Dupilumab provides sustained effectiveness on patient-reported outcomes and favorable safety in patients with moderate-to-severe atopic dermatitis: Up to 5-year results from the daily practice BioDay registry.

BACKGROUND: Long-term daily practice data on patient-reported benefits of dupilumab for atopic dermatitis (AD) remains limited. OBJECTIVE: To evaluate patient-reported outcome measures (PROMs) and the safety of dupilumab in patients with moderate-to-severe AD over a follow-up period of up to 5 years. METHODS: Data were extracted from the prospective, multicenter BioDay registry (October 2017-2022) of patients with moderate-to-severe AD treated with dupilumab in daily practice. RESULTS: In total 1223 patients, 1108 adults and 115 pediatric patients were included. After ≥1 year of treatment, mean Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Numeric rating scale (NRS)-pruritus ranged between 7.8 and 8.7, 3.5 and 4.2, and 2.9 and 3.1 in adults, respectively, whilst these patient-reported outcome measures (PROMs) ranged between 8.9 and 10.9, 4.4 and 6.4, and 3.0 and 3.7 in pediatric patients, respectively. At follow-up, overall work impairment decreased from 40.1% to 16.3% to 13.3% in adults. Furthermore, class I obesity and itch-dominant patients generally had less favorable treatment response. Of all patients, 66.8% reported ≥1 adverse event, with conjunctivitis being the most common (33.7%). LIMITATIONS: The overall percentage of missing values for selected PROMs was 26% in adults and 46% in pediatric patients. CONCLUSION: In addition to favorable safety, dupilumab has demonstrated sustained effectiveness across various PROMs, underscoring the treatment benefits from patients' perspectives.

Prevention of human exposure to livestock faecal waste in the household: a scoping study of interventions conducted in sub-Saharan Africa.

BACKGROUND: Poorly managed animal faecal waste can result in detrimental environmental and public health implications. Limiting human exposure to animal waste through Animal inclusive Water Sanitation and Hygiene (A-WASH) strategies is imperative to improve public health in livestock keeping households but has received little attention to date. A small number of A-WASH interventions have previously been identified through a systematic review by another research team, and published in 2017. To inform intervention design with the most up-to-date information, a scoping study was conducted to map the existing evidence for A-WASH in sub-Saharan Africa (SSA) emerging since the previous review. METHODS: This review followed PRISMA guidelines to identify interventions in SSA published between January 2016 to October 2022. Databases searched included PubMed, PMC Europe, CabDirect and Web of Science. Studies were eligible for inclusion if they were written in English and documented interventions limiting human contact with animal faecal material in the SSA context. Key data extracted included: the intervention itself, its target population, cost, measure of effectiveness, quantification of effect, assessment of success, acceptability and limitations. These data were synthesized into a narrative, structured around the intervention type. FINDINGS: Eight eligible articles were identified. Interventions to reduce human exposure to animal faecal matter were conducted in combination with 'standard' human-centric WASH practices. Identified interventions included the management of human-animal co-habitation, educational programs and the creation of child-safe spaces. No novel A-WASH interventions were identified in this review, beyond those identified by the review in 2017. Randomised Controlled Trials (RCTs) were used to evaluate six of the eight identified interventions, but as effect was evaluated through various measures, the ability to formally compare efficacy of interventions is lacking. CONCLUSION: This study indicates that the number of A-WASH studies in SSA is increasing and the use of RCTs suggests a strong desire to create high-quality evidence within this field. There is a need for standardisation of effect measures to enable meta-analyses to be conducted to better understand intervention effectiveness. Evaluation of scalability and sustainability of interventions is still lacking in A - WASH research.

[Analysis of the therapeutic efficacy and factors influencing sequential combination of nucleos(t)ide analogues with pegylated interferon alpha for 48~96 weeks in the treatment of patients with chronic hepatitis B].

