F4/80+Ly6Chigh Macrophages Lead to Cell Plasticity and Cancer Initiation in Colitis.

BACKGROUND & AIMS: Colorectal cancer is a leading cause of cancer death, and a major risk factor is chronic inflammation. Despite the link between colitis and cancer, the mechanism by which inflammation leads to colorectal cancer is not well understood. METHODS: To investigate whether different forms of inflammation pose the same risk of cancer, we compared several murine models of colitis (dextran sodium sulfate [DSS], 2,4,6-trinitrobenzene sulfonic acid, 4-ethoxylmethylene-2-phenyloxazol-5-one, Citrobacter rodentium, Fusobacterium nucleatum, and doxorubicin) with respect to their ability to lead to colonic tumorigenesis. We attempted to correlate the severity of colitis and inflammatory profile with the risk of tumorigenesis in both azoxymethane-dependent and Dclk1/APCfl/fl murine models of colitis-associated cancer. RESULTS: DSS colitis reproducibly led to colonic tumors in both mouse models of colitis-associated cancer. In contrast, all other forms of colitis did not lead to cancer. When compared with the colitis not associated with tumorigenesis, DSS colitis was characterized by significantly increased CD11b+F4/80+Ly6Chigh macrophages and CD11b+Ly6G+ neutrophils. Interestingly, depletion of the CD11b+F4/80+Ly6Chigh macrophages inhibited tumorigenesis, whereas depletion of CD11b+Ly6G+ neutrophils had no effect on tumorigenesis. Furthermore, the macrophage-derived cytokines interleukin-1ß, tumor necrosis factor-α, and interleukin-6 were significantly increased in DSS colitis and promoted stemness of Dclk1+ tuft cells that serve as the cellular origin of cancer. CONCLUSIONS: We have identified CD11b+F4/80+Ly6Chigh macrophages as key mediators of cancer initiation in colitis-associated cancer. Development of new therapies that target these cells may provide an effective preventative strategy for colitis-associated cancer.

The Defective in Autoregulation (DAR) gene of Medicago truncatula encodes a protein involved in regulating nodulation and arbuscular mycorrhiza.

BACKGROUND: Legumes utilize a long-distance signaling feedback pathway, termed Autoregulation of Nodulation (AON), to regulate the establishment and maintenance of their symbiosis with rhizobia. Several proteins key to this pathway have been discovered, but the AON pathway is not completely understood. RESULTS: We report a new hypernodulating mutant, defective in autoregulation, with disruption of a gene, DAR (Medtr2g450550/MtrunA17_Chr2g0304631), previously unknown to play a role in AON. The dar-1 mutant produces ten-fold more nodules than wild type, similar to AON mutants with disrupted SUNN gene function. As in sunn mutants, suppression of nodulation by CLE peptides MtCLE12 and MtCLE13 is abolished in dar. Furthermore, dar-1 also shows increased root length colonization by an arbuscular mycorrhizal fungus, suggesting a role for DAR in autoregulation of mycorrhizal symbiosis (AOM). However, unlike SUNN which functions in the shoot to control nodulation, DAR functions in the root. CONCLUSIONS: DAR encodes a membrane protein that is a member of a small protein family in M. truncatula. Our results suggest that DAR could be involved in the subcellular transport of signals involved in symbiosis regulation, but it is not upregulated during symbiosis. DAR gene family members are also present in Arabidopsis, lycophytes, mosses, and microalgae, suggesting the AON and AOM may use pathway components common to other plants, even those that do not undergo either symbiosis.

Sparassis latifolia and exercise training as complementary medicine mitigated the 5-fluorouracil potent side effects in mice with colorectal cancer: bioinformatics approaches, novel monitoring pathological metrics, screening signatures, and innovative management tactic.

