Neuronal Inactivity Co-opts LTP Machinery to Drive Potassium Channel Splicing and Homeostatic Spike Widening.

Homeostasis of neural firing properties is important in stabilizing neuronal circuitry, but how such plasticity might depend on alternative splicing is not known. Here we report that chronic inactivity homeostatically increases action potential duration by changing alternative splicing of BK channels; this requires nuclear export of the splicing factor Nova-2. Inactivity and Nova-2 relocation were connected by a novel synapto-nuclear signaling pathway that surprisingly invoked mechanisms akin to Hebbian plasticity: Ca2+-permeable AMPA receptor upregulation, L-type Ca2+ channel activation, enhanced spine Ca2+ transients, nuclear translocation of a CaM shuttle, and nuclear CaMKIV activation. These findings not only uncover commonalities between homeostatic and Hebbian plasticity but also connect homeostatic regulation of synaptic transmission and neuronal excitability. The signaling cascade provides a full-loop mechanism for a classic autoregulatory feedback loop proposed ∼25 years ago. Each element of the loop has been implicated previously in neuropsychiatric disease.

Swallowing outcomes after transoral robotic surgery and adjuvant treatment in unknown primary.

OBJECTIVES: Robotic transoral mucosectomy of the base of tongue was introduced as a diagnostic procedure in patients treated for head and neck cancer with unknown primary (CUP), increasing the identification rate of the primary tumour. For the treatment of CUP, a considerable percentage of patients require adjuvant (chemo)radiation. The aim of this study was to investigate swallowing outcomes among CUP patients after TORS and adjuvant treatment. SUBJECTS AND METHODS: A systematic review was carried out on studies investigating the impact of TORS and adjuvant treatment on swallowing-related outcomes among CUP patients In addition, a cross-sectional study was carried out on swallowing problems (measured using the SWAL-QOL questionnaire) among CUP patients in routine care who visited the outpatient clinic 1-5 years after TORS and adjuvant treatment. RESULTS: The systematic review (6 studies; n = 98) showed that most patients returned to a full oral diet. The cross-sectional study (n = 12) showed that all patients were able to return to a full oral diet, nevertheless, 50% reported swallowing problems in daily life (SWAL-QOL total score ≥14). CONCLUSION: Although after TORS and adjuvant treatment for CUP a full oral diet can be resumed, patients still experience problems with eating and drinking in daily life.

Are severity and location of facial trauma risk factors for cervical spine injuries? 10-year analysis based on the use of the AO spine injury classification and the comprehensive facial injury (CFI) score.

PURPOSE: This study aims to demonstrate a correlation between cervical spine injury and location and severity of facial trauma. METHODS: We did a 10-year retrospective analysis of prospectively collected patients with at least one facial and/or cervical spine injury. We classified facial injuries using the Comprehensive Facial Injury (CFI) score, and stratified patients into mild (CFI < 4), moderate (4 ≤ CFI < 10) and severe facial trauma (CFI ≥ 10). The primary outcome was to recognize the severity and topography of the facial trauma which predict the probability of associated cervical spine injuries. RESULTS: We included 1197 patients: 78% with facial injuries, 16% with spine injuries and 6% with both. According to the CFI score, 48% of patients sustained a mild facial trauma, 35% a moderate one and 17% a severe one. The midface was involved in 45% of cases, then the upper facial third (13%) and the lower one (10%). The multivariate analysis showed multiple independent risk factors for associated facial and cervical spine injuries, among them an injury of the middle facial third (OR 1.11 p 0.004) and the facial trauma severity, having every increasing point of CFI score a 6% increasing risk (OR 1.06 p 0.004). CONCLUSIONS: Facial trauma is a risk factor for a concomitant cervical spine injury. Among multiple risk factors, severe midfacial trauma is an important red flag. The stratification of facial injuries based on the CFI score through CT-scan images could be a turning point in the management of patients at risk for cervical spine injuries before imaging is available.

Phenotypic and genetic relationships among anogenital distance, anti-Müllerian hormone, and in vitro embryo production in Gyr dairy cattle.

