Role of matrix metalloproteinase-2 in newborn mouse lungs under hypoxic conditions

Hypoxia impairs normal neonatal pulmonary artery remodeling and alveolar development. Matrix metalloproteinase-2 (MMP-2), which regulates collagen breakdown, is important during development. Our objective was to test the hypothesis that hypoxia attenuates the normal postnatal increase in MMP-2 and evaluate alveolar development and pulmonary arterial remodeling in Mmp2 mice. C57BL/6 wild-type (WT), Mmp2, Mmp2, and MMP-inhibited (with doxycycline) mice were exposed to hypoxia (12% O2) or air from birth to 2 wk of age. Pulmonary arterial remodeling, alveolar development, and vascular collagen and elastin were evaluated. MMP-2 was estimated by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunohistochemistry, and zymography. We observed that 1) in WT mice, hypoxia led to thicker-walled pulmonary arteries and impaired alveolarization, accompanied by decreased MMP-2 and increased tissue inhibitor of metalloproteinases-2 (TIMP-2); 2) Mmp2 mice in air had thicker-walled arteries, impaired alveolarization, and increased perivascular collagen and elastin compared with WT; 3) hypoxia further inhibited alveolarization but did not alter arterial thickening in Mmp2 mice. Mmp2 and MMP-inhibited mice also had thicker-walled arteries than WT in air, but alveolarization was not different. We conclude that hypoxia reduces the postnatal MMP-2 increase in the lung, which may contribute to abnormal pulmonary arterial remodeling and impaired alveolarization.     

Exclusion Diets in Functional Dyspepsia

Functional dyspepsia represents one of the most common and prevalent disorders of the brain–gut interaction, with a large number of widespread risk factors being identified. With an intricate pathogenesis and symptomatology, it heavily impacts the quality of life and, due to the limited efficacy of traditional pharmacological agents, patients are likely to seek other medical and non-medical solutions to their problem. Over the last few years, significant research in this domain has emphasized the importance of various psychological therapies and nutritional recommendations. Nevertheless, a correlation has been established between functional dyspepsia and food intolerances, with more and more patients adopting different kinds of exclusion diets, leading to weight loss, restrictive eating behaviour and an imbalanced nutritional state, further negatively impacting their quality of life. Thus, in this systematic review, we aimed at analysing the impact and efficiency of certain exclusion diets undertook by patients, more precisely, the gluten-free diet and the low-FODMAP diet.     

Distinctive and common features of moderate aplastic anaemia

The therapy algorithm for severe aplastic anaemia (sAA) is established but moderate AA (mAA), which likely reflects a more diverse pathogenic mechanism, often represents a treatment/management conundrum. A cohort of AA patients (n = 325) was queried for those with non-severe disease using stringent criteria including bone marrow hypocellularity and chronic persistence of moderately depressed blood counts. As a result, we have identified and analyzed pathological and clinical features in 85 mAA patients. Progression to sAA and direct clonal evolution (paroxysmal nocturnal haemoglobinuria/acute myeloid leukaemia; PNH/AML) occurred in 16%, 11% and 1% of mAA cases respectively. Of the mAA patients who received immunosuppressive therapy, 67% responded irrespective of time of initiation of therapy while conservatively managed patients showed no spontaneous remissions. Genomic analysis of mAA identified evidence of clonal haematopoiesis with both persisting and remitting patterns at low allelic frequencies; with more pronounced mutational burden in sAA. Most of the mAA patients have autoimmune pathogenesis similar to those with sAA, but mAA contains a mix of patients with diverse aetiologies. Although progression rates differed between mAA and sAA (P = 0·003), cumulative incidences of mortalities were only marginally different (P = 0·095). Our results provide guidance for diagnosis/management of mAA, a condition for which no current standard of care is established.     

Adaptation of the prostate biopsy collaborative group risk calculator in patients with PSA less than 10 ng/ml improves its performance

International Urology and Nephrology - The prostate biopsy collaborative group risk calculator (PBCGRC) is a newly developed risk estimator for predicting prostate biopsy outcomes. However, its...     

