Prospective diagnostic test accuracy of transvaginal ultrasound posterior approach for uterosacral ligament and torus uterinus deep endometriosis.

OBJECTIVE: To determine the diagnostic test accuracy of transvaginal ultrasound (TVS) using a standardized technique for the diagnosis of deep endometriosis (DE) of the uterosacral ligaments (USLs) and adjacent torus uterinus (TU). METHODS: This was a prospective diagnostic test accuracy study conducted at the McMaster University Medical Center Tertiary Endometriosis Clinic, Hamilton, ON, Canada. Consecutive participants were enrolled if they successfully underwent TVS and surgery by our team from 10 August 2020 to 31 October 2021. The index test was TVS using a standardized posterior approach performed and interpreted by an expert sonologist. The reference standard included direct surgical visualization on laparoscopy by the same person who performed and interpreted the ultrasound scans. Accuracy, sensitivity, specificity, positive and negative predictive values (PPV and NPV) and positive and negative likelihood ratios were calculated for the TVS posterior approach for each location using the reference standard. RESULTS: There were 54 consecutive participants included upon completion of laparoscopy and histological assessment. The prevalence of DE for the left USL, right USL and TU was 42.6%, 22.2% and 14.8%, respectively. Based on surgical visualization as the reference standard, TVS demonstrated an accuracy of 92.6% (95% CI, 82.1-97.9%), sensitivity of 82.6% (95% CI, 61.2-95.1%), specificity of 100% (95% CI, 88.8-100%), PPV of 100% and NPV of 88.6% (95% CI, 76.1-95.0%) for diagnosing DE in the left USL. For DE of the right USL, TVS demonstrated an accuracy of 94.4% (95% CI, 84.6-98.8%), sensitivity of 75.0% (95% CI, 42.8-94.5%), specificity of 100% (95% CI, 91.6-100%), PPV of 100% and NPV of 93.3% (95% CI, 84.0-97.4%). For DE of the TU, TVS demonstrated an accuracy of 100% (95% CI, 93.4-100%), sensitivity of 100% (95% CI, 63.1-100%), specificity of 100% (95% CI, 92.3-100%), PPV of 100% and NPV of 100%. CONCLUSIONS: We observed high diagnostic test accuracy of the evaluated standardized TVS technique for assessing DE of the USLs and TU. Further studies evaluating this technique should be performed, particularly with less experienced observers, before considering this technique as the standard approach. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Risk factors for medication-related osteonecrosis of the jaws: A systematic review.

The purpose of this study was to identify the patient populations at risk of medication-related osteonecrosis of the jaw (MRONJ) and determine which medical and dental comorbidities are significant risk factors for this disease. An electronic search of Embase, MEDLINE, Cochrane Central Register of Controlled Trials, WHO International Clinical Trials Registry Platform and ProQuest Dissertations and Theses Global was conducted to identify all human studies that reported risk factors for MRONJ. Only a qualitative analysis was performed due to significant heterogeneity in the collected data. The search strategy identified 2872 records, of which 219 studies were eligible for inclusion. A total of 4106 patients with MRONJ were identified, 39 different systemic diseases were implicated, and 14 medical and 11 dental risk factors were reported, although no statistical analysis of the significance of each of these factors was possible. The clinical reach of MRONJ may be wider than anticipated, and more data on the significance of each potential risk factor are needed to guide the identification and management of at-risk patients.

Dental referrals for patients with diabetes: survey of barriers and enablers for medical and health professionals.