Anti-Müllerian hormone (AMH) concentration and number of recovered oocytes (ROOC) are phenotypic parameters associated with in vitro embryo production (IVEP). More recently, anogenital distance (AGD) has been proposed as a proxy for fertility in dairy cattle that is easy to collect at a low cost. The aim of this study was to characterize the AGD and its phenotypic and genetic associations with AMH and IVEP in Bos indicus Gyr dairy cattle. The hypothesis was that the number of ROOC, in vitro-produced embryos, and AMH concentration would increase as the AGD decreases. From July to December 2021, a single morphometrical measurement of AGD was collected in 552 donors from 6 herds in Brazil. A subset of donors had AMH assayed on the same day. Only ovum pick-up events that occurred up to 12 mo preceding and 7 mo succeeding the AGD measurement were used to assess the association between AGD, AMH, and IVEP. Thus, 472 donors (1,551 ovum pick-up events and 140 donors with AMH) were considered in the analysis. A raw average was calculated for each individual donor's ROOC, viable oocytes, total produced embryos, viability rate, and embryo rate (defined as total produced embryos/viable oocytes). Comparisons were conducted within the age categories of 3 to <6 yr or 6 to <10 yr. Phenotypic associations were performed in SAS software (SAS Institute Inc., Cary, NC). Genetic correlations were estimated using the BLUPF90 family of programs. The AGD (128.7 mm ± 14; mean ± standard deviation) had a normal distribution and was highly variable (83 to 172 mm) among the Gyr population. Our experimental hypothesis was partially supported by a phenotypic association of a greater number of total produced embryos (R2 = 0.023) as AGD decreased. Our results failed to support an increase in AMH concentration along with a decrease in AGD. In addition, positive and low genetic correlations were observed between AGD and viable oocytes (r = 0.08), and embryo rate (r = 0.20). A greater number of viable oocytes and embryos were observed in donors in the high compared with intermediate and low ROOC categories within both age categories. The age interval of 3 to <6 yr showed a greater number of recovered and viable oocytes for the high AMH compared with the low category, but no differences were observed among the AGD categories. In summary, for the Gyr breed, AGD was phenotypically inversely associated with a quantity-related parameter, such as the total number of produced embryos. In contrast, AGD showed a low genetic correlation with qualitative-related outcomes such as viable oocytes and embryo rate. Further studies should be performed to validate these retrospective analyses and to better understand the association between AGD and IVEP.

Genetic parameters for oocytes and embryo production and their association with linear type traits in dairy Gyr Cattle.

In vitro embryo production is one of the main reproductive techniques used in dairy Gyr cattle. In addition, linear type measures are well characterized and have been used in dairy Gyr breed selection for the last 4 decades. The estimation of genetic parameters for the number of aspirated oocytes and in vitro-produced embryos associated with the linear type measures would support genetic progress for animal breeding programs toward embryo production. This study aimed to estimate genetic parameters for aspirated oocytes, embryo in vitro production, and linear type traits, exploring the association between them. The repeatability model was applied to 14,251 ovum pick-up events from 1,916 Gyr donors. A subset of 604 donors from the same group had their body measurements taken. Single- and 2-trait analyses were carried out using the BLUPF90 family programs. Heritability estimates of 0.38, 0.34, and 0.20 were obtained for total oocytes, viable oocytes, and embryos, respectively,-and the heritability of the linear type traits ranged from 0.22 to 0.40. High genetic correlations between total oocytes and viable oocytes (0.99), and between oocytes (total and viable) and embryos (0.83) were obtained. Low to high genetic (-0.07 to 0.92) and phenotypic (0.32 to 0.86) correlations were obtained between the linear type traits. Moreover, low phenotypic correlations (0.01 to 0.13) were observed for oocytes (total and viable) and embryos with the linear type traits, whereas low to moderate genetic correlations (0.07 to 0.42) were observed between the same traits, especially for ilium width (0.42), rump area (0.38), and hip height (0.33). Thus, selection for in vitro production is achievable in Gyr dairy cattle, and superior genetic progress is associated with the selection of oocytes (total and viable). Furthermore, the moderate genetic association between oocytes and embryos with linear type traits, especially ilium width suggests that progress on in vitro embryo production may be achieved by accessing these measurements.

