[Long-term efficacy evaluation of coated metal stent implantation for ureteroscopic lithotripsy related refractory ureteral stricture].

OBJECTIVE: To comprehensively evaluate the long-term efficacy and safety of coated metal stent implantation for ureteroscopic lithotripsy related refractory ureteral stricture (URL-rUS). METHODS: Electronic medical records of 30 patients (31 affected renal units) receiving coated metal stent implantation for URL-rUS from Sept. 2018 to Aug. 2021 at Peking University People' s Hospital were reviewed for analysis. Coated metal stents were implanted in retrograde approach via ureteroscope. Last outpatient follow-up was set as endpoint. Baseline information, stricture characteristics and decompression strategy before coated metal stent implantation were retrospectively collected. Serum creatinine (Scr) concentration and renal pelvis width (RPW) were used as renal function indicators. Peri-operative and long-term complications and according outcomes were recorded. For the patients who had double J tubes implanted for drainage before operation, Ureteral Stent Symptom Questionnaire (USSQ) was applied to evaluate the stent-related discomforts and quality of life (QoL) before and after surgery. Data analysis was conducted with SPSS (version 25.0; SPSS, Chicago, IL, USA). RESULTS: Totally 30 patients with 31 affected renal units were included. All the patients previously underwent unsuccessful traditional endoscopic balloon dilation or endoureterotomy before receiving coated metal stent implantation. The mean age was (45.5±9.3) years old. The median follow-up time were 14 (6-36) months. All coated metal stents were successfully placed with a median duration of 60 (30-195) min. No severe peri-operative complications occurred. At endpoint, 28 (90.3%) sides of coated metal stents remained unobstructed with a longest indwelling time of 36 months. Causes of failures included stent migration (1 case, 3.2%), encrustation (1 case, 3.2%) and repeated stent related urinary tract infection (1 case, 3.2%). When compared with the baseline, significant reductions were observed in both Scr concentration and RPW at endpoint [(90.7±19.5) mmol/L vs. (83.1±18.5) µmol/L, P < 0.01, for Scr; (2.5±1.3) cm vs. (1.9±0.8) cm, P < 0.01, for RPW], indicating good preservation of renal function and remission of hydronephrosis. For 26 patients with double J stents before operation, significant reduction of USSQ average score (100.4±6.6 vs. 82.1±4.9, P < 0.01) evidenced better life quality preserving ability of coated metal stent versus double J stent. CONCLUSION: Coated metal stent implantation is a safe and minimally invasive management of ureteral stricture providing a satisfying long-term patency rate, after which the patients' quality of life and renal function could be both improved. This method could serve as a promising alternative long-term maintenance treatment option for patients with URL-US, especially when traditional endoscopic interventions failed.

[Management of complex renal stones by a novel ureterorenoscope with vacuum suctioning system combined with flexible ureteroscope].

