Levator ani muscle avulsion and subsequent vaginal delivery: 8-year longitudinal follow-up.

OBJECTIVES: To assess the evolution of levator ani muscle (LAM) avulsion from 1 year to 8 years after first delivery in women with and those without subsequent vaginal delivery. In addition, to assess whether women with full or partial avulsion 8 years after first delivery have larger LAM hiatal area and more symptoms of pelvic organ prolapse compared to women with normal LAM insertion. METHODS: In this single-center longitudinal study, 195 women who were primiparous at the start of the study were included and underwent transperineal ultrasound examination 1 year and 8 years after first delivery. Muscle insertion was assessed by tomographic ultrasound imaging in the axial plane. Full LAM avulsion was defined as abnormal muscle insertion in all three central slices. Partial LAM avulsion was defined as abnormal muscle insertion in one or two central slices. Eight years after the first delivery, LAM hiatal area was assessed at rest, during maximum pelvic floor muscle contraction and on maximum Valsalva maneuver. To assess symptoms of pelvic organ prolapse, the vaginal symptoms module of the International Consultation on Incontinence Questionnaire was used. RESULTS: At 1-year follow-up, 25 (12.8%) women showed signs of LAM avulsion, of whom 20 fulfilled the sonographic criteria of full avulsion and five of partial avulsion. Eight years after the first delivery, 35 (17.9%) women were diagnosed with avulsion, of whom 25 were diagnosed with full avulsion and 10 with partial avulsion. No woman with partial or full avulsion at 1 year had improved avulsion status at 8-year follow-up. Of the 150 women who had subsequent vaginal delivery, 21 (14.0%) women were diagnosed with partial or full LAM avulsion 1 year after first delivery, and 31 (20.7%) women were diagnosed with partial or full avulsion 8 years after first delivery. Of the 45 women without subsequent vaginal delivery, one woman with partial avulsion 1 year after first delivery was diagnosed with full avulsion at 8-year follow-up. All women with full avulsion at 1-year follow-up were diagnosed with full avulsion at 8-year follow-up regardless of whether they had subsequent vaginal delivery. At 8-year follow-up, women with full avulsion had statistically significantly larger LAM hiatal area compared to women with normal muscle insertion. Mean ± SD vaginal symptom scores ranged between 5.5 ± 5.7 and 6.0 ± 4.0 and vaginal symptom quality of life scores ranged between 0.9 ± 1.4 and 1.5 ± 2.2 and did not differ significantly between women with normal muscle insertion and women with partial or full avulsion at 8-year follow-up. CONCLUSIONS: More LAM avulsions were present 8 years compared with 1 year after first delivery in women with subsequent vaginal delivery. Except for one primipara, all women without subsequent vaginal delivery had unchanged LAM avulsion status between 1 year and 8 years after their first delivery. Larger LAM hiatal area was found in women with full avulsion compared to those with normal muscle insertion at 8-year follow-up. Vaginal symptoms scores were low and did not differ between women with normal muscle insertion and those with partial or full avulsion at 8-year follow-up. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Symmetry breaking of dark-mode metamaterials for voltage-switchable infrared absorption.

We propose electrically reconfigurable absorbers with switchable narrowband resonances in the infrared. Our absorbers consist of two coupled, identical resonators and support a dark supermode. We show that by dynamically breaking the symmetry of the system, the dark supermode can be made to couple to an incoming plane wave, producing a narrowband absorption peak in the spectrum. We use this effect to design and optimize absorbers consisting of coupled metal-insulator-metal resonators based on gallium arsenide. We show that the switching functionality of the designed device is robust to fabrication imperfections, and that it additionally serves as a spectrally tunable absorber. Our results suggest exciting possibilities for designing next-generation reconfigurable absorbers that could benefit several applications, such as energy harvesting and sensing.

LEP promoter methylation in the initiation and progression of clonal cytopenia of undetermined significance and myelodysplastic syndrome.