BACKGROUND: Prompt identification and assessment of the disease are essential for reducing the death rate associated with colorectal cancer (COL). Identifying specific causal or sensitive components, such as coding RNA (cRNA) and non-coding RNAs (ncRNAs), may greatly aid in the early detection of colorectal cancer. METHODS: For this purpose, we gave natural chemicals obtained from Sparassis latifolia (SLPs) either alone or in conjunction with chemotherapy (5-Fluorouracil to a mouse colorectal tumor model induced by AOM-DSS. The transcription profile of non-coding RNAs (ncRNAs) and their target hub genes was evaluated using qPCR Real-Time, and ELISA techniques. RESULTS: MSX2, MMP7, ITIH4, and COL1A2 were identified as factors in inflammation and oxidative stress, leading to the development of COL. The hub genes listed, upstream regulatory factors such as lncRNA PVT1, NEAT1, KCNQ1OT1, SNHG16, and miR-132-3p have been discovered as biomarkers for prognosis and diagnosis of COL. The SLPs and exercise, effectively decreased the size and quantity of tumors. CONCLUSIONS: This effect may be attributed to the modulation of gene expression levels, including MSX2, MMP7, ITIH4, COL1A2, PVT1, NEAT1, KCNQ1OT1, SNHG16, and miR-132-3p. Ultimately, SLPs and exercise have the capacity to be regarded as complementing and enhancing chemotherapy treatments, owing to their efficacious components.

Therapeutic potential of Pien Tze Huang in colitis-associated colorectal cancer: mechanistic insights from a mouse model.

BACKGROUND: Pien Tze Huang (PZH), a traditional Chinese medicine formulation, is recognized for its therapeutic effect on colitis and colorectal cancer. However, its protective role and underlying mechanism in colitis-associated colorectal cancer (CAC) remain to be elucidated. METHODS: A CAC mouse model was established using AOM/DSS. Twenty mice were randomly divided into four groups (n = 5/group): Control, PZH, AOM/DSS, and AOM/DSS + PZH groups. Mice in the PZH and AOM/DSS + PZH group were orally administered PZH (250 mg/kg/d) from the first day of experiment, while the control and AOM/DSS group received an equivalent volume of distilled water. Parameters such as body weight, disease activity index (DAI), colon weight, colon length, colon histomorphology, intestinal tumor formation, serum concentrations of pro-inflammatory cytokines, proliferation and apoptosis in colon tissue were assessed. RNA sequencing was employed to identify the differentially expressed transcripts (DETs) in colonic tissues and related signaling pathways. Wnt/ß-Catenin Pathway-Related genes in colon tissue were detected by QPCR and immunohistochemistry (IHC). RESULTS: PZH significantly attenuated AOM/DSS-induced weight loss, DAI elevation, colonic weight gain, colon shortening, histological damage, and intestinal tumor formation in mice. PZH also notably decreased serum concentration of IL-6, IL-1ß, and TNF-α. Furthermore, PZH inhibited cell proliferation and promote apoptosis in tumor tissues. RNA-seq and KEGG analysis revealed key pathways influenced by PZH, including Wnt/ß-catenin signaling pathway. IHC staining confirmed that PZH suppressed the expression of ß-catenin, cyclin D1 and c-Myc in colonic tissues. CONCLUSIONS: PZH ameliorates AOM/DSS-induced CAC in mice by suppressing the activation of Wnt/ß-catenin signaling pathway.

How common is otogenic meningitis? A retrospective study in southern Sweden over 18 years.

BACKGROUND: Bacterial meningitis is a rare, but life-threatening disease, which sometimes occurs as a complication to acute otitis media (AOM). The proportion of meningitis cases originating from AOM is not clear. PURPOSE: The aim of this study was to investigate the proportion of meningitis cases caused by AOM, to compare risk factors, bacteriology and outcome between otogenic and non-otogenic meningitis, and to analyse the incidence of bacterial meningitis after the introduction of conjugate pneumococcal vaccines (PCV). METHODS: The medical charts of all patients admitted to hospitals in southern Sweden with bacterial meningitis between 2000 and 2017 were retrieved. Based on otoscopy and/or imaging, the proportion of otogenic meningitis cases was calculated, as were annual incidences. RESULTS: A total of 216 patients were identified, 25 of whom died. The proportion of otogenic meningitis was 31% but varied from 6% among teenagers to 40% among adults. Before PCV, 23% of all meningitis cases were children < 2 years, compared to 1% post-PCV. The average incidence in the adult population, on the other hand, increased post-PCV, though there were large annual variations. S. pneumoniae was the most commonly identified pathogen in everyone but teenagers, in whom N. meningitidis was predominant. CONCLUSION: AOM is an important cause of meningitis in children and adults. Though bacterial meningitis almost disappeared in children < 2 years after the introduction of PCV, the incidence of pneumococcal meningitis in adults seems to have increased.