Objective: To evaluate the feasibility and safety of Sotn ureterorenoscope combined with flexible ureteroscope on managing complex renal stones. Methods: Patients treated with the Sotn ureterorenoscope combined with flexible ureteroscope between January 2010 and December 2019 were employed from the Sun Yat-sen Memorial Hospital of Sun Yat-sen University and Jiangmen Wuyi Traditional Chinese Medicine Hospital. The patients' information of age, gender, comorbidities, stone characteristics (stone size, hounsfield units, stone composition, stone location, etc.), operative time and console time, stone-free rate (SFR), and perioperative complication rate were collected. The primary outcome was defined as primary SFR in 1 month of operation, and the secondary outcome was the perioperative complication rate. The differences in preoperative and postoperative data between patients with different kinds of stones were compared. Results: A total of 347 patients were included in the study, with 220 males and 127 females. The age [M(Q1,Q3)] was 51 (42, 58) years. There were 94 patients suffered from multiple renal stones and 253 patients with staghorn renal stones. The operative time and console time age [M(Q1,Q3)] for all patients were 87 (55, 115) min and 59 (27, 75) min, respectively. The primary SFR was 81.3% [83.8% for multiple renal stones and 74.5% for staghorn renal stones (P=0.048)]. Complications occurred in 80 patients (23.1%), of which 79 cases were classified as Clavien-Dindo grade 1-2, and 1 case (0.3%) was grade 3-4. For patients with multiple renal stone, compared with the residual stone group, the complete stone-free group had smaller stone size [15.5 (12.0, 21.0) vs 22.0 (17.5, 28.1) mm, P<0.001], and lower hounsfield units [920.0 (658.0, 1 172.5) vs 1 125.0 (944.9, 1 247.5), P=0.022]. Patients with complications had longer operative time than those without complications [60.0 (38.5, 90.0) vs 75.0 (51.3, 110.0) min, P=0.022]. The SFR was higher in patients with stones size ≤ 20 mm compared to those with stones size > 20 mm (91.8% vs 67.5%, P<0.001), while the difference in complication rate was not statistically significant (P>0.05). In the staghorn renal stones group, compared with the residual stone group, the complete stone-free group had smaller stone size [35.0 (25.8, 45.3) vs 53.5 (39.3, 67.5) mm, P<0.001]. Patients with complications had larger stone size than those without complications [43.5 (34.8, 56.5) vs 36.0 (27.0, 50.0) mm, P=0.007]. Patients with stone size ≤ 40 mm had higher SFR (87.5% vs 55.3%, P<0.001) and lower complication rate(10.7% vs 31.6%, P=0.012) compared to those with stone size >40 mm. Conclusion: Sotn ureterorenoscope combined with flexible ureteroscope is an effective and safe choice for the treatment of complex renal calculi.

[Therapeutic effects of sacral neuromodulation on detrusor underactivity].

OBJECTIVE: To evaluate the effects of sacral neuromodulation (SNM) on detrusor underactivity (DUA). METHODS: From December 2019 to April 2020, 6 patients with DUA who had been treated with SNM were assessed retrospectively. The average age was 58 years (46-65 years), with 3 males and 3 females. All the patients were diagnosed with DUA by urodynamics examination. Obstruction of bladder outlet was excluded through the cystoscopy. No patient had the history of neurological disease. All the patients were placed with the bladder colostomy tube before SNM. One female patient accepted the trans-urethral resection of bladder neck. Two male patients accepted the trans-urethral resection of prostate. All the 3 patients had no improvement of void symptom after the urethral operation. Before SNM, the average 24 h times of voiding was 23.8 (18-33), average volume of every voiding was 34.2 mL (10-50 mL), average residual volume was 421.7 mL (350-520 mL). The preoperative and postoperative 24 h urine frequency, average voided volume, and average residual urine volume were compared respectively. RESULTS: Totally 6 patients underwent SNM with stage Ⅰ procedure. The operation time for stage Ⅰ procedure was 62-135 min (average 90 min). After an average follow-up of two weeks, stage Ⅱ procedure was performed on responders. Four patients accepted stage Ⅱ procedure (conversion rate 66.7%), the other two patients refused the stage Ⅱ procedure because the urine frequency did not reach the satisfied level. But all the patients had the improvement of residual urine volume. For the 4 patients at the follow-up of 10-15 months, the improvement of void was still obvious. For the all patients after stage Ⅰ procedure, the average 24 h urine frequency reduced to 13.5 times (9-18 times, P < 0.001), the average voided volume increased to 192.5 mL (150-255 mL, P < 0.001), and the average residual urine volume reduced to 97.5 mL (60-145 mL, P < 0.001). No adverse events, such as wound infection or electrode translocation were detected during an average follow-up of 11.3 months. Only one of the 4 patients who received the stage Ⅱ procedure did the intermittent catheterization for one time each day. CONCLUSION: SNM provides a minimal invasive approach for the management of DUA.

[Progressive necrosis of lipid: A case report].

