Interpreting the transmissibility of measles in two different post periods of supplementary immunization activities in Hubei,China

Although evidence has shown that supplementary immunization activity (SIA) campaigns greatly reduce the incidence of measles, their effects on disease transmissibility have seldom been monitored. A great decrease in the number of cases may be a false signal of early success towards measles elimination to policy makers. By interpreting the transmissibility in two different post-SIA periods in Hubei, China, the current study showed sustained measles transmissions despite a reduced number of cases. Two population-based cross-sectional serological surveys of measles antibodies were conducted in Hubei province in mid-2010 and mid-2011 after the implementation of SIAs. Immunoglobulin G (IgG) antibodies against measles were measured by enzyme-linked immunosorbent assay (ELISA). Based on the estimated age-specific susceptibility levels, the effective reproduction number (R), a key indicator of disease transmissibility, was determined by the next generation matrix in transmission model. The results revealed an overall IgG seroprevalence of 88.0% (95% confidence interval [CI]: 85.6–90.4%) and 89.6% (95%CI: 88.0–91.2%), respectively, in the two different periods. Comparatively lower seroprevalence rates were observed among children less than 24 months of age and young adults 15 to 19 years of age in 2011. The Rs were 0.76 and 1.53 for the two study periods. In conclusion, even though the incidence was reduced to below 1/100,000 in both 2010 and 2011, the reproduction number in 2011 indicates a high risk for sustained measles transmission. This finding was potentially due to a lower seropositivity rate among young adults that had not been covered in the first SIA. Thus, implementation of SIA targeted to appropriate age groups is recommended. Regular monitoring of seroprevalence is also suggested to track disease transmissibility and to align SIA with the appropriate age groups.     

全氟辛烷磺酸和全氟辛酸对秀丽隐杆线虫的生殖毒性

目的：探讨全氟辛烷磺酸（PFOS）和全氟辛酸（PFOA）对秀丽隐杆线虫的生殖毒性，寻找评价PFOS和PFOA生殖毒性的替代模型。方法：PFOS和PFOA分别设高、中、低3个染毒剂量（0.1、0.01、0.001 mmol/L）组和空白对照组，同步化后L4期幼虫在24孔板里染毒24 h，L1期幼虫染毒48 h，测定后代数目和世代时间。结果：L4期幼虫染毒24 h后，与对照组比较，PFOS高、中剂量组后代数目差异具有统计学意义（P<0.05），PFOA的3个剂量组后代数目差异均有统计学意义（P<0.05）；PFOS和PFOA各剂量组世代时间差异均无统计学意义（P>0.05）。L1期幼虫染毒48 h后，与对照组比较，PFOS和PFOA高、中剂量组后代数目差异具有统计学意义（P<0.05）；PFOS 3个剂量组的世代时间差异均具有统计学意义（P均<0.05）。结论：后代数目是PFOS和PFOA生殖毒性的敏感指标，L1期幼虫的世代时间对PFOS暴露比L4期幼虫更敏感，但PFOA不影响线虫的世代时间。线虫可能成为评价PFOS和PFOA生殖毒性的替代模型。     

Association of serine/threonine kinase 11 mutations and response to programmed cell death 1 inhibitors in metastatic gastric cancer

Programmed cell death 1 (PD-1) inhibitors have shown therapeutic efficacy in metastatic gastric cancer (mGC). However, no predictive biomarkers have been established in mGC. Inactivating mutations in serine/threonine kinase 11 (STK11) are associated with poor response to PD-1 inhibitors in KRAS-mutant lung adenocarcinoma. Therefore, we hypothesized that STK11 inactivating mutations would be associated with inferior clinical response to PD-1 inhibitors in mGC. We analyzed 59 mGC patients who had been treated with PD-1 inhibitors and whose tumors had been analyzed by targeted high-throughput sequencing. STK11 mutations were identified in 30 (50.8%) patients, and were all missense mutations. Three patients (5.1%) had STK11 gene amplification and mutation, simultaneously. Patients with STK11 mutations had prolonged overall survival (median: 19.0 vs 11.6 months, p = 0.15), and progression-free survival (4.2 vs 1.9 months, p = 0.06) when treated with PD-1 inhibitors, but these differences were not statistically significant. Patients with STK11 inactivating mutations without STK11 gene amplification had significantly prolonged progression-free survival compared to patients with wild type STK11 or STK11 gene amplification (4.8 vs 1.0 months, p = 0.04). However, in multivariate Cox regression analysis with high microsatellite instability (MSI-H), the number of tumor mutations, PD Ligand-1 (PD-L1)+, Epstein-Barr virus positivity (EBV)+, and type of PD-1 inhibitor used (pembrolizumab vs nivolumab), only MSI-H and PD-L1+ were significantly associated with longer progression-free survival. In mGC, the presence of STK11 mutation was not predictive of the response to PD-1 inhibitors. Instead, patients with MSI-H or PD-L1+ tumors displayed superior clinical responses to PD-1 inhibitors.     

