Fludarabine, cyclophosphamide, and rituximab as first-line treatment in patients with chronic lymphocytic leukemia: A long-term analysis of the German CLL Study Group (GCLLSG) registry.

Long-term data of chronic lymphocytic leukemia (CLL) patients with favorable risk who were treated with fludarabine, cyclophosphamide, and rituximab (FCR) within clinical trials show good efficacy. We here report long-term data collected within the GCLLSG registry. Altogether, 417 CLL patients who received first-line treatment with FCR were analyzed, of which 293 (70.3%) were treated outside of clinical trials. The median observation time from first-line was 95.8 (interquartile range 58.7-126.8) months. Focusing on data of 194 (46.5%) patients who received FCR first-line treatment after 2013 (start of data collection within GCLLSG registry), responses were documented in 85% of the patients, non-responses in 15%, and for 3.6% the assessment was missing. Median event-free survival (EFS, time until disease progression, subsequent treatment, or death) was 60.2 months with a 5-year EFS-rate of 50.6%. Patients with higher-risk disease, characterized by unmutated IGHV (N = 78), had a median EFS of 45.4 months with a 5-year EFS rate of 36.3%, while the median EFS was 77.5 months with a 5-year EFS rate of 60.3% in patients with mutated IGHV (N = 40). Median overall survival was not reached with a 5-year survival rate of 92.7%. In summary, first-line FCR was associated with long EFS, especially in patients exhibiting a mutated IGHV status.

Efficacy of Bacillus subtilis probiotic in preventing necrotic enteritis in broilers: a systematic review and meta-analysis.

Probiotics can enhance broiler chicken health by improving intestinal microbiota, potentially replacing antibiotics. They protect against bacterial diseases like necrotic enteritis (NE) in poultry. Understanding their role is crucial for managing bacterial diseases, including NE. This study conducted a meta-analysis to assess the effects of Bacillus subtilis probiotic supplementation on feed conversion ratio (FCR), NE lesion score, and mortality. Additionally, a systematic review analysed gut microbiota changes in broilers challenged with Clostridium perfringens with or without the probiotic supplementation. Effect sizes from the studies were estimated in terms of standardized mean difference (SMD). Random effect models were fitted to estimate the pooled effect size and 95% confidence interval (CI) of the pooled effect size between the control [probiotic-free + C. perfringens] and the treatment [Bacillus subtilis supplemented + C. perfringens] groups. Overall variance was computed by heterogeneity (Q). The meta-analysis showed that Bacillus subtilis probiotic supplementation significantly improved FCR and reduced NE lesion score but had no effect on mortality rates. The estimated overall effects of probiotic supplementation on FCR, NE lesion score and mortality percentage in terms of SMD were -0.91 (CI = -1.34, -0.49; P < 0.001*); -0.67 (CI = -1.11, -0.22; P = 0.006*), and -0.32 (CI = -0.70, 0.06; P = 0.08), respectively. Heterogeneity analysis indicated significant variations across studies for FCR (Q = 69.66; P < 0.001*) and NE lesion score (Q = 42.35; P < 0.001*) while heterogeneity was not significant for mortality (Q = 2.72; P = 0.74). Bacillus subtilis probiotic supplementation enriched specific gut microbiota including Streptococcus, Butyricicoccus, Faecalibacterium, and Ruminococcus. These microbiotas were found to upregulate expression of various genes such as TJ proteins occluding, ZO-1, junctional adhesion 2 (JAM2), interferon gamma, IL12-ß and transforming growth factor-ß4. Moreover, downregulated mucin-2 expression was involved in restoring the intestinal physical barrier, reducing intestinal inflammation, and recovering the physiological functions of damaged intestines. These findings highlight the potential benefits of probiotic supplementation in poultry management, particularly in combating bacterial diseases and promoting intestinal health.

Mutation of the TGN1412 anti-CD28 monoclonal antibody lower hinge confers specific FcγRIIb binding and retention of super-agonist activity.