Impact of the COVID-19 pandemic on women's perinatal mental health and its association with personality traits: An observational study.

INTRODUCTION: The burden of perinatal mental health problems was expected to increase during the COVID-19 pandemic. We prospectively investigated the impact of the COVID-19 pandemic on the mental health of pregnant and postpartum women in Norway and explored associations with their sociodemographic characteristics and personality traits. MATERIAL AND METHODS: Sociodemographic information and the self-reported impact of pandemic on wellbeing of pregnant women was collected using an online survey. To assess women's mental health, two validated questionnaires, the Edinburgh Postpartum Depression Scale (EPDS) and the Generalized Anxiety Disorder-7 item Scale (GAD-7), were used prenatally and postnatally. Personality traits were evaluated using HumanGuide, a web-based ipsative psychological evaluation instrument. RESULTS: 772 women were included prenatally, of which 526 also responded to the survey 4-6 weeks postnatally. The median age was 29 years, 53.6% of the women were nulliparous when enrolled, and 35.1% worked in the healthcare sector. The median EPDS (6.0; interquartile range [IQR] 3.0-10.0 vs 6.0; IQR: 3.0-10.0) and the median GAD-7 (5.0; IQR 2.0-9.0 vs 5.0; IQR 2.0-9.0) were similar pre-and postnatally. Prenatally, the proportion of women scoring ≥13 on EPDS and ≥10 on GAD-7 was 14.5% (112/772) and 21.5% (166/772), whereas the postnatal figures were 15.6% (82/526) and 21.5% (113/526), respectively. The differences were not significant (P = 0.59 and P = 0.99). Being <25 years of age, being on pre-pregnancy psychotherapy or psychotropic medication, frequent voluntary isolation, perception of maternity care not proceeding normally, avoiding seeking medical assistance due to fear of infection and having negative economic consequences during the COVID19 pandemic significantly increased the risk of both anxiety (GAD-7 ≥10) and depression (EPDS ≥13). Nullipara had a higher risk of anxiety, whereas being a healthcare worker had a lower risk. The personality trait factors Power (P = 0.008), Quality (P = 0.008), Stability (P < 0.001) and Contacts (P < 0.001) were significant predictors of depression among pregnant women, whereas the Quality (P = 0.005) and Contacts (P = 0.003) were significant predictors of anxiety. CONCLUSIONS: During the initial phase of the COVID-19 pandemic, the prevalence of depression (EPDS ≥ 13) and anxiety (GAD-7 ≥ 10) was 14.5% and 21.5%, respectively, among Norwegian pregnant women. Certain sociodemographic characteristics and personality traits were significant predictors of depression and anxiety.

Implications of differences between point-of-care blood gas analyser and laboratory analyser potassium results on hyperkalaemia diagnosis & treatment.

BACKGROUND: Hyperkalaemia is managed in the emergency department (ED) following measurement of potassium results by blood gas analysers (BGA) or laboratory analysers (LAB). AIMS: To determine the prevalence of clinically significant differences between BGA and LAB potassium results and the impact on ED hyperkalaemia management. METHODS: Retrospective analysis of time-matched ED BGA and LAB potassium samples from 2019 to 2020 (taken within 15 min, one or both results ≥6.0 mmol/L). Mean differences and 95% limits of agreement (LoA) were determined for pairs with one or both results ≥6.0 mmol/L and a separate 500 consecutive sample pairs. RESULTS: Four hundred eighty-eight matched BGA and LAB samples met the inclusion criteria. Of these, 201 (41.2%) differed by ≤0.5 mmol/L, 169 (34.6%) included a haemolysed LAB sample, and 12 (2.5%) had an unreportable BGA sample. One hundred six (21.7%) pairs differed by >0.5 mmol/L, and 60/106 (57%) had normal LAB potassium results, but BGA indicated moderate/severe hyperkalaemia (two of these pairs received hyperkalaemia treatment). Of patients with a haemolysed LAB sample, or where pairs differed by >0.5 mmol, 48 were treated with insulin and five (10.4%) experienced hypoglycaemia. Mean differences and LoA for pairs with LAB results <6.0 mmol/L but BGA ≥6.0 mmol/L demonstrated unacceptable agreement, with 18 (25.7%) BGA results exceeding 8.0 mmol/L. CONCLUSIONS: Potentially significant discordance may occur between BGA and LAB potassium results. Clinicians need to be aware of factors impacting both analytical methods' accuracy (such as poor venepuncture or sample handling, (K) EDTA interference) and undetectable haemolysis with BGA measurements. We recommend BGA hyperkalaemia be confirmed with LAB results using a non-haemolysed sample where time permits.

