Bortezomib-based induction improves progression-free survival of myeloma patients harboring 17p deletion and/or t(4;14) and overcomes their adverse prognosis.

Providing a risk-adapted treatment strategy has been a key goal in the ongoing research efforts aimed at providing treatment tailored to the individual genetic make-up. Eighty myeloma patients have been tested for presence of 17p deletion and/or t(4;14) by fluorescent in situ hybridization (FISH). Based on FISH results, they have been categorized into patients lacking them (standard risk) and those harboring them (high risk). Patients in each category were randomly assigned 1:1 to induction treatment by either vincristine, adriamycin and dexamethasone (VAD), or bortezomib and dexamethasone (VD) followed by autologous stem cell transplantation and thalidomide maintenance and were followed up for 32 months. 32.5 % of patients were high risk. Following induction, there were significantly higher rates of at least very good partial response achievement in VD arms in standard- and high-risk patients. Regarding complete response achievement, there were insignificant differences between VAD and VD arms in standard and high-risk patients. After a median follow-up of 17.5 months, there was insignificant difference in overall survival (OS) between VAD and VD arms in standard and high-risk patients. There was superior progression-free survival (PFS) in VD arms in standard- and high-risk patients. Among patients who received VD, those belonging to standard and high-risk groups had similar PFS. In conclusion, bortezomib-based induction is superior to non-bortezomib-based one in patients harboring 17p deletion and/or t(4;14) in terms of improving PFS but not OS. Also, it reduces progression risk in patients harboring these high risk cytogenetics.

Effects of Mint Oils on the Human Oral Microbiome: A Pilot Study.

The oral microbiome is a diverse and complex ecosystem essential for maintaining oral and systemic health. Our study is the first to define the oral microbial community in Egyptian young adults and investigate the effects of natural antimicrobials on the oral microbiome. SuperMint (SM) is a proprietary blend of peppermint, Japanese mint, bergamot mint, and spearmint essential oils encapsulated in a tiny soft beadlet. This work aimed to evaluate the effects of SM beadlets on the oral microbiome. This study recruited twenty healthy participants. A baseline investigation of the oral microbiome of the selected participants was performed by collecting saliva and swab samples before treatment. Treatment included chewing four SM beadlets twice a day for 7 days, and then, post-administration saliva and swab samples were collected at the end of treatment. The oral microbiome samples were analyzed by the high-throughput amplicon sequencing of 16S rRNA gene fragments, and the community composition was determined. The results showed that the abundance of some microbial genera and families decreased after using SM, including Prevotella, Streptococcus, Neisseria, and Haemophilus. However, some genera showed inconsistent patterns. We also found that the subject's gender and SM usage were significantly associated with diverse microbial composition. The results suggest that SM treatment decreased the abundance of several bacteria associated with halitosis and periodontal diseases, such as Actinomyces and Streptococcus. Furthermore, Corynebacterium species increased and Streptococcus decreased after SM usage. More research is needed to fully understand the antimicrobial effects of mint oils and their potential applications in maintaining good oral health.

Prognostic value of serum progranulin in de novo adult acute myeloid leukemia patients.

BACKGROUND: Elevated serum progranulin (PGRN) levels have been associated with a wide range of different human malignancies. However, data available on the role of PGRN in hematological malignancies are limited. METHODS: Measurement of the PGRN level in serum of adult de novo acute myeloid leukemia (AML) patients using enzyme-linked immunosorbent assay (ELISA) was performed. RESULTS: The mean serum PGRN level in AML patients was higher than that in controls (346.08 pg/ml ± 64.46 vs 155 pg/ml ± 63 respectively; p = 0.001). After a mean duration of follow-up equaling 140 days, patients with high serum PGRN (i.e., higher than 370.5 pg/ml) had inferior overall survival (OS) in comparison to patients with low serum PGRN (i.e., lower than 370.5 pg/ml) (OS = 25% vs 60.7%, mean survival = 107 days vs 256.5 days, p = 0.007). On the other hand, remitted patients on day 28 with high serum PGRN (i.e., higher than 307.5 pg/ml) did not differ from those with low serum PGRN (i.e., lower than 307.5 pg/ml) regarding disease-free survival (DFS) (DFS = 78.6% vs. 87.5%, mean survival = 301.3 days vs. 283.5 days, p = 0.789). Moreover, the serum PGRN level was associated with inferior OS (p = 0.024) on multivariate analysis. CONCLUSION: Adult de novo AML patients have elevated serum PGRN levels and a high PGRN level is associated with an inferior OS.

