Voriconazole metabolism is associated with the number of skin cancers per patient.

Voriconazole exposure is associated with skin cancer, but it is unknown how the full spectrum of its metabolizer phenotypes impacts this association. We conducted a retrospective cohort study to determine how variation in metabolism of voriconazole as measured by metabolizer status of CYP2C19 is associated with the total number of skin cancers a patient develops and the rate of development of the first skin cancer after treatment. There were 1,739 organ transplant recipients with data on CYP2C19 phenotype. Of these, 134 were exposed to voriconazole. There was a significant difference in the number of skin cancers after transplant based on exposure to voriconazole, metabolizer phenotype, and the interaction of these two (p < 0.01 for all three). This increase was driven primarily by number of squamous cell carcinomas among rapid metabolizes with voriconazole exposure (p < 0.01 for both). Patients exposed to voriconazole developed skin cancers more rapidly than those without exposure (Fine-Grey hazard ratio 1.78, 95% confidence interval 1.19-2.66). This association was similarly driven by development of SCC (Fine-Grey hazard ratio 1.83, 95% confidence interval 1.14-2.94). Differences in voriconazoles metabolism are associated with an increase in the number of skin cancers developed after transplant, particularly SCC.

Effects of a Singular Dose of Mangiferin-Quercetin Supplementation on Basketball Performance: A Double-Blind Crossover Study of High-Level Male Players.

Pre-exercise mangiferin-quercetin may enhance athletic performance. This study investigated the effect of mangiferin-quercetin supplementation on high-level male basketball players during a basketball exercise simulation test (BEST) comprising 24 circuits of 30 s activities with various movement distances. The participants were divided into two groups (EXP = 19 and CON = 19) and given a placebo one hour before the BEST (PRE-condition). The following week, the EXP group received mangiferin-quercetin (84 mg/140 mg), while the CON group received a placebo (POST-condition) before the BEST in a double-blind, cross-over design. The mean heart rate (HR) and circuit and sprint times (CT and ST) during the BEST were measured, along with the capillary blood lactate levels (La-), the subjective rating of muscle soreness (RPMS), and the perceived exertion (RPE) during a resting state prior to and following the BEST. The results showed significant interactions for the mean CT (p = 0.013) and RPE (p = 0.004); a marginal interaction for La- (p = 0.054); and non-significant interactions for the mean HR, mean ST, and RPMS. Moreover, the EXP group had significantly lower values in the POST condition for the mean CT (18.17 ± 2.08 s) and RPE (12.42 ± 1.02) compared to the PRE condition (20.33 ± 1.96 s and 13.47 ± 1.22, respectively) and the POST condition of the CON group (20.31 ± 2.10 s and 13.32 ± 1.16, respectively) (p < 0.05). These findings highlight the potential of pre-game mangiferin-quercetin supplementation to enhance intermittent high-intensity efforts in sports such as basketball.

Food insecurity in Dutch disadvantaged neighbourhoods: a socio-ecological approach.

Food insecurity is an important public health concern; however, research into this phenomenon within the Netherlands is limited. Food insecurity is not solely related to individual factors, but can also be influenced by various factors in the social and physical environment. Therefore, this study aimed to identify determinants of food insecurity within the personal, social and physical environment, based on the social ecological model (SEM), and to identify their relative importance for experiencing food insecurity. The study population consisted of 307 participants living in disadvantaged neighbourhoods of the Dutch city The Hague, of which approximately one-quarter were food insecure. Participant characteristics showing bivariate associations P < 0⋅20 were placed in a predetermined level of the SEM, after which a multivariate logistic regression was performed for each level and the Nagelkerke pseudo R 2 was presented. Determinants of food insecurity were BMI, gross monthly income, highest educational attainment, smoking status, diet quality, employment status, marital status and religion (P < 0⋅05). The results showed that 29⋅7 % of the total variance in food insecurity status was explained by all included determinants together. The personal, social and physical environment explained 20⋅6, 14⋅0 and 2⋅4 % of the total variance, respectively. Our findings suggest that determinants within the personal environment are most important for explaining differences in experienced food insecurity. The present study contributes to furthering the knowledge about the relative importance of the personal, social and physical environment, indicating that determinants within the personal environment may be most promising for developing targeted interventions to reduce food insecurity.

