Isthmin-1 (ISM1), a novel adipokine that reflects abdominal adipose tissue distribution in individuals with obesity.

BACKGROUND: The assessment of obesity-related health risks has traditionally relied on the Body Mass Index and waist circumference, but their limitations have propelled the need for a more comprehensive approach. The differentiation between visceral (VIS) and subcutaneous (SC) fat provides a finer-grained understanding of these risks, yet practical assessment methods are lacking. We hypothesized that combining the SC-VIS fat ratio with non-invasive biomarkers could create a valuable tool for obesity-related risk assessment. METHODS AND RESULTS: A clinical study of 125 individuals with obesity revealed significant differences in abdominal fat distribution measured by CT-scan among genders and distinct models of obesity, including visceral, subcutaneous, and the SC/VIS ratio. Stratification based on these models highlighted various metabolic changes. The SC/VIS ratio emerged as an excellent metric to differentiate metabolic status. Gene expression analysis identified candidate biomarkers, with ISM1 showing promise. Subsequent validation demonstrated a correlation between ISM1 levels in SC and plasma, reinforcing its potential as a non-invasive biomarker for fat distribution. Serum adipokine levels also correlated with the SC/VIS ratio. The Receiver Operating Characteristic analysis revealed ISM1's efficacy in discriminating individuals with favorable metabolic profiles based on adipose tissue distribution. Correlation analysis also suggested that ISM1 was involved in glucose regulation pathways. CONCLUSION: The study's results support the hypothesis that the SC-VIS fat ratio and its derived non-invasive biomarkers can comprehensively assess obesity-related health risks. ISM1 could predict abdominal fat partitioning and be a potential biomarker for evaluating obesity-related health risks.

Spectral Transmission of the Human Corneal Layers.

We have assessed the spectral transmittance of the different layers of the human cornea in the ultraviolet (UV), visible, and near-infrared (IR) spectral ranges. Seventy-four corneal sample donors were included in the study. Firstly, the corneal transmittance was measured using a spectrophotometer. Then, all samples were fixed for histopathological analysis, which allowed us to measure the thickness of each corneal layer. Finally, the absorption coefficients of the corneal layers were computed by a linear model reproducing total transmittance. The results show that corneal transmission was almost in unity at the visible and IR ranges but not at the UV range, in which the layer with higher transmission is Descemet's membrane, whereas the stroma showed the lowest transmittance. Regarding the absorption coefficient, the most absorptive tissue was Bowman's layer, followed by the endothelium. Variations on transmittance due to changes in the stroma, Bowman's layer, or Descemet layer were simulated, and important transmission increases were found due to stroma and Bowman changes. To conclude, we have developed a method to measure the transmittance and thickness for each corneal layer. All corneal layers absorb UV light to a greater or lesser extent. The absorption coefficient is higher for Bowman's layer, while the stroma is the layer with the lowest transmittance due to its thickness. Variations in stroma thickness or changes in the corneal tissue of Bowman's layer or the endothelium layer due to some pathologies or surgeries could affect, to a greater or lesser degree, the total transmission of the cornea. Thus, obtaining accurate absorption coefficients for different layers would help us to predict and compensate these changes.

Comparison of the Ultraviolet Light Filtering across Different Intraocular Lenses.

SIGNIFICANCE: We have analyzed the ultraviolet transmittance of some commercial intraocular lenses (IOLs). The results show differences of wavelength cutoff among them. PURPOSE: The purpose of this study was to measure and compare the ultraviolet light transmittance of different IOLs made out of acrylic hydrophobic, hydrophilic, and hydrophilic with hydrophobic surface materials from different manufacturers. METHODS: The spectral transmission curves of eight monofocal IOLs with the same dioptric power of +20.0 diopters were measured using a PerkinElmer Lambda 35 ultraviolet/visible spectrometer. Two IOLs of each type were tested three times. The ultraviolet cutoff wavelength at 10% transmission and the mean values were calculated. RESULTS: All lenses prevented transmission of ultraviolet C (200 to 280 nm) and B radiation (280 to 315 nm). However, not all IOLs provided the same filtering properties in ultraviolet A (315 to 380 nm). Within the ultraviolet A range, the ultraviolet radiation cutoff wavelength of 10% ranges from approximately 360 to 400 nm. HOYA iSert 250 provided a cutoff wavelength of 398.4 nm; AcrySof SA60AT, 396.2 nm; AcrySof SA60WF, 395.7 nm; CT Asphina 404, 378.34 nm; Tecnis ZCB00, 377.70 nm; CT Lucia 607P, 379 nm; C-Flex 570C, 377 nm; and enVista MX60, 360 nm. CONCLUSIONS: Intraocular lenses of different materials and manufacturers have different ultraviolet transmission characteristics. AcrySof (SA60AT and SA60WF) and HOYA iSert 250 provided the highest ultraviolet radiation transmission; the cutoff wavelength of 10% is close to 400 nm. In contrast, enVista IOL showed the lowest ultraviolet radiation cutoff.