Accuracy of medication histories derived from an Australian cloud-based repository of prescribed and dispensed medication records.

BACKGROUND: Obtaining accurate medication histories at transitions of care is challenging, but important for patient safety. Prescription exchange services (PES) securely transfer electronic prescription and dispensing records between prescribers and pharmacies, which is potentially useful data for determining medication histories. AIM: To evaluate the accuracy of PES-derived medication histories. METHODS: Prospective observational study, at two Australian tertiary-referral health services. A convenience sample of adult inpatients was recruited. The main outcome measure was: proportion of patients with ≥1 errors in their PES-derived pre-admission medication histories, compared with gold-standard best-possible medication histories, including prescribed and non-prescribed medications, obtained by pharmacists using multiple sources including patient/carer interview. RESULTS: Of 154 patients (median age 76 years; interquartile range (IQR) 64-84 years; median 10.0 pre-admission medications; IQR 6.0-14.0), 153 (99.4%) had ≥1 errors in their PES-derived medication history (median 6.0 errors per patient; IQR 4.0-9.0). Excluding when-required medications, 146 (94.8%) patients had >1 errors (median 4.0 errors per patient; IQR 2.0-6.0). Omission was the most common error, affecting 549 (33.3%) of 1648 current medications (median 3.0; IQR 1.0-5.0 per patient); 396 (72.1%) omissions were over-the-counter medicines. Dose-regimen errors affected 276 (25.1%) of 1099 current medications captured in PES-derived medication histories (median 1.0 error per patient; IQR 0.0-3.0). Commission errors (medications in PES-derived histories that were not current) affected 224 (16.9%) of 1323 medications (median 1.0 error per patient; IQR 1.0-2.0). CONCLUSIONS: Medication histories derived solely from a cloud-based medication record repository had a high error rate compared with patients' actual medication use. Like all medication history sources, data from cloud-based repositories need to be verified with additional sources including the patient and/or their carer.

Long-term reproductive effects in male rats prenatally exposed to sodium arsenite.

Arsenic is an environmental toxicant known to be a carcinogen and endocrine disruptor. Maternal exposure to arsenic has been associated with fetus malformation and reproductive disorders in male offspring. However, it is unclear the extent to which those effects remain during postnatal development and adulthood. Therefore, this study aimed to investigate the long-term effects of prenatal arsenic exposure on reproductive parameters of male offspring at peripubertal and adult periods. Pregnant female Wistar rats were exposed to 0 or 10 mg/L sodium arsenite in drinking water from gestational day 1 (GD 1) until GD 21 and male pups were analyzed at postnatal day 44 (PND 44) and PND 70. We observed that some reproductive parameters were affected differently by arsenic exposure at each age evaluated. The body and reproductive organs weights, as well as testicular and epididymal morphology were strongly affected in peripubertal animals and recovered at adult period. On the other hand, the antioxidant genes expression (SOD1, SOD2, CAT and GSTK1) and the endogenous antioxidant system were affected in the testes and epididymides from both peripubertal and adult rats. Finally, an impairment in daily sperm production and in sperm parameters was observed in adult animals. Taken together, our findings show that prenatal arsenic exposure affected reproductive parameters of peripubertal and adult male rats mainly due to oxidative stress. Collectively, those alterations may be affecting fertility potential of adult animals.

Antigenic Architecture of the H7N2 Influenza Virus Hemagglutinin Belonging to the North American Lineage.

