mTORC1 Controls Phase Separation and the Biophysical Properties of the Cytoplasm by Tuning Crowding.

Macromolecular crowding has a profound impact on reaction rates and the physical properties of the cell interior, but the mechanisms that regulate crowding are poorly understood. We developed genetically encoded multimeric nanoparticles (GEMs) to dissect these mechanisms. GEMs are homomultimeric scaffolds fused to a fluorescent protein that self-assemble into bright, stable particles of defined size and shape. By combining tracking of GEMs with genetic and pharmacological approaches, we discovered that the mTORC1 pathway can modulate the effective diffusion coefficient of particles ≥20 nm in diameter more than 2-fold by tuning ribosome concentration, without any discernable effect on the motion of molecules ≤5 nm. This change in ribosome concentration affected phase separation both in vitro and in vivo. Together, these results establish a role for mTORC1 in controlling both the mesoscale biophysical properties of the cytoplasm and biomolecular condensation.

Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab. / Algoritmo de tratamiento con omalizumab en urticaria crónica espontánea.

BACKGROUND AND OBJECTIVE: Pivotal trials with omalizumab for treatment of chronic spontaneous urticaria (CSU) are generally run over 12 to 24weeks. However, in clinical practice, many patients need longer treatment. In this article, we present an algorithm for treatment with omalizumab. MATERIAL AND METHODS: The consensus document we present is the result of a series of meetings by the CSU working group of "Xarxa d'Urticària Catalana i Balear" (XUrCB) at which data from the recent literature were presented, discussed, compared, and agreed upon. RESULTS: Treatment with omalizumab should be initiated at the authorized dose, and is adjusted at 3-monthly intervals according to the Urticaria Activity Score Over 7days, the Urticaria Control Test, or both. CONCLUSIONS: The algorithm proposed is designed to provide guidance on how to adjust omalizumab doses, how and when to discontinue the drug, and how to reintroduce it in cases of relapse.

Epidemiological Characteristics of the Largest Kidney Transplant Program in Mexico: Western National Medical Center, Mexican Institute of Social Security.

BACKGROUND: According to the National Transplant Center (CENATRA), in 2013, a total of 2707 transplantations were performed in Mexico; of them, 10% (270 transplantations) were done in our Tertiary Care Hospital (Western National Medical Center). This means that one in 10 transplant recipients undergoes transplantation at our medical center. The aim of our study was to describe the characteristics of and to compare changes in the kidney transplantation program over time. MATERIALS AND METHODS: This was a cross-sectional study. Data were collected from the hospital transplant registry from January 1994 to December 2014. RESULTS: During the study period, 3643 kidney transplantations were conducted; most were living donor 3236 (89%), and only 407 patients (11%) received a graft from a deceased donor. Of living donors, 2786 (87%) were related, and 450 (13%) were genetically unrelated. The average recipient age was 28 years, and the average age of the donor was 34 years. It was observed that siblings donated more frequently (51%), followed by parents (34%). Among unrelated donors, spouses donated the most (66%). In 80% of cases, the cause of end-stage renal disease (ESRD) was unknown (80%). The most frequent renal replacement therapy was peritoneal dialysis (54%), followed by hemodialysis (18%); only 5% of patients received preemptive kidney transplant. The most frequent immunosuppression scheme was tacrolimus, mycophenolate mofetil, and prednisone in 70% of patients. CONCLUSION: The Western National Medical Center is the largest kidney transplantation program in Mexico. The main activity is living donor transplantation. Recipients are relatively young persons with unknown etiology of ESRD.

Early Steroid Withdrawal in Recipients of a Kidney Transplant From a Living Donor: Experience of a Single Mexican Center.

BACKGROUND: Early steroid withdrawal (ESW) can improve lipid and hemodynamic profiles without severe acute rejection (AR) events in renal transplant patients. Our objective was to evaluate the effects of ESW on the frequency and severity of AR. METHODS: A randomized, open-label, controlled clinical trial was performed on renal transplant recipients with a follow-up of 12 months. In the ESW group, patients were selected for corticosteroid treatment withdrawal on the fifth day post transplantation. In the Control group, patients continued with steroid treatment. All patients were over 18 years of age with panel reactive antibody (PRA) class I and II HLA <20%. RESULTS: In total, 71 patients, 37 in the ESW group (52.1%) and 34 in the Control group (47.9%), had comparable AR incidences at the end of the follow-up (16% vs 15%) (NS) (RR = 1.20, 95% CI = 0.32-3.33). Although renal graft survival was similar between the ESW and Control groups (87% vs 94%), renal function was superior in the ESW group (85 vs 75 mL/min). Additionally, hypertension was less frequent in the ESW group (3% vs 35%), requiring the use of fewer antihypertensives (8% vs 50%). CONCLUSIONS: ESW was also associated with better blood pressure control and similar AR risk. The ESW group exhibited stable renal function.