The agonistic action of several immunomodulatory monoclonal antibodies (mAbs) requires both target antigen binding and clustering of this mAb:target complex by the Fcs interacting with Fcγ receptors (FcγRs), in particular FcγRIIb, on neighboring bystander cells. Fc mutations were made in the immunoglobulin G4 (IgG4)-based TGN1412 anti-CD28 mAb to define the role of FcγR interactions in its "super-agonist" activity. The dual mutation, IgG4-ED269,270 AA, ablated interaction with all human FcγRs and agonistic action was consequentially lost, confirming the FcγR dependence on the action of TGN1412. The IgG4 lower hinge region (F234 L235 G236 G237 ) was modified by L235 E mutation (F234 E235 G236 G237 ), a mutation commonly used to ablate FcγR binding, including in approved therapeutic mAbs. However, rather than ablating all FcγR binding, IgG4-L235 E conferred specific binding to FcγRIIb, the inhibitory Fc receptor. Furthermore, in combination with the core hinge-stabilizing mutation (IgG4-S228 P, L235 E), this mutation increased affinity for FcγRIIb compared with wild-type IgG4. In addition to having FcγRIIb specificity, these engineered TGN1412 antibodies retained their super-agonistic ability, demonstrating that CD28- and FcγRIIb-specific binding are together sufficient for agonistic function. The FcγRIIb-specific nature of IgG4-L235 E has utility for mAb-mediated immune agonism therapies that are dependent on FcγRIIb interaction and of anti-inflammatory mAbs in allergy and autoimmunity that harness FcγRIIb inhibitory signaling.

Perfectionism, intolerance of uncertainty and coping in relation to fear of cancer recurrence in breast cancer patients.

OBJECTIVE: Improved medical treatment has led to an increased cohort of cancer survivors. The prevalence of emotional problems in this group is high, with fear of cancer recurrence (FCR) being among the most prevalent and distressing conditions. In order to gain more insight in the psychological mechanisms playing a role in levels of FCR, this study examined the relationship between perfectionism and FCR in breast cancer patients, as well as the mediating role of intolerance of uncertainty (IU) and coping in this relationship. In order to contribute to a more comprehensive understanding of the mechanisms related to the experience of FCR in breast cancer patients, the purpose of the present study is to investigate the relationship between perfectionism and FCR, with IU and coping strategies as possible mediating factors. METHODS: Validated Dutch versions of the FCR Inventory, the Multidimensional Perfectionism Scale, the Intolerance of Uncertainty Scale and the Utrechtse Coping List were filled out by 146 breast cancer patients, at least one year after (finishing) medical treatment. Correlation analyses were conducted to administer the associations between FCR, perfectionism, IU, coping and demographic/medical variables. PROCESS was used to examine mediation mechanisms. RESULTS: A significant correlation was found between perfectionism and FCR (r = 0.19, p = 0.024). IU was found to mediate the relationship between perfectionism and FCR. In contrast, coping style did not emerge as a significant mediating factor. CONCLUSIONS: This study shows that intolerance of uncertainty mediates the relationship between perfectionism and FCR. Psychological interventions targeting FCR may benefit from incorporating specific modules on dealing with uncertainty. Future research is necessary to further increase understanding of the mechanisms that play a role in FCR, in order to optimize and personalize psychological treatment for cancer patients with this type of emotional distress.

A qualitative exploration of fear of cancer recurrence in caregivers.

OBJECTIVE: Fear of cancer recurrence (FCR) is one of the most common unmet needs for cancer patients and caregivers. Yet little is known about the potentially unique nature of caregiver FCR. Our research aimed to address this gap by qualitatively exploring the features and impact of caregiver FCR. METHODS: Eighteen semi-structured telephone interviews with cancer caregivers were conducted to explore the content and impact of caregiver fears and worries about cancer recurrence or progression. Data analysis used a Framework Approach. RESULTS: Qualitative analysis identified three themes (1) fear of the patient suffering, (2) the need to protect the patient from a recurrence and/or cancer-related distress, and (3) caregiver's sense of unpreparedness and uncertainty. Underpinning these themes was an overarching sense of personal responsibility for the life of the patient. This overarching theme was identified as a key driver of caregivers' personal and patient-centred fears. CONCLUSIONS: Our findings confirm the conceptual differences between patient and caregiver FCR. Future research must therefore acknowledge the unique experiences of caregivers and prioritise the development of empirically driven theoretical models, instruments, and interventions for caregiver FCR.

Host Specificity of Soilborne Pathogens in Hordeum Species and Their Relatives.

