Organoleptic characteristics and compositional profile of meat of growing Japanese quail fed different levels of poultry byproducts compost.

The poultry industry generates a lot of waste, including dead birds, manure, and poultry litter. Poultry waste should never be disposed of improperly because it can seriously harm the environment. The waste can be recycled as a feedstock for use in poultry feed by composting the litter and deceased birds. The compositional profile and organoleptic properties of the meat of growing Japanese quail were examined over the course of a 4-week trial to ascertain the effect of adding compost to the diet. In a completely randomized design (CRD), 1200 newly hatched quail chicks (Coturnix coturnix japonica) were divided into five treatment groups (diets with 0, 2.5, 5, 7.5, and 10% compost), each consisting of 40 birds with six replicates. The addition of compost to the diet had no noticeable effects on the organoleptic qualities of appearance, color, aroma, taste, texture, juiciness, tenderness, and acceptability (P>0.05). The compositional profile characteristics for chicks given compost at any level compared to chicks fed the control diet showed no differences (P>0.05). These findings suggest that the sensory characteristics and compositional profile of growing meat quails can be maintained when fed diets including up to 10% compost.

Assessing effect of feeding poultry byproducts compost on organoleptic characteristics and compositional profile of meat of broiler chickens.

Large amounts of waste, including dead birds, manure, and poultry litter, are produced by the poultry industry. Poultry waste should be disposed of properly to avoid major pollution and health risks. Composting litter and dead birds could be an option to recycle the waste and use in poultry feed. A study was conducted to investigate the effects of feeding composted poultry waste on the organoleptic qualities and compositional profile of the meat of broiler chickens. A total of 300 day-old broiler chicks (500-Cobb) were randomly allocated to five treatment groups replicated six times with 10 birds each, under a completely randomized design (CRD). Five iso-caloric and iso-nitrogenous diets including composted poultry byproducts at concentrations of 0, 2.5, 5, 7.5, and 10% were fed ad libitum to the birds from day 0 to day 35. The sensory grading and meat composition profile of 500 Cobb broiler chickens were tested at 35 days of age. The findings showed that there were no variations in the sensory profiles of the meat from birds given various diets (P>0.05). Although the results were somewhat lower for the chicks fed compost-containing diets than for the control group, this difference was deemed to be insignificant (P>0.05). Similarly, there were no variations in the compositional profile values of the meat between meat from birds fed various diets (P>0.05). These findings imply that broiler chickens may be raised on diets containing up to 10% poultry byproduct compost without any negative impacts on the meat's sensory quality or composition. Additionally, using compost into broiler diets may help to lower the cost of feed.

Two-year real-world outcome data from a single tertiary centre shows reduced ustekinumab persistence in a non-bio-naïve Crohn's disease cohort with penetrating disease, -ostomies and sarcopenia.

Background: Ustekinumab was approved in 2016 for the treatment of moderate-severe Crohn's disease (CD). Clinical trials and real-world studies have suggested ustekinumab to be a safe and effective treatment; however, studies to date infrequently use imaging techniques to predict response to biologics in CD. Objectives: We assessed the 2-year real-world effectiveness and safety of ustekinumab in a tertiary CD cohort with the use of novel imaging techniques. Design: Retrospective cohort study. Methods: Retrospective data were collected between 2016 and 2021. Study end points included ustekinumab persistence, biological and/or clinical response and remission at 12, 18 and 24 months. Statistical analysis included demographic and inferential analyses. Results: In all, 131 CD patients [57.3% female, median age of 26.0 (21.0-37.0)] were included. Patients were non-bio naïve, and the majority received ustekinumab as third- or fourth-line treatment. At 24 months, 61.0% (80/131) persisted with ustekinumab [52.7% (69/131) steroid free]. Clinical response was reported in 55.2% (37/67), clinical remission in 85.7% (57/67), biological response in 46.8% (22/47) and biological remission in 31.9% (15/47) of patients at 24 months. The low outcome numbers were attributable to missing data. Improvements in routine disease markers, including C-reactive protein and Harvey-Bradshaw Index, were also reflected in magnetic resonance imaging-derived disease scores. The presence of penetrating CD, an -ostomy and sarcopenia were all predictors of poorer ustekinumab outcomes (p < 0.05). Conclusion: Ustekinumab is effective in non-bio-naïve CD patients with non-stricturing, non-penetrating disease with an unremarkable safety profile but may be less effective in those with penetrating disease, -ostomies and sarcopenia.

