Severe diabetic nephropathy in type 1 diabetes and pregnancy--a case series.
Diabetes and nephropathy are important challenges during pregnancy, increasingly encountered because of the advances in maternal-fetal care. To evaluate the maternal and fetal outcomes recorded in "severe" diabetic nephropathy in type 1 diabetic patients referred to nephrological healtcare. The study was performed in an outpatient unit dedicated to kidney diseases in pregnancy (with joint nephrological and obstetric follow-up and strict cooperation with the diabetes unit). 383 pregnancies were referred to the outpatient unit in 2000-2012, 14 of which were complicated by type 1 diabetes. The report includes 12 deliveries, including 2 pregnancies in 1 patient; one twin pregnancy; 2 spontaneous abortions were not included. All cases had long-standing type 1 diabetes (median of 21 (15-31) years), relatively high median age (35 (29-40) years) and end-organ damage (all patients presented laser-treated retinopathy and half of them clinical neuropathy). Median glomerular filtration rate (GFR) at referral was 67 ml/min (48-122.6), proteinuria was 1.6 g/day (0.1-6.3 g/day). Proteinuria steeply increased in 11/12 patients, reaching the nephrotic range in nine (6 above 5 g/day). One patient increased by 2 chronic kidney disease (CKD) stages. Support therapy included blood pressure and diabetes control, bed rest, and moderate protein restriction. All children were preterm (7 early preterm); early spontaneous labor occurred in 4/12 patients. All singletons were appropriate for gestational age and developed normally after birth. The male twin child died 6 days after birth (after surgery for great vessel transposition). Diabetic patients with severe diabetic nephropathy are still present a considerable challenge. Therefore, further investigations are required, particularly on proteinuria management and the occurrence of spontaneous labor.


[Cell-associated complement regulatory proteins and their relation to disease processes].
C3-deposition is a key step for activation of the complement system, which involves C9-mediated immunocytolysis, immunoadherence, C3 receptor-mediated phagocytosis, NK potentiation, anaphylatoxin release, and amplification of C3 activation. Foreign material is eliminated even in the preimmune stage by these complement functions. Self cells, on the other hand, must circumvent the C3-attack, so that they express complement regulatory proteins, namely C3b/C4b receptor (CR1, CD35), decay-accelerating factor (DAF, CD55), membrane cofactor protein (MCP, CD46). We herein review the properties of these regulatory proteins and discuss the relationships between disease processes and the aberrance of these regulatory proteins.


Lipopolysaccharide-induced human enterocyte tolerance to cytokine-mediated interleukin-8 production may occur independently of TLR-4/MD-2 signaling.
Intestinal epithelial cells (IEC) are constantly exposed to bacterial components, such as LPS, without triggering proinflammatory immune responses. This study demonstrates that chronic exposure of human-derived IEC to LPS induces tolerance to an endogenous inflammatory cytokine (IL-1beta) activated IL-8 response that occurs independently of TLR-4/MD-2 signaling. IL-8 production in response to activation by unrelated TNF-alpha and PMA signaling pathways is also inhibited, indicating a broad-spanning tolerance. Quantitative rtPCR and IL-8 promoter-luciferase assays demonstrate that tolerance is regulated at the transcriptional level and occurs independently of IEC cytodifferentiation. By contrast, LPS does not significantly alter other proinflammatory signaling cascades in IEC that function independently of IL-8 production, e.g., IL-6 secretion and PEEC (Hepoxilin A3)-induced neutrophil transepithelial migration in response to invasive Salmonella typhimurium. Human IEC have therefore developed LPS-induced signaling cascades that promote an IL-8 hyporesponsiveness to proinflammatory cytokines while LPS exposure does not compromise the ability of IEC to mount other proinflammatory immune responses to invasive enteropathogens.


Capillarity-like growth of protein folding nuclei.
A full structural description of transition state ensembles in protein folding includes the specificity of the ordered residues composing the folding nucleus as well as spatial density. To our knowledge, the spatial properties of the folding nucleus and interface of specific nuclei have yet to receive significant attention. We analyze folding routes predicted by a variational model in terms of a generalized formalism of the capillarity scaling theory that assumes the volume of the folded core of the nucleus grows with chain length as V(f) approximately N(3nu). For 27 two-state proteins studied, the scaling exponent nu ranges from 0.2 to 0.45 with an average of 0.33. This average value corresponds to packing of rigid objects, although generally the effective monomer size in the folded core is larger than the corresponding volume per particle in the native-state ensemble. That is, on average, the folded core of the nucleus is found to be relatively diffuse. We also study the growth of the folding nucleus and interface along the folding route in terms of the density or packing fraction. The evolution of the folded core and interface regions can be classified into three patterns of growth depending on how the growth of the folded core is balanced by changes in density of the interface. Finally, we quantify the diffuse versus polarized structure of the critical nucleus through direct calculation of the packing fraction of the folded core and interface regions. Our results support the general picture of describing protein folding as the capillarity-like growth of folding nuclei.


An outbreak of visceral white nodules disease caused by Pseudomonas plecoglossicida at a water temperature of 12°C in cultured large yellow croaker (Larimichthys crocea) in China.
Visceral white nodules disease (VWND) caused by Pseudomonas plecoglossicida is a common disease in cage-farmed large yellow croaker (Larimichthys crocea) in China. VWND usually occurred at water temperature of 16-19℃, resulting in high mortality in farmed large yellow croaker. Now, P. plecoglossicida as its pathogen has been considered nonpathogenic at 7-12℃. During February 2019, an infectious disease outbreak was observed in cage-farmed large yellow croaker at a water temperature of 12℃ in Ningde, China. This disease is characterized by white granulomatous lesions in internal organs of the diseased fish, which was similar with the symptoms of the VWND in large yellow croaker. Then, we isolated a bacterial strain named PQLYC4 from visceral lesions of the diseased fish. The experimental infection studies demonstrated that the strain PQLYC4 was the pathogen of the disease, which was further identified as P. plecoglossicida by the analysis of morphology, 16s rRNA gene homology and average nucleotide identity based on the whole genome sequence. Our results revealed that P. plecoglossicida strain PQLYC4 could cause the outbreak of the VWND at 12℃, a water temperature lower than that reported previously, thus providing new knowledges of prevalence and prevention of the VWND in large yellow croaker.


Longitudinal Relationships of Fitness, Physical Activity, and Weight Status With Academic Achievement in Adolescents.
To examine associations of cardiorespiratory fitness, physical activity (PA) and weight status with academic achievement 1 year later. In addition, the mediating role of psychological variables was tested. Longitudinal analyses included 1011 German students (M = 14.1 years, SD = 0.6 years). Cardiorespiratory fitness was determined with the 20 m shuttle run test. Compliance with PA guidelines was assessed through questionnaire. Weight status was based on body mass index percentiles. As proxy of academic achievement students' self-reported grades in Mathematics and German in their midterm report were averaged. Mediation analyses were conducted at follow-up testing general self-efficacy, depressed affect, and attention/hyperactivity problems. High levels of cardiorespiratory fitness predicted higher educational attainment (p = .007), while we found no longitudinal association for PA and weight status (p > .253). However, students being insufficiently physically active at baseline but meet PA guidelines at follow-up showed a significant improvement in educational attainment. The cross-sectional association between PA and academic achievement was mediated by students' general self-efficacy. High fitness in adolescence is associated with higher subsequent academic achievement. The promotion of PA might benefit school performance because of enhanced fitness levels in the long-term and positive influences of PA in the shortterm. The association between weight status and educational attainment remains controversial.


Skin problems associated with pegylated liposomal doxorubicin-more than palmoplantar erythrodysesthesia syndrome.
Liposomal pegylated doxorubicin is an encapsulation form of doxorubicin, with an improved pharmacokinetic profile and the ability to selectively accumulate into tumor tissue. As a result, the tolerated dose of the drug can be increased, followed by a reduced incidence of neutropenia and cardiotoxicity in comparison to doxorubucin treatment. However, a common adverse dose-schedule limiting effect of the treatment is palmoplantar erythrodysesthesia syndrome. In this retrospective study we included six patients hospitalised in the University Hospital of Zurich during the last 2 years, in connection with side effects caused by pegylated liposomal doxorubicin. These patients received this chemotherapeutic agent for treatment of various malignancies such as breast cancer, ovarian cancer, mycosis fungoides and cutaneous B-cell lymphoma. Three of six patients in this study developed classical palmoplantar erythrodysesthesia, one developed palmoplantar erythrodysesthesia associated with extensive bullous disease, one developed eruption of lymphocyte recovery syndrome and one developed intertrigo like dermatitis with stomatitis. Pegylated liposomal doxorubicin induces various skin reactions including palmoplantar erythrodysesthesia syndrome. However, the exact clinical presentation might depend on pre-existing skin diseases.


Global and reflective rumination are related to suicide attempts among patients experiencing major depressive episodes.
Recent attention has focused on the role of rumination in suicidality, with evidence indicating that rumination may be positively related to suicidal ideation. There remains disagreement on the nature of the relationship between rumination and suicide attempts, especially in major affective disorders. This study was designed to identify whether rumination is a risk factor for attempted suicide. A total of 309 patients with major depressive episodes were recruited for this study, including 170 patients with major depression and 139 patients with bipolar disorder. All participants were categorized into two groups based on a series of clinical assessments: suicide attempters (n = 87) and non-suicide attempters (n = 222). Rumination was evaluated with the Ruminative Responses Scale. A binary logistic regression analysis was carried out to evaluate the relationship between rumination and suicide attempts. Both global ruminative levels and the two subtypes of rumination, brooding and reflection, were significantly higher in the suicide attempters than the non-suicide attempters. After controlling for age, current depression and anxiety symptoms, and episode frequency, it was found that global rumination and reflection (but not brooding) were positively associated with suicide attempts. These results suggest that rumination may be a risk factor for suicide attempts and highlight the maladaptive nature of reflection in patients with major depressive episodes.


The changing epidemiology of SARS-CoV-2.
We have come a long way since the start of the COVID-19 pandemic-from hoarding toilet paper and wiping down groceries to sending our children back to school and vaccinating billions. Over this period, the global community of epidemiologists and evolutionary biologists has also come a long way in understanding the complex and changing dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. In this Review, we retrace our steps through the questions that this community faced as the pandemic unfolded. We focus on the key roles that mathematical modeling and quantitative analyses of empirical data have played in allowing us to address these questions and ultimately to better understand and control the pandemic.


