Knowledge and Attitudes About Sterilization and Long-Acting Reversible Contraception.

OBJECTIVES: To describe understanding of the irreversible nature of permanent contraception and knowledge and attitudes about long-acting reversible contraception (LARC) among individuals seeking and not seeking permanent contraception. METHODS: We performed a cross-sectional survey among patients with Medicaid insurance attending an obstetrics and gynecology clinic in [location]. The survey consisted of 20 true/false and Likert questions assessing knowledge and perceptions about permanent contraception and LARC. Sixty-seven participants were needed to detect a small-to-medium Cohen's effect size f2 = 0.20, with 95% power and alpha = 0.05. RESULTS: Ninety potential participants were contacted and 67 were recruited. Forty-three participants desired permanent contraception and 24 did not. Approximately half of all participants were not aware that permanent contraception is irreversible. Participants who desired permanent contraception had lower LARC knowledge scores (62% correct versus 70%, p = 0.042) and more negative perceptions about LARC (54% versus 38%, p = 0.048). Fewer participants desiring permanent contraception identified LARC efficacy as equal to permanent contraception (32% versus 83%, p < 0.01), and fewer would consider using LARC (intrauterine device: 23% versus 58%, p < 0.01; implant: 16% versus 46%, p < 0.01). These differences persisted in multivariable models adjusting for age, gravidity, and parity. CONCLUSIONS FOR PRACTICE: Individuals who desire permanent contraception may not be aware of its permanence, or of equally effective alternatives. They were also found to have more negative perceptions of LARC in our sample. Additional research is needed to understand factors underlying these differences. Counseling practices should be tailored to ensure accurate knowledge about permanent contraception and LARC for all people seeking to avoid pregnancy.

Recombinant BCG Overexpressing phoP-phoR Confers Enhanced Protection against Tuberculosis.

The live tuberculosis vaccine Mycobacterium bovis BCG (Bacille Calmette-Guérin) comprises a number of genetically distinct substrains. In BCG-Prague, phoP of the PhoP-PhoR two-component system is a pseudogene due to a single insertion mutation. We hypothesized that this mutation partially accounts for the low immunogenicity of BCG-Prague observed in the 1970s. In this study, we showed that complementation with the M. bovis allele of phoP restored BCG-Prague's immunogenicity. Furthermore, we showed that overexpression of the M. bovis allele of phoP-phoR in BCG-Japan, a strain already containing a copy of phoP-phoR, further enhanced immunogenicity and protective efficacy. Vaccination of C57BL/6 mice with the recombinant strain rBCG-Japan/PhoPR induced higher levels of interferon-γ (IFN-γ) production by CD4+ T cells than that with the parental BCG. Guinea pigs vaccinated with rBCG-Japan/PhoPR were better protected against challenge with Mycobacterium tuberculosis than those immunized with the parental BCG, showing significantly longer survival time, reduced bacterial burdens, and less severe pathology. Taken together, our study has identified a genetic modification that could be generally applied to generate new recombinant BCG vaccines.

Silencing by H-NS potentiated the evolution of Salmonella.

The bacterial H-NS protein silences expression from sequences with higher AT-content than the host genome and is believed to buffer the fitness consequences associated with foreign gene acquisition. Loss of H-NS results in severe growth defects in Salmonella, but the underlying reasons were unclear. An experimental evolution approach was employed to determine which secondary mutations could compensate for the loss of H-NS in Salmonella. Six independently derived S. Typhimurium hns mutant strains were serially passaged for 300 generations prior to whole genome sequencing. Growth rates of all lineages dramatically improved during the course of the experiment. Each of the hns mutant lineages acquired missense mutations in the gene encoding the H-NS paralog StpA encoding a poorly understood H-NS paralog, while 5 of the mutant lineages acquired deletions in the genes encoding the Salmonella Pathogenicity Island-1 (SPI-1) Type 3 secretion system critical to invoke inflammation. We further demonstrate that SPI-1 misregulation is a primary contributor to the decreased fitness in Salmonella hns mutants. Three of the lineages acquired additional loss of function mutations in the PhoPQ virulence regulatory system. Similarly passaged wild type Salmonella lineages did not acquire these mutations. The stpA missense mutations arose in the oligomerization domain and generated proteins that could compensate for the loss of H-NS to varying degrees. StpA variants most able to functionally substitute for H-NS displayed altered DNA binding and oligomerization properties that resembled those of H-NS. These findings indicate that H-NS was central to the evolution of the Salmonellae by buffering the negative fitness consequences caused by the secretion system that is the defining characteristic of the species.

