Presenting a short video on Guidelines for advising CT Imaging.
Reference and Further Reading
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We aimed to assess the relationship between mandibular condylar volume and disc displacement status, in male and female adults.
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Osteonecrosis of the jaws (ONJ) represents a concern for patients taking antiresorptive drugs. The aim of this study was to test the hypothesis that preoperative individualized pharmacological control of the patient's osteometabolic profile could lead to predictable healing of the surgically treated region and minimize the incidence of complications.
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This study aimed to examine the expression of signaling transduction proteins and their possible correlation with different clinical subtypes of oral lichen planus (OLP).
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This special issue of Radiotherapy and Oncology is devoted to current trends in medical physics, as reflected in scientific meetings as well as in scientific journals. One such recent meeting was the annual ESTRO conference held in Vienna in May 2017 . This special issue follows the tradition of the Green Journal's regular such issues in highlighting outstanding contributions and important developments in the field of medical physics, mainly linked to the former biennial ESTRO physics meetings or the ESTRO forums, respectively [2–6].
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PARP inhibitors are currently evaluated in combination with radiotherapy and/or chemotherapy. As sensitizers, PARP inhibitors are active at very low concentrations therefore requiring highly sensitive pharmacodynamic (PD) assays. Current clinical PD-assays partly fail to provide such sensitivities. The aim of our study was to enable sensitive PD evaluation of PARP inhibitors for clinical sensitizer development.
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Brain Sciences, Vol. 7, Pages 151: Adolescent Alcohol Drinking Renders Adult Drinking BLA-Dependent: BLA Hyper-Activity as Contributor to Comorbid Alcohol Use Disorder and Anxiety Disorders
Brain Sciences doi: 10.3390/brainsci7110151
Authors: Mahsa Moaddab Elizabeth Mangone Madelyn Ray Michael McDannald
Adolescent alcohol drinking increases the risk for alcohol-use disorder in adulthood. Yet, the changes in adult neural function resulting from adolescent alcohol drinking remain poorly understood. We hypothesized that adolescent alcohol drinking alters basolateral amygdala (BLA) function, making alcohol drinking BLA-dependent in adulthood. Male, Long Evans rats were given voluntary, intermittent access to alcohol (20% ethanol) or a bitter, isocaloric control solution, across adolescence. Half of the rats in each group received neurotoxic BLA lesions. In adulthood, all rats were given voluntary, intermittent access to alcohol. BLA lesions reduced adult alcohol drinking in rats receiving adolescent access to alcohol, but not in rats receiving adolescent access to the control solution. The effect of the BLA lesion was most apparent in high alcohol drinking adolescent rats. The BLA is essential for fear learning and is hyper-active in anxiety disorders. The results are consistent with adolescent heavy alcohol drinking inducing BLA hyper-activity, providing a neural mechanism for comorbid alcohol use disorder and anxiety disorders.
IJMS, Vol. 18, Pages 2415: Regulation of Chemokine–Receptor Interactions and Functions
International Journal of Molecular Sciences doi: 10.3390/ijms18112415
Authors: Martin Stone
Inflammation is the body’s response to injury or infection. As early as 2000 years ago, the Roman encyclopaedist Aulus Cornelius Celsus recognised four cardinal signs of this response—redness, heat, swelling and pain; a fifth sign is loss of function.[...]
IJMS, Vol. 18, Pages 2411: The Impact of Synaptic Zn2+ Dynamics on Cognition and Its Decline
International Journal of Molecular Sciences doi: 10.3390/ijms18112411
Authors: Atsushi Takeda Hanuna Tamano
The basal levels of extracellular Zn2+ are in the range of low nanomolar concentrations and less attention has been paid to Zn2+, compared to Ca2+, for synaptic activity. However, extracellular Zn2+ is necessary for synaptic activity. The basal levels of extracellular zinc are age-dependently increased in the rat hippocampus, implying that the basal levels of extracellular Zn2+ are also increased age-dependently and that extracellular Zn2+ dynamics are linked with age-related cognitive function and dysfunction. In the hippocampus, the influx of extracellular Zn2+ into postsynaptic neurons, which is often linked with Zn2+ release from neuron terminals, is critical for cognitive activity via long-term potentiation (LTP). In contrast, the excess influx of extracellular Zn2+ into postsynaptic neurons induces cognitive decline. Interestingly, the excess influx of extracellular Zn2+ more readily occurs in aged dentate granule cells and intracellular Zn2+-buffering, which is assessed with ZnAF-2DA, is weakened in the aged dentate granule cells. Characteristics (easiness) of extracellular Zn2+ influx seem to be linked with the weakened intracellular Zn2+-buffering in the aged dentate gyrus. This paper deals with the impact of synaptic Zn2+ signaling on cognition and its decline in comparison with synaptic Ca2+ signaling.