Gestational exposure to a ketogenic diet increases sociability in CD-1 mice.

Postnatal administration of high-fat, low-carbohydrate ketogenic diets (KDs) is an established and effective treatment option for refractory epilepsy, with more recently identified therapeutic potential across a wide range of preclinical models of neurological and psychiatric disorders. However, the impact of gestational exposure to a KD (GKD) on offspring development remains unclear. Previous work has found that GKD exposure reduces depression- and anxiety-like behaviors in CD-1 mice, whereas postnatal KD improves sociability in several different rodent models of autism. Here we examined how sociability is impacted by GKD. Given that the neuropeptide oxytocin positively regulates affect, anxiety, and sociability, we also examined the effects of GKD on brain oxytocin expression. Male and female CD-1 mice exposed to either a standard diet (SD) or a KD gestationally were cross-fostered with SD dams at birth and remained on a SD from that point onward. These offspring were then tested for sociability and social novelty (three-chambered test) and depressive-like behaviors (forced swim test) at 10 weeks of age. At the conclusion of testing, brain tissue was collected and immunohistochemically processed for oxytocin expression in hypothalamic and limbic areas. We found that GKD increased sociability and reduced depressive-like symptoms, without affecting oxytocin expression in quantified areas. By expanding the scope of the lasting impact of gestational exposure to a ketogenic diet to include positive effects on sociability, these results indicate that GKDs may have novel therapeutic applications for individuals at risk for developmental disorders of social behavior, including autism and schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Prognostic significance of serum progranulin level in de novo adult acute lymphoblastic leukemia patients.

Increased expression of progranulin (PGRN) has been reported in some hematological cancers, but limited information regarding its significance in acute lymphoblastic leukemia (ALL) is available. This study involved 60 subjects (40 de novo adult ALL patients and 20 controls). Serum PGRN level was measured by enzyme-linked immunosorbent assay and was correlated with patient outcome. Serum PGRN level was significantly higher in patients than controls. Serum PGRN level did not correlate with age, total leukocytic count, hemoglobin, platelets, absolute blast count in peripheral blood, lactate dehydrogenase, percent of blasts in bone marrow, gender, comorbidities, the presence of central nervous system infiltration, ALL phenotype, cytogenetics and risk of the disease. High serum PGRN level was not associated with inferior overall survival (OS) on univariate analysis. Regarding cumulative incidence of relapse (CIR) and disease-free survival (DFS), high PGRN level was associated with poor results on univariate analysis. Moreover, it tended to be independent risk factor on multivariate analysis for CIR but was not an independent predictor of inferior DFS. Serum PGRN level is significantly elevated in de novo adult ALL patients and may be used as a predictor of increased relapse risk.

The potential role of herbal products in the treatment of Parkinson's disease.

Parkinson's disease (PD) is a multifactorial disorder of the nervous system in which there is a progressive loss of dopaminergic neurons. There is a disturbance in the movement in PD and these include resting tremors, rigidity, bradykinesia or akinesia, disturbance, posture and freezing (motor block). The substantia nigra and other parts of the brain are commonly affected. The disorder could be related to oxidative stress and there is an important role of reactive oxygen species (ROS). A number of herbal products contain active components which are known to possess antioxidant action. Hence, the potential role of herbal products in treating PD cannot be undermined. In the present narrative review, the main aim is to discuss the pathogenesis of PD, define the role of different potential herbal extracts on its pathogenesis which may form the basis of treatment. We also discuss in detail the active chemical compounds present each herb which are effective in the treatment of PD. These herbs include Baicalei, Erythrina velutin, Resveratrol, Peganum Harmal, Curcuma longa (Zingiberaceae), Carthamus tinctorius L. (Safflower), Pueraria lobate, Juglandis Semen (Walnut), Tianma Gouteng Yin (TGY), Lycium barbarum L fruit, Mucuna pruriens (Velvet bean), Chunghyuldan (CHD), Paeoniae Alba Radix. The present review may be beneficial for designing future drugs for effective treatment of PD.

