Inappropriate laboratory test utilization in outpatient tertiary care: Implications for value-based healthcare.

OBJECTIVES: To assess the rate of inappropriate repetition of laboratory testing and estimate the cost of such testing for thyroid stimulating hormone (TSH), total cholesterol, vitamin D, and vitamin B12 tests. METHODS: A retrospective cohort study was carried out in the Family Medicine and Polyclinic Department at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Clinical and laboratory data were collected between 2018-2021 for the 4 laboratory tests. The inappropriate repetition of tests was defined according to international guidelines and the costs were calculated using the hospital prices. RESULTS: A total of 109,929 laboratory tests carried out on 23,280 patients were included in this study. The percentage of inappropriate tests, as per the study criteria, was estimated to be 6.1% of all repeated tests. Additionally, the estimated total cost wasted amounted to 2,364,410 Saudi Riyals. Age exhibited a weak positive correlation with the total number of inappropriate tests (r=0.196, p=0.001). Furthermore, significant differences were observed in the medians of the total number of inappropriate tests among genders and nationalities (p<0.001). CONCLUSION: The study identified significantly high rates of inadequate repetitions of frequently requested laboratory tests. Urgent action is therefore crucial to overcoming such an issue.

Microbiome function and neurodevelopment in Black infants: vitamin B12 emerges as a key factor.

The early life gut microbiome affects the developing brain, and therefore may serve as a target to support neurodevelopment of children living in stressful and under-resourced environments, such as Black youth living on the South Side of Chicago, for whom we observe racial disparities in health. Microbiome compositions/functions key to multiple neurodevelopmental facets have not been studied in Black children, a vulnerable population due to racial disparities in health; thus, a subsample of Black infants living in urban, low-income neighborhoods whose mothers participated in a prenatal nutrition study were recruited for testing associations between composition and function of the gut microbiome (16S rRNA gene sequencing, shotgun metagenomics, and targeted metabolomics of fecal samples) and neurodevelopment (developmental testing, maternal report of temperament, and observed stress regulation). Two microbiome community types, defined by high Lachnospiraceae or Enterobacteriaceae abundance, were discovered in this cohort from 16S rRNA gene sequencing analysis; the Enterobacteriaceae-dominant community type was significantly negatively associated with cognition and language scores, specifically in male children. Vitamin B12 biosynthesis emerged as a key microbiome function from shotgun metagenomics sequencing analysis, showing positive associations with all measured developmental skills (i.e., cognition, language, motor, surgency, effortful control, and observed stress regulation). Blautia spp. also were identified as substantial contributors of important microbiome functions, including vitamin B12 biosynthesis and related vitamin B12-dependent microbiome functions, anti-inflammatory microbial surface antigens, competitive mechanisms against pathobionts, and production of antioxidants. The results are promising with respect to the potential for exploring therapeutic candidates, such as vitamin B12 nutritional or Blautia spp. probiotic supplementation, to support the neurodevelopment of infants at risk for experiencing racial disparities in health.

Recent Advances in Dietary Sources, Health Benefits, Emerging Encapsulation Methods, Food Fortification, and New Sensor-Based Monitoring of Vitamin B12: A Critical Review.

In this overview, the latest achievements in dietary origins, absorption mechanism, bioavailability assay, health advantages, cutting-edge encapsulation techniques, fortification approaches, and innovative highly sensitive sensor-based detection methods of vitamin B12 (VB12) were addressed. The cobalt-centered vitamin B is mainly found in animal products, posing challenges for strict vegetarians and vegans. Its bioavailability is highly influenced by intrinsic factor, absorption in the ileum, and liver reabsorption. VB12 mainly contributes to blood cell synthesis, cognitive function, and cardiovascular health, and potentially reduces anemia and optic neuropathy. Microencapsulation techniques improve the stability and controlled release of VB12. Co-microencapsulation of VB12 with other vitamins and bioactive compounds enhances bioavailability and controlled release, providing versatile initiatives for improving bio-functionality. Nanotechnology, including nanovesicles, nanoemulsions, and nanoparticles can enhance the delivery, stability, and bioavailability of VB12 in diverse applications, ranging from antimicrobial agents to skincare and oral insulin delivery. Staple food fortification with encapsulated and free VB12 emerges as a prominent strategy to combat deficiency and promote nutritional value. Biosensing technologies, such as electrochemical and optical biosensors, offer rapid, portable, and sensitive VB12 assessment. Carbon dot-based fluorescent nanosensors, nanocluster-based fluorescent probes, and electrochemical sensors show promise for precise detection, especially in pharmaceutical and biomedical applications.

