Sensitive and Specific Loop-Mediated Isothermal Amplification Assays for Detection of Salmonella, CTX-M-1 Group Genes, mph(A), and ermB in Stool and Blood Samples Based on Orange to Green Visible Dye.

Salmonella is a globally prevalent foodborne bacterium, and ceftriaxone and azithromycin have been regarded as drugs of choice for treating Salmonella infections, particularly in children. With the growing incidence of ceftriaxone and azithromycin resistance in Salmonella, there is an urgent requirement for a rapid and dependable gene testing approach to enhance the efficacy of treating Salmonella infections. Utilizing the orange to green visible dye approach, this study developed loop-mediated isothermal amplification (LAMP) assays for the sensitive and specific detection of Salmonella, ceftriaxone and azithromycin resistance genes (including CTX-M-1 group, mph(A), and ermB genes) in stool and blood samples. The specificity and sensitivity of primers during the LAMP assays for detection of Salmonella, CTX-M-1 group, mph(A), and ermB genes were determined in this study. The detection threshold for Salmonella was found to be 1.5 × 103 colony-forming units (CFU)/mL, while it was 1.5 × 102 CFU/mL for CTX-M-1 group genes (including blaCTX-M-3, blaCTX-M-15, and blaCTX-M-55), 1.5 × 102 CFU/mL for mph(A), and 1.5 × 102 CFU/mL for ermB, showing 10-103-fold, 103-fold, and 105-fold increased sensitivity compared with the polymerase chain reaction assay, respectively. Results indicated that the LAMP primers designed for Salmonella, CTX-M-1 group, mph(A), and ermB genes possess high specificity (100%) and sensitivity (over 94%). This novel approach advocates its application in detecting Salmonella, CTX-M-1 group, mph(A), and ermB genes.

Global, Regional, and National Epidemiology of Visual Impairment in Working-Age Individuals, 1990-2019.

Importance: Visual impairment in working-age individuals can affect their general health and employment prospects, leading to decreased social and economic productivity and increased poverty rates. Nonetheless, investigations in this population appear to be limited. Objective: To investigate the trends of visual impairment prevalence and disability-adjusted life-years (DALYs) in working-age individuals from 1990 to 2019. Design, Setting, and Participants: This cross-sectional, population-based study used data for individuals of working age (15-64 years) from 204 countries and territories obtained from the Global Burden of Disease 2019 study. The data analysis was performed between May 1 and 10, 2023. Exposure: Visual impairment, defined as visual acuity of less than 6/18 (20/60) or near visual acuity of less than 6/12 (20/40) distance equivalent as determined by Snellen chart. Main Outcomes and Measures: Trends of visual impairment prevalence, DALYs, and corresponding estimated annual percent changes (EAPCs) from 1990 to 2019 were stratified according to region, nation, and sociodemographic index (SDI). Results: There were 437 539 484 (95% uncertainty interval [UI], 325 463 851-575 573 588) prevalent cases of visual impairment globally (53.12% female and 46.88% male) in 2019, representing an increase of 91.46% from 1990 (prevalent cases, 228 530 964; 95% UI, 172 515 833-297 118 596). Over 3 decades, visual impairment-associated DALYs increased from 7 601 852 (95% UI, 5 047 030-11 107 897) to 12 563 276 (95% UI, 8 278 866-18 961 723). Among the 5 SDI groups, the low-SDI group had the largest increase in DALYs (898 167 [95% UI, 597 161-1 301 931] in 1990 to 1 634 122 [95% UI, 1 079 102-2 444 381] in 2019). Regionally, the greatest increase in prevalence was observed in Eastern Europe (EAPC, 0.10; 95% CI, 0.02-0.19). Among all countries and territories, Nepal had the highest national prevalence of visual impairment per 100 000 population in 2019 (26 008.45; 95% UI, 19 987.35-32 482.09), while South Sudan had the highest DALY rate per 100 000 population (480.59; 95% UI, 316.06-697.06). Conclusions and Relevance: Despite the mild decrease in visual impairment prevalence rates in less-developed countries, these findings suggest that the number of prevalent cases globally has increased substantially, with discernible unfavorable patterns in developed regions. The findings support the notion that visual impairment in working-age individuals is a growing global health challenge. A better understanding of its epidemiology may facilitate the development of appropriate measures for prevention and treatment from both medical and social perspectives.

