Effects of Simulated Microgravity In Vitro on Human Metaphase II Oocytes: An Electron Microscopy-Based Study.

The Gravity Force to which living beings are subjected on Earth rules the functionality of most biological processes in many tissues. It has been reported that a situation of Microgravity (such as that occurring in space) causes negative effects on living beings. Astronauts returning from space shuttle missions or from the International Space Station have been diagnosed with various health problems, such as bone demineralization, muscle atrophy, cardiovascular deconditioning, and vestibular and sensory imbalance, including impaired visual acuity, altered metabolic and nutritional status, and immune system dysregulation. Microgravity has profound effects also on reproductive functions. Female astronauts, in fact, suppress their cycles during space travels, and effects at the cellular level in the early embryo development and on female gamete maturation have also been observed. The opportunities to use space flights to study the effects of gravity variations are limited because of the high costs and lack of repeatability of the experiments. For these reasons, the use of microgravity simulators for studying, at the cellular level, the effects, such as those, obtained during/after a spatial trip, are developed to confirm that these models can be used in the study of body responses under conditions different from those found in a unitary Gravity environment (1 g). In view of this, this study aimed to investigate in vitro the effects of simulated microgravity on the ultrastructural features of human metaphase II oocytes using a Random Positioning Machine (RPM). We demonstrated for the first time, by Transmission Electron Microscopy analysis, that microgravity might compromise oocyte quality by affecting not only the localization of mitochondria and cortical granules due to a possible alteration of the cytoskeleton but also the function of mitochondria and endoplasmic reticulum since in RPM oocytes we observed a switch in the morphology of smooth endoplasmic reticulum (SER) and associated mitochondria from mitochondria-SER aggregates to mitochondria-vesicle complexes. We concluded that microgravity might negatively affect oocyte quality by interfering in vitro with the normal sequence of morphodynamic events essential for acquiring and maintaining a proper competence to fertilization in human oocytes.

Prolonged Opioid Use and Pain Outcome and Associated Factors after Surgery under General Anesthesia: A Prospective Cohort Association Multicenter Study.

BACKGROUND: There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery. METHODS: Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed. RESULTS: Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively. CONCLUSIONS: Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery.

Rates of Opioid Misuse Amongst Patients Receiving Pain Management for Sickle Cell Disease in An Urban Setting.

Background and Objective: Sickle Cell Disease (SCD) is known to cause acute severe pain episodes known as vaso-occlusive crisis (VOC) mainly treated with opioid analgesics. Since the opioid epidemic there is an interest in determining the opioid misuse potential in these patients. Therefore, the primary objective of this study is to determine the rates of opioid misuse among patients with SCD by assessing the rate of unexpected drug screening results in a sickle cell disease clinic. Methods: This was a retrospective chart review study conducted at the outpatient sickle cell disease clinic. The primary independent variables were the prescribed opioid medications while the primary dependent variable was the collected opioid metabolite. Descriptive statistics, linear regression and multivariate logistic regression analysis were conducted using SPSS version 24. Results: A total of 100 participants were recruited from July 1, 2018, to June 30, 2020 with 71 included in the analysis. The total mean of morphine milligram equivalents (MME) for all participants was 71.1±104.9 with 71% of participants having a daily calculated MME of <90MME. The odds of misusing an opioid were 6.72 times higher (P<.02) if a participant used marijuana compared to a participant who didn't. In addition, the odds of misusing an opioid were 2.47 times higher (P<.04) if the patient was prescribed an opioid daily dose greater than 90 MME as opposed to a daily dose less than 90 MME. Conclusion: Participants who consumed greater than 90 MME's per day and utilized marijuana were more likely to misuse opioids.

An Observational Study of the Pharmacokinetics of Surgeon-Performed Intercostal Nerve Blockade With Liposomal Bupivacaine for Posterior-Lateral Thoracotomy Analgesia.

BACKGROUND: Intercostal nerve blocks with liposomal bupivacaine are commonly used for thoracic surgery pain management. However, dose scheduling is difficult because the pharmacokinetics of a single-dose intercostal injection of liposomal bupivacaine has never been investigated. The primary aim of this study was to assess the median time to peak plasma concentration (Tmax) following a surgeon-administered, single-dose infiltration of 266 mg of liposomal bupivacaine as a posterior multilevel intercostal nerve block in patients undergoing posterolateral thoracotomy. METHODS: We chose a sample size of 15 adults for this prospective observational study. Intercostal injection of liposomal bupivacaine was considered time 0. Serum samples were taken at the following times: 5, 15, and 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours. The presence of sensory blockade, rescue pain medication, and pain level were recorded after the patient was able to answer questions. RESULTS: Forty patients were screened, and 15 patients were enrolled in the study. Median (interquartile range [IQR]) Tmax was 24 (12) hours (confidence interval [CI], 19.5-28.5 hours) with a range of 15 minutes to 48 hours. The median (IQR) peak plasma concentration (Cmax) was 0.6 (0.3) µg/mL (CI, 00.45-0.74 µg/mL) in a range of 0.3-1.2. The serum bupivacaine concentration was undetectable (<0.2 µg/mL) at 96 hours in all patients. There was significant variability in reported pain scores and rescue opioid medication across the 15 patients. More than 50% of patients had return of normal chest wall sensation at 48 hours. All patients had resolution of nerve blockade at 96 hours. No patients developed local anesthetic toxicity. CONCLUSIONS: This study of the pharmacokinetics of liposomal bupivacaine following multilevel intercostal nerve blockade demonstrates significant variability and delay in systemic absorption of the drug. Peak serum concentration occurred at 48 hours or sooner in all patients. The serum bupivacaine concentration always remained well below the described toxicity threshold (2 µg/mL) during the 96-hour study period.

