Expression analysis of mTOR-associated lncRNAs in multiple sclerosis

Metabolic Brain Disease - mTOR has been shown to be involved in the regulation of immune responses and differentiation of immune cells. This protein is a candidate molecule for unraveling the...     

Gentamicin may have no effect on mortality of staphylococcal prosthetic valve endocarditis

Purpose

To analyze the influence of adding gentamicin to a regimen consisting of β-lactam or vancomycin plus rifampicin on survival in patients suffering from Staphylococcal prosthetic valve endocarditis (SPVE).

One-pot sequential multicomponent reaction between in situ generated aldimines and succinaldehyde: facile synthesis of substituted pyrrole-3-carbaldehydes and applications towards medicinally important fused heterocycles

An efficient sequential multi-component method for the synthesis of N-arylpyrrole-3-carbaldehydes has been developed. This reaction involved a proline-catalyzed direct Mannich reaction-cyclization sequence between succinaldehyde and in situ generated Ar/HetAr/indolyl-imines, followed by IBX-mediated oxidative aromatization in one-pot operation. The practical utility of this procedure is shown at gram-scale and the synthesis of diverse bioactive fused heterocyclic scaffolds such as pyrroloquinoline, pyrrolo-oxadiazole, dihydro pyrroloquinoline, and pyrrolo-phenanthridine.

An efficient sequential multi-component method for the synthesis of N-arylpyrrole-3-carbaldehydes has been developed.     

Fungal Orbital Cellulitis: Presenting Features,Management and Outcomes at a Referral Center

Purpose: To report a series of patients with fungal orbital cellulitis who underwent exenteration surgery and describe presenting features, management and outcomes at a referral center.

Methods: Retrospective case series.

Results: From November 2011 to March 2014, four patients underwent orbital exenteration for fungal orbital cellulitis at the University of Illinois. Three patients had mucormycosis and one had aspergillosis. All patients were treated with intravenous antifungals and underwent orbital exenteration. Two patients were successfully treated with supplemental intra-orbital catheter delivery of amphotericin B. Presenting visual acuity in the affected eye ranged from 20/25 to no light perception. Some level of ophthalmoplegia was present in three patients. Significantly elevated intraocular pressure was found in two patients. All patients with mucormycosis were found to have uncontrolled diabetes mellitus. One patient had a history of myelodysplastic syndrome, chronic hepatitis C infection, polysubstance abuse and Crohn’s disease. Another patient had a history of alcoholic liver cirrhosis, Crohn’s disease treated with systemic immunosuppression and renal cell carcinoma. The patient with aspergillosis had myelodysplastic syndrome and portal hypertension, and the initial presentation resembled giant cell arteritis. Two of four patients died during their hospitalization.

Conclusions: Fungal orbital cellulitis has a high mortality rate despite aggressive antifungal treatment and orbital exenteration performed soon after the diagnosis is confirmed. Patients often have a history of immunosuppression and the onset may be insidious. There must be a high rate of suspicion for fungal orbital cellulitis given the appropriate signs and medical history in order to avoid treatment delay.     

Phenotypic Assays to Determine Virulence Factors of Uropathogenic Escherichia coli (UPEC) Isolates and their Correlation with Antibiotic Resistance Pattern

Objectives

Urinary tract infection caused by uropathogenic Escherichia coli (UPEC) strains is one of the most important infections in the world. UPEC encode widespread virulence factors closely related with pathogenesis of the bacteria. The purpose of this study was to evaluate the presence of different phenotypic virulence markers in UPEC isolates and determine their correlation with antibiotic resistance pattern.

Methods

UPEC isolates from patients with different clinical symptoms of UTI were collected and screened for biofilm and hemolysin production, mannose resistant, and mannose sensitive hemagglutination (MRHA and MSHA, respectively). In addition, antimicrobial resistance pattern and ESBL-producing isolates were recorded.

Results

Of the 156 UPEC isolates, biofilm and hemolysin formation was seen in 133 (85.3%) and 53 (34%) isolates, respectively. Moreover, 98 (62.8%) and 58 (37.2%) isolates showed the presence of Types 1 fimbriae (MSHA) and P fimbriae (MRHA), respectively. Our results also showed a relationship between biofilm formation in UPEC isolated from acute cystitis patients and recurrent UTI cases. Occurrence of UTI was dramatically correlated with the patients'' profiles. We observed that the difference in antimicrobial susceptibilities of the biofilm and nonbiofilm former isolates was statistically significant. The UPEC isolates showed the highest resistance to ampicillin, tetracycline, amoxicillin, and cotrimoxazole. Moreover, 26.9% of isolates were ESBL producers.

