Modifiable risk factors for mild cognitive impairment among cognitively normal community-dwelling older adults: A systematic review and meta-analysis.

Although numerous studies have investigated modifiable risk factors for mild cognitive impairment (MCI) among community-dwelling seniors, no meta-analysis has summarized these findings. Five databases were searched from January 1, 2000, to December 30, 2023. The protocol was registered with PROSPERO. Data were extracted and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant meta-analyses of modifiable risk factors were performed. The evidence of each factor was assessed by the GRADE for cohort studies. Of 16,651 citations, 87 studies involving 225,584 community-dwelling seniors were included. Fourteen meta-analyses involving 20 studies with 44,199 participants were performed. The analyses revealed low-to-moderate-quality evidence supporting that diabetes, 2 or more comorbidities, anxiety, apathy, depressive symptoms, and physical frailty were risk factors for incident MCI in older adults. Conversely, hypertension, agitation, and irritability might not be risk factors. Additionally, moderate-quality evidence supports the protective effect of engaging in cognitive-demanding activities on the onset of MCI. Collectively, this study constitutes the first extensive compilation of evidence regarding the various risk factors for the development of MCI in older adults. Our findings hold significant potential to guide the formulation of prevention and management strategies to either prevent or potentially reverse the onset of MCI.

Assessment of a Discogenic Pain Animal Model Induced by Applying Continuous Shear Force to Intervertebral Discs.

BACKGROUND: Chronic discogenic pain includes degeneration-driven changes under the mechanical macroenvironment of an internal disc, which leads to the progressive changes of biochemical microenvironment that induce abnormal ingrowth of the nociceptor. The propriety of the animal model reflecting the pathologic natural history has not been assessed. OBJECTIVES: This study investigated the biochemical evidence of chronic discogenic pain by employing a discogenic pain animal model induced by shear force. STUDY DESIGN: Animal study utilizing rats in vivo model of a shear force device. METHODS: Fifteen rats were divided into 3 groups (n = 5/group) according to the period for which sustained dorsoventral shear force was applied (1 week or 2 weeks); the control group received the spinous attachment unit, without a spring. Pain data were collected using von Frey hairs on the hind paws. Growth factor and cytokine abundance was analyzed in the dorsal root ganglion (DRG) and plasma. RESULTS: After the shear force devices were installed, the significant variables were found to markedly increase in the DRG tissues of the 2-week group; however, they were not altered in the 1-week group. Specifically, interleukin (IL)-6, neurogrowth factor (NGF), transforming growth factor (TGF)-alpha, platelet-derived growth factor (PDGF)-beta, and vascular endothelial growth factor (VEGF) were increased. Meanwhile, the plasma levels of tumor necrosis factor-alpha, IL-1beta, IL-5, IL-6, IL-12, and NGF were increased in the 1-week group; whereas, TGF-alpha, PDGF-beta, and VEGF were increased in the 2-week group. LIMITATIONS: The limitations include the general limitations of quadrupedal animals, the poor precision and flexural deformation of shear force devices, inaccuracies regarding the evaluation of histological denaturation, and short intervention and observational periods. CONCLUSIONS: This animal model effectively generated biochemical responses to shear loading with evidence of neurological changes induced without direct macrodamage to the outer annulus fibrosus. Chemical internals were induced by mechanical externals among the contributing factors of chronic discogenic pain.

Translation and validation of the Reaction to Impairment and Disability Inventory for Chinese population in Hong Kong.

