Association between levothyroxine replacement therapy and osteoporosis in Riyadh, Saudi Arabia: a matched case-control study.

Hypothyroidism is a common health problem among elder women. However, conflicting results were observed regarding the association between levothyroxine treatment and osteoporosis risk. Therefore, the current study aimed to evaluate the effect of levothyroxine replacement therapy on osteoporosis risk in the Saudi population. This study was a matched case-control study conducted from June to August 2020. Data were extracted from the electronic medical records and included sociodemographic, clinical characteristics, comorbid conditions, levothyroxine replacement therapy dose, duration, concomitant therapy, and bone mineral density. Cases were matched with controls (1:1 basis) by age; the study included 256 cases and 256 controls. In the multivariate conditional logistic regression analysis, thyroxine use was independently associated with an increased likelihood of osteoporosis. Therefore levothyroxine use in elderly females was associated with an increased risk of osteoporosis, and hence, clinicians must be aware of the levothyroxine replacement therapy outcomes in postmenopausal females at risk of osteoporosis.

Cigarette smoke exposure inhibits contact hypersensitivity via the generation of platelet-activating factor agonists.

Previous studies have established that pro-oxidative stressors suppress host immunity because of their ability to generate oxidized lipids with platelet-activating factor receptor (PAF-R) agonist activity. Although exposure to the pro-oxidative stressor cigarette smoke (CS) is known to exert immunomodulatory effects, little is known regarding the role of PAF in these events. The current studies sought to determine the role of PAF-R signaling in CS-mediated immunomodulatory effects. We demonstrate that CS exposure induces the generation of a transient PAF-R agonistic activity in the blood of mice. CS exposure inhibits contact hypersensitivity in a PAF-R-dependent manner as PAF-R-deficient mice were resistant to these effects. Blocking PAF-R agonist production either by systemic antioxidants or treatment with serum PAF-acetyl hydrolase enzyme blocked both the CS-mediated generation of PAF-R agonists and PAF-R-dependent inhibition of contact hypersensitivity (CHS) reactions, indicating a role for oxidized glycerophosphocholines with PAF-R agonistic activity in this process. In addition, cyclooxygenase-2 inhibition did not block PAF-R agonist production but prevented CS-induced inhibition of CHS. This suggests that cyclooxygenase-2 acts downstream of the PAF-R in mediating CS-induced systemic immunosuppression. Moreover, CS exposure induced a significant increase in the expression of the regulatory T cell reporter gene in Foxp3(EGFP) mice but not in Foxp3(EGFP) mice on a PAF-R-deficient background. Finally, regulatory T cell depletion via anti-CD25 Abs blocked CS-mediated inhibition of CHS, indicating the potential involvement of regulatory T cells in CS-mediated systemic immunosuppression. These studies provide the first evidence, to our knowledge, that the pro-oxidative stressor CS can modulate cutaneous immunity via the generation of PAF-R agonists produced through lipid oxidation.

Respecting shape memory to optimize peritoneal dialysis catheter outcomes.

Disruption of the shape memory of a peritoneal dialysis catheter at the time of insertion may be a factor responsible for tip migration and catheter dysfunction. The use of postimplantation radiology to confirm the preservation of both the swan neck angle and the inclination angle may have a role in standardizing insertion technique with the potential to reduce the impact of operator variation on catheter outcomes.

The environmental stressor ultraviolet B radiation inhibits murine antitumor immunity through its ability to generate platelet-activating factor agonists.

Ubiquitous pro-oxidative stressor ultraviolet B radiation (UVB) to human or mouse skin generates platelet-activating factor (PAF) and novel oxidatively modified glycerophosphocholines (Ox-GPCs) with PAF-receptor (PAF-R) agonistic activity. These lipids mediate systemic immunosuppression in a process involving IL-10. The current studies sought to determine the functional significance of UVB-mediated systemic immunosuppression in an established model of murine melanoma. We show that UVB irradiation augments B16F10 tumor growth and is dependent on host, but not melanoma cell; PAF-R-expression as UVB or the PAF-R agonist, carbamoyl PAF (CPAF), both promote B16F10 tumor growth in wild-type (WT) mice, independent of whether B16F10 cells express PAF-Rs, but do not augment tumor growth in Pafr -/- mice. UVB-mediated augmentation of experimental murine tumor growth was inhibited with antioxidants, demonstrating the importance of Ox-GPC PAF-R agonists produced non-enzymatically. Host immune cells are required as CPAF-induced augmentation of tumor growth which is not seen in immunodeficient NOD SCID mice. Finally, depleting antibodies against IL-10 in WT mice or depletion of CD25-positive cells in FoxP3(EGFP) transgenic mice block UVB and/or CPAF-induced tumor growth supporting a requirement for IL-10 and Tregs in this process. These findings indicate that UVB-generated Ox-GPCs with PAF-R agonistic activity enhance experimental murine melanoma tumor growth through targeting host immune cells, most notably Tregs, to mediate systemic immunosuppression.

