Efficacy and nephrotoxicity of polymyxin B in elderly patients with carbapenem resistant bacterial infection.

BACKGROUND: To study the efficacy and nephrotoxicity of polymyxin B in the treatment of elderly patients with carbapenem-resistant organism (CRO) infection. METHODS: The clinical and microbiological data of patients with CRO-infected sepsis treated with polymyxin B were retrospectively analyzed. The effective rate, bacterial clearance, incidence and recovery rate of acute renal injury (AKI) and prognosis-related indicators in AKI at different stages were compared. RESULTS: The effective rate of 215 elderly patients with CRO infection treated with polymyxin was 50.7%. The total bacterial clearance rate was 44.2%, the total incidence of AKI was 37.2%, the recovery rate of AKI was 35%, and the incidence range of polymyxin B-related AKI was 10.2-37.2%. Logistic multivariate regression analysis showed that the predictors of AKI in elderly patients were high APACHE II score, long duration of polymyxin, chronic renal insufficiency and ineffective outcome; the ROC curve showed that the cutoff value for predicting AKI was a serum creatinine concentration of 73 mmol/L before polymyxin B use, and the AUC was 0.931. CONCLUSIONS: Rational use of polymyxin B is safe and effective in elderly patients with CRO infection, and its effective outcome can improve the recovery rate of AKI.

The effects of ALDH2 Glu487Lys polymorphism on vasovagal syncope patients undergoing head-up tilt test supplemented with sublingual nitroglycerin.

BACKGROUND AND OBJECTIVE: Head-up tilt test (HUTT) is clinically advantageous for diagnosing patients with vasovagal syncope (VVS). Nitroglycerin is mainly used as a stimulant during HUTT, and mitochondrial aldehyde dehydrogenase 2 (ALDH2) is involved in the metabolism of nitroglycerin (NTG). ALDH2 Glu487Lys polymorphism (ALDH2 rs671) is the most common variant in the East Asian population. This study aimed to assess the effects of ALDH2 rs671 on VVS patients undergoing HUTT supplemented with sublingual NTG (HUTT-NTG).  METHODS: Patients with recurrent VVS (at least 2 times) who were admitted to the syncope center of our hospital were enrolled. All VVS patients have undergone HUTT. The polymorphism of Glu487Lys gene of ALDH2 was measured by the DNA Microarray Chip Method. The results of HUTT-NTG of VVS patients with different ALDH2 genotypes were compared and their hemodynamic characteristics were assessed. RESULTS: A total of 199 VVS patients were enrolled, including 101 patients in the ALDH2*1/*1 group and 98 patients in the ALDH2*2 group. Among patients undergoing HUTT-NTG, 70.3% of patients in the ALDH2*1/*1 group and 68.4% of patients in the ALDH2*2 group were positive, and the difference between the two groups was not statistically significant (P = 0.77). The proportions of VASIS I, VASIS II, and VASIS III were 40.6%, 8.9%, and 20.8% in the ALDH2*1/*1 group, respectively, and the corresponding proportions in the ALDH2*2 group were 36.7%, 11.2%, and 20.4%, respectively. There was no statistically significant difference between the two groups (P = 0.91). The hemodynamic characteristics of different genotypes in VVS patients undergoing HUTT-NTG were compared, and no statistically significant difference was found. The median time of syncopal episode occurred after NTG administration in the ALDH2*1/*1 group was 6 min (interquartile range [IQR]: 5.0-9.0), and it was 6.0 min in the ALDH2*2 group (IQR: 4.25-8.0, P = 0.64). CONCLUSION: ALDH2 Glu487Lys polymorphism did not affect the outcome of VVS patients undergoing HUTT-NTG, and no significant change in the hemodynamic characteristics of different genotypes was found.

Efficacy and safety of polymyxin B in carbapenem-resistant gram-negative organisms infections.

