Maturation of auditory cortex neural responses during infancy and toddlerhood.

The infant auditory system rapidly matures across the first years of life, with a primary goal of obtaining ever-more-accurate real-time representations of the external world. Our understanding of how left and right auditory cortex neural processes develop during infancy, however, is meager, with few studies having the statistical power to detect potential hemisphere and sex differences in primary/secondary auditory cortex maturation. Using infant magnetoencephalography (MEG) and a cross-sectional study design, left and right auditory cortex P2m responses to pure tones were examined in 114 typically developing infants and toddlers (66 males, 2 to 24 months). Non-linear maturation of P2m latency was observed, with P2m latencies decreasing rapidly as a function of age during the first year of life, followed by slower changes between 12 and 24 months. Whereas in younger infants auditory tones were encoded more slowly in the left than right hemisphere, similar left and right P2m latencies were observed by ∼21 months of age due to faster maturation rate in the left than right hemisphere. No sex differences in the maturation of the P2m responses were observed. Finally, an earlier left than right hemisphere P2m latency predicted better language performance in older infants (12 to 24 months). Findings indicate the need to consider hemisphere when examining the maturation of auditory cortex neural activity in infants and toddlers and show that the pattern of left-right hemisphere P2m maturation is associated with language performance.

Anticipatory anxiety and participation in cancer screening. A systematic review.

OBJECTIVES: To synthesize current evidence on the association between anticipatory anxiety, defined as apprehension-specific negative affect that may be experienced when exposed to potential threat or uncertainty, and cancer screening to better inform strategies to maximize participation rates. METHODS: Searches related to cancer screening and anxiety were conducted in seven electronic databases (APA PsycINFO, Scopus, Web of Science, Embase, Cochrane Library, PubMed, CINAHL), with potentially eligible papers screened in Covidence. Data extraction was conducted independently by multiple authors. Barriers to cancer screening for any type of cancer and relationships tested between anticipatory anxiety and cancer screening and intention were categorized and compared according to the form and target of anxiety and cancer types. RESULTS: A total of 74 articles (nparticipants  = 119,990) were included, reporting 103 relationships tested between anticipatory anxiety and cancer screening and 13 instances where anticipatory anxiety was reported as a barrier to screening. Anticipatory anxiety related to a possible cancer diagnosis was often associated with increased screening, while general anxiety showed no consistent relationship. Negative relationships were often found between anxiety about the screening procedure and cancer screening. CONCLUSION: Anticipatory anxiety about a cancer diagnosis may promote screening participation, whereas a fear of the screening procedure could be a barrier. Public health messaging and primary prevention practitioners should acknowledge the appropriate risk of cancer, while engendering screening confidence and highlighting the safety and comfort of screening tests.

Liposomal Bupivacaine Transversus Abdominis Plane Blocks in Laparoscopic Colorectal Resections: A Single-Institution Randomized Controlled Trial.

