cHL Group Research Articles

Combined intestinal microbiota and transcriptomic analysis to investigate the effect of different stocking densities on the ability of Pacific white shrimp (Litopenaeus vannamei) to utilize Chlorella sorokiniana

Aiming to investigate the impact of different stocking densities on the ability of Pacific white shrimp (Litopenaeus vannamei) to utilize Chlorella sorokiniana (CHL), a 3 × 2 factorial design stocking experiment was used in this study. Specifically, shrimp was fed with two dietary protein sources (fishmeal [FM] and CHL) at low (LSD; 100 per m3), medium (MSD; 200 per m3) and high (HSD; 300 per m3) stocking densities for 8 weeks. The growth performance and resistance to Vibrio parahaemolyticus (1.0 × 107 CFU/mL) of shrimp decreased with the increase of stocking density, but dietary CHL improved this result. Differences between the CHL and FM groups for V. parahaemolyticus resistance were significant only under high-density conditions (P < 0.05). Significant interactions between stocking density and protein source were found on the activities of catalase (CAT), superoxide dismutase (SOD) and phenol oxidase (PO), and the contents of malondialdehyde (MDA) in the hepatopancreas and the activities of intestinal amylase, most of which were significantly different between CHL and FM groups only at high stocking density (P < 0.05). Analysis of 16S rDNA sequencing showed that dietary CHL increased the alpha diversity of intestinal microbiota, inhibited the colonization of pathogenic bacteria and enhanced the abundance of beneficial bacteria. Transcriptomic results showed that at high stocking densities, differentially expressed genes (DEGs) in the FM vs CHL group were mostly upregulated and primarily enriched in immune and metabolic related pathways including Toll, immune deficiency (Imd) and glycolysis–gluconeogenesis pathways. Pearson correlation analysis revealed significant correlation between the top ten intestinal bacteria at the genus level and markedly enriched DEGs, also more were detected under high density situations. In conclusion, CHL has great potential as a novel protein source in the intensive farming of shrimp.

A Comparison of Three Protein Sources Used in Medium-Sized Litopenaeus vannamei: Effects on Growth, Immunity, Intestinal Digestive Enzyme Activity, and Microbiota Structure

The type of protein source in diets has many effects on shrimp. In this study, Litopenaeus vannamei with an initial body weight of 3.68 ± 0.002 g were fed for 8 weeks on three experimental diets (isoproteic: 41.00%; isolipidic: 7.61%) that were formulated using fish meal (FM), Chlorella sorokiniana (CHL), and Clostridium autoethanogenum protein (CAP) as the primary protein sources, respectively. This study examined the growth, non-specific immunity, intestinal digestion, and microbiota of L. vannamei after the feeding experiment concluded. Compared to the FM group, the findings indicate that the weight gain rate (WGR), specific growth rate (SGR), and protein efficiency ratio (PER) of L. vannamei were notably enhanced via dietary CAP. The CHL group exhibited the highest levels of catalase (CAT), phenoloxidase (PO), and superoxide dismutase (SOD) activities in the gills of L. vannamei, whereas the FM group had the lowest levels. Conversely, the malondialdehyde (MDA) content showed the opposite trend. Both dietary CHL and CAP promoted the digestive enzyme activities of L. vannamei, with dietary CAP having a more pronounced promotional effect. An analysis of alpha diversity indicated that the consumption of dietary CHL substantially enhanced the abundance and diversity of microbiota in the intestinal tract of L. vannamei. Furthermore, the dietary CHL significantly increased the colonization of immune-associated beneficial bacteria and inhibited the colonization of pathogenic bacteria in the intestinal tract of L. vannamei, whereas dietary CAP mainly increased the colonization of growth-associated beneficial bacteria. Functional predictions showed that different dietary protein sources affect various metabolic activities and signaling pathways of L. vannamei, and some functions, including signal transduction, cell motility, and the immune system, were significantly enhanced in the CHL group. In summary, both dietary CHL and dietary CAP promoted growth and immunity in L. vannamei compared to dietary FM. The results of this study could be helpful for the sustainable development of shrimp farming.

Efficacy and safety of pembrolizumab (pembro) in children and young adults with newly diagnosed classical Hodgkin lymphoma (cHL) with slow early response (SER) to front-line chemotherapy (chemo) in the phase 2, open-label, KEYNOTE-667 study.