Persistent Moderate-to-Weak Mediterranean Diet Adherence and Low Scoring for Plant-Based Foods across Several Southern European Countries: Are We Overlooking the Mediterranean Diet Recommendations?

The Mediterranean diet (MD) has been sponsored worldwide as a healthy and sustainable diet. Our aim was to update and compare MD adherence and food choices across several Southern European countries: Spain (SP), Portugal (PT), Italy (IT), Greece (GR), and Cyprus (CY) (MED, Mediterranean), and Bulgaria (BG) and the Republic of North Macedonia (NMK) (non-MED, non-Mediterranean). Participants (N = 3145, ≥18 y) completed a survey (MeDiWeB) with sociodemographic, anthropometric, and food questions (14-item Mediterranean Diet Adherence Screener, 14-MEDAS). The MED and non-MED populations showed moderate (7.08 ± 1.96) and weak (5.58 ± 1.82) MD adherence, respectively, with significant yet small differences across countries (SP > PT > GR > IT > CY > BG > NMK, p-value < 0.001). The MED participants scored higher than the non-MED ones for most of the Mediterranean-typical foods, with the greatest differences found for olive oil (OO) and white meat preference. In most countries, ≥70% of the participants reported quantities of red meat, butter, sweet drinks, and desserts below the recommended cutoff points, whereas <50% achieved the targets for plant-based foods, OO, fish, and wine. Being a woman and increasing age were associated with superior adherence (p-value < 0.001), but differences were rather small. Our results suggest that the campaigns carried out to support and reinforce the MD and to promote plant-based foods have limited success across Southern Europe, and that more hard-hitting strategies are needed.     

Hydro-distillation and microwave-assisted distillation of Sideritis raeseri: Comparison of the composition of the essential oil,hydrolat and residual water extract

Sideritis raeseri is widely used as a tea in the traditional medicine of many Mediterranean, Balkan, and Middle East countries. In this study, microwave-assisted hydro-distillation (MAHD) at different power levels (180 W, 360 W, and 600 W) of Sideritis raeseri essential oil was compared in terms of extraction time, yield, qualitative analysis, and operational cost with the conventional method of hydro-distillation (HD). Obtained essential oil, as well as hydrolats and residual water extracts, were chemically characterized. An extraction time of 16–32 min with MAHD at different powers provided yields of 0.61–0.67%, while HD gave 0.01% after 141 min. The main constituents in all essential oils were oxygenated sesquiterpenes, and their content was higher in MAHD (32.93–51.42%) than in oil from HD (17.62%). HD oil was characterized by higher concentration of oxygenated monoterpenes (14.95%) in relation to MAHD oil (8.87–14.16%). The essential oil obtained by MAHD at 600 W has a higher content of diterpenes (13.26%) than HD oil (8.59%). All hydrolats displayed the highest content of oxygenated monoterpenes. The highest contents of 8-hydroxyflavone 7-allosylglucosides compounds in residual water extracts were obtained by applying higher (600 W) microwave power. MAHD could be selected as a more appropriate extraction technique for S. reaseri essential oil than HD with respect to the extraction time, quality, and energy savings above 99%.     

Intrinsic signal optical imaging of brain function using short stimulus delivery intervals

Intrinsic signal optical imaging (ISOI) can be used to map cortical function and organization. Because its detected signal lasts 10+ s consisting of three phases, trials are typically collected using a long (tens of seconds) stimulus delivery interval (SDI) at the expense of efficiency, even when interested in mapping only the first signal phase (e.g., ISOI initial dip). It is unclear how the activity profile can change when stimuli are delivered at shorter intervals, and whether a short SDI can be implemented to improve efficiency. The goals of the present study are twofold: characterize the ISOI activity profile when multiple stimuli are delivered at 4 s intervals, and determine whether successful mapping can be attained from trials collected using an SDI of 4 s (offering >10× increase in efficiency). Our results indicate that four stimuli delivered 4 s apart evoke an activity profile different from the triphasic signal, consisting of signal dips in a series at the same frequency as the stimuli despite a strong rise in signal prior to the 2nd to 4th stimuli. Visualization of such signal dips is dependent on using a baseline immediately prior to every stimulus. Use of the 4-s SDI is confirmed to successfully map activity with a similar location in peak activity and increased areal extent and peak magnitude compared to using a long SDI. Additional experiments were performed to begin addressing issues such as SDI temporal jittering, response magnitude as a function of SDI duration, and application for successful mapping of cortical function topography.     