Objective: To explore the therapeutic efficacy and factors influencing the sequential combination of nucleos(t)ide analogues (NAs) with pegylated interferon alpha (Peg-IFN-α) in the treatment of patients with chronic hepatitis B (CHB). Methods: 144 CHB cases with NAs treatment for more than 1 year, HBV DNA < 20 IU/ml, hepatitis B surface antigen (HBsAg) quantification < 3 000 IU/ml, treated with a sequential combination of Peg-IFN-α treatment for 48 to 96 weeks, and followed up were selected from the Fifth Medical Center of the PLA General Hospital between May 2018 and May 2020. Intention-to-treat analysis was used to measure the HBsAg clearance rate at 96 weeks. The Kaplan-Meier method was used to compute the cumulative HBsAg clearance rate at 96 weeks. Univariate and multivariate logistic regression were used to analyze the factors influencing HBsAg clearance at 48 weeks of sequential combination therapy. Univariate and multifactorial COX proportional hazard models were used to analyze the factors influencing HBsAg clearance following 96 weeks of prolonged PEG-IFN-α treatment. The receiver operating characteristic curve was used to assess the predictive value of factors influencing HBsAg clearance. A Mann-Whitney U test was used to compare the measurement data between groups. The count data was compared using the χ(2) test between groups. Results: 41 (28.47%) cases achieved HBsAg clearance at 48 weeks of sequential combination therapy. The HBsAg clearance rate at 96 weeks was 40.28% (58/144) by intention-to-treat analysis. The Kaplan-Meier method computed that the cumulative HBsAg clearance rate at 96 weeks was 68.90%. Multivariate logistic regression analysis showed that HBsAg quantification at baseline (OR = 0.090, 95%CI: 0.034-0.240, P < 0.001) and a 24-week drop in HBsAg level (OR = 7.788, 95%CI: 3.408-17.798, P < 0.001) were independent predictors of HBsAg clearance in CHB patients treated sequentially in combination with NAs and Peg-IFN-α for 48 weeks. Receiver operating characteristic curve analysis showed that the baseline HBsAg quantification [area under the receiver operating characteristic curve (AUC), 0.911, 95% CI: 0.852-0.952)] and 24-week drop in HBsAg level (AUC = 0.881, 95%CI: 0.814-0.930) had equally good predictive value for 48-week HBsAg clearance, but there was no statistically significant difference between the two (Z = 0.638, P = 0.523). The value of the combination of baseline HBsAg quantification and 24-week drop in HBsAg level (AUC = 0.981, 95%CI: 0.941-0.997) was superior to that of single baseline HBsAg quantification (Z = 3.017, P = 0.003) and 24-week drop in HBsAg level (Z = 3.214, P = 0.001) in predicting HBsAg clearance rate at 48 weeks. Multivariate COX proportional hazards model analysis showed that HBsAg quantification at 48 weeks (HR = 0.364, 95%CI: 0.176-0.752, P = 0.006) was an independent predictor of HBsAg clearance with a prolonged course to 96 weeks of Peg-IFN-α treatment. Conclusion: The HBsAg clearance rate can be accurately predicted with baseline HBsAg quantification combined with a 24-week drop in HBsAg level in patients with CHB who are treated with a sequential combination of NAs and Peg-IFN-α therapy for 48 weeks. Prolonging the course of Peg-IFN-α treatment can enhance the HBsAg clearance rate's capability. An independent predictor of HBsAg clearance is HBsAg quantification at 48 weeks of sequential combination therapy with a prolonged course of 96 weeks of Peg-IFN-α treatment.

Remote Heart Rate Prediction in Virtual Reality Head-Mounted Displays Using Machine Learning Techniques.

Head-mounted displays are virtual reality devices that may be equipped with sensors and cameras to measure a patient's heart rate through facial regions. Heart rate is an essential body signal that can be used to remotely monitor users in a variety of situations. There is currently no study that predicts heart rate using only highlighted facial regions; thus, an adaptation is required for beats per minute predictions. Likewise, there are no datasets containing only the eye and lower face regions, necessitating the development of a simulation mechanism. This work aims to remotely estimate heart rate from facial regions that can be captured by the cameras of a head-mounted display using state-of-the-art EVM-CNN and Meta-rPPG techniques. We developed a region of interest extractor to simulate a dataset from a head-mounted display device using stabilizer and video magnification techniques. Then, we combined support vector machine and FaceMash to determine the regions of interest and adapted photoplethysmography and beats per minute signal predictions to work with the other techniques. We observed an improvement of 188.88% for the EVM and 55.93% for the Meta-rPPG. In addition, both models were able to predict heart rate using only facial regions as input. Moreover, the adapted technique Meta-rPPG outperformed the original work, whereas the EVM adaptation produced comparable results for the photoplethysmography signal.

Prevalence and risk factors for exposure to Toxoplasma gondii in slaughterhouse workers in western Kenya.