Obesity, colorectal cancer and MACC1 expression: A possible novel molecular association.

Obesity is a major and increasing public health concern, associated with an increased risk of and mortality from several types of cancer including colorectal cancer (CRC), being associated with cancer progression, metastasis and resistance to therapy. It was hypothesized that the expression of cancer/metastasis­inducing gene metastasis­associated in colon cancer 1 (MACC1) is increased in obesity, which may constitute a link to obesity­induced cancer. The present study thus analyzed circulating cell­free plasma MACC1 expression levels in human obese (vs. normal weight) adult individuals from independent studies, namely the Martin Luther University (MLU) study (n=32) and the Metabolic syndrome study (MetScan, Berlin) (n=191). Higher plasma MACC1 levels were found in obese individuals, increasing with a greater body fat mass and body mass index; these levels were predominantly observed in male and to a lesser extent in female individuals, although the results were not significant. A reduction in body fat mass following dietary intervention and physical exercise decreased the MACC1 expression levels in the MLU study. Furthermore, Wistar rats with diet­induced obesity exhibited slightly increased plasma MACC1 levels compared with rats of normal weight. The obese Wistar rats exposed to azoxymethane to induce colon cancer exhibited a more severe colon tumor outcome, which was associated with significantly increased MACC1 levels compared with their non­obese littermates. On the whole, the findings of the present study suggest an association between MACC1 and obesity, as well as with obesity­induced CRC.

Association of genetic polymorphisms with local steroid metabolism in human benign breasts.

PURPOSE: Although alterations of concentrations in circulating steroids have been linked to single nucleotide polymorphisms (SNPs) of steroidogenic enzymes, we hypothesized that SNPs of such enzymes located within the breast affect local steroid concentrations more than products of such SNPs absorbed from the circulation. METHODS: Steroids (estradiol, estrone, testosterone, androstenedione, DHEA, DHEA sulfate, progesterone) in nipple aspirate fluid (NAF) were purified by HPLC and they along with serum steroids were quantified by immunoassays. Polymorphisms of the transporter SLCO2B1 and enzymes HSD3B1, CYP19A1, HSD17B12, AKR1C3, CYP1B1, and SRD5A1 were measured in white blood cell DNA. RESULTS: Steroid concentrations in NAF of subjects with homozygous minor genotypes differed from those with heterozygotes, i.e., SLCO2B1 (rs2851069) decreased DHEAS (p = 0.04), HSD17B12 (rs11555762) increased estradiol (p < 0.004), and CYP1B1 (rs1056836) decreased estradiol (p = 0.017) and increased progesterone (p = 0.05). Also, in serum, CYP19A1 (rs10046 and rs700518) both decreased testosterone (p = 0.02) and SRD5A1 increased androstenedione (p = 0.006). Steroids in subjects with major homozygotes did not differ from those with heterozygotes indicating recessive characteristics. CONCLUSIONS: In the breast, SNPs were associated with decreased uptake of DHEAS (SLCO2B1), increased estradiol concentrations through increased oxidoreductase activity (HSD17B12), or decreased estradiol concentrations by presumed formation of 4-hydroxyestradiol (CYP1B1). CYP19A1 was associated with decreased testosterone concentrations in serum but had no significant effect on estrogen or androgen concentrations within the breast. The hormone differences observed in NAF were not usually evident in serum, indicating the importance of assessing the effect of these SNPs within the breast.

Use of oral glutamine in radiation-induced adverse effects in patients with thoracic and upper aerodigestive malignancies: Results of a prospective observational study.