Ethics and computer-mediated communication: implications for practice and policy.
Computer-mediated communication, or email, has become a common workplace practice. Interviews with Army nurse managers (n = 9) and their staff nurses (n = 13) revealed that nurses incorporate the ethical principles of autonomy, beneficence, nonmaleficence, and justice into their computer-mediated communication use, but to varying degrees. Without clearly defined policies to guide computer-mediated communication practices, informal norms evolve that have an impact on both individual and corporate communication. The authors provide insight into the ethical considerations that have an impact on computer-mediated communication use. The spectrum of participant interpretation of appropriate use of this type of communication suggests the need for policies to establish clear boundaries for workplace usage. Policy recommendations are included.


Emodin Alleviates High-Glucose-Induced Pancreatic β-Cell Pyroptosis by Inhibiting NLRP3/GSDMD Signaling.
Diabetes mellitus (DM) is a chronic noninfectious disease that is mainly featured by pancreatic β-cell (β-cell) dysfunction and impaired glucose homeostasis. Currently, the pathogenesis of dysfunction of the β-cells in DM remains unclear, and therapeutic approaches to it are limited. Emodin (EMD), a natural anthraquinone derivative, has been preliminarily proven to show antidiabetic effects. However, the underlying mechanism of EMD on β-cells still needs to be elucidated. In this study, we investigated the protective effects of EMD on the high glucose (50 mM)-induced INS-1 cell line and the underlying mechanism. INS-1 cells were treated with EMD (5, 10, and 20 μM) when exposed to high glucose. The effects of EMD were examined by using the inverted phase-contrast microscope, qRT-PCR, ELISA, and western blot. The results showed that EMD could alleviate cellular morphological changes, suppress IL-1β and LDH release, and promote insulin secretion in high-glucose-induced INS-1 cells. Furthermore, EMD inhibits NOD-like receptor protein 3 (NLRP3) activation and gasdermin D (GSDMD) cleavage to alleviate pyroptosis induced by high glucose. Overexpression of NLRP3 reversed the above changes caused by EMD. Collectively, our findings suggest that EMD attenuates high-glucose-induced β-cell pyroptosis by inhibiting NLRP3/GSDMD signaling.


Determination of organochlorine pesticides (OCPs) in the edible offal of Egyptian buffalo.
Environmental contamination by OCPs has a great concern, since most of these pesticide compounds are very toxic and harmful to human and ecosystems. This study was conducted to determine the concentrations of OCPs residues in the edible offal (livers, kidneys and tongues) of Egyptian buffalo collected from three locations (Zagazig, Ismailia and Mansoura) in Egypt. Examined samples from Mansura city had the highest OCPs contamination load. Tongues had the highest concentration of these toxic residues in a comparison to livers and kidneys in the examined samples. The overall results showed that OCPs residues did not exceed the Egyptian maximum permissible limits in all of the samples analyzed from the three different locations.


[Effects of sympathetic efferent in diabetic hyperalgesia in rat].
While sympathetic efferents and prostaglandins (PGs) play an important role in hyperalgesia of partial injury of peripheral nerves and inflammation, whether these are also involved in diabetic hyperalgesia is unknown. With intraperitoneal injection of 6-hydroxydopamine (6-OHDA) to eliminate effects of sympathetic postganglionic neurons (SPGNs) terminals, a model of diabetic rats with infused 6-OHDA could be set up by injection of streptozotocin (STZ). Nociceptive paw-withdrawal threshold (NPWT) and tail flick latency (TFL) in 6-OHDA/diabetic rats were not changed significantly in the following four weeks. However, in diabetic group rats, pain threshold was decreased significantly and accompanied by development of hyperalgesia. NPWT was significantly decreased with noradrenaline (NA) in diabetic hyperalgesic rats and increased with phentolamine or yohimbine, but not by prazocin. In the control rats, NPWT are not changed significantly by NA or phentolamine, and in 6-OHDA/diabetic rats, neither NA nor phentolamine also affected on NPWT significantly. However, NPWT may be significantly decreased by PGE1, PGE2 and PGD2 in both the control and the diabetic hyperalgesic rats. The above results suggested that SPGNs terminals are involved in hyperalgesia of diabetic rats, NA accelerated synthesis of PGs and released by way of presynaptic effect on alpha 2-adrenergic receptors at the SPGNs terminals, PGs, in turn, directly acted on the primary afferent nociceptors, producing hyperalgesia.


[Impact of risk factors for osteoporosis on bone mineral density in perimenopausal women of the City of Querétaro, México].
It is essential to evaluate osteoporosis risk factors, mainly the modifiable, like the lifestyle, in Mexican women in order to prevent it, since it is a serious public health problem. We studied 805 women (35-55 years old) in the City of Queretaro, México. We obtained: personal data, family history, habits, such as smoking, alcohol, caffeine (coffee and soft drink of cola) and physical activity. Participants complete the questionnaire on 19 risk factors for osteoporosis (International Osteoporosis Foundation) one of them with risk. We evaluated: body mass index (BMI), cardiovascular risk and corporal complexion. Bone densitometry was performed in two diagnostic regions: lumbar spine and total hip and participants were classified as normal bone mass density (BMD), low BMD and osteoporosis. The prevalence of osteoporosis was 7% and of low BMD was 34%, predominantly in the lumbar region and in those with menopause. In osteoporotic women, the age was higher (51 years) and 85% menopausal women, also lower values of weight, height, BMI, waist circumference and hip than women with normal bone mass density. The significantly modifiable risk factors were: low weight, smoking and consumption of soft drink of cola with 6,5, 1,2 and 1,4 (odds ratio), respectively (p < 0.05). The significantly non-modifiable risk factors were: menopause (surgical), history of fracture and risk. It is concluded that within the modifiable risk factors for the prevention ofosteoporosis, those with the greatest impact were low weight, cigarette and soft drink of cola.


Disc Oedema in A Patient with Chronic Kidney Disease: A Diagnostic Conundrum.
A 47-year-old woman who presented with headache and blurring of vision was referred to us due to suspicion of idiopathic intracranial hypertension or cerebral sinus venous thrombosis. She had chronic kidney disease and underwent dialysis through multiple ports including the right internal jugular vein (IJV). Her examination showed a best corrected visual acuity of 20/20 in each eye, normal anterior segments in each eye but bilateral papilloedema. Magnetic resonance imaging and venography (MRV) of her brain with contrast showed signs of raised intracranial pressure and a hypoplastic left transverse sinus. An MRV of her neck showed a thrombosis of the right IJV. Her symptoms and papilloedema resolved with carbonic anhydrase inhibitors and anticoagulants. This case highlights an uncommon presentation of papilloedema secondary to raised intracranial pressure from IJV thrombosis and its pathogenesis.


Genetic mapping of loci involved in oil tocopherol composition control in Russian sunflower (Helianthus annuus L.) lines.
Tocopherols are antioxidants that preserve oil lipids against oxidation and serve as a natural source of vitamin E in the human diet. Compared with other major oilseeds like rapeseed and soybean, sunflower (Helianthus annuus L.) exhibits low phenotypic diversity of tocopherol composition, both in wild and cultivated accessions from germplasm collections. Two major mutations that alter tocopherol composition were identified in genetic collections, and several studies suggested additional loci controlling tocopherol composition, with their expression possibly depending on the genetic background. In the present study, we performed QTL mapping of tocopherol composition in two independent F2 crosses between lines with contrasting tocopherol composition from the Pustovoit All-Russia Research Institute of Oil Crops (VNIIMK) collection. We used genotyping-bysequencing (GBS) to construct single nucleotide polymorphism-based genetic maps, and performed QTL mapping using quantitative and qualitative encoding for phenotypic traits. Our results support the notion that the tocopherol composition in the assessed crosses is controlled by two loci. We additionally selected and validated two single nucleotide polymorphism markers for each cross which could be used for marker-assisted selection.


Selection criteria for base metal alloys for use with porcelains.
Today's chromium alloys constitute a distinct alloy group that, because of favorable physical and chemical properties, is widely used for porcelain fused to metal restorations. In making a selection from within this alloy group, the individual should first be aware of how to modify casting techniques in order to produce complete and well-fitting castings. Differences in important mechanical characteristics, such as modulus of elasticity, hardness, and an alloy's formability, do exist between various Ni-Cr and Co-Cr alloys, and one needs to be cognizant of these differences if an optimal restoration design is to result. Because chromium alloys do not represent a homogeneous group, gross differences in castability and porcelain bonding behavior will be encountered between alloys with nominally similar compositions and mechanical properties. No universally accepted test for alloy-porcelain compatibility or bond strength exists, but the interested individual can perform some preliminary tests on new or untried alloy-porcelain combinations prior to fabrication of actual restorations. Although soldering the chromium alloys continues to be technique-sensitive, optimal results can be achieved by proper selection of high- and low-fusing solders for specific alloys.


A Rare Case of Bilateral Popliteal Artery Occlusion.
Peripheral arterial disease (PAD) is a common condition of the upper and lower extremities caused by atherosclerosis. It is often accompanied by symptomatic cardiovascular and cerebrovascular disease and is a major risk factor for amputation of an extremity. Timely diagnosis and intervention can prevent morbidity in these patients. We describe a case of a 48-year-old man with multiple co-morbidities who presented to our emergency department (ED) complaining of acute onset of bilateral leg pain. He was found to have bilateral acute popliteal artery occlusion confirmed by angiography of the lower limbs. Treatment was started early, right after reaching the provisional diagnosis. Popliteal artery occlusion is quite common, but it becomes a rare diagnosis when it happens bilaterally. Detailed evaluation of the peripheral arterial circulation and an early diagnosis seem to be important in the ED management of these patients.


Complete resolution of chronic pericardial effusion with an intensive course of inhaled iloprost in an adult patient with unrepaired ventricular septal defect, and life-threatening severe pulmonary arterial hypertension.
A 38-year-old male was diagnosed with unrepaired ventricular septal defect associated with severe pulmonary arterial hypertension, cyanosis, and significant exercise intolerance. His echocardiogram showed right ventricular dysfunction and moderate pericardial effusion with no signs of cardiac tamponade. He was treated with an intensive course of inhaled iloprost and sildenafil. He showed a dramatic clinical response; his saturation went up from 60% on admission to 90% on minimal oxygen with significant improvement in his symptoms and signs of heart failure and total resolution of pericardial effusion. On follow up 3 and 6 weeks later, he was stable and could walk 360 meters in a 6 minutes walk test with disappearance of pericardial effusion. With unavailability of intravenous prostacyclin, we have shown in this case that intensive administration of inhaled iloprost could be used intensively as a rescue therapy in severe cases of pulmonary arterial hypertension with excellent results.