BACKGROUND: Toxoplasma gondii is a zoonotic protozoan parasite infecting warm-blooded animals. Infection in people can occur through ingestion of oocysts passed in the faeces of the definitive hosts; ingestion of bradyzoites in the tissue of infected intermediate hosts; or exposure to tachyzoites in raw milk and eggs. Slaughterhouse workers are considered a high-risk group for T. gondii exposure because of their contact with raw meat, although a positive relationship between handling raw meat and T. gondii seropositivity has not been demonstrated in all studies. This study aimed to determine the seroprevalence of antibodies to T. gondii in slaughterhouse workers in Kenya and identify risk factors associated with seropositivity. METHODS: A survey of slaughterhouse workers was conducted in 142 slaughter facilities in the study area. Information regarding demographics, contact with livestock, meat consumption, and practices in the slaughterhouse was collected using structured questionnaires. Commercial ELISAs were used to detect IgM and IgG antibodies against T. gondii and a multi-level logistic regression model was used to identify potential risk factors for seropositivity in slaughterhouse workers. RESULTS: The apparent prevalence of antibodies to T. gondii was 84.0% (95% Confidence Interval (CI) 81.2-86.5%) for IgG and 2.2% (95% CI 1.3-3.5%) for IgM antibodies. All IgM positive individuals were IgG positive. Risk factors for exposure to T. gondii were: increasing age (Odds Ratio (OR) 1.03; 95% CI 1.01-1.05); owning poultry (OR 2.00; 95% CI 1.11-3.62); and consuming animal blood (OR 1.92; 95% CI 1.21-3.03). CONCLUSIONS: The seroprevalence of antibodies to T. gondii was very high in this population and considerably higher than published values in the general population. Risk factors included age, owning poultry and drinking animal blood which were consistent with previous reports but none were specifically associated with working in the slaughterhouse. In this instance slaughterhouse workers may represent a useful sentinel for the general population where the level of exposure is also likely to be high and may signify an unidentified public health risk to vulnerable groups such as pregnant women. A detailed understanding of the epidemiology of infection is required, which should include an assessment of incidence, mortality, and burden since T. gondii infection is likely to have life-long sequelae.

[Sporadic meningioangiomatosis: a clinicopathological analysis].

Objective: To analyze the clinicopathological characteristics, diagnosis and prognosis of meningioangiomatosis (MA), and to investige the possible origion of spindle cells. Methods: Seventeen cases of MA were collected at Xuanwu Hospital of Capital Medical University and the First Affiliated Hospital of Fujian Medical University, from June 2012 to March 2020. The clinical manifestations, radiologic, histopathologic, immunohistochemical features and patients' outcome were analyzed. The presumed origin of spindle cells was evaluated by immunohistochemical staining. Results: Of the 17 patients, 9 were males and 8 were females. The age ranged from 3 to 56 years old. Thirteen patients presented with seizure as the initial symptom. The lesions were solitary and located in the cerebral cortex. Histopathologically, there were proliferation of small blood vessels and perivascular spindle cells in the cerebral cortex. The spindle cells had no obvious atypia, mitoses and necrosis. Four cases were combined with transitional meningioma. Immunohistochemically, the proliferative perivascular spindle cells were positive for vimentin in all cases, and focally positive for EMA and SSTR2. Ki-67 proliferation index was low. Neurofibrillary tangles were demonstrated by AT8. All 17 patients received surgical treatment and were followed up for one to 93 months. None had seizure attacks or tumor recurrence. Conclusions: MA is a rare slow-growing intracranial lesion, and the perivascular spindle cells could be derived from meningothelial cells, and MA is often associated with degeneration of the cerebral cortex and meningioma. The patients have good prognosis after surgical treatment.

[The role of SMARCE1 in the diagnosis of clear cell meningioma].

Objective: To analyze the expression of SMARCE1 in clear cell meningioma (CCM), and evaluate the role of SMARCE1 in the differential diagnosis in morphologically similar diseases. Methods: Thirteen samples/11 cases of CCMs were collected from the First Affiliated Hospital of Fujian Medical University, Shandong Provincial Hospital, Xuanwu Hospital of Capital Medical University and Thaihe Hospital of Hubei Province from January 2000 to December 2018, as well as 17 cases of meningiomas with clear-cell-like morphology, 782 cases of other types of meningiomas and other intracranial tumors with clear-like morphology. A tissue microarray was made using these cases, on which immunohistochemical/histochemical staining of SMARCE1, SSTR2, EMA, Ki-67, p53, PAS and D-PAS were performed. Result: The tumor cells of CCM had sheet-like architecture, without typical whorl formation.The CCM had round to polygonal cells, with clear, glycogen-rich cytoplasm and prominent blocky perivascular and interstitial collagen. The immunohistochemistry staining showed that none of the CCMs expressed SMARCE1(0/13).However, all of the other types of lesions, including meningioma(782/782), meningiomas with clear-like morphology(17/17), intracranial metastatic clear cell renal cell carcinoma(10/10), haemangioblastoma(10/10), central neurocytoma(10/10), oligodendroglioma(10/10), ependymoma(13/13), lioblastoma(42/42), and solitary fibrous tumor/hemangiopericytoma(35/35) showed positive nuclear staining of SMARCE1. Ki-67 index were 1%-5%, and p53 positive-rate were 0-40% in CCMs. PAS stain showed cytoplasmic granular positive and D-PAS were negative in all CCMs and meningiomas with clear-like morphology. Conclusion: SMARCE1 is a useful marker for the diagnosis of CCM and its mimickers.