IJMS, Vol. 18, Pages 2413: Targeting Immune Cell Checkpoints during Sepsis
International Journal of Molecular Sciences doi: 10.3390/ijms18112413
Authors: Naeem Patil Yin Guo Liming Luan Edward Sherwood
Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Pre-clinical and clinical studies have shown that inhibitory immune checkpoint molecules, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cytotoxic T lymphocyte antigen-4 (CTLA-4), T cell membrane protein-3 (TIM-3), Lymphocyte activation-gene-3 (LAG-3) and 2B4, are upregulated during the course of sepsis. Engagement of these inhibitory molecules on various immune cells has been consistently shown to inhibit innate immune cell functions (e.g., phagocytosis, cytokine production and pathogen clearance) and also lead to impaired T cell competence. In numerous pre-clinical models of sepsis, therapeutic agents aimed at blocking engagement of inhibitory immune checkpoints on immune cells have been shown to improve innate and adaptive immune cell functions, increase host resistance to infection and significantly improve survival. Therefore, immunotherapy with immune cell checkpoint inhibitors holds significant potential for the future of sepsis therapy and merits further investigation.
IJMS, Vol. 18, Pages 2417: Environmental Burkholderia cenocepacia Strain Enhances Fitness by Serial Passages during Long-Term Chronic Airways Infection in Mice
International Journal of Molecular Sciences doi: 10.3390/ijms18112417
Authors: Alessandra Bragonzi Moira Paroni Luisa Pirone Ivan Coladarci Fiorentina Ascenzioni Annamaria Bevivino
Burkholderia cenocepacia is an important opportunistic pathogen in cystic fibrosis (CF) patients, and has also been isolated from natural environments. In previous work, we explored the virulence and pathogenic potential of environmental B. cenocepacia strains and demonstrated that they do not differ from clinical strains in some pathogenic traits. Here, we investigated the ability of the environmental B. cenocepacia Mex1 strain, isolated from the maize rhizosphere, to persist and increase its virulence after serial passages in a mouse model of chronic infection. B. cenocepacia Mex1 strain, belonging to the recA lineage IIIA, was embedded in agar beads and challenged into the lung of C57Bl/6 mice. The mice were sacrificed after 28 days from infection and their lungs were tested for bacterial loads. Agar beads containing the pool of B. cenocepacia colonies from the four sequential passages were used to infect the mice. The environmental B. cenocepacia strain showed a low incidence of chronic infection after the first passage; after the second, third and fourth passages in mice, its ability to establish chronic infection increased significantly and progressively up to 100%. Colonial morphology analysis and genetic profiling of the Mex1-derived clones recovered after the fourth passage from infected mice revealed that they were indistinguishable from the challenged strain both at phenotypic and genetic level. By testing the virulence of single clones in the Galleria mellonella infection model, we found that two Mex1-derived clones significantly increased their pathogenicity compared to the parental Mex1 strain and behaved similarly to the clinical and epidemic B. cenocepacia LMG16656T. Our findings suggest that serial passages of the environmental B. cenocepacia Mex1 strain in mice resulted in an increased ability to determine chronic lung infection and the appearance of clonal variants with increased virulence in non-vertebrate hosts.