10027 Background: Patients (pts) with cHL with SER to initial chemo are at higher risk of relapse, and chemo dose intensification and radiotherapy (RT) can increase the burden of late organ toxicities. The open-label, phase 2 KEYNOTE-667 study (NCT03407144) is evaluating pembro plus chemo in pts with cHL and SER to front-line chemo. Results of an interim analysis in pts with high-risk cHL (group 2) and SER are presented. Methods: Pts were aged 3-17 (children) or 18-25 y (young adults) with newly diagnosed stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL. Pts received induction with 2 cycles of vincristine, etoposide, prednisone/prednisolone, and doxorubicin (OEPA). Response was assessed after induction (early) and consolidation (late) therapy by PET/MRI/CT. After induction, pts with rapid early response at the early response assessment (ERA) received nonstudy therapy and pts with SER at ERA received consolidation with 4 cycles cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28) plus pembro 2 mg/kg up to 200 mg IV every 3 weeks (Q3W; aged 3-17 y) or 200 mg IV Q3W (aged 18-25 y). Pts with PET positivity (Deauville score 4-5) after consolidation (late response assessment [LRA]), received involved-site RT (28.8 Gy) to late PET-positive residua; RT was omitted in pts with PET negativity. All pts with SER received maintenance pembro Q3W for a total of 17 doses. Primary end point was ORR by blinded independent central review (BICR) per Cheson 2007 International Working Group criteria in pts with SER. Secondary end points included PET negativity after consolidation and safety. Results: At data cutoff (Sep 02, 2022), median follow-up was 15.3 mo (range, 3.2-30.5); 49 pts with high-risk cHL with SER were included. Median age was 15 y (range, 6-22), 24 (49%) pts had bulky disease, and 31 (63%) had Ann Arbor stage IV disease. 22 (45%) pts completed treatment and 24 (49%) were ongoing on consolidation/maintenance treatment. Median time on pembrolizumab was 10.4 mo (range, 0.5-11.8). 42 (86%) of 49 pts had a LRA, of whom 27 (64%) were PET negative by BICR (30 [71%] PET negative by investigator). All-cause adverse events (AEs) occurred in 42 (86%) pts, with 30 (61%) having a treatment-related AE. Grade ≥3 AEs occurred in 13 (27%) pts, with 7 (14%) having a serious AE. Grade ≥3 treatment-related AEs occurred in 6 (12%) pts. 4 (8%) pts had immune-mediated AEs (2 grade 1 hypothyroidism; 2 grade 2 hypothyroidism). Conclusions: In pediatric pts with high-risk cHL and SER to standard OEPA induction, pembro plus COPDAC-28 consolidation had manageable safety and resulted in 64% of pts having a PET-negative response at end of chemo and being spared RT. These results suggest adding pembro to COPDAC-28 consolidation may augment responses in this high-risk population. Clinical trial information: NCT03407144 .

Expressive vocabulary of school-age children with mild to moderately severe hearing loss.

The main goal of this study was to describe the expressive vocabulary of school-age children with mild to moderately severe hearing loss (CHL group) and to compare their performance with children with normal hearing (CNH group) of the same age. Another aim was to examine the interaction between nonword repetition and expressive vocabulary size. Furthermore, the interaction between results on vocabulary tests and background factors, such as the age of diagnosis, age of hearing aid fitting, and amount of hearing aid use, was explored. School-aged children with mild to moderately severe, permanent bilateral hearing loss and children with normal hearing were included in this cross-sectional study. The children participated in assessments of naming pictures, defining words, and repetition of nonwords and sentences. Results of the CHL group and the CNH group were compared. The analysis also included the degree of hearing loss, the age of diagnosis, amount of hearing aid use, and level of parental education. The CHL group performed significantly below the CNH group on all measures: picture naming, defining words, nonword repetition, and repetition of sentences. The proportion of words pronounced with correct phonological structure when picture naming was more limited in the CHL group than in the CNH group. There was a significant positive correlation between the amount of hearing aid use and nonword repetition ability in the CHL group. Age of diagnosis and age of hearing aid fitting was not significantly correlated with the outcomes of the vocabulary assessments in this study. Despite the technological advancement of hearing aids, the expressive vocabulary in school-aged children with mild to moderately severe, permanent bilateral, hearing impairment does not reach the same level as for children with normal hearing, although there is a variation in performance within the group. The variation in the CHL group was not uniquely impacted by either age, degree of hearing loss, or the age of diagnosis. The amount of hearing aid use seems to impact the perception of new words. More studies of expressive vocabulary are needed, because they capture a dimension of word learning that seems particularly sensitive to hearing loss and hearing aid use.

