Radiotherapy after radical prostatectomy: Effect of timing of postprostatectomy radiation on functional outcomes.
The timing of radiotherapy (RT) after prostatectomy is controversial, and its effect on sexual, urinary, and bowel function is unknown. This study seeks to compare patient-reported functional outcomes after radical prostatectomy (RP) and postprostatectomy radiation as well as elucidate the timing of radiation to allow optimal recovery of function. The Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study is a prospective, population-based, observational study of men with localized prostate cancer. Patient-reported sexual, urinary, and bowel functional outcomes were measured using the 26-item Expanded Prostate Index Composite at baseline and at 6, 12, 36, and 60 months after enrollment. Functional outcomes were compared among men undergoing RP alone, post-RP adjuvant radiation (RP + aRT), and post-RP salvage radiation (RP + sRT) using multivariable models controlling for baseline clinical, demographic, and functional characteristics. Among 1,482 CEASAR participants initially treated with RP for clinically localized prostate cancer, 11.5% (N = 170) received adjuvant (aRT, N = 57) or salvage (sRT, N = 113) radiation. Men who received post-RP RT had worse scores in all domains (sexual function [-9.0, 95% confidence interval {-14.5, -3.6}, P < 0.001], incontinence [-8.8, {-14.0, -3.6}, P < 0.001], irritative voiding [-5.9, {-9.0, -2.8}, P < 0.001], bowel irritative [-3.5, {-5.8, -1.2}, P = 0.002], and hormonal function [-4.5, {-7.2, -1.7}, P = 0.001]) compared to RP alone at 5 years of follow-up. Compared to men treated with RP alone in an adjusted linear model, sRT was associated with significantly worse scores in all functional domains. aRT was associated with significantly worse incontinence, urinary irritation, and hormonal function domain scores compared to RP alone at 5 years of follow-up. On multivariable modeling, RT administered approximately 24 months after RP was associated with the smallest decline in sexual domain score, with an adjusted mean decrease of 8.85 points (95% confidence interval [-19.8, 2.1]) from post-RP, pre-RT baseline. In men with localized prostate cancer, post-RP RT was associated with significantly worse sexual, urinary, and bowel function domain scores at 5 years compared to RP alone. Radiation delayed for approximately 24 months after RP may be optimal for preserving erectile function compared to radiation administered closer to the time of RP.


Hatching, survival and deformities of piracanjuba (Brycon orbignyanus) embryos subjected to different cooling protocols.
Groups of one hundred Brycon orbignyanus embryos at the stage of blastopore closure were subjected to different cooling protocols. Different combinations and concentrations of cryoprotectants were tested: sucrose, methanol, ethylene glycol and dimethyl sulfoxide (Me2SO); at different temperatures (0.0±2.0°C and 8.0±2.0°C) and refrigeration times (6, 10, 24, 72 and 168 h), with the exception of the positive control (incubation without previous cooling). At the end of each refrigeration time, the embryos were acclimatized, rehydrated and incubated to determine hatching, survival and deformity rates. Morphological analysis of embryos was also carried out. The results showed that temperature and refrigeration time are critical factors for embryo survival. No embryos survived after 24, 72 and 168 h of refrigeration. Furthermore, when the refrigeration time increased from 6 to 10h and the temperature decreased from 8.0±2.0°C to 0.0±2.0°C, mortality rates increased significantly. It was also found that in all protocols dead eggs and/or larvae with some degree of deformity were present. The main larval deformities observed were the malformation of the head, tail, yolk sac, vertebral column and eyes.


Treatment of intraoperative hypertension with enflurane, nicardipine, or human atrial natriuretic peptide: haemodynamic and renal effects.
The purpose of this study was to assess the effects of the calcium entry blocker nicardipine and alpha human atrial natriuretic peptide (hANP) on antihypertensive and diuretic activity in hypertensive surgical patients. The site of the diuretic actions of these drugs along the nephron were also investigated by measuring the excretion rate of inorganic phosphate (PO4). Hypertension during gastrectomy was treated by increasing the concentration of enflurane, by nicardipine infusion (0.5-2.0 micrograms.kg-1 x min-1), or by hANP infusion (0.05-0.2 microgram.kg-1 x min-1) under general anaesthesia. Enflurane, nicardipine and hANP all decreased arterial pressure to the same extent. Urine flow, Na and PO4 excretion increased following the administration of nicardipine or hANP. Fractional distal reabsorption of sodium was suppressed from 89.7 +/- 2.8% to 82.1 +/- 5.0% by the hANP, but not by the nicardipine infusion. Creatinine clearance was increased by hANP infusion, but did not change in the nicardipine group. It is concluded that nicardipine and hANP can be used safely for the treatment of hypertension during surgery. Both drugs induced phosphaturic diuresis, but the site of action of the two drugs on the nephron may be different. Phosphate reabsorption is considered to occur largely in the renal proximal tubule, so that its appearance in the urine in increased quantities without the change of renal circulation in the nicardipine group suggests a proximal tubular action of this drug. However, the site of action of hANP in the kidney was not determined because GFR increased and distal sodium reabsorption was suppressed due to the drug infusion.


Changes in Smoking Behavior Since the Declaration of the COVID-19 State of Emergency in Japan: A Cross-sectional Study From the Osaka Health App.
In April 2020, the Japanese government declared a state of emergency due to the COVID-19 pandemic, and infection control measures, including requests to work from home and stay-at-home restrictions, were introduced. This study examined changes in smoking behavior during the COVID-19 state of emergency. An online cross-sectional survey was conducted in Osaka, Japan. To assess differences in smoking behavior among 5,120 current smokers before and after the declaration of a state of emergency, prevalence ratios (PRs) for two outcomes, increased smoking and quitting smoking, were calculated using multivariable Poisson regression, adjusting for potential covariates. We found 32.1% increased the number of cigarettes smoked and 11.9% quit smoking. After adjustment for all variables, we found risk factors for COVID-19 (men and older age group) had both significantly higher PR for quitting smoking (men: PR 1.38; 95% confidence interval [CI], 1.17-1.62) and participants aged ≥65 years: PR 2.45; 95% CI, 1.92-3.12) and significantly lower PR of increased smoking (men: PR 0.85; 95% CI, 0.78-0.93 and participants ≥65 years: PR 0.38; 95% CI, 0.29-0.49). Additionally, respondents working from home or living alone had significantly higher PR for increased smoking (working from home: PR 1.29; 95% CI, 1.17-1.41 and living alone: PR 1.23; 95% CI, 1.10-1.38) and respondents who changed from cigarettes to heated tobacco products (HTPs) had significantly lower PR for quitting smoking (PR 0.150; 95% CI, 0.039-0.582). We suggest people who have high-risk factors for COVID-19 might change their smoking behavior for the better, while people who work from home or live alone might change their smoking behavior for the worse, during the COVID-19 state of emergency. Additionally, changing from smoking cigarettes to using HTPs makes smokers less likely to quit.


