Impact of rituximab and half-dose CHOP as primary therapy for untreated symptomatic Waldenström Macroglobulinemia: review of a combined regimen of rituximab with an alkylating agent.

BACKGROUND: Waldenström Macroglobulinemia (WM) is a rare subtype of indolent B-cell lymphoma, and prospective randomized studies on WM are scarce. The R-CHOP therapy [rituximab (R), cyclophosphamide, hydroxy-doxorubicin, vincristine, and prednisone] is a popular and recommended regimen for primary therapy, prescribed by several treatment guidelines for WM. However, treatment with R-CHOP is accompanied by severe myelosuppression and high rates of peripheral neuropathy. Therefore, we retrospectively evaluated the efficacy and toxicity of half-dose CHOP combined with R as a primary therapy for WM. METHODS: Patients with untreated symptomatic WM, treated at the Disaster Medical Center between April 2011 and September 2016, were retrospectively analyzed after administration of 6 cycles of half-dose R-CHOP for every 3 weeks. The response, median time to response, best response, progression-free survival, overall survival, and toxicities were evaluated. RESULTS: Of the 20 WM patients analyzed, 16 (80%) received half-dose R-CHOP without vincristine, and 13 (65%) responded to the treatment. With a median follow-up duration of 26.3 months, the 2-year progression-free survival and 2-year overall survival rates were 70 and 93.3%, respectively. The median time to response and best response were 6 and 9.9 weeks, respectively. Grade 3/4 leukocytopenia, neutropenia, febrile neutropenia, and Grade 1 peripheral neuropathy developed in 32, 37, 0, and 21% of patients, respectively. CONCLUSION: The half-dose R-CHOP is an effective and well-tolerated primary therapy for WM. To the best of our knowledge, this is the first study reporting the use of a reduced-dose R-CHOP regimen for the primary treatment of WM.

A comparative study of 2-year follow-up outcomes in lumbar spinal stenosis patients treated with physical therapy alone and those with surgical intervention after less successful physical therapy.

BACKGROUND: The efficacy of physical therapy for patients with lumbar spinal stenosis (LSS) has been reported only for the short term, and few reports have compared outcomes of surgical treatment with nonsurgical treatment after physical therapy. The purpose of this study was to assess 2-year outcomes of LSS patients treated with surgery or under follow-up observation after physical therapy for 6 weeks. METHODS: Patients presenting with neurogenic claudication, radiologically-confirmed central LSS affecting both legs and refractory symptoms to pharmacotherapy of more than 3 months were enrolled. Patients were treated with manual therapy, stretching and strengthening exercises, and body weight-supported treadmill walking once a week for 6 weeks. Clinical outcomes were measured using the Zurich Claudication Questionnaire (ZCQ), visual analog scale of low back pain, leg pain, and numbness, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire and the SF-36. Two years after physical therapy, patients were classified into the observation group (Group I) or the surgery group (Group II), whose patients failed to respond to physical therapy and wanted to undergo surgery. RESULTS: Thirty-eight patients were enrolled; 28 had complete data at 2 years: 21 and 7 in Groups I and II, respectively. Group II had a higher body mass index (BMI) than Group I. There were no significant differences in clinical outcomes at baseline. Six weeks after physical therapy, Group I had significantly better outcomes for symptom severity and physical function on the ZCQ subscales, physical functioning and bodily pain on the SF-36 subscales. These outcomes in Group I were maintained or improved and did not differ significantly between groups at 2-years. However, the physical function on the ZCQ subscales was improved in Group II more than those in Group I (mean difference -0.6; 95% CI: -1.2 to -0.03, P < 0.05) at 2 years. CONCLUSIONS: At 2 years, the outcomes except for the change in physical function score in the ZCQ subscale did not differ significantly between patients who had undergone surgery and those who avoided surgery.

Factors Associated with Neck and Shoulder Pain in Volunteers.