Cancer growth in host tissues features glutamine (gln) depletion over time, decreasing epithelial cells' optimal functioning. In addition, radiotherapy (RT) and/or chemotherapy (CT) cause damage to normal tissues, probably enhanced by this depletion. The present study prospectively examined the effect of gln supplementation on 72 patients with thoracic and upper aerodigestive malignancies (T&UAM) treated with sequential or concurrent RT-CT or RT alone. All patients received prophylactic gln powder 15 g bid for the full duration of treatment. The severity of acute radiation toxicities was graded according to the RT Oncology Group/European Organization for Research and Treatment of Cancer criteria. Primary endpoints were the incidence of grade >2 toxicities, weight loss and requirement for analgesics, and the secondary endpoint was the association of the length of irradiated esophagus from treatment planning with the use of opioids. The incidence of adverse effects was as follows: Grade >2 stomatitis, 25.0%; esophagitis, 60.5%; dysphagia, 54.2%; pain, 25.4%; mycosis, 40.8%. Stomatitis grade >2 was more frequent in patients with head and neck tumors (P<0.001) and in those with prior surgery (P<0.001). Esophagitis (P=0.020) and dysphagia (P=0.008) grade >2 were more frequent in patients with concurrent RT-CT. Regarding analgesics, 9.9% of patients received no pain treatment, 56.3% received simple analgesic therapy and 33.8% opioids. Patients on opioid therapy had a greater mean length of irradiated esophagus (P=0.024) or length >12 cm (P=0.018). In 54.2% of patients, weight loss was observed, particularly with concurrent RT-CT (P=0.007). Thus, the use of oral gln may have an important role in reducing acute radiation toxicities and weight loss, and in lowering the requirement for analgesics in patients with T&UAM. Further randomized trials are required to identify the appropriate gln dose, duration of treatment and precise radiation dosimetric parameters in this group of patients. The present clinical trial was retrospectively registered in the ClinicalTrials.gov Protocol Registration and Results System (registration no. NCT05054517/22-09-2021).

A Participant-Centered Approach to Understanding Risks and Benefits of Participation in Research Informed by the Kidney Precision Medicine Project.

An understanding of the ethical underpinnings of human subjects research that involves some risk to participants without anticipated direct clinical benefit-such as the kidney biopsy procedure as part of the Kidney Precision Medicine Project (KPMP)-requires a critical examination of the risks as well as the diverse set of countervailing potential benefits to participants. This kind of deliberation has been foundational to the development and conduct of the KPMP. Herein, we use illustrative features of this research paradigm to develop a more comprehensive conceptualization of the types of benefits that may be important to research participants, including respecting pluralistic values, supporting the opportunity to act altruistically, and enhancing benefits to a participant's community. This approach may serve as a model to help researchers, ethicists, and regulators to identify opportunities to better respect and support participants in future research that entails some risk to these participants as well as to improve the quality of research for people with kidney disease.

COVID-19 messed up my research: Insights from physical activity and nutrition translational research.

The COVID-19 pandemic led to significant challenges in conducting physical activity and nutrition translational research. This encompassed all phases of translational research, including recruitment (e.g., lack of trust in the scientific community), assessment (university regulations restricting in-person assessments), intervention (conversion of face-to-face interventions to online formats), and retention (loss of employment, phone service, or housing among study participants). The COVID-19 pandemic has had varying impacts on research productivity as well. While some groups found the pandemic led to increases in productivity (as evidenced by increases seen in both manuscript and grant submissions), junior faculty, women (particularly caregivers), African American, Asian, and Latinx faculty, and mid-career and senior scientists all faced unique career and personal challenges during this time. This included competing demands on time that interfered with research productivity and mental and physical health stressors. Therefore, in order to ensure we retain promising scientists in the field of translational physical activity and nutrition science, it will be important to consider these challenges when it comes time to review tenure files and grant applications. Reviewers of these applications should note creativity in moving research forward, continued mentoring of students or other faculty, and plans to get back on track after a pause in their ability to conduct impactful physical activity and nutrition work.

Another route of CO2 gas excretion independent of red blood cells in human lungs.

