[Clinical evaluation of intra-operative pelvic hyperthermochemotherapy combined with operation for rectal cancer].
In order to prevent local recurrence, intra-operative pelvic hyperthermochemotherapy (IOPHC) combined with surgery for rectal cancer has been performed. In this study, we evaluated the clinical effect of IOPHC in 20 patients who were given IOPHC, compared with 13 patients who underwent curative surgery without IOPHC (control group). The IOPHC procedure was as follows: After rectal amputation, the pelvic cavity was filled with a physiological saline containing 40 micrograms/ml of MMC. Then, the physiological saline was warmed and maintained by the apparatus (heater) we devised at 45 degrees C for 90 minutes. Local recurrence occurred in 2 cases of IOPHC group (2/20:10.0%), and in 3 cases in the control group (3/13:23.1%). On the other hand, distant metastases developed approximately at the same rate in the IOPHC group (4/20:20.0%) and control group (2/13:15.4%). Thus, IOPHC is a feasible approach to reduce local recurrence of rectal cancer.


Genetic variation within the hypothalamus-pituitary-ovarian axis in women with recurrent miscarriage.
Recurrent miscarriage affects 1-2% of couples trying to conceive, and is idiopathic in nearly half. Female fertility is controlled by the hypothalamus-pituitary-ovarian (HPO) axis and we hypothesize that genetic polymorphisms affecting the function of genes involved in regulating the HPO axis will be associated with recurrent miscarriage. Whole peripheral blood DNA from 227 women with recurrent miscarriage and 130 control women was obtained for this study. Using the Sequenom iPlex assay for fragment analysis, 31 single-nucleotide polymorphisms (SNPs) and 4 short tandem repeat (STR) polymorphisms in 20 candidate genes were evaluated for genetic association with recurrent miscarriage. Several candidate associations were identified with an uncorrected P-value of 0.05. Genotype distribution at an SNP (rs37389) in the prolactin receptor gene (P = 0.03), and allele distributions at an SNP (rs41423247) in the glucocorticoid receptor gene (P = 0.04) and an STR polymorphism in the estrogen receptor β gene (P = 0.03) were associated with recurrent miscarriage. The T allele of an SNP (rs2033962) within the activin receptor type 1 gene (ACVR1) was associated with increased number of miscarriages in an additive manner (P = 0.02). These candidate associations were not statistically significant after correcting for multiple analyses. Candidate associations were identified between recurrent miscarriage and genetic variation within ESR2, PRLR, GCCR and ACVR1 genes. Independent confirmation of these results is needed, as limitations of this study include the heterogeneous etiology of recurrent miscarriage, limited sample size, partial availability of reproductive history of the control group and investigation of only a subset of the genetic variation within each gene.


A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste.
Early treatment of mild SARS-CoV-2 infection might lower the risk of clinical deterioration in COVID-19. To determine whether oral camostat mesylate would reduce upper respiratory SARS-CoV-2 viral load in newly diagnosed outpatients with mild COVID-19, and would lead to improvement in COVID-19 symptoms. From June, 2020 to April, 2021, we conducted a randomized, double-blind, placebo-controlled phase 2 trial. Single site, academic medical center, outpatient setting in Connecticut, USA. Of 568 COVID-19 positive potential adult participants diagnosed within 3 days of study entry and assessed for eligibility, 70 were randomized and 498 were excluded (198 did not meet eligibility criteria, 37 were not interested, 265 were excluded for unknown or other reasons). The primary inclusion criteria were a positive SARS-CoV-2 nucleic acid amplification result in adults within 3 days of screening regardless of COVID-19 symptoms. Treatment was 7 days of oral camostat mesylate, 200 mg po four times a day, or placebo. The primary outcome was reduction of 4-day log10 nasopharyngeal swab viral load by 0.5 log10 compared to placebo. The main prespecified secondary outcome was reduction in symptom scores as measured by a quantitative Likert scale instrument, Flu-PRO-Plus modified to measure changes in smell/taste measured using FLU-PRO-Plus. Participants receiving camostat had statistically significant lower quantitative symptom scores (FLU-Pro-Plus) at day 6, accelerated overall symptom resolution and notably improved taste/smell, and fatigue beginning at onset of intervention in the camostat mesylate group compared to placebo. Intention-to-treat analysis demonstrated that camostat mesylate was not associated with a reduction in 4-day log10 NP viral load compared to placebo. The camostat group had more rapid resolution of COVID-19 symptoms and amelioration of the loss of taste and smell. Camostat compared to placebo was not associated with reduction in nasopharyngeal SARS-COV-2 viral load. Additional clinical trials are warranted to validate the role of camostat mesylate on SARS-CoV-2 infection in the treatment of mild COVID-19. Clinicaltrials.gov, NCT04353284 (04/20/20)(https://clinicaltrials.gov/ct2/show/NCT04353284?term=camostat+%2C+yale&draw=2&rank=1).


Juvenile hormone-induced histone deacetylase 3 suppresses apoptosis to maintain larval midgut in the yellow fever mosquito.
SignificanceJuvenile hormone (JH), a sesquiterpenoid, regulates many aspects of insect development, including maintenance of the larval stage by preventing metamorphosis. In contrast, ecdysteroids promote metamorphosis by inducing the E93 transcription factor, which triggers apoptosis of larval cells and remodeling of the larval midgut. We discovered that JH suppresses precocious larval midgut-remodeling by inducing an epigenetic modifier, histone deacetylase 3 (HDAC3). JH-induced HDAC3 deacetylates the histone H4 localized at the promoters of proapoptotic genes, resulting in the suppression of these genes. This eventually prevents programmed cell death of midgut cells and midgut-remodeling during larval stages. These studies identified a previously unknown mechanism of JH action in blocking premature remodeling of the midgut during larval feeding stages.


A nomogram to predict lateral lymph node metastases in lateral neck in patients with medullary thyroid cancer.
Medullary thyroid cancer (MTC) can only be cured by surgery, but the management of lateral lymph nodes is controversial, especially for patients with cN0+cN1a. To address this challenge, we developed a multivariate logistic regression model to predict lateral lymph node metastases (LNM). We retrospectively collected clinical data from 124 consecutive MTC patients who underwent initial surgery at our institution. The data of 82 patients (from 2010 to 2018) and 42 patients (from January 2019 to November 2019) were used as the training set for building the model and as the test set for validating the model, respectively. In the training group, the multivariate analyses indicated that male and MTC patients with higher preoperative basal calcitonin levels were more likely to have lateral LNM (P = 0.007 and 0.005, respectively). Multifocal lesions and suspected lateral LNM in preoperative ultrasound (US) were independent risk factors (P = 0.032 and 0.002, respectively). The identified risk factors were incorporated into a multivariate logistic regression model to generate the nomogram, which showed good discrimination (C-index = 0.963, 95% confidence interval [CI]: 0.9286-0.9972). Our model was validated with an excellent result in the test set and even superior to the training set (C-index = 0.964, 95% CI: 0.9121-1.000). Higher preoperative basal calcitonin level, male sex, multifocal lesions, and lateral lymph node involvement suspicion on US are risk factors for lateral LNM. Our model and nomogram will objectively and accurately predict lateral LNM in patients with MTC.


Endoscope-Assisted Retromastoid Intradural Suprameatal Approach for Trigeminal Schwannoma.
Dumbbell trigeminal schwannoma is the second most common type of intracranial schwannomas. Herein, we are describing and presenting a video of left trigeminal dumbbell schwannoma with a predominant posterior fossa component (modified Samii's grade C1), operated through left Retromastoid Intradural Suprameatal Approach (RISA). We demonstrate a step by step technique of a previously defined procedure for educational purpose. The patient was placed in the right lateral position, and left retromastoid craniotomy was done. Dura was opened based on transverse and sigmoid sinus to expose tumors in the suprameatal region. The tumor removed piecemeal under the microscope, and later endoscope was introduced to identify and remove the residual tumor in the superolateral part of Meckel's cave. The patient had an uneventful recovery. Trigeminal schwannoma with a predominantly posterior fossa component can be excised through retromastoid sub-occipital craniotomy. Endoscopic-assisted microsurgery should be considered in all skull base tumors. Aim for complete excision, but safe maximal resection with GKRS for residual can be considered in difficult cases.


FANCC suppresses short telomere-initiated telomere sister chromatid exchange.
Telomere shortening has been linked to rare human disorders that present with bone marrow failure including Fanconi anemia (FA). FANCC is one of the most commonly mutated FA genes in FA patients and the FANCC subtype tends to have a relatively early onset of bone marrow failure and hematologic malignancies. Here, we studied the role of Fancc in telomere length regulation in mice. Deletion of Fancc (Fancc(-/-)) did not affect telomerase activity, telomere length or telomeric end-capping in a mouse strain possessing intrinsically long telomeres. However, ablation of Fancc did exacerbate telomere attrition when murine bone marrow cells experienced high cell turnover after serial transplantation. When Fancc(-/-) mice were crossed into a telomerase reverse transcriptase heterozygous or null background (Tert(+/-) or Tert(-/-)) with short telomeres, Fancc deficiency led to an increase in the incidence of telomere sister chromatid exchange. In contrast, these phenotypes were not observed in Tert mutant mice with long telomeres. Our data indicate that Fancc deficiency accelerates telomere shortening during high turnover of hematopoietic cells and promotes telomere recombination initiated by short telomeres.


Audiovisual cues can enhance sit-to-stand in patients with Parkinson's disease.
We investigated whether preparatory signals, in the form of audiovisual cues, could enhance the performance of sit-to-stand (STS) in Parkinson's disease (PD) patients. Fifteen patients and fifteen control subjects similar in age, gender, weight, and height were examined. All subjects were instructed to carry out STS under self-initiated and cue-initiated conditions. A PEAK Motion Analysis System and two force plates were synchronized to record kinematic and kinetic data. In patients with PD, the addition of audiovisual cues was found to increase hip flexion and knee extension torques and decrease the time-to-peak joint torques, as well as increase peak horizontal and vertical velocities of the body center of mass and decrease the time taken to complete STS. Consequently, the performance of STS in these patients approached that of control subjects. In fact, during cue-initiated STS, no difference was found between the patient and control groups for the time-to-peak of all joint torques, the peak horizontal and vertical velocities, and the time taken to complete STS. Our findings thus demonstrated that audiovisual cues were effective in enhancing STS in patients with PD. These feed-forward signals could have enhanced the defective motor preparatory phase, thus leading to improved performance of the STS task. These findings provide a scientific basis for the use of audiovisual signals to enhance STS performance in patients with PD.