Soilborne pathogens destabilize the yields of Triticeae crops, including barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.). Although genetic resistance derived from relatives of these species has been utilized to prevent rust diseases (i.e., in the wheat-rye 1BL-1RS translocation line), research on resistance against soilborne pathogens remains limited. Here, we performed field trials using 76 genotypes representing 28 Hordeum, six Triticum, and two Aegilops species to examine resistance against three soilborne bymoviruses: barley yellow mosaic virus (BaYMV), barley mild mosaic virus (BaMMV), and wheat yellow mosaic virus (WYMV). We also performed greenhouse tests using the soilborne fungal pathogen Fusarium pseudograminearum, which causes Fusarium crown rot (FCR). Using RT-PCR, we detected BaMMV and BaYMV in several Hordeum species, whereas WYMV induced systemic infection in the Triticum and Aegilops species. The identification of FCR susceptibility in all species examined suggests that F. pseudograminearum is a facultative fungal pathogen in Triticeae. Intraspecies variation in FCR disease severity was observed for several species, pointing to the possibility of exploring host resistance mechanisms. Therefore, by unlocking the host specificity of four soilborne pathogens in Hordeum species and their relatives, we obtained insights for the further exploration of wild sources of soilborne pathogen resistance for future wheat and barley improvement programs.

Identification and Genome-Wide Association Analysis for Fusarium Crown Rot Resistance in Wheat.

Fusarium crown rot (FCR) is a fungal disease and severely decreases wheat production worldwide. Tibetan semiwild wheat, Yunnan hulled wheat, Xinjiang rice wheat, and Sichuan white wheat are four subspecies landraces endemic to western China and have rich genetic diversity in response to biotic and abiotic stresses. Here, a natural population, including 209 wheat accessions of four subspecies, was evaluated for FCR resistance. he genome-wide association study was performed using the wheat 55K single-nucleotide polymorphisms (SNPs). The results showed that the disease index (DI) ranged from 16.88 to 85.00, while six accessions showed moderate to high resistance (DI ≤ 30). Genome-wide association analysis identified 10 stable loci for FCR resistance on chromosomes 1B, 2A (5), 5A, 7A, 7B, and 7D. Four major loci-Qfcr.sicau.2A-1, Qfcr.sicau.2A-3, Qfcr.sicau.5A, and Qfcr.sicau.7D-explained 6.01 to 14.48, 9.76 to 13.11, 8.19 to 10.29, and 5.76 to 12.21% phenotypic variation, respectively. Quantitative trait loci (QTL) pyramiding analysis of these four major loci revealed that accessions with four resistance haplotypes could significantly decrease FCR severity by 9.35 to 31.61% compared with those without or with one to three resistance haplotypes. One kompetitive allele-specific PCR (KASP) marker each was successfully developed for Qfcr.sicau.2A-1 and Qfcr.sicau.7D. The KASP marker of Qfcr.sicau.2A-1 was used to genotype in an F6 recombinant inbred line population. The result showed that the lines carrying the resistance allele reduced FCR severity by 17.78%, demonstrating the importance of Qfcr.sicau.2A-1 in resistance breeding programs. Our findings provide valuable QTL and breeder-friendly PCR-based markers for applications in FCR resistance breeding programs. Our study also proved that gene pyramiding of major loci could enhance FCR resistance.

Immunomodulation of Antibody Glycosylation through the Placental Transfer.

Establishing an immune balance between the mother and fetus during gestation is crucial, with the placenta acting as the epicenter of immune tolerance. The placental transfer of antibodies, mainly immunoglobulin G (IgG), is critical in protecting the developing fetus from infections. This review looks at how immunomodulation of antibody glycosylation occurs during placental transfer and how it affects fetal health. The passage of maternal IgG antibodies through the placental layers, including the syncytiotrophoblast, stroma, and fetal endothelium, is discussed. The effect of IgG subclass, glycosylation, concentration, maternal infections, and antigen specificity on antibody transfer efficiency is investigated. FcRn-mediated IgG transport, influenced by pH-dependent binding, is essential for placental transfer. Additionally, this review delves into the impact of glycosylation patterns on antibody functionality, considering both protective and pathological effects. Factors affecting the transfer of protective antibodies, such as maternal vaccination, are discussed along with reducing harmful antibodies. This in-depth examination of placental antibody transfer and glycosylation provides insights into improving neonatal immunity and mitigating the effects of maternal autoimmune and alloimmune conditions.