BACKGROUND: Transversus abdominis plane blocks improve postoperative pain after colon and rectal resections, but the benefits of liposomal bupivacaine use for these blocks have not been clearly demonstrated. OBJECTIVE: This study aimed to determine whether using liposomal bupivacaine in transversus abdominis plane blocks improves postoperative pain and reduces opioid use after colorectal surgery compared to standard bupivacaine. DESIGN: This study was a single-blinded, single-institution, prospective randomized controlled trial comparing liposomal bupivacaine to standard bupivacaine in transversus abdominis plane blocks in patients undergoing elective colon and rectal resections. SETTINGS: This study was conducted at a single-institution academic medical center with 6 staff colorectal surgeons and 2 colorectal surgery fellows. PATIENTS: Ninety-six patients aged 18 to 85 years were assessed for eligibility; 76 were included and randomly assigned to 2 groups of 38 patients. INTERVENTIONS: Patients in the experimental group received liposomal bupivacaine transversus abdominis plane blocks, whereas the control group received standard bupivacaine blocks. MAIN OUTCOME MEASURES: The primary outcome was maximum pain score on postoperative day 2. Secondary outcomes included daily maximum and average pain scores in the 3 days after surgery, as well as daily morphine milligram equivalent use and length of hospital stay. RESULTS: Patients receiving liposomal bupivacaine blocks had lower maximum pain scores on the day of surgery (mean, 6.5 vs 7.7; p = 0.008). No other difference was found between groups with respect to maximum or average pain scores at any time point postoperatively, nor was there any difference in morphine milligram equivalents used or length of stay (median, 3.1 d). LIMITATIONS: This was a single-institution study with only patients blinded to group assignment. CONCLUSIONS: Liposomal bupivacaine use in transversus abdominis plane blocks for patients undergoing laparoscopic colorectal resections does not seem to improve postoperative pain, nor does it reduce narcotic use or decrease length of stay. Given its cost, use of liposomal bupivacaine in transversus abdominis plane blocks is not justified for colon and rectal resections. See Video Abstract at http://links.lww.com/DCR/B979 . CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Identifier: NCT04781075. BLOQUEOS TAP DE BUPIVACANA LIPOSOMAL EN RESECCIONES COLORRECTALES LAPAROSCPICAS UN ENSAYO CONTROLADO ALEATORIO DE UNA SOLA INSTITUCIN: ANTECEDENTES:Los bloqueos del plano transverso del abdomen, mejoran el dolor posoperatorio después de las resecciones de colon y recto, pero los beneficios del uso de bupivacaína liposomal para estos bloqueos, no se han demostrado claramente.OBJETIVO:Investigar la eficacia de la inyección con tejido adiposo autólogo recién recolectado en fístulas anales criptoglandulares complejas.DISEÑO:Ensayo controlado, aleatorio, prospectivo, simple ciego, de una sola institución, que compara la bupivacaína liposomal con la bupivacaína estándar en bloqueos del plano transverso del abdomen, en pacientes sometidos a resecciones electivas de colon y recto. Identificador de ClinicalTrials.gov : NCT04781075.ENTORNO CLINICO:Centro médico académico de una sola institución con seis cirujanos de plantilla y becarios de cirugía colorrectal.PACIENTES:Se evaluó la elegibilidad de 96 pacientes de 18 a 85 años; 76 fueron incluidos y aleatorizados en dos grupos de 38 pacientes.INTERVENCIONES:Los pacientes del grupo experimental recibieron bloqueos del plano transverso del abdomen con bupivacaína liposomal, mientras que el grupo de control recibió bloqueos de bupivacaína estándar.PRINCIPALES MEDIDAS DE VALORACION:El resultado primario fue la puntuación máxima de dolor en el segundo día posoperatorio. Los resultados secundarios incluyeron las puntuaciones máximas y medias diarias de dolor en los 3 días posteriores a la cirugía, así como el uso diario equivalente en miligramos de morfina y la duración de la estancia hospitalaria.RESULTADOS:Los pacientes que recibieron bloqueos de bupivacaína liposomal, tuvieron puntuaciones máximas de dolor más bajas, el día de la cirugía (media 6,5 frente a 7,7, p = 0,008). No hubo ninguna otra diferencia entre los grupos con respecto a las puntuaciones de dolor máximas o promedio en cualquier momento después de la operación, ni hubo ninguna diferencia en los equivalentes de miligramos de morfina utilizados o la duración de la estancia (mediana de 3,1 días).LIMITACIONES:Estudio de una sola institución con cegamiento de un solo paciente.CONCLUSIONES:El uso de bupivacaína liposomal en bloqueos del plano transverso del abdomen, para pacientes sometidos a resecciones colorrectales laparoscópicas, no parece mejorar el dolor posoperatorio, ni reduce el uso de narcóticos ni la duración de la estancia hospitalaria. Dado su costo, el uso de bupivacaína liposomal en bloqueos TAP no está justificado para resecciones de colon y recto. Consulte Video Resumen en http://links.lww.com/DCR/B797 . Traducción Dr. Fidel Ruiz Healy.

A comparison of resting-state eyes-closed and dark-room alpha-band activity in children.

