Advances in experimental medicine and biology最新文献

The development of a fully functional four-chambered heart is critically dependent on the correct formation of the structures that separate the atrial and ventricular chambers. Perturbation of this process typically results in defects that allow mixing of oxygenated and deoxygenated blood. Atrioventricular septal defects (AVSD) form a class of congenital heart malformations that are characterized by the presence of a primary atrial septal defect (pASD), a common atrioventricular valve (cAVV), and frequently also a ventricular septal defect (VSD). While AVSD were historically considered to result from failure of the endocardial atrioventricular cushions to properly develop and fuse, more recent studies have determined that inhibition of the development of other components of the atrioventricular mesenchymal complex can lead to AVSDs as well. The role of the dorsal mesenchymal protrusion (DMP) in AVSD pathogenesis has been well-documented in studies using animal models for AVSDs, and in addition, preliminary data suggest that the mesenchymal cap situated on the leading edge of the primary atrial septum may be involved in certain situations as well. In this chapter, we review what is currently known about the molecular mechanisms and animal models that are associated with the pathogenesis of AVSD.

Measuring oxygen (O₂) in tissues has been a central theme of the International Society on Oxygen Transport to Tissue (ISOTT) since its founding 50 years ago in 1973. The initial presentations by many distinguished members reflect this focus and demonstrate the importance of the contributions of the members of ISOTT. This paper considers their work and its legacy in the context of the continuing challenges of making meaningful measurements of O₂ in tissue. Because many technical, physiological, and pathophysiological factors are directly or implicitly involved in obtaining any measured value of O₂ in living tissues, interpretations of what the measured value represents and its biological implications need to take these factors into account. The challenges arise from two very simple but painfully true factors that make it challenging to obtain measurements of O₂ in tissues in vivo that are useful for the understanding of physiological and pathophysiological processes. First, throughout the volume of functioning tissue that is assessed by any technique, there is a complex spatial heterogeneity of O₂ levels. No technique can usually fully represent this complexity in a given measurement, because the heterogeneity extends from the environment in the tissue surrounding cells to variations within the cell. Therefore, the value of the output from a measurement inevitably consists of a complex, averaged summary of O₂ in the tissue. Second, the levels of O₂ are constantly changing in living tissues (variations occur in seconds, minutes, hours, and/or days and differ by location) at rates that are difficult to resolve for available techniques, because they occur faster than data acquisition time and/or cannot be used as frequently as needed to follow the longer-term changes. However, as demonstrated in research reported in the publications from ISOTT, studies of O₂ in tissue, in spite of the potential ambiguities in the measured values, can provide very valuable insights into physiology and pathophysiology. This is most likely to occur if researchers explicitly recognise why and how their measurement does not fully portray the complexity of O₂. When measurements can be repeated, the resulting change between measurements provides information about the dynamics of the physiology and pathophysiology. Assessing change in O₂ levels can also provide evidence about responses to treatments. Similarly, finding evidence of hypoxia, even though it does not capture the heterogeneity and dynamics actually happening in the tissue, can still inform clinical care if the measurement is well-understood.

The purpose of this study was to examine the effects on prefrontal cortex (PFC) activity of listening to pleasant sounds (PS) while walking, gum chewing (GCh), or performing the dual task of walking and gum chewing at the same time (walking + GCh). A total of 11 healthy adult male volunteers participated in the study (mean age: 29.54 ± 3.37). The block design of the trial consisted of a 30-sec rest, a 60-sec task (target task or control task), and a 30-sec rest. There were three target task conditions: walking, GCh, and the dual task. All of these were performed while listening to PS. The control condition was rest (no exercise) while listening to PS. The outcomes measured and measurements used were PFC activity using two-channel near-infrared spectroscopy and participant self-evaluation of the pleasantness of the experience using the visual analogue scale (VAS). Compared to the control condition, there was significantly greater PFC activation during the GCh and the walking + GCh tasks. Compared to the control condition, GCh and walking + GCh showed significantly greater activation on the VAS measure. In conclusion, listening to PS while GCh or walking + GCh increases PFC activity in the lower central region and induces positive emotional change.