Antibodies, Vol. 6, Pages 18: Monoclonal Antibody: A New Treatment Strategy against Multiple Myeloma
Antibodies doi: 10.3390/antib6040018
Authors: Shih-Feng Cho Liang Lin Lijie Xing Tengteng Yu Kenneth Wen Kenneth C. Anderson Yu-Tzu Tai
2015 was a groundbreaking year for the multiple myeloma community partly due to the breakthrough approval of the first two monoclonal antibodies in the treatment for patients with relapsed and refractory disease. Despite early disappointments, monoclonal antibodies targeting CD38 (daratumumab) and signaling lymphocytic activation molecule F7 (SLAMF7) (elotuzumab) have become available for patients with multiple myeloma in the same year. Specifically, phase 3 clinical trials of combination therapies incorporating daratumumab or elotuzumab indicate both efficacy and a very favorable toxicity profile. These therapeutic monoclonal antibodies for multiple myeloma can kill target cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent phagocytosis, as well as by direct blockade of signaling cascades. In addition, their immunomodulatory effects may simultaneously inhibit the immunosuppressive bone marrow microenvironment and restore the key function of immune effector cells. In this review, we focus on monoclonal antibodies that have shown clinical efficacy or promising preclinical anti-multiple myeloma activities that warrant further clinical development. We summarize mechanisms that account for the in vitro and in vivo anti-myeloma effects of these monoclonal antibodies, as well as relevant preclinical and clinical results. Monoclonal antibody-based immunotherapies have already and will continue to transform the treatment landscape in multiple myeloma.
Antioxidants, Vol. 6, Pages 90: Nox, Reactive Oxygen Species and Regulation of Vascular Cell Fate
Antioxidants doi: 10.3390/antiox6040090
Authors: Denise Burtenshaw Roya Hakimjavadi Eileen Redmond Paul Cahill
The generation of reactive oxygen species (ROS) and an imbalance of antioxidant defence mechanisms can result in oxidative stress. Several pro-atherogenic stimuli that promote intimal-medial thickening (IMT) and early arteriosclerotic disease progression share oxidative stress as a common regulatory pathway dictating vascular cell fate. The major source of ROS generated within the vascular system is the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family of enzymes (Nox), of which seven members have been characterized. The Nox family are critical determinants of the redox state within the vessel wall that dictate, in part the pathophysiology of several vascular phenotypes. This review highlights the putative role of ROS in controlling vascular fate by promoting endothelial dysfunction, altering vascular smooth muscle phenotype and dictating resident vascular stem cell fate, all of which contribute to intimal medial thickening and vascular disease progression.
Brain metastases are the most common intracranial tumors in adults, accounting for more than 50% of all such cases. The approach to and management of brain metastases have evolved significantly in recent years due to several reasons. These include advances in neurosurgical and radiotherapeutic techniques, improved systemic therapy options offering better systemic and intracranial disease control and prolongation of survival as a result of these improvements, making side-effects of proposed therapies (e.g. neurocognitive decline from whole brain radiotherapy) an important consideration. In this article, we review the the primary therapeutic approaches to the management of brain metastases, namely, surgery, stereotactic radiosurgery, and whole brain radiation therapy and the primary factors dictating choice.
Participants of the annual World Memory Championships regularly demonstrate extraordinary memory feats, such as memorising the order of 52 playing cards in 20 s or 1000 binary digits in 5 min. On a cognitive level, memory athletes use well-known mnemonic strategies, such as the method of loci. However, whether these feats are enabled solely through the use of mnemonic strategies or whether they benefit additionally from optimised neural circuits is still not fully clarified. Investigating 23 leading memory athletes, we found volumes of their right hippocampus and caudate nucleus were stronger correlated with each other compared to matched controls; both these volumes positively correlated with their position in the memory sports world ranking. Furthermore, we observed larger volumes of the right anterior hippocampus in athletes. Complementing these structural findings, on a functional level, fMRI resting state connectivity of the anterior hippocampus to both the posterior hippocampus and caudate nucleus predicted the athletes rank. While a competitive interaction between hippocampus and caudate nucleus is often observed in normal memory function, our findings suggest that a hippocampal–caudate nucleus cooperation may enable exceptional memory performance. We speculate that this cooperation reflects an integration of the two memory systems at issue-enabling optimal combination of stimulus-response learning and map-based learning when using mnemonic strategies as for example the method of loci.
