KCNQ1 and Long QT Syndrome in 1/45 Amish: The Road From Identification to Implementation of Culturally Appropriate Precision Medicine.
In population-based research exome sequencing, the path from variant discovery to return of results is not well established. Variants discovered by research exome sequencing have the potential to improve population health. Population-based exome sequencing and agnostic ExWAS were performed 5521 Amish individuals. Additional phenotyping and in vitro studies enabled reclassification of a KCNQ1 variant from variant of unknown significance to pathogenic. Results were returned to participants in a community setting. A missense variant was identified in KCNQ1 (c.671C>T, p.T224M), a gene associated with long QT syndrome type 1, which can cause syncope and sudden cardiac death. The p.T224M variant, present in 1/45 Amish individuals is rare in the general population (1/248 566 in gnomAD) and was highly associated with QTc on electro-cardiogram (P=5.53E-24, β=20.2 ms/allele). Because of the potential importance of this variant to the health of the population, additional phenotyping was performed in 88 p.T224M carriers and 54 noncarriers. There was stronger clinical evidence of long QT syndrome in carriers (38.6% versus 5.5%, P=0.0006), greater history of syncope (32% versus 17%, P=0.020), and higher rate of sudden cardiac death in first degree relatives<age 30 (4.5% versus 0%, P=0.026). Expression of p.T224M KCNQ1 in Chinese hamster ovary cells showed near complete loss of protein function. Our clinical and functional data enabled reclassification of p.T224M from a variant of unknown significance to pathogenic. Of the 88 carriers, 93% met criteria for beta-blocker treatment and 5/88 (5.7%) were on medications that may further prolong QTc. Carriers were provided a Clinical Laboratory Improvement Amendments confirmed report, genetic counseling, and treatment recommendations. Follow-up care was coordinated with local physicians. This work provides a framework by which research exome sequencing can be rapidly translated in a culturally appropriate manner to directly benefit research participants and enable population precision health.


Thyroid C cells in male and female rats with chronic renal failure.
The kidneys are responsible for iodine and of thyroid hormone biodegradation. The aim of this study was the histomorphological and immunohistochemical evaluation of the influence of sex on parafollicular thyroid C cells in rats with chronic renal failure. The experiment included 40 Wistar rats after subtotal nephrectomy, after sham operation, and without any surgical procedure. Two weeks after nephrectomy, fragments of thyroids were collected from the examined animals. Paraffin sections were stained with H+E and by silver impregnation. Calcitonin (CT), synaptophysin (SPh), somatostatin (ST), and neuron-specific enolase (NSE) were detected immunohistochemically in C cells. In rats with experimental uremia, immunostaining for the examined substances increased significantly in comparison to the controls. We also observed higher number of C cells with a stronger reaction in the group of males, compared to the female rats.


Partially reversible renal tubular damage in patients with obstructive jaundice.
Decreased serum uric acid levels resulting from renal urate wasting have been occasionally encountered in jaundiced patients. However, in these cases, there are no data concerning the underlying renal tubular defects. In the present study, we investigated the renal tubular function in 35 patients with obstructive jaundice of various severity and causes (11 with lithiasis, 17 with carcinoma, and 7 with intrahepatic cholestasis). A detailed study of the renal tubular function was performed. Beyond the conventional methods, (1)H-NMR spectroscopy of urine was used to evaluate noninvasively renal damage by the characteristic perturbation in the excretion pattern of low-molecular weight endogenous metabolites. On admission, patients with obstructive jaundice had significantly lower serum uric acid and phosphate levels and higher bile acid concentrations compared with 40 age- and sex-matched controls. Serum uric acid levels presented a negative correlation with the total and direct bilirubin as well as the fractional excretion of uric acid. Furthermore, a great number of the patients studied developed one or more proximal tubular dysfunction manifestations beyond uricosuria, such as renal glucosuria, phosphaturia, and increased excretion of alpha(1)-microglobulin. (1)H-NMR spectroscopy of the urine showed decreased levels of citrate and hippurate and increased levels of 3-hydroxybutyrate and acetate. In 12 patients partial or complete remission of jaundice was followed by an improvement of the proximal renal tubular damage. In conclusion, obstructive jaundice can cause a partially reversible generalized proximal tubular dysfunction.


Idiopathic autoimmune hemolytic anemia along with concomitant vitamin B12 deficiency in an adolescent girl: A rare occurrence.
Vitamin B12 deficiency is seen in countries like India mainly because of predominantly vegetarian diet and is a significant health problem. Patients present with various neurological and hematological manifestations of megaloblastic anemia. In this case report, we present a 14-year-old girl child having a history of past blood transfusions and iron deficiency anemia currently presenting with severe anemia due to idiopathic autoimmune hemolytic anemia (AIHA) and later found to have concomitant vitamin B12 deficiency. On investigating, she had vitamin B12 deficiency, raised homocysteine and methylmalonic acid levels, positive Direct Coombs Test (DCT), and negative glucose-6-phoshphatase deficiency and osmotic fragility tests. Thyroid profile and tissue transglutaminase IgA (tTg-IgA) tests were negative. Antinuclear antibodies (ANA) and anti-double stranded DNA antibody (anti-dsDNA) serum immunoglobulin were also normal. Bone marrow showed megaloblastic anemia picture. Although AIHA and vitamin B12 deficiency anemia are not common, clinicians should have a high index of suspicion when patients present with hemolytic picture and severe megaloblastic anemia.


Density functional theory simulations of amorphous high-κ oxides on a compound semiconductor alloy: a-Al2O3/InGaAs(100)-(4×2), a-HfO2/InGaAs(100)-(4×2), and a-ZrO2/InGaAs(100)-(4×2).
The structural properties of a-Al(2)O(3)∕In(0.5)Ga(0.5)As, a-HfO(2)∕In(0.5)Ga(0.5)As, and a-ZrO(2)∕In(0.5)Ga(0.5)As interfaces were investigated by density-functional theory (DFT) molecular dynamics (MD) simulations. Realistic amorphous a-Al(2)O(3), a-HfO(2), and a-ZrO(2) samples were generated using a hybrid classical-DFT MD "melt-and-quench" approach and tested against the experimental properties. For each stack type, two systems with different initial oxide cuts at the interfaces were investigated. All stacks were free of midgap states, but some had band-edge states which decreased the bandgaps by 0%-40%. The band-edge states were mainly produced by deformation, intermixing, and bond-breaking, thereby creating improperly bonded semiconductor atoms. The interfaces were dominated by metal-As and O-In∕Ga bonds which passivated the clean surface dangling bonds. The valence band-edge states were mainly localized at improperly bonded As atoms, while conduction band-edge states were mainly localized at improperly bonded In and Ga atoms. The DFT-MD simulations show that electronically passive interfaces can be formed between high-κ oxides dielectrics and InGaAs if the processing does not induce defects because on a short time scale the interface spontaneously forms electrically passive bonds as opposed to bonds with midgap states.


Lung Function, Respiratory Muscle Strength, and Thoracoabdominal Mobility in Women With Fibromyalgia Syndrome.
Fibromyalgia syndrome (FMS) is associated with a variety of symptoms, such as fatigue and dyspnea, which may be related to changes in the respiratory system. The objective of this work was to evaluate pulmonary function, respiratory muscle strength, and thoracoabdominal mobility in women with FMS and its association with clinical manifestations. The study included 23 women with FMS and 23 healthy women (control group). Pulmonary function, respiratory muscle strength, and thoracoabdominal mobility were assessed in all participants. Clinical manifestations such as number of active tender points, pain, fatigue, well-being, and general pressure pain threshold and pressure pain threshold in regions involved in respiratory function were also assessed. For data analysis, the Mann-Whitney test and Spearman correlation coefficient were used. The FMS group showed lower values of maximum voluntary ventilation (P = .030), maximal inspiratory pressure (P = .003), and cirtometry at the axillary and xiphoid levels (P < .001 and P < .001, respectively) as well as higher cirtometry at the abdominal level (P = .005) compared with the control group. However, there was no significant difference between groups for maximum expiratory pressure. In predicted percentage, maximal inspiratory pressure showed significant positive correlation with axillary cirtometry (r = 0.41, P = .049) and negative correlation with the number of active tender points (r = -0.44, P = .031) and fatigue (r = -0.41, P = .049). Subjects with FMS had lower respiratory muscle endurance, inspiratory muscle strength, and thoracic mobility than healthy subjects. In addition, inspiratory muscle strength was associated with the number of active tender points, fatigue, and axillary mobility.


[Physiological roles of rhodopsin phosphorylation and dephosphorylation and its relationship with retinitis pigmentosa].
Light signals are converted into electrical signals by vertebrate photoreceptor cells, and the generated electrical signals are then modulated within retinal neurons and brain. During the visual transduction precesses in the photoreceptor cells, there are basically three functions. That is, (1) photoexcitation, (2) quenching of the photoexcitation, and (3) adaptation. These functions are precisely regulated by enzymatic cascade reactions. Quite recently, it was shown that rhodopsin phosphorylation occurred at different sites with different kinetics, in vivo, and this may be a control mechanism for both quenching and adaptation. Furthermore, autosmal retinitis pigmentosa (RP) with rhodopsin mutation at 296 Lys, which in the binding site of 11-cis-retinal, showed constitutive activation of guanosine 5'-triphosphate (GTP) binding protein and no rhodopsin phosphorylation by rhodopsin kinase. These observations suggest that rhodopsin phosphorylation and dephosphorylation are critical for understanding visual transduction and pathophysiology of RP.


[Studies on the interaction of the metal complex of hydrazide of podophyllic acid with DNA].
The interaction between the metal complex of hydrazide of podophyllic acid and calf thymus (CT) DNA was studied by using absorption spectra, fluorescence spectra and DNA heat denaturation. It was found that the intensity of the maximal absorption peaks from absorption spectra is weakened in the presence of the metal complex of hydrazide of podophyllic acid compared with that in the absence of the metal complex. All the experimental results show that the intercalation mode was proved to exist between HDPP-Ni complexes and CT DNA.


[Professional caregivers as civilian first responders in prehospital cardiac arrest].
The chance of survival from a prehospital cardiac arrest has increased enormously in recent years thanks to the efforts of civilian first responders. They can start CPR and possibly defibrillate while waiting for the ambulance. These civilian first responders regularly include professional caregivers who can provide advanced life support (ALS) together with ambulance personnel. This article describes the opportunities and challenges, and discusses competence and ability, the use of expertise, and crew resource management (CRM) to ensure that the available knowledge and skills are managed in the right direction. This can further improve the quality of patient care and thus increase the chance of survival.


