Trends in sexually transmitted infection screening during COVID-19 and missed cases among adolescents.

OBJECTIVE: The COVID-19 pandemic disrupted sexual health services for young people, with potential consequences of decreasing preventive screening and increasing undiagnosed sexually transmitted infections (STIs). This study aimed to assess trends in asymptomatic screening among patients receiving STI testing and to estimate the number of STI cases that were missed during the early months of the pandemic. STUDY DESIGN: A cross-sectional study of electronic health records for chlamydia, gonorrhea, and trichomonas testing encounters from six pediatric primary care clinics in Philadelphia, July 2014 to November 2020. METHODS: A total of 35,548 testing encounters were analyzed, including 2958 during the pandemic. We assessed whether testing at each encounter was performed as asymptomatic screening, risk-based testing, or symptomatic testing. We evaluated screening trends over time and estimated the number of missed STI cases during the pandemic. RESULTS: The mean monthly testing encounters decreased from 479 per month prepandemic to 329 per month during the pandemic. The percent of tests performed as asymptomatic screening dropped from 72.5% prepandemic to a nadir of 54.5% in April 2020. We estimate that this decrease in asymptomatic screening would represent 159 missed cases (23.8% of expected cases) based on patient volume from the previous year. CONCLUSIONS: During the pandemic, the total volume of STI testing encounters and the proportion of tests performed as asymptomatic screening decreased, potentially resulting in missed diagnoses. Undiagnosed STIs can result in severe sequelae and contribute to community transmission of STIs. Efforts are needed to re-establish and sustain access to STI services for adolescents in response to disruptions caused by the pandemic.

Depression and anxiety in patients with diabetes in a Moroccan region.

AIMS: To estimate prevalence of anxiety and depression in patients with diabetes mellitus and identify their determinants. METHODS: A cross-sectional study was conducted at Hassan II University-Hospital of Fes in 2019-2020. Anxiety and depression were measured by using the Hospital Anxiety and Depression Scale (HADS). Multivariate analysis by logistic regression was used to determine factors associated with depression and anxiety, adjusting for confounding factors. All statistical analyses were conducted using EPIINFO7. RESULTS: A total of 243 diabetics were included in the study. The average age of the participants was 48.07±14.25 years, 58% were females and 72% were diagnosed with diabetes type II. The prevalence of depressive symptoms and anxiety symptoms was (18, 1%, CI95%=(13-23)) and (29.6%, CI95%=(24-35)), respectively. The prevalence of depression and anxiety was higher among women than man and increases with increasing duration of the disease. In multivariate analysis, illiterates (OR=3.19, CI95%=(1.46-6.98)), those with depression (OR=3.61, CI95%=(1.78-7.32)), and type 1 diabetics (OR=3.22, CI95%=(1.44-7.21)) are a higher risk of developing anxiety. Depression was associated with older age (OR=2, 65, CI95%=(1, 14-6, 14)), use of insulin (OR=3.77 CI95%=(1.50-9.44)) and anxiety symptoms (OR=4, 27, CI95%=(2, 05-8, 91)). CONCLUSION: High prevalence of depressive and anxiety symptoms in diabetics suggests consideration of psychological aspect in implementation of diabetes managing program.

Nuclear resonance reflectivity from a [57Fe/Cr]30 multilayer with the Synchrotron Mössbauer Source.

Mössbauer reflectivity spectra and nuclear resonance reflectivity (NRR) curves have been measured using the Synchrotron Mössbauer Source (SMS) for a [57Fe/Cr]30 periodic multilayer, characterized by the antiferromagnetic interlayer coupling between adjacent 57Fe layers. Specific features of the Mössbauer reflectivity spectra measured with π-polarized radiation of the SMS near the critical angle and at the `magnetic' maximum on the NRR curve are analyzed. The variation of the ratio of lines in the Mössbauer reflectivity spectra and the change of the intensity of the `magnetic' maximum under an applied external field has been used to reveal the transformation of the magnetic alignment in the investigated multilayer.

Risk factors for voriconazole hepatotoxicity at 12 weeks in lung transplant recipients.