In a relaxed and awake state with the eyes closed, 8-12 Hz neural oscillations are the dominant rhythm, most prominent in parietal-occipital regions. Resting-state (RS) alpha is associated with processing speed and is also thought to be central to how networks process information. Unfortunately, the RS eyes-closed (EC) exam can only be used with individuals who can remain awake with their eyes closed for an extended period. As such, infants, toddlers, and individuals with intellectual disabilities are usually excluded from RS alpha studies. Previous research suggests obtaining RS alpha measures in a dark room with the eyes open as a viable alternative to the traditional RS EC exam. To further explore this, RS EC and RS dark room (DR) eyes-open alpha activity was recorded using magnetoencephalography in children with typical development (TD; N = 37) and children with autism spectrum disorder (ASD; N = 30) 6.9-12.6 years old. Findings showed good reliability for the RS EC and DR peak alpha frequency (frequency with strongest alpha power; interclass correlation (ICC) = 0.83). ICCs for posterior alpha power were slightly lower (ICCs in the 0.70 s), with an ~ 5% reduction in posterior alpha power in the DR than EC condition. No differences in the EC and DR associations were observed between the TD and ASD groups. Finally, age was associated with both EC and DR peak alpha frequency. Findings thus indicate the DR exam as a viable way to obtain RS alpha measures in populations frequently excluded from electrophysiology RS studies.

"Hey, I'm still here!": Maintaining, managing and rebuilding social connections after brain tumour.

It is well recognized that social networks can buffer the adverse effects of chronic illness on psychological wellbeing. However, the functional impairments associated with brain tumour often affect social participation, which may reduce people's capacity to draw upon their social capital for support. This qualitative phenomenological study aimed to understand how brain tumour influences people's ability to manage, maintain, and rebuild their social networks. Participants were 20 individuals (65% female) aged 22-69 years with diverse types of primary brain tumour (50% high grade or malignant) who were on average 35 months post-diagnosis. Two semi-structured interviews, conducted three months apart, comprised a Social Identity Mapping exercise and questions exploring changes in social groups since diagnosis. Two overarching and interrelated themes emerged: engaging and connecting and then versus now. An interplay of barriers, facilitators and strategies influenced people's ability to engage and connect with their social groups, which in turn influenced whether they experienced stability; maintenance and expansion; loss and rebuilding; or loss and shrinkage of their social networks over time. These novel findings highlight the need to develop interventions that specifically focus on enhancing individuals' abilities to maintain or rebuild their social networks.

Effectiveness of sensory modulation for people with schizophrenia: A multisite quantitative prospective cohort study.

INTRODUCTION: Current research evidence suggests that people with schizophrenia have sensory processing difficulties. Sensory modulation has growing evidence for use in this population. This study aimed to evaluate the extent to which health, social, cognitive, and occupational functioning outcomes were impacted by sensory modulation interventions for people with schizophrenia. METHODS: A prospective observational cohort study using a waitlist control design was used in two large hospital and health services in Queensland, Australia. The study recruited patients who used sensory modulation (n = 30) across the two hospitals and those who did not use sensory modulation interventions as a control (n = 11). Results were analysed using a series of planned comparisons including independent and paired t-tests, and mixed ANOVA was used whenever statistically indicated. The analysed measures were pre- and post-intervention scores. RESULTS: This study found no statically significant differences between the control and intervention groups at both pre- and post-intervention. However, analysis of results from within the intervention group showed statistically significant improvements between pre- and post-test scores on distress, occupational functioning, and health and social functioning but not on sensory processing and global cognitive processing. Further analysis of results from this study, compared with those from an earlier study on the general population showed significant differences in Low Registration and Sensation Avoiding, as measured by the Adult/Adolescent Sensory Profile, between participants with schizophrenia and those without schizophrenia. CONCLUSION: This study provides evidence to suggest that sensory modulation interventions can be complementary to standard care when utilised appropriately in clinical settings. Findings also suggest that the sensory profile of people with schizophrenia is different to that of the general population and this may have clinical implications. Further longitudinal research is needed with larger and randomised samples, using more targeted measures to better explore effectiveness of sensory modulation interventions.