Methods evaluating the status of the injured brain have evolved over the past 63 years since Lundberg first reported clinical measurement of intracranial pressure (ICP) to evaluate the status of the injured brain (Lundberg, Acta Psychiatr Scand Suppl. 36:1-193, 1960). Subsequent evaluation involved measurement of the autoregulatory capacity of the brain by measuring cerebral blood flow (CBF) with decreasing mean arterial pressure (MAP) to define the critical CPP where the vasodilatory capacity of the cerebral circulation is exceeded and CBF begins to fall (CPP of 50 mmHg). A seminal advance was made by Marmarou (Marmarou et al., J Neurosurg. 48:332-344, 1978) who measured brain compliance by injecting a bolus of saline into the intracranial catheter while measuring the rise in intracranial pressure (ICP) otherwise known as induced pressure reactivity (iPRx). Seeking to utilise continuous measurement of iPRx in traumatic brain injury (TBI) patients with continuous monitoring of ICP, the ICP response to arterial pulsations was developed to evaluate the optimal CPP patients with raised ICP by the arterial pulsations-based iPRx. A similar approach was made with Doppler measurement of CBF with arterial pulsations for iCVRx to guide optimal CPP (CPPopt). Both iPRx and iCVRx are associated with microvascular shunts (MVS) and can accurately measure the critical CPP, whereas the CBF autoregulation curve by decreasing MAP does not. Sophisticated continuous multimodal monitoring established with ICM+ algorithms successfully identifies CPPopt for ICP control and identifies CBF dysregulation as related to outcome, but does not provide insights into the mechanisms involved in the loss of CBF autoregulation as related to increased ICP and potentially effective treatments (Froese et al., Neurocrit Care. 34:325-335, 2021).

Background: Tissue mimicking optical phantoms are commonly used to calibrate or validate the performance of near-infrared spectroscopy or tomography. Human tissue is not only irregular in shape, but also exhibits dynamic behaviour, which can cause changes in optical properties. However, existing phantoms lack complex structures and/or continuously varying optical properties.

Aim: The project aimed to design, fabricate and characterise a novel phantom system for testing near-infrared imaging devices.

Material and methods: We designed a dynamic tissue-mimicking phantom platform which features arbitrary internal shapes and variable optical properties. The solid part of phantom was made of silicone material with absorbing and scattering properties similar to the brain. We printed a semi-ellipsoidal sphere (a major axis = 20 mm and a minor axis = the third axis = 12 mm) using a water-soluble material polyvinyl alcohol (PVA). The shape was placed at the depth of 5 mm in the silicone bulk. The desired internal hollow structure was formed after curing and submerging the phantom in water. The liquid part contained dyes and Intralipid. The optical properties within the internal shape were adjusted by injecting the liquid solutions of varying dye concentrations with a syringe pump at a constant rate. The phantom was measured by a frequency domain near-infrared spectroscopy (FD NIRS) and imaged by a time domain near-infrared optical tomography (TD NIROT).

Results and discussion: A dynamic phantom system with a complex internal structure and varying optical properties was created. Changes in light intensity were detected by the FD NIRS. The internal structure of this phantom was accurately recovered by NIROT image reconstruction.

Conclusion: We successfully developed a novel phantom system with an internal complex shape and continuously adjustable optical properties. This phantom was accurately imaged using NIROT, and the changing light intensity was detected by NIRS. It is a valuable tool for validating optical technologies.

Recent studies revealed that excessive supplemental oxygen, such as inhaled 100% O₂, damages various organ functions in post-cardiac arrest (CA) patients. Optimal indicators of supplemental oxygen are therefore important to prevent hyperoxic organ injuries. In this study, we evaluated a hyperoxic pulmonary injury and assessed the association between alveolar-arterial oxygen difference (AaDO₂) and a degree of lung oedema. In this study, we focused on the hyperoxia-induced lung injury and its association with changes of gas-exchange parameters in post-CA rats. Rats were resuscitated from 10 min of asphyxial CA and stratified into two groups: those with inhaled 100% O₂ (CA-FiO₂ 1.0) and those with 30% O₂ (CA-FiO₂ 0.3). We prepared a sham surgery group for comparison (sham-FiO₂ 0.3). After 2 h, animals were sacrificed, and the lung wet-to-dry (W/D) weight ratio was measured. We collected blood gas results and measured the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (p/f ratio), and calculated AaDO₂. The lung W/D ratio in the CA-FiO₂ 1.0 group (5.8 ± 0.26) was higher than in the CA-FiO₂ 0.3 (4.6 ± 0.42) and sham-FiO₂ 0.3 groups (4.6 ± 0.38, p < 0.01). There was a significant difference in AaDO₂ between CA-FiO₂ 1.0 (215 ± 49.3) and, CA-FiO₂ 0.3 (36.8 ± 32.3), and sham-FiO₂ 0.3 groups (49.0 ± 20.5, p < 0.01). There were also significant changes in pH and blood lactate levels in the early phase among the three groups. AaDO₂ showed the strongest correlation with W/D ratio (r = 0.9415, p < 0.0001), followed by pH (r = -0.5131, p = 0.0294) and p/f ratio (r = -0.3861, p = 0.1135). Hyperoxic injury might cause the pulmonary oedema after CA. Measuring respiratory quotient (RQ) in rodents enabled an accurate calculation for AaDO₂ at a variety level of inhaled O₂. Given that AaDO₂ measurement is non-invasive, we therefore consider AaDO₂ to be a potentially optimal indicator of post-CA hyperoxic pulmonary injury.

