Clinical features and surgical outcomes of high grade pleomorphic xanthoastrocytomas: a single-center experience with a systematic review.
High grade pleomorphic xanthoastrocytomas (HGPXAs) are very rare and their management and prognostic outcomes remain unclear. To better understand the disease, we aimed to evaluate the risk factors for progression-free survival (PFS) and overall survival (OS), and propose a treatment protocol based on cases from our institute and cases from the literature. The authors reviewed the clinical data of 26 patients with HGPXAs who underwent surgical treatment in Department of Neurosurgery of Beijing Tiantan Hospital between August 2014 and September 2021. We also searched the PubMed database using the keywords "anaplastic" combined with "pleomorphic xanthoastrocytoma(s)" between January 1997 and October 2022. Risk factors for PFS and OS were evaluated in the pooled cases. The authors' cohort included 11 males and 15 females with a mean age of 36.7 ± 20.3 years (range: 5.5-71 years). Gross-total resection (GTR) and non-GTR were achieved in 17 (65.4%) and 9 (34.6%) patients, respectively. Radiotherapy and chemotherapy were administered to 22 and 20 patients, respectively. After a mean follow-up of 20.5 ± 21.2 months (range: 0.5-78.1 months), 7 patients suffered tumor recurrence and 6 patients died with a mean OS time of 19.4 ± 10.8 months (range: 8-36 months). In the literature between January 1997 and October 2022, 56 cases of HGPXAs were identified in 29 males and 27 females with a mean age of 29.6 ± 19.6 years (range; 4-74 years). Among them, 24 (44.4%) patients achieved GTR. Radiotherapy and chemotherapy was administered to 31 (62%) patients and 23 (46%) patients, respectively. After a median follow-up of 31.4 ± 35.3 months (range: 0.75-144 months), the mortality and recurrence rates were 32.5% (13/40) and 70% (28/40), respectively. Multivariate Cox regression model demonstrated that non-GTR (HR 0.380, 95% CI 0.174-0.831, p=0.015), age≥30 (HR 2.620, 95% CI 1.183-5.804, p=0.018), no RT (HR 0.334,95% CI 0.150-0.744, p=0.007) and no CT (HR 0.422, 95% CI 0.184-0.967, p=0.042) were negative prognostic factors for PFS. Non-GTR (HR 0.126, 95% CI 0.037-0.422, p=0.001), secondary HGPXAs (HR 7.567, 95% CI 2.221-25.781, p=0.001), age≥30 (HR 3.568, 95% CI 1.190-10.694, p=0.023) and no RT (HR 0.223,95% CI 0.073-0.681, p=0.008) were risk factors for OS. High grade pleomorphic xanthoastrocytomas are very rare brain tumors. Children and younger adults have better clinical outcome than elderly patients. Secondary HGPXAs had worse OS than primary HGPXAs. Complete surgical excision plus RT and CT is recommended for this entity. The frequency of BRAF mutations in HGPXAs is 47.5% (19/40) in this study, however, we do not find the connections between BRAF mutations and clinical outcomes. Future studies with larger cohorts are necessary to verify our findings.


Prenatal and postnatal exposure to NO2 and child attentional function at 4-5years of age.
Prenatal and postnatal exposure to air pollution has been linked to cognitive impairment in children, but very few studies have assessed its association with attentional function. To evaluate the association between prenatal and postnatal exposure to nitrogen dioxide (NO2) and attentional function in children at 4-5years of age. We used data from four regions of the Spanish INMA-Environment and Childhood-Project, a population-based birth cohort. Using land-use regression models (LUR), we estimated prenatal and postnatal NO2 levels in all of these regions at the participants' residential addresses. We assessed attentional function using the Kiddie-Conners Continuous Performance Test (K-CPT). We combined the region-specific adjusted effect estimates using random-effects meta-analysis. We included 1298 children with complete data. Prenatal exposure to NO2 was associated with an impaired standard error of the hit reaction time (HRT(SE)) (increase of 1.12ms [95% CI; 0.22 a 2.02] per 10μg/m3 increase in prenatal NO2) and increased omission errors (6% [95% CI; 1.01 to 1.11] per 10μg/m3 increase in prenatal NO2). Postnatal exposure to NO2 resulted in a similar but borderline significant increase of omission errors (5% [95% CI; =0.99 to 1.11] per 10μg/m3 increase in postnatal NO2). These associations did not vary markedly between regions, and were mainly observed in girls. Commission errors and lower detectability were associated with prenatal and postnatal exposure to NO2 only in some regions. This study indicates that higher exposure to ambient NO2, mainly during pregnancy and to a lesser extent postnatally, is associated with impaired attentional function in children at 4-5years of age.


Antibiotic combinations in polymicrobic diabetic foot infections.
The aim of this study was to evaluate synergistic potential of antibiotic combinations against pathogenic microorganisms isolated from patients with diabetic foot wounds. 272 diabetic foot patients were studied prospectively over a two-year period. Tissue curettage samples from ulcer base were processed microbiologically to isolate aerobic as well as anaerobic pathogens. [775 isolates] Antibiotic susceptibility testing [MIC/MBC], from amongst these organisms revealed 75 multiresistant organisms, of which only 69 strains could be further studied to assess synergistic effect of various antibiotic combinations by the microtitre checkerboard assay technique. The checkerboard synergy studies showed that overall, synergy could be demonstrated in 21.74% to 59.57%. Amongst the 14 combinations tested, it was found that four combinations could be of worthwhile clinical significance, namely Amikacin/Piperacillin [AK + PP] [77.50%]; Ampicillin-Sulbactum/Piperacillin [AS + PP] [76.92%]; Ampicillin Sulbactum/Cefoperazone [AS + CP] [74.47%], and Ofloxacillin/Cefotaxime [OF + CT] [71.43%]. Amikacin/Piperacillin is a combination that has been proven to be of synergistic potential. This study not only confirms this observation but also showed that Ampitum-Sulbactum in combination with either Piperacillin or Cefoperazone was equally efficacious. Furthermore, it was also observed that Ofloxacillin/Cefotaxime combination could be almost equally useful. The study thus emphasizes that antibiotic combinations which are synergistic can be of great clinical significance in the management of patients with diabetic foot infections.


Role of imaging in the evaluation of renal dysfunction in heart failure patients.
Heart failure and kidney disease share common pathophysiological pathways which can lead to mutual dysfunction, known as cardiorenal syndrome. In heart failure patients, renal impairment is related to hemodynamic and non-hemodynamic factors. Both decreased renal blood flow and renal venous congestion due to heart failure could lead to impaired renal function. Kidney disease and worsening renal function are independently associated with poor prognosis in heart failure patients, both in acute and chronic clinical settings. The aim of this review is to assess the role of renal imaging modalities in the evaluation and management of heart failure patients. Renal imaging techniques could complete laboratory data, as estimated glomerular filtration rate, exploring different pathophysiological factors involved in kidney disease and adding valuable information about renal structure and function. In particular, Doppler examination of arterial and venous hemodynamics is a feasible and non invasive technique, which has proven to be a reliable method for prognostic stratification in patients with cardiorenal syndrome. The renal resistance index, a measure related to renal hemodynamics, can be calculated from the Doppler evaluation of arterial flow. Moreover, the analysis of Doppler venous flow patterns can integrate information from the arterial study and evaluate renal congestion. Other imaging modalities are promising, but still confined to research purposes.


Sludge dewatering and disposal practices for small activated sludge wastewater treatment plants.
Sludge dewatering is a decisive step in the reduction of waste sludge volume, thus considerably affecting total sludge treatment and disposal costs. The construction of sludge dewatering facilities in small WwTPs though, is generally not cost effective. In this paper some experimental evidence is presented, that waste sludge dewatering in small WwTPs of the activated sludge extended aeration type, can be effectively achieved by a centrifuge type of equipment withdrawing sludge directly from the aeration tank; an economic evaluation of the possibility to employ a transportable type of similar equipment mounted on a truck, to serve a number of small WwTPs located in remote or isolated areas is also presented and discussed.


Long-term prognosis and psychosocial outcomes after surgery for MTLE.
To assess the seizure-freedom rates and self-perceived psychosocial changes associated with the long-term outcome of epilepsy surgery in patients with refractory medial temporal lobe epilepsy associated with hippocampal sclerosis. A standard questionnaire was given to 183 patients who underwent surgery between 1988 and 2004, and 110 were completed. The mean duration of follow-up after surgery was 7 years, with a maximum of 17 years. The probability that patients were seizure-free after surgery was dependent on the definition of the seizure freedom. For the patients who were seizure-free since surgery (Engel's class Ia), the probability was 97.6% at 1 year after surgery, 85.2% at 2 years after surgery, 59.5% at 5 years after surgery, and 42.6% at 10 years after surgery. For the patients who still experienced rare disabling seizures after surgery but were seizure-free at least 1 year before the time of assessment, the probability was of 97.6% at 1 year after surgery, 95% at 2 years after surgery, 82.8% at 5 years after surgery, and 71.1% at 10 years after surgery. The psychosocial long-term outcome, as measured by indices of driving, employment, familial and social relationships, and marital status, was similar to the psychosocial short-term outcome. It did not depend on seizure freedom or on follow-up time interval and was not influenced statistically by seizure frequency in cases of persisting seizures. Most but not all patients noticed a substantial overall improvement in their psychosocial condition; 48% drove (increased by 7%), 47% improved (14% worsened) in their employment status, and 68% improved (5% worsened) in their familial and social relationships. Overall, 91% of patients were satisfied with the surgery, and 92% did not regret their decision. The results of this study suggest that temporal lobe surgery has real long-term benefits. Two specific conclusions emerge: (a) the long-term rates of freedom from seizure depend on how seizure freedom is defined, and (b) the psychosocial long-term outcome does not change dramatically over years and does not depend on seizure freedom.


Newly detected specific hydrogenation of the conjugated double bond of unsaturated alkaloid lactones by Aspergillus sp.
A new isolate of Aspergillus sp. hydrogenated the gamma,delta-double bond of securinine (143 mg l(-1)) to give 14,15-dihydrosecurinine at over 98% (w/w) yield after 8 h. It also hydrogenated the C11(13) double bond of 3-hydroxy-1(10),3,11(13)-guaiatriene-12,6-olide-2-one (HGT) (200 mg l(-1)) to give 3-hydroxy-1(10),3-guaiadiene-12,6-olide-2-one with over 98% (w/w) conversion after 24 h.


