Monetary burden of neurocysticercosis on a hospitalized population in Muli County, China.

Neurocysticercosis (NCC) is a potentially life-threatening condition caused by the zoonotic cestode, Taenia solium. Pigs are the typical intermediate hosts for T. solium but humans can become infected and develop NCC upon ingesting parasite eggs that are shed in the feces of an infected person. The objective of this study was to estimate the monetary burden of neurocysticercosis (NCC) on hospitalized patients from Muli County, China. Muli is an agricultural county in Liangshan Prefecture, Sichuan Province, China where pigs are raised and the zoonotic cestode, Taenia solium, is endemic. Demographic and treatment data were collected from the Muli County Health Insurance Department on hospitalized individuals with an NCC diagnosis between 2014 and 2021. These patients represent residents of Muli County that purchased health insurance and received treatment in a public hospital in Sichuan Province. Hospital costs were converted from Chinese renminbi (RMB) to United States dollars (US$) for month and year of hospitalization and adjusted for inflation. Individuals with missing hospital information were excluded from analysis. For indirect costs, annual average salary for Liangshan Prefecture working-age adults was obtained to calculate productivity losses based on number of hospitalization days and travel days to and from the hospital. Transportation costs were evaluated based on estimated bus fare to and from the hospital. Out of 70 patients identified from 2014 to 2021, 68 had complete records, of which 47.1% were male (n = 33) and the median age at first hospitalization was 34 years. Total estimated cost for these patients was US$228,341.98. Direct costs contributed 62.5% (US$142,785.25) and indirect costs were 37.5% (US$85,556.73) of the total cost. The estimated median cost per case was US$2,078.69. Individuals with a single hospitalization (n = 41) cost a median of US$1,572.03 and those with multiple hospitalizations (n = 27) cost a median of US$4,169.95. The median total cost per NCC case was 18.6% of the average wage for a Liangshan Prefecture resident in 2021. While the study was limited to those with insurance coverage, monetary burden on the local population is likely substantial. Public health policies aimed at reducing transmission should be implemented to decrease the economic burden of NCC on this region.

Application of oyster shell powder reduces cadmium accumulation by inhibiting the expression of genes responsible for cadmium uptake and translocation in rice.

The application of waste oyster shell in agriculture is of extensive concern due to its benefits on improving yields and inhibiting cadmium (Cd) accumulation in edible parts of crops. However, the underlying mechanisms responsible for oyster shell powder (OSP) that decreases Cd accumulation in crops remain poorly understood. This study explored the effects of OSP on growth and Cd accumulation in rice via pot experiments and hydroponics. Pot experiments showed that the application of 1 g·kg-1 OSP improved rice yields and decreased Cd concentrations in all tissues of rice, especially in grains, which was reduced by 43.5%. The pH was increased and the phytoavailability of Cd in soil was reduced by OSP supplementation. In addition, OSP also exhibited high dissolution of Ca, Fe, Zn, and Se. In hydroponics, OSP supply also suppressed Cd accumulation in rice and increased plant growth. Pretreatment with OSP inhibited the accumulation of Cd in the roots and shoots. Simultaneously, OSP reduced the content of Cd in the root cell sap, cell wall, and xylem sap, and downregulated the expression of OsNramp5, OsNramp1, OsIRT1, and OsHMA2. These findings suggested that the application of OSP could reduce Cd accumulation by inhibiting the expression of genes responsible for Cd absorption and xylem loading in rice.

Clinical features of retinal amyloid angiopathy with transthyretin Gly83Arg variant.

AIM: To report on the clinical features of patients with retinal amyloid angiopathy (RAA) who were identified to be caused by the transthyretin (TTR) Gly83Arg variant. METHODS: Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021. The clinical features, therapeutic strategies, and prognoses of all patients were reviewed. RESULTS: Five patients with a mean age of 52.00±7.23y were diagnosed as RAA. These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant. Vitreous opacity was found in all 10 eyes, and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis. The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes (29%), neovascular glaucoma in 2 eyes (29%), and iris neovascularization in 1 eye (14%). Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography (FFA) in this group of cases, and the incidence of the retinal non-perfusion area was 67%. Although no cases of retinal neovascularization were found, the prognosis of visual acuity was not ideal. CONCLUSION: This is the first report of RAA in patients with the TTR Gly83Arg variant. Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients. Thereafter, regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential. And FFA after vitrectomy is very important, which can help ophthalmologists detect RAA earlier and treat it in time.