Risk Factors Influencing Outcome of Acute Leukemia Patients Who Experience Relapse After Allogeneic Hematopoietic Stem-Cell Transplantation.

BACKGROUND: Prognosis of acute leukemia patients who experience relapse after hematopoietic stem-cell transplantation (HSCT) remains poor. Identifying risk factors influencing outcome of these patients is essential. PATIENTS AND METHODS: Follow-up of 234 acute leukemia patients who underwent allogeneic HSCT from matched related donor was performed for occurrence of posttransplantation relapse. Statuses of remission and survival were assessed at 6 months after treatment of relapse. Analysis of risk factors influencing postrelapse overall survival (prOS), complete remission (CR), and nonrelapse mortality (NRM) was carried out. RESULTS: Posttransplantation relapse occurred in 43 patients (17.9%). After treatment, 11 patients (25.6%) experienced postrelapse remission, the prOS rate was 20.9% (9 patients), and the NRM rate was 25.6% (11 patients). Older age (P = .007) and failure to experience remission after relapse treatment (P = .027) were associated with lower prOS in multivariate analysis. Female sex (P = .027), posttransplantation extramedullary relapse (P = .001), and absence of postrelapse graft-versus-host disease P = .025) were associated with lower CR rate. Also, presence of extramedullary relapse (P = .011) was associated with lower risk of NRM whereas treatment of posttransplantation relapse with donor lymphocyte infusion with or without chemotherapy (P = .002) and occurrence of postrelapse graft-versus-host disease (P = .025) were associated with higher risk of NRM. CONCLUSION: Survival of acute leukemia patients who experience relapse after allogeneic HSCT is poor, especially in elderly patients and those who do not experience remission after relapse treatment.

Prognostic value of serum progranulin in de novo adult acute myeloid leukemia patients

Abstract Background Elevated serum progranulin (PGRN) levels have been associated with a wide range of different human malignancies. However, data available on the role of PGRN in hematological malignancies are limited. Methods Measurement of the PGRN level in serum of adult de novo acute myeloid leukemia (AML) patients using enzyme-linked immunosorbent assay (ELISA) was performed. Results The mean serum PGRN level in AML patients was higher than that in controls (346.08 pg/ml ± 64.46 vs 155 pg/ml ± 63 respectively; p= 0.001). After a mean duration of follow-up equaling 140 days, patients with high serum PGRN (i.e., higher than 370.5 pg/ml) had inferior overall survival (OS) in comparison to patients with low serum PGRN (i.e., lower than 370.5 pg/ml) (OS = 25% vs 60.7%, mean survival = 107 days vs 256.5 days, p= 0.007). On the other hand, remitted patients on day 28 with high serum PGRN (i.e., higher than 307.5 pg/ml) did not differ from those with low serum PGRN (i.e., lower than 307.5 pg/ml) regarding disease-free survival (DFS) (DFS = 78.6% vs. 87.5%, mean survival = 301.3 days vs. 283.5 days, p= 0.789). Moreover, the serum PGRN level was associated with inferior OS (p= 0.024) on multivariate analysis. Conclusion Adult de novo AML patients have elevated serum PGRN levels and a high PGRN level is associated with an inferior OS.

De novo deletion 17p13.1 as a predictor for disease progression in chronic lymphocytic leukemia.

To determine the prognostic impact of de novo deletion 17p13.1 (17p-) in previously untreated chronic lymphocytic leukemia (CLL) patients, we prospectively studied the outcome of 71 treatment-naïve CLL patients. About 18.3 % of them had 17p- detected by interphase fluorescent in situ hybridization (FISH) at diagnosis. There was statistically significant difference between 17p- negative and positive patients as regards 2-year overall survival [OS] (89.7 vs. 53.8 %, respectively; P = 0.001). On the other hand, 2-year progression-free survival [PFS] was also significantly higher in 17p- negative group than in 17p- positive one (82.8 vs. 23.1 %, respectively; P < 0.001). On univariate analysis for OS, 17p- positivity was significantly associated with shorter OS (P = 0.003). However, when we performed multivariate analysis, 17p- lost its significant impact. On the other hand, 17p- positivity was a significant risk factor for PFS in both univariate and multivariate analyses [independent risk factor] (P < 0.001 and P = 0.02, respectively). So, 17p- is a predictor for disease progression, but not for survival in CLL patients.