[Intravenous penicillin therapy in high doses in neurosyphilis: study of 62 cases. I. Clinical evaluation].
Sixty-two patients with symptomatic neurosyphilis were treated with 20 or 24 megaunits of intravenous penicillin G daily for 15 to 30 days. The mean follow-up time after the treatment was 30 months. Thirteen patients developed new neurological signs after the treatment. Their diagnosis were: general paresis (9), taboparesis (2), tabes dorsalis (1) and meningovascular neurosyphilis (1). After the treatment, thirty-six patients (58.1%) improved, 22 patients (35.5%) were unchanged and 4 patients (6.4%) deteriorated on clinical grounds. In two patients there was a progression to other forms of neurosyphilis. The results of the treatment of these patients with high doses of intravenous penicillin G were not different from the results verified with classical intramuscular penicillin that were reported in the literature, from the clinical standpoint.


Functional evidence of alpha1D-adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats.
The role of alpha1D-adrenoceptors in the vasculature of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY), of different ages was assessed in pithed rats by the use of the selective alpha1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-ethyl]-8-azaspiro [4.5]decane-7,9-dione dihydrochloride). BMY 7378 displaced the pressor effect of phenylephrine in young pre-hypertensive pithed SHR rats, but produced no effect in young WKY rats (dose ratio of 3.4 and 1.6, respectively), while in adult rats BMY 7378 produced a greater shift in the phenylephrine response curve than in younger animals (dose ratio of 3.2 and 6.2 in WKY and SHR, respectively). The presence of alpha1D-adrenoceptors in the vasculature of pre-hypertensive rats, suggests its role in the pathogenesis/maintenance of increased blood pressure.


CFTR Chloride Channels: Binding Partners and Regulatory Networks.
The cystic fibrosis gene encodes a chloride channel (CFTR) that regulates transepithelial salt and water transport. Two classes of CFTR-binding proteins appear to link the opposing cytoplasmic tails of this channel to distinct regulatory networks. Such interactions may constitute new paradigms for modulating CFTR activity in health and disease.


The partograph for the prevention of obstructed labor.
Obstructed labor is an important cause of maternal and perinatal mortality and morbidity. The partograph graphically represents key events in labor and provides an early warning system. The World Health Organization partographs are the best known partographs in low resource settings. Experiences with World Health Organization and other types of partographs in low resource settings suggest that when used with defined management protocols, this inexpensive tool can effectively monitor labor and prevent obstructed labor. However, challenges to implementation exist and these should be addressed urgently.


Clinical characterisation at onset of childhood psoriasis - a cross sectional study in Sweden.
Epidemiological data in childhood psoriasis are accumulating. However, reliable information captured at onset is lacking. In a cross sectional study we recruited 109 children < 16 years within 12 months of psoriasis onset and explored the clinical characteristics. Pre-pubertal children, especially boys, more often had inverse involvement (OR = 2.8, 95% CI = 1.1, 7.1, p ≤ 0.05). HLA-C*06 was positively associated with facial lesions (OR = 3.8, 95% CI = 1.5, 9.7, p < 0.01) and guttate phenotype and was more common in pubertal children. A high PASI score was not associated with overweight or early age at onset, and gender did not influence disease onset. Psoriasis can be difficult to diagnose in children, especially in pre-pubertals. Thorough examination of facial and genital areas can help in establishing the diagnosis. Our published genetic data in combination with the clinical findings presented herein indicate that puberty may separate different populations of childhood psoriasis.


Major Oncologic Surgery at a Community Hospital.
There is a national trend to refer patients requiring complex oncologic surgery to tertiary high-volume cancer centers. However, this presents major access challenges to Hawai'i patients seeking care. The purpose of this study is to demonstrate that complex oncologic surgery can be safely performed at community hospitals like those in Hawai'i. From July 2007 to December 2014, 136 patients underwent complex oncologic procedures at a community hospital in Hawai'i by a single general surgeon. Cases included esophagogastric, hepatobiliary, pancreatic, rectal, and retroperitoneal resections. A database of patients was created from information extracted from the EPIC database. Complications were evaluated using the Clavien-Dindo grading system. There was 0.7% mortality rate (grade V complication). The major morbidity rate was 12.5%, including 10.3% grade III complications and 2.2% grade IV complications. The median length of stay for all operations was 8 days. The mean estimated blood loss for all operations was 708 cc. There was a 2.9% hospital readmission rate within 30 days of initial discharge, and a 5.1% reoperation rate. Complex oncologic procedures can be safely performed at a low-volume community hospital, with outcomes similar to those from high-volume cancer centers.


Circular RNAs: Regulators of Cancer-Related Signaling Pathways and Potential Diagnostic Biomarkers for Human Cancers.
Circular RNAs (circRNAs) are newly discovered endogenous non-coding RNAs featuring structural stability, high abundance, and tissue-specific expression. CircRNAs are prevalent and conserved in mammalian cells. They are involved in cellular processes and regulate gene expression at the transcriptional or post-transcriptional level by interacting with microRNAs (miRNAs) and other molecules. Recent studies have shown that circRNAs play an important role in the progression of various human diseases including atherosclerosis, nervous system disorders, diabetes, and cancer. In this review, we summarize the advances on endogenous circRNAs in eukaryotic cells and elucidate their diagnostic and prognostic significance in human cancers. Especially, we highlight the involvement of circRNAs in signal transduction pathways as well as their clinical potential to serve as biomarkers.


[Atheromatous pseudo-occlusive stenosis of the internal carotid].
Pseudo-occlusion of the internal carotid artery is defined as an angiographically occluded but anatomically patent artery. Between january 1980 and december 1990, 14 cases were diagnosed in our institution. Preoperative Doppler examination of the internal carotid artery suggested almost complete thrombosis in 11 patients and occlusion in 3. The angiographic appearance suggested internal carotid occlusion in all but the presence of the slim sign was in favor of a patent artery. All 14 patients underwent surgery. There were no postoperative deaths; one patient presented an ipsilateral TIA post operatively; 3 others presented an ipsilateral TIA after 2, 16 and 30 months respectively. All carotid arteries were found to be patent. The frequency of pseudo-occlusion of the internal carotid artery is probably underestimated. It must be kept in mind whenever an apparently occluded internal carotid continues to be symptomatic. Diagnosis is based on comparative analysis of Doppler examination and angiographic findings. Surgery is indicated whenever doubt persists.


The University of Oklahoma College of Medicine summer medical program for high school students.
To enhance diversity of applicants to University of Oklahoma College of Medicine, a Summer Medical Program for High School Students was started in 2009. This comprehensive pipeline program included sessions on applying to medical school, interaction with a panel of minority physicians and health care professionals role models, clinically oriented didactics taught by physician faculty, shadowing experiences in clinics and hospitals, and presentation of student research reports. Students' assessments in 2009 showed increased understanding of the medical school application process, the medical curriculum and the medical field, and an increase in students'likeliness to choose a medical career. Importance of long-term mentoring and follow-up with students to sustain their medical interests is discussed.


Approaches to the treatment of patients with hormone-sensitive prostate cancer.
Androgen ablation therapy provides effective palliation for patients with advanced cancer of the prostate for only a short duration because the tumor eventually develops resistance. Among the many potential molecular mechanisms involved in the development of tumor resistance to both androgen ablation therapy and chemotherapy, mutations in the p53 tumor suppressor gene, overexpression of the antiapoptotic protein bcl-2, and overexpression of the multidrug resistance protein probably play a role. Because hormone-resistant tumors demonstrate greater expression of bcl-2 and because transfection of the bcl-2 gene into hormone-sensitive tumor cells confers resistance to both hormone therapy and chemotherapy, efforts to abrogate bcl-2 in prostate tumors represent one approach to improve clinical results. Of several agents recently shown to reduce prostate-specific antigen levels in phase II studies, 13-cis-retinoic acid and interferon-alpha can reduce the expression of bcl-2 and overcome bcl-2-mediated resistance to paclitaxel in resistant cell lines. For these reasons, our current studies test the hypothesis that reducing the expression of bcl-2 with 13-cis-retinoic acid and interferon-alpha in combination with taxanes will improve clinical results. Additionally, other studies test the hypothesis that treatment early, before the development of resistance mechanisms, in hormone-sensitive disease will improve results. Studies with docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) and with estramustine combination therapy are also ongoing.


Conformation of a beta-adrenoceptor-derived signal transducing peptide as inferred by circular dichroism and 1H NMR spectroscopy.
The peptide T345-359 representing the fourth intracellular loop of the avian beta-adrenoceptor has been shown to strongly inhibit receptor-mediated adenylate cyclase activity [Münch, G., Dees, C., Hekman, M., & Palm, D. (1991) Eur. J. Biochem. 198, 357-364]. Circular dichroism and two-dimensional 1H NMR techniques were used to investigate the three-dimensional structure of the peptide in trifluoroethanol, phospholipid micelles, and small unilamellar phospholipid vesicles. The prepared vesicles were tested for size distribution and stability by using electron microscopy, photon correlation spectroscopy, and 31P NMR spectroscopy. The peptide T345-359 adopted a predominantly alpha-helical conformation in either trifluoroethanol or phospholipid micelles and vesicles. No structural differences were found for the conformation of the peptide in the presence of phospholipid micelles or vesicles, respectively, using 2D 1H NMR techniques, suggesting a unique conformation of T345-359 when associated with model membranes. A computer-aided model of the micelle-associated peptide was derived. The relevance of the 3D structure of the intracellular loops of receptors to communicate with the G protein in the signal transduction cascade is discussed.


Newborn Clavicle Fractures: Does Clavicle Fracture Morphology Affect Brachial Plexus Injury?
Newborn clavicle fractures and brachial plexus injuries (BPIs) are rare but serious perinatal complications. The aim of this study was to examine the clinical relationship between the fracture morphology (spiral, oblique, transfer) of clavicle fractures that develop during delivery in newborns and BPI. We retrospectively reviewed all perinatal clavicle fractures diagnosed at our institution over 6 years. The study included 55 newborn infants with perinatal clavicle fracture. Of these, 60% (n=33) were male. Right-side clavicle fractures were present in 56.4% (n=31) and shoulder dystocia was present in 58.2% (n=32) of the patients. Of the fracture localization of the patients, 85.5% (n=47) (Allman I) and 14.5% (n=8) (Allman II) were lateral. Allman type I fractures were not associated with increased BPI (P>0.05). It was observed that 40% (n=22) of the clavicle fractures were characterized by oblique morphology, 34.5% (n=19) of the fractures by spiral morphology, and 25.5% (n=14) of the fractures by transfer morphology. In all, 41.8% (n=23) of the sample also had BPI. Of the entire sample, 40% (n=22) most frequently showed oblique morphology fractures, whereas the patient group with BPI showed spiral morphology as the most common fracture, at a rate of 52.2% (n=10). After examining the relationship between fracture morphology and BPI, the study determined a statistically significant correlation between spiral and oblique morphology fractures and the development of BPI. To our knowledge, our study is the first to examine the relationship between newborn clavicle fracture morphology and BPI. We think that they should be evaluated for increased BPI risk in newborn patients that have clavicle fractures with spiral and oblique morphology.