Effect of cigarette smoke extract on mitochondrial heme-metabolism: An in vitro model of oral cancer progression.
Tobacco smoking is considered as one of the major risk factors for development of oral cancer. In vitro studies indicate that cigarette smoke initiates transformation of epithelial cells toward development of oral cancer through altering mitochondrial metabolic pathways. However the present in vitro models need to be improved to correlate these molecular changes with epithelial transformations. In present study, we investigated the association of mitochondrial metabolic events with oral cancer progression under cigarette smoke extract (CSE). In this regard, an in vitro model of oral keratinocyte cell line (MOE1A) was developed by exposing them with different concentrations of CSE. Alterations in cellular phenomena were confirmed by Fourier-transform infrared spectroscopy (FTIR) study, which indicated changes in important functional groups of CSE-induced oral cells. Enhanced reactive oxygen species (ROS) of exposed cells altered the mitochondrial metabolic activities in terms of increased mitochondrial mass and DNA content. Further, mitochondrial heme-metabolism was investigated and real-time PCR study showed altered expression of important genes like ALAS1, ABCB6, CPOX, FECH, HO-1. Both transcriptomic and proteomic studies showed up- and down-regulation of important biomarkers related to cellular cancer progression. Overall data suggest that CSE alters mitochondrial heme metabolic pathway and initiates cancer progression through modifying cellar biomarkers in oral epithelial cells.


Selective interaction of alpha-adrenoceptors with myogenic regulation of microvascular smooth muscle.
The interaction of alpha 1- and alpha 2-adrenoceptor constriction of arterioles with the myogenic mechanism was examined in rat cremaster skeletal muscle using intravital microscopy. Intravascular pressure was increased or decreased by changing pressure from 0 to +30 and 0 to -20 mmHg in a chamber that surrounded the animal but not the cremaster. Arterioles of 110 microns in diameter were constricted by approximately 30% with the alpha 1-agonist, phenylephrine, or the alpha 2-agonist, UK-14304. Increases in microvascular (box) pressure caused stepwise constrictions of similar magnitude (10-30%) regardless of the prevailing type of alpha-adrenergic tone. In contrast, during alpha 2 tone, decreases in pressure caused a three- to fourfold greater dilation (myogenic inhibition) than during alpha 1 tone. Thus myogenic constriction, normally minimal in these large arterioles, was amplified similarly during either alpha 1 or alpha 2 tone; however, alpha 2 tone was much more susceptible than alpha 1 tone to myogenic inhibition. Similar results were obtained with tone produced by thromboxane A2 vs. the Ca2+ channel agonist, BAY K 8644. Thus the particular sensitivity of alpha 2 constriction to myogenic inhibition may relate to interactions between these stimuli at the postreceptor level. The degree and type of alpha-adrenoceptor tone at different microvasculature levels may be important in myogenic autoregulatory blood flow adjustments during changes in perfusion pressure.


Shared Genomic and Proteomic Contribution of Amyloid and Tau Protein Characteristic of Alzheimer's Disease to Brain Ischemia.
Post-ischemic brain damage is associated with the deposition of folding proteins such as the amyloid and tau protein in the intra- and extracellular spaces of brain tissue. In this review, we summarize the protein changes associated with Alzheimer's disease and their gene expression (amyloid protein precursor and tau protein) after ischemia-reperfusion brain injury and their role in the post-ischemic injury. Recent advances in understanding the post-ischemic neuropathology have revealed dysregulation of amyloid protein precursor, α-secretase, β-secretase, presenilin 1 and 2, and tau protein genes after ischemic brain injury. However, reduced expression of the α-secretase in post-ischemic brain causes neurons to be less resistant to injury. In this review, we present the latest evidence that proteins associated with Alzheimer's disease and their genes play a key role in progressive brain damage due to ischemia and reperfusion, and that an ischemic episode is an essential and leading supplier of proteins and genes associated with Alzheimer's disease in post-ischemic brain. Understanding the underlying processes of linking Alzheimer's disease-related proteins and their genes in post-ischemic brain injury with the risk of developing Alzheimer's disease will provide the most significant goals for therapeutic development to date.


Affect, affective resonance and a new theory for hypnosis.
New theory is most useful when it helps explain phenomena outside the observational realm within which it was derived. The growing body of evidence suggesting that adult human emotion is the result of neocortical modulation of phylogenetically earlier subcortical affect programs, and the logical system developed by Tomkins to explain the links between innate affect and adult behavior, has been reviewed in terms of newer work on infant observation. The study of interaffectivity and intersubjectivity leads to an understanding of the caregiver as an external modulator of infantile affect; the similarity between these processes of external modulation and the well known techniques of hypnotic induction suggests commonality. Save for a massive reorganization of our theories about affect and its relationship to the face, I do not think it can any longer be considered valid for an investigator to present data about hypnosis without meticulous attention to facial affect display.


The Effects of Hospital Closure on the Local Utilization of Total Joint Replacement The Queens Experience.
Since 2000, 31 hospitals have closed in New York State. This has primarily been due to the financial difficulties endured by these institutions, many of which were located in areas inhabited predominantly by patients of lower socioeconomic status. Additionally, recommendations by the NYS Depart- ment of Health (Berger Commission) cited excess hospital capacity as a driver for the struggles of the healthcare delivery system in New York, forcing financially stable in - stitutions to close their doors as well. Data has shown that outcomes are improved when complex procedures, such as joint arthroplasty, are performed at high volume hospitals. However, for patients in the outer boroughs of NYC, travel to these specialized centers may be too expensive and physi- cally difficult for poor patients with severe osteoarthritis. Using the SPARCS database, we identified a temporary decrease in utilization of lower extremity total joint replace - ment in the areas immediately adjacent to closed hospitals. This does not appear to have a lasting effect as illustrated by quick return back to pre-closure trends and further in- crease when compared with regional trends. This effect is more pronounced in urban areas where public transportation and traffic are more of an issue for patients, making it more difficult to travel with the goal of seeking care elsewhere.


Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes): A Potential Bioresource for Commercialization in Sikkim Himalaya, India.
Ophiocordyceps sinensis has a long history of use in Tibetan traditional medicine and traditional Chinese medicine as a powerful tonic and aphrodisiac. The species is inextricably linked to the trade of medicinal and aromatic plants in East Asia. Its demand has increased substantially in the international market, and its collection and trade have significantly improved the socioeconomic status of the people in some regions. Nonetheless, in Sikkim this resource is still untapped formally, but it is traded illegally. Formal legalization and the community's involvement will ensure the conservation and sustainability of the species, as well as proper management of harvesting areas and monitoring of pressure on Yartsa Gunbu to exploit it.


[Radiologic diagnosis following pancreas transplantation].
Technical complications are relatively common after pancreatic transplantation, and most require radiological evaluation. Ultrasonography and computed tomography are helpful in the identification of peripancreatic and intra-abdominal fluid collections. Sterile fluid collections can be effectively treated by percutaneous catheter drainage, whereas most intra-abdominal infections require surgical intervention. Angiography is performed primarily for diagnosis of vascular thrombosis. Recent results suggest that magnetic resonance imaging may be a useful non-invasive method for the detection of pancreatic transplant rejection. Further imaging studies are needed to better define the development of progressive fibrotic atrophy in long-term functioning pancreatic transplants.


Pyrimidine de novo synthesis during the life cycle of the intraerythrocytic stage of Plasmodium falciparum.
The 6 enzymes involved in de novo synthesis of pyrimidines were measured in Plasmodium falciparum isolated by saponin lysis from RBC's nonsynchronized and synchronized in vitro cultures. The total activities were found to be dependent on the stage of the P. falciparum cycle. In parasites isolated from synchronized cultures, the highest activities for all enzymes were found at about 27 hr after synchronization in the late trophozoite stage, or just before schizont formation. Merozoites and ring forms contained little de novo activity. The first enzyme of the pathway, carbamyl phosphate synthetase (CPS-II) preferentially utilized glutamine. Ammonia was a poor substrate. CPS-II was unstable in the absence of the cryoprotectants, dimethylsulfoxide and glycerol. The apparent Km for MgATP--was 3.8 +/- 0.7 mM and the enzyme in all morphological forms of P. falciparum (ring, mature trophozoites and schizonts) was inhibited by UTP. The activity of the fourth enzyme of the pathway, dihydroorotate dehydrogenase, appeared to be linked to the cell's respiratory chain; inhibitors of mammalian electron transport such as cyanide, amytal, antimycin A, thenoyltrifluoroacetone and ubiquinone analogs also inhibited the P. falciparum enzyme. The demonstration of the variation of activity of the pyrimidine enzymes correlates with the increased synthesis of nucleic acids in the late trophozoite stage. These observations provide a basis for the testing of the effectiveness of pyrimidine analogs as potential antimetabolites against various forms of the parasite.


Local recurrences after surgical treatment for rectal carcinoma.
In a retrospective study of patients treated between 1974 and 1979 with surgery alone for cancer of the rectum or rectosigmoid, a total of 293 patients were evaluated. All original histopathological specimens were re-examined and classified according to the Dukes' staging system and to the Astler - Coller 's modification of this system. Among the 197 (67%) patients operated upon for local cure, 74 patients developed a microscopically proven local recurrence (38%), and in 43 of them this was the only sign of recurrent cancer. There was no clear correlation, however, to the pathological stage. Possible explanations for this finding will be discussed.


Overview of salt fluoridation in Switzerland since 1955, a short history.
After an early start in 1955, the introduction and acceptance of fluoridated salt (FS) for domestic use was slow in Switzerland because up to around 1980 there was no consistent strategy for the support of the use of FS. Part of the dental community still supported water fluoridation, while others criticized the insufficient concentration of fluoride in the salt (90 ppm). All Swiss cantons have a historical monopoly on salt trade, and until 1983 most cantonal governments resolved to authorize the sale of fluoridated domestic salt. Some of the cantonal governments made fluoridated salt the only available type of "kitchen salt" in 1-kg packages. After the concentration had been increased to 250 ppm in 1983, the use of FS gained further acceptance. A temporary setback occurred in 1992-1994, but was successfully met with by making the FS available in several package sizes, while other types of salt (with or without iodine) were available in 500 g packages only. By 2004, the market share of fluoridated domestic salt reached 88%. Further endeavours aim at increasing the use of FS by large kitchens. FS is available in portions of 12.5 kg (since 2001) and 25 kg (since 1976).


