Portable near-infrared and Raman spectroscopic devices as complementary tools for instantaneous quality control of turmeric powder.

INTRODUCTION: Process analytical technology (PAT) guidance is implemented in the quality assurance of phytocompounds to achieve the Industry 4.0 concept. Near-infrared (NIR) and Raman spectroscopies are feasible for rapid, reliable quantitative analysis through transparent packaging without removing the samples from their original containers. These instruments can serve PAT guidance. OBJECTIVE: This study aimed to develop online portable NIR and Raman spectroscopic methods for quantifying total curcuminoids in turmeric samples through a plastic bag. The method mimicked an in-line measurement mode in PAT compared with placing samples into a glass vessel (at-line mode). MATERIALS AND METHODS: Sixty-three curcuminoid standard-spiked samples were prepared. Then, 15 samples were randomly selected as fixed validation samples, and 40 of the 48 remaining samples were chosen as calibration set. The results obtained from the partial least square regression (PLSR) models constructed by using the spectra acquired from NIR and Raman were compared with the reference values from high-performance liquid chromatography (HPLC). RESULTS: The optimum PLSR model of at-line Raman was achieved with three latent variables and a root mean square error of prediction (RMSEP) of 0.46. Meanwhile, the PLSR model of at-line NIR with one latent variable offered an RMSEP of 0.43. For the in-line mode, PLSR models created from Raman and NIR spectra had one latent variable with RMSEP of 0.49 and 0.42, respectively. The R2 values for prediction were 0.88-0.92. CONCLUSION: The models established from the spectra from portable NIR and Raman spectroscopic devices with the appropriate spectral pretreatments allowed the determination of total curcuminoid contents through plastic bag.

Incidence and Sequelae of Liver Injury Among Children Treated for Solid Tumors: Analysis of a Large Single-Center Prospective Cohort.

OBJECTIVES: Pediatric oncology patients are at risk of adverse drug events. The incidence and etiologies of liver injury in this population are not well characterized. We utilized a large, single-center pediatric oncology registry to investigate the incidence, causes, and outcomes of liver injury during treatment for solid tumor malignancies. METHODS: We reviewed all young individuals (age <25 years) who received treatment for any solid tumor at the University of Michigan between January 2004 and July 2016. Subjects with liver injury meeting predetermined laboratory criteria were identified. Cases were independently reviewed by 2 expert hepatologists to assign a cause of liver injury. Clinical characteristics of drug-induced liver injury (DILI) and non-DILI cases were compared. Cases of liver injury occurring after bone marrow or liver transplant were excluded. RESULTS: Of 1136 solid tumor patients, 160 (14%) experienced liver injury, and the overall frequency of DILI was 4%. DILI was the leading identified cause of liver injury (31%), followed by infection (17%), metastatic/malignant biliary disease (13%), and perioperative liver injury (13%). Most DILI cases (>90%) were mild acute hepatocellular injury episodes that did not result in modification to the chemotherapy plan, and all DILI eventually resolved. Severe presentations involving jaundice and/or prolonged hospital course were significantly more common among non-DILI versus DILI cases (23% vs 2%, P < 0.001). CONCLUSIONS: DILI is the leading cause of liver injury events among pediatric solid tumor patients. In our registry, DILI was of mild severity and did not result in an alteration of the treatment plan in most patients. In contrast, non-DILI-related liver injury events, including infection, were more likely to have a more severe presentation and a complicated course with a greater mortality during follow-up.

PNPLA3 I148M polymorphism is associated with elevated alanine transaminase levels in Mexican Indigenous and Mestizo populations.