Conversion of energy and protein rich food waste as an alternative feed ingredient in broiler feed formulation.

A series of experiments were performed to find out the impact of food waste on growth attributes and performance of broilers in a tropical climate. Two hundred and fifty-one-day-old broiler chicks were randomly separated into 5 groups, where each group comprised 50 animals. The broilers were fed with five different dietary treatments. Treatment 1 (T1), the diet consisted of food waste ingredients such as sprat heads, fish offal (protein), scraped coconut, and swill cooked rice as energy supplements; dietary treatment II (T2) diet was formulated with protein rich food waste; treatment III (T3) diet formulated with energy-rich food waste; treatment IV (T4) without any food waste materials, but a diet formulated with commercially available feed ingredients; and treatment V (T5), a 100% commercially-available broiler diet. Total feed intake per week and total weight gain were significantly (p < 0.05) higher in the commercial diet (T5) contrary to the formulated diets. The highest feed conversion ratio (FCR) was recorded in T3. The average dressing percentage was not significantly different (p > 0.05) in T1, T3, and T5. Average DM % in litter and DM % in feces were higher in T5, but average nitrogen % in droppings were lower in T4 and T5 compared to other diets. The study shows the potential application of food waste as an alternative feed in the broiler industry and its abundance and easy collection makes it a promising feeding regime in urban and suburban areas.

Clonal haematopoiesis as a risk factor for therapy-related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo-(immuno)therapy.

Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy-related myeloid neoplasms (t-MN). Using target next-generation sequencing (t-NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t-MN after treatment with chemo-(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t-MN (77%, median number of variants for patient: 2, range 0-6). The prevalence of CHIP was then backtracked in paired samples taken at CLL diagnosis in eight of these patients. Six of them carried at least one CHIP-variant at the time of t-MN (median: 2, range: 1-5), and the same variants were present in the CLL sample in five cases. CHIP variants were present in 34 of 285 patients from a population-based CLL cohort, which translates into a significantly higher prevalence of CHIP in patients with a CLL who developed a t-MN, compared to the population-based cohort (5/8, 62.5% vs. 34/285, 12%, p = 0.0001). Our data show that CHIP may be considered as a novel parameter affecting treatment algorithms in patients with CLL, and highlight the potential of using chemo-free therapies in CHIP-positive cases.

Comparison of originator and biosimilar monoclonal antibodies using HRMS, Fc affinity chromatography, and 2D-HPLC.

Due to the complex manufacturing process of therapeutic monoclonal antibodies, it is hardly possible to produce an identical copy of the original product (originator). Consequently, follow-on products (biosimilars) must demonstrate their efficacy being similar to the originator in terms of structure and function. During this process, a variety of analytical methods are required for this purpose. This study focuses on three particularly relevant analytical techniques: high-resolution mass spectrometry, fragment crystallisable (Fc) affinity chromatography, and two-dimensional peptide mapping. Each analytical method proved able to identify specific differences between originator and biosimilar. High-resolution mass spectrometry was used to characterize the glycan pattern. It was shown that a trastuzumab biosimilar did not have the G0:G0F sugar modification identified in the originator. The application of affinity chromatography to rituximab showed that originator and biosimilar interacted differently with the immobilized Fc receptor. Furthermore, 2D-HPLC peptide mapping demonstrated the influence of orthogonality of separation dimensions, leading to differentiation of a rituximab originator and biosimilar.

Fear of cancer recurrence and hope level in patients receiving surgery for non-small cell lung cancer: a study on the mediating role of social support.

PURPOSE: To study the level of fear of cancer recurrence (FCR) in patients receiving surgery for non-small cell lung cancer (NSCLC) and explore related factors that can increase levels of hope in this population, enhance the confidence to defeat the disease, and thus increase the quality of life. METHODS: A total of 327 postoperative NSCLC patients from the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were enrolled. All participants completed the General Questionnaire, Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Herth Hope Index (HHI) Scale, and Social Support Rating Scale (SSRS). RESULTS: The mean FoP-Q-SF score was (30.3 ± 9.48) points in postoperative NSCLC patients, Among them, there were 188 patients (57.5%) who had psychological dysfunction, indicated by a score of > / = 34. Patient sex and family income were independent risk factors for FCR (both p < 0.05). Correlation analysis revealed a negative association between FCR and hope level (p < 0.05) and a positive association between hope level and social support (p < 0.05). Notably, social support mediated the association between FCR and hope in patients receiving surgery for NSCLC (contribution effect: 30.24%). CONCLUSION: Postoperative NSCLC patients experience a moderate level of FCR, especially females and those with a low family income. Social support partially mediates the relationship between FCR and hope in this population. Therefore, an increase in the level of social support can increase hope among these patients and advancing recovery.