Stepwise approach for the control and eventual elimination of Taenia solium as a public health problem.

BACKGROUND: Taenia solium taeniosis/cysticercosis is a public health and agricultural problem, especially in low-income countries, and has been ranked the top foodborne parasitic hazard globally. In 2012, the World Health Organization published a roadmap that called for a validated strategy for T. solium control and elimination by 2015. This goal has not been met, and validated evidence of effective control or elimination in endemic countries is still incomplete. Measuring and evaluating success of control programmes remains difficult, as locally acceptable targets have not been defined as part of the 2012 roadmap nor from other sources, and the performance of tools to measure effect are limited. DISCUSSION: We believe that an international agreement supported by the tripartite World Health Organization, Food and Agriculture Organization of the United Nations, and World Organisation for Animal Health is needed to facilitate endemic countries in publicising SMART (Specific, Measurable, Achievable/attainable, Relevant, Time-bound) country-level control target goals. These goals should be achievable through locally acceptable adoption of options from within a standardised 'intervention tool-kit', and progress towards these goals should be monitored using standardised and consistent diagnostics. Several intervention tools are available which can contribute to control of T. solium, but the combination of these - the most effective control algorithm - still needs to be identified. In order to mount control efforts and ensure political commitment, stakeholder engagement and funding, we argue that a stepwise approach, as developed for Rabies control, is necessary if control efforts are to be successful and sustainable. CONCLUSIONS: The stepwise approach can provide the framework for the development of realistic control goals of endemic areas, the implementation of intervention algorithms, and the standardised monitoring of the evaluation of the progress towards obtaining the control target goals and eventually elimination.

[Efficacy and peripheral immunity analysis of allogeneic natural killer cells therapy in patients with hepatocellular carcinoma].

OBJECTIVE: To evaluate the safety and efficacy of allogeneic natural killer (NK) cells in the treatment of primary hepatocellular carcinoma (HCC), and to elucidate the mechanism of NK cells therapy. METHODS: Twenty-one patients with primary HCC treated with allogeneic NK cells at the Fifth Medical Center of the PLA General Hospital were followed up for 1 year. Peripheral blood mononuclear cells (PBMCs) were isolated from patient-related donors and cultured in vitro for 15 days and infused to the patients in two consecutive days. Clinical data and laboratory data were collected and analyzed, including survival, clinical features, imaging changes, hematology, immunology, and biochemical indicators to evaluate the safety and efficacy of allogeneic NK cell therapy. The changes of peripheral blood lymphocyte subsets after treatment were also analyzed to explore the possible anti-tumor mechanisms. RESULTS: (1) Of the 21 patients with primary HCC, 11 patients were treated once, 5 patients were treated twice, and 5 patients were treated 3 times. After allogeneic NK cells infusion, 10 patients had fever, 1 patient had slight hepatalgia and 1 patient had slight headache, no other adverse events occurred including acute and chronic graft-versus-host disease (GVHD). They resolved spontaneously within 8 hours without other treatment. (2) The total disease control rate was 76.2% during one-year follow-up. Among them, the patients with Barcelona clinic liver cancer (BCLC) stage A had a disease control rate of 100%, stable disease (SD) in 10 cases; BCLC stage B patients had a disease control rate of 60%, partial response (PR) in 1 case, and SD 2 in cases; BCLC stage C patients had a disease control rate of 50%, complete response (CR) in 1 case, and 2 cases of PR. (3) The frequencies of NK cells and CD8+ T cells in peripheral blood were significantly lower than that before at 24 hours after treatment, and the frequencies of CD4+ T cells and CD4/CD8 were significantly higher than the baseline. CONCLUSION: Allogeneic NK cells have good safety and efficacy in the treatment of primary HCC. The anti-tumor effect of the allogeneic NK cells may play an important role in the activation of the patient's natural immune system and delay disease progression, suggesting that allogeneic NK cells combined with sorafenib may be a very effective treatment for advanced HCC, and further large-sample multicenter randomized controlled clinical trials are needed to validate this result.

[Safety and efficacy of transarterial embolization combined with octreotide LAR on reducing tumor burden for neuroendocrine tumor liver metastasis].

