Recombinant Human Follicle-Stimulating Hormone Alfa Dose Adjustment in US Clinical Practice: An Observational, Retrospective Analysis of a Real-World Electronic Medical Records Database

PurposeTo determine the pattern of dose adjustment of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) during ovarian stimulation (OS) for assisted reproductive technology (ART) in a real-world setting.MethodsThis was an observational, retrospective analysis of data from an electronic de-identified medical records database including 39 clinics in the USA. Women undergoing OS for ART (initiated 2009–2016) with r-hFSH-alfa (Gonal-f® or Gonal-f RFF Redi-ject®) were included. Assessed outcomes were patients’ baseline characteristics and dosing characteristics/cycle.ResultsOf 33,962 ART cycles, 13,823 (40.7%) underwent dose adjustments: 23.4% with ≥1 dose increase, 25.4% with ≥1 dose decrease, and 8.1% with ≥1 increase and ≥1 decrease. Patients who received dose adjustments were younger (mean [SD] age 34.8 [4.58] years versus 35.9 [4.60] years, p<0.0001) and had lower BMI (25.1 [5.45] kg/m2 versus 25.5 [5.45] kg/m2, p<0.0001) than those who received a constant dose. The proportion of patients with non-normal ovarian reserve was 38.4% for those receiving dose adjustment versus 51.9% for those with a constant dose. The mean (SD) number of dose changes/cycle was 1.61 (0.92) for cycles with any dose adjustment, 1.72 (1.03) for cycles with ≥1 dose increase, 2.77 (1.00) for cycles with ≥1 dose increase and ≥1 decrease (n=2,755), and 1.88 (1.03) for cycles with ≥1 dose decrease.ConclusionsDose adjustment during OS is common in clinical practice in the USA and occurred more often in younger versus older patients, those with a high versus non-normal ovarian reserve or those with ovulation disorders/polycystic ovary syndrome versus other primary diagnoses of infertility.

Melanomacrophage Centers in Nile Tilapia (Oreochromis niloticus L.) as Biomarker for Carbamate Exposure

Melanomacrophage centers are aggregates of pigment-containing cells found in the animal’s hematopoietic tissues. Changes in its characteristics have been used to assess the influence of pesticide exposure, and as tools for potential monitoring for fish and environmental health. This study aimed to evaluate the pesticide-induced hepatic and splenic melanomacrophage center responses in Nile tilapia (Oreochromis niloticus L.) following exposure to fenobucarb in varying lengths of exposure. Five test groups were exposed to constant dose of fenobucarb at 0.08 mg L-1at different periods (0, 7, 14, 21, and 28 days). Fenobucarb only induced significant changes in the splenic melanomacrophage centers. Splenic melanomacrophage centers significantly increased in number in response to the increasing lengths of exposure. Increasing trend of size and cover was also observed, however, significant difference was only detected at 28 days exposure period. Significant difference in hemosiderin and lipofuscin pigments was also detected at 28 days exposure which suggests tissue destruction after prolonged exposure. This study confirms the potential of melanomacrophage centers as a sensitive biomarker for fenobucarb exposure indicated by the changes in its characteristics, particularly in the spleen.

Review of personal radiation exposure dose and history of the interventional procedure records for 40 years

Objective To inspect personal dose as an interventional radiologist for 40 years, to assess the enforcement number of interventional radiology (IR), and to check for radiation cataract. Materials and methods I evaluated my own effective dose, an equivalent dose to the lens of the eye (EDL), and the number of IR procedures between March 2019 and June 1979. I examined the lens in June 2019 as a radiologist for 40 years. Results The accumulation dose was 0 mSv in 1979–88. During 1989–93, the right crystalline lens equivalence of the value dose was measured. During 1993–96, two badge items for the head, neck, and abdomen were present. Both were distributed, but attaching to the same part and reversing occurred frequently. The EDL of the recent 5 years has exceeded 100 mSv. No association with the number of IR procedures was recognized. Posterior subcapsular vacuoles (PSV) as the early changes of the radiation cataract were recognized as four on the left and one on the right. Conclusion It is important to get accustomed to film badge wearing, and the cancelation of making a mistake in the wearing part. Radiologists should check the PSV at a stage beyond a certain constant dose.