Analysis of hydroxyl radical-induced oxidation process of glucagon by reversed-phase HPLC and ESI-MS/MS.
Structural modification of a polypeptide hormone, glucagon, by a hydroxyl radical in vitro was investigated by reversed-phase high-performance liquid chromatography (RP-HPLC), and the oxidized site of glucagon was detected by electrospray ionization tandem mass spectrometry (ESI-MS/MS). It was shown that (27)methionine (Met) was oxidized to (27)Met sulfoxide by hydroxyl radical, and the production rate of (27)Met sulfoxide was faster than that by hydrogen peroxide. In addition, production of (27)Met sulfoxide enantiomer was confirmed by RP-HPLC analysis. cAMP production in a HepG2 cell induced by (27)Met sulfoxide glucagon was reduced to approximately 75% as compared with that induced by the native form of glucagon.


Age-related differences in risk factors for prostatectomy for benign prostatic hyperplasia: the VA Normative Aging Study.
The Veterans Administration Normative Aging Study (VANAS) is an ongoing study of a cohort of 2,280 men assembled between 1963-1968 and followed to the present time. Among this cohort of men, urinary symptoms were found to be strongly predictive of surgery for benign prostatic hyperplasia (BPH), and this risk varied by age. Nocturia (OR 1.8) and hesitancy (OR 4.3) were found to be predictive of surgery for younger men (age range 49-55), while only nocturia (OR 2.4) was predictive among older men (age range 62-68). This age-related difference in both identification of risk factors and magnitude of association with surgery was independent of assessing other commonly studied risk factors. Ultimately, the decision to operate is a combination of patient's need, access to care, and patient's preference. Further research will be required to assess which factor or factors are responsible for the age-related differences in surgical risk factors.


Health-related quality of life and chronic wound characteristics among patients with chronic wounds treated in primary care: A cross-sectional study in Singapore.
Chronic wounds commonly decrease patients' quality of life. Understanding how chronic wounds impact a patient's health-related quality of life (HRQoL) is important for healthcare service delivery and treatment management. This study explored HRQoL among patients suffering from chronic wounds and investigated associations with patients' socio-demographics and wound characteristics. Two hundred and thirty-three patients across six primary care clinics were assessed and responded to a survey that collected information on socio-demographic, wound characteristics, and HRQoL using the EQ-5D-5L instrument. Data were analysed by descriptive statistics and generalised linear models. The mean age of patients was 61.2 (SD: 14.6) years; 68.2% were males; and 61.8% were of Chinese origin. Arterial ulcers had the greatest negative impact on HRQoL related to mobility, self-care, pain/discomfort and anxiety/depression, and the lowest VAS mean score 62.31 (SD: 28.3; range: 0-100) indicating the worst health. HRQoL related to mobility was significantly associated with age (β = 0.008, P < .001), non-Chinese ethnicity (β = 0.25, P = .001), mixed ulcers (β = -0.41, P = .022), atypical hard-to-heal wounds (β = -0.38, P = .021), wounds with low (β = 0.24, P = .044) to moderate (β = 0.29, P = .018) exudate level, and a wound duration ≥6 months (β = 0.19, P = .033). The findings can be used to improve healthcare delivery for patients with chronic wound to optimise their HRQoL.


Research progress in the estimation of the postmortem interval by Chinese forensic scholars.
The determination of time since death or the postmortem interval (PMI) is one of the most important and frequently asked questions in forensic medicine. Medicolegal scholars and forensic pathologists around the world have studied the estimation of PMI extensively in the past, and many novel methods and advanced technologies have now been applied in the field. For several centuries, Chinese forensic examiners have also worked on the estimation of the PMI, and there are a large number of excellent studies published in Chinese rather than in English, and these are not easily accessible or known internationally. Therefore we have conducted a review of relevant studies published by Chinese forensic scholars in the last few decades. The scope of this review is to provide a concise summary of the current progress in the estimation of PMI by Chinese forensic researchers using molecular biology, spectroscopic technology, entomological methods, energy changes, thanatochemistry and other methods.


[BIOLOGIC THERAPY FOR JUVENILE IDIOPATHIC ARTHRITIS].
Juvenile Idiopathic Arthritis (JIA) includes a group of systemic inflammatory disorders of unknown etiology for which no curative treatment currently exists. The traditional treatment for these disorders which includes the use of NSAIDs and disease modifying anti-rheumatic drugs (DMRADs) is only effective in a subset of patients. Recent advances in understanding the pathophysiology of the inflammatory response, have led to the development of a new class of medications, termed biologic agents which are capable of selectively inhibiting the principal mediators of inflammation. The introduction of biologic drugs has opened a new era in the treatment of rheumatic disorders in children. In this review we describe the characteristics of the currently available biologic agents in Israel, and the updated information regarding indications, efficacy and the safety of these drugs in pediatric patients. Disclosure: Consultant and participating in clinical trials for Novartis com.


From Peyer's patches to tonsils. Specific stimulation with ribosomal immunotherapy.
Ribosomal immunotherapy has been successfully used since the 1960s to boost the immune system and provide protection against microbial infections. We have investigated both whether and how these immunostimulants behave as natural immunogens in the mucosa-associated immune system. According to current understanding of the physiology of the mucosal immune response, intestinal Peyer's patches and the related solitary nodules are the primary inductive sites involved in the immune protection of all mucosal surfaces. Sensitised lymphocytes generated at these sites reach the general circulation through lymphatic drainage and relocate in mucosal areas by means of specialised 'high endothelial venules'. We hypothesised that orally administered ribosomal preparations would yield sensitised B cells specific for bacterial antigens from the parent strains. These cells should then be detectable in the peripheral blood after ribosomal intake, and identifiable as plasma cells in mucosae-associated tissues after completing their terminal differentiation. Ultimately, specific IgA should appear in secretions. To this end, we studied the immune responses generated in children and adults after 'Ribomunyl' administration, according to various consecutive protocols. The initial hypothesis was confirmed by the identification of specific B cells in the peripheral blood, plasma cells in the tonsillar tissue and specific IgA in the saliva. An animal model involving the use of twin sheep enabled detection of the specific cells in mesenteric and cervical lymph nodes. Analysis of these data indicates that ribosomal preparations trigger the production of lymphocytes specific for both ribosomes themselves and whole bacterial antigens. This supports the fact that small antigenic motifs are carried as partly synthesised peptides on the ribosomal particles. Therefore, ribosomes boost an array of B cells that are specific for many antigenic determinants of the bacteria from which they are extracted. We were also able to show that the stimulation provided was specific, since no response to other bacteria could be detected. Finally, analysis of the kinetics of this stimulation confirmed that oral immunisation generates rapid and transient secretory responses, building increased numbers of memory cells that are readily available to respond to further challenges by either more ribosomal preparations or potential pathogens.


Kinetic study of IO radical with RO2 (R = CH(3), C2H5, and CF3) using cavity ring-down spectroscopy.
The reactions of iodine monoxide radical, IO, with alkyl peroxide radicals, RO(2) (R = CH(3), C(2)H(5), and CF(3)), have been studied using cavity ring-down spectroscopy. The rate constant of the reaction of IO with CH(3)O(2) was determined to be (7.0 +/- 3.0) x 10(-11) cm(3) molecule(-1) s(-1) at 298 K and 100 Torr of N(2) diluent. The quoted uncertainty is two standard deviations. No significant pressure dependence of the rate constant was observed at 30-130 Torr total pressure of N(2) diluent. The temperature dependence of the rate constants was also studied at 213-298 K. The upper limit of the branching ratio of OIO radical formation from IO + CH(3)O(2) was estimated to be <0.1. The reaction rate constants of IO + C(2)H(5)O(2) and IO + CF(3)O(2) were determined to be (14 +/- 6) x 10(-11) and (6.3 +/- 2.7) x 10(-11) cm(3) molecule(-1) s(-1) at 298 K, 100 Torr of N(2) diluent, respectively. The upper limit of the reaction rate constant of IO with CH(3)I was <4 x 10(-14) cm(3) molecule(-1) s(-1).


[CHU Hao-ran's experience in treatment of diarrhea-predominant irritable bowel syndrome with acupuncture and moxibustion].
Professor CHU Hao-ran believes that the clinical diagnosis and treatment of diarrhea-predominant irritable bowel syndrome with acupuncture and moxibustion should concentrate on the integration of disease and syndrome differentiation. According to the evolution of pathogenesis, this disease is divided into 4 stages, i.e. invasion of exogenous pathogens, liver stagnation and spleen deficiency, spleen and kidney yang deficiency and interaction of cold and heat. Hence, the treatment should be provided by stages. Focusing on regulating the spleen and stomach, a specific acupuncture-moxibustion prescription is proposed, including Tianshu (ST 25), Zhongwan (CV 12), Zusanli (ST 36) and Shangjuxu (ST 37). Additionally, the combination of distal and nearby acupoints is considered and an unique needling manipulation, named the fight between dragon and tiger, is exerted. On the base of syndrome and meridian differentiation, the modern medicine is combined, stressing on the mind regulation and the mutual application of acupuncture and moxibustion in treatment. Eventually, a distinctive treatment system with acupuncture and moxibustion is formed for "regulating the spleen and stomach and differentiating meridians".


The correlation of cognitive decline with frontotemporal dementia induced annualized gray matter loss using diffeomorphic morphometry.
This study uses large deformation medical image registration to analyze, in a disease-specific normalized space, the annual rate of gray matter atrophy caused by frontotemporal dementia (FTD) and its correlation with cognitive decline. The analysis consists of three parts. First, a labeled structural MRI atlas is deformed into the shape of an average FTD brain. Second, annualized FTD-related atrophy of gray matter structures is estimated for each patient in the database. Third, the group-wise annualized atrophy rate caused by FTD is correlated, for each gray matter voxel, with declining performance on cognitive tests. This study gives insight into the relationship between FTD-related progressive cortical atrophy and loss in cognitive function.