PURPOSE: This study translated the reaction to impairment and disability inventory (RIDI) to Chinese and validated it for use in Hong Kong. METHODS: We conducted an instrument validation of the Chinese RIDI, with a sample of 244 persons with CID. The research questionnaire collected demographic information, illness-related variables, the Chinese version of RIDI (C-RIDI), and measures of resilience and well-being. We examined the factor structure, internal consistency, convergent validity, and criterion-related validity of the C-RIDI. RESULTS: The C-RIDI has good content validity and no major changes to the translated items were needed for the use in Hong Kong. For factor structure, we replicated the results of Livneh et al. The C-RIDI has two second-order factors of adaptive and nonadaptive scales, which interact with the two denial subscales. Internal consistency of the subscales is satisfactory except for the three-item denial subscales. Correlations of the C-RIDI subscales with illness-related variables, resilience, and mental well-being are consistent with our hypotheses and provide support for the convergent and criterion-related validity of the scale. CONCLUSIONS: The C-RIDI has satisfactory psychometric properties. The study results support its internal consistency, convergent validity, criterion-related validity, and factorial validity.IMPLICATIONS FOR REHABILITATIONEmotional adjustment to chronic illness and disability is a key determinant of illness self-management, mental well-being, and quality of life.The study translated the reaction to impairment and disability inventory into Chinese and conducted a psychometric evaluation of the translated instrument.The Chinese RIDI had a similar second-order factor structure as in the validation studies of the English version, and result of this confirmatory factor analysis support the theory underlying the design of the RIDI.The Chinese RIDI had satisfactory convergent and criterion-related validity and internal consistency, and is ready for application in rehabilitation practice and research in the Chinese context.

Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial.

BACKGROUND: No phase 3 trial has yet shown improved survival for patients with pleural or peritoneal malignant mesothelioma who have progressed following platinum-based chemotherapy. The aim of this study was to assess the efficacy and safety of nivolumab, an anti-PD-1 antibody, in these patients. METHODS: This was a multicentre, placebo-controlled, double-blind, parallel group, randomised, phase 3 trial done in 24 hospitals in the UK. Adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1, with histologically confirmed pleural or peritoneal mesothelioma, who had received previous first-line platinum-based chemotherapy and had radiological evidence of disease progression, were randomly assigned (2:1) to receive nivolumab at a flat dose of 240 mg every 2 weeks over 30 min intravenously or placebo until disease progression or a maximum of 12 months. The randomisation sequence was generated within an interactive web response system (Alea); patients were stratified according to epithelioid versus non-epithelioid histology and were assigned in random block sizes of 3 and 6. Participants and treating clinicians were masked to group allocation. The co-primary endpoints were investigator-assessed progression-free survival and overall survival, analysed according to the treatment policy estimand (an equivalent of the intention-to-treat principle). All patients who were randomly assigned were included in the safety population, reported according to group allocation. This trial is registered with Clinicaltrials.gov, NCT03063450. FINDINGS: Between May 10, 2017, and March 30, 2020, 332 patients were recruited, of whom 221 (67%) were randomly assigned to the nivolumab group and 111 (33%) were assigned to the placebo group). Median follow-up was 11·6 months (IQR 7·2-16·8). Median progression-free survival was 3·0 months (95% CI 2·8-4·1) in the nivolumab group versus 1·8 months (1·4-2·6) in the placebo group (adjusted hazard ratio [HR] 0·67 [95% CI 0·53-0·85; p=0·0012). Median overall survival was 10·2 months (95% CI 8·5-12·1) in the nivolumab group versus 6·9 months (5·0-8·0) in the placebo group (adjusted HR 0·69 [95% CI 0·52-0·91]; p=0·0090). The most frequently reported grade 3 or worse treatment-related adverse events were diarrhoea (six [3%] of 221 in the nivolumab group vs two [2%] of 111 in the placebo group) and infusion-related reaction (six [3%] vs none). Serious adverse events occurred in 90 (41%) patients in the nivolumab group and 49 (44%) patients in the placebo group. There were no treatment-related deaths in either group. INTERPRETATION: Nivolumab represents a treatment that might be beneficial to patients with malignant mesothelioma who have progressed on first-line therapy. FUNDING: Stand up to Cancer-Cancer Research UK and Bristol Myers Squibb.

Spontaneous Intramuscular Abscesses Involving the Rotator Cuff Muscles in Two Cases Presenting During the COVID-19 Pandemic.