Comparison of early fixation and delayed reconstruction after displacement in previously nondisplaced acromion fractures.
Scapular fractures account for approximately 1% of all fractures, and 8% to 10% are acromion fractures. We compared the results of early and delayed treatment for nondisplaced and type III acromion fractures, respectively, to investigate an early treatment method for nondisplaced acromion fractures. Patients treated between March 1999 and March 2006 with 2-year follow-up were selected for the study. The early fixation group comprised 16 patients, and the delayed reconstruction group comprised 18 patients. Moreover, the delayed reconstruction group was further divided into 2 additional groups: delayed group B and delayed group N. Delayed group B comprised 7 cases receiving bone graft, and delayed group N comprised 11 cases not receiving bone graft. Mean Constant scores were significantly greater for the early fixation group (92+/-6.6; range, 64-98) than for both delayed groups N (86+/-7.8; range, 54-96) and B (81+/-9.4; range, 58-92) (P=.042 and .024, respectively). Mean pain score was 14+/-4.8 (range, 5-15) in the early fixation group, 12+/-7.4 (range, 5-15) in delayed group N, and 9+/-8.8 (range, 5-15) in delayed group B (P=.052 and .018, respectively). Mean daily activity score was also significantly greater in the early fixation group (19+/-6.4; range, 16-20) than in both delayed group N (14+/-6.2; range, 10-18) and delayed group B (10+/-4.4; range, 8-18) (P=.048 and .021, respectively). The P values for Constant, pain, and daily activity scores between delayed groups N and B were .048, .038, and .052, respectively. In cases of young patients with type IC acromion fractures at the time of injury, a high activity level, and the early need for crutches or a walker, early surgical treatment should be considered.


A Comparison of the Effects of Chilling on Thylakoid Electron Transfer in Pea (Pisum sativum L.) and Cucumber (Cucumis sativus L.).
Experiments comparing the photosynthetic responses of a chilling-resistant species (Pisum sativum L. cv Alaska) and a chilling-sensitive species (Cucumis sativus L. cv Ashley) have shown that cucumber photosynthesis is adversely affected by chilling temperatures in the light, while pea photosynthesis is not inhibited by chilling in the light. To further investigate the site of the differential response of these two species to chilling stress, thylakoid membranes were isolated under various conditions and rates of photosynthetic electron transfer were determined. Preliminary experiments revealed that the integrity of cucumber thylakoids from 25 degrees C-grown plants was affected by the isolation temperature; cucumber thylakoids isolated at 5 degrees C in 400 millimolar NaCl were uncoupled, while thylakoids isolated at room temperature in 400 millimolar NaCl were coupled, as determined by addition of gramicidin. The concentration of NaCl in the homogenization buffer was found to be a critical factor in the uncoupling of cucumber thylakoids at 5 degrees C. In contrast, pea thylakoid membranes were not influenced by isolation temperatures or NaCl concentrations. In a second set of experiments, thylakoid membranes were isolated from pea and cucumber plants at successive intervals during a whole-plant light period chilling stress (5 degrees C). During wholeplant chilling, thylakoids isolated from cucumber plants chilled in the light were uncoupled even when the membranes were isolated at warm temperatures. Pea thylakoids were not uncoupled by the whole-plant chilling treatment. The difference in integrity of thylakoid membrane coupling following chilling in the light demonstrates a fundamental difference in photosynthetic function between these two species that may have some bearing on why pea is a chilling-resistant plant and cucumber is a chilling-sensitive plant.


The Association of Acute Cerebrospinal Fluid Pressure Reduction with Choroidal Thickness.
To investigate the changes in choroidal thickness (CT) after acute cerebrospinal fluid pressure (CSFP) reduction in human subjects. Before and 15 minutes after diagnostic lumbar puncture (LP), 44 patients underwent measurement of CT by swept-source optical coherence tomography. Thirty-two healthy volunteers imitated the body posture of LP procedure and underwent the same measurement before and 15 minutes after body posture change. After CSFP reduction from 10.9 ± 2.1 mmHg at baseline to 8.1 ± 1.5 mmHg (p < 0.001), CT decreased in subfoveal region (p = 0.005), small to medium vessel layer (SMVL, p < 0.001), peripapillary regions in temporal (p = 0.001), nasal (p < 0.001), superior (p < 0.001) and inferior (p < 0.001), respectively. However, no significant change in CT in the control group after body posture change (all p > 0.05). A significant association between CSFP and the ratio of small to medium vessel layer to total choroidal thickness was found (p = 0.009). The CSFP reduction rate was associated with the change rate of SMVL to total CT portion, for each percent decrease in CSFP was associated with a decrease by 0.22% in the rate of SMVL to total CT portion (R2 = 0.125, p = 0.018). A significant decrease in subfoveal CT, small to medium vessel layer and peripapillary region were observed following acute CSFP reduction. The CSFP reduction rate was associated with the change rate of small to medium vessel layer to total CT portion.


Incremental Hospital Cost and Length-of-Stay Associated With Treating Adverse Events Among Medicare Beneficiaries Undergoing Lumbar Spinal Fusion During Fiscal Year 2013.
A retrospective study. To report the incremental hospital resource consumption associated with treating selected adverse events experienced by Medicare beneficiaries undergoing a two- or three-level lumbar spinal fusion. Hospitals are increasingly at financial risk for the incremental resources consumed in treating patients experiencing adverse events because of public and private third-party payers' efforts to base hospital reimbursement on "pay for performance" measures. However, little is known about average incremental resources consumed in treating patients experiencing adverse events following lumbar spinal fusions. The 2013 fiscal year Medicare Provider Analysis and Review file was used to identify 83,658 Medicare beneficiaries who underwent two- or three vertebrae-level lumbar spinal fusion. International Classification of Diseases-9th-Clinical Modification diagnostic and procedure codes were used to identify the frequencies of nine adverse events. This study estimated both the observed and risk-adjusted incremental hospital resources consumed (cost and length of stay [LOS]) in treating Medicare beneficiaries experiencing each adverse event. Overall, 17.7% of Medicare beneficiaries undergoing lumbar spinal fusion experienced at least one of the study's adverse events. Medicare beneficiaries experiencing any complication consumed significantly more hospital resources (incremental cost of $8911) and had longer LOS (incremental stays of 5.7 days). After adjusting for patient demographics and comorbid conditions, incremental cost of treating adverse events ranged from a high of $32,049 (infection) to a low of $9976 (transfusion). Adverse events frequently occur and add substantially to the hospital resource costs of patients undergoing spinal fusion. Shared decision-making instruments should clearly provide these risk estimates to the patient before surgical consideration. Investment in activities that have been shown to reduce specific adverse events is warranted, and this project may allow health systems to prioritize performance improvement areas. 3.


Genetic network analysis of human immunodeficiency virus sexual transmission in rural Southwest China after the expansion of antiretroviral therapy: A population-based study.
This study is used to analyze the genetic network of HIV sexual transmission in rural areas of Southwest China after expanding antiretroviral therapy (ART) and to investigate the factors associated with HIV sexual transmission through the genetic network. This was a longitudinal genetic network study in Guangxi, China. The baseline survey and follow-up study were conducted among patients with HIV in 2015, and among those newly diagnosed from 2016 to 2018, respectively. A generalized estimating equation model was employed to explore the factors associated with HIV transmission through the genetic linkage between newly diagnosed patients with HIV (2016-2018) and those at baseline (2015-2017), respectively. Of 3,259 identified HIV patient sequences, 2,714 patients were at baseline, and 545 were newly diagnosed patients with HIV at follow-up. A total of 8,691 baseline objectives were observed by repeated measurement analysis. The prevention efficacy in HIV transmission for treated HIV patients was 33% [adjusted odds ratio (AOR): 0.67, 95% confidence interval (CI): 0.48-0.93]. Stratified analyses indicated the prevention efficacy in HIV transmission for treated HIV patients with a viral load (VL) of <50 copies/ml and those treated for 4 years with a VL of <50 copies/ml to be 41 [AOR: 0.59, 95% CI: 0.43-0.82] and 65% [AOR: 0.35, 95% CI: 0.24-0.50], respectively. No significant reduction in HIV transmission occurred among treated HIV patients with VL missing or treated HIV patients on dropout. Some factors were associated with HIV transmission, including over 50 years old, men, Zhuang and other nationalities, with less than secondary schooling, working as a farmer, and heterosexual transmission. This study reveals the role of ART in reducing HIV transmission, and those older male farmers with less than secondary schooling are at high risk of HIV infection at a population level. Improvements to ART efficacy for patients with HIV and precision intervention on high-risk individuals during the expansion of ART are urgently required.


Calcium-mediated protein secretion potentiates motility in Toxoplasma gondii.
Apicomplexans such as Toxoplasma gondii actively invade host cells using a unique parasite-dependent mechanism termed gliding motility. Calcium-mediated protein secretion by the parasite has been implicated in this process, but the precise role of calcium signaling in motility remains unclear. Here we used calmidazolium as a tool to stimulate intracellular calcium fluxes and found that this drug led to enhanced motility by T. gondii. Treatment with calmidazolium increased the duration of gliding and resulted in trails that were twice as long as those formed by control parasites. Calmidazolium also increased microneme secretion by T. gondii, and studies with a deletion mutant of the accessory protein m2AP specifically implicated that adhesin MIC2 was important for gliding. The effects of calmidazolium on gliding and secretion were due to increased release of calcium from intracellular stores and calcium influx from the extracellular milieu. In addition, we demonstrate that calmidazolium-stimulated increases in intracellular calcium were highly dynamic, and that rapid fluxes in calcium levels were associated with parasite motility. Our studies suggest that oscillations in intracellular calcium levels may regulate microneme secretion and control gliding motility in T. gondii.