The North American low pathogenic H7N2 avian influenza A viruses, which lack the 220-loop in the hemagglutinin (HA), possess dual receptor specificity for avian- and human-like receptors. The purpose of this work was to determine which amino acid substitutions in HA affect viral antigenic and phenotypic properties that may be important for virus evolution. By obtaining escape mutants under the immune pressure of treatment with monoclonal antibodies, antigenically important amino acids were determined to be at positions 125, 135, 157, 160, 198, 200, and 275 (H3 numbering). These positions, except 125 and 275, surround the receptor binding site. The substitutions A135S and A135T led to the appearance of an N-glycosylation site at 133N, which reduced affinity for the avian-like receptor analog and weakened binding with tested monoclonal antibodies. Additionally, the A135S substitution is associated with the adaptation of avian viruses to mammals (cat, human, or mouse). The mutation A160V decreased virulence in mice and increased affinity for the human-type receptor analog. Conversely, substitution G198E, in combination with 157N or 160E, displayed reduced affinity for the human-type receptor analog.

Non-Surgical Respiratory Management in Relation to Feeding and Growth in Patients with Robin Sequence; a Prospective Longitudinal Study.

OBJECTIVE: To reflect upon our non-surgical respiratory management by evaluating clinical outcomes regarding airway, feeding, and growth during the first year of life in patients with Robin Sequence. DESIGN: Prospective study. SETTING: Sophia Children's Hospital, Rotterdam, the Netherlands. PATIENTS/ PARTICIPANTS: 36 patients with Robin Sequence who were treated between 2011 and 2021. INTERVENTIONS: Positional therapy and respiratory support. MAIN OUTCOME MEASURE(S): Data on respiratory outcomes included polysomnography characteristics and capillary blood gas values. Feeding outcomes were based on the requirement of additional tube feeding. Outcomes on growth were expressed as standard-deviation-scores (SDS) for weight-for-age (WFA) and height-for-age (HFA). RESULTS: Twenty patients were treated with positional therapy (PT), whilst the other 16 patients required respiratory support. Twenty-two patients presented with non-isolated Robin Sequence (RS). During the first year of life, obstructive apnea hypopnea index decreased, oxygen levels enhanced, and capillary blood gas values improved. Eighty-six percent (31/36) experienced feeding difficulties, which completely resolved in 71% (22/31) during their first year of life. From start treatment, to stop treatment, to the age of 1 year, the SDS WFA worsened from -0.40 to -0.33 to -1.03, respectively. CONCLUSIONS: Non-surgical respiratory treatment resulted in an improvement of respiratory outcomes to near normal during the first year of life in patients with RS. These patients often experience feeding difficulties and endure impaired weight gain up to 1 year of age, despite near normalization of breathing. The high prevalence of feeding difficulties and impaired weight for age indicate the urgency for early recognition and adequate treatment to support optimal growth.

Pleiotropic Effects of Influenza H1, H3, and B Baloxavir-Resistant Substitutions on Replication, Sensitivity to Baloxavir, and Interferon Expression.

Baloxavir is an anti-influenza endonuclease inhibitor that targets the polymerase acidic (PA) protein of influenza A and B viruses. Our knowledge regarding the pleiotropic effects of baloxavir resistance-associated substitutions is limited. We generated recombinant A/California/04/09 (H1N1)-, A/Hong Kong/218849/2006 (H3N2)-, and B/Victoria/504/2000-like viruses that contained PA substitutions identified in baloxavir clinical trials and surveillance that could potentially be associated with baloxavir resistance. We characterized their susceptibility to baloxavir, impact on polymerase activity, viral growth, and ability to induce interferon (IFN) and IFN-stimulated genes expression in vitro. Four PA substitutions, H1N1 I38L/T, E199D, and B G199R, significantly reduced the sensitivity of the recombinant viruses to baloxavir (14.1-fold). We confirmed our findings by using the luciferase-based ribonucleoprotein minigenome assay and by using virus yield reduction assay in Calu-3 and normal human bronchial epithelial (NHBE) cells. We observed that I38L and E199D resulted in decreased viral replication of the H1N1 wild-type virus (1.4-fold) but the H1N1 I38T and B G199R substitutions did not significantly alter replication capacity in Calu-3 cells. In addition, H1N1 variants with PA I38L/T and E199D induced significantly higher levels of IFNB1 gene expression compared to the wild-type virus (4.2-fold). In contrast, the B variant, G199R, triggered the lowest levels of IFN genes in Calu-3 cells (1.6-fold). Because baloxavir is a novel anti-influenza therapeutic agent, identifying and characterizing substitutions associated with reduced sensitivity to baloxavir, as well as the impact of these substitutions on viral fitness, is paramount to the strategic implementation of this novel countermeasure.

