[A grave concern for the prevalence of monkeypox virus].

Monkeypox is a zoonosis caused by monkeypox virus. Monkeypox virus belongs to the Orthopoxviruses genus in the Poxviridae family, which is regarded as the most important Orthopoxvirus infection in human beings after the extinction of smallpox. Since the first human monkeypox case was reported in the Democratic Republic of the Congo in 1970, monkeypox has become endemic in Central and West African. From May 6 to July 15, 2022, monkeypox has broken out in many countries. Monkeypox cases have been detected in 62 countries and regions. Moreover, human to human transmission has occurred and attracted high global attention. Monkeypox virus has been discovered for more than 60 years, but the understanding and research of its natural host, epidemiological characteristics and treatment are still relatively limited. Therefore, this study analyzes the epidemic situation, the possible causes of the outbreak and the future key research directions, and puts forward countermeasures to provide scientific basis for the prevention and control of monkeypox.

[Etiological and epidemiological characteristics of Vibrio cholerae in Beijing, 2015-2021].

Objective: To analyze the etiological and epidemiological characteristics of Vibrio cholerae in Beijing during 2015-2021 and provide evidence for the prevention and control of cholera. Methods: The V. cholerae strains isolated in Beijing during 2015-2021 were analyzed by serotyping and virulence genes detection. Pulsed field gel electrophoresis (PFGE) was performed for the molecular typing of the strains. Based on the collected epidemiological and clinical data of cholera cases,the epidemiological characteristics of cholera were analyzed by descriptive epidemiology method. Results: A total of 76 Vibrio cholerae O1 strains were isolated in Beijing during 2015-2021, including 61 strains from human, 10 strains from environment and 5 strains from seafood. The 76 strains consisted of 68 Ogawa strains and 8 Inaba strains. Six Ogawa strains isolated from sporadic cases carried ctxAB. After NotⅠ digestion, 76 strains were divided into 33 PFGE patterns. From 2015 to 2021, a total of 38 cholera epidemics were reported in Beijing, most of them were sporadic ones, accounting for 92.11% (35/38). A total of 45 cases were reported, and the cases occurred during June-September accounted for 97.78% (44/45). Cholera cases occurred in 9 districts of Beijing, and the cases reported in Chaoyang district accounted for 42.22% (19/45) and in Changping district accounted for 31.11% (14/45). The age of the cholera cases ranged from 19 to 63 years. Except for one case with unknown clinical symptoms, 44 cases had diarrhea symptoms with 84.09% (37/44) of the cases reporting diarrhea (3-9 times/day), followed by yellow watery stool (95.45%, 42/44), abdominal pain (68.18%, 30/44), nausea and vomiting (40.91%, 18/44) and fever (36.36%, 16/44). Conclusion: Vibrio cholerae strains isolated in Beijing during 2015-2021 were mainly O1 serotype Ogawa,most of which were non-toxigenic. The PFGE of the strains varied. Cholera epidemics occurred in 9 districts of Beijing, but most were sporadic ones with incidence peak during June-September.

[Epidemiological characteristics of hand, foot and mouth disease among people aged 6 and over in Beijing, 2011-2020].

Objective: To analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) among people ≥6 years old in Beijing from 2011 to 2020. Methods: The incidence data of HFMD cases from 2011 to 2020 were collected from the National Notifiable Infectious Disease Reporting System of China Information for Disease Control and Prevention and the etiological surveillance of HFMD in 29 sentinel hospitals from 16 districts of Beijing. Descriptive epidemiological methods were used to analyze the distributions, pathogen constituents, and changes of HFMD cases in Beijing people ≥6 years old. Results: From 2011 to 2020, a total of 38 183 cases of HFMD were reported among people ≥6 years old in Beijing, of which 46 (0.12%) cases were severe. The average annual reported incidence was 19.04/100 000. The ratio of males to females were 1.37∶1(22 064∶16 119). The proportion of HFMD in people ≥6 years old increased from 7.56%(2 606/34 488) in 2011 to 24.54% (546/2 225) in 2020. The average incidence of HFMD was higher in Shunyi district, Yanqing district, and Tongzhou district than in other districts in Beijing. The positive rate of enterovirus in sentinel surveillance was 66.78% (1 976/2 959), the proportion of enterovirus group A 71 (EV-A71) was 45.29% (101/223) in 2014, no EV-A71 positive was detected in 2020, and the proportion of Coxsackievirus A 6 (CV-A6) increased from 15.11% (34/225) in 2016 to 81.08% (60/74) in 2020. Conclusions: From 2011 to 2020, the proportion of cases with HFMD in people ≥6 years old in Beijing increased yearly, and the proportion of EV-A71 positive patients decreased basically. Since 2016, CV-A6 has gradually become the dominant pathogen. More attention should be paid to the epidemic situation and dynamic pathogen changes of hand foot mouth disease in people ≥6 years old.