A general protein O-glycosylation machinery conserved in Burkholderia species improves bacterial fitness and elicits glycan immunogenicity in humans.

The Burkholderia genus encompasses many Gram-negative bacteria living in the rhizosphere. Some Burkholderia species can cause life-threatening human infections, highlighting the need for clinical interventions targeting specific lipopolysaccharide proteins. Burkholderia cenocepacia O-linked protein glycosylation has been reported, but the chemical structure of the O-glycan and the machinery required for its biosynthesis are unknown and could reveal potential therapeutic targets. Here, using bioinformatics approaches, gene-knockout mutants, purified recombinant proteins, LC-MS-based analyses of O-glycans, and NMR-based structural analyses, we identified a B. cenocepacia O-glycosylation (ogc) gene cluster necessary for synthesis, assembly, and membrane translocation of a lipid-linked O-glycan, as well as its structure, which consists of a ß-Gal-(1,3)-α-GalNAc-(1,3)-ß-GalNAc trisaccharide. We demonstrate that the ogc cluster is conserved in the Burkholderia genus, and we confirm the production of glycoproteins with similar glycans in the Burkholderia species: B. thailandensis, B. gladioli, and B. pseudomallei Furthermore, we show that absence of protein O-glycosylation severely affects bacterial fitness and accelerates bacterial clearance in a Galleria mellonella larva infection model. Finally, our experiments revealed that patients infected with B. cenocepacia, Burkholderia multivorans, B. pseudomallei, or Burkholderia mallei develop O-glycan-specific antibodies. Together, these results highlight the importance of general protein O-glycosylation in the biology of the Burkholderia genus and its potential as a target for inhibition or immunotherapy approaches to control Burkholderia infections.

The Role of Bowel Preparation in Colorectal Surgery: Results of the 2012-2015 ACS-NSQIP Data.

OBJECTIVE: To analyze potential benefits with regards to infectious complications with combined use of mechanical bowel preparation (MBP) and ABP in elective colorectal resections. BACKGROUND: Despite recent literature suggesting that MBP does not reduce infection rate, it still is commonly used. The use of oral antibiotic bowel preparation (ABP) has been practiced for decades but its use is also controversial. METHODS: Patients undergoing elective colorectal resection in the 2012 to 2015 American College of Surgeons National Surgical Quality Improvement Program cohorts were selected. Doubly robust propensity score-adjusted multivariable regression was conducted for infectious and other postoperative complications. RESULTS: A total of 27,804 subjects were analyzed; 5471 (23.46%) received no preparation, 7617 (32.67%) received MBP only, 1374 (5.89%) received ABP only, and 8855 (37.98%) received both preparations. Compared to patients receiving no preparation, those receiving dual preparation had less surgical site infection (SSI) [odds ratio (OR) = 0.39, P < 0.001], organ space infection (OR = 0.56, P ≤ 0.001), wound dehiscence (OR = 0.43, P = 0.001), and anastomotic leak (OR = 0.53, P < 0.001). ABP alone compared to no prep resulted in significantly lower rates of surgical site infection (OR = 0.63, P = 0.001), organ space infection (OR = 0.59, P = 0.005), anastomotic leak (OR = 0.53, P = 0.002). MBP showed no significant benefit to infectious complications when used as monotherapy. CONCLUSIONS: Combined MBP/ABP results in significantly lower rates of SSI, organ space infection, wound dehiscence, and anastomotic leak than no preparation and a lower rate of SSI than ABP alone. Combined bowel preparation significantly reduces the rates of infectious complications in colon and rectal procedures without increased risk of Clostridium difficile infection. For patients undergoing elective colon or rectal resection we recommend bowel preparation with both mechanical agents and oral antibiotics whenever feasible.

Abnormal maturation of the resting-state peak alpha frequency in children with autism spectrum disorder.