Use of Positron Emission Tomography in Patients with Classical Hodgkin Lymphoma Outside of Europe and North America: Results from the International, Multi-Center, Retrospective B-Holistic Study

Use of Positron Emission Tomography in Patients with Classical Hodgkin Lymphoma Outside of Europe and North America: Results from the International, Multi-Center, Retrospective B-Holistic Study

Spectral Properties of Chlorophyll f in the B800 Cavity of Light-harvesting Complex 2 from the Purple Photosynthetic Bacterium Rhodoblastus acidophilus.

The interactions of chlorophyll (Chl) and bacteriochlorophyll (BChl) pigments with the polypeptides in photosynthetic light-harvesting proteins are responsible for controlling the absorption energy of (B)Chls in protein matrixes. The binding pocket of B800 BChl a in LH2 proteins, which are peripheral light-harvesting proteins in purple photosynthetic bacteria, is useful for studying such structure-property relationships. We report the reconstitution of Chl f, which has the formyl group at the 2-position, in the B800 cavity of LH2 from the purple bacterium Rhodoblastus acidophilus. The Qy absorption band of Chl f in the B800 cavity was shifted by 14 nm to longer wavelength compared to that of the corresponding five-coordinated monomer in acetone. This redshift was larger than that of Chl a and Chl b. Resonance Raman spectroscopy indicated hydrogen bonding between the 2-formyl group of Chl f and the LH2 polypeptide. These results suggest that this hydrogen bonding contributes to the Qy redshift of Chl f. Furthermore, the Qy redshift of Chl f in the B800 cavity was smaller than that of Chl d. This may have arisen from the different patterns of hydrogen bonding between Chl f and Chl d and/or from the steric hindrance of the 3-vinyl group in Chl f.

Protective Effects of Antioxidant Chlorophyllin in Chemically Induced Breast Cancer Model In vivo.

Glutathione-related enzymes belong to the protection mechanism of the cells against harmful oxidative damage and chemicals. Glutathione S-transferase (GST) is frequently over-expressed in various cancer cells and is involved in drug resistance. Chlorophyllin is an antioxidant molecule interfering with the GST P1-1 activity. The purpose of this study is to evaluate the short- and long-term protective effects of chlorophyllin as an antioxidant molecule on DNA damage, antioxidant enzyme activities, trace elements, and minerals in chemically induced breast cancer model in vivo. In our study, N-methyl-N-nitrosourea (MNU) was used for inducing breast carcinogenesis in female Sprague-Dawley rats. A total of 36 rats were divided into groups as short term and long term. Each group was divided into four sub-groups as control group received physiological saline solution (n= 3), Chl group (n= 5) received chlorophyllin, MNU group (n= 5) was administered MNU, and Chl + MNU group (n= 5) was treated with both chlorophyllin and MNU. Results illustrated that chlorophyllin had a significant anti-genotoxic effect in the short term, and glutathione-related enzyme activities were protected by chlorophyllin treatment in MNU-induced breast cancer model. Additionally, MNU administration impaired mineral and trace element levels including Na, Mg, K, Fe, Zn, and Co in the liver, kidney, spleen, heart, and tumor tissues; however, adverse effects of MNU were recovered upon chlorophyllin treatment in the indicated tissues of the rats. In conclusion, chlorophyllin can be used as an antioxidant molecule to ameliorate adverse effects of MNU by enhancing antioxidant enzyme activities and regulating trace element and mineral balance in several organs and tumor tissue in the breast cancer model.

Results from the International, Multi-Center, Retrospective B-Holistic Study: Describing Treatment Pathways and Outcomes for Classical Hodgkin Lymphoma

Results from the International, Multi-Center, Retrospective B-Holistic Study: Describing Treatment Pathways and Outcomes for Classical Hodgkin Lymphoma

Aberrant peripheral blood CD4+ CD25+ FOXP3+ regulatory T cells/T helper-17 number is associated with the outcome of patients with lymphoma.