Spontaneous abscesses involving the rotator cuff muscles are a rare surgical occurrence. Patients with such abscesses are often initially misdiagnosed or there is a significant diagnostic delay. Herein, we report one case of a spontaneous intramuscular abscess involving the subscapularis muscle and a second case of an abscess involving the supraspinatus muscle. There is a multitude of predisposing risk factors to developing an intramuscular abscess formation, which includes immunodeficiency, trauma, injection drug use, concurrent infection, and malnutrition. The most significant risk factor in our cases was poorly controlled type 2 diabetes mellitus. Poorly controlled diabetes is known to cause impaired clearance of pathogens, predisposing patients to abscess formation. Both patients also delayed presenting to the hospital due to concerns surrounding the coronavirus disease of 2019 (COVID-19) pandemic. We describe the use of a deltoid-pectoral approach to access the subscapular abscess allowing surgical drainage. The supraspinatus abscess was drained by direct incision. We advocate utilising common and familiar approaches with or without arthroscopy where possible. These cases highlight the importance of early imaging in patients presenting with the physiological signs of infection and idiopathic shoulder pain.

Can a modified theory of planned behavior explain the effects of empowerment education for people with type 2 diabetes?

BACKGROUND: The effectiveness of the Patient Empowerment Program (PEP) has been demonstrated in people with diabetes mellitus (DM); however, the underlying reasons for its effectiveness remain unclear. To improve effectiveness, we need to study the psychological mechanism(s) of PEP to understand why it is effective. This study hypothesized that the Theory of Planned Behavior (TPB), modified specifically for people with DM, could describe the mechanism explaining PEP effects. METHODS: A longitudinal design was used. Patients with type 2 DM (n = 365; 151 males; mean age = 62.9 ± 9.6 years) received two education sessions (i.e. seminars delivered by registered nurses to provide disease-specific knowledge), and some (n = 210) further enrolled afterwards in five empowerment sessions (i.e. small-group interactive workshops conducted by social workers to practice action planning, problem solving, and experience sharing). Validated questionnaires were used to measure risk perception, health literacy, attitude, subjective norm, perceived behavioral control and behavioral intention on diabetes self-care behaviors, and four diabetes self-care behaviors (diet control, exercise, blood glucose monitoring, and foot care) at baseline. Three months later (i.e. at the end of PEP), all participants completed the behavioral intention and diabetes self-care behaviors measures again. Attitude, subjective norm, perceived behavioral control, behavioral intention, and diabetes self-care behaviors were assessed to represent the TPB constructs. Risk perception and health literacy elements relevant to people with DM were assessed and added to modify the TPB. RESULTS: The behavioral intention was associated with three diabetes self-care behaviors: exercise, blood glucose monitoring, and foot care. The behavioral intention was found to be a significant mediator in the following relationships: empowerment session participation and exercise (ß = 0.045, p = 0.04), and empowerment session participation and foot care (ß = 0.099, p < 0.001). CONCLUSIONS: The effects of enrollment of empowerment sessions in PEP on exercise and foot care were likely to be mediated through behavioral intention.

A Portable Phase-Domain Magnetic Induction Tomography Transceiver with Phase-Band Auto-Tracking and Frequency-Sweep Capabilities.

This paper presents a portable magnetic induction tomography (MIT) transceiver integrated circuit to miniaturize conventional equipment-based MIT systems. The miniaturized MIT function is enabled through single-chip transceiver implementation. The proposed MIT transceiver utilizes a phase-locked loop (PLL) for frequency sweeping and a phase-domain sigma⁻delta modulator with phase-band auto-tracking for a full-range fine-phase resolution. The designed transceiver is fabricated and verified to achieve the measured signal to noise and distortion ratio (SNDR) of 101.7 dB. Its system-level prototype including in-house magnetic sensor coils is manufactured and functionally verified for four different material types.

A Three-Step Resolution-Reconfigurable Hazardous Multi-Gas Sensor Interface for Wireless Air-Quality Monitoring Applications.