Assessment of vitamin B12 levels and cardiovascular risk factors in metformin- and non-metformin-treated type 2 diabetic patients.

Oxidative stress enhances cardiovascular risk. Metformin decreases intestinal absorption of vitamin B12. Our objective was the evaluation of type 2 diabetics focusing on differences due to their treatment. A prospective study on 224 type 2 diabetics was realized between 2015-2018 in Targu Mures, Romania, divided into 2 subgroups (metformin vs. other therapy - 2nd/3rd generation sulfonylureas, insulin, dietary regimen -, followed for at least one year) and non-diabetic controls (n=25) for oxidative stress level comparison. Serum homocysteine (HC), vitamin B12 were determined by chemiluminescence (Immulite One). Lipid peroxidation was assessed by serum malondialdehyde (MDA) measurement (HPLC). Biochemical tests, minerals, cystatin C, high-sensitivity C reactive protein (hs-CRP) were measured on Konelab20Xti, glycated hemoglobin on Nycocard Reader. GraphPad InStat-3 was used for statistics. Negative correlation occured between serum vitamin B12 and HC, this vitamin's level was significantly lower and serum zinc was significantly higher in patients on metformin. Hyperhomocysteinemia was present in 87% of the subjects, 46% had zinc deficiency and 41% elevated hs-CRP. Serum cystatin C showed positive correlation with creatinine. Serum MDA was significantly higher in diabetics compared to control patients. Elevated hs-CRP and homocysteine represent raised cardiovascular risk. Intense oxidative stress, vitamin, mineral deficiencies are frequent in diabetic subjects.

A Cell-Free Biosensor for Assessment of Hyperhomocysteinemia.

Hyperhomocysteinemia─a condition characterized by elevated levels of homocysteine in the blood─is associated with multiple health conditions including folate deficiency and birth defects, but there are no convenient, low-cost methods to measure homocysteine in plasma. A cell-free biosensor that harnesses the native homocysteine sensing machinery of Escherichia coli bacteria could satisfy the need for a detection platform with these characteristics. Here, we describe our efforts to engineer a cell-free biosensor for point-of-care, low-cost assessment of homocysteine status. This biosensor can detect physiologically relevant concentrations of homocysteine in plasma with a colorimetric output visible to the naked eye in under 1.5 h, making it a fast, convenient tool for point-of-use diagnosis and monitoring of hyperhomocysteinemia and related health conditions.

The Continued Need for the Routine Assessment of Folate Status.

OBJECTIVE: The Choosing Wisely initiative recommended cessation of folate measurement, suggesting folate supplementation in macrocytic anemia. This study reviewed the need for continued blood folate testing at a large SafetyNet county teaching hospital. METHODS: Red blood cell (RBC) folate, vitamin B12, iron, ferritin, and hemoglobin results were obtained for utilization review. RESULTS: Of the 593 RBC folate results, 69 (11.7%) were deficient and 30 (5%) had high values. Collectively, 369 (73.9%) had normal vitamin B12 levels, 342 (70%) had low hemoglobin, 184 (62.5) had normal and 57 (19.4%) had low ferritin, 122 (38.2%) had normal and 188 (59%) had low iron levels. A total of 41 (12%) had normal folate, low ferritin, low hemoglobin, and low iron, suggestive of iron deficiency anemia. There were 11 patients who exhibited low folate, low or normal ferritin, low hemoglobin, and low iron levels, suggesting combined folate and iron deficiency anemias. CONCLUSION: This study highlights the need for institutions to assess the applicability of national recommendations to their local population.