INTRODUCTION: The aims of the present study were 1) to examine the association between neck and shoulder pain (NSP) and lifestyle in the general population and 2) to examine if sagittal spino-pelvic malalignment is more prevalent in NSP. METHODS: A total of 107 volunteers (mean age, 64.5 years) were recruited in this study from listings of resident registrations in Kihoku region, Wakayama, Japan. Feeling pain or stiffness in the neck or shoulders was defined as an NSP. The items studied were: 1) the existence or lack of NSP and their severity (using VAS scale), 2) Short Form-36 (SF-36), 3) Self-Rating Questionnaire for Depression (SRQ-D), 4) Pain Catastrophizing Scale (PCS), 5) a detailed history consisting of 5 domains as being relevant to the psychosocial situation of patients with chronic pain, 6) A VAS of pain and numbness to the arm, and from thoracic region to legs. The radiographic parameters evaluated were also measured. Participants with a VAS score of 40 mm or higher and less were divided into 2 groups. Association of SF-36, SRQ-D, and PCS with NSP were assessed using multiple regression analysis. RESULTS: In terms of QoL, psychological assessment and a detailed history, bodily pain in SF-36, SRQ-D, and family stress were significantly associated with NSP. A VAS of pain and numbness to the arm, and from thoracic region to legs, was significantly associated with NSP. There were no statistical correlations between the VAS and radiographic parameters of the cervical spine. Among the whole spine sagittal measurements, multiple logistic regression analysis showed that sacral slope (SS) and sagittal vertical axis (SVA) were significantly associated with NSP. CONCLUSION: In this study, we showed the factors associated with NSP. Large SS and reduced SVA were significantly associated with NSP, while cervical spine measurements were not.

Effect of haptic assistance on learning vehicle reverse parking skills.

Compared to conventional visual- and auditory-based assisted driving technologies, haptic modality promises to be more effective and less disturbing assistance to the driver. However, in most previous studies, haptic assistance systems were evaluated from safety and stability viewpoints. Moreover, the effect of haptic assistance on human driving behavior has not been sufficiently discussed. In this paper, we introduce an assisted driving method based on haptic assistance for driver training in reverse parking, which is considered as an uncertain factor in conventional assisted driving systems. The proposed system assists the driver by applying a torque on the steering wheel to guide proper and well-timed steering. To design the appropriate assistance method, we conducted a measurement experiment to determine the qualitative reverse parking driver characteristics. Based on the determined characteristics, we propose a haptic assistance calculation method that utilizes the receding horizon control algorithm. For a simulation environment to assess the proposed assistance method, we also developed a scaled car simulator comprising a 1/10 scaled robot car and an omnidirectional camera. We used the scaled car simulator to conduct comparative experiments on subjects, and observed that the driving skills of the assisted subjects were significantly better than those of the control subjects.

Comparison of the effectiveness of acidified sodium chlorite and sodium hypochlorite in reducing Escherichia coli.

This study was designed to compare the effectiveness of acidified sodium chlorite (ASC) and sodium hypochlorite (NaClO) in reducing several Escherichia coli strains isolated from different retail meat and fresh produce. Forty nonpathogenic E. coli strains were isolated and used in this study. A type strain of E. coli (JCM 1649) and four O157:H7 serotypes of E. coli (CR-3, MN-28, MY-29, and DT-66) were used as reference. In vitro assay results revealed that the viable cell counts of each isolated E. coli strain and control strains exhibited a reduction of ∼ 4.3 ± 0.9 log and 7.8 ± 1.7 log CFU/mL after a 3-minute exposure to 100 mg/L NaClO and 20 mg/L ASC (pH 4.6), respectively, at 25°C, when compared with the viable bacterial counts obtained from phosphate-buffered saline. The one exception was the flocs-forming strain, which showed a reduction of only 1.0 log CFU/mL with both disinfectants. However, reductions of only 1.7 ± 0.3 log and 1.9 ± 0.4 log CFU/g were observed in lettuce after 5 minutes of washing with NaClO and ASC, respectively. On the other hand, reductions of 1.6 ± 0.2 log and 1.6 ± 0.4 log CFU/g were observed in spinach after 5 minutes of washing with NaClO and ASC, respectively. No reduction in the population was observed after washing the inoculated, fresh-cut vegetables with distilled water only. No significant difference in the reduction of E. coli was observed among all the tested strains with both sanitizers in the in vivo assay. These data suggest that the tested sanitizers exhibit a similar reduction of the surface-attached E. coli on leafy vegetables irrespective of the strain source.

Effectiveness of acidified sodium chlorite and other sanitizers to control Escherichia coli O157:H7 on tomato surfaces.