BACKGROUND: Idiopathic non-clonal cytopenia (ICUS) and clonal cytopenia (CCUS) are common in the elderly population. While these entities have similar clinical presentations with peripheral blood cytopenia and less than 10% bone marrow dysplasia, their malignant potential is different and the biological relationship between these disorders and myeloid neoplasms such as myelodysplastic syndrome (MDS) is not fully understood. Aberrant DNA methylation has previously been described to play a vital role in MDS and acute myeloid leukemia (AML) pathogenesis. In addition, obesity confers a poorer prognosis in MDS with inferior overall survival and a higher rate of AML transformation. In this study, we measured DNA methylation of the promoter for the obesity-regulated gene LEP, encoding leptin, in hematopoietic cells from ICUS, CCUS and MDS patients and healthy controls. We investigated whether LEP promoter methylation is an early event in the development of myeloid neoplasms and whether it is associated with clinical outcome. RESULTS: We found that blood cells of patients with ICUS, CCUS and MDS all have a significantly hypermethylated LEP promoter compared to healthy controls and that LEP hypermethylation is associated with anemia, increased bone marrow blast percentage, and lower plasma leptin levels. MDS patients with a high LEP promoter methylation have a higher risk of progression, shorter progression-free survival, and inferior overall survival. Furthermore, LEP promoter methylation was an independent risk factor for the progression of MDS in a multivariate Cox regression analysis. CONCLUSION: In conclusion, hypermethylation of the LEP promoter is an early and frequent event in myeloid neoplasms and is associated with a worse prognosis.

Impact of microwave thermolysis energy levels on patient-reported outcomes for axillary hyperhidrosis and osmidrosis.

OBJECTIVE: Microwave thermolysis (MWT) is an emerging treatment for axillary hyperhidrosis reducing both sweat and odor. No prior studies have investigated and compared the different available energy settings of the MWT device. This study evaluated patient-reported outcome measures (PROMs) for axillary hyperhidrosis and osmidrosis following MWT treatment with two different energy levels. METHODS: Twenty adults with axillary hyperhidrosis and osmidrosis reported sweat on Hyperhidrosis Disease Severity scale (HDSS: 1-4) and odor on Odor scale (OS: 1-10), respectively, supplemented by overall Dermatology Life Quality Index (DLQI: 0-30). This was a prospective, randomized, patient-blinded and intraindividually controlled study with 3 months follow-up (FU). Randomization comprised MWT treatment of one axilla with a standard medium energy setting (energy level 3) and the contralateral axilla with a standard high energy setting (energy level 5). RESULTS: At baseline, patients reported substantial sweat and odor, negatively affecting their quality of life. At 3 months FU, PROMs showed improved quality of life with significantly reduced odor and sweat. Overall DLQI was reduced from a median of 10 to 4, with a median 6.5-point reduction (p = 0.0002). HDSS was reduced from a median of 4 to 2 on both sides, with a median reduction of 1 for medium energy level and 2 points for high energy level (p = 0.014). OS was reduced from a median of 8 to 3 for both energy levels, with a median reduction of 3.5 and 4.5 points for the medium and high energy level, respectively (p = 0.017). Local skin reactions were mild and transient, but slightly more pronounced following treatment with the high energy level. CONCLUSION: MWT effectively improved patients' quality of life, axillary sweat, and odor 3 months after on baseline treatment. Treatment with the high energy level presented a subtle but significant increase of efficacy based on PROMs for both sweat and odor. Patients were willing to accept a higher amount of temporary local skin reactions from a higher energy setting when experiencing greater odor and sweat reduction.

Myeloproliferative and lymphoproliferative malignancies occurring in the same patient: a nationwide discovery cohort.