Attempts to suppress experimental allergic neuritis in the rat by pretreatment with antigen.
The injection of bovine dorsal root antigen in complete Freund's adjuvant can be used to produce experimental allergic neuritis (EAN) in rats. In this study attempts were made to prevent the development of the disease by prior injections of antigen. It was found that eight intradermal (i.d.) injections of antigen in either incomplete Freund's adjuvant or in saline failed to suppress EAN. A single intraperitoneal (i.p.) injection of antigen in saline produced only minimal protection against the disease. However, it was found that rats which had been given a primary course of EAN were subsequently completely unresponsive to a second injection of antigen.


Contribution of the geriatrician to the management of cancer in older patients.
With an increasingly aged population, many patients will present with cancer in their 80s and 90s. Although some may be very fit, frail individuals will require the input of geriatricians to aid in the assessment of co-existing morbidity, in an attempt to assess those most likely to benefit from active treatment of their cancer, and those in whom the 'giants of geriatric medicine' require special consideration before undergoing definitive cancer therapy. The role of the geriatrician in assessment and management of such patients, together with communication and end of life care, may be more important in ensuring a good quality of life, than the cancer therapy itself. Whilst numbers of geriatricians will not be adequate to care for all elderly patients with cancer, a variety of assessment scales will help target financial and manpower resources to those most at risk.


Medical Students Learning on the COVID-19 Front Line.
In this viewpoint, we share our perspectives, as medical students at Imperial College London, on our experiences during our Infectious Diseases placement at Northwick Park Hospital, touching upon other students' experiences at other sites as well. We highlight some of the main drivers of and barriers to medical students seeing patients with COVID-19.


[Radiofrequency ablation for lung neoplasms with isolated postsurgical local recurrences or metastases of non-small cell lung cancer].
Primary lung cancer is one of the most common malignancies worldwide. Surgical resection remains the first choice for the treatment of early stage non-small cell lung cancer (NSCLC). Relapse after surgery sharply reduces the patient's life expectancy. This relapse is referred to as isolated postsurgical local recurrences or metastases (IPSLROM), which can be treated via local therapy to achieve long-term survival or cure. In recent years, radiofrequency ablation (RFA) has been increasingly used as a non-surgical treatment option for patients with primary and metastatic lung tumors. This study aims to evaluate the efficacy of RFA among patients with IPSLROM of NSCLC. A total of 20 patients underwent computerd tomograghy (CT)-guided RFA for lung neoplasm with IPSLROM of NSCLC (with unresectable disease because of poor lung reserve or multifocality) in our hospital between December 2008 and November 2013. These patients comprised 15 males and 5 females with a mean age of 69.2 years (range: 45-85). All patients exhibited pathological evidence of neoplastic lesion (14 tumors were adenocarcinoma, and six were squamous cell carcinoma). The mean size of the lesions was 3.9 cm (range: 2.0 cm to 8.0 cm). Treatment complications, progression-free survival (PFS), and survival parameters were retrospectively analyzed. RFA was well tolerated by all patients with an average time of 34.3 min (range: 15 min to 60 min). Intraprocedural complications included eight cases of chest pain (40%). No procedure-related deaths occurred in all of the 20 ablation procedures. The median PFS was 25 months in all of the patients who received RFA. The median overall survival for the entire group of patients was 27.0 months. No differences were observed in the overall survival between patients with IPSLROM. The overall survival rates at 1 and 2 years after RFA were 92.9% and 57.0%, respectively. RFA is a safe and effective procedure in unresectable lung tumors with IPSLROM of NSCLC.


Tomographic ultrasound imaging of the fetal heart: a new technique for identifying normal and abnormal cardiac anatomy.
In 2003 and 2004, the American College of Radiology, the American Institute of Ultrasound in Medicine, and the American College of Obstetricians and Gynecologists published guidelines for the standard ultrasound examination of the fetus. Each group recommended that the outflow tracts of the fetal heart be examined if technically feasible. One method to accomplish this task is to perform a free-hand sweep of the transducer beam directed in a transverse plane from the 4-chamber view to the fetal neck. One problem with this approach is that the examiner may not direct the beam transversely and, therefore, may not accurately identify the outflow tract anatomy. A new technology, tomographic ultrasound imaging (TUI), allows the examiner to obtain a volume data set that simultaneously displays multiple images at specific distances from the 4-chamber view. This study examined TUI technology for identifying normal and abnormal fetal cardiac anatomy with the use of either static or spatiotemporal image correlation volume data sets. The 4 views used in the screening examination of the outflow tracts of the fetal heart (4-chamber, 5-chamber, 3-vessel, and tracheal views) could be identified with the use of TUI technology in fetuses between 13 and 40 weeks' gestation. Examples of fetuses with abnormal cardiac anatomy of the outflow tracts (tetralogy of Fallot, transposition of the great vessels, and pulmonary stenosis) all showed abnormal anatomy on TUI. Tomographic ultrasound imaging technology enables the fetal examiner to evaluate the 4-chamber view and the outflow tracts in a systematic manner to identify normal and abnormal cardiac anatomy.


