Isolation and characterization of an atypical Mycoplasma gallisepticum strain showing a new mgc2 variant.

Mycoplasma gallisepticum (MG) is an important pathogen of the poultry industry able to cause chronic respiratory disease in chickens and infectious sinusitis in turkeys. Despite the application of biosecurity measures and the availability of vaccines for chickens, monitoring systems routinely applied for MG detection are still essential for infection control. Pathogen isolation is time-consuming and not suitable for rapid detection, albeit it is a compulsory step for genetic typing and antimicrobial susceptibility evaluation of single strains. The mgc2 gene is a species-specific molecular target adopted by most of the PCR protocols available for MG diagnosis, which are also included in the WOAH Terrestrial Manual. We describe the case of an atypical MG strain, isolated in 2019 from Italian turkeys, characterized by an mgc2 sequence not detectable by common endpoint PCR primers. Considering the potential risk of false negative results during diagnostic screenings with the endpoint protocol, the authors propose an alternative mgc2 PCR endpoint protocol, named MG600, which should be considered as a further diagnostic tool.

The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials.

The article "The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials", by V. Panetta, A. Bacchieri, S. Papetti, E. De Stefani, P. Navarra, published in Eur Rev Med Pharmacol Sci 2020; 24 (2): 963-973-DOI: 10.26355/eurrev_202001_20082-PMID: 32017005, has been retracted based on commentary received from a new set of reviewers.  The authors will be able to resubmit a new article addressing the reviewers' comments for the Journal's consideration. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20082.

The safety profile of probiotic VSL#3®. A meta-analysis of safety data from double-blind, randomized, placebo-controlled clinical trials.

OBJECTIVE: A high-concentration of a multi-strain probiotic mixture, VSL#3® is widely used 'whenever it is useful to promote the balance of intestinal flora'. As a food supplement, VSL#3® has been so far scarcely investigated on the aspect of safety. To fill this gap, in this paper, we analyzed the adverse events (AEs) recorded during the conduct of three (3) double-blind, randomized, placebo-controlled trials carried out to explore the efficacy of VSL#3® in various clinical settings. Data from a large open-label observational trial were also considered. MATERIALS AND METHODS: All trials included in the analysis were carried out according to good clinical practice (GCP) rules. AEs were classified by System Organ Class (SOC), Preferred Term (PT) and frequency. Differences vs. placebo control were considered as statistically significant if the p-value was < 0.05. RESULTS: A total of 120 patients were analyzed, 70 patients being included in the randomized controlled trials. In this population, 45 patients had at least one AE, 20 (64.5%) in the placebo group and 25 (64.1%) in the VSL#3® group. 29 patients had at least one related AE, 14 (45.2%) and 15 (38.5%) in the two treatment groups, respectively. Only one AE was assessed as serious, i.e., Foetal malformation, which occurred in the placebo group and was considered unrelated. No significant difference was found between VSL#3® and placebo for any of the SOC considered, with the exception of Injury, poisoning and procedural complications, which was in favor of VSL#3®. CONCLUSIONS: Based on GCP-quality data from clinical trials, we conclude that VSL#3® is a safe and well-tolerated agent.

Usb1 controls U6 snRNP assembly through evolutionarily divergent cyclic phosphodiesterase activities.

U6 small nuclear ribonucleoprotein (snRNP) biogenesis is essential for spliceosome assembly, but not well understood. Here, we report structures of the U6 RNA processing enzyme Usb1 from yeast and a substrate analog bound complex from humans. Unlike the human ortholog, we show that yeast Usb1 has cyclic phosphodiesterase activity that leaves a terminal 3' phosphate which prevents overprocessing. Usb1 processing of U6 RNA dramatically alters its affinity for cognate RNA-binding proteins. We reconstitute the post-transcriptional assembly of yeast U6 snRNP in vitro, which occurs through a complex series of handoffs involving 10 proteins (Lhp1, Prp24, Usb1 and Lsm2-8) and anti-cooperative interactions between Prp24 and Lhp1. We propose a model for U6 snRNP assembly that explains how evolutionarily divergent and seemingly antagonistic proteins cooperate to protect and chaperone the nascent snRNA during its journey to the spliceosome.The mechanism of U6 small nuclear ribonucleoprotein (snRNP) biogenesis is not well understood. Here the authors characterize the enzymatic activities and structures of yeast and human U6 RNA processing enzyme Usb1, reconstitute post-transcriptional assembly of yeast U6 snRNP in vitro, and propose a model for U6 snRNP assembly.

