[Detection of the mecA gene in coagulase positive Staphylococcus isolated from cats].
Bacterial resistance is a global concern for public health. Reports of antimicrobial resistance, including that against methicillin, have increased in strains of coagulase positive Staphylococcus (CPS) isolated from pets, however in Chile this information is limited. To determine the antimicrobial susceptibility profiles and to detect the mecA gene in CPS strains isolated from cats in Chile. 134 samples were obtained from healthy cats and cats with skin lesions. These strains were characterized in their coagulase production and identified by BBL Crystal kit. The antimicrobial susceptibility was determined by Kirby Bauer method against 12 antimicrobials, including oxacillin. All strains were subjected to PCR to detect the mecA gene. 72 CPS strains were isolated, including S. aureus and S. intermedius. Antimicrobial resistance against at least one drug was detected in strains from both healthy cats (75%) and from cats with skin lesions (87.5%). The mecA gene was detected in eight methicillin-resistant strains and also in three sensitive strains, being in general multi-resistant. These results highlight the role of pets as reservoirs of bacterial resistance, and their potential impact on national public health.


What is the treatment effect of surgery compared with nonoperative treatment in patients with lumbar spinal stenosis at 1-year follow-up?
The aim of this study was to obtain an unbiased causal treatment estimate of the between-group difference of surgery versus nonoperative treatment with respect to outcomes on quality of life, pain, and disability in patients with degenerative lumbar spinal stenosis (DLSS) 12 months after baseline. The authors included DLSS patients from a large prospective multicenter observational cohort study. Propensity score matching was used, including 15 demographic, clinical, and MRI variables. Linear and logistic mixed-effects regression models were applied to quantify the between-group treatment effect. Unmeasured confounding was addressed in a sensitivity analysis, assessing the robustness of the results. A total of 408 patients were included in this study, 222 patients after matching, with 111 in each treatment group. Patients with nonoperative treatment had lower quality of life at the 12-month follow-up (−6.21 points, 95% CI −9.93 to −2.49) as well as lower chances of reaching a minimal clinically important difference in Spinal Stenosis Measure (SSM) symptoms (OR 0.26, 95% CI 0.13 to 0.53) and SSM function (OR 0.26, 95% CI 0.14 to 0.49), than patients undergoing surgery. These results were very robust in case of unmeasured confounding. The surgical complication rate was low; 5 (4.5%) patients experienced a durotomy during intervention, and 5 (4.5%) patients underwent re-decompression. The authors used propensity score matching to assess the difference in treatment efficacy of surgery compared with nonoperative treatment in elderly patients with DLSS. This study delivers strong evidence that surgical treatment is superior to nonoperative treatment. It helps in clinical decision-making, especially when patients suffer for a long time, sometimes over many years, hoping for a spontaneous improvement of their symptoms. In light of these new results, the number of years with disability can hopefully be reduced by providing adequate treatment at the right time for this ever-growing elderly and frail population. DLSS = degenerative lumbar spinal stenosis; HADS = Hospital Anxiety and Depression Scale; ITT = intention-to-treat; LSOS = Lumbar Stenosis Outcome Study; MCID = minimal clinically important difference; RCT = randomized controlled trial; SMD = standardized mean difference; SSM = Spinal Stenosis Measure.


Access to eye health services among indigenous Australians: an area level analysis.
This project is a community-level study of equity of access to eye health services for Indigenous Australians. The project used data on eye health services from multiple sources including Medicare Australia, inpatient and outpatient data and the National Indigenous Eye Health Survey.The analysis focused on the extent to which access to eye health services varied at an area level according to the proportion of the population that was Indigenous (very low = 0-1.0%, low = 1.1-3.0%, low medium = 3.1-6.0%, high medium = 6.1-10.0%, high = 10.1-20.0%, very high = 20 + %). The analysis of health service utilisation also took into account age, remoteness and the Socioeconomic Indices for Areas (SEIFA). The rate of eye exams provided in areas with very high Indigenous populations was two-thirds of the rate of eye exams for areas with very low indigenous populations. The cataract surgery rates in areas with high medium to very high Indigenous populations were less than half that reference areas. In over a third of communities with very high Indigenous populations the cataract surgery rate fell below the World Health Organization (WHO) guidelines compared to a cataract surgery rate of 3% in areas with very low Indigenous populations. There remain serious disparities in access to eye health service in areas with high Indigenous populations. Addressing disparities requires a co-ordinated approach to improving Indigenous people's access to eye health services. More extensive take-up of existing Medicare provisions is an important step in this process. Along with improving access to health services, community education concerning the importance of eye health and the effectiveness of treatment might reduce reluctance to seek help.


Exceptionally E- and β-selective NHC-Cu-catalyzed proto-silyl additions to terminal alkynes and site- and enantioselective proto-boryl additions to the resulting vinylsilanes: synthesis of enantiomerically enriched vicinal and geminal borosilanes.
An exceptionally site- and E-selective catalytic method for preparation of Si-containing alkenes through protosilylation of terminal alkynes is presented. Furthermore, the vinylsilanes obtained are used as substrates to generate vicinal or geminal borosilanes by another catalytic process; such products are derived from enantioselective protoborations of the Si-substituted alkenes. All transformations are catalyzed by N-heterocyclic carbene (NHC) copper complexes. Specifically, a commercially available imidazolinium salt, cheap CuCl (1.0 mol%) and Me(2)PhSi-B(pin), readily and inexpensively prepared in one vessel, are used to convert terminal alkynes to (E)-β-vinylsilanes efficiently (79-98% yield) and in >98% E and >98% β-selectivity. Vinylsilanes are converted to borosilanes with 5.0 mol% of a chiral NHC-Cu complex in 33-94% yield and up to 98.5:1.5 enantiomeric ratio (e.r.). Alkyl-substituted substrates afford vicinal borosilanes exclusively; aryl- and heteroaryl-substituted alkenes deliver the geminal isomers preferentially. Different classes of chiral NHCs give rise to high enantioselectivities in the two sets of transformations: C(1)-symmetric monodentate Cu complexes are most suitable for reactions of alkyl-containing vinylsilanes and bidentate sulfonate-bridged variants furnish the highest e.r. for substrates with an aryl substituent. Working models that account for the observed trends in selectivity are provided. Utility is demonstrated through application towards a formal enantioselective total synthesis of naturally occurring antibacterial agent bruguierol A.


Influence of age and maturation status on sprint acceleration characteristics in junior Australian football.
This study aimed to investigate the influence of chronological age and maturation status on sprint acceleration characteristics in junior Australian football (AF) players. Biological maturity of 109 subjects was assessed and subjects were grouped according to predicted years from peak height velocity (PHV) (pre-, mid-, and post-PHV) and chronological age (13 years, 14 years, and 15 years). A one-way multivariate analysis of variance and magnitude-based decisions were used to determine between-group differences. Instantaneous velocity was measured during two maximal 30m sprints via radar gun with the velocity-time data used to derive the force, velocity, and power characteristics. Chronologically, the greatest differences were observed between the 13 and 14 year old groups with the latter group producing likely greater relative maximum power (Pmax) (ES[effect size]=0.44) and theoretical maximal velocity (V0) (ES=0.49). The post-PHV group likely demonstrated a greater ability to apply force at faster velocity (V0; ES=0.59) and orient the force in a horizontal direction (Drf%; ES=-0.49) than the mid-PHV group. No differences in relative theoretical maximal force (F0) were observed between groups. Considering the findings, practitioners should aim to improve relative lower limb strength through heavy sled push or sled pulls and traditional strength training exercises to improve relative F0.


The living body in the psychoanalytic experience.
Instead of viewing body and psyche as two "substances," the author proposes that they be seen as two ways of experiencing the complex reality of the human being. Clinically, this translates into an exploration of the possibility of including the somatic in the territory of what can be represented--that is, recognizing in somatic and sensory elements and in bodily functions the potential for meaning and language, appreciating their status as precursors of representation. These somatic signals may be detected in a dialogue involving not only the minds of analyst and analysand, but also their bodies. Clinical examples are given involving different bodily functions.


Enhanced proapoptotic effects of tumor necrosis factor-related apoptosis-inducing ligand on temozolomide-resistant glioma cells.
Death receptor targeting is an attractive approach in experimental treatment for tumors such as malignant gliomas, which are resistant to radiation and chemotherapy. Among the family of cytokines referred to as death li gands, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted clinical interest. The aim of this study was to assess whether TRAIL can be used as an adjuvant to temozolomide (TMZ) for apoptosis induction in malignant glioma cell lines. Six human malignant glioma cell lines (A172, U87, U251, T98, U343, and U373) were exposed to human (h)TRAIL, TMZ, or an hTRAIL/TMZ combined treatment. Cell viability was assayed using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide and phase-contrast microscopy. Cell apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique and quantified using flow cytometric analysis. The apoptosis signaling cascade was studied with Western blotting. The additive effects of hTRAIL and TMZ resulted in a significant decrease in cell viability and an increased apoptotic rate. Expression of the death receptors DR5 and DR4 in two cell lines (A172 and U251) upregulated significantly when they were used in combination hTRAIL/TMZ treatment (p < 0.05 compared with baseline control), leading to activation of caspase-8 and caspase-3 (p < 0.05 compared with baseline control) and confirming an extrinsic apoptotic pathway. A cell intrinsic pathway through mitochondrial cytochrome c was not activated. Based on this work, one may infer that hTRAIL should be considered as an adjuvant treatment for TMZ-resistant human malignant gliomas.


Hepatitis B virus PreS2-mutant large surface antigen activates store-operated calcium entry and promotes chromosome instability.
Hepatitis B virus (HBV) is a driver of hepatocellular carcinoma, and two viral products, X and large surface antigen (LHBS), are viral oncoproteins. During chronic viral infection, immune-escape mutants on the preS2 region of LHBS (preS2-LHBS) are gain-of-function mutations that are linked to preneoplastic ground glass hepatocytes (GGHs) and early disease onset of hepatocellular carcinoma. Here, we show that preS2-LHBS provoked calcium release from the endoplasmic reticulum (ER) and triggered stored-operated calcium entry (SOCE). The activation of SOCE increased ER and plasma membrane (PM) connections, which was linked by ER- resident stromal interaction molecule-1 (STIM1) protein and PM-resident calcium release- activated calcium modulator 1 (Orai1). Persistent activation of SOCE induced centrosome overduplication, aberrant multipolar division, chromosome aneuploidy, anchorage-independent growth, and xenograft tumorigenesis in hepatocytes expressing preS2- LHBS. Chemical inhibitions of SOCE machinery and silencing of STIM1 significantly reduced centrosome numbers, multipolar division, and xenograft tumorigenesis induced by preS2-LHBS. These results provide the first mechanistic link between calcium homeostasis and chromosome instability in hepatocytes carrying preS2-LHBS. Therefore, persistent activation of SOCE represents a novel pathological mechanism in HBV-mediated hepatocarcinogenesis.