Age-related changes in resting-state (RS) neural rhythms in typically developing children (TDC) but not children with autism spectrum disorder (ASD) suggest that RS measures may be of clinical use in ASD only for certain ages. The study examined this issue via assessing RS peak alpha frequency (PAF), a measure previous studies, have indicated as abnormal in ASD. RS magnetoencephalographic (MEG) data were obtained from 141 TDC (6.13-17.70 years) and 204 ASD (6.07-17.93 years). A source model with 15 regional sources projected the raw MEG surface data into brain source space. PAF was identified in each participant from the source showing the largest amplitude alpha activity (7-13 Hz). Given sex differences in PAF in TDC (females > males) and relatively few females in both groups, group comparisons were conducted examining only male TDC (N = 121) and ASD (N = 183). Regressions showed significant group slope differences, with an age-related increase in PAF in TDC (R2 = 0.32) but not ASD (R2 = 0.01). Analyses examining male children below or above 10-years-old (median split) indicated group effects only in the younger TDC (8.90 Hz) and ASD (9.84 Hz; Cohen's d = 1.05). In the older ASD, a higher nonverbal IQ was associated with a higher PAF. In the younger TDC, a faster speed of processing was associated with a higher PAF. PAF as a marker for ASD depends on age, with a RS alpha marker of more interest in younger versus older children with ASD. Associations between PAF and cognitive ability were also found to be age and group specific.

Adaptations to cognitive problems reported by breast cancer survivors seeking cognitive rehabilitation: A qualitative study.

OBJECTIVE: Qualitative studies have elucidated cancer survivors' experiences of cognitive changes associated with cancer and cancer treatment. This study specifically explored experiences of women treated for breast cancer who were seeking cognitive rehabilitation. The objective was to characterise the frequency and nature of cognitive changes and adaptations to cognitive change reported by these participants to better understand treatment needs of this group. METHOD: Australian women who had completed primary treatments for breast cancer (surgery, chemotherapy, and/or radiotherapy) and volunteered to participate in one of two cognitive rehabilitation intervention studies were interviewed via telephone. Interview responses regarding cognitive changes and adaptations to cognitive change were transcribed by the interviewers, then coded and analysed by two researchers using content analysis. RESULTS: Among the 95 participants (age M=54.3 years, SD=9.6), the most commonly reported cognitive change was memory (79% of participants) and 61% reported more than one type of cognitive change. Adaptations to change were reported by 87% of participants, with written or electronic cues the most common (51%). Most often, participants reported using a single type of adaptation (48%) with only 39% reporting multiple types of adaptations. CONCLUSIONS: Women treated for breast cancer, who were seeking cognitive rehabilitation, most commonly reported memory changes, which were mainly managed through a single type of adaptation. These results suggest that there is considerable scope for increasing the range of cognitive adaptations to improve the quality of life of cancer survivors who experience adverse cognitive changes.

Emerging Gram-negative bacteria: pathogenic or innocent bystanders.

PURPOSE OF REVIEW: The current review examines the current literature around 'emerging' Gram-negative bacteria other than Pseudomonas aeruginosa in cystic fibrosis (CF), paying particular focus on the recent literature for those that are more frequently encountered: Pandoraea, Achromobacter, Ralstonia and Stenotrophomonas species. RECENT FINDINGS: The recent literature is evolving our understanding of the clinical consequences of infection with an 'emerging' Gram-negative bacteria in CF. There is an increase in reported prevalence for many species. They are commonly isolated from patients who already have low baseline lung function. Initial infection can lead to chronic carriage, often with evidence of an associated host immune response and subsequent clinical deterioration. For some species occasional cases of bacteraemia have been reported. SUMMARY: There are a number of Gram-negative organisms, other than P. aeruginosa, that can cause chronic infection in patients with CF. There is data to suggest that some of these so-called emerging Gram-negative bacteria are increasing in prevalence and can be pathogenic in patients with CF. The prevalence and clinical consequences however differ from species to species. There is a pressing need to agree a definition of chronic infection for these organisms to compare data between studies.

Web-based cognitive rehabilitation for survivors of adult cancer: A randomised controlled trial.

