Statewide Linkage Study of Salmonella Infection and Colorectal Cancer Incidence in Michigan, United States.

Objective: Nontyphoidal Salmonella infection is one of the most common foodborne illnesses, and its oncogenic potential has been documented in animal models. The primary goal of this study was to examine whether individuals who were exposed to enteric Salmonella infection are more likely to develop colorectal cancer (CRC) than the general population through the linkage of 2 statewide public health surveillance databases. Materials and Methods: We designed a 2-stage probabilistic linkage, starting with 17,587 records of enteric salmonellosis reported to Michigan Department of Health and Human Services between 1992 and 2020. These records did not include unique identifiers (such as Social Security number [SSN]). The initial linkage to LexisNexis address history was conducted to obtain information to calculate each person's time in Michigan as well as SSN for the second linkage. The linkage to the state cancer registry was performed to obtain the observed number of CRC cases, while the expected number of CRC cases was calculated according to corresponding state CRC incidence by age, sex, and calendar year. Results: Ninety-three percent of the initially identified salmonellosis records were sent to LexisNexis linkage, which returned address history, death, and SSN for 97% of the records. Further linkage to the statewide cancer registry identified 98 incident CRC cases. Overall, the observed-to-expected (O/E) ratio was not different from unity (0.833; 95% CI, 0.627-1.003). Conclusions: While the new linkage strategy was found effective and should be applicable to other health conditions, we cannot rule out bias due to incomplete or underreporting of the infection in estimating the risk of CRC.

Caffeine Concentrations in Human Milk Donated to a Human Milk Bank in Japan.

BACKGROUND: Human milk banks have been established to provide human milk to preterm infants who are unable to obtain milk from their mothers. Donor screening methods vary, and prospective donors are commonly screened for drug and recreational substance use through behavioral screening. Although the risk of illegal drug consumption in Japan is extremely low, caffeine may be consumed unknowingly and can be found in human milk. To date, only a few reports have been conducted on the concentration of caffeine in donor milk. RESEARCH AIM: This study aimed to examine the pre-pasteurization levels of caffeine in human milk donated to a milk bank in Japan. METHODS: This was a cross-sectional, observational study of caffeine concentrations in human milk donated to a human milk bank in Japan. Caffeine concentration in the donor milk was measured using high-performance liquid chromatography. RESULTS: Caffeine was detected in 70% of the donor milk samples (N = 350). The median (range) of caffeine concentration was 0.46 [< 0.10, 7.54] mg/L, and 64.0% of the samples had less than 1 mg/L of caffeine. The caffeine concentration varied widely among as well as within individuals. CONCLUSION: The average caffeine concentration in Japanese donor milk samples was higher than that previously reported in samples from Spain, but the range was similar. Donors should be informed that caffeine intake should be within a moderate range, to further increase the safety of donor milk.

Developmental changes in neonatal hemodynamics during tactile stimulation using whole-head functional near-infrared spectroscopy.

Neural-activity-associated hemodynamic changes have been used to noninvasively measure brain function in the early developmental stages. However, the temporal changes in their hemodynamics are not always consistent with adults. Studies have not evaluated developmental changes for a long period using the same stimuli; therefore, this study examined the normalized relative changes in oxygenated hemoglobin (Δ[oxy-Hb]) in full-term infants and compared them with neonates up to 10 months of age during the administration of tactile vibration stimuli to their limbs using whole-head functional near-infrared spectroscopy. The time to peak of normalized Δ[oxy-Hb] was not affected by age. The amplitude of normalized Δ[oxy-Hb] showed an effect of age in broader areas, including sensorimotor-related but excluding supplementary motor area; the amplitude of normalized Δ[oxy-Hb] decreased the most in the 1-2-month-old group and later increased with development. We hypothesized that these results may reflect developmental changes in neural activity, vasculature, and blood oxygenation.

Bacterial, Viral and Parasitic Pathogens and Colorectal Cancer.

Several viral, bacterial, and parasitic pathogens have been designated as human carcinogens by the World Health Organization [...].

Oncogenic potential of Campylobacter infection in the gastrointestinal tract: narrative review.