Myeloid and lymphoid malignancies are postulated to have distinct pathogenetic mechanisms. The recent observation that patients with a myeloproliferative neoplasm have an increased risk of developing lymphoproliferative malignancy has challenged this assumption. We collected a nationwide cohort of patients with both malignancies. Patients diagnosed in 1990-2015 were identified through the national Danish Pathology Registry. We identified 599 patients with myeloproliferative neoplasm and a concomitant or subsequent diagnosis of lymphoma. Histopathological review of the diagnostic samples from each patient led to a final cohort of 97 individuals with confirmed dual diagnoses of myeloproliferative neoplasm and lymphoma. The age range at diagnosis was 19-94 years (median: 71 years). To avoid the inclusion of cases of therapy-induced myeloproliferative neoplasm occurring in patients previously treated for lymphoma, only patients with myeloproliferative neoplasm diagnosed unequivocally before the development of lymphoma were included. The average time interval between the diagnoses of the two malignancies was 1.5 years. In the majority of patients (90%) both diagnoses were established within 5 years from each other. Among the lymphoma entities, the frequency of peripheral T-cell lymphomas was markedly increased. Interestingly, all but one of the T-cell lymphomas were of angioimmunoblastic type. These findings suggest that myeloproliferative neoplasm and lymphoproliferative malignancy developing in the same patient may have common pathogenetic events, possibly already at progenitor level. We believe that the molecular characterization of the newly developed biorepository will help to highlight the mechanisms driving the genesis and clonal evolution of these hematopoietic malignancies.

Is pelvic floor muscle training effective for symptoms of overactive bladder in women? A systematic review.

BACKGROUND: Overactive bladder (OAB) syndrome can be very bothersome and is associated with impaired quality of life and work productivity. OBJECTIVE: To evaluate the effect of pelvic floor muscle training (PFMT) on OAB symptoms in women. Furthermore, to assess the influence of PFMT on pelvic floor muscle (PFM) function, satisfaction with treatment, side effects, adherence and the quality of exercise reporting. DATA SOURCES: Systematic review of randomized controlled trials (RCTs). Electronic search was conducted on MEDLINE/PubMed, Embase, CINAHL, SciELO, SCOPUS, Web of Science and Physiotherapy Evidence Database (PEDro). The risk of bias was assessed using the PEDro scale. The Consensus on Exercise Reporting Template (CERT) was used to assess the quality of exercise reporting. STUDY SELECTION: Full text RCTs including non-pregnant female participants, investigating PFMT vs inactive control or usual care, other life style modifications or other interventions. SYNTHESIS METHODS: Descriptive analysis. RESULTS: Eleven RCTs were included. There was considerable heterogeneity of PFMT protocols, outcome measures and follow-up periods. Hence, a qualitative analysis was undertaken. PFMT provided a significant reduction of OAB symptoms in five studies with a reduction in urinary frequency (n=1), and urgency urinary incontinence (n=4). PFM function was assessed in three studies, and two studies found improvement in favor of PFMT. LIMITATIONS: A meta-analysis was not possible due to huge heterogeneity of included studies. CONCLUSION: PFMT might reduce OAB symptoms, however, due to many limitations of the published studies it is not possible to clearly determine the effect of PFMT on OAB symptoms and PFM function. Systematic Review Registration Number PROSPERO CRD42018085640.

Oxymatrine therapy inhibited epidermal cell proliferation and apoptosis in severe plaque psoriasis.