Design of few-layer carbon nitride/BiFeO3 composites for efficient organic pollutant photodegradation.
Heterojunction-driven photocatalysis can degrade various organic pollutants, and developing carbon nitride-based composite photocatalysts is of great significance and gains growing interest. In this study, a two-dimensional graphitic carbon nitride nanosheets/BiFeO3 (GCNNs/BiFeO3) Z-scheme heterojunction has been synthesized through the electrostatic spinning and post-calcination The obtained GCNNs/BiFeO3 nanofibers show large surface contact between GCNNs the and BiFeO3 nanostructures. The Z-scheme heterojunction shows a remarkably enhanced photocatalytic performance, which could degrade 94% of tetracycline (TC) and 88% of Rhodamine B (RhB) under LED visible light irradiation in 150 min. Radical trapping experiments demonstrate the effective construction of Z-scheme heterojunctions, and •O2- and h+ are the main active species in the photocatalytic degradation process. This study realizes a novel nanostructured GCNNs/BiFeO3 heterojunction for photodegradation applications, which would guide the design of next-generation efficient photocatalysts.


Sintilimab plus chemotherapy achieved symptom relief in stage IV lung squamous cell carcinoma with superior vena cava syndrome: a case report.
Lung cancer is the second most common and mortality disease in the world. Most patients with lung cancer are already at the advanced stage when diagnosed. There are multiple treatments for advanced lung cancer. Among them, immunotherapy plus chemotherapy has gradually become the first-line treatment. Lung cancer has multiple complications, superior vena cava syndrome (SVCS) is a common complication of patients with advanced lung cancer. The current treatments include radiotherapy, chemotherapy, and stent implantation. Stent implantation has the disadvantages of invasiveness and poor efficacy. Immunotherapy, as an emerging treatment for tumors, has shown significant advantages in treating patients with advanced lung cancer. However, the treatment of advanced lung cancer with SVCS using immunotherapy has rarely been reported. Here, we reported a 48-year-old male patient with stage IV (T4N3M1) lung squamous cell carcinoma. After receiving 1 cycle (3 weeks) of comprehensive treatment with sintilimab plus chemotherapy, the tumor mass shrank by 30% to achieve partial response (PR), collateral circulation was formed, and most of the symptoms caused by SVCS disappeared. After 3 cycles of treatment, the tumor shrank by nearly 90%, and the superior and inferior vena cava opened larger than before. Our case provides a novel treatment strategy for such patients.


Reappraisal of amoxycillin absorption kinetics.
Interest in the intestinal absorption mechanisms of drugs has increased because transepithelial passage across the gut does not necessarily follow a passive diffusion process. Amoxycillin, like other amino-beta-lactam antibiotics, has been demonstrated in vitro to use the dipeptide carrier-mediated system in rodent small intestine. In order to assess the in-vivo relevance of these data, we applied the Loo-Riegelman method for a reappraisal of amoxycillin absorption kinetics in healthy human volunteers. The results showed evidence of a saturable carrier-mediated uptake of this antibiotic. With respect to the in-vitro data previously published, the dipeptide carrier system would appear to be the most likely transport mechanism.


Hirayama disease: the importance of flexion imaging.
Hirayama disease is a rare cervical myelopathy characterised by asymmetrical upper limb weakness and muscle atrophy in the forearm and hand. MRI of the cervical spine plays an essential role in diagnosis, however, the characteristic findings are often only seen when the patient is imaged with the neck in flexion. We present a case of a 15-year-old male who presented with left forearm and hand weakness with muscle wasting. An MRI of the cervical spine with the neck in a neutral position demonstrated atrophy of the spinal cord with intrinsic signal abnormality between C5 and C7. Further imaging with the patient's neck in flexion demonstrated the hallmark features of Hirayama disease. There was anterior displacement of the thecal sac and spinal cord, and an enlarged, crescent-shaped dorsal epidural space which enhanced following i.v. gadolinium administration. The atrophic segment of cord contacted the posterior vertebral bodies when the neck was in full flexion. This case highlights the importance of imaging patients suspected of having this entity with the neck in full flexion in order to make a diagnosis.


The experiences of risk managers in providing emotional support for health care workers after adverse events.
Risk managers often meet with health care workers who are emotionally traumatized following adverse events. We surveyed members of the American Society for Health care Risk Management (ASHRM) about their training, experience, competence, and comfort with providing emotional support to health care workers. Although risk managers reported feeling comfortable and competent in providing support, nearly all respondents prefer to receive additional training. Risk managers who were comfortable listening to and supporting health care workers were more likely to report prior training. Health care organizations implementing second victim support programs should not rely solely on risk managers to provide support, rather engage and train interested risk managers and provide them with opportunities to practice.


Diagnostic and prognostic test assessment in emergency medicine: likelihood and diagnostic odds ratios.
Emergency physicians use diagnostic and prognostic tests on a daily basis to assess for life-threatening illness and to inform clinical decisions. Current and new tests must be scientifically evaluated for their diagnostic utility. We discuss the evaluation of diagnostic and prognostic tests using the Bayesian likelihood ratio (LR) and logistic regression diagnostic odds ratio (OR) frameworks. These approaches can be applied to a single test in isolation using univariate techniques, or to a group of tests as commonly applied in clinical practice using multivariate methods. We compare and contrast the relative benefits and challenges of the LR and OR approaches, and assess their interchangeability. The concepts of diagnostic multivariate testing also underlie the framework of clinical decision rules which have gained acceptance in emergency medicine. Clinical decision rules can be viewed as a subanalysis within the joint LR framework. Ultimately, a variety of approaches may be acceptable and even complementary to assess a diagnostic test, each with its own merits and limitations.


[Progress in surgical treatment of perianal abscess].
There were more and more patients suffered from perianal abscess. The patient's condition will become even worse if the patients cannot be treated properly. Selecting proper operation method according to special condition is the key point of increasing curative effect, decreasing suffering and relapse rate and promoting quality of life of patients. The authors summarized operation methods, including abscess incision drainage, radical incision and thread-drawing, and staging incision and thread-drawing, etc. in treating perianal abscess in clinic.


Derived acoustically evoked brainstem responses by means of narrow-band and notched-noise masking in normal-hearing subjects.
Derived acoustically evoked brainstem responses determined by narrow-band and notched-noise masking at 2000 Hz frequencies and below were investigated and compared with those obtained in the use of the common high-pass masking technique. With all three masking methods a dominant late wave Wa could be detected at less than or equal to 1 600 Hz centre frequencies of the derived band and this wave is typical of the excitation of the apical section of the cochlea. The latency of this wave increases when the centre frequency is decreased at a constant stimulation level. For a constant centre frequency of the derived band the latency of wave Wa increases when the stimulation level of the click and in parallel to that the masking level is decreased. Wave Wa could be found near the hearing threshold in all three masking methods. The notched-noise masking method offers major advantages provided that full masking of the frequency regions above and below the notch frequency range is carried out. A direct frequency-specific stimulation takes place and there is no need for subtracting one response from a second one. This reduces the investigation time and the memory capacity of the measuring device. The advantages and applicability of the notched-noise masking method have to be re-checked in patients with different frequency-dependent loss of hearing.


Isolated avulsion fracture of the lesser tuberosity of the humerus.
Six cases of isolated avulsions of the lesser tuberosity of the humerus were encountered within a short period of time. Although it seldom has been described in the literature, it might be a more common fracture than suspected. Physical examination revealed a painful shoulder with limited function in all six patients. In retrospect, all diagnoses could have been made on the primary plain roentgenograms. However, the fragment of the lesser tuberosity was easily misdiagnosed. An axillary view showed the fragment clearly in all cases. Computed tomography is useful for making an accurate diagnosis because it establishes the size and displacement of the fragment and determines additional injuries, such as a ruptured biceps tendon. Five patients with displacement of the lesser tuberosity were operated on after several weeks or months. The lesser tuberosity was reattached in all cases. After 6 months three patients had slight impairment of elevation and external rotation, and one of them suffered from pain during movements of the arm. The patient with no fracture displacement was treated conservatively with a good result. In conclusion, we recommended an axillary roentgenogram as part of the posttrauma radiologic series of the shoulder. A nondisplaced avulsion fracture of the lesser tuberosity of the humerus can be treated conservatively. We recommend reattachment of displaced fractures.


World Health Day is a day for safer motherhood.
Every year, April 7 is kept as World Health Day. This year [1998] marks the 50th anniversary of the foundation of WHO. However, the day has a double significance because the theme of this year's World Health Day is safe motherhood. All around the world people will mark this day and remind communities and leaders that there is still much work to be done to make pregnancy and childbirth safer. World leaders in Washington will be doing their part on this day, for without high-level political commitment it is hard to get things done. However, this effort is not just for a day. The whole year is dedicated to the theme of safe motherhood. Please let us know about the initiatives taking place in your country, and do send photographs] We can all do something this year to make things better for women and their newborns. Please send your stories and photos to the Editor, Safe Motherhood (address on back page). As well as the 10 action messages that were developed at the technical consultation to mark the 10th anniversary of the Safe Motherhood Initiative, fact sheets and slides are also available either by writing to WHO or on the Internet.


Understanding why racial/ethnic inequities along the HIV care continuum persist in the United States: a qualitative exploration of systemic barriers from the perspectives of African American/Black and Latino persons living with HIV.
Racial/ethnic inequities along the HIV care continuum persist in the United States despite substantial federal investment. Numerous studies highlight individual and social-level impediments in HIV, but fewer foreground systemic barriers. The present qualitative study sought to uncover and describe systemic barriers to the HIV care continuum from the perspectives of African American/Black and Latino persons living with HIV (PLWH) with unsuppressed HIV viral load, including how barriers operated and their effects. Participants were African American/Black and Latino PLWH with unsuppressed HIV viral load (N = 41). They were purposively sampled for maximum variability on key indices from a larger study. They engaged in semi-structured in-depth interviews that were audio-recorded and professionally transcribed. Data were analyzed using directed content analysis. Participants were 49 years old, on average (SD = 9), 76% were assigned male sex at birth, 83% were African American/Black and 17% Latino, 34% were sexual minorities (i.e., non-heterosexual), and 22% were transgender/gender-nonbinary. All had indications of chronic poverty. Participants had been diagnosed with HIV 19 years prior to the study, on average (SD = 9). The majority (76%) had taken HIV medication in the six weeks before enrollment, but at levels insufficient to reach HIV viral suppression. Findings underscored a primary theme describing chronic poverty as a fundamental cause of poor engagement. Related subthemes were: negative aspects of congregate versus private housing settings (e.g., triggering substance use and social isolation); generally positive experiences with health care providers, although structural and cultural competency appeared insufficient and managing health care systems was difficult; pharmacies illegally purchased HIV medication from PLWH; and COVID-19 exacerbated barriers. Participants described mitigation strategies and evidenced resilience. To reduce racial/ethnic inequities and end the HIV epidemic, it is necessary to understand African American/Black and Latino PLWH's perspectives on the systemic impediments they experience throughout the HIV care continuum. This study uncovers and describes a number of salient barriers and how they operate, including unexpected findings regarding drug diversion and negative aspects of congregate housing. There is growing awareness that systemic racism is a core determinant of systemic barriers to HIV care continuum engagement. Findings are interpreted in this context.


