Intravital microscopic observation of the microvasculature during hemodialysis in healthy rats

Hemodialysis (HD) provides life-saving treatment for kidney failure. Patient mortality is extremely high, with cardiovascular disease (CVD) being the leading cause of death. This results from both a high underlying burden of cardiovascular disease, as well as additional physiological stress from the HD procedure itself. Clinical observations indicate that HD is associated with microvascular dysfunction (MD), underlining the need for a fundamental pathophysiological assessment of the microcirculatory consequences of HD. We therefore successfully developed an experimental small animal model, that allows for a simultaneous real-time assessment of the microvasculature. Using in-house built ultra-low surface area dialyzers and miniaturized extracorporeal circuit, we successfully dialyzed male Wistar Kyoto rats and combined this with a simultaneous intravital microscopic observation of the EDL microvasculature. Our results show that even in healthy animals, a euvolemic HD procedure can induce a significant systemic hemodynamic disturbance and induce disruption of microvascular perfusion (as evidence by a reduction in the proportion of the observed microcirculation receiving blood flow). This study, using a new small animal hemodialysis model, has allowed direct demonstration that microvascular blood flow in tissue in skeletal muscle is acutely reduced during HD, potentially in concert with other microvascular beds. It shows that preclinical small animal models can be used to further investigate HD-induced ischemic organ injury and allow rapid throughput of putative interventions directed at reducing HD-induced multi-organ ischemic injury.

Direct demonstration of complete combustion of gas-suspended powder metal fuel combustion using bomb calorimetry

Off-the-shelf calorimeters are typically used for hydrocarbon-based fuels and not designed for simulating metal powder oxidation in gaseous environments. We have developed a method allowing a typical bomb calorimeter to accurately measure heat released during combustion and achieve nearly 100% of the reference heat of combustion from powder fuels such as aluminum. The modification uses a combustible organic dispersant to suspend the fuel particles and promote more complete combustion. The dispersant is a highly porous organic starch-based material (i.e., packing peanut) and allows the powder to burn as discrete particles thereby simulating dust-type combustion environments. The demonstrated closeness of measured Al heat of combustion to its reference value is evidence of complete metal combustion achieved in our experiment. Beyond calorific output under conditions simulating real reactive systems, we demonstrate that the calorimeter also allows characterization of the temporal heat release from the reacting material and this data can be extracted from the instrument. The rate of heat release is an important additional parameter characterizing the combustion process. The experimental approach described will impact future measurements of heat released during combustion from solid fuel powders and enable scientists to quantify the energetic performance of metal fuel more accurately as well as the transient thermal behavior from combusting metal powders.

Pendampingan pengajaran Metode Iqro’ untuk guru-guru di TPA Hayatinnur Tambun Selatan Bekasi

The Iqra method is one of the methods in teaching the Qur'an. This method uses the Iqra book, consisting of 6 levels or volumes. Each volume has its difficulties, from volume 1 being the easiest to volume 6 being the most difficult. Many Al-Qur’an Education Parks (TPA) use this method, but in reality, TPA teachers still do not fully understand this Iqra teaching method. Therefore, this PKM aims to identify and improve the quality standards of teaching reading Al-Qur’an using the Iqra method through mentoring activities. Partners in this service come from all teachers and guardians of students at TPA Hayatinnur. This service was held on February 15-16, 2021, at the Hayatinnur TPA hall, attended by four teachers and 24 student guardians divided into two shifts. The method used in this implementation is a direct demonstration or training on the Iqra Method Teaching technique, Class Management, and Classical Iqra Teaching & Problem Solving. After the mentoring was done, it was clear that the teachers had begun to master teaching techniques.

