Stereoselective synthesis of beta-lactams with polyaromatic imines: entry to new and novel anticancer agents

We present herein stereoselective synthesis of novel beta-lactams using polyaromatic imines following the Staudinger reaction. Consistent mechanisms for these results have been advanced. As a measure of cytotoxicity, some of these compounds have been assayed against nine human cancer cell lines. Structure-activity study has revealed that 1-N-chrysenyl and 1-N-phenanthrenyl 3-acetoxy-4-aryl-2-azetidinones have potent anticancer activity. The presence of the acetoxy group at C(3) of the beta-lactams has proven to be obligatory for their anticancer activity.     

Longitudinal follow-up of patients with alpha(1)-protease inhibitor deficiency before and during therapy with IV alpha(1)-protease inhibitor

BACKGROUND: The efficacy of IV augmentation therapy with human alpha(1)-protease inhibitor (alpha(1)-Pi) in patients with severe alpha(1)-Pi deficiency is still under debate. STUDY OBJECTIVES: To evaluate the progression of emphysema in patients with alpha(1)-Pi deficiency before and during a period in which they received treatment with alpha(1)-Pi. DESIGN: Multicenter, retrospective cohort study. SETTING: Outpatient clinics of 26 university clinics and pulmonary hospitals. PATIENTS: Ninety-six patients with severe alpha(1)-Pi deficiency receiving weekly augmentation therapy with human alpha(1)-Pi, 60 mg/kg of body weight, had a minimum of two lung function measurements before and two lung function measurements after augmentation therapy was started. Lung function data were followed up for a minimum of 12 months both before and during treatment (mean, 47.5 months and 50.2 months, respectively). MEASUREMENTS AND RESULTS: Patients were grouped according to the severity of their lung function impairment. The change in FEV(1) was compared during nontreatment and treatment periods. In the whole group, the decline in FEV(1) was significantly lower during the treatment period (49.2 mL/yr vs 34.2 mL/yr, p = 0.019). In patients with FEV(1) > 65%, IV alpha(1)-Pi treatment reduced the decline in FEV(1) by 73.6 mL/yr (p = 0.045). Seven individuals had a rapid decline of FEV(1) before treatment, and the loss in FEV(1) could be reduced from 256 mL/yr to 53 mL/yr (p = 0.001). CONCLUSION: Some patients with severe alpha(1)-Pi deficiency and well-preserved lung function show a rapid decline in FEV(1). These patients profit from weekly IV therapy with human alpha(1)-Pi and have less rapid decline if treated. Early detection of patients at risk and early start of augmentation therapy may prevent accelerated loss of lung tissue.     

Psychosocial adjustment of patients and caregivers prior to allogeneic bone marrow transplantation

There are many studies that examine the psychosocial adjustment of survivors of bone marrow transplantation (BMT). On the other hand, there are relatively few studies that examine the psychosocial adjustment of patients prior to BMT, and even fewer that focus on the psychosocial adjustment of the patient's caregiver. The purpose of the present study was to assess performance status and psychosocial adjustment to illness, mood and stress response of patients and caregivers prior to admission for allogeneic BMT. Forty patients and their 39 caregivers were assessed using standardized measures. One-fourth of the patients reported clinical levels of psychosocial maladjustment on the Psychosocial Adjustment to Illness Scale and had greater adjustment problems than BMT survivors. Approximately one-third (35%) and one-quarter (23%) of the patients reported significant symptoms of intrusive and avoidance stress responses, respectively on the Impact of Events Scale. Caregivers reported more impairments in family relationships than patients, but overall reported similar distress to that of patients. Information about the pre-BMT process appears to be critical to understanding the psychosocial impact that BMT can have on patients and their caregivers.     