Preparation of the orthotopic autotransplanted pancreas for long-term exocrine studies.
The operative technique for the construction of an orthotopically autotransplanted pancreas with a permanent pancreatic fistula has been described. The operation is performed in two stages, with preparation of the transplant based on the gastroduodenal artery and superior pancreaticoduodenal vein in the first stage and construction of a Herrera-type permanent pancreatic fistula in the second stage. Elimination of warm ischemic time by dividing and reanastomosing the vessels on which the transplant will be based during the first stage while the pancreas continues to be perfused by its other vessels resulted in a uniformly successful outcome. The pancreatic transplant functioned well. The dogs were neither diabetic nor exocrine pancreatic deficient. Their responses to stimulation with exogenous secretin and the cholecystokinin analogue, cerulein, were only slightly less than those of dogs without a pancreatic transplant. This preparation should enable studies to be carried out that will better define the interactions of nerves and hormones in the control of pancreatic secretion.


Unveiling the histopathologic spectrum of MRI-guided breast biopsies: an institutional pathological-radiological correlation.
Breast magnetic resonance imaging (MRI) has high sensitivity but suffers from low specificity, resulting in many benign breast biopsies for MRI-detected lesions. We sought to compare histologic findings between patients who underwent MRI-guided breast biopsy versus biopsy via other imaging modalities as well as to examine features associated with malignancy in the MRI cohort to help inform MRI-biopsy practice. A 2-year (2018-2019) retrospective review of breast biopsies at our enterprise was conducted. Biopsies were categorized as stereotactic, ultrasound, MRI, or palpation guided. Pathology was categorized as benign (further divided into nine categories), atypical, or malignant (subdivided into in situ and invasive carcinoma). Pathology was compared between biopsy groups. Clinical, pathologic, and imaging features were compared between pathology groups within the MRI cohort. 5828 biopsies from 4154 patients were reviewed, including 548 MRI-guided biopsies with stratification of MRI-biopsy pathology as follows: 69% benign, 13.8% atypical, and 17.2% malignant. Among benign MRI biopsies, there was higher frequency of "clustered cysts with papillary apocrine metaplasia" (56/548; 10.2%) and lower rate of fibroadenoma/fibroadenomatous change (55/548; 10%) compared to other modalities (158 or 3% and 1144 or 21.7% of 5280 biopsies, respectively). Multivariate analysis revealed indication of breast cancer (p < .0001), ipsilateral cancer (p < .0001) and rapid initial phase kinetics (p = .017) to remain significantly associated with malignant MRI-biopsy pathology. A concurrent or recent breast cancer diagnosis was most predictive of malignancy on MRI-guided breast biopsy. Combined MRI feature evaluation and radiologic-pathologic concordance activities may allow for prognostic refinement and improved risk stratification.


Predictions of hydration free energies from continuum solvent with solute polarizable models: the SAMPL2 blind challenge.
This paper reports the results of our attempt to predict hydration free energies on the SAMPL2 blind challenge dataset. We mostly examine the effects of the solute electrostatic component on the accuracy of the predictions. The usefulness of electronic polarization in predicting hydration free energies is assessed by comparing the Electronic Polarization from Internal Continuum model and the self consistent reaction field IEF-PCM to standard non-polarizable charge models such as RESP and AM1-BCC. We also determine an optimal restraint weight for Dielectric-RESP atomic charges fitting. Statistical analysis of the results could not distinguish the methods from one another. The smallest average unsigned error obtained is 1.9 +/- 0.6 kcal/mol (95% confidence level). A class of outliers led us to investigate the importance of the solute-solvent instantaneous induction energy, a missing term in PB continuum models. We estimated values between -1.5 and -6 kcal/mol for a series of halo-benzenes which can explain why some predicted hydration energies of non-polar molecules significantly disagreed with experiment.


Large reductions in composite monosynaptic EPSP amplitude following conditioning stimulation are not accounted for by increased postsynaptic conductances in motoneurons.
A compartmental neuronal model was used to show that increased compartmental leak conductances distal to the site of excitatory postsynaptic potential (EPSP) generation have little effect on EPSP amplitude but decrease half-width markedly. Using intracellular recording from cat hindlimb motoneurons, reductions of composite Ia EPSP amplitude by up to 70% unaccompanied by reductions in half-width were seen following conditioning stimuli to hindlimb nerves. Appropriate condition-test intervals produced large reductions in EPSP amplitude that were unaccompanied by detectable increases in motoneuron conductance. These observations suggest that presynaptic inhibition and not increased postsynaptic motoneuron conductances is responsible for large EPSP amplitude reductions following conditioning stimulation.


Management of colonic fistulas in patients with infected pancreatic necrosis being treated with a step-up approach.
Colonic fistula is a potentially fatal complication in acute necrotizing pancreatitis (ANP), especially in patients with infected pancreatic necrosis (IPN). The aim of this study was to evaluate the feasibility of a step-up approach including percutaneous catheter drainage (PCD) and continuous negative pressure irrigation (CNPI) in a group of patients with colonic fistula. A retrospective review of a prospectively collected data was performed. Data were extracted for patients complicated by colonic fistula from January 2010 to January 2017. A total of 1750 patients were admitted with ANP during the study period. Of these patients, 711 (41%) developed IPN and colonic fistula was present in 132 (19%). A step-up approach was adopted for all patients, with 47% avoiding surgery. The mortality in patients requiring surgery (37%) was higher than that in patients managed non-surgically (19%) constituting an overall mortality rate of 29%. In patients managed conservatively, 92% had spontaneous closure of the fistula. Colonic fistula is not a rare complication in ANP occurring in 19% of patients with IPN in the current study. A step-up approach was effective and safe in managing colonic fistula and surgery could be obviated in nearly half of the patients.


Using correlation analysis to assess the reliability of evoked potential components identified by signal averaging.
Signal averaging is the conventional method of enhancing the signal-to-noise ratio in recordings of evoked potentials (EPs) from the skin surface in humans. However there may be difficulties in reliably identifying the features of interest especially when a low number of trials are averaged or when large artefacts with similar waveform as the signal are present. This method uses the median cross-correlation coefficient of every possible pair of recording repetitions within user-defined windows across the time course of the evoked potential. This is shown to be a good surrogate of signal-to-noise ratio and can be superimposed on the averaged trace to provide reliability information for all components of interest. We applied our method both to simulated signals embedded within the noise component of EP recordings and to real examples of somatosensory EPs. We demonstrated that it can assess the reliability of recorded components independently from their amplitude and could identify artefacts which mimicked genuine components. There have been a number of previous approaches to this problem but none has found widespread support. This method adds additional information to a common existing technique and is easy to interpret and apply. This method is used as a visual adjunct to the existing interpretation of averaged evoked potentials and will allow judgements of the reliability of each observed component to be made. This is particularly valuable for situations where few repetitions are possible such as nociceptive evoked potentials, which are of increasing clinical interest.