Study on Deterioration Process of Magnesium Oxychloride Cement under the Environment of Dry-Wet Cycles.

To reveal the deterioration process of magnesium oxychloride cement (MOC) in an outdoor, alternating dry-wet service environment, the evolution of the macro- and micro-structures of the surface layer and inner core of MOC samples as well as their mechanical properties and increasing dry-wet cycle numbers were investigated by using a scanning electron microscope (SEM), an X-ray diffractometer (XRD), a simultaneous thermal analyser (TG-DSC), a Fourier transform infrared spectrometer (FT-IR), and an microelectromechanical electrohydraulic servo pressure testing machine. The results show that as the number of dry-wet cycles increases, the water molecules gradually invade the interior of the samples, causing the hydrolysis of P 5 (5Mg(OH)2·MgCl2·8H2O) and hydration reactions of unreacted active MgO. After three dry-wet cycles, there are obvious cracks on the surface of the MOC samples, and they suffer from warped deformation. The microscopic morphology of the MOC samples changes from a gel state and a short, rod-like shape to a flake shape, which is a relatively loose structure. Meanwhile, the main phase composition of the samples becomes Mg(OH)2, and the Mg(OH)2 contents of the surface layer and inner core of the MOC samples are 54% and 56%, respectively, while the P 5 amounts are 12% and 15%, respectively. The compressive strength of the samples decreases from 93.2 MPa to 8.1 MPa and reduces by 91.3%, and their flexural strength declines from 16.4 MPa to 1.2 MPa. However, their deterioration process is delayed compared with the samples that were dipped in water continuously for 21 days whose compressive strength is 6.5 MPa. This is primarily ascribed to the fact that during the natural drying process, the water in the immersed samples evaporates, the decomposition of P 5 and the hydration reaction of unreacted active MgO both slow down, and the dried Mg(OH)2 may provide the partial mechanical properties, to some extent.

[Rotating Scarf osteotomy in treating hallux valgus combined with the first metatarsal rotation].

OBJECTIVE: To explore clinical effect of rotational Scarf osteotomy in treating hallux valgus (HV) with rotation of the first metatarsal bone. METHODS: From January 2018 to October 2019, 35 patients (40 feet) with HV and rotation deformity of the first metatarsal were treated with rotational Scarf osteotomy, including 5 males and 30 females;aged from 25 to 76 years old with an average of (40.32±5.43) years old. Hallux valgus angle(HVA), intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), the first metatarsal length (FML) were observed and compared, American Orthopedic Foot and Ankle Society(AOFAS) of hallux metatarsophalangeal interphalangeal joint score and visual analogue scale (VAS) were used to evaluate functional evaluation. RESULTS: Thirty-five patients(40 feet) were followed up from 12 to 36 months with an average of (14.35±3.62) months. HVA, IMA and DMAA were corrected from (36.32±4.51) °, (14.21±3.22) ° and (28.35±4.32) ° before operation to (14.32±5.71) °, (5.83±3.97) ° and (7.32±2.14) ° after operation respectively (P<0.05). There was no satistical difference in FML before and after operation (P>0.05). AOFAS score and VAS improved from (57.00±4.31) and (6.00±1.21) before operation to (90.31±3.28) and (1.42±0.83) after operation, respectively, and had significant difference(P<0.05);according to AOFAS score, 23 feet got excellent results, 15 feet good and 2 feet fair. CONCLUSION: Rotational Scarf osteotomy with strong correction and high dimension could effectively correct HV combined with rotation deformity of the first metatarsal bone, improve function of the forefoot, and obtain good clinical results.

Comparison of the Efficacy and Safety of Neuroendoscopic Endonasal Transsphenoidal Surgeries and Intracranial Endoscopic Pterional Approach in Resection of Tuberculum Sellae Meningiomas.