Intrauterine growth retardation: study of placental apoptosis.

We studied the rate of apoptosis in the placental tissue of pregnancies complicated with intrauterine growth retardation (IUGR) and compared it with the results obtained in normal placentas. Our results clearly demonstrate a strongly increased rate of apoptosis in placentas of children born with IUGR, suggesting severe placental dysfunction. The significance of these findings needs further study.

Effect of exposure to light on physico-chemical quality attributes of sliced dry-cured Iberian ham under different packaging systems.

Dry-cured Iberian ham slices were stored under vacuum and under two different atmospheres (N(2)=70% N(2)+30% CO(2); Ar=70% Ar+30% CO(2)) and exposed to lightness or darkness. Physico-chemical, sensory and microbial analysis was carried out throughout 60 days storage. Vacuum samples showed the highest a*-value compared to N(2) and Ar after 30 (P<0.05) and 60 days (P<0.05). The influence of illumination during storage was evident after 60 days of storage, L* and a*-values being lower (P<0.01) in hams exposed to light than those kept in darkness, which can be ascribed to the lower nitrosylmioglobin content in samples exposed to light after 60 days (P=0.001). Ham slices stored in darkness showed the lowest TBARS values (P<0.05) and hexanal content (P<0.05) after 60 days. Slices of ham packed in vacuum showed lower TBARS values than N(2) and Ar batches (P=0.001), these samples being perceived as more rancid (P<0.05). The rest of the sensory attributes were not generally affected by gas mixture or illumination (P>0.05).

Evaluation of two natural extracts (Rosmarinus officinalis L. and Melissa officinalis L.) as antioxidants in cooked pork patties packed in MAP.

Two natural extracts, from rosemary (Rosmarinus officinalis L.; Nutrox) and lemon balm (Melissa officinalis L.; Meliox) showing a potential antioxidant activity, have been evaluated and compared with a synthetic antioxidant (Butylated hydroxytoluene; BHT) and a control batch. Pork meat patties were made by addition of the mentioned compounds, cooked and packed in modified atmosphere and stored under illumination for 6 days. A descriptive sensory analysis was also conducted. The patties with natural extracts showed higher a*-values (P<0.001) than control and BHT samples. Cooked pork hardness was the lowest for Meliox batch after 0 and 3 days of storage in comparison with the rest of the batches. Nutrox batch showed the lowest TBARS values and hexanal content (P<0.05) throughout the storage period. The batches with natural antioxidants produced the highest concentrations of free thiol groups after 0 and 3 days. Differences in sensory attributes among batches were not detected by the judge panel.

Modified atmosphere packaging and vacuum packaging for long period chilled storage of dry-cured Iberian ham.

Dry-cured Iberian ham slices were stored under vacuum and under four different modified atmospheres (60/40=60%N(2)+40%CO(2); 70/30=70%N(2)+30%CO(2); 80/20=80%N(2)+20%CO(2); argon=70%argon+30%CO(2)) at 4+/-1 degrees C during 120 days. Gas composition, moisture content, pH, colour, pigment content, and lipid stability were measured, as well as sensory and microbial analysis were carried out throughout storage. A loss of intensity of red colour (a(*)-values) was observed during storage in ham slices (P<0.05). Consistently, MbFe(II)NO content also decreased throughout storage (P>0.05). Slices of ham packed in 40%CO(2) (60/40) and 30%CO(2) (70/30) showed lower a(*)-values than the rest of the batches after 60 days (P<0.05), though differences were not evident after 120 days (P>0.05). TBARs values showed an upward trend during the storage of packaged slices (P<0.05). Vacuum-packed slices showed the lowest TBARs values and those packed with 40%CO(2), the highest. Sensory attributes did not vary significantly (P>0.05) throughout storage under refrigeration and packed either in vacuum or in modified atmospheres. No safety problems were detected in relation to the microbial quality in any case.