Fabrication of a Vitamin B12-Loaded Carbon Dot/Mixed-Ligand Metal Organic Framework Encapsulated within the Gelatin Microsphere for pH Sensing and In Vitro Wound Healing Assessment.

Bacterial invasion is a serious concern during the wound healing process. The colonization of bacteria is mainly responsible for the pH fluctuation at the wound site. Therefore, the fabrication of a proper wound dressing material with antibacterial activity and pH monitoring ability is necessary to acquire a fast healing process. Therefore, this work is dedicated to designing a vitamin B12-loaded gelatin microsphere (MS) decorated with a carbon dot (CD) metal-organic framework (MOF) for simultaneous pH sensing and advanced wound closure application. The resultant MS portrayed a high specific surface area and a hierarchically porous structure. Furthermore, the surface of the resultant MS contained numerous carboxyl groups and amine groups whose deprotonation and protonation with the pH alternation are accountable for the pH-sensitive properties. The vitamin B12 release study was speedy from the MOF structure in an acidic medium, which was checked by gelatin coating, and a controlled drug release behavior was observed. The system showed excellent cytocompatibility toward the L929 cell line and remarkable antibacterial performance against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. Furthermore, the combined effect of Zn2+, the imidazole unit, and CDs produces an outstanding bactericidal effect on the injury sites. Finally, the in vitro wound model suggests that the presence of the vitamin B12-loaded gelatin MS accelerates the proliferation of resident fibroblast L929 cells and causes tissue regeneration in a time-dependent manner. The relative wound area, % of wound closure, and wound healing speed values are remarkable and suggest the requirement for assessing the response of the system before exploiting its prospective in vivo application.

An assessment of serum vitamin B12 and folate in patients with Crohn's disease.

Crohn's disease is a chronic inflammatory condition that can involve any area in the gastrointestinal tract often involving the distal ileum where vitamin B12 is specifically absorbed. The aim of this study was to ascertain serum vitamin B12 and folate levels in order to investigate the correlation among these vitamin levels and disease activation, localization, duration and age at the onset of the disease. Study population included 103 patients with Crohn's disease and a healthy control group of 114 individuals. C-reactive protein, vitamin B12, folate levels were studied along with hemogram analyses. The results were evaluated in statistical comparisons. While serum vitamin B12 levels and serum folate levels were 161.9 ±â€…63.2(73-496) pg/mL and 4.9 ±â€…1.4(1.2-9.4) ng/mL in the Crohn's patient group respectively, they were 321.7 ±â€…126.3(85-680) pg/mL and 7.6 ±â€…3.8(3-25.1) ng/mL in the control group respectively. Vitamin B12 and folate levels were distinctly lower in patients with Chron's disease than those of the control group (P < .001). The intragroup analysis of the patient group revealed that low vitamin B12 levels were significantly lower in the moderate group classified according to the Crohn's Disease Activity Index (P < .001), along with those in the L1 group with terminal/distal ileal involvement (P < .001). Vitamin B12 and folate deficiencies are quite prevalent in patients with Crohn's disease while this condition can lead to various complications and they prove to be important risk factors associated especially with thrombosis and its complications. Patients must be regularly followed-up for vitamin B12 and folate levels to supplement them where needed.

Affordable Nutrient Density in Brazil: Nutrient Profiling in Relation to Food Cost and NOVA Category Assignments.

Affordable nutrient density is provided by low-cost and nutrient-rich foods. We explored nutrient density, cost, and NOVA category assignments within and across food groups in Brazil. The nutrient density of the foods (n = 591) was assessed using the Nutrient Rich Food Index (NRF9.3) based on protein, fiber, vitamin A (RAE), vitamin C, vitamin E (mg), Ca, Fe, K and Mg; and NRF6.3 score for priority nutrients: Ca, Fe, Zn, vitamin A, vitamin B12, and folate. Nutrients to limit (LIM) were saturated fat, added sugar, and sodium. Affordability was defined as the ratio of energy and/or nutrient density of foods and retail price per 100 kcal. Foods were classified as minimally processed (n = 106), processed (n = 188), ultra-processed (n = 286), and culinary ingredients (n = 11). Nutrient density was positively linked to per 100 kcal food cost. Ultra-processed foods (UPF) contained more energy, fat, sugar, and salt and had lower NRF scores compared to minimally processed (MPF) foods. UPF was also less expensive than MPF foods. Nutrient-rich foods below the median per 100 kcal costs included MPF foods, but also processed foods (PF) and UPF. Affordable nutrient-rich foods can be found in the different categories of the NOVA classification.