Voriconazole is commonly used for prophylaxis and treatment of invasive aspergillosis in lung transplant recipients. However, the use of voriconazole may at times be limited by the development of hepatotoxicity. Our goal is to determine predictors of voriconazole-associated hepatotoxicity in lung transplant recipients. We conducted a single center retrospective cohort study of lung transplant recipients from 2006 to 2010 who received voriconazole therapy. We compared characteristics of patients who developed hepatotoxicity and those who did not. One hundred five lung transplant recipients received voriconazole. Hepatotoxicity occurred in 51% (54/105) of patients and lead to discontinuation in 34% (36/105). In univariate analysis, age less than 40 years, cystic fibrosis, use of azathioprine, history of liver disease and early initiation of voriconazole were associated with hepatotoxicity. In multivariable logistic regression analysis, perioperative initiation of voriconazole (within 30 days of transplantation) was independently associated with hepatotoxicity (OR 4.37, 95% CI: 1.53-12.43, p = 0.006). The five risk factors identified in the univariate analysis were used to build a K-nearest neighbor algorithm predictive model for hepatotoxicity. This model predicted hepatotoxicity with an accuracy of 70%. Voriconazole therapy initiated within the first 30 days of transplantation is associated with a greater risk of developing hepatotoxicity.

Strategies for the structural analysis of multi-protein complexes: lessons from the 3D-Repertoire project.

Structural studies of multi-protein complexes, whether by X-ray diffraction, scattering, NMR spectroscopy or electron microscopy, require stringent quality control of the component samples. The inability to produce 'keystone' subunits in a soluble and correctly folded form is a serious impediment to the reconstitution of the complexes. Co-expression of the components offers a valuable alternative to the expression of single proteins as a route to obtain sufficient amounts of the sample of interest. Even in cases where milligram-scale quantities of purified complex of interest become available, there is still no guarantee that good quality crystals can be obtained. At this step, protein engineering of one or more components of the complex is frequently required to improve solubility, yield or the ability to crystallize the sample. Subsequent characterization of these constructs may be performed by solution techniques such as Small Angle X-ray Scattering and Nuclear Magnetic Resonance to identify 'well behaved' complexes. Herein, we recount our experiences gained at protein production and complex assembly during the European 3D Repertoire project (3DR). The goal of this consortium was to obtain structural information on multi-protein complexes from yeast by combining crystallography, electron microscopy, NMR and in silico modeling methods. We present here representative set case studies of complexes that were produced and analyzed within the 3DR project. Our experience provides useful insight into strategies that are more generally applicable for structural analysis of protein complexes.

Polymorphisms in multiple genes contribute to the spontaneous mitochondrial genome instability of Saccharomyces cerevisiae S288C strains.

The mitochondrial genome (mtDNA) is required for normal cellular function; inherited and somatic mutations in mtDNA lead to a variety of diseases. Saccharomyces cerevisiae has served as a model to study mtDNA integrity, in part because it can survive without mtDNA. A measure of defective mtDNA in S. cerevisiae is the formation of petite colonies. The frequency at which spontaneous petite colonies arise varies by approximately 100-fold between laboratory and natural isolate strains. To determine the genetic basis of this difference, we applied quantitative trait locus (QTL) mapping to two strains at the opposite extremes of the phenotypic spectrum: the widely studied laboratory strain S288C and the vineyard isolate RM11-1a. Four main genetic determinants explained the phenotypic difference. Alleles of SAL1, CAT5, and MIP1 contributed to the high petite frequency of S288C and its derivatives by increasing the formation of petite colonies. By contrast, the S288C allele of MKT1 reduced the formation of petite colonies and compromised the growth of petite cells. The former three alleles were found in the EM93 strain, the founder that contributed approximately 88% of the S288C genome. Nearly all of the phenotypic difference between S288C and RM11-1a was reconstituted by introducing the common alleles of these four genes into the S288C background. In addition to the nuclear gene contribution, the source of the mtDNA influenced its stability. These results demonstrate that a few rare genetic variants with individually small effects can have a profound phenotypic effect in combination. Moreover, the polymorphisms identified in this study open new lines of investigation into mtDNA maintenance.

Reversed halo sign in lymphomatoid granulomatosis.

Lymphomatoid granulomatosis is a rare lymphoproliferative disorder which affects extranodal sites, most commonly lung. Radiologically, it typically presents with multiple nodular opacities that may wax and wane. The reversed halo sign has previously been reported in cryptogenic organizing pneumonia and more recently in South American blastomycosis. We describe a case of histologically proven lymphomatoid granulomatosis in a patient who presented initially with the more typical nodular opacities, which subsequently progressed into the reversed halo sign. To the best of our knowledge, this association has not been previously described.