BACKGROUND: Oral health care improves diabetes management; however, medical and other health practitioners do not commonly refer their patients with diabetes for oral health care. This study aimed to understand barriers to and enablers of dental referrals for patients with diabetes. METHODS: Quantitative data were collected from a cross-sectional survey of health care providers attending a virtual Grand Rounds on the relationship between oral health and diabetes. Attendees were invited to complete and share a Forms survey. Barriers to and enablers of dental referrals were compared for 18 health professionals working in inpatient/ward settings to 23 working in community/primary care settings using the chi-square test. RESULTS: Across both work settings, only 12% of respondents often or always discussed the importance of oral health and only 8% often or always referred their patients with diabetes for dental care. Time barriers, awareness and knowledge of how/where to send dental referrals were significant barriers, while online referral pathways, more education and availability of brochures for the patient to take home were identified as key enablers for dental referrals. CONCLUSIONS: Online referral pathways, targeted oral health education and resources for medical and health professionals caring for patients with diabetes may increase the number of patients being referred for dental care as part of their diabetes managements. © 2023 Australian Dental Association.

Capturing cold-stress-related sequence diversity from a wild relative of common bean (Phaseolus angustissimus).

One restriction to the cultivation of common bean, Phaseolus vulgaris L., is its limited tolerance to low temperatures. In the present study, subtraction suppression hybridization was employed to enrich for stress responsive genes in both a chilling-susceptible common bean and a relatively more chilling-tolerant wild bean species, Phaseolus angustissimus. For each species, approximately 11 000 expressed sequence tags were generated. Comparative sequence analysis of the EST collection with the available annotated genome sequences of the model Fabaceae species Medicago truncatula and Glycine max identified protein homologues for approximately 65% and 80% of the Phaseolus sequences, respectively. This difference reflects the closer phylogenetic relationship between the genera Phaseolus and Glycine compared with Medicago. Annotation of the Phaseolus sequences was facilitated through this comparative analysis and indicated that several heat shock proteins, cytochrome P450s, and DNA binding factors were uniquely found among the sequences from the wild species P. angustissimus. The Phaseolus sequences have been made available on a GBrowse implementation using M. truncatula as the reference genome, providing rapid access to the sequence data and associated comparative genome data.

A link between prompt optical and prompt gamma-ray emission in gamma-ray bursts.

The prompt optical emission that arrives with the gamma-rays from a cosmic gamma-ray burst (GRB) is a signature of the engine powering the burst, the properties of the ultra-relativistic ejecta of the explosion, and the ejecta's interactions with the surroundings. Until now, only GRB 990123 had been detected at optical wavelengths during the burst phase. Its prompt optical emission was variable and uncorrelated with the prompt gamma-ray emission, suggesting that the optical emission was generated by a reverse shock arising from the ejecta's collision with surrounding material. Here we report prompt optical emission from GRB 041219a. It is variable and correlated with the prompt gamma-rays, indicating a common origin for the optical light and the gamma-rays. Within the context of the standard fireball model of GRBs, we attribute this new optical component to internal shocks driven into the burst ejecta by variations of the inner engine. The correlated optical emission is a direct probe of the jet isolated from the medium. The timing of the uncorrelated optical emission is strongly dependent on the nature of the medium.

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225.

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10'') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Developing a prototype for integrated dental and diabetes care: understanding needs and priorities.

BACKGROUND: Periodontal treatment may be a useful adjunct to medical management of diabetes; however, oral health has not been integrated into multidisciplinary diabetes care in Australia. This study aimed to understand the needs of patients and staff at a diabetes clinic to inform a prototype of integrated dental and diabetes care. METHODS: Quantitative and qualitative data were collected from patients and staff at West Moreton Diabetes Clinic (WMDC) between September-October 2019. Clinical information, survey responses and dental screening results were analysed for 41 patients. Semi-structured interviews were held with six patients and a focus group with seven staff. RESULTS: Most patients (83%) had not seen a dentist in the previous year. Of the 37 patients with remaining natural teeth, 84% required periodontal assessment and 46% had multiple carious lesions. Unmet treatment needs and rates of access were similar for private and public dental patients. Staff and patients reported high levels of support for incorporation of dental care at WMDC. CONCLUSIONS: Integrating oral health into diabetes management is well-supported by patients and staff to address significant unmet dental needs for both public and private dental patients. Incorporating dental screening/services within diabetes clinics may increase uptake and improve awareness of its importance in diabetes management.

Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein.

Haemophilus influenzae undergoes phase variation in expression of the phosphorylcholine (ChoP) epitope, a structure present on several invasive pathogens residing in the human respiratory tract. In this study, structural analysis comparing organisms with and without this epitope confirmed that variants differ in the presence of ChoP on the cell surface-exposed outer core of the lipopolysaccharide. During nasopharyngeal carriage in infant rats, there was a gradual selection for H. influenzae variants that express ChoP. In addition, genotypic analysis of the molecular switch that controls phase variation predicted that the ChoP+ phenotype was predominant in H. influenzae in human respiratory tract secretions. However, ChoP+ variants of nontypable H. influenzae were more sensitive to the bactericidal activity of human serum unrelated to the presence of naturally acquired antibody to ChoP. Serum bactericidal activity required the binding of C-reactive protein (CRP) with subsequent activation of complement through the classical pathway. Results of this study suggested that the ability of H. influenzae to vary expression of this unusual bacterial structure may correlate with its ability both to persist on the mucosal surface (ChoP+ phenotype) and to cause invasive infection by evading innate immunity mediated by CRP (ChoP- phenotype).

Increasing frequency and severity of odontogenic infection requiring hospital admission and surgical management.

Odontogenic infections can become life-threatening if not managed in a timely manner, and they increase the physical cost of treatment to the patient and the financial cost to the public health system. We investigated the number of admissions to a Queensland tertiary hospital within a decade, and differences in the patients' characteristics, severity at presentation, and clinical outcomes. We compared patients with odontogenic infections who were taken to theatre at the Royal Brisbane & Women's Hospital (RBWH) between January 2003 and December 2004 with those treated between January 2013 and December 2014, a total of 292. Data on demographics, presentation, previous history, antimicrobial treatment, and admissions, were collated and analysed. There were no significant differences in demographics. In the 2013/2014 group there was a two-fold increase in infections related to lower third molars (p=0.001), a 50% increase in trismus (p=0.001), and a 20% increase in submandibular swelling (p=0.010). The percentage of patients admitted to the intensive care unit (ICU) was three and a half times higher in the 2013/2014 group (p=0.001). The presentation of odontogenic infections has increased in the decade from 2003/2004 to 2013/2014. Measures of the severity of disease have increased, while the basic characteristics of the patients have remained constant. Improved primary preventative measures and early interventions are therefore needed to alleviate the burden that these infections place on the public health system.

Onset of keratin 17 expression coincides with the definition of major epithelial lineages during skin development.

The type I keratin 17 (K17) shows a peculiar localization in human epithelial appendages including hair follicles, which undergo a growth cycle throughout adult life. Additionally K17 is induced, along with K6 and K16, early after acute injury to human skin. To gain further insights into its potential function(s), we cloned the mouse K17 gene and investigated its expression during skin development. Synthesis of K17 protein first occurs in a subset of epithelial cells within the single-layered, undifferentiated ectoderm of embryonic day 10.5 mouse fetuses. In the ensuing 48 h, K17-expressing cells give rise to placodes, the precursors of ectoderm-derived appendages (hair, glands, and tooth), and to periderm. During early development, there is a spatial correspondence in the distribution of K17 and that of lymphoid-enhancer factor (lef-1), a DNA-bending protein involved in inductive epithelial-mesenchymal interactions. We demonstrate that ectopic lef-1 expression induces K17 protein in the skin of adult transgenic mice. The pattern of K17 gene expression during development has direct implications for the morphogenesis of skin epithelia, and points to the existence of a molecular relationship between development and wound repair.

Entamoeba histolytica causes intestinal secretion: role of serotonin.

Lysates of the protozoan parasite Entamoeba histolytica altered active electrolyte transport when present on the serosal surface of rabbit ileum and rat colon. The lysate-induced effects on electrolyte transport were similar to those caused by serotonin, and were blocked by bufotenine, an analog known to inhibit the action of serotonin. The transport effects were partially inhibited by antibody to serotonin. The amebic lysates were shown to contain serotonin by radioimmunoassay, high-performance liquid chromatography, and thin-layer chromatography. These results suggest that the serotonin present in Entamoeba histolytica may be important in the diarrhea seen in amebiasis.