Randomized clinical trial: Long-term Staphylococcus aureus decolonization in patients on home parenteral nutrition.

BACKGROUND & AIMS: Staphylococcus aureus decolonization has proven successful in prevention of S. aureus infections and is a key strategy to maintain venous access and avoid hospitalization in patients receiving home parenteral nutrition (HPN). We aimed to determine the most effective and safe long-term S. aureus decolonization regimen. METHODS: A randomized, open-label, multicenter clinical trial was conducted. Adult intestinal failure patients with HPN support and carrying S. aureus were randomly assigned to a 'continuous suppression' (CS) strategy, a repeated chronic topical antibiotic treatment or a 'search and destroy' (SD) strategy, a short and systemic antibiotic treatment. Primary outcome was the proportion of patients in whom S. aureus was totally eradicated during a 1-year period. Secondary outcomes included risk factors for decolonization failure and S. aureus infections, antimicrobial resistance, adverse events, patient compliance and cost-effectivity. RESULTS: 63 participants were included (CS 31; SD 32). The mean 1-year S. aureus decolonization rate was 61% (95% CI 44, 75) for the CS group and 39% (95% CI 25, 56) for the SD group with an OR of 2.38 (95% CI 0.92, 6.11, P = 0.07). More adverse effects occurred in the SD group (P = 0.01). Predictors for eradication failure were a S. aureus positive caregiver and presence of a (gastro)enterostomy. CONCLUSION: We did not demonstrate an increased efficacy of a short and systemic S. aureus decolonization strategy over a continuous topical suppression treatment. The latter may be the best option for HPN patients as it achieved a higher long-term decolonization rate and was well-tolerated (NCT03173053).

The level and distribution of selected organochlorine pesticides in water of River Satluj Pakistan.

The study was aimed to identify different environmental factors (selected organochlorine pesticides) affecting the river water of Satluj. River Sutlej is about 1400 kilometers long and its water is extensively used for irrigation in Punjab, located both in India and Pakistan, which was also a reason of dispute between both countries for its water share. The study area was divided into four zones, Sulemanki Zone, Islam Zone, Mailsi Syphone Zone and Panjnad Zone. Liquid Liquid Extraction (LLE) technique was used for the collected water samples followed by high performance liquid chromatography (HPLC) UV-Visible detector The current finding revealed that aldrin was not detected during summer period in water samples of SZ-1 (Sulemanki Barrage), SZ-2 and SZ-3 (Maisli Siphon) of the study area. Lindane and DDE were found more in the samples of sediments from the study area at SZ-4 ranging from 2.238-8.226 ppb and 4.234-6.876 ppb, respectively. Heaptachlor (in sediments) was found to be0.032-234 ppb only at SZ-4.Endosulfan concentrations in water (winter) at SZ-3 was 0.06 ppb and at SZ-4,it was 0.05 ppb; dieldrin in water (winter) at SZ-4 was 0.0314 ppb and heptachlor was detected at SZ-1 (0.0315 ppb) and SZ-2 (0.0310 ppb) in water during winter season, were reaching to the Maximum Concentrations Limits (MCL), while all other residues investigated were found below the MCLin all the compartments of the study area set by various agencies like WHO/FAO- Codex Alimenterious. Present findings revealed that although the organochlorine pesticides are banned for agricultural use in many countries, including Pakistan, their presence in various samples might be due to illegal use of these pesticides in the study area and its neighboring regions. The overall study area comprises of mainly urban, suburban and agricultural land being the largest cotton growing area of the country. There is a need to take serious steps to minimize water pollution caused by pesticides to achieve a healthy lifestyle.

Presence of selected organochlorine pesticides (OCPs) in sediments and biota of River Satluj, Pakistan: first report.