Regional Differences in Human Biliary Tissues and Corresponding In Vitro-Derived Organoids.

BACKGROUND AND AIMS: Organoids provide a powerful system to study epithelia in vitro. Recently, this approach was applied successfully to the biliary tree, a series of ductular tissues responsible for the drainage of bile and pancreatic secretions. More precisely, organoids have been derived from ductal tissue located outside (extrahepatic bile ducts; EHBDs) or inside the liver (intrahepatic bile ducts; IHBDs). These organoids share many characteristics, including expression of cholangiocyte markers such as keratin (KRT) 19. However, the relationship between these organoids and their tissues of origin, and to each other, is largely unknown. APPROACH AND RESULTS: Organoids were derived from human gallbladder, common bile duct, pancreatic duct, and IHBDs using culture conditions promoting WNT signaling. The resulting IHBD and EHBD organoids expressed stem/progenitor markers leucine-rich repeat-containing G-protein-coupled receptor 5/prominin 1 and ductal markers KRT19/KRT7. However, RNA sequencing revealed that organoids conserve only a limited number of regional-specific markers corresponding to their location of origin. Of particular interest, down-regulation of biliary markers and up-regulation of cell-cycle genes were observed in organoids. IHBD and EHBD organoids diverged in their response to WNT signaling, and only IHBDs were able to express a low level of hepatocyte markers under differentiation conditions. CONCLUSIONS: Taken together, our results demonstrate that differences exist not only between extrahepatic biliary organoids and their tissue of origin, but also between IHBD and EHBD organoids. This information may help to understand the tissue specificity of cholangiopathies and also to identify targets for therapeutic development.

Certolizumab pegol treatment in axial spondyloarthritis mitigates fat lesion development: 4-year post-hoc MRI results from a phase 3 study.

OBJECTIVES: Fat lesions (FLs) on MRI T1 sequences are considered to be early indicators of structural spinal progression in axial spondyloarthritis (axSpA) patients. In this post-hoc analysis from RAPID-axSpA, we assess whether tumour necrosis factor inhibitor (TNFi) treatment over 4 years impacts FLs in spinal vertebral edges (VEs) of patients with axSpA. METHODS: In RAPID-axSpA (NCT01087762), a 4-year, phase 3 randomized trial, participants were randomized to certolizumab pegol (CZP; 400 mg loading dose at Weeks 0/2/4 then 200/400 mg every 2/4 weeks) or placebo (PBO) at baseline; PBO-randomized participants switched to CZP at Week 16/24 (denoted PBO-randomized/CZP). Spinal MRI scans were taken at Weeks 0, 12, 48, 96 and 204. Changes in proportions of VEs with FLs are reported as odds ratios (ORs) between time points. RESULTS: Overall, 136 participants (CZP: 89, PBO-randomized/CZP: 47) had a baseline and ≥1 post-baseline MRI. The OR (95% confidence interval) vs baseline of FLs was higher in PBO-randomized/CZP vs CZP-randomized participants at Weeks 48 [3.35 (2.16-5.19) vs 1.45 (1.07-1.97)], 96 [2.62 (1.77-3.88) vs 1.84 (1.36-2.48)] and 204 [2.55 (1.59-4.06) vs 1.71 (1.23-2.37)]. Across 204 weeks, FLs increased more in VEs with baseline inflammation [Week 204 OR: 4.84 (2.56-9.18)] than those without [OR: 1.15 (0.78-1.71)]. VEs in which inflammation was resolved by Week 12 had lower FL prevalence at Weeks 48, 96 and 204 compared with VEs with unresolved inflammation. CONCLUSIONS: Early and sustained suppression of inflammation mitigates the risk of long-term FL development in the spine in study participants with axSpA evaluated over 4 years. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT01087762.