Hot infusions and risk of colorectal cancer in Uruguay: a case-control study.

BACKGROUND/OBJECTIVES: The evidence of possible roles for the most common hot infusions intake (tea and coffee) in the risk of colorectal cancer (CRC) needs additional data. Regarding 'mate' intake (infusion of Ilex paraguariensis herb), a previous multi-site study reported lack of association for its highest intake on CRC risk. The present study was conducted to better understand the associations between the intake of this and other infusions and CRC risk. SUBJECTS/METHODS: Patients (611 CRC incident cases and 2394 controls, all belonging to public hospitals) were interviewed through a questionnaire, including socio-demographic, reproductive and lifestyle variables, and a food-frequency questionnaire of 64 items, analyzing tea, 'mate' and coffee intake (consumer status, daily intake, age at start and at quit). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated through unconditional logistic regression, adjusting for relevant potential confounders. RESULTS: Tea and coffee intake displayed significant and inverse associations with CRC risk, mainly among men (OR=0.54, 95% CI 0.38-0.76 for tea and OR=0.59, 95% CI 0.41-0.85 for coffee). Mate intake showed a significant inverse association among women (OR=0.50, 95% CI 0.33-0.77), with a marginal heterogeneity between sexes (P=0.07). Concerning age strata, tea intake displayed inverse associations in all ages, whereas 'mate' and coffee intake showed stronger inverse associations for age ⩾70, suggesting a gradient along time. CONCLUSIONS: We found evidence of different significant inverse associations for tea, 'mate' and coffee intake and CRC risk. To our knowledge, this is the first epidemiologic study reporting inverse results on 'mate' intake and CRC, which are explained by a stronger association among women.European Journal of Clinical Nutrition advance online publication, 23 August 2017; doi:10.1038/ejcn.2017.130.

MaxiK channel interactome reveals its interaction with GABA transporter 3 and heat shock protein 60 in the mammalian brain.

Large conductance voltage and calcium-activated potassium (MaxiK) channels are activated by membrane depolarization and elevated cytosolic Ca(2+). In the brain, they localize to neurons and astrocytes, where they play roles such as resetting the membrane potential during an action potential, neurotransmitter release, and neurovascular coupling. MaxiK channels are known to associate with several modulatory proteins and accessory subunits, and each of these interactions can have distinct physiological consequences. To uncover new players in MaxiK channel brain physiology, we applied a directed proteomic approach and obtained MaxiK channel pore-forming α subunit brain interactome using specific antibodies. Controls included immunoprecipitations with rabbit immunoglobulin G (IgG) and with anti-MaxiK antibodies in wild type and MaxiK channel knockout mice (Kcnma1(-/-)), respectively. We have found known and unreported interactive partners that localize to the plasma membrane, extracellular space, cytosol and intracellular organelles including mitochondria, nucleus, endoplasmic reticulum and Golgi apparatus. Localization of MaxiK channel to mitochondria was further confirmed using purified brain mitochondria colabeled with MitoTracker. Independent proof of MaxiK channel interaction with previously unidentified partners is given for GABA transporter 3 (GAT3) and heat shock protein 60 (HSP60). In human embryonic kidney 293 cells containing SV40 T-antigen (HEK293T) cells, both GAT3 and HSP60 coimmunoprecipitated and colocalized with MaxiK channel; colabeling was observed mainly at the cell periphery with GAT3 and intracellularly with HSP60 with protein proximity indices of ∼ 0.6 and ∼ 0.4, respectively. In rat primary hippocampal neurons, colocalization index was identical for GAT3 (∼ 0.6) and slightly higher for HSP60 (∼ 0.5) association with MaxiK channel. The results of this study provide a complete interactome of MaxiK channel the mouse brain, further establish the localization of MaxiK channel in the mouse brain mitochondria and demonstrate the interaction of MaxiK channel with GAT3 and HSP60 in neurons. The interaction of MaxiK channel with GAT3 opens the possibility of a role of MaxiK channel in GABA homeostasis and signaling.

