Geriatric Inclusive Art and Length of Stay in Acute Care Unit: A Case-Control Pilot Study

International audienc

Whey- vs Casein-Based Enteral Formula and Gastrointestinal Function in Children With Cerebral Palsy.

Objectives: Children with severe cerebral palsy (CP) commonly have gastrointestinal (GI) dysfunction. Whey-based enteral formulas have been postulated to reduce gastroesophageal reflux (GOR) and accelerate gastric emptying (GE). The authors investigated whether whey-based (vs casein-based) enteral formulas reduce GOR and accelerate GE in children who have severe CP with a gastrostomy and fundoplication. Methods: Thirteen children received a casein-based formula for 1 week and either a 50% whey whole protein (50% WWP) or a 100% whey partially hydrolyzed protein (100% WPHP) formula for 1 week. Reflux episodes, gastric half-emptying time (GE t1/2), and reported pain and GI symptoms were measured. Results: Whey formulas emptied significantly faster than casein (median [interquartile range (IQR)] GE t1/2, 33.9 [25.3-166.2] min vs 56.6 [46-191] min; P = .033). Reflux parameters were unchanged. GI symptoms were lower in children who received 50% WWP (visual analog symptom score, median [IQR], 0[0-11.8]) vs 100% WPHP (13.0 [2.5-24.8]) (P = .035). Conclusion: This pilot study shows that in children who have severe CP with a gastrostomy and fundoplication, GE of the whey-based enteral formula is significantly faster than casein. The acceleration in GE does not alter GOR frequency, and there appears to be no effect of whey vs casein in reducing acid, nonacid, and total reflux episodes. The results indicate that enteral formula selection may be particularly important for children with severe CP and delayed GE. (JPEN J Parenter Enteral Nutr. 2012;36:118S-123S

Pyrethroid resistance in the Sudan Savannah Region in Nigeria: a study of the resistance profile and resistance mechanism of Anopheles populations from Hadejia Town in Jigawa State

Insecticide-based control measures are key strategies against malaria vectors, and pyrethroid is the only recommended class of insecticide for public health use. The work aimed at determining the pyrethroid resistance in Anopheline mosquitoes and the frequency of the knockdown resistance (kdr) gene determinant. Larval samples were collected from two sites in Hadejia Town, Jigawa State in April 2020 and November/December 2020, and reared to adulthood in Bayero University Kano Biochemistry's insectary. Samples were identified by morphological and molecular techniques. Three to five-day-old adult mosquitoes were exposed to standard concentrations of 0.75% permethrin and 0.05% deltamethrin according to WHO criteria. Kdr mutations were investigated using PCR. Results of morphological identification showed an abundance (100%) of the Anopheles gambiae complex. However, molecular identification showed varying percentages of An. gambiae s.s (15% and 35%), An. coluzzii (80% and 45%), and An. arabiensis (5% and 20%) each for agricultural and industrial sites, respectively. The result also revealed relatively higher KT50 and KT50 in the agricultural site and was relatively higher with permethrin based on the KT50. Higher insecticide resistance of Anopheles mosquitoes observed in the agricultural site suggests that the practice may affect resistance development. The frequency of negative (homozygous) L1014F kdr mutation genotype was 70% in the resistant (alive) mosquito population and 50% in the susceptible (dead) mosquito population. The frequency of kdr mutation for agricultural and industrial sites was 35% and 15%, respectively. This finding suggests that the kdr gene determinant may not be the only mechanism involved in the resistance of the Anopheline mosquito to pyrethroid

Context-specific regulation of surface and soluble IL7R expression by an autoimmune risk allele.

IL-7 is a key factor in T cell immunity and common variants at IL7R, encoding its receptor, are associated with autoimmune disease susceptibility. IL7R mRNA is induced in stimulated monocytes, yet a function for IL7R in monocyte biology remains unexplored. Here we characterize genetic regulation of IL7R at the protein level in healthy individuals, and find that monocyte surface and soluble IL7R (sIL7R) are markedly induced by lipopolysaccharide. In monocytes, both surface IL7R and sIL7R expression strongly associate with allelic carriage of rs6897932, a disease-associated IL7R polymorphism. Monocytes produce more sIL7R than CD4 + T cells, and the amount is additionally correlated with the expression of DDX39A, encoding a splicing factor. Synovial fluid-derived monocytes from patients with spondyloarthritis are enriched for IL7R+ cells with a unique transcriptional profile that overlaps with IL-7-induced gene sets. Our data thus suggest a previously unappreciated function for monocytes in IL-7 biology and IL7R-associated diseases

Molecular Epidemiology of Endemic Human T-Lymphotropic Virus Type 1 in a Rural Community in Guinea-Bissau

Human T-Lymphotropic Virus type 1 (HTLV-1) affects millions of people worldwide. It is very similar to Simian T-Lymphotropic Virus, a virus that circulates in monkeys. HTLV-1 causes a lethal form of leukemia (Adult T-cell Leukemia) and a debilitating neurological syndrome (HTLV-associated myelopathy/tropical spastic paraparesis) in approximately 5% of infected people. Based on sequence variation, HTLV-1 can be divided into 7 subtypes (1a–1g) with the Cosmopolitan subtype 1a further subdivided into subgroups (A–E). We examined HTLV-1 diversity in a rural area in Guinea-Bissau, a country in West Africa with a high HTLV-1 prevalence (5%). We found that most viruses belong to the Cosmopolitan subtype 1a, subgroup D, but 2 viruses belonged to subtype 1g. This subtype had thus far only been found in monkey hunters in Cameroon, who were probably recently infected by monkeys. Our findings indicate that this subtype has spread beyond Central Africa. An important, unresolved question is whether persons with this subtype were infected by monkeys or through human-to-human transmission