Hepatocellular integrity in liver donors and recipients indicated by glutathione transferase alpha.
Glutathione transferase Alpha (GSTA) is a sensitive indicator of hepatocellular integrity. Its reference range is low (0.7-14 microgram/L) and its half-life is short (1 hr) in serum. We evaluated the changes in GSTA concentration in 18 recipients during and after liver transplantation. The respective liver donors were also included in 13 cases. The baseline GSTA concentrations were normal or slightly elevated in all donors, 1.2-79 micrograms/L (median 5.1 micrograms/L) and recipients, 1.1-34 micrograms/L (median 6.4 micrograms/L). Surgical dissection of donor liver caused a moderate or even large increase in GSTA concentration, peak 80-6500 microgram/L (median 800 micrograms/L). In the recipients the peak of GSTA concentrations varied from 1400 to 47000 micrograms/L (median 5000 micrograms/L), and it was always observed within 45 min after reperfusion of the graft. The highest GSTA values were observed after long cold ischemia and in patients transplanted for acute liver failure. However, they were not associated with early graft dysfunction. There was a correlation between the AUC of GSTA and cold ischemia time in the recipients with chronic nonalcoholic liver failure (r=0.94). There was no correlation between GSTA values in the donors and recipients (r=0.14). The apparent half-life of GSTA in serum was 56 min (median). Perioperative GSTA concentrations in the donors had no obvious predictive value. In the recipients an exceptionally long apparent half-life of GSTA immediately after transplantation or a large second increase in GSTA were predictors of postoperative complications.


Gradient boosting for linear mixed models.
Gradient boosting from the field of statistical learning is widely known as a powerful framework for estimation and selection of predictor effects in various regression models by adapting concepts from classification theory. Current boosting approaches also offer methods accounting for random effects and thus enable prediction of mixed models for longitudinal and clustered data. However, these approaches include several flaws resulting in unbalanced effect selection with falsely induced shrinkage and a low convergence rate on the one hand and biased estimates of the random effects on the other hand. We therefore propose a new boosting algorithm which explicitly accounts for the random structure by excluding it from the selection procedure, properly correcting the random effects estimates and in addition providing likelihood-based estimation of the random effects variance structure. The new algorithm offers an organic and unbiased fitting approach, which is shown via simulations and data examples.


[Effectiveness of combined surgery for treating severe obstructive sleep apnea hypopnea syndrome].
To explore the efficiency of a comprehensive surgical approach of genioglossus advancement and hyoid suspension (GAHM) plus uvulopalatopharyngoplasty (UPPP) for treating severe obstructive sleep apnea hypopnea syndrome (OSAHS) and to evaluate related factors on surgery outcomes. Eighteen patients with severe OSAHS (apnea hypopnea index, AHI > 40/h) confirmed with polysomnography received genioglossus advancement and hyoid suspension plus uvulopalatopharyngoplasty. The obstruction in both the oropharynx and the hypopharynx were evaluated by preoperative physical examination, fiberoptic pharyngolaryngoscopy, cephalometry, and computed tomography of the upper airway. The follow up was at least 6 months postoperatively. The Wilcoxon signed rank test was used to compare the preoperative and postoperative results by SPSS 11.0 for windows. The Mann-Whitney test was used to analyze the difference between responders and nonresponders. The follow up time ranges from 6 to 24 months, there were statistically significance in all but body mass index (BMI) between preoperative and postoperative measurements. Mean AHI was reduced from preoperative (x +/- s, 63.8 +/- 16.3)/h to postoperative (23.6 +/- 19.5)/h, lowest mean oxygen saturation increased from 0.72 +/- 0.07 to 0.81 +/- 0.13(x +/- s). According to criterion at home, the 6-month rate of responder is 83%, if AHI <20/h and decreased by at least 50% as success, the rate of success is 67%. The age, posterior airway space (PAS) and percentage of time with oxyhemoglobin saturation below 0.90 (CT90) were (39.1 +/- 7.4) years, (8.3 +/- 0.9) mm, (18.5 +/- 10.9)% in responder, while (52.5 +/- 9.4) years, (6.8 +/- 1.3) mm, (37.7 +/- 23.6) % in nonresponder, and there are statistically significant between responder and nonresponder. GAHM plus UPPP is effective surgical approach for patients with severe OSAHS who suffer from oropharyngeal and hypopharyngeal obstruction. Age, PAS and CT90 were possible affective factors on surgical outcomes.


Synergistic Effects of Fluorine and WO3 Nanoparticles on the Surface of TiO2 Hollow Spheres for Enhanced Photocatalytic Activity under Visible Light Irradiation.
TiO2 is an attractive catalyst for the photocatalytic degradation of organic pollutants. However, owing to its large band gap, it can only be activated by ultraviolet (UV) light, which constitutes a small portion of solar energy. Therefore, there has been significant interest in extending its light absorption range from UV to visible light. In this study, fluorinated TiO2 hollow spheres (FTHSs) were prepared via a rapid and simple wet chemical process using ammonium hexafluorotitanate, and then FTHS/WO3 heterostructures with different weight ratios of the FTHS and WO3 nanoparticles were synthesized via a simple wet impregnation method. The formation of the hybrid structure was confirmed by various characterization techniques. The photocatalytic activity of the synthesized photocatalysts in the photodegradation of rhodamine B, a model pollutant, was evaluated under visible light irradiation. The FTHS/WO3 heterostructures exhibited significantly improved photocatalytic activity compared to the bare FTHS or WO3 nanoparticles. The photodegradation efficiency of the FTHS/WO3 heterostructure in the present study was up to 0.0581 min-1. Detailed mechanisms that lead to the enhanced photocatalytic activity of the heterostructures are discussed. In addition, comparative experiments reveal that the photodegradation efficiency of the FTHS/WO3 heterostructure under visible light irradiation is superior to that of the P25/WO3 heterostructure prepared from the commercially available TiO2 catalyst (P25) via the same impregnation method.


[The role of CT and MR imaging in the diagnosis of lung cancer].
CT and MR imaging can play an important role in the diagnosis of lung cancer. Evaluation of a solitary pulmonary nodule is usually carried out using CT. High-resolution CT is useful in the morphologic diagnosis of a solitary pulmonary nodule. The enhancement characteristics of a pulmonary nodule in contrast-enhancement CT can be a method of distinguishing benign and malignant nodules. MR imaging is superior to CT in contrast resolution and multidirectional imaging capability. Contrast-enhancement MR imaging can describe the enhancement characteristics of the pulmonary lesion better than contrast-enhancement CT. The extent of chest wall and mediastinal invasion of lung cancer can be better shown using MR imaging than CT.


Long-term outcome of patients with mild intermittent claudication under secondary prevention.
The known natural history of peripheral arterial disease (PAD) is determined by the generalization of atherosclerosis with resulting high cardiovascular and cerebrovascular morbidity and mortality. The aim of this prospective study was to record all vascular and non-vascular events in patients with mild intermittent claudication (IC) undergoing secondary preventive measures in a 10-year follow-up and to determine the time-points at which systemic localizations of atherosclerotic events develop. Patients who originally had an isolated Fontaine stage IIa PAD were included in the follow-up which involved assessments carried out on an annual basis. The incidence and timepoints of vascular (i.e., myocardial infarction, stroke, critical limb ischemia, vascular death), and nonvascular events (i.e., cancer, non vascular death) were recorded and compared with the known natural history. 534 events (vascular: 433) concerning 109 claudicants (M/F: 88/21; 60.8 +/- 8.8 years; ABI 0.66 +/- 0.11) were recorded over an average follow-up period of 104 months. 25.7% of the claudicants died, 39% due to vascular events, 36% due to cancer disease and 25% due to other events. A deterioration of PAD (n = 108) was the most frequent event after 20 months, followed by angina pectoris (n = 41) and cancer diseases (n = 20) after 42 and 45 months, stroke (n = 19) after 58 months, myocardial infarction (n = 12) after 63 months, and finally critical limb ischemia (n = 27) and amputations (n = 10) after 80 and 114 months (median). 111 revascularizations were carried out. 62.3% of the claudicants developed a polyvascular disease, with 20% in a trivascular territory. A high vascular comorbidity also develops under secondary prevention as an expression of the continuing generalization of the atherosclerotic process in PAD. The causes for death are determined both by the vascular and the tumor related comorbidity.


Diversity and Host Specificity Revealed by Biological Characterization and Whole Genome Sequencing of Bacteriophages Infecting Salmonella enterica.
Phages infecting members of the opportunistic human pathogen, Salmonella enterica, are widespread in natural environments and offer a potential source of agents that could be used for controlling populations of this bacterium; yet, relatively little is known about these phages. Here we describe the isolation and characterization of 45 phages of Salmonella enterica from disparate geographic locations within British Columbia, Canada. Host-range profiling revealed host-specific patterns of susceptibility and resistance, with several phages identified that have a broad-host range (i.e., able to lyse >40% of bacterial hosts tested). One phage in particular, SE13, is able to lyse 51 out of the 61 Salmonella strains tested. Comparative genomic analyses also revealed an abundance of sequence diversity in the sequenced phages. Alignment of the genomes grouped the phages into 12 clusters with three singletons. Phages within certain clusters exhibited extraordinarily high genome homology (>98% nucleotide identity), yet between clusters, genomes exhibited a span of diversity (<50% nucleotide identity). Alignment of the major capsid protein also supported the clustering pattern observed with alignment of the whole genomes. We further observed associations between genomic relatedness and the site of isolation, as well as genetic elements related to DNA metabolism and host virulence. Our data support the knowledge framework for phage diversity and phage-host interactions that are required for developing phage-based applications for various sectors, including biocontrol, detection and typing.


CD34 expression is associated with poor survival in pediatric T-cell acute lymphoblastic leukemia.
Children with T-lineage acute lymphoblastic leukemia (T-ALL) have an inferior outcome with combination chemotherapy compared to B-lineage ALL, and still about 30% of the patients relapse within the first 2 years following diagnosis. As CD34 has been related with poor outcome in ALL in general, we investigated the prognostic significance of the stem cell marker CD34, as well as the association of CD34 positivity with the expression of several multidrug resistance (MDR) genes. In this retrospective study, we investigated the prognostic significance of the expression of the early T-cell differentiation marker CD34 and the expression of MDR genes in relation to outcome in a cohort of 72 newly diagnosed pediatric T-ALL patients. CD34 expression was related to a poor 5-year disease-free-survival and a poor 5-year overall survival. Using the Cox proportional hazard model, CD34 expression predicted for increased risk for relapse and death. Expression of CD34 was associated with elevated MDR1 and MRP1 mRNA expression levels. For the entire T-ALL cohort, these expression levels of MDR1 or MRP1 did not independently predict for poor outcome. We conclude that CD34-positive T-ALL has a relatively poor survival that is not explained by the mRNA expression levels of MDR1, LRP, or MRP1.