[The perception of health, social support and family function in HIV seropositivity].
To discover the perception of health, social support and family function for asymptomatic HIV carriers. This was an observation crossover study, using validated questionnaires. Almanjayar and Cartuja Health Centres in Granada. 58 HIV+ patients belonging to the two basic areas were included. They were selected from the archives of the health centres and from the infectious diseases clinic of the referral hospital. There were an equal number of controls with similar socio-demographic characteristics. The questionnaires used were as follows: GHQ, DUKE-UNC, the family APGAR, which measure health perception, social support and family function, respectively. Of seropositive patients, 58% presented a negative perception of their health, mainly expressed through symptoms of anguish and anxiety; as against 25% of the control group. As to social support, 29% of the HIV+ carriers perceived low levels of support, as against 6.9% of the control group. We found family dysfunction among 46% of seropositive patients, as against 12% of the control group. The Chi squared test was used for the analysis: all the differences were significant. Patients who are HIV carriers, even when they are asymptomatic, have a poor health perception, which can be attributed to the nature of the illness. The low level of social support detected, linked to the stress involved in being seropositive, may be the origin of the family dysfunction observed in 46% of our sample. We recommend action at individual, family and community levels in order to improve these patients' quality of life, strength their support structures and restore balance to family function.


Novel Insights into the Therapeutic Potential of Lung-Targeted Gene Transfer in the Most Common Respiratory Diseases.
Over the past decades, a better understanding of the genetic and molecular alterations underlying several respiratory diseases has encouraged the development of new therapeutic strategies. Gene therapy offers new therapeutic alternatives for inherited and acquired diseases by delivering exogenous genetic materials into cells or tissues to restore physiological protein expression and/or activity. In this review, we review (1) different types of viral and non-viral vectors as well as gene-editing techniques; and (2) the application of gene therapy for the treatment of respiratory diseases and disorders, including pulmonary arterial hypertension, idiopathic pulmonary fibrosis, cystic fibrosis, asthma, alpha-1 antitrypsin deficiency, chronic obstructive pulmonary disease, non-small-cell lung cancer, and COVID-19. Further, we also provide specific examples of lung-targeted therapies and discuss the major limitations of gene therapy.


Cervical vestibular evoked myogenic potential (cVEMP) findings in adults with sensorineural hearing loss (SNHL): comparisons between 500 Hz tone burst and narrowband CE-Chirp stimuli.
There has been a growing interest in studying the usefulness of chirp stimuli in recording cervical vestibular evoked myogenic potential (cVEMP) waveforms. Nevertheless, the study outcomes are debatable and require verification. In view of this, the aim of the present study was to compare cVEMP results when elicited by 500 Hz tone burst and narrowband (NB) CE-Chirp stimuli in adults with sensorineural hearing loss (SNHL). Fifty adults with bilateral SNHL (aged 20-65 years) underwent the cVEMP testing based on the established protocol. The 500 Hz tone burst and NB CE-Chirp (centred at 500 Hz) stimuli were presented to each ear at an intensity level of 120.5 dB peSPL. P1 latency, N1 latency, and P1-N1 amplitude values were analysed accordingly. The NB CE-Chirp stimulus produced significantly shorter P1 and N1 latencies (p < 0.001) with large effect sizes (d > 0.80). In contrast, both stimuli elicited cVEMP responses with P1-N1 amplitude values that were not statistically different from one another (p = 0.157, d = 0.15). Additionally, age and hearing level were found to be significantly correlated (r = 0.56, p < 0.001), as were age and cVEMP amplitude for each stimulus (p < 0.001). To conclude, since both stimuli were presented at an equivalent intensity level (in dB peSPL), the shorter P1 and N1 latencies of cVEMP produced by the NB CE-Chirp stimulus (centred at 500 Hz) were unlikely due to enhanced saccular stimulation. Another more sensible reason is the temporal adjustment of the chirp stimulus.


Aspartic proteinases in normal lung and interstitial pulmonary diseases.
Two aspartic proteinases, pepsinogen II (PgII) and cathepsin E (CathE), were identified immunocytochemically in lung epithelia. In normal lung, type II pneumocytes were characterized by PgII immunoreactivity of variable intensity, while bronchiolar Clara cells reacted with CathE antibodies. With the exception of small groups of nonciliated bronchial cells overlying lymphoid follicles, no other CathE-immunoreactive cell was found in the lung. Immunoblots of crude protein extracts of lung tissue using PgII and CathE antibodies showed reactivity with single molecular species co-migrating with analogous bands obtained from gastric mucosa (molecular weight, 40,500 for PgII and 42,000 to 44,000 for CathE). In 75 cases of non-neoplastic lung disease, a highly significant correlation was found between the severity of histopathologic lesions and expression of both PgII (P < 0.001) and CathE (P < 0.001). Epithelial hyperplasia contributed more than inflammation and fibrosis to this relationship. Proteinase overexpression was not specific to any particular disease and was found in both focal and diffuse lesions. Segregation of PgII and CathE in different cells was lost in hyperplastic epithelium, where coexpression of both proteinases by the same cell was frequently observed. The location of both proteinases in distal airways and their enhanced expression in the proliferative, hyperplastic phase of several non-neoplastic pneumopathies suggest their possible involvement in the process of parenchymal remodeling that occurs in fibrosing lung diseases.


Late Feeding Tube Dependency in Head and Neck Cancer Patients Treated with Definitive Radiation Therapy and Concurrent Systemic Therapy.
Objective The study aimed to evaluate the impact of late swallowing dysfunction leading to percutaneous endoscopic gastrostomy (PEG) tube dependence on the overall survival (OS) in a cohort of locally advanced head and neck cancer patients treated and cured with definitive radiotherapy (RT) and concurrent systemic therapy (CST). Materials and methods A total of 62 patients with locally advanced head and neck cancer were included in the analysis based on the following selection criteria: stage III, IVA, or IVB disease, treated with definitive RT and CST, no major head and neck surgery, no evidence of local or distant recurrent disease, and at least one post-RT modified barium swallow study. Patients were classified as PEG dependent or PEG independent at the time of the last follow-up. Estimates of OS were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to evaluate the impact of various clinical factors on OS. Results The median follow-up was 48 months (range: 7.6-235 months). The five-year OS was 64.3% in the PEG-dependent group and 86.1% in the PEG-independent group (p=0.022). Age over 70 at diagnosis was also associated with poorer OS (p=0.044). On univariate analysis, PEG dependency maintained a significantly worse OS (hazard ratio [HR]: 2.59; 95% confidence interval [CI]: 1.11-5.99, p=0.028). On multivariate analysis, PEG dependency (HR: 4.25; 95% CI: 1.33-13.62; p=0.015), advanced N stage (HR: 4.74; 95% CI: 1.17-19.26, p=0.035), and older age at diagnosis (HR: 4.37; 95% CI: 1.21-15.84; p=0.025) were significantly associated with worse OS. Conclusions Late PEG dependency is associated with poor OS in head and neck cancer patients cured with definitive RT and CST. Interventions designed to help head and neck cancer patients maintain swallowing function may result in improved outcomes.


Effects of Tranexamic Acid Based on its Population Pharmacokinetics in Pediatric Patients Undergoing Distraction Osteogenesis for Craniosynostosis: Rotational Thromboelastometry (ROTEMTM) Analysis.
Background: Distraction osteogenesis for craniosynostosis is associated with significant hemorrhage. Additionally, patients usually require several transfusions. Tranexamic acid (TXA) is effective for reducing blood loss and the need for transfusions during surgeries. However, the significance of TXA infusion has not been thoroughly described yet. Methods: Forty-eight children undergoing distraction osteogenesis for craniosynostosis were administered intraoperative TXA infusion (loading dose of 10 mg/kg for 15 min, followed by continuous infusion at 5 mg/kg/h throughout surgery; n = 23) or normal saline (control, n = 25). Rotational thromboelastometry (ROTEMTM) was conducted to monitor changes in coagulation perioperatively. Results: Blood loss during surgery was significantly lower in the TXA-treated group than it was in the control group (81 vs. 116 mL/kg, P = 0.003). Furthermore, significantly fewer transfusions of red blood cells and fresh frozen plasma were required in the TXA group. In the control group, clotting time during the postoperative period was longer than it was during the preoperative period. Similarly, clot strength was weaker during the postoperative period. D-dimer levels dramatically increased in the control group compared with the TXA group after surgery. The duration of mechanical ventilation and the number of postoperative respiratory-related complications were significantly greater in the control group than they were in the TXA group. Conclusions: TXA infusion based on population pharmacokinetic analysis is effective in reducing blood loss and the need for transfusions during the surgical treatment of craniosynostosis. It can also prevent the increase in D-dimer levels without affecting systemic hemostasis.


Denys-Drash syndrome associated WT1 glutamine 369 mutants have altered sequence-preferences and altered responses to epigenetic modifications.
Mutations in human zinc-finger transcription factor WT1 result in abnormal development of the kidneys and genitalia and an array of pediatric problems including nephropathy, blastoma, gonadal dysgenesis and genital discordance. Several overlapping phenotypes are associated with WT1 mutations, including Wilms tumors, Denys-Drash syndrome (DDS), Frasier syndrome (FS) and WAGR syndrome (Wilms tumor, aniridia, genitourinary malformations, and mental retardation). These conditions vary in severity from individual to individual; they can be fatal in early childhood, or relatively benign into adulthood. DDS mutations cluster predominantly in zinc fingers (ZF) 2 and 3 at the C-terminus of WT1, which together with ZF4 determine the sequence-specificity of DNA binding. We examined three DDS associated mutations in ZF2 of human WT1 where the normal glutamine at position 369 is replaced by arginine (Q369R), lysine (Q369K) or histidine (Q369H). These mutations alter the sequence-specificity of ZF2, we find, changing its affinity for certain bases and certain epigenetic forms of cytosine. X-ray crystallography of the DNA binding domains of normal WT1, Q369R and Q369H in complex with preferred sequences revealed the molecular interactions responsible for these affinity changes. DDS is inherited in an autosomal dominant fashion, implying a gain of function by mutant WT1 proteins. This gain, we speculate, might derive from the ability of the mutant proteins to sequester WT1 into unproductive oligomers, or to erroneously bind to variant target sequences.