Inhibition of Salmonalla enterica by a novel strain of Bacillus subtilis isolated from the faeces of healthy chickens.

1. The objective of the study was to demonstrate that Bacillus subtilis strain VL28 (BS-VL28), a novel strain isolated from faeces of healthy chicken, has potential as a probiotic.2. The study evaluated the probiotic properties of BS-VL28 and the effects of dietary supplementation of this strain on growth performance and mortality in chickens challenged with Salmonella enterica CT01.3. BS-VL28 exhibited a specific inhibitory activity against Escherichia coli CT11, Salmonella enterica CT01, Staphylococcus spp. CT21 and Streptococcus spp. CT31.4. BS-VL28 also showed an auto-aggregation percentage of 82%, co-aggregation activity greater than 60%, high tolerance to low pH (<2.0) under the presence of 0.05% bile salts. However, the results from the antibiotic susceptibility tests demonstrated that this strain was sensitive to erythromycin, gentamycin, doxycycline, norfloxacin, oxytetracycline, trimethoprim-sulfamethoxazole, enrofloxacin but was intermediate to neomycin.5. Inclusion of probiotic (5 g BS-VL28 (107 CFU/g) per kg of feed to diet of challenged chickens showed better performance and feed conversion rates (FCR). There was a significant decrease (p < 0.05) in mortality in the probiotic-treated group compared to the control and antibiotic-treated groups.6. From these results, BS-VL28 could potentially function as a probiotic for broilers.

A combination of garlic oil and cooked chilli oil could be effective and efficient for pigeon production.

This study was conducted to investigate whether the combination of garlic oil and cooked chilli oil is worth using for pigeon production in the context of a total ban on antibiotics in feed additives in China. Two hundred female white king pigeons aged 23 days were randomly divided into five groups with ten replicates (four birds each). In the 47 days trial, the control group was fed with a basal diet, treatment groups were given a basal diet supplemented with 20 mg/kg neomycin sulphate or 2 g/kg corresponding oil (garlic oil or cooked chilli oil or their mixture) respectively. The mixed oil showed obvious antibacterial activity against gram-positive bacterium and its minimal bactericidal concentration against St. aureus, Salmonella and Escherichia coli were all no more than 1.0 mg/ml. In the feeding experiment, pigeons feed with garlic oil with strong bacteriostatic activity had lower FCR and better protein metabolism, and chilli oil showed strong effects of promoting feed intake and weight gain on pigeons but increased serum glucose and lipid content. Compared with the control and the antibiotic group, the mixed oil got increased growth performance, less drip loss of meat, better protein metabolism promoting, and more complete intestinal structure of pigeon. In addition, the breast meat in the mixed oil group had higher total points in the sensory test. The mixed oil combined the strong bacteriostasis of garlic oil with the feeding promotion effect of cooked chilli oil, it improved the comprehensive performance of pigeons and had the feasibility to be popularized as a non-antibiotic strategy in pigeon production.

Beneficial impact of dietary methyl methionine sulfonium chloride and/or L-carnitine supplementation on growth performance, feed efficiency, and serum biochemical parameters in broiler chicken: role of IGF-1 and MSTN genes.

The purpose of this study was to examine the effect of dietary supplementation with methyl methionine sulfonium chloride (MMSC), and L-carnitine (L-CAR) alone or in combination on the growth performance of broilers through their impact on the expression of IGF-1 and MSTN genes associated with growth in broilers. One-day-old female Ross 308 broiler chicks were allocated into four groups, each of which received a broiler starter diet and water daily ad libitum. The control group (group 1) was given drinking water without any additives. Group 2 received 0.25 g L-carnitine per liter of drinking water, group 3 received 0.25 g MMSC per liter of drinking water, and group 4 received 0.25 g of both L-carnitine and MMSC per liter of drinking water. Birds were given a starter diet to 21 days after which they received a broiler grower diet to 35 days when the experiment ended. There were five replicate groups of 12 birds per treatment. Body weights and feed intake were recorded weekly. Compared to the control group of birds, supplementation with MMSC either alone or in combination with L-carnitine resulted in an increase in growth rate or feed utilization efficiency; L-carnitine by itself had no effect. MMSC supplementation, again either alone or in combination with L-carnitine, increased jejunal and ileal villi height, increased serum total proteins and globulins, downregulated myostatin (MSTN) mRNA, and upregulated insulin growth factor-1 (IGF-1) mRNA expression. Supplementation with L-carnitine alone showed none of these effects. We conclude that MMSC supplementation improved growth performance through the upregulation of IGF-1 mRNA expression and downregulation of MSTN mRNA expression.