Objective: To evaluate the tumor burden reducing efficacy and safety of transcatheter arterial embolization (TAE) combined with octreotide LAR on neuroendocrine tumor liver metastasis (NETLM). Methods: Twenty-nine NETLM patients treated in the First Affiliated Hospital of Sun Yat-sen University from October 2014 to August 2018 were retrospectively recruited, including 12 males and 17 females. The mean age was 25-69(50±11) years. All patients were histologically proved as well-differentiated NET liver metastasis. Seventeen patients underwent combined treatment of TAE plus octreotide LAR (combined group) and 12 patients treated with only octreotide LAR (control group). Response of hepatic lesions were assessed according to RECIST 1.1. Objective response rates (ORR) of two groups were compared and analyzed. Safety and tolerance to TAE were also evaluated. Results: There were 13 PR and 4 SD in combined group, but only 1 PR and 9 PD in the control group. The ORR between the two groups were significantly different (13/17 vs 1/12, P<0.01).The main complication post TAE was post embolization syndrome, including abdominal pain (12/17), vomiting (6/17), fever (4/17), elevated transaminase (8/17) and bilirubinemia (3/17). Tumor lysis syndrome was observed in one patient. Conclusion: Compared to administration of octreotide LAR, TAE combined with octreotide LAR can effectively reduce tumor burden in patients with NETLM. TAE is safe and well-tolerated.

[Neuropathologic study of massive subcortical heterotopia].

Objective: To investigate the clinicpathologic features and probable mechanisms of massive subcortical heterotopia. Methods: Clinical data, histologic features and neuropathologic data were analyzed in five cases of massive subcortical heterotopia collected from Xuanwu Hospital, Capital Medical University from January 2014 to October 2017. Results: All five patients (three males and two females) had a history of refractory epilepsy with a mean period of 15.4 years (range 7 to 21 years). The median age at surgery was 28.6 years(range 20 to 39 years). Magnetic resonance imaging showed that the lesions were located in the temporal lobe (two cases), parietal lobe (one case), both temporal and occipital lobes (one case) and both temporal and parietal lobes (one case). Pathologic examination disclosed that massive gray matter in subcortical and deep white matter with various shape and size. Moreover, one case also showed subpial and periventricular heterotopias and polymicrogyria. Polymicrogyria or hippocampal sclerosis were seen in the remaining three cases. None of the five patients experienced seizure attacks during the follow-up period. Conclusions: Heterotopia is malformations due to abnormal neuronal migration. Massive subcortical heterotopia due to widespread abnormal neuronal migration is relatively rare. The mechanism of heterotopia together with polymicrogyria needs further discussion.

An integrated study of human and animal infectious disease in the Lake Victoria crescent small-holder crop-livestock production system, Kenya.

BACKGROUND: The neglected zoonotic diseases (NZD) are an understudied group that are a major cause of illness throughout the developing world. In general, little is known about the prevalence and burden of NZDs in affected communities, particularly in relation to other infectious diseases with which they are often co-endemic. We describe the design and descriptive epidemiological outputs from an integrated study of human and animal zoonotic and non-zoonotic disease in a rural farming community in western Kenya. METHODS: This cross-sectional survey involved 2113 people, their cattle (n = 983) and pigs (n = 91). People and animals were tested for infection or exposure to a wide range of zoonotic and non-zoonotic pathogens. Prevalence estimates, with adjustment for the complex study design, were derived. Evidence for spatial clustering in exposure or infection was identified using the spatial scan statistic. RESULTS: There was a high prevalence of human parasitism in the community, particularly with hookworm (Ancylostoma duodenale or Necator americanus) (36.3% (95% CI 32.8-39.9)), Entamoeba histolytica/dispar (30.1% (95% CI 27.5-32.8)), and Plasmodium falciparum (29.4% (95% CI 26.8-32.0)). Human infection with Taenia spp. was also prevalent (19.7% (95% CI 16.7-22.7)), while exposure to other zoonotic pathogens was comparatively rarer (Brucella spp., 0.6% (95% CI 0.2-0.9); Coxiella burnetii, 2.2% (95% CI 1.5-2.9); Rift Valley fever, 0.5% (95% CI 0.2-0.8)). A low prevalence of exposure to Brucella spp. was observed in cattle (0.26% (95% CI 0-0.56). This was higher for Rift Valley fever virus (1.4% (95% CI 0.5-2.22)) and C. burnetii (10.0% (95% CI 7.7-12.2)). The prevalence of Taenia spp. cysticercosis was 53.5% (95% CI 48.7-58.3) in cattle and 17.2% (95% CI 9.1-25.3) in pigs. Mycobacterium bovis infection was found in 2.2% of cattle (95% CI 1.3-3.2), while the prevalence of infection with Mycobacterium spp. was 8.2% (95% CI 6.8-9.6) in people. CONCLUSION: Zoonotic infections in people and animals occur in the context of a wide range of co-endemic pathogens in a rural community in western Kenya. The wide diversity of pathogens under study provides a unique opportunity to explore the distribution and determinants of infection in a multi-pathogen, multi-host system.