Processed meat consumption and risk of cancer: a multisite case-control study in Uruguay.

BACKGROUND: The role of processed meat in the aetiology of several cancers was explored in detail. METHODS: In the time period 1996-2004, a multisite case-control study was conducted in Montevideo, Uruguay. The study included 6 060 participants (3 528 cases and 2 532 controls) corresponding to cancers of the oral cavity, pharynx, oesophagus, stomach, colon, rectum, larynx, lung, female breast, prostate, urinary bladder, and kidney (renal cell carcinoma only). RESULTS: The highest odds ratios (ORs) were positively associated with cancers of the colon, rectum, stomach, oesophagus, and lung. With the exception of renal cell carcinoma, the remaining cancer sites were significantly associated with elevated risks for processed meat consumption. Furthermore, mortadella, salami, hot dog, ham, and salted meat were strongly associated with risk of several cancer sites. CONCLUSION: It could be concluded that processed meat intake could be a powerful multiorgan carcinogen.

Dietary folate intake and the risk of 11 types of cancer: a case-control study in Uruguay.

BACKGROUND: There is limited, but inconclusive, epidemiological evidence that high folate intake decreases the risk of colorectal and esophageal cancers. For other cancer sites, the evidence is even less consistent or extensive. MATERIALS AND METHODS: We conducted a case-control study of dietary folate intake and risk of 11 cancer sites in Uruguay between 1996 and 2004, including 3539 cancer cases and 2032 hospital controls. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of cancer associated with folate intake. RESULTS: In the multivariable model, there was a significant decrease in the risk of cancers of the oral cavity and pharynx (OR = 0.49, 95% CI 0.24-0.98), esophagus (OR = 0.29, 95% CI 0.14-0.60), upper aerodigestive tract (OR = 0.41, 95% CI 0.26-0.65), colorectum (OR = 0.42, 95% CI 0.23-0.76) and kidney (OR = 0.35, 95% CI 0.13-0.93) for the highest versus the lowest quartile of dietary folate intake. CONCLUSIONS: Our results not only confirm earlier findings of decreased risk of colorectal and esophageal cancers with a high dietary folate intake but also suggest decreased risk of several other cancers. However, we cannot exclude the possibility that residual confounding, multiple comparisons or other forms of bias could explain these results.

Passive mechanical properties of cardiac tissues in heart hypertrophy during pregnancy.

We evaluated changes in passive mechanical properties in cardiac tissues during rat pregnancy. Left and right ventricular free walls were dissected from hearts of nonpregnant, late-pregnant, and postpartum rats. Mechanical experiments in ventricular strips were done by stretch-release cycles using a step motor. The results show that during pregnancy, there is cardiac hypertrophy associated with (1) an increase in myocyte size, particularly of augmented myocyte length, (2) a decrease in passive tension developed by the myocardial walls, and (3) a decrease in both elastic modulus and hysteresis. All changes observed during rat pregnancy were reversed during postpartum. In conclusion, a heart with less ventricular rigidity could contribute to facilitating the ventricular filling in conditions of a greater circulating volume characteristic of pregnancy.

Ca2+- and thromboxane-dependent distribution of MaxiK channels in cultured astrocytes: from microtubules to the plasma membrane.

Large-conductance, voltage- and Ca2+-activated K+ channels (MaxiK) are broadly expressed ion channels minimally assembled by four pore-forming alpha-subunits (MaxiKalpha) and typically observed as plasma membrane proteins in various cell types. In murine astrocyte primary cultures, we show that MaxiKalpha is predominantly confined to the microtubule network. Distinct microtubule distribution of MaxiKalpha was visualized by three independent labeling approaches: (1) MaxiKalpha-specific antibodies, (2) expressed EGFP-labeled MaxiKalpha, and (3) fluorophore-conjugated iberiotoxin, a specific MaxiK pore-blocker. This MaxiKalpha association with microtubules was further confirmed by in vitro His-tag pulldown, co-immunoprecipitation from brain lysates, and microtubule depolymerization experiments. Changes in intracellular Ca2+ elicited by general pharmacological agents, caffeine or thapsigargin, resulted in increased MaxiKalpha labeling at the plasma membrane. More notably, U46619, an analog of thromboxane A2 (TXA2), which triggers Ca2+-release pathways and whose levels increase during cerebral hemorrhage/trauma, also elicits a similar increase in MaxiKalpha surface labeling. Whole-cell patch clamp recordings of U46619-stimulated cells develop a approximately 3-fold increase in current amplitude indicating that TXA2 stimulation results in the recruitment of additional, functional MaxiK channels to the surface membrane. While microtubules are largely absent in mature astrocytes, immunohistochemistry results in brain slices show that cortical astrocytes in the newborn mouse (P1) exhibit a robust expression of microtubules that significantly colocalize with MaxiK. The results of this study provide the novel insight that suggests that Ca2+ released from intracellular stores may play a key role in regulating the traffic of intracellular, microtubule-associated MaxiK stores to the plasma membrane of developing murine astrocytes.