OBJECTIVE: To investigate how to use polymyxin B rationally in order to produce the best efficacy and safety in patients with carbapenem-resistant gram-negative organisms (CRO) infection. METHODS: The clinical characteristics and microbiological results of 181 patients caused by CRO infection treated with polymyxin B in the First Affiliated Hospital from July 2018 to May 2020 were retrospectively analyzed. The bacterial clearance rate, clinical efficacy, adverse drug reactions and 28 days mortality were evaluated. RESULTS: The overall effective rate of 181 patients was 49.72%, the total bacterial clearance rate was 42.0%, and the 28 day all-cause mortality rate was 59.1%. The effective rate and bacterial clearance rate in the group of less than 24 h from the isolation of CRO to the use of polymyxin B were significantly higher than those in the group of more than 24 h. Logistics multivariate regression analysis showed that the predictive factors for effective treatment of CRO with polymyxin B were APACHEII score, duration of polymyxin B treatment, combination of polymyxin B and other antibiotics, and bacterial clearance. 17 cases (9.36%) of acute kidney injury were considered as polymyxin B nephrotoxicity and 4 cases (23.5%) recovered after polymyxin B withdrawal. After 14 days of polymyxin B use, 3 cases of polymyxin B resistance appeared, and there were 2 cases of polymyxin B resistance in the daily dose 1.5 mg/kg/day group. CONCLUSION: For CRO infection, the treatment of polymyxin B should be early, combined, optimal dose and duration of treatment, which can achieve better clinical efficacy and microbial reactions, and reduce the adverse reactions and drug resistance.

Integrated microRNA-mRNA analysis reveals the roles of microRNAs in the muscle fat metabolism of Yanbian cattle.

Fat deposition is an important economic trait in farm animals. However, it is difficult to genetically improve intramuscular fat deposition via trait-based cattle breeding. The main objectives of this study were to analyze the factors about beef flavor, and to detect functional microRNA (miRNA, miR) associated with intramuscular fat deposition in Yanbian cattle. Longissimus dorsi samples from six steers were separated into high- and low-fat groups (n = 3 each) based on the marbling score, and transcriptomic analysis was performed using miRNA sequencing. A total of 33 miRNAs and 38 genes were found to be differentially expressed in the high- and low-fat groups. Quantitative real-time polymerase chain reaction was performed to validate the sequencing results. Integrated miRNA-mRNA analysis revealed that miRNA-associated target genes were primarily associated with skeletal muscle development. However, some of the miRNAs (miR-424 etc.) and genes (ATF3 etc.) were also associated with fat metabolism. A targeted relationship between miR-22-3p and the WFIKKN2 gene and its involvement in adipocyte differentiation were confirmed experimentally. The study findings may provide potential candidate molecular targets for the selection of cattle with improved meat quality.

Bovine bta-microRNA-1271 Promotes Preadipocyte Differentiation by Targeting Activation Transcription Factor 3.

Yanbian yellow cattle are one of the top five largest breeds of cattle in China. We had previously found that bta-miR-1271 is differentially expressed in the longissimus dorsi muscles of Yanbian yellow bulls and steers. However, whether bta-miR-1271 affects bovine fat formation is unclear. In this study, we used target gene prediction, dual-luciferase reporter assay, and transfection-mediated overexpression and inhibition of bta-miR-1271 in a culture of Yanbian yellow cattle preadipocytes to investigate the role of bta-miR-1271 in adipogenesis. We showed that bta-miR-1271 directly targets the 3'-untranslated region (3'-UTR) of the activating transcription factor 3 (ATF3) mRNA and downregulates its expression. Overexpression of bta-miR-1271 enforced by the miRNA mimics promoted triglyceride accumulation and significantly upregulated expression of the adipogenic peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer-binding protein α (C/EBPα) genes at both the protein and mRNA levels, as demonstrated by RT-qPCR and Western blot analyses. Conversely, inhibition of bta-miR-1271 expression produced the opposite effect. Our results show that bta-miR-1271 regulates differentiation of Yanbian yellow cattle preadipocytes by inhibiting ATF3 expression, which highlights the importance of microRNA-mediated regulation of adipogenesis. miR-1271 and its target gene(s) may provide a new research direction for investigating biological agents affecting intramuscular fat deposition in cattle.

Comparison of MAP method with classical methods for bandpass correction of white LED spectra.

The bandwidth of a spectrometer is an important error-influencing factor in spectral measurement. To obtain accurate results, bandpass correction is an indispensable step in spectral data processing. To deal with such a problem, several methods have been proposed, including the differential operator method using a local polynomial approximation and the Richardson-Lucy method combined with a regularization. Here we employ a method based on the maximum a posteriori estimation. The efficiency of the method is verified through a large number of experiments on the spectra of white light-emitting diodes. By comparing the error of the reference spectrum, it was found that this method can effectively correct spectra, thus providing more accurate information for further analysis.