Objective: To compare of the efficacy and safety of neuroendoscopic endonasal transsphenoidal surgeries and intracranial endoscopic pterional approach in resection of tuberculum sellae meningioma. Methods: From January 2014 to June 2021, 60 patients with tuberculum sellae meningioma diagnosed and treated in our hospital were enrolled and randomly divided into study group and control group. The tuberculum sellae meningioma was removed by neuroendoscopic endonasal transsphenoidal surgeries in the study group, while the intracranial endoscopic pterional approach was used in the control group. The chi-square test was used to compare the differences of tumor complete resection rate, visual acuity improvement rate, total effective rate at 3 months after operation, and adverse reactions between the two groups. Results: The clinical characteristics of the two groups were comparable (P > 0.05). After surgical treatment, the complete resection rate in the study group was higher than that in the control group (93.3% vs 70.0%), and the difference was statistically significant (P=0.020). After treatment, the visual acuity improvement rate of the study group was 83.3% (25/30), which was significantly higher than that of the control group (60.0%, 18/30), and the difference was statistically significant (χ 2 = 4.022, P=0.045). After surgical treatment, the total effective rate at 3 months after operation was higher in the study group than in the control group (96.7% vs 83.3%), with statistical significance (P=0.041). There was no significant difference in postoperative adverse reactions between the study group and control group (33.3% vs 30.0%, P=0.781). Conclusion: The neuroendoscopic endonasal transsphenoidal surgeries has significant efficacy and can significantly improve the visual acuity of patients without increasing adverse reactions, which is worthy of clinical promotion.

Effect of Calcination Temperature on Mechanical Properties of Magnesium Oxychloride Cement.

In order to make full use of magnesium chloride resources, the development and utilisation of magnesium oxychloride cement have become an ecological and economic goal. Thus far, however, investigations into the effects on these cements of high temperatures are lacking. Herein, magnesium oxychloride cement was calcinated at various temperatures and the effects of calcination temperature on microstructure, phase composition, flexural strength, and compressive strength were studied by scanning electron microscopy, X-ray diffraction, and compression testing. The mechanical properties varied strongly with calcination temperature. Before calcination, magnesium oxychloride cement has a needle-like micromorphology and includes Mg(OH)2 gel and a trace amount of gel water as well as 5 Mg(OH)2·MgCl2·8H2O, which together provide its mechanical properties (flexural strength, 18.4 MPa; compressive strength, and 113.3 MPa). After calcination at 100 °C, the gel water is volatilised and the flexural strength is decreased by 57.07% but there is no significant change in the compressive strength. Calcination at 400 °C results in the magnesium oxychloride cement becoming fibrous and mainly consisting of Mg(OH)2 gel, which helps to maintain its high compressive strength (65.7 MPa). When the calcination temperature is 450 °C, the microstructure becomes powdery, the cement is mainly composed of MgO, and the flexural and compressive strengths are completely lost.

Associated risk factors of postoperative pain after glaucoma surgery: a prospective study.

PURPOSE: This study aimed to determine degree of postoperative pain and the incidence of serious postoperative pain after glaucoma surgery and further to identify the associated risk factors. METHODS: A total of 194 consecutive patients who were diagnosed with glaucoma and underwent glaucoma surgery were enrolled in this study. The intensity of postoperative pain was evaluated using numerical rating scale (NRS) within 24 h after surgery; NRS ≥ 5 was considered as clinically significant postoperative pain. Risk factors associated with the development of postoperative pain were analyzed by multivariate logistic regression analysis. RESULTS: Clinically significant postoperative pain was experienced at any time after glaucoma surgery in 41.75% of the patients, which peak at 2 h. 27.8% of the patients requested analgesic medication within 24 h after surgery. According to multivariate logistic regression analysis, preoperative anxiety (OR = 4.13 [1.29-13.2], p = 0.017), cyclophotocoagulation (OR = 30.9 [3.47-375.1], p = 0.002), and phacotrabeculectomy combined with or without intraocular lens implantation (OR = 30.0 [2.69-335.6], p = 0.006) were associated with increased clinically significant postoperative pain. Interestingly, patients with diabetes and/or hypertension were associated with less postoperative pain after glaucoma surgery (OR = 0.23 [0.08-0.64], p = 0.005). CONCLUSION: Patients undergoing glaucoma surgery tend to experience postoperative pain in the early postoperative period. Anxiety level and surgery types of cyclophotocoagulation and phacotrabeculectomy are risk factors for postoperative pain. Patients with diabetes and/or hypertension are less likely to develop postoperative pain.