The patatin like phospholipase domain-containing (PNPLA3) I148M variant is the strongest genetic factor associated with elevated alanine transaminase (ALT) levels in different populations, particularly in Hispanics who have the highest 148M risk allele frequency reported to date. It has been suggested that Indigenous ancestry is associated with higher ALT levels in Mexicans. The aim of the present study was to assess the frequency of the PNPLA3 148M risk allele in Mexican indigenous and Mestizo individuals, and to examine its association with serum ALT levels. The study included a total of 1624 Mexican individuals: 919 Indigenous subjects from five different native groups and 705 Mexican Mestizo individuals (141 cases with ALT levels ≥ 40 U/L and 564 controls with ALT <40 U/L). The I148M polymorphism was genotyped by TaqMan assays. The frequency of elevated ALT levels in Indigenous populations was 18.7%, and varied according to obesity status: 14.4% in normal weight, 19.9% in overweight and 24.5% in obese individuals. The Mexican indigenous populations showed the highest reported frequency of the PNPLA3 148M risk allele (mean 0.73). The M148M genotype was significantly associated with elevated ALT levels in indigenous individuals (OR = 3.15, 95 % CI 1.91-5.20; P = 7.1 × 10(-6)) and this association was confirmed in Mexican Mestizos (OR = 2.24, 95% CI 1.50-3.33; P = 8.1 × 10(-5)). This is the first study reporting the association between M148M genotype and elevated ALT levels in Indigenous Mexican populations. The 148M allele risk may be considered an important risk factor for liver damage in Mexican indigenous and Mestizo populations.

Epitope identification of a Lys63 linkage ubiquitin antibody by mass spectrometric epitope excision and extraction approaches.

Ubiquitin, a conserved protein in eukaryotic cells, exists as a monomer or polyubiquitin chains known as isopeptide-linked polymers. These chains are attached to a substrate or other ubiquitin molecules through a covalent bond between the α-amino group of lysine in ubiquitin and glycine in the C-terminal of the subsequent ubiquitin unit. The choice of the specific lysine residue in ubiquitin for forming ubiquitin-ubiquitin chains determines its biochemical and biological function. A detailed chemical structure-function evaluation of the respective polyubiquitin chain is required. Interestingly, specific lysine linkage polyubiquitin chains become covalently bonded to many pathological inclusions seen in serious human disease states which appear to be resistant to normal degradation, so the interaction between polyubiquitin chains and ubiquitin antibodies is very useful. For example, the neurofibrillary tangles of Alzheimer's disease and the Lewy bodies seen in Parkinson's disease are heavily ubiquitinated and can be readily visualized using specific ubiquitin antibodies. This study utilized synthetic ubiquitin building block peptides that contained various lysine residues (K6, K11, K33, K48, and K63) linked to a Gly-Gly dipeptide, with the aim of exploring the recognition specificity of the Lys63-polyubiquitin antibody. The interaction studies between different ubiquitin building blocks and the specific Lys63-ubiquitin (K63-Ub) antibody were performed by affinity-mass spectrometry (Affinity-MS) and immunoblotting which enables direct protein identification from biological material with unprecedented selectivity. Affinity-MS and dot blot data proved the specific binding of the K63-Ub antibody to the ubiquitin peptides containing Lys6 or Lys63 residues. In epitope excision for mass spectrometric epitope identification, the ubiquitin building block with Lys63 residue bound to the immobilized K63-Ub antibody was proteolytically cleaved using pronase. The resulting epitope and non-epitope fractions were subjected to matrix-assisted laser desorption/ionization-time of flight analysis, revealing that the epitope is located within the sequence ubiquitin(60-66). Epitope extraction-MS consistently confirmed these findings.

Challenges connecting emergency department patients with oral health care: A qualitative analysis of patients, emergency department clinicians, and dentists.

BACKGROUND: Unmet dental need shares many risk factors with unmet health-related social needs (HRSN) such as housing and food security and are a common cause for seeking treatment at the emergency department (ED). METHODS: The authors recruited a purposive sample of English-speaking and Spanish-speaking patients, ED clinicians at 3 urban EDs, and dentists from nearby communities to participate in qualitative interviews to explore barriers to and facilitators of screening for HRSN and unmet dental needs in the ED. Themes were identified from transcripts using a modified grounded theory approach. RESULTS: Interviews were conducted with 25 ED patients, 19 ED clinicians, and 4 dentists. Four themes were identified: (1) a preference for formalized resources, which more frequently exist for HRSN than for oral health; (2) frequent use of ad hoc resources that are less reliable or structured, particularly for dental referral information; (3) limited knowledge of oral health care resources in the community; and (4) desire for more assistance with identifying and addressing resource needs for both HRSN and oral health. Patients were amenable to screening through a variety of modalities and felt it would be helpful, but clinicians emphasized the need for easier referral processes because of frequent failure to connect patients to oral health care. CONCLUSIONS: More robust infrastructure and clinician support are needed to ensure successful referral and screening without undue provider burden for both medical and dental clinicians. PRACTICAL IMPLICATIONS: Patients are amenable to screening for unmet oral health needs and HRSN in the ED, which may improve access to care.