We demonstrated pulmonary arteriolar blood flow-mediated CO2 gas excretion in rabbit lungs. The shear stress stimulation produced CO2 gas in cultured human endothelial cells of pulmonary arterioles via the activation of F1/Fo ATP synthase. To confirm the findings in human subjects undergoing the operation with heart-lung machines, we aimed to evaluate the effects of a stepwise switch, from a partial to a complete cardiopulmonary bypass, of the circulatory blood volume (BV, 100% = 2.4 × cardiac index), on the end-expiratory CO2 pressure (PetCO2), maximal flow velocity in the pulmonary artery (Max Vp), the inner diameter (ID) of pulmonary artery, pulmonary arterial CO2 pressure (P mix v CO2), pulmonary arterial O2 pressure (P mix v O2), hematocrit (Hct), pH, the concentration of HCO3-, and base excess (BE) in mixed venous blood in 9 patients with a mean age of 72.3 ± 3.4 years. In addition, the effects of the decrease in Hct infused with physiological saline solution (PSS) on PetCO2 were investigated in the human subjects. An approximately linear relationship between the PetCO2 and Max Vp was observed. The pumping out of 100% BV produced little or no change in the Hct, pH, P mix v CO2, and P mix v O2, respectively. The hemodilution produced by intravenous infusion of PSS caused a significant decrease in the Hct, but not in the PetCO2. In conclusion, another route of CO2 gas excretion, independent of red blood cells, may be involved in human lungs.

Taming Time: Configuring Cancer Patients as Research Subjects.

This article explores how incurable cancer patients in the affluent Danish welfare state are recruited to clinical trials. We show that patients' impending death constitutes their potential for being configured as research subjects. To produce valuable data, patients who enroll in trials and health care professionals must engage in daily "time practices" that prolong the threshold between life and death. When death becomes inevitable, the limit of configuring dying cancer patients as research subjects is reached. Navigating this temporal logic, health care professionals balance the boundary between patients' instrumental worth as research subjects and their intrinsic worth as dying cancer patients. Whereas previous studies have critically uncovered how clinical trials operate at socioeconomic margins, we point to the ways in which clinical trials operate through temporal margins. We argue that clinical trials are dependent on configuring marginal societal spaces and marginal bodies from which to produce knowledge.

Análisis comparativo de las pautas del consejo de organizaciones internacionales de ciencias médicas (CIOMS) 2016: (Parte 2 de 3) / Comparative analysis of the standards of the council of international organizations of medical sciences (CIOMS) 2016. (Part 2 of 3)

Como parte de la evaluación de la asignatura Bioética e Investigación de la Maestría en Bioética, se solicitó a los estudiantes de la VI Cohorte que realizarán un análisis comparativo de las Pautas CIOMS 2016 con documentos anteriores. En esta segunda parte, se presentan las pautas relacionadas con el consentimiento informado, la recolección, almacenamiento y uso de materiales biológicos y datos relacionados, así como la rendición pública de cuentas y la publicación de las investigaciones. Estas pautas son fundamentales para la realización de investigaciones científicas en seres humanos por eso el objetivo de estos trabajos es proporcionar a los investigadores un aporte en su formación y una rápida adaptación a la nueva propuesta CIOMS(AU)

As part of the evaluation of the Bioethics and Research subject of the Master in Bioethics, students of the VI Cohort were asked to make a comparative analysis of the CIOMS 2016 Guidelines with previous documents. In this second part, the guidelines related to informed consent, collection, storage and use of biological materials and related data, as well as public accountability and publication of research are presented. These guidelines are fundamental for carrying out scientific research on human beings, and for this reason the objective of this work is to provide researchers with a contribution in their training and a rapid adaptation to the new CIOMS proposal(AU)

Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women.

To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases. This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important "exercise-responsive" genes that could attenuate metabolic disease.

Impact of menthol delivery methods on smoker sensory perceptions.

