Artificial Neural Networks in Cardiovascular Diseases and its Potential for Clinical Application in Molecular Imaging.
In medical imaging, Artificial Intelligence is described as the ability of a system to properly interpret and learn from external data, acquiring knowledge to achieve specific goals and tasks through flexible adaptation. The number of possible applications of Artificial Intelligence is also huge in clinical medicine and cardiovascular diseases. To describe for the first time in literature, the main results of articles about Artificial Intelligence potential for clinical applications in molecular imaging techniques, and to describe its advancements in cardiovascular diseases assessed with nuclear medicine imaging modalities. A comprehensive search strategy was used based on SCOPUS and PubMed databases. From all studies published in English, we selected the most relevant articles that evaluated the technological insights of AI in nuclear cardiology applications. Artificial Intelligence may improve patient care in many different fields, from the semi-automatization of the medical work, through the technical aspect of image preparation, interpretation, the calculation of additional factors based on data obtained during scanning, to the prognostic prediction and risk-- group selection. Myocardial implementation of Artificial Intelligence algorithms in nuclear cardiology can improve and facilitate the diagnostic and predictive process, and global patient care. Building large databases containing clinical and image data is a first but essential step to create and train automated diagnostic/prognostic models able to help the clinicians to make unbiased and faster decisions for precision healthcare.


Feasibility and benefits of the ewe as a model for vaginal surgery training.
The objective was to evaluate the ewe as an animal model for teaching and training in vaginal surgery. Twenty-nine postgraduate surgeons attended a training course on vaginal prolapse surgery. After a review of human and sheep anatomy, the participants performed transvaginal meshes, vaginal hysterectomy, SSLF (Richter), and OAS repair in ewes and human cadavers. Participants completed questionnaires on the whole course. Questionnaires showed the significant superiority of ewes over human cadavers for all items evaluated regarding surgical dissections. Only identification of the sacrospinous ligament and the spine were judged to be similar in ewes and human cadavers. Participants noticed that ewe model is appropriate for vaginal prolapse surgery training for resident and for postgraduate surgeons. Two vaginal hysterectomies were also performed. Operating time, surgery, and anatomy were nearly identical to that of humans. The same conclusions were made while performing sacrospinous ligament fixation (Richter) and obstetric anal sphincter injury repair. This series indicates that the ewe is a useful animal model for teaching vaginal surgery.


The effect of feeding soybean trypsin inhibitor and repeated injections of cholecystokinin on rat pancreas.
The effects of dietary soybean trypsin inhibitor (SBTI, Kunitz type) or repeated i.p. injections of 95% pure cholecystokinin (CCK-39) on rat pancreas were investigated in a 10-day experiment. SBTI and CKK -39 induced similar increases in pancreatic weight, which led to both cellular hypertrophy and hyperplasia. Trypsin and chymotrypsin activity increased with an increase in pancreatic weight. Amylase activity increased only after CCK-39 injection, whereas lipase activity was not affected by either SBTI or CCK-39 treatment. After both treatments, insulin content showed only a slight tendency to increase, whereas glucagon content was not different from controls. The results indicate that SBTI and CCK-39 mainly exert their effects on the exocrine pancreas in a similar but not identical manner. It is therefore suggested that SBTI is not only a potent stimulator of the secretion of CCK activity but also of other unidentified gastrointestinal factor(s).


Youth with Behavioral Health Disorders Aging Out of Foster Care: a Systematic Review and Implications for Policy, Research, and Practice.
This systematic review aimed to (1) identify and summarize empirical studies on youth with behavioral health disorders aging out of foster care and (2) address implications for behavioral health policy, research, and practice. We identified previous studies by searching PubMed, PsycINFO, EBSCO, and ISI Citation Indexes and obtaining references from key experts in the child welfare field. A total of 28 full articles published between 1991 and 2014 were reviewed and summarized into the key areas including systems of care, disability type, transition practice area, study methods, study sample, transition outcome measures, study analysis, and study findings. Considering how fast youth who have behavioral health disorders fall through the crack as they exit foster care, one cannot understate the importance of incorporating timely and appropriate transition planning and care coordination for youth who have behavioral health disorders aging out of foster care into the usual case management performed by behavioral health systems and service providers.


Local positional cues in the neuroepithelium guide retinal axons in embryonic Xenopus brain.
Growing retinal axons home to their distant target, the tectum, even when they are displaced from their normal pathway. This argues for long-range guidance mechanisms in the embryonic brain. Growth cones may orientate to diffusible attractants released from the target, as proposed in other systems, or they may use a stable distribution of positional information in the neuroepithelium. To distinguish between these possibilities, small pieces of the presumptive optic tract, through which retinal axons will normally grow, were rotated by approximately 90 degrees either clockwise or counterclockwise. When the retinal axons later encountered the rotated neuroepithelium, they also turned clockwise or counterclockwise, in correspondence with the direction of rotation. This demonstrates that long-range navigation of retinal axons in the vertebrate brain is based partly on stable, local positional factors, rather than on remote diffusible factors.


Six high-intensity interval training sessions over 5 days increases maximal oxygen uptake, endurance capacity, and sub-maximal exercise fat oxidation as much as 6 high-intensity interval training sessions over 2 weeks.
High-intensity interval training (HIIT) induces similar or even superior adaptations compared to continuous endurance training. Indeed, just 6 HIIT sessions over 2 weeks significantly improves maximal oxygen uptake (VO2max), submaximal exercise fat oxidation, and endurance performance. Whether even faster adaptations can be achieved with HIIT is not known. Thus, we aimed to determine whether 2 sessions of HIIT per day, separated by 3 h, every other day for 5 days (double HIIT (HIIT-D), n = 15) could increase VO2max, submaximal exercise fat oxidation, and endurance capacity as effectively as 6 sessions of HIIT over 2 weeks (single HIIT (HIIT-S), n = 13). Each training session consisted of 10 × 60 s of cycling at 100% of VO2max interspersed with 75 s of low-intensity cycling at 60 watt (W). Pre- and post-training assessments included VO2max, time to exhaustion at ∼80% of VO2max, and 60-min cycling trials at ∼67% of VO2max. Similar increases (p < 0.05) in VO2max (HIIT-D: 7.7% vs. HIIT-S: 6.0%, p > 0.05) and endurance capacity (HIIT-D: 80.1% vs. HIIT-S: 79.2%, p > 0.05) were observed. Submaximal exercise carbohydrate oxidation was reduced in the 2 groups after exercise training (HIIT-D: 9.2%, p = 0.014 vs. HIIT-S: 18.8%, p = 0.012) while submaximal exercise fat oxidation was significantly increased in HIIT-D (15.5%, p = 0.048) but not in HIIT-S (9.3%, p = 0.290). Six HIIT sessions over 5 days was as effective in increasing VO2max and endurance capacity and was more effective in improving submaximal exercise fat oxidation than 6 HIIT sessions over 2 weeks.


Excitatory amino acid-induced cytotoxicity in primary cultures of mouse cerebellar granule cells correlates with elevated, sustained c-fos proto-oncogene expression.
An elevated, sustained expression of c-fos mRNA was found in primary cultures of mouse cerebellar granule cells following exposure to toxic concentrations of the excitatory amino acids, L-glutamate, L-homocysteate, S-sulpho-L-cysteine and N-methyl-D-aspartate (NMDA), using leakage of lactate dehydrogenase (LDH) as an indicator of cytotoxicity. In contrast, when used at non-toxic concentrations these compounds induced a rapid and transient increase in c-fos mRNA levels. Both LDH release and elevated, sustained c-fos mRNA induction were blocked (in the case of L-homocysteate) or reduced (in the case of L-glutamate and S-sulpho-L-cysteine) by the selective NMDA receptor antagonist (DL(+/-)-2-amino- 5-phosphonopentanoic acid) whereas 6-cyano-7-nitroquinoxaline-2,3-dione (a selective antagonist at non-NMDA ionotropic receptors) had no effect. These data suggest a role for altered c-fos mRNA expression in excitotoxic mechanisms.


Integrated reactive absorption process for synthesis of fatty esters.
Reactive separations using green catalysts offer great opportunities for manufacturing fatty esters, involved in specialty chemicals and biodiesel production. Integrating reaction and separation into one unit provides key benefits such as: simplified operation, no waste, reduced capital investment and low operating costs. This work presents a novel heat-integrated reactive absorption process that eliminates all conventional catalyst related operations, efficiently uses the raw materials and equipment, and considerably reduces the energy requirements for biodiesel production--85% lower as compared to the base case. Rigorous simulations based on experimental results were carried out using Aspen Plus and Dynamics. Despite the high degree of integration, the process is well controllable using an efficient control structure proposed in this work. The main results are provided for a plant producing 10 ktpy fatty acid methyl esters from methanol and waste vegetable oil with high free fatty acids content, using sulfated zirconia as solid acid catalyst.


Handedness as a predictor of side of onset of Parkinson's disease.
The prevalence and predictive factors of asymmetry in Parkinson's disease have hardly been investigated. The aim of this study was to determine the rate of asymmetric features in patients with Parkinson's disease. The study group consisted of 307 patients with idiopathic Parkinson's disease. The dominant hand was recorded in each case, and right-left differences in tremor, bradykinesia, and rigidity was defined as a difference of more than 4 points on the Unified Parkinson Disease Rating Scale. Asymmetric presentation was noted in 260 patients [84.7%]. The initial symptoms appeared on the right side in 47% of the right-handed patients [on the left side in 38% of the right-handed patients], and on the left side in 52% of the left-handed patients [on the right side in 36% of them] [p=0.06]. In conclusion, Parkinson's disease appears to be characterized by asymmetry of symptoms. There was a trend toward symptoms onset on the dominant side.


Canine parvovirus in asymptomatic feline carriers.
Canine parvovirus (CPV) and feline panleukopaenia virus (FPLV) are two closely related viruses, which are known to cause severe disease in younger unvaccinated animals. As well as causing disease in their respective hosts, CPV has recently acquired the feline host range, allowing it to infect both cats and dogs. As well as causing disease in dogs, there is evidence that under some circumstances CPV may also cause disease in cats. This study has investigated the prevalence of parvoviruses in the faeces of clinically healthy cats and dogs in two rescue shelters. Canine parvovirus was demonstrated in 32.5% (13/50) of faecal samples in a cross sectional study of 50 cats from a feline only shelter, and 33.9% (61/180) of faecal samples in a longitudinal study of 74 cats at a mixed canine and feline shelter. Virus was isolated in cell cultures of both canine and feline origin from all PCR-positive samples suggesting they contained viable, infectious virus. In contrast to the high CPV prevalence in cats, no FPLV was found, and none of 122 faecal samples from dogs, or 160 samples collected from the kennel environment, tested positive for parvovirus by PCR. Sequence analysis of major capsid VP2 gene from all positive samples, as well as the non-structural gene from 18 randomly selected positive samples, showed that all positive cats were shedding CPV2a or 2b, rather than FPLV. Longitudinally sampling in one shelter showed that all cats appeared to shed the same virus sequence type at each date they were positive (up to six weeks), despite a lack of clinical signs. Fifty percent of the sequences obtained here were shown to be similar to those recently obtained in a study of sick dogs in the UK (Clegg et al., 2011). These results suggest that in some circumstances, clinically normal cats may be able to shed CPV for prolonged periods of time, and raises the possibility that such cats may be important reservoirs for the maintenance of infection in both the cat and the dog population.