Endocytic trafficking signals in KCNMB2 regulate surface expression of a large conductance voltage and Ca(2+)-activated K+ channel.

Large conductance voltage and calcium-activated K(+) channels play critical roles in neuronal excitability and vascular tone. Previously, we showed that coexpression of the transmembrane beta2 subunit, KCNMB2, with the human pore-forming alpha subunit of the large conductance voltage and Ca(2+)-activated K(+) channel (hSlo) yields inactivating currents similar to those observed in hippocampal neurons [Hicks GA, Marrion NV (1998) Ca(2+)-dependent inactivation of large conductance Ca(2+)-activated K(+) (BK) channels in rat hippocampal neurones produced by pore block from an associated particle. J Physiol (Lond) 508 (Pt 3):721-734; Wallner M, Meera P, Toro L (1999b) Molecular basis of fast inactivation in voltage and Ca(2+)-activated K(+) channels: A transmembrane beta-subunit homolog. Proc Natl Acad Sci U S A 96:4137-4142]. Herein, we report that coexpression of beta2 subunit with hSlo can also modulate hSlo surface expression levels in HEK293T cells. We found that, when expressed alone, beta2 subunit appears to reach the plasma membrane but also displays a distinct intracellular punctuated pattern that resembles endosomal compartments. beta2 Subunit coexpression with hSlo causes two biological effects: i) a shift of hSlo's intracellular expression pattern from a relatively diffuse to a distinct punctated cytoplasmic distribution overlapping beta2 expression; and ii) a decrease of hSlo surface expression that surpassed an observed small decrease in total hSlo expression levels. beta2 Site-directed mutagenesis studies revealed two putative endocytic signals at the C-terminus of beta2 that can control expression levels of hSlo. In contrast, a beta2 N-terminal consensus endocytic signal had no effect on hSlo expression levels. Thus, beta2 subunit not only can influence hSlo currents but also has the ability to limit hSlo surface expression levels via an endocytic mechanism. This new mode of beta2 modulation of hSlo may depend on particular coregulatory mechanisms in different cell types.

KCNMB1 regulates surface expression of a voltage and Ca2+-activated K+ channel via endocytic trafficking signals.

Voltage-dependent and calcium-activated K(+) (MaxiK, BK) channels are ubiquitously expressed and have various physiological roles including regulation of neurotransmitter release and smooth muscle tone. Coexpression of the pore-forming alpha (hSlo) subunit of MaxiK channels with a regulatory beta1 subunit (KCNMB1) produces noninactivating currents that are distinguished by high voltage/Ca(2+) sensitivities and altered pharmacology [McManus OB, Helms LM, Pallanck L, Ganetzky B, Swanson R, Leonard RJ (1995) Functional role of the beta subunit of high conductance calcium-activated potassium channels. Neuron 14:645-650; Wallner M, Meera P, Ottolia M, Kaczorowski G, Latorre R, Garcia ML, Stefani E, Toro L (1995) Characterization of and modulation by a beta-subunit of a human maxi K(Ca) channel cloned from myometrium. Receptors Channels 3:185-199]. We now show that beta1 can regulate hSlo traffic as well, resulting in decreased hSlo surface expression. beta1 subunit expressed alone is able to reach the plasma membrane; in addition, it exhibits a distinct intracellular punctated pattern that colocalizes with an endosomal marker. Coexpressing beta1 subunit with hSlo, switches hSlo's rather diffuse intracellular expression to a punctate cytoplasmic localization that overlaps beta1 expression. Furthermore, coexpressed beta1 subunit reduces steady-state hSlo surface expression. Site-directed mutagenesis underscores a role of a putative endocytic signal at the beta1 C-terminus in the control of hSlo surface expression. We propose that aside from its well-established role as regulator of hSlo electrical activity, beta1 can regulate hSlo expression levels by means of an endocytic mechanism. This highlights a new beta1 subunit feature that regulates hSlo channels by a trafficking mechanism.