BACKGROUND: Psoriasis is a chronic skin disorder that manifests as epidermal keratinocyte hyperplasia. OBJECTIVES: We examined the effect of oxymatrine treatment on cell proliferation and apoptosis in skin lesions of psoriasis. PATIENTS AND METHODS: Patients with severe plaque psoriasis were treated with oxymatrine or with acitretin. The skin lesions were stained with proliferating cell nuclear antigen (PCNA), Ki-67 and Bcl-2, as well as examined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). We performed correlations of the Psoriasis Area and Severity Index (PASI) and the proliferation and apoptosis index. RESULTS: Oxymatrine significantly reduced the psoriasis lesions as demonstrated by the reduced PASI score after treatment [6·91; 95% confidence interval (CI) 5·00-8·81, P < 0·001]. In the oxymatrine group, the mitotic index was 26·15 (95% CI 24·80-27·49) before oxymatrine treatment, decreasing to 14·52 (95% CI 13·82-15·25; P < 0·001) after treatment, but remained higher than the normal group (6·24; 95% CI 5·87-6·61, P < 0·001). Oxymatrine also inhibited the proliferation of epidermal cells in the skin lesion as indicated by the reduced proliferation index after treatment (P < 0·01). In addition, oxymatrine treatment reduced cellular apoptosis as shown by increased Bcl-2 expression and a decrease in TUNEL-positive cells. The PASI score was positively correlated with mitotic index, proliferation index and apoptotic index (TUNEL), but negatively correlated with Bcl-2 expression. CONCLUSIONS: Oxymatrine treatment reduced proliferation but inhibited apoptosis of cells in the skin lesion. The balance between cell proliferation and turnover may contribute to the significant alleviation of psoriasis by oxymatrine. What's already known about this topic? Psoriasis manifests as epidermal keratinocyte hyperplasia with proliferation, keratinocyte maturation and turnover rates. Current drugs for psoriasis may inhibit cell proliferation but could not adjust the balance of cell division, differentiation and apoptosis. What does this study add? We studied the efficacy of oxymatrine in the treatment of psoriasis and analysed the correlation of skin lesions, proliferation and apoptosis index before and after oxymatrine treatment. What is the translational message? Our study has demonstrated that oxymatrine is effective in the treatment of severe plaque psoriasis. It has comparable efficacy with acitretin. Because acitretin treatment was sometimes associated with metabolic abnormalities, our study suggests oxymatrine therapy as an alternative treatment for psoriasis in the context of acitretin allergy or adverse reactions.

Effect of pelvic floor and transversus abdominis muscle contraction on inter-rectus distance in postpartum women: a cross-sectional experimental study.

OBJECTIVES: To investigate the effect of acute isometric contraction of the pelvic floor muscles (PFM) and transversus abdominis muscle (TrAM) on inter-rectus distance (IRD) from resting values in postpartum women with diastasis rectus abdominis (DRA). DESIGN: Cross sectional experimental study. SETTING: Physiotherapy clinic. PARTICIPANTS: Thirty eight postpartum women presenting with DRA of at least two finger widths. METHODS: Two dimensional ultrasound images of IRD were recorded using a linear probe (5 to 10MHz) at rest, during PFM contraction, during TrAM contraction, and during combined PFM and TrAM contraction. IRD data were normally distributed. MAIN OUTCOME MEASURE: Change in IRD. RESULTS: There was a significant increase in IRD during PFM and TrAM contraction compared with IRD at rest. At 2cm above the umbilicus, mean PFM was 26.9 [standard deviation (SD) 8.8] mm vs rest 25.7 (SD 8.5) mm {mean difference 1.2 [95% confidence interval (CI) 0.7 to 1.7] mm}; and mean TrAM was 28.4 (SD 9.0) mm vs rest 25.7 (SD 8.5) mm [mean difference 2.8 (95% CI 1.9 to 3.6) mm]. Similarly, 2cm below the umbilicus, mean PFM was 22 (SD 8.3) mm vs rest 21 (SD 7.9) mm [mean difference 0.9 (95% CI 0.4 to 1.6) mm]; and mean TrAM was 23.3 (SD 8.7) mm vs rest 21 (SD 7.9) mm [mean difference 2.3 (95% CI 1.5 to 3.1) mm]. Combined TrAM and PFM contraction measured 2cm above the umbilicus caused the greatest increase in IRD: mean PFM+TrAM 29.6 (SD 9.4) mm vs rest 25.7 (SD 8.5) mm [mean difference 3.9 (95% CI 2.8 to 5.0) mm]. CONCLUSION: Both PFM and TrAM contraction, and combined PFM and TrAM contraction increased IRD in postpartum women with DRA.