A Retrospective Study on Clinical Assessment of Cognitive Impairment in a Swedish Cohort: Is There Inequality Between Natives and Foreign-Born?

BACKGROUND: People with a migration background are underrepresented in dementia research and disfavored in assessment and treatment, and many foreign-born individuals with dementia remain undiagnosed. OBJECTIVE: The aim of this study was to examine whether there is inequality in the clinical assessment of dementia between native and foreign-born individuals in Sweden. METHODS: Information was gathered retrospectively from a cohort of 91 native and 36 foreign-born patients attending four memory clinics in Skåne, Sweden. Data included information on cognitive test results, cerebrospinal fluid biomarkers, scores at structural imaging scales of global cortical atrophy (GCA), medial temporal lobe atrophy (MTA) and the Fazekas scale, laboratory measures of thyroid-stimulating hormone, calcium, albumin, homocysteine, hemoglobin, cobalamin (vitamin B12), and folate (vitamin B9), contact with health care, and treatment. RESULTS: Foreign-born patients had lower educational level and scored lower on Mini-Mental State Examination and Clock Drawing Test (p < 0.001-0.011). Relatives initiated contact with health care to a higher extent in the foreign-born group (p = 0.031). Foreign-born patients had less white matter lesions (p = 0.018). Additionally, Alzheimer's disease (AD) biomarkers were significantly less used in foreign-born patients to support an AD diagnosis (p = 0.001). No significant differences were found for scores on GCA and MTA, laboratory measures, or initiated treatment. CONCLUSION: Although native and foreign-born patients were predominantly homogenous regarding examined variables, differences in the diagnostic process and underlying biological correlates of dementia exist and need to be further investigated in a larger sample.

Association Between Folic Acid Prescription Fills and Suicide Attempts and Intentional Self-harm Among Privately Insured US Adults.

Importance: Suicide is a leading cause of death in the United States, having increased more than 30% from 2000 to 2018. An inexpensive, safe, widely available treatment for preventing suicidal behavior could reverse this trend. Objective: To confirm a previous signal for decreased risk of suicide attempt following prescription fills for folic acid in a national pharmacoepidemiologic study of patients treated with folic acid. Design, Setting, and Participants: A within-person exposure-only cohort design was used to study the dynamic association between folic acid (vitamin B9) prescription fills over a 24-month period and suicide attempts and intentional self-harm. Data were collected from a pharmacoepidemiologic database of US medical claims (MarketScan) for patients with private health insurance who filled a folic acid prescription between 2012 and 2017. The same analysis was repeated with a control supplement (cyanocobalamin, vitamin B12). Data were analyzed from August 2021 to June 2022. Exposure: Folic acid prescription fills. Main Outcome and Measure: Suicide attempt or intentional self-harm resulting in an outpatient visit or inpatient admission as identified by codes from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification. Results: Data on 866 586 patients were collected; 704 514 (81.30%) were female, and 90 296 (10.42%) were 60 years and older. Overall, there were 261 suicidal events during months covered by a folic acid prescription (5 521 597 person-months) for a rate of 4.73 per 100 000 person-months, compared with 895 suicidal events during months without folic acid (8 432 340) for a rate of 10.61 per 100 000 person-months. Adjusting for age and sex, diagnoses related to suicidal behavior, diagnoses related to folic acid deficiency, folate-reducing medications, history of folate-reducing medications, and history of suicidal events, the hazard ratio (HR) for folic acid for suicide events was 0.56 (95% CI, 0.48-0.65), with similar results for the modal dosage of 1 mg of folic acid per day (HR, 0.57; 95% CI, 0.48-0.69) and women of childbearing age (HR, 0.60; 95% CI, 0.50-0.73). A duration-response analysis (1-mg dosage) revealed a 5% decrease in suicidal events per month of additional treatment (HR, 0.95; 95% CI, 0.93-0.97). The same analysis for the negative control, cyanocobalamin, found no association with suicide attempt (HR, 1.01; 95% CI, 0.80-1.27). Conclusions and Relevance: This large-scale pharmacoepidemiologic study of folic acid found a beneficial association in terms of lower rates of suicide attempts. The results warrant the conduct of a randomized clinical trial with suicidal ideation and behavior as outcomes of interest. If confirmed, folic acid may be a safe, inexpensive, and widely available treatment for suicidal ideation and behavior.

