"Discordant" increases in CD4 cell count relative to plasma viral load in a closely followed cohort of patients initiating antiretroviral therapy

BACKGROUND: In HIV-positive persons receiving antiretroviral therapy, CD4 cell responses are associated with optimal suppression of viral replication. However, increases in CD4 cell counts in the absence of viral suppression have been reported. We characterized plasma viral load (pVL) and CD4 cell count increases in closely followed patients to evaluate determinants and the prevalence of CD4 cell responses at a populational level. METHODS: All HIV-positive patients in the province of British Columbia, Canada, who were antiretroviral naive and initiated therapy between August 1996 and May 1998 were eligible for the study. The selection criteria were that patients had to have CD4 cell counts and pVLs measured at baseline and at least once during eight 16-week periods after the initiation of therapy. We characterized CD4 cell responses and sought patients who had a "discordant" increase at 1 year, which was defined as an increase in CD4 cell count of >or=50/mm3 with a <1 log10 decrease in pVL. We also evaluated adherence and antiretroviral use. RESULTS: Overall, when baseline and 1-year pVLs and CD4 cell counts were compared, 6.2% of patients had CD4 cell count increases without pVL decreases of >or=1 log10. However, when all pVLs before 1 year were considered, 92% of the discordant increases could be attributed to prior transient or partial viral suppression. Furthermore, although substantial increases in CD4 cell counts were observed in transient virologic responders, the cumulative number of antiretroviral agents used by this group was significantly higher than that used by full virologic responders (p <.001). CONCLUSIONS: Our results demonstrate that virtually all CD4 cell count increases can be attributed to transient or partial pVL suppression. Unmeasured pVL suppression likely explains discordant responses that have been previously reported. Similarities between transient and full virologic responders also appear to be time limited and are often associated with greater cumulative use of antiretroviral therapy by transient virologic responders.     

Synthesis and characterization of halogen-containing polyisophthalamides

Two series of aromatic polyamides were prepared from m-phenylenediamine (MPD) and 4,4′-diaminodiphenyl sulfone (DDS) in combination with a set of new halogenated diacyl chlorides, namely, 5-fluoroisophthaloyl chloride, 5-chloroisophthaloyl chloride, 5-bromoisophthaloyl chloride and 5-iodoisophthaloyl chloride. The polymers were synthesized in high yields and in high molecular weight (as determined by gel permeation chromatography) by means of the low temperature condensation method. Noticeable changes in the spectral characteristics of the halogen-modified polyisophthalamides were observed compared to those of the corresponding unmodified polyisophthalamides. Slight improvements were observed for the glass transition temperatures, which increased 5–30°C relative to those of the conventional polyisophthalamides. Moreover, a correlation was found between the size of the halogen substituents and the increase in T_g values. Thermogravimetric analysis showed that the new polymers are almost as thermally resistant as the unmodified ones, while solubility in organic solvents was some-what poorer.     

Contribution of head movement to gaze command coding in monkey frontal cortex and superior colliculus

Most of what we know about the neural control of gaze comes from experiments in head-fixed animals, but several "head-free" studies have suggested that fixing the head dramatically alters the apparent gaze command. We directly investigated this issue by quantitatively comparing head-fixed and head-free gaze trajectories evoked by electrically stimulating 52 sites in the superior colliculus (SC) of two monkeys and 23 sites in the supplementary eye fields (SEF) of two other monkeys. We found that head movements made a significant contribution to gaze shifts evoked from both neural structures. In the majority of the stimulated sites, average gaze amplitude was significantly larger and individual gaze trajectories were significantly less convergent in space with the head free to move. Our results are consistent with the hypothesis that head-fixed stimulation only reveals the oculomotor component of the gaze shift, not the true, planned goal of the movement. One implication of this finding is that when comparing stimulation data against popular gaze control models, freeing the head shifts the apparent coding of gaze away from a "spatial code" toward a simpler visual model in the SC and toward an eye-centered or fixed-vector model representation in the SEF.     

Interleukin-1 gene complex in schizophrenia: an association study.

The aim of this study is to investigate the association between three polymorphisms of the interleukin-1 (IL-1) gene complex and schizophrenia. We genotyped 228 outpatients with schizophrenia (DSM-IV criteria) and 419 unrelated healthy controls. The following polymorphisms were analyzed: IL-1alpha -889 C/T, IL-1beta +3953 C/T, and IL-1RA (86 bp)n. No significant differences in genotype or in allelic distribution of the Il-1alpha, IL-1beta, and IL-1RA polymorphisms were found. Estimated haplotype frequencies were similar in both groups. Our data do not suggest that genetically determined changes in the IL-1 gene complex confer increased susceptibility for schizophrenia.     