A 61-year-old woman was referred to our department with a 11-year-erythra. In the anterior tibia of both lower extremities, we could see large dark red infiltrating erythema, waxy luster, clear boundary, slight central atrophy, depression and capillary dilatation. He was diagnosed with "dermatitis contusiformis" in local hospitals, but the treatment of traditional Chinese medicine and external drugs was not effective. She had normal laboratory findings for blood routine test, biochemical indexes, C reactive protein(CRP) and erythrocyte sedimentation rate(ESR)．Furthermore, autoimmune antibodies were all negative. The skin pathology showed degeneration and necrosis of collagen fibers, chronic granulomatous inflammation in the dermis, and there were more acute and chronic inflammatory cell infiltration around the small vessels and in the wall of the tube. We eventually diagnosed it as necrobiosis lipoidica (NL) according to the history, erythra morphology and skin pathology. After treatment of low dose hormone and thalidomide for 1 year, the color and range of skin lesions gradually alleviated. NL was a rare chronic granulomatous inflammatory disease. There appeared to be a predominance in females. The incidence of NL was higher in patients with diabetes mellitus, although this asscoiation was currently questioned. NL might also be connected with autoimmune diseases, such as rheumatoid arthritis, sarcoidosis, ulcerative colitis and Crohn's disease. The pathological changes of the tissue were mainly in the dermis, including necrotic type, granulomatous type or mixed type. NL typically presented on the pretibial surface of lower extremities. Less typical locations included the face, scalp, vulva and upper limbs. Leisions usually began with small papules and nodules that gradually infiltrated into brownyellow patches and developed central wax-like atrophy. The diagnosis is often based on clinical examination and skin biopsy. NL is rare and easy to be misdiagnosed. For rheumatologists, we should carefully compare with the nodular erythema, the microscopic polyangitis and allergic purpura. It is significant for differential diagnosis to perform skin biopsy. Lacking of randomized controlled trials, no specific treatment has proven to be the gold standard. First-line therapy mainly consists of intralesional and systemic corticosteriods. Additionally, other reported treatment options include immunomodulator, biological agent, antiplatelet aggregation drug and plateletrich plasma. These patients need long term follow up continuously for progression of the disease, ulcerations, and possibility of malignant tranformation.

Sensitivity of urinary pathogens for patients discharged from the emergency department compared with the hospital antibiogram.

BACKGROUND: Data for hospital antibiograms are typically compiled from all patients, regardless of disposition, demographics and other comorbidities. OBJECTIVE: We hypothesized that the sensitivity patterns for urinary pathogens would differ significantly from the hospital antibiogram in patients that were discharged from the emergency department (ED). METHODS: We evaluated a retrospective cohort of all adult patients with positive urine cultures treated in the 2016 calendar year at an inner-city academic ED. Positive urine cultures defined by our institution's microbiology department. Investigators conducted a structured review of an electronic medical record (EMR) to collect demographic, historical and microbiology records. We utilized a one-sample test of proportion to compare the sensitivity of each organism for discharged patients to the hospital published antibiogram. Alpha set at 0.05. RESULTS: During the study period, 414 patients were discharged from the ED and found to have positive urine cultures; 20% age > 60 years old, 85% female, 79% Hispanic, 33% diabetic. The most common organisms was E. coli (78%). E. coli was sensitive to Trimethoprim-Sulfamethoxazole for 59% vs. 58% in our antibiogram (p = 0.77), Ciprofloxacin 81% vs. 69% (p < 0. 001), Nitrofurantoin 96% vs 95%; (p = 0.25). K. pneumoniae was sensitive to Trimethoprim-Sulfamethoxazole 87% vs. 80% in our antibiogram (p = 0.26), Ciprofloxacin 100% vs. 92% (p = 0.077), Nitrofurantoin 86% vs 41% (p < 0.001). CONCLUSIONS: For our predominantly Hispanic study group with a high prevalence of diabetes, we found that our hospital antibiogram had relatively good value in guiding antibiotic therapy though for some organism/antibiotic combinations sensitivities were higher than expected.

[A brief textual research on Mei shi fang (Prescriptions of Master Mei) and Yi men fang (Prescriptions of Medical Professionals)].

Mei shi fang (Prescriptions of Master Mei) cited in Zheng lei ben cao (Classified Syndromes Materia Medica) and Yi men fang (Prescriptions of Medical Professionals) cited in Yi xin fang (Ishinpo) are actually the same book with different titles, which is actually called Yi men mi lu (Secret Records of Medical Professionals) with 5 volumes or the 5-volume Mei chong xian fang (Prescriptions of Mei Chongxian) approximately compiled during the years of Zhenyuan to Yuanhe reigns of the Tang Dynasty (785-820) written by Mei Chongxian, a Tang taoist. Mei Chongxian and Mei Biao, the author of Shi yao er ya (Dictionary of Mineral Medicines), might probably be the same person. According to the citations of Yi xin fang and Zheng lei ben cao, Yi men mi lu should be a comprehensive medical book including theories, methods, prescriptions and medications, recorded classical prescriptions of predecessors extensively, with some innovations and high clinical and documentary significance.