Little is known about the clinical significance of the peripheral blood CD4+ CD25+ FOXP3+ regulatory T cells (Tregs) and T helper-17 (Th17) cells in lymphoma patients. In this study, the prognostic and clinical significance of peripheral blood Tregs and Th17 cells were evaluated in lymphoma patients during different phases. The frequency of Tregs and Th17 lymphocytes was measured by flow cytometry method in 47 classical Hodgkin's lymphoma (cHL) and 48 diffuse large B cell lymphoma (DLBCL) patients. Our results showed that the frequency of Tregs and absolute Treg count was significantly reduced in relapsed patients compared to patients at the remission phase, as well as with newly diagnosed untreated patients in both groups. Patients who reached complete remission had elevated frequency of CD4+ FOXP3+ lymphocytes, Tregs, absolute Treg count, Treg/CD4 and Treg/Th17 ratio in the cHL group and CD4+ CD25+ cells in DLBCL group. The frequency of Tregs, absolute Treg count and Treg/Th17 ratio in cHL patients and CD4+ FOXP3+ and CD4+ CD25+ cells in DLBCL patients positively associated with survival rate. Moreover, the percentage of Tregs and absolute Treg count positively correlated with white blood cell, platelet count and ESR level in cHL patients and with white blood cell count in DLBCL patients. The initial number of Tregs/Th17 cells and also the Treg/Th17 ratio was not associated with changes in disease-free survival (DFS) in both groups. Therefore, higher frequency of peripheral blood Tregs and Treg/Th17 ratio might be associated with a favorable outcome in lymphoma patients, better response to chemotherapy and lower rate of relapse.

Combined effects of calcium hydroxide and photobiomodulation therapy on apexogenesis of immature permanent teeth in dogs

Treatment of high-risk traumatic immature teeth due to incomplete root development is challenging. Apexogenesis is currently the ideal treatment option that allows normal root development. The purpose of this study was to evaluate the apexogenesis process of immature permanent teeth of dogs when co-administered with calcium hydroxide and photobiomodulation therapy (PBMT). A total of 36 immature permanent anterior and premolar teeth were selected from three 4–6-month-old dogs of Iranian mixed generation. The teeth were categorized into two groups, calcium hydroxide with laser irradiation (CHL) and calcium hydroxide without laser irradiation (CH). All the selected teeth received calcium hydroxide pulpotomy. After restoring teeth with amalgam, the CHL group received gallium‑aluminum-arsenide (GaAlAs) diode laser (810 nm, 4.2 J/cm2, 0.3 W, 9 s,CW) on apical one-third of both buccal and lingual roots. The irradiation was repeated every 48 h for fourteen days. Intravenous tetracycline was used to observe newly formed dentin in the first, third, seventh, and fourteenth days. The distance between tetracycline lines (DTL) was examined by Fluorescence microscopy. Generalized estimating equations (GEE) were used for data analysis. In all assessments, the mean DTL were greater in the CHL group. However, the two groups had no significant differences in the amount of deposited dentin between the first and third, third and seventh, and first and seventh lines. Meanwhile, there was a significant difference between the two groups in terms of the distances between lines 7 and 14, 1 and 14 and also 3 to 14 (P < .001). In other words, from the 7th day onwards, there was a significant difference between the two groups. Within the limitation of this study, the combination therapy of PBMT and pulpotomy with calcium hydroxide accelerated apexogenesis in immature permanent dogs' teeth.

Clinical Characteristics and Prognosis of 56 Lymphoma Patients with Mediastinal Masses