Public health investigation and response to a hepatitis A outbreak from imported scallops consumed raw-Hawaii, 2016.

During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.

[The effect of human islet amyloid polypeptide on autophagy in murine INS-1 cells and potential mechanisms].

Objective: The aims of the study were to investigate the effects of human islet amyloid polypeptide (hIAPP) on autophagy in INS-1 cells and its underlying mechanism, and to explore the role of autophagy in hIAPP-induced cytotoxicity and oxidative stress. Methods: INS-1 cells were treated with hIAPP (10 µmol/L) for 24 h in the presence or absence of N-acetyl-L-cysteine (NAC), compound C, 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) and 3-methyladenine (3-MA), respectively. Transmission electron microscopy was used to observe the number of autophagosome in cells. Cell viability was determined by methyl thiazolyl tetrazolium (MTT) test. 2',7'-dichlorofluorescin diacetate (DCFH-DA) assay was used to measure the relative levels of reactive oxygen species (ROS). Western blot was used to detect expression of adenosine monophosphate-activated protein kinase (AMPK) and autophagic markers p62 and microtubule associated protein 1 light chain3 (LC3). Results: Treatment of INS-1 cells with hIAPP resulted in a significant increase in the number of autophagosomes and the expression of LC3-Ⅱ/LC3-Ⅰ (both P<0.05). Meanwhile, treatment of INS-1 cells with hIAPP enhanced the level of ROS to 1.76 times of control cells (P<0.01). Co-treatment with NAC, an antioxidant, inhibited hIAPP-induced ROS generation, and the expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK in the INS-1 cells (all P<0.05). Pretreatment of INS-1 cells with AMPK inhibitor compound C suppressed hIAPP and AICAR, an activator of AMPK, induced expression of LC3-Ⅱ/LC3-Ⅰ and p-AMPK (all P<0.05). Autophagic inhibitor 3-MA and compound C aggravated the hIAPP-induced cell death and ROS generation in INS-1 cells (All P<0.05). The cytotoxic effects of hIAPP were significantly attenuated by co-treatment with AICAR (P<0.05). Conclusion: Autophagy may act as an adaptive mechanism to alleviate hIAPP-induced oxidative damage and toxicity in INS-1 cells.

[Effects of calcineurin gene silencing on the remodeling of transient outward potassium current ionic channel in hypertrophic ventricular myocytes from neonatal rats].

Objective: To investigate the effects of calcineurin gene silencing on the remodeling of transient outward potassium current (Ito) ionic channel and action potential duration (APD) in phenylephrine (PE)-induced hypertrophic ventricular myocytes from neonatal rats. Methods: The ventricular myocytes of 1-day-old Sprague-Dawley rats were isolated and cultured for 48 h. RNA interference mediated by adenovirus carrying short hairpin RNA was used to knock down the gene which encodes the beta subtype of calcineurin A subunit (CnAß) and the cells were divided into 4 groups as Ad-null group, Ad-null+ PE group, Ad-CnAßshRNA1(A1) group and A1+ PE group, and then cultured for 48 h. The gene expression of Kv4.2 was assayed by real-time reverse transcriptase-polymerase chain reaction. The protein expressions of CnAß and Kv4.2 were assayed by Western blot test. Whole cell patch clamp technique was used to record Ito and action potential. Results: Treatment of the neonatal rat ventricular myocytes with PE induced the cell hypertrophy, up-regulated the protein expression of CnAß, attenuated the gene and protein expressions of Kv4.2 and the Ito current density, and prolonged APD. Silencing of CnAß in the neonatal rat ventricular myocytes using Ad-CnAßshRNA1 inhibited the aforementioned ability of PE significantly. Conclusion: CnAß gene silencing inhibits the remodeling of transient outward potassium current ionic channel and change of APD in PE-induced hypertrophic ventricular myocytes from neonatal rats.

[Analysis of eight-year follow-up data of plateau workers by color doppler echocardiography].