The percutaneous learning curve of 3rd generation minimally-invasive Chevron and Akin osteotomy (MICA)

BackgroundMinimally-invasive Chevron and Akin osteotomy (MICA) represents the third-generation percutaneous hallux valgus surgery which is characterized by an extra-articular osteotomy, stable internal fixation and a high potential for correction. Compared to other percutaneous techniques of the foot, MICA is generally regarded as an advanced and demanding surgical procedure with a flat learning curve. The aim of this study is to analyze a single-surgeons experience with his first 50 consecutive MICA procedures.MethodsBetween May 2018 and February 2021, 50 consecutive MICA procedures performed by the author with the "K-wires-First technique" were prospectively analyzed focusing on surgery duration, number of fluoroscopies, correction results and surgery-associated complications. A modification of the original MICA technique as described by its inaugurators Redfern and Vernois allows the use of a standard-sized C-arm and aims to reduce revison rates and conversion to open surgery by placing the guidewires prior to performing the osteotomy.ResultsThe average surgery time for all MICA procedures was 46.8 min (SD 12.1, range 31–90 min). The average amount of fluoro shots required to perform MICA was n = 126.6 (SD 40.8, range 65–231). Comparing the preoperative and 6-week postoperative radiographs, the IMA decreased after MICA by a mean of 10.8° from 16.2° to 5.4° and the HVA by a mean of 22.1° from 30.6° to 8.5°. One case required intraoperative conversion to open hallux correction. There were 4 feet in three patients with secondary screw removal of the Chevron fixation due to prominent proximal screw tips.ConclusionsAlthough the learning curve of 3rd generation MICA is flat and requires specific training and intensive practice, the rate of complications is not elevated compared to other percutaneous hallux valgus techniques. Strict adherence to the principles of 3rd generation MICA with stable fixation and meticulous intraoperative control of each surgical step helps to reduce surgery-associated complications. The learning curve showed a continous improvement in regard to surgery time and use of fluoroscopy. After 40 procedures, the surgery time consistently dropped under 45 min and required less than 100 fluoro-shots. The modified surgical technique may help reduce Chevron screw mal-positioning when using large C-arm fluoroscopy for this procedure.     

Multiple Biomarker Testing Tissue Consumption and Completion Rates With Single-gene Tests and Investigational Use of Oncomine Dx Target Test for Advanced Non–Small-cell Lung Cancer: A Single-center Analysis

Introduction

First-line targeted therapies have been developed for advanced non–small-cell lung cancer (NSCLC). However, small biopsy samples pose a challenge to testing all relevant biomarkers. The present study characterized clinician-ordered single-gene lung cancer testing and evaluated tissue stewardship and the ability to successfully determine mutation status with single-gene testing or investigational use of the Oncomine Dx Target Test.

A high-throughput sequencing determination method for upstream genetic structure (UGS) of ISEcp1-blaCTX-M transposition unit and application of the UGS to classification of bacterial isolates possessing blaCTX-M

IntroductionBecause bla_CTX-M is responsible for resistance of bacteria to the third generation cephalosporins, location of bla_CTX-M could be a good indicator for classifying bacterial isolates harboring bla_CTX-M in molecular epidemiology. However, determination of bla_CTX-M location has been difficult when multiple copies of ISEcp1 were found on bacterial genome. We aimed to establish a high-throughput analytical method for upstream genetic structures (UGS) of ISEcp1 to facilitate determination of bla_CTX-M location.MethodsExtracted DNA samples obtained from 168 Escherichia coli isolates possessing bla_CTX-M were digested by restriction enzyme, HaeIII, and the digested DNA fragments were ligated with homemade barcode adaptors. Then, DNA fragments containing UGS of ISEcp1 were amplified and subjected to the Nanopore sequencer.ResultsNucleotide sequences and locations of 168 UGSs obtained from the examined E. coli isolates were determined. Among the 168 determined UGSs, 150 (89.3%) UGS were confirmed on plasmid and classified into eight types. Interestingly, coding sequence of ISEcp1 transposase gene in seven of the eight types were disrupted by IS26 insertion. The remaining 18 (10.7%) UGSs were observed in identical chromosomal region. The obtained nucleotide sequences the locations of UGSs were confirmed by conventional capillary sequencer and Southern blotting, respectively, and any discrepant result was not observed with these confirmation procedures.ConclusionsOur results indicated that the established method was efficient for simultaneously determining at least 100 different UGS, and suggested that the determined UGSs of ISEcp1-bla_CTX-M transposition unit was useful for classification of bacterial isolates harboring bla_CTX-M.     

Should I care for my mum or for my kid? Sandwich generation and depression burden in Italy

Setting and objectiveIn Italy, over the last decades, elderly care has been mostly provided by family members, especially adult offspring, and in particular daughters. This paper investigates the relationship between informal caregiving and mental distress among Italians aged 35–59, with a focus on gender effect and parenthood responsibilities.DataThe dataset is the European Health Interview Survey (EHIS), second wave, year 2015. As far as it is known, the Italian EHIS has not been used for studies on ageing and caregiving.MethodsUsing selected subsamples, a Propensity Score Matching between caregivers and non-caregivers aged 35–59 is implemented, with the aim of measuring the difference in level of depression, if any, between the two groups.ResultsFindings show that women providing their frail relatives with informal care are less likely to suffer from mental distress compared to non-carers. However, results change radically if they have children aged less than 15 at home, and a higher probability of being depressed is detected for women overwhelmed by the double responsibility of assisting both dependent relatives and their own children. Results are not significant for men.     

Why women may live longer than men do? A telomere-length regulated and diet-based entropic assessment

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