The need and safety of vitamin supplementation in adults with obesity within 9 months post sleeve gastrectomy (SG): assessment based on intake.

The aim of the study was to assess the need and safety of vitamin supplementation in adults with obesity post bariatric surgery (SG), based on intake assessment. Patients with obesity class III, and with obesity class II with comorbidities were followed up at 3, 6 and 9 months post bariatric surgery. Based on a 4-day food record questionnaire, the intake of vitamins and calories was assessed and an interview regarding the consumption of supplements was conducted. The study showed a deficiency in the dietary intake of vitamin D, folate (B9) and vitamin B1 (in 93-100% of respondents), vitamins E and C (in 53-67% of respondents), vitamins A, PP and vitamins B2 and B6 (in 10 to 23% of respondents) and vitamin B12 (only 1 woman). The intake of multivitamin supplements was implemented by 72% of respondents, independently, all patients were taking a vitamin D supplement. Vitamin deficiencies were only reported in a small percentage of patients (3-17%), who did not take supplements throughout the observation period. Supplementation with vitamins D, E, C, B1 and folic acid (B9), used regularly, supplemented the nutritional deficiencies of patients. The intake of vitamin A, B2, PP, and B6 with supplements did not significantly affect the overall intake. Supplementation with vitamin B12 turned out to be unjustified to the nutritional recommendations. The dietary and/or supplemental intake of vitamins did not exceed the tolerable upper intake level (UL). The results of the study confirm the need to implement vitamin supplementation for bariatric patients and its safety.

Assessment of Photoreleasable Linkers and Light-Capturing Antennas on a Photoresponsive Cobalamin Scaffold.

Cobalamin has shown promise as a light-sensitive drug delivery platform owing to its ease of modification and the high quantum yields for drug photorelease. However, studies to date on the general photochemistry of alkyl cobalamins have primarily focused on methyl and adenosyl-substituted derivatives, the natural cofactors present in various enzymatic species. We describe the synthesis and photolytic behavior of cobalamin conjugates comprised of different combinations of fluorophores and ß-axial ligands. In general, cobalamin conjugates containing ß-axial alkyl substituents undergo efficient photolysis under aqueous conditions, with quantum yields up to >40%. However, substituents that are large and hydrophobic, or unable to readily support the presumed radical intermediate, suffer less efficient photolysis (<15%) than smaller, water-soluble, analogs. By contrast, quantum yields improve by 2-fold in DMF for cobalamins containing large hydrophobic ß-axial substituents. This suggests that drug release from carriers comprised of membranous compartments, such as liposomes, may be significantly more efficient than the corresponding photorelease in an aqueous environment. Finally, we explored the impact of fluorophores on the photolysis of alkyl cobalamins under tissue-mimetic conditions. Cobalamins substituted with efficient photon-capturing fluorophores display up to 4-fold enhancements in photolysis relative to unsubstituted derivatives. In summary, we have shown that the photosensitivity of alkyl cobalamin conjugates can be tuned by altering the Co-appended alkyl moiety, modulating the polarity of the environment (solvent), and installing photon-capturing fluorophores onto the cobalamin framework.