In-depth computational analysis of calcium-dependent protein kinase 3 of Toxoplasma gondii provides promising targets for vaccination.
The Toxoplasma gondii calcium-dependent protein kinase-3 (CDPK3) is a key enzyme for parasite egress, control of calcium-dependent permeabilization in parasitophorous vacuole membrane and tissue cyst formation. In this study, we comprehensively explored the bioinformatics features of this protein to improve vaccine design against T. gondii. Various web servers were employed for the analysis of physico-chemical properties, post-translational modifications, localization in the subcellular milieu, secondary and tertiary structures, as well as B-cell, major histocompatibility complex (MHC)-binding and cytotoxic T-lymphocyte (CTL) epitopes. This protein was a 537 amino acid antigenic and non-allergenic molecule with a molecular weight of 60.42 kDa, a grand average of hydropathicity score of -0.508, and aliphatic index of 79.50. There exists 46.74% alpha helix, 12.48% extended strand, and 40.78% random coil in the secondary structure. Ramachandran plot of the refined model demonstrated 99.3%, 0.7%, and 0.0% of residues in the favored, allowed and outlier areas, respectively. Besides, various potential B-cell (continuous and conformational), MHC-binding and CTL epitopes were predicted for Toxoplasma CDPK3 protein. This article provides a foundation for further investigations, and laid a theoretical basis for the development of an appropriate vaccine against T. gondii infection.


Qualitative analysis of the questions raised by patients with gynecologic cancers and their relatives in an educational support group.
People's knowledge of cancer is generally inadequate to help them cope with a diagnosis of cancer. Educational support groups may allow cancer patients to receive information they want that is normally not covered in the individual clinical encounter. It was desired to identify the content of such information as reflected in the questions asked by cancer patients and their relatives in such support groups. The 329 questions asked by 41 patients and 11 of their relatives in 40 group sessions were analyzed and categorized. The categories found are described. Almost 100 questions could be allocated to the category "the illness," of which the most common was, "Is cancer hereditary?" The questions made it clear that the patients had a wish and a need to understand cancer. An educational support group provides a complement to, and not a substitute for, the clinical provision of medical information.


Reading the phase of a Raman excitation with a multi-state atomic interferometer.
Atomic memories for flying photonic qubits are an essential ingredient for many applications like e.g. quantum repeaters. Verification of the coherent transfer of information from a light field to an atomic superposition is usually obtained using an optical read-out. In this paper we report the direct detection of the atomic coherence by means of atom interferometry. We experimentally verified both that a bichromatic laser field closing a Raman transition imprints a distinct, controllable phase on the atomic coherence and that it can be recovered after a variable time delay.


Flow-cytometric assessment of lymphocyte cytokine production in tuberculosis.
We assessed by flow-cytometry the Th1/Th2 profiles in peripheral blood lymphocytes (PBL) from patients with active tuberculosis (TB), before and after antituberculous therapy, and from healthy tuberculin-positive and -negative reactors. PBL from patients showed a reduced potential for Th1-cytokine (notably IFN- gamma) production after culture with a policlonal stimulus. When these PBL from patients were cultured with a M. tuberculosis (MTB)-specific antigen such as PPD (10 microg/ml), there was no detectable production of Th1 cytokines. Only the Th2 cytokine IL10 was detected in PBL from patients but not from controls. However, at the site of the tuberculosis disease, T lymphocytes from bronchoalveolar lavage, after culture with PPD, produced IFN- gamma. After completion of tuberculosis therapy, PBL did not produce IL10. These data indicate that the immunosuppression observed in PBL during active tuberculosis infection may be related to IL10 production, and to the compartmentalization of the antigen-Th1 response to sites of active MTB infection.


May the morphological findings in the first-trimester abortion materials be indicative of inherited thrombophilia?
İnherited thrombophilia is associated with severe pregnancy complications including recurrent spontaneous abortion. In the light of this strong association, the impact of thrombophilic mutations on the placenta and their morphological reflections has aroused attention of both clinicians and pathologists. In the present study, we aimed to show the association between placental abnormalities with thrombophilia by examining the morphological findings in a wide range of first-trimester chorionic villi. We performed a histological examination on the abortion specimens obtained from 129 patients with recurrent pregnancy losses that were evaluated with respect to inherited thrombophilia based on the presence of Factor V Leiden (G1691A), Prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations detected by genetic analysis. Abortion materials either with and without thrombophilia were evaluated in terms of the morphological parameters such as hydropic change, vascularity, fibrosis, fibrinoid degeneration, Hofbauer macrophage, syncytiotrophoblast knotting, villitis, calcification, villous contour and villous size, hemorrhage, thrombus, proliferation of trophoblasts, villous stromal or villous vascular karyorrhexis. No statistically significant difference was found between the patient groups with and without thrombophilia in terms of morphological findings except vascularity of chorionic villi. The avascular chorionic villi (<3 vessels per villus) were found in 62.9% and 16.9% obtained from the women with and without thrombophilic mutation, respectively. This difference was statistically significant (P < 0.001). As a conclusion, it could be stated that the analysis of morphological findings in the abortion specimen is not a time-wasting process. Particularly, data related with vascularity of chorionic villi would be precious and beneficial. We suggest that highlighting the presence of avascular villi in the pathology report as a parameter would be guiding for clinicians regarding the impact of the thrombophilic gene mutations.


Optical learning neurochip with internal analog memory.
An optical neurochip with learning capability and a memory function is reported for the first time, to our knowledge. The neurochip is a three-dimensional optoelectronic integrated circuit consisting of a light-emitting diode array and a variable-sensitivity photodetector array. The principle of operation and the fundamental characteristics of the neurochip are described in detail. The synaptic weights, which, are acquired through learning, are stored in the variable-sensitivity photodetector as the detection sensitivity with analog values. Both the positive and the negative synaptic weights are memorized with one variable-sensitivity photodetector element by changing the polarity of the electric signal applied to the photodetector. A storage time of ~20 min. was obtained. With a fabricated optical neurochip that had 32 neurons and 32 x 32 synapses, experiments of on-chip learning for pattern classification were performed successfully.


Surface Acoustic Wave Nebulization with Atmospheric-Pressure Chemical Ionization for Enhanced Ion Signal.
Many ambient desorption/ionization mass spectrometry (ADI-MS) techniques rely critically on thermal desorption. Meanwhile, the analyte classes that are successfully studied by any particular ADI-MS methods are strongly dependent on the type of ionization source. Generally, spray-based ionization sources favor polar analytes, whereas plasma-based sources can be used for more hydrophobic analytes and are more suitable for molecules with small molar masses. In the present work, classic atmospheric-pressure chemical ionization (APCI) is used. To provide improved desorption performance for APCI, a surface acoustic wave nebulization (SAWN) device was implemented to convert liquid analytes into fine airborne particles. Compared to conventional SAWN that is used solely as an ionization source for liquid samples, the coupling of SAWN and APCI significantly improves ion signal by up to 4 orders of magnitude, reaching comparable ion abundances to those of electrospray ionization (ESI). Additionally, this coupling also extends the applicable mass range of an APCI source, conventionally known for the ionization of small molecules <500 Da. Herein, we discuss cursory evidence of this applicability to a variety of analytes including both polar and nonpolar small molecules and novel peptides that mimic biomolecules upward of 1000 Da. Observed species are similar to ESI-derived ions including doubly charged analyte ions despite presumably different charging mechanisms. SAWN-APCI coupling may thus involve more nuanced ionization pathways in comparison to other ADI approaches.


Hypoglycemia incidence and risk factors assessment in hospitalized neonates.
To assess the incidence and risk factors of hypoglycemia in hospitalized neonates in China. Blood glucose level in hospitalized neonates was monitored routinely. Also, in high-risk newborns and neonates with abnormal blood glucose levels in initial detection, the blood sugar level was monitored daily until it was back to normal and stable. Hypoglycemia was detected in 113 out of 668 hospitalized neonates, and the incidence of hypoglycemia was 16.9%. The statistical analysis also showed that hypoglycemia always occurred within one week after birth, especially within three days after birth. Neonates with premature birth, low birth weight and perinatal asphyxia were susceptible to hypoglycemia. Active and continuous monitoring of blood glucose level should be performed in the early newborns, especially in high-risk children, and attention should be paid to timely feeding for the early diagnosis and treatment of neonatal hypoglycemia to reduce its impact on the newborns.


Cross talk between Ca2+ and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca2+ release channels.
Calcium release mediated by the ryanodine receptors (RyR) Ca2+ release channels is required for muscle contraction and contributes to neuronal plasticity. In particular, Ca2+ activation of RyR-mediated Ca2+ release can amplify and propagate Ca2+ signals initially generated by Ca2+ entry into cells. Redox modulation of RyR function by a variety of non-physiological or endogenous redox molecules has been reported. The effects of RyR redox modification on Ca2+ release in skeletal muscle as well as the activation of signalling cascades and transcription factors in neurons will be reviewed here. Specifically, the different effects of S-nitrosylation or S-glutathionylation of RyR cysteines by endogenous redox-active agents on the properties of skeletal muscle RyRs will be discussed. Results will be presented indicating that these cysteine modifications change the activity of skeletal muscle RyRs, modify their behaviour towards both activators and inhibitors and affect their interactions with FKBP12 and calmodulin. In the hippocampus, sequential activation of ERK1/2 and CREB is a requisite for Ca2+-dependent gene expression associated with long-lasting synaptic plasticity. The effects of reactive oxygen/nitrogen species on RyR channels from neurons and RyR-mediated sequential activation of neuronal ERK1/2 and CREB produced by hydrogen peroxide and other stimuli will be discussed as well.