[An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for the conservative and non-pharmacological management of female pelvic floor dysfunction]. / Traduction française de la terminologie commune de l'International Urogynecological Association (IUGA) et de l'International Continence Society (ICS) relative à la prise en charge conservatrice et non pharmacologique des troubles pelvi-périnéaux de la femme.

INTRODUCTION: There has been an increasing need for the terminology for the conservative management of female pelvic floor dysfunction to be collated in a clinically-based consensus report. METHODS: This report combines the input of members and elected nominees of the Standardization and Terminology Committees of two International Organizations, the International Urogynecological Association (IUGA) and the International Continence Society (ICS), assisted at intervals by many external referees. An extensive process of nine rounds of internal and external review was developed to exhaustively examine each definition, with decision-making by collective opinion (consensus). Before opening up for comments on the webpages of ICS and IUGA, five experts from physiotherapy, neurology, urology, urogynecology and nursing were invited to comment on the paper. RESULTS: A terminology report for the conservative management of female pelvic floor dysfunction, encompassing over 200 separate definitions, has been developed. It is clinically-based with the most common symptoms, signs, assessments, diagnoses and treatments defined. Clarity and user-friendliness have been key aims to make it interpretable by practitioners and trainees in all the different specialty groups involved in female pelvic floor dysfunction. Ongoing review is not only anticipated but will be required to keep the document updated and as widely acceptable as possible. CONCLUSION: A consensus-based terminology report for the conservative management of female pelvic floor dysfunction has been produced aimed at being a significant aid to clinical practice and a stimulus for research.

Efficacy and safety of daylight photodynamic therapy after tailored pretreatment with ablative fractional laser or microdermabrasion: a randomized, side-by-side, single-blind trial in patients with actinic keratosis and large-area field cancerization.

BACKGROUND: Physical pretreatments can potentiate the efficacy of daylight photodynamic therapy (dPDT), but clinical comparative studies remain limited. OBJECTIVES: Performed in large skin areas with actinic keratoses (AKs) and photodamage, this blinded, randomized clinical trial compared the efficacy and safety of dPDT after tailored skin pretreatment using ablative fractional laser (AFL) or microdermabrasion (MD). METHODS: Two ≥ 50-cm2 side-by-side skin areas were randomized to receive a single treatment with AFL-dPDT or MD-dPDT. Pretreatment parameters were tailored according to AK grade and skin constitution to ensure standardized immediate end points. Subsequently, methyl aminolaevulinate was applied, followed by 2-h daylight exposure. The primary outcome comprised blinded assessment of AK clearance at the 3-month follow-up. RESULTS: In 18 patients with 832 AKs, AFL-dPDT provided significantly higher AK clearance (81% vs. 60%, P < 0·001), led to fewer new AKs (P < 0·001) and showed superior improvement in dyspigmentation (P = 0·003) and skin texture (P = 0·001) vs. MD-dPDT. Peaking at days 3-6, AFL-PDT induced more intensified local skin responses (P = 0·004), including instances of Staphylococcus aureus infection (n = 3). Patients nonetheless preferred AFL-dPDT (P = 0·077), due to lower pretreatment-related pain (P = 0·002) and superior cosmesis (P = 0·035) and efficacy compared with MD-dPDT. CONCLUSIONS: AFL-dPDT is an effective treatment for patients with AK with extensive field cancerization, although AFL pretreatment is associated with intensified local skin reactions.

Effects on repetitive 24-hour ambulatory blood pressure in subjects with type II diabetes randomized to liraglutide or glimepiride treatment both in combination with metformin: a randomized open parallel-group study.