An endoplasmic reticulum trafficking signal prevents surface expression of a voltage- and Ca2+-activated K+ channel splice variant.

Protein delivery to restricted plasma membrane domains is exquisitely regulated at different stages of the cell trafficking machinery. Traffic control involves the recognition of export/retention/retrieval signals in the endoplasmic reticulum (ER)/Golgi complex that will determine protein fate. A splice variant (SV), SV1, of the voltage- and Ca(2+)-activated K(+) channel alpha-subunit accumulates the channel in the ER, preventing its surface expression. We show that SV1 insert contains a nonbasic, hydrophobic retention/retrieval motif, CVLF, that does not interfere with proper folding and tetramerization of SV1. Localization of proteins in the ER by CVLF is independent of its position; originally, on the first internal loop, SV1 insert or CVLF perform equally well if placed at the middle or end of the alpha-subunit intracellular carboxyl terminus. Also, CVLF is able to restrict the traffic of an independently expressed transmembrane protein, beta 1-subunit. CVLF is present in proteins across species and in lower organisms. Thus, CVLF may have evolved to serve as a regulator of cellular traffic.

Differential expression of alpha 1 and beta subunits of voltage dependent Ca2+ channel at the neuromuscular junction of normal and P/Q Ca2+ channel knockout mouse.

Voltage-dependent calcium channels (VDCC) have a key role in neuronal function transforming the voltage signals into intracellular calcium signals. They are composed of the pore-forming alpha(1) and the regulatory alpha(2)delta, gamma and beta subunits. Molecular and functional studies have revealed which alpha(1) subunit gene product is the molecular constituent of each class of native calcium channel (L, N, P/Q, R and T type). Electrophysiological and immunocytochemical studies have suggested that at adult mouse motor nerve terminal (MNT) only P/Q type channels, formed by alpha(1A) subunit, mediate evoked transmitter release. The generation of alpha(1A)-null mutant mice offers an opportunity to study the expression and localization of calcium channels at a synapse with complete loss of P/Q calcium channel. We have investigated the expression and localization of VDCCs alpha(1) and beta subunits at the wild type (WT) and knockout (KO) mouse neuromuscular junction (NMJ) using fluorescence immunocytochemistry. The alpha(1A) subunit was observed only at WT NMJ and was absent at denervated muscles and at KO NMJ. The subunits alpha(1B), alpha(1D) and alpha(1E) were also present at WT NMJ and they were over- expressed at KO NMJ suggesting a compensatory expression due to the lack of the alpha(1A). On the other hand, the beta(1b), beta(2a) and beta(4) were present at the same levels in both genotypes. The presence of other types of VDCC at WT NMJ indicate that they may play other roles in the signaling process which have not been elucidated and also shows that other types of VDCC are able to substitute the alpha(1A) subunit, P/Q channel under certain pathological conditions.

Food groups and risk of squamous cell carcinoma of the oesophagus: a case-control study in Uruguay.

In the time period January 1998-December 2000, a case-control study on squamous cell cancer of the oesophagus was conducted in Montevideo, Uruguay. The main objective of the study was to estimate the odds ratios (ORs) associated with main food groups. For this purpose, 166 patients afflicted with squamous cell oesophageal cancer and 664 hospitalised controls were frequency matched on age and sex. Both series of patients were administered with a structured questionnaire. Aside from queries related with tobacco smoking, alcohol drinking and maté drinking, patients were interviewed with a food-frequency questionnaire (FFQ) on 64 items, representative of the usual Uruguayan diet. Red meat, salted meat and boiled meat displayed strong direct associations (OR for red meat 2.4, 95% CI 1.4-4.2). On the other hand, fish and total white meat showed moderate protective effect (OR for total white meat 0.5, 95% CI 0.3-0.9). Total fruit intake displayed a strong inverse association (OR 0.2, 95% CI 0.1-0.4), whereas total vegetable consumption presented a weak inverse association (OR for total vegetable intake 0.7, 95% CI 0.4-1.2). These results suggest that vegetables, mainly cooked vegetables, are rich in thermolabile protective substances. On the other hand, boiled (stewed) meat, which is ingested at high temperature could be, like maté, a risk factor for squamous cell cancer of the oesophagus.