Pathways from maternal depressive symptoms to children's academic performance in adolescence: A 13-year prospective-longitudinal study.

The pathways through which exposure to maternal depressive symptoms in early childhood are linked to academic performance during adolescence are poorly understood. This study tested pathways from maternal depressive symptoms (age 2-5) to adolescent academic performance (age 15) through cumulative parenting risk (age 7) and subsequent child functioning (age 10), using multi-informant data from a prospective longitudinal community study spanning 13 years (N = 389, 47% male, 68% White). Structural equation models testing indirect effects revealed small associations between maternal depressive symptoms and increased cumulative parenting risk and poorer child functioning, and, via these pathways, with poorer academic performance. Thus, childhood exposure to maternal depressive symptoms may be associated with pathways of risk that could limit children's educational opportunities.

Endocapsular artificial iris implantation for iris defects: Reducing symptoms, restoring visual function and improving cosmesis.

BACKGROUND: To investigate repair of iris defects by endocapsular implantation of an artificial iris, in relation to visual outcomes, safety profile and patient satisfaction. METHODS: Retrospective, consecutive case series from Greenlane tertiary teaching hospital and Eye Institute, Auckland, New Zealand. Medical records of patients implanted with an endocapsular artificial iris were reviewed and followed for minimum 3 months. Patient characteristics, surgical management, clinical outcomes and subjective responses were recorded. RESULTS: Nineteen artificial irises were implanted in 18 patients. Etiologies were iris melanotic lesion excision (73.7%), trauma (10.5%), congenital aniridia (10.5%) and Urrets-Zavalia syndrome (5.3%). During postoperative follow-up [14.1 ± 12.4 months (range: 3 to 59 months)], best corrected visual acuity (BCVA) and intraocular pressure (IOP) did not change significantly [BCVA, 0.23 logarithm of the minimum angle of resolution (logMAR) (20/32 Snellen) preoperatively vs. 0.18 logMAR postoperatively (20/25 Snellen) (Z = -0.222, p = 0.824); IOP, 15 mmHg preoperatively vs. 17 mmHg postoperatively (Z = 1.377, p = 0.1447)]. Mild or self-limiting complications included: elevated IOP (42.1%), cystoid macular oedema (15.8%); persisting postoperative uveitis (15.8%) and minor vaulting of the prosthesis (15.7%). Moderate or severe complications included significant vaulting of prosthesis requiring surgical revision (5.3%) and a single eye (5.3%) with trabeculectomy and corneal graft failure. 94.4% of patients were very satisfied with the cosmesis and would be highly likely to have the procedure again. CONCLUSIONS: This study confirms that endocapsular insertion of an artificial iris is typically associated with good functional and cosmetic results and a relatively low risk of significant complications.

Generation and characterization of interferon-beta-resistant H1N1 influenza A virus.

Interferons (IFNs) mediate innate antiviral activity against many types of viruses, including influenza viruses. In light of their potential use as anti-influenza agents, we examined whether resistance to these host antiviral proteins can develop. We generated IFN-ß-resistant variants of the A/California/04/09 (H1N1) virus by serial passage in a human airway epithelial cell line, Calu-3, under IFN-ß selective pressure. The combination of specific mutations (i.e., L373I in PB1, K154E1, D222G1, I56V2, and V122I2 in HA, and M269I in NA) correlated with decreased ability of the virus to induce expression of IFN (IFNB1, IFNL1, and IFNL2/3) and IFN-stimulated genes (IFIT1, IFIT3, OAS1, IRF7, and MX1) by target respiratory epithelial cells. In addition, the IFN-induced mutations were associated with decreased HA binding affinity to α2,6 sialyl receptors, reduced NA enzyme catalytic activity, and decreased polymerase transcription activity. Our findings demonstrate that the mutations in the influenza HA, NA, and PB1 proteins induced by IFN-b selective pressure significantly increase viral ability to productively infect and replicate in host cells. Keywords: influenza A virus; interferon-ß; lung epithelial cells; interferon response.

A structured expressive writing activity targeting body image-related distress among head and neck cancer survivors: who do we reach and what are the effects?