Objective: To analyze the heart rate changes and risk factors, as a result of high altitude. Methods: Retrospective analysis of echocardiographic data of plateau workers at a railway maintenance company from 2006 to 2013. The survival curve method was used to analyze the abnormal rate of the heart. Kaplan-Meier method and Cox proportional hazards regression model were used to analyze the influencing factors. Results: In the first occurrence of cardiac abnormalities, the main types of abnormalities were right atrium enlargement (53.47%) , right ventricle enlargement (17.36%) , and tricuspid regurgitation (16.67%) . Cox regression analysis showed that workplace altitude and first physical examination age are two influencing factors of cardiac abnormalities, and their relative risk was 1.661 and 1.039. At high altitudes (3 600~4 000 m) , nearly 40% of workers heart has not changed. But this adaptation does not observed in the ultra-high altitudes (≥4 000 m) . Conclusion: There are individual differences in human adaptability to high altitude. We should take more stringent measures of health care for older people and those who work at more than 4000m. And we should abide by the rotation system for railways that are suitable for the plateau.

Bandwidth correction in the spectral measurement of light-emitting diodes.

Light-emitting diodes (LEDs) are widely employed in industrial applications and scientific research. However, spectral distortions will occur due to the broadening effects of the spectrometer when an LED spectrum is obtained with a spectrometer. In this paper, a novel approach is put forward to correct bandwidth for an LED spectrum based on a Levenberg-Marquardt algorithm and He-Zheng model. We compare estimation errors of different LED spectra by using the proposed method along with the Richardson-Lucy method and differential operator approach. The experimental results show that the effect of the proposed approach is better than that of the other two methods.

Accurate wavelength calibration method for compact CCD spectrometer.

Wavelength calibration is an important step in charge-coupled device (CCD) spectrometers. In this paper, an accurate calibration method is proposed. A model of a line profile spectrum is built at the beginning, followed by noise reduction, bandwidth correction, and automatic peak-seeking treatment. Experimental tests are conducted on the USB4000 spectrometer with a mercury-argon calibration light source. Compared with the traditional method, the results show that this wavelength calibration procedure obtains higher accuracy and the deviations are within 0.1 nm.

Dual-grating dielectric accelerators driven by a pulse-front-tilted laser.

This paper investigates numerically dual-grating dielectric laser-driven accelerators driven by a pulse-front-tilted (PFT) laser, which extends the interaction length and boosts the electrons' energy gain. The optical system necessary to generate PFT laser beams with an ultrashort pulse duration of 100 fs is also studied in detail. Through two-dimensional particle-in-cell simulations, we show that such a PFT laser effectively increases the energy gain by (91±25) % compared to that of a normally incident laser with a waist radius of 50 µm for a 100-period dual-grating structure.

The effect of nerve mobilization exercise in patients with rheumatoid arthritis: a pilot study.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the joints. The neurogenic inflammatory mechanism plays an important role in the inflammatory process of RA, and pathological changes in neural tissues in RA have also been noted. We aim to investigate treatment of the nervous system to relieve joint pain and inflammation in RA. Nerve mobilization, a nervous system-specific therapeutic exercise, was applied on RA patients to determine the effect of nerve mobilization on joint inflammation. Twelve RA patients were recruited from the community and were randomised into an experimental and a control group. In the experimental group, the subjects were taught a set of nerve mobilization exercises while the subjects in the control group were taught a set of gentle joint mobilization exercises. Both groups were instructed to practice the exercises daily. After a 4-week period, their RA pain scale (RAPS) and pain scores were examined, as well as the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Subjects in the experimental group showed improvements in RAPS and pain scores after 4 weeks of nerve mobilization exercises, while CRP and ESR values remained unaffected. These preliminary data showed that nerve mobilization exercises might be beneficial in controlling joint pain in RA patients.

[The alterations and clinical significance of serum thyroid hormone levels in patients with acute exacerbation of chronic obstructive pulmonary disease].