Long-term and preventive effects of sublingual allergen-specific immunotherapy: a retrospective, multicentric study.

There is now an increasing body of evidence to support the practice of allergen-specific sublingual-swallow immunotherapy (SLIT) in the treatment of IgE-mediated respiratory allergies. Recent studies on traditional injection therapy have pointed out that this form of treatment is not only capable to decrease actual allergic symptoms, but may also have long-term clinical and preventive effects and may influence atopy natural history. In the year 2000, our group published a retrospective, multicenter study showing the efficacy and safety of SLIT in a survey of 302 patients. We now carried out a second study on the same patients, with the aim of investigating long-term and preventive effects of SLIT. Beside the well-known safety and efficacy of this treatment (80.8% of patients reported clinical benefits), SLIT proved also to elicit long term clinical effects: over a mean follow-up of 11.6 months after the end of treatment, 80.8% of patients still maintained the previously achieved benefits. During the follow-up period, only 1% of non-asthma patients reported an onset of respiratory symptoms, and only 9.6% of patients undergoing new skin tests showed new sensitizations. All the clinical benefits were strongly linked to the length of treatment: patients with long-lasting benefits were treated for a mean length of 29.1 months, while patients showing a return to pre-SLIT condition were treated for a mean 13.3 months. SLIT can obtain long-term and preventive effects so far attributed to injection immunotherapy.

Dairy foods and risk of breast cancer: a case-control study in Montevideo, Uruguay.

In order to investigate possible associations of milk and dairy products and the risk of breast cancer (BC) in Montevideo, the authors performed a case-control study in the period 1999-2001. A total of 333 women were interviewed with a specific questionnaire; 111 of them had been diagnosed with BC and 222 were frequency-matched healthy women, with a recent normal mammography (BIRADS 1). The questionnaire included a detailed 120-item food-frequency section, as well as questions related to socio-demographic, reproductive, familial, medical and lifestyle variables. There was particular emphasis on types of milk and dairy products. After controlling for age, years of urban status, education, body mass index, age at menarche, menopausal status, family history of BC, number of childbirths, total energy and total fruits, a multivariate analysis found that high intakes of whole milk, chocolate milk and Gruyère cheese were associated with significant increased risk of BC, whereas ricotta cheese and skim yoghurt were associated with significant decreased risks. Low-fat and fermented products combined appear to be the most protective dairy foods. The results suggest that separate analyses for types of milk and cheese, as well as for dairy products in general should be performed in the future.

Plant foods and differences between colon and rectal cancers.

A case-control study on plant food intake and its role in the risk of colon and rectal cancers was carried out in Montevideo, Uruguay. Four hundred and eighty-four (484) cases of colorectal cancer and 1452 controls were frequency matched on age, sex, residence and urban/rural status. Among cases, 260 patients had colon cancer whereas 224 had rectal tumours. Controls had non-neoplastic conditions. Both cases and controls were interviewed in the four major hospitals in Montevideo shortly after admittance for diagnosis or treatment. The questionnaire included a section on frequency of foods, which included 64 items, in particular, queries on 18 vegetables, 10 fruits and 6 cereal dishes were included. Thus, the amount of plant foods consumed was complete and included the main plant foods in the Uruguayan diet. The analysis showed that rectal cancer displayed inverse associations with total plant foods, total vegetables, cooked vegetables, potatoes and legumes. When data were stratified by tumour site and sex, only men showed a protective effect of plant foods (odds ratio (OR) of rectal cancer for men 0.4, 95% confidence interval (CI) 0.2-0.7). In contrast, women with rectal carcinoma were not associated with plant food intake. It can be concluded that plant foods are protective factors for men afflicted with colorectal cancer but that plant food intake is not associated with risk in women. This is, at least in part, due to the high risk associated with bread intake in this gender.