Modulation of MAPK ERK1 and ERK2 in VDR-positive and -negative breast cancer cell lines.
1alpha-25-Dihydroxyvitamin D3 (calcitriol), the biologically active metabolite of vitamin D, is known to regulate calcium and phosphate levels in bone metabolism. It is also known to influence proliferation and differentiation in carcinoma cells mediated by the vitamin D receptor (VDR). The antiproliferative effects of calcitriol are believed to be mediated by the nuclear pathway via binding the activated receptor to vitamin D-responsive elements. This induces the vitamin D-responsive genes. Another possible pathway might be the MAPK-cascade or rapid response pathway. The interaction of calcitriol and the MAP-kinase-cascade was evaluated on VDR-positive MCF-7 cells and VDR-negative MDA-MB-231 breast cancer cells. The cells were incubated with calcitriol solution at 10(-7) M and 10(-9) M, or ethanol as controls, for up to 48 h. The effects of calcitriol were measured by semi-quantitative Western blotting. Calcitriol stimulated the MAP-kinases ERK1 and ERK2. A biphasic activation was found for calcitriol in VDR-positive cells after incubation for 5 to 20 min and from 2 to 24 h. However, early activation of ERK1 and ERK2 was also demonstrated in VDR-negative cells. In the controls, ethanol also induced the MAPK-cascade at 5 to 10 min. Calcitriol induction was demonstrated after incubation from 2 to 24 h. In conclusion, it seems that the early induction of the MAPK-cascade was independent of the VDR. A calcitriol-induced MAPK activation was shown after 4 h, which may have been caused by activation of the nuclear receptor pathway.


Denver group gives up FFS, successfully converts seniors to Medicare managed care.
Three tips to move your practice from fee-for-service Medicare to managed care only. New West Physicians, a 63-provider primary care group in Denver, has given up fee-for-service Medicare and will only see seniors enrolled in Medicare HMOs. Find out how the group made the change and in the process retained its patients.


Biomechanical researches on tissue engineering bone constructed by deproteinated bone.
To study biomechanical changes of newly formed bones 24 weeks after repairing large defects of long bones of goats using heterogeneous deproteinated bone (DPB) prepared by modified methods as an engineering scaffold. According to a fully randomized design, 18 goats were evenly divided into three groups: normal bone control group (Group A), autologous bone group (Group B) and experimental group (Group C). Each goat in Groups B and C were subjected to the periosteum and bone defect at middle-lower part of the right tibia (20% of the whole tibia in length), followed by autologous bone or DPB plus autologous MSCs + rhBMP2 implantation, respectively and semi-ring slot fixation; while goats in Group A did not perform osteotomy. At 24 weeks after surgery, biomechanical tests were carried out on the tibias. At 24 weeks after surgery, the results of anti-compression test on tibias in three groups were recorded by a functional recorder presented as linear pressure-deformation curve. The shapes of the curves and their change tendency were similar among three groups. The ultimate pressure values were 10.74 MPa+/-1.23 MPa, 10.11 MPa+/-1.35 MPa and 10.22 MPa+/-1.32 MPa and fracture compression rates were 26.82%+/-0.87%, 27.17%+/-0.75% and 28.22%+/-1.12% in Groups A, B and C, respectively. Comparisons of anti-compression ultimate pressures and fracture compression rates among three groups demonstrated no significant difference (P(AB) equal to 0.415, P(BC) equal to 0.494). Three-point anti-bend test on tibias was recorded as load-deformation curves, and the shapes of the curves and their change tendency were similar among three groups. The ultimate pressure values of the anti-bend test were 481.52 N+/-12.45 N, 478.34 N+/-14.68 N and 475.62 N+/-13.41 N and the fracture bend rates were 2.62 mm+/-0.12 mm, 2.61 mm+/-0.15 mm and 2.81 mm+/-0.13 mm in Groups A, B and C, respectively. There was no significant difference between groups (P(AB) equal to 0.7, P(BC) equal to 0.448). The ultimate anti-torsion torque values were 6.55 Nm+/-0.25 Nm, 6.34 Nm+/-0.18 Nm and 6.42 Nm+/-0.21 Nm and fracture torsion rates were 29.51 degree+/-1.64degree, 28.88 degree+/-1.46 degree and 28.81 degree+/-1.33 degree in Groups A, B and C, respectively. There was no significant difference between groups (P(AB) equal to 0.123, P(BC) equal to 0.346). The biomechanical characteristics of newly formed bones from heterogeneous DPB for repairing large segmental long bone defect are comparable to those of normal bones and autologous bones. DPB has the potential for clinical usage as bone graft material.


Stress, senescence, and specialized metabolites in bryophytes.
Life on land exposes plants to varied abiotic and biotic environmental stresses. These environmental drivers contributed to a large expansion of metabolic capabilities during land plant evolution and species diversification. In this review we summarize knowledge on how the specialized metabolite pathways of bryophytes may contribute to stress tolerance capabilities. Bryophytes are the non-tracheophyte land plant group (comprising the hornworts, liverworts, and mosses) and rapidly diversified following the colonization of land. Mosses and liverworts have as wide a distribution as flowering plants with regard to available environments, able to grow in polar regions through to hot desert landscapes. Yet in contrast to flowering plants, for which the biosynthetic pathways, transcriptional regulation, and compound function of stress tolerance-related metabolite pathways have been extensively characterized, it is only recently that similar data have become available for bryophytes. The bryophyte data are compared with those available for angiosperms, including examining how the differing plant forms of bryophytes and angiosperms may influence specialized metabolite diversity and function. The involvement of stress-induced specialized metabolites in senescence and nutrient response pathways is also discussed.


CRM197-Coupled Der p 2 Peptides Suppress Allergic Airway Inflammation in a Der p 2-Induced Asthma Mouse Model.
Allergic diseases affect more than 25% of the global population. Der p 2 is the major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus. Allergen-specific immunotherapy is the only treatment to change the course of allergic diseases. In this study, two synthesized Der p 2 peptides coupled to cross-reacting material 197 (CRM197) showed reduced IgE reactivity and allergenic activity. CRM197-coupled Der p 2 peptides induced rDer p 2-specific IgG1 antibodies in mice, which could inhibit HDM-allergic patients' IgE binding to rDer p 2. The immunity effects of CRM197-coupled Der p 2 peptides were studied in an rDer p 2-induced asthma mouse model. CRM197-coupled Der p 2 peptides can suppress asthmatic airway inflammation in this model. Analysis of IL-4, IL-5, and IFN-γ levels in bronchoalveolar lavage fluid revealed that the suppression was associated with a shift from a Th2 to a Th1 response. Thus, CRM197-bound Der p 2 peptides exhibited less allergenic activity than the rDer p 2 allergen, which preserved immunogenicity and may be candidates for mite allergy vaccines.


[Pain therapy in emergency medicine. Focus on emergency admissions].
With a prevalence of 50-80 % pain is one of the main symptoms of emergency admission patients worldwide; however, study results demonstrate that only 30-50 % of patients receive adequate analgesia. Therefore, in the USA quality indicators have been established by the Centers for Medicare & Medicaid Services (CMS) since 2010 within the framework of quality assurance of emergency admissions, e.g. the time window until the start of pain therapy. Despite the prescribed pain evaluation as part of many existing triage systems, e.g. the Manchester triage system (MTS), emergency severity index (ESI), Australasian triage scale (ATS), Canadian triage and acuity scale (CATS), in most emergency rooms there is no standardized, documented pain assessment and pain intensity is documented by using the appropriate pain scales in only 30 % of cases. Lack of knowledge and training and lack of awareness by the nursing and medical staff regarding pain perception and management represent the main causal factors. Studies on the situation of pain therapy in German emergency departments are not currently available. Due to the increasing number of central emergency departments and interdisciplinary teams of physicians and nurses, it seems sensible to introduce interdisciplinary standards of treatment to achieve the greatest possible safety in the use of analgesics in the emergency room. It is important to incorporate the experiences of the various clinical departments in the standards. This article aims to provide an overview of the situation in pain management in emergency departments and to serve as a basis for recommendations for pain therapy in German emergency departments. This article particularly discusses the possibilities of pain evaluation, treatment options with various medications and under specific conditions, e.g. for children, pregnant women or the elderly or alternative ways of pain management.


Genetic analysis of periplasmic binding protein dependent transport in Escherichia coli. Each lobe of maltose-binding protein interacts with a different subunit of the MalFGK2 membrane transport complex.
Escherichia coli is able to accumulate maltose and maltodextrins by an ATP-binding cassette transporter known as the maltose transport system. This transport system is comprised of five proteins: the LamB protein in the outer membrane; the periplasmic maltose-binding protein (MBP); two integral inner membrane proteins, MalF and MalG; and MalK, which is associated with the cytoplasmic face of the inner membrane. It has been previously suggested that MBP interacts with MalF and MalG during sugar transport across the inner membrane. In two independent genetic studies, reported here, residue 210 of MBP has been identified as an important site for its interaction with MalF. In one study, allele-specific suppressors of a malF mutation, malF506, were isolated and yielded mutations which altered residue tyrosine 210 of MBP to aspartic acid. In the other study, dominant mutations in malE (the structural gene of MBP) were isolated; one of these altered the same tyrosine residue (210) to cysteine. It was shown that the Y210C MBP mutant is also an allele-specific suppressor malF506, and that of the suppressor MBP alleles also exhibited dominant-negative phenotypes. Previously it was shown that alterations at residues glycine 13 and aspartate 14 of MBP can result in suppression of a malG mutant. From these results and those described, it is possible to propose a simple model in which the amino-terminal lobe of MBP interacts with MalG and the carboxy-terminal lobe of MBP interacts with MalF. The locations of residues 13, 14 and 210 on the three-dimensional structure of MBP are in keeping with this model.


Polythioethers by thiol-ene click polyaddition of α,ω-alkylene thiols.
The straightforward synthesis of a series of poly(thioether)s by photoinduced thiol-ene click polyaddition of α,ω-alkylene thiols is reported. It is found that linear and telechelic poly(thioether)s can be directly obtained from α,ω-alkylene thiols with, for example, alkyl chain length of m = 1,2,3, and 9. The reaction proceeds without additives such as (radical) initiators or metal compounds and can simply be carried out by UV-irradiation of the bulk monomer or monomer solution. Ex situ kinetic studies reveal that the reaction proceeds by a typical a step-growth polyaddition mechanism. As the homologue series of poly(thioether)s are now synthetically accessible, new direct pathways to tailored poly(alkyl sulphoxide)s and poly(alkyl sulfone)s are now possible.


Characteristics and complete genome analysis of a novel jumbo phage infecting pathogenic Bacillus pumilus causing ginger rhizome rot disease.
Tailed phages with genomes larger than 200 kbp are classified as jumbo phage and exhibit extremely high diversity. In this study, a novel jumbo phage, vB_BpuM_BpSp, infecting pathogenic Bacillus pumilus, the cause of ginger rhizome rot disease, was isolated. Notable features of phage vB_BpuM_BpSp are the large phage capsid of 137 nm and baseplate-attached curly tail fibers. The genome of the phage is 255,569 bp in size with G+C content of 25.9 %, and it shows low similarity to known biological entities. The phage genome contains 318 predicted coding sequences. Among these predicted coding sequences, 26 genes responsible for nucleotide metabolism were found, and seven structural genes could be identified. The findings of this study provide new understanding of the genetic diversity of phages.