Computed tomographic method for measurement of inclination angles and motion of the sacroiliac joints in German Shepherd Dogs and Greyhounds.
To develop an in vivo CT method to measure inclination angles and motion of the sacroiliac joints in dogs of performance breeds. 10 German Shepherd Dogs and 12 Greyhounds without signs of lumbosacral region pain or neurologic problems. CT of the ilium and sacrum was performed in flexed, neutral, and extended hind limb positions. Lines were drawn on volume-rendered images acquired in the flexed and extended positions to measure motion of the ilia relative to the sacra. Inclination angles of the synovial and ligamentous components of the sacroiliac joints were measured on transverse-plane CT images acquired at cranial and caudal locations. Coefficients of variance of measurements were calculated to determine intraobserver variability. Coefficients of variance of measurements ranged from 0.17% to 2.45%. A significantly higher amount of sacroiliac joint rotational motion was detected for German Shepherd Dogs versus Greyhounds. The cranial synovial joint component had a significantly more sagittal orientation in German Shepherd Dogs versus Greyhounds. No significant differences were detected between breeds for x- or y-axis translational motion or caudal synovial or ligamentous joint component inclination angles. The small amounts of sacroiliac joint motion detected in this study may buffer high-frequency vibrations during movement of dogs. Differences detected between breeds may be associated with the predisposition of German Shepherd Dogs to develop lumbosacral region signs of pain, although the biological importance of this finding was not determined. Future studies are warranted to compare sacroiliac joint variables between German Shepherd Dogs with and without lumbosacral region signs of pain.


Evaluation of biometric methods for measuring the anterior chamber depth in the non-contact mode.
High-resolution biometry of the anterior ocular segment is now becoming more and more important against a background of refractive surgery and the evaluation of potentially accommodative lens replacement materials. The aim of this study was a systematic investigation of the currently available non-contact methods for measuring the anterior chamber depth (ACD). The ACDs of 50 phakic eyes of 27 patients aged between 19 and 59 years were measured with the IOL-Master (Zeiss), the AC-Master (Zeiss), the Pentacam (Oculus) and slit-lamp pachymetry by Jaeger (Haag-Streit). The median anterior chamber depth in the investigated eyes was 3.63 mm for the IOL-Master (minimum 2.88 mm, maximum 4.22 mm), 3.802 mm for the AC-Master (2.816 mm-4.373 mm), 3.915 mm for the Pentacam (minimum 2.994 mm, maximum 4.614 mm) and 3.75 mm for Jaeger (2.887 mm-4.29 mm). With a probability of error of alpha=0.05 there were no significant differences concerning the ACD between the methods of Jaeger and AC-Master, Jaeger and IOL-Master, or Pentacam and AC-Master (Wilcoxon and Wilcox). The intra-individual variability was +/-5.4 microm for AC-Master, +/-12.7 microm for Pentacam, +/-24.5 microm for IOL-Master and +/-41.2 microm for Jaeger. The maximum method-dependent difference in ACD determination was 285 microm. All the methods allow non-contact biometry, but the results might differ due to measuring principles inherent to the system, experience of the examiner and compliance of the patient. Partial coherence interferometry with the AC-Master offers the advantage of measurement exactly along the optical axis with the highest reproducibility and patient compliance.


Removal of histological sections from glass for electron microscopy: use of Quetol 651 resin and heat.
A method is described for using the epoxy resin Quetol 651 and heat for convenient and rapid separation of conventional histological sections from glass slides for subsequent ultrathin sectioning for retrospective electron microscopy. The same method is useful when Epon-Araldite is substituted for the Quetol 651 resin.


Computed tomography angiographic findings in hepatocellular carcinoma less than 2 cm detected during follow-up in 29 patients.
The early stage of hepatocarcinogenesis is not well understood pathologically and clinically. The present study was designed to define small (early) hepatocellular carcinoma (HCC) angiographically using the angio-helical computed tomography (CT) system. Arterial portography CT and hepatic arteriography CT were carried out in 29 patients in whom small HCC < or = 20 mm was detected during follow-up. There were 17 males and 12 females, aged 47 to 85 years. The offending virus was hepatitis B in four, hepatitis C in 24 and no virus marker in one case. The follow-up period varied from less than a year to 17 years, averaging 6.4 years. The underlying disease was cirrhosis in 12 and chronic hepatitis in 17 cases. The mass was solitary in 16 and multiple in 13 cases, while the size of the mass ranged from 8-20 mm. All lesions were low in attenuation on arterial portography CT, and in 23 of 30 lesions hepatic arteriography CT showed high attenuation, suggesting arterial blood supply. In the remaining 7 cases, lesions were perhaps in the transition from portal to arterial. It was concluded that HCC develops frequently in a liver with chronic hepatitis, often muticentrically, and that early HCC lesions are more often overt HCC already with arterial blood supply, rather than extremely well-differentiated supplied by the portal vein as generally believed.


Use of Diabetes Medications before and after a Heart Failure-Related Hospitalization among Nursing Home Residents.
Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardiovascular benefits, whereas thiazolidinediones (TZDs) and sulfonylureas (SUs) increase cardiovascular risk. The objective of this study was to describe the use of SGLT-2is, GLP-1RAs, TZDs, and SUs before and after a heart failure (HF)-related hospitalization in nursing home (NH) residents with type 2 diabetes (T2D). This was a cohort study using a 20% sample of Medicare claims linked with Minimum Data Set resident assessments. The study population was long-stay NH residents with T2D and an HF-related hospitalization between January 1, 2013, and August 31, 2018. For individuals with multiple HF hospitalizations, 1 hospitalization was randomly selected. We ascertained diabetes medications using Medicare Part D claims during the 120 days before and after hospital discharge (or skilled nursing facility discharge, where applicable). We calculated (1) the proportion of study participants who received a medication class of interest during pre- and posthospitalization periods; (2) the proportion of continuous users; and (3) the proportion of posthospitalization users who were new users. A total of 12,990 NH residents with T2D and an HF-related hospitalization were included (mean age 78 years, 66% female, 19% Black). Before hospitalization, 1.5% received TZDs, 14.1% received SUs, 1.2% received GLP-1RAs, and 0.3% received SGLT-2is. Among prehospitalization users of TZDs, SUs, GLP-1RAs, and SGLT-2is, 49%, 62%, 60%, and 40% continued the medications, respectively. Among posthospitalization users of TZDs, SUs, GLP-1RAs, and SGLT-2is, 37%, 10%, 28%, and 11%, respectively, were new users. Among NH residents with hospitalized HF, GLP-1RAs and SGLT-2is were seldom used. TZDs and SUs were still used by many residents with T2D after HF hospitalizations. Barriers may exist in the use of newer diabetes medications to prevent heart failure in NH residents with T2D, which warrants further studies in older adults with multimorbidity.


Predictors of extrahepatic recurrence after resection of colorectal liver metastases.
It is important to identify patients at high risk of extrahepatic recurrence after surgery for liver metastases, in order to maximize the survival benefit obtained by prophylactic regional chemotherapy. Data from 68 patients who underwent resection of colorectal liver metastases but who did not receive hepatic arterial chemotherapy or intravenous systemic chemotherapy were collected. Twenty-two variables were examined by univariate and multivariate analyses to determine which factors were relevant to extrahepatic recurrence. A scoring system was developed that included the most relevant factors. The extrahepatic recurrence rate at 3 years after hepatectomy was 57.8 per cent. Three variables were independently associated with extrahepatic recurrence including raised serum level of carcinoembryonic antigen after hepatectomy (relative risk (RR) 5.4, P < 0.001), venous invasion of the primary tumour (RR 4.0, P = 0.001) and high-grade budding of the primary tumour (RR 3.1, P = 0.006). Patients with none of these risk factors had a 3-year extrahepatic recurrence rate of 7.1 per cent, compared with 61.6 per cent for those with one risk factor and 100 per cent for those with two or three risk factors. It was possible to identify patients at high risk of disease relapse at extrahepatic sites. This system might be used on an individual basis to select patients with colorectal liver metastases for regional chemotherapy or systemic chemotherapy after surgical intervention.


Cross-over limb replantation: a case report.
Following traumatic bilateral arm amputation in a 46-year-old woman, orthotopic replantation was not possible. The patient underwent replantation of the left forearm to the right proximal forearm. At two years she has a sensate hand, with good recovery of her long flexors of the hand and wrist extensors. DASH score is 93.9 and Chen's score is III (medium). We demonstrate a high level of function compared to the contralateral prosthetic limb. There have only been four similar cases described. Although a rare circumstance, a cross-limb replant can provide a level of function and independence superior to a simple prosthesis. Cross-limb transfer should be considered in situations where bilateral arm amputation is present and neither can be orthotopically replanted.


Experimental detection of retinal ganglion cell damage in vivo.
In vivo detection of retinal ganglion cell (RGC) damage should have experimental and clinical relevance. A number of experimental models have been recently described to visualize RGCs in vivo. With retrograde injection of fluorescent tracers into the superior colliculus, lateral geniculate body, or optic nerve, RGCs can be detected in vivo with confocal laser scanning microscopy, fluorescent microscopy, or confocal scanning laser ophthalmoscopy. Although the resolution of these imaging techniques is limited to detecting only the cell bodies, the addition of adaptive optics has allowed in vivo visualization of axonal and dendritic processes. An ideal experimental model for detection of RGC damage should be non-invasive and reproducible. The introduction of a strain of transgenic mice that express fluorescent proteins under the control of Thy-1 promoter sequence has offered a non-invasive approach to detect RGCs. Long- term serial monitoring of RGCs over a year has been shown possible with this technique. In vivo imaging of RGCs could provide crucial information to investigating the mechanisms of neurodegenerative diseases and evaluating the treatment response of neuroprotective agents.