Mapping Oral health and Local Area Resources (MOLAR): protocol for a randomised controlled trial connecting emergency department patients with social and dental resources.

INTRODUCTION: There are substantial inequities in oral health access and outcomes in the USA, including by income and racial and ethnic identity. People with adverse social determinants of health (aSDoH), such as housing or food insecurity, are also more likely to have unmet dental needs. Many patients with dental problems present to the emergency department (ED), where minimal dental care or referral is usually available. Nonetheless, the ED represents an important point of contact to facilitate screening and referral for unmet oral health needs and aSDoH, particularly for patients who may not otherwise have access to care. METHODS AND ANALYSIS: Mapping Oral health and Local Area Resources is a randomised controlled trial enrolling 2049 adult and paediatric ED patients with unmet oral health needs into one of three trial arms: (a) a standard handout of nearby dental and aSDoH resources; (b) a geographically matched listing of aSDoH resources and a search link for identification of geographically matched dental resources; or (c) geographically matched resources along with personalised care navigation. Follow-up at 3, 6, 9 and 12 months will evaluate oral health-related quality of life, linkage to resources and dental treatment, ED visits for dental problems and the association between linkage and neighbourhood resource density. ETHICS AND DISSEMINATION: All sites share a single human subjects review board protocol which has been fully approved by the Mass General Brigham Human Subjects Review Board. Informed consent will be obtained from all adults and adult caregivers, and assent will be obtained from age-appropriate child participants. Results will demonstrate the impact of addressing aSDoH on oral health access and the efficacy of various forms of resource navigation compared with enhanced standard care. Our findings will facilitate sustainable, scalable interventions to identify and address aSDoH in the ED to improve oral health and reduce oral health inequities. TRIAL REGISTRATION NUMBER: NCT05688982.

A Comparative Study of Benchtop and Portable NIR and Raman Spectroscopic Methods for the Quantitative Determination of Curcuminoids in Turmeric Powder.

Turmeric consumption is continually increasing worldwide. Curcuminoids are major active constituents in turmeric and are associated with numerous health benefits. A combination of spectroscopic methods and chemometrics shows the suitability of turmeric for food quality control due to advantages such as speed, versatility, portability, and no need for sample preparation. Five calibration models to quantify curcuminoids in turmeric were proposed using benchtop and portable devices. The most remarkable results showed that Raman and NIR calibration models present an excellent performance reporting RMSEP of 0.44% w/w and 0.41% w/w, respectively. In addition, the five proposed methods (FT-IR, Raman, and NIR) were compared in terms of precision and accuracy. The results showed that benchtop and portable methods were in good agreement and that there are no significant differences between them. This study aims to foster the use of portable devices for food quality control in situ by demonstrating their suitability for the purpose.

Quantification of Mucosal Activity from Colonoscopy Reports via the Simplified Endoscopic Mucosal Assessment for Crohn's Disease.

BACKGROUND: Endoscopic mucosal healing is the gold standard for evaluating Crohn's disease (CD) treatment efficacy. Standard endoscopic indices are not routinely used in clinical practice, limiting the quality of retrospective research. A method for retrospectively quantifying mucosal activity from documentation is needed. We evaluated the simplified endoscopic mucosal assessment for CD (SEMA-CD) to determine if it can accurately quantify mucosal severity recorded in colonoscopy reports. METHODS: Pediatric patients with CD underwent colonoscopy that was video recorded and evaluated via Simple Endoscopic Score for CD (SES-CD) and SEMA-CD by central readers. Corresponding colonoscopy reports were de-identified. Central readers blinded to clinical history and video scoring were randomly assigned colonoscopy reports with and without images. The SEMA-CD was scored for each report. Correlation with video SES-CD and SEMA-CD were assessed with Spearman rho, inter-rater, and intrarater reliability with kappa statistics. RESULTS: Fifty-seven colonoscopy reports were read a total of 347 times. The simplified endoscopic mucosal assessment for CD without images correlated with both SES-CD and SEMA-CD from videos (rho = 0.82, P < .0001 for each). The addition of images provided similar correlation. Inter-rater and intrarater reliability were 0.93 and 0.92, respectively. CONCLUSIONS: The SEMA-CD applied to retrospective evaluation of colonoscopy reports accurately and reproducibly correlates with SES-CD and SEMA-CD of colonoscopy videos. The SEMA-CD for evaluating colonoscopy reports will enable quantifying mucosal healing in retrospective research. Having objective outcome data will enable higher-quality research to be conducted across multicenter collaboratives and in clinical registries. External validation is needed.