Newborn care is basic to safe motherhood.
Each year nearly 13 million children die before they reach their fifth birthday. One third of them die during the first days of life, often because of poor care of the mother during pregnancy and delivery or because the newborn baby is not given the care it needs when it comes into the world. Newborn health is often overlooked in international health efforts, according to Dr. Tomris Turmen, director of WHO's Division of Family Health. "We cannot hope to achieve lower infant mortality rates in the developing world if we do not interview in the critical period when one-third of all child deaths occur," Dr. Turmen says. More than 65 million deliveries take place each year without any skilled assistance. In many cases the mother and baby are completely alone. Yet at least the bare minimum of health care at birth is "the right of every laboring woman and every infant struggling to be born," Dr. Turmen argues. Newborn care, she says, does not require sophisticated technology but rather "common sense and awareness of the problems with which an infant is confronted during the first weeks of life." Safe pregnancy and delivery benefit both mother and child. Safe motherhood means a package of health care for both mother and baby. The health care package benefits equally the pregnant woman and the newborn infant. Each element of the package can be modified to apply at the community level, at the health center, or at the first referral facility. The mother and baby health package is comprised of the following: before, during pregnancy--prenatal registration and care; recognition, early detection, and management of complications; good nutrition and rest; information and services for family planning; tetanus toxoid immunization; iron and folic acid for the mother; during delivery access to emergency care at health center, referral facilities; clean and safe (atraumatic) delivery; after delivery-clean cord cutting and care; keeping the baby warm and dry; establishing breathing, resuscitation; putting the baby to the breast immediately; preventing blindness; postpartum care for the mother.


Estimating the prevalence of missing experiments in a neuroimaging meta-analysis.
Coordinate-based meta-analyses (CBMA) allow researchers to combine the results from multiple functional magnetic resonance imaging experiments with the goal of obtaining results that are more likely to generalize. However, the interpretation of CBMA findings can be impaired by the file drawer problem, a type of publication bias that refers to experiments that are carried out but are not published. Using foci per contrast count data from the BrainMap database, we propose a zero-truncated modeling approach that allows us to estimate the prevalence of nonsignificant experiments. We validate our method with simulations and real coordinate data generated from the Human Connectome Project. Application of our method to the data from BrainMap provides evidence for the existence of a file drawer effect, with the rate of missing experiments estimated as at least 6 per 100 reported. The R code that we used is available at https://osf.io/ayhfv/.


Detection and treatment of childhood malnutrition in Papua New Guinea.
This paper reviews the importance of childhood malnutrition in Papua New Guinea and other developing countries. Emphasis is given to two important causes: chronic disease and limited food supply. Definitions and diagnostic criteria for malnutrition are discussed with particular focus on the mid-upper-arm circumference (MUAC). The design of a MUAC measuring tape with written treatment guidelines for use at the aid post level and a pilot project used to test the tape are described. The rationale for six treatment steps for malnutrition are described. The importance of community education, support through church groups and effective ongoing preventive health programs at the village level are stressed.


Sound source elevation and external ear cues influence the discrimination of spectral notches by the big brown bat, Eptesicus fuscus.
Measurements of external ear transfer functions in the echolocating bat Eptesicus fuscus have revealed a prominent spectral notch that decreases in center frequency (50 to 30-35 kHz) as elevation decreases [Wotton et al., J. Acoust. Soc. Am. 98, 1423-1445 (1995)]. To examine the influence of this notch, four Eptesicus were trained to discriminate between two sets of electronically generated artificial echoes. The negative (unrewarded) stimulus contained a test spectral notch at a specific frequency that varied from 30 to 50 kHz, while the positive (rewarded) stimulus contained no test notch. The vertical position of the loudspeakers delivering these simulated echoes was changed daily. When echoes were returned from an elevation at which the external ear introduced a spectral notch at the same frequency as the test notch, then the discrimination should have been difficult. The bats' performance conformed to this prediction: All bats discriminated the presence of a 35-kHz notch at all elevations except -10 degrees. As the frequency of the synthesized notch increased, the elevation at which bats could not perform the discrimination also increased. The movement of the bat's "blind spot" for the test notch of different frequencies followed the movement of the external ear notch at different elevations.


The Association of Blood Biomarkers and Body Mass Index in Knee Osteoarthritis: A Cross-Sectional Study.
Despite massive efforts, there are no diagnostic blood biomarkers for knee osteoarthritis (KOA). This study investigated several candidate diagnostic biomarkers and the metabolic phenotype in end-stage KOA in the context of obesity. In this cross-sectional study, adult patients undergoing knee arthroplasty were enrolled and KOA severity was assessed using the Lequesne index. Blood biomarkers with an important role in obesity, the metabolic syndrome, or KOA (oxidized form of low-density lipoprotein [oxLDL], advanced glycation end product [AGE], soluble AGE receptor [sRAGE], fatty acid binding protein 4 [FABP4], phospholipase A2 group IIA [PLA2G2A], fibroblast growth factor 23 [FGF-23], ghrelin, leptin, and resistin) were measured using enzyme-linked immunosorbent assay (ELISA; n = 70) or Luminex technique (subgroup of n = 35). H1-NMR spectroscopy was used for the quantification of metabolite levels (subgroup of n = 31). The hip-knee-ankle angle was assessed. Multivariable and multivariate regression analysis was used to examine the relationship of biomarkers with body mass index (BMI) and KOA severity in complete case and multiple imputation analysis. While most of the investigated biomarkers were not associated with KOA severity, FABP4 and leptin were found to correlate with BMI and gender. Resistin was associated with Lequesne index in complete case analysis. Using a targeted metabolomics approach, BMI-dependent changes in the metabolome were hardly visible. Our findings confirm studies on FABP4, leptin, and resistin with regard to obesity and the metabolic syndrome. There was no association of the investigated biomarkers with KOA severity, most likely due to the patient selection (end-stage KOA patients). Based on this absence of BMI-dependent changes in the metabolome, we might assume that BMI is not correlated with KOA severity in this specific patient group.


Presentation and Management Outcomes of Goitres at a District Hospital in Abuja, North Central Nigeria: A 15-Year-Review.
The clinical and pathologic spectrums of goitres are wide. Even though Nigeria's Federal Capital Territory is within the geographic goitre bed, there is a paucity of thyroidrelated data from this region. The objective of this study was to determine the clinical presentation, management and outcomes of patients with goitre operated-on at the Department of Surgery, Asokoro District Hospital, in Abuja, Nigeria. This is a retrospective study involving patients managed between January 2001 and December 2015. Data were extracted from patients' medical records, operation registers, and histopathology records. Variables were; age, sex, diagnosis, types of operation performed, post-operative complications and histological findings. All patients had general anaesthesia via cuffed endotracheal intubation and the surgical technique used was skin crease transverse collar stud incision. One hundred and thirty four (134) patients were involved in the study: 124(92.5%) were females and 10(7.5%) males. Mean age was 38years±11.0SD. Seventy-seven (57.5%) patients had simple multi-nodular goitre, followed by simple left nodular goitre 20(14.9%) and simple right nodular goitre 17(12.7%). One hundred and twenty-one (90.5%) patients did not have any complications. On histologic examination, most of the lesions were multinodular goitres 60(44.8%), followed by simple nodular goitres, 23(17.2%). Follicular adenoma was the commonest neoplastic variant accounting for 12(9.1%) cases. The pattern of goitres in Abuja simulates that from other parts of Nigeria and many other African countries though with fewer malignancies in the present study. The management and outcome of goitres in Asokoro District Hospital Abuja is comparable to those obtained from other centres in Nigeria. Pre-and postoperative complications were also minimal.


Therapeutic Effect and Metabolic Mechanism of A Selenium-Polysaccharide from Ziyang Green Tea on Chronic Fatigue Syndrome.
Ziyang green tea was considered a medicine food homology plant to improve chronic fatigue Ssyndrome (CFS) in China. The aim of this research was to study the therapeutic effect of selenium-polysaccharides (Se-TP) from Ziyang green tea on CFS and explore its metabolic mechanism. A CFS-rats model was established in the present research and Se-TP was administrated to evaluate the therapeutic effect on CFS. Some serum metabolites including blood urea nitrogen (BUN), blood lactate acid (BLA), corticosterone (CORT), and aldosterone (ALD) were checked. Urine metabolites were analyzed via gas chromatography-mass spectrometry (GC-MS). Multivariate statistical analysis was also used to check the data. The results selected biomarkers that were entered into the MetPA database to analyze their corresponding metabolic pathways. The results demonstrated that Se-TP markedly improved the level of BUN and CORT in CFS rats. A total of eight differential metabolites were detected in GC-MS analysis, which were benzoic acid, itaconic acid, glutaric acid, 4-acetamidobutyric acid, creatine, 2-hydroxy-3-isopropylbutanedioic acid, l-dopa, and 21-hydroxypregnenolone. These differential metabolites were entered into the MetPA database to search for the corresponding metabolic pathways and three related metabolic pathways were screened out. The first pathway was steroid hormone biosynthesis. The second was tyrosine metabolism, and the third was arginine-proline metabolism. The 21-hydroxypregnenolone level of rats in the CFS group markedly increased after the Se-TP administration. In conclusion, Se-TP treatments on CFS rats improved their condition. Its metabolic mechanism was closely related to that which regulates the steroid hormone biosynthesis.


A flying Schrödinger's cat in multipartite entangled states.
Schrödinger's cat originates from the famous thought experiment querying the counterintuitive quantum superposition of macroscopic objects. As a natural extension, several "cats" (quasi-classical objects) can be prepared into coherent quantum superposition states, which is known as multipartite cat states demonstrating quantum entanglement among macroscopically distinct objects. Here, we present a highly scalable approach to deterministically create flying multipartite Schrödinger's cat states by reflecting coherent-state photons from a microwave cavity containing a superconducting qubit. We perform full quantum state tomography on the cat states with up to four photonic modes and confirm the existence of quantum entanglement among them. We also witness the hybrid entanglement between discrete-variable states (the qubit) and continuous-variable states (the flying multipartite cat) through a joint quantum state tomography. Our work provides an enabling step for implementing a series of quantum metrology and quantum information processing protocols based on cat states.


