Abstractobjective Shandong Province has implemented the standardised treatment of multidrug-resistant tuberculosis (MDR-TB) supported by the Global Fund. The study aimed to understand the managements and delays of patients with MDR-TB before initiating their treatments.methods All patients with MDR-TB who had completed intensive phase treatment from January 2010 to May 2012 were interviewed using a structured questionnaire. Delays and treatments were analysed. Diagnosis delay is defined as the period between having sputum smear results and drug susceptibility test (DST) results. Treatment delay was defined as starting MDR-TB treatment more than 2 days after receiving the diagnosis of MDR-TB. Total delay is the sum of diagnosis delay and treatment delay.results In total, 110 patients with MDR-TB participated in the study. Median delay for diagnosis was 102 days. Over 80% of patients had a diagnosis delay longer than 90 days. MDR-TB treatments commenced after a median of 9 days after DST results, and over 37% of the patients with MDR-TB experienced treatment delays. Chronic cases or patients with indifferent attitude had significantly longer treatment delay than other groups (P = 0.03 and 0.03, respectively). During their delays, of 44 patients with retreatment failures, 12 (27.3%) were treated through adding single second line drugs (SLDs) to first-line regimens, and 25 (56.8%) were treated with first-line drugs. A high proportion of initial treatment failure/relapsed/returned cases (37%) and new cases (43%) were administered with SLDs.

Reticulocalbin 1 (RCN1), an endoplasmic reticulum (ER)‐resident Ca2+‐binding protein, is dysregulated in cancers, but its pathophysiological roles are largely unclear. Here, we demonstrate that RCN1 is overexpressed in clinical prostate cancer (PCa) samples, associated with cyclin B, not cyclin D1 expression, compared to that of benign tissues in a Chinese Han population. Downregulation of endogenous RCN1 significantly suppresses PCa cell viability and arrests the cell cycles of DU145 and LNCaP cells at the S and G2/M phases, respectively. RCN1 depletion causes ER stress, which is evidenced by induction of GRP78, activation of PERK and phosphorylation of eIF2α in PCa cells. Remarkably, RCN1 loss triggers DU145 cell apoptosis in a caspase‐dependent manner but mainly causes necroptosis in LNCaP cells. An animal‐based analysis confirms that RCN1 depletion suppresses cell proliferation and promotes cell death. Further investigations reveal that RCN1 depletion leads to elevation of phosphatase and tensin homolog (PTEN) and inactivation of AKT in DU145 cells. Silencing of PTEN partially restores apoptotic cells upon RCN1 loss. In LNCaP cells, predominant activation of CaMKII is important for necroptosis in response to RCN1 depletion. Thus, RCN1 may promote cell survival and serve as a useful target for cancer therapy.

Compared to mono-species biofilm, biofilms formed by cross-kingdom pathogens are more refractory to conventional antibiotics, thus complicating clinical treatment and causing significant morbidity. Lemongrass essential oil and its bioactive component citral were previously demonstrated to possess strong antimicrobial efficacy against pathogenic bacteria and fungi. However, their effects on polymicrobial biofilms remain to be determined. In this study, the efficacy of lemongrass (Cymbopogon flexuosus) essential oil and its bioactive part citral against dual-species biofilms formed by Staphylococcus aureus and Candida species was evaluated in vitro. Biofilm staining and viability test showed both lemongrass essential oil and citral were able to reduce biofilm biomass and cell viability of each species in the biofilm. Microscopic examinations showed these agents interfered with adhesive characteristics of each species and disrupted biofilm matrix through counteracting nucleic acids, proteins and carbohydrates in the biofilm. Moreover, transcriptional analyses indicated citral downregulated hyphal adhesins and virulent factors of Candida albicans, while also reducing expression of genes involved in quorum sensing, peptidoglycan and fatty acids biosynthesis of S. aureus. Taken together, our results demonstrate the potential of lemongrass essential oil and citral as promising agents against polymicrobial biofilms as well as the underlying mechanisms of their activity in this setting.

This study is the first to have surveyed the population of black-necked cranes (Grus nigricollis) at the Longbao National Nature Reserve, Qinghai, China, throughout most of the 7.5 month annual crane residence period, with 17 crane counts having been made on the reserve's main wetland between 6 April and 16 November 2011. In 2011, the first cranes are believed to have arrived at Longbao at the end of March, and the last are believed to have departed between 7 and 11 November. The peak adult black-necked crane count was 216 on 25 April, while the low count was 81 on 23 October, which increased to 153 during migration staging on 6 November. This represents a 9-fold increase in the peak annual adult crane count since the earliest known count from 1984. Twenty-nine nests were observed in the survey area in May and June, and on 12 September 2011, 21 of 29 nesting pairs had surviving chicks, with 9 crane pairs having a pair of surviving chicks, while 12 crane pairs had a single surviving chick. Threats to cranes at Longbao include untied dogs, which harass breeding cranes, eat eggs, and kill chicks; recently erected power lines along the wetland, which may prove hard for cranes to see and avoid; and disturbance of nesting cranes from humans and their livestock. Other threats include climate change, which is drying up shallow wetlands in the Longbao region and elsewhere on the Tibetan Plateau, and severe degradation of hillslope pastures, which is forcing local herders to keep their yaks on the main wetland pastures for longer periods each year and will inevitably cause increased disturbance to cranes and further degradation of the wetland. The Longbao Wetland presently qualifies for Ramsar designation based on its black-necked crane population under Ramsar Criteria 2 and 6.