T cell lymphoproliferative disorders associated with anti-tumor necrosis factor alpha antibody therapy for ulcerative colitis: literature summary

The enhanced risk of development of lymphoproliferative disorders in patients with inflammatory bowel disease has been attributed to immunosuppressive/immunomodulatory therapies. Infliximab is a chimeric monoclonal immunoglobulin G1 antibody directed against tumor necrosis factor alpha (TNF-α) that was approved by the Food and Drug Administration (FDA) in 1998 as an effective therapeutic agent against inflammatory bowel disease. Malignant lymphomas of both B and T cell lineage have been described in patients undergoing therapy involving TNF-α blockade. To date, eight cases of Epstein–Barr virus (EBV)-negative hepatosplenic T cell lymphoma associated with infliximab have been reported to the FDA’s Adverse Event Reporting System, as well as several other T cell lymphoproliferative disorders with aggressive clinical outcomes. We present the histologic, immunophenotypic, and molecular features of a T cell lymphoproliferative disorder involving the axillary lymph node of a 33-year-old male following infliximab treatment for ulcerative colitis. These EBV-negative lymphomas suggest that lymphoproliferative disorders following infliximab treatment for inflammatory bowel disease may involve EBV-independent immune dysregulation. The spectrum of lymphoproliferative disorders associated with infliximab and the potential mechanisms by which they occur are discussed

Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström’s Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study

[Purpose]: The double-blind, randomized, placebo-controlled phase III iNNOVATE study showed sustained efficacy of ibrutinib-rituximab in Waldenström's macroglobulinemia (WM). Here, we present the final analysis from iNNOVATE. [Methods]: Patients had confirmed symptomatic WM, either previously untreated or previously treated; patients with prior rituximab had at least a minor response to their last rituximab-based regimen. Patients were randomly assigned to once-daily ibrutinib 420 mg plus rituximab or placebo plus rituximab (n = 75 per arm). The primary end point was progression-free survival (PFS). Secondary end points included response rate, time to next treatment, hemoglobin improvement, overall survival, and safety. [Results]: With a median follow-up of 50 (range, 0.5-63) months, median (95% CI) PFS was not reached (57.7 months to not evaluable) with ibrutinib-rituximab versus 20.3 months (13.0 to 27.6) with placebo-rituximab (hazard ratio, 0.250; P < .0001). PFS benefit was regardless of prior treatment status, MYD88 and CXCR4 mutation status, or key patient characteristics. Higher response rates (partial response or better) were observed with ibrutinib-rituximab (76% v 31% with placebo-rituximab; P < .0001) and were sustained over time. Median time to next treatment was not reached with ibrutinib-rituximab versus 18 months with placebo-rituximab. More patients receiving ibrutinib-rituximab versus placebo-rituximab had sustained hemoglobin improvement (77% v 43%; P < .0001). Median overall survival was not reached in either arm. Ibrutinib-rituximab maintained a manageable safety profile; the prevalence of grade ≥ 3 adverse events of clinical interest generally decreased over time. [Conclusion]: In the final analysis of iNNOVATE with a median follow-up of 50 months, ibrutinib-rituximab showed ongoing superiority across clinical outcomes in patients with WM regardless of MYD88 or CXCR4 mutation status, prior treatment, and key patient characteristics.Supported by Pharmacyclics LLC, an AbbVie Company. Pharmacyclics LLC sponsored and designed the study.Peer reviewe

A constructive approach for discovering new drug leads: Using a kernel methodology for the inverse-QSAR problem

<p>Abstract</p> <p>Background</p> <p>The inverse-QSAR problem seeks to find a new molecular descriptor from which one can recover the structure of a molecule that possess a desired activity or property. Surprisingly, there are very few papers providing solutions to this problem. It is a difficult problem because the molecular descriptors involved with the inverse-QSAR algorithm must adequately address the forward QSAR problem for a given biological activity if the subsequent recovery phase is to be meaningful. In addition, one should be able to construct a feasible molecule from such a descriptor. The difficulty of recovering the molecule from its descriptor is the major limitation of most inverse-QSAR methods.</p> <p>Results</p> <p>In this paper, we describe the reversibility of our previously reported descriptor, the vector space model molecular descriptor (VSMMD) based on a vector space model that is suitable for kernel studies in QSAR modeling. Our inverse-QSAR approach can be described using five steps: (1) generate the VSMMD for the compounds in the training set; (2) map the VSMMD in the input space to the kernel feature space using an appropriate kernel function; (3) design or generate a new point in the kernel feature space using a kernel feature space algorithm; (4) map the feature space point back to the input space of descriptors using a pre-image approximation algorithm; (5) build the molecular structure template using our VSMMD molecule recovery algorithm.</p> <p>Conclusion</p> <p>The empirical results reported in this paper show that our strategy of using kernel methodology for an inverse-Quantitative Structure-Activity Relationship is sufficiently powerful to find a meaningful solution for practical problems.</p