Porcine reproductive and respiratory syndrome virus (PRRSV) is an important swine pathogen causing tremendous economic losses to the swine industry. To investigate the prevalence of PRRSV of genotype 2 (North American type, NA-type) in southwestern China, the Nsp2 hypervariable region (Nsp2 HV) and ORF5 of 61 PRRS viruses collected during 2012–2016 were sequenced and analyzed. All the virus detected clustered into the JXA1-like (52/61), VR-2332-like (7/61), and NADC30-like (2/61) sub-genotypes. Five deletions in Nsp2 HV were detected in addition to the typical 30aa discontinuous deletion in HP-PRRSV, and two of these five were not reported previously. Strikingly, two PRRS virus (SCnj16 and SCcd16) isolated in 2016 contained the classic HP-PRRSV molecular marker in the Nsp2-coding region, but belonged to the NADC30-like sub-genotype on the ORF5 gene. Further recombination and phylogenetic analysis on the two complete genomic sequences revealed that they may have originated from recombination events between the NADC30 and Chinese HP-PRRSV strains. The present study suggests that the endemic PRRSVs in the region have continuously evolved and new vaccine strategies are necessary for more efficient control of the virus.
Dysregulation in immune responses during pregnancy increases the risk of a having a child with an autism spectrum disorder (ASD). Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. We recently developed a mouse model of maternal allergic asthma (MAA) that induces changes in sociability, repetitive, and perseverative behaviors in the offspring. Since epigenetic changes help a static genome adapt to the maternal environment, activation of the immune system may epigenetically alter fetal microglia, the brain's resident immune cells. We therefore tested the hypothesis that epigenomic alterations to microglia may be involved in behavioral abnormalities observed in MAA offspring. We used the genome-wide approaches of whole genome bisulfite sequencing to examine DNA methylation and RNA sequencing to examine gene expression in microglia from juvenile MAA offspring. Differentially methylated regions were enriched for immune signaling pathways and important microglial developmental transcription factor binding motifs. Differential expression analysis identified genes involved in controlling microglial sensitivity to the environment and shaping neuronal connections in the developing brain. Differentially expressed genes significantly overlapped genes with altered expression in human ASD cortex, supporting a role for microglia in the pathogenesis of ASD.
Several promising chemopreventive agents have for lung cancer emerged in preclinical models and in retrospective trials. These agents have been shown to modulate pathways altered in carcinogenesis and reduce markers of carcinogenesis in animal and cell culture models. Cancer-prone transgenic mice with oncogenic Kras expressed in the airway epithelium (CcspCre/+; KrasLSL-G12D/+) were raised on diets compounded with myo-inositol. These animals form lung premalignant lesions in a stereotypical fashion over the ten weeks following weaning. Mice raised on myo-inositol containing diets showed potent reduction in the number, size, and stage of lesions as compared to those raised on control diets. myo-inositol has previously been reported to inhibit phosphoinositide 3-kinase (PI3K) signaling. However, in mice raised on myo-inositol, total PI3K signaling was largely unaffected. Proteomic and cytokine analyses revealed large reduction in IL-6 related pathways, including STAT3 phosphorylation. This effect was not due to direct inhibition of IL-6 production and autocrine signaling within the tumor cell, but rather through alteration in macrophage recruitment and in phenotype switching, with an increase in antitumoral M1 macrophages. This article is protected by copyright. All rights reserved.
Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO-Ab positivity and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4-related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO-Ab level, and TPO-Ab-related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid-related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer. This article is protected by copyright. All rights reserved.