Multicenter Perioperative Outcomes Group Enhanced Observation Study Postoperative Pain Profiles, Analgesic Use, and Transition to Chronic Pain and Excessive and Prolonged Opioid Use Patterns Methodology.

To study the impact of anesthesia opioid-related outcomes and acute and chronic postsurgical pain, we organized a multicenter study that comprehensively combined detailed perioperative data elements from multiple institutions. By combining pre- and postoperative patient-reported outcomes with automatically extracted high-resolution intraoperative data obtained through the Multicenter Perioperative Outcomes Group (MPOG), the authors sought to describe the impact of patient characteristics, preoperative psychological factors, surgical procedure, anesthetic course, postoperative pain management, and postdischarge pain management on postdischarge pain profiles and opioid consumption patterns. This study is unique in that it utilized multicenter prospective data collection using a digital case report form integrated with the MPOG framework and database. Therefore, the study serves as a model for future studies using this innovative method. Full results will be reported in future articles; the purpose of this article is to describe the methods of this study.

Safety profile of intraoperative methadone for analgesia after major spine surgery: An observational study of 1,478 patients.

OBJECTIVE: To investigate the incidence of perioperative adverse events in patients receiving intravenous methadone for major spine surgery. DESIGN: Retrospective review of perioperative records from March 2011 and February 2016. SETTING: University of Virginia Healthsystem. PATIENTS: Adult patients undergoing elective spinal fusion of two or more levels. MAIN OUTCOME MEASURES: Incidence of respiratory depression, time to extubation, hypotension, hypoxemia, reintubation, cardiac complications, and death. RESULTS: Reviewed 1,478 patient records. Mean intraoperative methadone dose was 0.14 ± 0.07 mg/kg. A total of 1,142 patients (77.4 percent) were extubated in the operating room, 543 (36.8 percent) experienced respiratory depression, 1,180 (79.8 percent) hypoxemia, and 22 (1.5 percent) required reintubation. Cardiac complications included arrhythmias (289 patients, 29.9 percent), QTc prolongation (568 patients, 58.8 percent), and myocardial infarction (16 patients, 1.1 percent). Two in hospital deaths occurred (0.14 percent). CONCLUSIONS: Mild-moderate respiratory depression is observed following a one-time dose of intraoperative methadone, and monitoring in an appropriate postoperative setting is recommended.

Dysregulated innate lymphocytes in patients with primary antibody deficiency treated with intravenous immunoglobulin

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Clinical complications after transvaginal oocyte retrieval in 7,098 IVF cycles.

We report the complications observed after transvaginal oocyte retrieval guided by ultrasound in 7,098 IVF cycles. The frequency of severe complications in our patients was 0.08%, of which four cases were intraperitoneal bleeding (0.06%) and two were cases of ovarian abscess (0.003%).

MicroRNA profiling in human medulloblastoma.

Medulloblastoma is an aggressive brain malignancy with high incidence in childhood. Current treatment approaches have limited efficacy and severe side effects. Therefore, new risk-adapted therapeutic strategies based on molecular classification are required. MicroRNA expression analysis has emerged as a powerful tool to identify candidate molecules playing an important role in a large number of malignancies. However, no data are yet available on human primary medulloblastomas. A high throughput microRNA expression profiles was performed in human primary medulloblastoma specimens to investigate microRNA involvement in medulloblastoma carcinogenesis. We identified specific microRNA expression patterns which distinguish medulloblastoma differing in histotypes (anaplastic, classic and desmoplastic), in molecular features (ErbB2 or c-Myc overexpressing tumors) and in disease-risk stratification. MicroRNAs expression profile clearly differentiates medulloblastoma from either adult or fetal normal cerebellar tissues. Only a few microRNAs displayed upregulated expression, while most of them were downregulated in tumor samples, suggesting a tumor growth-inhibitory function. This property has been addressed for miR-9 and miR-125a, whose rescued expression promoted medulloblastoma cell growth arrest and apoptosis while targeting the proproliferative truncated TrkC isoform. In conclusion, misregulated microRNA expression profiles characterize human medulloblastomas, and may provide potential targets for novel therapeutic strategies.

The possible role of hyperhomocysteinemia on IVF outcome.

PURPOSE: To evaluate the effect of the hyperhomocysteinemia on pregnancy rate, implantation rate and abortion rate after IVF. METHOD: Data from a total of 48 infertile couples with hyperhomocysteinemia were prospectively collected for this study. All patients underwent a standard down regulation protocol for ovarian stimulation. Oocytes recovery was performed at 36 h after hCG administration. Embryo transfer took place at 48 h after insemination. The patients were matched in two groups that received or did not receive therapy (group A and B respectively) to normalize homocysteine plasma level. RESULTS: Pregnancy rate, implantation rate and abortion rate varied significantly (p