SAR and QSAR research on tyrosinase inhibitors using machine learning methods.

Tyrosinase is a key rate-limiting enzyme in the process of melanin synthesis, which is closely related to human pigmentation disorders. Tyrosinase inhibitors can down-regulate tyrosinase to effectively reduce melanin synthesis. In this work, we conducted structure-activity relationship (SAR) study on 1097 diverse mushroom tyrosinase inhibitors. We applied five kinds of machine learning methods to develop 15 classification models. Model 5B built by fully connected neural networks and ECFP4 fingerprints achieved the highest prediction accuracy of 91.36% and Matthews correlation coefficient (MCC) of 0.81 on the test set. The applicability domains (AD) of classification models were defined by d S T D - P R O method. Moreover, we clustered the 1097 inhibitors into eight subsets by K-Means to figure out inhibitors' structural features. In addition, 10 quantitative structure-activity relationship (QSAR) models were constructed by four machine learning methods based on 813 inhibitors. Model 6 J, the best QSAR model, was developed by fully connected neural networks with 50 RDKit descriptors. It resulted in a coefficient of determination (r 2) of 0.770 and a root mean squared error (RMSE) of 0.482 on the test set. The AD of Model 6 J was visualized by Williams plot. The models built in this study can be obtained from the authors.

Time Regularity of Morphology of Blood Pools.

ABSTRACT: Objective To provide reference indexes and theoretical basis for age estimation of blood pools by investigating the entire drying process and monitoring the change of morphology and mass. Methods Four 15 mL blood pool samples were prepared on the clean ceramic plate. The change of morphology and mass of blood pools in a closed dark environment with a temperature of （20.0±0.5） ℃ and a humidity of 35%-45% were dynamically observed from 0 h to 60 h. Images of the blood pools were recorded by digital camera. The area of blood pools was calculated by MATLAB R2014b, the length of cracks was measured by Image J and the statistical analysis was performed by SPSS 16.0. Results By summarizing and analyzing, the drying of blood pools was divided into five stages： coagulation （0-4.5 h）, gelation （>4.5-20.0 h）, gel-solid mixing （>20.0-37.0 h）, solid （>37.0-40.0 h） and final desiccation （>40.0-45.0 h）. From 0 to 45 h, the mass of the blood pools decreased linearly with time, and the decrease was not obvious from 45.0 to 60.0 h. The standardized mass （y2） showed strong correlation with the time （x） y2=0.018 2 x+0.271 4（R2=0.967 9）. The area change rate of blood pools, the distance that the edge of blood pools moved, the average length of radical cracks had little correlation with the time that passed. Conclusion The overall morphological characteristics of blood pools show a certain regularity with the time and the standardized indexes established provide a reference for the age estimation of blood pools.

[Summary of research in economic burden of hand, foot, and mouth disease in China].

Since 2010, the incidence of hand, foot, and mouth disease (HFMD) has ranked top in notifiable infectious disease in China, causing economic losses to many families and the society of China. This paper summarizes the related methods, results and problems systematically in the research of economic burden of HFMD in China to provide reference for the better estimation of the economic burden caused by HFMD. Many studies showed that HFMD, especially severe and fatal cases, had posed heavy economic burden on the society. To mitigate the burden caused by HFMD, it is necessary to decrease the risk of severe and fatal cases, as well as to reduce the incidence of mild cases.

[Review on the etiology and complications of hand, foot and mouth disease, using data from the national sentinel surveillance program, in China, 2015-2016].