Oxyresveratrol Inhibits IL-1β-Induced Inflammation via Suppressing AKT and ERK1/2 Activation in Human Microglia, HMC3.
Oxyresveratrol (OXY), a major phytochemical component derived from several plants, has been proved to have several pharmacological properties. However, the role of OXY in regulating neuroinflammation is still unclear. Here, we focused mainly on the anti-neuroinflammatory effects at the cellular level of OXY in the interleukin-1 beta (IL-1β)-stimulated HMC3 human microglial cell line. We demonstrated that OXY strongly decreased the release of IL-6 and MCP-1 from HMC3 cells stimulated with IL-1β. Nevertheless, IL-1β could not induce the secretion of TNF-α and CXCL10 in this specific cell line, and that OXY did not have any effects on reducing the basal level of these cytokines in the sample culture supernatants. The densitometry analysis of immunoreactive bands from Western blot clearly indicated that IL-1β does not trigger the nuclear factor-kappa B (NF-κB) signaling. We discovered that OXY exerted its anti-inflammatory role in IL-1β-induced HMC3 cells by suppressing IL-1β-induced activation of the PI3K/AKT/p70S6K pathway. Explicitly, the presence of OXY for only 4 h could strongly inhibit AKT phosphorylation. In addition, OXY had moderate effects on inhibiting the activation of ERK1/2. Results from immunofluorescence study further confirmed that OXY inhibited the phosphorylation of AKT and ERK1/2 MAPK upon IL-1β stimulation in individual cells. These findings suggest that the possible anti-inflammatory mechanisms of OXY in IL-1β-induced HMC3 cells are mainly through its ability to suppress the PI3K/AKT/p70S6K and ERK1/2 MAPK signal transduction cascades. In conclusion, our study provided accumulated data that OXY is able to suppress IL-1β stimulation signaling in human microglial cells, and we believe that OXY could be a probable pharmacologic agent for altering microglial function in the treatment of neuroinflammation.


Effect of short-term, low dose aspirin supplementation on the activation of pro-inflammatory NF-kappaB in aged rats.
The basis of our recently proposed "molecular inflammation theory of aging" is that activated inflammatory transcription factors, including versatile NF-kappaB, occur widespread in the organism during aging. NF-kappaB plays a key role in pro-inflammatory gene expression, such as cyclooxygenase (COX). Aspirin is one of the most commonly used non-steroidal anti-inflammatory drugs because of its ability to inhibit COX activity. Thus, in the present study, we investigated the effect of short-term, low dose aspirin intake on the modulation of pro-inflammatory NF-kappaB activation in old rats. To conduct the study, 24-month-old Fischer 344 rats were supplemented with low dose aspirin (0.015%) for 10 days. Biochemical analyses showed suppressed reactive species (RS) and COX-2 activity. The data also showed that NF-kappaB activation and its associated gene expressions, such as COX-2, iNOS, VCAM-1 and ICAM-1, were all suppressed by the low dose aspirin supplementation through the inhibition of phosphorylation and degradation of IkappaBalpha via the NIK/IKK pathway. Our molecular exploration further revealed that aspirin's suppressive action of NF-kappaB was mediated by its ability to inhibit the nuclear translocation of cytosolic thioredoxin and redox factor-1. These findings showed for the first time that in aged rat short-term low dose dietary aspirin feeding modulates the molecular signal transduction involved in the inflammatory process.


The HIV/AIDS pandemic: new ways of preventing infection in men.
Nelson Mandela has recently said that HIV/AIDS is the greatest health crisis in human history. At the end of 2001, UNAIDS estimated that there were 40 million people living with the infection, with 5 million new cases, and 3 million deaths per year. About half the infected individuals are men, and heterosexual intercourse is the commonest route of infection. Although condoms remain the first line of defence, they are unpopular in parts of Africa, where the pandemic is worst, so an alternative is needed. Post-coital penile hygiene has received little attention. Wiping the glans penis and inner foreskin immediately after intercourse with an acidic solution like lemon or lime juice, or even vinegar, should immediately kill the virus and might prevent infection; clinical trials are urgently needed. Several studies in Africa and India have now conclusively demonstrated a 2-7-fold protective effect of male circumcision against HIV infection. Circumcision removes the inner foreskin and the frenulum, which are the prime sites of HIV entry into the penis. Since male circumcision also protects men from human papilloma virus infection, and their wives from cervical carcinoma, the procedure should be encouraged in developed and developing countries.


Paediatric trainees' training experiences during the COVID-19 pandemic: a national survey.
This study examines trainees' experiences of paediatric education and training during the COVID-19 pandemic. Paediatric trainees across the UK undertook an online survey. 368 of approximately 4000 trainees responded; quantitative and qualitative data were collected. Although the majority of trainees remained in their specialties, there was significant disruption to training events, teaching and learning opportunities. Despite this, for many, novel opportunities presented themselves that may not have otherwise been accessible. Trainees reported increased virtual learning, reflection, leadership and management opportunities. A breadth of trainee-identified web-based paediatric training resources were also highlighted. As the COVID-19 pandemic persists, these trainee experiences inform educators to adopt helpful training practices from other regions, including sharing of virtual learning regionally and acting-up opportunities. Trainees highlighted previously under-recognised areas of concern that can inform quality improvement initiatives, such as enhancing patient safety through tackling trainee fatigue, combating reduced clinical experience or instituting protected supporting professional activity time.


An unusual clinical presentation of plasma cell gingivitis related to "Acacia" containing herbal toothpaste.
A 17-year-old female patient presented with unusual enlargement of the gingiva with generalized alveolar bone loss. In spite of periodontal therapy, including plaque control, scaling, root planning and surgical treatment, recurrence with the same degree of the gingival enlargement and further loss of attachment level occurred. Biopsy revealed dense infiltration of normal plasma cells separated by collagenous stroma. Discontinuation of herbal toothpaste resulted in remarkable remission of the gingival enlargement within 2 weeks. Enzyme-linked immunosorbent assay of toothpaste components disclosed "Acacia" as an etiologic antigenic agent and confirmed the diagnosis of plasma cell gingivitis (PCG). Usually, PCG is not associated with the loss of attachment. This case report appears to be the first publication to document an atypical presentation of PCG with generalized aggressive periodontitis related to the use of herbal toothpaste containing "Acacia" extract from the tree "Acacia Arabica."


The role of prostate-specific antigen as part of the diagnostic triad and as a guide when to perform a biopsy.
The authors reviewed the results and relationship of prebiopsy prostate-specific antigen (PSA) assay, digital rectal examination (DRE), and transrectal ultrasound (TRUS) in 124 consecutive patients who underwent a prostate biopsy because of abnormal results of either DRE or TRUS. Results of the three tests (PSA, DRE, and TRUS) showed abnormalities in 54%, 75%, and 84.6% of patients, respectively; biopsy results were positive for cancer in 45.2%. Cancer detection rate increased as the PSA value increased from less than or equal to 4 ng/ml (17.5%) to more than 4 ng/ml (68.7%) to more than 20 ng/ml (83.3%), and as the number of positive tests increased (6.9% for one, 32.7% for two, and 82.6% for three). The PSA assay was the most important parameter of the diagnostic triad. These results suggested that regardless of DRE and TRUS findings, PSA less than or equal to 4 ng/ml confers a low prostate cancer risk, PSA more than 4 ng/ml but less than or equal to 10 ng/ml confers an intermediate prostate cancer risk, and PSA more than 10 ng/ml confers a high prostate cancer risk. Regardless of other findings, all patients with a PSA value more than 10 ng/ml require biopsy because of the high likelihood of cancer. All patients with abnormal DRE or TRUS results still require biopsy despite a low index of suspicion of prostate cancer when the PSA value is less than or equal to 4 ng/ml.


A Comparative Study of the Molecular Characteristics of Familial Gliomas and Other Cancers.
Familial cancers are those that co-occur among first-degree relatives without showing Mendelian patterns of inheritance. In this analysis, we compare the genomic characteristics of familial and sporadic cancers, with a focus on low-grade gliomas (LGGs) using sequence and expression data from the Cancer Genome Atlas. Familial cancers show similar genomic and molecular biomarker profiles to sporadic cancers, consistent with the similarity in their clinical features. There are no statistically significant differences among somatic mutation, copy number variant, or gene expression patterns between familial and sporadic cancers; methylation profiles are the only class of molecular data to show significant differences. Familial cancers are likely driven by multiple, individually weak contributions to familiality (i.e. large numbers of alleles and/or shared environmental risks). Consequently, these risk factors tend to be obscured by stronger confounding variables such as clinical or molecular variation among cancer subtypes.


The effect of diclofenac (Voltaren) on the contraction of collagen lattices.
The inhibition of prostaglandin synthesis by diclofenac was studied with regard to effects on connective-tissue contraction and on the chemotaxis of fibroblasts stimulated by platelet-derived growth factor type BB (PDGF-BB). Collagen lattices populated with human fibroblasts responded to diclofenac with significantly increased contraction; the peak effect occurred at a dose of 5 micrograms/ml. Using a two-chamber system, PDGF-BB significantly increased the chemotactic activity of fibroblasts, and addition of diclofenac further increased this activity. Higher doses of diclofenac resulted in cell death, which was also reflected in lessened contraction of lattices with 50 micrograms/ml diclofenac, half of the cells were dead. The study showed that inhibition of prostaglandin synthesis by diclofenac increases the contraction of collagen lattices populated with human fibroblasts and increases the chemotactic activity of fibroblasts stimulated with PDGF-BB.


[A case of malignant lymphoma of the gallbladder after chemotherapy for malignant lymphoma of the skin and right intraocular].
A case is a 65-year-old female. She was diagnosed as T-cell malignant lymphoma (skin and right intraocular). Chemotherapy( THP-COP) was performed for 6 months and she was in remission. A gallbladder tumor was pointed out in August 2010, and she was admitted to our department for the purpose of excision biopsy of the gallbladder tumor. In abdominal US, we confirmed an iso-hypoechoic tumor. The tumor size was 24 × 14 mm. We considered the invasion depth was subserosa. We observed the tumor which had the imaging effectiveness in the body of gallbladder by abdominal CT. The invasion was suspected in the liver bed side. In PET-CT, We observed an accumulation of SUVmax 8 . 5 in the body of gallbladder. The protruded lesion of 33 .5 mm in diameter was detected by MRI to the body of gallbladder, and an invasion was also suspected. Cholecystectomy was performed to this case. By operative US, the gallbladder tumor was SMT and existed in the symmetric side of liver bed. Pathological diagnosises were malignant lymphoma and peripheral T-cell lymphoma.


