Usefulness of a Titratable Mandibular Positioner During Sleep Endoscopy as a Prediction Tool for Treatment Outcome with Mandibular Advancement Devices: DISE-SAM Protocol

Mandibular advancement devices (MAD) are an effective alternative treatment to CPAP. However, different maneuvers have been performed during the performance of drug sleep-induced endoscopy (DISE) to mimic the effect of MAD. Using the Selector Avance Mandibular (SAM) device, we aimed to identify MAD candidates during DISE using a titratable, reproducible, and measurable maneuver. This DISE-SAM protocol may help to find the relationship between the severity of the respiratory disorder and the degree of response, and to determine the advancement required to improve the collapsibility of the upper airway. Explorations were performed in 161 patients (132 males; 29 females) with a mean age of 46.81 (SD = 11.42) years, a BMI of 27.90 (SD = 4.19) kg/m2 and a mean AHI of 26.51 (SD = 21.23). Results showed no relationship between severity and MAD recommendation. Also, there was a weak positive relationship between the advancement required to obtain a response and the disease severity. Using the DISE-SAM protocol, the response and the range of mandibular protrusion were assessed, avoiding the inter-examiner bias of the jaw thrust maneuver. We suggest prescribing MAD as a single, alternative, or multiple treatment approaches following the SAM recommendations in a personalized design.

Microencapsulation Technology a Holistic Approach in the Field of Pharmaceutical Sciences a Review

Microencapsulation is a technique that uses a coating to encapsulate microscopic particles or droplets in order to generate miniature capsules with therapeutic properties. The substance contained within the microcapsule is referred to as the core, internal phase, or fill, whereas the wall is referred to as a shell, coating, or membrane. A microcapsule is a small object that contains essential items, internal components, or fillers and is encased by a shell, cover, or membrane. Microcapsules range in size from 1 to 1000 micrometres. This approach is frequently used for medication administration, molecular protection, and robustness. The microencapsulation programme has been established as a different delivery mechanism for multiple treatment regimens and offers potential benefits beyond those of normal medication delivery systems. Microencapsulation is a well-established review dedicated to the preparation, properties, and applications of individually encapsulated novel small particles, as well as significant improvements to tried-and-tested techniques relevant to micro and nano particles and their use in a wide range of industrial, engineering, pharmaceutical, biotechnology, and research applications. Its scope extends beyond conventional microcapsules to all other small particulate systems, such as self-assembling structures that involve preparative manipulation.

Multiple Treatment Cycles of Neural Stem Cell Delivered Oncolytic Adenovirus for the Treatment of Glioblastoma

Tumor tropic neural stem cells (NSCs) can improve the anti-tumor efficacy of oncovirotherapy agents by protecting them from rapid clearance by the immune system and delivering them to multiple distant tumor sites. We recently completed a first-in-human trial assessing the safety of a single intracerebral dose of NSC-delivered CRAd-Survivin-pk7 (NSC.CRAd-S-pk7) combined with radiation and chemotherapy in newly diagnosed high-grade glioma patients. The maximum feasible dose was determined to be 150 million NSC.CRAd-Sp-k7 (1.875 × 1011 viral particles). Higher doses were not assessed due to volume limitations for intracerebral administration and the inability to further concentrate the study agent. It is possible that therapeutic efficacy could be maximized by administering even higher doses. Here, we report IND-enabling studies in which an improvement in treatment efficacy is achieved in immunocompetent mice by administering multiple treatment cycles intracerebrally. The results imply that pre-existing immunity does not preclude therapeutic benefits attainable by administering multiple rounds of an oncolytic adenovirus directly into the brain.

Targeting the Tumor Immune Microenvironment Could Become a Potential Therapeutic Modality for Invasive Pituitary Adenoma.