Objective: To understand the characteristics relating to the etiology and complications of hand, foot and mouth disease (HFMD) based on data from the pilot National Sentinel Surveillance (NSS) program so as to explore the feasibility, advantages and disadvantages of the NSS. Methods: Data were extracted from the NSS system, conducted in 11 provinces of China from November 2015 to October 2016. Characteristics regarding the etiology, complications of HFMD and factors related to the positive rates of HFMD specimens were analyzed under the logistic regression method by SPSS 20.0 software. Results: A total of 4 783 specimens were collected, including 3 390 from mild, 1 390 from severe and 3 from death cases. The overall positive rate was 81.43% (3 895/4 783). Other enteroviruses (non EV71/Cox A16 enteroviruses) appeared the major serotype (52.68%, 1 482/2 813) for mild infection of the disease while EV71 was for the severe cases (65.31%, 706/1 081). The serotype spectrum revealed by the pilot NSS was almost identical with the existing surveillance system. Other enteroviruses tended to infect younger children (χ(2)=130.17, P<0.001) than EV71 and Cox A16, in China. The multivariate logistic regression results showed that higher positive rate was associated with specimens which were collected from males, at children' hospitals, in peak seasons, timely and in stools. The positive rates presented downwarding trends with the extension of the onset-sampling interval (χ(2)=14.47, P<0.001 in stool specimen; χ(2)=31.99, P<0.001 in throat swab; χ(2)=24.26, P<0.001 in anal swab). Aseptic meningitis, non-brainstem encephalitis and brainstem encephalitis appeared the top three complications of both EV71-associated and other enteroviruses-associated severe HFMD cases. Conclusions: Factors as gender, season/place/timeliness of specimen collection, and types of hospital all appeared independently influenced the positive rates. NSS seemed feasible to be used as an alternative or supplement tool to the existing surveillance program in China.

Characterization of microbial community profiles associated with quality of Chinese strong-aromatic liquor through metagenomics.

AIMS: Microorganisms in fermentation pits (FPs) play key roles for Chinese-strong-aromatic-liquor (CSAL) production. However, the microbial community in the FPs is still poorly understood. Here, the aim of this study was to reveal the diversity and potential functions of microbiota in FPs. METHODS AND RESULTS: Sequencing-by-synthesis-based metagenomic sequencing and annotation results revealed that the microbiota of FPs was primarily composed of Firmicutes (54·6%), Euryarchaeota (15·3%), Bacteroidetes (10·1%), Gammaproteobacteria (5·8%), Opisthokonta (5·7%) and Unclassified_Bacteria (2·3%). And 133 genera were identified as the dominant genera of this fermentative food. Lactobacillus, Sedimentibacter, Syntrophomonas, Methanoculleus, Methanobacterium, Bacillus, Clostridium, Galactomyces, Candida, Pichia, Penicillium and Aspergillus were defined as active populations for biosynthesizing the characteristic volatile compounds of CSAL. The study also revealed that the microbial community structures changed significantly with different cellar ages and over different geographical regions. (i) The presence of Bacteroidetes was the most distinctive feature that characterized the different FPs ages. (ii) Distinct contents of Gammaproteobacteria and Euryarchaeota were observed at different positions in the FPs. (iii) Euryarchaeota markedly contributed to the generation of the character of the liquors with distinct geographical associations. CONCLUSIONS: This study demonstrated that the changes of microbial communities determined the different quality characteristics of CSAL. SIGNIFICANCE AND IMPACT OF THE STUDY: This research contributes to a deeper understanding of the FPs microbial composition and shows a new microbial resource for biotechnological applications.

[Severe cases with hand, foot and mouth disease: data based on national pilot hand, foot and mouth disease surveillance system].