This paper presents a resolution-reconfigurable wide-range resistive sensor readout interface for wireless multi-gas monitoring applications that displays results on a smartphone. Three types of sensing resolutions were selected to minimize processing power consumption, and a dual-mode front-end structure was proposed to support the detection of a variety of hazardous gases with wide range of characteristic resistance. The readout integrated circuit (ROIC) was fabricated in a 0.18 µm CMOS process to provide three reconfigurable data conversions that correspond to a low-power resistance-to-digital converter (RDC), a 12-bit successive approximation register (SAR) analog-to-digital converter (ADC), and a 16-bit delta-sigma modulator. For functional feasibility, a wireless sensor system prototype that included in-house microelectromechanical (MEMS) sensing devices and commercial device products was manufactured and experimentally verified to detect a variety of hazardous gases.

Reliability of measurements for sub-painful and painful perception on artificial electrical stimulations.

Artificial electrical stimulation is a common type of stimulus to induce sub-painful and painful sensation in clinical or neuroscience experiments. The Numerical Rating Scale (NRS) is often used to evaluate subjective perception due to external stimulations. Yet the relationship between the intensity levels of electrical stimulations and self-perception has seldom been examined. The aim of the study was to obtain evidence on the reliability and accuracy of sub-painful and painful perceptions of healthy participants using the NRS under different levels of electrical stimulus. A total of 72 pain-free healthy volunteers (female=44) were recruited. In the first experiment, each participant was given different levels of a non-nociceptive or nociceptive electrical stimulus and then asked to give a perception rating based on an 11-point NRS. In the second experiment, each participant was asked to memorize 5 levels of sub-nociceptive or nociceptive stimuli and to recognize the level of stimulus given each time. For the NRS rating task, intraclass coefficients (ICCs) reached satisfactory level for sub-nociceptive (0.85

Salience of Somatosensory Stimulus Modulating External-to-Internal Orienting Attention.

Shifting between one's external and internal environments involves orienting attention. Studies on differentiating subprocesses associated with external-to-internal orienting attention are limited. This study aimed to reveal the characteristics of the disengagement, shifting and reengagement subprocesses by using somatosensory external stimuli and internally generated images. Study participants were to perceive nociceptive external stimuli (External Low (EL) or External High (EH)) induced by electrical stimulations (50 ms) followed by mentally rehearsing learned subnociceptive images (Internal Low (IL) and Internal High (IH)). Behavioral responses and EEG signals of the participants were recorded. The three significant components elicited were: fronto-central negativity (FCN; 128-180 ms), fronto-central P2 (200-260 ms), and central P3 (320-380 ms), which reflected the three subprocesses, respectively. Differences in the FCN and P2 amplitudes during the orienting to the subnociceptive images revealed only in the EH but not EL stimulus condition that are new findings. The results indicated that modulations of the disengagement and shifting processes only happened if the external nociceptive stimuli were of high salience and the external-to-internal incongruence was large. The reengaging process reflected from the amplitude of P3 correlated significantly with attenuation of the pain intensity felt from the external nociceptive stimuli. These findings suggested that the subprocesses underlying external-to-internal orienting attention serve different roles. Disengagement subprocess tends to be stimulus dependent, which is bottom-up in nature. Shifting and reengagement tend to be top-down subprocesses, which taps on cognitive control. This subprocess may account for the attenuation effects on perceived pain intensity after orienting attention.

A latent profile analysis on patient empowerment programme in a Hong Kong primary care setting.

OBJECTIVE: This study identified the profiles of subgroups of type 2 diabetic (T2DM) patients of the Patient Empowerment Programme (PEP) by different levels of benefits gained in diabetic self-management behaviors, self-efficacy, and health literacy. METHODS: This study adopted a non-experimental repeated-measures design on T2DM patients who joined PEP, using structured questionnaires. Latent profile analysis (LPA) was used to identify patterns of participants' change on the outcome measures. RESULTS: Findings of LPA revealed that participants who were older, unemployed, weaker in diabetic self-management, and having a higher self-perception in personal disease risk were more likely to join the empowerment sessions and gained more benefits from the program. Participants with lower impairment in energy function and lower autonomy in personal health care showed more improvement in the outcomes. CONCLUSION: The study identified significant factors associated with patients' participation on and benefits gained from a service delivery model integrating health education and patient empowerment in a primary care setting. PRACTICE IMPLICATION: Findings from this study shed light on strategies to improve the PEP design in order to meet the needs of individuals with different health-related profiles.