The selective autophagy receptor p62 forms a flexible filamentous helical scaffold.
The scaffold protein p62/SQSTM1 is involved in protein turnover and signaling and is commonly found in dense protein bodies in eukaryotic cells. In autophagy, p62 acts as a selective autophagy receptor that recognizes and shuttles ubiquitinated proteins to the autophagosome for degradation. The structural organization of p62 in cellular bodies and the interplay of these assemblies with ubiquitin and the autophagic marker LC3 remain to be elucidated. Here, we present a cryo-EM structural analysis of p62. Together with structures of assemblies from the PB1 domain, we show that p62 is organized in flexible polymers with the PB1 domain constituting a helical scaffold. Filamentous p62 is capable of binding LC3 and addition of long ubiquitin chains induces disassembly and shortening of filaments. These studies explain how p62 assemblies provide a large molecular scaffold for the nascent autophagosome and reveal how they can bind ubiquitinated cargo.


CARM1 inhibition reduces histone acetyltransferase activity causing synthetic lethality in CREBBP/EP300-mutated lymphomas.
Somatic mutations affecting CREBBP and EP300 are a hallmark of diffuse large B-cell lymphoma (DLBCL). These mutations are frequently monoallelic, within the histone acetyltransferase (HAT) domain and usually mutually exclusive, suggesting that they might affect a common pathway, and their residual WT expression is required for cell survival. Using in vitro and in vivo models, we found that inhibition of CARM1 activity (CARM1i) slows DLBCL growth, and that the levels of sensitivity are positively correlated with the CREBBP/EP300 mutation load. Conversely, treatment of DLBCLs that do not have CREBBP/EP300 mutations with CARM1i and a CBP/p300 inhibitor revealed a strong synergistic effect. Our mechanistic data show that CARM1i further reduces the HAT activity of CBP genome wide and downregulates CBP-target genes in DLBCL cells, resulting in a synthetic lethality that leverages the mutational status of CREBBP/EP300 as a biomarker for the use of small-molecule inhibitors of CARM1 in DLBCL and other cancers.


Genetical differences in sensitivity to tremorine and oxotremorine in mice.
Male mice from 14 strains were injected i.p. with tremorine (3.0 mg/kg) or oxotremorine (0.15 or 0.1 mg/kg). Large inter-strain differences in the degree and duration of the subsequent hypothermia were noted. 2 strains, BALB/c and Simpson, were particularly sensitive to the hypothermic effect of oxotremorine. The offspring from a cross between BALB/c and Simpson were less sensitive than the parental strains, suggesting genetic complementation. A set of 7 recombinant inbred (RI) lines derived from strains C57BL and BALB/c were tested with oxotremorine. 5 RI lines resembled strain C57BL in their response and 2 RI lines resembled strain BALB/c. It was concluded that strains C57BL and BALB/c differ at a gene which has a major effect on the response to oxotremorine.


Taxonomic study of the genus Eucriotettix hebard (Orthoptera: Tetrigidea) from China.
The genus Eucriotettix Hebard from China was reviewed and 13 were species recorded, including two new species: Eucriotettix nigripennis Deng & Zheng n. sp. and Eucriotettix strictivertex Deng & Zheng n. sp. A key to the species of Eucriotettix from China is provided. Type specimens were deposited in the Institute of Zoology, Shaanxi Normal University.


The first perforating branch of the deep femoral artery: A reliable recipient vessel for vascularized fibular grafts: An anatomical study.
Although the perforating branches of the deep femoral artery have been introduced as recipient vessels for vascularized fibular grafts in the treatment of osteonecrosis of the femoral head, comprehensive knowledge of the related anatomy is deficient. The aims of this study were to provide detailed anatomical data for the perforating branches of the deep femoral artery and validate their usefulness as recipient vessels for vascularized fibular grafts. Anatomical dissection was performed on 11 fresh human cadaveric lower extremities. The number, locations, and diameters of the perforating branches were documented. The topographic relationships with the vastus ridge and the tendinous insertion of the gluteus maximus were clarified. The diameters of the perforating branches were compared with those of the ascending branch of the lateral circumflex femoral and the peroneal arteries. The mean number of perforating branches was 3.5. The mean distances from the vastus ridge to the first, second, and third perforating branches were 8.1, 13.7, and 20.4 cm, respectively. The first perforating branch was always located medial to the tendinous insertion of the gluteus maximus, whereas the second perforating branch was always located distal to the gluteus maximus. The mean diameters of the first, second, third, and fourth perforating branches were 3.1, 2.3, 1.6, and 1.2 mm, respectively. The mean diameters of the ascending branch of the lateral circumflex femoral and the peroneal arteries were 2.0 and 3.6 mm, respectively. The first perforating branch of the deep femoral artery is an appropriate alternative recipient vessel for vascularized fibular grafts in the treatment of osteonecrosis of the femoral head. It has a very consistent anatomy with a suitable location and diameter for anastomosis of the peroneal artery.


Volume composition of the lateral cervical nucleus in the cat. I. A stereological and electron microscopical study of normal and deafferentated animals.
The neuropil of the lateral cervical nucleus (LCN) has been studied by means of ultrastructural stereological methods. Estimates of the fractional volumes of axons, glial cells (three types), extracellular space, boutons, bouton mitochondria, dendrites, dendritic mitochondria, neuronal somata and blood vessels were calculated for four normal cats and eight cats which had been subjected to spinal deafferentation 2, 4, 9, and 14 days before perfusion. 14 days after operation the fractional volume of boutons and dendrites in the nucleus was considerably lower on the operated side, corresponding to a reduction of 67% and 64% respectively. The bouton reduction was higher than could have been expected from findings in earlier qualitative studies. The reduction in dendritic volume, which was already present after 4 days, had not been detected in earlier studies of the LCN. Dark dendrites were found both in normal animals and on the normal and operated sides in operated animals. The variation from animal to animal was great but the figures for the deafferented sides were significantly higher. The general value of the stereological technique in ultrastructural neuroanatomical research is discussed and it is concluded that quantitative methods are more sensive to small and gradual changes and should give a better estimation of transneuronal effects and of the amount of degeneration than purely qualitative methods.


Time to first birth and its predictors among reproductive age women in high fertility countries in Sub-Saharan Africa: Inverse Weibull gamma shared frailty model.
Early initiation of childbearing leads to an increase in total fertility rate and population growth. It has been linked with both maternal and child morbidity and mortality. However, there is limited information on the timing of the first birth and its predictors in the area so far. Therefore, determining the time to first birth and its predictors will help to design strategies to improve fertility rate, maternal and child survival. The survey used recent (2010 - 2018) Demographic and Health data; a stratified, two-stage cluster sampling technique was used to select the sample. Inverse Weibull gamma shared frailty model was used to model the data at 95% confidence interval. Adjusted hazard ratio (AHR) and median hazard ratio (MHR) were reported as effect size. Statistical significance was declared at p value < 0.05. The overall median age at first birth was found to be 19 years (IQR: 16, 21 years). Rural residency (AHR = 1.02, 95%, CI 1.00,1.04), agricultural employee (AHR = 1.14, 95%, CI 1.13, 1.17), and nonagricultural employee (AHR = 1.06, 95%, CI 1.05, 1.08), marriage below 15 years (AHR = 5.47, 95%, CI 5.37, 5.57) and 15-17 years (AHR = 3.27, 95%, CI 3.22, 3.32), had sex below 15 years (AHR = = 1.57, 95%, CI 1.54, 1.61) and 15-17 years (AHR = 1.38, 95%, CI 1.38, 1.43), women who had unmet need for contraceptive (AHR = 1.39, 95%, CI 1.37, 1.42), and met need (AHR = 1.32, 95%, CI 1.30, 1.35), high spousal age gap (AHR = 1.17, 95%, CI 1.15, 1.19), not heard family planning message (AHR = 1.02, 95%, CI 1.01,1.04) were the higher hazard of early childbirth. The median age at first birth was found to be 19 years. This is lower than the optimal age for giving first birth, which is between late 20 s and early 30 s years. Rural residences, occupation, hearing family planning massage in the media, early sexual intercourse, early age at first marriage, high spousal gap, and unmet need for family planning were predictors of first birth at an early age. Thus, governments and non-governmental organizations should strive to implement programs that aim to reduce early age at first birth by considering these factors.


Temperature dependence of contraction characteristics in developing rat muscles.
Contractions of rat extensor digitorum longus (EDL, a fast muscle) and soleus (SOL, a slow muscle) muscles of different ages (1-4 weeks) were recorded in vitro with direct stimulation and at different temperatures (range 35-10 degrees C). Twitch tension in 4-week-old EDL muscle increased in cooling from 35 to 20 degrees C (cooling potentiation); the tension decreased in further cooling below 20 degrees C. This pattern of temperature dependence of twitch tension was seen in fast muscles of all ages (1-4 weeks). Twitch tension in 4-week-old SOL muscle decreased monotonically in cooling from 35 to 10 degrees C (cooling depression). This pattern of cooling depression was not clearly evident in younger SOL muscles. There was a marked hysteresis in the temperature dependence of twitch tension in the 1-week-old SOL muscles. Tetanic tension was depressed by low temperature in both EDL and SOL muscles at 1 week and at 4 weeks of age. Results show that the processes concerned with contractile activation are nearly fully developed in the fast muscle fibers at an early age (1 week), whereas they develop later in the slow muscle fibers.


RNA segment 9 exists as a duplex concatemer in an Australian strain of epizootic haemorrhagic disease virus (EHDV): Genetic analysis and evidence for the presence of concatemers as a normal feature of orbivirus replication.
This paper reports a concatemeric RNA in a strain of epizootic haemorrhagic disease virus (EHDV) serotype 5. Sequencing showed that the concatemeric RNA contains two identical full-length copies of genome segment 9, arranged in series, which has apparently replaced the monomeric form of the segment. In vitro translation demonstrated that the concatemeric RNA can act as a viable template for VP6 translation, but that no double-sized protein is produced. Studies were also performed to assess whether mutations might be easily introduced into the second copy (which might indicate some potential evolutionary significance of a concatemeric RNA segment), however multiple (n=40) passages generated no changes in the sequence of either the upstream or downstream segments. Further, we present results that demonstrate the presence of concatemers or partial gene duplications in multiple segments of different orbiviruses (in tissue culture and purified virus), suggesting their generation is likely to be a normal feature of orbivirus replication.