A rapid method for measuring intraocular lens power in vitro with a focimeter.

In this paper we describe a new method for measuring the intraocular lens (IOL) power using a focimeter, a negative ophthalmic lens and a saline solution (0.9% NaCl). To test this we measured the power of 58 different IOLs and we compared them with the power stated by the manufacturer. Despite the limitations, the results show a good correlation.

The FAT expandability (FATe) Project: Biomarkers to determine the limit of expansion and the complications of obesity.

BACKGROUND: Obesity is an excessive accumulation of fat frequently, but not always, associated with health problems, mainly type 2 diabetes and cardiovascular disease. During a positive energy balance, as caused by excessive intake or sedentary lifestyle, subcutaneous adipose tissue expands and accumulates lipids as triglycerides. However, the amount of adipose tissue per se is unlikely to be the factor linking obesity and metabolic complications. The expandability hypothesis states that, if this positive energy balance is prolonged, a point is eventually reached where subcutaneous adipose tissue can not further expand and energy surplus no longer can be safely stored. Once the limit on storage capacity has been exceeded, the dietary lipids start spilling and accumulate ectopically in other organs (omentum, liver, muscle, pancreas) forming lipid byproducts toxic to cells. METHODS/DESIGN: FATe is a multidisciplinary clinical project aimed to fill gaps that still exist in the expandability hypothesis. Imaging techniques (CT-scan), metabolomics, and transcriptomics will be used to identify the factors that set the limit expansion of subcutaneous adipose tissue in a cohort of caucasian individuals with varying degrees of adiposity. Subsequently, a set of biomarkers that inform the individual limits of expandability will be developed using computational and mathematical modeling. A different validation cohort will be used to minimize the risk of false positive rates and increase biomarkers' predictive performance. DISCUSSION: The work proposed here will render a clinically useful screening method to predict which obese individuals will develop metabolic derangements, specially diabetes and cardiovascular disease. This study will also provide mechanistic evidence that promoting subcutaneous fat expansion might be a suitable therapy to reduce metabolic complications associated with positive energy balance characteristic of Westernized societies.

Multichannel functional testing in normal subjects, glaucoma suspects, and glaucoma patients.

PURPOSE: To evaluate visual function with a novel multichannel functional test named the ATD Multichannel Functional Test. METHODS: This multicenter study had a prospective and cross-sectional design. A total of 186 eyes were included: 42 with glaucoma, 14 glaucoma suspects due to optic nerve characteristics, 25 ocular hypertensives, and 105 normal eyes. All patients performed standard visual fields (Humphrey 24-2) and ATD with eight stimuli configurations: four achromatic (A), two red-green (T), and two blue-yellow (D). To derive main outcome measures, mean sensitivity, mean defect (MD), and pattern standard deviation (PSD) were calculated and compared among groups and types of stimuli with the Kruskal-Wallis test. The percentage of cases outside normal limits (ONL) was calculated. RESULTS: MD and PSD were significantly different in glaucoma eyes than in normal subjects for all types of stimuli except D-0.5 cycles per degree (cpd)/12Hz. PSD was also lower for normals than for all pathologic groups with A-4cpd/2Hz, A-4cpd/12Hz, D-0.5cpd/2Hz, and T-0.5cpd/2Hz. The highest percentage of ONL cases was obtained with the two low-spatial-frequency chromatic stimuli, with D-0.5cpd/2Hz and T-0.5cpd/2Hz using PSD, which classified as ONL 81.6% and 86.7% of glaucoma eyes, 51.8% and 44.5% of hypertensives, and 72.2% and 41.2% of optic disc suspects, respectively. CONCLUSIONS: ATD assessed different aspects of visual function, and the most sensitive tests to detect glaucomatous damage were the low-temporal-frequency chromatic tests.

Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial.