The effect of vitreomacular interface in neovascular age-related macular degeneration treated with intravitreal injection of anti-VEGF.

BACKGROUND: The purpose of this study is to study the effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on vitreomacular interface. METHODS: Neovascular age-related macular degeneration patients who received intravitreal injections of anti-VEGF drugs were included. Eyes with severe vitreous opacity, uveitis, complicated cataract surgery and previous vitrectomy were excluded. Vitreomacular interface, best corrected visual acuity (BCVA) and central retinal thickness (CRT) assessment were performed once a month for at least 3 months. The nature and time of the change event are recorded. Groups were divided according to whether vitreomacular interface change events occurred. To analyse the risk factors of vitreomacular interface changes and their influence on treatment effect. RESULTS: A total of 87 eyes were evaluated. Vitreomacular interface change event occurred in 9 eyes. Pre-existing vitreomacular interface abnormality (VMIA) was a risk factor for the VMI change (P = 0.033, OR = 16.518, 95% CI: 1.258 to 216.939). 60% of interface events occurred in the first 3 months of treatment. The final BCVA of eyes with vitreomacular interface unchanged was significantly higher than that at baseline (P = 0.001), and the final CRT was also significantly lower than that at baseline (P < 0.001). The final CRT of eyes vitreomacular interface changed was significantly lower than that at baseline (P = 0.015), however, there was no statistical significance in BCVA (P = 0.468). CONCLUSION: Intravitreal injection of anti-VEGF drugs has a certain probability to cause changes in the vitreomacular interface, and the risk is higher in eyes with pre-existing vitreomacular interface abnormality. The effect of intravitreal injections on the vitreomacular interface was concentrated in the first three injections, and subsequent increases in the number of injections did not significantly increase the risk of vitreomacular interface abnormality. Ophthalmologists should increase attention to the vitreomacular interface in the early stages of anti-VEGF therapy and counsel patients accordingly.

Von Hipple-Lindau disease complicated with central retinal vein occlusion: a case report.

BACKGROUND: Central Retinal Vein Occlusion (CRVO) is a rare complication of von Hipple-Lindau (VHL) disease. This report presents the first case of VHL disease complicated with CRVO caused by VHL c.208G > A mutation. CASE PRESENTATION: A 20 s man whose left eye visual acuity gradually declined for half a year. The visual acuity of the left eye is counting fingers. Fundus examination revealed that retinal hemangioblastoma was also found in addition to typical CRVO signs such as tortuous expansion of retinal veins and flame-shaped hemorrhage of the retina. Liver tumor, cerebral infarction and erythrocytosis were found during systemic examination, and the diagnosis of polycythemia was confirmed by bone marrow smear. Furthermore, both family history and genetic analysis indicated that the patient had VHL disease caused by VHL c.208G > A. In this patient, a large number of bone marrow erythrocytes proliferated due to VHL disease, which led to the increase of blood viscosity and erythrocyte vascular adhesion, resulting in the obstruction of central retinal vein blood flow, and finally CRVO. For CRVO and its pathogenic factor polycythemia, patient received laser retinal photocoagulation and phlebotomies. After a 1-year follow-up, the vision in the left eye improved to 0.2 logMAR. CONCLUSIONS: This is a rare case of polycythemia complicated by CRVO in patient with VHL disease. It reminds us that the systemic disease factors should be fully considered in the diagnosis of young patients with CRVO, and that treatment requires a coordinated effort of physicians.

Influence of Melatonin on Behavioral and Neurological Function of Rats with Focal Cerebral Ischemia-Reperfusion Injury via the JNK/FoxO3a/Bim Pathway.