Antiproliferative activity of CCN3: involvement of the C-terminal module and post-translational regulation.

Previous work had suggested that recombinant CCN3 was partially inhibiting cell proliferation. Here we show that native CCN3 protein secreted into the conditioned medium of glioma transfected cells indeed induces a reduction in cell proliferation. Large amounts of CCN3 are shown to accumulate both cytoplasmically and extracellularly as cells reach high density, therefore highlighting new aspects on how cell growth may be regulated by CCN proteins. Evidence is presented establishing that the amount of CCN3 secreted into cell culture medium is regulated by post-translational proteolysis. As a consequence, the production of CCN3 varies throughout the cell cycle and CCN3 accumulates at the G2/M transition of the cycle. We also show that CCN3-induced inhibition of cell growth can be partially reversed by specific antibodies raised against a C-terminal peptide of CCN3. The use of several clones expressing various portions of CCN3 established that the CT module of CCN3 is sufficient to induce cell growth inhibition.

Effects of long-term hormone treatment and of tibolone on monoamines and monoamine metabolites in the brains of ovariectomised, Cynomologous monkeys.

The effects of long-term hormone treatment on monoamines and monoamine metabolites in different regions of the primate brain were examined and compared. Ovariectomised Cynomologous monkeys received daily oral administration of either conjugated equine oestrogens (CEE), CEE + medroxyprogesterone acetate (MPA), or a low or high dose of tibolone, for a period of 2 years. Tissue punches collected from frozen sections through various regions of the forebrain, midbrain, and hindbrain were assayed for levels of dopamine, dihydroxyphenylacetic acid (DOPAC), serotonin, 5-hydroxyindole acetic acid (5-HIAA), and norepinephrine by high-performance liquid chromatography. Few differences between hormone-treated animals and ovariectomised controls were observed. No statistically significant effects of CEE relative to controls were detected in any of the seven brain regions analysed. Animals treated with CEE + MPA showed significant reductions in 5-HIAA in the dorsal raphe nucleus, a significant reduction in dopamine in the hypothalamus, and a significant reduction in serotonin (5-HT) levels in area 8AD of the frontal cortex. Similar to CEE, no significant effects of tibolone relative to controls were detected; however, animals treated with high-dose tibolone showed a decrease in 5-HT levels in the frontal cortex that approached significance and was similar to the effect of CEE + MPA. Collectively, the findings suggest that long-term oral administration of these compounds has relatively few effects on the levels of dopamine, serotonin, and their primary metabolites in the primate brain. This differs from the significant effects on serotonergic and dopaminergic systems detected following parenteral treatment with oestradiol and progesterone, and likely reflects differences between the effects of treating with CEE + MPA versus oestradiol and progesterone on brain monoaminergic systems.

Neocortical system abnormalities in autism: an fMRI study of spatial working memory.

OBJECTIVE: To test the hypothesis that deficits in spatial working memory in autism are due to abnormalities in prefrontal circuitry. METHODS: Functional MRI (fMRI) at 3 T was performed in 11 rigorously diagnosed non-mentally retarded autistic and six healthy volunteers while they performed an oculomotor spatial working memory task and a visually guided saccade task. RESULTS: Autistic subjects demonstrated significantly less task-related activation in dorsolateral prefrontal cortex (Brodmann area [BA] 9/46) and posterior cingulate cortex (BA 23) in comparison with healthy subjects during a spatial working memory task. In contrast, activation of autistic individuals was not reduced in other regions comprising the neural circuitry for spatial working memory including the cortical eye fields, anterior cingulate cortex, insula, basal ganglia, thalamus, and lateral cerebellum. Autistic subjects also did not demonstrate reduced activation in any brain regions while performing visually guided saccades. CONCLUSION: Impairments in executive cognitive processes in autism may be subserved by abnormalities in neocortical circuitry as evidenced by decreased activation in prefrontal and posterior cingulate circuitry during a spatial working memory task.

Bioethics for clinicians: 24. Brain death.

Brain death is defined as the complete and irreversible absence of all brain function. It is diagnosed by means of rigorous testing at the bedside. The advent of neurologic or brain death criteria to establish the death of a person was a significant departure from the traditional way of defining death and remains ethically challenging to some. We review the ethical, cultural, religious and legal issues surrounding brain death and outline an approach to establishing a diagnosis of brain death in clinical practice.