Azoxymethane-induced carcinogenesis-like model of mouse intestine and mouse embryonic stem cell-derived intestinal organoids.

BACKGROUND: Tumor modeling using organoids holds potential in studies of cancer development, enlightening both the intracellular and extracellular molecular mechanisms behind different cancer types, biobanking, and drug screening. Intestinal organoids can be generated in vitro using a unique type of adult stem cells which are found at the base of crypts and are characterized by their high Lgr5 expression levels. METHODS AND RESULTS: In this study, we successfully established intestinal cancer organoid models by using both the BALB/c derived and mouse embryonic stem cells (mESCs)-derived intestinal organoids. In both cases, carcinogenesis-like model was developed by using azoxymethane (AOM) treatment. Carcinogenesis-like model was verified by H&E staining, immunostaining, relative mRNA expression analysis, and LC/MS analysis. The morphologic analysis demonstrated that the number of generated organoids, the number of crypts, and the intensity of the organoids were significantly augmented in AOM-treated intestinal organoids compared to non-AOM-treated ones. Relative mRNA expression data revealed that there was a significant increase in both Wnt signaling pathway-related genes and pluripotency transcription factors in the AOM-induced intestinal organoids. CONCLUSION: We successfully developed simple carcinogenesis-like models using mESC-based and Lgr5 + stem cell-based intestinal organoids. Intestinal organoid based carcinogenesi models might be used for personalized cancer therapy in the future.

Diagnostic methods and written advice for acute otitis media in primary health care.

BACKGROUND: Otomicroscopy and pneumatic methods are superior to otoscopy alone in diagnosing acute otitis media (AOM). There is a lack of knowledge regarding the use of different diagnostic methods for AOM in primary health care in Sweden and Norway. METHODS: This cross-sectional study included a questionnaire completed by general practitioners (GPs) and specialist trainees (STs/residents/registrars) working in primary care in Sweden and Norway. Multivariable binary logistic regressions were performed to evaluate the use of diagnostic methods and written advice adjusted for educational level, sex and country. RESULTS: Otoscopy was the most frequently used method. Sweden had greater access to the more accurate diagnostic methods. In Norway, the following methods were used to a lesser extent: pneumatic otoscopy, adjusted OR 0.15 (95% CI 0.10-0.23; p < .001), otomicroscopy, adjusted OR 0.013 (95% CI 0.070-0.027; p < .001), pneumatic otomicroscopy, adjusted OR 0.028 (95% CI 0.010-0.078; p < .001) and tympanometry, adjusted OR 0.31 (95% CI 0.21-0.45; p < .001). Written advice was used to a greater extent in Norway, adjusted OR 4.5 (95% CI 3.1-6.7; p < .001). The STs used pneumatic otoscopy and pneumatic otomicroscopy to a lesser extent, adjusted OR 0.65 (95% CI 0.45-0.93; p = .019) and 0.63 (95% CI 0.43-0.92; p = .016). CONCLUSIONS: Swedish physicians both used and had greater access to the significantly better diagnostic methods compared with Norwegian physicians while the opposite applied to the use of written information. The GPs used pneumatic otoscopy and pneumatic otomicroscopy to a greater extent than STs. Compared with 2012, the Swedish physicians now more frequently used pneumatic otoscopy.

108 m Underwater Wireless Optical Communication Using a 490 nm Blue VECSEL and an AOM.