OBJECTIVE: Cognitive dysfunction associated with cancer is frequently reported and can reduce quality of life. This study evaluated a Web-based cognitive rehabilitation therapy program (eReCog) in cancer survivors compared with a waitlist control group. METHODS: Adult cancer survivors with self-reported cognitive symptoms who had completed primary treatment at least 6 months prior were recruited. Participants completed telephone screening and were randomly allocated to the 4-week online intervention or waitlist. Primary outcome was perceived cognitive impairment assessed with the Functional Assessment of Cancer Therapy-Cognitive Function version 3. Secondary outcomes were additional measures of subjective cognitive functioning, objective cognitive functioning, and psychosocial variables. RESULTS: Seventy-six women were allocated to the intervention (n = 40) or waitlist (n = 36). A significant interaction was found on the instrumental activities of daily living measure of self-reported prospective memory whereby the intervention group reported a greater reduction in prospective memory failures than the waitlist group. Interaction trends were noted on perceived cognitive impairments (P = .089) and executive functioning (P = .074). No significant interactions were observed on other measures of objective cognitive functioning or psychosocial variables. CONCLUSIONS: The Web-based intervention shows promise for improving self-reported cognitive functioning in adult cancer survivors. Further research is warranted to better understand the mechanisms by which the intervention might contribute to improved self-reported cognition.

Morbidity Following Coloanal Anastomosis: A Comparison of Colonic J-Pouch vs Straight Anastomosis.

BACKGROUND: Low rectal tumors are often treated with sphincter-preserving resection followed by coloanal anastomosis. OBJECTIVE: The purpose of this study was to compare the short-term complications following straight coloanal anastomosis vs colonic J-pouch anal anastomosis. DESIGN: Patients were identified who underwent proctectomy for rectal neoplasia followed by coloanal anastomosis in the 2008 to 2013 American College of Surgeons National Surgical Quality Improvement Program database. Demographic characteristics and 30-day postoperative complications were compared between groups. SETTINGS: A national sample was extracted from the American College of Surgeons National Surgical Quality Improvement Project database. PATIENTS: Inpatients following proctectomy and coloanal anastomosis for rectal cancer were selected. MAIN OUTCOME MEASURES: Demographic characteristics and 30-day postoperative complications were compared between the 2 groups. RESULTS: One thousand three hundred seventy patients were included, 624 in the straight anastomosis group and 746 in the colonic J-pouch group. Preoperative characteristics were similar between groups, with the exception of preoperative radiation therapy (straight anastomosis 35% vs colonic J-pouch 48%, p = 0.0004). Univariate analysis demonstrated that deep surgical site infection (3.7% vs 1.4%, p = 0.01), septic shock (2.25% vs 0.8%, p = 0.04), and return to the operating room (8.8% vs 5.0%, p = 0.0006) were more frequent in the straight anastomosis group vs the colonic J-pouch group. Major complications were also higher (23% vs 14%, p = 0.0001) and length of stay was longer in the straight anastomosis group vs the colonic J-pouch group (8.9 days vs 8.1 days, p = 0.02). After adjusting for covariates, major complications were less following colonic J-pouch vs straight anastomosis (OR, 0.57; CI, 0.38-0.84; p = 0.005). Subgroup analysis of patients who received preoperative radiation therapy demonstrated no difference in major complications between groups. LIMITATIONS: This study had those limitations inherent to a retrospective study using an inpatient database. CONCLUSION: Postoperative complications were less following colonic J-pouch anastomosis vs straight anastomosis. Patients who received preoperative radiation had similar rates of complications, regardless of the reconstructive technique used following low anterior resection. See Video Abstract at http://links.lww.com/DCR/A468.

Clopidogrel bisulfate (Plavix) does not increase bleeding complications in patients undergoing rubber band ligation for symptomatic hemorrhoids.