The Effect of the Linguistic Status of Text Previewing in Arabic on the Reading Comprehension Outcomes Among Second and Sixth Grade Native Arabs Readers: A Cross-Sectional View.
The current study examined the effect of the linguistic status of the verbal previewing strategy on the outcomes of reading comprehension tasks among second (N = 25, age 7.08 ± .3), and sixth-grade students (N = 25, age 11.75 ± .25), with typical reading development. The texts for each group were carefully matched and were divided into three conditions of verbal previewing: (a) Standard Arabic previewing (hereafter: StA previewing); (b) spoken Arabic previewing (hereafter: SpA previewing); (c) without previewing. The results showed that for the second-grade readers, SpA previewing had a significant contribution to the reading comprehension outcomes compared to the other conditions of previewing while for the sixth-grade readers; StA previewing had a significant contribution to the outcomes of reading comprehension. The findings were explained according to the assumption that relatively native Arab speaking students develop a progressive change toward activation of StA representations for verbal learning. Such representations become more efficient as a result of the dominant exposure to StA during performing reading and writing tasks.


Biological activities of glucosamine and its related substances.
Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. We revealed that among GlcN-derivatives (GlcN and N-acetyl-d-glucosamine) and uronic acids (d-glucuronic acid and d-galacturonic acid), only GlcN induces the production of hyaluronic acid (HA) by synovial cells and chondrocytes, and the production level is much higher (>10-fold) in synovial cells compared with chondrocytes. Moreover, GlcN increases the expression of HA-synthesizing enzymes (HAS) in synovial cells and chondrocytes. These observations indicate that GlcN likely exhibits the chondroprotective action on OA by modulating the expression of HAS and inducing the production of HA (a major component of glycosaminoglycans contained in the synovial fluid) especially by synovial cells. The pathological change of subchondral bone is implicated in the initiation and progression of cartilage damage in OA. Thus, we further determined the effect of GlcN on the bone metabolism (osteoblastic cell differentiation). The results indicated that GlcN increases the mineralization of mature osteoblasts and the expression of middle and late stage markers (osteopontin and osteocalcin, respectively) during osteoblastic differentiation, and reduces the expression of receptor activator of NF-κB ligand (RANKL), a differentiation and activation factor for osteoclasts. These observations likely suggest that GlcN has a potential to induce the osteoblastic cell differentiation and suppress the osteoclastic cell differentiation, thereby increasing bone matrix deposition and decreasing bone resorption to modulate bone metabolism in OA.


Two-stage operations of small bowel in infancy and childhood.
Out of 813 laparotomies performed for surgical problems of small bowel in infants and children, resections were necessary in 327 patients. A primary enterostomy was done in 75 cases with subsequent anastomosis. The different surgical problems, the operative findings, the various procedures adopted and the results thereof are discussed here. The greatest danger was seen to arise from the ischaemia of the bowel and from peritonitis. In doubtful conditions of small bowel two-stage operation seems advisable.


Laser interstitial thermal therapy for an eloquent region supratentorial brain lesion.
Laser interstitial thermal therapy (LITT) is a minimally invasive stereotactic technique that causes tumor ablation using thermal energy. LITT has shown to be efficacious for the treatment of deep-seated brain lesions, including those near eloquent areas. In this video, the authors present the case of a 62-year-old man with a history of metastatic melanoma who presented with worsening right-sided hemiparesis. MRI revealed a contrast-enhancing lesion in left centrum semiovale in close proximity to corticospinal tracts, consistent with radiation necrosis. The authors review their stepwise technique of LITT with special attention to details for a lesion located near eloquent area. The video can be found here: https://youtu.be/ndrTgi6MXqE .


Using Adversarial Images to Assess the Robustness of Deep Learning Models Trained on Diagnostic Images in Oncology.
Deep learning (DL) models have rapidly become a popular and cost-effective tool for image classification within oncology. A major limitation of DL models is their vulnerability to adversarial images, manipulated input images designed to cause misclassifications by DL models. The purpose of the study is to investigate the robustness of DL models trained on diagnostic images using adversarial images and explore the utility of an iterative adversarial training approach to improve the robustness of DL models against adversarial images. We examined the impact of adversarial images on the classification accuracies of DL models trained to classify cancerous lesions across three common oncologic imaging modalities. The computed tomography (CT) model was trained to classify malignant lung nodules. The mammogram model was trained to classify malignant breast lesions. The magnetic resonance imaging (MRI) model was trained to classify brain metastases. Oncologic images showed instability to small pixel-level changes. A pixel-level perturbation of 0.004 (for pixels normalized to the range between 0 and 1) resulted in most oncologic images to be misclassified (CT 25.6%, mammogram 23.9%, and MRI 6.4% accuracy). Adversarial training improved the stability and robustness of DL models trained on oncologic images compared with naive models ([CT 67.7% v 26.9%], mammogram [63.4% vs 27.7%], and MRI [87.2% vs 24.3%]). DL models naively trained on oncologic images exhibited dramatic instability to small pixel-level changes resulting in substantial decreases in accuracy. Adversarial training techniques improved the stability and robustness of DL models to such pixel-level changes. Before clinical implementation, adversarial training should be considered to proposed DL models to improve overall performance and safety.


[Endothelial dysfunction as a marker of vascular aging syndrome on the background of hypertension, coronary heart disease, gout and obesity].
Under observation were 40 hypertensive patients with coronary heart disease, gout and obesity I and II degree. Patients with hypertension in combination with coronary heart disease, gout and obesity, syndrome of early vascular aging is shown by increased stiffness of arteries, increased peak systolic flow velocity, pulse blood presure, the thickness of the intima-media complex, higher level endotelinemia and reduced endothelial vasodilation. Obtained evidence that losartan in complex combination with basic therapy and metamaks in complex combination with basic therapy positively affect the elastic properties of blood vessels and slow the progression of early vascular aging syndrome.


A Helminth Survey of Northern Bobwhite Quail (Colinus virginianus) and Passerines in the Rolling Plains Ecoregion of Texas.
The Northern bobwhite quail (Colinus virginianus) is a popular game bird that has been experiencing a well-documented decline throughout Texas since the 1960s. While much of this decline has been attributed to habitat loss and fragmentation, recent studies have identified other factors that may also contribute to decreasing quail populations. Parasites, in particular, have become increasingly recognized as possible stressors of quail, and some species, particularly the eyeworm (Oxyspirura petrowi) and cecal worm (Aulonocephalus pennula) are highly prevalent in Texas quails. Eyeworm infection has also been documented in some passerines, suggesting helminth infection may be shared between bird species. However, the lack of comprehensive helminth surveys has rendered the extent of shared infection between quail and passerines in the ecoregion unclear. Thus, helminth surveys were conducted on bobwhite, scaled quail (Callipepla squamata), Northern mockingbirds (Mimus polyglottos), curve-billed thrashers (Toxistoma curvirostre), and Northern cardinals (Cardinalis cardinalis) to contribute data to existing parasitological gaps for birds in the Rolling Plains ecoregion of Texas. Birds were trapped across 3 counties in the Texas Rolling Plains from March to October 2019. Necropsies were conducted on 54 individuals (36 quail and 18 passerines), and extracted helminths were microscopically identified. Nematode, cestode, and acanthocephalan helminths representing at least 10 helminth species were found. Specifically, A. pennula and O. petrowi had the highest prevalence, and O. petrowi was documented in all of the study species. This research adds to the body of knowledge regarding parasitic infections in quail and passerines of the Rolling Plains ecoregion and highlights the potential consequences of shared infection of eyeworms among these bird species.


Interactions between acid- and base-functionalized surfaces.
In this paper we present an AFM force study on interactions between chemically modified surfaces. Surfaces with terminal groups of either NH(2) or COOH were obtained by chemisorption of a silane-based compound (3-amino-propyltriethoxysilane) on silica or a thiol compound (11-mercapto undecanoic acid) on gold. The surfaces were characterized by streaming potential and contact angle measurements. For the NH(2) surfaces the density of functional groups strongly depends on the pretreatment of the silica. Both the NH(2) and COOH surfaces show a steady and ongoing loss of functional groups, but on the time scale of our force measurements they can be considered to be stable. Interaction curves for the various combinations of surfaces in aqueous solutions show a strong correlation with the ionization state of the surface groups. The approach curves can be explained on the basis of electrostatic interactions. On retraction a pH-dependent adhesion is found, the strongest being between NH(2) and COOH surfaces as a result of acid-base interactions. Between NH(2) layers and between COOH layers there is also adhesion, due to the formation of H bonds. The corresponding work of adhesion W was calculated using the DMT (Derjaguin, Muller, Toporov) equation. The values of W obtained are small compared to literature data and suggest that only a fraction of the functional groups in the contact area is involved in acid-base or H-bond interactions. This is attributed mainly to the roughness of the surfaces, which substantially reduces adhesion. A rough estimate is made for the rupture force of the NH(2)-COOH acid-base bond in water.


