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Interstitial nephritis in melanoma patients secondary to PD-1 checkpoint inhibitor
No full textAbstract
Background
Immune checkpoint inhibitors have become the first line therapy in melanoma treatment and their use is extending to other malignancies. However, we are still learning about immune side effects produced by these drugs and their severity especially in patients with history of inflammatory diseases.
Case presentation
We present two cases of metastatic melanoma treated with nivolumab and pembrolizumab (anti PD-1). Both patients developed acute interstitial nephritis during immune checkpoint therapy. We emphasize the causal association between immune checkpoint inhibitors and the nephritis. The timing of drug administration and appearance of nephritis is suggestive of a causal relation between the checkpoint inhibitor therapy and this adverse event.
Conclusions
Although uncommon, some side effects from checkpoint inhibitors can be severe and may need to be addressed with immunosuppression. Given the increasing frequency of immunotherapy use, awareness should be raised in regards to immune side effects and their appropriate management
Comparing internal and external impacts of sustainable innovation: an exploratory study
No full textAbstract
Sustainable business impact is growing within the field of impact assessment, however, the field, specifically in regard to Entrepreneurship, would benefit from theory based on comparisons of external and internal impacts of environmental and social innovation. This exploratory study bridges this gap by analyzing an aggregate of case studies of sustainable innovation. Significant differences were found in comparing forms of innovations where product focused innovations favored the environment and service or new business usage innovations favored society. Significant differences were also found in comparing external impacts where either a reduction of waste or an increase in clean energy favored environmental innovations while benefits for under-served populations or improvements in markets favored social innovations as expected. The comparison with the internal impacts showed an increase in revenue and sales favored both types of innovations yet a significant difference was still found between the two. Suggested theories for future research are provided
Every breath you take: physiology and the ecology of knowing in meditative practice
No full textAbstract
As a physiologist interested in contemplative practice and meditation I have enjoyed the opportunity of lecturing to students engaged in the study of contemplation. My pedagogic role was to expose them to some of what we know of the biological phenomena that are or may be taking place during various meditative states \u2014 explicating for them the details of how the human body actually works. In the course of working with students and faculty engaged in meditation I formulated the following questions relating biological science and contemplative practice: What should a practitioner or a teacher of meditation know about basic human anatomy and physiology? Is it necessary for someone engaging in contemplative practice to understand how the human organism is actually put together and how it works? Will knowledge of how the various organs work with one another enhance one's ability to meditate or can we dispense with this information and suffer no consequences in our practice? The fundamental importance of somatic or physical phenomena in meditative practice (for example in control of breath, heart rate, or metabolism) and most people's lack of understanding of basic human anatomy and physiology led me to answer yes to all of these questions. In this paper I outline the physiological knowledge and particular insights I have found useful for enhancing a person's understanding of how we breathe, how we regulate our heart rate, and how we control our metabolic rate in 'control' or non-meditative states and the kinds of changes we might expect in a meditating subject. I link what is perhaps the fundamental principle of physiology, the concept of 'homeostasis', with the balance and integration of the body systems sought by people engaged in contemplation. Mind-body harmony or an enhanced awareness of this linkage between the mind and the body can, in my opinion, be more fully realized when coupled with an understanding of what Hippocrates called, 'the nature of the body', that is, what the body actually does and how it does it
An efficient multi-stage fermentation strategy for the production of microbial oil rich in arachidonic acid in Mortierella alpina
No full textAbstract
Background
Fungal morphology and aeration play a significant role in the growth process of Mortierella alpina . The production of microbial oil rich in arachidonic acid (ARA) in M. alpina was enhanced by using a multi-stage fermentation strategy which combined fed-batch culture with precise control of aeration and agitation rates at proper times.
Results
The fermentation period was divided into four stages according to the cultivation characteristics of M. alpina . The dissolved oxygen concentration was well suited for ARA biosynthesis. Moreover, the ultimate dry cell weight (DCW), lipid, and ARA yields obtained using this strategy reached 41.4, 22.2, 13.5\ua0g/L, respectively. The respective values represent 14.8, 25.8, and 7.8% improvements over traditional fed-batch fermentation processes.