Objective: To investigate the clinical severity, etiological classification and risk factors of severe cases with hand, foot and mouth disease (HFMD). Methods: A total of 1 489 records on severe and fatal HFMD cases reported to the national pilot surveillance system of HFMD were used to analyze the demographic, medical treatment, etiological classification of the cases. Treatment outcome related risk factors were also studied with multi-variable stepwise logistic regression method. Results: Seven out of the 1 489 severe HFMD cases died of this disease. A total of 960 (72.9%) were under three years old and 62.9% were male and most of the cases (937, 62.9%) resided in rural areas. Among all the cases, 494 (33.2%) went to seek the first medical assistance at the institutions of village or township level. Durations between disease onset and first medical attendance, being diagnosed as the disease or diagnosed as severe cases were 0(0-1) d, 1 (0-2) d and 2 (1-4) d, respectively. In total, 773 (51.9%) of the severe HFMD cases were diagnosed as with aseptic meningitis, 260 (17.5%) with brainstem encephalitis, 377 (25.3%) with non-brainstem encephalitis, 6 (0.4%) with encephalomyelitis, 1 (0.1%) with acute flaccid paralysis, 4 (0.3%) with pulmonary hemorrhage/pulmonary edema and 68 (4.6%) with cardiopulmonary failure. Of the etiologically diagnosed 1 217 severe and fatal HFMD cases, 642 (52.8%) were with EV71, other enterovirus 261 (21.5%), Cox A16 36 (3.0%), 1 (0.1%) with both EV71 and Cox A16. However, 277 (22.8%) showed negative on any pathogenic virus. Complication (Z=3.15, P=0.002) and duration between onset and diagnosed as severe cases (Z=3.95, P<0.001) were shown as key factors related to treatment outcomes. Conclusions: Most severe HFMD cases appeared in boys, especially living in the rural areas. Frequently seen complications would include aseptic meningitis, non-brainstem encephalitis and brainstem encephalitis. EV71 was the dominant etiology for severe and fatal cases. Early diagnosis and complication control were crucial, related to the treatment outcome of HFMD.

Reduction of Lactobacillus in the milks of cows with subclinical mastitis.

Clinical and subclinical bovine mastitis are the most frequent diseases encountered on dairy farms worldwide, which cause significant economic loss and veterinary cost. The mastitic disease status is associated with increases in both milk bacterial pathogens and somatic cell count (SCC). Although it is well established that the mastitic pathogens generally correlate with the milk SCC, to our knowledge, the correlation between the probiotic genus, Lactobacillus, and the mastitic causative bacteria and SCC have not been determined previously. Thus, in this study, milk samples from 12 mild and 28 severe subclinical mastitic dairy cows were collected from the same farm. The overall milk bacterial load was quantified with the total plate count method. The Lactobacillus genus and 4 common clinical and subclinical mastitic pathogens (Escherichia coli, Staphylococcus aureus, Streptococcus agalactiae, and Trueperella pyogenes) in the sampled milk were enumerated by quantitative PCR. Mild and severe subclinical mastitic samples were distinctly separated on the principal component analysis score plot generated based on the quantities of these 5 target bacteria, suggesting that clear differences existed in the microbiological composition between the two sample groups. Based on comparison with the pairwise Mann-Whitney test, the mild subclinical mastitic dairy cows had a significantly higher amounts of lactobacilli (P=0.0175), but lower E. coli (P=0.0002), S. aureus (P<0.0001), S. agalactiae (P=0.0001) and T. pyogenes (P=0.0044) quantities, while an opposite trend occurred in the severe subclinical mastitic group. The negative correlation between Lactobacillus and the pathogenic bacteria, as well as the SCC, was confirmed with Spearman correlation analysis. Data generated from the current study may hint to a close relationship between Lactobacillus and the health of bovine udder.

A randomized trial comparing standard outcomes in two treatment models for substance users with tuberculosis.

SETTING: Chicago Department of Public Health (CDPH), TB Control Program. OBJECTIVES: To compare anti-tuberculosis treatment outcomes using two different types of directly observed therapy (DOT) outreach workers. METHODS: Substance users diagnosed with TB from October 1996 to July 2000 were randomized to DOT administered by either 1) CDPH personnel (standard arm) or 2) previous substance-using human immunodeficiency virus/acquired immune-deficiency syndrome outreach workers (enhanced arm). Treatment completion was physician-determined, and adherence was estimated based on risk of missed DOT appointments. RESULTS: Of 94 patients, 46 were randomized to the standard and 48 to the enhanced arm. The standard arm had a significantly higher risk of non-completion of treatment (39% vs. 15%, RR 2.7, 95%CI 1.2-5.8), and a significantly higher risk of missing DOT appointments (RR 2.6, 95%CI 1.4-4.8). For both outcomes, housing instability was a significant predictor in multivariate analyses. CONCLUSIONS: TB treatment completion and adherence among substance users was improved by the enhanced intervention; the familiarity of enhanced-arm DOT workers with the patients' social norms due to their own previous substance use may have made them more effective. Successful DOT in hard-to-reach populations may require strategies that directly address the population's circumstances and utilize DOT workers who are intimately familiar with patients' life situations.