Platinum-based chemotherapy (PBC) in combination with the 3rd generation drugs is the first-line treatment for patients with advanced non-small cell lung cancer (NSCLC); however, the efficacy is severely hampered by grade 3-4 toxicities. Nucleotide excision repair (NER) pathway is the main mechanism of removing platinum-induced DNA adducts, contributing to the toxicity and outcome of PBC. We analyzed data from 710 Chinese NSCLC patients treated with PBC and assessed the associations of 25 potentially functional single nucleotide polymorphisms (SNPs) in eight NER core genes with overall, gastrointestinal and hematologic toxicities. Through a two-phase screening study, we found that ERCC4 rs1799798 was significantly associated with overall and gastrointestinal toxicities [all patients: GA/AA vs. GG, odds ratio (OR)adj=1.61 and 2.35, 95% confidence interval (CI)=1.11-2.33 and 1.25-4.41, Padj=0.012 and 0.008, respectively]. Our prediction model for the overall toxicity incorporating rs1799798 demonstrated a significant increase in the area under the curve (AUC) value, compared with that for clinical factors only (all patients: AUC=0.61 vs. 0.59, 95% CI=0.57-0.65 vs. 0.55-0.63, P=0.010). Furthermore the ERCC4 rs1799798 A allele was associated with lower ERCC4 mRNA expression levels according to eQTL analysis. This study provided some new clue in future development of biomarkers for assessing toxicity and outcomes of platinum drugs in cancer treatment. This article is protected by copyright. All rights reserved.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest major cancers, with a five year survival rate of less than 8%. With current therapies only giving rise to modest life extension, new approaches are desperately needed. Even though targeting polyamine metabolism is a proven anticancer strategy, there are no reports which thoroughly survey the literature describing the role of polyamine biosynthesis and transport in PDAC. This review seeks to fill this void by describing what is currently known about polyamine metabolism in PDAC and identifies new targets and opportunities to treat this disease. Due to the pleiotropic effects that polyamines play in cells, this review covers diverse areas ranging from polyamine metabolism (biosynthesis, catabolism, and transport), as well as the potential role of polyamines in desmoplasia, autophagy and immune privilege. Understanding these diverse roles provides the opportunity to design new therapies to treat this deadly cancer via polyamine depletion. This article is protected by copyright. All rights reserved.
Understanding the molecular changes in tumors in response to anti-VEGF chemotherapy is crucial for optimization of the treatment strategy for metastatic colorectal cancer. We prospectively investigated changes in the amount and constitution of circulating tumor DNA (ctDNA) in serial peripheral blood samples during chemotherapy. Sixty-one plasma samples taken at different time points (baseline, remission, and post-progression) and pre-treatment tumor samples were collected from 21 patients who received bevacizumab-containing first-line chemotherapy. Extracted DNA was sequenced by next-generation sequencing using a panel of 90 oncogenes. Candidate ctDNAs in plasma were validated using mutational data from matching tumors. ctDNAs encoding one to six trunk mutations were found in all 21 cases, and the mutant allele frequency (MAF) was distributed over a wide range (1-89%). Significant decreases in the MAF at remission and increases in the MAF after progression were observed (p<0.001). Reduction in the MAF to below 2% in the remission period was strongly associated with better survival (16.6 vs. 32.5 months, P<0.001). In two cases, mutations (in CREBBP and FBXW7 genes) were newly detected in ctDNA at a low frequency of around 1% in the post-progression period. The use of ctDNA allows elucidation of the tumor clonal repertoire and tumor evolution during anti-VEGF chemotherapy. Changes in ctDNA levels could be useful as predictive biomarkers for survival. Mutations newly detected in ctDNA in the late treatment period might reveal the rise of a minor tumor clone that may show resistance to anti-VEGF therapy. This article is protected by copyright. All rights reserved.
Farmers occasionally need to add nitrogen fertilizer to their farms and gardens to make available just the precise nutrients for their plants’ growth. The applications of inorganic nitrogen fertilizers to various crops have been continuously increasing since last many decades globally. Although nitrogen fertilizer contributes substantially to yield enhancement, but excessive use of this manure has posed serious threats to environment and human health. Rate of nitrogen fertilizers application has a close relationship with nitrate accumulation in surrounding environment, groundwater, as well as leafy and root vegetables. Consumption of diets having high nitrate contents has contributed to endogenous nitrosation, which could lead to thyroid condition, various kinds of human cancers, neural tube defects (during fetus development), and diabetes. In this short review, the authors have tried to create awareness among general public, farming community, health practitioners, and agricultural scientists for the risk involved with excessive use of nitrogen fertilizers to human health. Carcinogenic activity and other adverse effects of N-nitroso compounds might be prevented by consuming vitamin C and antioxidants containing fruits and vegetables.
Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced immunoglobulin serum levels and absent or impaired antibody production. Clinical manifestations, including infections, inflammatory and autoimmune diseases, and malignancies, also involve various segments of the gastrointestinal tract. Chronic diarrhea is one of the most common gastrointestinal symptoms and may cause a wide spectrum of potentially life-threatening conditions as malabsorption and protein-energy malnutrition. We describe three female CVID adult patients presenting with chronic diarrhea, weight loss, and protein-energy malnutrition due to different underlying conditions. Our review of the literature explores the various gastrointestinal involvements in CVID and points out several histopathological findings proper of the disease, thus highlighting the relevance of the endoscopic and histological assessment in CVID patients presenting with chronic diarrhea.
IJERPH, Vol. 14, Pages 1387: Cross-Cultural Adaptation of the Social Vulnerability Index for Use in the Dutch Context
International Journal of Environmental Research and Public Health doi: 10.3390/ijerph14111387
Authors: Steven Bunt Nardi Steverink Melissa K. Andrew Cees P. van der Schans Hans Hobbelen
Being able to identify socially frail older adults is essential for designing interventions and policy and for the prediction of health outcomes, both on the level of individual older adults and of the population. The aim of the present study was to adapt the Social Vulnerability Index (SVI) to the Dutch language and culture for those purposes. A systematic cross-cultural adaptation of the initial Social Vulnerability Index was performed following five steps: initial translation, synthesis of translations, back translation, a Delphi procedure, and a test for face validity and feasibility. The main result of this study is a face-valid 32 item Dutch version of the Social Vulnerability Index (SVI-D) that is feasible in health care and social care settings. The SVI-D is a useful index to measure social frailty in Dutch-language countries and offers a broad, holistic quantification of older people’s social circumstances related to the risk of adverse health outcomes.
The purpose of this review is to update what is currently known about the major non-IgE-mediated food allergies: food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP), and food protein-induced enteropathy (FPE). These conditions are similar in that symptoms are regulated to the gastrointestinal tract; therefore understanding their specific features is important for diagnosis and management.
The most progress has been made in understanding FPIES with several recent large cohorts being described. The first international consensus guidelines for FPIES were published in 2017 and propose specific diagnostic criteria for acute FPIES as well as guidance for diagnosing chronic FPIES. Recent studies in FPIAP have challenged our thinking about the recommended duration of food avoidance and that cow’s milk avoidance is the primary management with reports of self-resolution without dietary management. FPE continues to appear to be on the decline.
FPIES, FPIAP, and FPE are distinguished from one another by their main clinical features: delayed repetitive vomiting in FPIES, benign blood in stool in FPIAP, and chronic diarrhea in FPE. Due to the risk of nutritional deficiencies with food avoidance in both infant and maternal diets if breastfeeding, confirmation of diagnosis with challenges is encouraged. Additional studies are needed for these conditions to elucidate pathophysiology, search for diagnostic markers, and understand natural history.
Polypharmacy is common in geriatric Parkinson’s disease (PD) patients in advanced disease stages with multiple comorbidities, bearing multiple risks for drug safety in theory.
The aim of this study was to empirically identify the most frequent and relevant contraindications and drug interactions actually occurring and compromising drug safety in PD in real life.
We conducted a prospective observational study in a multimorbid cohort of PD patients with polypharmacy admitted to a specialized hospital. Inclusion criteria were the presence of at least one comorbidity requiring pharmacotherapy and at least five different drugs in the discharge prescription. Hoehn and Yahr stage during the ‘on’ state, therapeutic problems related to motor and non-motor PD symptoms, comorbidities, and drug regimens on admission and discharge were analyzed for contraindications and interactions.
Overall, 127 patients were included (medium Hoehn and Yahr stage = IV, range II–V). Interactions with the anti-PD medication were mainly caused by other central nervous system (CNS)-active substances, cytochrome P450-metabolized substances, and QT-time prolonging substances. Contraindications against the anti-PD medication mainly occurred from internal, haematopoietic, neurologic and psychiatric diseases, and QT-time prolonging drugs. The highest frequency of interactions and contraindications were identified with levodopa (n = 119 at admission/n = 126 at discharge), entacapone (n = 46/42), pramipexole (n = 44/24), and amantadine (n = 32/30).
