Block of Tetrodotoxin-resistant Na+ Channel Pore by Multivalent Cations: Gating Modification and Na+ Flow Dependence

Tetrodotoxin-resistant (TTX-R) Na+ channels are much less susceptible to external TTX but more susceptible to external Cd2+ block than tetrodotoxin-sensitive (TTX-S) Na+ channels. Both TTX and Cd2+ seem to block the channel near the “DEKA” ring, which is probably part of a multi-ion single-file region adjacent to the external pore mouth and is involved in the selectivity filter of the channel. In this study we demonstrate that other multivalent transitional metal ions such as La3+, Zn2+, Ni2+, Co2+, and Mn2+ also block the TTX-R channels in dorsal root ganglion neurons. Just like Cd2+, the blocking effect has little intrinsic voltage dependence, but is profoundly influenced by Na+ flow. The apparent dissociation constants of the blocking ions are always significantly smaller in inward Na+ currents than those in outward Na+ current, signaling exit of the blocker along with the Na+ flow and a high internal energy barrier for “permeation” of these multivalent blocking ions through the pore. Most interestingly, the activation and especially the inactivation kinetics are slowed by the blocking ions. Moreover, the gating changes induced by the same concentration of a blocking ion are evidently different in different directions of Na+ current flow, but can always be correlated with the extent of pore block. Further quantitative analyses indicate that the apparent slowing of channel activation is chiefly ascribable to Na+ flow–dependent unblocking of the bound La3+ from the open Na+ channel, whereas channel inactivation cannot happen with any discernible speed in the La3+-blocked channel. Thus, the selectivity filter of Na+ channel is probably contiguous to a single-file multi-ion region at the external pore mouth, a region itself being nonselective in terms of significant binding of different multivalent cations. This region is “open” to the external solution even if the channel is “closed” (“deactivated”), but undergoes imperative conformational changes during the gating (especially the inactivation) process of the channel

An Effective Cold Start Recommendaton Method Using A Web Of Trust

Cold start recommendations are important because they help build user loyalty, which is the key to the success of e-services and e-commerce systems. Recommending useful information for new users generally creates a sense of belonging and loyalty, and encourages them to visit e-commerce systems frequently. However, as new users take time to become familiar with recommendation systems, the systems usually have limited information about newcomers and have difficulty providing appropriate recommendations. The cold start phenomenon has a serious impact on the performance of recommendation systems. To address the problem, we propose a cold start recommendation method that integrates a web of trust with a user model to identify trustworthy users. The suggestions of those users are then aggregated to provide useful recommendations for cold start users. Experiments based on the well-known Epinions dataset demonstrate that the proposed method is effective and efficient, and outperforms well-known recommendation methods by a significant margin

JUMPS IN DIFFERENT LEVELS OF WATER: AN OPTIMAL ENVIRONMENT TO JUMP ON LAND

The purpose of this study was to compare rate of force development (RFD) and rate of impact force (RIF) among on-land and in different levels of water jumps. Fourteen male participants were recruited in this study. Participants carried out the testing on land first and followed by testing in knee-high (LOW), trochanter major high (MID), and nasal-high (HIGH) of water. In each condition, participants performed 3 countermovement jumps (CMJ) separated by 15 sec rest. RFD and RIF were calculated. A repeated measure ANOVA was used for assessing the differences of variables among different conditions. The results showed that RFD for LOW is significantly lower than the others, and loading impact on-land is significantly higher than the others. Jumping in MID and HIGH are optimal levels of water for jumps training

An overview of out-of-step protection in power systems

Power system is subjected to an extensive variety of little or bigger disturbance to the system during the operation. The power system that designed as one of the main requirement is to survive from the larger type of disturbances like faults. The power swing in certain system is the variation in three phase power flow in the power system. This paper mainly discussed the power swing and distance relay and the effect of the power swing on the distance relay and demonstrate about the basic power system stability and power swing phenomena. Moreover, out of step protection and detection applications are revised as well. At the end, the paper also demonstrated the past study of out of step application of TNB 275 KV network

Preventive and therapeutic role of traditional Chinese herbal medicine in hepatocellular carcinoma

AbstractHepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. The clinical management of HCC remains a substantial challenge. Although surgical resection of tumor tissues seems promising, a high recurrence and/or metastasis rate accounting for disease-related death has led to an urgent need for improved postsurgical preventive/therapeutic clinical intervention. Developing advanced target-therapy agents such as sorafenib appears to be the only effective clinical intervention for patients with HCC to date, but only limited trials have been conducted in this regard. Because of their enhanced preventive/therapeutic effects, traditional Chinese herbal medicine (CHM)-derived compounds are considered suitable agents for HCC treatment. The CHM-derived compounds also possess multilevel, multitarget, and coordinated intervention effects, making them ideal candidates for inhibition of tumor progression and HCC metastasis. This article reviews the anticancer activity of various CHMs with the hope of providing a better understanding of how to best use CHM for HCC treatment

Experience with adjuvant chemotherapy for pseudomyxoma peritonei secondary to mucinous adenocarcinoma of the appendix with oxaliplatin/fluorouracil/leucovorin (FOLFOX4)