Peer-reviewed publications in orthopaedic surgery from lower income countries: A comparative analysis.

INTRODUCTION: Musculoskeletal (MSK) disease is a substantial global burden, especially in lower income countries. However, limited research has been published on MSK health by scholars from these countries. We aimed to study the distribution of authorships, including trends in peer-reviewed orthopaedic publications based on each author's affiliated institution's country income status. METHODS: Based on a bibliometric search, 119 orthopaedic-related journals were identified using the Journal Citation Reports database. Details of all scientific articles published in these journals between 2012 and 2021 were used to study trends and association between each of the author's affiliated institution's country income status, using the World Bank Classification. RESULTS: Of the 133,718 unique articles, 87.6% had at least one author affiliation from a high-income country (HIC), 7.0% from an upper-middle income country (UMIC), 5.2% from a lower-middle income country (LMIC), and 0.2% from a low-income country (LIC). Overall, these articles were cited 1,825,365 times, with 92.5% of citations from HIC-affiliated authors and < 0.1% from LIC-affiliated authors. Over the 10-year study period, HIC-affiliated articles demonstrated the largest increase in the number of publications (9107-14,619), compared to UMIC-affiliated (495-1214), LMIC-affiliated (406-874), and LIC-affiliated articles (4-28). CONCLUSIONS: There are large and persistent disparities in orthopaedic research publications based on the country income status of the author's affiliated institution, especially in the higher impact orthopaedic journals. Efforts should be made to increase opportunities for scholars from LICs and LMICs to publish their research in high-impact orthopaedic journals.

Effects of mechanical stimulation on mastectomy scars within 2 months of surgery: A single-center, single-blinded, randomized controlled trial.

BACKGROUND: One common complication after mastectomy is thickened scars at the surgical site that impair shoulder function. This study aimed to investigate the effects of mechanical stimulation on scar appearance, arm function, and quality of life of breast cancer survivors after mastectomy. METHODS: This was a single-center, single-blinded (assessor), randomized controlled trial with a 3-month follow-up. Women who had undergone mastectomy in the preceding 6 weeks for breast cancer were randomly allocated to an experimental group and a control group by permuted block randomization (block size=6). The experimental group received conventional treatment (mobilization and strengthening exercises) and mechanical stimulation applied to the mastectomy scar twice a week for 6 weeks (12 sessions). The control group received 12 sessions of conventional treatment only. Primary outcome measures included the Vancouver Scar scale (VSS) to assess scar quality. The secondary outcomes were spectrophotometry, the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire; shoulder range of motion; the Numeric Pain Rating scale; hand grip strength; and Functional Assessment of Chronic Illness Therapy-Breast Cancer (FACT-B). RESULTS: One hundred and eight participants were equally randomized to 2 groups. All follow-up assessments were completed in September 2018. Intention-to-treat analysis revealed a significant group × time interaction on the VSS (η² = 0.161, p < 0.001), DASH (η² = 0.060, p = 0.003), and FACT-B functional well-being scores (η² = 0.033, p = 0.034), indicating that the experimental group (n=54) showed greater improvement in these outcomes than the control group (n=54). Post-hoc analysis showed that the improvements in the VSS and DASH scores remained apparent at the 3-month follow-up. Other outcomes did not yield significant group × time interaction. No adverse effects were reported. CONCLUSION: The addition of mechanical stimulation to a conventional intervention program improved scar appearance, arm function, and functional well-being compared with conventional intervention alone.