Prevalence of HIV infection among inpatients and outpatients in Department of Veterans Affairs health care systems: implications for screening programs for HIV

Objectives. We sought to determine the prevalence of HIV in both inpatient and outpatient settings in 6 Department of Veterans Affairs (VA) health care sites.Methods. We collected demographic data and data on comorbid conditions and then conducted blinded, anonymous HIV testing. We conducted a multivariate analysis to determine predictors of HIV infection.Results. We tested 4500 outpatient blood specimens and 4205 inpatient blood specimens; 326 (3.7%) patients tested positive for HIV. Inpatient HIV prevalence ranged from 1.2% to 6.9%; outpatient HIV prevalence ranged from 0.9% to 8.9%. Having a history of hepatitis B or C infection, a sexually transmitted disease, or pneumonia also predicted HIV infection. The prevalence of previously undocumented HIV infection varied from 0.1% to 2.8% among outpatients and from 0.0% to 1.7% among inpatients.Conclusions. The prevalence of undocumented HIV infection was sufficiently high for routine voluntary screening to be cost effective in each of the 6 sites we evaluated. Many VA health care systems should consider expanded routine voluntary HIV screening.Early identification of HIV infection through screening substantially lengthens the life of the person identified and provides an important public health benefit from reduced HIV transmission.1 HIV screening in health care settings is also cost effective, even when the prevalence of HIV infection is as low as 0.05% to 0.1%.1^–3 Newly revised guidelines for HIV screening from the Centers for Disease Control and Prevention (CDC) recommend one-time screening in all health care settings unless the prevalence of undiagnosed HIV infection is documented to be less than 0.1%.4The prevalence of undiagnosed HIV infection has been documented in few health care settings in the era of highly active antiretroviral therapy. The Sentinel Hospital Study, which assessed HIV prevalence in a probability sample of nonfederal US hospitals, showed that the prevalence of HIV infection ranged from 0.1% to 7.8% among sentinel hospital populations (inpatients and outpatients combined) in 1989; however, currently, few people with HIV are hospitalized, so both inpatient and outpatient prevalence rates may differ from previous estimates. Although total HIV prevalence has been evaluated in many settings, the most important factor in determining the usefulness of an HIV screening program is the prevalence of unidentified, rather than known, HIV infection.The preferred method for determining an unbiased estimate of prevalence in a population is a blinded (anonymous) serological survey, an approach recommended by the CDC.6^,7 In a blinded serological survey, blood that is drawn for other purposes is stripped of identifiers and tested for HIV. Because the patient’s identity cannot be determined, informed consent is not required. Other approaches that depend on patients’ acceptance of screening are limited by selection bias that occurs when patients decline testing.8^–10 This selection bias can be substantial, and the prevalence of HIV among patients who have declined testing may be either higher or lower than the prevalence among patients who accept testing.11 Blinded serological surveys have been used widely, most notably in the Sentinel Hospital Study.5We conducted a blinded serological survey to determine the prevalence of HIV infection among outpatients and inpatients in 6 Department of Veterans Affairs (VA) health care systems. The VA is one of the largest integrated health care systems and the largest provider of HIV care in the United States. Our goal was to assess the prevalence of both documented and undocumented HIV infection and to assess demographic and clinical predictors of documented and undocumented infection. Although predictors of undocumented HIV infection have been evaluated in emergency departments,12^,13 they have not been well studied in VA populations.