In the developed countries, the use of OCPs (organochlorine pesticides) has been banned. However, in South Asia several of them are still in use. In Pakistan and India a constant addition of OCPs into the atmosphere has been indicated by various researchers. In this study levels of selected organochlorine pesticide residues were assessed in sediment and biota collected from four (4) water reservoirs (3 Barrages & 1 Siphon) on the River Satluj Pakistan, along 231 miles (372 km) of River stretch which was further divided into 12 sampling sites. It was aimed to find out the levels of organochlorine pesticide (OCPs) residues in sediments and from selected fish species (Labeo rohita, Wallagu attu, Cyprinus carpio) of the River Satluj Pakistan. The Organochlorine residues (seven pesticides) present in samples of sediments and biota were investigated through multi residue method, using Gas Chromatograph (GC-ECD).In the current study, the concentration of DDT, was investigated in Wallago attu (0.786-3.987 ppb), Labeo rohita (0.779-4.355 ppb) and Cyprinus carpio (1.234-5.654 ppb). DDE was also found in Cyprinus carpio (1.244-6.322 ppb), Wallag attu (0.877-4.221 ppb) and Labeo rohita (2.112-5.897 ppb). Aldrin was not observed in Labeo rohita and Wallago attu. Currently, lindane and DDE was found predominately high in the sediments of study area at SZ-4 (Panjnad Barrage) ranging (2.238-8.226 ppb) and (4.234-6.876 ppb), respectively. Heaptachlor was found only at SZ-4 (Panjnad Barrage) from the sediments with concentration ranging (0.032-234 ppb). In short all other residues investigated were found below the MCL (maximum concentration level) in all the compartments of the study area set by various agencies like WHO/FAO- Codex Alimenterious.

The Role of Diet and Gut Microbiota in Regulating Gastrointestinal and Inflammatory Disease.

Diet is an important lifestyle factor that is known to contribute in the development of human disease. It is well established that poor diet plays an active role in exacerbating metabolic diseases, such as obesity, diabetes and hypertension. Our understanding of how the immune system drives chronic inflammation and disease pathogenesis has evolved in recent years. However, the contribution of dietary factors to inflammatory conditions such as inflammatory bowel disease, multiple sclerosis and arthritis remain poorly defined. A western diet has been associated as pro-inflammatory, in contrast to traditional dietary patterns that are associated as being anti-inflammatory. This may be due to direct effects of nutrients on immune cell function. Diet may also affect the composition and function of gut microbiota, which consequently affects immunity. In animal models of inflammatory disease, diet may modulate inflammation in the gastrointestinal tract and in other peripheral sites. Despite limitations of animal models, there is now emerging evidence to show that anti-inflammatory effects of diet may translate to human gastrointestinal and inflammatory diseases. However, appropriately designed, larger clinical studies must be conducted to confirm the therapeutic benefit of dietary therapy.

Assessing growth performance, morphometric traits, meat chemical composition and cholesterol content in four phenotypes of naked neck chicken.

The present study was conducted to assess the growth performance, morphometric traits, muscle chemical composition and cholesterol content in four phenotypes of naked neck chicken (black, white-black, light brown and dark brown). A total of 320-day-old chicks, 80 from each phenotype, were randomly stratified into 20 replicates (16/replicate), according to a completely randomized design. The results showed higher final body weight, weight gain, and better FCR in both light brown and dark brown phenotypes whereas time of gains was found to be greater in dark brown phenotype. Keel length and shank circumference were greater in dark brown whereas wing spread was found to be higher in light brown phenotype. Drumstick circumference and body length did not show any significant differences (P > 0.05) across the phenotypes. Dry matter was found to be higher in white black, crude protein in black, white black and dark brown, moisture in light brown, and cholesterol content in black whereas ether extract and ash content were found to be greater in black and white black phenotypes. In conclusion, both light brown and dark brown phenotypes showed superior growth performance and morphometric traits. Similarly, from a health point of view, the dark brown and light brown phenotypes seem superior because their cholesterol content was low. Thus, it is strongly recommended that there should be a conscious effort to improve economically important traits of the light and dark brown birds to be used as dual-purpose slow growing chicken, especially in developing countries.

Morphometrics of the indian false vampire bat (Megaderma lyra) from district Jhelum, Pakistan / Morfometria do falso morcego vampiro indiano (Megadermalyra) do distrito de Jhelum, Paquistão

Abstract During the present study thirteen Megaderma lyra bats were observed roosting in dark, domed shaped room of Rohtas Fort, district Jhelum. Out of these, six specimens were captured from the roosting site, using hand net. All captured specimens were male. These bats were identified through their unique facial features, an erect and elongated nose-leaf, large oval ears that joined above the forehead and no tail. Mean head and body length of captured specimens was 80 mm, forearm length was 67 mm while average lengths of 3rd, 4th and 5th metacarpals were 51.73 mm, 55.17 mm and 60.42 mm, respectively. Mean skull length was 29.84 mm, breadth of braincase was 12.77 mm. Average Penis length of two specimens was 6.6 mm and total bacular length was 3.08 mm respectively. This is the first record of Megaderma lyra from district Jhelum.

