Pathways of hepatic and renal damage through non‐classical activation of the renin‐angiotensin system in chronic liver disease

In liver cirrhosis, renin‐angiotensin system (RAS) activation sustains renal sodium retention and hepatic fibrogenesis. New information has recently enlivened the traditional concept of RAS. For instance, renin and prorenin bind their ubiquitous receptors, resulting in the local production of angiotensin (Ang) II; increased serum calcium and calcimimetic agents, through stimulation of extracellular calcium‐sensing receptors (CaSR), blunt renin production and lead to natriuretic effects in human and experimental cirrhosis. Alongside systemic production, there is Ang II tissue production within various organs through RAS enzymes different from angiotensin‐converting enzyme (ACE), that is chymase, tissue plasminogen activator and several cathepsins. In experimental cirrhosis, inhibition of chymase leads to natriuretic and hepatic antifibrotic effects, without changes in systemic haemodynamics. In the kidney, local RAS coordinates proximal and distal tubular sodium reabsorption. However, renalase, whose plasma and tissue levels are severely altered in experimental cirrhosis, degrades systemic and renal tubule catecholamines, antagonizing the effects of renal RAS. Angiotensinogen‐derived natriuretic and vasodilating peptides (Ang1‐9, Ang1‐7, Ang3‐8) and their receptors have been described. Receptor agonists or antagonists are available to affect portal hypertension and sodium retention in cirrhosis. ACE2‐dependent generation of Ang1‐7 may inhibit experimental liver fibrosis. inhibition of Ang1‐7 clearance by means of neprilysin blockade has portal hypotensive and natriuretic effects. Ang1‐12, whose production renin does not regulate, is converted to several different angiotensin peptides via chymase. Finally, Ang II behaves as either an antinatriuretic or a natriuretic agent, based on the tissue content of AT₁R and AT₂R receptors, their ratio being prone to pharmacological modulation.     

Suppression of Complex Visual Hallucinatory Experiences by Occipital Transcranial Magnetic Stimulation: A Case Report

We report a patient with visual hallucinations and illusions along with an associated visual field defect after bilateral ischemic damage to his occipital visual cortex. These hallucinations were long-standing and of both simple and complex (well-formed) type. Application of low frequency (1 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) to the occipital cortex led to a complete cessation of visual hallucinatory symptoms. The use of TMS to probe the neurophysiology, and possibly alleviate, visual hallucinatory experiences is discussed.     

Glycosaminoglycan entrapment by fibrin in engineered heart valve tissues

Tissue engineered heart valves (TEHVs) may provide a permanent solution to congenital heart valve disease by permitting somatic valve growth in the pediatric patient. However, to date, TEHV studies have focused primarily on collagen, the dominant component of valve extracellular matrix (ECM). Temporal decreases in other ECM components, such as the glycosaminoglycans (GAGs), generally decrease as cells produce more collagen under mechanically loaded states; nevertheless, GAGs represent a key component of the valve ECM, providing structural stability and hydration to the leaflets. In an effort to retain GAGs within the engineered constructs, here we investigated the utility of the protein fibrin in combination with a valve-like, cyclic flexure and steady flow (flex–flow) mechanical conditioning culture process using adult human periodontal ligament cells (PLCs). We found both fibrin and flex–flow mechanical components to be independently significant (p < 0.05), and hence important in influencing the DNA, GAG and collagen contents of the engineered tissues. In addition, the interaction of fibrin with flex–flow was found to be significant in the case of collagen; specifically, the combination of these environments promoted PLC collagen production resulting in a significant difference compared to dynamic and statically cultured specimens without fibrin. Histological examination revealed that the GAGs were retained by fibrin entrapment and adhesion, which were subsequently confirmed by additional experiments on native valve tissues. We conclude that fibrin in the flex–flow culture of engineered heart valve tissues: (i) augments PLC-derived collagen production; and (ii) enhances retention of GAGs within the developing ECM.     

The general surgery workforce shortage is worse when assessed at county level

Background

Multiple studies have documented a significant decrease in the general surgery workforce in the United States, both rural and urban, for the past 3 decades. This 11-year study evaluates the Texas general surgery workforce at both the state and local level in 2002 and 2012.