A lesson from history? Worsening mortality and the rise of the Nazi Party in 1930s Germany.
The aim of the study was to test the hypothesis that worsening mortality rates in the early 1930s were associated with increasing votes for the Nazi Party. The study consist of panel data with fixed effects. We used district- and city-level regression models of Nazi vote shares on changes in all-cause mortality rates in 866 districts and 214 cities during federal elections from 1930 to 1933, adjusting for election and district/city-level fixed effects and sociodemographic factors. As a falsification test, we used a subset of deaths less susceptible to sociopolitical factors. Historical downward trends in mortality rates reversed in the early 1930s in Germany. At the district/city level, these increases were positively associated with a rising Nazi vote share. Each increase of 10 deaths per 1000 population was associated with a 6.51-percentage-point increase in Nazi vote share (95% confidence interval = 1.17-11.8). The strongest associations were with deaths due to infectious and communicable diseases, suicides, and alcohol-related deaths. Worsening mortality had no association with votes for the Communist Party or for other contemporary political parties. Greater welfare payments were associated with smaller increases in both mortality and Nazi vote share, and adjusting for welfare generosity mitigated the association by approximately one-third. Worsening mortality rates were positively associated with the rise of the Nazi Party in 1930s Germany. Social security mitigated the association between mortality and Nazi vote share. Our findings add to the growing evidence that population health declines can be a 'canary in the coal mine' for the health of democracies.


Reduction of inappropriate medications among older nursing-home residents: a nurse-led, pre/post-design, intervention study.
Medication-related problems are common in the growing population of older adults and inappropriate prescribing is a preventable risk factor. Explicit criteria such as the Beers criteria provide a valid instrument for describing the rate of inappropriate medication (IM) prescriptions among older adults. To reduce IM prescriptions based on explicit Beers criteria using a nurse-led intervention in a nursing-home (NH) setting. The pre/post-design included IM assessment at study start (pre-intervention), a 4-month intervention period, IM assessment after the intervention period (post-intervention) and a further IM assessment at 1-year follow-up. 204-bed inpatient NH in Bern, Switzerland. NH residents aged ≥60 years. The intervention included four key intervention elements: (i) adaptation of Beers criteria to the Swiss setting; (ii) IM identification; (iii) IM discontinuation; and (iv) staff training. IM prescription at study start, after the 4-month intervention period and at 1-year follow-up. The mean ± SD resident age was 80.3 ± 8.8 years. Residents were prescribed a mean ± SD 7.8 ± 4.0 medications. The prescription rate of IMs decreased from 14.5% pre-intervention to 2.8% post-intervention (relative risk [RR] = 0.2; 95% CI 0.06, 0.5). The risk of IM prescription increased nonstatistically significantly in the 1-year follow-up period compared with post-intervention (RR = 1.6; 95% CI 0.5, 6.1). This intervention to reduce IM prescriptions based on explicit Beers criteria was feasible, easy to implement in an NH setting, and resulted in a substantial decrease in IMs. These results underscore the importance of involving nursing staff in the medication prescription process in a long-term care setting.


Elevated velocity of prostacyclin degradation in blood as a possible risk factor in patients with cerebrovascular disorders.
Blood and plasma from 193 patients at risk of cerebrovascular disorders and 87 patients with brain infarction were tested to study prostacyclin (PGI2) degradation. It has been reported that patients at risk for cerebrovascular disorders and especially with brain infarction have an enhanced velocity of PGI2 degradation. The increase in velocity was more marked in blood than in plasma. A direct relation between this enhancement and the manifestation of intravascular platelet activation was observed. These data suggest that elevated PGI2 degradation might be a risk factor for thromboembolic events in patients with cerebrovascular disorders.


Two residues determine the product profile of the class II diterpene synthases TPS14 and TPS21 of Tripterygium wilfordii.
The medicinal plant Tripterygium wilfordii (Celastraceae) contains a pair of class II diterpene synthases (diTPS) of specialized labdane-type metabolism that, despite remarkably close homology, form strikingly different products. TwTPS21 catalyzes bicyclization of the linear C20 precursor geranylgeranyl diphosphate to ent-copal-8-ol diphosphate, while TwTPS14 forms kolavenyl diphosphate. To determine the amino acid signature controlling the functional divergence of the homologues, we modeled their structures based on an existing crystal structure of the Arabidopsis ent-copalyl diphosphate synthase, archetypal of diTPSs in general metabolism of gibberellin phytohormones. Of the residues differing between TwTPS21 and TwTPS14 two located to the predicted active site, and we hypothesized that these are responsible for the functional differentiation of the enzymes. Using site-directed mutagenesis, we generated a panel of six variants, where one, or both positions were exchanged between the enzymes. In coupled heterologous assays with a corresponding class I diTPS, TwTPS2, complete product interchange was observed in variants with both reciprocal mutations, while substitutions of either residue gave mixed product profiles. Two mutants, TwTPS14:Y265H and TwTPS21:A325V, also produced ent-copalyl diphosphate, highlighting the evolutionary potential of enzymes of this family to drive rapid diversification of plant diterpene biosynthesis through neo-functionalization. Our study contributes to the understanding of structure-function relation in plant class II diTPSs and complements previous mutational studies of Arabidopsis ent-copalyl diphosphate synthase with additional examples from the specialized metabolism of T. wilfordii.


A peer approach to high risk youth.
Denver's Gang Rescue and Support Project (GRASP) is a peer run intervention for youth involved in gangs and those feeling pressure to affiliate with them. GRASP utilizes small group meetings and mentoring to encourage young people to pursue positive life-style changes.