The diversity of intestinal microbiota of Mongolians living in Inner Mongolia, China.

The Mongolian nationality has developed their unique lifestyle and dietary habit for thousands of years. However, by now, little research has been focused on Mongolian gut microbiota and how it is related to different dietary habits. In this study, denaturing gradient gel electrophoresis (DGGE) and quantitative polymerase chain reaction (qPCR) methods were applied to reveal the diversity of predominant gut bacteria of 48 healthy Mongolians recruited from Hohhot city and the Xilin Gol pasturing area in Inner Mongolia. Compared to similar studies of other nationalities, results from the present study have confirmed that the composition of Mongolian gut microbiota is highly similar at the phylum level (Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria) but variable at the genus level. Especially, the numbers of Phascolarctobacterium, Lactobacillus and Bifidobacterium are rather high. DGGE profiles of Lactobacillus and Bifidobacterium revealed that Lactobacillus casei, Bifidobacterium longum and Bifidobacterium animalis subsp. lactis were predominant in the gut of the Mongolian subjects studied. On the contrary, Lactobacillus helveticus was detected in every pasturing area Mongolian, but not in any of the Hohhot city Mongolians. qPCR results revealed that the numbers of Lactobacillus and Bifidobacterium of Xilin Gol Mongolians were significantly higher (P<0.05) than that of Hohhot Mongolians, whereas the numbers of Enterobacterium were significantly lower (P<0.05). In addition, by partial least squares discriminate analysis and cluster analysis of data generated from DGGE and qPCR experiments, a striking difference in the composition of intestinal microbiota of Mongolians living in Hohhot city and the Xilin Gol pasturing area has been found. This study clearly shows that diet affects the microbiota composition of Mongolians living in different circumstances, i.e. urban versus rural.

Allergy sensitization and asthma among 13-14 year old school children in Nigeria.

BACKGROUND: The prevalence of asthma and role of atopy in asthma among children has not been clearly defined in Nigeria. OBJECTIVE: To determine the prevalence of asthma and investigate risk factors related to allergy sensitization among urban and rural school children in southwest Nigeria. METHODS: Validated ISAAC questionnaire was administered to 1736 high school children in randomly selected schools in rural and urban communities. Identified asthma cases were matched to controls. Allergy skin tests, blood eosinophil count, serum IgE and stool examination for parasites were performed. Dust samples from homes were also collected and analyzed for allergens. RESULTS: The prevalence of asthma was 7.5% (95% CI 6.0 to 9.2%) and 8% (95% CI 6.0-10.4%) in the rural and urban communities respectively . Risk factors for asthma included cigarette-smoking, cats in the home and family size. Eosinophil count (109/L) was elevated in asthmatics [0.70 (95% CI 0.48-1.11) vs. 0.32 (95% CI 0.19-0.69); p<0.01], but IgE levels were similar between the two groups (298±229 IU/mL vs. 288±257; p=0.97). Positive skin tests to cat hair, cockroach, mango blossom and mouse epithelium were more frequent in asthmatics than in healthy controls, especially in the rural communities. There was no correlation between allergens in dust collected from homes and skin test reactivity. CONCLUSION: Asthma prevalence is similar in rural and urban children in Southwest Nigeria and atopy with elevated IgE was not observed to be a major factor for asthma in our cohort of children in both communities.

SNP discovery, expression and cis-regulatory variation in the UGT2B genes.

UGT2B enzymes metabolize multiple endogenous and exogenous molecules, including steroid hormones and clinical drugs. However, little is known about the inter-individual variation in gene expression and its determinants. We re-sequenced candidate regulatory regions and the partial coding regions (41.1 kb) of UGT2B genes and identified 332 genetic variants. We measured gene expression in normal breast and liver samples and observed different patterns. The expression levels varied greatly across individuals in both tissues and were significantly correlated with each other in liver. Genotyping of tagging single-nucleotide polymorphisms (SNPs) in the same samples and association tests between genotype and transcript levels identified 62 variants that were associated with at least one UGT2B mRNA levels in either tissue. Most of these cis-regulatory SNPs were not shared between tissues, suggesting that this gene family is regulated in a tissue-specific manner. Our results provide insight into studying the role of UGT2B variation in hormone-dependent cancers and drug response.