Several medically relevant risk factors (interactions and contraindications) frequently occurred in advanced PD patients. These findings provide a basis for developing programmes for awareness, education, monitoring, and preventive interventions to avoid adverse incidents. Future studies will need to evaluate preventive efficacy of structured drug safety programmes.
Sequence of photos shows a squad of ants over 4 hours as they move in and take apart a palm-sized spider left as a sacrifice by a curious photographer
In this study, the effect of gamma irradiation on the shelf life and properties of cucumber was investigated. These properties include weight reduction, fruit density, juice, tissue firmness, total soluble solids (TSS), total titratable acidity, chlorophyll and vitamin C, pH, marketability, flavor, frostbite and fungal effects. For this purpose, cucumbers were irradiated with dose of 2, 2.5 and 3 kGy. The exposure time was calculated by MCNP4C; the Monte Carlo particle transport code. Three types of fungi (white-Sclerotinia sclerotiorum, gray-Botrytis cinerea and olive-Cladosporium cucumerinum), were used to infect some samples. The chlorophyll and vitamin C preservation abilities were increased to about 3 and 1.4 times, respectively with irradiation treatment. Also, the shelf life was increased about 1 week, while chilling injuries is decreased. Samples’ resistance to the fungal growth was evident and the process of fungal growth on the irradiated samples was delayed up to 1 week. The best properties were obtained at the irradiation dose of 2 kGy since it had less effect on flavor, TSS and tissue firmness.
This is a first kind of study on genotype diversity of starches of Moth Bean an underutilized pulse of India. Physicochemical properties like amylose content (7.8–21.4%), swelling power (11–13.5 g/g), solubility (5.9–9.0%) of starches were observed to differ significantly among the six moth bean starches. Swelling power of all the moth bean starches was observed to increase in the temperature range of 55–95 °C. Scanning electron microscopy indicated polyhedral, irregular shape of granule. X-ray diffraction studies indicated a ‘C’ type crystalline structure and the starches differed significantly in relative crystallinity (17–34%) which affected significantly retro gradation tendencies of the starches. Peak viscosity of starches varied significantly and ranged between 4580 and 5087 cP. Resistant starch content of starches also varied significantly among the cultivars and ranged between 57.3 and 75.6%.
In this study, the effects of conventional and microwave roasting on phenolic compounds, free acidity, peroxide value, fatty acid composition and tocopherol content of pecan walnut kernel and oil was investigated. The oil content of pecan kernels was 73.78% for microwave oven roasted at 720 W and 73.56% for conventional oven roasted at 110 °C. The highest free fatty acid content (0.50%) and the lowest peroxide value (2.48 meq O2/kg) were observed during microwave roasting at 720 W. The fatty acid profiles and tocopherol contents of pecan kernel oils did not show significant differences compared to raw samples. Roasting process in microwave oven at 720 W caused the reduction of some phenolic compounds, while the content of gallic acid exhibited a significant increase.
The present investigation was undertaken to develop paranthas suiting diabetic population with added health benefits. Paranthas were prepared using fresh and dry segments of pomelo. The increase in the concentration of segments decreased the texture value from 1080 to 1022 g force (fresh segments) and 1005 to 870 g force (dry segments). Naringin along with other bioactive compounds were retained to a greater extent in Paranthas containing dry pomelo fruit segments. Paranthas prepared using 20% (fresh) and 5% (dry) were sensorily acceptable. The pomelo incorporated paranthas had higher levels of resistance starch fractions (12.94%) with low predicted glycemic index (49.89%) compared to control Paranthas at 5.54 and 58.64% respectively. The fortified paranthas with an considerable content of bioactive compounds and low glycemic index indicate the possibility of using it as a dietary supplement. Thus utilization of pomelo fortification helps in improving the nutritional and functional property of paranthas suiting diabetes as well as general population.