INTRODUCTION: Menthol can be added to cigarettes in several ways; these different delivery methods of menthol may lead to changes in sensory attributes, as well as perceived risk and appeal of these products. METHODS: Using a randomized, controlled study design, 18 current, established menthol smokers were asked to sample Camel Crush and Camel Menthol cigarette products, crushed and uncrushed. Smoking behavior, exhaled carbon monoxide, subjective ratings, and perceived risk measures were assessed for each product. RESULTS: Cigarette Evaluation Scale relief of craving scores for participants' preferred brand (mean: 5.3, SE: 0.3) were significantly higher (p=0.012) than Camel Menthol crushed (mean: 4.6, SE: 0.3) as were the Sensory Scale satisfaction scores (preferred brand mean: 6.9, SE: 0.7 compared to Camel Menthol crushed mean: 5.1, SE: 0.6; p=0.004). In addition, the average Sensory Scale smoke strength scores for participants' preferred brand (mean: 6.9, SE: 0.5) was also significantly higher than Camel Crush crushed (mean: 5.0, SE: 0.5; p=0.022). There were no significant differences in smoking topography measures, CO boosts, or perceived risk between Camel Crush or Camel Menthol products. CONCLUSIONS: The delivery method and amount of menthol present in cigarettes did not appear to affect short-term smoking behavior, sensory perceptions, or perceived product risk among a small sample of current established adult menthol smokers. It is possible that consumers of cigarette products may be attracted to the innovative technology of the crushable filter capsule as opposed to the taste experience, however, further research is needed.

Effects of short-term exposures to ultrafine particles near an airport in healthy subjects.

BACKGROUND: Recent studies reported elevated concentrations of ultrafine particles (UFP) near airports. Little is known about the health effects of UFP from aviation. Since UFP can deposit deep into the lungs and other organs, they may cause significant adverse health effects. OBJECTIVE: We investigated health effects of controlled short-term human exposure to UFP near a major airport. METHODS: In this study, 21 healthy non-smoking volunteers (age range: 18-35 years) were repeatedly (2-5 visits) exposed for 5 h to ambient air near Schiphol Airport, while performing intermittent moderate exercise (i.e. cycling). Pre- to post-exposure changes in cardiopulmonary outcomes (spirometry, forced exhaled nitric oxide, electrocardiography and blood pressure) were assessed and related to total- and size-specific particle number concentrations (PNC), using linear mixed effect models. RESULTS: The PNC was on average 53,500 particles/cm3 (range 10,500-173,200). A 5-95th percentile increase in exposure to UFP (i.e. 125,400 particles/cm3) was associated with a decrease in FVC of -73.8 mL (95% CI -138.8 - -0.4) and a prolongation of the corrected QT (QTc) interval by 9.9 ms (95% CI 2.0 - 19.1). These effects were associated with particles < 20 nm (mainly UFP from aviation), but not with particles > 50 nm (mainly UFP from road traffic). DISCUSSION: Short-term exposures to aviation-related UFP near a major airport, was associated with decreased lung function (mainly FVC) and a prolonged QTc interval in healthy volunteers. The effects were relatively small, however, they appeared after single exposures of 5 h in young healthy adults. As this study cannot make any inferences about long-term health impacts, appropriate studies investigating potential health effects of long-term exposure to airport-related UFP, are urgently needed.

Supplementation with a Mango Leaf Extract (Zynamite®) in Combination with Quercetin Attenuates Muscle Damage and Pain and Accelerates Recovery after Strenuous Damaging Exercise.

Prolonged or unusual exercise may cause exercise-induced muscle damage (EIMD). To test whether Zynamite®, a mango leaf extract rich in the natural polyphenol mangiferin, administered in combination with quercetin facilitates recovery after EIMD, 24 women and 33 men were randomly assigned to two treatment groups matched by sex and 5 km running performance, and ran a 10 km race followed by 100 drop jumps to elicit EIMD. One hour before the competition, and every 8 hours thereafter for 24 hours, they ingested placebo (728 mg of maltodextrin) or 140 mg of Zynamite® combined with 140 mg of quercetin (double-blind). Although competition times were similar, polyphenol supplementation attenuated the muscle pain felt after the competition (6.8 ± 1.5 and 5.7 ± 2.2 a.u., p = 0.035) and the loss of jumping performance (9.4 ± 11.5 and 3.9 ± 5.2%, p = 0.036; p = 0.034) and mechanical impulse (p = 0.038) 24 hours later. The polyphenols attenuated the increase of serum myoglobin and alanine aminotransferase in men, but not in women (interaction p < 0.05). In conclusion, a single dose of 140 mg Zynamite® combined with 140 mg of quercetin, administered one hour before competition, followed by three additional doses every eight hours, attenuates muscle pain and damage, and accelerates the recovery of muscle performance.