OBJECTIVE: To investigate the influence of melatonin on behavioral and neurological function of rats with focal cerebral ischemia-reperfusion injury via the JNK/FoxO3a/Bim pathway. METHODS: One hundred and twenty healthy male SD rats were randomized into the model group (Model: the middle cerebral artery occlusion (MCAO) model was constructed and received an equal volume of normal saline containing 5% DMSO), sham operation group (Sham: received no treatment except normal feeding), and low, medium, and high dose of melatonin group (L-MT, M-MT, and H-MT intraperitoneally injected 10, 20, and 40 mg/kg melatonin 30 min after IR, respectively), with 24 rats in each group. Following 24 h of reperfusion, the rats in each of the above groups were tested for neurological deficit symptoms and behavioral changes to screen the rats included in the study. HE and TUNEL stainings were performed to observe pathological changes. Levels of oxidative stress-related indexes, inflammatory factor-related indexes, nuclear factor-κB p65 (NF-κB p65), and interferon-γ (IFN-γ) in the rat brain were measured by ELISA. The JNK/FoxO3a/Bim pathway-related proteins as well as Bcl-2, Caspase-3, and Bax were examined using Western blot. RESULTS: Detection of behavioral indicators showed that the MACO model was successfully constructed in rats. L-MT, M-MT, and L-MT groups presented reduced malondialdehyde (MDA), reactive oxygen species (ROS), tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-1ß, IFN-γ, NF-κB p65, and apoptosis compared with the Model group (P < 0.05), and the improvement degree was better in the M-MT group versus the L-HT group. Bcl-2 protein expression in the brain tissue of L-MT, M-MT, and H-MT groups increased significantly, while Bax, Caspase-3, p-JNK, p-FoxO3a, and Bim protein expression declined markedly, versus the Model group (P < 0.05). The changes of indexes were greater in the M-MT group compared with that in the L-MT group. No significant difference was observed in all the above indexes between the M-MT group and the H-MT group (P > 0.05). CONCLUSIONS: In the MACO rat model, melatonin can effectively reduce Bax and Caspase-3 levels by modulating the JNK/FoxO3a/Bim pathway, inhibit neuronal apoptosis, and alleviate neurological deficits by reducing the release of proinflammatory mediators, with anti-inflammatory and antioxidant effects. In addition, 20 mg/kg is the optimal melatonin concentration.

New insights on the Taenia solium tapeworm using molecular tools: age-based human definitive host prevalence and deliberation on parasite life span.

Information on age-based Taenia solium taeniasis prevalence is crucial for control of cysticercosis. T. solium taeniasis prevalence was determined for a village in Liangshan Prefecture, Sichuan Province, China that was co-endemic for T. solium, Taenia saginata asiatica, and Taenia saginata. Individuals who were Taenia egg-positive by stool microscopy and/or expelled tapeworms or proglottids post-treatment were diagnosed as having taeniasis. Infecting species was identified via multiplex PCR on tapeworm specimens or coproPCR followed by sequencing. In addition, initial stool samples from 10 children with taeniasis suspected of having spontaneous expulsion of tapeworms within the period between diagnosis and treatment were subject to species confirmation via coproPCR and sequencing. Of the 389 study subjects, 194 (49.9%) were diagnosed with taeniasis. Children (< 16 years of age) had a higher T. solium taeniasis prevalence (8.8%) than older individuals (2.5%) (P = 0.0127). Molecular analysis of initial stool samples from 7 of 10 children suspected of spontaneously passing tapeworms indicated 6 infections due to T. solium and 1 infection due to T. saginata. This study found that young children had a higher T. solium taeniasis prevalence than older individuals, providing additional support for the belief that adult T. solium likely has a relatively short lifespan compared to other Taenia species with human definitive hosts.

A multiplex PCR for differential detection of Echinococcus granulosus sensu stricto, Echinococcus multilocularis and Echinococcus canadensis in China.

BACKGROUND: Echinococcosis caused by Echinococcus is one of the most major infectious diseases in north-west highland of China. E. granulosus sensu strict, E. multilocularis, and E. canadensis are known to be the only three species related to human health transmitting in the areas. To achieve targeted treatment and control of echinococcosis, the accurate identification and discrimination of the species are important. However, currently the available diagnostic approaches do not present ideal results either in accuracy or efficiency. METHODS: In the study, a set of primers were designed to aim at the three human-pathogenic Echinococcus species in China. The one-step multiplex PCR assay was developed and evaluated for the specificity and sensitivity. A total of 73 parasitic lesions and 41 fecal materials obtained from human and various animals collected in the clinic and the field were tested to assess the applicability of this method. RESULTS: The multiplex PCR effectively detected the individual DNA from the targeted species and their random mixtures generating with distinguishable expected size of products. The detection limit of the assay for each of the three species was 5 pg/µl when they were tested separately. When DNA mixtures of the targeted species containing the same concentration were used as templates, the lowest amount of DNA which can be detected was 50 pg/µl, 10 pg/µl and 5 pg/µl for E. granulosus s. s., E. multilocularis, and E. canadensis respectively. No cross-reactivity was observed when DNA from eight genetically close species was used as control templates. The multiplex PCR identifications of all samples were in line with the original sequencing results except for those infected with E. shiquicus, which showed negative signals in the developed assay. Of all the tested stool materials, 16 were previously found positive for Echinococcus by visual and microscopic examination. Among these 16 samples, 13 were confirmed by the multiplex PCR, and the other three tested negative. Additionally, the multiplex PCR identified another 14 positive feces from the remained 25 stool samples which absence of worms. CONCLUSIONS: The developed multiplex PCR shows advantages in fast diagnosis and large-scale epidemiological investigation, which proven to be a promising tool utilized in clinic and surveillance system.