Resumo Durante o presente estudo, 13 morcegos Megadermalyra foram observados empoleirados em uma sala escura em forma de cúpula no Forte Rohtas, distrito de Jhelum, dos quais 6 espécimes foram capturados no local usando rede manual. Todos os espécimes capturados eram machos. Esses morcegos foram identificados por suas características faciais únicas, uma folha nasal ereta e alongada, grandes orelhas ovais que se juntam acima da testa e sem cauda. O comprimento médio da cabeça e do corpo dos espécimes capturados foi de 80 mm, o comprimento do antebraço foi de 67 mm, enquanto os comprimentos médios do 3º, 4º e 5º metacarpos foram de 51,73 mm, 55,17 mm e 60,42 mm, respectivamente. O comprimento médio do crânio foi de 29,84 mm, e a largura da caixa craniana, de 12,77 mm. O comprimento médio do pênis de duas amostras foi de 6,6 mm, e o comprimento total do báculo foi de 3,08 mm. Este é o primeiro registro de Megadermalyra no distrito de Jhelum.

The role of the microbiome in gastrointestinal inflammation.

The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms whilst still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns (MAMPs) and generation of microbe-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homoeostasis, promote protective immune responses, and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiota to help reverse dysbiosis, reduce inflammation, and ultimately prevent disease progression.

Morphometrics of the indian false vampire bat (Megaderma lyra) from district Jhelum, Pakistan.

During the present study thirteen Megaderma lyra bats were observed roosting in dark, domed shaped room of Rohtas Fort, district Jhelum. Out of these, six specimens were captured from the roosting site, using hand net. All captured specimens were male. These bats were identified through their unique facial features, an erect and elongated nose-leaf, large oval ears that joined above the forehead and no tail. Mean head and body length of captured specimens was 80 mm, forearm length was 67 mm while average lengths of 3rd, 4th and 5th metacarpals were 51.73 mm, 55.17 mm and 60.42 mm, respectively. Mean skull length was 29.84 mm, breadth of braincase was 12.77 mm. Average Penis length of two specimens was 6.6 mm and total bacular length was 3.08 mm respectively. This is the first record of Megaderma lyra from district Jhelum.

Photodissociation of S2 (X3Σg-, a1Δg, and b1Σg+) in the 320-205 nm Region.

Photodissociation of vibrationally and electronically excited sulfur dimer molecules (S2) has been studied in a combined experimental and computational quantum chemistry study in order to characterize bound-continuum transitions. Ab initio quantum chemistry calculations are carried out to predict the potential energy curves, spin-orbit coupling, transition moments, and bound-continuum spectra of S2 for comparison with the experimental data. The experiment uses velocity map imaging to measure S-atom production following S2 photoexcitation in the ultraviolet region (320-205 nm). A pulsed electric discharge in H2S produces ground-state S2 X3Σg-(v = 0-15) as well as electronically excited singlet sulfur and b1Σg+(v = 0, 1), and evidence is presented for the production and photodissociation of S2 a1Δg. In a previous paper, we reported threshold photodissociation of S2X3Σg-(v = 0) in the 282-266 nm region. In the present study, S(3PJ) fine structure branching and angular distributions for photodissociation of S2 (X3Σg-(v = 0), a1Δg and b1Σg+) via the B″3Πu, B3Σu- and 11Πu excited states are reported. In addition, photodissociation of the X3Σg-(v = 0) state of S2 to the second dissociation limit producing S(3P2) + S(1D) is characterized. The present results on S2 photodynamics are compared to those of the well-studied electronically isovalent O2 molecule.

Optimized laser-induced breakdown spectroscopy for the determination of high toxic lead in edible colors.