Evidence for the presence of African swine fever virus in an endemic region of Western Kenya in the absence of any reported outbreak.

BACKGROUND: African swine fever (ASF), caused by African swine fever virus (ASFV), is a severe haemorrhagic disease of pigs, outbreaks of which can have a devastating impact upon commercial and small-holder pig production. Pig production in western Kenya is characterised by low-input, free-range systems practised by poor farmers keeping between two and ten pigs. These farmers are particularly vulnerable to the catastrophic loss of livestock assets experienced in an ASF outbreak. This study wished to expand our understanding of ASFV epidemiology during a period when no outbreaks were reported. RESULTS: Two hundred and seventy six whole blood samples were analysed using two independent conventional and real time PCR assays to detect ASFV. Despite no recorded outbreak of clinical ASF during this time, virus was detected in 90/277 samples analysed by conventional PCR and 142/209 samples analysed by qPCR. Genotyping of a sub-set of these samples indicated that the viruses associated with the positive samples were classified within genotype IX and that these strains were therefore genetically similar to the virus associated with the 2006/2007 ASF outbreaks in Kenya. CONCLUSION: The detection of ASFV viral DNA in a relatively high number of pigs delivered for slaughter during a period with no reported outbreaks provides support for two hypotheses, which are not mutually exclusive: (1) that virus prevalence may be over-estimated by slaughter-slab sampling, relative to that prevailing in the wider pig population; (2) that sub-clinical, chronically infected or recovered pigs may be responsible for persistence of the virus in endemic areas.

[Let-7 miRNA silencing promotes Kaposi's sarcoma-associated herpesvirus lytic replication via activating mitogen-activated protein kinase kinase kinase kinase 4 and its downstream factors].

OBJECTIVE: To explore the effect of let-7 miRNA silencing on Kaposi's sarcoma-associated herpesvirus (KSHV) lytic replication and the underling mechanism. METHODS: The pEGFP-C2-let-7 sponge vector was transfected into BCBL-1 and 293T cells with Lipofectamine 2000 to silence the expression of let-7 miRNAs. Quantitative real-time PCR (qRT-PCR) was used to quantify the expression of let-7 miRNAs, the transcriptional levels of mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), cyclooxygenase-2 (COX-2) and matrix metalloproteinase 13 (MMP-13), and the DNA copy numbers of KSHV open reading frame 50 (ORF50) and open reading frame 72 (ORF72). Western blot was used to detect the total and phosphorylated protein levels of MAP4K4, COX-2, extracellular regulated protein kinases (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK. RESULTS: The expression of let-7 miRNAs was dramatically decreased in the let-7 sponge transfected BCBL-1 and 293T cells compared with that in the vector-transfected cells (P<0.05 for all). The gene copy number and mRNA transcriptional level of KSHV ORF50 were significantly increased in the let-7 sponge transfected BCBL-1 cells compared with that in the vector-transfected cells (1.00±0.10 vs. 2.33±0.18 and 1.08±0.48 vs 3.22±0.27, respectively,P<0.001 for both). The gene copy number and mRNA transcriptional level of KSHV ORF72 were also significantly increased in let-7 sponge transfected BCBL-1 cells compared with those in the vector-transfected cells(1.07±0.49 vs 1.67±0.45 and 1.01±0.19 vs 1.54±0.11, respectively,P<0.05 for both). Furthermore, the mRNA transcriptional levels of MAP4K4, COX-2 and MMP-13 were significantly increased in the let-7 sponge transfected BCBL-1 cells compared with those in the vector-transfected cells (1.00±0.05 vs 5.73±0.96, 1.00±0.05 vs 2.68±0.19, 1.00±0.02 vs 2.69±0.25, respectively,P<0.001 for all). Let-7 miRNAs silencing also increased the protein expression levels of MAP4K4, COX-2 and phospho-ERK1/2, while the phospho-JNK and phospho-p38 were not changed in the BCBL-1 and 293T cells. CONCLUSIONS: Let-7 silencing may activate the replication of KSHV, possibly through up-regulating MAP4K4 and its downstream molecules COX-2, MMP-13, and phosphorylation of ERK1/2, finally results in the progression of Kaposi sarcoma.