Toward a chronobiological characterization of obesity and metabolic syndrome in clinical practice.
To test several circadian rhythm variables in a female population to identify the best tool to assess chronodisruption in obesity and metabolic syndrome (MetS) to define a score to be used for chronodisruption characterization in clinical practice. Anthropometric measurements and markers of circadian rhythms, such as sleep and feeding diary, Horne-Ostberg questionnaire, melatonin and cortisol measurements, and wrist temperature measurements, were determined. MetS variables were also analyzed. Study was conducted in 70 women. Data were subjected to factor analysis. Receiver operating characteristic curves were used as predictors of chronodisruption risk, and a score was calculated to classify the subjects of risk. Factor analysis showed that the first-factor grouped variables were related to the skin temperature measurement. Second factor consisted of variables related to salivary cortisol levels and obesity-related measurements. Third factor included variables related to sleep-wake cycle. Fourth factor referred to peripheral temperature variables and included the classification of subjects according to the Horne-Ostberg questionnaire. To obtain a final punctuation we performed the weighted mean of the first four factors. The final range was from 27 to 57, mean value of 42. Punctuation was defined as the "chronodisruption score." Women displaying higher chronodisruption scores had higher MetS risk. The study demonstrates that wrist temperature recordings, together with two questions of sleep onset and offset, and one morning salivary cortisol determination could be enough to characterize the chronobiology of obesity and MetS, a new chronodisruption score was developed.


Impact of laboratory work-up of lymphoma guidelines on cytopathology practices.
A multi-society expert panel recently published evidence-based guidelines and recommendations for the primary diagnosis and classification of lymphoma, which included a public comment period. The guideline concludes: "primary diagnosis and classification of lymphoma can be achieved with a variety of specimens." The guideline recommends that fine-needle aspiration biopsy (FNAB) cytomorphology not be used without ancillary testing, and that either flow cytometry or immunohistochemical immunophenotyping be performed for any type of specimen. Either excisional or core biopsy should be obtained when there is a high suspicion of lymphoma, and excision is recommended when feasible for Hodgkin lymphoma primary diagnosis. The use of cerebrospinal fluid to diagnose central nervous system lymphoma is discussed. For any patient with initial negative biopsy or fluid specimens and a high suspicion of lymphoma, additional tissue samples should be obtained. Additional molecular testing and good practice statements are summarized in the guideline. Cytopathologists should continue to advocate for judicious use of lymph node FNAB as an excellent triage tool that may require additional tissue biopsy for definitive diagnosis.


Cloud-based services for electronic civil registration and vital statistics systems.
This paper examines the hosting options for electronic civil registration and vital statistics (CRVS) systems, particularly the use of data centers versus cloud-based solutions. A data center is a facility that houses computer systems and associated hardware and software components, such as network and storage systems, power supplies, environment controls, and security devices. An alternative to using a data center is cloud-based hosting, which is a virtual data center hosted by a public cloud provider. The cloud is used on a pay-as-you-go basis and does not require purchasing and maintaining of hardware for data centers. It also provides more flexibility for continuous innovation in line with evolving information and communications technology.


Excitation in the goldfish retina: evidence for a non-linear intensity code.
1. Experiments were done on isolated photopic goldfish retinas. They were stimulated by brief flashes of red light, and the spike activity of single ganglion cells was monitored by micro-electrodes. Red-ON-units were used exclusively.2. The spatial integration of intensity was investigated using concentric disks of various diameters. Under these conditions, Ricco's relation (1877) was obtained.3. Two small spots of light were positioned on two equisensitive sites in the receptive field; the (equal) intensities of both were varied in unison, and the responses recorded. An identical response was evoked by simultaneous illumination of both sites with an intensity, I, or by illumination of a single one of the sites with an intensity, KI. K always exceeded 2 (it averaged about 4) and it was constant in any one experiment.4. The analysis of these results employed the assumption that an hypothetical quantity, the excitation, intervenes between the stimulus (light intensity) and the response (spike train). The excitation is a function of intensity, and it determines the response. The excitation from two spots is assumed to be twice that from one.5. It was inferred that the excitation (E) was a power function of the intensity (I): E = CI(n), in which C and n are constants. The exponent, n, was always less than unity.6. Two other experiments tested the predictive value of this inference. It accurately predicted the responses to a single spot anywhere in the field, and to two unequal intensities simultaneously illuminating two equisensitive sites.


Comparison of transthoracic electrical impedance and thermodilution methods for measuring cardiac output.
Cardiac output was measured 120 times in 27 critically ill patients using the thermodilution and transthoracic electrical impedance methods. Both the minimum and mean values for the distance between the inner electrodes, and a variety of values for the resistivity of blood (rho) were substituted in the Kubicek's empiric formula for calculating cardiac output by transthoracic electrical impedance. Using the mean distance between the inner electrodes and a rho-value of 150 ohm X cm gave the best agreement between the methods (mean difference 0.17 +/- 2.4 L/min). Ventilation alone or with positive end-expiratory pressure did not significantly affect the bias of the estimate, but both affected its precision when compared with measurements in spontaneously breathing patients (SD of mean difference 2.4 and 3.2 L/min, respectively, vs. 1.5 L/min). The pulmonary artery wedge pressure was significantly higher in patients with an abnormal diastolic impedance waveform (zero-wave), but there was no relationship between wedge pressure and base impedance per unit length between the measuring electrodes.


Carbonate chemistry variability in the southern Yellow Sea and East China Sea during spring of 2017 and summer of 2018.
Marginal seas are highly productive and disproportionately large contributors to global air-sea CO2 fluxes. Due to complex physical and biogeochemical conditions, the southern Yellow-East China Sea is an ideal site for studying carbonate chemistry variability. The carbonate system was investigated in the area in spring of 2017 and summer of 2018. Dissolved inorganic carbon (DIC) and total alkalinity (TA) concentrations were higher in the SYS than the ECS due to material from carbonate weathering and erosion carried by the Yellow River. High pH and low DIC and TA were observed in the Zhe-Min Coastal Current in spring due to high primary productivity caused by Changjiang River input and the Taiwan Warm Current. Temperature and biological activity were the primary drivers controlling the partial pressure of CO2 (pCO2) in the SYS, pCO2 was controlled by primary productivity related to nutrients carried by the Changjiang River and physical mixing in the Changjiang River plume and inner/middle shelves of the ECS, whereas temperature was the dominant factor determining pCO2 distributions in the ECS outer shelf waters influenced by the Kuroshio Current. Overall, the entire study area shifted from a CO2 sink (-4.18 ± 5.60 mmol m-2 d-1) to a weak source (1.02 ± 4.87 mmol m-2 d-1) from spring to summer. Specifically, the SYS and ECS offshore waters changed from CO2 sinks in spring to sources in summer, while the Changjiang River plume was always a CO2 sink.