Loss of elongation factor P disrupts bacterial outer membrane integrity.

Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S-nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits increased uptake of the hydrophobic dye 1-N-phenylnaphthylamine (NPN). Analysis of the membrane proteomes of wild-type and efp mutant Salmonella strains reveals few changes, including the prominent overexpression of a single porin, KdgM, in the efp mutant outer membrane. Removal of KdgM in the efp mutant background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious overexpression of an outer membrane porin.

Whole-genome sequences of four Mycobacterium bovis BCG vaccine strains.

Mycobacterium bovis Bacille Calmette-Guérin (BCG) is the only vaccine available against tuberculosis (TB). A number of BCG strains are in use, and they exhibit biochemical and genetic differences. We report the genome sequences of four BCG strains representing different lineages, which will help to design more effective TB vaccines.

Lsr2 of Mycobacterium tuberculosis is a DNA-bridging protein.

Lsr2 is a small, basic protein present in Mycobacterium and related actinomycetes. Recent studies suggest that Lsr2 is a regulatory protein involved in multiple cellular processes including cell wall biosynthesis and antibiotic resistance. However, the underlying molecular mechanisms remain unknown. In this article, we performed biochemical studies of Lsr2-DNA interactions and structure-function analysis of Lsr2. Analysis by atomic force microscopy revealed that Lsr2 has the ability to bridge distant DNA segments, suggesting that Lsr2 plays a role in the overall organization and compactness of the nucleoid. Mutational analysis identified critical residues and selection of dominant negative mutants demonstrated that both DNA binding and protein oligomerization are essential for the normal functions of Lsr2 in vivo. These results provide strong evidence that Lsr2 is a DNA bridging protein, which represents the first identification of such proteins in bacteria phylogenetically distant from the Enterobacteriaceae. DNA bridging by Lsr2 also provides a mechanism of transcriptional regulation by Lsr2.

BCG vaccines: their mechanisms of attenuation and impact on safety and protective efficacy.

Mycobacterium bovis Bacille Calmette-Guérin (BCG) was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, the mechanisms of attenuation of BCG remain poorly understood. BCG is not a single organism, but comprises a number of substrains that differ in genotypes and phenotypes. The impacts of these differences on BCG vaccine properties are largely unknown. Nevertheless, in the past decade, the development of sophisticated genome analysis techniques, coupled with advances in knowledge of the virulence mechanisms of Mycobacterium tuberculosis, have provided greater insights into the attenuation and evolution of BCG. This review article discusses these new developments, focusing on molecular mechanisms that contribute to the attenuation of BCG substrains. It is evident that BCG strains comprise natural mutants of major virulence factors of M. tb, including ESX-1, PDIM/PGL and PhoP, and that BCG substrains differ markedly in virulence level. The impacts of these findings on vaccine properties including adverse reaction effect, tuberculin reactivity and protective efficacy are discussed. These new insights have extremely important implications for national immunization programs and the development of future vaccines.

Novel genome polymorphisms in BCG vaccine strains and impact on efficacy.

Bacille Calmette-Guérin (BCG) is an attenuated strain of Mycobacterium bovis currently used as a vaccine against tuberculosis. Global distribution and propagation of BCG has contributed to the in vitro evolution of the vaccine strain and is thought to partially account for the different outcomes of BCG vaccine trials. Previous efforts by several molecular techniques effectively identified large sequence polymorphisms among BCG daughter strains, but lacked the resolution to identify smaller changes. In this study, we have used a NimbleGen tiling array for whole genome comparison of 13 BCG strains. Using this approach, in tandem with DNA resequencing, we have identified six novel large sequence polymorphisms including four deletions and two duplications in specific BCG strains. Moreover, we have uncovered various polymorphisms in the phoP-phoR locus. Importantly, these polymorphisms affect genes encoding established virulence factors including cell wall complex lipids, ESX secretion systems, and the PhoP-PhoR two-component system. Our study demonstrates that major virulence factors are different among BCG strains, which provide molecular mechanisms for important vaccine phenotypes including adverse effect profile, tuberculin reactivity and protective efficacy. These findings have important implications for the development of a new generation of vaccines.