Advanced light sources in the blue-green band are crucial for underwater wireless optical communication (UWOC) systems. Vertical-external-cavity surface-emitting lasers (VECSELs) can produce high output power and good beam quality, making them suitable for UWOC. This paper presents a 108 m distance UWOC based on a 100 mW 490 nm blue VECSEL and an acousto-optic modulator (AOM). The high-quality beam, which is near diffraction-limited, undergoes relatively small optical attenuation when using a conventional avalanche photodiode (APD) as the detector and employing 64-pulse position modulation (PPM). At the time-slot frequency of 50 MHz, the bit error rate (BER) of the UWOC was 2.7 × 10-5. This is the first reported AOM-based UWOC system with a transmission distance over 100 m. The estimated maximum transmission distance may be improved to about 180 m by fully utilizing the detection accuracy of the APD according to the measured attenuation coefficient of the blue VECSEL used. This type of UWOC system, composed of a high-beam-quality light source and a conventional detector, make it more closely suited to practical applications.

Characterization of the redox-active extracellular polymeric substances in an anaerobic methanotrophic consortium.

Anaerobic oxidation of methane (AOM) is a microbial process of importance in the global carbon cycle. AOM is predominantly mediated by anaerobic methanotrophic archaea (ANME), the physiology of which is still poorly understood. Here we present a new addition to the current physiological understanding of ANME by examining, for the first time, the biochemical and redox-active properties of the extracellular polymeric substances (EPS) of an ANME enrichment culture. Using a 'Candidatus Methanoperedens nitroreducens'-dominated methanotrophic consortium as the representative, we found it can produce an EPS matrix featuring a high protein-to-polysaccharide ratio of ∼8. Characterization of EPS using FTIR revealed the dominance of protein-associated amide I and amide II bands in the EPS. XPS characterization revealed the functional group of C-(O/N) from proteins accounted for 63.7% of total carbon. Heme-reactive staining and spectroscopic characterization confirmed the distribution of c-type cytochromes in this protein-dominated EPS, which potentially enabled its electroactive characteristic. Redox-active c-type cytochromes in EPS mediated the EET of 'Ca. M. nitroreducens' for the reduction of Ag+ to metallic Ag, which was confirmed by both ex-situ experiments with extracted soluble EPS and in-situ experiments with pristine EPS matrix surrounding cells. The formation of nanoparticles in the EPS matrix during in-situ extracellular Ag + reduction resulted in a relatively lower intracellular Ag distribution fraction, beneficial for alleviating the Ag toxicity to cells. The results of this study provide the first biochemical information on EPS of anaerobic methanotrophic consortia and a new insight into its physiological role in AOM process.

Infliximab Inhibits Colitis Associated Cancer in Model Mice by Downregulating Genes Associated with Mast Cells and Decreasing Their Accumulation.

Inflammatory bowel diseases (IBDs), such as Crohn's disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in vivo, and to identify the genes involved in colitis-associated cancer. We found that TNF-α (50 ng/mL) inhibited the proliferation, migration, and invasion of HCT8 and COLO205 colon cancer cell lines and that anti TNF-α Ab neutralized TNF-α inhibition in vitro. The effects of anti TNF-α Ab, infliximab (10 mg/kg) were investigated in mouse models of colitis-associated cancer induced by intraperitoneally injected azoxymethane (AOM: 10 mg/kg)/orally administered dextran sodium sulfate (DSS: 2.5%) (AOM/DSS) in vivo. Infliximab significantly attenuated the development of colon cancer in these mice. Microarray analyses and RT-qPCR revealed that mast cell protease 1, mast cell protease 2, and chymase 1 were up-regulated in cancer tissue of AOM/DSS mice; however, those mast cell related genes were downregulated in cancer tissue of AOM/DSS mice with infliximab. These results suggested that mast cells play a pivotal role in the development of cancer associated with colitis in AOM/DSS mice.

Panaxynol alleviates colorectal cancer in a murine model via suppressing macrophages and inflammation.