Bone-specific antibodies in sera from patients with celiac disease: characterization and implications in osteoporosis

Osteopenia and osteoporosis are well-known complications detected in celiac disease patients with still obscure pathogenesis. In the present study we investigated the presence of circulating anti-bone autoantibodies in patients with celiac disease and explored their role in the associated bone disease. We evaluated serum samples from 33 patients at the time of diagnosis and from 20 of them after treatment. Sera from patients with inflammatory bowel disease (n = 9), nonceliac osteoporotic (n = 18), and healthy individuals (n = 10) were used as controls. The presence of IgA specific anti-bone antibodies was first investigated using indirect immunofluorescence on cryosections of fetal rat tibia (20-day pregnancy). Furthermore, samples were homogenized and total tissue extracts were subjected to Western blot analysis to confirm immunoreactivity. At diagnosis, sera from 51.5% (17/33) of celiac patients had antibodies that recognized antigenic structures in chondrocytes and the extracellular matrix along mature cartilage, bone interface, and perichondrium of fetal rat bone. Among controls, only two osteoporotic patients showed very low titles of anti-bone autoantibodies. The immunostaining was localized in areas where an active mineralization process occurred and was similar to the distribution of the native bone tissue transglutaminase. The frequency of patients with positive baseline titers of anti-bone antibodies diminished significantly after treatment (P = 0.048). Western blot assays confirmed the presence of autoantibodies in sera from patients with a positive immunofluorescence staining. Autoantibodies recognized a major protein band on tissue extracts with a molecular weight of 77–80 kDa, which could be displaced when sera were preadsorbed with human recombinant tissue transglutaminase. We provide original evidence that patients with celiac disease have IgA-type circulating autoantibodies against intra- and extracellular structures of fetal rat tibia. Our findings suggest that these antibodies recognize bone tissue transglutaminase as the autoantigen, and based on the localization of the immunoreactivity we speculate that they might have an active role in the pathophysiology of celiac disease-associated bone complications.     

Dielectric relaxation properties of linear polythioethers

Values of the dielectric loss tangent were obtained as a function of temperature for poly(pentamethylene sulfide) (P5MS) and poly(1,3-dithiocane) (PDTC). Both P5MS and PDTC exhibit a β absorption, located in the vicinity of their respective glass transition temperatures, ?105°C and ?73°C, which is believed to be associated with micro-Brownian motions in the amorphous phase of the crystalline polymers. The glass-rubber transitions of the polymers are discussed in terms of the flexibility of the chains, as expressed by their conformational partition functions and entropies.     

Role of High Energy Breakfast “Big Breakfast Diet” in Clock Gene Regulation of Postprandial Hyperglycemia and Weight Loss in Type 2 Diabetes

Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of β-cell function and prevent cardiovascular complications. Most of the metabolic processes involved in PPHG, i.e., β-cell secretory function, GLP-1 secretion, insulin sensitivity, muscular glucose uptake, and hepatic glucose production, are controlled by the circadian clock and display daily oscillation. Consequently, postprandial glycemia displays diurnal variation with a higher glycemic response after meals with the same carbohydrate content, consumed at dusk compared to the morning. T2D and meal timing schedule not synchronized with the circadian clock (i.e., skipping breakfast) are associated with disrupted clock gene expression and is linked to PPHG. In contrast, greater intake in the morning (i.e., high energy breakfast) than in the evening has a resetting effect on clock gene oscillations and beneficial effects on weight loss, appetite, and reduction of PPHG, independently of total energy intake. Therefore, resetting clock gene expression through a diet intervention consisting of meal timing aligned to the circadian clock, i.e., shifting most calories and carbohydrates to the early hours of the day, is a promising therapeutic approach to improve PPHG in T2D. This review will focus on recent studies, showing how a high-energy breakfast diet (Bdiet) has resetting and synchronizing actions on circadian clock genes expression, improving glucose metabolism, postprandial glycemic excursions along with weight loss in T2D.     

Hospital-at-Home Expands Hospital Capacity During COVID-19 Pandemic

A Coronavirus Disease 2019 (COVID-19)–specific Hospital-at-Home was implemented in a 400-bed tertiary hospital in Barcelona, Spain. Senior or immune-compromised physicians oversaw patient care. The alternative to inpatient care more than doubled beds available for hospitalization and decreased the risk of transmission among patients and health care professionals. Mild cases from either the emergency department or after hospital discharge were deemed suitable for admission to the Hospital-at-Home. More than half of all patients had pneumonia. Standardized protocols and management criteria were provided. Only 6% of cases required referral for inpatient hospitalization. These results are promising and may provide valuable insight for centers undertaking Hospital-at-Home initiatives or in the case of new COVID-19 outbreaks.