In this post hoc study, we aimed to investigate liraglutide treatment on repetitive 24-hour blood pressure (BP) in patients with type II diabetes. Sixty-two individuals with type II diabetes (45 males) were randomized to 1.8 mg liraglutide once daily or 4 mg glimepiride together with 1 g metformin twice daily. Ambulatory 24-hour systolic and diastolic blood pressure (sBP/dBP) was repetitively measured at baseline, 2 weeks, and 18 weeks. Outcomes were evaluated as treatment change from baseline, 2 weeks, and 18 weeks. Baseline clinical characteristics of liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. No statistically significant difference in 24-hour sBP/dBP between three time periods and groups was observed. There was no treatment change for 24-hour sBP at week 2 or after week 18. There was a transient treatment change in 24-hour dBP in the liraglutide group at week 2 (3.2 ± 5.4 vs. -1.2 ± 4.5 mm Hg, P < .01). A treatment change in 24-hour heart rate at week 2 (4.9 ± 6.8 vs. 1.0 ± 6.0 bpm, P = .03) and at week 18 (5.9 ± 7.8 vs. 0.2 ± 6.3 bpm, P < .01) was observed in the liraglutide group. In conclusion, liraglutide treatment did not lower BP. However, a small diurnal variation in dBP without affecting BP variability or nocturnal BP dipping was observed.

Genetic variants in CYP7A1 and risk of myocardial infarction and symptomatic gallstone disease.

Aims: Myocardial infarction (MI) and gallstone disease (GSD) are intrinsically linked via cholesterol metabolism. We tested the hypothesis that genetic variants in the gene encoding cholesterol 7 alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver, are associated with risk of MI and GSD in the general population. Methods and results: We performed tests of association between lipid levels and eight rare non-synonymous mutations and two common variants, rs2081687 and rs3808607, in CYP7A1 in 100 149 individuals from the general population. We further tested whether weighted allele scores for rs2081687 and rs3808607, which were associated with increased plasma levels of low-density lipoprotein (LDL) cholesterol, were associated with an increased risk of both MI and symptomatic GSD. During a mean follow-up of 7 years (0-23 years), MI developed in 2326 individuals and GSD in 2007. For rare mutations, CYP7A1 allele count was associated with an increase in LDL cholesterol of 12% (0.4 mmol/L) for individuals with the highest vs. the lowest allele count (P for trend = 3 × 10-4). For common variants, CYP7A1 weighted allele scores in individuals with a score >0.04 vs. ≤0 were associated with stepwise increases in LDL cholesterol of up to 2.4% (0.08 mmol/L), and with corresponding multifactorially adjusted hazard ratios of 1.25 [95% confidence interval (CI) 1.10-1.41] for MI and 1.39 (95% CI 1.22-1.59) for GSD (P for trend = 5 × 10-4 and 2 × 10-7, respectively). Results were similar in meta-analyses including publicly available data from large consortia. Conclusion: Genetic variants in CYP7A1 which are associated with increased levels of LDL cholesterol, are associated with an increased risk of both MI and GSD.

Photodynamic therapy is more effective than imiquimod for actinic keratosis in organ transplant recipients: a randomized intraindividual controlled trial.

BACKGROUND: Actinic keratoses (AKs) in solid organ transplant recipients (OTRs) are difficult-to-treat premalignancies and comparison of topical therapies is therefore warranted. OBJECTIVES: In an intraindividual study to compare the efficacy and safety of field treatment with methyl aminolaevulinate photodynamic therapy (MAL-PDT) and imiquimod (IMIQ) for AKs in OTRs. METHODS: OTRs (n = 35) with 572 AKs (grade I-III) in two similar areas on the face, scalp, dorsal hands or forearms were included. All patients received one MAL-PDT and one IMIQ session (three applications per week for 4 weeks) in each study area according to randomization. Treatments were repeated after 2 months (IMIQ) and 3 months (PDT) in skin with incomplete AK response. Outcome measures were complete lesion response (CR), skin reactions, laboratory results and treatment preference. RESULTS: The majority of study areas received two treatment sessions (PDT n = 25 patients; IMIQ n = 29 patients). At 3 months after two treatments, skin treated with PDT achieved a higher rate of CR (AK I-III median 78%; range 50-100) compared with IMIQ-treated skin areas (median 61%, range 33-100; P < 0·001). Fewer emergent AKs were seen in PDT-treated skin vs. IMIQ-treated skin (0·7 vs. 1·5 AKs, P = 0·04). Patients developed more intense inflammatory skin reactions following PDT, which resolved more rapidly compared with IMIQ (median 10 days vs. 18 days, P < 0·01). Patient preference (P = 0·47) and cosmesis (P > 0·30) were similar for PDT and IMIQ. CONCLUSIONS: Compared with IMIQ, PDT treatment obtained a higher rate of AK clearance at 3-month follow-up and achieved shorter-lasting, but more intense, short-term skin reactions.