[The clinical and pathological features of 85 cases with positive cerebrospinal fluid cytology by thin-layer centrifugal cytological test].

Objective: To evaluate cytological test of cerebrospinal fluid in the diagnosis of meningeal dissemination of tumor cells. Methods: The clinical and imaging features of 85 cases with tumor cells diagnosed by thin-layer centrifugal cytological test of cerebrospinal fluid were retrospectively reviewed. The characteristics of cellular morphology and immunocytochemical staining were analyzed. Results: The main presentations of all the patinets was meningeal irritation and neurological dysfunction. The features of the brain MRI were meningeal thicking and enhancement, intracranial abnormal signals and intracranial space occupying lesion in part of the patients. Atypical cells were found in 84 cases (98.8%) with the first sample test and immunocytochemical staining was conducted in 48 cases to identify the tissue origin. Meningeal carcinomatosis was shown to be the majority with lung cancer as the dominated tissue type and adenocarcinoma as the most common histological type. Others were lymphatic hematopoietic system (13 cases), melanomas(5 cases), primitive neuroectodermal tumor (3 cases) and glioma (1 case). In addition, 12 cases were only proved to be cancer by cytological test of cerebrospinal fluid. Conclusion: The thin-layer centrifugal cytological test of cerebrospinal fluid has a relatively high accuracy for detecting disseminated tumor cells of meninges and could be of great help to identify the source and type of lesion with immunocytochemical staining.

[Transplantation of adipose derived mesenchymal stem cells alleviated osteoarthritis induced with anterior cruciate ligament transection].

OBJECTIVE: To explore the therapeutic potential of transplantation of adipose derived mesenchymal stem cells (ADMSCs) in rats osteoarthritis caused by anterior cruciate ligament transection. METHODS: Rats peritoneal adipose tissues were used to extract ADMSCs.Cell morphological appearance was documented and flow cytometric cell cycle was used to identify ADMSCs. Anterior cruciate ligament transection was used to induce knee osteoarthritis in rats. ADMSCs were injected into the knee cavities. Knee joint pathology was performed to observe the treatment effects. QRT-PCR and Western blot were used to identify the targets of ADMSCs. RESULTS: ADMSCs were successfully extracted, separated, cultured and identified. Two and eight weeks after ADMSCs transplantation, pathology showed significantly attenuation of arthritis including osteophyte and synovitis, reflecting in significantly improvement of both osteophyte and synovitis grading compared to the controls. QRT-PCR and Western blot revealed that collagen Ⅱ expression was significantly up-regulated after ADMSCs transplantation compared to the controls.MMP-13, but not other MMP-1, MMP-3 or MMP-9 was reduced when ADMSCs were co-cultured with primary chondrocytes. DDR-2 expression in chondrocyte was heavily up-regulated when stimulated by TNF-α in vitro. However, ADMSCs could reverse the effect when co-cultured with chondrocyte, implying that ADMSCs may suppress the expression of DDR-2. IL-1ß suppressed the cartilage differentiation of ADMSCs, and Actinomycin D (DDR-2 inhibitor) could reverse the effect. CONCLUSION: ADMSCs can attenuate osteoarthritis induced by anterior cruciate ligament transection in rats by suppressing the expression of MMP-13, and the upstream target spot may be DDR-2.

Prevalence of porcine cysticercosis in the Lake Kyoga Basin, Uganda.

BACKGROUND: Taenia solium is a zoonotic helminth with the potential to cause life threatening epilepsy in people through the aberrant larval infection of the brain called Neurocysticercosis (NCC). The pig is the intermediate host for T. solium where the larval form, cysticercus cellulosae, normally develops after the pig eats eggs of the parasite. Humans are the definitive host where the adult tapeworm develops and are infected through the consumption of poorly cooked, infected meat. T. solium has been acknowledged by the World Health Organization (WHO), Food and Agriculture Organization (FAO) and UK Department for International Development (DFID) as being a neglected zoonotic disease, and was recently included in the WHO roadmap for control of neglected tropical diseases. This neglect encompasses a lack of epidemiological data and a lack of validated, effective control strategies being adopted. Understanding the epidemiology of this parasite in the intermediate host is the first step towards designing suitable intervention strategies for the improvement of public health. This study was undertaken to provide an accurate and up-to-date estimate for the prevalence of porcine cysticercosis in the Lake Kyoga basin. RESULTS: Sera from 378 pigs were analysed with the HP10 Antigen Enzyme Linked Immunosorbant Assay (ELISA) and the prevalence was found to be 25.7% (95% confidence interval 21.0% to 30.0%). Previous sero- surveillance in this region, using the B158/B60 Ag Elisa had indicated a prevalence of 8.6% in 2005 indicating a dramatic increase in prevalence (J. Parasitol Res, Article ID 375493, 2009) within a 6 year period. CONCLUSION: This increasing prevalence in the disease indicates to us that there is currently no effective control of this parasite and that in this region of Uganda at least; cysticercosis remains a neglected zoonotic disease.