Differential Light Responses of Photosynthesis by Triazine-resistant and Triazine-susceptible Senecio vulgaris Biotypes.
Studies were conducted to determine a physiological basis for competitive differences between Senecio vulgaris L. biotypes which are either resistant or susceptible to triazine herbicides. Net carbon fixation of intact leaves of mature plants was higher at all light intensities in the susceptible biotype than in the resistant biotype. Quantum yields measured under identical conditions for each biotype were 20% lower in the resistant than in the susceptible biotype. Oxygen evolution in continuous light measured in stroma-free chloroplasts was also higher at all light intensities in the susceptible biotype than in the resistant biotype. Oxygen evolution in response to flashing light was measured in stroma-free chloroplasts of both biotypes. The steady-state yield per flash of resistant chloroplasts was less than 20% that of susceptible chloroplasts. Susceptible chloroplasts displayed oscillations in oxygen yield per flash typically observed in normal chloroplasts, whereas the pattern of oscillations in resistant chloroplasts was noticeably damped. It is suggested that modification of the herbicide binding site which confers s-triazine resistance may also affect the oxidizing side of photosystem II, making photochemical electron transport much less efficient. This alteration has resulted in a lowered capacity for net carbon fixation and lower quantum yields in whole plants of the resistant type.


Isolation and characterization of two basic internal proteins from the T-even bacteriophages.
Two species of basic internal proteins were found in osmotic shock supernatant solutions of bacteriophages T4B, T4D, T2H, T2L, and T6. The major species of protein isolated had a molecular weight of approximately 21,000 daltons, whereas the minor protein molecular weight was near 9,500 daltons. The two protein species exhibited unique isoelectric points and amino acid compositions. The 21,000-dalton protein of T2L showed major electrophoretic and compositional differences from the other 21,000-dalton proteins isolated. Similarities between the 21,000-dalton proteins and phage lysozyme are discussed.


Prevention of hepatitis C in partners of anti-HCV positive subjects by periodic gammaglobulin administration.
Since hepatitis C is sexually transmitted, this poses the problem of protecting the anti-HCV negative partners of anti-HCV positive subjects. Since no specific prophylaxis exists for hepatitis C, I suggest that 4 ml of normal human gammaglobulin should be given to the anti-HCV negative partners intramuscularly every two months until a vaccine against hepatitis C virus is available.


[Clinicopathologic features of 18 cases of cryptogenic organizing pneumonia].
To analyze the characteristics of pathologically proved cases of cryptogenic organizing pneumonia (COP) including manifestation of CT scan, bronchoalveolar lavage (BAL) fluid cytology, pulmonary histopathological appearance. Twenty-three consecutive patients from April 1994 to October 2005 in Peking Union Medical College Hospital with pathologic features of organizing pneumonia were enrolled in the study. Eighteen patients were diagnosed as COP. Percutaneous lung biopsy/transbronchial lung biopsy was performed in 10 patients, while open lung biopsy/video-assistant thorascopic biopsy was performed in 8 patients. There were 8 males and 10 females, aged (53.5 +/- 11.0) yr. Dyspnea, cough, inspiratory crackles were the most common symptoms and signs. Lung function tests showed a restrictive ventilatory defect (11/18), and impairment of carbon monoxide transfer factor (T(LCO), 18/18). Chest computed tomography scan in 18 cases mainly showed ground glass opacities (4/18), patchy areas of alveolar consolidation (13/18) with air bronchograms (3/18), and pleural effusion (4/18). BAL fluid cytological analysis showed the percentage of lymphocyte was 0.40 +/- 0.16, neutrophil 0.15 +/- 0.08, eosinophil 0.05 +/- 0.03; the CD(4)/CD(8) ratio was 0.43 +/- 0.21. All patients were treated with corticosteroids. Sixteen were alive and clinically improved or stabilized at the last follow up (8.7 +/- 6.2 months after diagnosis). Two patients died, one of respiratory failure, and another of pulmonary infection. The diagnosis of COP is usually suggested by clinical-radiological findings, but needs to be confirmed histopathologically. The combination of BAL fluid cytological findings and lung histological appearance obtained during a bronchoscopic procedure appears to be an effective method for diagnosing this disease.


The temporal sequence of spontaneous repair of osteochondral defects in the knees of rabbits is dependent on the geometry of the defect.
Damage to articular cartilage is a common injury, for which there is no effective treatment. Our aims were to investigate the temporal sequence of the repair of articular cartilage and to define a critical-size defect. Full-thickness defects were made in adult male New Zealand white rabbits. The diameter (1 to 4 mm) of the defects was varied in order to determine the effect that the size and depth of the defect had on its healing. The defects were made in the femoral groove of the knee with one defect per knee and eight knees per group. The tissues were fixed in formalin at days 3, 7, 14, 21, 28, 42, 84 and 126 after operation and the sections stained with Toluidine Blue. These were then examined and evaluated for several parameters including the degree of metachromasia and the amount of subchondral bone which had reformed in the defect. The defects had a characteristic pattern of healing which differed at different days and for different sizes of defect. Specifically, the defects of 1 mm first peaked in terms of metachromasia at day 21, those of 2 mm at day 28, followed by defects of 3 mm and 4 mm. The healing of the subchondral bone was slowest in defects of 1 mm.


Rh nanoparticle catalyzed hydroaminomethylation of 1-octene in thermoregulated ionic liquid and organic biphasic system.
Thermoregulated ionic liquid and organic biphasic system composed of ionic liquid [CH3(OCH2 CH2)22N+Et3][CH3SO3-] (abbreviated as IL(PEG1000)) containing IL(PEG1000)-stabilized Rh nanoparticles and organic solvent, which allows for not only highly efficient homogeneous reaction but also an easy biphasic separation, was applied to the hydroaminomethylation of 1-octene for the first time. Under the optimized conditions, the conversion of 1-octene and the amine selectivity were 100% and 90%, respectively. After reaction, the Rh nanoparticle catalyst could be easily separated by simple decantation and reused for four times without evident loss in activity.


[Use of codons in plant lectins].
Codon usage in the coding region of mature lectins has been examined for 11 plant species (8 leguminoseae, 1 euphorbiaceae, 2 gramineae). The different legume lectins exhibit nearly the same codon usage pattern whereas the choice for the silent position of codons is non-random.


Golden berry juice attenuates the severity of hepatorenal injury.
The aim of the present work is to investigate the potential of Physalis peruviana fruits as a hepatorenal protective agent against carbon tetrachloride (CCl4)-induced hepatic and renal fibrosis. The phytochemical screening test revealed the presence of alkaloids, free withanolides, glycowithanolides, and flavonoids. Acute toxicity study (500, 1000, and 1500 mg/kg body weight) revealed extract safety. The biological evaluation was conducted on different animal groups: control, control treated with fruit, CCl4 group, CCl4 treated with fruit, and CCl4 treated with silymarin drug. The evaluation was done through measuring oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO). Liver function indices such as aspartate and alanine aminotransferases (AST & ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin, and total protein were estimated. Kidney disorder biomarkers such as creatinine, urea, and serum protein were also evaluated. Treatment improved all the investigated parameters, and the histopathological analysis confirmed our results. In conclusion, Physalis peruviana fruit succeeded to protect liver and kidney against fibrosis. Further studies are needed to identify the molecules responsible for its pharmacological application.


Sodium cromoglycate on plasma protein exudation to topically-applied substance P in the tracheal airways of rats or guinea-pigs in vivo.
Sodium cromoglycate (SCG) was examined against substance P(SP)-induced plasma protein exudation in the trachea of anaesthetized rats and guinea-pigs in vivo to determine whether SCG is a tachykinin receptor antagonist in the airways. A segment of trachea was prepared in situ for continuous perfusion with normal saline. Plasma-derived protein in the perfusion fluid (airway lumen) was increased after topical application of SP (1 microM, 5 min contact). In rats, the SP response was not attenuated by iv SCG but was inhibited (29%) by topical SCG under certain experimental conditions and using a high concentration of SCG (500 microM, 5 min contact, 30 min before SP and with SP). The NK(1)receptor antagonist, RP 67 580 (67 microM) abolished the SP response in rats. Sodium cromoglycate did not inhibit the SP response in guinea-pigs (same protocol as in rats). Thus, SCG attenuates plasma protein exudation (and presumably microvascular leak) induced by SP in rat tracheal airways but, if SCG is a tachykinin receptor (NK(1)) antagonist, it not only lacks potency but is species-selective, i.e. more effective in rats than in guinea-pigs.


Comparison of direct and alternating current vacuum ultraviolet lamps in atmospheric pressure photoionization.
A direct current induced vacuum ultraviolet (dc-VUV) krypton discharge lamp and an alternating current, radio frequency (rf) induced VUV lamp that are essentially similar to lamps in commercial atmospheric pressure photoionization (APPI) ion sources were compared. The emission distributions along the diameter of the lamp exit window were measured, and they showed that the beam of the rf lamp is much wider than that of the dc lamp. Thus, the rf lamp has larger efficient ionization area, and it also emits more photons than the dc lamp. The ionization efficiencies of the lamps were compared using identical spray geometries with both lamps in microchip APPI mass spectrometry (μAPPI-MS) and desorption atmospheric pressure photoionization-mass spectrometry (DAPPI-MS). A comprehensive view on the ionization was gained by studying six different μAPPI solvent compositions, five DAPPI spray solvents, and completely solvent-free DAPPI. The observed reactant ions for each solvent composition were very similar with both lamps except for toluene, which showed a higher amount of solvent originating oxidation products with the rf lamp than with the dc lamp in μAPPI. Moreover, the same analyte ions were detected with both lamps, and thus, the ionization mechanisms with both lamps are similar. The rf lamp showed a higher ionization efficiency than the dc lamp in all experiments. The difference between the lamp ionization efficiencies was greatest when high ionization energy (IE) solvent compositions (IEs above 10 eV), i.e., hexane, methanol, and methanol/water, (1:1 v:v) were used. The higher ionization efficiency of the rf lamp is likely due to the larger area of high intensity light emission, and the resulting larger efficient ionization area and higher amount of photons emitted. These result in higher solvent reactant ion production, which in turn enables more efficient analyte ion production.