Cardiovascular effects of coxibs.
A new class of drugs, the selective cyclooxygenase-2 (COX-2) inhibitors, or coxibs, have recently been marketed as an alternative to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) on the basis of a lower risk of gastrointestinal side effects. The recent withdrawal of rofecoxib, along with safety concerns about other COX-2 selective inhibitors raises important questions about the cardiovascular toxicity of these drugs. Recently some concerns arose even for a possible cardiotoxicity of nonselective nonsteroidal anti-inflammatory drugs. From data available so far, it seems that coxibs still remain a rational choice for patients with low cardiovascular risk and high gastrointestinal risk. Long-term studies with a cardiovascular endpoint involving both selective and nonselective anti-inflammatory drugs are warranted.


[Lincomycin applied to the alveolus on TCP carrier and its effect on wound healing after surgical extraction of a third molar].
The dental surgeon is often confronted by complications particularly after extraction ofunerupted lower third molars. The most common complication is alveolar periostitis. The healing process after extraction is accompanied by physiologic atrophy of the alveolus involving on the average 30% of bone tissue. Beta-tricalcium phosphate (TCP) is a synthetic material used in medicine to fill up bone defects caused by pathologic processes. The properties of TCP are appropriate for the material to be used as a carrier for drugs, in particular antibiotics. This study was undertaken to determine whether lincomycin applied to the alveolus on TCP carrier can be used to accelerate wound healing and reduce inflammation after surgical extraction of a third molar. We enrolled 80 patients (males and females between the age of 18 and 50 years) who underwent extraction of a third molar at the Department of Dental Surgery, Pomeranian Medical University in Szczecin. Surgical difficulty in the patients according to the Pederson scale corresponded to grade 2 or 3 (medium or high difficulty). The study group consisted of 40 patients who received lincomycin on TCP. Beta-tricalcium phosphate (300-700 microm pores) obtained from the Department of Technology of Ceramics and Refractories, AGH University of Science and Technology in Cracow, was soaked with 500 mg of lincomycin in solution and applied to the dental alveolus after tooth extraction. The alveolus was tightly sutured. The control group comprised 40 patients not treated with lincomycin. The patients reappeared for examination on the first, third, and seventh day after surgery. Attention during follow-up was directed to alveolar periostitis, pain, and trismus. Pain intensity was assessed with the 10-degree Visual Analog Scale (VAS). We analyzed the subjective pain intensity reported during follow-up by the patients. In the study group, 20 patients reported no pain 24 hours after extraction. On the third day after surgery, alveolar periostitis was present in 15% of patients in the study group and 75% of patients in the control group. On the last day of follow-up, periostitis was present in only 2.5% of patients in the study group as opposed to 45% of patients in the control group. The differences were statistically significant (chi-square 36.05, p < 0.0001). (1) Lincomycin on TCP can be used to prevent alveolar periostitis. (2) Lincomycin on TCP reduces complications in the form of pain and trismus. (3) Beta-tricalcium phosphate prevents atrophy of the alveolar process.


A dual-layer macro/mesoporous structured TiO2 surface improves the initial adhesion of osteoblast-like cells.
A dual-layer TiO2 surface with hierarchical macro and mesoporous structure was prepared by a combinational approach of micro-arc oxidation followed by evaporation-induced self-assembly of nano-crystallites. The mesoporous layer contains pores with an average size of <10nm and consists of anatase TiO2 nanocrystallites. The dual-layer hierarchical macro/mesoporous structured TiO2 surface improves the hydrophilicity and fibronectin adsorption ability in comparison with the sole macroporous or smooth TiO2 surface. With the formation of an additional mesoporous layer on macroporous TiO2 surface, the attached number of human osteogenic sarcoma cells (SaOS-2) increases in the initial incubation of 4h but it does not show significant difference after 24h compared to that attached on the macroporous or smooth surfaces. Whereas, it was noticed that SaOS-2 cells have larger spread area and more stress fibers on the macro/mesoporous structured surface than those on the other surfaces. To understand the intracellular mechanism of the initial cell adhesion on the macro/mesoporous surface, the Rho/ROCK pathway was investigated to reveal the topography-induced biological functions by introducing the ROCK inhibitor Y-27632 during cell culture. In the presence of Y-27632, cells on the macroporous surface and macro/mesoporous surface both show stellate appearance, with poor assembly stress fibers and long cell membrane protrusions. Cells on the smooth surface have larger spread areas compared to the former two surfaces. And the attached cells significantly reduced but there are no differences among the three surfaces. It reveals that the ROCK inhibitor invalidates the promotion of initial cell adhesion on the macro/mesoporous structure. This study may shed light on the mechanism behind the enhancement effect of macro/mesoporous structure for initial cell adhesion.


Screening for colorectal cancer with fecal occult blood testing and sigmoidoscopy.
The high incidence of and mortality from colorectal cancer (160,000 new cases and 60,000 deaths in the United States each year) are compelling public health concerns. Following the evolution of effective surgery for this disease since the 1960s, the focus has been on improving methods of detection and integrating them into effective screening programs. This was the first study to evaluate the effectiveness, in a setting of comprehensive medical examinations, of using the fecal occult blood test in conjunction with sigmoidoscopy, rather than sigmoidoscopy alone, to screen for colorectal cancer. Our end points were extent of compliance with fecal occult blood test and sigmoidoscopy, numbers of cancers detected, and mortality rate. From 1975 through 1979, a total of 21,756 patients (aged 40 and older) who presented at the Preventive Medicine Institute-Strang Clinic for routine medical examinations were enrolled by calendar period into study and control groups. Study patients were offered annually both rigid sigmoidoscopy examinations and fecal occult blood tests requiring two stool specimens per day for 3 days, while control patients were offered only annual sigmoidoscopy. The majority of fecal occult blood test cards were not rehydrated before assay. Patients with positive tests were referred for double-contrast barium enema and colonoscopy. Two distinct trials were carried out. Trial I was primarily a demonstration of feasibility of using the fecal occult blood test as a supplemental screening method. Of the 9277 participants, 7168 (77%) were assigned to the study group and offered the fecal occult blood test. In trial II, approximately half of the 12,479 patients were assigned to each group. Patients in both trials had follow-up through 1984. Compliance with the fecal occult blood test was initially high in both trials, but diminished such that only 56% of study patients in trial I and 20% of those in trial II returned for second tests. On the initial (prevalence) screen, a substantial number of early-stage cancers were detected by the fecal occult blood test, primarily in trial II. In trial II, survival probability was significantly greater (P < .001) in the study group than in the controls (70% versus 48%), and colorectal cancer mortality was lower (0.36 versus 0.63) with borderline significance (P = .053, one-sided). The screening of average-risk individuals (aged 50 and older) for colorectal cancer through use of the fecal occult blood test in conjunction with sigmoidoscopy can increase the likelihood of early detection of this disease. This practice, coupled with prompt diagnostic work-up following positive tests, will result in treatment of earlier stage cancers and increased survival after treatment.


Osteobiographic analysis of skeleton I, Sítio Toca dos Coqueiros, Serra da Capivara National Park, Brazil, 11,060 BP: first results.
This paper presents an osteobiographic analysis of a single skeleton found in a small rock shelter known as Toca dos Coqueiros, Piauí, Brazil. This find is of interest because of an exceptionally old radiocarbon date associated with it. The date (11,060 BP) was obtained from charcoal associated directly with the skeleton. This is an interesting find because of the rarity of osteobiographic studies of skeletons of such antiquity. Despite the existence of two projectile points in association with the burial, the morphological and molecular analyses of the skeleton demonstrated that this was a female. She was about 35-45 years of age at death. The skeleton exhibited acute and chronic bone lesions. Oral pathology was also observed, including an interproximal dental groove, probably caused by the therapeutic use of a cactus thorn. This could be one of the oldest cases of an analgesic plant used in the prehistoric Americas.


Impaired Processing of Serial Order Determines Working Memory Impairments in Alzheimer's Disease.
Working memory (WM) problems are commonly observed in Alzheimer's disease (AD), but the affected mechanisms leading to impaired WM are still insufficiently understood. The ability to efficiently process serial order in WM has been demonstrated to be fundamental to fluent daily life functioning. The decreased capability to mentally process serial position in WM has been put forward as the underlying explanation for generally compromised WM performance. Determine which mechanisms, such as order processing, are responsible for deficient WM functioning in AD. A group of AD patients (n = 32) and their partners (n = 25), assigned to the control group, were submitted to an extensive battery of neuropsychological and experimental tasks, assessing general cognitive state and functioning of several aspects related to serial order WM. The results revealed an impaired ability to bind item information to serial position within WM in AD patients compared to controls. It was additionally observed that AD patients experienced specific difficulties with directing spatial attention when searching for item information stored in WM. The processing of serial order and the allocation of attentional resources are both disrupted, explaining the generally reduced WM functioning in AD patients. Further studies should now clarify whether this observation could explain disease-related problems for other cognitive functions such as verbal expression, auditory comprehension, or planning.


Coherence-OAM matrix properties of a twisted Gaussian Schell model beam.
Based on the cross-spectral density (CSD) function, the coherence-orbital angular momentum (COAM) matrix of twisted Gaussian Schell-model (TGSM) beam is proposed, and the COAM matrix is used to describe the correlation between OAM modes in TGSM optical field. The COAM matrix characteristics of TGSM beam are analyzed by numerical simulation. The results show that the COAM matrix characteristics of TGSM beam depend on the initial parameters of the beam. In addition, a method of generating TGSM beam by superposition of COAM matrix element modes is described, and the influence of different initial parameters on the superposition characteristics is studied. The results reveal the internal relationship between the coherent structure of the optical field, the twist phase and the OAM modes. Our work helps to explore new expressions of partially coherent beams and promote the practical application of optimizing partially coherent beams.