Quantitative risk assessment of human listeriosis from consumption of soft cheese made from raw milk.
Microbial hazards have been identified in soft cheese made from raw milk. Quantification of the resulting risk for public health was attempted within the frame of the Codex Alimentarius Commission, 1995 approach to quantitative risk assessment, using Monte Carlo simulation software. Quantitative data could only be found for Listeria monocytogenes. The complete process of cheese making was modeled, from milking to consumption. Using data published on the different sources of milk contamination (environment and mastitis) and bacterial growth, distributions were assumed for parameters of the model. Equations of Farber, J.M., Ross, W.H., Harwing, J. (1996) for general and at-risk populations were used to link the ingested dose of L. monocytogenes to the occurrence of listeriosis. The probability of milk contamination was estimated to be 67% with concentration ranging from 0 to 33 CFU ml-1. The percentage of cheese with a predicted concentration of L. monocytogenes greater than 100 CFU g-1 was low (1.4%). The probability of consuming a contaminated cheese serving was 65.3%. Individual annual cumulative risk of listeriosis, in a population each consuming 50 servings of 31 g, ranged from 1.97 x 10(-9) to 6.4 x 10(-8) in a low-risk sub-population and 1.04 10(-6) to 7.19 10(-5) in a high-risk sub-population. The average number of expected cases of listeriosis per year was 57 for a high-risk sub-population and one for a low-risk healthy sub-population. When the frequency of environmental milk contamination was reduced in the model and L. monocytogenes mastitis was eliminated, the expected incidence of listeriosis decreased substantially; the average number of expected cases was reduced by a factor of 5. Thus the usefulness of simulation to demonstrate the efficiency of various management options could be demonstrated, even if results should be interpreted with care (as many assumptions had to be made on data and their distributions.


Improved efficiency of focal point conformational analysis with truncated correlation consistent basis sets.
It has been suggested that the computational cost of correlated ab initio calculations could be reduced efficiently by using truncated basis sets on hydrogen atoms (Mintz et al., J Chem Phys 2004, 121, 5629). We now explore this proposal in the context of conformational analysis of small molecules, such as hydrogen peroxide, dimethyl ether, ethyl methyl ether, formic acid, methyl formate, and several small alcohols. It is found that truncated correlation consistent basis sets that lack certain higher angular momentum functions on hydrogen atoms offer accuracy similar to traditional Dunning's basis sets for conformational analysis. Combination of such basis sets with the basis set extrapolation technique to estimate Hartree-Fock and Møller-Plesset second order energies provides composite extrapolation model chemistries that are significantly more accurate and faster than analogous single point calculations with traditional correlation consistent basis sets. Root mean square errors of best composite extrapolation model chemistries on the used set of molecules are within 0.03 kcal/mol of traditional focal point conformational energies. The applicability of composite extrapolation methods is illustrated by performing conformational analysis of tert-butanol and cyclohexanol. For comparison, conformational energies calculated with popular molecular mechanics force fields are also given.


Removal of Cadmium from Contaminated Groundwater Using a Novel Silicon/Aluminum Nanomaterial: An Experimental Study.
Cadmium (Cd) is a harmful element to human health and biodiversity. The removal of Cd from groundwater is of great significance to maintain the environmental sustainability and biodiversity. In this work, a novel low-temperature roasting associated with alkali was applied to synthesize an eco-friendly adsorbent using coal fly ash. Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy were applied to analyze the physical and chemical characteristics of the adsorbent. The experiments show that a significant improvement in specific surface area and activity of adsorbent was observed in this study. The functional groups of Na-O and Fe-O were verified to be beneficial in the removal of Cd2+. The material capacity to adsorb Cd2+ was considerably improved, and the maximum uptake capacity was 61.8 mg g-1 for Cd2+ at 25 °C. Furthermore, pH and ionic strength play critical roles in the adsorption process. The Langmuir and pseudo-second-order models can appropriately describe the adsorption behavior, and the enhanced adsorption ability of Cd2+ by modified coal fly ash was attributed to ion-exchange, co-precipitation, and complexation. Higher sorption efficiency was maintained after two regeneration cycles. These results offer valuable insights to develop high-performance adsorbent for Cd2+ removal.


Grazing greatly reduces the temporal stability of soil cellulolytic fungal community in a steppe on the Tibetan Plateau.
Excessive livestock grazing degrades grasslands ecosystem stability and sustainability by reducing soil organic matter and plant productivity. However, the effects of grazing on soil cellulolytic fungi, an important indicator of the degradation process for soil organic matter, remain less well understood. Using T-RFLP and sequencing methods, we investigated the effects of grazing on the temporal changes of cellulolytic fungal abundance and community structure in dry steppe soils during the growing months from May to September, on the Tibetan Plateau using T-RFLP and sequencing methods. The results demonstrated that the abundance of soil cellulolytic fungi under grazing treatment changed significantly from month to month, and was positively correlated with dissolved organic carbon (DOC) and soil temperature, but negatively correlated with soil pH. Contrastingly, cellulolytic fungal abundance did not change within the fencing treatment (ungrazed conditions). Cellulolytic fungal community structure changed significantly in the growing months in grazed soils, but did not change in fenced soils. Grazing played a key role in determining the community structure of soil cellulolytic fungi by explaining 8.1% of the variation, while pH and DOC explained 4.1% and 4.0%, respectively. Phylogenetically, the cellulolytic fungi were primarily affiliated with Ascomycota (69.65% in relative abundance) and Basidiomycota (30.35%). Therefore, grazing substantially reduced the stability of soil cellulolytic fungal abundance and community structure, as compared with the fencing treatment. Our finding provides a new insight into the responses of organic matter-decomposing microbes for grassland managements.


Ulnar neuropathy and medial elbow pain in women's fastpitch softball pitchers: a report of 6 cases.
Elite-level women's fastpitch softball players place substantial biomechanical strains on the elbow that can result in medial elbow pain and ulnar neuropathic symptoms. There is scant literature reporting the expected outcomes of the treatment of these injuries. This study examined the results of treatment in a series of these patients. We identified 6 female softball pitchers (4 high school and 2 collegiate) with medial elbow pain and ulnar neuropathic symptoms. Trials of conservative care failed in all 6, and they underwent surgical treatment with subcutaneous ulnar nerve transposition. These patients were subsequently monitored postoperatively to determine outcome. All 6 female pitchers had early resolution of elbow pain and neuropathic symptoms after surgical treatment. Long-term follow-up demonstrated that 1 patient quit playing softball because of other injuries but no longer reported elbow pain or paresthesias. One player was able to return to pitching at the high school level but had recurrent forearm pain and neuritis 1 year later while playing a different sport and subsequently stopped playing competitive sports. Four patients continued to play at the collegiate level without further symptoms. Medial elbow pain in women's softball pitchers caused by ulnar neuropathy can be treated effectively with subcutaneous ulnar nerve transposition if nonsurgical options fail. Further study is necessary to examine the role of overuse, proper training techniques, and whether pitching limits may be necessary to avoid these injuries.


Nurses' attitudes toward computerised care plans in intensive care. Part 1.
The purpose of this quantitative study was to measure nurses' attitudes towards the use of computerised nursing care plans in intensive care. 41 nurses, working in an adult intensive care unit (ICU), completed the closed-structured questionnaire. The results of the study revealed that age, type of shift worked, length of time qualified and length of time employed on the unit influenced nurses' attitudes towards computerised care plans. It was concluded that prior to the introduction of a computerised care planning system, it is essential that nurses' attitudes are identified. In so doing, a system can be introduced that will match the capabilities of and acceptance by the nursing staff.


Effect of porcine relaxin and estradiol-17 beta on the incorporation of tritiated thymidine by fibroblasts isolated from guinea pig uteri.
Fibroblasts isolated from the uteri of 5 guinea pigs were cultured in vitro to determine the effect of relaxin and estradiol. Both relaxin and estradiol increased thymidine uptake by fibroblasts. Thymidine incorporation with 1.5 micrograms/ml relaxin and no estradiol was 107% of control while 600 pg/ml estradiol and no relaxin gave 112% of control. Thymidine incorporation in the presence of 1.5 micrograms/ml relaxin and 600 pg/ml estradiol was 128% of control. This indicated a significant interaction between relaxin and estradiol.


The use of electroconvulsive therapy (ECT) en bloc in Denmark: a nationwide register-based study.
Electroconvulsive therapy (ECT) en bloc is defined as ECT administered on 2-3 consecutive days. In Denmark, ECT en bloc is recommended for severe conditions such as catatonia, treatment-resistant mania/psychosis, or imminent risk of suicide. To our knowledge, there are no recent reports on the use of ECT en bloc in clinical practice. Here, we provide such a report. We characterized the use of ECT en bloc in the period from 2006-2019 based on data from Danish national registers. Furthermore, we compared mortality rates between patients receiving ECT en bloc and patients receiving standard regimen ECT (not en bloc). We identified 2173 patients who received a total of 2734 ECT en bloc treatment courses in Denmark in the period from 2006 to 2019 (6% of the total number of ECT treatment courses). The use of ECT en bloc was stable over the study period (range: 138-196 patients per year). The most common treatment indications were unipolar depression (41%), psychotic disorder (23%), and bipolar disorder (20%). The vast majority (90%) received ECT en bloc voluntarily. The 1-year mortality rate ratio for ECT en bloc compared to standard regimen ECT was 1.42 (95%CI: 1.03-1.95). The use of ECT en bloc in Denmark is stable both in terms of the number of patients treated and treatment indications. In keeping with ECT en bloc being used for severe conditions, those receiving this treatment have a higher mortality rate compared to those receiving standard ECT, warranting careful monitoring during follow-up.


Characterization of the human PAP1 gene and its homologue possible involvement in mouse embryonic development.
We have identified PAP1 gene, a novel member of the immunoglobulin superfamily (IGSF) from U251-pTet-p53 cell line, which carried a wild-type p53 transgene. The gene has been localised to chromosome 16p12-13. Alignment of the predicted protein sequence for Human, Pan troglodytes, Canis, Mus musculus and Gallus gallus revealed it was highly conserved. Its homologue, IGSF6, possible involves in mouse embryonic development. The presence of IGSF6 specific transcript was detected by Northern blot in the RNAs extracted from 11 to 14 day postconception. IGSF6 expression is different in mouse embryos of the different ages. In situ hybridization performed on mice embryos sections showed the differential presence of IGSF6 in developing lung and kidney. This structure and differential expression suggests a function involvement in embryonic development, perhaps involvement in cell proliferation.