Low-dose fludarabine and cyclophosphamide combined with rituximab in the first-line treatment of elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL): long-term results of project Q-lite by the Czech CLL Study Group.

Therapeutic options used to be very limited for treatment-naïve elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) before the introduction of chemo-immunotherapy. Because dose-reduced fludarabine-based regimens yielded promising results, the Czech CLL Study Group initiated a prospective observational study to assess safety and efficacy of low-dose fludarabine and cyclophosphamide combined with rituximab (FCR) in elderly/comorbid patients. Between March 2009 and July 2012, we enrolled 107 patients considered ineligible for full-dose FCR (median age, 70 years; median Cumulative Illness Rating Scale score, 5; median creatinine clearance, 69 ml/min). Notably, 77% patients had unfavourable biological prognosis [unmutated immunoglobulin heavy-chain variable-region gene (IGHV), 74%; deletion 17p, 9%). Fludarabine was reduced to 12 mg/m2 intravenously (iv) or 20 mg/m2 orally on days 1-3 and cyclophosphamide to 150 mg/m2 iv/orally on days 1-3. Grade 3-4 neutropenia occurred in 56% of the patients, but there were serious infections in only 15%. The median progression-free survival was 29 months, but was markedly longer in patients with mutated IGHV (median 53 months), especially in absence of del 11q or 17p (median 74 months). Low-dose FCR is a well-tolerated and effective first-line regimen for selected elderly/comorbid patients with CLL/SLL with favourable biology. The study was registered at clinicaltrials.gov (NCT02156726).

Cellular and molecular immune response and production performance of Indian white shrimp Penaeus indicus (H. Milne-Edwards, 1837), reared in a biofloc-based system with different protein levels of feed.

The present study focuses on the immunity and growth of Penaeus indicus fed with varying protein levels (25%, 30%, and 35%) in a biofloc based rearing system. A 120 days growth trial was carried out using juvenile Penaeus indicus (0.71 ± 0.01) with dietary protein level, 25% (LP), 30% (MP), and 35% (HP), and a control diet-fed with 35% acted as control group resulting in 4 treatments each with four replicates and were randomly assigned 16 tank units (7500 L each). A combination of different carbon sources (molasses, wheat flour, and rice bran in 2:1:1 ratio), yeast and a probiotic (Bacillus sp.) consortium were used for the development of biofloc. At the end of the trial, the growth parameters of shrimps viz., initial weight, feed conversion ratio (FCR), and daily growth coefficient (DGC) were computed. The results indicated that shrimp fed with medium (30%) protein (MP) diet recorded significantly (P < 0.05) improved growth performance compared to high protein fed group (35%) and low protein (25%) fed group (LP) in a biofloc system and control group (35%). The immunological parameters such as hemagglutination activity (HA) assay, serum protein, lysozyme, phenol oxidase (PO), and inhibition of superoxide dismutase (SOD) activity were observed in serum, plasma, and hemocyte lysate supernatant (HLS). The HA activity, PO activity in plasma was found to be higher in high protein fed animals, whereas medium protein resulted in enhanced PO activity in serum. Similarly, lysozyme and SOD were inhibited well in high protein fed animals compared to the low protein fed group. The vital immune genes's mRNA profiling showed a potential rise in the expressional pattern in MP and HP treatments compared to LP and control. BGBP (beta-1,3-glucan binding protein) and hemocyanin mRNA transcript levels were highly upregulated in the HP (5 fold) and moderately expressed in MP (2 fold) and LP (1-2 fold). The transcripts of peroxinectin, antimicrobial peptides like crustin showed significant upregulation in HP followed by in MP and LP and control. Likewise, other immune genes, such as SOD, prophenoloxidase (proPO), showed a similar trend in a marginal way, indicating immunomodulation in the biofloc groups. This study suggested that biofloc with high protein (35%) supplementation can substantially enhance the immune response of shrimps, although medium protein level (30%) is optimum for improving the survival, growth, and in turn economic return in Indian white shrimp.