Hospital policy on appropriate use of life-sustaining treatment. University of Toronto Joint Centre for Bioethics/Critical Care Medicine Program Task Force.

OBJECTIVE: To describe the issues faced, and how they were addressed, by the University of Toronto Critical Care Medicine Program/Joint Centre for Bioethics Task Force on Appropriate Use of Life-Sustaining Treatment. The clinical problem addressed by the Task Force was dealing with requests by patients or substitute decision makers for life-sustaining treatment that their healthcare providers believe is inappropriate. DESIGN: Case study. SETTING: The University of Toronto Joint Centre for Bioethics/Critical Care Medicine Program Task Force on Appropriate Use of Life-Sustaining Treatment. PARTICIPANTS: The 24-member Task Force included physician and nursing leaders from five critical care units, bioethicists, a legal scholar, a health administration expert, a social worker, and a hospital public relations professional. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our specific lessons learned include a) a policy focus on process; b) use of a negotiation and mediation model, rather than a hospital ethics committee model, for this process; and c) the policy development process is itself a negotiation, so we recommend equal involvement of interested groups including patients, families, and the public. CONCLUSIONS: This article describes the key issues faced by the Task Force while developing its policy. It will provide a useful starting point for other groups developing policy on appropriate use of life-sustaining treatment.

Prospective randomized trial of 10% povidone-iodine versus 0.5% tincture of chlorhexidine as cutaneous antisepsis for prevention of central venous catheter infection.

A multicenter prospective, randomized, controlled trial, with 0.5% tincture of chlorhexidene versus 10% povidone-iodine as cutaneous antisepsis for central venous catheter (CVC) insertion, was conducted for patients in intensive care units. Of 374 patients, 242 had a CVC inserted for >3 days and were used for the primary analysis. Outcomes included catheter-related bacteremia, significant catheter colonization (> or = 15 colony-forming units [cfu]), exit-site infection, serial quantitative exit-site culture (every 72 h), and molecular subtyping of all isolates. Patients in both study groups were comparable with respect to age, sex, underlying disease, length of hospitalization, reason for line insertion, and baseline APACHE II score. Documented catheter-related bacteremia rates were 4.6 cases per 1000 catheter-days in the chlorhexidine group (n=125) and 4.1 cases per 1000 catheter-days in the povidone-iodine group (n=117; not significant [NS]). Significant catheter-tip colonization occurred in 24 (27%) of 88 patients in the povidone-iodine group and in 31 (34%) of 92 patients in the chlorhexidine group (NS). A mean exit-site colony count of 5.9 x 10(5) cfu/mL per 25 cm(2) of the surface area of skin in the povidone-iodine group versus 3.1 x 10(5) cfu/mL per 25 cm(2) in the chlorhexidine group (NS) was found. There was a trend toward fewer exit-site infections in the chlorhexidine group (0 of 125 patients) versus those in the povidone-iodine group (4 of 117 patients; P=.053). Results of an intention-to-treat analysis were unchanged from the primary analysis. No difference was demonstrable between 0.5% tincture of chlorhexidine and 10% povidone-iodine when used for cutaneous antisepsis for CVC insertion in patients in the intensive care unit.

Dual structural requirements for multilineage hematopoietic-suppressive activity of chemokine-derived peptides.

Many chemokines have direct suppressive activity in vitro and in vivo on primitive hematopoietic cells. However, few chemokine-derived peptides have shown a significant activity in inhibiting hematopoiesis. Interestingly, a peptide derived from the 34-58 sequence of the CXC chemokine platelet factor 4 (PF4) produced a 30-40% inhibition of proliferation of murine hematopoietic progenitors (CFU-MK, CFU-GM, and BFU-E) in vitro, at concentrations of 30-60-fold lower than PF4. The aim of the present work was to define the structural parameters and motifs involved in conferring biological activity to the peptide PF4(34-58). Both structural predictions and determinations revealed a new helical motif that was further localized between residues 38 and 46. This helix was necessary for binding of the peptide and for permitting the functional DLQ motif at position 54-56 to activate the putative receptor site. Peptides lacking either the helical or the DLQ motif were devoid of inhibitory activity on the hematopoietic progenitors in vitro. However, among inactive peptides, only those having the helical motif counteracted the inhibition induced by the active peptide PF4(34-58). This suggested that the helix might be required for peptide interactions with a putative receptor site, whereas the DLQ motif would be implicated in the activation of this receptor. These results identify for the first time the dual requirements for the design of chemokine-derived peptides with high suppressive activity on hematopoiesis, as well as for the design of molecules with antagonistic action.