Cardiovascular side-effects of modern cancer therapy.
Recent advances in chemotherapy have substantially improved the prognosis of cancer patients. However, many anticancer drugs, especially newly developed ;molecular-target drugs', such as the anti-HER2 blocking antibody and the anti-vascular endothelial growth factor antibody, have serious cardiovascular side-effects such as heart failure, thromboembolism, severe hypertension and lethal arrhythmia, which interrupt cancer treatment and decrease the patient's quality of life. Despite the increasing clinical significance, cardiologists have not been focusing enough of their attention on this issue. The major cardiovascular complications associated with anticancer drugs, and current diagnosis, treatment and prevention strategies are reviewed. Close collaborations between oncologists and cardiologists is necessary to tackle cardiovascular complications and advance cancer treatment.


The fellowship of the rings: distinct pools of proliferating cell nuclear antigen trimer at work.
The proliferating cell nuclear antigen (PCNA) is a homotrimeric ring-shaped protein that, by encircling DNA, may function as a sliding platform for proteins participating in various DNA transactions. PCNA plays a fundamental role in DNA replication and repair, but also in postreplicative events, like DNA methylation, chromatin assembly and remodeling, sister chromatid cohesion, and coordinates these activities with cell cycle control. However, relevant aspects of PCNA function are still not well understood, like the role of PCNA in the association with partner proteins, and how multiple protein interactions are orchestrated. Based on emerging evidence, I suggest that 1) PCNA interacting proteins may be reclassified in three major categories, namely, a) cell cycle control; b) DNA replication/repair; c) chromatin regulation/transcription. 2) PCNA is a negative regulator, rather than a processivity/recruitment factor, of chromatin-modifying enzymes. 3) At DNA replication sites, PCNA function may be envisaged with a model of "dynamic hand-off" of interacting partners that rapidly and transiently exchange in a mutually exclusive manner, while cyclin-dependent kinase (Cdk) 2 (CDK2) is stably bound to PCNA. The partner exchange might occur through a conformational change of the PCNA/protein/DNA complex allowing CDK2 to phosphorylate the partner protein, thereby enabling its hand-off from PCNA.


Stability of Blood Biomarkers of Traumatic Brain Injury.
Blood biomarker tests were recently approved for clinical diagnosis of traumatic brain injury (TBI), yet there are still fundamental questions that need attention. One such question is the stability of putative biomarkers in blood over the course of several days after injury if the sample is unable to be processed into serum or plasma and stored at low temperatures. Blood may not be able to be stored at ultra-low temperatures in austere combat or sports environments. In this prospective study of 20 adult patients with positive head computed tomography imaging findings, the stability of three biomarkers (glial fibrillary acidic protein [GFAP], ubiquitin C-terminal hydrolase-L1 [UCH-L1], and S100 calcium binding protein B [S100B]) in whole blood and in serum stored at 4-5°C was evaluated over the course of 72 h after blood collection. The amount of time whole blood and serum were refrigerated had no significant effect on GFAP concentration in plasma obtained from whole blood and in serum (p = 0.6256 and p = 0.3687, respectively), UCH-L1 concentration in plasma obtained from whole blood and in serum (p = 0.0611 and p = 0.5189, respectively), and S100B concentration in serum (p = 0.4663). Concentration levels of GFAP, UCH-L1, and S100B in blood collected from patients with TBI were found to be stable at 4-5°C for at least 3 days after blood draw. This study suggests that the levels of the three diagnostic markers above are still valid for diagnostic TBI tests if the sample is stored in 4-5°C refrigerated conditions.


Analysis of resting heart rate and clinical characteristics in outpatients with stable coronary artery disease in Turkey: PULSE study.
An association between resting heart rate (RHR) and cardiovascular morbidity and mortality has been shown in patients with coronary artery disease (CAD). We aimed to evaluate the RHR and its relationship with clinical variables in outpatients with stable CAD at secondary and tertiary care centers in Turkey. Adults with stable CAD in sinus rhythm were included in this non-interventional, national, cross-sectional, multicenter study. Data were collected at a single study visit from 83 centers. The mean ± standard deviation age of all patients (n = 2,919) was 61 ± 10 years and 73% were males. The mean (SD) RHR was 73 ± 12 bpm, and 62% of patients had RHR of ≥ 70 bpm. Females more frequently had RHR ≥ 70 bpm compared with males (67% vs. 60%; p = 0.002). RHR was significantly higher in patients with angina than in those without (76 ± 13 vs. 73 ± 11 bpm, p < 0.001). Left ventricular ejection fraction and heart rate lower-ing drug use were significantly lower in patients with a RHR ≥ 70 bpm (p < 0.05). The RHR of outpatients with stable CAD was not within the level recommended by the guidelines.


Focal delivery of neurotrophins into the central nervous system using fluorescent latex microspheres.
A new technique for in vivo and in vitro delivery of neurotrophins is described. The method is based upon the ability of certain fluorescent latex microspheres to adsorb large quantities of neurotrophin and then release the factor for at least three to four days. Injection of such neurotrophin-coated microspheres in vivo provides focal delivery of neurotrophins to distinct populations of neurons. The fluorescence of the microspheres accurately identifies the region of neurotrophin treatment in vivo; two independent methods indicate that microsphere-born proteins do not diffuse significantly beyond the site of injection. In addition to providing focal delivery and labeling of the site of application, labeled microspheres are retrogradely transported by neurons; thus, neurons whose distant terminals are exposed to neurotrophin can be identified and analyzed. This approach provides a powerful method for the introduction of neuroactive proteins into defined and localized regions of the central nervous system.


Acute Retinal Necrosis Caused by the Zoster Vaccine Virus.
We report acute retinal necrosis caused by the vaccine Oka strain following immunization of a 78-year-old woman with live zoster vaccine. Whole genome sequencing confirmed the ocular vOka strain to be derived from the vaccine and excluded the presence of new mutations or recombination with wild-type Varicella zoster virus.


[Long lasting symptoms of dyspnea, cough and fatigue after COVID-19 - narrative review of epidemiological studies].
"Long-COVID" is described as long-term effects of SARS‑ CoV‑2 infection that last >4 weeks after the acutephase of infection. The aim of this narrative reviews to evaluate the frequency of occurrence of 3 symptoms often observed in Long-COVID, i.e., chronic fatigue, shortness of breath and cough, and whether comorbidities such as diabetes and arterial hypertension increase the risk of complications after a history of SARS‑ CoV‑2 infection. The method of narrative review was used in this paper. PubMed (May 31, 2021) search was performed to retrieve articles concerning the occurrence of long COVID-19 chronic fatigue, dyspnoea and chronic cough. Studies in which the observation period was <30 days and the average age of subjects exceeded 60 years, as well as studies with no information on the methodology used, in particular without the method of recruiting people for the study, were excluded. Populations with a high frequency of diabetes were defined as the prevalence >10%, and in the case of arterial hypertension >40%. The average frequency of diabetes <10%, hypertension 40%. It can be concluded that in the period of >30 days after discharge from the hospital, in populations with a high incidence of diabetes and hypertension, the incidence of chronic fatigue and cough was higher than in the other analyzed groups. Symptoms of dyspnea were most frequently reported in populations with high rates of diabetes, but at the same time in the average percentage of people with arterial hypertension. Persistent symptoms specific to "Long-COVID" can significantly reduce the ability to perform work. In this situation, check-ups performed before returning to work after long-term leave tape on a new dimension. Med Pr. 2021;72(6):711-20.


The antithrombotic nature of vascular prosthetic pseudointima.
Morphologic functional, and biochemical studies were performed on pseudointima obtained from woven Dacron aortic prostheses harvested from eight dogs 2 to 3 years after placement. In vivo platelet reactivity with prostheses was assessed by serial 51Cr-platelet survival measurements which documented that platelet survival returned towards normal but never attained preoperative levels. The extent of luminal coverage of prosthesis with pseudointima of the time of harvest was 60.3% +/- 2.4%. Morphologic techniques, including conventional light microscopy, immunoperoxidase light microscopy for endothelial factor VIII-related antigen, and scanning and transmission electron microscopy, demonstrated that pseudointima was composed of endothelial cells of varying maturity lining mesenchymal tissue. Areas of the prostheses with poorly formed pseudointima containing exposed Dacron fibers were covered with exuberant, platelet-rich thrombi. Ability of pseudointima to produce prostacyclin was assessed by bioassay of platelet antiaggregatory activity and radioimmunoassay of 6 keto PGF1 alpha, a metabolite of prostacyclin. These experiments confirmed that pseudointima produced abundant prostacyclin, although not as much as native aortic tissue. These studies document that vascular prosthetic pseudointima is nonreactive with platelets, presumably because of prostacyclin generation.


Investigation and management of abnormal uterine bleeding in reproductive-aged women: a descriptive review of national and international recommendations.
To review and compare the most recently published recommendations on the investigation and management of abnormal uterine bleeding (AUB). A descriptive review of recommendations from the American College of Obstetricians and Gynaecologists (ACOG), the National Institute for Health and Care Excellence (NICE), the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG), the Society of Obstetricians and Gynaecologists of Canada (SOGC) and the International Federation of Gynaecology and Obstetrics (FIGO) on AUB in reproductive-aged women was carried out. There is a consensus that detailed personal and family history along with physical examination are essential in the investigation of menstrual, intermenstrual or postcoital AUB. All the medical societies recommend transvaginal ultrasound as the first-line imaging modality to determine the AUB cause. Moreover, they agree (except for RANZCOG) that, in women with AUB, endometrial biopsy should only be performed if additional risk factors for endometrial cancer are present. Laboratory tests may be helpful in the AUB investigation; however, there are several discrepancies among the recommendations. Regarding AUB management, NICE, ACOG and SOGC agree that the administration of hormonal or non-hormonal medications should be the first-line treatment modality in bleeding disorders and absent or minor structural pelvic pathology. Surgical management should be preferred in cases of identified polyps, large fibroids or unsuccessful pharmacological treatment. Since AUB affects a significant proportion of reproductive-aged women, the main objective is to improve the quality of life of these patients without missing cases of malignancy.