BackgroundThe TB operational guideline (the deskguide) is a detailed action guide for county TB doctors aiming to improve the quality of DOTS, while the China national TB policy guide is a guide to TB control that is comprehensive but lacks operational usability for frontline TB doctors. This study reports the process of deskguide adaptation, its scale-up and lessons learnt for policy implications.MethodsThe deskguide was translated, reviewed, and revised in a working group process. Details of the eight adaptation steps are reported here. An operational study was embedded in the adaptation process. Two comparable prefectures were chosen as pilot and control sites in each of two participating provinces. In the pilot sites, the deskguide was used with the national policy guide in routine in-service training and supervisory trips; while in the control sites, only the national policy guide was used. In-depth interviews and focus groups were conducted with 16 county TB doctors, 16 township doctors, 17 village doctors, 63 TB patients and 57 patient family members. Following piloting, the deskguide was incorporated into the national TB guidelines for county TB dispensary use.ResultsQualitative research identified that the deskguide was useful in the daily practice of county TB doctors. Patients in the pilot sites had a better knowledge of TB and better treatment support compared with those in the control sites.ConclusionThe adaptation process highlighted a number of general strategies to adapt generic guidelines into country specific ones: 1) local policy-makers and practitioners should have a leading role; 2) a systematic working process should be employed with capable focal persons; and 3) the guideline should be embedded within the current programmes so it is sustainable and replicable for further scale-up.

BackgroundCongenital syphilis continues to be a preventable cause of global stillbirth and neonatal morbidity and mortality. Shortages of injectable penicillin, the only recommended treatment for pregnant women and infants with syphilis, have been reported by high-morbidity countries. We sought to estimate current and projected annual needs for benzathine penicillin in antenatal care settings for 30 high morbidity countries that account for approximately 33% of the global burden of congenital syphilis.MethodsProportions of antenatal care attendance, syphilis screening coverage in pregnancy, syphilis prevalence among pregnant women, and adverse pregnancy outcomes due to untreated maternal syphilis reported to WHO were applied to 2012 birth estimates for 30 high syphilis burden countries to estimate current and projected benzathine penicillin need for prevention of congenital syphilis.ResultsUsing current antenatal care syphilis screening coverage and seroprevalence, we estimated the total number of women requiring treatment with at least one injection of 2.4 MU of benzathine penicillin in these 30 countries to be 351,016. Syphilis screening coverage at or above 95% for all 30 countries would increase the number of women requiring treatment with benzathine penicillin to 712,030. Based on WHO management guidelines, 351,016 doses of weight-based benzathine penicillin would also be needed for the live-born infants of mothers who test positive and are treated for syphilis in pregnancy. Assuming availability of penicillin and provision of treatment for all mothers diagnosed with syphilis, an estimated 95,938 adverse birth outcomes overall would be prevented including 37,822 stillbirths, 15,814 neonatal deaths, and 34,088 other congenital syphilis cases.ConclusionPenicillin need for maternal and infant syphilis treatment is high among this group of syphilis burdened countries. Initiatives to ensure a stable and adequate supply of benzathine penicillin for treatment of maternal syphilis are important for congenital syphilis prevention, and will be increasingly critical in the future as more countries move toward elimination targets.

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Colorectal cancer (CRC) is one of the most pressing health issues in today's society. As such, it is imperative that the scientific community devise effective methods to inhibit the proliferation and metastasis of CRC cells. Ferroptosis is a recently discovered regulatory cell death mode mainly manifested by dysregulation of cellular iron metabolism and mitochondrial lipid peroxidation. ACADSB is a member of the acyl-CoA dehydrogenase. This study finds that ACADSB is lowly expressed in CRC tissues. Its expression is negatively correlated with N-and M-stage CRC but positively correlated with the overall survival rate of CRC patients. In addition, it finds that ACADSB is found in the mitochondria of cells. Overexpression of ACADSB inhibits CRC cell migration, invasion, and proliferation, while ACADSB knockdown has the opposite effect. More importantly, the study finds that ACADSB negatively regulates expression of glutathione reductase and glutathione peroxidase 4, the two main enzymes responsible for clearing glutathione (GSH) in CRC cells. ACADSB overexpression enhances the concentration of malondialdehyde, Fe + , superoxide dismutase, and lipid peroxidation in CRC cells, but reduces the concentration of GSH. This is significant, as all of these are important indicators of ferroptosis. Evaluating the data as a whole, this paper speculates that ACADSB affects CRC cell migration, invasion, and proliferation by regulating CRC cell ferroptosis.