To analyze the incidence, clinical characteristics, treatment efficacy and prognosis of lymphoma patients with mediastinal masses. The clinical data of 56 lymphoma patients with mediastinal masses treated in our hospital from February 2007 to January 2018 were collected, and the clinical characteristics, typing, staging, treatment efficacy as well as prognosis analyzed retrospectively. Among the 56 patients, male and female were 25 (45%) cases and 31(55%) cases, respectively. The median age was 31 (17-72) years old, out of them 48 (86%) patients aged below 40 years old. According to pathological classification, 9 (16.1%) cases were diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS), 26(46.4%) cases were primary mediastinal large B cell lymphoma (PMBCL), 17 (30.4%) cases were classical Hodgkin's lymphoma (cHL), and 4 (7.1%) cases were primary mediastinal grey zone lymphoma (MGZL). All the patients were treated with chemotherapy or immuno-chemotherapy.The median follow-up time was 54.5(11-149) months. In cHL group, 10 cases received involved field radiotherapy (IFRT), 10 (58.8%) cases achieved complete remission (CR), 2 (11.8%) cases achieved partial remisson (PR), and 5 (29.4%) patients experienced progressive disease (PD) , 6 patients with relapsed/refractory disease received autologous hematopoietic stem cell transplantation (auto-HSCT), the 1, 2, and 5 year overall survival (OS) rates of cHL group were 94.1%, 88.2%, and 67.2%, respectively. In MGZL group, 3 cases combined with IFRT, 1 case with auto-HSCT, 2 (50%) cases achieved CR, 2 (50%) cases experienced PD, the 1, 2, 5 year OS rates of MGZL group were 66.7%, 66.7%, and 33.3%, respectively. In PMBCL group, 8 cases combined with IFRT, 7 cases with auto-HSCT, 22 (84.0%) cases achieved CR, 2 (8.0%) cases achieved PR, 1 (4.0%) case was stable disease (SD) and 1 (4.0%) case experienced PD, the 1, 2 year OS rates of PMBCL group were both 100%, and 5 year OS rate was 95.7%. In DLBCL-NOS group, 3 cases combined with IFRT, 2 cases with auto-HSCT, 4 (44.5%) cases achieved CR, 2 (22.2%) cases achieved PR, 1 (11.1%) case was stable disease (SD) and 2 (22.2%) cases experienced PD, the 1 year OS rate of DLBCL-NOS cohort was 100%, 2, and 5 year OS rates were both 77.8%. There was a significant difference of OS rate among these 4 group (P＜0.05). In intra-group comparison, OS rate in PMBCL group were significantly longer than both MGZL group (P＜0.01) and cHL group(P＜0.05), and showed no significant difference from DLBCL-NOS group (P＞0.05). Mediastinal masses are characterized by unique clinical features due to their unique anatomical location. Several B cell originated lymphomas including cHL,MGZL,PMBCL and DLBCL-NOS, manifested primary or secondary mediastina involvement, tend to occur in young adults and have similar clinical features. However, their therapeutic response was significantly different. The prognosis of PMBCL is prior to MGZL and cHL.

How water-mediated hydrogen bonds affect chlorophyll a/b selectivity in Water-Soluble Chlorophyll Protein

The Water-Soluble Chlorophyll Protein (WSCP) of Brassicaceae is a remarkably stable tetrapyrrole-binding protein that, by virtue of its simple design, is an exceptional model to investigate the interactions taking place between pigments and their protein scaffold and how they affect the photophysical properties and the functionality of the complexes. We investigated variants of WSCP from Lepidium virginicum (Lv) and Brassica oleracea (Bo), reconstituted with Chlorophyll (Chl) b, to determine the mechanisms by which the different Chl binding sites control their Chl a/b specificities. A combined Raman and crystallographic investigation has been employed, aimed to characterize in detail the hydrogen-bond network involving the formyl group of Chl b. The study revealed a variable degree of conformational freedom of the hydrogen bond networks among the WSCP variants, and an unexpected mixed presence of hydrogen-bonded and not hydrogen-bonded Chls b in the case of the L91P mutant of Lv WSCP. These findings helped to refine the description of the mechanisms underlying the different Chl a/b specificities of WSCP versions, highlighting the importance of the structural rigidity of the Chl binding site in the vicinity of the Chl b formyl group in granting a strong selectivity to binding sites.

285TiP - Phase II, open-label study of pembrolizumab in children and young adults with newly diagnosed classical Hodgkin lymphoma (cHL) with slow early response (SER) to frontline chemotherapy: KEYNOTE-667

BackgroundHigh risk for relapse is observed in cHL patients (pts) with SER to initial chemotherapy and organ toxicities may be higher following dose intensification. Trial designThe phase 2 KEYNOTE-667 (NCT03407144) study will enroll 440 pts aged 3-17 (children) or 18-25 years (young adults) with newly-diagnosed, confirmed stage IA, IB, or IIA cHL without bulky disease (Group 1 [low-risk]) or stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL (Group 2 [high-risk]); measurable disease; performance status per Lansky Play-Performance Scale ≥50 (age ≤16 years) or Karnofsky score ≥50 (age >16 years). Pts will receive induction with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD; Group 1) or vincristine, etoposide/etoposide phosphate, prednisone/prednisolone, doxorubicin (OEPA; Group 2) for 2 cycles, then early response assessment by PET/CT/MRI. Pts with rapid early response (Deauville score 1-3) will receive non-study consolidation chemotherapy. Pts with SER (Deauville score 4-5) will receive consolidation with pembro 2 mg/kg Q3W to 200 mg (children) or 200 mg Q3W (young adults) plus 2 cycles AVD (Group 1) or 4 cycles cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28; Group 2). PET/CT for late response assessment (LRA) will be performed after consolidation. After LRA, Group 1 SER pts and Group 2 pts (Deauville score 4-5) will receive radiotherapy (RT). All pts will receive maintenance pembro Q3W concomitantly with RT. Pembro will continue for 17 administrations, with option to stop after 8-administrations due to CR, or until progression, unacceptable toxicity, or withdrawal. Primary endpoint: ORR per Cheson 2007 IWG criteria by group in SER pts. Secondary endpoints: SERs with PET negativity after consolidation, 2-yr event-free survival (EFS), OS, RT frequency and details by group, RERs with PET negativity after ABVD induction, 3-yr EFS by investigator, OS by risk group, serum TARC levels at screening in SERs by risk group. ORR with 95% CI will be estimated by Clopper-Pearson method. EFS and OS will be estimated by Kaplan-Meier method. Safety will be assessed in all-treated pts. Clinical trial identificationNCT03407144. Legal entity responsible for the studyMerck & Co., Inc. FundingMerck & Co., Inc., Kenilworth, NJ, USA. DisclosureK. Kelly: Research grant / Funding (institution): Merck & Co., Inc. F. Keller: Research grant / Funding (institution): Merck & Co., Inc. A. Nahar: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. L. Giulino-Roth: Research grant / Funding (institution): Merck & Co., Inc. All other authors have declared no conflicts of interest.