Problematic smartphone use (PSU) is common among young people and linked to poor academic performance. However, how PSU affects learning processes remains unclear. This study investigated the influence of auditory cue stimulation during a reading task on the mental workload and prefrontal brain activity of young individuals with PSU. Sixteen university students with PSU and 14 healthy controls (HC) performed a silent reading task, during which fake notification sounds were introduced. Their mental workload was assessed using the NASA Task Load Index (NASA-TLX), and prefrontal brain activity was measured using functional near-infrared spectroscopy (fNIRS). The results of the NASA-TLX suggest that the PSU group experienced greater frustration than the HC group. The fNIRS results showed that in the right medial prefrontal region of the HC group, O₂Hb levels increased following cue stimulation, whereas no change was observed in the PSU group. Moreover, in the HC group, HHb levels in the left lateral prefrontal region decreased after cue stimulation. The findings of the present study demonstrate that university students with PSU experience frustration and exhibit deactivation in the prefrontal regions associated with the executive control network during silent reading in realistic learning situations.

Poxviruses target innate immunity mediators such as tumor necrosis factors, interleukins, interferons, complement, and chemokines. It also targets adaptive immunity such as CD4⁺ T cells, CD4⁺ T cells, and B cells. Emerging of the recent epidemic of monkeypox virus (MPXV), a zoonotic disease native to Central and Western Africa, besides the lack of permitted treatments for poxviruses infections, encouraged researchers to identify effective inhibitors to help in preventing and treating poxviruses infections. Natural bioactive components, particularly polyphenolics, are promising for creating powerful antioxidants, anti-inflammatory, immune-stimulating, and antiviral agents. As a result, they are potentially effective therapies for preventing and treating viral diseases, such as infections caused by poxviruses including the recent pandemic MPXV. Polyphenolics: rosmarinic acid, caffeic acid, resveratrol, quercitrin, myricitrin, gingerol, gallotannin, and propolis-benzofuran A, as well as isoquinoline alkaloids: galanthamine and thalimonine represent prospective antiviral agents against MPXV, they can inhibit MPXV and other poxviruses via targeting different viral elements including DNA Topoisomerase I (TOP1), Thymidine Kinase (TK), serine/threonine protein kinase (Ser/Thr kinase), and protein A48R. The bioactive extracts of different traditional plants including Guiera senegalensis, Larrea tridentata, Sarracenia purpurea, Kalanchoe pinnata (Lam.) Pers., Zingiber officinale Roscoe, Quercus infectoria, Rhus chinensis, Prunella vulgaris L., Salvia rosmarinus, and Origanum vulgare also can inhibit the growth of different poxviruses including MPXV, vaccinia virus (VACV), variola virus, buffalopox virus, fowlpox virus, and cowpox virus. There is an urgent need for additional molecular studies to identify and confirm the anti-poxviruses properties of various natural bioactive components, especially those that showed potent antiviral activity against other viruses.

Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Additionally, obese and postmenopausal women are at higher risk of all-cause and breast cancer-specific mortality compared with non-obese women with breast cancer. In this context, increased levels of estrogens, excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, adipocyte-derived adipokines, hypercholesterolemia, and excessive oxidative stress contribute to the development of breast cancer in obese women. Genetic evaluation is an integral part of diagnosis and treatment for patients with breast cancer. Despite trimodality therapy, the four-year cumulative incidence of regional recurrence is significantly higher. Axillary lymph nodes as well as primary lesions have diagnostic, prognostic, and therapeutic significance for the management of breast cancer. In clinical setting, because of the obese population primary lesions and enlarged lymph nodes could be less palpable, the diagnosis may be challenging due to misinterpretation of physical findings. Thereby, a nomogram has been created as the "Breast Imaging Reporting and Data System" (BI-RADS) to increase agreement and decision-making consistency between mammography and ultrasonography (USG) experts. Additionally, the "breast density classification system," "artificial intelligence risk scores," ligand-targeted receptor probes," "digital breast tomosynthesis," "diffusion-weighted imaging," "18F-fluoro-2-deoxy-D-glucose positron emission tomography," and "dynamic contrast-enhanced magnetic resonance imaging (MRI)" are important techniques for the earlier detection of breast cancers and to reduce false-positive results. A high concordance between estrogen receptor (ER) and progesterone receptor (PR) status evaluated in preoperative percutaneous core needle biopsy and surgical specimens is demonstrated. Breast cancer surgery has become increasingly conservative; however, mastectomy may be combined with any axillary procedures, such as sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection whenever is required. As a rule, SLNB-guided axillary dissection in breast cancer patients who have clinically axillary lymph node-positive to node-negative conversion following neoadjuvant chemotherapy is recommended, because lymphedema is the most debilitating complication after any axillary surgery. There is no clear consensus on the optimal treatment of occult breast cancer, which is much discussed today. Similarly, the current trend in metastatic breast cancer is that the main palliative treatment option is systemic therapy.