Infliximab therapy for patients with moderate to severe hidradenitis suppurativa: a randomized, double-blind, placebo-controlled crossover trial.

BACKGROUND: Biologic therapies with anti-tumor necrosis factor agents are promising treatments for hidradenitis suppurativa (HS). OBJECTIVE: We assessed the efficacy and safety of infliximab (IFX) for the treatment of moderate to severe HS. METHODS: A prospective double-blind treatment phase of 8 weeks where patients received IFX or placebo was followed by an open-label phase where patients taking placebo were given the opportunity to cross over to IFX, and an observational phase. Primary treatment efficacy was based on HS Severity Index. Secondary end points included Dermatology Life Quality Index, visual analog scale, and Physician Global Assessment scores. Inflammatory markers erythrocyte sedimentation rate and C-reactive protein were also assessed. RESULTS: More patients in the IFX than in the placebo group showed a 50% or greater decrease from baseline HS Severity Index score. In addition, statistically and clinically significant improvement from baseline was observed at week 8 in Dermatology Life Quality Index score, visual analog scale score, erythrocyte sedimentation rate, and C-reactive protein compared with placebo. Patients in the placebo group treated with IFX after week 8 (crossover) responded similarly to the original IFX group. Many patients withdrew during the observational phase to continue anti-tumor necrosis factor-alfa therapy. No unexpected serious adverse events were observed. LIMITATIONS: Results are representative of a single center, patients were treated by a single physician, some patients did not return after their last infusion, and the HS Severity Index requires validation. CONCLUSIONS: This clinical study represents the first formal assessment of IFX for treatment of moderate to severe HS. IFX was well tolerated, no unexpected safety issues were identified, and improvements in pain intensity, disease severity, and quality of life were demonstrated with concomitant reduction in clinical markers of inflammation.

Community-based prevention of epidemic Rocky Mountain spotted fever among minority populations in Sonora, Mexico, using a One Health approach.

BACKGROUND: Rocky Mountain spotted fever (RMSF) is a significant public health problem in Sonora, Mexico, resulting in thousands of cases and hundreds of deaths. Outbreaks of RMSF are perpetuated by heavy brown dog tick infestations in and around homes. During 2009-2015, there were 61 RMSF cases and 23 deaths in a single community of Sonora (Community A). METHODS: An integrated intervention was carried out from March-November 2016 aimed at reducing tick populations with long-acting acaricidal collars on dogs, environmental acaricides applied to peri-domestic areas and RMSF education. Tick levels were measured by inspection of community dogs to monitor efficacy of the intervention. A similar neighborhood (Community B) was selected for comparison and received standard care (acaricide treatment and education). RESULTS: The prevalence of tick-infested dogs in Community A declined from 32.5% to 8.8% (p<0.01). No new cases of RMSF were identified in this area during the subsequent 18 mo. By comparison, the percentage of tick-infested dogs in Community B decreased from 19% to 13.4% (p=0.36) and two cases were reported, including one death. CONCLUSIONS: Community-based interventions using an integrated approach to control brown dog ticks can diminish the morbidity and mortality attributable to RMSF.

The importance of recognizing and treating low levels of high-density lipoprotein cholesterol: a new era in atherosclerosis management.

Low levels of high-density lipoprotein cholesterol (HDL-C) represent a major cardiovascular risk factor, with a stronger relationship to coronary heart disease than that seen with elevated levels of low-density lipoprotein cholesterol (LDL-C). HDL-C has important antiatherogenic effects, including reverse cholesterol transport, inhibition of LDL-C oxidation, and antiplatelet and anti-inflammatory actions. Patients with low HDL-C are also at an amplified risk of coronary heart disease due to the common coexistence of other risk factors, including excess adiposity, metabolic syndrome, type 2 diabetes mellitus, hypertriglyceridemia, and the atherogenic dyslipidemia characterized by small dense LDL-C. First-line therapy of low HDL-C generally consists of nonpharmacologic measures such as improved fitness and weight loss. Current pharmaceutical options include statins, fibrates, and nicotinic acid. A host of novel approaches involving HDL-C and reverse cholesterol transport hold the promise of fundamentally changing the natural history of atherosclerosis, the most common and important chronic disease in humans.

