Deciphering mitochondrial dysfunction: Pathophysiological mechanisms in vascular cognitive impairment.

Vascular cognitive impairment (VCI) encompasses a range of cognitive deficits arising from vascular pathology. The pathophysiological mechanisms underlying VCI remain incompletely understood; however, chronic cerebral hypoperfusion (CCH) is widely acknowledged as a principal pathological contributor. Mitochondria, crucial for cellular energy production and intracellular signaling, can lead to numerous neurological impairments when dysfunctional. Recent evidence indicates that mitochondrial dysfunction-marked by oxidative stress, disturbed calcium homeostasis, compromised mitophagy, and anomalies in mitochondrial dynamics-plays a pivotal role in VCI pathogenesis. This review offers a detailed examination of the latest insights into mitochondrial dysfunction within the VCI context, focusing on both the origins and consequences of compromised mitochondrial health. It aims to lay a robust scientific groundwork for guiding the development and refinement of mitochondrial-targeted interventions for VCI.

Nunchaku: optimally partitioning data into piece-wise contiguous segments.

MOTIVATION: When analyzing 1D time series, scientists are often interested in identifying regions where one variable depends linearly on the other. Typically, they use an ad hoc and therefore often subjective method to do so. RESULTS: Here, we develop a statistically rigorous, Bayesian approach to infer the optimal partitioning of a dataset not only into contiguous piece-wise linear segments, but also into contiguous segments described by linear combinations of arbitrary basis functions. We therefore present a general solution to the problem of identifying discontinuous change points. Focusing on microbial growth, we use the algorithm to find the range of optical density where this density is linearly proportional to the number of cells and to automatically find the regions of exponential growth for both Escherichia coli and Saccharomyces cerevisiae. For budding yeast, we consequently are able to infer the Monod constant for growth on fructose. Our algorithm lends itself to automation and high throughput studies, increases reproducibility, and should facilitate data analyses for a broad range of scientists. AVAILABILITY AND IMPLEMENTATION: The corresponding Python package, entitled Nunchaku, is available at PyPI: https://pypi.org/project/nunchaku.

Dexmedetomidine in combination with ketamine for pediatric procedural sedation or premedication: A meta-analysis.

OBJECTIVE: To evaluate effectiveness of combinational use of dexmedetomidine and ketamine (DEX-KET) for pediatric procedural sedation or premedication. METHODS: Relevant studies were identified after a literature search in electronic databases and study selection was based on precise eligibility criteria. Meta-analyses of mean differences were performed to examine differences in sedation onset and recovery times between DEX-KET and comparators. Changes from baseline in heart rate (HR), respiratory rate, oxygen saturation, and mean arterial pressure (MAP), were pooled. Meta-analyses of proportions were performed to estimate incidence of adverse events. RESULTS: 15 studies (1087 patients) were included. Onset of sedation was significantly shorter in DEX-KET than in DEX group. HR declined in DEX-KET group from start (-3.5 beats per minute (BPM) [95% CI: -5.1, -1.9]) through midpoint (-7.2 BPM [95% CI: -12.1, -2.3]) and at end of sedation (-8.7 BPM [95% CI: -13.1, -4.4]). Decrease in HR after DEX administration at start was -11.6 BPM [95% CI: -16.0, -7.1] and remained consistent afterward. There was no change in MAP during DEX-KET sedation. However, after DEX administration, MAP decreased by -6.9 [95% CI: -10.4, -3.3] at start, -7.8 [95% CI: -11.4, -4.2] at middle, and by -6.6 [95% CI: -14.4, 1.1] at end of sedation. Incidence of hypotension was 3% [95% CI: 0, 9] in DEX-KET, 7% [95% CI: 2, 14] in DEX, and 0% [95% CI: 0, 2] in KET groups. Incidence of bradycardia was 2% [95% CI: 0, 6] with DEX-KET and 12% [95% CI: 5, 20] with DEX. Incidence of oxygen desaturation was 3% [95% CI: 0, 8] in DEX-KET, 2% [95% CI: 0, 6] in DEX, 12% [95% CI: 5, 20] in KET, and 13% [95% CI: 6, 21] in PROP-KET groups. MIDA-KET sedation had 13% [95% CI: 4, 25] incidence of tachycardia. CONCLUSIONS: DEX-KET for pediatric sedation results in better sedation outcomes than DEX or KET by shortening onset of sedation and recovery while maintaining hemodynamic and respiratory stability with low incidence of adverse events. DEX sedation was associated with higher incidence of bradycardia. Higher incidence of oxygen desaturation was observed with KET and PROP-KET whereas MIDA-KET was associated with higher incidence of tachycardia.