The treatment of pneumopericardium in the newborn infant.
Pneumopericardium with cardiac tamponade is a life-threatening emergency in the newborn infant. The case fatality rate is high (75% in 41 documented cases in the English literature), and diagnosis often delayed (in 13 of 29 deaths the pneumopericardium was diagnosed postmortem). Treatment is frequently unsatisfactory, and recurrence of the pneumopericardium with tamponade is likely after initial pericardial needle aspiration--an incidence of 53%. A case of pneumopericardium in a critically ill newborn is reported; the details of successful management, using a large bore intrapericardial catheter with continuous drainage, are discussed.


COST Action "EuroTelepath": digital pathology integration in electronic health record, including primary care centres.
Digital pathology includes the information technology that allows for the management of information, including data and images, generated in an anatomic pathology department. COST ACTION IC0604: The integration of digital slides in the electronic health record is one of the main objectives of COST Action IC0604 "Telepathology Network in Europe" (EURO-TELEPATH). Fostering use of medical informatics standards and adapting them to current needs is needed to manage efficiently extremely large medical images, like digital slide files. Digital slides can play a role in disease prevention, primary diagnosis, and second opinion. In all these tasks, automated image analysis can also be a most valuable tool. In order to achieve an efficient interoperability between pathology information systems with other clinical information systems, obtaining a seamless integration of pathology images (gross pictures and digital slides) with LIS-Pathology Information system in a web environment is an important task. Primary care information systems should also be included in the integration, since primary care centres play an essential role in the generation of clinical information and specimen collection. A common terminology, based in SNOMED CT is also needed. Main barrier in the integration of digital slides in pathology workflow and eHealth record is the cost of current digital slide scanners. Pathology information system vendors should participate in standardization bodies.


Caenorhabditis elegans: a new model system for the study of learning and memory.
The extensive information on the neuroanatomy, development and genetics of Caenorhabditis (C.) elegans make it an ideal candidate model system for the analysis of the mechanisms underlying learning and memory. A first step in this analysis is the demonstration of the capacity of C. elegans to learn. In these experiments non-associative learning in C. elegans was investigated by observing changes in reversal reflex response amplitude to a mechanical vibratory stimulus. The results from these studies of non-associative learning show that C. elegans is capable of short-term habituation, dishabituation and sensitization, as well as long-term retention of habituation training lasting for at least 24 h. These findings set the stage for detailed developmental, genetic and physiological analyses of learning and memory.


Frankel 2 appliance versus the Modified Twin Block appliance for Phase 1 treatment of Class II division 1 malocclusion in children and adolescents: A randomized clinical trial.
To compare Phase 1 treatment, using the Frankel 2 (FR2) or the modified Twin Block (MTB), for Class II division 1 malocclusion in children and adolescents with respect to: treatment duration, number of appliance breakages, occlusal outcome, and patient and parent perspectives. Sixty participants with a Class II division 1 malocclusion were randomly assigned to either the FR2 or MTB appliance in a two-armed parallel randomized clinical trial with an allocation ratio of 1 to 1. Time to achieve a Class I incisor relationship was the primary outcome. The number of appliance breakages was recorded. The Peer Assessment Rating (PAR) index was used to evaluate pre- and post-treatment occlusal outcome on study models. Participants completed the child OHRQoL (oral health-related quality of life), Piers-Harris, Standard Continuum of Aesthetic Need (SCAN), and Oral Aesthetic Subjective Impact Score (OASIS) questionnaires pre- and post-treatment; parents completed a SCAN questionnaire. Forty-two participants completed treatment (FR2: 20; MTB: 22). Multiple imputation was used to impute missing data for noncompleters. Mean treatment duration was similar for the two appliances (FR2: 376 days [SD 101]; MTB: 340 days [SD 102]; P = .41). There were no significant differences in mean number of appliance breakages (FR2: 0.3 SD 0.7; MTB: 0.4 SD 0.8; P = .67 or mean PAR score P = .48). Patient and parent perspectives did not differ between appliances (P > .05). Phase 1 treatment duration, number of appliance breakages, occlusal outcome, and patient and parent perspectives were similar in 11-14 year olds with Class II division 1 malocclusion treated using the FR2 or MTB appliance.


Thyroid dysfunction in patients treated with sunitinib or sorafenib.
Sunitinib and sorafenib are tyrosine kinase inhibitors used in metastatic renal cell carcinoma and are known to cause hypothyroidism in a subset of patients. The goal of this study was to better characterize the development of hypothyroidism in patients and to examine its relationship to progression-free survival. A retrospective chart review was performed on patients treated with sunitinib or sorafenib from January 1, 2005, to January 1, 2011. Data pertaining to the treatment course and development of hypothyroidism were extracted. Patients with hypothyroidism at the beginning of treatment were analyzed separately. A total of 73 treatment periods had sufficient data to analyze. Among patients with normal baseline thyroid function, 15 (44%) of 34 patients treated with sunitinib and 6 (27%) of 22 patients treated with sorafenib developed hypothyroidism. The hazard ratio for the development of hypothyroidism with sorafenib vs. sunitinib treatment was significant, at 0.38 (95% CI, 0.14-0.97). There was a statistically significant difference in the progression-free survival between patients who developed hypothyroidism while receiving treatment compared with those who did not, 18.2 vs. 10.1 months (P = .01). This study demonstrated a significant difference in the incidence of hypothyroidism during treatment with sunitinib and sorafenib, with a higher incidence of hypothyroidism in patients treated with sunitinib. The development of hypothyroidism was associated with a longer progression-free survival.