High prevalence of taeniasis and Taenia solium cysticercosis in children in western Sichuan, China.

Data in China on human Taenia infections, including Taenia solium cysticercosis, is largely lacking. We aimed to determine the prevalence of taeniasis with all three human Taenia species as well as T. solium cysticercosis in primary school-aged children in minority areas of western Sichuan, China. During April 2016 to December 2017, we did a cross-sectional study in five western Sichuan Province primary schools in Liangshan (3 schools), Ganzi (1 school) and Aba (1 school) prefectures. Diagnosis of taeniasis was made by stool microscopy for presence of Taenia eggs, as well as recovery of taeniid tapeworms or proglottids by medicinal treatment followed by species identification using multiplex PCR. Diagnosis of T. solium cysticercosis was made serologically using an ELISA with low-molecular-weight antigens purified from T. solium cyst fluid to detect specific IgG antibodies. A total of 1672 children were screened for taeniasis and 1639 were evaluated for cysticercosis antibodies. Overall prevalence of taeniasis was 7.5% but was as high as 15.6% at one school site (e.g., Shuiluo). Of the three known human Taenia species, adult T. solium tapeworms were detected in 42 children from four of the five schools (all three schools in Liangshan and one in Aba), giving a prevalence of T. solium taeniasis of 2.5% (95% confidence interval 0-6.7%). Cysticercosis antibody seropositivity by school varied from 2.3% to 15.6% (overall 7.5%). T. solium taeniasis carriers were more likely to have cysticercosis antibodies than children without T. solium taeniasis (43.6% vs 6.6%). Schools with higher prevalences of T. solium taeniasis were more likely to have children with human cysticercosis IgG antibodies. This study shows a high prevalence of taeniasis and T. solium cysticercosis in primary school-aged children in minority areas of western Sichuan, suggesting an urgent necessity for school-based disease control.

[Impact of the neglected Cysticercus cellulose infection on mental health among school-aged children in Tibetan agricultural areas].

OBJECTIVE: To determine the impact of Cysticercus cellulose (C. cellulose) infection on mental health among school-aged children in Tibetan agricultural areas of Sichuan Province.
 Methods: In October 2015, all primary schools located in Tibetan agricultural areas in Yajiang, Ruoergai, and Muli county of Sichuan Province were selected as the research sites. All school-aged children at five- and six-grade were enrolled for the study by a multistage stratified cluster sampling method. Antibodies against C. cellulose were detected. Mental Health Test and questionnaire survey were conducted for school-aged children to collect data. The impact of C. cellulose infection on mental health among school-aged children was analyzed with the multilevel linear regression.
 Results: A total of 2 453 school-aged children were investigated. The C. cellulose seropositive rate was 6.03% (148/2 453). There were 0.16% (4/2 453) patients with seropositive accompanied by seizure, 2.28% (56/2 453) with seropositive accompanied by headache, 2.08% (51/2 453) with seropositive accompanied by frequent weak, and 0.41% (10/2 453) were seropositive accompanied by frequent nausea. The rate of C. cellulose infection was 4.53% (111/2 453). The mean score of the mental health test was 6.59±2.61. There were significant difference in score of mental health test in children whose demographic characteristics were different. The mental health scores of school-aged children were clustered at the school level. After controlling the factors of demographic characteristics, the result of multilevel model demonstrated that the factor of school-aged children with C. cellulose seropositive accompanied by headache was statistically significant (ß=1.14, P=0.017).
 Conclusion: The status of C. cellulose infection among school-aged children in Tibetan agricultural areas is not optimistic. C. cellulose infection has impacted on mental health of local school-aged children. It is necessary to strengthen the prevention and control of C. cellulose infection in epidemic area.