A glimpse into the future of systemic lupus erythematosus.
This viewpoint article on a forecast of clinically meaningful changes in the management of systemic lupus erythematosus (SLE) in the next 10 years is based on a review of the current state of the art. The groundwork has been laid by a robust series of classification criteria and treatment recommendations that have all been published since 2019. Building on this strong foundation, SLE management predictably will take significant steps forward. Assessment for lupus arthritis will presumably include musculoskeletal sonography. Large-scale polyomics studies are likely to unravel more of the central immune mechanisms of the disease. Biomarkers predictive of therapeutic success may enter the field; the type I interferon signature, as a companion for use of anifrolumab, an antibody against the common type I interferon receptor, is one serious candidate. Besides anifrolumab for nonrenal SLE and the new calcineurin inhibitor voclosporin in lupus nephritis, both of which are already approved in the United States and likely to become available in the European Union in 2022, several other approaches are in advanced clinical trials. These include advanced B cell depletion, inhibition of costimulation via CD40 and CD40 ligand (CD40L), and Janus kinase 1 (Jak1) and Tyrosine kinase 2 (Tyk2) inhibition. At the same time, essentially all of our conventional therapeutic armamentarium will continue to be used. The ability of patients to have successful SLE pregnancies, which has become much better in the last decades, should further improve, with approaches including tumor necrosis factor blockade and self-monitoring of fetal heart rates. While we hope that the COVID-19 pandemic will soon be controlled, it has highlighted the risk of severe viral infections in SLE, with increased risk tied to certain therapies. Although there are some data that a cure might be achievable, this likely will remain a challenge beyond 10 years from now.


An Emergency Department Presentation of Secondary Syphilis.
In the United States, the rate of primary and secondary syphilis has increased by 18% in 2016, the highest rate since 1993. These patients can often present to the emergency department (ED) in various stages. Although syphilis is well described in the literature, there is a paucity of ED reports of atypical cases. A 22-yr-old male presented to the ED complaining of neck pain. The patient was found to have right-sided tender cervical lymphadenopathy causing neck pain. A thorough physical exam revealed diffuse lymphadenopathy. Without an obvious infectious etiology, the patient underwent a broad workup, which revealed a reactive rapid plasma reagin (RPR) assay with a titer of 1:64. The patient had no history of the classic painless penile ulcer. The ED presentation of secondary syphilis can be very insidious, and physicians should be aware of its various presentations.


MR contrast agents: an overview.
In this article an overview of current and potential MR contrast agents is given. The mechanism of action of contrast agents and their relationship to both T1 and T2 relaxation are explored. Both paramagnetic and superparamagnetic substances are considered. Various physical states of these materials, including small ionic, lipophilic, and macromolecular forms are explored as possible contrast agents. Several clinical examples are given and speculation is made about the future potential of MR contrast agents.


In search of a function for the E3B1/Abi2/Argbp1/NESH family (Review).
An E3B1/Abi2/Argbp1/NESH protein family has recently emerged from analysis of the sequence and structural similarities. These are adaptor proteins possessing homeobox homology domain, proline rich region and Src-homology 3 (SH3) domain that interact with Abl-family tyrosine kinases. Some of the members of this family are involved in cytoskeletal reorganization that plays important roles in membrane-ruffling, lamellipodia formation and cell migration. Furthermore, it seems likely that this family may also regulate cancer development through modulation of the oncogenic Abl kinase. The knowledge of this status is helpful in thinking of the regulatory mechanisms to cell metastasis and to malignant transformation of cancer. We discuss how these interesting molecules work and consider their involvement in cancer.


Passive immunotherapy rapidly increases structural plasticity in a mouse model of Alzheimer disease.
Senile plaque-associated changes in neuronal connectivity such as altered neurite trajectory, dystrophic swellings, and synapse and dendritic spine loss are thought to contribute to cognitive dysfunction in Alzheimer's disease and mouse models. Immunotherapy to remove amyloid beta is a promising therapy that causes recovery of neurite trajectory and dystrophic neurites over a period of days. The acute effects of immunotherapy on neurite morphology at a time point when soluble amyloid has been cleared but dense plaques are not yet affected are unknown. To examine whether removal of soluble amyloid beta (Abeta) has a therapeutic effect on dendritic spines, we explored spine dynamics within 1 h of applying a neutralizing anti Abeta antibody. This acute treatment caused a small but significant increase in dendritic spine formation in PDAPP brain far from plaques, without affecting spine plasticity near plaques or average dendritic spine density. These data support the hypothesis that removing toxic soluble forms of amyloid-beta rapidly increases structural plasticity possibly allowing functional recovery of neural circuits.


Developmental delay, intellectual disability, short stature, subglottic stenosis, hearing impairment, onychodysplasia of the index fingers, and distinctive facial features: A newly reported autosomal recessive syndrome.
We report on a multiply consanguineous Syrian family where two siblings, a boy and a girl, presented with a compilation of symptoms including developmental delay, severe intellectual disability, absent speech, hearing impairment, short stature, subglottic stenosis, increased length of the palpebral fissures, onychodysplasia of index fingers, scoliosis, genu valgum, and malpositioned toes. Two other individuals from the extended family with similar clinical features are also described. Array-CGH did not reveal any pathological copy number variation. Exome sequencing failed to find any causal variants. Differential diagnoses and the possibility that we might be reporting a hitherto unknown syndrome are discussed.


Brevundimonas lenta sp. nov., isolated from soil.
A Gram-negative, rod-shaped, Brevundimonas-like bacterial strain, DS-18(T), was isolated from soil in Dokdo, Korea, and its exact taxonomic position was investigated by using a polyphasic approach. Strain DS-18(T) grew optimally at pH 6.5-7.0 and 25 degrees C without NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain DS-18(T) belonged to the genus Brevundimonas. Strain DS-18(T) contained Q-10 as the predominant ubiquinone and C(18 : 1)omega7c and C(16 : 0) as the major fatty acids. The DNA G+C content was 68.7 mol%. Strain DS-18(T) exhibited levels of 16S rRNA gene sequence similarity of 96.3-98.7 % to the type strains of Brevundimonas species and Mycoplana bullata. Mean DNA-DNA relatedness values between strain DS-18(T) and the type strains of phylogenetically related Brevundimonas species and M. bullata were in the range 15-32 %. Strain DS-18(T) differed from Brevundimonas species and M. bullata in several phenotypic characteristics. On the basis of phenotypic, phylogenetic and genetic data, strain DS-18(T) represents a novel species of the genus Brevundimonas, for which the name Brevundimonas lenta sp. nov. is proposed. The type strain is DS-18(T) (=KCTC 12871(T) =JCM 14602(T)).


Probing losses of dielectric multilayers by means of Bloch surface waves.
We exploit the excitation of electromagnetic surface waves on high-quality dielectric multilayers to measure the very low extinction coefficient of the structures, with a resolution down to 4·10(-7) and in a simple optical configuration. The effect of exposition to a rhodamine 6G solution in water and ethanol is also reported, including dye adsorption in the layers and bleaching upon resonant excitation.


Isocyanurate Formation During Oxazolidinone Synthesis from Epoxides and Isocyanates Catalysed by a Chromium(Salphen) Complex.
Chromium(salphen) complex 10 is found to be a catalyst for the preparation of oxazolidinones from epoxides and isocyanates. Using the optimal reaction conditions (1.5 mol % of chromium(salphen) complex 10 at 80 °C in toluene for 4 hours), six epoxides were reacted with five isocyanates, providing 15 oxazolidinones in up to 90 % yield. With electron-deficient isocyanates, cyclotrimerisation of the isocyanate to the corresponding isocyanurates is a competing reaction, showing the importance of matching catalyst activity to that of the substrates.


Spinopelvic sagittal realignment and incidence of adjacent segment disease after single-segment posterior lumbar inter-body fusion using 12° lordotic cages-a 2-year prospective cohort study.
The importance of spinopelvic sagittal alignment for adjacent segment disease (ASD) after lumbar fusion surgery has been reported. However, no longitudinal cohort studies have determined the extent to which segmental alignment and spinopelvic global alignment can be achieved using 12° lordotic cages in posterior lumbar inter-body fusion (PLIF) and the extent to which the development of ASD can be prevented. The purpose of this study was to analyze changes in segmental and spinopelvic sagittal alignment after single-segment PLIF with 12° lordotic cages, to clarify the relationship between changes in segmental and spinopelvic sagittal alignment, and to report the incidence of ASD at 2 years postoperatively. Subjects in this 2-year prospective longitudinal cohort study were 28 patients who had undergone L4/5 PLIF using 12° lordotic cages. Incidence of operative ASD (O-ASD) was evaluated as clinical outcomes. Radiological measurements were examined preoperatively and at 3 months, 1 year and 2 years postoperatively. The following radiographic spinopelvic parameters were measured: segmental lordosis (SL) at L4/5; sagittal vertical axis (SVA); T1 pelvic angle (TPA); thoracic kyphosis (TK); lumbar lordosis (LL); sacral slope (SS); pelvic tilt (PT); and pelvic incidence (PI). With respect to radiological outcomes, changes in SL (ΔSL) and spinopelvic parameters and the incidence of radiological ASD (R-ASD) were evaluated. Correlations of ΔSL and changes in other spinopelvic parameters (ΔSVA, ΔTPA, ΔTK, ΔLL, ΔSS, ΔPT, and ΔPI-LL) between preoperatively and 3 months postoperatively were examined. The follow-up rate was 100% (n=28) at 1 year postoperatively and 96.4% (n=27) at 2 years postoperatively. No cases of O-ASD were seen during 2 years of follow-up. Significant realignment was observed and maintained at 2 years postoperatively in almost all spinopelvic sagittal parameters (SL, SVA, TPA, LL, PT, PI-LL). Regarding the correlation between ΔSL and other parameters, significant correlations were detected with ΔSVA (r=-0.37, P<0.05) and ΔLL (r=0.538, P<0.01). Three cases (11.1%) showed R-ASD at 2 years postoperatively. PLIF with 12° lordotic cages for L4 degenerative spondylolisthesis improved SL and global sagittal realignment, and achieved satisfactory clinical outcomes with a low incidence of ASD during 2 years of follow-up.


Identification of prognostic collagen signatures and potential therapeutic stromal targets in canine mammary gland carcinoma.
Increasing evidence indicates that the tumor microenvironment plays a critical role in regulating the biologic behavior of breast cancer. In veterinary oncology, there is a need for improved prognostic markers to accurately identify dogs at risk for local and distant (metastatic) recurrence of mammary gland carcinoma and therefore would benefit from adjuvant therapy. Collagen density and fiber organization have been shown to regulate tumor progression in both mouse and human mammary tumors, with certain collagen signatures predicting poor outcomes in women with breast cancer. We hypothesized that collagen signatures in canine mammary tumor biopsies can serve as prognostic biomarkers and potential targets for treatment. We used second harmonic generation imaging to evaluate fibrillar collagen density, the presence of a tumor-stromal boundary, tumor associated collagen signatures (TACS) and individual collagen fiber characteristics (width, length and straightness) in grade I/II and grade III canine mammary tumors. Collagen density, as well as fiber width, length and straightness, were inversely correlated with patient overall survival time. Notably, grade III cases were less likely to have a tumor-stromal boundary and the lack of a boundary predicted poor outcome. Importantly, a lack of a defined tumor-stromal boundary and an increased collagen fiber width were associated with decreased survival even when tumor grade, patient stage, ovariohysterectomy status at the time of mammary tumor excision, and histologic evidence of lymphovascular invasion were considered in a multivariable model, indicating that these parameters could augment current methods to identify patients at high risk for local or metastatic progression/recurrence. Furthermore, these data, which identify for the first time, prognostic collagen biomarkers in naturally occurring mammary gland neoplasia in the dog, support the use of the dog as a translational model for tumor-stromal interactions in breast cancer.