Comparative cost and performance of light-emitting diode microscopy in HIV-tuberculosis-co-infected patients.

Light-emitting diode (LED) microscopy has recently been endorsed by the World Health Organization (WHO). However, it is unclear whether LED is as accurate and cost-effective as Ziehl-Neelsen (ZN) microscopy or mercury vapour fluorescence microscopy (MVFM) in tuberculosis (TB)-HIV-co-infected subjects. Direct and concentrated sputum smears from TB suspects were evaluated using combinations of LED microscopy, ZN microscopy and MVFM. Median reading time per slide was recorded and a cost analysis performed. Mycobacterial culture served as the reference standard. 647 sputum samples were obtained from 354 patients (88 (29.8%) were HIV-infected and 161 (26%) were culture-positive for Mycobacterium tuberculosis). Although overall sensitivity of LED compared with ZN microscopy or MVFM was similar, sensitivity of all three modalities was lower in HIV-infected patients. In the HIV-infected group, the sensitivity of LED microscopy was higher than ZN microscopy using samples that were not concentrated (46 versus 39%; p = 0.25), and better than MVFM using concentrated samples (56 versus 44; p = 0.5). A similar trend was seen in the CD4 count <200 cells · mL(-1) subgroup. Median (interquartile range) reading time was quicker with LED compared with ZN microscopy (1.8 (1.7-1.9) versus 2.5 (2.2-2.7) min; p ≤ 0.001). Average cost per slide read was less for LED microscopy (US$1.63) compared with ZN microscopy (US$2.10). Among HIV-TB-co-infected patients, LED microscopy was cheaper and performed as well as ZN microscopy or MVFM independent of the staining (ZN or auramine O) or processing methods used.

Initial Mapping of the New York City Wastewater Virome.

Bacteriophages are abundant members of all microbiomes studied to date, influencing microbial communities through interactions with their bacterial hosts. Despite their functional importance and ubiquity, phages have been underexplored in urban environments compared to their bacterial counterparts. We profiled the viral communities in New York City (NYC) wastewater using metagenomic data collected in November 2014 from 14 wastewater treatment plants. We show that phages accounted for the largest viral component of the sewage samples and that specific virus communities were associated with local environmental conditions within boroughs. The vast majority of the virus sequences had no homology matches in public databases, forming an average of 1,700 unique virus clusters (putative genera). These new clusters contribute to elucidating the overwhelming proportion of data that frequently goes unidentified in viral metagenomic studies. We assigned potential hosts to these phages, which appear to infect a wide range of bacterial genera, often outside their presumed host. We determined that infection networks form a modular-nested pattern, indicating that phages include a range of host specificities, from generalists to specialists, with most interactions organized into distinct groups. We identified genes in viral contigs involved in carbon and sulfur cycling, suggesting functional importance of viruses in circulating pathways and gene functions in the wastewater environment. In addition, we identified virophage genes as well as a nearly complete novel virophage genome. These findings provide an understanding of phage abundance and diversity in NYC wastewater, previously uncharacterized, and further examine geographic patterns of phage-host association in urban environments.IMPORTANCE Wastewater is a rich source of microbial life and contains bacteria, viruses, and other microbes found in human waste as well as environmental runoff sources. As part of an effort to characterize the New York City wastewater metagenome, we profiled the viral community of sewage samples across all five boroughs of NYC and found that local sampling sites have unique sets of viruses. We focused on bacteriophages, or viruses of bacteria, to understand how they may influence the microbial ecology of this system. We identified several new clusters of phages and successfully associated them with bacterial hosts, providing insight into virus-host interactions in urban wastewater. This study provides a first look into the viral communities present across the wastewater system in NYC and points to their functional importance in this environment.