An Enhanced Hybrid Screening Approach to Identify Potent Inhibitors for the SARS-CoV-2 Main Protease From the NCI Compound Library.
The emergence and rapid spread of SARS-CoV-2, the pathogen of COVID-19, have caused a worldwide public health crisis. The SARS-CoV-2 main protease (Mpro) is an essential enzyme for the virus and therefore an appealing target for the development of antivirals to treat COVID-19 patients. Recently, many in silico screenings have been performed against the main protease to discover novel hits. However, the actual hit rate of virtual screening is often low, and most of the predicted compounds are false positive hits. In this study, we developed a refined virtual screening strategy that incorporated molecular docking and post-docking filtering based on parameters including molecular weight and surface area, aiming to achieve predictions with fewer false positive hits. We applied this strategy to the NCI library containing 284,176 compounds against Mpro. In vitro potency analyses validated several potent inhibitors and thus confirmed the feasibility of our virtual screening strategy. Overall, The study resulted in several potent hit Mpro inhibitors, in which two inhibitors have IC50 values below 1 μM, that are worth being further optimized and explored. Meanwhile, the refined virtual screen strategy is also applicable to improve general in silico screening hit rates and is useful to accelerate drug discovery for treating COVID-19 and other viral infections.


[Evaluation of DNA-probe assay for the clinical diagnosis of Mycoplasma pneumoniae infections].
DNA probe-assay using the Gen-Probe kit was carried out to detect Mycoplasma pneumoniae infections. Fifteen children visited Ota General Hospital complaining of dry cough and high grade fever. Throat swabs of the patients were examined to detect M. pneumoniae ribosomal RNA by Gen-Prove kit. Five out of 15 patients were positive for DNA probe assay of M. pneumoniae. Clinical and laboratory data including serological examinations were compatible with M. pneumoniae infection in these cases. Following the improvement of clinical symptoms and signs by receiving erythromycin or minocycline, the positivity for DNA probe assay turned to negative. Among the ten patients, who were negative for DNA probe assay, 2 cases were suspected of M. pneumoniae infection on the basis of clinical and laboratory findings. One patient had already taken antibiotics. Therefore, in these two patients, there was a possibility that the bacterial numbers were too small to be detected by DNA-probe assay. The data described above support that DNA-probe assay is useful for the diagnosis of M. pneumoniae infections in the early stage. DNA-probe assay is also valuable to follow up the clinical course of the patients.


Preparation of insulating SiO2 nanostructured thin films by the sol-gel process.
Organic dispersion agents can effectively decrease the surface roughness of films. Here, films containing organic dispersion agents are used to produce metal-insulator-metal structures. It was found that addition of Triton caused films to become denser, and thicker, and the leak current of devices to decrease by 10 times compared with that without Triton because of its uniform dispersion in the films. The resulting films were used as the insulator layer of thin film transistors containing a semiconductor layer of evaporated pentacene. The interface between the insulator and semiconductor layers was found to affect the arrangement of pentacene, and O2 plasma was used to improve the interface activity to increase the order of the pentacene molecules and enhance the carrier mobility of the devices.


End-of-life discussions, goal attainment, and distress at the end of life: predictors and outcomes of receipt of care consistent with preferences.
Physicians have an ethical obligation to honor patients' values for care, including at the end of life (EOL). We sought to evaluate factors that help patients to receive care consistent with their preferences. This was a longitudinal multi-institutional cohort study. We measured baseline preferences for life-extending versus symptom-directed care and actual EOL care received in 325 patients with advanced cancer. We also measured associated sociodemographic, health, and communication characteristics, including EOL discussions between patients and physicians. Preferences were assessed a median of 125 days before death. Overall, 68% of patients (220 of 325 patients) received EOL care consistent with baseline preferences. The proportion was slightly higher among patients who recognized they were terminally ill (74%, 90 of 121 patients; P = .05). Patients who recognized their terminal illness were more likely to prefer symptom-directed care (83%, 100 of 121 patients; v 66%, 127 of 191 patients; P = .003). However, some patients who were aware they were terminally ill wished to receive life-extending care (17%, 21 of 121 patients). Patients who reported having discussed their wishes for EOL care with a physician (39%, 125 of 322 patients) were more likely to receive care that was consistent with their preferences, both in the full sample (odds ratio [OR] = 2.26; P < .0001) and among patients who were aware they were terminally ill (OR = 3.94; P = .0005). Among patients who received no life-extending measures, physical distress was lower (mean score, 3.1 v 4.1; P = .03) among patients for whom such care was consistent with preferences. Patients with cancer are more likely to receive EOL care that is consistent with their preferences when they have had the opportunity to discuss their wishes for EOL care with a physician.


Modeling secondary organic aerosol formation from volatile chemical products.
Volatile chemical products (VCPs) are commonly-used consumer and industrial items that are an important source of anthropogenic emissions. Organic compounds from VCPs evaporate on atmospherically relevant time scales and include many species that are secondary organic aerosol (SOA) precursors. However, the chemistry leading to SOA, particularly that of intermediate volatility organic compounds (IVOCs), has not been fully represented in regional-scale models such as the Community Multiscale Air Quality (CMAQ) model, which tend to underpredict SOA concentrations in urban areas. Here we develop a model to represent SOA formation from VCP emissions. The model incorporates a new VCP emissions inventory and employs three new classes of emissions: siloxanes, oxygenated IVOCs, and nonoxygenated IVOCs. VCPs are estimated to produce 1.67 μg m-3 of noontime SOA, doubling the current model predictions and reducing the SOA mass concentration bias from -75% to -58% when compared to observations in Los Angeles in 2010. While oxygenated and nonoxygenated intermediate volatility VCP species are emitted in similar quantities, SOA formation is dominated by the nonoxygenated IVOCs. Formaldehyde and SOA show similar relationships to temperature and bias signatures indicating common sources and/or chemistry. This work suggests that VCPs contribute up to half of anthropogenic SOA in Los Angeles and models must better represent SOA precursors from VCPs to predict the urban enhancement of SOA.


Teenage Male with Cough and Recurrent Bruit.
A general pediatrician is skilled at continuity; through longitudinal evaluation, they serve as front-line providers in the recognition and referral of unusual pathology. The majority of arteriovenous malformations (AVM) are diagnosed with history and physical examination. AVM are inherently progressive by nature; their expansion is what creates the risk of morbidity. With higher-risk vascular lesions, relative risk is important when discussing management with observation versus with invasive intervention. Size, location, and expected course of progression of the lesion help generate a timeline for action. Collaboration of physicians with diverse expertise generates optimal plan of therapy, particularly when faced with an unusual clinical finding. Genetics referral may be beneficial, as the body of literature on AVM is growing, and databases on associated syndromes are evolving. Establishing concrete follow-up is imperative to assess for recurrence of AVM or development of additional symptoms. This can be with the interventionalist or with the generalist.


[Endoscopic hemostasis in the treatment of bleeding peptic ulcer].
Upper gastrointestinal bleeding is still an important clinical problem, even though about 80% of bleedings due to peptic lesions stop spontaneously. Starting from 1970, a lot of endoscopic hemostatic procedures has been developed and employed with good results, but, at present, the key problem is represented by the selection and management of the patients at highest risk of rebleeding. This work reviews both techniques and devices most commonly used, but at present none of them can be considered actually better than the other ones. According to the SIED (Società Italiana di Endoscopia Digestiva) guidelines, the techniques of choice should be cheap, effective, safe and easy to perform, the pivotal role in determining the success rate of endoscopic hemostasis being played by the endoscopist's experience.


Validation of the Hong Kong Chinese version of the St. George Respiratory Questionnaire in patients with bronchiectasis.
To validate the Hong Kong Chinese version of the St. George Respiratory Questionnaire (SGRQ-HK) in patients with bronchiectasis. Outpatients (93 patients; 61 women; mean age [+/- SD], 59.0 +/- 14.2 years) were assessed at baseline by the SGRQ-HK, the Hong Kong Chinese version of the 36-item short form health survey (SF-36-HK), and the hospital anxiety and depression scale (HADS). Forty randomly selected patients also were reassessed at 2 weeks for repeatability. Seventy-two patients were further reassessed at 6 months for responsiveness. Cronbach alpha coefficients, which reflected internal consistency, were > 0.7 for all SGRQ-HK components except for symptoms (alpha = 0.59), and the intraclass correlation coefficients between baseline and the 2-week follow-up visits were between 0.80 and 0.94 (p > 0.05). SGRQ-HK component scores and total scores correlated with all the component scores of the SF-36-HK and the HADS (p < 0.02). SGRQ-HK component scores and total scores correlated with the scores of the SF-36-HK and the HADS, confirming the concurrent validity. All SGRQ-HK scores correlated negatively with FEV(1), FVC, and arterial oxygen saturation (p < 0.005), while the activity score correlated with the Karnofsky performance scale and the number of bronchiectatic lobes (p < 0.001). SGRQ-HK scores positively correlated with Borg scale scores, exacerbation frequency, and 24-h sputum volumes (p < 0.03). Patients with 24-h sputum volumes of > or = 10 mL or < 10 mL had significantly different SQRG-HK component scores and total scores (p < 0.002), although this sensitivity was not displayed by scores on the HADS or the SF-36-HK. Patients with 25% reductions in 24-h sputum volumes had significant improvements in SGRQ-HK activity scores, impact scores, and total scores (p < 0.02), but not in other quality-of-life measures or clinical parameters, indicating the responsiveness of the SGRQ-HK. The SGRQ-HK is a valid and sensitive instrument for determining quality of life in bronchiectasis patients.


Exploration of basal immune parameters in healthy infants receiving an infant milk formula supplemented with prebiotics.
This double-blind, randomized, placebo-controlled study, aimed to explore the effect of an infant milk formula (IMF) with 6 g/l short-chain galacto- and long-chain fructo-oligosaccharides (scGOS/lcFOS, ratio 9:1) on basal immune parameters in 215 healthy, term infants during the first 26 wk of life. After birth, the infants received breast milk or were randomized to receive an IMF with or without scGOS/lcFOS. Blood samples were collected at the age of 8 wk and 26 wk for the analysis of serum immunoglobulins, lymphocyte subpopulations, and cytokines. The scGOS/lcFOS group and the control group were compared in the statistical analysis. A breast fed group was included as a reference. In total, 187 Infants completed the study. No significant differences were observed between both formula groups in the different studied immune parameters at weeks 8 and 26. This explorative study indicates that supplementation of infant formula with a mixture of prebiotic oligosaccharides did not change the basal level of the measured parameters of the developing immune system in healthy infants with a balanced immune system during the first 6 months of life in comparison to feeding a standard infant formula and in comparison to exclusive breastfeeding.