Immune checkpoint inhibitors combined with tyrosine kinase inhibitors or immunotherapy for treatment-naïve metastatic clear-cell renal cell carcinoma-A network meta-analysis. Focus on cabozantinib combined with nivolumab.
Introduction: The combination of immunotherapy and targeted therapy is currently marking a new era in the treatment of renal cancer. The latest clinical guidelines recommend the use of drug combinations for the first-line treatment of advanced renal cancer. The aim of this review is to compare the efficacy of combined cabozantinib + nivolumab therapy with other immune checkpoint inhibitors combined with tyrosine kinase inhibitors or monoclonal antibodies blocking the CTLA-4 (cytotoxic T cell antigen 4) in the first-line treatment of metastatic clear-cell renal cell carcinoma (RCC). Methodology: A systematic literature search was carried out in the PubMed and EMBASE databases. Randomized controlled trials (RCTs) on therapies recommended by the latest EAU and ESMO guidelines for treatment-naïve metastatic RCC (i.e., lenvatinib + pembrolizumab, axitinib + pembrolizumab and nivolumab + ipilimumab) were searched. A network meta-analysis (NMA) was performed for data synthesis. The methodology of included RCTs was assessed using the Cochrane RoB two tool. The data were analyzed in the overall population as well as in risk subgroups defined according to the International Metastatic Database Consortium (IMDC) i.e., patients with a favorable and intermediate or poor prognoses. The most recent cut-off dates from included studies were analyzed. Results: Four RCTs (CheckMate 9 ER, KEYNOTE-426, CLEAR and CheckMate 214) were included in the review. No studies directly comparing cabozantinib + nivolumab with any of the drug combinations included in this review were available. NMA showed that cabozantinib + nivolumab was superior compared to axitinib + pembrolizumab and nivolumab + ipilimumab in all analyzed comparisons (overall population and IMDC risk subgroups), both in terms of overall survival and progression-free survival (PFS). The advantage of cabozantinib + nivolumab was statistically significant only for PFS when compared to nivolumab + ipilimumab in the overall population. The results for the comparison of cabozantinib + nivolumab with lenvatinib + pembrolizumab showed numerical superiority of lenvatinib + pembrolizumab combination in terms of overall survival, but none of the results were statistically significant. The advantage of lenvatinib + pembrolizumab over cabozantinib + nivolumab in terms of PFS was statistically significant in the overall and favorable prognosis population. Conclusion: Inclusion of the most recent cut-off data from CheckMate 9 ER did not affect the role of the cabozantinib + nivolumab combination for treatment-naïve metastatic RCC. Cabozantinib + nivolumab is an effective therapeutic option for the first-line treatment of advanced renal cancer that is recommended both in the latest European and American guidelines for all IMDC risk groups.


Tendon involvement in the feet of patients with gout: a dual-energy CT study.
To examine the frequency and patterns of monosodium urate (MSU) crystal deposition in tendons and ligaments in patients with gout using dual-energy CT (DECT). Ninety-two patients with tophaceous gout had DECT scanning of both feet. Two readers scored the DECT scans for MSU crystal deposition at 20 tendon/ligament sites and 42 bone sites (total 1840 tendon/ligament sites and 3864 bone sites). MSU crystal deposition was observed by both readers in 199/1840 (10.8%) tendon/ligament sites and in 399/3864 (10.3%) bone sites (p=0.60). The Achilles tendon was the most commonly involved tendon/ligament site (39.1% of all Achilles tendons), followed by the peroneal tendons (18.1%). Tibialis anterior and the extensor tendons were involved less commonly (7.6-10.3%), and the other flexor tendons, plantar fascia and deltoid ligaments were rarely involved (<5%) (p<0.0001 between sites). Involvement of the enthesis alone was more common in the Achilles tendon (OR (95% CI) 74.5 (4.4 to 1264), p<0.0001), as was any involvement of the enthesis (OR (95% CI) 6.8 (3.6 to 13.0), p<0.0001). Tendons are commonly affected by MSU crystal deposition in patients with tophaceous gout. The patterns of MSU crystal deposition suggest that biomechanical strain or other local factors may contribute to deposition of MSU crystals.


Neurocytotoxic antibodies in serum of patients with systemic lupus erythematosus.
Sera from patients with systemic lupus erythematosus (SLE) have been tested for antibody to a human neuronal cell line, SK-N-SH, derived from a metastatic neuroblastoma. With a complement-dependent (51)Cr-release cytotoxicity assay, 75% of SLE sera had antineuronal activity mediated by IgM antibody. Most of the sera containing this IgM neurocytotoxic antibody were also cytotoxic to the human glial cell lines A-172 and U-118MG. The sera did not mediate complement-dependent (51)Cr release when tested against normal human fibroblasts or peripheral blood lymphocytes. IgG antineuronal antibody was detected in 17% of SLE sera by an antibody-dependent, cell-mediated cytotoxicity assay with SK-N-SH cells as targets. The relationship of IgM and IgG antineuronal antibodies to the antilymphocyte antibodies present in SLE sera was evaluated by a series of crossabsorption experiments using SK-N-SH cells to remove neuronal antibodies and WI-L2 (human lymphoblasts) to remove antilymphocyte antibodies. Most of the complement-dependent neurocytotoxicity was not removed by multiple lymphoblast absorptions, although the WI-L2 cells readily removed lymphocytotoxic activity as assayed on normal lymphocytes. Absorption with SK-N-SH cells removed most, but not all, of the lymphocytotoxic antibody. Thus, although lymphocytotoxic antibodies reactive with membrane antigens shared by lymphocytes and brain may constitute a subset of the antibodies to neural cells, most of the antineuronal activity in SLE serum is directed at other cell surface antigens expressed on neuronal and glial cells. Should they gain access to the brain, these antibodies have the potential to produce neuropathology, but their presence in the nervous system of patients with the neuropsychiatric manifestations of SLE is yet to be documented.


[Exteroceptive reflex control of the levator palpebrae muscle in man (author's transl)].
Exteroceptive periorbital stimulation is reported to evoke an early and a late bilateral pause in the activity of the m. levator palpebrae. The early levator pause appears at lower threshold than the blink reflex components in the m. orbicularis oculi. It is suggested that antagonistic muscles at papebral level are subjected to a differential exteroceptive reflex control.


Distinct patterns of plasticity in prefrontal cortex neurons that encode slow and fast responses to stress.
The prefrontal cortex (PFC) has been implicated in cognitive and affective responses to acute and chronic stress; however, direct evidence for the reactivity or adaptability of PFC neurons to stress is lacking. We followed the unit activity of medial PFC (mPFC) neurons in awake rats during two consecutive exposures to restraint stress or to a non-aversive novel object. The majority (75%) of mPFC neurons had significant responses to the initial restraint that was differentiated into one of three temporal patterns: (i) phasic increase in firing rate during the restraint period, (ii) slow onset increase in firing rate that was sustained for > 2 h after restraint, and (iii) brief bi-phasic responses to initiation and termination of restraint. Exposure to a novel object elicited an exposure-locked phasic response in 40% of the neurons. None of the neurons displayed the sustained activation that was prominent after restraint. A second exposure to the object no longer elicited this phasic response while neurons in the three restraint-responsive groups modified their firing rate during the second restraint in a manner that was specific to their pattern of response to the first restraint. These findings demonstrate that whereas some mPFC neurons respond phasically to novel stimuli irrespective of their aversive nature, a separate population of PFC neurons responds to a stressful stimulus with a sustained increase in firing rate that persists in the absence of that stimulus. These neurons may be a substrate for adaptive responses that are necessary for behavioral modification.


Supramolecular assembly of Mg(II) complexes directed by associative lone pair-pi/pi-pi/pi-anion-pi/pi-lone pair interactions.
Two Mg(II) malonate complexes with protonated 2-aminopyridine and protonated 2-amino-4-picoline as counterions, namely, (C(5)H(7)N(2))(4)[Mg(C(3)H(2)O(4))(2)(H(2)O)(2)](ClO(4))(2) (1) and (C(6)H(8)N(2)H)(2)[Mg(C(3)H(2)O(4))(2)(H(2)O)(2)] x 4 H(2)O (2) [C(5)H(7)N(2) = protonated 2-aminopyridine, C(3)H(4)O(4) = malonic acid, C(6)H(8)N(2)H = protonated 2-amino-4-picoline], have been synthesized from purely aqueous media, and their crystal structures have been determined by single-crystal X-ray diffraction. The role of lone pair...pi interactions in stabilizing the self-assembly process appears to be of great importance in both complexes. Additional weak forces like anion...pi and noncovalent O...O interactions are also found to be operating in 1. A rare combination of lone pair...pi and anion...pi interactions in 1, of the type lone pair...pi/pi...pi/pi...anion...pi/pi...lone pair, is observed, and this unusual supramolecular network is fully described here. An attempt to prepare an analogous complex with 2-amino-4-picoline resulted in 2, which is isomorphous with our recently reported transition-metal complexes of the type (C(6)H(8)N(2)H)(2)[M(C(3)H(2)O(4))(2)(H(2)O)(2)] x 4 H(2)O (M = Ni/Co/Mn). A high-level DFT-D study (RI-B97-D/TZVP) has been used to characterize the different noncovalent interactions present in the solid state. We have also analyzed some crystal fragments to examine energetically some important assemblies that drive the crystal packing. Finally, we have studied the influence of magnesium on some hydrogen-bonding interactions.