Assessment of the Choice Behavior Under Cued Conditions (CBUCC) paradigm as a measure of motivation to smoke under laboratory conditions.

BACKGROUND AND AIMS: The Choice Behavior under Cued Conditions (CBUCC) task uses three indices of tobacco use (consumption, money spent to access a cigarette and latency to reach for a cigarette) to assess motivation to smoke under laboratory conditions. Initial research with this procedure has shown that it can evince cue-specific craving and differential responding for smoking versus a neutral cue. This study aimed to replicate these findings and assess the interaction of cue-specific craving and behavior with abstinence prior to testing. DESIGN: A mixed repeated-measures between-groups factorial design was used. Participants attended a morning laboratory session in which they were randomized to remain abstinent or smoke as usual (between-groups factor) and returned in the afternoon to complete CBUCC. In this, participants were exposed to 40 experimental trials. In each trial they were exposed to a cigarette or water cue behind a movable glass door (repeated-measures factor). SETTING: University at Buffalo, New York, USA. PARTICIPANTS: Participants were 106 daily non-treatment-seeking cigarette smokers, data from 102 were used. MEASUREMENTS: On each of 40 trials, participants rated cigarette craving, and behavioral measures from the CBUCC (money spent, latency to access the cue, puff duration) were recorded. FINDINGS: Craving and CBUCC behavioral measures showed high internal reliability across trials (Cronbach alphas ranged from 0.88 to 0.98). Craving and money spent were higher in trials with the cigarette cue than the water cue (F(1100)  = 45.49, P < 0.001 and F(1100)  = 116.26, P < 0.001). Other CBUCC measures did not show a significant effect of cue type. The difference in spending between cigarette and water cues was larger for abstinent participants than non-abstinent participants (F(1100)  = 5.0, P = 0.03). Other CBUCC measures did not show a significant interaction between abstinence and cue type. Craving on smoking trials was significantly correlated with cigarette spending (r = 0.54, P < 0.001) in the non-abstinence condition but not in the abstinence condition. CONCLUSIONS: Craving and 'money spent' in the Choice Behavior under Cued Conditions task (CBUCC) appears to be responsive to cigarette versus water cues, and money spent appears to show greater difference in responsiveness to cigarette than water cues after abstinence.

Reprioritizing Risk and Benefit: The Future of Study Design in Early-Phase Cancer Research.

The scientific purpose of phase I trials is to determine the maximum tolerated dose and/or optimal biological dose of experimental agents. Yet most participants in phase I oncology trials enroll hoping for direct medical benefit. The most common phase I trial designs use low starting doses and escalate cautiously in a "risk-escalation" model focused on minimizing risk for each participant. This approach ensures that a proportion of subjects will likely not receive any benefit, even if the intervention proves to be successful at appropriate doses. In this article, we propose that trial designs should employ dosing strategies that increase chances of providing benefit if the investigational agent should prove to be successful while limiting risk to reasonable levels. We then describe how adaptive trial designs can facilitate refined dose optimization based on both therapeutic benefit and toxicity, which can simultaneously decrease the risk of harm while increasing the chances of benefit.

Intense Light-Mediated Circadian Cardioprotection via Transcriptional Reprogramming of the Endothelium.