Chinese Calligraphy Writing for Augmenting Attentional Control and Working Memory of Older Adults at Risk of Mild Cognitive Impairment: A Randomized Controlled Trial.

BACKGROUND: Nonpharmacological intervention for individuals with mild cognitive impairment (MCI) needs further investigation. OBJECTIVE: Test efficacy of an eight-week Chinese calligraphy writing training course in improving attentional control and working memory. METHODS: Ninety-nine participants with MCI were randomized into the eight-week calligraphy writing (n = 48) or control (tablet computer) training (n = 51). Outcomes of the interventions were attentional control, working memory, visual scan and processing speed. They were measured at baseline, post-training, and six-month follow-up. RESULTS: Calligraphy writing, when compared with control, significantly improved working memory as reflected from DST-Backward sequence (p = 0.009) and span scores (p = 0.002), and divided attention as reflected from CTT2 (p < 0.001), and at the post-training. The unique improvement in working memory (span: p < 0.001; sequence: p = 0.008) of the intervention group was also found at follow-up when comparing with those at baseline. Changes in the other outcome measures were not statistically significant. CONCLUSION: The findings provide support that Chinese calligraphy writing training for eight weeks using a cognitive approach would improve working memory and to a lesser extent attentional control functions of patients with early MCI. They also demonstrate the usefulness of using mind-and-body practice for improving specific cognitive functions.

Filling potholes on the implementation highway: Evaluating the implementation of Parent-Child Interaction Therapy in Los Angeles County.

In October 2012, first 5 LA funded a unique collaboration between Los Angeles County Department of Mental Health (DMH) and UC Davis PCIT Training Center (UCD PCIT) to train county-contracted agencies to provide Parent-Child Interaction Therapy (PCIT). This $20 million dollar, 5-year grant represented the largest implementation effort of an empirically based treatment to date. The purpose of this paper was to describe the first 2 years of the implementation process of this project, beginning with project start up and pre-implementation phases, and to present agency training and client performance outcomes from our first year of training. Results presented in this evaluation suggest that it is possible to train LA County providers in PCIT, and that PCIT is an effective intervention for DMH-contracted providers in LA County. This evaluation also discusses challenges to successful implementation. Barriers to progress included unanticipated delays building county infrastructure, trainee attrition, and insufficient client referrals. We discuss the results of the current implementation with respect to theory, research, and others' training models, with the aim of evaluating and prioritizing different implementation drivers, noting the ongoing competition between knowing what to do and the need for action.

Differentiating cognitive functions of poststroke patients with specific brain lesions: A preliminary study on the clinical utility of Cognistat-P.

The Cognistat is widely used to measure the cognitive profile of neurological patients. This study aimed to further obtain evidence on the construct and discriminative validity of the Putonghua version of the Cognistat (Cognistat-P) on poststroke patients with specific brain lesions. Cognistat-P was administered to poststroke patients (n = 98), as well as healthy elderly (n = 40) and adult (n = 34) participants as the control groups. Poststroke patients were further categorized into 4 lesion groups using standard brain slice templates. Exploratory factory analysis reflected a 2-factor structure for the Cognistat-P that resembles that for the original English version. The Construction, Similarities, and Judgment subtests were found to differentiate patients with frontal or parietal lesions from those with subcortical lesions (p < .01, R(2) = .48). The Construction subtest, tapping the "fluid" ability, was the most useful for differentiating patients with parietal lesions from those with subcortical lesions. The Similarities subtest together with the Construction subtest was the most useful for differentiating patients with frontal lesions from those with subcortical lesions. This study established the validity of the Cognistat-P for differentiating poststroke patients with specific brain lesions. Future studies should replicate the results on a larger sample size and test the clinical significance of the Cognistat-P profiles.