Prevalence and factors associated with underweight children: a population-based subnational analysis from Pakistan.
This study aims to determine the prevalence of and factors associated with underweight children under the age of 5 in Punjab, Pakistan. We analysed cross-sectional household-level subnationally representative Multiple Indicator Cluster Survey. Punjab province, Pakistan. 24 042 children under 5 years of age. Multilevel multivariate logistic regression analysis. Prevalence of moderately and severely underweight children was found to be (33.3% and 11.3%, respectively). Multivariate multilevel logistic regression results show that as the child grows older the likelihood of the child being underweight increases significantly (eg, children between 12 and 23 months are one and half times more likely to be underweight, whereas children between the ages of 36 and 47 months are two and a half times more likely to be underweight). Gender was found to be another significant factor contributing to underweight prevalence among children under the age of 5. The likelihood of a girl child being underweight is more than that of a boy child being underweight (OR 0.92, 95% CI 0.8 to 1.0). Similarly, a child whose birth order is three or more is two times more likely to be underweight (OR 1.96, 95% CI 1.5 to 2.5) relative to a child of a lower birth order. Moreover, diarrhoea also significantly increases the likelihood of the child being underweight (OR 1.31, 95% CI 1.1 to 1.5). Child size is another determinant for underweight prevalence among children under 5, for example, a child with a size smaller than average at the time of birth is 2.7 times more likely to be moderately underweight than a child with an average or larger than average size at the time of birth. Rigorous community-based interventions should be developed and executed throughout the province to improve this grave situation of underweight prevalence in Punjab. Mother's education should be uplifted by providing them formal education and providing awareness about the importance of proper nutrition for children.


H2S, endoplasmic reticulum stress, and apoptosis of insulin-secreting beta cells.
Cystathionine gamma-lyase (CSE) is a key enzyme in the trans-sulfuration pathway, which uses L-cysteine to produce hydrogen sulfide (H2S). Functional changes of pancreatic beta cells induced by endogenous H2S have been reported, but the effect of the CSE/H2S system on pancreatic beta cell survival has not been known. In this study, we demonstrate that H2Sat physiologically relevant concentrations induced apoptosis of INS-1E cells, an insulin-secreting beta cell line. Transfection of INS-1E cells with a recombinant defective adenovirus containing the CSE gene (Ad-CSE) resulted in a significant increase in CSE expression and H2S production. Ad-CSE transfection also stimulated apoptosis. The other two end products of CSE-catalyzed enzymatic reaction, ammonium and pyruvate, had no effects on INS-1E cell apoptosis, indicating that overexpression of CSE may stimulate INS-1E cell apoptosis via increased endogenous production of H2S. Both exogenous H2S (100 microM) and Ad-CSE transfection inhibited ERK1/2 but activated p38 MAPK. Interestingly, BiP and CHOP, two indicators of endoplasmic reticulum (ER) stress, were up-regulated in H2S-and CSE-mediated apoptosis in INS-1E cells. After suppressing CHOP mRNA expression, H2S-induced apoptosis of INS-1E cells was significantly decreased. Inhibition of p38 MAPK, but not of ERK1/2, inhibited the expression of BiP and CHOP and decreased H2S-stimulated apoptosis, suggesting that p38 MAPK activation functions upstream of ER stress to initiate H2S-induced apoptosis. It is concluded that H2S induces apoptosis of insulin-secreting beta cells by enhancing ER stress via p38 MAPK activation. Our findings may help unmask a novel role of CSE/H2S system in regulating pancreatic functions under physiological condition and in diabetes.


Urinary Liver-Type Fatty-Acid-Binding Protein Predicts Long-Term Adverse Outcomes in Medical Cardiac Intensive Care Units.
We prospectively investigated the prognostic value of urinary liver-type fatty-acid-binding protein (L-FABP) levels on hospital admission, both independently and in combination with serum creatinine-defined acute kidney injury (AKI), to predict long-term adverse outcomes in 1119 heterogeneous patients (mean age; 68 years) treated at medical (non-surgical) cardiac intensive care units (CICUs). Patients with stage 5 chronic kidney disease were excluded from the study. Of these patients, 47% had acute coronary syndrome and 38% had acute decompensated heart failure. The creatinine-defined AKI was diagnosed according to the "Kidney Disease: Improving Global Outcomes" criteria. The primary endpoint was a composite of all-cause death or progression to end-stage kidney disease, indicating the initiation of maintenance dialysis therapy or kidney transplantation. Creatinine-defined AKI occurred in 207 patients, with 44 patients having stage 2 or 3 disease. During a mean follow-up period of 41 months after enrollment, the primary endpoint occurred in 242 patients. Multivariate Cox regression analyses revealed L-FABP levels as independent predictors of the primary endpoint (p < 0.001). Adding L-FABP to a baseline model with established risk factors further enhanced reclassification and discrimination beyond that of the baseline model alone, for primary-endpoint prediction (both; p < 0.01). On Kaplan-Meier analyses, increased L-FABP (≥4th quintile value of 9.0 ng/mL) on admission or presence of creatinine-defined AKI, correlated with an increased risk of the primary endpoint (p < 0.001). Thus, urinary L-FABP levels on admission are potent and independent predictors of long-term adverse outcomes, and they might improve the long-term risk stratification of patients admitted at medical CICUs, when used in combination with creatinine-defined AKI.


Endometrial histology and post-partum mares treated with progesterone and synthetic GnRH (AY-24,031).
Foal heat was significantly delayed in 15 Thoroughbred and Quarter-horse mares by 200 mg progesterone in oil from Days 5--14 post partum. Nine of these mares subsequently received daily i.v. injections of 2 mg of a synthetic GnRH preparation (AY-24,031) from Day 2 of the progesterone-delayed oestrus but this treatment did not significantly shorten oestrus or hasten ovulation. Uterine biopsies taken on Day 15 post partum from all the mares showed a mixed endometrial morphology having both oestrous and dioestrous characteristics. There was an increased proliferation of endometrial glands in these animals at the time of ovulation compared to control mares having a normal foal heat.


The Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program: protocol for a two-arm parallel partially nested randomized controlled feasibility trial with progression to full-scale trial.
Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. We completed an initial feasibility trial of an online self-administered version of the Scleroderma Patient-centered Intervention Network Self-Management (SPIN-SELF) Program using the cohort multiple randomized controlled trial (RCT) design. Due to low intervention offer uptake, we will conduct a new feasibility trial with progression to full-scale trial, using a two-arm parallel, partially nested RCT design. The SPIN-SELF Program has also been revised to include facilitator-led videoconference group sessions in addition to online material. We will test the group-based intervention delivery format, then evaluate the effect of the SPIN-SELF Program on disease management self-efficacy (primary) and patient activation, social appearance anxiety, and functional health outcomes (secondary). This study is a feasibility trial with progression to full-scale RCT, pending meeting pre-defined criteria, of the SPIN-SELF Program. Participants will be recruited from the ongoing SPIN Cohort ( http://www.spinsclero.com/en/cohort ) and via social media and partner patient organizations. Eligible participants must have SSc and low to moderate disease management self-efficacy (Self-Efficacy for Managing Chronic Disease (SEMCD) Scale score ≤ 7.0). Participants will be randomized (1:1 allocation) to the group-based SPIN-SELF Program or usual care for 3 months. The primary outcome in the full-scale trial will be disease management self-efficacy based on SEMCD Scale scores at 3 months post-randomization. Secondary outcomes include SEMCD scores 6 months post-randomization plus patient activation, social appearance anxiety, and functional health outcomes at 3 and 6 months post-randomization. We will include 40 participants to assess feasibility. At the end of the feasibility portion, stoppage criteria will be used to determine if the trial procedures or SPIN-SELF Program need important modifications, thereby requiring a re-set for the full-scale trial. Otherwise, the full-scale RCT will proceed, and outcome data from the feasibility portion will be utilized in the full-scale trial. In the full-scale RCT, 524 participants will be recruited. The SPIN-SELF Program may improve disease management self-efficacy, patient activation, social appearance anxiety, and functional health outcomes in people with SSc. SPIN works with partner patient organizations around the world to disseminate its programs free-of-charge. ClinicalTrials.gov NCT04246528 . Registered on 27 January 2020.


Sediment delivery to sustain the Ganges-Brahmaputra delta under climate change and anthropogenic impacts.
The principal nature-based solution for offsetting relative sea-level rise in the Ganges-Brahmaputra delta is the unabated delivery, dispersal, and deposition of the rivers' ~1 billion-tonne annual sediment load. Recent hydrological transport modeling suggests that strengthening monsoon precipitation in the 21st century could increase this sediment delivery 34-60%; yet other studies demonstrate that sediment could decline 15-80% if planned dams and river diversions are fully implemented. We validate these modeled ranges by developing a comprehensive field-based sediment budget that quantifies the supply of Ganges-Brahmaputra river sediment under varying Holocene climate conditions. Our data reveal natural responses in sediment supply comparable to previously modeled results and suggest that increased sediment delivery may be capable of offsetting accelerated sea-level rise. This prospect for a naturally sustained Ganges-Brahmaputra delta presents possibilities beyond the dystopian future often posed for this system, but the implementation of currently proposed dams and diversions would preclude such opportunities.


ABCG2 regulated by MAPK pathways is associated with cancer progression in laryngeal squamous cell carcinoma.
ATP-binding cassette, subfamily G, member 2 (ABCG2) overexpression has been associated with multidrug resistance and cancer progression by promoting proliferation and/or suppressing apoptosis, but how this process happens remains to be determined. In this study, the roles and the mechanisms of ABCG2 in the progression of Laryngeal squamous cell carcinoma (LSCC) were investigated. We found that introduction of ABCG2 siRNA into Hep-2 and Hep-2T cells significantly enhanced the intracellular accumulation of mitoxantrone (MX). Down-regulation of ABCG2 by transient RNAi inhibited cell proliferation and blocked cell cycle progression by regulating the expression of cyclin D3 and p21 Cip1. ABCG2 silence also induced cell apoptosis by regulating the expression of surviving, bcl-2 and the cleavage of poly (ADP-ribose) polymerase (PARP) in Hep-2 and Hep-2T cells. ABCG2-specific inhibitor, fumitremorgin C (FTC), and mitogen-activated protein kinase (MAPK) pathway inhibitor, U0126, inhibited cell proliferation and promoted cell apoptosis by degrading endogenous ABCG2 in Hep-2T cells. Furthermore, inhibition of MAPK pathway by U0126 enhanced anti-cancer effects of MX in vivo. In conclusion, suppression of ABCG2 inhibits the procession of LSCC tumor growth by regulating cell proliferation and apoptosis. Our data also provide more evidence for the importance of the MAPK pathway as a suitable therapeutic target for LSCC.


Minitracheostomy: an alternative to "blind" endotracheal suctioning.
The critical care nurse is frequently challenged to clear respiratory secretions for patients with thick, copious mucous and a weak cough. The traditional interventions nurses use are chest physiotherapy, incentive spirometry, and "blind" endotracheal suctioning to facilitate the removal of secretions, but these are sometimes ineffective and cause complications. Nurses who identify patients needing a more effective way to remove secretions can request consideration of a new method, suctioning through a minitracheostomy.