Prevalence of Lower-Extremity Arterial Calcification in Patients with Diabetes Mellitus Complicated by Foot Disease at an Urban US Tertiary-Care Center.

BACKGROUND: We sought to determine the prevalence of lower-extremity arterial calcification in a cohort of patients with diabetes and associated foot pathology receiving inpatient treatment at an urban US tertiary health-care system. METHODS: The primary outcome measure was defined as either radiographic evidence of vessel calcification or noninvasive vascular testing that resulted in any reporting of vessel noncompressibility or an ankle-brachial index greater than 1.1. Radiographic evidence of vessel calcification was defined as radiodense calcification in the proximal first intermetatarsal space (deep plantar perforating artery), anterior ankle (anterior tibial artery), or posterior ankle (posterior tibial artery) on dorsoplantar and lateral foot projections. RESULTS: Of the 367 individuals included in the study, 359 underwent radiography, with radiographic evidence of calcification in 192 (53.5%). Noninvasive vascular testing was performed on 265 participants, with any reporting of noncompressibility or an ankle-brachial index greater than 1.1 observed in 153 (57.7%). Ninety-four participants (25.6%) demonstrated evidence of arterial calcification on the radiographs and noninvasive testing, meaning that 251 participants (68.4%) demonstrated evidence of arterial calcification on at least one test, including 63.6% of participants classified as black/African American race, 65.4% as white race, and 78.3% as Hispanic/Latino ethnicity. CONCLUSIONS: The results of this investigation increase the body of knowledge with respect to the evaluation and treatment of diabetic foot disease and may lead to future investigations on the topic of lower-extremity arterial calcification.

In line monitoring of the powder flow behavior and drug content in a Fette 3090 feed frame at different operating conditions using Near Infrared spectroscopy.

Near infrared (NIR) spectroscopy was used to determine the drug concentration in 3% (w/w) acetaminophen blends within the complex flow regime of the tablet press feed frame just before tablet compaction. NIR spectra also provided valuable information on the powder flow behavior within the feed frame and were used to track when a process enters or leaves the steady state. A partial least squares regression calibration model was developed with powder mixtures that varied from 1.5 to 4.5% (w/w) by obtaining 135 spectra after steady state for each concentration while the feed frame and die disc operated at 30.5 revolutions per minute (rpm). The calibration model determined drug concentration in validation blends with a root mean square error of prediction and bias below 0.1% (w/w). The robustness of the NIR calibration model was evaluated by determining the effect of variation on the operating conditions (paddle wheel speed and die disc speed) on NIR predictions. This work found that the paddle wheel speed can be increased up to 30% and the die disc speed decrease 10% without affecting NIR predictions. The results demonstrated that paddle wheel speed has a significant effect on the wave powder behavior (frequency and amplitude) but does not have significant effect on the mass hold-up within feed frame. The die disc speed does not affect wave powder behavior but affects significantly the mass hold-up inside the feed frame. This information can be used to reduce the tablet weight variability and ensure that this critical attribute is met.

Process analytical technology in continuous manufacturing of a commercial pharmaceutical product.

The implementation of process analytical technology and continuous manufacturing at an FDA approved commercial manufacturing site is described. In this direct compaction process the blends produced were monitored with a Near Infrared (NIR) spectroscopic calibration model developed with partial least squares (PLS) regression. The authors understand that this is the first study where the continuous manufacturing (CM) equipment was used as a gravimetric reference method for the calibration model. A principal component analysis (PCA) model was also developed to identify the powder blend, and determine whether it was similar to the calibration blends. An air diagnostic test was developed to assure that powder was present within the interface when the NIR spectra were obtained. The air diagnostic test as well the PCA and PLS calibration model were integrated into an industrial software platform that collects the real time NIR spectra and applies the calibration models. The PCA test successfully detected an equipment malfunction. Variographic analysis was also performed to estimate the sampling analytical errors that affect the results from the NIR spectroscopic method during commercial production. The system was used to monitor and control a 28 h continuous manufacturing run, where the average drug concentration determined by the NIR method was 101.17% of label claim with a standard deviation of 2.17%, based on 12,633 spectra collected. The average drug concentration for the tablets produced from these blends was 100.86% of label claim with a standard deviation of 0.4%, for 500 tablets analyzed by Fourier Transform Near Infrared (FT-NIR) transmission spectroscopy. The excellent agreement between the mean drug concentration values in the blends and tablets produced provides further evidence of the suitability of the validation strategy that was followed.