This work was designed to obtain the valuable compounds with antioxidant, anti-proliferative and anti-inflammatory activities from Astragalus chinensis. Ethyl acetate fraction obtained from A. chinensis L.f. had significant antioxidant, anti-proliferative and anti-inflammatory activities. Subsequently, five single compounds were separated and purified, which were identified as formononetin (1), rhamnocitrin (2), calycosin (3), β-daucosterol (4), rhamnocitrin-3-O-β-d-glucoside (5). The results displayed that formononetin and rhamnocitrin exhibited significant cytotoxicity actions against tumor cell lines. Calycosin exerted the strongest anti-inflammatory effect of inhibition effects on NO production in macrophages.
Ultrasound-assisted extraction was used to investigate the polyphenolic compounds, particularly anthocyanins, present in myrtle alcoholic extracts. This type of extract is typical in the making of liqueurs obtained from herbs or plants, especially medicinal plants. The leaf extracts were found to contain flavonoids from the quercetin and myricetin families. Besides these, the berry extracts also showed the presence of anthocyanins, hydrolysable tannins and quinic acid. The antioxidant capacity was studied using the ORAC and TEAC methods and the polyphenol content was measured using the Folin–Ciocalteu method. The results showed that the values produced by the ORAC and TEAC methods were in agreement and that the antioxidant capacity correlated with the polyphenol content. The results showed that the leaf extracts exhibited higher antioxidant capacity than the berry extracts. The extraction method was easily implementable, and proved to be a swift method for obtaining bioactive compounds from vegetable matrices.
Malt sprout (MS), a by-product of the malt industry obtained by removing rootlets and sprouts from the seed of germinated barley (Hordeum vulgare L.), was used as culture, dehydration and storage medium of three strains of lactobacilli: Lactobacillus salivarius CM-CIDCA 1231B and CM-CIDCA 1232Y and Lactobacillus plantarum CIDCA 83114. The three strains were grown in MS and MS supplemented with 20% w/v fructo-oligosaccharides (MS FOS). Bacterial growth was determined by registering the decrease of pH and by plate counting. Comparable results with those of microorganisms grown in MRS (controls) were observed in terms of lag times, ΔpH and acidification rates. Furthermore, during fermentation, a significant increase of DP6 (FOS with degree of polymerization 6) was observed at expenses of inulin and DP7, probably indicating their hydrolysis. A concomitant decrease of DP3, sucrose and monosaccharides was also observed, as result of their bacterial consumption during growth. The presence of FOS in the fermented media protected microorganisms during freeze-drying and storage, as no decrease of culturability was observed after 60 days at 4 °C (> 108 CFU/mL). Using MS appears as an innovative strategy for the production of lactobacilli at large scale, supporting their use for the elaboration of functional foods containing prebiotics and probiotics.
Poultry production is considered one of the prospective opportunities to accomplish sustainable and quick production of superior protein to challenge the growing mandate for animal protein. Therefore, this study was aimed to explore the difference on growth performance, carcass traits, meat quality and amino acid profile of different Japanese quails strains. A total of 480 quail chicks of four different plumage colors (120 of each white, golden, gray and brown) were collected after hatching. At 6 week of age, birds were stunned and decapitated to determine the physical meat quality, thiobarbituric acid reactive substances and amino acid profile. White quails had the highest weight of slaughter, carcass, dressing, carcass yield, liver, gizzard, heart and spleen (197.27 g, 169.27 g, 91%, 82%, 6.63 g, 6.53 g, 2.27 g and 0.40 g, respectively). Also, they had the highest PhU, lightness, yellowness and water holding capacity with the lowest level of redness, cooking losses and thiobarbituric acid in pectoral (6.28, 46.40, 12,46, 22.17, 9.20, 19.21 and 0.44, respectively) and thigh muscles (6.37, 42.30, 11.51, 26.01, 10.12 and 0.93, respectively). Moreover, they possessed the highest level of all essential (11.68 and 10.16 g/100 g protein in pectoral and thigh muscles, respectively) and non essential amino acids (13.27 and 12.54 g/100 g protein in pectoral and thigh muscles, respectively). Therefore, the current study revealed that white quails had the heaviest body weight with the best carcass traits and meat quality.