The Role of Knotless Barbed Suture in Gynecologic Surgery: Systematic Review and Meta-Analysis.
Knotless barbed sutures are an innovative suturing material that can facilitate laparoendoscopic operations. The purpose of this study is to examine the available evidence on the application of barbed sutures on both laparoscopic and robotic operations in the field of gynecologic surgery. A systematic search was performed in PubMed, Scopus, and Cochrane databases. In total, 1991 patients were included in the study. The duration of closure with knotless suture ranged from 3.9 to 13 minutes, which was less than the use of conventional suture in every study. The duration of suturing was significantly less in the barbed suture group during hysterectomy, the mean difference between the observed groups was 2.41 minutes per operation (95% confidence interval, 1.23-3.59) whereas in myomectomy there was no statistically significant difference between compared groups. Concerning the estimated blood loss and the presence of major bleeding in hysterectomy, no statistical difference between the 2 groups was observed, while the estimated blood loss in myomectomy was found to be statistically significant (P = .04). Regarding the dehiscence of vaginal cuff in hysterectomy, no statistically significant difference was observed (1031 patients, odds ratio = 1.63; 95% confidence interval = 0.37-7.25). The complete absence of knots, the even distribution of tissue strength along the wound, and the reduction of operation time are the main advantages of this type of sutures. Additional clinical trials of higher methodological quality are necessary to further clarify suturing advantages and postoperative outcomes of the barbed sutures.


Increase of the neuron number in some cerebral cortical areas of a lizard, Podarcis hispanica, (Steind., 1870), during postnatal periods of life.
Neuronal counts in the medial, dorso-medial, and dorsal areas of the cerebral cortex of a common lizard, Podarcis hispanica, have been performed on a set of different sized (aged) animals. With age, (size), there is a significant increase in the number of neuronal somata of the inner plexiform and granular strata of both the medial and dorso-medial areas. In the granular stratum of the medial cortex, this increase appears to be mostly due to addition of small somata, whereas in the granular stratum of the dorso-medial cortex, the increase must be due to addition of large somata. The dorsal cortex does not show a conspicuous increase in itscell population, but postnatal development implies aggregation in "clusters" of some neuronal somata of the inner plexiform layer. The postnatal increase of neurons in the cerebral cortex of this lizard is correlated with the postnatal appearance and growth of both the dorso-medial area and the septocortical Timm's positive system of axonic endings of this species, close similar to the hippocampal mossy fiber system of Mammals.


Lactobacillus crispatus DSM25988 as novel bioactive agent to co-aggregate Streptococcus pyogenes and to exclude it by binding to human cells.
Streptococcus pyogenes, a group A streptococcus, is the major bacterial pathogen responsible for acute bacterial infection of the human oropharynx and the causative agent of scarlet fever. Estimates of the global burden of S. pyogenes related diseases revealed 616 million cases of pharyngitis, and at least 517,000 deaths due to severe invasive diseases and sequelae. Here we describe Lactobacillus crispatus DSM25988 that was identified among hundreds of Lactobacillus strains (referring to all organisms that were classified as Lactobacillaceae until 2020) showing ability to prevent adhesion of S. pyogenes to Detroit 562 cells, and to exhibit a masking and co-aggregating effect on S. pyogenes in vitro. L. crispatus DSM25988 also inhibits invasion of cultured human epithelial pharyngeal cells by S. pyogenes. Competitive binding to fibronectin might be involved in the inhibition process. Antiviral activity of the L. crispatus DSM25988 cells were identified in an in vitro cell model demonstrating that L. crispatus effectively excludes viruses from epithelial cells using SARS-CoV2 proteins as a model. This finding points to the potential of DSM25988 to protect cells from virus infection. Biological activity is retained in heat treated cells. The heat-treated Lactobacillus strain was further developed into functional throat lozenges, wherein its biological activity is stably maintained in the formulation. Lozenges containing L. crispatus DSM25988 underwent testing in an uncontrolled, prospective user study in 44 subjects with symptoms of sore throat for a period of up to 14 days. The study data shows promising safety and efficacy of the medical device when used against symptoms of sore throat like scratchy feeling, hoarse voice and swallowing pain.


Symptoms, exercise capacity and exercise hemodynamics: interrelationships and their role in quantification of the valvular lesion.
To compare the symptoms with the objectively-determined exercise capacity, the symptoms as well as the exercise capacity with the exercise hemodynamics and the symptoms, exercise capacity and exercise hemodynamics with the severity of the valvular lesion, in 154 patients with aortic regurgitation, mitral regurgitation, aortic stenosis or mitral stenosis, the symptoms were classified according to the New York Heart Association and the exercise capacity was determined by means of bicycle ergometry with simultaneous measurement of heart rate, blood pressure, pulmonary artery pressure, cardiac output and the left ventricular ejection fraction. Among the parameters studied, no relationships could be established; to a certain degree, the exercise hemodynamics correlated with the severity of the valvular lesion in that a markedly pathologic response was associated with the presence of a high-grade valvular lesion. Since the symptoms were not indicative of the exercise capacity, nor the symptoms or the exercise capacity of either the exercise hemodynamics, the exercise ejection fraction or the severity of the valvular lesion, the symptoms and the exercise capacity should be evaluated on the basis of the exercise hemodynamics before they are taken into consideration for meaningful decision-making processes such as establishment of the indication for surgery.


Gene expression profiling of anti-GBM glomerulonephritis model: the role of NF-kappaB in immune complex kidney disease.
Immune complexes may cause an irreversible onset of chronic renal disease. Most patients with chronic renal disease undergo a final common pathway, marked by glomerulosclerosis and interstitial fibrosis. We attempted to draw a molecular map of anti-glomerular basement membrane (GBM) glomerulonephritis in mice using oligonucleotide microarray technology. Kidneys were harvested at days 1, 3, 7, 11, and 16 after inducing glomerulonephritis by using anti-GBM antibody. In parallel with examining the biochemical and histologic changes, gene expression profiles were acquired against five pooled control kidneys. Gene expression levels were cross-validated by either reverse transcription-polymerase chain reaction (RT-PCR), real-time PCR, or immunohistochemistry. Pathologic changes in anti-GBM glomerulonephritis were confirmed in both BALB/c and C57BL/6 strains. Among the 13,680 spotted 65mer oligonucleotides, 1112 genes showing significant temporal patterns by permutation analysis of variance (ANOVA) with multiple testing correction [false discovery ratio (FDR) < 0.05] were chosen for cluster analysis. From the expression profile, acute inflammatory reactions characterized by the elevation of various cytokines, including interleukin (IL)-1 and IL-6, were identified within 3 days of disease onset. After 7 days, tissue remodeling response was prominent with highly induced extracellular-matrix (ECM) genes. Although cytokines related to lymphocyte activation were not detected, monocyte or mesangial cell proliferation-related genes were increased. Tumor necrosis factor-alpha (TNF-alpha) and nuclear factor-kappaB (NF-kappaB) pathway were consistently activated along the entire disease progression, inducing various target genes like complement 3, IL-1b, IL-6, Traf1, and Saa1. We made a large-scale gene expression time table for mouse anti-GBM glomerulonephritis model, providing a comprehensive overview on the mechanism governing the initiation and the progression of inflammatory renal disease.


Crystallization and preliminary X-ray analysis of the rhamnogalacturonan lyase YesW from Bacillus subtilis strain 168, a member of polysaccharide lyase family 11.
Rhamnogalacturonan lyases degrade rhamnogalacturonan I, a major component of pectin, through a beta-elimination reaction. YesW from Bacillus subtilis strain 168 is a novel rhamnogalacturonan lyase classified into polysaccharide lyase family 11 (PL-11). The enzyme was crystallized at 293 K using the sitting-drop vapour-diffusion method with 2-methyl-2,4-pentanediol (MPD) as a precipitant. Preliminary X-ray analysis revealed that the YesW crystals belong to space group P2(1) and diffract to 2.40 angstroms resolution, with unit-cell parameters a = 56.7, b = 105.6, c = 101.4 A, beta = 94.9 degrees. This is the first report on the crystallization and preliminary X-ray analysis of a family PL-11 rhamnogalacturonan lyase.


Fibronectin on the surface of biliary drain materials--a role in bacterial adherence.
The present study deals with the demonstration of deposited fibronectin (Fn) on the surfaces of implanted biliary drain materials and the role of deposited Fn in promotion of bacterial adherence. Rubber pieces that had been implanted in the biliary tracts of rats for 4 weeks were retrieved and the following approaches employed for further investigations: (1) adherence of [methyl-3H]thymidine-labeled Escherichia coli to implanted and unimplanted rubber pieces; (2) blocking the adherence of radiolabeled bacteria with anti-Fn antibodies; (3) detection of deposited Fn by 125I-labeled anti-Fn IgG; and (4) immunoblotting of the surface eluate from implanted rubber pieces. The results show that in the presence of serum, plasma, or bile, the number of E. coli cells adherent to implanted rubber pieces was 10 times higher than that adherent to the unimplanted pieces (P < 0.001) and that the adherence was reduced by pretreatment of implanted pieces with anti-Fn antibodies. Furthermore, the implanted pieces appeared to have a high affinity for 125I-labeled rabbit anti-Fn IgG rather than the 125I-IgG without anti-Fn fraction. Fn was also found in the surface eluate of implanted pieces by immunoblotting of the eluate. The results in the present study suggest that Fn may be involved in implant-associated infections in the biliary tract.


Moving to Serene Nature May Prevent Poor Mental Health--Results from a Swedish Longitudinal Cohort Study.
Green spaces are recognized for improving mental health, but what particular kind of nature is required is yet not elucidated. This study explores the effect of specific types of recreational nature qualities on mental health. Longitudinal data (1999/2000 and 2005) from a public health survey was distributed to a stratified sample (n = 24,945) of a Swedish population. People from rural or suburban areas (n = 9230) who had moved between baseline and follow-up (n = 1419) were studied. Individual geographic residence codes were linked to five predefined nature qualities, classified in geographic information systems (GIS). Any change in the amount of or type of qualities within 300 m distance between baseline and follow-up was correlated to any change in mental health (as measured by the General Health Questionnaire) by logistic regression models. On average, the population had limited access to nature qualities both pre- and post-move. There was no significant correlation between change in the amount of qualities and change in mental health. However, the specific quality "serene" was a significant determinant with a significantly decreased risk for women of change to mental ill-health at follow-up. The objective definition of the potentially health-promoting quality may facilitate implication in landscape practice and healthy planning.