[Structural changes of brain gray matter in male long-term smokers under magnetic resonance imaging].

Objective: To evaluate gray matter structure changes in long-term male smokers by voxel-based morphological method. Methods: Fifty long-term smokers and 37 non-smoking healthy volunteers were scanned with Siemens Skyro 3.0T magnetic resonance scanner from August 2014 to August 2016. The subjects underwent routine MRI (excluding intracranial lesions) sequences and 3D-T1 structural sequences (3D-mprage). SPM8 pretreatment based on Matlab was used to analyze the structural data. All of the data were analyzed by SPM8 software. The data were compared between groups with independent sample t test. Spearman correlation analysis was used to analyze the relationship between gray matter volume (GMV) and smoking data of two groups. Results: The gray matter volume of bilateral thalamic, right supramarginal gyrus, left supramarginal gyrus and left putamen of smoking group were (0.55±0.07), (0.40±0.05), (0.48±0.07) and (0.14±0.04) voxels, respectively, and the gray matter volume of the corresponding gyri in control group were (0.61±0.09), (0.43±0.06), (0.54±0.07) and (0.16±0.03) voxels, respectively; and the gray matter volume of smoking group were all lower than those in control group (t=-3.81, -3.51, -3.86, -2.33, all P<0.05), family wise error (FWE) correction (P<0.05). The gray matter volume of bilateral thalamus, right supramarginal gyrus and left putamen was negatively correlated with smoking index (r=-0.368, -0.189, -0.274, all P<0.05), and also negatively correlated with smoking years (r=-0.391, -0.221, -0.355, all P<0.05), and bilateral thalamus gray matter volume was negatively correlated with daily cigarette smoking (r=-0.186, P<0.05). Conclusion: The changes of brain structure of smokers mainly occur on reward-related pathways and marginal systems, and related to accumulation of cigarette smoking.

Short-term supplementation of isocaloric meals with L-tryptophan affects pig growth.

L-Tryptophan (Trp) and some of its metabolites regulate the circadian rhythm in mammals. We aimed to investigate the effects of short-term supplementation of Trp in isocaloric meals on growth performance using the parameters of multiple blood biomarkers and free amino acids in growing pigs. A total of 32 Landrace × Yorkshire barrows with a mean body weight of 8.64 (±1.13) kg were randomly assigned to four groups and then fed with various concentrations of Trp diets daily. Our results showed that sequential supplementation of different concentrations of Trp in isocaloric meals decreased the feed:gain (F:G) ratio (P = 0.079) and plasma urea and albumin (P = 0.019), whereas the level of total protein did not. Among the essential and conditionally essential amino acids, the concentrations of histidine, isoleucine, proline, threonine, arginine, and valine in the plasma decreased (P < 0.05), whereas the concentrations of Trp, glycine, serine, and methionine increased (P < 0.01). In addition, concentrations of branched chain amino acids also significantly decreased (P = 0.004), while the rate of conversion of Trp to branched chain amino acids increased (P < 0.001). Taken together, we show that administration of a high concentration of Trp in breakfast with decreasing concentrations of Trp in lunch and dinner positively affected feed utilization and improved feed efficiency, at least in part, through the optimization of amino acid interconversions and nitrogen utilization.

[Trends in Gleason scores of Chinese prostate carcinoma from 1995 to 2014].