Ten-year survival outcomes for patients with early stage classical Hodgkin lymphoma: An analysis from Kentucky Cancer Registry

Objective/BackgroundEarly stage classical Hodgkin lymphoma (cHL) has an excellent outcome. Recent studies focus on decreasing toxicity related to the addition of radiation along with chemotherapy. Real-life reporting of the addition of radiation to chemotherapy is lacking. This study investigates the outcomes obtained from a statewide cancer registry for early stage cHL patients treated with chemotherapy alone (CT) versus patients treated with the combined modality of chemotherapy and radiation (CMT). MethodsA retrospective study of cHL patients diagnosed and treated was identified using a statewide cancer registry from 2005 to 2014. Patients with early stage disease (I, II) were then grouped on the basis of the presence of B symptoms into favorable and unfavorable groups. Baseline characteristics (age, gender, extranodal involvement, and histology) as well as overall survival were compared for both groups depending on whether they received CT or CMT as first line therapy for their cHL. ResultsA total of 961 patients were identified; of those, 127 were excluded as they received only radiation or another form of treatment. Of the remaining patients, 293 were categorized as early stage favorable cHL (Group 1) and 130 adults were in the unfavorable cHL (Group 2). There were 335 patients with advanced stage cHL (Group 3) and 76 patients in an unknown stage. The 10-year overall survival for Group 1 was 81.3% versus 76.3% for Group 2 and 52.7% for Group 3. For Group 1, 10-year overall survival was 86.7% with CMT versus 75.1% for those receiving CT only (p = .004). For Group 2, there was no difference in 10-year overall survival between the CMT group (80.0%) and CT (72.5%) (p = .73). ConclusionWhile radiation therapy might increase long-term toxicity in cHL, in our large data cohort, radiotherapy consolidation as part of the initial therapy for early stage disease provides superior survival at 10 years, especially in favorable risk cHL.

Modification of the daily blood pressure profile in hypertensive patients with type 2 diabetes mellitus