[IT systems for clinical databases--status and perspectives].
Generally, the use of clinical databases for quality development in the hospital sector has not been satisfactory. A substantial problem attaches to the IT systems used hitherto. This article describes a number of requirements which the National Indicator Project has specified for a forthcoming second generation of clinical database system. Besides, the second generation system Clinical Performance Measurements which is used in the Copenhagen Hospital Corporation for several disease areas and for The Danish Vascular Registry is described. This experience emphasizes the need for central management of development initiatives within clinical quality databases. The management must allow for coordination, rational management and experience-based further development of IT systems for the clinical databases and integration with present and forthcoming systems including electronic patient record systems. The management should also allow for the decisive interaction between clinical quality development and medical informatics.


[Expression of integrin beta3 and osteopontin in endometrium of patients with adenomyosis].
To investigate the expression of integrin beta3 and osteopontin (OPN) in eutopic and ectopic endometrium of adenomyosis. From January 2007 to July 2008, the endometrium specimens were collected from 43 patients with adenomyosis undergoing hysterectomy in Peking University First Hospital. Eutopic endometrium were 11 in proliferative phase and 32 in secretory phase (18 cases in mid-secretory phase) were collected. Ectopic endometriums were also collected. In the mean time, it was chosen 41 cases with pure subserous uterine myoma or cervical intraepithelial neoplasia (CIN) II-III treated by hysterectomy as controls including 12 endometrium in proliferative phase and 29 endometrium in secretory phase (19 cases in mid-secretory phase). The expression of Integrin beta3 subunit and OPN in the endometrium were assessed by immunohistochemical staining and quantitative real-time polymerase chain reaction. (1) Immunohistochemical staining showed that positive staining of integrin beta3 and OPN were present predominantly in eutopic and ectopic endometrial glandular epithelium. There was significant different protein expression of integrin beta3 and OPN, which were 1.6 +/- 0.8 and 1.7 +/- 0.7 in eutopic endometrium, 1.7 +/- 0.7 and 1.8 +/- 0.9 in ectopic endometrium, 2.1 +/- 0.9 and 2.0 +/- 0.9 in control endometrium (P < 0.05). The protein expression of integrin beta3 and OPN in eutopic endometrium of adenomyosis in the proliferative phase (0.8 +/- 0.4 and 0.7 +/- 0.3) were remarkably lower than those of the secretory phase (1.8 +/- 0.8 and 1.9 +/- 0.8, P < 0.01). The protein expression of integrin beta3 and OPN in the endometrium of controls in the proliferative phase (1.0 +/- 0.4 and 1.0 +/- 0.4) were significantly lower than those of the secretory phase (2.5 +/- 0.7 and 2.5 +/- 0.7) (P = 0.000). In the mid-secretory phase, the protein expression of integrin beta3 (2.0 +/- 0.9) and OPN (2.1 +/- 0.8) in eutopic endometrium of adenomyosis were significantly lower than that of control endometrium (2.7 +/- 0.5 and 2.7 +/- 0.7) (P < 0.01). (2) The mRNA expression level of integrin beta and OPN in eutopic and ectopic endometrium were assessed by quantitative real-time PCR (result was shown by median index). It was observed that integrin beta3 mRNA and OPN mRNA were significantly lower in the eutopic endometrium of adenomyosis (4.69 and 4.23), when compared with ectopic endometrium (7.96 and 14.84) and controls (13.47 and 17.40) (P < 0.05). Eutopic endometrium had higher mRNA expression of integrin beta and OPN mRNA in the secretory phase (5.54 and 11.40) than that in the proliferative phase (2.69 and 3.30) (P < 0.01). The mRNA expression level of integrin beta and OPN of control endometrium in the proliferative phase (3.12 and 4.75) were significantly lower than that in the secretory phase (19.94 and 21.00, P = 0.000). The mRNA expression of integrin beta and OPN were 10.10 and 14.34 in the mid-secretory phase, which were significantly lower than 21.50 and 24.18 in control endometrium (P < 0.05). High expression of integrin beta3 and OPN in ectopic endometrium of adenomyosis may cause endometriotic lesions; abnormal expression of integrin beta3 and OPN in the endometrium of adenomyosis during the implantation window may contribute to infertility in some patients.


Curcumin Modulates the Crosstalk Between Macrophages and Bone Mesenchymal Stem Cells to Ameliorate Osteogenesis.
Bone healing is thought to be influenced by the cross-talk between bone forming and immune cells. In particular, macrophages play a crucial role in the regulation of osteogenesis. Curcumin, the major bioactive polyphenolic ingredient of turmeric, has been shown to regulate inflammatory response and osteogenic activities. However, whether curcumin could regulate macrophage polarization and subsequently influence osteogenesis remain to be elucidated. In this study, the potential immunomodulatory capability of curcumin on inflammatory response and phenotype switch of macrophages and the subsequent impact on osteogenic differentiation of MSCs are investigated. We demonstrated that curcumin exhibited significant anti-inflammatory effect by polarizing the macrophages toward anti-inflammatory phenotype, with increased expression of IL-4, IL-10, and CD206, and decreased expression of IL-1β, TNF-α, CCR7, and iNOS. In addition, curcumin could improve the osteo-immune microenvironment via promoting osteogenesis-related regenerative cytokine BMP-2 and TGF-β production. Moreover, the co-cultured test of macrophages and BMSCs showed that curcumin-modulated macrophages conditioned medium could promote osteogenic differentiation of BMSCs with increased gene (ALP, Runx-2, OCN, and OPN) and protein (Runx-2 and OCN) expression levels, enhanced ALP activity, and obvious formation of mineralized nodules. Taken together, with the interaction between curcumin-conditioned macrophage and curcumin-stimulated BMSCs, curcumin could remarkably enhance the osteogenic differentiation of BMSCs in LPS-activated inflammatory macrophage-BMSCs coculture system.


Insulin hypoglycemia test and releasing hormone (corticotropin-releasing hormone and growth hormone-releasing hormone) stimulation in patients with pituitary failure of different origin.
To investigate the efficacy of endocrine evaluation in diagnosing and localizing the cause of anterior pituitary failure, 17 patients with suprasellar space-occupying lesions, 4 patients with intrasellar tumors, 8 patients with no detectable anatomical lesion, 1 patient with posttraumatic failure and 1 patient with septooptical dysplasia were investigated. Endocrine evaluation consisted of measuring adrenocorticotropic hormone (ACTH), cortisol, and growth hormone (GH) levels during insulin hypoglycemia test (IHT) and after administration of corticotropin-releasing hormone (CRH) and growth hormone-releasing hormone (GRH). In addition, basal prolactin levels, gonadal and thyroid function were evaluated. The results showed that 4 of 17 patients with suprasellar tumors had normal ACTH and GH responses during IHT and after releasing hormone (RH) administration. Five of these patients had a normal ACTH or cortisol rise but no GH response during IHT. All 5 had a normal ACTH and 3 had normal GH rise after RH. Seven patients with suprasellar tumors had no ACTH or GH response during IHT, but all had an ACTH response to CRH. Only 3 of this group had a GH response to GRH. There was one exception of a patient who showed a GH and ACTH rise during IHT but only a blunted ACTH and no GH rise after RH administration. Four patients with pituitary failure and no demonstrable lesion had an ACTH rise after CRH but no GH rise after GRH, whereas in 3 patients with isolated ACTH deficiency no ACTH rise after CRH was seen. In 4 patients with nonsecreting pituitary tumors normal ACTH responses to IHT and CRH were seen, whereas GH rose during IHT only in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)


Conservative Management of an Intraoperative Chyle Leak: A Case Report and Literature Review.
Chyle leaks are a rare but potentially fatal complication of head and neck surgery carrying an incidence as high as 8.3%. The development of a chyle leak carries significant morbidity ranging from delayed wound healing to oropharyngeal fistulas. Presented here is a case of a chyle leak that developed following a left posterolateral neck dissection that was successfully managed with a combination of drain suction, pressure dressing, and a fat-restricted diet. However, the patient's course was complicated by repeated chyle leak recurrences that may have been associated with the initiation of medium-chain triglyceride supplementation. Although further research is required to establish a causal relationship, these findings support the concerns of other investigators about the possible counterproductive role of medium-chain triglyceride supplementation in the management of chyle leaks.


[Studies on the pathophysiology of paraneoplastic syndromes: both cancer cells and host immune cells are responsible for the pathophysiology of leukocytosis associated with oral cancer].
Leukocytosis associated with malignant disease has been known as a paraneoplastic syndrome and occurs occasionally in patients with oral malignancies. In this study, mechanisms underlying leukocytosis associated with malignancy was investigated, using a squamous cell carcinoma of the maxilla from a patient who manifested marked leukocytosis. When the patient's tumor was inoculated into nude mice, it formed squamous cell carcinoma (MH85) and induced leukocytosis and splenomegaly. Leukocytosis and splenomegaly paralleled tumor growth. Surgical excision of MH85 tumor resulted in a dramatic reduction of leukocyte count and spleen weight, indicating an involvement of humoral mediators released by MH85. MH85 cells conditioned medium (MH85CM) were shown to contain granulocyte-colony stimulating factor (G-CSF) activity, which is a potent growth factor specific for granulocytes. These results suggest G-CSF or G-CSF like substance secreted by MH85 cells is responsible for leukocytosis in MH85 bearing nude mice (MH85 mice) and in the patient. MH85 cell growth was stimulated by G-CSF and inhibited by anti-G-CSF antibody, thus suggesting that G-CSF like substance is a autocrine growth factor for MH85 cells. Splenectomized MH85 mice developed less severe leukocytosis than did non-splenectomized mice. This finding indicated that not only G-CSF like substance secreted by MH85 cells but other humoral factors released by the hyperplastic spleen contribute to the development of leukocytosis. Splenic monocytes derived from MH85 mice and MH85CM-stimulated splenic monocytes showed increased secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1), both of which have been reported to induce neutrophilia in animals. Moreover, injection of anti-TNF-antibody into neutrophilic MH85 mice significantly, although not completely, decreased leukocyte count. Thus, it seemed likely that increased secretion of TNF and IL-1 by spleen cells that are stimulated by humoral factors released from MH85 also contributes to the progression of leukocytosis. In splenectomized mice, enlargement of MH85 tumor was retarded and metastases were impaired compared these in nonsplenectomized mice. Coculture of splenocytes from MH85 mice with normal spleen cells, inhibited blastogenesis in response to mitogen. The result suggests that splenocytes from MH85 mice played as immune suppressive cells. MH85CM conferred immune suppressive activity on normal spleen cells. This suppressor cell-inducing factor (SCIF) in MH85CM was found to have an apparent molecular weight of approximately 25kd, and its biological activity was neutralized by anti-G-CSF antibody. Therefore, SCIF secreted by MH85 cells was likely to be G-CSF like substance.(ABSTRACT TRUNCATED AT 400 WORDS)