Avaliação da deficiência de vitamina B12 em idosos usuários e não usuários de metformina / Assessment of B12 deficiency in older adults using metformin or not

Introdução: Sendo a metformina um dos principais tratamentos para o Diabetes Mellitus, torna-se necessário verificar seus efeitos colaterais. A redução nos níveis de vitamina B12 está entre os causadores de consequências importantes na população. Este estudo objetivou determinar o nível de vitamina B12 em usuários e não usuários de metformina de um ambulatório de geriatria no sul de Santa Catarina e avaliar fatores que possam interferir no nível desta vitamina. Métodos: Caracteriza-se como pesquisa quantitativa, observacional, retrospectiva, com coleta de dados secundários. Foram incluídos na pesquisa pacientes idosos com níveis de vitamina B12 documentados em prontuário e excluídos prontuários com ausência de dados e pacientes que fazem suplementação da vitamina. Após a seleção, foram analisados 131 prontuários de pacientes atendidos no período de 2016 e 2017 no Ambulatório de Geriatria das Clínicas Integradas de Saúde da Universidade do Extremo Sul Catarinense. Resultados: Dos pacientes que possuem deficiência de vitamina B12, 26,4% fazem uso de metformina. Dos pacientes que usam metformina, 36,8% possuem deficiência de vitamina B12. No uso de IBP, 39,6% apresentaram deficiência, e naqueles em uso concomitante de metformina e IBP, 9,4% apresentaram deficiência da vitamina. Conclusão: Apesar dos testes estatísticos não apresentarem associação estatisticamente significativa entre o uso de metformina e a deficiência de vitamina B12, os dados do presente estudo mostraram prevalência de deficiência da vitamina na amostra (40,4%). Sugere-se que isso é uma consequência importante da droga e mostra a necessidade de novos estudos na deficiência da vitamina e as suas consequências.

Introduction: As metformin is one of the main treatment options for diabetes mellitus, it is necessary to analyze its side effects. A reduction in B12 levels is one of the causes of important consequences to the population. This study aimed to determine B12 levels in patients who used metformin and those who did not in a geriatric outpatient clinic in southern Santa Catarina, assessing factors that could interfere with the levels of this vitamin. Methods: This is a quantitative, observational, retrospective study, with secondary data collection. We included older patients with B12 levels registered in their medical records and excluded records with missing data and patients who did vitamin replacement. After patient selection, we analyzed 131 medical records of patients seen between 2017 and 2017 at the geriatric outpatient clinic of Clínicas Integradas de Saúde, at Universidade do Extremo Sul Catarinense. Results: Among patients with B12 deficiency, 26.4% used metformin. Out of those using metformin, 36.8% had vitamin B12 deficiency. Among those who used proton-pump inhibitors (PPI), 39.6% had a vitamin deficiency, and considering those who simultaneously used metformin and PPI, 9.4% had a vitamin deficiency. Conclusion: Although statistical tests did not identify a statistically significant association between metformin use and vitamin B12 deficiency, our data showed a prevalence of vitamin deficiency in our sample (40.4%). We suggest that this could be an important consequence of this medication and highlight the need for new studies on B12 deficiency and its consequences.

Clinicopathological Analysis and Prognostic Assessment of TCN1 in Patients with Gastric Cancer.

BACKGROUND: Stomach cancer is the fourth most common type of cancer worldwide. TCN1 mainly encodes the vitamin B12 transporter, transcobalamin. TCN1 is a marker of gastrointestinal tumor progression, but the impact of TCN1 on survival is unclear. MATERIAL/METHODS: Gastrointestinal tumor records were reviewed and analyzed, clinicopathological data were summarized, immunohistochemical detection of TCN1 was performed again, and the protein expression in tumor tissue, non-tumor tissue, and lymph nodes was semi-quantitatively analyzed. Patients were followed up for 5 years to determine the 5-year survival rates. RESULTS: The strong immune reactivity of the TCN1 protein was significantly correlated with tumor invasion depth, regional lymph nodes, and a tumor diameter of >5 cm (Z = -2.531 and P = .016; Z = 3.785 and P < .001; Z = 2.541 and P = .049). Kaplan-Meier survival analysis showed that the total survival time of patients in the low-expression TCN1 group was significantly longer than that in the high-expression TCN1 group (P = .001; Table 2 and Figure 5). The mean survival time of all patients was 49.774 months (95% CI: 47.871-51.676; Table 4) and the 5-year overall survival rates were 73.3, 50.8, and 34.0%, respectively. Multivariate analysis revealed that regional lymph nodes (HR = 1.253; 95% CI: 1.031-1.747, P = .012), TCN1 immune expression status (HR = 2.707; 95% CI: 1.068-1.886, P = .016), and pTNM staging (HR = 2.293; 95% CI: 1.583-3.321; P = .001) were independent risk factors for poor survival. CONCLUSION: The high expression of TCN1 in gastric tumor tissues was found to be associated with the clinicopathological factors of patients, and the high expression of TCN1 was shown to indicate a poor clinical prognosis.