Objective. To evaluate the effect of combinations azilsartan medoxomil / chlorthalidone (Az-M/Chl) vs. perindopril / indapamide (Pr / Yn) regarding the modification of the daily blood pressure profile (BP) and augmentation index level in hypertensive patients (hypertension 2 nd degree, HTN), the blood pressure profile “nondipper” or “night-peaker” and type 2 diabetes mellitus (DM). Design and methods . The study included 51 HTN (mean age 73 ± 11,7 years) patients (25 patients in the group Az-M / Chl and 26 patients in the group Pr / Yn, the groups were comparable by the main clinical parameters) with blood pressure profile “non-dipper” or “night-peaker”, DM (compensation stage). All patients have been receiving stable but ineffective antihypertensive therapy for at least 3 months before inclusion. The level of salt consumption was defined by the questionnaire “Charlton: SaltScreener”. Ambulatory 24-hour blood pressure monitoring (ABPM) was performed using BPLab® device (software Vasotens, Russia) which enables analysis of central hemodynamics. Statistica 10.0 software and software R using readxl, psych, ggplot2, ggpubr, gridExtra packages were used for statistical data processing. Results. Twenty-seven (53 %) patients reported consumption of more than 6 g of salt per day: 14 (56 %) patients in the Az-M / Chl group, and 13 (50 %) patients in the Pr / Yn group. Mean daily BP was 161,2 / 102 ± 8,77 / 9,31 mm Hg in the Az-M / Chl group, and 158,3 / 96,7 ± 10,4 / 7,21 mm Hg in the group Pr / In (p > 0,05); mean daily systolic BP (MAP) was 161,2/102,0 ± 8,8 / 9,3 mm Hg and 158,3 / 96,7 ± 10,4 / 7,2 mm Hg, respectively (p > 0,05); aortic augmentation index — 4,88 ± 15,9 % and 2,7 ± 10,9 %, respectively (p > 0,05). At randomization (baseline), the non-dipping BP profile was found in 86,3 % (n = 44) patients, and the night-peaker profile — in 13,7 % (n = 7) patients. At the final visit, all patients achieved target BP level; mean daily systolic BP was 130,2 ± 8,8 and 139,9 ± 8,2 mm Hg in the Az-M/Chl and Pr / In groups, respectively (W = 140, p-value = 0.000497). The Az-M / Chl group demonstrated a more significant reduction in arterial stiffness. In addition, in the AZ-M / Chl group, 18 (72 %) patients showed change to a dipping BP profile, while only 5 (19 %) patients demonstrated the change in the Pr / Yin group. Conclusion . The combination of azilsartan medoxomil/chlorthalidone showed a more significant compared with the combination of perindopril/indapamide: (1) a decrease in mean blood pressure per day; (2) the effect on the modification of the daily profile of blood pressure; (3) alteration of GI in aorta.

Phase 2, open-label study of pembrolizumab in children and young adults with newly diagnosed classical Hodgkin lymphoma (cHL) with slow early response (SER) to frontline chemotherapy: KEYNOTE-667.

TPS7567 Background: High risk for relapse is observed in cHL patients (pts) with SER to initial chemotherapy and organ toxicities may be higher following dose intensification. Methods: The phase 2 KEYNOTE-667 study will enroll 440 pts aged 3 to 17 (children) or 18 to 25 years (young adults) with newly diagnosed, confirmed stage IA, IB, or IIA cHL without bulky disease (Group 1 [low-risk]) or stage IIEB, IIIEA, IIIEB, IIIB, IVA, or IVB cHL (Group 2 [high-risk]); measurable disease; and performance status per Lansky Play-Performance Scale ≥50 (age ≤16 years) or Karnofsky score ≥50 (age &gt;16 years). Pts will receive induction with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD; Group 1) or vincristine, etoposide/etoposide phosphate, prednisone/prednisolone, doxorubicin (OEPA; Group 2) for 2 cycles, then early response assessment by PET/CT/MRI. Pts with rapid early response (Deauville score 1-3) will receive standard therapy. Pts with SER (Deauville score 4-5) will receive consolidation with pembro 2 mg/kg Q3W up to 200 mg (children) or 200 mg Q3W (young adults) plus 2 cycles AVD (Group 1) or 4 cycles cyclophosphamide, vincristine, prednisone/prednisolone, dacarbazine (COPDAC-28; Group 2). PET/CT for late response assessment (LRA) will be performed after consolidation. After LRA, Group 1 pts with SER and Group 2 pts with Deauville score 4-5 will receive radiotherapy (RT). All pts will receive maintenance with pembro Q3W concomitantly with RT. Pembro will continue up to 17 administrations, with an option to stop after 24 weeks due to CR, or until progression, unacceptable toxicity, or withdrawal. The primary endpoint is ORR per Cheson 2007 IWG criteria by group in SER pts. Secondary endpoints are SERs with PET negativity after consolidation, 2-yr event-free survival (EFS), OS, and RT frequency and details by group, RERs with PET negativity after ABVD induction, 3-yr EFS by investigator, and OS by risk group, and serum TARC levels at screening in SERs by risk group. ORR with 95% CI will be estimated by Clopper-Pearson method. EFS and OS will be estimated by Kaplan-Meier method. Safety will be assessed in all treated pts. Clinical trial information: NCT03407144.