Conclusion

This study indicated that there is a relationship between the phenotypic virulence traits of the UPEC isolates, patients'' profiles, and antibiotic resistance. Detection of the phenotypic virulence factors could help to improve understanding of pathogenesis of UPEC isolates and better medical intervention.     

Continuation rates and reasons for discontinuation of intra-uterine device in three provinces of Pakistan: results of a 24-month prospective client follow-up

Background

Long-acting reversible contraceptives, such as the intrauterine device (IUD), remain underutilised in Pakistan with high discontinuation rates. Based on a 24-month prospective client follow-up (nested within a larger quasi-experimental study), this paper presents the comparison of two intervention models, one using private mid-level providers branded as “Suraj” and the other using community midwives (CMWs) of Maternal Newborn and Child Health Programme, for method continuation among IUD users. Moreover, determinants of IUD continuation and the reasons for discontinuation, and switching behaviour were studied within each arm.

Methods

A total of 1,163 IUD users, 824 from Suraj and 339 from the CMW model, were enrolled in this 24-month prospective client follow-up. Participants were followed-up by female community mobilisers physically every second month to ascertain continued IUD usage and to collect information on associated factors, switching behaviour, reasons for discontinuation, and pregnancy occurrence. The probabilities of IUD continuation and the risk factors for discontinuation were estimated by life table analysis and Cox proportional-hazard techniques, respectively.

Results

The cumulative probabilities of IUD continuation at 24 months in Suraj and CMW models were 82% and 80%, respectively. The difference between the two intervention areas was not significant. The probability distributions of IUD continuation were also similar in both interventions (Log rank test: χ² = 0.06, df = 1, P = 0.81; Breslow test: χ² = 0.6, df = 1, P = 0.44). Health concerns (Suraj = 57.1%, CMW = 38.7%) and pregnancy desire (Suraj = 29.3%, CMW = 40.3%) were reported as the most prominent reasons for IUD discontinuation in both intervention arms. IUD discontinuation was significantly associated with place of residence in Suraj and with age (15–25 years) in the CMW model.

Conclusion

CMWs and private providers are equally capable of providing quality IUD services and ensuring higher method continuation. Pakistan’s National Maternal Newborn and Child Health programme should consider training CMWs and providing IUDs through them. Moreover, private sector mid-level providers could be engaged in promoting the use of IUDs.

     

Differences in COVID-19 Preventive Behavior and Food Insecurity by HIV Status in Nigeria

AIDS and Behavior - The aim of the study was to assess if there were significant differences in the adoption of COVID-19 risk preventive behaviors and experience of food insecurity by people living...     

Ventricular fibrillation in a left ventricular assist device patient: Can the echocardiogram be misleading?

Sustained ventricular tachycardia and ventricular fibrillation (VF) are life-threatening arrhythmias which remain highly prevalent in patients with advanced heart failure. These ventricular arrhythmias may impair the support provided by continuous-flow left ventricular assist devices (CF-LVADs) and lead to frequent hospitalizations, antiarrhythmic medication use, external defibrillations, and need for heart transplantation. We report a case in which a patient with a CF-LVAD and an implantable cardioverter defibrillator at end of life presented with asymptomatic low-flow alarms and was found to have VF of unknown duration. Unique in our case was the presence of apparent organized contractility and rhythmic opening of the mitral valve on echocardiogram despite VF on electrocardiogram.     

A randomized study comparing triple versus double antiretroviral therapy or no treatment in HIV-1-infected patients in very early stage disease: the Spanish Earth-1 study