Generalization of Context-Specific Training in Individuals with Mild Cognitive Impairment: An Event-Related Potential Study.

BACKGROUND: This study examined the neural processes associated with the generalization of the effect of context-specific (CS) training to noncontextual situations among individuals with mild cognitive impairment (MCI). METHODS: Fourteen and 16 participants with MCI were randomly allocated to a Chinese calligraphy writing (CW) training or a control group, respectively. The CW participants learned how to write Chinese strokes in a semicursive style to construct characters, tapping on working memory functions. The control group, on the other hand, learned how to use a tablet computer without emphasis on working memory functions. They then performed two 2-back tasks with CS semicursive strokes and non-context-specific (NCS) digits. Event-related electroencephalogram signals were concurrently recorded. RESULTS: The CW participants had a significantly shorter reaction time in the CS than in the NCS task (p < 0.05). They showed significantly longer latency in working memory updating (N200; t₁₁ = 4.70, p = 0.05) and shorter latency in the evaluation of visual representation (P300; t₁₂ = 4.67; p = 0.05) than the control group when performing the 2-back CS task. Shorter P300 latency was also revealed in the 2-back NCS task (t₁₂ = 5.15, p = 0.041), suggesting a possible generalization of the training effect among the CW participants. CONCLUSION: The results suggest that CS working memory is likely to be generalized to NCS domains among individuals with MCI. Future research should extend the scope of the generalization and apply it beyond experimental conditions.

Natural Loss of eyeless/Pax6 Expression in Eyes of Bicyclus anynana Adult Butterflies Likely Leads to Exponential Decrease of Eye Fluorescence in Transgenics.

Commonly used visible markers for transgenesis use fluorescent proteins expressed at the surface of the body, such as in eyes. One commonly used marker is the 3xP3-EGFP cassette containing synthetic binding sites for the eyeless/Pax6 conserved transcription factor. This marker cassette leads to fluorescent eyes in a variety of animals tested so far. Here we show that upon reaching adulthood, transgenic Bicyclus anynana butterflies containing this marker cassette exponentially loose fluorescence in their eyes. After 12 days, transgenic individuals are no longer distinguishable from wild type individuals. The decreased eye fluorescence is likely due to significantly decreased or halted eyeless/Pax6 expression observed in wild type animals upon adult emergence. Implications from these findings include care in screening transgenic animals before these reach adulthood, or shortly thereafter, and in using adult animals of the same age for quantitative screening of likely homozygote and heterozygote individuals.

A conceptual model of patient-professional communication as a self-management skill: A latent growth change modeling.

BACKGROUND: Patient Communication with healthcare professionals is an integral self-management skill. Yet the underlying mechanisms explaining how such communication might be enhanced across time have not been well studied. OBJECTIVES: Based on the transtheoretical model, the study aimed to develop an across-time Attitude-Social Influence-Efficacy model in order to explain changes in participants' patient-professional communication behaviors in the Chronic Disease Self-management Program (CDSMP). Readiness-to-change construct was hypothesized to be the overall predictors of psychological and behavioral parameters. It was hypothesized that social norm and attitude toward behaviors would be the indirect predictors of communication behavior. METHODS: One hundred and thirty-six Chinese participants with chronic diseases underwent a 6-week CDSMP. Their attitude toward behavior, self-efficacy, social norm, readiness to change and communication behavior were obtained at 1st, 4th and 6th week of the structured program. RESULTS: A modified latent growth change curve model yielded satisfactory model fit (χ(2)/df = 1.32; RMSEA = 0.063 (90% CI = 0.018-0.96)). The results showed that readiness to change had a positive influence on attitude and self-efficacy. Both attitude and social norm positively affected self-efficacy. Attitude and self-efficacy in turn positively influenced communication behavior at the beginning of the program. Across 6 weeks, self-efficacy imposed a negative influence on communication behavior while social norm exerted a positive influence on the behavior. CONCLUSION: This study revealed possible underlying mechanisms influencing CDSMP participants' communication with professionals. The results could shed light on further improvement of the structured program.