Voxel size effects in three-dimensional nuclear magnetic resonance microscopy performed for trabecular bone dosimetry

An important problem in internal dosimetry is the assessment of energy deposition by beta particles within trabecular regions of the skeleton. Recent dosimetry methods for trabecular bone are based on Monte Carlo particle transport simulations within three-dimensional (3D) images of real human bone samples. Nuclear magnetic resonance (NMR) microscopy is a 3D imaging technique of choice due to the large signal differential between bone tissue and the water-filled marrow cavities. Image voxel sizes currently used in NMR microscopy are between 50 microm and 100 microm, but the images are time consuming to acquire and can only be performed at present for in vitro samples. It is therefore important to evaluate what resolution is best suitable in order to properly characterize the trabecular microstructure, to adequately predict the tissue dosimetry, and to minimize imaging time. In this work, a mathematical model of trabecular bone, composed of a distribution of spherical marrow cavities, was constructed. The mathematical model was subsequently voxelized with different voxel sizes (16 microm to 1,000 microm) to simulate 3D NMR images. For each image, voxels are assigned to either bone or marrow according to their enclosed marrow fraction. Next, the images are coupled to the EGS4 electron transport code and absorbed fractions to bone and marrow are calculated for a marrow source of monoenergetic electrons. Radionuclide S values are also determined for the voxelized images with results compared to data calculated for the pure mathematical sample. The comparison shows that for higher energy electrons (>400 keV), good convergence of the results is seen even within images of poor resolution. Above 400 keV, a voxel resolution as large as 300 microm results in dosimetry errors below 5%. For low-energy electrons and high-resolution images, the self-dose to marrow is also determined to within 5% accuracy. Nevertheless, increased voxelization of the image overestimates the surface area of the bone-marrow interface leading to errors in the cross-dose to bone as high as 25% for some low-energy beta emitters.     

SARS-CoV-2, surgeons and surgical masks

The exact risk association of coronavirus disease 2019 (COVID-19) for surgeons is not quantified which may be affected by their risk of exposure and individual factors. The objective of this review is to quantify the risk of COVID-19 among surgeons, and explore whether facemask can minimise the risk of COVID-19 among surgeons. A systematised review was carried out by searching MEDLINE to locate items on severe acute respiratory syndrome coronavirus 2 or COVID-19 in relation to health care workers (HCWs) especially those work in surgical specialities including surgical nurses and intensivists. Additionally, systematic reviews that assessed the effectiveness of facemask against viral respiratory infections, including COVID-19, among HCWs were identified. Data from identified articles were abstracted, synthesised and summarised. Fourteen primary studies that provided data on severe acute respiratory syndrome coronavirus 2 infection or experience among surgeons and 11 systematic reviews that provided evidence of the effectiveness of facemask (and other personal protective equipment) were summarised. Although the risk of COVID-19 could not be quantified precisely among surgeons, about 14% of HCWs including surgeons had COVID-19, there could be variations depending on settings. Facemask was found to be somewhat protective against COVID-19, but the HCWs’ compliance was highly variable ranging from zero to 100%. Echoing surgical societies’ guidelines we continue to recommend facemask use among surgeons to prevent COVID-19.     

Prolonged analgesia by adding midazolam and hyperbaric bupivacaine in subarachnoid block for lower uterine caesarian section

Antinociceptive effect and safety of sub-arachnoid (SAB) midazolam is well established in animals and human beings. In this randomized, prospective placebo control clinical study, we investigated the addition of 2.5mg midazolam to bupivacaine on the quality of surgical anaesthesia and duration of first analgesic in the post operative period after lower uterine caesarean section (LUCS). Sixty ASA I or II pregnant women scheduled for elective lower uterine caesarean section were selected for the study. The patients were randomly allocated to receive 2ml of 0.5% hyperbaric bupivacaine with either 0.5ml of 5% dextrose in aqua or 2.5 mg (0.5ml) midazolam. The duration of first analgesic demand, quality of anaesthesia, haemodynamic changes and neonatal condition were assessed. The duration of analgesia (the time interval in minutes between the sub-arachnoid injection and the first analgesic demand by the patient) was significantly longer in the Group II than Group I (197min vs. 112min; p<0.001). The quality of surgical anaesthesia was excellent or good throughout the surgical procedure in 90% (n = 27) of the patients in Group II (p = 0.01). Systolic Blood pressure was significantly lower in the group I at 10 min and 20 min after administration of SAB than group II (p = 0.005 and p = 0.007) but comparable at other times. Sedation level, Apgar score was comparable in both groups. No neurological deficit or other significant adverse effects were recorded. The addition of midazolam with hyperbaric low dose bupivacaine in SAB significantly improves the quality of surgical anaesthesia and prolongs the duration of analgesia without any adverse effects.     