Scorpion envenomation and serotherapy in Morocco.

A clinical and biologic study was conducted in Morocco to assess the efficiency of antivenom therapy for treating victims of scorpion stings. Epidemiologic and clinical data were collected from 275 patients envenomed by Androctonus mauretanicus mauretanicus and Buthus occitanus scorpions. Patients received antivenom or other drugs. Blood samples were collected at the time of hospital admission and 1 hr and 3 hr after treatment. Serum venom levels were quantified by using an ELISA. An association was found between clinical signs of envenoming and the level of venom in serum. Patients classified as grade II (moderate envenoming) had higher serum levels of venom level than patients classified as grade I (mild envenoming). At admission to the hospital, the mean venom concentration was not significantly different between the group not treated with antivenom, the group who received 2-5 ml of antivenom, and the group who received 10 ml of antivenom. A significant decrease in serum venom levels and an improvement in the clinical conditions were observed in patients administered 10 ml of antivenom. The lower decrease in serum venom levels in patients who received 2-5 ml of antivenom was due to lower doses of antivenom. No difference in the venom concentration was observed in patients who were not treated with antivenom. The absence of administration of antivenom increased the risk of developing clinical signs at the end of the hospitalization period. However, this risk was much higher when more than 1 hr elapsed between the time of the scorpion sting and the time of hospital admission. The results demonstrate that antivenom is effective in decreasing circulating venom and morbidity. Serotherapy is more efficient when given as soon as possible after envenomation and with adequate quantities of antivenom.

Experimental investigation of preservation injury in animal kidneys after reperfusion with Euro-Collins.

The authors evaluated the pathomorphologic alterations of removed and reperfused dog kidneys by means of light and electronmicroscopic examination. In each sample the following reversible signs were found: Hypereosinophilia (HE), Hydropic dystrophy (HD), Nuclear polymorphism (NP), Epithelial desquamation (ED), Brush border lesion (BBL), Single cell necrosis (SCN), Total tubular epithel necrosis (TTEN), Interstitial edema (IE), Perivascular edema (PE). The irreversible signs were: Basement membrane rupture (BMR), Cellular infiltration (CI), Glomerular mesangial matrix expansion (GME) and vascular lesions (VL). The most severe and mostly irreversible alterations occur in the 54-72 hours after harvesting. The authors emphasize the significance of basement membrane rupture, because the impossibility of tubular epithelial regeneration, the cellular infiltration due to its fibrogenic effect, glomerular lesion because it makes decrease the glomerular filtration rate, proceeding juxtaglomerular cell proliferation and hypertension through renin-angiotensin mechanism and vascular lesions causing renovascular hypertension and tubulopathy. The authors believe that reperfusion injury is very important factor in kidney allograft survival. Its mechanism is similar to the normal necrosis pathway, but the timing is delayed. Further investigations are needed to understand what specific alterations may occurred under blood circulation in the host to reveal more exact cause of primary graft failure after transplantation.

Evaluation of urinary enzymes in renal allograft damages by histology examination.

Acute allograft rejection (ARE) is one of the most current problem in kidney transplantation. Urinary enzymes (glutathione-S-transferase /GST/. dipeptidil-dipeptidase /DPP/) are frequently used as prognostic factors of ARE. The authors compared the results of light microscopic study (by Banff scheme), and the GST, and DPP secretion in acute rejection. The correlation between the laboratory, and histology findings wasn't significant. our results suggest that both GST, and DPP are very sensitive, but less specific indicators in ARE, since their activity increases in many other damages as well.

Bioethics for clinicians: 5. Substitute decision-making.

Substitute decision-making is a means of making health care decisions on behalf of people who are incapable of making these decisions for themselves. It is based on the ethical principle of respect for autonomy. Substitute decision-making poses two main questions: Who-should make the decision for the incapable person, and, How should the decision be made? Because the applicable statutory and common law varies across Canada, clinicians should become familiar with the legal requirements of their own province or territory.