OBJECTIVE: To assess the changing trends in Gleason score (GS) of Chinese prostate carcinoma (PCa) from January 1995 to December 2014. METHODS: In the study, 875 patients admitted to hospital from January 1995 to December 2004 (1995-2004) and from January 2005 to December 2014 (2005-2014) were divided into two groups. The mean levels and proportions of GS, primary and secondary grades were studied. The patients were divided into four groups according to age: <60, 60-69, 70-79 and ≥80 years. Types of specimen included needle biopsy (NB), transurethral resection of the prostate (TURP) and radical prostatectomy (RP). Histological types were made up by acinar carcinoma and other types (including atrophic, pseudohyperplastic, foam, signet ring cell and ductal carcinoma, and so on). The total prostate-specific antigen (tPSA) involved groups of <20.0 µg/L and ≥20.0 µg/L. We observed the mean levels and proportions of GS in age, types of specimen, histological types and total prostate-specific antigen in different periods, and used SPSS 17.0 software for statistical analysis. RESULTS: Compared with 1995-2004, the mean levels of GS, primary and secondary grades decreased 0.32 (P=0.003), 0.19 (P=0.001) and 0.12 (P=0.016) in 2005-2014, respectively. The proportions of ≤6 in GS increased 10.9% (P=0.003), and ≥8 decreased 14.0% (P<0.001). The difference of GS 7 was not statistically significant. In the primary grade, the ratio of grades≤3 increased 12.8% (P=0.001), and grade 4 decreased 7.4% (P=0.037), grade 5 decreased 5.5% (P=0.007). The ratio of secondary grades ≤3 increased 7.6% (P=0.037). The difference of grades 4 and 5 was not statistically significant. CONCLUSION: GS in Chinese patients with PCa showed a downward trend, which is one of the notable features in the past 20 years in China. The types of specimen and age are important factors in GS, while the histological types and tPSA have less impact on the GS.

A variant on the kappa opioid receptor gene (OPRK1) is associated with stress response and related drug craving, limbic brain activation and cocaine relapse risk.

Stress increases drug craving and relapse risk. The kappa opioid receptor gene (OPRK1) mediates stress responses. Here, we examined whether the OPRK1 rs6989250 C>G affects stress-induced cocaine craving and cortisol responses, subsequent cocaine relapse risk and the neural response to stress using functional magnetic resonance imaging (fMRI) in cocaine dependence. Sixty-seven treatment-engaged, abstinent cocaine-dependent African-Americans were genotyped (CG: N=10; CC: N=57) and participated in a 3-day experiment in which they were exposed to personalized script-driven imagery of stress, drug cues and neutral scenarios, one condition per day, randomly assigned and counterbalanced across subjects. Repeated measures of craving and cortisol were obtained. The subjects were followed prospectively for 90 days to assess relapse risk. A follow-up preliminary fMRI experiment assessed neural responses to stress, drug cue and neutral conditions in matched CG (N=5) and CC (N=8) subgroups. We found greater stress-induced craving (P=0.019), higher cortisol during stress and cue relative to the neutral condition (P's<0.003), and increased cocaine relapse risk (P=0.0075) in the CG compared with the CC group. The CG relative to the CC group also showed greater activation of limbic and midbrain regions during stress and cues relative to the neutral condition with additional stress-induced activation in the right amygdala/hippocampus (P<0.05, whole-brain corrected). These results suggest that OPRK1 is associated with stress-induced craving and cortisol, hyperactive hypothalamus/thalamus-midbrain-cerebellum responses, and also associated with greater subsequent cocaine relapse risk. Future studies to replicate these findings in a larger sample size are warranted.

New alkaloids from the seeds of Notopterygium incisum.

Three new alkaloids, N-hexacosanoylanthranilic acid (1), N-octacosanoylanthranilic acid (2) and N-eicosanoyltyramine (3), along with 19 known compounds, were isolated from the seeds of Notopterygium incisum, whose rhizomes are used as a traditional Tibetan medicine. Their structures were elucidated by 1D, 2D NMR spectra and ESI-MS spectrometer evidence.

A foot drop correcting FES envelope design method using tibialis anterior EMG during healthy gait with a new walking speed control strategy.

Restoring walking functions will greatly improve the foot-drop patients' life quality. In this work, we sampled 10 healthy subjects' gait data when walking in 4 different stride frequency overground and developed a dynamic Functional Electrical Stimulation (dFES) system for foot-drop patients' walk training, using the processed tibialis anterior (TA) muscle EMG signal. The data sampled under the new strategy can be used by FES system directly. And the dFES system can provide dynamic Pulse Width Modulation (PWM) FES serial according to the healthy subjects' TA EMG intensity features.