BACKGROUND: The incidence of postprocedural bleeding in patients undergoing rubber band ligation (RBL) for symptomatic internal hemorrhoids while taking clopidogrel bisulfate is unknown. To determine the postprocedural bleeding risk of RBL for patients taking clopidogrel compared with age- and sex-matched controls. MATERIALS AND METHODS: This is a retrospective case-controlled cohort study analyzing data from 2005 to 2013 conducted at a single tertiary care academic center. The study included a total of 80 rubber bands placed on 41 patients taking clopidogrel bisulfate and 72 bands placed on 41 control patients not taking clopidogrel matched for age and sex. The 30-d rates of significant and insignificant bleeding events after RBL were recorded. A bleeding event was considered significant if the patient required admission to the hospital, transfusion of blood products, or additional procedures to stop the bleeding. Insignificant bleeding was defined as passage of blood or clots per rectum with spontaneous cessation and no need for additional intervention. RESULTS: There was no significant difference in the number of bleeding events per band placed in the clopidogrel group when compared with the control group (3.75% versus 2.78%, P = 0.7387). The rate of significant (2.5% versus 1.39%, P = 0.6244) and insignificant bleeding events (1.25% versus 1.39%, P = 0.9399) was also similar between the two groups. Two significant bleeding events occurred in the clopidogrel group requiring intervention: cauterization in one patient and colonoscopy and transfusion in the other. CONCLUSIONS: The risk of a bleeding complication after RBL for hemorrhoids does not appear to be increased in patients taking clopidogrel. Our results support the practice of continuing clopidogrel bisulfate in the periprocedural period as the associated risk of thrombosis is greater than the risk of bleeding.

The implementation of web-based cognitive rehabilitation in adult cancer survivors: examining participant engagement, attrition and treatment fidelity.

PURPOSE: Low engagement and high attrition are common challenges in web-based interventions. Typical measures of engagement reported in the literature are not meaningful for describing participant activity within the intervention and can be misleading. This research aimed to develop a more meaningful method of measuring engagement in an online cognitive rehabilitation program whilst monitoring treatment fidelity. METHODS: A pilot study and randomised controlled trial (RCT) were conducted. Data from 60 participants were analysed from three intervention groups: pilot cancer group, pilot non-cancer group and RCT cancer group. Groups completed the 4-week eReCog program comprised of four online modules. Engagement scores were calculated based on activities completed in each module. Attrition, interaction with the program facilitator and correlations with outcome measures were analysed. RESULTS: Overall engagement in the intervention was high. The non-cancer group participated significantly less than the cancer groups (p = < 0.001), whereby the percentage of activity items completed was 92, 87 and 78% in the pilot cancer, RCT cancer and pilot non-cancer groups, respectively. Attrition was higher in the pilot non-cancer group (24%) compared to the pilot cancer group (8%) and the RCT cancer group (16%). Total engagement was correlated with fewer prospective memory problems on instrumental activities of daily living (p = 0.018). CONCLUSIONS: Measuring completed activities in online interventions appears a more meaningful measure of engagement than other conventional methods described in the literature and has the potential to increase treatment fidelity in web-based research.

The critical roles of tumor-initiating cells and the lymph node stromal microenvironment in human colorectal cancer extranodal metastasis using a unique humanized orthotopic mouse model.

Colorectal cancer (CRC) is the second-most common cause of cancer-related mortality. The most important prognostic factors are lymph node (LN) involvement and extranodal metastasis. Our objective is to investigate the interactions between CD133(+)CXCR4(+) (CXC receptor 4) colorectal cancer tumor-initiating cells (Co-TICs) and the LN stromal microenvironment in human CRC extranodal metastasis. We established a unique humanized orthotopic xenograft model. Luciferase-tagged CRC cell lines and human cancer cells were injected intrarectally into nonobese diabetic/SCID mice. Mesenteric LN stromal cells, stromal cell line HK, or CXCL12 knockdown HK (HK-KD-A3) cells were coinoculated with CRC cells. Tumor growth and metastasis were monitored by bioluminescent imaging and immunohistochemistry. We found that this model mimics the human CRC metastatic pattern with CRC cell lines or patient specimens. Adding LN stromal cells promotes CRC tumor growth and extranodal metastasis (P < 0.001). Knocking down CXCL12 impaired HK cell support of CRC tumor formation and extranodal metastasis. When HK cells were added, sorted CD133(+)CXCR4(+) Co-TICs showed increased tumor formation and extranodal metastasis capacities compared to unseparated and non-Co-TIC populations. In conclusion, both Co-TIC and LN stromal factors play crucial roles in CRC metastasis through the CXCL12/CXCR4 axis. Blocking Co-TIC/LN-stromal interactions may lead to effective therapy to prevent extranodal metastasis.