Effect of contact lens wear on central corneal thickness measurements.
To compare central corneal thickness measurements as a function of contact lens wear in patients presenting for refractive surgery. Gimbel Eye Centre, Saskatoon, Saskatchewan, Canada. A retrospective study of charts yielded 634 eyes meeting the inclusion criterion. Pachymetry measurements of spectacle-wearing control eyes were compared to those of full-time soft contact lens wearers and rigid gas-permeable contact lens wearers. All measurements were taken with the DGH ultrasonic pachymeter by a single observer. Soft contact lens wearers had a mean reduction in corneal thickness measurements of 22 micrometers compared to the control population (P =.00001). Rigid gas-permeable lens wearers had a reduction of 24 micrometers compared to the control population (P =.00001). There was a clinically significant reduction in corneal thickness measurements associated with full-time contact lens wear.


(Washington University case conference): acute pancreatitis, hyperlipemia, and normal amylase.
This case focuses on the biochemical findings in acute pancreatitis and the role of the laboratory in the diagnosis and management of such patients. It also illustrates a major unappreciated problem in the use of amylase determinations in patients with acute pancreatitis: normal serum amylase activity in the presence of hyperlipemia.


Monitoring clusterin and fibrillar structures in aging and dementia.
Clusterin is involved in a variety of physiological processes, including proteostasis. Several clusterin polymorphisms were associated with an increased risk of developing Alzheimer's disease, the world-leading cause of dementia. Herein, the effect of a clusterin polymorphism, aging and dementia in the levels of clusterin in human plasma were analysed in a primary care-based cohort, and the association of this chaperone with fibrillar structures discussed. 64 individuals with dementia (CDR≥1) and 64 age- and sex-matched Controls from a Portuguese cohort were genotyped for CLU rs1136000 polymorphism, and the plasma levels of clusterin and fibrils were assessed. An increased prevalence of the CC genotype was observed for the dementia group, although no significant robustness was achieved. CLU rs11136000 SNP did not significantly change plasma clusterin levels in demented individuals. Instead, clusterin levels decreased with aging and even more in individuals with dementia. Importantly, plasma clusterin levels correlated with the presence of fibrillar structures in Control individuals, but not in those with dementia. This study reveals a significant decrease in plasma clusterin in demented individuals with aging, which related to altered clusterin-fibrils dynamics. Potentially, plasma clusterin and its association with fibrillar structures can be used to monitor dementia progression along aging.


Virulence of nosocomial isolates of Serratia marcescens for NMRI mice: correlation with O-antigens O6 and O14.
Nosocomially significant Serratia marcescens strains with O-antigens O6 or O14, or the serogroup complex O6/O14, proved somewhat more virulent for juvenile NMRI mice following intraperitoneal injection, than strains carrying other O-antigens. There was no correlation between virulence and extent of casein proteolytic activity or resistance against fresh normal human serum.


Anatomic structure-based deformable image registration of brachytherapy implants in the treatment of locally advanced cervix cancer.
To examine the impact of anatomic structure-based image sets in deformable image registration (DIR) for cervical cancer patients. CT examinations of 7 patients previously treated for locally advanced cervical cancer with external beam radiation therapy and from three to five fractions of high-dose-rate brachytherapy (HDR-BT) were used. Structure-based image sets were created from "free" structures already made for planning purposes, with each structure of interest assigned a unique, homogeneous Hounsfield number. Subsequent HDR fractions were registered to the pretreatment external beam radiation therapy and/or the first HDR fraction using commercially available software by rigid alignment (RIG) followed by DIR. Comparison methods included quantification of external contour displacement between source and target images and calculation of mean voxel displacement values. Registration results for structure-based image sets were then compared and contrasted to intensity-based registrations of the original grayscale images. Utilization of anatomic structure-based image sets resulted in better initial rigid matching (A-RIG) with more importance on applicator positioning and soft tissue structures. Subsequent DIR of anatomic structure-based images allowed for intermodality registrations, whereas all intermodality registrations using original CT images failed to produce anatomically feasible results. We have investigated the use of structure-based CT image sets for image registrations and have produced anatomically favorable registrations with excellent matching of external contours as compared to registrations of original grayscale images. Commercial software registrations using treatment-planning structures required no manual tweaking on a per-patient basis, suggesting results are reproducible and broadly applicable.


CTLA4-Ig treatment induces M1-M2 shift in cultured monocyte-derived macrophages from healthy subjects and rheumatoid arthritis patients.
In rheumatoid arthritis (RA), macrophages play an important role in modulating the immunoinflammatory response through their polarisation into "classically" (M1) or "alternatively activated" (M2) phenotypes. In RA, CTLA4-Ig (abatacept) reduces the inflammatory activity of macrophages by interacting with the costimulatory molecule CD86. The study aimed to investigate the efficacy of CTLA4-Ig treatment to induce an M2 phenotype both in M1-polarised monocyte-derived macrophages (MDMs) obtained from healthy subjects (HS) and in cultured MDMs obtained from active RA patients. Cultured MDMs were obtained from peripheral blood mononuclear cells of 7 active RA patients and from 10 HS after stimulation with phorbol myristate acetate (5 ng/mL) for 24 h. HS-MDMs were then stimulated with lipopolysaccharide (LPS, 1 mg/mL) for 4 h to induce M1-MDMs. M1-MDMs and RA-MDMs were treated with CTLA4-Ig (100 μM and 500 μM) for 3, 12, 24, and 48 h. The gene expression of CD80, CD86, and TLR4 (M1 markers); CD163, CD204, and CD206 (surface M2 markers); and MerTK (functional M2 marker) was evaluated by qRT-PCR. The protein synthesis of surface M2 markers was investigated by Western blotting. The statistical analysis was performed by the Wilcoxon t-test. In LPS-induced HS-M1-MDMs, CTLA4-Ig 100 μM and 500 μM significantly downregulated the gene expression of M1 markers (3 h p<0.01 for all molecules; 12 h p<0.05 for TLR4 and CD86) and significantly upregulated that of M2 markers, primarily after 12 h of treatment (CD163: p < 0.01 and p < 0.05; CD206: p < 0.05 and p < 0.01; CD204: p < 0.05 by 100 mg/mL). Moreover, in these cells, CTLA4-Ig 500 μM increased the protein synthesis of surface M2 markers (p < 0.05). Similarly, in RA-MDMs, the CTLA4-Ig treatment significantly downregulated the gene expression of M1 markers at both concentrations primarily after 12 h (p < 0.05). Furthermore, both concentrations of CTLA4-Ig significantly upregulated the gene expression of CD206 (after 3 h of treatment; p < 0.05), CD163, and MerTK (after 12 h of treatment, p < 0.05), whereas CD204 gene expression was significantly upregulated by the high concentration of CTLA4-Ig (p < 0.05). The protein synthesis of all surface markers was increased primarily by CTLA4-Ig 500 μM, significantly for CD204 and CD206 after 24 h of treatment (p < 0.05). CTLA4-Ig treatment seems to induce the in vitro shift from M1 to M2 macrophages, of both HS-M1-MDMs and RA-MDMs, as observed by the significant downregulation exerted on selected M1 markers and the upregulation of selected M2 markers suggesting an additional mechanism for its modulation of the RA inflammatory process.


Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing.
Bats are the only mammals capable of true, powered flight, which drives an extremely high metabolic rate. The "Free Radical Theory of Ageing" (FTRA) posits that a high metabolic rate causes mitochondrial heteroplasmy and the progressive ageing phenotype. Contrary to this, bats are the longest-lived order of mammals given their small size and high metabolic rate. To investigate if bats exhibit increased mitochondrial heteroplasmy with age, we performed targeted, deep sequencing of mitogenomes and measured point heteroplasmy in wild, long lived Myotis myotis. Blood was sampled from 195 individuals, aged between <1 and at 6+ years old, and whole mitochondria deep-sequenced, with a subset sampled over multiple years. The majority of heteroplasmies were at a low frequency and were transitions. Oxidative mutations were present in only a small number of individuals, suggesting local oxidative stress events. Cohort data showed no significant increase in heteroplasmy with age, while longitudinal data from recaptured individuals showed heteroplasmy is dynamic, and does not increase uniformly over time. We show that bats do not suffer from the predicted, inevitable increase in heteroplasmy as posited by the FRTA, instead heteroplasmy was found to be dynamic, questioning its presumed role as a primary driver of ageing.


Anterolateral thigh flap: an ideal soft tissue flap.
Microsurgical reconstruction has evolved to a stage where a nearly 100% success rate has been achieved. Therefore, refinement of the functional and aesthetic result, as well as a decrease in donor site morbidity have become the major concerns. The anterolateral thigh flap meets these requirements; its wide application to various fields is based on the following charateristics. Its reliable vascularity. Its vascular pedicle is long and large, at least 8 cm (can be 20 cm). Flap territory is large and easy to design. The pedicle can be at the periphery of the flap. Its length can be 40 cm and its width can be half of the thigh, with the maximal dimension as large as 40 x 20 cm (800 cm2). Primary trimming of the flap to 3 mm to 5 mm in thickness does not compromise its vascularity. The subcutaneous fat can be included to facilitate gliding of the underlying tendons. To harvest chimeric flaps, the following components can be included: muscles, fascia and bone (an osseous flap can be joined to the flap with microvascular anastomoses). A two-team approach is possible, because the recipient site is usually far away from the donor site. Usually it does not require that the patient change position. It can be closed primarily without skin graft if its width is less than 8 cm. The donor site is easily covered with clothes, and the motor function is least affected. Care should be taken in flap dissection, inset, and postoperative care, as well as strategies for re-exploration.


Experimental demonstration of robustness and accuracy of a DLI-based OSNR monitor under changes in the transmitter and link for different modulation formats and baud rates.
We experimentally studied the performance of a delay-line interferometer-based optical signal-to-noise ratio (OSNR) monitor that is pre-calibrated in optimal conditions for 25-Gbaud pol-muxed quadrature-amplitude-modulation (QAM) signals, when unpredicted changes outside the monitor occurred either in the transmitter or the link.


DC plasma emission spectroscopic analysis of pancreatic calculi.
Previous studies on pancreatic calculi (PC) from alcoholic pancreatitis and our recent studies on calculi from tropical pancreatitis have shown them to consist mainly of CaCO3 with minute quantities of Mg. However, no attempt was made to look for other elements in PC. This is because of the difficulty in obtaining adequate samples of PC, coupled with the technical limitations in analyzing multi-elements from small samples. In this study, our aim was to analyze the major, minor and trace elements of PC from different parts of the world. DC plasma emission spectroscopy, a modern method that permits determination of multiple elements from small samples, was used in elemental analysis. We identified 17 elements in addition to calcium. Selenium was looked for but was absent. It was interesting that the elemental composition of PC in four patients from different geographical areas with divergent etiological factors remained the same. Absence of Se is of interest, as Se deficiency is associated with pancreatic fibrosis in experimental animals and it is often noted in chronic alcoholics and the malnourished. This preliminary study emphasizes the need for analysis of the elemental composition of pancreatic juice in normals and in conditions predisposing to chronic pancreatitis, to understand lithogenesis and possibly also the etiology of, at least, some types of pancreatitis.