The Role of COL5A2 in Patients With Muscle-Invasive Bladder Cancer: A Bioinformatics Analysis of Public Datasets Involving 787 Subjects and 29 Cell Lines.
Bladder cancer (BC) is one of the most common malignancies. Two previous studies identified collagen type V alpha 2 (COL5A2) as a potential biomarker in BC, both are simple reanalysis of a single transcriptomic dataset without subgroup analysis for muscle-invasive BC (MIBC). We focused in MIBC patients and explored the role of COL5A2 from an integration perspective, using refined methodology covering individual participant data meta-analysis and bioinformatics analysis. Eight transcriptomic datasets of 787 MIBC patients (including one dataset containing genomic mutation information) and two drug sensitivity datasets of 29 cell lines in which more than 250 compounds were analyzed. We found subjects with increased COL5A2 gene expression exhibited poorer prognosis, and the power analysis confirmed adequate sample size. FGFR3 was the only gene differential mutated between the COL5A2 high and low expression groups. Differential expression and co-expression network analysis suggested potential association between COL5A2 expression and essential pathways involved in cancer invasion and dissemination, including cell adhesion, extracellular matrix organization, and epithelial-mesenchymal transition. Coordinately, analysis of drug screening datasets and gene-drug interaction also revealed COL5A2 expression linked to cell morphogenesis, angiogenesis, blood vessel development, and urogenital development. The utility and feasibility of COL5A2 for clinically applicable prognosis prediction and risk classification and the exact underlying molecular mechanism should be further investigated in subsequent studies.


Antimicrobial Activity of Penicillin G and N-acetylcystein on Planktonic and Sessile Cells of Streptococcus suis.
The aim of this study was to investigate the capacity of Streptococcus suis strains to form biofilms and to evaluate the antimicrobial activity of Penicillin G and N-acetylcystein (NAC) on both S. suis sessile and planktonic forms. Only non-typeable isolates of S. suis were correlated with a greater biofilm formation capacity. The MCI of Penicillin G and NAC required for inhibiting biofilm growth were higher than the required concentration for inhibiting planktonic growth. The combinations of NAC and Penicillin G showed a strong synergistic activity that inhibited biofilm formation and disrupted the pre-formed biofilm of S. suis.


Unusual clinical presentations of intermediate lymphocytic lymphoma.
Three patients with previously unreported presentations of the follicular or mantle zone variant of intermediate lymphocytic lymphoma are described. In each case lymph node histopathology showed the presence of non-neoplastic follicular structures containing germinal centre-like areas and widened mantle zones in which the component small lymphocytes consisted of an admixture of a typical lymphoid cells. The nuclear contour of these cells was irregular or indented and they expressed an IgM lambda phenotype. The patients were typical in being over 50 years of age, anaemic with stage IV disease by virtue of bone marrow involvement, and having generalized lymphadenopathy and marked hepatosplenomegaly. Conversely, the clinical features in each case were unusual, being the nephrotic syndrome due to mesangioproliferative glomerulonephritis in one, extensive lymphomatous involvement of the ileum in the second, and recurrent pneumonia and abscess formation in the third. These associations are further examples of the way in which patients with this unusual lymphoma may present.


Development of a rapid SNP-typing assay to differentiate Bifidobacterium animalis ssp. lactis strains used in probiotic-supplemented dairy products.
Identification at the genus, species, and strain levels is desirable when a probiotic microorganism is added to foods. Strains of Bifidobacterium animalis ssp. lactis (BAL) are commonly used worldwide in dairy products supplemented with probiotic strains. However, strain discrimination is difficult because of the high degree of genome identity (99.975%) between different genomes of this subspecies. Typing of monomorphic species can be carried out efficiently by targeting informative single nucleotide polymorphisms (SNP). Findings from a previous study analyzing both reference and commercial strains of BAL identified SNP that could be used to discriminate common strains into 8 groups. This paper describes development of a minisequencing assay based on the primer extension reaction (PER) targeting multiple SNP that can allow strain differentiation of BAL. Based on previous data, 6 informative SNP were selected for further testing, and a multiplex preliminary PCR was optimized to amplify the DNA regions containing the selected SNP. Extension primers (EP) annealing immediately adjacent to the selected SNP were developed and tested in simplex and multiplex PER to evaluate their performance. Twenty-five strains belonging to 9 distinct genomic clusters of B. animalis ssp. lactis were selected and analyzed using the developed minisequencing assay, simultaneously targeting the 6 selected SNP. Fragment analysis was subsequently carried out in duplicate and demonstrated that the assay yielded 8 specific profiles separating the most commonly used commercial strains. This novel multiplex PER approach provides a simple, rapid, flexible SNP-based subtyping method for proper characterization and identification of commercial probiotic strains of BAL from fermented dairy products. To assess the usefulness of this method, DNA was extracted from yogurt manufactured with and without the addition of B. animalis ssp. lactis BB-12. Extracted DNA was then subjected to the minisequencing protocol, resulting in a SNP profile matching the profile for the strain BB-12.


Spectral composition of heart sounds before and after mechanical heart valve implantation using a modified forward-backward Prony's method.
This paper investigates the impact of the lung-thorax and heart-valve system on the overall spectral composition of the externally recorded heart sounds. The study concentrates in the case of the first and the second heart sounds for normal patients and patients before and after implantation of a mechanical valve in the mitral or aortic position. The analysis is performed using a modified forward-backward overdetermined Prony's method (MFBPM) which uses a forward-backward mean filter and a modified procedure for estimating the position of the signal poles. In terms of the normalized cross-correlation coefficient, this method has an average modeling accuracy of 99.62% for representing the first and second heart sounds and an average least square time-domain error of 0.43%. Results obtained from 40 subjects show that the condition of the native mitral or aortic valve affects mostly the distribution of the amplitudes of the spectral components, whereas the number of the spectral components or their respective relative energy remains more or less unchanged. It has been found that the amplitudes of frequency components in the range 120-250 Hz are more affected by abnormalities of native mitral valves. Furthermore, in the case of the second heart sound the region 250-400 Hz has been found to be more affected by abnormalities in the aortic valve. It has also been found that the mechanical prosthetic heart valve affects mostly the spectrum beyond 400 Hz. A clear difference has been observed in the frequency spectrum above 400 Hz between both normally and abnormally functioning native valves and normally functioning mechanical valves. Preliminary results in some malfunctioning cases of mechanical prosthesis suggest that spectral components beyond 400 Hz can be used to monitor the condition of these prostheses.


Voltage-dependent inactivation of slow calcium channels in intact twitch muscle fibers of the frog.
Inactivation of slow Ca2+ channels was studied in intact twitch skeletal muscle fibers of the frog by using the three-microelectrode voltage-clamp technique. Hypertonic sucrose solutions were used to abolish contraction. The rate constant of decay of the slow Ca2+ current (ICa) remained practically unchanged when the recording solution containing 10 mM Ca2+ was replaced by a Ca2+-buffered solution (126 mM Ca-maleate). The rate constant of decay of ICa monotonically increased with depolarization although the corresponding time integral of ICa followed a bell-shaped function. The replacement of Ca2+ by Ba2+ did not result in a slowing of the rate of decay of the inward current nor did it reduce the degree of steady-state inactivation. The voltage dependence of the steady-state inactivation curve was steeper in the presence of Ba2+. In two-pulse experiments with large conditioning depolarizations ICa inactivation remained unchanged although Ca2+ influx during the prepulse greatly decreased. Dantrolene (12 microM) increased mechanical threshold at all pulse durations tested, the effect being more prominent for short pulses. Dantrolene did not significantly modify ICa decay and the voltage dependence of inactivation. These results indicate that in intact muscle fibers Ca2+ channels inactivate in a voltage-dependent manner through a mechanism that does not require Ca2+ entry into the cell.


High pressure and elastic properties of a guanidinium-formate hybrid perovskite.
The high pressure and elastic properties of a hybrid ABX3-type perovskite, [C(NH2)3][Cd(HCOO)3] (CdGF), based on the A-site guest molecules are revealed via combining the high-pressure synchrotron X-ray diffraction experiments with density functional theory (DFT) calculations. The experimental results indicate that the anisotropic axial compressibilities are Ka = 2.8(4) and Kc = 20.9(10) TPa-1 within the pressure scope of 4.12 GPa, and calculations reveal the microscopic evolution of structure under pressure and demonstrate that this structural anisotropy is a consequence of the directional guest molecule and the cooperative effect of hydrogen bonding and octahedral tilting. In addition, full elastic constants of the perovskite were calculated to describe Young's moduli, shear moduli and Poisson's ratios. Notably, these discrete moduli are governed by the orientational guest molecule suggesting that the perovskite may display positive (negative) linear compression if it is flexible (rigid) along one principal axis.


Effects of Gait Strategy and Speed on Regularity of Locomotion Assessed in Healthy Subjects Using a Multi-Sensor Method.
The regularity of pseudo-periodic human movements, including locomotion, can be assessed by autocorrelation analysis of measurements using inertial sensors. Though sensors are generally placed on the trunk or pelvis, movement regularity can be assessed at any body location. Pathological factors are expected to reduce regularity either globally or on specific anatomical subparts. However, other non-pathological factors, including gait strategy (walking and running) and speed, modulate locomotion regularity, thus potentially confounding the identification of the pathological factor. The present study's objectives were (1) to define a multi-sensor method based on the autocorrelation analysis of the acceleration module (norm of the acceleration vector) to quantify regularity; (2) to conduct an experimental study on healthy adult subjects to quantify the effect on movement regularity of gait strategy (walking and running at the same velocity), gait speed (four speeds, lower three for walking, upper two for running), and sensor location (on four different body parts). Twenty-five healthy adults participated and four triaxial accelerometers were located on the seventh cervical vertebra (C7), pelvis, wrist, and ankle. The results showed that increasing velocity was associated with increasing regularity only for walking, while no difference in regularity was observed between walking and running. Regularity was generally highest at C7 and ankle, and lowest at the wrist. These data confirm and complement previous literature on regularity assessed on the trunk, and will support future analyses on individuals or groups with specific pathologies affecting locomotor functions.