Objective: To observe the alterations of serum thyroid hormone levels in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients without thyroid disease and therefore to investigate the association between serum thyroid hormone levels and the severity and prognosis of AECOPD. Methods: Serum thyroid hormone levels including TT4, TT3, TSH, FT4 and FT3 were measured by chemiluminescence immunoassay in 84 hospitalized patients with AECOPD [male 52, female 32, aged 50-93 years, average (78±10) years] and in 35 healthy subjects [male 20, female 15, aged 51-87 years, average (73±11) years] from 2013 to 2014. Results: The serum TT4, TT3 and FT3 levels in AECOPD patients before therapy were significantly lower than those after therapy(P<0.05). The serum TT4, TT3 and FT3 levels in AECOPD post-therapy were significantly lower than those in the healthy control group(TT4: 80±18, 89±18, 113±21; TT3: 0.84±0.25, 1.37±0.31, 1.60±0.35; FT3: 2.57±0.73, 3.49±0.64, 4.21±0.75, P<0.05). The serum FT4 level in AECOPD pre-therapy was significantly lower than that in AECOPD post-therapy and the control group(15.0±2.8, 16.3±2.5, 16.7±2.4, P<0.05). The difference of serum FT4 level between AECOPD post-therapy group and the control group was not statistically significant(P>0.05). The Serum TT4, TT3, FT4 and FT3 levels in type Ⅰ respiratory failure subgroup and type Ⅱ respiratory failure subgroup were both significantly lower than those in the non-respiratory failure subgroup(TT4: 78±14, 70±16, 92±17; TT3: 0.73±0.16, 0.73±0.23, 1.04±0.21; FT4: 14.4±2.4, 14.1±2.4, 16.3±2.9; FT3: 2.27±0.65, 2.32±0.66, 3.05±0.62, P<0.05). The differences of serum TT4, TT3, FT4 and FT3 levels between type Ⅰ respiratory failure subgroup and type Ⅱ respiratory failure subgroup were not statistically significant(P>0.05). The serum TT3 and FT3 levels in the survival subgroup were significantly higher than those in the fatal subgroup(TT3: 0.90±0.25, 0.68±0.18; FT3: 2.76±0.67, 2.07±0.68, P<0.05). The differences of serum TT4(82±18, 75±17), FT4(15.2±2.8, 14.2±2.7) and TSH(1.1±1.1, 1.5±1.5) levels between the 2 subgroups were not statistically significant(P>0.05). Conclusion: Serum thyroid hormone levels are related to the condition of AECOPD. They are reduced in patients with AECOPD and can recover to different degrees as the primary disease improves. Hypoxia and carbon dioxide retention can result in decreased levels of serum thyroid hormones. Serum thyroid hormone levels are significantly associated with the severity and prognosis of patients with AECOPD.

[Extensive burns complicated with infective endocarditis and septic pulmonary embolism: case report and literature review].

Objective: To improve the clinical recognition of infective endocarditis (IE) and septic pulmonary embolism (SPE) in patients with extensive burns. Methods: A case of large area burn complicated with IE and SPE confirmed by blood cultures and echocardiography was described. A literature review was performed with "burn" and "infective endocarditis" as the Chinese key words in Wanfang database; with "burn" and "infective endocarditis" as Mesh terms in PubMed. Results: The patient was a 37-year-old male with large area burn, who presented with fever and hemoptysis. Blood cultures were positive for methicillin resistant Staphylococcus aureus (MRSA). Echocardiography disclosed vegetations located in the tricuspid valve. Multiple wedge-shaped lesions were found on chest CT. From January 1978 to December 2015, 26 related articles were retrieved and 134 burned patients complicated with endocarditis were reported, of which, 97 cases were IE and 1 case with SPE. Of the 134 cases, 120 cases were dead, 12 cases cured and 2 cases unknown. The mortality was 89.6%. Conclusions: There was a high mortality of burned patients complicated with IE. SPE should be considered for patients with multiple peripheral nodules in both lungs and a positive blood culture. Combination and prolonged anti-infective therapy may increase the treatment success and reduce the risk of recurrence.

[An investigation of prevalence of occupational diseases and treatment implementation in migrant workers in Hunan, China].

Objective: To investigate the prevalence of occupational diseases and treatment implementation in migrant workers in Hunan, China, and to provide a scientific basis for related departments to develop preventive and treatment measures and social security system for migrant workers. Methods: A retrospective investigation was performed in 2015 to collect the information of occupational diseases in migrant workers, and age, type of work, type of occupational disease, and implementation of employment injury insurance for occupation diseases were analyzed. Results: The migrant workers with occupational diseases accounted for 50.43% (11 280/22 368) of all patients with occupational diseases in Hunan, among whom 99.4% (11 212/11 280) were male workers. The mean age of migrant workers with occupational diseases was 55 years. The types of occupational diseases involved 6 categories such as occupational pneumoconiosis and occupational skin diseases, totaling 42 legal occupational diseases; 98.31% of all migrant workers (11 089/11 280) had occupational pneumoconiosis. The main types of work were underground coal miners (62.42%) , heading drivers (29.79%) , and haulage workers (2.20%) in coal mines and non-coal mines. A total of 27.25% migrant workers with occupational diseases (2 072/7 605) enjoyed employment injury insurance, and 20.84% (1 585/7 605) did not receive any medical or life compensations. Conclusion: The occupational diseases in migrant workers in Hunan are mainly pneumoconiosis, and a large proportion of those with occupational diseases do not enjoy implementation of treatment. Coal mines and non-coal mines are the high-risk areas for occupational diseases in migrant workers and should be the focus of prevention and control.