Economic impact of gastrointestinal nematodes in Morada Nova sheep in Brazil / Impacto econômico de nematódeos gastrintestinais em ovinos Morada Nova no Brasil

Abstract This study evaluated the economic impact of gastrointestinal nematode (GIN) infection in Morada Nova lambs under different parasite chemical control conditions. For this, 246 lambs, in the rainy and dry season, were randomized into groups according to their anthelmintic treatment with levamisole: control (CT: no treatment); routine treatment (RT: treated every 42 days); and targeted selective treatment (TST: treated according to the average daily weight gain, DWG). From 63 days of age (D63) to D210, the lambs were weighed and monitored for GIN infection parameters. Spending on anthelmintics in the production system was 1.3% of the total economic result. The economic result per animal (R$ 5.00 = US$ 1.00) was higher in the RT group, amounting to US$ 6.60 in the rainy and US$ 5.69 in the dry season, due to higher DWG. Thus, RT presented economic results 14.4% and 10.9% higher than CT, and 7.2% and 1.9% higher than TST, in the rainy and dry season, respectively. However, fast development of resistance made RT unfeasible. Here, the economic impact of GIN infection on a national scale is discussed, demonstrating its importance and the impossibility of profitable and sustainable sheep production without adequate control.

Resumo Este estudo avaliou o impacto econômico da infecção por nematoides gastrintestinais (NGI), em cordeiros Morada Nova, sob diferentes condições de controle químico dos parasitas. Para isso, 246 cordeiros, na estação chuvosa e seca, foram randomizados em grupos de acordo com o tratamento com levamisol: controle (TC: sem tratamento); tratamento rotineiro (TR: tratado a cada 42 dias); e tratamento seletivo direcionado (TST: tratado de acordo com o ganho de peso médio diário, GMD). Dos 63 dias de idade (D63) ao D210, os cordeiros foram pesados ​​e monitorados quanto aos parâmetros de infecção por NGI. O gasto com anti-helmínticos no sistema produtivo foi de 1,3% do resultado econômico total. O resultado econômico por animal (R$ 5,00 = US$ 1,00) foi maior no grupo RT, totalizando US$ 6,60 na estação chuvosa e US$ 5,69 na seca, devido ao maior GMD. Assim, o RT apresentou resultados econômicos 14,4% e 10,9% superiores ao TC, e 7,2% e 1,9% superiores ao TST, no período chuvoso e seco, respectivamente. Entretanto o rápido desenvolvimento de resistência inviabiliza o TR. O impacto econômico da infecção por NGI em escala nacional são aqui discutidos, demonstrando sua importância e a impossibilidade de uma ovinocultura lucrativa e sustentável sem o controle adequado.

Microbial and Genetic Resources for Cobalamin (Vitamin B12) Biosynthesis: From Ecosystems to Industrial Biotechnology.

Many microbial producers of coenzyme B12 family cofactors together with their metabolically interdependent pathways are comprehensively studied and successfully used both in natural ecosystems dominated by auxotrophs, including bacteria and mammals, and in the safe industrial production of vitamin B12. Metabolic reconstruction for genomic and metagenomic data and functional genomics continue to mine the microbial and genetic resources for biosynthesis of the vital vitamin B12. Availability of metabolic engineering techniques and usage of affordable and renewable sources allowed improving bioprocess of vitamins, providing a positive impact on both economics and environment. The commercial production of vitamin B12 is mainly achieved through the use of the two major industrial strains, Propionobacterium shermanii and Pseudomonas denitrificans, that involves about 30 enzymatic steps in the biosynthesis of cobalamin and completely replaces chemical synthesis. However, there are still unresolved issues in cobalamin biosynthesis that need to be elucidated for future bioprocess improvements. In the present work, we review the current state of development and challenges for cobalamin (vitamin B12) biosynthesis, describing the major and novel prospective strains, and the studies of environmental factors and genetic tools effecting on the fermentation process are reported.