Comparison of alternative risk adjustment measures for predictive modeling: high risk patient case finding using Taiwan's National Health Insurance claims.
Predictive modeling presents an opportunity to contain the expansion of medical expenditures by focusing on very few people. Evaluation of how risk adjustment models perform in predictive modeling in Taiwan or Asia has been rare. The aims of this study were to evaluate the performance of different risk adjustment models (the ACG risk adjustment system and prior expenditures) in predictive modeling, using Taiwan's National Health Insurance (NHI) claims data, and to compare characteristics of potentially high-expenditure subjects identified through different models. A random sample of NHI enrollees continuously enrolled in 2002 and 2003 (n = 164,562) was selected. Health status measures and total expenditures derived from 2002 NHI claims data were used to predict the possibility of becoming 2003 top users. Statistics-based indicators (C-statistics, sensitivity, & Predictive Positive Value) and characteristics of identified top groups by different models (expenditures and prevalence of manageable diseases) were presented. Both diagnosis-based and prior expenditures models performed much better than the demographic model. Diagnosis-based models were better in identifying top users with manageable diseases; prior expenditures models were better in statistics-based indicators and identifying people with higher average expenditures. Prior expenditures status could correctly identify more actual top users than diagnosis-based or demographic models. The proportions of actual top users that could be identified by diagnosis-based models alone were much lower than that identified by prior expenditures status. Predicted top users identified by different models have different characteristics and there is little agreement between modes regarding which groups would be potentially top users; therefore, which model to use should depend on the purpose of predictive modeling. Prior expenditures are a more powerful tool than diagnosis-based risk adjusters in terms of correctly identifying more actual high expenditures users. There is still much room left for improvement of diagnosis-based models in predictive modeling.


Non-invasive imaging of vascular inflammation.
In large-vessel vasculitides, inflammatory infiltrates may cause thickening of the involved arterial vessel wall leading to progressive stenosis and occlusion. Dilatation, aneurysm formation, and thrombosis may also ensue. Activated macrophages and T lymphocytes are fundamental elements in vascular inflammation. The amount and density of the inflammatory infiltrate is directly linked to local disease activity. Additionally, patients with autoimmune disorders have an increased cardiovascular (CV) risk compared with age-matched healthy individuals as a consequence of accelerated atherosclerosis. Molecular imaging techniques targeting activated macrophages, neovascularization, or increased cellular metabolic activity can represent effective means of non-invasive detection of vascular inflammation. In the present review, novel non-invasive imaging tools that have been successfully tested in humans will be presented. These include contrast-enhanced ultrasonography, which allows detection of neovessels within the wall of inflamed arteries; contrast-enhanced CV magnetic resonance that can detect increased thickness of the arterial wall, usually associated with edema, or mural enhancement using T2 and post-contrast T1-weighted sequences, respectively; and positron emission tomography associated with radio-tracers such as [(18)F]-fluorodeoxyglucose and the new [(11)C]-PK11195 in combination with computed tomography angiography to detect activated macrophages within the vessel wall. Imaging techniques are useful in the diagnostic work-up of large- and medium-vessel vasculitides, to monitor disease activity and the response to treatments. Finally, molecular imaging targets can provide new clues about the pathogenesis and evolution of immune-mediated disorders involving arterial vessels.


Imaging of sinonasal tumors.
Imaging of the paranasal sinuses and the nasal cavity provides important anatomic information in the evaluation of suspected neoplasia. The primary modalities employed are conventional films, computed tomography (CT) and magnetic resonance imaging (MRI). Although plain sinus films remain the screening procedure of choice, CT is the preferred modality for more detailed assessment of the paranasal sinuses and the nasal cavity. When soft tissue discrimination is required, MRI is indicated. Imaging studies are used to define the limits of disease, not to diagnose malignancy.


CPR: cardiac phosphatase in resuscitation.
Out-of-hospital cardiac arrest is associated with a dismal mortality rate and low long-term survival. A large pharmacological knowledge gap exists in identifying drugs that preserve neurological function and increase long-term survival after cardiac arrest. In this issue of the JCI, Li, Zhu, and colleagues report on their engineering of a 20-amino acid cell-permeable peptide (TAT-PHLPP9c) that antagonized the phosphatase PHLPP1 and prevented PHLPP1-mediated dephosphorylation and AKT inactivation. TAT-PHLPP9c administration maintained activated AKT after arrest and led to AKT-mediated beneficial effects on the heart, brain, and metabolism, resulting in increased cardiac output and cerebral blood flow and rescue of ATP levels in affected tissues. TAT-PHLPP9c improved neurological outcomes and increased survival after cardiac arrest in murine and porcine models of cardiac arrest. These findings provide proof of concept that pharmacological targeting of PHLPP1 may be a promising approach to augmenting long-term survival after cardiac arrest.


Striatal D2 dopamine receptor characteristics in neuroleptic-naive schizophrenic patients studied with positron emission tomography.
According to the D2 dopamine receptor hypothesis of schizophrenia, there is an increased number of D2 receptors in the brains of schizophrenic patients than in those of healthy controls. We tested this hypothesis in 13 newly admitted neuroleptic-naive schizophrenic patients and 10 healthy volunteers using positron emission tomography. The quantification of striatal D2 dopamine receptor density (Bmax) and affinity (Kd) was done using an equilibrium model described for raclopride labeled with carbon 11. No statistically significant alterations were found in D2 receptor densities or affinities between the patient and control groups. However, a subgroup of four patients with a relatively high striatal D2 dopamine density was identified. Two patients, especially, had D2 dopamine densities almost twice as high as the mean control Bmax value. The Kd values also tended to be higher in this subset of patients than in the controls. No consistent striatal D2 dopamine receptor laterality was observed in schizophrenic patients or controls. However, an association of high D2 dopamine density in the left striatum and the mass of raclopride injected in the scan with low-specific radioactivity was observed in patients but not in controls. There are no general changes in D2 dopamine receptor Bmax or Kd values in neuroleptic-naive schizophrenics, but there may be a subgroup of patients with aberrant striatal D2 dopamine receptor characteristics in vivo.


[Gender role orientation and tobacco and alcohol use among youth in Morelos, Mexico].
To quantify the association between gender role orientation and tobacco and alcohol use among young people of the State of Morelos. Study conducted in 2004-2005, students aged 14 to 24 years (n = 1 730). Sociodemographic variables (area of residence, socioeconomic status), family (parental education and violence), psycho-sociological (gender role, self-esteem, depression, alcohol consumption, tobacco, locus of control, sexual abuse). Logistic regression analysis. Factors associated with use of tobacco: In women, being androgynous undesirable, masculine role, attempted sexual abuse and urban areas. For men, depression and submission. Factors associated with alcohol use: In women, masculine gender role; and in men to be older than 20 years, living in semi-urban and urban area, and internal locus. The machismo is one of the gender role orientations with greater association with the use of tobacco primarily in girls in Mexico, and the masculine or instrumental role with alcohol.


Novel Bioengineered Cassava Expressing an Archaeal Starch Degradation System and a Bacterial ADP-Glucose Pyrophosphorylase for Starch Self-Digestibility and Yield Increase.
To address national and global low-carbon fuel targets, there is great interest in alternative plant species such as cassava (Manihot esculenta), which are high-yielding, resilient, and are easily converted to fuels using the existing technology. In this study the genes encoding hyperthermophilic archaeal starch-hydrolyzing enzymes, α-amylase and amylopullulanase from Pyrococcus furiosus and glucoamylase from Sulfolobus solfataricus, together with the gene encoding a modified ADP-glucose pyrophosphorylase (glgC) from Escherichia coli, were simultaneously expressed in cassava roots to enhance starch accumulation and its subsequent hydrolysis to sugar. A total of 13 multigene expressing transgenic lines were generated and characterized phenotypically and genotypically. Gene expression analysis using quantitative RT-PCR showed that the microbial genes are expressed in the transgenic roots. Multigene-expressing transgenic lines produced up to 60% more storage root yield than the non-transgenic control, likely due to glgC expression. Total protein extracted from the transgenic roots showed up to 10-fold higher starch-degrading activity in vitro than the protein extracted from the non-transgenic control. Interestingly, transgenic tubers released threefold more glucose than the non-transgenic control when incubated at 85°C for 21-h without exogenous application of thermostable enzymes, suggesting that the archaeal enzymes produced in planta maintain their activity and thermostability.


Gonadotropin releasing hormone-independent precocious puberty in a 5 year-old girl with suprasellar germ cell tumor secreting beta-hCG and alpha-fetoprotein.
A 5 year-old girl presented with typical features of isosexual precocity with breast and pubic hair development (Tanner stage 3) and menarche, following a few months history of hirsutism of the back and thighs. Stimulation testing revealed GnRH-independent precocious puberty, tertiary hypothyroidism, hyperprolactinemia and mild testosteronemia. The ovaries in ultrasound examination were prepubertal. Tumor markers beta-hCG and AFP were markedly elevated and a 2.5 x 1.5 cm suprasellar germ cell tumor (GCT) was visualized by MRI. Combined chemotherapy followed by radiotherapy resulted in normalization of pubertal features along with estrogen and marker levels. Our observations support the possibility of hCG-dependent precocious puberty (PP) in girls caused by suprasellar hCG-secreting tumor. We emphasize the need of diagnostic management of hCG-dependent PP not only in boys, but also in girls, especially when they present even slight features of androgenization. We hypothesize that the rarity of isosexual PP in girls with hCG-secreting suprasellar GCT results not only from the lower occurrence of these tumors in girls than in boys, but above all from a rare simultaneous concomitant incidence of both high tumor aromatase activity and hCG secreting potency.


Polyphenol rich botanicals used as food supplements interfere with EphA2-ephrinA1 system.
The Eph tyrosine kinase receptors and their ephrin ligands play a central role in several human cancers and their deregulated expression or function promotes tumorigenesis, inducing aggressive tumor phenotypes. Green tea extracts (GTE) have been recently found to inhibit Eph-kinase phosphorylation. In order to evaluate the potential contribution of edible and medicinal plants on EphA2-ephrinA1 modulation, 133 commercially available plant extracts used as food supplements, essential and fixed oils were screened with an ELISA-based binding assay. Nine plant extracts, rich of polyphenols, reversibly inhibited binding in a dose-dependent manner (IC₅₀ 0.83-24 μg/ml). Functional studies on PC3 prostate adenocarcinoma cells revealed that active extracts antagonized ephrinA1-Fc-induced EphA2-phosphorylation at non-cytotoxic concentrations (IC₅₀ 0.31-11.3 μg/ml) without interfering with EGF-induced EGFR activation, suggesting a specific effect. These findings could furnish an interesting starting point regarding the potential relationship between diet, edible plant secondary metabolites and Eph-ephrin system, suggesting their possible involvement in cancer development modulation.


