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Since 2015, 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program in Taiwan. Subsequently, the serotypes of the main circulating Streptococcus pneumoniae strains have changed. PCV administration is also associated with changes in the antimicrobial susceptibility of S. pneumoniae strains. Therefore, in this study, we analyzed the serotype distribution and antimicrobial susceptibility of S. pneumoniae in pediatric infections.Children with S. pneumoniae infections, including invasive pneumococcal disease (IPD) and non-IPD, were enrolled from January 2010 to December 2020. The samples were collected from Mackay Memorial Hospital, MacKay Children's Hospital, and Hsinchu Mackay Hospital in Taiwan. We analyzed the epidemiology of sample collection site, infection diagnosis, and the serotype and antimicrobial susceptibility of S. pneumoniae strains. The study period was divided into time points before and after PCV13 administration.In total, 322 isolates were collected during the study period. The incidence of IPD declined annually, from 29.7% before 2015 to 7.3% after 2015 (p 0.001). The prevalence of serotype 19 A had increased gradually since 2010 but declined rapidly after 2013. Serotypes 15 A and 23 A were the most common serotypes after 2015. The non-susceptibility of the S. pneumoniae isolates to penicillin, cefotaxime, and ceftriaxone decreased. Based on meningitis breakpoints, the non-susceptibility to cefotaxime and ceftriaxone gradually decreased, but increased in 2020.PCV13 was considerably effective in reducing the incidence of IPD in children; however, the prevalence of serotypes 15 A and 23 A increased. The increase in antimicrobial non-susceptibility caused by non-vaccine serotypes must be continuously monitored.

Prone position ventilation (PPV) is resource-intensive, yet the optimal strategy for PPV in intubated patients with COVID-19 is unclear.Does a prolonged (24 or more hours) PPV strategy improve mortality in intubated COVID-19 patients compared to intermittent (∼16 hours with daily supination) PPV?Multicenter, retrospective cohort study of consecutively admitted intubated COVID-19 patients treated with PPV between March 11 - May 31, 2020. The primary outcome was 30-day all-cause mortality. Secondary outcomes included 90-day all-cause mortality and prone-related complications. Inverse probability treatment weights (IPTW) were used to control for potential treatment selection bias.Of the COVID-19 patients who received PPV, 157 underwent prolonged and 110 underwent intermittent PPV. Patients undergoing prolonged PPV had reduced 30-day (adjusted hazard ratio [aHR] 0.475, 95% CI 0.336-0.670, P value0.001) and 90-day (aHR 0.638, 95% CI 0.461-0.883, P value = 0.006) mortality compared to intermittent PPV. In patients with PAmong intubated COVID-19 patients who received PPV, prolonged PPV was associated with reduced mortality. Prolonged PPV was associated with fewer pronation and supination events and a small increase in rates of facial edema. These findings suggest that prolonged PPV is a safe, effective strategy for mortality reduction in intubated COVID-19 patients.

Urinary tract infections (UTIs) are the most common bacterial infection in young children. This study aimed to formulate nomogram plots for clinicians to predict UTIs in children aged3 years by evaluating the risk factors for UTIs in these children.This retrospective study was conducted at a tertiary medical center from December 2017 to November 2020. Children less than three years of age were eligible for the study if they had undergone both urine culture and urinalysis during the study period. Mixed-effects logistic regression models with a stepwise procedure were used to determine the relationship between outcome (positive/negative UTI) and covariates of interest (e.g., weight percentile, laboratory) for each patient. Nomogram plots were constructed on the basis of significant factors. We repeated the analysis thrice to adapt it to three different medical settings: medical centers, regional hospitals, and local clinics.In the medical center setting, the two most significant factors were urine leukocyte count ≥100 (OR =8.87; 95% CI (Confidence Interval), 4.135-19.027) and urine nitrite level (OR =8.809; 95% CI, 5.009-15.489). The two factors showed similar significance at the regional hospital and local clinic settings. Abnormal renal echo findings were positively correlated with UTI in the medical center setting (OR =2.534; 95% CI 1.757-3.655). Three nomogram plots for the prediction of UTIs were drawn for medical centers, regional hospitals, and local clinics.Using the three nomogram plots, frontline doctors can formulate the probabilities of pediatric UTIs for better decision-making.