Zoledronate reverses mandibular bone loss in osteoprotegerin-deficient mice.

UNLABELLED: To characterize the changes in osteoprotegerin-deficient (OPG-/-) mice mandibles and the possible mandibular bone loss prevention by zoledronate. This preventive effect in the mandible differed from that in the proximal tibia and was independent of the OPG pathway. INTRODUCTION: The study aimed to characterize both the changes in the mandible in osteoprotegerin-deficient (OPG-/-) mice and possible mandibular bone loss prevention by zoledronate. METHODS: Twenty-eight 6-week-old female mice (C57BL/6J), including OPG-/- (n = 21) and wild-type (WT) (n = 7) mice, were assigned to four groups after 2 weeks of acclimatization to local vivarium conditions: wild mice with vehicle (WT group); OPG-/- mice with vehicle (OPG-/- group); and OPG-/- mice that were subcutaneously injected with either 50 or 150 microg/kg zoledronate (Zol-50 and Zol-150 groups, respectively). Mice were sacrificed at 4 weeks after these treatments and after fasting for 12 h. Sera were harvested for biochemical analyses. The right mandible and tibia of each mouse were selected for microCT analysis. Student's t-test was performed for comparisons of bone parameters at different sites in the WT group. Analysis of variance (ANOVA) was used to compare the biomarkers and bone parameters in the different treatment groups. RESULTS: Serum bone-specific alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) were significantly decreased in WT mice as compared to the levels in the OPG-/- mice (P < 0.05). Zoledronate treatment decreased the high serum B-ALP activity observed in OPG-/- mice to the levels seen in WT mice, while serum TRACP-5b concentrations were decreased to levels even lower than those in WT mice. There were substantial variations in BMD and microstructure of the mandibular and proximal tibial trabeculae. Mandibular bone loss was less affected by OPG gene deprivation than the proximal tibia was. Both zoledronate groups showed greater BMD, trabecular BV/TV, Tb.Th, Tb.N, and Conn.D and a significant decrease in Tb.Sp and SMI as compared to the findings in OPG-/- mice (P < 0.05). However, higher apparent BMD and more compact plate-like trabeculae were observed in the mandible after treatment with zoledronate as compared to the findings in the proximal tibia. No significant differences were found in any parameter in both zoledronate groups. CONCLUSIONS: The present study showed that zoledronate could reverse the significant bone loss in mice mandibles that was induced by OPG gene deficiency. This preventive effect, which was accompanied with considerable inhibition of bone turnover, differed in the mandible and in the proximal tibia and was independent of the OPG pathway.

Recovery oriented phosphorus adsorption process in decentralized advanced Johkasou.

Decentralized advanced wastewater treatment using adsorption and desorption process for recovery and recycling oriented phosphorus removal was developed. Adsorbent particles made of zirconium were set in a column, and it was installed as subsequent stage of BOD and nitrogen removal type Johkasou, a household domestic wastewater treatment facility. The water quality of the effluent of adsorption column in a number of experimental sites was monitored. The effluent phosphorus concentration was kept below 1 mg l(-1) during 90 days at all the sites. Furthermore, over 80% of the sites achieved 1 mg l(-1) of T-P during 200 days. This adsorbent was durable, and deterioration of the particles was not observed over a long duration. The adsorbent collected from each site was immersed in alkali solution to desorb phosphorus. Then the adsorbent was reactivated by soaking in acid solution. The reactivated adsorbent was reused and showed almost the same phosphorus adsorption capacity as a new one. Meanwhile, the desorbed phosphorus was recovered with high purity as trisodium phosphate by crystallization. It is proposed as a new decentralized system for recycling phosphorus that paves the way to high-purity recovery of finite phosphorus.

The complementarity and substitution between unconventional and mainstream medicine among racial and ethnic groups in the United States.