<p>Abstract</p> <p>Background</p> <p>Pseudomyxoma peritonei (PMP) is a rare condition characterized by mucinous tumors, disseminated intra-peritoneal implants, and mucinous ascites. So far its diagnosis remains challenging to most clinicians.</p> <p>Case presentation</p> <p>A 55-year-old male patient had suffered from acute onset of abdominal pain and abdominal distension for one day prior to his admission. Physical examination revealed tenderness over the right lower quadrant of the abdomen without diffuse muscle guarding. A large amount of ascites was identified by abdominal computed tomography (CT) scan. Paracentesis showed the appearance of sticky mucinous ascites. He underwent laparotomy under the impression of pseudomyxoma peritonei. There was a lot of mucinous ascites, one appendiceal tumor and multiple peritoneal implants disseminated from the subphrenic space to the recto-vesicle pouch. Pseudomyxoma Peritonei caused by mucinous adenocarcinoma of appendiceal origin, was confirmed by histopathology. We performed an excision of the appendiceal tumor combined with copious irrigation and debridement. After the operation, he received 10 cycles of systemic chemotherapy with FOLFOX4 regimen, without specific morbidity. Follow-up of abdominal CT and colonoscopy at post-operative 17 months showed excellent response without evidence of local recurrence or distal metastasis. He made an uneventful recovery (up to the present) for 21 months after the operation.</p> <p>Conclusion</p> <p>This case report emphasizes the possible new role of systemic chemotherapy in the treatment of patients with this rare clinical syndrome.</p

KINETIC AND EMG ANALYSIS OF THE NEW DEDIGN STEPWISE LOADING SYSTEM

The great muscle strength and power are important factors for successful sport performance. Many strength coaches instructed their athletes to move the weight for developing muscle strength. However, most weight training systems consist of lifting a steady load, this having the drawback of nol accounting for the change in strength with the change in muscle length. In order to solve this problem, this study developed a stepwise weight training system using linkage which is capable of increasing the load in isotonic contraction, then compared kinetics and muscle activation between the stepwise contraction and the traditional isotonic contraction. The results showed that both the normalized peak tension and the angle of peak tension of the stepwise contraction were significantly larger than traditional isotonic contraction. The normalized impulse and the integrated EMG of the stepwise contraction was more than traditional isotonic contraction but not reached the significance The findings suggest that stepwise loading system can provide greater stimulus to muscle training effect than traditional weight training systems

Age-specific associations between Systolic Blood Pressure and Cardiovascular Disease: A 10-years diabetes cohort study

Abstract: Background The relationship between systolic blood pressure (SBP) and cardiovascular disease (CVD) among patients with diabetes mellitus remains unclear. The study aimed to explore age‐specific associations between SBP and CVD. Methods and Results: A population‐based retrospective cohort study was conducted on 180 492 Chinese adults with type 2 diabetes mellitus in 2008–2010, with follow‐up to 2017. Age‐specific associations (<50, 50–59, 60–69, and 70–79 years) between the average SBP in the previous 2 years and CVD risk were assessed by adjusted Cox proportional hazards regression with age‐specific regression dilution ratios and patient characteristics stratified by subgroups. During a median follow‐up of 9.3 years (1.5 million person‐years), 32 545 patients developed a CVD, with an incidence rate of 23.4 per 1000 person‐years. A positive and log‐linear association between SBP and CVD risk was observed among the 4 age groups without evidence of a threshold down to 120 mm Hg, but the magnitude of SBP effect on CVD attenuated with increased age. The CVD risk in the age group <50 years was ≈22% higher than the age group 70 to 79 years (hazard ratio [HR], 1.33 [95% CI, 1.26–1.41] versus HR, 1.09 [95% CI, 1.07–1.11]). Each 10‐mm Hg higher SBP was associated with 12% (HR, 1.12 [95% CI, 1.10–1.13]), 11% (HR, 1.11 [95% CI, 1.10–1.13]), and 20% (HR, 1.20 [95% CI, 1.17–1.22]) higher risk of all composite CVD events, individual CVD, and CVD mortality, respectively. Conclusions: There is a significant log‐linear relationship between baseline SBP and the risk of CVD among patients with diabetes mellitus in China. The risk increases from an SBP of 120 mm Hg onward. Age influences this relationship significantly, with younger patients (<50 years) having a greater risk of CVD for a similar rise in SBP as compared with those who are older. These findings suggest that differential target blood pressures stratified by age maybe usefu

Cyclosporine A Eye Drop-Induced Elongated Eyelashes: A Case Report

Purpose: The most common ocular adverse event following the use of cyclosporine A (CsA) 0.05% ophthalmic emulsion is ocular burning (17%). Other adverse effects that have been reported include conjunctival hyperemia (1–5%), discharge, epiphora, eye pain, foreign body sensation, pruritus, stinging and blurred vision. Here, we report a specific side effect of CsA, namely eye drop-induced eyelash elongation in a patient with refractory giant papillary conjunctivitis. Design: Observational case report. Methods: Case report and review of the literature. Results: A 32-year-old female with giant papillary conjunctivitis on the left eye, who had undergone papillectomy 3 years previously and was refractory to topical steroid therapy, was treated with CsA 0.05% ophthalmic emulsion (Restasis) 4 times a day, preservative-free artificial tears and gentamicin ophthalmic solution in the left eye. After 5 months of topical CsA treatment, elongated eyelashes of her left eye were observed without other adverse effects. Conclusion: Although hypertrichosis and trichomegaly have been documented in the literature as side effects of systemic CsA, topical CsA 0.05% eye drop-induced elongated eyelashes have not been reported, and we believe ophthalmologists should be mindful and inform patients about this specific side effect