Revision surgery for incidental gallbladder cancer: factors influencing operability and further evidence for T1b tumours.
There is a need to increase the available data on revision radical surgery for incidental gallbladder cancer and to determine factors influencing operability. We aimed to assess the impact of stage of disease (pT) and the type of primary surgery (laparoscopy versus open) on resectability rates. The data of 90 consecutive patients referred to the Tata Memorial Hospital between 1 January 2003 and 30 April 2007 for revision radical surgery for incidental gallbladder cancer were reviewed retrospectively. Of the 90 patients who underwent revision surgery, accurate data on T-stage was available in 76, and of these 76 patients, 44 (57.8%) had prior laparoscopic simple cholecystectomy, while 32 (42.2%) had undergone open surgery. The median time interval between the two surgeries was 2 months (range 4 weeks to 11 months). By T-stage, 23 patients had T1b disease, while 33 and 20 patients had T2 and T3 disease, respectively. Successful revision surgery could be undertaken in 71% of patients (54/76) and 29.6% of these had residual disease confirmed by histopathological examination. T-stage is an important factor in determining operability as confirmed by our study. As the T-stage of the disease increased, the chances of finding residual disease increased, while operability decreased. Furthermore, the case for revision surgery is strengthened because the incidence of lymph nodal disease is high even for pT1b cancers. The type of primary surgery does not affect operability in patients undergoing revision radical surgery for incidental gallbladder cancer.


The impact of the improvement of insomnia on blood pressure in hypertensive patients.
This study investigated the impact of the improvement of insomnia on the blood pressure levels of hypertensive patients. A total of 402 patients with a diagnosis of insomnia and hypertension were selected and randomly divided into two groups. The treatment group (202 cases) received standard anti-hypertensive treatment with Estazolam, and the control group (200 cases) received standard anti-hypertensive treatment with placebo. The sedentary diastolic and systolic blood pressures were measured before the treatment and every 7 days during the experiment. To assess the sleep quality and anxiety and depression levels of patients, the scores of the Pittsburgh Sleep Quality Index, the Hamilton Anxiety Rating Scale and the Hamilton Depression Scale-17 were reported at the same time points. At the conclusion of the experiment, the Pittsburgh Sleep Quality Index, Hamilton Anxiety Rating Scale and Hamilton Depression Scale-17 scores of the treatment group were significantly lower than those of the control group (P < 0.001). The insomnia treatment efficacy of Estazolam in the treatment group was 67.3%, significantly higher than that (14.0%) of the control (P < 0.001). The blood pressure of the treatment group showed significant improvement throughout the experiment. By Day 28, the decrease of sedentary diastolic and systolic blood pressures in the treatment group was significantly greater than that of the control (sedentary systolic blood pressure: 10.5 ± 3.9 versus 3.4 ± 2.5 mmHg; sedentary diastolic blood pressure: 8.1 ± 3.6 versus 2.7 ± 2.1 mmHg, P < 0.001), and the compliance rate of goal blood pressure (< 140/90 mmHg) was 74.8% with Estazolam, compared with 50.5% with placebo (P < 0.001). Thus, the current findings indicated that the improvement of insomnia can significantly help lower blood pressure in hypertensive patients.


Substrate-induction of veratric acid O-demethylase in Nocardia sp.
Nocardia sp. demethylates veratric acid to vanillic and isovanillic acids, and subsequently to protocatechuic acid. The accumulation of specific mRNA observed during incubation of Nocardia sp. cells with substrate, as well as the effect of inhibitors of transcription and translation point to the inducible character of demethylation processes.


Respiratory Rate Estimation Using U-Net-Based Cascaded Framework From Electrocardiogram and Seismocardiogram Signals.
At-home monitoring of respiration is of critical urgency especially in the era of the global pandemic due to COVID-19. Electrocardiogram (ECG) and seismocardiogram (SCG) signals-measured in less cumbersome contact form factors than the conventional sealed mask that measures respiratory air flow-are promising solutions for respiratory monitoring. In particular, respiratory rates (RR) can be estimated from ECG-derived respiratory (EDR) and SCG-derived respiratory (SDR) signals. Yet, non-respiratory artifacts might still be present in these surrogates of respiratory signals, hindering the accuracy of the RRs estimated. In this paper, we propose a novel U-Net-based cascaded framework to address this problem. The EDR and SDR signals were transformed to the spectro-temporal domain and subsequently denoised by a 2D U-Net to reduce the non-respiratory artifacts. We have shown that the U-Net that fused an EDR input and an SDR input achieved a low mean absolute error of 0.82 breaths per minute (bpm) and a coefficient of determination (R2) of 0.89 using data collected from our chest-worn wearable patch. We also qualitatively provided insights on the complementariness between EDR and SDR signals and demonstrated the generalizability of the proposed framework. ECG and SCG collected from a chest-worn wearable patch can complement each other and yield reliable RR estimation using the proposed cascaded framework. We anticipate that convenient and comfortable ECG and SCG measurement systems can be augmented with this framework to facilitate pervasive and accurate RR measurement.


Long term peritoneal dialysis--is it a reality?
The use of peritoneal dialysis (PD) has increased dramatically over the last two decades since the introduction of continuous ambulatory peritoneal dialysis (CAPD). With this has also been the improvement in outcomes. In the medium term (up to five years), there is no difference in patient survival when CAPD is compared with hemodialysis (HD); PD technique survival is also improving, though is somewhat less than on HD. Problem areas for PD appear to be peritoneal membrane related changes, residual function, and peritonitis and these would need to be impacted on to improve outcome and long-term survival on PD. Current data would suggest that not many patients continue on peritoneal dialysis beyond ten years. However there are developments which show promise and are likely to enhance the outcome. It is possible to maximise renal replacement therapy by using peritoneal dialysis as the initial therapy. Arguments that favour this are discussed.


The multicellular nature of filamentous heterocyst-forming cyanobacteria.
Cyanobacteria carry out oxygenic photosynthesis, play a key role in the cycling of carbon and nitrogen in the biosphere, and have had a large impact on the evolution of life and the Earth itself. Many cyanobacterial strains exhibit a multicellular lifestyle, growing as filaments that can be hundreds of cells long and endowed with intercellular communication. Furthermore, under depletion of combined nitrogen, filament growth requires the activity of two interdependent cell types: vegetative cells that fix CO2 and heterocysts that fix N2. Intercellular molecular transfer is essential for signaling involved in the regulation of heterocyst differentiation and for reciprocal nutrition of heterocysts and vegetative cells. Here we review various aspects of multicellularity in cyanobacterial filaments and their differentiation, including filament architecture with emphasis on the structures used for intercellular communication; we survey theoretical models that have been put forward to understand heterocyst patterning and discuss the factors that need to be considered for these models to reflect the biological entity; and finally, since cell division in filamentous cyanobacteria has the peculiarity of producing linked instead of independent cells, we review distinct aspects of cell division in these organisms.


Effect of altitude on hand-held peak flowmeters.
To quantify the effect of altitude on the operational characteristics of hand-held peak flowmeters. Altitude simulation within a hypobaric chamber combined with five constant simulated peak flows delivered from a computerized pump were used to test commercially available peak flowmeters. F.G. Hall Hyperbaric/Hypobaric facilities located at Duke University School of Medicine. Two each of nine models of commercially available hand-held peak flowmeters and a volume spirometer were tested at six simulated altitudes (100, 500, 1,000, 1,500, 2,000, and 3,000 m) using five target peak flows. Each peak flow was injected into each meter twice. Forward stepwise regression was used to check for nonlinear relationships between altitude and peak expiratory flowmeter readings. Linear regression equations were fit to the data at each target flow across altitude. Effect of absolute peak flow was tested by analysis of covariance. For these altitudes, linear relationships were found between altitude and measured peak flow. For all meters tested, the average decrease in peak flow ranged from -8.7% at the lowest target flow (123 L/min) to -6.5% at the highest target flow (702 L/min) for each 100 mm Hg decrease in barometric pressure (PB). Individual meters ranged from -12.3% at the lowest target flow to -4.4% at the highest target flow for 100 mm Hg decrease in PB. The spirometer had no significant changes associated with changes in PB. In all cases, the magnitude of the altitude effect, measured by percent change, decreased with increasing peak flow. Peak expiratory flowmeters underread PEF as a function of both increasing altitude and increasing target peak flow.


Blastic plasmacytoid dendritic cell neoplasm with genetic mutations in multiple epigenetic modifiers: a case report.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematodermic malignancy derived from plasmacytoid dendritic cell precursors. Despite advances in our understanding of tumor cell surface markers, the pathogenesis of BPDCN remains largely unknown. No standard or optimal treatments are available for BPDCN, and the prognosis is usually poor. We report herein a case of BPDCN that harbored multiple genetic mutations in epigenetic modifiers such as TET2 and ZRSR2. Genetic studies in patients with BPDCN may provide insights into the underlying pathogenesis, prediction of clinical prognosis, and development of better targeted therapeutics for this rare clinical entity.


Massive Gravitons as Feebly Interacting Dark Matter Candidates.
We detail our discovery of a chiral enhancement in the production cross sections of massive spin-2 gravitons, below the electroweak symmetry breaking scale, that makes them ideal dark matter candidates for the freeze-in mechanism. The result is independent of the physics at high scales and points toward masses in the keV-MeV range. The graviton is, therefore, a sub-MeV dark matter particle, as favored by the small scale galaxy structures. We apply the novel calculation to a Randall-Sundrum model with multiple branes, showing a significant parameter space where the first two massive gravitons saturate the dark matter relic density.


Domestic abuse--an underreported problem in general dental practice?
'Child abuse' is a topic about which clinicians will be well informed. There are protocols relating to the management of patients suspected of having sustained non-accidental injuries and clinical staff will be expected, as part of mandatory training, to receive education in this area. Domestic abuse (DA) is an under-reported, but relatively common problem and has many implications in the management of traumatic injuries in adults. The objective of this paper is to discuss the aetiology, history and presentation of patients who have been subjected to domestic abuse, and to help provide a strategy for their management. Domestic abuse is a relatively common problem and, as such, dentists should be aware of this important area and how to manage patients they suspect of having been abused, or who inform them that they have' been subjected to DA.