A phase II Japanese trial of fludarabine, cyclophosphamide and rituximab for previously untreated chronic lymphocytic leukemia.

OBJECTIVE: Fludarabine, cyclophosphamide and rituximab (FCR) is the standard regimen for fit patients with untreated CD20-positive chronic lymphocytic leukemia (CLL). However, this combination is unavailable in Japan because rituximab is not approved for CLL. We investigated the efficacy and safety of FCR in this single-arm, multicenter study designed as a bridging study to the CLL8 study by the German CLL Study Group. METHODS: The study enrolled previously untreated patients with CLL of Binet stage B or C with active disease. Patients with a Cumulative Illness Rating Scale score of ≤6 and creatinine clearance of ≥70 ml/min were eligible. Patients received 6 cycles of FCR every 28 days and were followed for up to 1 year. RESULTS: Seven patients were enrolled. The best overall response rate according to the 1996 NCI-WG Guidelines, the primary endpoint of the study, was 71.4% (95% confidence interval, 29.0-96.3%), with one patient achieving complete response. No deaths or progression occurred during follow-up. The main adverse event was hematotoxicity. CD4-positive T-cell count decreased in all patients; most patients showed no reduction in serum immunoglobulin G. CONCLUSION: Although the number of patients was limited, FCR appears to be effective with manageable toxicity for treatment-naïve fit Japanese patients with CD20-positive CLL. CLINICAL TRIAL NUMBER: JapicCTI-132285.

Factor structure of the Fear of Cancer Recurrence Inventory (FCRI): Comparison of international FCRI factor structure data and factor analysis of the Dutch FCRI-NL using three predominantly breast cancer samples.

OBJECTIVE: Factor structure results of Fear of Cancer Recurrence Inventory (FCRI) translations are inconclusive. Through investigating the factor structure, this study aimed to improve the FCRI and its usability. Therefore, we did a comprehensive comparison of the factor structure results of all translations, by exploring and improving the structure of the Dutch FCRI-NL and by testing this new factor structure in two patient samples. METHODS: To compare factor structure results of FCRI translations, we did a literature search using PubMed and Google Scholar. We performed exploratory factor analysis (EFA) in a mixed cancer sample. The confirmatory factor analyses (CFAs) were secondary analyses performed in two randomized controlled trial samples: consecutive breast cancer patients and distressed, mainly breast cancer patients. RESULTS: All translations showed comparable and reasonable factor structure results; however, the FCRI factor structure can be improved. The EFA resulted in a four-factor solution: fear of cancer recurrence (FCR) severity, cognitive coping, impact of FCR on functioning and behavioural coping. However, the 4-factor CFAs did not fit the sample 2 and 3 data well. CONCLUSION: Further exploring the FCRI-NL factor structure did not result in a psychometrically stronger FCRI-NL. Therefore, we recommend retaining the 7-factor FCRI-NL.

Differences between Human and Mouse IgM Fc Receptor (FcµR).

Both non-immune "natural" and antigen-induced "immune" IgM are important for protection against pathogens and for regulation of immune responses to self-antigens. Since the bona fide IgM Fc receptor (FcµR) was identified in humans by a functional cloning strategy in 2009, the roles of FcµR in these IgM effector functions have begun to be explored. In this short essay, we describe the differences between human and mouse FcµRs in terms of their identification processes, cellular distributions and ligand binding activities with emphasis on our recent findings from the mutational analysis of human FcµR. We have identified at least three sites of human FcµR, i.e., Asn66 in the CDR2, Lys79 to Arg83 in the DE loop and Asn109 in the CDR3, responsible for its constitutive IgM-ligand binding. Results of computational structural modeling analysis are consistent with these mutational data and a model of the ligand binding, Ig-like domain of human FcµR is proposed. Serendipitously, substitution of Glu41 and Met42 in the CDR1 of human FcµR with mouse equivalents Gln and Leu, either single or more prominently in combination, enhances both the receptor expression and IgM binding. These findings would help in the future development of preventive and therapeutic interventions targeting FcµR.