BACKGROUND: Campylobacter jejuni is the leading cause of zoonotic gastroenteritis. The other emerging group of Campylobacters spp. are part of human oral commensal, represented by C. concisus (CC), which has been recently linked to non-oral conditions. Although long-term gastrointestinal (GI) complications from these two groups of Campylobacters have been previously reviewed individually, overall impact of Campylobacter infection on GI carcinogenesis and their inflammatory precursor lesions has not been assessed collectively. AIMS: To evaluate the available evidence concerning the association between Campylobacter infection/colonization and inflammatory bowel disease (IBD), reflux esophagitis/metaplasia colorectal cancer (CRC) and esophageal cancer (EC). METHODS: We performed a comprehensive literature search of PubMed for relevant original publications and systematic reviews/meta-analyses of epidemiological and clinical studies. In addition, we gathered additional information concerning microbiological data, animal models and mechanistic data from in vitro studies. RESULTS: Both retrospective and prospective studies on IBD showed relatively consistent increased risk associated with Campylobacter infection. Despite lack of supporting prospective studies, retrospective studies based on tissue/fecal microbiome revealed consistent enrichment of Campylobacter in CRC samples. Studies on EC precursor lesions (esophagitis and metaplasia) were generally supportive for the association with Campylobacter, while inconsistent observations on EC. Studies on both IBD and EC precursors suggested the predominant role of CC, but studies on CRC were not informative of species. CONCLUSIONS: There is sufficient evidence calling for concerted effort in unveiling direct and indirect connection of this organism to colorectal and esophageal cancer in humans.

Developmental changes in visual-cognitive and attentional functions in infancy.

BACKGROUND: Identifying developmental changes in visual-cognitive and attentional functions during infancy may lead to early diagnosis of neurodevelopmental disorders such as ASD and ADHD. AIMS: To clarify the developmental changes in visual-cognitive and attentional functions during infancy (3-36 months of age). STUDY DESIGN: Cross-sectional study. SUBJECTS: We included 23, 24, 31, and 26 participants aged 3, 9, 18, and 36 months, respectively (full-term births). Fifteen children who cried intensely or whose data could not be accurately recorded were excluded. OUTCOME MEASURES: Three activities were given to each child while they were seated in front of a gaze-tracking device to evaluate re-gaze, motion transparency, and color-motion integration. We analyzed whether the child's attention shifted to the new stimulus in their peripheral vision in the re-gaze task. In the motion transparency and color-motion integration tasks, two images were presented simultaneously on the screen. In the motion transparency task, participants preferred random dots moving in opposite directions; in the color-motion task, they preferred subjective contours from apparent motion stimuli consisting of random red and green dots with different luminance. RESULTS: In the re-gaze task, fewer 3-month-olds gazed at the new target than other age groups participants. All ages showed preference for target stimuli in the motion transparency task, but 3-month-olds showed significantly lower preference in the color-motion integration task. CONCLUSION: These tasks may be useful for measuring visual-cognitive and attentional functions in infants.

Microbiome and Diet in Colon Cancer Development and Treatment.

ABSTRACT: Diet plays critical roles in defining our immune responses, microbiome, and progression of human diseases. With recent progress in sequencing and bioinformatic techniques, increasing evidence indicates the importance of diet-microbial interactions in cancer development and therapeutic outcome. Here, we focus on the epidemiological studies on diet-bacterial interactions in the colon cancer. We also review the progress of mechanistic studies using the experimental models. Finally, we discuss the limits and future directions in the research of microbiome and diet in cancer development and therapeutic outcome. Now, it is clear that microbes can influence the efficacy of cancer therapies. These research results open new possibilities for the diagnosis, prevention, and treatment of cancer. However, there are still big gaps to apply these new findings to the clinical practice.

Phylogenetic origin of Helicobacter pylori pathogenicity island and risk of stomach cancer and high-grade premalignant gastric lesions.