OBJECTIVES: To describe racial and ethnic differences in the utilization patterns of 12 common types of complementary and alternative medicine (CAM) and mainstream medicine (MSM) and to test whether a specific CAM type is a substitute for or a complement to MSM among five racial and ethnic groups in the United States. METHODS: The Medical Expenditure Panel Survey in 1996 and 1998 were used. The sample of 46,673 respondents was stratified into non-Hispanic whites (NHW), Hispanics, blacks, Asians, and other races. Twelve types of CAM visits and visits to office-based and outpatient physicians were used to describe the pattern of CAM and MSM use. Utilization patterns among each racial and ethnic group were established and compared. Multivariate analyses were conducted to test whether each type of CAM and MSM were complements or substitutes within a racial and ethnic group, controlling for respondents' sociodemographics and health. RESULTS: Significant intergroup differences in the prevalence rates of using various types of CAM were found. In particular, for some racial and ethnic groups, CAM can be either a substitute for or a complement to MSM visits, depending on the CAM type. More complementary relationships between CAM and physician visits were found in NHW and Asians than in other groups. All significant relationships between CAM types and physician visits among Hispanics and other races (predominantly Native American Indians) were substitution. CONCLUSIONS: Complementarity and substitution of CAM and MSM varied by racial and ethnic groups and by type of CAM. Culturally sensitive approaches are needed in successful integration of CAM in treatment management.

The 44 kDa Pim-1 kinase directly interacts with tyrosine kinase Etk/BMX and protects human prostate cancer cells from apoptosis induced by chemotherapeutic drugs.

Protein kinase Pim-1 has been implicated in the development of hematopoietic and prostatic malignancies. Here, we present the evidence that two isoforms, the 44 and 33 kDa Pim-1, are expressed in all human prostate cancer cell lines examined. The subcellular localization of human 44 kDa Pim-1 is primarily on the plasma membrane, while the 33 kDa isoform is present in both the cytosol and nucleus in PCA cells. The 44 kDa Pim-1 contains the proline-rich motif at the N-terminus and directly binds to the SH3 domain of tyrosine kinase Etk. Such interaction leads to the activation of Etk kinase activity possibly by competing with the tumor suppressor p53. This is corroborated by the fact that overexpression of the 44 kDa Pim-1 in prostate cancer cells confers the resistance to chemotherapeutic drugs. Our results suggest that these two isoforms of Pim-1 kinase may regulate distinct substrates and the 44 kDa Pim-1 may play a more prominent role in drug resistance in prostate cancer cells.

Older persons' evaluations of health care: the effects of medical skepticism and worry about health.

OBJECTIVE: To describe how skepticism about medical care and other individual differences, including worry about health status, are associated with evaluations of health care among the noninstitutionalized elderly. DATA SOURCES/STUDY SETTING: Data were collected through a survey of approximately 5,000 community-dwelling elders (aged 65 and older) in a southwestern region of the United States. STUDY DESIGN: Global evaluations of health care were measured with two items from the Consumer Assessment of Health Plans Study (CAHPS) instrument, an overall care rating (OCR) and a personal doctor rating (PDR). Multivariate ordered logit regression models were tested to examine how medical skepticism and other factors were associated with ratings of 0-7, 8-9, and 10. PRINCIPAL FINDINGS: Consumers who were skeptical of prescription drugs relative to home remedies, who held attitudes that they understand their health better than most doctors, and who worried about their health had worse OCR and PDR. Those who held attitudes that individual behavior determines how soon one gets better when sick had better PDR and OCR. CONCLUSIONS: Health policymakers, managers, and providers may need to consider the degree to which they should attempt to satisfy skeptical consumers, many of whom may never rate their care highly. Alternatively, they may need to target skeptical consumers with educational efforts explaining the benefits of medical care.

The use of midazolam and small-dose ketamine for sedation and analgesia during local anesthesia.