[A Social Network Perspective on the Transmission of Cysticercuscellulose Infections in Tibetan School Children in Sichuan].

OBJECTIVE: To determine the transmission characteristics of Cysticercuscellulose infections from a social network perspective in Tibetan school children in Sichuan. METHODS: A cluster sampling strategy was adopted to select two primary schools with high level of Cysticercuscellulose infections in the Tibetan agriculture areas of Liangshan prefecture, Sichuan province. All of the students from the selected schools were enrolled in the study. Their social network data, including classroom seating, dormitory roommates, best playmates, and those who shared meals and snacks etc, were collected by trained investigators. Stool and blood samples of the students were collected for parasite detection. The transmission network of Cysticercuscellulose infections and the overall social network of school children were analysed. RESULTS: A total of 644 children participated in the study. Taenia solium were found in 6.11% of the stool samples and 13.25% blood samples returned with seropositive. The transmission was centered around the sources of infections: dormitory-clustering in the boarding school and playmate-clustering in the day school. The overall social network analysis revealed "core people" (more relationships), "information disseminators" (closer to other nodes) and "information hubs" (between two nodes) in both schools. CONCLUSION: Close contacts in dormitories and playgrounds are the main sources of transmission of cysticercosis in the Tibetan schools. The "core people" "information disseminators" and "information hubs" are critical for the prevention and control of cysticercosis in the future.

A mouse model of a novel missense mutation (Gly83Arg) in a Chinese kindred manifesting vitreous amyloidosis only.

The purpose of this study is to establish a mouse model of transthyretin (TTR) Gly83Arg gene mutation by the technique of gene targeting for research on hereditary vitreous amyloidosis (HVA) and to confirm whether this point mutation is a genetic feature of HVA. A vector (pBR322-MK-TTR) was constructed to target ES cells. The successfully transfected ES cells were used for blastocyst injection, thus generating F0. F0 and Flp mice were mated to generate F1 (TTR+/-, Flp +/-) mice that lacked the neo gene but carried the Flp gene. F1 mice were mated with C57BL/6N wild type mice to generate F2 (TTR+/-) mice. F3 homozygous and heterozygous mice were generated by mating F2 mice with each other. PCR and sequencing were performed for F3 mice. Amyloid was detected using Congo red stain and polarized light. Immunohistochemistry was used to detect the expression of TTR in the tissues. Quantitative fluorescent PCR and Western blotting were used to detect the expression of TTR mRNA and TTR protein, respectively. Two F0-generation, 2 F1-generation and 15 F3-generation mice were obtained. The gene sequencing of F3 mice showed TTR Gly83Arg mutation. When examined with Congo red and polarized light, the vitreous of TTR Gly83Arg mutant mice tested positive for amyloid. The hearts, livers, brains and kidneys of the experimental group and control group were all negative by Congo red staining. Immunohistochemical staining showed that the vitreous of TTR Gly83Arg mutant mice and the livers of the control mice were positive, but the kidneys, hearts and brains of both groups were negative. Quantitative fluorescent PCR showed that the mRNA expression of mutant mice was significantly lower than that of wild-type mice (F = 0.295, P = 0.023). Western blotting showed that the expression of TTR protein was significantly lower in the model mice than in the wild-type mice (t = 3.224, P = 0.018). TTR gene mutation is indeed a molecular characteristic of HVA and manifest in the eye disease only. A C57BL/6 mouse line carrying the TTR Gly83Arg gene mutation was successfully established. This strain of mice can be used for the study of HVA.

BAR Domain-Containing FAM92 Proteins Interact with Chibby1 To Facilitate Ciliogenesis.