Infection by Helicobacter pylori (Hp) has been causally linked to risk of gastric cancer (GC). The coevolution of Hp and humans shaped the risk of GC as our species left Africa and migrated to the other continents. Latin America (LatAm) is a high GC incidence region where Hp evolved uniquely in the 500 years since European colonization. Differential virulence of the Hp cagA -pathogenicity island (cagPAI) by ancestral origin has been reported. We hypothesized that Hp phylogenetic origin might play a role in determining GC risk in LatAm. We used genotypes of 50 Hp genetic variants mapping to the Hp cagPAI, studied in 1220 subjects from Venezuela, Colombia, Mexico and Paraguay, who were infected with cagA-positive Hp, including 150 GC, 177 high-grade premalignant lesions (HGPMLs) and 893 low-grade premalignant lesions. We estimated the phylogenetic origin of Hp cagPAI in all study subjects by use of the STRUCTURE software and principal component analysis (PCA) and tested whether the estimated African ancestry percentage was associated with the risk of GC or HGPML. African ancestral component estimates by STRUCTURE and PCA were highly correlated. STRUCTURE-based African origin estimate was not significantly associated with the risk of HGPML, but it was inversely associated with GC risk: the OR associated with the continuous values of African component was 0.09 (95% CI, 0.01-0.85; P = 0.035). Similar trends were observed for GC with PCA-based estimates, but the association was not statistically significant. These results suggest that Hp ancestral origin may play a role in gastric carcinogenesis.

Impact of hydrogen gas inhalation during therapeutic hypothermia on cerebral hemodynamics and oxygenation in the asphyxiated piglet.

We previously reported the neuroprotective potential of combined hydrogen (H2) gas ventilation therapy and therapeutic hypothermia (TH) by assessing the short-term neurological outcomes and histological findings of 5-day neonatal hypoxic-ischemic (HI) encephalopathy piglets. However, the effects of H2 gas on cerebral circulation and oxygen metabolism and on prognosis were unknown. Here, we used near-infrared time-resolved spectroscopy to compare combined H2 gas ventilation and TH with TH alone. Piglets were divided into three groups: HI insult with normothermia (NT, n = 10), HI insult with hypothermia (TH, 33.5 ± 0.5 °C, n = 8), and HI insult with hypothermia plus H2 ventilation (TH + H2, 2.1-2.7%, n = 8). H2 ventilation and TH were administered and the cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation (ScO2) were recorded for 24 h after the insult. CBV was significantly higher at 24 h after the insult in the TH + H2 group than in the other groups. ScO2 was significantly lower throughout the 24 h after the insult in the TH + H2 group than in the NT group. In conclusion, combined H2 gas ventilation and TH increased CBV and decreased ScO2, which may reflect elevated cerebral blood flow to meet greater oxygen demand for the surviving neurons, compared with TH alone.

Association of calcium and vitamin D supplementation with cancer incidence and cause-specific mortality in Black women: Extended follow-up of the Women's Health Initiative calcium-vitamin D trial.

Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow-up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause-specific mortality endpoints among Black women. Intent-to-treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52 230 total person-years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, posttrial follow-up period and overall periods combined. We found that total mortality, cause-specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation.

Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative.

Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.

Adherence to the American Cancer Society Guidelines on nutrition and physical activity for cancer prevention and obesity-related cancer risk and mortality in Black and Latina Women's Health Initiative participants.

BACKGROUND: Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity-related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women's Health Initiative (WHI). METHODS: Semi-Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking. RESULTS: Over a median of 11.1, 12.5, and 3.7 years of follow-up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all-cause deaths (Black/Latina women: 1576/394), and 341 ORC-related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause-specific hazard ratio [CSHR]highvs.low : 0.72; 95% CI, 0.55-0.94) and Latina (CSHRhighvs.low : 0.58, 95% CI, 0.36-0.93) women; but not conditional all-cause mortality (Black hazard ratio [HR]highvs.low : 0.86; 95% CI, 0.53-1.39; Latina HRhighvs.low : 0.81; 95% CI, 0.32-2.06). Higher adherence was associated with lower incidence of less common ORC (Ptrend  = .025), but conditional mortality events were limited. Adherence and ORC-specific deaths were not associated and there was no evidence of effect modification. CONCLUSIONS: Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC-related mortality. LAY SUMMARY: Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color. Adherence to the guidelines and risk of developing one of 13 obesity-related cancers among Black and Latina women in the Women's Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity-related cancer. These findings support public health interventions to reduce growing racial/ethnic disparities in obesity-related cancers.