Conditional CRISPR-Cas Genome Editing in Drosophila to Generate Intestinal Tumors.
CRISPR-Cas has revolutionized genetics and extensive efforts have been made to enhance its editing efficiency by developing increasingly more elaborate tools. Here, we evaluate the CRISPR-Cas9 system in Drosophila melanogaster to assess its ability to induce stem cell-derived tumors in the intestine. We generated conditional tissue-specific CRISPR knockouts using different Cas9 expression vectors with guide RNAs targeting the BMP, Notch, and JNK pathways in intestinal progenitors such as stem cells (ISCs) and enteroblasts (EBs). Perturbing Notch and BMP signaling increased the proliferation of ISCs/EBs and resulted in the formation of intestinal tumors, albeit with different efficiencies. By assessing both the anterior and posterior regions of the midgut, we observed regional differences in ISC/EB proliferation and tumor formation upon mutagenesis. Surprisingly, high continuous expression of Cas9 in ISCs/EBs blocked age-dependent increase in ISCs/EBs proliferation and when combined with gRNAs targeting tumor suppressors, it prevented tumorigenesis. However, no such effects were seen when temporal parameters of Cas9 were adjusted to regulate its expression levels or with a genetically modified version, which expresses Cas9 at lower levels, suggesting that fine-tuning Cas9 expression is essential to avoid deleterious effects. Our findings suggest that modifications to Cas9 expression results in differences in editing efficiency and careful considerations are required when choosing reagents for CRISPR-Cas9 mutagenesis studies. In summary, Drosophila can serve as a powerful model for context-dependent CRISPR-Cas based perturbations and to test genome-editing systems in vivo.


Metabolism of adenine nucleotides in human blood.
Biologically active concentrations of potently vasoactive and platelet-active adenine nucleotides are generated in plasma by a variety of pathophysiological mechanisms. Although there is evidence that ATP and ADP are inactivated by endothelial ectonucleotidases, there has been little attempt to study the metabolic routes of their catabolism in blood or to assess the contribution of this process to their clearance in vivo. Therefore, we have studied the rates and patterns of catabolism of ATP, ADP, and AMP in whole blood, plasma, and isolated blood cells. Rates of degradation of each nucleotide in cell-free plasma ranged from 0.07-0.32 nmol/min/ml with 1 microM substrates to 1.1-3.6 nmol/min/ml with 100 microM substrates. The pattern of catabolism indicated that sequential dephosphorylation from ATP----ADP----AMP----adenosine occurs. In whole blood, the pattern was similar although ATP and ADP (but not AMP) breakdown was more rapid. This was due to leukocyte ectonucleotidase activity. The use of selective inhibitors demonstrated that catabolism was not due to nonspecific phosphatase activity and that plasma 5'-nucleotidase is distinct from ATPase or ADPase. In leukocytes, ATPase and ADPase activities were distinguishable, and each contributed substantially to the rates of catabolism in whole blood. Leukocyte 5'-nucleotidase did not measurably contribute to AMP dephosphorylation in blood. By comparison, ecto-ATPase and ecto-ADPase activities on cultured human umbilical vein endothelial cells were similar to those on leukocytes while endothelial 5'-nucleotidase per 10(6) cells was equivalent to the soluble activity in 1 ml of blood or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)


Bridging the gap between climate change and maritime security: Towards a comprehensive framework for planning.
For the past two decades, the need to shield strategic maritime interests, to tackle criminality and terrorism at or from the sea and to conserve valuable marine resources has been recognized at the highest political level. Acknowledging and accounting for the interplay between climate change, the vulnerability of coastal populations and the occurrence of maritime criminality should be part of any ocean governance process. Still, given the complex interactions between climate change and socio-economic components of the marine realm, it has become urgent to establish a solid methodological framework, which could lead to sound and effective decisions. We propose that any such framework should not be built from scratch. The adaptation of well tested, existing uncertainty-management tools, such as Cumulative Effect Assessments, could serve as a solid basis to account for the magnitude and directionality of the dependencies between the impacts of climate change and the occurrence of maritime criminality, offering spatial explicit risk evaluations. Multi-Criteria Decision Making could then be employed to better and faster inform decision-makers. These mechanisms could provide a framework for comparison of alternative mitigation and adaptation actions and are essential in assessing responses to tackle maritime crime in the context of climate change.


Warmer temperatures enhance beneficial mutation effects.
Temperature determines the rates of all biochemical and biophysical processes, and is also believed to be a key driver of macroevolutionary patterns. It is suggested that physiological constraints at low temperatures may diminish the fitness advantages of otherwise beneficial mutations; by contrast, relatively high, benign, temperatures allow beneficial mutations to efficiently show their phenotypic effects. To experimentally test this "mutational effects" mechanism, we examined the fitness effects of mutations across a temperature gradient using bacterial genotypes from the early stage of a mutation accumulation experiment with Escherichia coli. While the incidence of beneficial mutations did not significantly change across environmental temperatures, the number of mutations that conferred strong beneficial fitness effects was greater at higher temperatures. The results therefore support the hypothesis that warmer temperatures increase the chance and magnitude of positive selection, with implications for explaining the geographic patterns in evolutionary rates and understanding contemporary evolution under global warming.


Aberrant Arterial Anatomy at the Floor of the Third Ventricle: Video Case Report.
A 65-year-old woman presented with a 2-month progressive history of forgetfulness, headaches, and decline in mobility. Imaging showed a large, enhancing pineal region tumor with triventricular hydrocephalus. She underwent an endoscopic third ventriculostomy and biopsy after appropriate consent was gained. Video 1 demonstrates the endoscopic procedure during which 2 aberrant arteries were identified at the floor of the third ventricle. The endoscopic third ventriculostomy was performed between these 2 arteries with great care to preserve them. The patient improved postoperatively with resolution of the hydrocephalus. Histology showed a metastatic malignant melanoma. To the best of our knowledge, no similar anatomy has been shown in an endoscopic procedure. We speculate that these are perforating arteries from the posterior communicating artery (premamillary artery) or a branch from the first part of the posterior cerebral artery P1 (thalamoperforators). Other options include perforators from the ophthalmic segment of the internal carotid artery, the communicating segment of the internal carotid artery, the superior hypophyseal artery, or a branch of the medial posterior choroidal arteries. We look at each in turn.


Comprehensive functional core microbiome comparison in genetically obese and lean hosts under the same environment.
Our study provides an exhaustive comparison of the microbiome core functionalities (captured by 3,936 microbial gene abundances) between hosts with divergent genotypes for intramuscular lipid deposition. After 10 generations of divergent selection for intramuscular fat in rabbits and 4.14 phenotypic standard deviations (SD) of selection response, we applied a combination of compositional and multivariate statistical techniques to identify 122 cecum microbial genes with differential abundances between the lines (ranging from -0.75 to +0.73 SD). This work elucidates that microbial biosynthesis lipopolysaccharides, peptidoglycans, lipoproteins, mucin components, and NADH reductases, amongst others, are influenced by the host genetic determination for lipid accretion in muscle. We also differentiated between host-genetically influenced microbial mechanisms regulating lipid deposition in body or intramuscular reservoirs, with only 28 out of 122 MGs commonly contributing to both. Importantly, the results of this study are of relevant interest for the efficient development of strategies fighting obesity.


Comparison of the efficacy of 0.03% tacrolimus eye drops diluted in olive oil and linseed oil for the treatment of keratoconjunctivitis sicca in dogs.
To compare the efficacy of 0.03% tacrolimus eye drops diluted in two different vehicles (linseed oil and olive oil) for the treatment of keratoconjunctivitis sicca (KCS) in dogs. This study included 60 dogs. Of this group, 20 were healthy and allocated to the control group, and 40 were diagnosed with bilateral KCS and randomly allocated to either the TO (tacrolimus in olive oil) or the TL (tacrolimus in linseed oil) groups. Ophthalmic examinations, Schirmer Tear Test-1 (STT-1), Tear Film Break-up Time (TBUT) and Fluorescein Test (FT) were carried out monthly, along with cytological and histopathological examinations at the beginning and end of the study. The clinical signs, corneal ulcers, Schirmer Tear Test-1 values, and Tear Film Break-up Time values improved in both groups after one month of treatment. Cytological examination at the end of the study showed decreased lymphocytes, neutrophil, metaplastic, and squamous cell counts in both groups, while the histopathological analysis showed decreases in lymphocytes and neutrophils and an increase in goblet cell density (cells/mm2). The decreases in neutrophil count were more significant (p<0.05) in the TL group for both types of examination. In sum, 0.03% tacrolimus eye drops diluted in olive oil and linseed oil were effective in the treatment of keratoconjunctivitis sicca. None of the evaluated parameters differed significantly between the two groups, except for neutrophil count which was significantly lower in the TL group. Thus, linseed oil may be considered as an alternative diluent for tacrolimus eye drops.


Correlates of caregivers' involvement in the management of older adults' medications.
Family caregivers are actively involved in medication management, yet little is known about factors associated with caregivers' involvement in this role and how that information can be utilized to engage caregivers in the healthcare system. To explore factors associated with caregiver involvement in various aspects of older adults' medication management (i.e., ordering, keeping track or ensuring the correct medication is taken at the correct time, and injecting medications). A retrospective analysis of two national surveys, the 2011 National Health and Aging Trends Study and the National Study of Caregiving was performed. Multivariate logistic regression models were used to examine the associations between demographic and caregiving variables with caregiver involvement in three medication management activities. Approximately two-thirds of family caregivers (N = 1369) were involved in one or more medication management activities. Factors associated with caregivers' assistance with ordering medications included being female, high frequency of involvement in instrumental activities of daily living (IADLs), involvement in medically-related activities, and caring for an older, less educated, or Hispanic care-recipient and individuals with lung disease or dementia (p < 0.05). Caregiver living arrangement, high frequency of involvement in activities of daily living (ADLs) and IADLs, involvement in medically-related activities along with care-recipient's race/ethnicity and having a dementia diagnosis were all associated with caregiver assistance in keeping track of medications (p < 0.05). Factors associated with assistance in injecting medications were caring for older adults with diabetes or stroke, or being involved in medically-related activities (p < 0.05). Different demographic and caregiving factors were associated with caregiver involvement in various medication management activities. Recurring factors included race/ethnicity, certain care-recipient disease states, and caregiver involvement in IADLs and medically-related activities. Healthcare providers can play a proactive role in engaging caregivers in discussion about medication management and these findings can help practitioners more effectively target caregivers for education and support.