Fourier transform visible and infrared difference spectroscopy for the study of P700 in photosystem I from Fischerella thermalis PCC 7521 cells grown under white light and far-red light: Evidence that the A–1 cofactor is chlorophyll f

(P700+ – P700) Fourier transform visible and infrared difference spectra (DS) have been obtained using photosystem I (PSI) complexes isolated from cells of Fischerella thermalis PCC 7521 grown under white light (WL) or far-red light (FRL). PSI from cells grown under FRL (FRL-PSI) contain ~8 chlorophyll f (Chl f) molecules (Shen et al., Photosynth. Res. Jan. 2019). Both the visible and infrared DS indicate that neither the PA or PB pigments of P700 are Chl f molecules, but do support the conclusion that at least one of the A–1 cofactors is a Chl f molecule.The FTIR DS indicate that the hydrogen bond to the 131-keto CO group of the PA pigment of P700 is weakened in FRL-PSI, as might be expected given that the proteins that bind the P700 pigments are substantially different in FRL-PSI (Gan et al., Science 345, 1312–1317, 2014).The FTIR DS obtained using FRL-PSI display a band at 1664 cm−1 that is assigned (based on density functional theory calculations) to the 21-formyl CO group of Chl f, that upshifts 5 cm−1 upon P700+ formation. This is much less than expected for a cation-induced upshift, indicating that the Chl f molecule is not one of the pigments of P700.In WL-PSI the A–1 cofactor is a Chl a molecule with 131-keto and 133-methylester CO mode vibrations at 1696 and 1750 cm−1, respectively. In FRL-PSI the A–1 cofactor is a Chl f molecule with 131-keto and 133-methylester CO mode vibrations at 1702 and 1754 cm−1, respectively.

Spectral signatures of five hydroxymethyl chlorophyll a derivatives chemically derived from chlorophyll b or chlorophyll f.

Chlorophylls (Chls) are pigments involved in light capture and light reactions in photosynthesis. Chl a, Chl b, Chl d, and Chl f are characterized by unique absorbance maxima in the blue (Soret) and red (Qy) regions with Chl b, Chl d, and Chl f each possessing a single formyl group at a unique position. Relative to Chl a the Qy absorbance maximum of Chl b is blue-shifted while Chl d and Chl f are red-shifted with the shifts attributable to the relative positions of the formyl substitutions. Reduction of a formyl group of Chl b to form 7-hydroxymethyl Chl a, or oxidation of the vinyl group of Chl a into a formyl group to form Chl d was achieved using sodium borohydride (NaBH4) or β-mercaptoethanol (BME/O2), respectively. During the consecutive reactions of Chl b and Chl f using a three-step procedure (1. NaBH4, 2. BME/O2, and 3. NaBH4) two new 7-hydroxymethyl Chl a species were prepared possessing the 3-formyl or 3-hydroxymethyl groups and three new 2-hydroxymethyl Chl a species possessing the 3-vinyl, 3-formyl, or 3-hydroxymethyl groups, respectively. Identification of the spectral properties of 2-hydroxymethyl Chl a may be biologically significant for deducing the latter stages of Chl f biosynthesis if the mechanism parallels Chl b biosynthesis. The spectral features and chromatographic properties of these modified Chls are important for identifying potential intermediates in the biosynthesis of Chls such as Chl f and Chl d and for identification of any new Chls in nature.

Comparison of flow cytometric and immunohistochemical immunophenotyping data for diagnosis of B-cell neoplasms and classic hodgkin's lymphoma

Objective: This study was aimed to compare the results of immunophenotyping by flow cytometry (FC) and immunohistochemistry (IHC) in the diagnosis of B-cell lymphomas and classic Hodgkin's lymphoma (cHL). Methods: This was a retrospective cohort study of 280 patients with chronic B-cell neoplasms and cHL performed between 2008 and 2013. Percentages of B- and T-cell markers detected by FC and IHC were compared regardless of the final diagnosis. Results: FC and IHC results were obtained from 280 patient medical records. There were 155 (55.4%) patients with non-Hodgkin's lymphoma (NHL), 110 (39.3%) with cHL, and 15 (5.4%) with chronic lymphocytic leukemia (CLL). Disparity between FC and IHC was observed for CD19 expression in cHL group where 73.6% (n = 81) CD19 expression was detected by FC and 59.1% (n = 65) detected by IHC (P

Interim Analysis Results from an International, Multi-Centre, Non-Interventional Retrospective Study to Describe Treatment Pathways, Outcomes, and Resource Use in Patients with Classical Hodgkin Lymphoma: B-CD30+ Hodgkin Lymphoma International Multi-Centre Retrospective Study of Treatment Practices and Outcomes (B-HOLISTIC)

Interim Analysis Results from an International, Multi-Centre, Non-Interventional Retrospective Study to Describe Treatment Pathways, Outcomes, and Resource Use in Patients with Classical Hodgkin Lymphoma: B-CD30+ Hodgkin Lymphoma International Multi-Centre Retrospective Study of Treatment Practices and Outcomes (B-HOLISTIC)