Relationship between genetic variation at PPP1R3B and levels of liver glycogen and triglyceride.

Genetic variation at rs4240624 on chromosome 8 is associated with an attenuated signal on hepatic computerized tomography, which has been attributed to changes in hepatic fat. The closest coding gene to rs4240624, PPP1R3B, encodes a protein that promotes hepatic glycogen synthesis. Here, we performed studies to determine whether the x-ray attenuation associated with rs4240624 is due to differences in hepatic glycogen or hepatic triglyceride content (HTGC). A sequence variant in complete linkage disequilibrium with rs4240624, rs4841132, was genotyped in the Dallas Heart Study (DHS), the Dallas Liver Study, and the Copenhagen Cohort (n = 112,428) of whom 1,539 had nonviral liver disease. The minor A-allele of rs4841132 was associated with increased hepatic x-ray attenuation (n = 1,572; P = 4 × 10-5 ), but not with HTGC (n = 2,674; P = 0.58). Rs4841132-A was associated with modest, but significant, elevations in serum alanine aminotransferase (ALT) in the Copenhagen Cohort (P = 3 × 10-4 ) and the DHS (P = 0.004), and with odds ratios for liver disease of 1.13 (95% CI, 0.97-1.31) and 1.23 (1.01-1.51), respectively. Mice lacking protein phosphatase 1 regulatory subunit 3B (PPP1R3B) were deficient in hepatic glycogen, whereas HTGC was unchanged. Hepatic overexpression of PPP1R3B caused accumulation of hepatic glycogen and elevated plasma levels of ALT, but did not change HTGC. CONCLUSION: These observations are consistent with the notion that the minor allele of rs4841132 promotes a mild form of hepatic glycogenosis that is associated with hepatic injury. (Hepatology 2018;67:2182-2195).

Efficacy of oxymatrine for treatment and relapse suppression of severe plaque psoriasis: results from a single-blinded randomized controlled clinical trial.

BACKGROUND: Drugs that are currently used in the treatment of psoriasis are associated with drawbacks such as rapid recrudescence, high costs and unwanted side-effects. Oxymatrine has a long history of clinical use in the treatment of hepatitis and cancer in China. OBJECTIVES: To explore the efficacy and safety of intravenous oxymatrine in patients with severe plaque psoriasis. METHODS: A total of 67 patients were randomly allocated to receive oxymatrine injections (0.6 g per day for 8 weeks) or acitretin capsules (0.75 mg kg-1 per day from week 0 to week 2 and 20-30 mg per day from week 3 to week 8) and followed up for another 24 weeks. The primary end point was the percentage of patients with ≥ 50% reduction of Psoriasis Area and Severity Index (PASI 50) at week 32. The secondary end points included the skin classification grade and the Dermatology Quality of Life Index (DLQI) score. Side-effects were recorded throughout the whole study to assess the safety profile. RESULTS: Treatment with oxymatrine or acitretin for 8 weeks significantly decreased PASI score, skin classification grade and DLQI score (P < 0.001), with no significant differences between the oxymatrine and acitretin groups in terms of PASI 50. However, at week 32, the relapse rate in the oxymatrine group was significantly lower than that of the acitretin group (P < 0.001). Moreover, while there was an increase in the number of patients with metabolic abnormalities in the acitretin group, a significant reduction was observed in the oxymatrine group. Furthermore, rates of adverse reactions were significantly decreased in the oxymatrine group compared with that of the acitretin group (P < 0.001). CONCLUSIONS: Treatment with oxymatrine effectively ameliorated severe plaque psoriasis, and was accompanied by only minor adverse effects.