Currently available colorectal cancer (CRC) therapies have limited efficacy and severe adverse effects that may be overcome with the alternative use of natural compounds. We previously reported that panaxynol (PA), a bioactive component in American ginseng, possesses anticancer properties in vitro and suppresses murine colitis through its proapoptotic and anti-inflammatory properties. Because colitis is a predisposing factor of CRC and inflammation is a major driver of CRC, we sought to evaluate the therapeutic potential of PA in CRC. Azoxymethane-dextran sodium sulfate (AOM/DSS) mice (C57BL/6) were administered 2.5 mg/kg PA or vehicle 3 times/wk via oral gavage over 12 wk. PA improved clinical symptoms (P ≤ 0.05) and reduced tumorigenesis (P ≤ 0.05). This improvement may be reflective of PA's restorative effect on intestinal barrier function; PA upregulated the expression of essential tight junction and mucin genes (P ≤ 0.05) and increased the abundance of mucin-producing goblet cells (P ≤ 0.05). Given that macrophages play a substantial role in the pathogenesis of CRC and that we previously demonstrated that PA targets macrophages in colitis, we next assessed macrophages. We show that PA reduces the relative abundance of colonic macrophages within the lamina propria (P ≤ 0.05), and this was consistent with a reduction in the expression of important markers of macrophages and inflammation (P ≤ 0.05). We further confirmed PA's inhibitory effects on macrophages in vitro under CRC conditions (P ≤ 0.05). These results suggest that PA is a promising therapeutic compound to treat CRC and improve clinical symptoms given its ability to inhibit macrophages and modulate the inflammatory environment in the colon.NEW & NOTEWORTHY We report that panaxynol (PA) reduces colorectal cancer (CRC) by improving the colonic and tumor environment. Specifically, we demonstrate that PA improves crypt morphology, upregulates crucial tight junction and mucin genes, and promotes the abundance of mucin-producing goblet cells. Furthermore, PA reduces macrophages and associated inflammation, important drivers of CRC, in the colonic environment. This present study provides novel insights into the potential of PA as a therapeutic agent to ameliorate CRC tumorigenesis.

Microbial methane cycling in sediments of Arctic thermokarst lagoons.

Thermokarst lagoons represent the transition state from a freshwater lacustrine to a marine environment, and receive little attention regarding their role for greenhouse gas production and release in Arctic permafrost landscapes. We studied the fate of methane (CH4 ) in sediments of a thermokarst lagoon in comparison to two thermokarst lakes on the Bykovsky Peninsula in northeastern Siberia through the analysis of sediment CH4 concentrations and isotopic signature, methane-cycling microbial taxa, sediment geochemistry, lipid biomarkers, and network analysis. We assessed how differences in geochemistry between thermokarst lakes and thermokarst lagoons, caused by the infiltration of sulfate-rich marine water, altered the microbial methane-cycling community. Anaerobic sulfate-reducing ANME-2a/2b methanotrophs dominated the sulfate-rich sediments of the lagoon despite its known seasonal alternation between brackish and freshwater inflow and low sulfate concentrations compared to the usual marine ANME habitat. Non-competitive methylotrophic methanogens dominated the methanogenic community of the lakes and the lagoon, independent of differences in porewater chemistry and depth. This potentially contributed to the high CH4 concentrations observed in all sulfate-poor sediments. CH4 concentrations in the freshwater-influenced sediments averaged 1.34 ± 0.98 µmol g-1 , with highly depleted δ13 C-CH4 values ranging from -89‰ to -70‰. In contrast, the sulfate-affected upper 300 cm of the lagoon exhibited low average CH4 concentrations of 0.011 ± 0.005 µmol g-1 with comparatively enriched δ13 C-CH4 values of -54‰ to -37‰ pointing to substantial methane oxidation. Our study shows that lagoon formation specifically supports methane oxidizers and methane oxidation through changes in pore water chemistry, especially sulfate, while methanogens are similar to lake conditions.

Microbial Stratification Affects Conversions of Nitrogen and Methane in Biofilms Coupling Anammox and n-DAMO Processes.