Purpose This study examined the efficacy of prescribing antibiotics, specifically a single dose of vancomycin, in reducing the incidence of culture-positive and culture-negative sepsis prior to the removal of peripherally inserted central catheters (PICCs). Materials and methods We retrospectively reviewed charts of infants who had PICCs in a tertiary level hospital during the period from 2010 to 2019. The incidence of post-catheter removal clinical sepsis between the groups with or without antibiotics was compared. The antibiotic group was defined by receiving a single dose of vancomycin or any other antibiotic prior to line removal. Results We enrolled 585 PICC removal episodes in 546 infants for analysis. Antibiotics were given prior to removal in 257 cases (43.9%) and not given prior to removal in 328 cases (56.1%). There were 13 episodes of post-catheter removal clinical sepsis detected within 72 h (2.2%), 2 of which were culture-positive (0.3%). A 9.3-fold decrease in the odds for clinical sepsis was observed in the antibiotic group (p = 0.01). The incidence of post-catheter removal sepsis was decreased by a single prophylactic dose of vancomycin (p = 0.02), whereas the use of other antibiotics showed no effect (p = 0.35). Logistic regression analysis demonstrated that comorbidities with gastrointestinal diseases (p = 0.01), PICC insertion sites in the scalp and neck (p = 0.04), and no vancomycin administration prior to line removal (p = 0.02) were independent risk factors for subsequent clinical sepsis. Conclusion A single prophylactic dose of vancomycin prior to PICC line removal might reduce clinical sepsis events in infants.

Purpose This study aimed to compare the safety and efficacy of clarithromycin-naproxen-oseltamivir combination therapy to that of oseltamivir therapy alone in hospitalized pediatric influenza patients. Methods This prospective, single-blind study included children aged 1–18 years hospitalized with influenza, in MacKay Children’s Hospital, Taiwan, between December 2017 and December 2019. The primary outcomes were the time to defervescence and decrease of the Pediatric Respiratory Severity Score (PRESS) during hospitalization. The secondary outcomes were serial changes in virus titers, measured using real-time polymerase chain reaction. Results Fifty-four patients were enrolled (28 in the control group and 26 in the combination group) in total. There were no differences in the patients’ baseline characteristics between the groups. The time to defervescence was significantly shorter in the combination group than the oseltamivir group (13.2 hours vs. 32.1 hours, p=0.002). The decrease in the virus titer from days 1 to 3 (log Δ13) was more pronounced in the combination group than the oseltamivir group. (39% vs. 19%, p=0.001). There were no differences in adverse effects such as vomiting, diarrhea, and abdominal pain during the study or within 30 days after antiviral therapy. Conclusion The clarithromycin-naproxen-oseltamivir combination group experienced a more rapid defervescence and a more rapid decline of influenza virus titer than the group treated with oseltamivir alone. Further consideration should be given to whether the overall benefits of combination therapy in hospitalized pediatric influenza patients outweigh the risks.

Background: Children with tracheostomy are at increased risk for respiratory tract infections, yet the risk involved in tracheostomy related infections is unclear. Methods: We conducted a retrospective review of the medical records of children who underwent tracheostomy between January 2002 and December 2016 at a teaching hospital in Taipei. Demographics, underlying disease, indication for tracheostomy, laboratory data and management, and long-term outcome data were collected. Infection episodes were grouped into definite, possible, non-bacterial pneumonia, and local infection groups. Results: Ninety patients were enrolled. Forty-two (46.7%) patients had infections that required hospitalization. Definite bacterial pneumonia accounted for 12 (8.5%) episodes, 113 episodes (80.1%) were possible bacterial pneumonia, 12 (8.5%) were non-bacterial pneumonia, and 4 (2.8%) were local infections. Patients with definite and possible bacterial pneumonia were found to have a longer hospital duration than patients with non-bacterial pneumonia (p=0.024), with mean hospitalization stays of 8.83±5.59 days and 5.67±2.55 days, respectively. The median duration from tracheostomy to bacterial pneumonia was 1.78 years (range, 0.04- 11.38) whereas for the non-bacterial pneumonia group it was 0.57 years (range, 0.04-6.61). Cerebral palsy (CP) (adjusted odds ratio [AOR] 3.65; 95% confidence interval [CI]: 1.11-11.99; p=0.033) and gastroesophageal reflux disease (GERD) (AOR 2.84; 95% CI: 1.09-7.38; p=0.033) were independently associated with respiratory tract infections in these children. Conclusion: In this study, CP and GERD were associated with infections in children with tracheostomy. Bacterial and non-bacterial pneumonia are difficult to differentiate clinically which may lead to unnecessary antibiotics use. Keywords: Children, Respiratory tract infections, Tracheostomy