Gender considerations in One Health: a framework for researchers.

One Health research and intervention outcomes are strongly influenced by gender dynamics. Women, men, girls, and boys can be negatively affected by gender-based disadvantage in any of the three One Health domains (animal, human, and environmental health), and where this occurs in more than one domain the result may be a compounding of inequity. Evidence worldwide shows that women and girls are more likely to suffer from such gender-based disadvantage. A thoughtfully implemented One Health intervention that prioritizes gender equity is more likely to be adopted, has fewer unintended negative consequences, and can support progress toward gender equality, however there is limited evidence and discussion to guide using a gender lens in One Health activities. We propose a framework to identify key gender considerations in One Health research for development - with a focus on Low-and Middle-Income Countries. The framework encourages developing two types of research questions at multiple stages of the research process: those with a bioscience entry-point and those with a gender entry-point. Gender considerations at each stage of research, institutional support required, and intervention approaches is described in the framework. We also give an applied example of the framework as it might be used in One Health research. Incorporation of gender questions in One Health research supports progress toward more equitable, sustainable, and effective One Health interventions. We hope that this framework will be implemented and optimized for use across many One Health challenge areas with the goal of mainstreaming gender into One Health research.

Consumer preferences and willingness to pay for safe pork products in rural Kenya.

Designing interventions to support the safe development of rapidly growing livestock value chains in sub-Saharan Africa requires a clear understanding of consumer demands. This study aimed to determine purchase patterns, consumers' preferences, and willingness to pay for safe pork attributes; specifically, the presence of a veterinary inspection stamp and the cleanliness of the butchery. A discrete choice experiment-based survey was used to investigate the purchasing behavior of 401 pork consumers: 253 buying raw pork for household consumption, and 148 buying cooked pork for out-of-home consumption. The study findings indicate that the average quantity of pork purchased by consumers was approximately 0.4 Kg per transaction, with the majority of consumers making several purchases per week. The average price per Kg of pork was KES 310 (Approx. 2.60 USD) at the time of the study. Data from the choice experiment showed that consumers were willing to pay a price premium of KES 245 (Approx. 2.1 USD) and KES 164 (Approx. 1.4 USD) per Kg for evidence of better veterinary meat inspection and higher butchery hygiene respectively; further, these were the two most important attributes they considered while making a pork purchase decision. These findings highlight the potential to leverage consumers' willingness to pay to improve the food safety within pork value chains in this context. Investing to increase consumer awareness on food safety issues should be considered to generate an effective market demand, especially in rural areas with relatively lower literacy levels.

Cortisol secretion autonomy associated with weight loss outcome after laparoscopic sleeve gastrectomy: a prospective cohort study in Asian patients.

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is a widely recognized effective bariatric surgery. However, variable weight loss outcomes post-surgery remained a clinical challenge. Currently, there is no established consensus on the factors influencing weight loss failure following LSG. This study aimed to explore the association between preoperative cortisol secretion autonomy and postoperative weight loss in obese patients undergoing LSG. PATIENTS AND METHODS: A cohort of 181 patients with simple obesity (BMI ≥ 28 kg/m2) who underwent LSG and were followed up for one year was analyzed. Weight loss was measured by the percentage of excess weight loss (%EWL), and cortisol secretion autonomy was evaluated using a 1 mg dexamethasone suppression test (DST). Regression models were used to analyze the correlation between preoperative 1 mg DST results and %EWL one year after laparoscopic sleeve gastrectomy (LSG). RESULTS: Cortisol secretion autonomy was significantly lower in the %EWL ≥ 75% group and higher in the %EWL < 75% group, showing a negative correlation with %EWL (R = -0.336, p = 0.001). Logistic regression analysis indicated that high cortisol secretion autonomy was significantly correlated with %EWL < 75% after LSG. The likelihood of %EWL being < 75% was 10.47 times greater in patients with high cortisol secretion autonomy compared to those with low cortisol secretion autonomy (odds ratio 10.472, confidence interval: 1.660-66.048, p = 0.012). CONCLUSIONS: Cortisol secretion autonomy emerges as an independent predictor of weight loss outcomes in Asian patients undergoing LSG. This finding suggests the potential for cortisol secretion autonomy to inform preoperative assessments and personalized treatment strategies in bariatric surgery.