The use of a suitable sanitizer can reduce the risk of produce-related foodborne illnesses. We evaluated the effectiveness of several sanitizers to reduce inoculated Escherichia coli O157:H7 on the surface of cherry tomatoes (Solanum lycopersicum var. cerasiform). Depending on the method of inoculation (dipping/spotting), each of 80 g (eight tomatoes) of inoculated cherry tomatoes was washed in 400 mL of sanitizer solutions or 400 mL distilled water for 5 minutes. The effectiveness of sanitizers on spot-inoculated E. coli O157:H7 on tomato surfaces was found higher than on dip-inoculated tomatoes. Washing with water or chlorine water (0.1 g/L as free chlorine) could reduce 1.3 log CFU/g of E. coli O157:H7 in dip-inoculated (6.8 log CFU/g) tomatoes. Washing with lactic acid (LA) solution (1.0 g/L), phytic acid solution (1.0 g/L), calcinated seashells (oyster/sakhalin surf clam), and 1.0 g/L chitosan in 0.5 g/L LA (Chito) did not exhibit a significant higher effectiveness than that of water wash alone (1.0 log CFU/g). Acidified sodium chlorite (ASC) solution prepared from 0.5 g/L of sodium chlorite and 1.0 g/L LA or phytic acid reduced 3.5 log CFU/g of E. coli O157:H7 in dip-inoculated tomato surfaces. ASC (0.5 g/L of sodium chlorite and 1.0 g/L of LA) wash followed by a second wash with LA exhibited an additional sanitary effectiveness compared to a single wash with ASC. However, washing with ASC followed by a second wash with Chito exhibited an additional 1.0 log CFU/g reduction compared to a secondary wash with water. No significant difference of color, taste, and texture was observed among the washed cherry tomatoes.

[Does self-worth mediate the effects of socio-environmental experiences on depression among fifth and sixth grade students?].

This study investigated self-worth as a mediator between socio-environmental experiences and depression. A sample of 255 fifth and sixth grade students completed self-report questionnaires assessing self-worth, depression, and socio-environmental experiences of social support and stressors. Data for both males and females showed a direct effect of "friend support" on depression. However, for males, but not females, self-worth also mediated the influence of "friend support" on depression.

Keratinocyte growth inhibition through the modification of Wnt signaling by androgen in balding dermal papilla cells.

CONTEXT/OBJECTIVE: Androgen induces androgenetic alopecia (AGA), which has a regressive effect on hair growth from the frontal region of the scalp. Conversely, Wnt proteins are known to positively affect mammalian hair growth. We hypothesized that androgen reduces hair growth via an interaction with the Wnt signaling system. The objective of this study was to investigate the effect of androgen on Wnt signaling in dermal papilla (DP) cells. DESIGN: The effect of androgen and Wnt3a on keratinocyte proliferation was measured by use of a coculture system consisting of DP cells and keratinocytes. The molecular mechanisms of androgen and Wnt pathway interactions in DP cells were examined by analyzing the expression, intracellular localization, and activity of the androgen receptor (AR) and also downstream Wnt signaling molecules. RESULTS: Wnt3a-dependent keratinocyte growth was suppressed by the addition of dihydrotestosterone in coculture with DP cells that were derived from AGA patients, but growth was not suppressed in coculture with DP cells from non-AGA males. Whereas DP cells from both scalp regions expressed AR protein, the expression levels of AR and cotranslocation with beta-catenin, a downstream Wnt signaling molecule, were higher in DP cells of AGA patients than in DP cells from non-AGA males. In addition, significant suppression of Wnt signal-mediated transcription in response to dihydrotestosterone treatment was observed only in DP cells from AGA patients. CONCLUSION: These results suggest that Wnt signaling in DP cells is regulated by androgen and this regulation plays a pivotal role in androgen's action on hair growth.

Immunoregulatory T cells in the peripheral blood of melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination.