Background: Campylobacter and Non-typhoidal Salmonella (NTS) are the two most common bacterial pathogens associated with acute gastroenteritis in children. This study aims to elucidate the epidemiology of Campylobacter and NTS gastroenteritis and develop a scoring system to differentiate them. Materials and methods: This retrospective study enrolled 886 children ≤18 years of age, hospitalized due to acute gastroenteritis with stool culture-proven Campylobacter or NTS infection from July 2012 to December 2015. Pearson's chi-square test and multivariate logistic regression were used to compare clinical manifestations and laboratory data. Receiver operating characteristic curves were plotted to evaluate the scoring system. Results: Seasonality was found in NTS gastroenteritis from May to September, but no seasonality in Campylobacter gastroenteritis. Campylobacter jejuni and Salmonella serogroup B were the most common pathogens. The median ages were 68.2 and 18.5 months and the incidence rates of bacteremia were 0.6% and 7.1% in the Campylobacter and NTS groups, respectively. Salmonella serogroup C2 infection had the highest risk of bacteremia (OR: 5.9, 95% CI: 2.8–12.7, p

To evaluate the clinical manifestations, management, and outcomes of Mycobacterium bovis Bacillus Calmette-Guérin (BCG) osteitis/osteomyelitis.We reviewed 71 cases of BCG osteitis/osteomyelitis registered in Taiwan's vaccine injury compensation program (VICP) in 1998-2014. Demographic, clinical, laboratory, treatment, and outcome data were compared according to site(s) of infection.Involvement of a long bone of the lower extremity was present in 36.6% of the children, followed by foot bone (23.9%), rib or sternum (15.5%), upper extremity long bone (9.9%), hand bone (7%), multiple bones (4.2%), and vertebrae (2.8%). Children with lower extremity long bone involvement had a longer interval from receipt of BCG vaccine to presentation (median, 16.0 months; P = .02), and those with foot bone infection had higher rates of swelling (94.1%; P = .02) and local tenderness (76.5%; P = .004). Surgical intervention was performed in 70 children, with no significant difference in the number of procedures by site (median, 1.0 procedure per patient). Among the 70 children who received antimicrobial therapy, those with vertebral and multifocal infections had a longer duration of treatment (P .001) and/or second-line antituberculosis medications (P = .002). Three children with vertebral and multifocal infections had major sequelae with kyphosis or leg length discrepancy. Outcomes were good for children with involvement of the ribs, sternum, and peripheral bones without multifocal involvement. The average time for functional recovery was 6.2 ± 3.9 months.Children with BCG osteitis/osteomyelitis in different bones had distinct presentations and outcomes. Pediatricians should consider BCG bone infection in young vaccinated children with insidious onset of signs and symptoms, and consider affected site(s) in the management plan.

Background Mutations in PKD1 or PKD2 gene lead to autosomal dominant polycystic kidney disease (ADPKD). The mechanism of ADPKD progression and its link to increased cardiovascular mortality is still elusive. Methods We differentiated ADPKD patient induced pluripotent stem cells (iPSCs) to cardiomyocytes (CMs). The electrophysiological properties at the cellular level were analyzed by calcium imaging and whole cell patch clamping. Findings The ADPKD patient iPSC-CMs had decreased sarcoplasmic reticulum calcium content compared with Control-CMs. Spontaneous action potential of the PKD2 mutation line-derived CMs demonstrated slower beating rate and longer action potential duration. The PKD1 mutation line-derived CMs showed a comparable dose-dependent shortening of phase II repolarization with the Control-CMs, but a significant increase in beating frequency in response to L-type calcium channel blocker. The PKD1-mutant iPSC-CMs also showed a relatively unstable baseline as a greater percentage of cells exhibited delayed afterdepolarizations (DADs). Both the ADPKD patient iPSC-CMs showed more β-adrenergic agonist-elicited DADs compared with Control-CMs. Interpretation Characterization of ADPKD patient iPSC-CMs provides new insights into the increased clinical risk of arrhythmias, and the results enable disease modeling and drug screening for cardiac manifestations of ADPKD. Fund Ministry of Science and Technology, National Health Research Institutes, Academia Sinica Program for Technology Supporting Platform Axis Scheme, Thematic Research Program and Summit Research Program, and Kaohsiung Medical University Hospital, Taiwan.

Background: Concerns about non-typeable Haemophilus influenzae (NTHi) in otitis media (OM) have grown after the introduction of pneumococcal conjugate vaccine (PCV). We aim to better understand the clinical role of NTHi in pediatric OM. Methods: Middle ear fluid samples from children

Bardet-Biedl syndrome is a autosomal recessive hereditary disorder characterized by polydactyly, multiple renal cysts, retinal cone-rod dystrophy, obesity, and variable neural development or cognitive impairment. We reported the generation and characterization of an iPS cell line, IBMS-iPSC-063-06, from a patient carrying the BBS2 homologous c534 + 1G > T mutation. The generated iPS cell line retains the mutation and exhibits pluripotency and differentiation ability both in vivo and in vitro condition.