Xylaria hypoxylon Lectin as Adjuvant Elicited Tfh Cell Responses.

Foot-and-mouth disease (FMD) caused by FMD virus (FMDV) is a major health and economic problem in the farming industry. Vaccination of livestock against this highly infectious viral disease is crucial, and inactivated FMD vaccine has been effective at controlling infection. However, accumulated data show that the inactivated vaccine generates weak immune responses and that the oil formulation results in undesirable side effects. Mushroom lectins have recently been shown to display adjuvant effects when incorporated into DNA vaccines. In this study, to enhance the cellular immune response of FMDV antigen (146S), C57BL/6 mice were immunized with 146S combined with Xylaria hypoxylon lectin (XHL). The oil formulation (146S/Oil) was served as control group. Strong humoral immune responses were elicited in mice immunized with 146S/XHL as shown by high 146S antigen-specific IgG levels, and also in 146S/Oil group. Interestingly, XHL in conjunction with inactivated FMD vaccine activated strong Th1 and Tc1 cell responses, especially Tfh cell responses, in immunized mice. XHL stimulated dendritic cell maturation by upregulating expression of major histocompatibility complex II (MHCII) molecules and co-stimulatory molecules CD40 and CD86 in immunized mice. No XHL-specific IgG or inflammatory factors were detected indicating the safety of XHL as an adjuvant. Taken together, these results suggest the effectiveness of XHL at inducing cellular immune responses and therefore confirm its suitability as an adjuvant for inactivated FMD vaccine.

Bolivian kindred with combined spinocerebellar ataxia types 2 and 10.

BACKGROUND: Spinocerebellar ataxias (SCA) are a group of rare hereditary neurodegenerative disorders. Rare cases of two SCA mutations in the same individual have been reported in the literature, however, family descriptions are lacking. AIMS: To characterize a family with combined SCA2 and SCA10 mutations. MATERIALS & METHODS: Analysis of the clinical features and genetic findings of a Bolivian family expressing both SCA2 and SCA10 mutations. RESULTS: The index case and his mother had both SCA2 and SCA10 mutations with a combined clinical phenotype of both disorders, including slow saccades (SCA2) and seizures (SCA10). The uncle of the index case had only an SCA10 mutation. DISCUSSION: Although the presence of two SCA mutations in the same individuals may be coincidental, the low probability of having both mutations suggests that these mutations might be particularly prevalent in Bolivian population. CONCLUSION: This is the first description of a family with two SCA mutations with affected subjects having a combined SCA2 and SCA10 phenotype.

Withaferin A attenuates lipopolysaccharide-induced acute lung injury in neonatal rats.

Withaferin A (WFA) is an active compound from Withania somnifera and has been reported to exhibit a variety of pharmacological activities such as anti—inflammatory, immunomodulatory and anti—tumor properties. In the present study, we investigated the potential protective role of WFA on acute lung injury in neonatal rats induced by lipopolysaccharide (LPS). We found that WFA significantly attenuated the pathological changes of lungs induced by LPS injection. Administration with WFA obviously decreased pulmonary neutrophil infiltration accompanied with decreased MPO concentrations. WFA also reduced the expression of pro—inflammatory cytokines including MIP—2, TNF—α, IL—1β and IL—6. Meanwhile, the expression levels of anti—inflammatory mediators such as TGF—β1 and IL—10 were significantly increased following WFA administration. Moreover, WFA protected LPS—treated rats from oxidative damage via up—regulation of TBARS and H2O2 concentrations and down—regulation of ROS contents. Taken together, the present study demonstrated that WFA administration attenuated LPS—induced lung injury through inhibition of inflammatory responses and oxidative stress.