Unintended molecular interactions in transgenic plants expressing clinically useful proteins: the case of bovine aprotinin traveling the potato leaf cell secretory pathway.

We assessed the impact of subcellular targeting on the heterologous expression of a clinically useful protease inhibitor, bovine aprotinin, in leaves of potato, Solanum tuberosum. Transgenic potato lines targeting aprotinin to the cytosol, the ER or the apoplast were first generated, and then assessed for their ability to accumulate the recombinant protein. On-chip detection and quantitation of aprotinin variants by SELDI TOF MS showed the inhibitor to be absent in the cytosol, but present under different forms in the ER and the apoplast. No visible phenotypic effects of aprotinin were observed for the transgenic lines, but aprotinin retention in the ER was associated with a significant decrease of leaf soluble protein content. A 2-D gel assessment of control and transgenic lines revealed a possible link between this altered protein content and the down-regulation of proteins implicated in protein synthesis and maturation. These observations, supported by complementary 2-DE analyses with potato lines targeting aprotinin to the apoplast, suggest an aprotinin-mediated feedback in planta negatively altering protein anabolism. From a practical viewpoint, these data illustrate the importance of taking into account not only the characteristics of recombinant proteins expressed in heterologous environments, but also their possible effects on protein accumulation in the host plant factory.

A SELDI-TOF MS procedure for the detection, quantitation, and preliminary characterization of low-molecular-weight recombinant proteins expressed in transgenic plants.

We describe a SELDI-TOF MS procedure for the rapid detection and quantitation of low-molecular-weight recombinant proteins expressed in plants. Transgenic lines of potato (Solanum tuberosum L.) expressing the clinically useful protein bovine aprotinin or the cysteine protease inhibitor corn cystatin II were generated by Agrobacterium tumefaciens-mediated transformation, and then used as test material for the analyses. Real-time RT-PCR amplifications and detection of the recombinant proteins by immunoblotting were first conducted for transformed potato lines accumulating the proteins in different cell compartments. Both proteins were found at varying levels in leaves, depending on their final cellular destination and transgene expression rate. These conclusions drawn from standard immunodetection assays were easily confirmed by SELDI-TOF MS comparative profiling, after immobilizing the leaf proteins of control and transformed lines on protein biochips for weak cationic exchange. This procedure, carried out in less than 2 h, allows for the rapid comparison of recombinant protein levels in transgenic plant lines. The molecular weight of immobilized proteins can also be determined directly from the MS spectra, thus providing a simple way to assess the structural integrity and homogeneity of recombinant proteins in planta, and to identify the most suitable cellular compartments for their heterologous production.

Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis.

BACKGROUND: The diagnosis of smear-negative pulmonary tuberculosis (TB) is problematic. There are limited data on the profile of alveolar TB antigen-specific T cells, and their utility for the rapid immunodiagnosis of pulmonary TB is unclear. METHODS: Antigen-specific interferon gamma (IFNgamma) responses to the RD-1 antigens ESAT-6 and CFP-10 (T-SPOT.TB and QuantiFERON-TB-Gold-In-Tube), heparin-binding haemagglutinin and purified protein derivative were evaluated, using alveolar lavage cells, in 91 consecutively recruited South African patients suspected of having TB. RESULTS: Of 85 evaluable patients (29% HIV+), 24, 11, 48 and 2 had definite TB, probable TB, non-TB and an uncertain diagnosis, respectively. Between 34% (T-SPOT.TB) and 41% (QuantiFERON-TB-Gold-In-Tube) of all test results were inconclusive. Failure of the positive control was significantly higher with the QuantiFERON-TB-Gold-In-Tube than with T-SPOT.TB (85% vs 46% of inconclusive results; p = 0.001). Using staphylococcal enterotoxin B, compared with phytohaemagglutinin, substantially reduced failure of the positive control (25% to 3%; p = 0.02). In evaluable samples, when the definite and non-TB groups were used for outcome analysis, the percentage sensitivity, specificity, positive predictive value and negative predictive value for T-SPOT.TB (> or = 20 spots/million alveolar mononuclear cells) and QuantiFERON-TB-Gold-In-Tube (0.35 IU/ml) were 89, 94, 89 and 94% (n = 55) and 55, 86, 77 and 69% (n = 46), respectively. Rapid diagnosis of TB was achieved more frequently with T-SPOT.TB than with smear microscopy (14/24 (58%) vs. 7/24 (29%) of definite TB cases; p = 0.02). Heparin-binding haemagluttinin and purified protein derivative alveolar lymphocyte IFNgamma responses had poor performance outcomes. CONCLUSION: Provided evaluable results are obtained, the RD-1, but not the heparin-binding haemagglutinin or purified protein derivative, alveolar lymphocyte IFNgamma ELISPOT response is a useful rapid immunodiagnostic test for TB. However, test utility in high-burden settings may be limited by the high proportion of inconclusive results.

Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis.

The clinical utility of antigen-specific interferon (IFN)-gamma release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification. We compared the diagnostic utility of unstimulated pleural IFN-gamma levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.(R)TB, QuantiFERON(R)-TB Gold In-tube), purified protein derivative (PPD) and heparin-binding haemagglutinin (HBHA)) in 78 South African TB suspects. Test results were compared against a clinical score and a reference standard. Out of 74 evaluable subjects 48, seven and 19 had definite, probable and no TB, respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the definite TB cases) had total cell counts that were inadequate for T-cell processing. In the remaining 63 samples, the sensitivity, specificity, positive predictive value and negative predictive value of different diagnostic methods were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T-SPOT.(R)TB: 86, 60, 84 and 64%, respectively; QuantiFERON(R)-TB Gold In-tube: 57, 80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%, respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural fluid unstimulated IFN-gamma: 97, 100, 100 and 94%, respectively. Unstimulated IFN-gamma was the most accurate test for distinguishing TB from non-TB effusions in a high-burden setting. The antigen-specific T-cell IGRAs were limited by suboptimal accuracy and the inability to isolate sufficient mononuclear cells to perform the assay.

Synthesis of thiazolo- and 7,8-dihydrothiazolo[4,5-e]benzoisoxazoles.

The first examples of thiazolo[4,5-e]benzoisoxazoles are obtained from bromination of dihydrobenzo[d]isoxazol-4(5H)-one followed by cyclocondensation with thiourea, in the presence of DDQ. Analogously, cyclocondensation with thioamides provided 7,8-dihydrothiazolo[4,5-e]benzoisoxazoles. A 55-member library of these heterocycles is reported.

Clinical and microbiological features of bacteraemia with Gram-positive anaerobic cocci: a population-based retrospective study.

OBJECTIVES: Gram-positive, anaerobic cocci (GPAC) can cause infections in humans. Only a few cases of bacteraemia with GPAC have been reported. We describe the clinical and microbiological characteristics of GPAC bacteraemia. METHODS: A retrospective population-based study of GPAC bacteraemia 2012-2016 in southern Sweden was performed. GPAC were identified using matrix-associated laser desorption ionization time-of-flight mass spectrometry or 16S rRNA gene sequencing. Etests were used to determine antibiotic susceptibilities. Data on patient and infection characteristics, treatment, and outcome were collected from the medical records. RESULTS: A total of 226 episodes of GPAC bacteraemia in adults were studied; this corresponds to an annual incidence of 3.4 cases per 100,000 persons per year. The bacteria identified were Anaerococcus spp. (n = 43), Atopobium spp. (n = 7), Blautia spp. (n = 1), Finegoldia spp. (n = 15), Parvimonas spp. (n = 100), Peptoniphilus spp. (n = 52), Peptostreptococcus spp. (n = 2), and Ruminococcus spp. (n = 9) of which 200 isolates were identified to the species level. Resistance to imipenem and piperacillin was not identified, whereas resistance among the 229 isolates to penicillin was detected in four, to metronidazole in six, and clindamycin in 16 isolates. The median age of patients was 73 years (55-83, IQR), 57% were male and comorbidities were common. Fifty-one per cent of infections were polymicrobial. In 60% of cases a focus of infection was identified. Forty per cent of patients had either organ dysfunction or shock. The 30-day mortality was 11%, and nosocomial infections were over-represented among the deceased. CONCLUSIONS: GPAC bacteraemia is much more common than previously reported. GPAC-bacteraemia is a condition with significant mortality mainly affecting elderly persons with comorbidities.

Variability in response to salinity stress in natural Tunisian populations of Hordeum marinum subsp. marinum.