Comparative Analysis of Binary Similarity Measures for Compound Identification in MassSpectrometry-Based Metabolomics.

Compound identification is a critical step in untargeted metabolomics. Its most important procedure is to calculate the similarity between experimental mass spectra and either predicted mass spectra or mass spectra in a mass spectral library. Unlike the continuous similarity measures, there is no study to assess the performance of binary similarity measures in compound identification, even though the well-known Jaccard similarity measure has been widely used without proper evaluation. The objective of this study is thus to evaluate the performance of binary similarity measures for compound identification in untargeted metabolomics. Fifteen binary similarity measures, including the well-known Jaccard, Dice, Sokal-Sneath, Cosine, and Simpson measures, were selected to assess their performance in compound identification. using both electron ionization (EI) and electrospray ionization (ESI) mass spectra. Our theoretical evaluations show that the accuracy of the compound identification was exactly the same between the Jaccard, Dice, 3W-Jaccard, Sokal-Sneath, and Kulczynski measures, between the Cosine and Hellinger measures, and between the McConnaughey and Driver-Kroeber measures, which were practically confirmed using mass spectra libraries. From the mass spectrum-based evaluation, we observed that the best performing similarity measures were the McConnaughey and Driver-Kroeber measures for EI mass spectra and the Cosine and Hellinger measures for ESI mass spectra. The most robust similarity measure was the Fager-McGowan measure, the second-best performing similarity measure in both EI and ESI mass spectra.

Identification of Tumor-Suppressive miR-30e-3p Targets: Involvement of SERPINE1 in the Molecular Pathogenesis of Head and Neck Squamous Cell Carcinoma.

Recently, our studies revealed that some passenger strands of microRNAs (miRNAs) were closely involved in cancer pathogenesis. Analysis of miRNA expression signatures showed that the expression of miR-30e-3p (the passenger strand of pre-miR-30e) was significantly downregulated in cancer tissues. In this study, we focused on miR-30e-3p (the passenger strand of pre-miR-30e). We addressed target genes controlled by miR-30e-3p that were closely associated with the molecular pathogenesis of head and neck squamous cell carcinoma (HNSCC). Ectopic expression assays demonstrated that the expression of miR-30e-3p attenuated cancer cell malignant phenotypes (e.g., cell proliferation, migration, and invasive abilities). Our analysis of miR-30e-3p targets revealed that 11 genes (ADA, CPNE8, C14orf126, ERGIC2, HMGA2, PLS3, PSMD10, RALB, SERPINE1, SFXN1, and TMEM87B) were expressed at high levels in HNSCC patients. Moreover, they significantly predicted the short survival of HNSCC patients based on 5-year overall survival rates (p < 0.05) in The Cancer Genome Atlas (TCGA). Among these targets, SERPINE1 was found to be an independent prognostic factor for patient survival (multivariate Cox regression; hazard ratio = 1.6078, p < 0.05). Aberrant expression of SERPINE1 was observed in HNSCC clinical samples by immunohistochemical analysis. Functional assays by targeting SERPINE1 expression revealed that the malignant phenotypes (e.g., proliferation, migration, and invasion abilities) of HNSCC cells were suppressed by the silencing of SERPINE1 expression. Our miRNA-based approach will accelerate our understanding of the molecular pathogenesis of HNSCC.

Low-dose ionizing radiation and cancer mortality among enlisted men stationed on nuclear-powered submarines in the United States Navy.