Methods

Data were obtained from the Texas Medical Board, the United States Census Bureau/Texas State Library and Archives Commission, and the Texas Department of State Health Services for 2002 and 2012. A benchmark target of 7 general surgeons per 100,000 population was used.

Results

During the study period, the Texas population increased 21%, and actively practicing physicians increased 44%. All surgical specialists increased by 26%. General surgeons increased 4%; however, the number of general surgeons per 100,000 population decreased 14% (from 6.7 to 5.8/10⁵). Using the total Texas population for 2012, an additional 329 general surgeons are needed by benchmark standards. However, when analyzed by individual county population, 449 additional general surgeons are needed in the individual counties. These effects were greater in the nonmetropolitan areas of Texas where per capita general surgeons decreased by 21%.

Conclusions

The absolute increase in Texas general surgeons over the past decade has not kept pace with an increase in the Texas population. The general surgery workforce deficit based on the Texas state population underestimates the local workforce shortage, particularly in the nonmetropolitan areas of Texas.     

A qualitative study of Korean music therapist's turnover experiences

Nine Korean music therapists’ turnover experiences were examined using consensual qualitative research. Five domains and 24 categories were created from the cross-analysis of the data. The domains of this study were: (a) factors contributing to turnover; (b) burnout; (c) turnover procedure; (d) changes after turnover; and (e) factors contributing to retention. Based on the frequency label of each category, three types of categories were generated: general (8–9 cases), typical (5–7 cases), and variant (2–3 cases). The result showed that the lack of recognition for music therapy among administrators, supervisors, and peer therapists contributed to music therapists’ turnover decision. However, it was found that these participants had a strong sense of professionalism, which was expressed through their work, regardless of the various challenges posed by environmental conditions. In fact, financial sources such as work conditions and salary were only categorized as variant whereas the professional incentives were identified generally across participants in this study.     

Long‐lasting intrinsic persistent firing in rat CA1 pyramidal cells: A possible mechanism for active maintenance of memory

The hippocampus is critical for memory tasks which require an active maintenance of memory for a short period of time; however, the underlying neural mechanisms remain unknown. Most theoretical and computational models, which date back to the classic proposals by Donald Hebb in 1949 , have been self‐constrained by anatomy, as most models rely on the recurrent connectivity in region CA3 to support “reverberating activity” capable of memory maintenance. However, several physiological and behavioral studies have specifically implicated region CA1 in tasks which require an active maintenance of memory. Here, we demonstrate that despite limited recurrent connectivity, CA1 contains a robust cellular mechanism for active memory maintenance in the form of self‐sustained persistent firing. Using in vitro whole‐cell recordings, we demonstrate that brief stimulation (0.2–2 s) reliably elicits long‐lasting (> 30 s) persistent firing that is supported by the calcium‐activated non‐selective cationic current. In contrast to more traditional ideas, these data suggest that the hippocampal region CA1 is capable of active maintenance of memory. © 2013 Wiley Periodicals, Inc.     

膜技术富集脉络宁注射液生产废水中小分子药效成分的工艺优化研究

目的利用聚醚砜中空纤维膜对脉络宁注射液生产废水的小分子药效物质进行富集。方法以共性高分子(蛋白质、鞣质、淀粉、果胶)截留率和小分子药效物质绿原酸的渗透率为考察指标,优选出超滤膜过程停止时间和膜型号,进而采用Box-Behnken中心组合设计建立数学模型,优化出超滤膜过程的最佳工艺参数。结果在共性高分子截留率中,影响因素A(温度)B(错流压差)C(进料速率),并且与温度呈负相关性;在绿原酸透过率中,影响因素A(温度)B(错流压差)C(进料速率),并且在温度与速率一定时,绿原酸透过率与错流压差存在"∩"型关系。优化工艺结果为药液温度35℃,进料体积流量为262 mL/min,错流压差15.0 psi(1 psi=6.895 kPa),工艺验证绿原酸透过率为(91.470±0.988)%,高分子截留率为(80.080±2.296)%,综合评分为(85.780±1.641)%,RSD为0.46%,与预测工艺偏差较小。结论中空纤维膜对于生产废水中的小分子药效物质有良好的渗透率,并对共性大分子有优良的截留效果,是一种可持续的、绿色资源化利用方式。