An optimized laser-induced breakdown spectroscopy (LIBS) system was utilized as a robust tool for the detection of high toxic lead (Pb) in often used edible colors available in local markets. Edible colors are extensively used in different food stuffs and sweet dish items. To attain a highly sensitive LIBS system for the determination of trace amounts of toxic Pb in edible colors and to achieve the best detection limit, various parametric dependence studies were performed. The quantitative determinations were accomplished under the condition of local thermodynamic equilibrium in terms of optically thin plasma. Besides toxic Pb, other elements like Ca, Mg, Fe, and Na were also detected in edible colors. To estimate the concentration of toxic lead in edible colors, calibration curves were plotted by preparing standard samples of different lead concentrations in an edible colors matrix. Results of the LIBS technique were compared with the outcomes of the same samples studied using a standard analytical technique of inductively coupled plasma-optical emission spectroscopy to confirm the contemporary LIBS setup. The color samples were found above the safe permissible level due to the mass of toxic lead. Limit of detection of the LIBS setup was found at 0.86+/-0.03 ppm for toxic lead present in edible color samples.

Determination of toxic and essential metals in rock and sea salts using pulsed nanosecond laser-induced breakdown spectroscopy.

A spectrometer based on pulsed nanosecond laser-induced breakdown spectroscopy (LIBS) was employed for the quantitative determination of heavy and essential metals in salts from various sources available in Pakistan. Six salt samples were collected from sea salt and rock salt. Toxic metals (Cu, Cd, and Ni) and other microessentials (Fe, Ca, Co, Mg, Mn, S, and Zn) were investigated from the recorded spectra. The detection system was calibrated using a parametric dependence study. The quantitative analyses were accomplished under the assumption of local thermodynamic equilibrium and optically thin plasma. The results by the LIBS technique were in agreement with the outcomes of the same samples studied using a more standard approach like inductively coupled plasma-atomic emission spectroscopy (ICP-AES). When the concentrations of heavy and essential metals were calculated using a calibration-free LIBS method that does not need a standard salt specimen and dilution, both LIBS and ICP-AES were also in good agreement. The limit of detection of the experimental set up was determined for the observed heavy metals in the studied samples.

Morphometrics of the indian false vampire bat (Megaderma lyra) from district Jhelum, Pakistan

Abstract During the present study thirteen Megaderma lyra bats were observed roosting in dark, domed shaped room of Rohtas Fort, district Jhelum. Out of these, six specimens were captured from the roosting site, using hand net. All captured specimens were male. These bats were identified through their unique facial features, an erect and elongated nose-leaf, large oval ears that joined above the forehead and no tail. Mean head and body length of captured specimens was 80 mm, forearm length was 67 mm while average lengths of 3rd, 4th and 5th metacarpals were 51.73 mm, 55.17 mm and 60.42 mm, respectively. Mean skull length was 29.84 mm, breadth of braincase was 12.77 mm. Average Penis length of two specimens was 6.6 mm and total bacular length was 3.08 mm respectively. This is the first record of Megaderma lyra from district Jhelum.

Resumo Durante o presente estudo, 13 morcegos Megadermalyra foram observados empoleirados em uma sala escura em forma de cúpula no Forte Rohtas, distrito de Jhelum, dos quais 6 espécimes foram capturados no local usando rede manual. Todos os espécimes capturados eram machos. Esses morcegos foram identificados por suas características faciais únicas, uma folha nasal ereta e alongada, grandes orelhas ovais que se juntam acima da testa e sem cauda. O comprimento médio da cabeça e do corpo dos espécimes capturados foi de 80 mm, o comprimento do antebraço foi de 67 mm, enquanto os comprimentos médios do 3º, 4º e 5º metacarpos foram de 51,73 mm, 55,17 mm e 60,42 mm, respectivamente. O comprimento médio do crânio foi de 29,84 mm, e a largura da caixa craniana, de 12,77 mm. O comprimento médio do pênis de duas amostras foi de 6,6 mm, e o comprimento total do báculo foi de 3,08 mm. Este é o primeiro registro de Megadermalyra no distrito de Jhelum.

Stapled α-helical peptide drug development: a potent dual inhibitor of MDM2 and MDMX for p53-dependent cancer therapy.