Vaccination strategies to enhance local immunity and protection against Mycobacteriun tuberculosis.
To determine the immunogenicity and protective efficacy of the Mycobacterium tuberculosis 10 kD culture filtrate protein (CFP10), and to evaluate strategies that enhance local immunity, we used C57Bl/6 DR4 mice that were transgenic for human HLA DRB1 0401, because CFP10 contains epitopes for DRB1 0401 but not for C57Bl/6 mice. Intramuscular immunization with a DNA vaccine encoding CFP10 elicited production of IFN-gamma by systemic CD4+ T cells, and one intravenous dose of the CFP10-based DNA vaccine coated with polyethylenimine (PEI) stimulated IFN-gamma production by lung CD4+ cells and reduced the pulmonary bacillary burden. We conclude that CFP10 is a potential vaccine candidate and that coating vaccines with PEI enhances local protective immunity to tuberculosis


'Pygmaiobacter massiliensis' sp. nov., a new bacterium isolated from the human gut of a Pygmy woman.
This study supports the main characteristics of a new genus 'Pygmaiobacter' and a new species 'Pygmaiobacter massiliensis' strain Marseille-P3336 (CSUR P3336); that was isolated from a stool sample of a healthy 47-year-old Pygmy woman. The Institut Fédératif de Recherche ethics committee, gave approval for this study under the number 09-022. Samples were collected for microbial content description as part of the human microbiome description by culturomics.


Radiative transfer in water and ice clouds in the visible and infrared region.
The radiance and polarization are calculated at six wavelengths from 0.7 micro to 6.05 micro for the photons reflected from and transmitted through two model clouds representing water and ice clouds with modal radii of 12 micro and 50 micro, respectively. The single scattering matrix is obtained from the Mie theory for spherical particles from the measured values of the complex index of refraction for water and ice. Multiple scattering to all orders is taken into account by a Monte Carlo technique which computes the exact three-dimensional paths of the photons. The upward and downward radiance and polarization are given as a function of optical thickness for each cloud model. The mean optical path of the photon, the cloud albedo, and the flux at the lower and upper boundaries are also given. The reflected radiance is considerably less for the ice than for the nimbostatus (water) model at all angles at most infrared wavelengths, particularly at wavelengths of 1.7 micro, 2.1 micro, and 3.5 micro. The polarization of the reflected photons is often very much greater for the ice than for the nimbostratus model, particularly at wavelengths of 1.7 micro, 2.1 micro, and 3.5 micro. These differences may be used in order to discriminate between water and ice clouds from measurements of the reflected radiation.


ESCRT Requirements for Murine Leukemia Virus Release.
The Murine Leukemia Virus (MLV) is a gammaretrovirus that hijack host components of the endosomal sorting complex required for transport (ESCRT) for budding. To determine the minimal requirements for ESCRT factors in MLV viral and viral-like particles (VLP) release, an siRNA knockdown screen of ESCRT(-associated) proteins was performed in MLV-producing human cells. We found that MLV VLPs and virions primarily engage the ESCRT-I factor Tsg101 and marginally the ESCRT-associated adaptors Nedd4-1 and Alix to enter the ESCRT pathway. Conversely, the inactivation of ESCRT-II had no impact on VLP and virion egress. By analyzing the effects of individual ESCRT-III knockdowns, VLP and virion release was profoundly inhibited in CHMP2A- and CHMP4B-knockdown cells. In contrast, neither the CHMP2B and CHMP4A isoforms nor CHMP3, CHMP5, and CHMP6 were found to be essential. In case of CHMP1, we unexpectedly observed that the CHMP1A isoform was specifically required for virus budding, but dispensable for VLP release. Hence, MLV utilizes only a subset of ESCRT factors, and viral and viral-like particles differ in ESCRT-III factor requirements.


Experimental and modelling evidence of splash effects on manure borne Escherichia coli washoff.
In tropical montane South-East Asia, recent changes in land use have induced increased runoff, soil erosion and in-stream suspended sediment loads. Land use change is also contributing to increased microbial pathogen dissemination and contamination of stream waters. Escherichia coli (E. coli) is frequently used as an indicator of faecal contamination. Field rain simulations were conducted to examine how E. coli is exported from the surface of upland, agricultural soils during runoff events. The objectives were to characterize the loss dynamics of this indicator from agricultural soils contaminated with livestock waste, and to identify the effect of splash on washoff. Experiments were performed on nine 1 m2 plots, amended or not with pig or poultry manure. Each plot was divided into two 0.5 m2 sub-plots. One of the two sub-plots was protected with a mosquito net for limiting the raindrop impact effects. Runoff, soil detachment by raindrop impact and its entrainment by runoff, and E. coli loads and discharge were measured for each sub-plot. The results show that raindrop impact strongly enhances runoff generation, soil detachment and entrainment and E. coli export. When the impact of raindrops was reduced with a mosquito net, total runoff was reduced by more than 50%, soil erosion was on average reduced by 90% and E. coli export from the amended soil surface was on average 3 to 8 times lower. A coupled physics-based approach was performed using the Cast3M platform for modelling the time evolutions of runoff, solid particles detachment and transfer and bacteria transport that were measured for one of the nine plots. After estimation of the saturated hydraulic conductivity, soil erodibility and attachment rate of bacteria, model outputs were consistent with measured runoff coefficients, suspended sediment and E. coli loads. This work therefore underlines the need to maintain adequate vegetation at the soil surface to avoid the erosion and export of soil borne potential pathogens towards downstream aquatic systems.


Frontal lobe damage and tests of executive processing: a meta-analysis of the category test, stroop test, and trail-making test.
The Category Test, Trails B, and the interference task of the Stroop Test are among the most commonly administered measures of frontal lobe functioning and are thought to tap different cognitive functions mediated by these brain regions. Two meta-analyses were conducted on these tests to determine their sensitivity to frontal and lateralized frontal brain damage. Study 1 compared participants with frontal lobe damage to those with damage to posterior brain regions, whereas Study 2 compared participants with left and right frontal lobe damage. For each study, effect sizes based on performance differences between the above groups were calculated for the Category Test, Trail-Making Test Parts A and B, and the Stroop Test, including Word, Color, and Color-Word subtests. In Study 1 significant differences between groups were found for Trails A and all Stroop tasks, but in Study 2 the only difference between left and right frontal participants was on the Stroop Color-Word task. Potential reasons why Trails A and the Stroop Test are sensitive to frontal lobe damage are discussed, such as novelty and processing speed, as are clinical implications of these findings. The challenges of research on assessment of frontal lobe functioning are discussed and new developments in this area are highlighted.


Human postthymic precursor cells in health and disease. IV. Abnormalities in immunoregulatory T cell circuits in mixed connective tissue disease.
Human T cells are capable of forming rosettes with autologous erythrocytes (Tar cells) and behave as postthymic precursors. Thus, they generate Tgamma and Tmu cells as well as suppression and spontaneous cytotoxicity and participate in a pokeweed mitogen-driven system akin to that of feedback inhibition in which murine postthymic precursors participate. Tar cells were increased in 7 patients with mixed connective tissue disease (MCTD) compared to normal age/sex-matched controls. Despite this increase of precursor cells, decreased Tgamma cells and abrogation in the generation of suppression and of feedback inhibition were noted. These functional defects were not correctable with serum thymic factor but could be corrected by the addition of either allogenic Tmu or mononuclear cells depleted of Tar cells. Our findings suggest that the immunoregulatory T cell circuits in MCTD may be adequate both in postthymic precursor cells and in the thymic factor prompting. They are probably abnormal either at the site of Tmu signaling to Tar cells in feedback inhibition or in the Tmu reception of suppressor signals from Tgamma cells. The decrease of Tgamma cells in MCTD could be due to the decreased stimulus from feedback inhibition and/or to the penetration of anti-ribonucleoprotein antibody. Abnormalities of immunoregulatory T cell circuits in MCTD are quite different from those found previously in systemic lupus erythematosus, scleroderma, and rheumatoid arthritis. These differences support the notion that MCTD is a distinct entity.


Pastoralist health care in Kenya.
Health care for the Kenyan pastoralist people has serious shortcomings and it must be delivered under difficult circumstances. Often, the most basic requirements cannot be met, due to the limited accessibility of health care provisions to pastoralists. This adds major problems to the daily struggle for life, caused by bad climatic circumstances, illiteracy and poverty. We argue that strong, integrated and community based primary health care could provide an alternative for these inadequacies in the health system. The question then is how primary health care, which integrates a diversity of basic care provisions, such as pharmaceutical provision, child delivery assistance, mother and childcare and prevention activities, can be implemented. In our view, an appropriate mix of decentralisation forms, warranting better conditions on the one hand and relying on the current community and power structures and culture on the other hand, would be the best solution for the time being.


Topical administration of tranexamic acid in hip arthroplasty.
The purpose of this study was to assess the efficacy of a newly designed topical administration of tranexamic acid (TXA) in reducing post-operative bleeding in total hip arthroplasty (THA) and bipolar hip hemiarthroplasty (BHA). A consecutive series of 160 patients who underwent hip arthroplasty was enrolled in this study. Topical administration of TXA was done in group 1 (40 patients underwent THA and 40 BHA). We compared the amount of blood loss and rates of post-operative transfusion in group 1 with those of group 2 (40 cases of THA and 40 cases of BHA) in which TXA solution was not applied. The total amount of blood loss in THA group 1 and THA group 2 was 793 ± 50 mL and 1086 ± 73 mL, respectively (p = 0.001). The transfusion rates of THA group 1 and THA group 2 was 27.5 % and 50 %, respectively (p = 0.039). The transfusion rates of BHA group 1 and BHA group 2 was 45 % and 60 %, respectively (p = 0.179). The amounts of blood loss through the drainage tube were 186 ± 22 mL and 257 ± 24 mL in THA group 1 and THA group 2, respectively, and 101 ± 11 mL and 147 ± 16 mL in BHA group 1 and BHA group 2, respectively, showing statistical significance. No complications such as infection, deep vein thrombosis or cardiovascular disease were observed during the hospital stay and the last follow-up. Topical administration of TXA is an effective and safe method to reduce post-operative bleeding and transfusion rates in hip arthroplasty.