Chibby1 (Cby1) is a small, conserved coiled-coil protein that localizes to centrioles/basal bodies and plays a crucial role in the formation and function of cilia. During early stages of ciliogenesis, Cby1 is required for the efficient recruitment of small vesicles at the distal end of centrioles to facilitate basal body docking to the plasma membrane. Here, we identified family with sequence similarity 92, member A (FAM92A) and FAM92B, which harbor predicted lipid-binding BAR domains, as novel Cby1-interacting partners using tandem affinity purification and mass spectrometry. We found that in cultured cell lines, FAM92A colocalizes with Cby1 at the centrioles/basal bodies of primary cilia, while FAM92B is undetectable. In airway multiciliated cells, both FAM92A and -92B colocalize with Cby1 at the base of cilia. Notably, the centriolar localization of FAM92A and -92B depends largely on Cby1. Knockdown of FAM92A in RPE1 cells impairs ciliogenesis. Consistent with the membrane-remodeling properties of BAR domains, FAM92A and -92B in cooperation with Cby1 induce deformed membrane-like structures containing the small GTPase Rab8 in cultured cells. Our results therefore suggest that FAM92 proteins interact with Cby1 to promote ciliogenesis via regulation of membrane-remodeling processes.

Cryptic diversity in hymenolepidid tapeworms infecting humans.

An adult hymenolepidid tapeworm was recovered from a 52-year-old Tibetan woman during a routine epidemiological survey for human taeniasis/cysticercosis in Sichuan, China. Phylogenetic analyses based on sequences of nuclear 28S ribosomal DNA and mitochondrial cytochrome c oxidase subunit 1 showed that the human isolate is distinct from Hymenolepis diminuta and Hymenolepis nana, the common parasites causing human hymenolepiasis. Proglottids of the human isolate were unfortunately unsuitable for morphological identification. However, the resultant phylogeny demonstrated the human isolate to be a sister species to Hymenolepis hibernia from Apodemus mice in Eurasia. The present data clearly indicate that hymenolepidid tapeworms causing human infections are not restricted to only H. diminuta and H. nana.

Protective effect of neovibsanin B on spatial cognitive functions of rats with cerebrovascular hypoperfusion.

Neovibsanins are believed to be promising candidates for the development of novel therapeutic agents to treat neurological diseases like Alzheimer's disease. It has been shown that chronic cerebral hypoperfusion is linked to neurodegenerative disorders and their subsequent cognitive impairment. In the present study effect of neovibsanin B (NVB) on spatial cognitive functions of rats with lobal cerebrovascular hypoperfusion was investigated. The cerebrovascular hypoperfusion rat model was prepared by bilateral common carotid arteries occlusion (2VO). Morris water maze (MWM) test was employed to examine the effect of NVB on spatial cognitive function before and after 2VO intervention. The animals were divided into two groups; long-term memory (LTM) and short-term memory (STM) groups. Each of the groups was subdivided into 3 subgroups: control, untreated and NVB treated groups. After ten weeks of the surgery, all the subgroups were tested with MWM. The results of working memory test for both control and NVB treated groups revealed that escape latency time and total distance travelled were significantly lower compared to untreated group. Similarly, the maze test performance was observed to be significantly improved for control and NVB treated groups. Moreover, the probe memory test performance for control and NVB treated groups was markedly better than untreated group. Thus NVB has a significant effect on the spatial cognitive preservation in rats with chronic cerebral hypoperfusion. Thus NVB can be a promising agent for the spatial cognitive functions improvement.

Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation.

Airway multiciliated epithelial cells play crucial roles in the mucosal defense system, but their differentiation process remains poorly understood. Mice lacking the basal body component Chibby (Cby) exhibit impaired mucociliary transport caused by defective ciliogenesis, resulting in chronic airway infection. In this paper, using primary cultures of mouse tracheal epithelial cells, we show that Cby facilitates basal body docking to the apical cell membrane through proper formation of ciliary vesicles at the distal appendage during the early stages of ciliogenesis. Cby is recruited to the distal appendages of centrioles via physical interaction with the distal appendage protein CEP164. Cby then associates with the membrane trafficking machinery component Rabin8, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rab8, to promote recruitment of Rab8 and efficient assembly of ciliary vesicles. Thus, our study identifies Cby as a key regulator of ciliary vesicle formation and basal body docking during the differentiation of airway ciliated cells.

Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism.