Rat sensitivity to multipoint statistics is predicted by efficient coding of natural scenes

Efficient processing of sensory data requires adapting the neuronal encoding strategy to the statistics of natural stimuli. Previously, in Hermundstad et al., 2014, we showed that local multipoint correlation patterns that are most variable in natural images are also the most perceptually salient for human observers, in a way that is compatible with the efficient coding principle. Understanding the neuronal mechanisms underlying such adaptation to image statistics will require performing invasive experiments that are impossible in humans. Therefore, it is important to understand whether a similar phenomenon can be detected in animal species that allow for powerful experimental manipulations, such as rodents. Here we selected four image statistics (from single- to four-point correlations) and trained four groups of rats to discriminate between white noise patterns and binary textures containing variable intensity levels of one of such statistics. We interpreted the resulting psychometric data with an ideal observer model, finding a sharp decrease in sensitivity from two- to four-point correlations and a further decrease from four- to three-point. This ranking fully reproduces the trend we previously observed in humans, thus extending a direct demonstration of efficient coding to a species where neuronal and developmental processes can be interrogated and causally manipulated.

Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response

Oropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivated by these findings, neurotropism and neuropathogenesis of OROV have been investigated in vivo in murine models, which do not fully recapitulate the complexity of the human brain. Here we have used slice cultures from adult human brains to investigate whether OROV is capable of infecting mature human neural cells in a context of preserved neural connections and brain cytoarchitecture. Our results demonstrate that human neural cells can be infected ex vivo by OROV and support the production of infectious viral particles. Moreover, OROV infection led to the release of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and diminished cell viability 48 h post-infection, indicating that OROV triggers an inflammatory response and tissue damage. Although OROV-positive neurons were observed, microglia were the most abundant central nervous system (CNS) cell type infected by OROV, suggesting that they play an important role in the response to CNS infection by OROV in the adult human brain. Importantly, we found no OROV-infected astrocytes. To the best of our knowledge, this is the first direct demonstration of OROV infection in human brain cells. Combined with previous data from murine models and case reports of OROV genome detection in cerebrospinal fluid from patients, our data shed light on OROV neuropathogenesis and help raising awareness about acute and possibly chronic consequences of OROV infection in the human brain.

Unilateral Corneal Insult Also Alters Sensory Nerve Activity in the Contralateral Eye

After the unilateral inflammation or nerve lesion of the ocular surface, the ipsilateral corneal sensory nerve activity is activated and sensitized, evoking ocular discomfort, irritation, and pain referred to the affected eye. Nonetheless, some patients with unilateral ocular inflammation, infection, or surgery also reported discomfort and pain in the contralateral eye. We explored the possibility that such altered sensations in the non-affected eye are due to the changes in their corneal sensory nerve activity in the contralateral, not directly affected eye. To test that hypothesis, we recorded the impulse activity of the corneal mechano- and polymodal nociceptor and cold thermoreceptor nerve terminals in both eyes of guinea pigs, subjected unilaterally to three different experimental conditions (UV-induced photokeratitis, microkeratome corneal surgery, and chronic tear deficiency caused by removal of the main lacrimal gland), and in eyes of naïve animals ex vivo. Overall, after unilateral eye damage, the corneal sensory nerve activity appeared to be also altered in the contralateral eye. Compared with the naïve guinea pigs, animals with unilateral UV-induced mild corneal inflammation, showed on both eyes an inhibition of the spontaneous and stimulus-evoked activity of cold thermoreceptors, and increased activity in nociceptors affecting both the ipsilateral and the contralateral eye. Unilateral microkeratome surgery affected the activity of nociceptors mostly, inducing sensitization in both eyes. The removal of the main lacrimal gland reduced tear volume and increased the cold thermoreceptor activity in both eyes. This is the first direct demonstration that unilateral corneal nerve lesion, especially ocular surface inflammation, functionally affects the activity of the different types of corneal sensory nerves in both the ipsilateral and contralateral eyes. The mechanisms underlying the contralateral affectation of sensory nerves remain to be determined, although available data support the involvement of neuroimmune interactions. The parallel alteration of nerve activity in contralateral eyes has two main implications: a) in the experimental design of both preclinical and clinical studies, where the contralateral eyes cannot be considered as a control; and, b) in the clinical practice, where clinicians must consider the convenience of treating both eyes of patients with unilateral ocular conditions to avoid pain and secondary undesirable effects in the fellow eye.