Objective: The study aimed to explore the relationship between the invasiveness and immune cell infiltration in pituitary adenoma (PA) and provide the basis for immuno-targeting therapies.Methods: One hundred three patients who underwent surgery at a single institution were retrospectively identified. The infiltration of macrophages and T lymphocytes was quantitatively assessed in PA.Results: The number of CD68+ macrophages was positively correlated with Knosp (P=0.003) and MMP-9 grades (P=0.00). The infiltration of CD163+ macrophages differed among Knosp (P=0.022) and MMP-9 grades (P=0.04). CD8+ tumor-infiltrating lymphocytes (TILs) were also positively associated with Knosp (P=0.002) and MMP-9 grades (P=0.01). Interestingly, MGMT expression was positively correlated with MMP-9 staining extent (P=0.000). The quantity of CD8+ TILs (P= 0.016), CD68+ macrophages (P=0.000) and CD163+ macrophages (P=0.043) were negatively associated with MGMT expression levels. The number of CD68+ macrophages in the PD-L1 negative group was significantly more than in the PD-L1 positive group (P=0.01). The rate of PD-L1 positivity had positive correlations with the Ki-67 index (P=0.046) and p53 expression (P =0.029). Conclusion: Targeted therapy for macrophages and CD8+ TILs could be a helpful treatment in the future for invasive PA. Temozolomide (TMZ) may have better effects on the treatment of PA infiltrating more immune cells. Anti-PD-L1 therapy may better respond to PA with higher Ki-67, p53 expression and more infiltrating CD68+ macrophages. Multiple treatment modalities, especially combined immunotherapy, or immunotherapy with TMZ combination, could become a novel therapeutic strategy for invasive PA.

Comparison of Frequentist and Bayesian Generalized Linear Models for Analyzing the Effects of Fungicide Treatments on the Growth and Mortality of Piper Nigrum

Foot rot disease poses a devastating threat to pepper agriculture. In Vietnam, conventionally, fungicides are the control methods used against the disease. However, the practical effectiveness of fungicide treatment has yet to be quantitatively assessed. To fill this gap a three-factorial experiment was conducted, the factors of which were fungicide application, soil type, and infection pathway, with plant mortality and plant growth as the target variables. Two of the most common fungicides were chosen, including Agrifos 400 (potassium phosphonate) and Aliette 800WG (fosetyl-Al). The two fungicides were used in multiple treatment plans, with soil drenching selected as the means of controlling foot rot disease on red basalt soil and red basalt soil added with organic matter in a greenhouse experiment. Three-month-old pepper (Piper nigrum) plants were treated with Agrifos (application interval of 10 and 20 days), Aliette (application interval of 30 and 60 days), and a combination of both fungicides at half doses. Pepper plants were infected with the fungus Pythium spp. from soil or by direct inoculation. To assess the effect of fungicides on foot rot mortality and the growth of pepper plants, multiple generalized linear models were set up using frequentist and Bayesian approaches. Generally, both procedures suggest the same conclusions for model selection in terms of the Akaike information criterion (AIC) and the deviance information criterion (DIC). Fungicide type was found to be the main factor that affected the survival of plants. Most of the treatments (except Aliette, with an interval of 60 days) effectively reduced the mortality. The usage of fungicides affected the growth of plants in interaction with soil types. Aliette suppressed the growth of plants, especially on red soil, while Agrifos had no effect on the growth of pepper plants. The combined application of Agrifos and Aliette with half doses proves to be a promising solution for balancing cost and effectiveness in protecting plants against foot rot pathogens without affecting their growth. In our case, under the inhomogeneity of variance and unbalanced samples, the Bayesian inference appeared to be the most useful because of its flexibility in terms of model structure.

Treatment patterns of patients diagnosed with major depressive disorder and suicidal ideation or attempt: a U.S. population-based study utilizing real-world data

Background There is a knowledge gap regarding the treatment patterns of patients with major depressive disorder (MDD) who experience suicidal ideation or a suicide attempt (SI/SA). Methods Patients with SI/SA were identified from a large US-based claims database covering 84 million lives, during 1/1/2014–3/31/2020. Patients with MDD were indexed at their first diagnosis for SI/SA and followed up to 365 days. Treatment patterns were captured at the class level and included procedures of electroconvulsive therapy and transcranial magnetic stimulation, and pharmacotherapy including selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, other antidepressants, anxiolytics, hypnotics/sedatives, antipsychotics, psychostimulants, and lithium. Results There were 42,204 MDD + SI/SA patients identified. In the year prior to the index event > 40% of individuals received an SSRI and more than one-third received an anxiolytic. Within 1 year following, 84.4% received ≥1 of the treatments of interest. Of those, 70.2% went on to a subsequent class-based regimen, 46.3% received a third, and 28.1% received ≥4. More than three-quarters of patients received multiple treatment classes simultaneously. SSRIs were the most common treatments during follow-up (61.9%), followed by other antidepressants (51.3%), anxiolytics (50.8%) and anticonvulsants (43.6%). Conclusions There was a large amount of variability and polypharmacy in the treatments received by MDD patients with SI/SA, and is much more complex than what has been previously observed in the general MDD population. Within one-year, many patients received four or more unique class-based regimens and most patients received treatments from multiple classes simultaneously, indicating the high unmet medical need and therapy refractoriness of this patient population.