Association of the catechol-O-methyltransferase polymorphism with methylphenidate response in a classroom setting in children with attention-deficit hyperactivity disorder.
It has been postulated that the prefrontal cortex plays a key role in attention-deficit hyperactivity disorder (ADHD). The catechol-O-methyltransferase (COMT) enzyme degrades synaptic catecholamines and plays a specific role in the catabolism of prefrontal cortex dopamine. We investigated the association between the COMT valine (Val) 108/158 methionine (Met) polymorphism and the response to treatment with methylphenidate (MPH) in children with ADHD. This study included 124 children with ADHD in South Korea. Those patients who had an improvement after 8 weeks of treatment greater than or equal to 50% compared with the baseline ADHD rating scale scores before treatment were considered to be the 'good response' group. After performing genotyping for COMT, we examined the correlation of the COMT polymorphism with response to treatment with MPH using the chi test. We found that whereas 62.5% of the patients showing a good response to MPH treatment had the Val/Val genotype, 41.7 and 11.7% of the patients showing a poor response to MPH treatment as assessed by their teachers had the Val/Met and Met/Met genotypes (chi=6.58, d.f.=2, P=0.035). Our findings provide evidence of an association between the COMT genotype and MPH response as assessed by the teachers of children with ADHD.


Fixed-bed column study of phosphate adsorption using immobilized phosphate-binding protein.
Bio-adsorption using high-affinity phosphate-binding proteins (PBP) has demonstrated effective phosphorus removal and recovery in batch-scale tests. Subsequent optimization of design and performance of fixed-bed column systems is essential for scaling up and implementation. Here, continuous-flow fixed-bed column tests were used to investigate the adsorption of inorganic phosphate (orthophosphate, Pi) using phosphate-binding proteins immobilized on resin (PBP-NHS) targeting Pi removal to ultra-low levels followed by recovery. Time to breakthrough decreased with higher influent Pi concentration, smaller bed volume, and higher influent flow rates. The Thomas and Yoon-Nelson breakthrough models adequately described PBP-NHS resin performance with a correlation coefficient of R2 > 0.95. The sharp S-shape of the breakthrough curves for both Pi-only solution and multi-ion solution indicated highly favorable and selective separation of Pi using PBP-NHS resin, beyond that achieved using LayneRT™, a commercial ion exchange resin. The Pi adsorption capacity of the PBP-NHS column was unaffected by competing anions, whereas capacity of the LayneRT™ column dropped by 20%. Tertiary wastewater effluent was also successfully treated in PBP-NHS column tests with a typical S-shaped breakthrough curve. Operating the fixed-bed column in multi-cycle mode evidenced the reusability of PBP-NHS resin with no significant decline in column performance. The results of this study contribute to efforts to scale up designs of PBP-NHS adsorption systems.


Comparative assessment of immunological tolerance in fish with natural immunodeficiency.
Natural occurrences of immunodeficiency by definition should lead to compromised immune function. The major histocompatibility complexes (MHC) are key components of the vertebrate adaptive immune system, charged with mediating allorecognition and antigen presentation functions. To this end, the genomic loss of the MHC II pathway in Syngnathus pipefishes raises questions regarding their immunological vigilance and allorecognition capabilities. Utilising allograft and autograft fin-transplants, we compared the allorecognition immune responses of two pipefish species, with (Nerophis ophidion) and without (Syngnathus typhle) a functional MHC II. Transcriptome-wide assessments explored the immunological tolerance and potential compensatory measures occupying the role of the absent MHC II. Visual observations suggested a more acute rejection response in N. ophidion allografts compared with S. typhle allografts. Differentially expressed genes involved in innate immunity, angiogenesis and tissue recovery were identified among transplantees. The intriguing upregulation of the cytotoxic T-cell implicated gzma in S. typhle allografts, suggests a prominent MHC I related response, which may compensate for the MHC II and CD4 loss. MHC I related downregulation in N. ophidion autografts hints at an immunological tolerance related reaction. These findings may indicate alternative measures evolved to cope with the MHC II genomic loss enabling the maintenance of appropriate tolerance levels. This study provides intriguing insights into the immune and tissue recovery mechanisms associated with syngnathid transplantation, and can be a useful reference for future studies focusing on transplantation transcriptomics in non-model systems.


Mmh/Ogg1 gene inactivation results in accumulation of 8-hydroxyguanine in mice.
The major mutagenic base lesion in DNA caused by exposure to reactive oxygen species is 8-hydroxyguanine or 7, 8-dihydro-8-oxoguanine (8-OH-G). Products of the human MMH/OGG1 gene are known to catalyze in vitro the reactions repairing this DNA lesion. To analyze the function of Mmh in vivo, we generated a mouse line carrying a mutant Mmh allele by targeted gene disruption. Mmh homozygous mutant mice were found to have a physically normal appearance, but to have lost nicking activity in liver extracts for substrate DNA containing 8-OH-G, exhibiting a 3-fold increased accumulation of this adduct at 9 weeks of age compared with wild-type or heterozygous mice. Further elevation to 7-fold was observed in 14-week-old animals. Substantial increase of spontaneous mutation frequencies was clearly identified in Mmh mutant mice bearing transgenic gpt genes. These results indicate that exposure of DNA to endogenous oxidative species continuously produces the mutagenic adduct 8-OH-G in mice, and Mmh plays an essential role in repair of this DNA damage.


Organization of Chlorophyll a in the Light-Harvesting Chlorophyll a/b Protein Complex as Shown by Circular Dichroism : Liquid Crystal-Like Domains.
The development of thylakoid stacking, accumulation of the light-harvesting chlorophyll a/b protein complex (LHCP), and the changes of circular dichroism (CD) which reflect the organization of chlorophyll molecules in greening thylakoids of bean Phaseolus vulgaris cv Red Kidney leaves were investigated.Chloroplasts formed under intermittent light contained large double sheets of membrane with extensive appression in addition to separate lamellae. Thylakoids of such chloroplasts were devoid of LHCP and exhibited a relatively small CD in the chlorophyll absorption region. Upon continuous illumination, the rearrangement of membranes to characteristic grana and the accumulation of the LHCP was accompanied by the gradual appearance of the very intense CD signal with peaks at 682 to 684 (+) and 665 to 672 nanometers (-). The magnitude of differential absorption was approximately 100 times larger than that of the chlorophyll a in solution. This suggests a superhelical liquid crystal-like organization for LHCP, a texture which can be altered by changes of the electric field in the photosynthetic membranes.


Identification of PSMB9 and CXCL13 as Immune-related Diagnostic Markers for Rheumatoid Arthritis by Machine Learning.
Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes significant physical and psychological damage. Although researchers have gained a better understanding of the mechanisms of RA, there are still difficulties in diagnosing and treating RA. We applied a data mining approach based on machine learning algorithms to explore new RA biomarkers and local immune cell status. We extracted six RA synovial microarray datasets from the GEO database and used bioinformatics to obtain differentially expressed genes (DEGs) and associated functional enrichment pathways. In addition, we identified potential RA diagnostic markers by machine learning strategies and validated their diagnostic ability for early RA and established RA, respectively. Next, CIBERSORT and ssGSEA analyses explored alterations in synovium-infiltrating immune cell subpopulations and immune cell functions in the RA synovium. Moreover, we examined the correlation between biomarkers and immune cells to understand their immune-related molecular mechanisms in the pathogenesis of RA. We obtained 373 DEGs (232 upregulated and 141 downregulated genes) between RA and healthy controls. Enrichment analysis revealed a robust correlation between RA and immune response. Comprehensive analysis indicated PSMB9, CXCL13, and LRRC15 were possible potential markers. PSMB9 (AUC: 0.908, 95% CI: 0.853-0.954) and CXCL13 (AUC: 0.890, 95% CI: 0.836-0.937) also showed great diagnostic ability in validation dataset. Infiltrations of 16 kinds of the immune cell were changed, with macrophages being the predominant infiltrating cell type. Most proinflammatory pathways in immune cell function were activated in RA. The correlation analysis found the strongest positive correlation between CXCL13 and plasma cells, PSMB9, and macrophage M1. There is a robust correlation between RA and local immune response. The immune-related CXCL13 and PSMB9 were identified as potential diagnostic markers for RA based on a machine learning approach. Further in-depth exploration of the target genes and associated immune cells can deepen the understanding of RA pathophysiological processes and provide new insights into diagnosing and treating RA.


Task Migration and Scheduler for Mixed-Criticality Systems.
The interference between software components is increasing in safety-critical domains, such as autonomous driving. Low-criticality (LC) tasks, such as vehicle communication, may control high-criticality (HC) tasks, such as acceleration. In such cases, the LC task should also be considered as an HC task because the HC tasks relies on the LC task. However, the difficulty in guaranteeing these LC tasks is the catastrophic cost of computing resources, the electronic control unit in the domain of vehicles, required for every task. In this paper, we theoretically and practically provide safety-guaranteed and inexpensive scheduling for LC tasks by borrowing the computational power of neighbored systems in distributed systems, obviating the need for additional hardware components. As a result, our approach extended the schedulability of LC tasks without violating the HC tasks. Based on the deadline test, the compatibility of our approach with the task-level MC scheduler was higher than that of the system-level MC scheduler, such that the task-level had all dropped LC tasks recovered while the system-level only had 25.5% recovery. Conversely, from the worst-case measurement of violated HC tasks, the HC tasks were violated by the task-level MC scheduler more often than by the system-level MC scheduler, with 70.3% and 15.4% average response time overhead, respectively. In conclusion, under the condition that the HC task ratio has lower than 47% of the overall task systems at 80% of total utilization, the task-level approach with task migration has extensively higher sustainability on LC tasks.


D2 receptor partial agonists: treatment of CNS disorders of dopamine function.
A remarkable diversity of psychiatric and neurological disorders have been associated with dysfunction of dopamine (DA)-containing neurons, including schizophrenia, bipolar disorder (BD), Parkinson's disease (PD), and restless legs syndrome (RLS). In such disorders, transmission in discrete DA pathways may range from hypoactivation to hyperactivation of DA receptors, particularly those of the D(2) subtype, providing the rationale for treatment approaches that activate or block D(2) receptors, respectively. However, full agonists or pure D(2) receptor antagonists may not be optimal therapeutic approaches for their respective disorders for a number of reasons, including an inability to restore the aberrant DA pathways to a normal level of basal tone. D(2) receptor partial agonists (D(2)PAs) are proposed to stabilize activity in DA pathways by dampening excessive (and/or by restoring deficient) D(2) receptor stimulation thereby shepherding DA neurons back to a desired level of basal activity. Stabilizing aberrant DA activity without disrupting non-dysfunctional DA neurons may provide a potentially improved approach for treating DA disorders. The status of DA D(2)PAs and their potential application to schizophrenia, BD, PD, and RLS is reviewed. Preclinical and clinical evidence supports the idea that dysfunctions of D(2) receptors contribute to these CNS disorders. Diseases in which both hyper- and hypofunction of DA pathways are present may be particularly promising, and challenging, targets for D(2)PAs. Furthermore, different DA disorders may respond optimally to D(2)PAs with differing levels of intrinsic activity, with "DA deficiency" diseases responding more effectively to higher intrinsic activity D(2)PAs than "DA hyperactivation" diseases. Overall, current evidence supports the conclusion that D(2)PAs have significant potential as improved CNS therapies relative to classic full agonists and antagonists at D(2) receptors.


