited access to contract fractionation may necessitate a stepwise approach, which may include small‐scale preparation of versions of essential plasma proteins as an intermediate phase towards the manufacture of industrial‐scale PDMPs from domestic plasma. [ABSTRACT FROM AUTHOR] more...

Industrial plasma fractionation, a complex and highly regulated technology, remains largely inaccessible to many low‐ and middle‐income countries (LMICs). This, combined with the limited availability and high cost of plasma‐derived medicinal products (PDMPs), creates deficiency of access to adequate treatment for patients in resource‐limited countries, and leads to their suffering. Meanwhile, an increasing number of LMICs produce surplus plasma, as a by‐product of red blood cell preparation from whole blood, that is discarded because of the lack of suitability for fractionation. This article reviews pragmatic technological options for processing plasma collected from LMICs into therapies and supports a realistic stepwise approach aligned with recent World Health Organization guidance and initiatives launched by the Working Party for Global Blood Safety of the International Society of Blood Transfusion. When industrial options based on contract or toll plasma fractionation programme and, even more, domestic fractionation facilities require larger volumes of quality plasma than is produced, alternative methods should be considered. In‐bag minipool or small‐scale production procedures implementable in blood establishments or national service centres are the only realistic options available to gradually reduce plasma wastage, provide safer treatments for patients currently treated with non‐pathogen‐reduced blood products and concurrently improve Good Manufacturing Practice (GMP) levels with minimum capital investment. As a next step, when the available volume of quality‐assured plasma reaches the necessary thresholds, LMICs could consider engaging with an established fractionator in a fractionation agreement or a contract in support of a domestic fractionation facility to improve the domestic PDMP supply and patients' treatment. [ABSTRACT FROM AUTHOR] more...

Explores the effect of note-taking instruction on ninth graders' comprehension of high- and low-interest passages on teacher-made, objective tests. Finds a statistically significant interaction between note-taking training and passage type that suggests the training was more effective for the low-interest than the high-interest passage. Concludes that there was no statistically significant interaction between ability level and passage type. (SC) more...