Facial growth after treatment of unilateral temporomandibular joint ankylosis in childhood without growth centre transplantation. A serial cephalomorphometric study.
Our aim was to study the influence of early surgical treatment of temporomandibular joint ankylosis on further facial growth and development. At the Department of Maxillo-Facial Surgery, Zurich, 11 children with a unilateral TMJ-ankylosis met the criteria of a maximal preoperative interincisal mouth opening of 15 mm, of a minimal long-term postoperative interincisal mouth opening of 30 mm, and of excellent documentation. 30 anatomical landmarks were defined on the copies of the follow-up cephalograms using the structure-superimposition technique. The points were perforated and digitized. Analysis and graphic-plotting were followed by computer. The hypothesis that mandibular growth continues once the ankylosis was successfully treated (without transplantation of a growth centre) and mandibular function definitely restored, was confirmed. The treatment does normalize the growth rate, but it seems that abnormal growth patterns cannot be influenced by it. As a consequence, the surgical release of the ankylosis should be performed as early as possible.


Clinical Characteristics and Outcomes of Patients with Aneurysmal Subarachnoid Hemorrhage: A Prospective Multicenter Study in a Middle-Income Country.
Aneurysmal subarachnoid hemorrhage (SAH) is associated with high mortality and long-term functional impairment. Data on clinical management and functional outcomes from developing countries are scarce. We aimed to define patient profiles and clinical practices and evaluate long-term outcomes after SAH in a middle-income country. This was a prospective study including consecutive adult patients admitted with SAH to two reference centers in Brazil from January 2016 to February 2020. The primary outcome was functional status at 6 months using the modified Rankin Scale. Mixed multivariable analysis was performed to determine the relationship between clinical variables and functional outcomes. From 471patients analyzed, the median time from symptom onset to arrival at a study center was 4 days (interquartile range 0-9). Median age was 55 years (interquartile range 46-62) and 353 (75%) patients were women. A total of 426 patients (90%) were transferred from nonspecialized general hospitals, initial computed tomography revealed thick hemorrhage in 73% of patients (modified Fisher score of 3 or 4), and 136 (29%) had poor clinical grade (World Federation of Neurological Surgeons score of 4 or 5). A total of 312 (66%) patients underwent surgical clipping, and 119 (25%) underwent endovascular coiling. Only 34 patients (7%) underwent withdrawal or withholding of life-sustaining therapy during their hospital stay, and in-hospital mortality was 24%. A total of 187 (40%) patients had an unfavorable long-term functional outcome (modified Rankin Scale score of 4 to 6). Factors associated with unfavorable outcome were age (adjusted odds ratio [OR] 1.05, 95% confidence interval [CI] 1.03-1.08), hypertension (adjusted OR 1.81, 95% CI 1.04-3.16), poor clinical grade (adjusted OR 4.92, 95% CI 2.85-8.48), external ventricular drain (adjusted OR 3.8, 95% CI 2.31-6.24), postoperative deterioration (adjusted OR 2.33, 95% CI 1.32-4.13), cerebral infarction (adjusted OR 3.16, 95% CI 1.81-5.52), rebleeding (adjusted OR 2.95, 95% CI 1.13-7.69), and sepsis (adjusted OR 2.68, 95% CI 1.42-5.05). Our study demonstrated that SAH management in a middle-income country diverges significantly from published cohorts and current guidelines, despite comparable clinical profiles on presentation and admission to high-volume referral centers. Earlier aneurysm occlusion and increased use of endovascular therapy could potentially reduce modifiable in-hospital complications and improve functional outcomes in Brazil.


Behavioral and emotional factors: comparisons of anovulatory infertile women with fertile and other infertile women.
This controlled study compared behavioral and emotional factors in a group of anovulatory infertile women requesting treatment to achieve pregnancy. The sample comprised 49 women with secondary amenorrhea or oligomenorrhea in the treatment group, 141 women in the fertile comparison group, and 104 women with diagnoses other than anovulation in an infertile comparison group. Scores on the Hopkins Symptom Checklist (HSCL-90), the Eysenck Personality Inventory, the Langner Screening Scale, a Mood Analog Scale, and the Minnesota Multiphasic Personality Inventory (MMPI) were in the normal range and did not differ significantly between the groups. On other measures, the treatment group rated itself significantly less potent than to partner, mother, or father and reported more inhibited sexual attitudes than the comparison groups. Conclusions were that neurotic personality structure or psychopathology were not significantly greater in the treatment group than in the comparison groups. Whether the lower self-esteem and inhibited sexual attitudes of the treatment group resulted from or preceded infertility could not be determined.


Characterisation of serum transthyretin by electrospray ionisation-ion mobility mass spectrometry: Application to familial amyloidotic polyneuropathy type I (FAP-I).
Transthyretin (TTR) is a homotetrameric protein which is known to misfold and aggregate causing different types of amyloidosis, such as familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR (Met30)) that can be easily detected analysing the monomeric forms of the mutant protein. Meanwhile, the mechanism of protein aggregation onset, which could be triggered by structural changes on the native tetrameric protein complex, remains uncertain. We developed and described herein a new sample pretreatment based on immunoprecipitation (IP) to purify TTR from serum under non-denaturing conditions. Later, a nano-electrospray ionization-ion mobility mass spectrometry (nano-ESI-IM-MS or IM-MS) method was optimised to analyse the protein complexes in serum samples from healthy controls and FAP-I patients. IM-MS allowed separation and characterisation of tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time, which is related to ion size and charge. The tetramer-to-dimer abundance ratio was differential between healthy controls and FAP-I patients (asymptomatic, symptomatic and an iatrogenic patient originally without the mutation who received a liver transplant from an FAP-I patient), and was also indicative of the effectiveness of liver transplantation as a treatment for FAP-I.


Use of genetic models of idiopathic hypogonadotrophic hypogonadism in mice and men to understand the mechanisms of disease.
Mutations in the genes encoding the neuropeptides kisspeptin and neurokinin B, as well as their receptors, are associated with gonadotrophin-releasing hormone (GnRH) deficiency and a failure to initiate and/or progress through puberty. Although the total number of patients studied to date is small, mutations in the kisspeptin pathway appear to result in lifelong GnRH deficiency. Mice with mutations in kisspeptin and the kisspeptin receptor, Kiss1(-/-) and Kiss1r(-/-), respectively, appear to be phenocopies of the human with abnormal sexual maturation and infertility. In contrast, mutations in the neurokinin B pathway lead to a more variable adult reproductive phenotype, with a subset of hypogonadotrophic individuals demonstrating paradoxical recovery of reproductive function later in life. While 'reversal' remains poorly understood, the ability to recover reproductive function indicates that neurokinin B may play different roles in the initiation of sexual maturation compared with the maintenance of adult reproductive function. Mice with mutations in the gene encoding the neurokinin B receptor, Tacr3, have abnormal oestrous cycles and subfertility but, similar to their human counterparts, appear less severely affected than mice with kisspeptin deficiency. Further investigations into the interaction between the kisspeptin and neurokinin B pathways will reveal key insights into how GnRH neuronal modulation occurs at puberty and throughout reproductive life.


Inhibition of PACAP activity by a receptor antagonist results in changes in cell cycle and apoptotic proteins in chick neuroblasts.
We showed previously that early chick neuroblasts stop proliferating and undergo apoptosis when deprived of endogenous pituitary adenylate cyclase-activating polypeptide (PACAP). To identify proteins involved in these processes, we blocked the primary PACAP receptor and determined protein changes using isotope-coded affinity tag (ICAT) analysis. Cell cycle exit was characterized by a decrease in proteins regulating ribosome biogenesis and protein translation. Apoptosis was linked directly to a tumor suppressor that increases apoptosome activity and indirectly to reduced mitochondrial activity. ICAT analysis, combined with flow cytometric analysis, suggested that some cells were differentiating, rather than undergoing apoptosis. In summary, we have confirmed that withdrawal of PACAP from early chick neuroblasts causes cell cycle exit and apoptosis, and identified proteins involved in proliferation, exit, apoptosis, and possibly differentiation.


Olfactory bulb maturation in Acomys cahirinus: is neural growth similar in precocial and altricial murids?
Olfactory bulb maturation was assessed in the precocial murid Acomys cahirinus by quantifying developmental changes in laminar volume and glomerular and mitral cell size. At the time of birth (38 days postconception), the Acomys bulb is in a developmental state similar to that of altricial murids of the same gestational age. Rapid growth occurs in Acomys during the first 10 postnatal days with more gradual changes occurring thereafter. Altricial murids also exhibit accelerated bulb development in early postnatal period, but growth rates have declined by 38 days after conception. These results suggest that maturation is not similar in precocial and altricial murids and that rapid postnatal development is a necessary feature of murid brain development.


Fear of devaluation: understanding the experience of intersexed women with androgen insensitivity syndrome.
We aim to provide an understanding of the psychological sequela of androgen insensitivity syndrome (AIS) in phenotypic females in order to begin to inform psychosocial health care services. Eight adult women with AIS were recruited through the Androgen Insensitivity Syndrome Support Group-United Kingdom (AISSG-UK). Data was collected via two semi-structured interviews with each woman. Transcripts were analysed using grounded theory and a conceptual model was developed which suggests a way of understanding the AIS distress experienced by the participants. The pivotal concept is a woman's fear of devaluation. This is connected to her level of adaptation and perception of having a compromised womanhood. These, in turn, are related to her medical management and involvement with others via a support group and in talking about AIS. Participants showed a clear preference for open communication about their condition throughout the process of medical management. We recommend sensitive, pacing of information to allow young women and their families to make informed decisions about treatment and a realistic adaptation to life with AIS.