Kinetic Study of Congo-Red Photo-Catalytic Degradation in Aqueous Media Using Zinc Oxide as Photo Catalyst Under Led Light

The kinetic of photo catalytic degradation of Congo red dye using semiconductor in aqueous solution of ZnO has been studied. All photochemical experiments have been carried out in quartz photo cell 25ml capacity and the solvent used for all experiment was distilled water (D. W). The influence of temperature has been investigated as well. Spectrophotometric method was utilized for this work. Degradation kinetic has been done for absorption peak of Congo red at 497 nm and 344 nm. Different method was applied for this purpose, and the results show that the degradation of Congo red was first order at 497nm and zero order at 344 nm. The degradation of CR dye were increased by increasing temperature from 20 oC to 40 oC and then degreased at 50 oC and this is due to desorption that occur at the semiconductor surface while; in case of 10 oC the rate constant was higher than 20 oC. However, when changing the concentration the rate constant dose not changed regularly, this perhaps due to the fact that it does not follow the same order throughout the degradation process, and it does not obey Arrhenius law of activation energy.

dCas9 regulator to neutralize competition in CRISPRi circuits

CRISPRi-mediated gene regulation allows simultaneous control of many genes. However, highly specific sgRNA-promoter binding is, alone, insufficient to achieve independent transcriptional regulation of multiple targets. Indeed, due to competition for dCas9, the repression ability of one sgRNA changes significantly when another sgRNA becomes expressed. To solve this problem and decouple sgRNA-mediated regulatory paths, we create a dCas9 concentration regulator that implements negative feedback on dCas9 level. This allows any sgRNA to maintain an approximately constant dose-response curve, independent of other sgRNAs. We demonstrate the regulator performance on both single-stage and layered CRISPRi-based genetic circuits, zeroing competition effects of up to 15-fold changes in circuit I/O response encountered without the dCas9 regulator. The dCas9 regulator decouples sgRNA-mediated regulatory paths, enabling concurrent and independent regulation of multiple genes. This allows predictable composition of CRISPRi-based genetic modules, which is essential in the design of larger scale synthetic genetic circuits.

Water capacity of red-stemmed feathermoss (Pleurozium schreberi Mitt.)

<p>Mosses (bryophyta) have the ability to absorb and retain large amounts of water. This property results from the specific way in which these organisms uptake, conduct, and store water.</p><p>The aim of the study was to investigate the water storage capacity (S) of red-stemmed feathermoss<strong> </strong>Pleurozium schreberi (Mitt.) in the fresh state (current capacity) and after drying (maximum capacity), depending on the initial moisture content, and depending on the percentage of the various structural parts of the moss sample which included soil.</p><p>Forty moss samples of equal size were used in the study; they were sprayed with a constant dose of water in laboratory conditions. The actual water capacity was obtained from the difference in the weight of the sample after spraying with a constant dose of water, and the weight of the sample in the fresh state. After the stimulated rainfall cycle, the samples were divided into individual fractions (part with green leaves, stalks and rhizoids, and soil) and dried in an airoven for 24 hours at 105<sup>o</sup>C.</p><p>The weight of the dry sample, the initial moisture, the maximum water capacity, and the current water capacity were calculated. The analyses conducted led to the conclusion that water capacity of moss is extremely important for the water cycle as it retained, on average, as much as 29% of the total rainfall.</p><p>The initial moisture depends above all on the amount of soil that dominated the entire sample volume. <strong>Retention capacity of the moss must be higher than that of the soil, as each additional gram of soil reduced the initial moisture content of the samples.</strong></p><p><strong>Experiments have additionally shown that the higher the initial moisture, i.e. the more water in the fresh moss samples collected with the soil lump, the higher the maximum capacity.</strong> The calculated maximum water capacity relates to the dry weight of the entire sample. This conclusion can be compared to the water properties of soil where the wetter fresh soil is able to retain more water, and the excessively dry soil becomes hydrophobic.</p><p><strong>In turn, the higher the initial moisture, the less water is retained in the fresh moss sample after rainfall.</strong> This observation is similar to the actual situation that occurs in natural conditions, e.g. in a forest. This may be due to the fact that the more water is contained in the moss assimilation apparatus, the higher the cell turgor pressure, which makes the surface tighter. The moss absorbs water from the atmosphere, and the largest increases in retained water are recorded for drier samples. This may also result from external and internal structure of moss, which is different than in vascular plants. The leaves of bryophytes have characteristic vertical rows of cells of the collenchyma on their upper surface. Such arrangement of cells promotes water absorption.</p><p>The obtained results remain in line with the research on the hydrological properties of forest ecosystems, and they show that the role of moss in the forest is very important but not yet fully understood.</p>

Reinforcement Learning for Radiotherapy Dose Fractioning Automation

External beam radiotherapy cancer treatment aims to deliver dose fractions to slowly destroy a tumor while avoiding severe side effects in surrounding healthy tissues. To automate the dose fraction schedules, this paper investigates how deep reinforcement learning approaches (based on deep Q network and deep deterministic policy gradient) can learn from a model of a mixture of tumor and healthy cells. A 2D tumor growth simulation is used to simulate radiation effects on tissues and thus training an agent to automatically optimize dose fractionation. Results show that initiating treatment with large dose per fraction, and then gradually reducing it, is preferred to the standard approach of using a constant dose per fraction.