Retinal tear and raised intraocular pressure following unintentional intraocular botulinum toxin type A injection.

CASE REPORT: A 67-year-old woman with a 30-year history of dysthyroid orbitopathy and diplopia had an inadvertent injection of botulinum toxin type A into the vitreous cavity. Full pupil mydriasis and an intraocular pressure (IOP) of 50 mm Hg in the right eye were noted after the injection. An attack of acute angle closure was initially suspected despite a patent peripheral iridotomy (PI). The episode resolved with topical and intravenous IOP-lowering agents. Postoperative retinal examination revealed a retinal tear, which was successfully treated with laser photocoagulation. Visual acuity returned to baseline within 2 weeks, and the results of further retinal examinations remained stable. COMMENTS: This case supports the animal studies and human case reports that have demonstrated no retinal toxicity after intraocular injections of botulinum toxin type A. Temporary mydriasis and elevated IOP that may occur after injection do not appear to be detrimental and can be treated with topical and intravenous IOP-lowering agents. Transiently elevated IOP after injection is most likely due to volume increase, though acute angle closure with occlusion of the PI might be considered.

Surgical waiting times for ocular and periocular cancer patients in Toronto.

BACKGROUND: The purpose of this study was to evaluate surgical waiting times experienced by intraocular and periocular cancer patients in Toronto and to assess the period of greatest delay between certain stages of ocular cancer care. METHODS: A retrospective chart review was performed on cases of adult patients who underwent surgery between January 2002 and December 2004 for malignant or premalignant tumours of the eye and ocular adnexa. Waiting time intervals were calculated between 5 time points: initial presentation to referring physician or optometrist, date of referral to oculoplastics or ocular oncology, initial assessment, consent date, and surgery date. Total surgical waiting time was the period between the initial presentation and surgery date. RESULTS: The mean total surgical waiting time was 85.93 (standard error [SE] 212.70) days. The 5% trimmed mean total waiting time was 51.07 days. The longest mean total waiting time averaged 94.16 (SE 18.69) days for patients with orbital or lacrimal tumours. For all patients, the interval of greatest delay was between initial assessment and consent (according to means) or between referral and initial assessment (according to 5% trimmed means). For patients with lid, brow, or conjunctival tumours the interval of greatest delay was between referral and initial assessment, and for those with orbital, lacrimal, or intraocular tumours it was between initial assessment and consent. INTERPRETATION: By measuring the period between consent and surgery, the Ontario government is not measuring the interval of greatest delay in ocular cancer care. The wait-time registry may benefit from including data from patients with periocular tumours.

Fusobacterium and Escherichia: models of colorectal cancer driven by microbiota and the utility of microbiota in colorectal cancer screening.

Intestinal microbiota has emerging roles in the development of colorectal cancer (CRC). Intestinal dysbiosis, with altered levels of specific bacteria, is consistently seen in CRC. The heart of the debate lies in whether these bacteria are a cause or consequence of CRC. Two bacteria in particular, Fusobacterium nucleatum and Escherichia coli, have consistently been associated with CRC. This review will examine evidence supporting oncogenic roles of F. nucleatum and E. coli. The proposed mechanisms of tumor formation follow two models: bacterial induced chronic inflammation leads to cell proliferation and tumor formation and virulence factors directly induce tumor formation. This review will further examine the potential for microbiota as biomarkers in CRC, with a focus on F. nucleatum.

Impact of attending a health care conference in Toronto during the severe acute respiratory syndrome crisis: survey of delegates.