Berberine-Loaded Biomimetic Nanoparticles Attenuate Inflammation of Experimental Allergic Asthma via Enhancing IL-12 Expression.

Asthma is one of the most common chronic pulmonary disorders, affecting more than 330 million people worldwide. Unfortunately, there are still no specific treatments for asthma so far. Therefore, it is very important to develop effective therapeutics and medicines to deal with this intractable disease. Berberine (Ber) has fabulous anti-inflammatory and antibacterial effects, while its low water solubility and bioavailability greatly limit its curative efficiency. To improve the nasal mucosa absorption of poorly water-soluble drugs, such as Ber, we developed a platelet membrane- (PM-) coated nanoparticle (NP) system (PM@Ber-NPs) for targeted delivery of berberine to the inflammatory lungs. In vivo, PM@Ber-NPs exhibited enhanced targeting retention in the inflammatory lungs compared with free Ber. In a mouse model of house dust mite- (HDM-) induced asthma, PM@Ber-NPs markedly inhibited lung inflammation, as evident by reduced inflammatory cells and inflammatory cytokines in the lung compared with free Ber. Collectively, our study demonstrated the inhibitory actions of nasally delivered nanomedicines on HDM-induced asthma, primarily through regulating Th1/Th2 balance by enhancing IL-12 expression which could potentially reduce lung inflammation and allergic asthma.

Research and Engineering Application of Salt Erosion Resistance of Magnesium Oxychloride Cement Concrete.

Aiming at the problem that ordinary cement concrete is subjected to damage in heavy saline soil areas in China, a new type of magnesium oxychloride cement concrete is prepared by using the gelling properties of magnesium oxychloride cement in this study, and the erosion resistance of the synthesized magnesium oxychloride cement concrete in concentrated brine of salt lakes is studied through the full immersion test. The effects of concentrated brine of salt lakes on the macroscopic, microscopic morphology, phase composition and mechanical properties of magnesium oxychloride cement concrete are investigated by means of macro-morphology, erosion depth, SEM, XRD and strength changes. The salt erosion resistance mechanism of magnesium oxychloride cement concrete is revealed. The results demonstrate that under the environment of full immersion in concentrated brine of salt lakes, there is no macroscopic phenomenon of concrete damage due to salt crystallization, and the main phase composition is basically unchanged. The microscopic morphology mostly changes from needle-rod-like to gel-like. Due to the formation of a new 5·1·8 phase on the surface layer and the increase in compactness, its compressive strength has a gradual increase trend. Based on the engineering application of magnesium oxychloride cement concrete, it is further confirmed that magnesium oxychloride cement concrete has excellent salt erosion resistance and good weather resistance, which provides theoretical support for future popularization and application.

Preparation of Low-Cost Magnesium Oxychloride Cement Using Magnesium Residue Byproducts from the Production of Lithium Carbonate from Salt Lakes.

Magnesium oxychloride cement (abbreviated as MOC) was prepared using magnesium residue obtained from Li2CO3 extraction from salt lakes as raw material instead of light magnesium oxide. The properties of magnesium residue calcined at different temperatures were researched by XRD, SEM, LSPA, and SNAA. The preparation of MOC specimens with magnesium residue at different calcination temperatures (from 500 °C to 800 °C) and magnesium chloride solutions with different Baume degrees (24 Baume and 28 Baume) were studied. Compression strength tests were conducted at different curing ages from 3 d to 28 d. The hydration products, microstructure, and porosity of the specimens were analyzed by XRD, SEM, and MIP, respectively. The experimental results showed that magnesium residue's properties, the BET surface gradually decreased and the crystal size increased with increasing calcination temperature, resulting in a longer setting time of MOC cement. Additionally, the experiment also indicated that magnesium chloride solution with a high Baume makes the MOC cement have higher strength. The MOC specimens prepared by magnesium residue at 800 °C and magnesium chloride solution Baume 28 exhibited a compressive of 123.3 MPa at 28 d, which met the mechanical property requirement of MOC materials. At the same time, magnesium oxychloride cement can be an effective alternative to Portland cement-based materials. In addition, it can reduce environmental pollution and improve the environmental impact of the construction industry, which is of great significance for sustainable development.