Comparison of chemical compounds associated with sclerites from healthy and diseased sea fan corals (Gorgonia ventalina).

BACKGROUND: The roles of gorgonian sclerites as structural components and predator deterrents have been widely studied. Yet their role as barriers against microbes has only recently been investigated, and even less is known about the diversity and roles of the chemical compounds associated with sclerites. METHODS: Here, we examine the semi-volatile organic compound fraction (SVOCs) associated with sclerites from healthy and diseased Gorgonia ventalina sea fan corals to understand their possible role as a stress response or in defense of infection. We also measured the oxidative potential of compounds from diseased and healthy G. ventalina colonies. RESULTS: The results showed that sclerites harbor a great diversity of SVOCs. Overall, 70 compounds were identified, the majority of which are novel with unknown biological roles. The majority of SVOCs identified exhibit multiple immune-related roles including antimicrobial and radical scavenging functions. The free radical activity assays further confirmed the anti-oxidative potential of some these compounds. The anti-oxidative activity was, nonetheless, similar across sclerites regardless of the health condition of the colony, although sclerites from diseased sea fans display slightly higher anti-oxidative activity than the healthy ones. DISCUSSION: Sclerites harbor great SVOCs diversity, the majority of which are novel to sea fans or any other corals. Yet the scientific literature consulted showed that the roles of compounds found in sclerites vary from antioxidant to antimicrobial compounds. However, this study fell short in determine the origin of the SVOCs identified, undermining our capacity to determine the biological roles of the SVOCs on sclerites and sea fans.

Uso de biológicos para el tratamiento de la psoriasis / Biologic therapies for psoriasis

La psoriasis es una enfermedad inflamatoria crónica, mediada por los linfocitos T, que afecta a 1 por ciento-3 por ciento de la población mundial. Afectando primordialmente la piel y las articulaciones (artritis psoriática), también está asociada con otras condiciones inflamatorias, como son la enfermedad intestinal inflamatoria y patología coronaria, entre otras. El tratamiento de la psoriasis viene dado según su extensión y severidad, variando desde modalidades locales (tópicas e intralesionales), fototerapia, hasta regímenes sistémicos. Estos últimos generalmente conllevan efectos secundarios cuando son utilizados a largo plazo. Hoy en día, gracias a los últimos avances científicos, se ha logrado profundizar el entendimiento de la patogénesis de la psoriasis, dando lugar a terapias específicamente dirigidas conocidas como “biológicos”. A continuación se discutirán los principales biológicos utilizados en el tratamiento de la psoriasis en placa moderada a severa: efalizumab, alefacept, etanercept, infliximab, adalimumab e inhibidores de la interleuquina (IL) 12/23.

Psoriasis is a chronic T cell-mediated inflammatory disease that mainly affects the skin and joints, and is present in 1 percent-3 percent of world population. It is also associated to other inflammatory conditions such as inflammatory intestinal disease and coronary pathologies, among others. Conventional treatments for moderate to severe psoriasis are associated to broad band immunosuppression and/or organ-toxicities which can be problematic when used in a long-term. Advances in the understanding of psoriasis pathogenesis have led to targeted therapy in the form of biologics. These agents have gained popularity as safe, effective and convenient alternatives for the treatment of chronic moderate to severe plaque psoriasis. This review focuses on the main biologics used in the treatment of moderate to severe plaque psoriasis: efalizumab, alefacept, etanercept, infliximab, adalimumab and interleukin inhibitors (IL) 12/23. Mechanisms of action, guidelines for usage, efficacy data, and safety concerns will be discussed for each biologic. In addition, the new Th17 biologics and their role in psoriasis pathogenesis will also be examined.