Impaired Direction Selectivity in the Nucleus of the Optic Tract of Albino Mice.
Human albinos have a low visual acuity. This is partially due to the presence of spontaneous erroneous eye movements called pendular nystagmus. This nystagmus is present in other albino vertebrates and has been hypothesized to be caused by aberrant wiring of retinal ganglion axons to the nucleus of the optic tract (NOT), a part of the accessory optic system involved in the optokinetic response to visual motion. The NOT in pigmented rodents is preferentially responsive to ipsiversive motion (i.e., motion in the contralateral visual field in the temporonasal direction). We compared the response to visual motion in the NOT of albino and pigmented mice to understand if motion coding and preference are impaired in the NOT of albino mice. We recorded neuronal spiking activity with Neuropixels probes in the visual cortex and NOT in C57BL/6JRj mice (pigmented) and DBA/1JRj mice with oculocutaneous albinism (albino). We found that in pigmented mice, NOT is retinotopically organized, and neurons are direction tuned, whereas in albino mice, neuronal tuning is severely impaired. Neurons in the NOT of albino mice do not have a preference for ipsiversive movement. In contrast, neuronal tuning in visual cortex was preserved in albino mice and did not differ significantly from the tuning in pigmented mice. We propose that excessive interhemispheric crossing of retinal projections in albinos may cause the disrupted left/right direction encoding we found in NOT. This, in turn, impairs the normal horizontal optokinetic reflex and leads to pendular albino nystagmus.


A distinctive phospholipid-stimulated protein kinase of normal and malignant murine hemopoietic cells.
This report describes the activity of a novel phospholipid-stimulated protein kinase from mouse DA-1 leukemic cells. The kinase was activated by phosphatidylglycerol or phosphatidylinositol. Phospholipid-stimulated protein phosphorylation occurred in the presence of Mn2+ or Mg2+; kinase activity was greater with Mg2+ than with Mn2+ from 4 to 10 mM, although at lower divalent cation concentrations Mn2+ was preferred. A Mr 75,500-77,000 endogenous protein doublet and a Mr 42,000 endogenous protein were phosphorylated in whole cell extracts under these conditions. These substrates contrasted with those identified under protein kinase C conditions. Of the exogenous proteins tested, phospholipid-stimulated phosphorylation was highest with histone H2B followed by other histones. In addition to DA-1 cells, phospholipid-stimulated protein kinase also was detected in high levels in normal mouse spleen, marrow, and kidney but not detectable in brain extracts. The phosphatidylglycerol-stimulated kinase was separated from protein kinase C by anion-exchange chromatography on DEAE-Sephacel, from which it eluted at 0.2 to 0.3 M NaCl. Physiological dissociation of the two types of kinase activity was demonstrated by down regulation of protein kinase C over 24 h by phorbol 12-myristate 13-acetic acid. Under these conditions phosphatidylglycerol kinase activity and subcellular distribution were unaffected. Thus, phosphatidylglycerol-stimulated kinase was detectable in both normal and malignant cells and contrasted with, and was separable from, protein kinase C in numerous respects. Phosphatidylglycerol-stimulated protein kinase basic biochemistry and physiological roles are topics worthy of further investigation.


Successful international clones of blaCTX-M-15-producing Klebsiella pneumoniae with coexpression of plasmid-mediated quinolone resistance (PMQR) determinants in Tehran hospitals.
The dissemination of plasmid-mediated multidrug resistance in Enterobacteriaceae is a major public health concern. We investigated the prevalence of plasmid-mediated quinolone resistance (PMQR), 16S rRNA methylases, CTX-M, and acquired AmpC enzymes in ESBL-producing Klebsiella pneumoniae (n=40) from Tehran hospitals. Plasmid replicon typing, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were carried out for typing. CTX-M group 1 (confirmed as bla(CTX-M-15) in selected isolates) was found in 35/40 isolates. Thirty-two isolates hosted PMQR genes. Twenty isolates featured aac(6')-Ib-CR only; 9 isolates had aac(6')-Ib-CR and qnrB; 2 isolates had aac(6')-Ib-CR and qnrS; and 1 isolate had aac(6')-Ib-CR, qnrS, and qepA. The 16S rRNA methylase RmtB was found in 1 isolate; and acquired AmpC enzymes, in 6 isolates. PFGE detected 7 pulsotypes, the largest corresponded to sequence type 16. The successful clone ST101 was also found. The emergence of successful clones of K. pneumoniae in Tehran hospitals is concerning.


Efficient transfer of HSV-1 amplicon vectors into embryonic stem cells and their derivatives.
The derivation of specialized differentiated cells from embryonic stem (ES) cells is now a major focus for future therapies involving cell and organ replacement in humans. To obtain populations of differentiated cells for transplantation into the human body, highly optimized protocols are needed that allow direction of the development of ES cells and their derivatives. These protocols mostly include the use of a combination of growth factors that control the differentiation of ES cells into highly specialized cells found in adult organs. The introduction of different growth factors into ES cells and their derivatives via viral gene transfer may greatly facilitate the optimization of these protocols. In this chapter, we describe a method based on herpes simplex virus type 1, which allows efficient gene transfer during several steps of a protocol, directed to obtain neural progenitors from ES cells. This protocol therefore may allow the study of potential factors influencing the cell fate or differentiation of ES cells and their derivatives.


Non-canonical role of UCKL1 on ferroptosis defence in colorectal cancer.
Pyrimidine nucleotides fuel the growth of colorectal cancer (CRC), making their associated proteins potential targets for cancer intervention. Uridine-Cytidine Kinase Like-1(UCKL1) is an enzyme involved in the pyrimidine salvage pathway. It is highly expressed in multiple cancers. But the function and underlying mechanism of UCKL1 in CRC are yet to study. Large-scale genomic analysis was performed to search for potential CRC players related to pyrimidine metabolism. The function of UCKL1 in CRC were examined by RNA interference coupled with in vitro and in vivo assays. GSH/GSSG assay, NADP+ assay, ROS, and Lipid peroxidation assays were performed to check the function of UCKL1 in ferroptosis. Metabolomics analyses, RNA sequencing, western blotting, and rescue assays were done to reveal the underlying mechanisms of UCKL1. Xenograft mouse model was used to examine the therapeutic potential of UCKL1 as a target in combination with other ferroptosis inducers. UCKL1 was identified to repress ferroptosis in CRC cells. It was highly expressed in CRC. It regulated CRC cells proliferation and migration. Downregulation of UCKL1 led to enhanced tumour lipid peroxidation. Intriguingly, UCKL1 reduction-mediated ferroptosis was not related to its role in catalyzing uridine monophosphate (UMP) and cytidine monophosphate (CMP) synthesis. Instead, UCKL1 stabilized Nrf2, which in turn promoted the expression of SLC7A11, a classical repressor of ferroptosis. Moreover, downregulation of UCKL1 sensitized CRC cells to GPX4 inhibitors in vitro and in vivo. Our study demonstrates that UCKL1 plays a non-canonical role in repressing ferroptosis through a UCKL1-Nrf2-SLC7A11 axis in CRC cells. Combinatorial strategy in targeting ferroptosis by depletion of UCKL1 and application of GPX4 inhibitors may serve as a new effective method for CRC treatment. This study was supported in part by fund from National Natural Science Foundation of China (Grant No. 31970674 to PY), by the Basic and Applied Basic Research Program of Guangdong Province (Grant No. 2023A1515030245 to KL), by the program of Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), and by National Key Clinical Discipline.


Spatial and temporal coordination of mitosis by Ran GTPase.
The small nuclear GTPase Ran controls the directionality of macromolecular transport between the nucleus and the cytoplasm. Ran also has important roles during mitosis, when the nucleus is dramatically reorganized to allow chromosome segregation. Ran directs the assembly of the mitotic spindle, nuclear-envelope dynamics and the timing of cell-cycle transitions. The mechanisms that underlie these functions provide insights into the spatial and temporal coordination of the changes that occur in intracellular organization during the cell-division cycle.


Rapid mechanical and thermal changes in the garfish olfactory nerve associated with a propagated impulse.
Mechanical and thermal changes associated with a propagated nerve impulse were determined using the garfish olfactory nerve. Production of an action potential was found to be accompanied by swelling of the nerve fibers. The swelling starts nearly at the onset of the action potential and reaches its peak at the peak of the action potential. There is a decrease in the length of the fibers while an impulse travels along the fibers. The time-course of the initial heat was determined at room temperature using heat-sensors with a response-time of 2-3 ms. Positive heat production was found to start and reach its peak nearly simultaneously with the action potential. The rise in temperature of the nerve was shown to be 23 (+/- 4) mu degrees C. In the range between 10 degrees and 20 degrees C, the temperature coefficient of heat production is negative, primarily due to prolongation of the period of positive heat production at low temperatures. The amount of heat absorbed during the negative phase varies widely between 45 and 85% of the heat evolved during the positive phase. It is suggested that both mechanical and thermal changes in the nerve fibers are associated with the release and re-binding of Ca-ions in the nerve associated with action potential production.


Analysis of chromosome abnormalities by comparative genomic hybridization in malignant peripheral primitive neuroectodermal tumor of the ovary.
Malignant primitive neuroectodermal tumor (PNET) originating from the ovary rather than from the central nervous system is extremely rare. The aim of this study is to demonstrate the chromosomal abnormalities in a case of peripheral primitive neuroectodermal tumor (PPNET) arising from the ovary of a girl. The 13-year-old girl underwent exploratory laparotomy because of a huge pelvic tumor in lower abdomen and pelvis. She underwent removal of ovaries, tubes, omentum, peritoneal nodules, and portion of urinary bladder. Tumor specimens were sent for pathology, short-term tissue culture, and for storage in deep freezer for laboratory studies. Immunohistochemical stainings of the tumor with antibodies against O-13 (MIC/CD99), NSE, GFAP, S-100, cytokeratin AE1/AE3, desmin, NF, and AFP were performed. Short-term cell culture of fresh tumor was done for analysis of chromosomal aberrations by the technique of comparative genomic hybridization (CGH). Names of specific genes corresponding to the losses or gains on gene map loci were identified from OMIM (Online Mendelian Inheritance in Man) of the NCBI website,. The overexpressions of N-myc and EGFR as well as underexpressions of Rb and ARHI were detected by RT-PCR analysis. The patient expired 17 months later despite of chemotherapy, repeated surgery, and radiation therapy. The histopathology of the specimens revealed malignant neuroectodermal tumor, involving ovaries, tubes, bladder, omentum, and peritoneum. Immunohistochemical stainings of PPNET of the ovary showed positive reaction for O-13 (MIC2/CD99) and NSE, but negative for GFAP, S-100, cytokeratin AE1/AE3, desmin, NF, and AFP. Analysis of CGH revealed multiple chromosomal abnormalities including losses of chromosomes in 1p, 1q, 4q, 6p, 6q, 7q, 8q, 13q, and 19q; as well as gains of chromosomes in 1q, 2p, 7p, 9q, 18q, and Xq. Losses of 13q14.1-q14.2, 1p31, and 4q34-q35 indicated that Rb gene, ARHI, and FAT were deleted. Gains of 2p24.1, 1q23, and 7p12.3-p12.1 demonstrated that N-myc oncogene, FASL, GITRL, and EGFR were amplified. RT-PCR analysis showed that N-myc and EGFR were overexpressed, while Rb and ARHI were underexpressed. This report is the first to show multiple chromosomal aberrations in PPENT arising from the ovary. The deletions of Rb, ARHI, and FAT, as well as amplification of N-myc, FASL, GITRL, and EGFR, may be the crucial factors for tumorigenesis and the aggressive biological behavior of PPNET.