Conclusions
This strategy provides promising control insights for the mass production of ARA-rich oil on an industrial scale. Pellet-like fungal morphology was transformed into rice-shaped particles which were beneficial for oxygen transfer and thus highly suitable for biomass accumulation
Case report on managing incomplete bone formation after bilateral sinus augmentation using a palatal approach and a dilating balloon technique
No full textAbstract
Background
Patients with resorbed edentulous alveolar ridges in the posterior maxilla often require lateral window sinus augmentation procedures prior to implant placement. Lateral window sinus augmentation procedures can produce incomplete bone augmentation as consequence of surgical and healing complications producing unusual and complex sinus anatomy. Although incomplete bone formation after sinus augmentation has been described in a previous case reports, this is the first case report that describes grafting these compromised sites prior to implant placement.
Case presentation
A 65-year-old male patient with no known medical conditions presented with severe chronic localized periodontitis and a combined periodontal-endodontic lesion affecting three first molars. Initial ridge preservation and lateral window sinus augmentation resulted in incomplete bone formation and complex sinus floor anatomy on both right and left sides. A dilating balloon technique on one side and a palatal approach on the other side were utilized for additional sinus augmentation using particulate allograft and resorbable collagen membranes. Healing was uneventful, and implants could be placed and restored at all sites. Periodontal maintenance was conducted every 3\ua0months, and the implants have been in function and periodontally healthy for 2\ua0years.
Conclusion
Despite initial failure of sinus augmentation to produce suitable implant sites, it is possible to rescue these sites with re-entry grafting procedures and allow successful implant placement and restoration
Comparative analysis of the root transcriptomes of cultivated sweetpotato (Ipomoea batatas [L.] Lam) and its wild ancestor (Ipomoea trifida [Kunth] G. Don)
No full textAbstract
Background
The complex process of formation of storage roots (SRs) from adventitious roots affects sweetpotato yield. Identifying the genes that are uniquely expressed in the SR forming cultivated species, Ipomoea batatas ( Ib ), and its immediate ancestral species, Ipomoea trifida ( It ), which does not form SRs, may provide insights into the molecular mechanisms underlying SR formation in sweetpotato.
Results
Illumina paired-end sequencing generated ~208 and ~200 million reads for Ib and It , respectively. Trinity assembly of the reads resulted in 98,317 transcripts for Ib and 275,044 for It, after post-assembly removal of trans -chimeras. From these sequences, we identified 4,865 orthologous genes in both Ib and It , 60 paralogous genes in Ib and 2,286 paralogous genes in It . Among paralogous gene sets, transcripts encoding the transcription factor RKD , which may have a role in nitrogen regulation and starch formation, and rhamnogalacturonate lyase ( RGL ) family proteins, which produce the precursors of cell wall polysaccharides, were found only in Ib. In addition, transcripts encoding a K
+
efflux antiporter ( KEA5 ) and the ERECTA protein kinase, which function in phytohormonal regulation and root proliferation, respectively, were also found only in Ib . qRT-PCR indicated that starch and sucrose metabolism genes, such as those encoding ADP-glucose pyrophosphorylase and beta-amylase, showed lower expression in It than Ib , whereas lignin genes such as caffeoyl-CoA O-methyltransferase ( CoMT ) and cinnamyl alcohol dehydrogenase ( CAD ) showed higher expression in It than Ib. A total of 7,067 and 9,650 unique microsatellite markers, 1,037,396 and 495,931 single nucleotide polymorphisms (SNPs) and 103,439 and 69,194 InDels in Ib and It, respectively, were also identified from this study.