Tuning cellular response by modular design of bioactive domains in collagen.

Collagen's ability to direct cellular behavior suggests that redesigning it at the molecular level could enable manipulation of cells residing in an engineered microenvironment. However, the fabrication of full-length collagen mimics of specified sequence de novo has been elusive, and applications still rely on material from native tissues. Using a bottom-up strategy, we synthesized modular genes and expressed recombinant human collagen variants in Saccharomyces cerevisiae. The resulting biopolymers contained prescribed cell-interaction sites that can direct and tune cellular responses, with retention of the important triple-helical self-assembled structure. Removal of the native integrin-binding sites GROGER, GAOGER, GLOGEN, GLKGEN, and GMOGER in human collagen III yielded collagen that did not support adhesion of mammalian cells. Introduction of GFOGER sequences to this scaffold at specified locations and densities resulted in varying degrees of cellular attachment. The recruitment of focal adhesion complexes on the different collagens ranged from a 96% reduction to a 56% increase over native collagen I. Adhesion to the GFOGER-containing variants was entirely dependent and partially dependent on the ß1 and α2 subunits of integrin, respectively, with cell adhesion on average reduced by 86% with anti-ß1 and 38% with anti-α2 integrin antibody incubation. Results support the importance of local context in collagen-cell interactions. The investigation demonstrates the flexibility of this approach to introduce targeted changes throughout the collagen polymer for producing fully-prescribed variants with tailored properties.

First cases of KPC-type carbapenemase-producing bacteria in patients in New Zealand hospitals.

The emergence and global spread of Klebsiella pneumoniae carbapenemases (KPCs) is a significant public health problem. Between October 2010 and July 2013, KPC-producing K. pneumoniae were isolated from four patients in New Zealand hospitals. These cases are the first known isolations of KPC-producing organisms in New Zealand. All four patients were transferred from, or had recently been in, hospitals in countries where KPC-producing organisms are prevalent (China, India, Greece and Italy). The blaKPC-2 gene was identified in the isolates from three patients and blaKPC-3 was identified in the isolate from the remaining patient. The isolates belonged to different multilocus sequence type clonal complexes, usually those prevalent in the country in which the patient had been previously hospitalised. Currently in New Zealand, the common factor associated with having a KPC-producing organism is prior hospitalisation in another country where these organisms are prevalent.

Early detection of clinically significant prostate cancer at diagnosis: a prospective study using a novel panel of TMPRSS2:ETS fusion gene markers.

We explore noninvasive clinical applications of multiple disease-specific fusion markers recently discovered in prostate cancer to predict the risk of cancer occurrence and aggressiveness at diagnosis. A total of 92 men who were prostate-specific antigen (PSA) screened and scheduled for diagnostic biopsy were enrolled for this study. Prospectively collected urine was blind coded for laboratory tests. RNA from urine sediments was analyzed using a panel of 6 TMPRSS2:ETS fusion markers with a sensitive quantitative PCR platform. The pathology reported 39 biopsy-positive cases from 92 patients (42.4%). In urine test, 10 unique combinations of fusion types were detected in 32 of 92 (34.8%) prebiopsy samples. A novel combination of fusion markers, termed Fx (III, IV, ETS), was identified with a sensitivity of 51.3% and an odds ratio of 10.1 in detecting cancer on biopsy. Incorporating a categorical variable of Fx (III, IV, ETS) with urine PCA3 and serum PSA, a regression model was developed to predict biopsy outcomes with an overall accuracy of 77%. Moreover, the overexpression of Fx (III, IV, or ETS) was shown to be an independent predictor to the high-grade cancer, with a predictive accuracy of 80% when coupled with PSA density. The individualized risk scores further stratified a high-risk group that is composed of 92% high-grade cancers and a low-risk group that harbors mainly clinically insignificant cancers. In conclusion, we have identified a novel combination of fusion types very specific to the clinically significant prostate cancer and developed effective regression models to predict biopsy outcomes and aggressive cancers at diagnosis.