BACKGROUND: Twice-daily raltegravir with once-daily tenofovir-emtricitabine is an effective initial antiretroviral regimen for patients with HIV-1. On the basis of pharmacokinetic data suggesting efficacy of once-daily raltegravir and because adherence is often improved with once-daily dosing, we aimed to compare these dosing schedules. METHODS: In our international, double-blind, randomised, phase 3 non-inferiority study, we enrolled antiretroviral-naive patients with HIV RNA loads of more than 5000 copies per mL and no baseline resistance to tenofovir or emtricitabine at 83 centres worldwide. We randomly allocated patients (1:1) by use of a computer-generated sequence to receive raltegravir once daily (two 400 mg tablets taken together every 24 h), or twice daily (one 400 mg tablet every 12 h), both in combination with once-daily co-formulated tenofovir 300 mg plus emtricitabine 150 mg. The primary outcome was virological response at 48 weeks (viral RNA loads <50 copies per mL) in patients who received at least one dose of study drug, counting non-completers as failure. We assessed non-inferiority in terms of the proportion of patients in both treatment groups who achieved the primary outcome, with a non-inferiority margin of -10%. This study is registered with ClinicalTrials.gov, number NCT00745823. FINDINGS: From Oct 15, 2008, to Nov 2, 2009, we randomly allocated 775 patients, of whom 382 (99%) of 386 patients in the once-daily group and 388 (99%) of 389 in the twice-daily group received at least one dose of study drug. At baseline, 304 (39%) of 770 treated patients had viral loads of more than 100,000 copies per mL and 188 (24%) had CD4 cell counts of fewer than 200 cells per µL. 318 (83%) of 382 patients in the once-daily group had virological response compared with 343 (89%) of 386 in the twice-daily group (difference -5·7%, 95% CI -10·7 to -0·83; p=0·044). Serious adverse events were reported in 26 (7%) of 382 once-daily recipients and 40 (10%) of 388 twice-daily recipients, and adverse events leading to discontinuation occurred in four (1%) patients in each group. INTERPRETATION: Despite high response rates with both regimens, once-daily raltegravir cannot be recommended in place of twice-daily dosing. FUNDING: Merck.

[Infectious pulmonary complications in HIV-infected patients in the high by active antiretroviral therapy era in Spain]. / Complicaciones infecciosas pulmonares en los pacientes con infección por el virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividad en España.

Pulmonary complications in HIV-infected patients are at present a first-rate problem. They are the main cause of hospital admission of these patients in our country. Most HIV-patients have a pulmonary complication during the evolution of the infection. The main etiologic diagnosis is bacterial pneumonia, especially pneumococcal pneumonia; the second most frequent cause is Pneumocystis jiroveci (previously named P. carinii) pneumonia and the third cause is mycobacteriosis, particularly Mycobacterium tuberculosis. From early studies, important changes in the epidemiology of HIV-related pulmonary complications have occurred. General prescription of P. jiroveci primary prophylaxis is probably one of the main causes, and, more recently, the use of highly active antiretroviral therapy may also be an underlying explanation. In this review, epidemiology, diagnosis and outcome of HIV-related pulmonary complications in our country are update.

Complicaciones infecciosas pulmonares en los pacientes con infección por el virus de la inmunodeficiencia humana en la era del tratamiento antirretroviral de gran actividad en España / Infectious pulmonary complications in HIV-infected patients in the high by active antiretroviral therapy era in Spain

Las complicaciones pulmonares en los pacientes con infección por el virus de la inmunodeficiencia humana (VIH) son, actualmente, un problema de primer orden. En España son la primera causa de ingreso hospitalario de estos pacientes. Además, la mayoría experimenta alguna complicación de este tipo durante su evolución. La etiología más frecuente es la neumonía bacteriana, particularmente las producidas por neumococos; en segundo lugar, la neumonías por Pneumocystis jiroveci (anteriormente P. carinii), y en tercer lugar, las micobacterias, sobre todo la tuberculosis. Desde las primeras descripciones de complicaciones pulmonares, su epidemiología ha experimentado cambios notables. Entre las causas principales se encuentra la introducción de la profilaxis primaria frente a P. jiroveci, y más recientemente, la generalización del tratamiento antirretroviral combinado de elevada eficacia. En esta revisión se actualizan las principales causas en la actualidad de complicaciones pulmonares en los pacientes infectados por el VIH en España, su diagnóstico y pronóstico

Pulmonary complications in HIV-infected patients are at present a first-rate problem. They are the main cause of hospital admission of these patients in our country. Most HIV-patients have a pulmonary complication during the evolution of the infection. The main etiologic diagnosis is bacterial pneumonia, especially pneumococcal pneumonia; the second most frequent cause is Pneumocystis jiroveci (previously named P. carinii) pneumonia and the third cause is mycobacteriosis, particularly Mycobacterium tuberculosis. From early studies, important changes in the epidemiology of HIV-related pulmonary complications have occurred. General prescription of P. jiroveci primary prophylaxis is probably one of the main causes, and, more recently, the use of highly active antiretroviral therapy may also be an underlying explanation. In this review, epidemiology, diagnosis and outcome of HIV-related pulmonary complications in our country are update