Osteonecrosis of the jaws: a 14-year retrospective survey of hospital admissions.

BACKGROUND: Osteonecrosis of the jaw (ONJ) is a serious complication of both radiation and antiresorptive therapies. This study aimed to determine how many patients have been treated for medication-related osteonecrosis of the jaws (MRONJ) and osteoradionecrosis (ORN), and whether the number of diagnoses has decreased over time with improved awareness and preventative measures. METHODS: Medical records at the Royal Brisbane and Women's Hospital, Gold Coast University Hospital and Robina Hospital were reviewed to identify patients diagnosed with MRONJ and ORN between January 2003 and May 2017. Data on patient demographics, year of admission and primary disease were analysed. RESULTS: Two hundred and thirty-eight patients were diagnosed with ONJ, of which 74.4% were ORN and 25.6% were MRONJ. Tongue (24.6%), floor of mouth (17.3%) and tonsillar (15.1%) squamous cell carcinomas were the most common primary diseases associated with ORN, with a strong male predominance (80%). Of patients diagnosed with MRONJ, 52.5% were taking low-dose antiresorptives for osteoporosis (44.2%), rheumatoid arthritis (4.6%) or Paget's disease (3.3%), while 47.5% were oncology patients receiving high-dose antiresorptives. CONCLUSIONS: The number of patients diagnosed with MRONJ and ORN has trended upwards since 2003. ORN affected three times more patients than MRONJ, and patients on low-dose antiresorptives accounted for over half of the MRONJ cases.

Ectopic expression of Hel-N1, an RNA-binding protein, increases glucose transporter (GLUT1) expression in 3T3-L1 adipocytes.

3T3-L1 preadipocytes ectopically expressing the mammalian RNA-binding protein Hel-N1 expressed up to 10-fold more glucose transporter (GLUT1) protein and exhibited elevated rates of basal glucose uptake. Hel-N1 is a member of the ELAV-like family of proteins associated with the induction and maintenance of differentiation in various species. ELAV proteins are known to bind in vitro to short stretches of uridylates in the 3' untranslated regions (3'UTRs) of unstable mRNAs encoding growth-regulatory proteins involved in transcription and signal transduction. GLUT1 mRNA also contains a large 3'UTR with a U-rich region that binds specifically to Hel-N1 in vitro. Analysis of the altered GLUT1 expression at the translational and posttranscriptional levels suggested a mechanism involving both mRNA stabilization and accelerated formation of translation initiation complexes. These findings are consistent with the hypothesis that the Hel-N1 family of proteins modulate gene expression at the level of mRNA in the cytoplasm.

Neuropilin-1 is upregulated in the adaptive response of prostate tumors to androgen-targeted therapies and is prognostic of metastatic progression and patient mortality.

Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define NRP1 as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC). Using short hairpin RNA (shRNA)-mediated suppression of NRP1, we demonstrate that NRP1 regulates the mesenchymal phenotype of mCRPC cell models and the invasive and metastatic dissemination of tumor cells in vivo. In patients, immunohistochemical staining of tissue microarrays and mRNA expression analyses revealed a positive association between NRP1 expression and increasing Gleason grade, pathological T score, positive lymph node status and primary therapy failure. Furthermore, multivariate analysis of several large clinical prostate cancer (PCa) cohorts identified NRP1 expression at radical prostatectomy as an independent prognostic biomarker of biochemical recurrence after radiation therapy, metastasis and cancer-specific mortality. This study identifies NRP1 for the first time as a novel androgen-suppressed gene upregulated during the adaptive response of prostate tumors to ATTs and a prognostic biomarker of clinical metastasis and lethal PCa.

Glucose transporter gene expression: regulation of transcription and mRNA stability.