BACKGROUND: Men stationed on nuclear-powered submarines are occupationally exposed to external ionizing radiation at very low levels and radiation dose for each individual is closely monitored. Little is known about ionizing radiation (IR) risks of cancer mortality for populations with levels of cumulative ionizing radiation exposure this low. MATERIALS AND METHODS: This historical cohort study followed 85,033 enlisted men who had served on a nuclear-powered submarine in the U.S. Navy between 1969 and 1982 to determine patterns of cancer mortality. Occupational radiation doses were measured by badge dosimeters for each individual for all periods of Navy service potentially involving radiation exposure. Deaths were ascertained through 1995 by searches of multiple national mortality databases. Within-cohort dose-response relationships for cancer mortality were estimated using linear Poisson regression models. Individual-level smoking status was not available so cancer risks were estimated separately for cancers with and without previously published evidence of consistently moderate or strong associations with smoking. RESULTS: A total of 584 cancer deaths occurred during a follow-up period of up to 27 years. The mean and median cumulative occupational radiation doses received while in the Navy were 5.7 and 1.1 milliSieverts (mSv), respectively, range 0-242 mSv. Mortality Excess Relative Risks (ERRs) per 10 mSv and 95% confidence intervals (CI) were 0.053 (CI -0.03, 0.17) for all cancers, 0.052 (CI -0.03, 0.18) for all solid cancers, and 0.003 (CI -0.29, 0.30) for leukemias excluding chronic lymphocytic leukemia. The ERRs per 10 mSv were 0.052 (CI -0.07, 0.17) for cancers previously associated with smoking and 0.012 (CI -0.10, 0.12) for cancers that were not. CONCLUSIONS: The ERR point estimates for solid cancers and leukemia were statistically compatible with those reported in previously published studies of other ionizing radiation-exposed and monitored cohorts, albeit with wide confidence intervals. This study, with high-quality measurements of in-Navy occupational external IR doses, high follow-up proportion, and detailed IR dose-response analyses, is consistent with the premise of small excess cancer risks from low-dose IR.

Bacterial-Viral Interactions in Human Orodigestive and Female Genital Tract Cancers: A Summary of Epidemiologic and Laboratory Evidence.

Infectious agents, including viruses, bacteria, fungi, and parasites, have been linked to pathogenesis of human cancers, whereas viruses and bacteria account for more than 99% of infection associated cancers. The human microbiome consists of not only bacteria, but also viruses and fungi. The microbiome co-residing in specific anatomic niches may modulate oncologic potentials of infectious agents in carcinogenesis. In this review, we focused on interactions between viruses and bacteria for cancers arising from the orodigestive tract and the female genital tract. We examined the interactions of these two different biological entities in the context of human carcinogenesis in the following three fashions: (1) direct interactions, (2) indirect interactions, and (3) no interaction between the two groups, but both acting on the same host carcinogenic pathways, yielding synergistic or additive effects in human cancers, e.g., head and neck cancer, liver cancer, colon cancer, gastric cancer, and cervical cancer. We discuss the progress in the current literature and summarize the mechanisms of host-viral-bacterial interactions in various human cancers. Our goal was to evaluate existing evidence and identify gaps in the knowledge for future directions in infection and cancer.

Impact of 18-Month Soy Protein Supplementation on Steroid Hormones and Serum Biomarkers of Angiogenesis, Apoptosis, and the Growth Hormone/IGF-1 Axis: Results of a Randomized, Placebo-Controlled Trial in Males Following Prostatectomy.

Many studies have addressed the effects of dietary supplementation with soy protein on cancer risk and mortality, but there are only few randomized studies with soy in males. We used serum samples from a two-year trial of soy protein isolate supplementation in middle-aged to older males at risk of recurrence of prostate cancer after radical prostatectomy to determine soy effects on steroid hormones involved in prostate cancer (testosterone, SHBG, and estradiol) and explore the effects on biomarkers of the growth hormone/IGF-1 axis, apoptosis, and angiogenesis. Compared with a casein-based placebo, 18 mo, of consumption of 19.2 g/day of whole soy protein isolate containing 24 mg genistein-reduced circulating testosterone and SHBG, but not free testosterone, and did not affect serum concentrations of estradiol, VEGF, IGF-1, IGFBP-3, IGF-1/IGFBP-3 ratio, soluble Fas, Fas-ligand, and sFas/Fas-ligand ratio. Thus, soy protein supplementation for 18 mo, affected the androgen axis, but the effects on other cancer biomarkers remain to be more definitively determined. The study was registered at clinicaltrials.gov (NCT00765479).