Genome-wide minor histocompatibility matching as related to the risk of graft-versus-host disease.

The risk of acute graft-versus-host disease (GVHD) is higher after allogeneic hematopoietic cell transplantation (HCT) from unrelated donors as compared with related donors. This difference has been explained by increased recipient mismatching for major histocompatibility antigens or minor histocompatibility antigens. In the current study, we used genome-wide arrays to enumerate single nucleotide polymorphisms (SNPs) that produce graft-versus-host (GVH) amino acid coding differences between recipients and donors. We then tested the hypothesis that higher degrees of genome-wide recipient GVH mismatching correlate with higher risks of GVHD after allogeneic HCT. In HLA-genotypically matched sibling recipients, the average recipient mismatching of coding SNPs was 9.35%. Each 1% increase in genome-wide recipient mismatching was associated with an estimated 20% increase in the hazard of grades III-IV GVHD (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.05-1.37; P = .007) and an estimated 22% increase in the hazard of stage 2-4 acute gut GVHD (HR, 1.22; 95% CI, 1.02-1.45; P = .03). In HLA-A, B, C, DRB1, DQA1, DQB1, DPA1, DPB1-phenotypically matched unrelated recipients, the average recipient mismatching of coding SNPs was 17.3%. The estimated risks of GVHD-related outcomes in HLA-phenotypically matched unrelated recipients were low, relative to the large difference in genome-wide mismatching between the 2 groups. In contrast, the risks of GVHD-related outcomes were higher in HLA-DP GVH-mismatched unrelated recipients than in HLA-matched sibling recipients. Taken together, these results suggest that the increased GVHD risk after unrelated HCT is predominantly an effect of HLA-mismatching.

Effect of postpartum pelvic floor muscle training on vaginal symptoms and sexual dysfunction-secondary analysis of a randomised trial.

OBJECTIVE: Evaluate effect of pelvic floor muscle training (PFMT) on vaginal symptoms and sexual matters, dyspareunia and coital incontinence in primiparous women stratified by major or no defects of the levator ani muscle. DESIGN: Randomised controlled trial (RCT). SETTING: Akershus University Hospital, Norway. SAMPLE: About 175 primiparous women with a singleton vaginal delivery. METHODS: Two-armed assessor blinded parallel group RCT from 6 weeks to 6 months postpartum comparing effect of PFMT versus control. MAIN OUTCOME MEASURES: International Consultation on Incontinence Modular Questionnaire-vaginal symptoms questionnaire (ICIQ-VS) and ICIQ sexual matters module (ICIQ-FLUTSsex). RESULTS: Overall, analysis (n = 175) showed no difference between training and control groups in women having vaginal symptoms or symptoms related to sexual dysfunction 6 months postpartum. The majority of women (88%) had intercourse and there was no difference between groups. Unadjusted subgroup analysis of women with a major defect of the levator ani muscle (n = 55) showed that women in the training group had 45% less risk of having the symptom 'vagina feels loose or lax' compared with the control group (relative risk 0.55, 95% confidence interval 0.31, 0.95; P = 0.03). CONCLUSIONS: Unadjusted analysis showed that in women with major defect of the levator ani muscle, significantly fewer in the training group had the symptom 'vagina feels loose or lax' compared with the control group. No difference was found between groups for symptoms related to sexual dysfunction. More studies are needed to explore effect of PFMT on vaginal symptoms and sexual dysfunction. TWEETABLE ABSTRACT: Unadjusted analysis shows that PFMT might prevent symptoms of 'vagina feels loose or lax'.