UNLABELLED: Small-dose ketamine in combination with sedative drugs has increasingly been used for sedation and analgesia in local anesthesia. We compared the clinical efficacy of midazolam with two different ketamine infusion regimens during plastic surgery under local anesthesia. Sixty patients undergoing plastic surgery procedures with local anesthesia were randomly assigned to two groups of 30 patients each in a double-blinded fashion. All patients received a bolus of 0.05 mg/kg midazolam, followed by a stepwise infusion: 1.67 microg x kg(-1) x min(-1) for the first 30 min, then reduced to 1.33 microg x kg(-1) x min(-1) for 90 min and subsequently to 1 microg x kg(-1) x min(-1). Two minutes before the infiltration of local anesthetic solution, a bolus of ketamine 0.3 mg/kg IV was administered, followed by a stepwise infusion of ketamine: Group A, 16.67 microg x kg(-1) x min(-1) for 30 min, 13.3 microg x kg(-1) x min(-1) for 90 min, and subsequently 10 microg x kg(-1) x min(-1); Group B, 8.33 microg x kg(-1) x min(-1) for 30 min, 6.67 microg x kg(-1) x min(-1) for 90 min, and then 5 microg x kg(-1) x min(-1). The level of sedation was evaluated by using the modified Observer's Assessment of Alertness/Sedation scale. We observed the effects of the two ketamine infusion regimens on sedation levels, respiratory and cardiovascular variables, and perioperative side effects. In both groups, midazolam and ketamine produced adequate sedation (with Observer's Assessment of Alertness/Sedation scores of 2-4) without significant respiratory and cardiovascular depression during surgery. However, there were fewer disruptive movements and there was less postoperative vomiting in Group B (P < 0.01). In conclusion, ketamine and midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in both groups. However, side effects associated with ketamine occurred less often in the smaller-dose ketamine group. IMPLICATIONS: Sedation and analgesia are often provided during local anesthesia. This study demonstrates that a small-dose ketamine infusion in combination with midazolam provided satisfactory intraoperative sedation, analgesia, and amnesia in healthy plastic-surgery patients when it was used to supplement local anesthesia.

Discovery of a new inhibitor lead of adenovirus proteinase: steps toward selective, irreversible inhibitors of cysteine proteinases.

Using the computer docking program EUDOC, in silico screening of a chemical database for inhibitors of human adenovirus cysteine proteinase (hAVCP) identified 2,4,5,7-tetranitro-9-fluorenone that selectively and irreversibly inhibits hAVCP in a two-step reaction: reversible binding (Ki = 3.09 microM) followed by irreversible inhibition (ki = 0.006 s(-1)). The reversible binding is due to molecular complementarity between the inhibitor and the active site of hAVCP, which confers the selectivity of the inhibitor. The irreversible inhibition is due to substitution of a nitro group of the inhibitor by the nearby Cys122 in the active site of hAVCP. These findings suggest a new approach to selective, irreversible inhibitors of cysteine proteinases involved in normal and abnormal physiological processes ranging from embryogenesis to apoptosis and pathogen invasions.

Il-10 up-regulates macrophage expression of the S100 protein S100A8.

The murine calcium binding protein S100A8 (A8) is a leukocyte chemoattractant, but high levels may be protective and scavenge hypochlorite. A8 is induced by LPS, IFN-gamma, and TNF in elicited macrophages. Th2 cytokines generally suppress proinflammatory gene expression, and IL-4 and IL-13 partially decreased A8 induction in macrophages and endothelial cells stimulated by LPS or IFN. In contrast, IL-10 synergized with LPS and IFN to increase mRNA levels > or =9-fold and secreted A8 levels approximately 4-fold. IL-10 decreased the optimal time of mRNA expression induced by LPS from 24 to 8 h. Blocking experiments indicated that endogenous IL-10 contributes to gene induction by LPS. Cooperation between IL-10 and LPS was not due to altered mRNA stability but was dependent on de novo protein synthesis. Transfection analysis with A8 luciferase constructs confirmed that synergy was due to increased transcription. The region of the promoter involved was localized to a 178-bp fragment flanking the transcription start site of the gene. This region was also responsible for the suppressive effects of IL-4 and IL-13. Forskolin, CTP-cAMP, and PGE(2) also enhanced LPS- and IFN-induced A8 mRNA, whereas indomethacin significantly reduced synergy between IL-10 and LPS. Mitogen-activated protein kinase/cyclooxygenase 2/cAMP pathways involving CCAAT-enhancing binding protein, located within the active promoter, may mediate A8 gene up-regulation in a manner mechanistically distinct to genes regulated by IL-10 via the STAT pathway. A8 exhibits pleiotropic effects, and the high levels secreted as a result of IL-10 synergy may regulate untoward inflammatory damage by virtue of its an antioxidant capacity.