Quality of life of patients with allergic rhinitis at a South African referral hospital: a prospective cross-sectional study.
Allergic rhinitis causes nasal as well as extranasal symptoms, and may adversely affect quality of life. The aims of this study were to determine the impact of allergic rhinitis on the health-related quality of life of adult patients attending the Ear Nose and Throat clinic at Universitas Academic Hospital, a public referral hospital, in Bloemfontein, South Africa, and to determine the change in the health-related quality of life of patients with allergic rhinitis after one month of treatment. This was a prospective cross-sectional study of adult patients who were newly diagnosed with allergic rhinitis. Patients completed the Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) at initial presentation and at follow-up after one month of appropriate treatment. Eighty-five (85) patients were included. At the initial visit, patients were most troubled by activity limitations and nasal symptoms, with a blocked nose being the most troublesome nasal symptom. There was a statistically significant improvement in scores of all domains after one month of treatment, with the mean total symptom score improving from 2.05±0.73 to 0.94±0.49. Allergic rhinitis had a negative impact on quality of life of patients. Appropriate treatment resulted in an improvement in quality of life.


Identification of a critical ankyrin-binding loop on the cytoplasmic domain of erythrocyte membrane band 3 by crystal structure analysis and site-directed mutagenesis.
The cytoplasmic domain of erythrocyte membrane band 3 (cdb3) serves as a center of membrane organization, interacting with such proteins as ankyrin, protein 4.1, protein 4.2, hemoglobin, several glycolytic enzymes, a tyrosine phosphatase, and a tyrosine kinase, p72(syk). The crystallographic structure of the cdb3 dimer has revealed that residues 175-185 assume a beta-hairpin loop similar to a putative ankyrin-binding motif at the cytoplasmic surface of the Na(+)/K(+)-ATPase. To test whether this hairpin loop constitutes an ankyrin-binding site on cdb3, we have deleted amino acids 175-185 and substituted the 11-residue loop with a Gly-Gly dipeptide that bridges the deletion without introducing strain into the structure. Although the deletion mutant undergoes the same native conformational changes exhibited by wild type cdb3 and binds other peripheral proteins normally, the mutant exhibits no affinity for ankyrin. This suggests that the exposed beta-hairpin turn indeed constitutes a major ankyrin-binding site on cdb3. Other biochemical studies suggest that ankyrin also docks at the NH(2) terminus of band 3. Thus, antibodies to the NH(2) terminus of cdb3 block ankyrin binding to the cdb3, and ankyrin binding to cdb3 prevents p72(syk) phosphorylation of cdb3 at its NH(2) terminus (predominantly at Tyr-8). However, a truncation mutant of cdb3 lacking the NH(2)-terminal 50 residues displays the same binding affinity as wild type cdb3. These data thus suggest that the NH(2) terminus of cdb3 is proximal to but not required for the cdb3-ankyrin interaction.


Effect of Obesity on Early, In-Hospital Amputation Risk Following Popliteal Artery Injury Using an Analysis of the National Trauma Data Bank.
Popliteal artery injury is associated with a high risk of limb loss; identifying factors associated with increased morbidity and mortality is hampered by its rare occurrence and confounding factors. Anecdotal observations suggest delay in diagnosis of obese patients may be associated with amputation. We aimed to determine whether there is an increased risk of early amputation and if diagnosis is delayed in obese patients with popliteal artery injuries. We conducted a retrospective cohort study using National Trauma Data Bank (NTDB) data from 2013 to 2017. We extracted those sustaining popliteal artery injury, assigning obesity class based on body mass index. We included select demographic and clinical variables, using time to imaging as a surrogate for time to diagnosis. Statistical models were used to calculate the impact of obesity on amputation rates and time to diagnosis. We identified 4803 popliteal artery injuries in the data set; 3289 met inclusion criteria. We calculated an 8.5% overall amputation rate, which was not significantly different between obese (N = 1305; 39.7%) and nonobese (N = 1984; 60.3%) patients. Statistical analysis identified peripheral vascular disease, diabetes, and smoking as risk factors for amputation. Time to imaging was similar for obese and nonobese patients. Analysis of NTDB data suggests that obesity is associated with neither increased early amputation rate nor longer time to imaging in patients with popliteal artery injury. However, our study suggests that underlying comorbidities of peripheral vascular disease and diabetes are associated with an increased risk for amputation in these patients.


Antigen-specific Th9 cells exhibit uniqueness in their kinetics of cytokine production and short retention at the inflammatory site.
Recently reported lines of Th9 cells, producing IL-9 and IL-10, were generated by polarization with IL-4 and TGF-β and activation with Abs against CD3 and CD28. In this paper, we analyzed features of Th9 lines similarly polarized but activated by the "natural mode" (i.e., exposure of CD4 cells to their target Ag, hen egg lysozyme [HEL] and APCs). Main observations are the following: 1) both IL-9 and IL-10 were expressed by the line cells, but with strikingly different kinetics, with IL-9 being produced rapidly, reaching a peak on day 3 in culture and declining sharply thereafter, whereas IL-10 production increased gradually, resembling IL-4 and IL-17 production by their corresponding lineage cells; 2) reactivation of Th9, following expansion, triggered faster and higher production of both IL-9 and IL-10; 3) incubating Th9 cells in polarizing media specific for other phenotypes stimulated moderate levels of phenotype switching to Th1 or Th17 but a massive switching to Th2; 4) Th9 cells induced moderate inflammation in HEL-expressing recipient eyes but only when producing high levels of IL-9; and 5) IL-9-producing donor cells were detected in the blood of Th9 recipients but not in their inflamed eyes, suggesting that similar to findings in culture, exposure to HEL in these eyes arrested the IL-9 production in Th9 cells. Collectively, these data provide new information concerning Th9 cells and reveal their uniqueness, in particular with regard to the unusual production kinetics of IL-9 and the short retention of these cells in affected target tissues.


Fishes regulate tail-beat kinematics to minimize speed-specific cost of transport.
Energetic expenditure is an important factor in animal locomotion. Here we test the hypothesis that fishes control tail-beat kinematics to optimize energetic expenditure during undulatory swimming. We focus on two energetic indices used in swimming hydrodynamics, cost of transport and Froude efficiency. To rule out one index in favour of another, we use computational-fluid dynamics models to compare experimentally observed fish kinematics with predicted performance landscapes and identify energy-optimized kinematics for a carangiform swimmer, an anguilliform swimmer and larval fishes. By locating the areas in the predicted performance landscapes that are occupied by actual fishes, we found that fishes use combinations of tail-beat frequency and amplitude that minimize cost of transport. This energy-optimizing strategy also explains why fishes increase frequency rather than amplitude to swim faster, and why fishes swim within a narrow range of Strouhal numbers. By quantifying how undulatory-wave kinematics affect thrust, drag, and power, we explain why amplitude and frequency are not equivalent in speed control, and why Froude efficiency is not a reliable energetic indicator. These insights may inspire future research in aquatic organisms and bioinspired robotics using undulatory propulsion.


[Effect of moxibustion on M2 and P2X3 receptors of bladder tissue in rats with neurogenic bladder of detrusor areflexia after lumbar-sacral spinal cord injury].
To observe the effect of moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) on acetylcholine (Ach), adenosine triphosphate (ATP) and muscarinic-type choline receptor (M2) and purine receptor P2X3 in bladder tissue in the rats with neurogenic bladder (NB) of detrusor areflexia after lumbar-sacral spinal cord injury and explore the underlying mechanism of moxibustion for promoting detrusor contraction. Sixty SD rats were randomly divided into a model preparation group (n=45) and a sham-operation group (n=15). In the model preparation group, the modified Hassan Shaker spinal cord transection method was used to prepare the model of NB. In the sham-operation group, the spinal cord transection was not exerted except laminectomy and spinal cord exposure. Among the rats with successfully modeled, 30 rats were selected and divided randomly into a model group and a moxibustion group, with 15 rats in each one. On the 15th day after the operation, moxibustion was applied at "Guanyuan" (CV 4) and "Shenque" (CV 8) in the moxibustion group, 10 min at each acupoint, once a day. The consecutive 7-day treatment was as one course and the intervention for 2 courses was required. Urodynamic test was adopted to evaluate bladder function in rats. Using HE staining, the morphological changes in bladder tissue were observed. The content of Ach and ATP in bladder tissue was measured with biochemical method, and the protein and mRNA expression levels of M2 and P2X3 receptors in bladder tissue were detected with Western blot and real-time fluorescence quantification PCR method. Compared with the sham-operation group, the maximum bladder capacity, leakage point pressure and bladder compliance were increased in the rats of the model group (P<0.05). Compared with the model group, the maximum bladder capacity, the leakage point pressure and bladder compliance were decreased in the rats of the moxibustion group (P<0.05). In the model group, the detrusor fibres were arranged irregularly, bladder epithelial tissues were not tightly connected and cell arrangement was disordered, combined with a large number of vacuolar cells. In the moxibustion group, compared with the model group, the detrusor fibres were arranged regularly, bladder epithelial cells were well distributed and vacuolar cells were reduced. Compared with the sham-operation group, the content of Ach and ATP in bladder tissue was decreased (P<0.05), the protein and mRNA expression levels of M2 and P2X3 receptors were reduced (P<0.05) in the model group. In the moxibustion group, the content of Ach and ATP in bladder tissue was increased (P<0.05) and the protein and mRNA expression levels of M2 and P2X3 receptors were increased (P<0.05) as compared with the model group. Moxibustion at "Guanyuan" (CV 4) and "Shenque" (CV 8) may effectively improve bladder function in the rats with NB of detrusor areflexia after lumbar-sacral spinal cord injury and its underlying mechanism is related to promoting the release of Ach and up-regulating the expression of M2 receptor, thereby enhancing the release of ATP and increasing the expression of P2X3 receptor. Eventually, detrusor contraction is improved.


[Problem of HIV-infected patients receiving dialysis].
According to UNAIDS data there are 40 millions of HIV infected people in the world. 7880 people are infected with HIV (official statistics) in Poland. Because of improvement of dialysis accessibility in Poland there is no limitations of qualification for dialysis for HIV infected patients. In this article authors present general information about HIV infection (epidemiology, diagnostic, clinical picture and treatment), post exposure management and prophylaxis in dialysis centers. We present also algorithms of management with patient with acute/chronic renal failure in dependence on result of HIV test.