Quality improvement collaborative: A novel approach to improve infection prevention and control. Perceptions of lead infection prevention nurses who participated.
In response to the ongoing infection prevention (IP) challenges in England, a 90-day quality improvement (QI) collaborative programme was developed. The paper discusses the approach, benefits, challenges and evaluation of the programme. The objective of the collaborative was to develop new approaches to enable sustainable and effective IP. Six trusts in the region participated in the collaborative. Each defined their bespoke IP focus. There was no expectation that statistically significant measurable improvements would be identified during the short time frame. The experiences of the participants were sought both during the programme to facilitate its constant review and at the end of the programme to evaluate its effectiveness. The feedback focused on achievements, barriers to change and benefits of participating in a QI collaborative. To measure the potential success of the projects, participants completed the Model for Understanding Success in Quality framework. (MUSIQ; Kaplan et al., 2012). Since each trusts IP focus was bespoke commonalities of success were not evaluated. Participants identified a positive outcome from their QI interventions. The MUSIQ score identified the projects had the potential for success. The feedback from the participants demonstrated that it is worthy of further development.


Recent developments on coronavirus main protease/3C like protease inhibitors.
Coronaviruses have been thrust into the spotlight by the recurring novel human coronavirus infections following the 2003 SARS pandemic. In the years since the initial SARS outbreak, the arsenal to fight this virus family has been significantly increased by the rapid growth of coronavirus research. Among the potential viral drug targets, coronavirus 3C like proteases (3Cl) have emerged as the most popular drug target. A number of patented inhibitors with promising clinical potential have been developed via different methods of drug discovery, including virtual screening, natural product isolation and structure assisted rational drug design. This review serves as a summary of the progress in both the method of drug discovery and the related inhibitors against the coronavirus 3Cl protease.


High local concentrations without systemic adverse effects after impaction of netilmicin-impregnated bone.
When cancellous bone is impregnated with antibiotics the subsequent release of antibiotics from the bone shows a high early release. Hence, impaction of large amounts of netilmicin-impregnated bone may cause toxic netilmicin values in serum. We studied kidney and otovestibular function after impacting 50 g of netilmicin-impregnated cancellous bone during revision hip or knee arthroplasty in 20 patients. The bone was impacted in the acetabulum (n = 8), proximal femur (n = 9) and distal femur/proximal tibia (n = 3). Serum creatinine concentration was measured and audiometry was performed before and after the operation. Netilmicin concentrations in serum, joint fluid, and in urine were recorded postoperatively at regular intervals. We analyzed pharmacokinetics in two study groups receiving bone impregnated with netilmicin (50 mL), at either 50 mg netilmicin/mL (group I) or 100 mg netilmicin/mL (group II). Neither netilmicin-induced renal toxicity, nor otovestibular toxicity was registered. Peak serum netilmicin values in group I and group II were 0.9 (0.5-1.3) mg/L and 1.8 (0.6-4.0) mg/L, respectively (p = 0.04). Peak netilmicin concentrations in wound drainage fluid in group I and group II were 237 (9-647) mg/L and 561 (196-1132) mg/L, respectively (p = 0.01). In both groups, netilmicin was recovered in urine samples for approximately 4 weeks. 50 grams of cancellous bone impregnated with 100 mg/mL netilmicin solution was impacted in the hip or knee joint with no adverse effects. Extremely high local concentrations of netilmicin in joint fluid were recorded postoperatively. The use of antibioitic-impregnated cancellous could be an option when performing revision of hip and knee prostheses.


Investigating the Effect of Medium Chain Triglycerides on the Elasticity of Pulmonary Surfactant.
In recent years, vaping has increased in both popularity and ease of access. This has led to an outbreak of a relatively new condition known as e-cigarette/vaping-associated lung injury (EVALI). This injury can be caused by physical interactions between the pulmonary surfactant (PS) in the lungs and toxins typically found in vaping solutions, such as medium chain triglycerides (MCT). MCT has been largely used as a carrier agent within many cannabis products commercially available on the market. Pulmonary surfactant ensures proper respiration by maintaining low surface tensions and interface stability throughout each respiratory cycle. Therefore, any impediments to this system that negatively affect the efficacy of this function will have a strong hindrance on the individual's quality of life. Herein, neutron spin echo (NSE) and Langmuir trough rheology were used to probe the effects of MCT on the mechanical properties of pulmonary surfactant. Alongside a porcine surfactant extract, two lipid-only mimics of progressing complexity were used to study MCT effects in a range of systems that are representative of endogenous surfactant. MCT was shown to have a greater biophysical effect on bilayer systems compared to monolayers, which may align with biological data to propose a mechanism of surfactant inhibition by MCT oil.


Analysis of remote synchronization in complex networks.
A novel regime of synchronization, called remote synchronization, where the peripheral nodes form a phase synchronized cluster not including the hub, was recently observed in star motifs [Bergner et al., Phys. Rev. E 85, 026208 (2012)]. We show the existence of a more general dynamical state of remote synchronization in arbitrary networks of coupled oscillators. This state is characterized by the synchronization of pairs of nodes that are not directly connected via a physical link or any sequence of synchronized nodes. This phenomenon is almost negligible in networks of phase oscillators as its underlying mechanism is the modulation of the amplitude of those intermediary nodes between the remotely synchronized units. Our findings thus show the ubiquity and robustness of these states and bridge the gap from their recent observation in simple toy graphs to complex networks.


Effect of cerebrocrast, a new long-acting compound on blood glucose and insulin levels in rats when administered before and after STZ-induced diabetes mellitus.
Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by selective destruction of insulin secreting pancreatic islets beta-cells. The formation of cytokines (IL-1beta, IL-6, TNF-alpha, etc.) leads to extensive morphological damage of beta-cells, DNA fragmentation, decrease of glucose oxidation, impaired glucose-insulin secretion and decreased insulin action and proinsulin biosynthesis. We examined the protective effect of a 1,4-dihydropyridine (DHP) derivative cerebrocrast (synthesized in the Latvian Institute of Organic Synthesis) on pancreatic beta-cells in rats possessing diabetes induced with the autoimmunogenic compound streptozotocin (STZ). Cerebrocrast administration at doses of 0.05 and 0.5 mg/kg body weight (p.o.) 1 h or 3 days prior to STZ as well as at 24 and 48 h after STZ administration partially prevented pancreatic beta-cells from the toxic effects of STZ, and delayed the development of hyperglycaemia. Administration of cerebrocrast starting 48 h after STZ-induced diabetes in rats for 3 consecutive days at doses of 0.05 and 0.5 mg/kg body weight (p.o.) significantly decreased blood glucose level, and the effect remained 10 days after the last administration. Moreover, in these rats, cerebrocrast evoked an increase of serum immunoreactive insulin (IRI) level during 7 diabetic days as compared to both the control normal rats and the STZ-induced diabetic control rats. The STZ-induced diabetic rats that received cerebrocrast had a significantly high serum IRI level from the 14th to 21st diabetic days in comparison with the STZ-induced diabetic control. The IRI level in serum as well as the glucose disposal rate were significantly increased after stimulation of pancreatic beta-cells with glucose in normal rats that received cerebrocrast, administered 60 min before glucose. Glucose disposal rate in STZ-induced diabetic rats as a result of cerebrocrast administration was also increased in comparison with STZ-diabetic control rats. Administration of cerebrocrast in combination with insulin intensified the effect of insulin. The hypoglycaemic effect of cerebrocrast primarily can be explained by its immunomodulative properties. Moreover, cerebrocrast can act through extrapancreatic mechanisms that favour the expression of glucose transporters, de novo insulin receptors formation in several cell membranes as well as glucose uptake.


Percutaneous ablation for atrial fibrillation: the role of cross-sectional imaging.
Percutaneous ablation is a well-established technique for treating cardiac arrhythmia by removing or isolating tissue at the site of the abnormal impulse formation. Various forms of energy for ablation procedures may be delivered via a catheter with fluoroscopic guidance. The procedures most commonly performed are radiofrequency ablation and cryotherapy. Atrial fibrillation, the most frequently occurring supraventricular tachyarrhythmia, may be initiated by ectopic beats that originate in the ostia of the pulmonary veins. The clinical efficacy of isolation (or focal ablation) of the pulmonary veins for treatment of atrial fibrillation has been well demonstrated. Pre- and postprocedural examinations with computed tomography (CT) or magnetic resonance (MR) imaging are frequently performed to depict the anatomy and to obtain baseline measurements of the pulmonary veins to enable early detection of complications from ablation. Venous stenosis or thrombosis and pulmonary hypertension may occur after radio-frequency ablation. Familiarity with the appearance of normal anatomic variants at CT and MR imaging and with the normal range of pulmonary vein diameters is essential for preoperative management and early detection of procedure-related complications.


Voltage dependence of ATP secretion in mammalian taste cells.
Mammalian type II taste cells release the afferent neurotransmitter adenosine triphosphate (ATP) through ATP-permeable ion channels, most likely to be connexin (Cx) and/or pannexin hemichannels. Here, we show that ion channels responsible for voltage-gated (VG) outward currents in type II cells are ATP permeable and demonstrate a strong correlation between the magnitude of the VG current and the intensity of ATP release. These findings suggest that slowly deactivating ion channels transporting the VG outward currents can also mediate ATP secretion in type II cells. In line with this inference, we studied a dependence of ATP secretion on membrane voltage with a cellular ATP sensor using different pulse protocols. These were designed on the basis of predictions of a model of voltage-dependent transient ATP efflux. Consistently with curves that were simulated for ATP release mediated by ATP-permeable channels deactivating slowly, the bell-like and Langmuir isotherm-like potential dependencies were characteristic of ATP secretion obtained for prolonged and short electrical stimulations of taste cells, respectively. These observations strongly support the idea that ATP is primarily released via slowly deactivating channels. Depolarizing voltage pulses produced negligible Ca(2+) transients in the cytoplasm of cells releasing ATP, suggesting that ATP secretion is mainly governed by membrane voltage under our recording conditions. With the proviso that natural connexons and pannexons are kinetically similar to exogenously expressed hemichannels, our findings suggest that VG ATP release in type II cells is primarily mediated by Cx hemichannels.


A Self-assessment Tool for Screening Young Adults at Risk of Type 2 Diabetes Using Strong Heart Family Study Data.
The purpose of this study is to characterize risk factors associated with type 2 diabetes in young adults aged 18 to 29 years to develop a noninvasive risk assessment tool for use with younger American populations. The self-assessment tool was developed with the Strong Heart Family Study data. A total of 590 young American Indian adults (242 men) who had normoglycemia and were not receiving diabetes treatment were included. Risk factors recommended by the American Diabetes Association were used to assess diabetes risk in these young adults. A logistic regression model was developed to calculate the predicted probability. The area under the receiver operating characteristic curve was used to evaluate the model. The final model showed that parental history of diabetes, obesity level, alcohol consumption, and high fasting glucose, even within normal range, were significantly associated with onset of prediabetes/diabetes in 5 years. The area under the receiver operating characteristic curve value was 0.68 with original and validated data, indicating that the risk assessment tool had reasonably good discrimination ability. This new noninvasive screening tool, based on data from American Indian young adults, has potential to screen young adults' early-onset diabetes risk. Future studies are warranted to test this risk assessment tool in other racial/ethnic young adults.