[Research progress in Achilles tendinopathy].

OBJECTIVE: To explore the classification, diagnosis, and clinical treatment of Achilles tendinopathy. METHODS: The literature about Achilles tendinopathy at home and abroad was reviewed. The research results of classification and terms, imaging diagnosis, and clinical treatment of Achilles tendinopathy were summarized. RESULTS: The classification and name of Achilles tendinopathy are not completely unified, and the concept is vague, the cause of disease is not clear. There are many treatment plans, but there is no effective evidence-based medicine research. CONCLUSION: The diagnosis and treatment of Achilles tendinopathy is complicated. According to the characteristics of Achilles tendon anatomy and etiology, the classification and definition of Achilles tendinopathy need to be further studied in order to guide clinical treatment more effectively and facilitate experience exchange and learning.

Long non-coding RNA SNHG3 accelerates progression in glioma by modulating miR-384/HDGF axis.

Glioma is a malignant primary brain tumor that occurs in the central nervous system and has threatened the well-being of millions of patients. It is well acknowledged that long non-coding RNA (lncRNA) SNHG3 participates in the regulation of proliferation, inflation, differentiation, and metastasis in many cancers. However, the regulatory effect of SNHG3 on glioma progression is still controversial. The expression of SNHG3 and HDGF was upregulated, whereas miR-384 was downregulated in glioma tissues, compared with the normal tissues. Interestingly, high SNHG3 contributed to low survival rate while low SNHG3 showed the opposite result. Moreover, SNHG3 or HDGF knockdown significantly suppressed proliferation, migration, and invasion and induced apoptosis in glioma. Meanwhile, restoration of HDGF abrogated the inhibition of SNHG3 silencing on glioma cell progression. Besides, miR-384 inhibitor attenuated SNHG3 silencing induced inhibition on HDGF mRNA and protein expression in A172 and SHG44 cells. LncRNA SNHG3 promotes cell proliferation, migration, and invasion in glioma by enhancing HDGF expression via miR-384 sponging, representing the promising targets for the development of novel therapeutic strategies.

Haploinsufficiency of GCP4 induces autophagy and leads to photoreceptor degeneration due to defective spindle assembly in retina.

Retinopathy, owing to damage to the retina, often causes vision impairment, and the underlying molecular mechanisms are largely unknown. Using a gene targeting strategy, we generated mice with the essential gene Tubgcp4 knocked out. Homozygous mutation of Tubgcp4 resulted in early embryonic lethality due to abnormal spindle assembly caused by GCP4 (gamma-tubulin complex protein 4, encoded by Tubgcp4) depletion. Heterozygotes were viable through dosage compensation of one wild-type allele. However, haploinsufficiency of GCP4 affected the assembly of γ-TuRCs (γ-tubulin ring complexes) and disrupted autophagy homeostasis in retina, thus leading to photoreceptor degeneration and retinopathy. Notably, GCP4 exerted autophagy inhibition by competing with ATG3 for interaction with ATG7, thus interfering with lipidation of LC3B. Our findings justify dosage effects of essential genes that compensate for null alleles in viability of mutant mice and uncover dosage-dependent roles of GCP4 in embryo development and retinal homeostasis. These data have also clinical implications in genetic counseling on embryonic lethality and in development of potential therapeutic targets associated with retinopathy.

[Application of modified internal fixation and fusion for type â ¡ painful accessory navicular in adults].