Clinical HDAC Inhibitors Are Effective Drugs to Prevent the Entry of SARS-CoV2.

The outbreak of COVID-19 by the end of 2019 has posed serious health threats to humanity and jeopardized the global economy. However, no effective drugs are available to treat COVID-19 currently and there is a great demand to fight against it. Here, we combined computational screening and an efficient cellular pseudotyped virus system, confirming that clinical HDAC inhibitors can efficiently prevent SARS-CoV-2 and potentially be used to fight against COVID-19.

[Comparison between Ye Tianshi and Xue Shengbai in treatment of diarrfea with damp-heat].

Ye Tianshi and Xue Shengbai are two febrile disease specialists in same time, and for the treatment of dampness and heat, they have different medication ideas. With the help of traditional Chinese medicine(TCM), author has studied two specialists' consilias of dampness and heat, through the statistics and analysis of their medicine during the treatment of dampness and heat, summarizes the similarities and differences of Ye and Xue's medicine application's assoations and models. Ye Tianshi and Xue Shengbai were both thought that the reason of dampness and heat was damp heat pathogenic factors, for this reason, the spleen and stomach conduction disordered, They both treated from the middle-jiao of Yangming and Taiyin, focused on warm-natured medicine, cold-natured medicine, used less cool-natured and heat-natured medicine, and more bitter, pungent, sweet medicine; Ye Tianshi usually use Scutellariae Radix, Paeoniae Radix Alba, Coptidis Rhizoma, Polyporus, Poria, Alismatis Rhizoma; Xue Shengbai commonly use Poria, Citri Reticulatae Pericarpium, Magnoliae officinalis Cortex, Patchouli, Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Paeoniae Radix Alba, Lablab Semen Album, Puerariae Lobatae Radix, Mume Fructus, Tsaoko Fructus, Amomi Fructus, Coptidis Rhizoma and Phellodendri Chinensis Cortex. The differences between the two masters in medicine application provide a reference for the clinical treatment of dampness and heat.

[Comparison between Ye Tianshi and Xue Shengbai in treatment of distention with damp-heat].

Ye Tianshi and Xue Shengbai were both epidemic febrile diseases specialists in same time of Qing dynasty. The Traditional Chinese Medicine Inheritance Support System was used to compare and analyze the therapeutic characteristics of these two specialists in treating damp-heat type fullness or distension in stomach. Distension is commonly caused by qi stagnation accompanied with damp-heat from internal and external factors. In treatment, separation of damp and heat and removing dampness and heat from sanjiao separately were their common therapeutic principles. Both Ye Tianshi and Xue Shengbai paid much greater attention to eliminating dampness, and the herbs with bitter and pungent flavor, warm in property were usually chosen to regulate qi flow and reduce dampness. Invigorating spleen, nourishing stomach and dispersing lung were the frequently used treatment to balance the organs'harmony. The difference between specialist Ye and specialist Xue was the preference of herbs. Hou Pu (Magnoliae Officinalis Cortex), Xing Ren (Armeniacae Semen Amarum), Chen Pi (Citri Reticulatae Pericarpium), and Hua Shi (Talcum) were often used in both administrations. Besides, Ye Tianshi preferred to use Ban Xia (Pinelliae Rhizoma), Huang Qin (Scutellariae Radix), Huang Lian (Coptidis Rhizoma), Fuling, et al. Xue Shengbai on the other hand enjoyed using Fu Lingpi(Poriae Cutis), Cao Guo (Tsaoko Fructus), and Guang Huoxiang (Pogostemonis Herba), et al. In herbs compatibility, both of the two specialists were fond of using Chen Pi-Hou Pu, Hou Pu-Xing Ren. Moreover, Ye Tianshi often used Ban Xia- Xing Ren, Ban Xia-Huang Qin, and Hua Shi-Xing Ren to achieve the expected outcome of the treatment. While, Chen Pi, Fu Lingpi, and Hou Pu were the common combination with each other in Xue's cases. The similarities and differences of their administration should have the guidance in current clinical Chinese medicine practice for damp-heat type fullness or distension in stomach.