Colonoscopy is superior to neostigmine in the treatment of Ogilvie's syndrome.
Colonic pseudo-obstruction in critically ill patients may lead to devastating colonic perforation. Neostigmine is often the first-line intervention, because colonoscopy is more invasive and labor intensive. A retrospective 10-year review at a tertiary medical center identified 100 patients with Ogilvie's syndrome, in whom treatment course and clinical and radiographic response were evaluated. Colonoscopy was significantly more successful than neostigmine (defined as no further therapy) after 1 or 2 interventions (75.0% vs 35.5%, P = .0002, and 84.6% vs 55.6%, P = .0031, respectively). One colonoscopy was more effective than 2 neostigmine administrations (75.0% vs 55.6%, P = .044). Clinical response (poor, fair, or good) was significantly better after colonoscopy than neostigmine after 1 or 2 interventions (P = .0028 and P = .00079). Cecal diameters decreased significantly more after colonoscopy than neostigmine (from 10.2 ± .5 cm to 7.1 ± .4 cm vs from 10.5 ± .5 cm to 8.8 ± .5 cm, P = .026). Neostigmine administration before colonoscopy did not affect outcomes. There were 3 perforations (3.7%): 1 each after colonoscopy, neostigmine, and no intervention. Neostigmine dose or repetition did not affect radiographic (P = .41) or clinical (P = .31) response. Colonoscopy is superior to neostigmine for Ogilvie's syndrome and should be considered first-line therapy, although neostigmine is useful in select patients and repeat interventions.


Non-destructive 3D characterization of the blood vessel wall microstructure in different species and blood vessel types using contrast-enhanced microCT and comparison with synthetic vascular grafts.
To improve the current treatment for vascular diseases, such as vascular grafts, intravascular stents, and balloon angioplasty intervention, the evaluation of the native blood vessel microstructure in full 3D could be beneficial. For this purpose, we used contrast-enhanced X-ray microfocus computed tomography (CECT): a combination of X-ray microfocus computed tomography (microCT) and contrast-enhancing staining agents (CESAs) containing high atomic number elements. In this work, we performed a comparative study based on staining time and contrast-enhancement of 2 CESAs: Monolacunary and 1:2 Hafnium-substituted Wells-Dawson polyoxometalate (Mono-WD POM and Hf-WD POM, respectively) for imaging of the porcine aorta. After showing the advantages of Hf-WD POM in terms of contrast enhancement, we expanded our imaging to other species (rat, porcine, and human) and other types of blood vessels (porcine aorta, femoral artery, and vena cava), clearly indicating microstructural differences between different types of blood vessels and different species. We then showed the possibility to extract useful 3D quantitative information from the rat and porcine aortic wall, potentially to be used for computational modeling or for future design optimization of graft materials. Finally, a structural comparison with existing synthetic vascular grafts was made. This information will allow to better understand the in vivo functioning of native blood vessels and to improve the current disease treatments. STATEMENT OF SIGNIFICANCE: Synthetic vascular grafts, used as treatment for some cardiovascular diseases, still often fail clinically, potentially because of a mismatch in mechanical behaviour between the native blood vessel and the graft. To better understand the causes of this mismatch, we studied the full 3D microstructure of blood vessels. For this, we identified Hafnium-substituted Wells-Dawson polyoxometalate as contrast-enhancing staining agent to perform contrast-enhanced X-ray microfocus computed tomography. This technique allowed to show important differences in the microstructure of different types of blood vessels and in different species, as well as with that of synthetic grafts. This information can lead to a better understanding of the functioning of blood vessels and will allow to improve current disease treatments, such as vascular grafts.


Contemporary trends for urological training and management of stress urinary incontinence in Ireland.
The aim of this study is to evaluate the trends in stress urinary incontinence (SUI) surgery since the 2018 pause on use of the polypropylene (PP) mid-urethral sling (MUS) and to quantify the effect this has had on surgical training. Two anonymous surveys were sent to all current urology trainees and to all consultant surgeons who specialise in stress urinary incontinence surgery. Prior to the pause, 86% (6 out of 7) of consultant urologists and 73% (11 out of 15) of consultant gynaecologists would "always"/"often" perform MUS for SUI. After that, 100% (22 out of 22) of consultants reported that they "never" perform MUS. There has been a modest increase in the use of urethral bulking agent (UBA) procedures among urologists, with 43% (3 out of 7) now "often" performing this, compared with 71% (5 out of 7) "never" performing it pre-2018. Trainee exposure to SUI surgery reduced by 75% between 2016 and 2020. Despite a ten-fold increase in UBA procedures logged by trainees, the decline in MUS has resulted in a major reduction in total SUI surgeries. Coinciding with this decrease in surgeries, there was a 56% reduction in trainees' self-assessed competence at SUI surgery. Thirteen percent of trainees are interested in specialising in Female Urology and those trainees had significantly greater exposure to SUI procedures during their training than those who did not (p = 0.0072). This study has identified a downward trend in SUI surgery, which is concerning for the undertreatment of females with SUI. A decline in SUI surgery training has resulted in reduced trainee confidence and interest in this subspecialty.


Effects of data preprocessing on results of the epidemiological analysis of coronary heart disease and behaviour-related risk factors.
We carried out this study to demonstrate the effects of outcome sensitivity, participant exclusions, and covariate manipulations on results of the epidemiological analysis of coronary heart disease (CHD) and its behaviour-related risk factors. Our study population consisted of 1592 54-year-old men, who participated in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. We used the Cox proportional-hazards model to predict the hazard of CHD and applied different sets of outcomes concerning outcome sensitivity and data preprocessing procedures regarding participant exclusions and covariate manipulations. The mean follow-up time was 23 years, and 730 men received the CHD diagnosis. Cox regressions based on data with no participant exclusions most often discovered statistically significant associations. Loose inclusion criteria for study participants with any CVD during the follow-up and strict exclusion criteria for participants with no CVD were best in discovering the associations between risk factors and CHD. Outcome sensitivity affected the associations, whereas the covariate type, continuous or categorical, did not. This study suggests that excluding study participants who are not disease-free at baseline is probably unnecessary for epidemiological analyses. Epidemiological research reports should present results based on no data exclusions together with results based on reasoned exclusions.


Alterations in the expression of ELAM-1, ICAM-1 and VCAM-1 after in vitro infection of endothelial cells with a clinical isolate of human cytomegalovirus.
Human cytomegalovirus (HCMV) infection of endothelial cells resulted in increased adhesion of the cells to peripheral blood leukocytes. It was demonstrated by flow cytometry that increased adhesiveness parallels the increased expression of cell surface adhesion molecules (ELAM-1, ICAM-1, VCAM-1). The increased adhesion of PMN and T-lymphocytes was due to upregulation in the expression of ELAM-1 and ICAM-1. The upregulation of VCAM-1 resulted in the increased adhesiveness of monocytes and T-lymphocytes to HCMV-infected HUVEC. The increased adhesiveness to leukocytes was caused by HCMV replication since endothelial cells exposed to HCMV-free supernatants and UV-inactivated HCMV did not show any increase in adhesiveness to any of the leukocytes tested.