BACKGROUND: Autism is a pervasive neurodevelopmental disorder. At present there are no defined mechanisms of pathogenesis and therapy is mostly limited to behavioral interventions. Stem cell transplantation may offer a unique treatment strategy for autism due to immune and neural dysregulation observed in this disease. This non-randomized, open-label, single center phase I/II trial investigated the safety and efficacy of combined transplantation of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in treating children with autism. METHODS: 37 subjects diagnosed with autism were enrolled into this study and divided into three groups: CBMNC group (14 subjects, received CBMNC transplantation and rehabilitation therapy), Combination group (9 subjects, received both CBMNC and UCMSC transplantation and rehabilitation therapy), and Control group (14 subjects, received only rehabilitation therapy). Transplantations included four stem cell infusions through intravenous and intrathecal injections once a week. Treatment safety was evaluated with laboratory examinations and clinical assessment of adverse effects. The Childhood Autism Rating Scale (CARS), Clinical Global Impression (CGI) scale and Aberrant Behavior Checklist (ABC) were adopted to assess the therapeutic efficacy at baseline (pre-treatment) and following treatment. RESULTS: There were no significant safety issues related to the treatment and no observed severe adverse effects. Statistically significant differences were shown on CARS, ABC scores and CGI evaluation in the two treatment groups compared to the control at 24 weeks post-treatment (p < 0.05). CONCLUSIONS: Transplantation of CBMNCs demonstrated efficacy compared to the control group; however, the combination of CBMNCs and UCMSCs showed larger therapeutic effects than the CBMNC transplantation alone. There were no safety issues noted during infusion and the whole monitoring period. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01343511, Title "Safety and Efficacy of Stem Cell Therapy in Patients with Autism".

Advances in diagnosis and spatial analysis of cysticercosis and taeniasis.

Human cysticercosis, caused by accidental ingestion of eggs of Taenia solium, is one of the most pathogenic helminthiases and is listed among the 17 WHO Neglected Tropical Diseases. Controlling the life-cycle of T. solium between humans and pigs is essential for eradication of cysticercosis. One difficulty for the accurate detection and identification of T. solium species is the possible co-existence of two other human Taenia tapeworms (T. saginata and T. asiatica, which do not cause cysticercosis in humans). Several key issues for taeniasis/cysticercosis (T/C) evidence-based epidemiology and control are reviewed: (1) advances in immunological and molecular tools for screening of human and animals hosts and identification of Taenia species, with a focus on real-time detection of taeniasis carriers and infected animals in field community screenings, and (2) spatial ecological approaches that have been used to detect geospatial patterns of case distributions and to monitor pig activity and behaviour. Most recent eco-epidemiological studies undertaken in Sichuan province, China, are introduced and reviewed.

Detection of human taeniases in Tibetan endemic areas, China.

Detection of taeniasis carriers of Taenia solium is essential for control of cysticercosis in humans and pigs. In the current study, we assessed the positive detection rate of a self-detection tool, stool microscopy with direct smear and coproPCR for taeniasis carriers in endemic Tibetan areas of northwest Sichuan. The self-detection tool through questioning about a history of proglottid expulsion within the previous one year showed an overall positive detection rate of more than 80% for Taenia saginata, T. solium and T. asiatica. The positive detection rate was similar for T. saginata and T. solium. In 132 taeniid tapeworm carriers, 68 (51·5%) were detected by microscopy and 92 (69·7%) were diagnosed by coproPCR. A combination of microscopy and coproPCR increased the positive detection rate to 77·3%. There remained 10 cases (7·6%) coproPCR negative but microscopy positive. Due to the high cost and complicated process, coproPCR is required for the identification of Taenia species only when necessary, though it had a significant higher positive detection rate than microscopy. Combined use of self-detection and stool microscopy are recommended in community-based mass screening for taeniases in this Tibetan area or in other situation-similar endemic regions.

Development of three PCR assays for the differentiation between Echinococcus shiquicus, E. granulosus (G1 genotype), and E. multilocularis DNA in the co-endemic region of Qinghai-Tibet plateau, China.

To investigate echinococcosis in co-endemic regions, three polymerase chain reaction (PCR) assays based on the amplification of a fragment within the NADH dehydrogenase subunit 1 (ND1) mitochondrial gene were optimized for the detection of Echinococcus shiquicus, Echinococcus granulosus G1, and Echinococcus multilocularis DNA derived from parasite tissue or canid fecal samples. Specificity using parasite tissue-derived DNA was found to be 100% except for E. shiquicus primers that faintly detected E. equinus DNA. Sensitivity of the three assays for DNA detection was between 2 and 10 pg. Ethanol precipitation of negative PCR fecal samples was used to eliminate false negatives and served to increase sensitivity as exemplified by an increase in detection from 0% to 89% of E. shiquicus coproDNA using necropsy-positive fox samples.