Soil salinity is one of the most serious environmental factors affecting crop productivity around the world. In this study, we analysed morpho-physiological variation in responses to salt stress in Tunisian populations of Hordeum marinum subsp. marinum. The plants were grown under two treatments (0 and 200 mm NaCl) until maturity. A total of 19 quantitative traits were measured before and during the harvest. It was observed that most studied traits are influenced by the increasing salinity. High to moderate broad-sense heritability (H2 ) were noted for most of parameters under control and salt treatment, implying that salt tolerance is moderately heritable and environmental variation plays an equally important role. The majority of correlations between measured traits under the two treatments are positive, where the strongest correlations were between spike number (SN) and weight (SW). Based on the salt response index (SRI) values, SN and SW are the most affected by salinity. The 150 studied lines formed three groups according to the SRI values of the 19 quantitative parameters, of which 101 were moderately sensitive, 27 tolerant and 22 highly tolerant. Overall genetic variation of H. marinum in response to salt stress may provide novel insight to identify genes responsible for salt tolerance.

Surgical peritonitis in patients on peritoneal dialysis.

In this short review we highlight the diagnostic challenge presented by surgical peritonitis in peritoneal dialysis patients, giving attention to etiology, clinical presentation, diagnosis, and management. Despite improvements in medical imaging and a reduction in overall rates of peritonitis in peritoneal dialysis, the mortality of surgical peritonitis has not changed in recent years and remains a challenge for the clinical team.

Clinical characteristics and causes of heart failure, adherence to treatment guidelines, and mortality of patients with acute heart failure: Experience at Groote Schuur Hospital, Cape Town, South Africa.

BACKGROUND: There is limited information on acute heart failure (AHF) and its treatment in sub-Saharan Africa. OBJECTIVE: To describe the clinical characteristics and causes of heart failure (HF), adherence to HF treatment guidelines, and mortality of patients with AHF presenting to Groote Schuur Hospital (GSH), Cape Town, South Africa. METHODS: This sub-study of The Sub-Saharan Africa Survey of Heart Failure (THESUS-HF) was a prospective and observational survey that focused on the enrolment and follow-up of additional patients with AHF presenting to GSH and entered into the existing registry after publication of the primary THESUS-HF article in 2012. The patients were classified into prevalent (existing) or incident (new) cases of HF. RESULTS: Of the 119 patients included, 69 (58.0%) were female and the mean (standard deviation) age was 49.9 (16.3) years. The majority of prevalent cases were patients of mixed ancestry (63.3%), and prevalent cases had more hypertension (70.0%), diabetes mellitus (36.7%), hyperlipidaemia (33.3%) and ischaemic heart disease (IHD) (36.7%) than incident cases. The top five causes of HF were cardiomyopathy (20.2%), IHD (19.3%), rheumatic valvular heart disease (RHD) (18.5%), cor pulmonale (11.8%) and hypertension (10.1%), with the remaining 20.1% consisting of miscellaneous causes including pericarditis, toxins and congenital heart disease. Most patients received renin-angiotensin system blockers and loop diuretics on discharge. There was a low rate of beta-blocker, aldosterone antagonist and digoxin use. Rehospitalisation within 180 days occurred in 25.2% of cases. In-hospital mortality was 8.4% and the case fatality rate at 6 months was 26.1%. CONCLUSION: In Cape Town, the main causes of AHF are cardiomyopathy, IHD and RHD. AHF affects a young population and is associated with a high rate of rehospitalisation and mortality. There is serious under-use of beta-blockers, aldosterone antagonists and digoxin. Emphasis on the rigorous application of treatment guidelines is needed to reduce readmission and mortality.

Transoral migration of the inferior end of a ventriculoperitoneal shunt: A case report with literature review.

Ventriculoperitoneal (VP) shunt surgery is the most widely used technique for the treatment of hydrocephalus. However, it can incur certain complications. Beside frequent complications (infection, obstruction), migration of the peritoneal catheter is a rare but dangerous complication. This report presents the case of a 4-year-old boy who had undergone VP shunt for hydrocephalus. One month later, the patient presented with protrusion of the peritoneal catheter through his mouth. He underwent another procedure to remove the peritoneal catheter, retaining the original ventricular catheter and valve chamber. Progression was favorable. To the best of our knowledge, only 7 cases of VP shunt transoral extrusion were reported, but many risk factors were identified. Bowel perforation is a serious complication of VP shunt surgery, sometimes leading to fatal outcome.