Atopy is associated with asthma in adults living in rural and urban southwestern Nigeria.

RATIONALE: Factors affecting the course of asthma are not clearly understood in rural and urban communities within low-resource countries. Furthermore, the interactions between atopy, environmental exposure, and helminthic infections in modulating asthma have not been well investigated. OBJECTIVES: To conduct a feasibility study to examine the relationship between atopy and asthma in adults at two rural Health Centers and urban university college hospital in southwestern Nigeria. METHODS: A convenient sample of 55 consecutive patients with stable physician-diagnosed asthma and 55 age-matched nonasthmatic controls seen at the outpatient clinics in two rural Health Centers and an urban university hospital were enrolled. All subjects underwent blood test, allergy skin test, and stool examination for ova and parasites. Wilcoxon sign-rank tests were used to compare serum eosinophilia and allergy skin test between the two groups. RESULTS: Asthmatics in both urban and rural settings had significantly more positive skin reactions to house dust mite, cockroach, mold, and mouse epithelium than nonasthmatic controls (p < .05). Mean total serum IgE was also significantly higher in asthmatics than in nonasthmatic controls (360 vs. 90 IU/L, p <.001). Stool parasitemia was infrequent in both groups and not statistically significant. CONCLUSION: Atopy is associated with adult asthma in southwest Nigeria. Larger studies to confirm the nature of this association and to examine the role of helminthic infection and other environmental factors on the expression of asthma are needed.

Effects of L-ascorbic acid, alpha-tocopherol and co-culture on in vitro developmental potential of porcine cumulus cells free oocytes.

The maturation and developmental potential on cumulus-cell-free oocytes is of great importance theoretically and practically. The present study was to investigate the effects of l-ascorbic acid, alpha-tocopherol and co-culture on in vitro developmental potential of porcine denuded oocytes (DOs). Porcine DOs were cultured in maturation medium supplemented with vitamin C (0, 50, 100, 250, 500, 750 microM) and vitamin E (0, 10, 20, 50, 100, 250 microm), respectively. And they were also co-cultured with dispersed cumulus cells (group CCscoculture), intact cumulus cells oocyte complexes (COCs) (group COCscoculture), and COCs whose oocytes were removed (group OOXcoculture), respectively. After 44 h incubation, the maturation rates, cleavage rates and blastocyst rates after parthenogenetic activation in three experiments mentioned above were collected and analysed, respectively. L-Ascorbic acid promoted porcine DOs in vitro maturation and blastocyt development after parthenogenetic activation while alpha-tocopherol did not increase the in vitro maturation rates, but improved the blastocyst rate. None of the three co-culture manner promoted the in vitro maturation and the cleavage of porcine DOs after parthenogenetic activation, but all the co-culture manners improved the blastocyst rates. Both Vitamin C and E enhance the in vitro developmental potential of porcine DOs. Co-culture increases the developmental potential of porcine DOs.

Lack of association of the TP53 Arg72Pro SNP and the MDM2 SNP309 with systemic lupus erythematosus in Caucasian, African American, and Asian children and adults.

The p53 tumour suppressor is the central regulator of apoptosis. Previously, the functional TP53 Arg72Pro polymorphism was found to be associated with systemic lupus erythematosus (SLE) in Koreans but not Spaniards. MDM2 is the major negative regulator of p53. An intronic polymorphism in MDM2, the SNP309, attenuates p53 activity and is associated with accelerated tumour development in premenopausal women. Polymorphic variation in MDM2 has never been studied in SLE. The aim of this study is to further assess the contribution of p53-pathway genetic variation to SLE by testing the association of the TP53 Arg72Pro polymorphism and the MDM2 SNP309 with SLE in a well-characterised and ethnically diverse cohort of patients with both childhood- and adult-onset SLE (n = 314). No association was found between the TP53 Arg72Pro polymorphism and SLE in patients of European descent, Asian descent or in African Americans, nor was an association found between the MDM2 SNP309 and SLE in patients of European descent or in African Americans. In addition, there was no correlation between either variant and early-onset disease or nephritis, an index of severe disease. It is concluded that neither the TP53 Arg72Pro polymorphism nor the MDM2 SNP309 contributes significantly to either susceptibility or disease severity in SLE.