A New Approach for Dry Eye Management By Mucoadhesive In situ Gel of Vitamin B12: Formulation, In vitro and In vivo Assessment.

The commitment of the existent study was to develop a mucoadhesive in situ gel systems of vitamin B12 for the management of dry eye disease. The gels were prepared using pluronic F-127 and either of chitosan, carbapol 971P, sodium alginate, or hydroxy propyl methyl cellulose. Drug-excipients compatibility was investigated by means of differential scanning calorimetry and Fourier transform infrared spectroscopy. The gels were characterized for pH, clarity, gelling capacity, viscosity, and adhesion. In vitro release of vitamin B12 from the selected gels was investigated. In vivo effectiveness of the selected gel was determined in rabbit models using Schirmer's and fluorescein tests. The compatibility studies revealed the possibility of incidence of drug/polymer interaction in some formulations. F2-containing pluronic F127 and hydroxypropyl methyl cellulose showed the most appropriate physical characterization and in vitro release profile. The prepared gels showed prolonged drug release with drug release mechanism of combined diffusion and erosion. The in vivo study revealed good effectiveness of the prepared mucoadhesive in situ gel system of vitamin B12 in the treatment of dry eye disease that was comparable to that of the marketed drops.

[Vitamin B12 in practice: When to test ? How to test ? And who should be treated?] / Vitamine B12 en pratique : quand tester ? Comment tester ? Et qui substituer ?

Vitamin B12 deficiency is common in outpatients and inpatient populations, with potentially severe neuropsychiatric and hematological impact, which requires timely diagnosis and treatment. The different diagnostic tests all have their limitations but can be combined, sequentially. We propose to review the treatment options according to the different etiologies of the deficiency, highlighting the costs of the therapies and their coverage by the health insurance.

La carence en vitamine B12 est fréquente en médecine ambulatoire et hospitalière, avec des conséquences neuropsychiatriques et hématologiques potentiellement sévères, nécessitant un diagnostic et un traitement adéquat. Les différents tests diagnostiques ont tous leurs limitations mais peuvent être utilisés de manière complémentaire. Nous proposons de refaire un point sur les possibilités de traitement en fonction des différentes étiologies de la carence, en mettant notamment en exergue les différents coûts des thérapies et leur prise en charge par l'assurance de base.

Folate and Cobalamin Serum Levels in Healthy Children and Adolescents and Their Association with Age, Sex, BMI and Socioeconomic Status.

This study proposes age- and sex-specific percentiles for serum cobalamin and folate, and analyzes the effects of sex, age, body mass index (BMI), and socioeconomic status (SES) on cobalamin and folate concentrations in healthy children and adolescents. In total, 4478 serum samples provided by healthy participants (2 months-18.0 years) in the LIFE (Leipzig Research Centre for Civilization Diseases) Child population-based cohort study between 2011 and 2015 were analyzed by electrochemiluminescence immunoassay (ECLIA). Continuous age-and sex-related percentiles (2.5th, 10th, 50th, 90th, 97.5th) were estimated, applying Cole's LMS method. In both sexes, folate concentrations decreased continuously with age, whereas cobalamin concentration peaked between three and seven years of age and declined thereafter. Female sex was associated with higher concentrations of both vitamins in 13- to 18-year-olds and with higher folate levels in one- to five-year-olds. BMI was inversely correlated with concentrations of both vitamins, whilst SES positively affected folate but not cobalamin concentrations. To conclude, in the assessment of cobalamin and folate status, the age- and sex-dependent dynamic of the respective serum concentrations must be considered. While BMI is a determinant of both vitamin concentrations, SES is only associated with folate concentrations.