Anabolic agent use in adults with cystic fibrosis.

The use of non-prescribed anabolic agents amongst non-athletes is increasing with young, adult males with cystic fibrosis (CF) in the highest risk demographic. There is evidence that anabolic agents increase weight and muscle mass in adults with a variety of catabolic conditions but there is no evidence for their use in hormone sufficient adults with CF. We report a case of anabolic agent use in a male adult with CF and review the clinical features of anabolic agent use with a focus on adults with CF.

The microbiome and emerging pathogens in cystic fibrosis and non-cystic fibrosis bronchiectasis.

Chronic pulmonary sepsis is the predominant cause of morbidity for patients with cystic fibrosis (CF) and non-CF bronchiectasis. Previously it was thought that respiratory infection in these patients was mostly limited to a very small number of typical pathogens; however, in recent years there have been increasing reports of infection with other emerging potential pathogens including Burkholderia, Stenotrophomonas, Achromobacter, Ralstonia, Pandoraea, nontuberculous mycobacteria, and fungal species. Furthermore, culture-independent methodologies have established that the lungs of patients with CF and non-CF bronchiectasis comprise mixed microbiological communities of aerobic and anaerobic bacteria, fungal and viral species, collectively referred to as the lung microbiome. This article addresses the clinical relevance of emerging pathogens and the lung microbiome in CF and non-CF bronchiectasis.

Convergence of the transcriptional responses to heat shock and singlet oxygen stresses.

Cells often mount transcriptional responses and activate specific sets of genes in response to stress-inducing signals such as heat or reactive oxygen species. Transcription factors in the RpoH family of bacterial alternative σ factors usually control gene expression during a heat shock response. Interestingly, several α-proteobacteria possess two or more paralogs of RpoH, suggesting some functional distinction. We investigated the target promoters of Rhodobacter sphaeroides RpoH(I) and RpoH(II) using genome-scale data derived from gene expression profiling and the direct interactions of each protein with DNA in vivo. We found that the RpoH(I) and RpoH(II) regulons have both distinct and overlapping gene sets. We predicted DNA sequence elements that dictate promoter recognition specificity by each RpoH paralog. We found that several bases in the highly conserved TTG in the -35 element are important for activity with both RpoH homologs; that the T-9 position, which is over-represented in the RpoH(I) promoter sequence logo, is critical for RpoH(I)-dependent transcription; and that several bases in the predicted -10 element were important for activity with either RpoH(II) or both RpoH homologs. Genes that are transcribed by both RpoH(I) and RpoH(II) are predicted to encode for functions involved in general cell maintenance. The functions specific to the RpoH(I) regulon are associated with a classic heat shock response, while those specific to RpoH(II) are associated with the response to the reactive oxygen species, singlet oxygen. We propose that a gene duplication event followed by changes in promoter recognition by RpoH(I) and RpoH(II) allowed convergence of the transcriptional responses to heat and singlet oxygen stress in R. sphaeroides and possibly other bacteria.

Development of a brief measure of generativity and ego-integrity for use in palliative care settings.

OBJECTIVE: Our aim was to develop and test a brief measure of generativity and ego-integrity that is suitable for use in palliative care settings. METHOD: Two measures of generativity and ego-integrity were modified and combined to create a new 11-item questionnaire, which was then administered to 143 adults. A principal-component analysis with oblique rotation was performed in order to identify underlying components that can best account for variation in the 11 questionnaire items. RESULTS: The two-component solution was consistent with the items that, on conceptual grounds, were intended to comprise the two constructs assessed by the questionnaire. SIGNIFICANCE OF RESULTS: Results suggest that the selected 11 items were good representatives of the larger scales from which they were selected, and they are expected to provide a useful means of measuring these concepts near the end of life.