BACKGROUND: Regulatory T cells (Treg) may inhibit monocyte-derived melanoma antigen-pulsed dendritic cells (DC) vaccination in treatment of melanoma. However, the Treg level in peripheral blood mononuclear cells (PBMCs) following DC vaccination has not been examined in melanoma patients in Japan. OBJECTIVE: To evaluate differences in the helper T cell and Treg population and mRNA levels of Treg in pre- and post-DC vaccination PBMCs obtained from melanoma patients. METHODS: Levels of intracellular forkhead box protein 3 (Foxp3) mRNA as well as levels of CD4(+)CD25(+)Foxp3(+) and CD4(+)CD25(+) T cells were examined by real-time PCR and flow cytometry using PBMCs from 9 patients who received DC vaccination. RESULTS: Eight of the 9 cases and 7 of the 9 cases showed increased populations of CD4(+)CD25(+) T cells and CD4(+)CD25(+)Foxp3(+) T cells, respectively after repeated DC vaccination. Five of 8 cases showed an increase of Foxp3 mRNA after treatment. Four of these 5 cases also had increased CD4(+)CD25(+) and CD4(+)CD25(+)Foxp3(+) T cells, but the fifth case showed a decrease in CD4(+)CD25(+)Foxp3(+) T cells. Three cases showed a decrease of Foxp3 mRNA. One of these 3 cases showed decreased population of CD4(+)CD25(+)Foxp3(+) T cells, but two cases showed increased population of CD4(+)CD25(+)Foxp3(+) T cells. In 3 of 8 cases Foxp3 expression at the cellular (protein) and mRNA level were inconsistent. CONCLUSION: Repeated DC vaccination may commonly induce Treg and helper T cells at the cellular level. However, there are a few discrepancies of Treg expression at cellular and mRNA level.

Effect of dietary docosahexaenoic acid connecting phospholipids on the lipid peroxidation of the brain in mice.

The effect of dietary docosahexaenoic acid (DHA, C22:6n-3) with two lipid types on lipid peroxidation of the brain was investigated in streptozotocin (STZ)-induced diabetic mice. Each group of female Balb/c mice was fed a diet containing DHA-connecting phospholipids (DHA-PL) or DHA-connecting triacylglycerols (DHA-TG) for 5 wk. Safflower oil was fed as the control. The lipid peroxide level of the brain was significantly lower in the mice fed the DHA-PL diet when compared to those fed the DHA-TG and safflower oil diets, while the alpha-tocopherol level was significantly higher in the mice fed the DHA-PL diet than in those fed the DHA-TG and safflower oil diets. The DHA level of phosphatidylethanolamine in the brain was significantly higher in the mice fed the DHA-PL diet than in those fed the safflower oil diet. The dimethylacetal levels were significantly higher in the mice fed the DHA-PL diet than in those fed the safflower oil and DHA-TG diets. These results suggest that the dietary DHA-connecting phospholipids have an antioxidant activity on the brain lipids in mice, and the effect may be related to the brain plasmalogen.

Effect of ovary lipid of skipjack tuna on rat serum components after stress application.

Lipid extracted from the ovary of skipjack tuna by the method that we developed is rich in phospholipid-type docosahexaenoic acid. The ovary lipid of skipjack tuna (OLS) was studied for its anti-stress activity in male Wistar rats, focusing on stress-related blood components: recovery from stress was examined after application of water immersion restraint stress. As a result, serum corticosterone (CORT) secretion was inhibited and decreased rapidly after stress application in rats given OLS compared with control rats. As CORT acts as a glucocorticoid, non-esterified fatty acid (NEFA) is expected to increase by stress application. However, the concentration tended to be lower in rats given OLS than in control rats. With respect to OLS concentration, OLS increased serum dehydroepiandrosterone, secretion concentration-dependently. In addition, as with the recovery study, it tended to inhibit the increase in NEFA. These results indicate that OLS may have an anti-stress activity against acute stress.

Effect of ovary lipid of Skipjack tuna (Katsuwonus pelamis) on anxious behavior in rats.

Ovary lipid of Skipjack tuna (OLS) (Katsuwonus pelamis) contains a high level of docosahexaenoic acid combined with phospholipids. In this study, we examined the effect of OLS in male Wistar rats given OLS mixed in feed (0.9%) for 42 days, using an animal model of anxiety, the elevated T-maze test. The avoidance latency at the 1st trial was significantly shorter in the OLS ingestion group than in the control group. Those at the 2nd and 3rd trials showed a similar tendency. There was almost no difference in escape latency at the 1st trial between the two groups but the escape latencies at the 2nd and 3rd trials tended to be longer in the OLS group. These results suggested that OLS inhibits anxious behavior in rats.