Estrus detection in cattle is very important for breeding management. The detection results help determine the optimum time for artificial insemination. The success of estrus detection not only increases conception rates but also raises milk production for the herd. The proposed image processing method to detect cows in heat from video is passive and therefore does not require devices to be attached to the cow’s body. The observed scene is a commercial dairy farm, where Holstein cattle are reared in roofed cowsheds. The proposed method is based on the inherent behavior of cows in heat which is characterized by a cow following another cow before mounting it for a short period of a few seconds. A region of interest was first determined around image locations where high levels of motion occurred across the video frames. Foreground segmentation then follows to partition the moving target object from the region of interest in each image frame. The following and mounting behaviors are identified based on the changes of moving object lengths. When an estrus event is declared, the detected event is recorded into the computer to be verified later. The detection system observed 20 cows in a cowshed from the top view. Over the period of 800 h (80 days at 10 h each day), only 0.33% of video frames detected were false positive indicating the system was reliable at detecting mating and estrus behavior from the video frames. Using the method the farmer is required to view the recorded video frames for approximately 2 min per day to confirm that the detection results are true estrus events. The proposed method is capable of real-time detection of mating and estrus behavior speeds with a processing rate of 35 fps.

A recessive mutation in PLA2G6, which is known to cause a heterogeneous neurodegenerative clinical spectrum, has recently been shown to be responsible for autosomal-recessive familial forms of Parkinson's disease (PD). Here, we generated induced pluripotent stem cells (iPSCs) from the peripheral blood mononuclear cells of a female patient with a homozygous PLA2G6 c.991G > T (p.D331Y) mutation by using the Sendai-virus delivery system. The resulting iPSCs showed pluripotency confirmed by immunofluorescent staining for pluripotency markers and differentiated into the 3 germ layers in vivo. This cellular model will provide a good resource for further pathophysiological studies of PD.

Composite membranes used for proton exchange membrane fuel cells comprising of polybenzimidazole (PBI) and carbon nanotubes with certain functional groups were studied, because they could enhance both the mechanical property and fuel cell performance at the same time. In this study, sodium poly(4-styrene sulfonate) functionalized multiwalled carbon nanotubes (MWNT-poly(NaSS))/PBI and imidazole functionalized multiwalled carbon nanotubes (MWNT-imidazole)/PBI composite membranes were prepared. The functionalization of carbon nanotubes involving non-covalent modification and covalent modification were confirmed by FITR, XPS, Raman spectroscopy, and TGA. Compared to unmodified MWNTs and MWNT-poly(NaSS), MWNT-imidazole provided more significant mechanical reinforcement due to its better compatibility with PBI. For MWNT-poly(NaSS)/PBI and MWNT-imidazole/PBI composite membranes at their saturated doping levels, the proton conductivities were up to 5.1 × 10−2 and 4.3 × 10−2 S/cm at 160 °C under anhydrous condition respectively, which were slightly higher than pristine PBI (2.8 × 10−2 S/cm). Also, MWNT-poly(NaSS)/PBI and MWNT-imidazole/PBI composite membranes showed relatively improved fuel cell performance at 170 °C compared to pristine PBI.

Intestinal ischemia/reperfusion (I/R) induces mucosal barrier dysfunction and bacterial translocation (BT). Neutrophil-derived oxidative free radicals have been incriminated in the pathogenesis of ischemic injury in various organs, but their role in the bacteria-containing intestinal tract is debatable. Primed neutrophils are characterized by a faster and higher respiratory burst activity associated with more robust bactericidal effects on exposure to a second stimulus. Hypoxic preconditioning (HPC) attenuates ischemic injury in brain, heart, lung and kidney; no reports were found in the gut. Our aim is to investigate whether neutrophil priming by HPC protects against intestinal I/R-induced barrier damage and bacterial influx. Rats were raised in normoxia (NM) or kept in a hypobaric hypoxic chamber (380 Torr) 17 h/day for 3 weeks for HPC, followed by sham operation or intestinal I/R. Gut permeability was determined by using an ex vivo macromolecular flux assay and an in vivo magnetic resonance imaging-based method. Liver and spleen homogenates were plated for bacterial culturing. Rats raised in HPC showed diminished levels of BT, and partially improved mucosal histopathology and epithelial barrier function compared with the NM groups after intestinal I/R. Augmented cytokine-induced neutrophil chemoattractant (CINC)-1 and -3 levels and myeloperoxidase activity correlated with enhanced infiltration of neutrophils in intestines of HPC-I/R compared with NM-I/R rats. HPC alone caused blood neutrophil priming, as shown by elevated production of superoxide and hydrogen peroxide on stimulation, increased membrane translocation of cytosolic p47(phox) and p67(phox), as well as augmented bacterial-killing and phagocytotic activities. Neutrophil depletion reversed the mucosal protection by HPC, and aggravated intestinal leakiness and BT following I/R. In conclusion, neutrophil priming by HPC protects against I/R-induced BT via direct antimicrobial activity by oxidative respiratory bursts and through promotion of epithelial barrier integrity for luminal confinement of enteric bacteria.