Noggin1 and Follistatin-like2 function redundantly to Chordin to antagonize BMP activity.
In Xenopus, the dorso-ventral (D/V) axis is thought to be specified by the bone morphogenetic proteins (Bmp) activity arising through interaction with antagonists such as Noggin, Chordin and Follistatin. We report here, through inactivation of noggin1 (nog1) that this gene is not essential by itself to establish the D/V patterning. However, at blastula stage, inactivation of nog1 strongly amplifies chordin (chd) phenotype, revealing redundant functions of these two genes on D/V axis formation. Substantial dorsal tissues remaining in the double nog1-chd morphant suggested that other anti-Bmp factors may pattern the D/V axis. We isolated two potential candidates, the follistatin-like (fstl) genes. We found that fstl2 is an early gastrula expressed gene. Its inactivation, similar to nog1, strongly enhances the chd phenotype. Moreover, the penetrance of the ventralization phenotype is much higher when we inactivated simultaneously chd, nog1 and fstl2. Altogether, our data reveal that, while Chordin is the main player of the D/V axis, sufficient to maintain proper activity of Bmp gradient, the structures remaining in the chd mutant (namely dorsal and dorso-lateral territories, in both mesodermal and ectodermal layers) result from the anti-Bmp activity carried by Nog1 and Fstl2 at blastula and gastrula stages.


Unified Deep Learning Architecture for Modeling Biology Sequence.
Prediction of the spatial structure or function of biological macromolecules based on their sequences remains an important challenge in bioinformatics. When modeling biological sequences using traditional sequencing models, long-range interaction, complicated and variable output of labeled structures, and variable length of biological sequences usually lead to different solutions on a case-by-case basis. This study proposed a unified deep learning architecture based on long short-term memory or a gated recurrent unit to capture long-range interactions. The architecture designs the optional reshape operator to adapt to the diversity of the output labels and implements a training algorithm to support the training of sequence models capable of processing variable-length sequences. The merging and pooling operators enhances the ability of capturing short-range interactions between basic units of biological sequences. The proposed deep-learning architecture and its training algorithm might be capable of solving currently variable biological sequence-modeling problems under a unified framework. We validated the model on one of the most difficult biological sequence-modeling problems, protein residue interaction prediction. The results indicate that the accuracy of obtaining the residue interactions of the model exceeded popular approaches by 10 percent on multiple widely-used benchmarks.


The nephrotoxicity risk in rats subjected to heavy muscle activity.
When the body is exposed to insults, the kidneys exhibit adaptive changes termed renal cytoresistance, characterized by cholesterol accumulation in the membranes of the tubule cells. However, heavy muscle activity has not yet been accepted as one of the stressors that could lead to cytoresistance. In order to study the renal functional characteristics of animals exposed to heavy muscle activity, rats were subjected to exhaustive treadmill exercise for 5 days and their data was compared to those of sedentary controls. It was found that in exercised rats, blood lactate, muscle citrate synthase and proximal tubule peroxynitrite levels were all elevated, suggesting the presence of oxidative stress in the proximal tubule segments. However, mean arterial pressure, renal blood flow, glomerular filtration rate, fractional excretion of sodium and potassium, and organic anion excretion remained normal. Despite unchanged blood cholesterol levels, cholesterol loading in the proximal tubule segments, especially the free form, and decreased lactate dehydrogenase release from cytoresistant proximal tubule segments indicated the development of renal cytoresistance. However, this resistance did not seem to have protected the kidneys as expected because organic anion accumulation associated with glycosuria and proteinuria, in addition to the elevated urinary cholesterol levels, all imply the presence of an impaired glomerular permeability and reabsorption in the proximal tubule cells. Therefore, we suggest that in response to heavy muscle activity the tubular secretion may remain intact, although cytoresistance in the proximal tubule cells may affect the tubular reabsorptive functions and basolateral uptake of substances. Thus, this differential sensitivity in the cytoresistance should be taken into account during functional evaluation of the kidneys. Key pointsThe cholesterol loading and decreased LDH release from PTSs isolated from exhausted rats indicate the heavy muscle activity induced renal cytoresistance.Heavy muscle activity-induced renal cytoresistance did not preserve the kidney functions.Organic anion accumulation as well as failure in the absorptive capacity of the tubule cells suggest the presence of some biochemical changes and elevated vulnerability of kidneys against nephrotoxic agents in rats subjected to heavy muscle activity.


Being forgotten: implications for the experience of meaning in life.
Two studies investigated the effects of being forgotten on the target of memory. In Study 1, undergraduate women (N = 96) who had completed a lab session two days prior, were randomly assigned to be remembered, forgotten, complimented, or to a control group. In the absence of effects on mood or social self-esteem, being forgotten resulted in lower meaning in life. In Study 2, participants (N = 47) who had completed a group exercise were informed two days later that no one remembered them, that everyone remembered them, or that no one wanted to work with them. Being forgotten led to lower meaning in life than being remembered but did not differ from being excluded. Being forgotten may be considered a type of incipient ostracism that influences meaning in life but not mood or state social self-esteem.


Association of Retromer Deficiency and Tau Pathology in Down Syndrome.
Retromer deficiency is reported in Down syndrome and correlates with amyloidosis, however, its association with tau neuropathology remains unclear. Down syndrome and control brain tissues were evaluated for phosphorylated tau, tau modulators, and cathepsin-D activity. Several kinases and phosphatase PP2A were unchanged, but tau phosphorylation was elevated, and cathepsin-D activity decreased in aged patients with Down syndrome. Retromer proteins positively associated with soluble tau, whereas pathogenic tau negatively correlated with retromer proteins and cathepsin-D activity. Retromer deficiency and consequent reduction of cathepsin-D activity may contribute to pathogenic tau accumulation, thus, retromer represents a viable therapeutic target against tau pathology in Down syndrome. ANN NEUROL 2022;91:561-567.


Distribution of hepatitis C virus genotypes amongst the beta-thalassemia patients in North of Iran.
Beta-thalassemia patients have high prevalence for HCV infection. In developing countries, HCV antibody is reported to be high in this group of patients. This study carried out to determine the distribution of HCV genotypes amongst the beta-thalassemia patients in North of Iran. The present study has been carried out between February and March 2010 amongst a group of 245 beta-thalassemia patients (125 male and 120 female) referred to the hospitals Mazandaran and Guilan provinces for a blood transfusion. Qualitative analysis of these samples using ELISA and PCR. The PCR positive samples were subjected to genotyping by RFLP method. Of total 245 beta-thalassemia patients who were the subjects of this study, 28 of these patients were diagnosed through PCR test to have RNA virus. For this reason, the prevalence of this illness in this study group was estimated as 11.42%. By using the RFLP technique, the above genotyping were identified and the prevalence of three genotypes, including 3a, 1a and 1b were proved. The genotype 3a was most prevalent. Out of 28 positive samples, 18 (64.3%) samples had this genotype. After that, genotype 1a with 9 positive occurrences (32.1%) and genotype 1b with only 1 positive occurrence (3.6%) were most prevalent. This study demonstrated that the main reason the beta-thalassemia patients became infected with the genotype of the virus was due to receiving infected blood that entered into Iran during the past two decades.


Assessment of private dental practice: implications for dental education.
The development and testing methods for assessing the quality of private general dental practice are described. The assessment instrument, evolved through the contributions of a panel of private practitioners, provides for the evaluation of the structure, process, and outcome of practice. General practitioners, trained as evaluators, tested the instrument in 300 urban group, urban nongroup, and rural practices in 14 states. The distribution of assessment scores for the entire project sample is compared with those of the sample dentists who graduated before and after 1974. The implications of the project and its results to dental education are discussed.


Presumptive nickel dermatitis from hemodialysis.
Presumptive cutaneous hypersensitivity to nickel administered intravenously during hemodialysis was observed in a patient with nickel sensitivity. The source of the nickel was a 316 stainless-steel fitting that came in contact with 6N hydrochloride during dialysis. An in vitro experiment was performed to demonstrate the ability of nickel to be dialyzed into blood through a standard hemodialysis system. A plasma nickel level 89% higher than that of the original dialysate was achieved with a single cycle of dialysis. This is consistent with the plasma protein binding of nickel.


Structure-activity relationship for FR901464: a versatile method for the conversion and preparation of biologically active biotinylated probes.
The structure-activity relationship for FR901464, a potent cell-cycle inhibitor, was examined by synthesizing its analogs. A versatile method for converting FR901464 was devised. This method made it possible to synthesize biologically active FR901464-biotin conjugates which could be used to isolate the binding proteins.


Animal models of ultraviolet radiation (UVR)-induced cutaneous melanoma.
The incidence of cutaneous melanoma continues to increase in many parts of the world including the United States. The American Cancer Society predicts that there will be approximately 53,600 new cases of melanoma in the United States during 2002 and that there will be 7,400 deaths from melanoma during the same time period. Increased understanding of the underlying mechanisms and risk factors involved in the induction of this deadly disease will require the use of suitable animal models of melanoma. To date, the induction of cutaneous melanoma with ultraviolet radiation (UVR) alone has been observed only in a few diverse animal models: a South American opossum, Monodelphis domestica; a hybrid fish, Xiphophorus; several stocks of transgenic mice; and in Angora goats. Most of these models are not completely suitable due to: 1) the target cell for melanoma formation; 2) the location of the melanocytes in the skin (i.e.- dermal as opposed to epidermal in humans); or 3) problems associated with husbandry and experimental manipulation. Recent studies have identified a mouse, the hepatocyte growth factor/scatter factor (HGF/SF) transgenic mouse, as an attractive model with which to study the induction of melanoma following a single, neonatal exposure to a moderate dose of UVR.