BACKGROUND: Most current guidelines state that antiretroviral therapy should be considered for HIV-infected patients with plasma HIV RNA > 5000-10000 copies/ml and CD4 cells > 500 x 10(6) cells/l. However, there is increasing concern about whether this is the optimal point to begin treatment or whether it is better to delay the initiation to more advanced stages. OBJECTIVE: To study the immunological and virological benefits of starting antiretroviral therapy at these early stages. METHODS: A total of 161 HIV-infected asymptomatic patients with CD4 cell count > 500 x 10(6) cells/l and viral load > 10000 copies/ml were randomly assigned to one of five treatment groups: no treatment, twice daily zidovudine and thrice daily zalcitabine (ZDV-ddC), twice daily zidovudine and didanosine (ZDV-ddI), twice daily stavudine and didanosine (D4T-ddI), or a twice daily three-drug regimen with stavudine and lamivudine and ritonavir. The endpoints were progression to < 350 x 10(6) cells/l CD4 cells, to < 500 x 10(6) cells/l with either two Centers for Disease Control class B symptoms or an increase of viral load > 0.5 log10 copies/ml above baseline, or to AIDS or death. In various substudies, the lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to mitogens and cytomegalovirus, and HIV-1 specific antigens and other immunophenotypic markers were also analysed. RESULTS: Progression rates to study endpoints within 1 year were greater in the control group (31%) than in all groups receiving antiretroviral therapy pooled together (5%; estimated hazard ratio 7.41; 95% confidence interval 5.72-74.55; P < 0.001). The peak mean viral load decrease was greater in the three-drug group when compared with any of the three groups with a two-drug regimen (2.32, 1.65, 1.72 and 1.84, respectively; P < or = 0.001). At 1 year, viral load remained below 20 copies/ml in 30 out of 33 patients in the three-drug group (91%) and in only eight out of 94 patients (9%) in two-drug groups (P = 0.001). The peak mean increase in CD4 cells was also greater in the three-drug group than in the double treatment arms (259 versus 85, 144 and 145 x 10(6) cells/l, respectively; P = 0.001). By comparison, 36% of patients in the three-drug group regimen had to change the therapy as a result of adverse events. Substudies were performed in 60 patients recruited at two sites. Tonsillar tissue HIV RNA was measured in seven patients (two in the two-drug groups and five in the three-drug group) in whom plasma HIV RNA was < 20 copies/ml at 1 year. It was 15151 and 133333 copies/mg tissue in the two patients from the two-drug group, < 40 copies/mg tissue in four patients in the three-drug group, and 485 copies/mg in one patient in the three-drug group. At 1 year there was a mean increase of 4.21+/-2.94% in CD8+CD38+ cells in the control group and a decrease of 9.48+/-3.36% in the two-drug groups (P = 0.01), and 19.87+/-3.64 in the three-drug group (P = 0.001 and P = 0.05, for comparisons with control group and two-drug groups, respectively). Although proliferative responses to cytomegalovirus antigens were significantly greater in those receiving antiretroviral therapy, response to HIV-1 p24 antigen was not detected in any patient in either treatment group. CONCLUSIONS: This study supports the recommendation to start antiretroviral therapy with a three-drug combination during very early stages of HIV-1 disease, at least if viral load is above a cut-off point (10000 copies/ml in our study). The risk of progression was sevenfold higher in non-treated patients at 8 months of follow-up. Some immune system parameters improved toward normal values after 1 year of antiretroviral therapy, but the proliferative response of CD4 T lymphocytes against the p24 HIV-1 antigen was not recovered. Therapeutic approaches with more potent, better-tolerated and more convenient regimens will increasingly favour early intervention with antiretroviral t     

Effect of obstruction on longitudinal left ventricular shortening in hypertrophic cardiomyopathy.

OBJECTIVES: We investigated the cause of the midsystolic drop (MSD) in left ventricular (LV) ejection velocities that are observed with hypertrophic cardiomyopathy (HCM) and severe obstruction. BACKGROUND: Dynamic obstruction is an important determinant of symptoms and adverse outcome. The MSD in velocity and flow occurs in patients with gradients >60 mm Hg. The nadir velocity in the LV occurs simultaneously with peak gradient. METHODS: We studied 36 patients with obstructive HCM and an MSD and compared them with 15 patients with HCM and no obstruction and with 25 age-matched normal control subjects. We measured LV ejection velocity proximal and distal to LV obstruction as well as tissue Doppler velocities and time intervals. RESULTS: The duration of contraction of both the septum and lateral wall is shorter in obstructed patients with the MSD than in nonobstructed HCM patients: septal contraction 203 +/- 68 ms vs. 271 +/- 41 ms (p < 0.001). Parallel reduction in the length of shortening was noted: 1.2 +/- 0.6 cm vs. 1.9 +/- 0.4 cm (p < 0.001). The ejection velocity nadir follows the septal and lateral peak velocities by 100 ms and 60 ms, respectively. The velocity nadir occurs as both walls rapidly decelerate to their premature termination: septal deceleration 79 +/- 35 cm/s2 vs. 48 +/- 21 cm/s2 (p < 0.001). With medical abolition of obstruction the MSD disappears and the duration and length of contraction normalizes. CONCLUSIONS: These data indicate that the MSD is caused by premature termination of LV segmental shortening and is a manifestation of systolic dysfunction.