Two overlapping confidence intervals have been used in the past to conduct statistical inferences about two population means and proportions. Several authors have examined the shortcomings of Overlap procedure and have determined that such a method distorts the significance level of testing the null hypothesis of two population means and reduces the statistical power of the test. Nearly all results for small samples in Overlap literature have been obtained either by simulation or by formulas that may need refinement for small sample sizes, but accurate large sample information exists. Nevertheless, there are aspects of Overlap that have not been presented and compared against the standard statistical procedure. This article will present exact formulas for the maximum % overlap of two independent confidence intervals below which the null hypothesis of equality of two normal population means or variances must still be rejected for any sample sizes. Further, the impact of Overlap on the power of testing the null hypothesis of equality of two normal variances will be assessed. Finally, the noncentral t-distribution is used to assess the Overlap impact on type II error probability when testing equality of means for sample sizes larger than 1.

Infection with Giardia duodenalis is one of the most common causes of waterborne diarrheal disease worldwide. Mechanisms of pathogenesis and host response in giardiasis remain incompletely understood. Previous studies have shown that exposure to G. duodenalis products induce apoptosis in enterocytes. We recently discovered that sodium-dependent glucose cotransporter (SGLT)-1-mediated glucose uptake modulates enterocytic cell death induced by bacterial lipopolysaccharide. The aim of this study was to examine whether enhanced epithelial SGLT-1 activity may constitute a novel mechanism of host defense against G. duodenalis-induced apoptosis. SGLT-1-transfected Caco-2 cells were exposed to G. duodenalis products in low (5mM) or high (25mM) glucose media. In low glucose environments, G. duodenalis-induced caspase-3 activation and DNA fragmentation in these cells. These apoptotic phenomena were abolished in the presence of high glucose. A soluble proteolytic fraction of G. duodenalis was found to upregulate SGLT-1-mediated glucose uptake in a dose- and time-dependent manner, in association with increased apical SGLT-1 expression on epithelial cells. Kinetic analysis showed that this phenomenon resulted from an increase in the maximal rate of sugar transport (V(max)) by SGLT-1, with no change in the affinity constant (K(m)). The addition of phloridzin (a competitive inhibitor for glucose binding to SGLT-1) abolished the anti-apoptotic effects exerted by high glucose. Together, the findings indicate that SGLT-1-dependent glucose uptake may represent a novel epithelial cell rescue mechanism against G. duodenalis-induced apoptosis.

Proliferins (also termed mitogen-regulated proteins; MRP/PLFs) belong to the prolactin gene family. Mrp/Plfs are involved in angiogenesis of the uterus and placenta and maximally expressed during midgestation and decline through the remainder of the gestation period in mouse placenta. The tissue expressions of Mrp/Plfs are mainly documented in placenta, hair follicles of skin and in wound healing. In this report, we demonstrate that Plf1, Plf1 minus exon3, Plf2 and Mrp3 but not Mrp4 are expressed in mouse whole brain by diagnostic RT-PCR and Western blotting. The expression levels of Mrp/Plf mRNAs in mouse brains were low during the neonatal period, but higher in embryonic and adult stages, indicating Mrp/Plfs expression profiles are different in mouse brain and placenta. Interestingly, endogenous Mrp/Plfs were detected using immunostaining both in mouse brain sections and the neuroblastoma cell line, Neuro-2a cells. The function of PLF1 was explored by expressing exogenous PLF1 in Neuro-2a cells. This resulted in increased microvilli. Neuro-2a cells with stable expression of PLF1 had increased proliferation compared with normal and stable expressing EGFP cells when cell reached saturation density. Together these data, strongly suggest that MRP/PLFs mediate microvilli formation and contribute to cell proliferation of neuroblastoma cells.