OBJECTIVE: To describe the impact on delegates of attending the Canadian Pain Society's annual meeting in Toronto during the severe acute respiratory syndrome (SARS) crisis in May 2003. METHODS: A prospective survey design was used. Surveys were sent to all delegates (n=432) who attended the conference, and 294 delegates responded (68% response rate). The survey was developed to determine the level of concern about travelling to Toronto; the adequacy of screening measures; the level of stress about attending; and the occupational consequences of attending. RESULTS: Fifty per cent of the participants were not concerned about travelling to Toronto, while the other 50% expressed some concern ranging from mild to serious. Concerns included being exposed to SARS and fear of transmitting it to others upon return. Reasons for attending the conference despite concern included a desire for continuing education, decrease in the number of reported SARS cases, and perceived minimal risk. Almost one-half (n=140) felt the screening measures at the conference were adequate, while 4% felt they were inadequate and 9% somewhat adequate. Delegates (n=99) suggested that temperature-taking (32.2%), improved screening vigilance (14.4%), SARS screening forms checked daily (9.1%), strictly controlled entry (8.1%) and adopting hospital screening procedures (7.1%) should have been instituted. CONCLUSION: Health care professionals planning conferences in this era of new respiratory diseases can benefit from understanding the responses of delegates who attended conferences during outbreaks. Clear communication about the potential risks and benefits, as well as instituting full screening precautions, will help to allay concerns.

Monovision correction for small-angle diplopia.

PURPOSE: To assess quantitatively the efficacy of monovision correction in the treatment of acquired small-angle binocular diplopia in adult patients. DESIGN: Prospective, interventional case series. METHODS: Twenty patients with symptomatic diplopia were enrolled in a prospective treatment trial at a tertiary university neuro-ophthalmology practice. All had stable deviations of 10 prism diopters or less for more than 3 months. Each received monovision spectacles, contact lenses, or both with distance correction in the dominant eye. Half received a +3.00-diopter add and the others received +2.50 diopters. The validated and standardized Diplopia Questionnaire and Amblyopia and Strabismus Questionnaire were used to quantify the efficacy of monovision correction for diplopia by measuring the functional impact on vision-specific quality of life. RESULTS: primary outcome: Based on the results of the Diplopia Questionnaire, 85% of patients experienced significant improvement in diplopia symptoms after monovision correction. There was a statistically significant 58.6% improvement in the Diplopia Questionnaire score in our patients (P < .0001). secondary outcome: The Amblyopia and Strabismus Questionnaire scores demonstrated improved quality of life and daily function after monovision correction (P = .03), especially in the areas of double vision(P = .0003) and social contact and appearance (P = .0002). CONCLUSIONS: Monovision decreased the frequency of diplopia and improved subjects' quality of life. Monovision may be a feasible alternative for presbyopic diplopic patients who are dissatisfied with other conservative treatment options.

Peripheral ulcerative keratitis in a child.

Peripheral ulcerative keratitis is a destructive process involving perilimbal corneal inflammation and an overlying epithelial defect. It can be a manifestation of systemic autoimmune diseases or can be secondary to an infectious process. We present a case of a 7-year-old girl with peripheral ulcerative keratitis of unknown etiology. To the best of our knowledge, this is the first such case reported in a child.

A survey of orthopedic surgeons' attitudes and knowledge regarding regional anesthesia.

UNLABELLED: We conducted a survey to explore the surgical attitudes and preferences regarding regional anesthesia among Canadian orthopedic surgeons. Surveys were returned by 468 (61%) of 768 surgeons. Forty-eight percent of respondents directed their patients' choice of anesthetic. Forty percent of surgeons directed their patients to choose regional anesthesia. The principal reasons for favoring regional anesthesia were less postoperative pain (32%), decreased nausea and vomiting (12%), and safety (14%). Reasons for not favoring regional anesthesia were delays in the induction of anesthesia (43%) and an unpredictable success rate (12%). This survey suggests that orthopedic surgeons are supportive of regional anesthesia. Barriers to increased popularity include perceived delays and unreliability. IMPLICATIONS: Orthopedic surgeons understand the benefits of and are supportive of the use of regional anesthesia in their practices. Barriers to increased popularity include perceived operating room delays and lack of reliability.