Dosimetric comparison of constant dose rate volumetric modulated arc therapy (CDR-VMAT) and intensity-modulated radiation therapy (IMRT) for gallbladder cancer

Aim: To study the feasibility of constant dose rate volumetric modulated arc therapy (CDR-VMAT) in radiotherapy for gallbladder cancer by comparing dosimetric parameter suggested by International Commission on Radiation Units and Measurements-83 (ICRU-83) with step and shoot intensity-modulated radiation therapy (SS IMRT). Methods: For this study, we selected 21 post-operative gallbladder cancer patients, which were treated with the IMRT technique from 2016 to 2019. For each patient, we generated SS IMRT plan and CDR-VMAT plan and were dosimetrically compared by parameters suggested by ICRU-83 for PTV. Homogeneity Index (HI) and Conformity Index (CI) were also calculated. For evaluation of Organ at Risk (OAR), we compared the mean doses, volume doses to the right kidney, left kidney, both kidneys combined, liver and max dose to the spinal cord. Monitor units (MUs) and treatment delivery time were also compared. Results: On comparing, we found that CDR-VMAT plans were highly conformed as CI and PCI (CI define by Paddick) were found more (0·98 ± 0·01 vs. 0·97 ± 0·03 and 0·86 ± 0·05 vs. 0·85 ± 0·05) than IMRT plans but not statistically significant. Better dose HI was found for IMRT plans with statistical significant difference (p < 0·001). The tumour coverage was found similar 98·24% and 97·83% for SS IMRT and CDR-VMAT, respectively. For D2%, the maximum dose to PTV was significantly lower in IMRT (p = 0·001). D50% and mean dose to PTV were also comparable to IMRT with no statistically significant difference. The OAR parameters were comparable in both the techniques. The mean doses and volume doses V10, V20 and V30 to the right kidney, left kidney and liver were also comparable with no significant difference (p > 0·05) was noted among them. However, the maximum dose to the spinal cord was significantly less in CDR-VMAT (21·1 Gy vs. 25·1Gy) than SS IMRT with p = 0·006. More MUs were associated with the CDR-VMAT technique, but shorter treatment delivery time than the IMRT technique. Conclusions: On dosimetric comparison of two treatment techniques, we conclude that CDR-VMAT can be a valid option in radiotherapy as it achieved highly conformed dose distribution, comparable tumour coverage and OAR sparing as IMRT technique for gallbladder cancer.

Effect of Homeopathic Preparations on Lettuce, Parasitized or Not by Meloidogyne enterolobii

Background There are relatively few scientific works on the use of homeopathy to manage plant pathogens, particularly nematodes. A handful of studies focused on Meloidogyne spp. parasitizing vegetables have brought contradictory results on nematode control and enhancement of plant tolerance to parasitism. Objective Our goal was to assess the effect of Cina—a well-known anti-nematode ingredient—on Meloidogyne enterolobii parasitizing lettuce. Methods Cina was applied daily on nematode-inoculated plants, from the seedling stage until harvest. We tested an evenly spaced range of Hahnemannian concentrations (c), which were applied though irrigation with a constant dose of the ingredient. Several absolute and relative controls were employed to allow the assessment of the effect of Cina on nematode reproduction and lettuce growth. Results Cina affected growth of non-parasitized plants, both positively and negatively; this effect was modulated by the c applied and the thermal stress suffered by the plants in one of the assays. The effect of Cina on the growth of nematode-parasitized plants was neutral or negative. Cina reduced nematode reproduction by 25–36%. Conclusion Based on the moderate negative effect of Cina on M. enterolobii reproduction, it seems this ingredient may be useful as a complementary strategy for Meloidogyne control. But Cina did not enhance the tolerance of lettuce to Meloidogyne spp.

Radiobiological effects of the interruption time in radiation therapy with photon beams based on the microdosimetric kinetic model

Background: We investigated the effect of the interruption time on the radiobiological effectiveness with photon beams based on a modified microdosimetric kinetic model. Background: The interruption time is used is that irradiation interruption occurs at sites and operations such as the gantry, collimator, couch rotation, and patient set-up in radiotherapy. However, the effect of interruption time on photon beams for tumor cells is little evaluated.Methods: The dose-mean lineal energy yD (keV/µm) of 6 MV photon beams was calculated by the particle and heavy ion transport system (PHITS). We set the absorbed dose to 2 or 8 Gy, and the interruption time (τ) was set to 1, 3, 5, or 10 min. The biological parameters values were acquired from a human non-small cell lung cancer cell line (NCI-H460) for the mMK model. We used two-field and four-field irradiation with a constant dose rate (3 Gy/min); the photon beams were paused for interruption time τ. We calculated the relative biological effectiveness (RBE) to evaluate the interruption time's effect compared with photon beams that were not interrupted as a reference. Results: The RBE with four-field irradiation for 8 Gy was decreased to 0.997, 0.992, 0.987, and 0.975 for τ = 1, 3, 5, and 10 min, respectively. The decrease in the RBE was within 3% compared with the non-interrupted photon beams. Conclusions: The effect of RBE was decreased by increasing the interruption time, indicating that an escalation of the prescribed dose might be necessary when the interruption time was large.