Conclusion
The detection of genes involved in the biosynthesis of RGL family proteins, the transcription factor RKD , and genes encoding a K
+
efflux antiporter ( KEA5 ) and the ERECTA protein kinase only in I. batatas indicate that these genes may have important functions in SR formation in sweetpotato. Potential molecular markers (SNPs, simple sequence repeats and InDels) and sequences identified in this study may represent a valuable resource for sweetpotato gene annotation and may serve as important tools for improving SR formation in sweetpotato through breeding
Atherosclerotic and thrombotic genetic and environmental determinants in Egyptian coronary artery disease patients: a pilot study
No full textAbstract
Background
Coronary artery disease (CAD) is the leading cause of morbidity and mortality worldwide. Multiple genetic variants in combination with various environmental risk factors have been implicated. This study aimed to investigate the association of twelve thrombotic and atherosclerotic gene variants in combination with other environmental risk factors with CAD risk in a preliminary sample of Egyptian CAD patients.
Methods
Twenty three consecutive CAD patients undergoing diagnostic coronary angiography and 34 unrelated controls, have been enrolled in the study. Genotyping was based on polymerase chain reaction and reverse multiplex hybridization. Five genetic association models were tested. Data distribution and variance homogeneity have been checked by Shapiro-Wilk test and Levene test, respectively; then the appropriate comparison test was applied. Spearman\u2019s rank correlation coefficient was used for correlation analysis and logistic regression has been performed to adjust for significant risk factors. Clustering the study participants according to gene-gene and gene-environment interaction has been done by Detrended Correspondence Analysis (DCA).
Results
The univariate analysis indicated that the five variants; rs1800595 ( FVR2; factor 5), rs1801133 ( MTHFR ; 5,10-methylenetetrahydrofolate reductase), rs5918 ( HPA-1; human platelet antigen 1), rs1799752 ( ACE; angiotensin-converting enzyme), and rs7412 and rs429358 ( ApoE; apolipoprotein E) were significantly associated with CAD susceptibility under different genetic models. Multivariate analysis revealed clustering of the study population into three patient groups (P) and one control group. FVR 2 was the most variant associated with CAD patients, combined with the factor V Leiden ( FVL ) variant in P1 cluster and with both ACE and MTHFR 667C\u2009>\u2009T in P2. Whereas, P3 was mostly affected by both MTHFR 667C\u2009>\u2009T and FXIII (factor 13) V89L mutations. When combined with traditional risk factors, P1 was mostly affected by dyslipidemia, smoking and hypertension, while P2 was mostly affected by their fasting blood sugar levels and ApoE variant.
Conclusions
Taken together, these preliminary results could have predictive value to be applied in refining a risk profile for our CAD patients, in order to implement early preventive interventions including specific antithrombotic therapy. Further large scale and follow-up studies are highly recommended to confirm the study findings
The safety of introducing a new generation TAVR device: one departments experience from introducing a second generation repositionable TAVR
No full textAbstract
Background
In the evolving field of transcatheter aortic valve replacements a new generation of valves have been introduced to clinical practice. With the complexity of the TAVR procedure and the unique aspects of each TAVR device, there is a perceived risk that changing or adding a new valve in a department could lead to a worse outcome for patients, especially during the learning phase. The objective was to study the safety aspect of introducing a second generation repositionable transcatheter valve (Boston Scientific Lotus valve besides Edwards Sapien valve) in a department.
Methods
In a retrospective study, 53 patients receiving the Lotus system, and 47 patients receiving the Sapien system over a period of three years were compared for short-term outcome according to VARC-2 definitions and 1-year survival.
Results
Outcome in terms VARC-2 criteria for early safety and clinical efficacy, stroke rate, and survival at 30\ua0days and at 1\ua0year were similar. The Lotus valve had less paravalvular leakage, where 90% had none or trace aortic insufficiency as compared to only 48% for the Sapien system.
Conclusions
Introduction of a new generation valve can be done with early device success and safety, and without jeopardizing the outcome for patients up to one year. We found no adverse effects by changing valve type and observed improved outcome in terms of lower PVL-rates. Both existing and new centers starting a TAVR program can benefit from the use of a new generation device
Clinical importance of personality difficulties: diagnostically sub-threshold personality disorders
No full textAbstract
Background
Current categorical classification of personality disorders has been criticized for overlooking the dimensional nature of personality and that it may miss some sub-threshold personality disturbances of clinical significance. We aimed to evaluate the clinical importance of these conditions. For this, we used a simple four-level dimensional categorization based on the severity of personality disturbance.