OBJECTIVE: To explore the effectiveness of modified internal fixation and fusion in treatment of type Ⅱ painful accessory navicular (PAN) in adults. METHODS: Between January 2016 and December 2017, 29 patients (37 feet) with type Ⅱ PAN were treated with modified internal fixation and fusion. There were 12 males and 17 females with an average age of 41.4 years (range, 18-50 years). The injury caused by sprain in 24 cases and no obvious inducement occurred in 5 cases. All patients received conservative treatment for more than 6 months with no significant improvement. The effectiveness was evaluated by American Orthopaedic Foot and Ankle Society (AOFAS) score before operation and at last follow-up. The inclination angle of calcaneus, the first metatarsal angle of talus, the inclusion angle of talonavicular joint, and the second metatarsal angle of talus were measured on X-ray films. RESULTS: Superficial infection of incision occurred in 1 case after operation, and the incision healed after enhanced dressing change. The incisons of the other patients healed by first intention. There was no deep infection or osteomyelitis. All patients were followed up 12-33 months (mean, 25.1 months). X-ray films showed that the articular surfaces healed at 2-5 months after operation, with an average of 3.4 months. No loosening or rupture of internal fixator was found during the follow-up. At last follow-up, the pain, function, alignment scores, and total score of AOFAS were significantly improved when compared with those before operation (P<0.05). The inclusion angle of talonavicular joint, the first metatarsal angle of talus, and the second metatarsal angle of talus were also significantly improved when compared with those before operation (P<0.05). But there was no significant difference in the inclination angle of calcaneus between pre- and post-operation (t=1.097, P=0.276). CONCLUSION: Modified internal fixation and fusion in treatment of type Ⅱ PAN can effectively relieve the symptoms and obtain good recovery of feet function with less complications.

P11 Loss-of-Function is Associated with Decreased Cell Proliferation and Neurobehavioral Disorders in Mice.

Although depression is associated with anxiety and memory deficit in humans, the molecular mechanisms of the complication remain largely unknown. In this study, we generated P11 knockout mice using CRISPR/Cas9 technology, as well as P11 knockout MEF cell lines, and confirmed depression-like phenotype. We observed that knockout of P11 in MEFs led to a decreased cell proliferation compared with P11+/+ MEFs. Moreover, P11 knockout resulted in a larger cell size, which resulted probably from accumulated F-actin stress fibers. The number of proliferating cells was decreased in the hippocampus of P11 KO mice. We observed anxiety-like disorder in addition to depression phenotype in the knockout mice. In addition, knockout of P11 led to memory deficit in female mice, but not in males. These data indicated that P11 is involved in regulating cell proliferation and cell size. The molecular associations of depression behavior with anxiety and memory deficit suggested a potential approach to improve therapeutic intervention through P11 in these disorders.

Crystal field modulation-control, bandgap engineering and shallow/deep traps tailoring-guided design of a color-tunable long-persistent phosphor (Ca, Sr)Ga4O7:Mn2+,Bi3+ .

In this paper, a new color tunable long persistent phosphor (Ca, Sr)Ga4O7:Mn2+,Bi3+ has been successfully synthesized via a high-temperature solid-state reaction. Crystal field modulation and band gap engineering controlled by Sr2+ substitution for Ca2+ realizes the color tunable Mn2+ emission from 580 to 556 nm. Guided by the tailoring of traps distribution, the long persistence luminescence (LPL) performance of CaGa4O7:Mn2+ is greatly enhanced to 33 times higher brightness and much longer persistent time through Bi3+ co-doping. Furthermore, aided by the Rietveld refinement method, steady/transient-state fluorescence and thermoluminescence (TL) techniques with the combination of DFT calculations, the crystal structure evolution, electronic structure, trap distribution tailoring, self reduction of Mn4+, and the related color tunable Mn2+ photoluminescence/enhanced LPL properties are systematically characterized. Finally, a schematic diagram is proposed for a detailed illustration of the photoluminescence and LPL mechanisms.

Genome-wide mapping and characterization of microsatellites in the swamp eel genome.