A methane-based membrane biofilm reactor (MBfR) has a suitable configuration to incorporate anammox and nitrite/nitrate-dependent anaerobic methane oxidation (n-DAMO) processes because of its high gas-transfer efficiency and efficient biomass retention. In this study, the spatial distribution of microorganisms along with the biofilm depth in methane-based MBfRs was experimentally revealed, showing the dominance of anammox bacteria, n-DAMO bacteria, and n-DAMO archaea in the outer layer, middle layer, and inner layer of biofilms, respectively. The long-term and short-term experimental investigations in conjunction with mathematical modeling collectively revealed that microorganisms living in the outer layer of biofilms tend to use substrates from wastewater, while microorganisms inhabiting the inner layer of biofilms tend to use substrates originating from biofilm substratum. Specifically, anammox bacteria dominating the biofilm surface preferentially removed the nitrite provided from wastewater, while n-DAMO bacteria mostly utilized the nitrite generated from n-DAMO archaea as these two methane-related populations spatially clustered together inside the biofilm. Likewise, the methane supplied from the membrane was mostly consumed by n-DAMO archaea, while the dissolved methane in wastewater would be primarily utilized by n-DAMO bacteria. This study offers novel insights into the impacts of microbial stratification in biofilm systems, not only expanding the fundamental understanding of biofilms and microbial interactions therein but also providing a rationale for the potential applications of methane-based MBfRs in sewage treatment.

Incidence of acute otitis media from 2003 to 2019 in children ≤ 17 years in England.

BACKGROUND: The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2006 and the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 in the UK. PCVs are active immunization for the prevention of invasive disease, pneumonia and acute otitis media (AOM) caused by Streptococcus pneumoniae in children. The aim of this observational study was to estimate incidence rates (IRs) of AOM in children ≤17 years from 2003 to 2019 in England, before and after the introduction of pneumococcal conjugate vaccines (PCVs). METHODS: AOM episodes were identified using Read diagnosis codes in children aged ≤17 years in the Clinical Practice Research Datalink (CPRD) Gold database from 2003 to 2019. Annual IRs with 95% confidence intervals (CI) by age group were calculated as the number of episodes/person-years (PY) at risk. Interrupted time series analyses were conducted to estimate incidence rate ratios (IRR) across post-PCV7 (2007-2009), early post-PCV13 (2011-2014) and late post-PCV13 (2015-2019) periods compared to the pre-PCV7 period (2003-2005) using generalized linear models. RESULTS: From 2003 to 2019, 274,008 all-cause AOM episodes were identified in 1,500,686 children. The overall AOM IR was 3690.9 (95% CI 3677.1-3704.8) per 100,000 PY. AOM IRs were highest in children aged < 5 years and decreased by age; < 2 years: 8286.7 (95% CI 8216.8-8357.1); 2-4 years: 7951.8 (95% CI 7902.5-8001.4); 5-17 years: 2184.4 (95% CI 2172.1-2196.8) (per 100,000 PY). Overall AOM IRs declined by 40.3% between the pre-PCV7 period and the late-PCV13 period from 4451.9 (95% CI 4418.1-4485.9) to 2658.5 (95% CI 2628.6-2688.7) per 100,000 PY, and across all age groups. IRRs indicated a significant decrease in AOM IRs in all the post-vaccination periods, compared to the pre-PCV7 period: post-PCV7 0.87 (95% CI 0.85-0.89), early post-PCV13 0.88 (95% CI 0.86-0.91), and late post-PCV13 0.75 (95% CI 0.73-0.78). CONCLUSIONS: The AOM IRs declined during the 2003-2019 period; however, the clinical burden of AOM remains substantial among children ≤17 years in England.

A narrative review of approved and emerging anti-obesity medications.

Background: Recently, many drugs have been approved for halting overweight and obesity-few types of research shifted to using Anti-obesity medications (AOM) solely for well-being and shape-keeping. Objective: This narrative review's objective was to explore the use of AOM in relation to their medical indications, efficacy, and cardiovascular safety. Methods and materials: We have conducted a narrative review of the literature on approved/non-approved AOM used for obesity and overweight. We have shed light on the emerging trials of therapies and evolving remedies. Results: Recently, there has been an enormous change in the use of AOM with high consumption that deserves extensive surveillance for the long-term consequences and impact on social, mental, and physical health. Nearly six AOMs and combined therapy are approved by the Food and Drug Administration. The recent guidelines for obesity management have shifted the focus from weight loss to goals that the patient considers essential and toward targeting the root cause of obesity. Conclusion: The use of AOM increased enormously despite its sometimes-dubious safety and ineffectiveness. The public and medical professionals should be vigilant to the real-world benefits of anti-obesity drugs and their achieved effectiveness with an improved safety profile.

