Tongue Pressure During Swallowing in Adults with Down Syndrome and Its Relationship with Palatal Morphology

In individuals with Down syndrome, hypotonicity of the tongue and an underdeveloped maxilla may lead to poor oral motor coordination, which adversely affects the oral phase of swallowing. This study aimed to evaluate the characteristics of pressure produced by the tongue against the hard palate during swallowing in individuals with Down syndrome. In addition, the relationship between tongue pressure and palatal morphology was examined. We studied nine adults with Down syndrome and ten healthy adults as controls. Tongue pressure while swallowing 5 mL water was recorded by a sensor sheet system with five measuring points attached to the hard palate. Palatal length, depth, width, curvature, and slope were measured by three-dimensional digital maxillary imaging. The order of onset of tongue pressure on the median line of the hard palate was the same in all participants, except for three with Down syndrome. The duration and maximal magnitude of tongue pressure on the median line in nine participants with Down syndrome were significantly shorter and lower than those of controls. In participants with Down syndrome, significant positive correlations were observed between the duration of tongue pressure at the mid-median part of the hard palate and palatal depth and width, and between the duration and maximal magnitude of tongue pressure at the posterior-median part and palatal length. These findings suggest that impaired tongue activity, poor tongue control, and constrained tongue motion due to a short and narrow palate contribute to swallowing difficulty in individuals with Down syndrome.     

Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia

Predicting the response to immunosuppressive therapy could provide useful information to help the clinician define treatment strategies for patients with aplastic anemia. In our current study, we evaluated the relationship between telomere length of lymphocytes at diagnosis and the response to immunosuppressive therapy in 64 children with aplastic anemia, using flow fluorescence in situ hybridization. Median age of patients was ten years (range 1.5–16.2 years). Severity of the disease was classified as very severe in 23, severe in 21, and moderate in 20 patients. All patients were enrolled in multicenter studies using antithymocyte globulin and cyclosporine. The response rate to immunosuppressive therapy at six months was 52% (33 of 64). The probability of 5-year failure-free survival and overall survival were 56% (95% confidence interval (CI): 41–69%) and 97% (95%CI: 87–99%), respectively. Median telomere length in responders was −0.4 standard deviation (SD) (−2.7 to +3.0 SD) and −1.5 SD (−4.0 to +1.6 (SD)) in non-responders (P<0.001). Multivariate analysis showed that telomere length shorter than −1.0 SD (hazard ratio (HR): 22.0; 95%CI: 4.19–115; P<0.001), platelet count at diagnosis less than 25×10⁹/L (HR: 13.9; 95%CI: 2.00–96.1; P=0.008), and interval from diagnosis to immunosuppressive therapy longer than 25 days (HR: 4.81; 95%CI: 1.15–20.1; P=0.031) were the significant variables for poor response to immunosuppressive therapy. Conversely to what has been found in adult patients, measurement of the telomere length of lymphocytes at diagnosis is a promising assay in predicting the response to immunosuppressive therapy in children with aplastic anemia.     

First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy

The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86–90) versus 92% (90–94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54–59) versus 87% (85–90); P<0.0001]. There was no significant improvement in outcomes over the two time periods (1992–1999 versus 2000–2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia.     

Mental health of patients with human immunodeficiency virus in Japan: a comparative analysis of employed and unemployed patients

In developed countries, human immunodeficiency virus (HIV) has become a chronic disease. The aims of this study were to clarify the physical, social, and psychological factors affecting Japanese HIV patients in a stable condition and to identify factors related to mental health of employed and unemployed HIV patients. The target subjects were people with HIV infection who were treated as outpatients at core hospitals for acquired immune deficiency syndrome (AIDS) treatment in Japan. A questionnaire including items from the Hospital Anxiety and Depression Scale (HADS) was sent to each medical facility with a request for participation from the HIV-infected outpatients. Responses from 1199 patients were analyzed. Mental health was reportedly better in the employed patients than in the unemployed patients. The unemployed patients were more likely to have resigned from their jobs because of poor health, to have resigned voluntarily, or to have been unfairly dismissed. Once the patients stopped working because of HIV, returning to work became difficult. In the employed patients, a good workplace environment was strongly related to lower scores on HADS. Higher HADS scores were recorded for employed patients infected with HIV for six years or more. For the unemployed patients, a relationship was observed between strong feelings of stigmatization and HADS scores. Quitting a job because of an experience related to HIV status may be related to feelings of stigmatization.     