Radiation-induced lung toxicity - cellular and molecular mechanisms of pathogenesis, management, and literature review.
Lung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on radiotherapy as a major part of multi-modality care, and treatment-related toxicities, such as radiation-induced pneumonitis and/or lung fibrosis, are important dose limiting factors with direct impact on patient outcomes and quality of life. In this review, we summarize the current understanding of radiation-induced pneumonitis and pulmonary fibrosis, present predictive factors as well as recent diagnostic and therapeutic advances. Novel candidates for molecularly targeted approaches to prevent and/or treat radiation-induced pneumonitis and pulmonary fibrosis are discussed.


Poly(ADP-ribose) polymerase, a potential target for drugs: Cellular regulatory role of the polymer and the polymerase protein mediated by catalytic and macromolecular colligative actions (Review).
The cellular coenzymatic role of NAD, being a pleiotropic cofactor for diverse cellular reactions, is extended to poly(ADP-ribose) and to the highly abundant nuclear protein, poly(ADP-ribose) polymerase, with special focus on the pharmacological action of ligands on the latter. The polymer is defined to possess a helical configuration. From direct analyses of the polymer under physiological conditions, it is concluded that the polymerase is dormant in normal tissues, but is activated under certain pathological conditions: malignancy, retroviral integrate containing cells, and in a variety of inflammatory states. The interaction of poly(ADP-ribose) polymerase ligands with the DNA component of the active poly (ADP-ribose) polymerase - DNA complex is shown. A major cellular function of the poly(ADP-ribose) polymerase protein is its binding capacity to a large number of nuclear proteins and DNA sites, an effect which is induced by drugs that inhibit the polymerase activity. The malignancy-reverting effect of poly(ADP-ribose) polymerase ligand drugs is illustrated in chemically and oncovirally transformed cancer cells. The poly(ADP-ribose) polymerase ligand-induced cessation of HIV replication is analyzed. Peroxynitrite-induced DNA damage-initiated pathological responses are shown to be inhibited by a specific poly(ADP-ribose) polymerase ligand. The irreversibly acting C-NO drugs oxidize asymmetric zinc fingers [poly(ADP-ribose) polymerase, HIV gag-precursor protein] and act as anti-cancer and anti-HIV agents, an effect that is regulated by cellular concentration of GSH.


A generic scenario analysis of end-of-life plastic management: Chemical additives.
Plastic growing demand and the increment in global plastics production have raised the number of spent plastics, out of which over 90% are either landfilled or incinerated. Both methods for handling spent plastics are susceptible to releasing toxic substances, damaging air, water, soil, organisms, and public health. Improvements to the existing infrastructure for plastics management are needed to limit chemical additive release and exposure resulting from the end-of-life (EoL) stage. This article analyzes the current plastic waste management infrastructure and identifies chemical additive releases through a material flow analysis. Additionally, we performed a facility-level generic scenario analysis of the current U.S. EoL stage of plastic additives to track and estimate their potential migration, releases, and occupational exposure. Potential scenarios were analyzed through sensitivity analysis to examine the merit of increasing recycling rates, using chemical recycling, and implementing additive extraction post-recycling. Our analyses identified that the current state of plastic EoL management possesses high mass flow intensity toward incineration and landfilling. Although maximizing the plastic recycling rate is a reasonably straightforward goal for enhancing material circularity, the conventional mechanical recycling method requires improvement because major chemical additive release and contamination routes act as obstacles to achieving high-quality plastics for future reuse and should be mitigated through chemical recycling and additive extraction. The potential hazards and risks identified in this research create an opportunity to design a safer closed-loop plastic recycling infrastructure to handle additives strategically and support sustainable materials management efforts to transform the US plastic economy from linear to circular.


Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo.
CD47 is a ubiquitously expressed transmembrane glycoprotein that regulates inflammatory responses and tissue repair. Here, we show that normal mice treated with anti-CD47 antibodies, and Cd47-null mice have impaired intestinal mucosal wound healing. Furthermore, intestinal epithelial cell (IEC)-specific loss of CD47 does not induce spontaneous immune-mediated intestinal barrier disruption but results in defective mucosal repair after biopsy-induced colonic wounding or Dextran Sulfate Sodium (DSS)-induced mucosal damage. In vitro analyses using primary cultures of CD47-deficient murine colonic IEC or human colonoid-derived IEC treated with CD47-blocking antibodies demonstrate impaired epithelial cell migration in wound healing assays. Defective wound repair after CD47 loss is linked to decreased epithelial β1 integrin and focal adhesion signaling, as well as reduced thrombospondin-1 and TGF-β1. These results demonstrate a critical role for IEC-expressed CD47 in regulating mucosal repair and raise important considerations for possible alterations in wound healing secondary to therapeutic targeting of CD47.


Anti-idiotypes against an anti-haloperidol antibody bind to sigma receptors.
Anti-idiotypic monoclonal antibodies that interact with the binding site of sigma receptors were generated. First, BALB/c mice were immunized with a haloperidol-bovine serum albumin conjugate, and monoclonal anti-haloperidol antibodies that recognize the piperidinyl moiety of haloperidol molecule were obtained. Second, for generation of anti-idiotypic antibodies, BALB/c mice were immunized with the anti-haloperidol monoclonal antibodies coupled to keyhole limpet hemocyanin. Anti-idiotypic antisera and three hybridomas secreting anti-idiotypic monoclonal antibodies were obtained. All of them were shown to inhibit [3H]haloperidol binding to the anti-haloperidol antibodies. The anti-idiotypes were potent in displacing the binding of [3H]haloperidol to rat brain sigma receptors. Furthermore, they significantly immunoprecipitated the sigma receptors from a detergent-solubilized preparation. These findings demonstrate the generation of anti-idiotypic monoclonal antibodies specifically interacting with membrane-bound and solubilized sigma receptors.


Kinetics and Thermodynamics of Reactions Involving Criegee Intermediates: An Assessment of Density Functional Theory and Ab Initio Methods Through Comparison with CCSDT(Q)/CBS Data.
Reactions involving Criegee intermediates (CIs, R1 R2 COO) are important in atmospheric ozonolysis models. In recent years, density functional theory (DFT) and CCSD(T)-based ab initio methods are increasingly being used for modeling reaction profiles involving CIs. We obtain highly accurate CCSDT(Q)/CBS reaction energies and barrier heights for ring-closing reactions involving atmospherically important CIs (R1 /R2 = H, Me, OH, OMe, F, CN, cyclopropene, ethylene, acetaldehyde, and acrolein). We use this benchmark data to evaluate the performance of DFT, double-hybrid DFT (DHDFT), and ab initio methods for the kinetics and thermodynamics of these reactions. We find that reaction energies are more challenging for approximate theoretical procedures than barrier heights. Overall, taking both reaction energies and barrier heights into account, only one of the 58 considered DFT methods (the meta-GGA MN12-L) attains near chemical accuracy, with root-mean-square deviations (RMSDs) of 3.5 (barrier heights) and 4.7 (reaction energies) kJ mol-1 . Therefore, MN12-L is recommended for investigations where CCSD(T)-based methods are not computationally feasible. For reaction barrier heights performance does not strictly follow Jacob's Ladder, for example, DHDFT methods do not perform better than conventional DFT methods. Of the ab initio methods, the cost-effective CCSD(T)/CBS(MP2) approach gives the best performance for both reaction energies and barrier heights, with RMSDs of 1.7 and 1.4 kJ mol-1 , respectively. All the considered Gaussian-n methods show good performance with RMSDs below the threshold of chemical accuracy for both reaction energies and barrier heights, where G4(MP2) shows the best overall performance with RMSDs of 2.9 and 1.5 kJ mol-1 , respectively. © 2019 Wiley Periodicals, Inc.


Effects of the uncI gene on expression of uncB, the gene coding for the a subunit of the F1F0 ATPase of Escherichia coli.
The eight genes coding for the subunits of the E. coli F1F0 ATPase are preceded by a gene, designated uncI. A homologous gene, or a gene coding for an analagous protein, is found preceding the ATPase genes of several microorganisms. No function for the 1 gene has been described. Using lac fusions to measure gene expression in vivo, we tested the effects of deleting uncI on the expression of the adjacent gene uncB, which codes for the a subunit of the F0 sector of the ATPase. Deleting uncI reduced the expression of three uncB'-'lacZ fusion genes in vivo, but had no effect on the expression of two uncB'-'lacZ fusion genes containing a relatively smaller amount of the uncB coding region. The uncI deletion also reduced the relative synthesis of the a subunit in vitro. The I gene therefore appears to specifically affect the expression of uncB or the synthesis of the a subunit at some step after translational initiation of uncB.


Abundance, transcription levels and phylogeny of bacteria capable of nitrous oxide reduction in a municipal wastewater treatment plant.
Nitrous oxide (N2O) production and expression of genes capable of its reduction were investigated in two full-scale parallel plug-flow activated sludge systems. These two systems continuously received wastewater with the same constituents, but operated under distinct nitrification efficiencies due to mixed liquor suspended solid (MLSS) concentration and the different hydraulic retention times (HRTs). A shorter HRT in system 2 resulted in a lower nitrification efficiency (40-60%) in conjunction with a high N2O emission (50.6 mg-N/L/day), whereas there was a higher nitrification efficiency (>99%) in system 1 with low N2O emission (22.6 mg-N/L/day). The DNA abundance of functional genes responsible for nitrification and denitrification were comparable in both systems, but transcription of nosZ mRNA in the lower N2O emission system (system 1) was one order of magnitude higher than that in the higher N2O emission system (system 2). The diversity and evenness of the nosZ gene were nearly identical; however, the predominant N2O reducing bacteria were phylogenetically distinct. Phylogenetic analysis indicated that N2O-reducing strains only retrieved in system 1 were close to the genera Rhodobacter, Oligotropha and Shinella, whereas they were close to the genera Mesorhizobium only in system 2. The distinct predominant N2O reducers may directly or indirectly influence N2O emissions.