Breastfeeding initiation and duration and acute otitis media among children less than two years of age in Jordan: results from a case-control study.

BACKGROUND: Acute otitis media (AOM) is one of the most common infectious diseases that affects children. Breastfeeding has been linked to a lower risk of AOM in the first three years of childhood. The aim of this study was to identify the association between exclusive breastfeeding and the development of acute otitis media (AOM) and investigate the influence of breastfeeding duration on the presence of AOM. METHODS: In a retrospective case-control study, a sample of 98 children (cases) who were diagnosed with AOM and 98 children (controls) who were not diagnosed with AOM and were younger than two years old were selected from the Jordan University Hospital. Medical records were used to identify children with AOM. For both the case and control groups, the children's mothers completed a self-administered questionnaire about factors linked to the incidence of AOM.The type of feeding and the duration of breastfeeding were assessed using a validated questionnaire. RESULTS: The data indicated that among children who developed AOM, 23.5%were artificiallyfed, while 22.4% and 13.3% were exclusively breastfed for 3 months and 6 months, respectively. Approximately 70.7% of the children without AOM were exclusively breastfed for 6 months, compared with only 29.3% of the children without AOM who were exclusively breastfed for 3 months.Logistic regression revealed that nonexclusive breastfeeding, exclusive breastfeeding for 3 months, and exclusive breastfeeding for 6 months were protective factors against AOM (OR = 0.23, 0.18, and 0.25, respectively; P < 0.05). A short duration of exclusive breastfeeding was considered a risk factor for the development of AOM (OR = 1.7, P < 0.05). CONCLUSIONS: The escalation of AOM is tightly connected to the early introduction of formula feeding in the first six months of life. Breastfeeding had a protective impact on the occurrence of AOM. Understanding factors that are associated with the occurrence of AOM in children may support the role of public health institutions and primary health care in the prevention and reduction of AOM episodes and the need for national health strategies to promote breastfeeding.

Incidence of acute otitis media in children < 16 years old in Germany during 2014-2019.

BACKGROUND: Acute otitis media (AOM) remains a common infection in children despite the introduction of pneumococcal conjugate vaccines. This study estimated AOM incidence rates (IRs) over time in children < 16 years old in Germany following PCV13 introduction. METHODS: AOM episodes were identified in the InGef healthcare claims database from 2014-2019 in children aged < 16 years. Each AOM episode was classified as either simple or recurrent. Recurrent AOM was defined as 3 or more episodes identified within a 6-month period; or 4 or more episodes within a 12-month period with at least one episode in the prior 6 months. AOM-related surgical procedures within 12 months and complications within 21 days of an AOM episode were also identified. Annual IRs were calculated as number of episodes/child-years (CY) at risk. 95% Confidence intervals (95%CI) were calculated using the Wilson method. The Mann-Kendall test was used to assess trends over time. RESULTS: Between 2014 and 2019, the study population comprised 916,805 children with 327,726 AOM episodes, of which 15% (49,011) of all episodes were identified as recurrent AOM and 85% (278,715) as simple AOM. There were significant declines in AOM (p = 0.003) in the study population overall and in all age groups over the study period; from 101 (95%CI 101-102)/1000 CY to 79 (95%CI 78-80)/1000 CY in the total study population, from 209 (95%CI 206-212)/1000 CY to 147 (95%CI 145-150)/1000 CY in < 2-year-olds, from 239 (95%CI 237-242) to 179 (95%CI 177-182)/1000 CY in 2-4-year-olds, and from 50 (95%CI 49-50) to 38 (95%CI 37-39)/1000 CY in 5-15-year-olds. No significant trends were identified for AOM-related surgical procedures over the study period; however, AOM-related complications overall increased (p = 0.003). CONCLUSION: Between 2014 and 2019, AOM incidence overall declined in children aged 0-15 years in Germany. Over the study period, the incidence of complicated AOM cases increased, however the incidence of AOM-related surgical procedures remained constant. Despite the impact of PCV13, the burden associated with AOM in Germany remains substantial.

Antibiotic oral provocation challenge in children.