Stapled α-helical peptides have emerged as a promising new modality for a wide range of therapeutic targets. Here, we report a potent and selective dual inhibitor of MDM2 and MDMX, ATSP-7041, which effectively activates the p53 pathway in tumors in vitro and in vivo. Specifically, ATSP-7041 binds both MDM2 and MDMX with nanomolar affinities, shows submicromolar cellular activities in cancer cell lines in the presence of serum, and demonstrates highly specific, on-target mechanism of action. A high resolution (1.7-Å) X-ray crystal structure reveals its molecular interactions with the target protein MDMX, including multiple contacts with key amino acids as well as a role for the hydrocarbon staple itself in target engagement. Most importantly, ATSP-7041 demonstrates robust p53-dependent tumor growth suppression in MDM2/MDMX-overexpressing xenograft cancer models, with a high correlation to on-target pharmacodynamic activity, and possesses favorable pharmacokinetic and tissue distribution properties. Overall, ATSP-7041 demonstrates in vitro and in vivo proof-of-concept that stapled peptides can be developed as therapeutically relevant inhibitors of protein-protein interaction and may offer a viable modality for cancer therapy.

Shotgun cholanomics of ileal fluid.

In this study we have developed a rapid method for the shotgun analysis of bile acids in intestinal fluid. The method is semi-quantitative, and requires little sample preparation. Bile salts might contribute to the pathogenesis of Crohn's disease. In a pilot study we demonstrate the method by analysing the bile acid content of ileal fluid from seven Crohn's disease patients and three healthy controls. The dominant bile acids observed were di and/or trihydroxycholanoates, di- and/or trihydroxycholanoylglycines, di- and/or tri-hydroxycholanoyltaurines, monosulphated dihydroxycholanoates and monosulphated dihydroxycholanoylglycine. The method can be similarly applied to samples derived from other parts of the intestine.

Lipidomic profiling in Crohn's disease: abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition.

Crohn's disease is a chronic inflammatory condition largely affecting the terminal ileum and large bowel. A contributing cause is the failure of an adequate acute inflammatory response as a result of impaired secretion of pro-inflammatory cytokines by macrophages. This defective secretion arises from aberrant vesicle trafficking, misdirecting the cytokines to lysosomal degradation. Aberrant intestinal permeability is also well-established in Crohn's disease. Both the disordered vesicle trafficking and increased bowel permeability could result from abnormal lipid composition. We thus measured the sphingo- and phospholipid composition of macrophages, using mass spectrometry and stable isotope labelling approaches. Stimulation of macrophages with heat-killed Escherichia coli resulted in three main changes; a significant reduction in the amount of individual ceramide species, an altered composition of phosphatidylcholine, and an increased rate of phosphatidylcholine synthesis in macrophages. These changes were observed in macrophages from both healthy control individuals and patients with Crohn's disease. The only difference detected between control and Crohn's disease macrophages was a reduced proportion of newly-synthesised phosphatidylinositol 16:0/18:1 over a defined time period. Shotgun lipidomics analysis of macroscopically non-inflamed ileal biopsies showed a significant decrease in this same lipid species with overall preservation of sphingolipid, phospholipid and cholesterol composition.

Defective tumor necrosis factor release from Crohn's disease macrophages in response to Toll-like receptor activation: relationship to phenotype and genome-wide association susceptibility loci.

BACKGROUND: Recent work provides evidence of a failure of acute inflammation in Crohn's disease (CD), and suggests that the primary defect operates at the level of the macrophage and cytokine release. Here we extend the characterization of the innate immune defect in CD by investigating the macrophage response to Toll-like receptor (TLR) agonists and assess potential links between genome-wide association study (GWAS) susceptibility loci, disease phenotype, and therapeutic regimens on tumor necrosis factor α (TNF) release. METHODS: Peripheral blood-derived macrophages were cultured from control subjects and patients with CD, stimulated with TLR ligands, and the release of TNF measured. Genomic DNA was purified from blood and genotyped for 34 single nucleotide polymorphisms (SNPs) identified as being associated with CD by GWAS. RESULTS: All stimuli resulted in a reduction (32%-48%) in TNF release from macrophages derived from CD patients (n = 28-101) compared to those from healthy control (HC) subjects. All phenotypes demonstrated impaired TNF release, with the greatest defect in patients with colonic disease. There was no detectable relationship between the level of TNF released and the presence of GWAS susceptibility loci in CD patients. Reduced TNF levels were not influenced by age, gender, or use of aminosalicylate (5-ASA) medication. CONCLUSIONS: This study supports the hypothesis of defective proinflammatory cytokine secretion and an innate immunodeficiency in CD. Abnormal TNF secretion is evident downstream of multiple TLRs, affects all disease phenotypes, and is unrelated to 34 polymorphisms associated with CD by GWAS.