PURPOSE: The aim of this pretest-posttest study was to investigate the reach and effects of My Changed Body (MyCB), an expressive writing activity based on self-compassion, among head and neck cancer (HNC) survivors. METHODS: This pilot study had a pretest-posttest design. HNC survivors received an invitation to complete a baseline survey on body image-related distress. At the end of the survey, HNC survivors were asked if they were interested in the intervention study. This entailed the writing activity and a survey 1 week and 1 month post-intervention. The reach was calculated by dividing the number of participants in the intervention study, by the number of (1) eligible HNC survivors and (2) those who filled in the baseline survey. Linear mixed models were used to analyze the effect on body image-related distress. Logistic regression analysis was used to investigate factors associated with the reach and reduced body image-related distress. MyCB was evaluated using study-specific questions. RESULTS: The reach of MyCB was 15-33% (depending on reference group) and was associated with lower education level, more social eating problems, and fewer wound healing problems. Among the 87 participants, 9 (10%) showed a clinically relevant improvement in body image-related distress. No significant effect on body image-related distress was found. Self-compassion improved significantly during follow-up until 1 month post-intervention (p=0.003). Users rated satisfaction with MyCB as 7.2/10. CONCLUSION: MyCB does not significantly improve body image-related distress, but is likely to increase self-compassion, which sustains for at least 1 month.

Symptom monitoring in cancer and fully automated advice on supportive care: Patients' perspectives on self-management strategies and the eHealth self-management application Oncokompas.

OBJECTIVE: The web-based application Oncokompas was developed to support cancer patients to self-manage their symptoms. This qualitative study was conducted to obtain insight in patients' self-management strategies to cope with cancer and their experiences with Oncokompas as a fully automated behavioural intervention technology. METHODS: Data were collected from semi-structured interviews with 22 participants (10 head and neck cancer survivors and 12 incurably ill patients). Interview questions were about self-management strategies and experiences with Oncokompas. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Participants applied several self-management strategies, among which trying to stay in control and make the best of their situation. They described Oncokompas' added value: being able to monitor symptoms and having access to a personal online library. Main reasons for not using Oncokompas were concentration problems, lack of time or having technical issues. Recommendations were made for further development of Oncokompas, relating to its content, technical and functional aspects. CONCLUSIONS: Survivors and incurably ill patients use various self-management strategies to cope with cancer. The objectives of self-management interventions as Oncokompas correspond well with these strategies: taking a certain responsibility for your well-being and being in charge of your life as long as possible by obtaining automated information (24/7) on symptoms and tailored supportive care options.

Applying an association weight matrix in weighted genomic prediction of boar taint compounds.

Biological information regarding markers and gene association may be used to attribute different weights for single nucleotide polymorphism (SNP) in genome-wide selection. Therefore, we aimed to evaluate the predictive ability and the bias of genomic prediction using models that allow SNP weighting in the genomic relationship matrix (G) building, with and without incorporating biological information to obtain the weights. Firstly, we performed a genome-wide association studies (GWAS) in data set containing single- (SL) or a multi-line (ML) pig population for androstenone, skatole and indole levels. Secondly, 1%, 2%, 5%, 10%, 30% and 50% of the markers explaining the highest proportions of the genetic variance for each trait were selected to build gene networks through the association weight matrix (AWM) approach. The number of edges in the network was computed and used to derive weights for G (AWM-WssGBLUP). The single-step GBLUP (ssGBLUP) and weighted ssGBLUP (WssGBLUP) were used as standard scenarios. All scenarios presented predictive abilities different from zero; however, the great overlap in their confidences interval suggests no differences among scenarios. Most of scenarios of based on AWM provide overestimations for skatole in both SL and ML populations. On the other hand, the skatole and indole prediction were no biased in the ssGBLUP (S1) in both SL and ML populations. Most of scenarios based on AWM provide no biased predictions for indole in both SL and ML populations. In summary, using biological information through AWM matrix and gene networks to derive weights for genomic prediction resulted in no increase in predictive ability for boar taint compounds. In addition, this approach increased the number of analyses steps. Thus, we can conclude that ssGBLUP is most appropriate for the analysis of boar taint compounds in comparison with the weighted strategies used in the present work.