Technical Note: A direct ray-tracing method to compute integral depth dose in pencil beam proton radiography with a multilayer ionization chamber.
To introduce a fast ray-tracing algorithm in pencil proton radiography (PR) with a multilayer ionization chamber (MLIC) for in vivo range error mapping. Pencil beam PR was obtained by delivering spots uniformly positioned in a square (45 × 45 mm2 field-of-view) of 9 × 9 spots capable of crossing the phantoms (210 MeV). The exit beam was collected by a MLIC to sample the integral depth dose (IDDMLIC). PRs of an electron-density and of a head phantom were acquired by moving the couch to obtain multiple 45 × 45 mm2 frames. To map the corresponding range errors, the two-dimensional set of IDDMLIC was compared with (i) the integral depth dose computed by the treatment planning system (TPS) by both analytic (IDDTPS) and Monte Carlo (IDDMC) algorithms in a volume of water simulating the MLIC at the CT, and (ii) the integral depth dose directly computed by a simple ray-tracing algorithm (IDDdirect) through the same CT data. The exact spatial position of the spot pattern was numerically adjusted testing different in-plane positions and selecting the one that minimized the range differences between IDDdirect and IDDMLIC. Range error mapping was feasible by both the TPS and the ray-tracing methods, but very sensitive to even small misalignments. In homogeneous regions, the range errors computed by the direct ray-tracing algorithm matched the results obtained by both the analytic and the Monte Carlo algorithms. In both phantoms, lateral heterogeneities were better modeled by the ray-tracing and the Monte Carlo algorithms than by the analytic TPS computation. Accordingly, when the pencil beam crossed lateral heterogeneities, the range errors mapped by the direct algorithm matched better the Monte Carlo maps than those obtained by the analytic algorithm. Finally, the simplicity of the ray-tracing algorithm allowed to implement a prototype procedure for automated spatial alignment. The ray-tracing algorithm can reliably replace the TPS method in MLIC PR for in vivo range verification and it can be a key component to develop software tools for spatial alignment and correction of CT calibration.


Liver disease as risk factor for cystic fibrosis-related diabetes development.
To evaluate clinical and genetic factors, besides pancreatic insufficiency, associated with increased risk of cystic fibrosis-related diabetes. Case-control (1:1) study on 138 cystic fibrosis patients. Data were collected on gender, age at diagnosis, reason for cystic fibrosis diagnosis, family history of type 1 or 2 diabetes mellitus, pre-existing severe liver disease, and class of cystic fibrosis transmembrane regulation mutation. Moreover, information was obtained on lung involvement and degree of exocrine pancreatic insufficiency evaluated 1 year before the diagnosis of cystic fibrosis-related diabetes in patients and age-matched controls. Compared to controls, patients with cystic fibrosis-related diabetes had a higher probability of having already been diagnosed with liver disease (16.7% versus 1.7%, OR = 11.6, 95% CI 1.43-93.0). Moreover, in the year before diabetes onset, cases had slightly worse pulmonary function compared to controls (FEV1 = 58.4 +/- 27% predicted versus 67.4 +/- 21% predicted; p = 0.05). No significant effects related to the other factors considered were found. Severe liver disease was found to significantly increase the risk of developing cystic fibrosis-related diabetes. Patients with liver disease should be scheduled for earlier diabetes screening in order to identify and possibly treat glucose intolerance.


Barriers to Gestational Diabetes Management and Preferred Interventions for Women With Gestational Diabetes in Singapore: Mixed Methods Study.
Gestational diabetes mellitus (GDM) is associated with risks for both the mother and child. The escalated prevalence of GDM because of obesity and changes in screening criteria demands for greater health care needs than before. This study aimed to understand the perception of patients and health care providers of the barriers to GDM management and preferred interventions to manage GDM in an Asian setting. This mixed methods study used a convergent parallel design. Survey data were collected from 216 women with GDM, and semistructured interviews were conducted with 15 women and with 8 health care providers treating patients with GDM. Participants were recruited from 2 specialized GDM clinics at the National University Hospital, Singapore. The patients were predominantly Chinese (102/214, 47.6%), employed (201/272, 73.9%), with higher education (150/216, 69.4%) and prenatal attendance at a private clinic (138/214, 64.2%), already on diet control (210/214, 98.1%), and receiving support and information from the GDM clinic (194/215, 90.2%) and web-based sources (131/215, 60.9%). In particular, working women reported barriers to GDM management, including the lack of reminders for blood glucose monitoring, diet control, and insufficient time for exercise. Most women preferred getting such support directly from health care providers, whether at the GDM clinic (174/215, 80.9%) or elsewhere (116/215, 53.9%). Smartphone apps were the preferred means of additional intervention. Desirable intervention features identified by patients included more information on GDM, diet and exercise options, reminders for blood glucose testing, a platform to record blood glucose readings and illustrate or understand trends, and a means to communicate with care providers. A GDM-focused smartphone app that is able to integrate testing, education, and communication may be a feasible and acceptable intervention to provide support to women with GDM, particularly for working women.


Performance Comparison of CGM Systems: MARD Values Are Not Always a Reliable Indicator of CGM System Accuracy.
The ongoing progress of continuous glucose monitoring (CGM) systems results in an increasing interest in comparing their performance, in particular in terms of accuracy, that is, matching CGM readings with reference values measured at the same time. Most often accuracy is evaluated by the mean absolute relative difference (MARD). It is frequently overseen that MARD does not only reflect accuracy, but also the study protocol and evaluation procedure, making a cross-study comparison problematic. We evaluate the effect of several factors on the MARD statistical properties: number of paired reference and CGM values, distribution of the paired values, accuracy of the reference measurement device itself and the time delay between data pairs. All analysis is done using clinical data from 12 patients wearing 6 sensors each. We have found that a few paired points can have a potentially high impact on MARD. Leaving out those points for evaluation thus reduces the MARD. Similarly, accuracy of the reference measurements greatly affects the MARD as numerical and graphical data show. Results also show that a log-normal distribution of the paired references provides a significantly different MARD than, for example, a uniform distribution. MARD is a reasonable parameter to characterize the performance of CGM systems when keeping its limitations in mind. To support clinicians and patients in selecting which CGM system to use in a clinical setting, care should be taken to make MARD more comparable by employing a standardized evaluation procedure.


Subclinical nephrotoxicity associated with occupational silica exposure among male Kenyan industrial workers.
To determine early signs of renal injury due to occupational silica exposure. Cross-sectional analytical research. Kenyatta National Hospital for the referent population and Clayworks ceramics, bricks and tiles factory for the assessment of occupational silica exposure. Thirty three non-smoking silica-exposed male industrial workers and 38 non-smoking male referents participated in this study. Silica-exposed males excreted significantly increased levels of U.TP, U.Malb, U.ALP, U.y-GT and U.LDH compared to referent males. Among the silica-exposed males, U.Si negatively correlated significantly with age, U.TP correlated significantly to each of U.ALP and U.LDH. However, no correlation was observed between work duration and U.Si. The present study shows that there is associated glomerular and proximal tubular damage among silica exposed workers which is not duration related and is seemingly subclinical and nonprogressive and urinary silica levels appears to be similar in all groups and are not affected by exposure and work duration: the reason for which is unclear.


Efficacy of opioids for traumatic pain in the emergency department: a systematic review and Bayesian network meta-analysis.
Aim: To systematically assess and rank the efficacy of opioid medications for traumatic pain in the emergency department in terms of pain relief, adverse events and rescue analgesia. Methods: Four databases were systematically searched until 26 September 2022: PubMed, Embase, Cochrane Library, and Web of Science. Outcomes were pain relief, adverse events (dizziness, hypotension, pruritus, sedation), and rescue analgesia. For each outcome, network plots were drawn to exhibit direct and indirect comparisons, and rank probabilities were utilized to rank the efficacy of different opioids. Results: Twenty studies of 3,040 patients were eligible for this network meta-analysis. According to the rank probabilities, the top three analgesic medications for pain relief may be sufentanil (78.29% probability of ranking first), buprenorphine (48.54% probability of ranking second) and fentanyl (53.25% probability of ranking third); buprenorphine (31.20%), fentanyl (20.14%) and sufentanil (21.55%) were least likely to cause dizziness; the top three analgesic medications which were least likely to cause hypotension were buprenorphine (81.64%), morphine (45.02%) and sufentanil (17.27%); butorphanol (40.56%), morphine (41.11%) and fentanyl (14.63%) were least likely to cause pruritus; the top three medications which were least likely to cause sedation were hydrocodone + acetaminophen (97.92%), morphine (61.85%) and butorphanol (55.24%); patients who received oxycodone (83.64%), butorphanol (38.31%) and fentanyl (25.91%) were least likely to need rescue analgesia in sequence. Conclusion: Sufentanil, buprenorphine and fentanyl may be superior to other opioid medications in terms of pain relief and the incidence of dizziness, hypotension and pruritus, which might be selected as opioid analgesics for traumatic pain in the emergency setting.


Phagocytosis measured as inhibition of uridine uptake: a method that distinguishes between surface adherence and ingestion.
Polymorphonuclear leucocytes selectively inhibited the incorporation of 14C-uridine by intracellular staphylococci. Within specified limits, the amount of radiolabel incorporated by extracellular staphylococci was related to bacterial concentration. The incorporation of labelled uridine can thus be exploited to assay the extent to which association between staphylococci and polymorphonuclear leucocytes reflects surface adherence as opposed to ingestion. A comparison of the new method with a conventional viable-count determination of leucocyte-associated bacteria shows it to be comparable in efficiency when non-immune serum is used as opsonin and superior when specific opsonin is used.