Consistent daylight oscillations and abundant oxygen availability are fundamental to human health. Here, we investigate the intersection between light-sensing (Period 2 [PER2]) and oxygen-sensing (hypoxia-inducible factor [HIF1A]) pathways in cellular adaptation to myocardial ischemia. We demonstrate that intense light is cardioprotective via circadian PER2 amplitude enhancement, mimicking hypoxia-elicited adenosine- and HIF1A-metabolic adaptation to myocardial ischemia under normoxic conditions. Whole-genome array from intense light-exposed wild-type or Per2-/- mice and myocardial ischemia in endothelial-specific PER2-deficient mice uncover a critical role for intense light in maintaining endothelial barrier function via light-enhanced HIF1A transcription. A proteomics screen in human endothelia reveals a dominant role for PER2 in metabolic reprogramming to hypoxia via mitochondrial translocation, tricarboxylic acid (TCA) cycle enzyme activity regulation, and HIF1A transcriptional adaption to hypoxia. Translational investigation of intense light in human subjects identifies similar PER2 mechanisms, implicating the use of intense light for the treatment of cardiovascular disease.

VMP35 MNC, a novel iron-free supplement, enhances cytoprotection against anemia in human subjects: a novel hypothesis.

BACKGROUND: The American Society of Hematology reported that according to the National Heart, Lung, and Blood Institute (NHLBI) anemia is the most common blood disorder, which affects more than 3 million Americans, while the Global Burden of Disease 2016 (GBD 2016) reported that iron deficiency anemia (IDA) is the leading cause of anemia, which affects 1.93 billion people worldwide. Anemia is intricately linked to chronic inflammation, chronic kidney disease, gastrointestinal and gynecological malignancies, and autoimmune disorders. Hemorrhagic anemia results in substantial loss of blood, which causes significant alterations in all blood parameters, including reduced iron. The other type of anemia is chronic anemia syndrome (CAS), which is a constellation of disorders and chronic inflammatory events caused by an increasing anaerobic/acidic environment (promoting the growth of anaerobic organisms), inducing a defensive expenditure of alkalinizing buffers in hemoglobin (i.e. histidine), to prevent a dangerous lowering of blood pH. In this process, iron is cleaved from heme groups and transferred out of blood circulation into other organs, like the liver, appearing to be IDA, where excessive accumulation can lead to hemochromatosis, also known as 'iron overload anemia'. DESIGN: A pilot clinical study was conducted in 38 subjects (men = 10; women = 28; age = 22-82 years) to evaluate the rate of absorption and effects on blood of VMP35 multi-nutrient complex (MNC), a non-iron containing liquid nutraceutical supplement. Subjects consumed either placebo or VMP35 (30 mL) over a period of 0, 5, or 30 min. METHODS: Changes in peripheral blood smears from 38 subjects were observed using live blood cell imaging (LBCI) with phase contrast microscopy. Adverse events were rigorously monitored. RESULTS: VMP35 caused positive changes in the blood, including morphological, hematological (including restoration of hemoglobin), and rheological changes following 5 min of administration, which were sustained for at least 30 min. CONCLUSION: Overall, the non-iron containing VMP35 can induce improvements in blood properties and potential benefits for subjects even with compromised digestive systems. No adverse events were reported. Further research studies are in progress to explore the mechanistic insight.

Whole genome sequencing of pairwise human subjects reveals DNA mutations specific to developmental dysplasia of the hip.

Developmental dysplasia of the hip (DDH) is a common congenital malformation characterized by mismatch in shape between the femoral head and acetabulum, and leads to hip dysplasia. To date, the pathogenesis of DDH is poorly understood and may involve multiple factors, including genetic predisposition. However, comprehensive genetic analysis has not been applied to investigate a genetic component of DDH. In the present study, 10 pairs of healthy fathers and DDH daughters were enrolled to identify genetic hallmarks of DDH using high throughput whole genome sequencing. The DDH-specific DNA mutations were found in each patient. Overall 1344 genes contained DDH-specific mutations. Functional enrichment analysis showed that these genes played important roles in the cytoskeleton, microtubule cytoskeleton, sarcoplasm and microtubule associated complex. These functions affected osteoblast and osteoclast development. Therefore, we proposed that the DDH-specific mutations might affect bone development, and caused DDH. Our pairwise high throughput sequencing results comprehensively delineated genetic hallmarks of DDH. Further research into the biological impact of these mutations may inform the development of DDH diagnostic tools and allow neonatal gene screening.