We described genome-wide screening and characterization of microsatellites in the swamp eel genome. A total of 99,293 microsatellite loci were identified in the genome with an overall density of 179 microsatellites per megabase of genomic sequences. The dinucleotide microsatellites were the most abundant type representing 71% of the total microsatellite loci and the AC-rich motifs were the most recurrent in all repeat types. Microsatellite frequency decreased as numbers of repeat units increased, which was more obvious in long than short microsatellite motifs. Most of microsatellites were located in non-coding regions, whereas only approximately 1% of the microsatellites were detected in coding regions. Trinucleotide repeats were most abundant microsatellites in the coding regions, which represented amino acid repeats in proteins. There was a chromosome-biased distribution of microsatellites in non-coding regions, with the highest density of 203.95/Mb on chromosome 8 and the least on chromosome 7 (164.06/Mb). The most abundant dinucleotides (AC)n was mainly located on chromosome 8. Notably, genomic mapping showed that there was a chromosome-biased association of genomic distributions between microsatellites and transposon elements. Thus, the novel dataset of microsatellites in swamp eel provides a valuable resource for further studies on QTL-based selection breeding, genetic resource conservation and evolutionary genetics.

Low-frequency stimulation of the pedunculopontine nucleus affects gait and the neurotransmitter level in the ventrolateral thalamic nucleus in 6-OHDA Parkinsonian rats.

The pedunculopontine nucleus (PPN) is connected to spinal, cerebellar and cerebral motor control structures and can be activated with external electrodes. Intrinsic cholinergic neuronal degeneration in the PPN is associated with postural instabilities and gait disturbances (PIGD) in advanced Parkinson's disease (PD). Clinical studies have demonstrated that PPN stimulation may improve PIGD. We investigated this claim and the underlying mechanisms using the 6-hydroxydopamine (6-OHDA) hemilesion model of PD. In this study, gait-related parameters, including the base of support (BOS), stride length, and maximum contact area, were analyzed via CatWalk gait analysis following PPN-low frequency stimulation (LFS) of rats with unilateral 6-OHDA lesions. Additionally, neurotransmitter concentrations in the ventrolateral thalamic nucleus (VL) were measured by microdialysis and liquid chromatography-mass spectrometry (LC-MS). Our data revealed that unilateral 6-OHDA lesions of the medial forebrain bundle (MFB) induced significant gait deficits. PPN-LFS significantly improved the BOS (hindlimb) and maximum contact area (impaired forelimb) scores, whereas no other gait parameters were significantly affected. Unilateral 6-OHDA MFB lesions significantly decreased acetylcholine (ACh) and moderately decreased noradrenaline (NA) concentrations in the VL. PPN-LFS mildly reversed the ACh loss in the VL in the lesioned rats but did not alter the NA levels. Taken together, our data indicate that PPN-LFS is useful for treating gait deficits of PD and that these effects are probably mediated by a rebalancing of ACh levels in the PPN-VL pathway. Thus, our findings provide possible insight into the mechanisms underlying PIGD in PD.

Gait analysis in three different 6-hydroxydopamine rat models of Parkinson's disease.

Gait deficits are important clinical symptoms of Parkinson's disease (PD) but are rarely studied. In this study we made three different rat PD models by administration of 6-hydroxydopamine into caudate putamen (CPU), medial forebrain bundle (MFB) and substantia nigra compact (SNC). We evaluated the gait changes in these models by using a computer-assisted CatWalk system. Correlations of gait parameters with tyrosine hydroxylase protein levels in the CPU and SNC were also investigated. The gait readouts were significantly impaired in both the MFB and SNC groups. However, the MFB group showed a more pronounced impairment than the SNC group. In contrast, only mild and incomplete gait impairment occurred in the CPU group. In addition, some gait parameters demonstrated close correlation with the protein levels of TH. This paper suggests that the 6-hydroxydopamine-induced MFB model is more propitious to study gait dysfunction than the other two models and the CatWalk system can provide reliable and objective criteria to stratify gait changes arising from 6-hydroxydopamine lesioned rats. These findings may hold promise in the study of PD disease progression and new therapeutic methods.