Methods
The sample consisted of 352 patients admitted to mental health services. All underwent diagnostic assessments (SCID-I and SCID-II) and filled in questionnaires concerning their social situation and childhood adversities, and other validated tools, including the Beck Depression Inventory (BDI), Alcohol Use Disorders Identification Test (AUDIT), health-related quality of life (15D), and the five-item Mental Health Index (MHI-5). The patients were categorized into four groups according to the level of personality disturbance: 0\u2009=\u2009No personality disturbance, 1\u2009=\u2009Personality difficulty (one criterion less than threshold for one or more personality disorders), 2\u2009=\u2009Simple personality disorder (one personality disorder), and 3\u2009=\u2009Complex/Severe personality disorder (two or more personality disorders or any borderline and antisocial personality disorder).
Results
The proportions of the groups were as follows: no personality disturbance 38.4% ( n \u2009=\u2009135), personality difficulty 14.5% ( n \u2009=\u200951), simple personality disorder 19.9% ( n \u2009=\u200970), and complex/severe personality disorder 24.4% ( n \u2009=\u200986). Patients with no personality disturbance were significantly differentiated (p\u2009<\u20090.05) from the other groups regarding the BDI, 15D, and MHI-5 scores as well as the number of Axis I diagnoses. Patients with complex/severe personality disorders stood out as being worst off. Social dysfunction was related to the severity of the personality disturbance. Patients with a personality difficulty or a simple personality disorder had prominent symptoms and difficulties, but the differences between these groups were mostly non-significant.
Conclusions
An elevated severity level of personality disturbance is associated with an increase in psychiatric morbidity and social dysfunction. Diagnostically sub-threshold personality difficulties are of clinical significance and the degree of impairment corresponds to actual personality disorders. Since these two groups did not significantly differ from each other, our findings also highlight the complexity related to the use of diagnostic ..
Are risk predicting models useful for estimating survival of patients with rheumatoid arthritis-associated interstitial lung disease?
No full textAbstract
Background
Risk predicting models have been applied in idiopathic pulmonary fibrosis (IPF), but still not validated in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The purpose of this study was to test the suitability of three prediction models as well as individual lung function and demographic factors for evaluating the prognosis of RA-ILD patients.
Methods
Clinical and radiological data of 59 RA-ILD patients was re-assessed. GAP (gender, age, physiologic variables) and the modified interstitial lung disease (ILD)-GAP as well as the composite physiologic indexes (CPI) were tested for predicting mortality using the goodness-of-fit test and Cox model. Potential predictors of mortality were also sought from single lung function parameters and clinical characteristics.
Results
The median survival was 152 and 61\ua0months in GAP / ILD-GAP stages I and II ( p \u2009=\u20090.017). Both GAP and ILD-GAP models accurately estimated 1-year, 2-year and 3-year mortality. CPI ( p \u2009=\u20090.025), GAP ( p \u2009=\u20090.008) and ILD-GAP ( p \u2009=\u20090.028) scores, age ( p \u2009=\u20090.002), baseline diffusion capacity to carbon monoxide (DLCO) ( p \u2009=\u20090.014) and hospitalization due to respiratory reasons ( p \u2009=\u20090.039), were significant predictors of mortality in the univariate analysis, whereas forced vital capacity (FVC) was not predictive. CPI score (HR 1.03, p \u2009=\u20090.018) and baseline DLCO (HR 0.97, p \u2009=\u20090.011) remained significant predictors of mortality after adjusting for age.
Conclusions
GAP and ILD-GAP are applicable for evaluating the risk of death of patients with RA-ILD in a similar manner as in those with IPF. Baseline DLCO and CPI score also predicted survival