Once vs twice daily administration of a fixed combination of captopril plus hydrochlorothiazide in essential hypertension: a double-blind crossover study in known responders to a standard combination.
The purpose of this randomized, double-blind, crossover trial was to compare the hypotensive effects of a fixed combination of captopril (C) 50 mg and hydrochlorothiazide (HCTZ) 25 mg (C 50/HCTZ 25) once daily with those of a fixed combination of C 25 mg and HCTZ 12.5 mg (C 25/HCTZ 12.5) twice daily. We studied 199 patients (108 M, 91 F) with mild to moderate essential hypertension whose BP was already controlled by the co-administration of C 25 mg and HCTZ 12.5 mg twice daily. They were randomly assigned to either C 25/HCTZ 12.5 twice daily during the first 6 weeks and C 50/HCTZ 25 once daily during the second 6 weeks or C 50/HCTZ 25 once daily followed by C 25/HCTZ 12.5 twice daily. Both regimens showed comparable efficacy on office diastolic BP (91.6 vs 91.3 mm Hg). Systolic BP was slightly but significantly higher (P = 0.02) with the once daily formulation (141.2 vs 139.1 mm Hg). Fixed combinations once daily and twice daily resulted in identical working ambulatory BP (133.7 +/- 13/83.6 +/- 8 mm Hg vs 132.4 +/- 11/83.3 +/- 7 mm Hg) without affecting heart rate. Adverse events were reported by 16% of patients and cough was the most common occurring in 7%. In conclusion, these results indicate that the fixed combination of C 50/HCTZ 25 given once daily controls office and working BP as well as the fixed combination C 25/HCTZ 12.5 given twice daily in patients with mild to moderate hypertension.


Effect of confinement on coil-globule transition.
The equilibrium thermodynamic properties of a linear polymer chain confined to a space between two impenetrable walls (lines) at a distance D under various solvent conditions have been studied using series analysis and exact enumeration technique. We have calculated the end-to-end distance of polymer chain, which shows a nonmonotonic behavior with inter wall separation D. The density distribution profile shows a maxima at a particular value of (D=)D*. Around this D*, our results show that the collapse transition occurs at higher temperature as compared to its bulk value of 2d and 3d. The variation of theta-temperature with D shows a re-entrance behavior. We also calculate the force of compression exerted by the walls (lines) on the polymer.


Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway.
During the process of tumorigenesis most colon cancer cells acquire resistance to apoptosis. The short chain fatty acid butyrate is well established as an antitumour agent which selectively induces apoptosis in colon cancer cells but not in normal intestinal epithelial cells. To analyse the signalling pathway of butyrate induced apoptosis. Using Caco-2 cells we focused on the bcl family of proteins, mitochondrial pathway, and caspase signalling cascade involved in butyrate induced apoptosis. Techniques employed included western blots, immunofluorescence, as well as experiments with peptide inhibitors of specific caspases. Butyrate induced a clear shift of the mitochondrial bcl rheostat towards a proapoptotic constellation, as demonstrated by upregulation of proapoptotic bak accompanied by reduced antiapoptotic bcl-x(L) levels. This was associated with translocation of cytochrome-c from the mitochondria to the cytosol, resulting in activation of the caspase cascade via caspase-9. Key executioner enzymes were caspases-3 and -1. No effect of butyrate on regulatory proteins of the inhibitor of apoptosis family was observed. Butyrate induced Caco-2 cell apoptosis via the mitochondrial pathway. Upregulation of bak and translocation of cytochrome-c were upstream of the caspase cascade. Subsequently, this cascade was activated via the formation of an apoptosome.


The rehabilitation of oral defects by osseointegrated implants.
So far, preprosthetic surgery for oral defects improved prosthetic retention problems for only a limited amount of time and led to many side-effects. The alternative offered by the osseointegration technique developed by P.-I. Brånemark changed the concept of preprosthetic surgery dramatically. By means of a few permucosal titanium screws, bridges or overdentures can be retained even in cases of advanced jaw bone resorption. When the latter is extreme, an autologous free bone graft fixed by means of self-tapping titanium implants can offer the necessary support for sometimes elaborate prosthetic reconstructions. The marginal bone loss around Brånemark implants is very limited after a 1st year of bone remodelling, even when an autologous transplant has been used.


Salt sensitivity of children with low birth weight.
Compromised intrauterine fetal growth leading to low birth weight (<2500 g) is associated with adulthood renal and cardiovascular disease. The aim of this study was to assess the effect of salt intake on blood pressure (salt sensitivity) in children with low birth weight. White children (n=50; mean age: 11.3+/-2.1 years) born with low (n=35) or normal (n=15) birth weight and being either small or appropriate for gestational age (n=25 in each group) were investigated. The glomerular filtration rate was calculated using the Schwartz formula, and renal size was measured by ultrasound. Salt sensitivity was assigned if mean 24-hour blood pressure increased by >or=3 mm Hg on a high-salt diet as compared with a controlled-salt diet. Baseline office blood pressure was higher and glomerular filtration rate lower in children born with low birth weight as compared with children born at term with appropriate weight (P<0.05). Salt sensitivity was present in 37% and 47% of all of the low birth weight and small for gestational age children, respectively, higher even than healthy young adults from the same region. Kidney length and volume (both P<0.0001) were reduced in low birth weight children. Salt sensitivity inversely correlated with kidney length (r(2)=0.31; P=0.005) but not with glomerular filtration rate. We conclude that a reduced renal mass in growth-restricted children poses a risk for a lower renal function and for increased salt sensitivity. Whether the changes in renal growth are causative or are the consequence of the same abnormal "fetal programming" awaits clarification.


The rise of resin for cementing restorations.
Resin cements are popular and well-accepted for veneers, tooth-colored inlays, onlays and crowns, Maryland bridges and salvaging old useful crowns and fixed prostheses. Although used by a few practitioners for routine cementation of all crowns and fixed prostheses, it is doubtful that this trend will grow. A new category of cements--glass ionomer resin--soon will be available from several companies. It should be considered a routine cement as soon as it has proved itself. Its properties appear promising and nearly ideal.


Is an Inductive Effect Explicit Account Required for Atomic Charges Aimed at Use within the Force Fields?
Polarization and inductive effects are the concepts that have been widely used in qualitative and even quantitative descriptions of experimentally observed properties in chemistry. The polarization effect has proven to be important in cases of biomolecular modeling though still the vast majority of molecular simulations use the classical non-polarizable force fields. In the last few decades, a lot of effort has been put into promoting the polarization effect and incorporating it into modern force fields and charge calculation methods. In contrast, the inductive effect has not attracted such attention and is effectively absent in both classic and modern force fields. Thus, a question is whether this difference corresponds to the difference in the physical significance of the effects and their explicit account, or is an artifact that should be corrected in the next generation of force fields. The significance of the electronic effects is studied in this paper through the prism of performance of specific models for atomic charge calculation that take into explicit account a nested set of effects: the formal charge, the nearest neighbors, the inductive effect, and finally the model, which takes into account all effects, which are possible to account for using atomic charges. The specific choice for the methods is the following: formal charges, MMFF94 bond charge increments, Dynamic Electronegativity Relaxation (DENR), and RESP. We propose a special scheme for the separate estimation of each particular effect contribution. By pairwise comparing the residual molecular electrostatic potential (MEP) errors of those charge models (aimed at best reproducing the quantum chemical reference MEP), we sequentially revealed how the account of each effect contributes to the better-quality MEP reproduction. The following relative importance of effects was estimated; thus, the natural hierarchy of the effects was established. First, the account of formal charges is of primordial importance. Second, the nearest neighbors account is the next in significance. Third, the explicit account of inductive effect in empirical charge calculation schemes was shown to significantly─both qualitatively and quantitatively─improve the quality of MEP reproduction. Fourth, the contribution of polarization is indirectly assessed. Surprisingly, it is of the order of magnitude of the inductive effect even for the molecular systems, for which it is anticipated to be more significant. Finally, the relative importance of anisotropic effects in neutral molecules was additionally reviewed.


Variable otolith contribution to the galvanically induced vestibulo-ocular reflex.
The torsional eye movements elicited by sinusoidal galvanic vestibular stimulation (GVS) (0.012-3.13 Hz) were examined in healthy humans. GVS consistently induced sinusoidal modulation of the torsional slow phase velocity (SPV), which was linearly related to stimulus intensity. At low frequencies (< 0.1 Hz) nystagmic responses could be discriminated from an underlying 'tonic' modulation of eye position, which was prominent in some, but negligible in other subjects, and was not correlated with the SPV modulation. The actual SPV modulation consistently exceeded the (hypothetical) velocity modulation derived from the tonic positional components, albeit variably by almost 20-fold across subjects. This indicates that the contribution of possibly otolith-related response components to the galvanic vestibulo-ocular reflex may vary considerably in normal individuals.


Economic contribution of rural children and the family fertility behavior: a rationale for high fertility in India.
"This paper aims at analysing the economic contribution of children and its effect on parental decisions. It is shown that, under conditions of [India's agricultural structure,] the children's contribution towards family resources is highly valued by parents, and this acts as an incentive to raise more...children. Thus, high fertility in rural areas of India can be justified in so far as the positive net economic contribution of children is highly valued by parents."


Biomarker analysis revealed distinct profiles of innate and adaptive immunity in infants with ocular lesions of congenital toxoplasmosis.
Toxoplasma gondii is the main infectious cause of human posterior retinochoroiditis, the most frequent clinical manifestation of congenital toxoplasmosis. This investigation was performed after neonatal screening to identify biomarkers of immunity associated with immunopathological features of the disease by flow cytometry. The study included infected infants without NRL and with retinochoroidal lesions (ARL, ACRL, and CRL) as well as noninfected individuals (NI). Our data demonstrated that leukocytosis, with increased monocytes and lymphocytes, was a relevant hematological biomarker of ARL. Immunophenotypic analysis also revealed expansion of CD14(+)CD16(+)HLA-DR(high) monocytes and CD56(dim) cytotoxic NK-cells in ARL. Moreover, augmented TCRγ δ (+) and CD8(+) T-cell counts were apparently good biomarkers of morbidity. Biomarker network analysis revealed that complex and intricated networks underscored the negative correlation of monocytes with NK- and B-cells in NRL. The remarkable lack of connections involving B-cells and a relevant shift of NK-cell connections from B-cells toward T-cells observed in ARL were outstanding. A tightly connected biomarker network was observed in CRL, with relevant connections of NK- and CD8(+) T-cells with a broad range of cell subsets. Our findings add novel elements to the current knowledge on the innate and adaptive immune responses in congenital toxoplasmosis.