Accuracy of genomic selection for age at puberty in a multi-breed population of tropically adapted beef cattle.
Genomic selection is becoming a standard tool in livestock breeding programs, particularly for traits that are hard to measure. Accuracy of genomic selection can be improved by increasing the quantity and quality of data and potentially by improving analytical methods. Adding genotypes and phenotypes from additional breeds or crosses often improves the accuracy of genomic predictions but requires specific methodology. A model was developed to incorporate breed composition estimated from genotypes into genomic selection models. This method was applied to age at puberty data in female beef cattle (as estimated from age at first observation of a corpus luteum) from a mix of Brahman and Tropical Composite beef cattle. In this dataset, the new model incorporating breed composition did not increase the accuracy of genomic selection. However, the breeding values exhibited slightly less bias (as assessed by deviation of regression of phenotype on genomic breeding values from the expected value of 1). Adding additional Brahman animals to the Tropical Composite analysis increased the accuracy of genomic predictions and did not affect the accuracy of the Brahman predictions.


Automated protein sequence database classification. I. Integration of compositional similarity search, local similarity search, and multiple sequence alignment.
Genome sequencing projects require the periodic application of analysis tools that can classify and multiply align related protein sequence domains. Full automation of this task requires an efficient integration of similarity and alignment techniques. We have developed a fully automated process that classifies entire protein sequence databases, resulting in alignment of the homologous sequences. The successive steps of the procedure are based on compositional and local sequence similarity searches followed by multiple sequence alignments. Global similarities are detected from the pairwise comparison of amino acid and dipeptide compositions of each protein. After the elimination of all but one sequence from each detected cluster of closely related proteins, the remaining sequences are compiled in a suffix tree which is self-compared to detect local sequence similarities. Sets of proteins which share similar sequence segments are then weighted according to their closeness and multiply aligned using a fast hierarchical dynamic programming algorithm. Computational strategies were devised to minimize computer processing time and memory space requirements. The accuracy of the sequence classifications has been evaluated for 12 462 primary structures distributed over 341 known families. The percentage of sequences with missed or incorrect family assignments was 6.8% on the test set. This low error level is only twice that of the manually constructed PROSITE database ( 3.4% ) and is substantially better than that found for the automatically built PRODOM database ( 34.9% ). The resulting database, called DOMO, is available through database search routine SRS at Infobiogen (http://www.infobiogen.fr/srs5/), EBI (http://srs.ebi.ac.uk:5000/) and EMBL (http://www.embl-heidelberg.de/srs5/) World Wide Web sites. email@example.com


Dysfunction of mitochondrial Lon protease and identification of oxidized protein in mouse brain following exposure to MPTP: Implications for Parkinson disease.
Compelling evidence suggests that mitochondrial dysfunction leading to reactive oxygen species (ROS) production and protein oxidation could represent a critical event in the pathogenesis of Parkinson's disease (PD). Pioneering studies have shown that the mitochondrial matrix contains the Lon protease, which degrades oxidized, dysfunctional, and misfolded protein. Using the PD animal model of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxication in mice, we showed that Lon protease expression increased in the ventral mesencephalon of intoxicated animals, concomitantly with the appearance of oxidized proteins and dopaminergic cell loss. In addition, we report that Lon is inactivated by ROS. Moreover, proteomic experiments provide evidence of carbonylation in α-ketoglutarate dehydrogenase (KGDH), aconitase or subunits of respiratory chain complexes. Lon protease inactivation upon MPTP treatment in mice raises the possibility that Lon protease dysfunction is an early event in the pathogenesis of PD.


Properties of Cement-Based Composites Modified with Magnetite Nanoparticles: A Review.
Despite the many available studies on the evaluation of the influence of nanomaterials on the properties of cement-based composites, the effects of some nanoparticles have not yet been fully recognized. Among the unrecognized nanomaterials are magnetite nanoparticles (MN). The literature devoted to this subject is limited. This paper reviews state-of-the-art research carried out on the effect of MN on the properties of cement-based composites. Detailed descriptions of the processing, microstructures (hydration products), properties (hydration, workability, mechanical and functional properties, and durability), and probability applications of MN-engineered cementitious composites are presented. Particular attention has been paid to MN application methods to the cement composite. Finally, the risks, challenges, and future development of MN-modified cement-based composites is discussed.


[Mucinous tubular and spindle-cell carcinoma of the kidney].
4 cases (2 males and 2 females) of mucinous tubular and spindle-cell carcinoma of the kidney were studied. The patients' age was 43 to 87 years. Microscopically, this tumor comprised two major cell populations. One of them involved spindle cells with a sparse cytoplasm, which were arranged in the fascicular pattern, often resembling low-grade smooth muscle tumors. The other population was small cuboidal cells with round nuclei and an eosinophilic cytoplasm. The mitotic activity was low. Only one tumor had both cell components. The other three tumors were represented by the second type cells. Immunohistochemical staining with avidin-biotin was performed by using cytokeratin, vimentin, SMA, p53, Bcl 2, EMA, and CD10. All cases were stained positively with antibodies to the cytokeratins AE1-AE2 and vimentin. The expression of EMA, Bcl 2, and CK7 was varying in different tumors. Responses to smooth muscle actin, p53, CK20, and CD10 were negative in all cases. Mucinous tubular and spindle-cell carcinoma of the kidney should be differentiated from angiomyolipoma with the preponderance of a leiomyomatous component, renal smooth muscle neoplasms, metanephrotic adenoma, and renal cell carcinoma with sarcomatoid differentiation.


Relationship of strain magnitude to morphological variation in the primate skull.
In a comparative study of variation in primate skulls, Wood and Lieberman ([2001] Am. J. Phys. Anthropol. 116:13-25) proposed that a predictable relationship exists between in vivo bone-strain magnitudes and the extent of morphological variation in skeletal structures. They hypothesized that regions subject to high strains are prone to enhanced levels of variation. Three questions are posed with respect to the plausibility of this hypothesis. First, does the proposed relationship hold at different levels of analysis (e.g., for more restricted anatomical regions in which large strain gradients are present)? Second, is the biomechanical rationale for the hypothesis sound, given the current understanding of bone biology? Third, is the hypothesis obviated by consideration of the functional matrix concept of skull development, in which osseous growth is posited to be governed by surrounding soft tissues (e.g., muscle and tendon) and developing spaces (e.g., the nasal capsule)? The different perspectives explored by these questions suggest that the validity of the hypothesis, despite having a defensible theoretical rationale, is likely to be context-specific. A direct role for strain magnitude in conditioning morphological variation is difficult to demonstrate either comparatively or theoretically, and it is unlikely that a single strain threshold or interval can be directly associated with elevated variation in the skeleton. The conceptual framework of the functional matrix (which allows for independent growth among different regions of the skull) conceivably contravenes the premise of a uniform relationship of strain magnitude to morphological variability.


Iron therapy in iron-deficiency patients with heart failure with preserved ejection fraction: A protocol for meta-analysis.
Nearly half of patients with heart failure (HF) have preserved ejection fraction (EF) and the mortality and morbidity of patients with HF with preserved EF (HFpEF) are high. However, there is no established therapy to improve survival in these patients. HFpEF patients are often elderly and their primary chronic symptom is severe exercise intolerance. Thus, improvement of exercise capacity presents another important clinical outcome in HFpEF patients. Iron deficiency is common in HF patients, and the presence of iron deficiency, regardless of concomitant anemia, is associated with worse symptoms, impaired exercise capacity, and higher mortality and hospitalization in these patients. Several meta-analyses of randomized controlled trials reported that iron administration improved HF symptoms, exercise capacity, and clinical outcomes in iron-deficiency patients with HF with reduced EF. However, there is insufficient evidence as to the effect of iron administration in iron-deficiency HFpEF patients. This meta-analysis will include randomized controlled trials on the effects of iron administration on HF symptoms, exercise capacity, and health-related quality of life in iron-deficiency HFpEF patients. Information of studies will be collected from PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov. The primary outcome will be exercise capacity (6-minute walking distance). The secondary outcomes will be HF symptoms, health-related quality of life, and mortality and hospitalization rates. This meta-analysis will evaluate the effect of iron therapy in iron-deficiency HFpEF patients, providing evidence as to the iron administration in these patients. PROSPERO CRD42020205297.


Separation of chiral enantiomers by optical force and torque induced by tightly focused vector polarized hollow beams.
Enantioseparation is important for biology, chemistry and even pharmaceutical industries. We propose an approach for discriminating and separating chiral enantiomers by tightly focused vector polarized hollow beams, which possess a transverse spin angular momentum that can rotate the chiral particles along the transverse direction. We demonstrate the different optomechanical behaviours of the particles upon illumination with different vector polarized (azimuthally and radially) hollow beams by numerically calculating the optical force and spin torque. It is believed that this interesting approach may have potential applications in enantioseparation due to its simplicity and accessibility.


[Livedo reticularis and cerebrovascular accidents].
The authors report the case of three middle-aged women admitted to the hospital because of cerebro-vascular accidents, in whom examination disclosed idiopathic livedo reticularis. This association has only been described recently, but does not seem fortuitous; some of the clinical manifestations are characteristic, but the histology is usually nonspecific and the basic abnormality remains unknown. The main problem is prognostic and therapeutic. In an attempt to prevent the neurological defects, tobacco and contraception should not be permitted to female patients showing widespread acquired livedo reticularis; high blood-pressure should be treated systematically.