Pemberdayaan Masyarakat dalam Pemanfaatan Kalakai (Stenochlaena palustris (Burm. F) Bedd.) sebagai Antioksidan Alami pada Kelompok Ibu-Ibu PKK di Kelurahan Palam, Kecamatan Cempaka, Banjarbaru

Prevention of the spread of Covid-19 is an essential effort when there are still highly favorable rates & deaths. The provision of education to prevent the spread of Covid-19 is always carried out with community awareness-based programs to maintain immunity. Community service by utilizing kalakai as a natural antioxidant becomes one of the alternatives to support the government. Kalakai (Stenochlaena palustris (Burm. F) Bedd.)) is a nail plant that is one of the plants with antioxidants typical of Kalimantan whose history is used as traditional medicine. This potential can be utilized and applied through the empowerment of the community of Palam Village, Cempaka Subdistrict, where many Kalakai plants grow wild. The problems found include lack of information and lack of skills of citizens in food processing based on Kalakai plants, especially in terms of food processing with high antioxidants in the form of counseling to the PKK mothers group Palam Cempaka-Banjarbaru Village. The activity method is the extension of educational provision, namely the theory of antioxidants and the potential of Kalakai, and the direct demonstration/practice of making syrups, teas, and kalakai candy. Residents expect to develop processed food products into UMKM, especially of Palam village, as a business opportunity to improve people's living standards.

Psychological Insulin Resistance: Key Factors and Intervention

Insulin is a mainstay of treatment in patients with type 2 diabetes mellitus to control blood sugar levels and reduce the risk of diabetes complications, but psychological insulin resistance can delay insulin treatment. Psychological insulin resistance can be defined as a negative attitude and feelings toward insulin treatment experienced by diabetics. Factors influencing psychological insulin resistance include a lack of understanding of diabetic pathophysiology, a negative attitude toward insulin treatment, anxiety about insulin therapy complications and hypoglycemia, distorted beliefs, daily constraints, fear or pain from injections, and discomfort. Various approaches to psychological insulin resistance involve direct demonstration of the insulin administration processes, education regarding diabetic pathophysiology and insulin action, assessment and evaluation of the degree of psychological insulin resistance, patient group training, building correct support systems, and providing contacts (e.g., diabetes center, diabetes nurse educator). The role of healthcare providers is important in reducing patients’ psychological insulin resistance through various interventions.

Psychological Insulin Resistance: Key Factors and Intervention

Insulin is a mainstay of treatment in patients with type 2 diabetes mellitus to control blood sugar levels and reduce the risk of diabetes complications, but psychological insulin resistance can delay insulin treatment. Psychological insulin resistance can be defined as a negative attitude and feelings toward insulin treatment experienced by diabetics. Factors influencing psychological insulin resistance include a lack of understanding of diabetic pathophysiology, a negative attitude toward insulin treatment, anxiety about insulin therapy complications and hypoglycemia, distorted beliefs, daily constraints, fear or pain from injections, and discomfort. Various approaches to psychological insulin resistance involve direct demonstration of the insulin administration processes, education regarding diabetic pathophysiology and insulin action, assessment and evaluation of the degree of psychological insulin resistance, patient group training, building correct support systems, and providing contacts (e.g., diabetes center, diabetes nurse educator). The role of healthcare providers is important in reducing patients’ psychological insulin resistance through various interventions.

Tracking extracellular vesicle (EV) cargo as a platform for studying EVomics, signaling, and targeting in vivo

Extracellular vesicle (EV)-based signaling is a challenge to study, due to EV small size, heterogeneity, and limited information on cargo content in vivo. We present Caenorhabditis elegans as a discovery platform that allows single EV tracking from source to target tissue in living animals. We enriched ciliary EVs using GFP-tagged PKD-2 cargo followed by mass spectrometry analysis to identify 2,888 cargo candidates. By integrating our dataset with single-cell transcriptomic data, we identified EV cargo produced by individual neurons and other cell and tissue types. A single cilium produces multiple EVs with distinct protein content. Ciliary EVs carry nucleic acid binding proteins. We observed transfer of EV cargo from the male reproductive tract to the hermaphrodite uterus during mating, a direct demonstration of animal-to-animal EV targeting.