Low-dose radioiodine therapy for patients with intermediate- to high-risk differentiated thyroid cancer

Annals of Nuclear Medicine - The efficacy of low-dose radioiodine therapy (RIT) for intermediate-risk or high-risk differentiated thyroid cancer (DTC) patients is controversial. Because of the...     

Type 2C protein phosphatases directly regulate abscisic acid-activated protein kinases in Arabidopsis

Abscisic acid (ABA) signaling is important for stress responses and developmental processes in plants. A subgroup of protein phosphatase 2C (group A PP2C) or SNF1-related protein kinase 2 (subclass III SnRK2) have been known as major negative or positive regulators of ABA signaling, respectively. Here, we demonstrate the physical and functional linkage between these two major signaling factors. Group A PP2Cs interacted physically with SnRK2s in various combinations, and efficiently inactivated ABA-activated SnRK2s via dephosphorylation of multiple Ser/Thr residues in the activation loop. This step was suppressed by the RCAR/PYR ABA receptors in response to ABA. However the abi1–1 mutated PP2C did not respond to the receptors and constitutively inactivated SnRK2. Our results demonstrate that group A PP2Cs act as ‘gatekeepers’ of subclass III SnRK2s, unraveling an important regulatory mechanism of ABA signaling.     

Successful therapy of macrophage activation syndrome with dexamethasone palmitate

Macrophage activation syndrome (MAS) is a severe and potential life-threatening complication of childhood systemic inflammatory disorders. Corticosteroids are commonly used as the first-line therapy for MAS. We report four patients with MAS who were successfully treated with dexamethasone palmitate (DexP), a liposome-incorporated dexamethasone, much more efficient than free corticosteroids. DexP effectively inhibited inflammation in MAS patients in whom the response to pulse methylprednisolone was not sufficient to manage their diseases. DexP was also effective as the first-line therapy for MAS. Based on these findings, DexP is an effective therapy in treating MAS patients.     

Antitumor Effect of Intratumoral Administration of Biological Response Modifiers: Induction of Immunosuppressive Acidic Protein, a Type of α1-Acid Glycoprotein, in Mice

The antitumor effects of biological response modifiers (BRMs) in an experimental mouse model, the "double grafted tumor system" were analyzed. Male BALB/c mice received simultaneous inoculations of Metn-A fibrosarcoma cells on the right flank (10⁶ cells) and left flank (2 × 10⁵ cells) on day 0, and BRMs were injected intratumorally into the right tumor on days 3, 4 and 5. PSK (a protein-bound polysaccharide preparation), interleuldn-1 (IL-1) and cepharanthin (R) cured not only the right, but also the left, non-treated tumor in a double grafted tumor system. OK-432 (a Streptococcus preparation) and BCG and tumor necrosis factor (TNF) cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) and IL-6 inhibited neither the right nor the left tumor. Immunosuppressive acidic protein (IAP) in serum was increased transiently soon after intradermal injection of PSK, CR, OK-432 and TNF in BALB/c mice. Lentinan, however, did not induce IAP. IAP in serum was gradually increased after intradermal inoculation of Meth-A tumor in BALB/c mice. The biochemical difference between PSK-induced IAP (early, inflammatory IAP) and Meth-A-induced IAP (late, tumor-induced IAP) was investigated by crossed affinity immunoelectrophoresis with concanavalin A. IAP of murine serum was separated into 4 peaks. IAP in normal mouse was rich in high-mannose type sugar chain (Peak 3) and contained no hybrid-type sugar chain (Peak 4), which was present in inflammatory and tumor-induced IAP. Inflammatory IAP was rich in biantennary sugar chain (Peak 2) and tumor-induced IAP was rich in tri-tetraantennary sugar chain (Peak 1).