Biological parameters, discolouration and radiopacity of calcium silicate-based materials in a simulated model of partial pulpotomy.
To analyse the discolouration, radiopacity, pH and calcium ion release of Biodentine (BD), Bio-C repair (BCR) and Bio-C temp (BCT), as well as their biological effects on human dental pulp cells (hDPCs). Sixty-four extracted bovine incisors were prepared to simulate crown fractures with pulp exposure and open root apex. The roots were filled using a mixture of agar and blood (control), and BD, BCR or BCT were placed over this mixture. Colour assessment analyses of the samples were performed before and immediately after material insertion and repeated at 30 and 90 days, using a spectrophotometer. The colour change of each specimen was evaluated at the crown and calculated based on the CIELab colour space. Digital radiographs were acquired for radiopacity analysis. hDPCs were placed in contact with different dilutions of culture media previously exposed to such materials and tested for cell viability using the MTT assay. The pH and calcium ion release of all materials were measured after 24 h; the data were assessed using one-way analysis of variance (ANOVA). Cell viability was analysed by two-way ANOVA. Differences in colour parameters and wound-healing data were assessed by two-way repeated measures ANOVA (α = 0.05). Tukey's and Dunnett's tests were used to compare the experimental groups with the control group. BCR had grater radiopacity and smaller colour alteration (ΔEab/ΔE00) than the other materials tested (p < .005; p < .001). No significant differences in pH were found amongst the tested materials (p > .05). BCT was associated with the largest release of calcium ions (p < .0001). BD had cell viability similar to that of the control at the lowest dilutions, and BCR was similar to that of the control, regardless of the dilution tested (p > .05). BCT had a lower percentage of viability than that of the control at all tested dilutions (p < .0001). Cell migration rates in BD and BCR were similar to those in the control group after 24 h and 48 h (p > .05), whilst BCT had larger voids than the control in both periods (p < .0001). BCR, BCT and BD were associated with tooth discolouration. BCR had the lowest staining values, the highest radiopacity and viability greater than 80% hDPCs.


An EMR-based tool to support collaborative planning for medication use among adults with diabetes: design of a multi-site randomized control trial.
Patients with type II diabetes often struggle with self-care, including adhering to complex medication regimens and managing their blood glucose levels. Medication nonadherence in this population reflects many factors, including a gap between the demands of taking medication and the limited literacy and cognitive resources that many patients bring to this task. This gap is exacerbated by a lack of health system support, such as inadequate patient-provider collaboration. The goal of our project is to improve self-management of medications and related health outcomes by providing system support. The Medtable™ is an Electronic Medical Record (EMR)-integrated tool designed to support patient-provider collaboration needed for medication management. It helps providers and patients work together to create effective medication schedules that are easy to implement. We describe the development and initial evaluation of the tool, as well as the process of integrating it with an EMR system in general internal medicine clinics. A planned evaluation study will investigate whether an intervention centered on the Medtable™ improves medication knowledge, adherence, and health outcomes relative to a usual care control condition among type II diabetic patients struggling to manage multiple medications.


In-vivo evaluation of the "HIA-VAD": a new German ventricular assist device.
Helmholtz Ventricular Assist Devices (VAD) are pneumatically driven polyurethane membrane pumps with various volumes. The pumps are placed paracorporeally and connected with commercially available cannulas between the left atrium and aorta (left ventricular assist device) and/or right atrium and pulmonary artery (right ventricular assist device, bi-ventricular assist device). The pumps can be driven with a stand-alone driving system or with a Helmholtz IABP-console interface. Seventeen animal experiments (on calves) with Helmholtz VAD's were performed to evaluate experimental protocols, to optimize surgical techniques, and to improve design and manufacturing techniques. Blood chemistry and cell counts demonstrated that the tested HIA-70 produces low mechanical blood damage. In the course of the animal experiments the Helmholtz VAD's were made totally transparent, whereby they became easy to de-air, efficient, and affordable.


Distinct inflammatory signatures of upper and lower body adipose tissue and adipocytes in women with normal weight or obesity.
Upper and lower body fat accumulation poses an opposing obesity-related cardiometabolic disease risk. Depot-differences in subcutaneous adipose tissue (SAT) function may underlie these associations. We aimed to investigate the inflammatory signatures of abdominal (ABD) and femoral (FEM) SAT in postmenopausal women with normal weight or obesity. We included 23 postmenopausal women with normal weight (n = 13) or obesity (n = 10). In vivo secretion of adipokines from ABD and FEM SAT was measured using the arterio-venous balance technique. Adipokine gene expression and adipocyte morphology were examined in ABD and FEM SAT. Furthermore, adipokine expression and secretion were investigated in vitro using differentiated human primary ABD and FEM subcutaneous adipocytes derived from the study participants. Plasma leptin and plasminogen activator inhibitor (PAI)-1 concentrations were higher, and ABD and FEM adipocytes were larger in women with obesity than normal weight. No differences in adipocyte size and blood flow were apparent between ABD and FEM SAT. We found significant release of leptin and monocyte chemoattractant protein (MCP)-1 from ABD and FEM SAT, with higher fractional release of MCP-1 from ABD than FEM SAT. Gene expression of leptin, PAI-1, and tumor necrosis factor-α was lower in ABD than FEM SAT and higher in women with obesity than normal weight. In ABD adipocytes, interleukin-6, PAI-1, and leptin gene expression were higher, while adiponectin and dipeptidyl-peptidase-4 gene expression were lower than in FEM adipocytes. Finally, ABD adipocytes secreted less MCP-1 compared to FEM adipocytes. These findings demonstrate that upper and lower body SAT and adipocytes are characterized by distinct inflammatory signatures in postmenopausal women, which seem independent of adipocyte size.


Collision tumor of kidney: A case of renal cell carcinoma with metastases of prostatic adenocarcinoma.
Simultaneous occurrence of prostatic adenocarcinoma and renal cell carcinoma is well documented in the literature. However, metastatic prostatic adenocarcinoma in a kidney harboring a renal cell carcinoma (RCC) is quite rare. Although renal cell carcinoma is the most common tumor that can harbor metastasis, metastatic prostatic adenocarcinoma in a kidney harboring a RCC is quite rare. There are four cases in the literature showing metastasis of prostatic adenocarcinoma to RCC. However, as per our knowledge, this is the first case of a collision between RCC and metastatic prostatic adenocarcinoma.


Poverty, Health Care Access Barriers, and Functional Limitations among Individuals with Chronic Obstructive Pulmonary Disease: An 11-Year Cross-sectional Analysis, 2008-2018.
To assess the relationship between poverty, delayed care, unaffordable care, and functional limitations among individuals with chronic obstructive pulmonary disease (COPD). Using the National Health Interview Survey data, we selected respondents with COPD, aged 40 years and older. The predictor variables were poverty and measures of delayed and unaffordable care. The outcome variable was functional limitations. We performed a survey-weighted multivariate logistic regression analysis, adjusting for sociodemographic characteristics. Respondents classified as poor had three times the odds of functional limitations compared with those classified as not poor. Respondents who reported having measures of delayed care or unaffordable care had two to nine times and two to four times the adjusted odds of functional limitations compared with those who did not report such measures of delayed and unaffordable care, respectively. Poverty and delayed and unaffordable care are associated with functional limitations among individuals with COPD.


Cold weather field evaluation of the 18-Man Arctic Tray Pack Ration Module, the meal, ready-to-eat, and the Long Life Ration Packet.
The Army Field Feeding System was evaluated for its ability to provide adequate nutrition and hydration during a 10-day cold weather field exercise. Soldiers consumed the 18-Man Arctic Tray Pack Ratio Module with either a wet-pack (Meal, Ready-to-Eat) or a dehydrated (Long Life Ration Packet) individual ration. Both feeding regimens were acceptable, meeting protein and micronutrients requirements. However, the soldiers consumed only 70% of their energy requirement, thus losing an average of 0.9% of body weight. This weight loss, although not excessive, underscores the importance of maintaining an adequate food intake during extended cold weather military field operations.


Serial Backward Locomotor Treadmill Training Improves Bidirectional Walking Performance in Chronic Stroke.
Walking impairment remains a major limitation to functional independence after stroke. Yet, comprehensive and effective strategies to improve walking function after stroke are presently limited. Backward Locomotor Treadmill Training (BLTT) is a promising training approach for improving walking function; however, little is known about its mechanism of effect or the relationship between backward walking training and resulting overground forward walking performance. This study aims to determine the effects of serial BLTT on spatial aspects of backward and forward walking in chronic post-stroke individuals with residual walking impairment. Thirty-nine adults (>6 months post-stroke) underwent 6 days of BLTT (3 × /week) over 2 weeks. Outcome measures included PRE-POST changes in backward and forward walking speeds, paretic and non-paretic step lengths, and single-support center of pressure distances. To determine the association between BLTT and overground walking, correlation analyses comparing training-related changes in these variables were performed. We report an overall improvement in BLTT and overground walking speeds, bilateral step lengths, and single-support center of pressure distances over six training sessions. Further, there were weak positive associations between PRE-POST changes in BLTT speed, BLTT paretic step length, and overground forward walking speed. Our findings suggest that individuals with chronic post-stroke walking impairment experience improvements in spatial walking measures during BLTT and overground. Therefore, BLTT may be a potential adjunctive training approach for post-stroke walking rehabilitation.


Oral activity of ether lipid ester prodrugs of cidofovir against experimental human cytomegalovirus infection.
Infection with human cytomegalovirus (HCMV) can cause serious complications in bone-marrow and solid-organ transplant recipients, and current therapies are not optimal. We evaluated 2 orally active ether lipid ester analogues of cidofovir (CDV)--hexadecyloxypropyl-CDV (HDP-CDV) and octadecyloxyethyl-CVD (ODE-CDV)--in severe combined immunodeficient mice in which either human fetal retinal tissue or human fetal thymus and liver tissue had been implanted and was later infected with HCMV. Our results indicate that orally administered treatment with either HDP-CDV or ODE-CDV is 4-8-fold more active, on a molar basis, than is intraperitoneally administered CDV. These data suggest that HDP-CDV and ODE-CDV should be further evaluated as potential antiviral agents for treatment of HCMV infection.


[A study on the preparing of magnetic doxorubicin nanoparticles and its heat effect under a magnetic field].
The aim of this research report is to introduce a method of making Doxorubicin magnetic nanoparticles for tumor treatment and to evaluate its heat effect under 100 KHz magnetic field. The preparing of the nanoparticles was carried out by stirring with supersonic mixer and cold drying. The shape and diameter of the nanoparticles were observed by penetrating electron microscopy. The nanoparticles were spherical in shape, and most of them were 200 nm in diameter. The changes of the temperature under a magnetic field in agarose gel and distilled water were measured respectively. The temperature went up with the increase of the amount of nanoparticles and the magnetic field intensity. The temperature finally remained constant due to the balance of heat generation and its transfer to the surroundings. The heat transfer was faster in water in the agarose gel.