Parity and breastfeeding are protective against breast cancer in Nigerian women.

As the relation between reproductive factors and breast cancer risk has not been systematically studied in indigenous women of sub-Saharan Africa, we examined this in a case-control study in Nigeria. In-person interviews were conducted using structured questionnaires to collect detailed reproductive history in 819 breast cancer cases and 569 community controls between 1998 and 2006. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI). Compared with women with menarcheal age<17 years, the adjusted OR for women with menarcheal age>or=17 years was 0.72 (95% CI: 0.54-0.95, P=0.02). Parity was negatively associated with risk (P-trend=0.02) but age at first live birth was not significant (P=0.16). Importantly, breast cancer risk decreased by 7% for every 12 months of breastfeeding (P-trend=0.005). It is worth noting that the distribution of reproductive risk factors changed significantly from early to late birth cohorts in the direction of increasing breast cancer incidence. Our findings also highlight the heterogeneity of breast cancer aetiology across populations, and indicate the need for further studies among indigenous sub-Saharan women.

Outcomes of patients with AML and MDS who relapse or progress after reduced intensity allogeneic hematopoietic cell transplantation.

We describe treatment, outcomes and prognostic factors for patients who relapse following transplantation with a reduced intensity conditioning regimen. Seventy consecutive patients with high-risk myeloid malignancies underwent transplant and 25 (36%) relapsed, a median of 120 days later. The median percentage of bone marrow blasts at relapse was 24, the median donor chimerism was 73% and new karyotypic abnormalities occurred in 8 out of 20 (40%) evaluable patients. Twenty-one patients (84%) received aggressive treatment for relapse, including chemotherapy (60%), second hematopoietic cell transplantation (HCT; 52%) and/or donor lymphocyte infusion (DLI; 12%). Thirteen achieved a complete response (CR) and four remain in CR. Median overall survival (OS) after relapse was 6 months (95% confidence interval=2.7-9.9 months), and actuarial 1 year OS was 24%. Most deaths were due to disease progression (17/20, 85%). We did not observe an advantage for cellular therapy (DLI or second transplant) compared to chemotherapy. Salvage therapy for relapse after reduced intensity HCT is feasible, associated with low treatment-related mortality, and may result in prolonged survival in select patients. Studies exploring the optimal treatment for relapse following reduced intensity HCT are warranted.

Up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression: an important role for SAPK signalling in prostatic neoplasia.

Identification of the signalling cascades that are differentially activated during prostatic tumourigenesis is a crucial step in the search for future molecular targets in this disease. The stress-activated protein kinase (SAPK) signalling cascade culminates in the phosphorylation of the JNK and p38 mitogen-activated protein kinases (MAPKs). Recently, the upstream activators of these proteins, the MAPK kinases (MKKs), have been implicated as inhibitors of tumour progression in a variety of clinical and experimental tumour models. This study evaluates MKK4, MKK6 and MKK7 expression during prostate cancer progression in humans and in the transgenic adenocarcinoma of a mouse prostate (TRAMP) model of prostate tumourigenesis. Benign prostate, prostatic intraepithelial neoplasia (PIN) lesions and tumour tissues were collected from 37 TRAMP mice. Additionally, six tissue microarrays were constructed with tumours from a matched group of 102 men who underwent radical prostatectomy. Tissues from 20 patients with extensive high-grade prostatic intraepithelial neoplasia (HGPIN) were also analysed. For all samples, immunohistochemical staining for MKK4, MKK6 and MKK7 was scored in normal and neoplastic glands. Staining intensities of MKK4, MKK6 and MKK7 were significantly increased in HGPIN and prostate cancer compared to surrounding normal glands in both the TRAMP and human samples (p < 0.0001 for all markers). Increased levels of MKK4 or MKK7 correlated with higher pathological stage at prostatectomy (p = 0.01 and p = 0.04). Using multivariate analysis, there was no association between protein levels and time to biochemical recurrence in the human samples. The up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression in both TRAMP and human tissues highlights an important role for the SAPK signalling cascade in prostatic neoplasia. The finding that higher MKK4 and MKK7 expression is associated with higher-stage prostatic tumours underscores the dynamic regulation of these proteins during prostatic tumourigenesis.