AIM: The main objective of this study was to see how many of the children, with a suspected antibiotic allergy, developed an allergic or adverse reaction to a drug provocation test. METHODS: Data on children that had undergone a drug provocation test for a suspected antibiotic allergy were compiled retrospectively for the period from 2007-2018. The median age at the first provocation was 2.25 years (1.5-5.7). Standardised questionnaires, the children's parents had answered before the provocation, were used to evaluate the originally suspected allergic reaction, previous health, atopic diseases and family history. RESULTS: Ninety-two (6.4%) of the 1440 children showed a possible mild allergic reaction. Sixty-four of the 92 children underwent a second drug provocation test 1-2 years later. At that time, only eleven developed a positive- or a possible-delayed reaction. CONCLUSION: An immediate moderate or severe allergic reaction was excluded in all cases of suspected antibiotic allergy in this study. Our study indicates that an oral drug provocation test is safe. It may be appropriate to wait for 6 months or more after the initial event of ADR before these tests are performed. A second oral provocation 1-2 years after the first one shows that ADRs are outgrown in most children.

Timing of symptomatic subsequent vertebral compression fracture associated with different demographic factors.

BACKGROUND: Symptomatic subsequent vertebral compression fracture (VCF; SVCF) is a common complication associated with poor outcomes. Accumulating evidence shows that demographic factors and incidences of symptomatic SVCFs differ during different periods after the primary vertebroplasty (VP). PURPOSE: To investigate the incidence and demographic factors of symptomatic SVCFs after the primary VP in different periods using registry data in the Taiwan National Health Insurance Research Database. METHODS: This retrospective cohort study included 28,343 patients aged ≥ 50 years with painful VCF treated with VP from 2002 to 2016. Symptomatic SVCF was defined as SVCF requiring another VP or re-admission. During the 2-year follow-up, 1955 patients received subsequent VP while 1,407 were readmitted. Cox proportional hazard models were used to compare the risks of subsequent VP or readmission. RESULTS: The cumulative incident rate of subsequent VP and re-hospitalization was 0.87 [95% confidence interval (CI), 0.82 ~ 0.92] and 0.62 (95% CI, 0.58 ~ 0.66) per 100 person-months, respectively, within the first 6 months after the primary VP, and it decreased over time. A multiple Cox regression model showed that age, osteopenia or osteoporosis, Charlson comorbidity index (CCI) were significant independent risk factors of subsequent VP or readmission within the first 6 months. CONCLUSIONS: This study demonstrated that the incidence of symptomatic SVCF peaked in the first 6 months after the primary VP. Age, osteoporosis or osteopenia, and CCI were determined to be risk factors in the first 6 months, but only osteoporosis or osteopenia and CCI were risk factors thereafter.

Multi-objective optimization of ultrasonic algae removal technology by using response surface method and non-dominated sorting genetic algorithm-II.

Ultrasonic technology is an environment-friendly method in algae-laden water treatment with the advantages of wonderful efficiency and no chemical additions. However, ultrasonic technology is costly and can lead to the release of algae organic matter (AOM). Few studies considered algae removal efficiency, water safety, and economy. In this study, a Response Surface Methodology (RSM) and Elitist Non-dominated Sorting Genetic Algorithm (NSGA-II) integrated method was used to investigate the influence of ultrasound parameters on algal removal efficiency band AOM release and conduct the multi-objective optimization of ultrasonic technology for satisfactory algal removal, environment protection, and improved economy. The maximum algae removal rate (ρ), minimal energy consumption, and minimal UV254 value of algal solution were calculated. Quadratic polynomial models were obtained to illustrate the relationship between ultrasonic parameters and the responses. Ultrasonic frequency was the most important factor affecting algal removal efficiency, and high frequency was beneficial for algal removal because of its contribution to the break of air bubbles. High power density significantly increased the UV254 value, and the concentration of soluble microbial metabolites and humic acid-like substances significantly increased after ultrasound. The optimization solutions calculated by NSGA-II showed low deviation from single-objective optimization solution by RSM, demonstrating that the multi-objective optimization results were reliable. This study presents a novel RSM and NSGA-II combined method in optimizing ultrasonic technology for effective, safe, and economic algal removal. The optimization results can provide references for ultrasonic parameters to be selected in practical applications.