The facilitated diffusion of D-glucose across the plasma membrane is carried out by a set of stereospecific transport proteins known as the glucose transporters. These integral membrane proteins are members of a gene family where tissue-specific expression of one or more members will determine in part the net rate of glucose entry into the cell. The regulation of glucose transporter gene expression is a critical feature of cellular homeostasis, as defects in specific transporter expression can lead to profound alterations in cellular physiology. In this review, we provide a brief descriptive background on the family of glucose transporters and examine in depth the regulation of the two transporters expressed in adipose tissue, GLUTI, a basal growth-related transporter and GLUT4, the insulin-responsive glucose transporter.

A multigene array for measurable residual disease detection in AML patients undergoing SCT.

AML is a diagnosis encompassing a diverse group of myeloid malignancies. Heterogeneous genetic etiology, together with the potential for oligoclonality within the individual patient, have made the identification of a single high-sensitivity marker of disease burden challenging. We developed a multiple gene measurable residual disease (MG-MRD) RQ-PCR array for the high-sensitivity detection of AML, retrospectively tested on 74 patients who underwent allo-SCT at the NHLBI in the period 1994-2012. MG-MRD testing on peripheral blood samples prior to transplantation demonstrated excellent concordance with traditional BM-based evaluation and improved risk stratification for post-transplant relapse and OS outcomes. Pre-SCT assessment by MG-MRD predicted all clinical relapses occurring in the first 100 days after allo-SCT compared with 57% sensitivity using WT1 RQ-PCR alone. Nine patients who were negative for WT1 prior to transplantation were correctly reclassified into a high-risk MG-MRD-positive group, associated with 100% post-transplant mortality. This study provides proof of principle that a multiple gene approach may be superior to the use of WT1 expression alone for AML residual disease detection.

Mycobacterium avium intracellulare complex infection in HIV-infected children.

OBJECTIVE: To describe the incidence of, and risk factors for, Mycobacterium avium intracellulare complex (MAC) infection in HIV-infected children. SETTING: University-affiliated children's hospital. DESIGN AND METHODS: The medical records of 70 HIV-infected infants and children were reviewed retrospectively. RESULTS: Seven children (10% of the HIV-infected patients; 18% of those with AIDS) developed disseminated MAC (dMAC). An additional seven children had gastrointestinal colonization with MAC. Risk of dMAC was associated with increasing age, decreasing CD4 cell count, and (possibly) long-term steroid therapy. CONCLUSIONS: HIV-infected children are at risk of developing dMAC. Children older than 60 months and those with a CD4 cell count < 100 x 10(6)/l are most at risk.

Keratin 17 expression in the hard epithelial context of the hair and nail, and its relevance for the pachyonychia congenita phenotype.

The hard-keratin-containing portion of the murine hair shaft displays a positive immunoreactivity with an antibody against the soft epithelial keratin, K17. The K17-expressing cell population is located in the medulla compartment of the hair. Consistent with this observation, K17-containing cells also occur in the presumptive medulla precursor cells located in the hair follicle matrix. Western blot analysis of hair extracts prepared from a number of mouse strains confirms this observation and suggests that K17 expression in the hair shaft is a general trait in this species. The expression of K17 in human hair extracts is restricted to eyebrow and facial hair samples. These are the major sites for the occurrence of the pili torti (twisted hair) phenotype in the type 2 (Jackson-Lawler) form of pachyonychia congenita, previously shown to arise from inherited K17 mutations. Given that all forms of pachyonychia congenita show an involvement of the nail, we compared the expression of the two other genes mutated in pachyonychia congenita diseases, K6 and K16, with that of K17 in human nail. All three keratins are abundantly expressed within the nail bed epithelium, whereas K17 protein is expressed in the nail matrix, which contains the epithelial cell precursors for the nail plate. Our data suggest a role for K17 in the formation and maintenance of various skin appendages and directly support the concept that pachyonychia congenita is a disease of the nail bed.