Sensitization of primary afferents to mechanical and heat stimuli after incision in a novel in vitro mouse glabrous skin-nerve preparation

In this study, we recorded activity from afferent fibers innervating the mouse plantar skin, the same region evaluated in pain behavior experiments. We compared responses of afferents from incised and unincised hind paw skin. The plantar skin together with attached medial and lateral plantar nerves was dissected until they could be completely removed intact and placed in an organ bath chamber continuously perfused with oxygenated Kreb’s solution with the temperature maintained at 32 °C. Afferent nerve activities to feedback-controlled mechanical and heat stimuli and cooling were recorded. Eighty-five single Aδ- and C-fiber afferents were recorded, 42 from control and the remainder from incised animals. A greater proportion of C-fibers (11/34) from incised skin had spontaneous activity than in the unincised preparation (2/32). The mechanical thresholds of both Aδ- and C-fiber units were not different between control and incised groups but the responses to suprathreshold mechanical stimulation were increased in low threshold Aδ- and C-fibers. The greatest change in heat sensitivity was apparent when multi-fiber total activity was measured; threshold was reduced, total spikes were greater and the peak discharge frequency was increased. In summary, feedback-controlled stimulation identified mechanical sensitization after incision in an in vitro preparation. Few fibers were excited by cooling. Heat sensitization of primary afferents was more prominent when activities of unclassified afferents are included. The preparation allows us to study afferent function of the same tissue that is examined for in vivo pain behavior assays in mice.     

An image-based skeletal model for the ICRP reference adult male-specific absorbed fractions for neutron-generated recoil protons

Recoiling hydrogen nuclei are a principle mechanism for energy deposition from incident neutrons. For neutrons incident on the human skeleton, the small sizes of two contrasting media (trabecular bone and marrow) present unique problems due to a lack of charged-particle (protons) equilibrium. Specific absorbed fractions have been computed for protons originating in the human skeletal tissues for use in computing neutron dose response functions. The proton specific absorbed fractions were computed using a pathlength-based range-energy calculation in trabecular skeletal samples of a 40 year old male cadaver.     

Body fatness in relation to physical activity and selected socioeconomic parameters of adolescents aged 15–17 years in Merida,Yucatan

Background: Increasing rates of overweight and obesity in adolescents are major concerns in many countries, including Mexico.

Objectives: To study anthropometric and body composition characteristics (BCC) and their relations with socioeconomic status (SES), biological history and physical activity (PA) of school-going adolescent boys and girls in the city of Merida, Yucatan, Mexico.

Subjects and methods: In this cross-sectional study, a sample of 321 adolescents (156 boys and 165 girls) aged 15–17 years from public and private schools in Merida, was taken from a study carried out in 2008–2009.

Results: Body mass index had significant correlations to BCC (fat mass and fat-free mass). The rate of stunting was higher in girls (18.20%) than in boys (7.69%). Stunted adolescents had higher body fat (%) than normally growing peers. High rates of overweight (boys 26.28%, girls 24.24%) and obesity (boys 10.26%, girls 6.06%) were recorded. SES (parents’ age, education and occupation; crowding index in the family; household food expenditure), participants’ biological history and PA are related with height and BCC by age and sex.

Conclusion: Adolescents with excess weight (overweight?+?obesity) reported being less physically active. SES and PA were strongly related to growth and body fatness in the studied adolescents.