Magnetic Iron Oxide Nanoparticles for Biomedical Applications.
Owing to the quantum confinement at the nanoscale, magnetic iron oxide nanoparticles (MIONs) consisting of magnetite and maghemite nanocrystals have unique physical properties, enabling a wide range of biomedical applications by utilizing mechanical, magnetic, chemical, and thermal effects of MIONs respectively. For example, MIONs can serve as a contrast agent for magnetic resonance imaging (MRI), convert electromagnetic energy into thermal energy for hyperthermia therapy, and carry drug/gene for targeted in vivo delivery. In this review, we discuss the recent development of MION based engineering approaches and their biomedical applications, including sensitive protein quantification, magnetic nanoparticle heating, in vivo molecular imaging, and drug delivery. The opportunities and challenges in further exploring the biomedical applications of MIONs are also briefly discussed.


Intracardiac ectopic thyroid.
The case of a patient with an intracardiac ectopic thyroid is reported. A lesion was found in a 25-year-old man and was diagnosed by two-dimensional echocardiography as a right intraventricular tumor. An operation was performed. Histologic and ultrastructural studies showed that the tumor was a thyroid mass. The origin of intracardiac ectopic thyroids is probably to be found in disturbances occurring early in embryogenesis.


Programmable broadband optical field spectral shaping with megahertz resolution using a simple frequency shifting loop.
Controlling the temporal and spectral properties of light is crucial for many applications. Current state-of-the-art techniques for shaping the time- and/or frequency-domain field of an optical waveform are based on amplitude and phase linear spectral filtering of a broadband laser pulse, e.g., using a programmable pulse shaper. A well-known fundamental constraint of these techniques is that they can be hardly scaled to offer a frequency resolution better than a few GHz. Here, we report an approach for user-defined optical field spectral shaping using a simple scheme based on a frequency shifting optical loop. The proposed scheme uses a single monochromatic (CW) laser, standard fiber-optics components and low-frequency electronics. This technique enables efficient synthesis of hundreds of optical spectral components, controlled both in phase and in amplitude, with a reconfigurable spectral resolution from a few MHz to several tens of MHz. The technique is applied to direct generation of arbitrary radio-frequency waveforms with time durations exceeding 100 ns and a detection-limited frequency bandwidth above 25 GHz.


Off-target effects dominate a large-scale RNAi screen for modulators of the TGF-β pathway and reveal microRNA regulation of TGFBR2.
RNA interference (RNAi) screens have been used to identify novel components of signal-transduction pathways in a variety of organisms. We performed a small interfering (si)RNA screen for novel members of the transforming growth factor (TGF)-β pathway in a human keratinocyte cell line. The TGF-β pathway is integral to mammalian cell proliferation and survival, and aberrant TGF-β responses have been strongly implicated in cancer. We assayed how strongly single siRNAs targeting each of 6,000 genes affect the nuclear translocation of a green fluorescent protein (GFP)-SMAD2 reporter fusion protein. Surprisingly, we found no novel TGF-β pathway members, but we did find dominant off-target effects. All siRNA hits, whatever their intended direct target, reduced the mRNA levels of two known upstream pathway components, the TGF-β receptors 1 and 2 (TGFBR1 and TGFBR2), via micro (mi)RNA-like off-target effects. The scale of these off-target effects was remarkable, with at least 1% of the sequences in the unbiased siRNA library having measurable off-target effects on one of these two genes. It seems that relatively minor reductions of message levels via off-target effects can have dominant effects on an assay, if the pathway output is very dose-sensitive to levels of particular pathway components. In search of mechanistic details, we identified multiple miRNA-like sequence characteristics that correlated with the off-target effects. Based on these results, we identified miR-20a, miR-34a and miR-373 as miRNAs that inhibit TGFBR2 expression. Our findings point to potential improvements for miRNA/siRNA target prediction methods, and suggest that the type II TGF-β receptor is regulated by multiple miRNAs. We also conclude that the risk of obtaining misleading results in siRNA screens using large libraries with single-assay readout is substantial. Control and rescue experiments are essential in the interpretation of such screens, and improvements to the methods to reduce or predict RNAi off-target effects would be beneficial.


Rapid DNA crossmatch analysis of HLA class II genotypic polymorphisms by temperature gradient gel electrophoresis in unrelated bone marrow donor selection.
The present paper demonstrates the usefulness of the temperature gradient gel electrophoresis (TGGE) as a precise method for the rapid identification of HLA-DR full matched donors by molecular crossmatch analysis. The resulting TGGE fingerprints are highly diverse for different HLA-DR genotypes and identical for samples with identical HLA-DR type, as shown for a panel of 25 randomly selected PCR-SSO pretyped DNA samples. In addition, TGGE analysis of a panel of homozygous typing cell lines (HTCs) established, that even subtle differences in the DR4 subtypes are detectable by TGGE crossmatch analysis. Furthermore, TGGE crossmatch analysis of unrelated donor/patient pairs demonstrated, that only HLA-DR identical patient/donor combinations showed identical TGGE patterns. Thus crossmatch analysis by TGGE presents a novel basis for a rapid and safe unrelated bone marrow donor selection strategy. Only HLA class I identical donors which also show HLA-DR identity in the TGGE crossmatch test are selected for the final confirmation of the HLA class II genes by a suitable DNA subtyping method.


Effects of prostaglandins and oxytocin on calcium release from a uterine microsomal fraction.
A microsomal fraction resembling striated muscle sarcoplasmic reticulum was isolated from uterine smooth muscle. ATP induces calcium accumulation in this fraction. Increased temperature enhances calcium accumulation and calcium-activated ATPase. In the absence of ATP, approximately 35% of the intrinsic calcium exchanges with the 45Ca in the incubation medium. In the presence of ATP, exchange of intrinsic calcium with 45Ca increases by an amount which equals the ATP-dependent calcium binding. In preparations partially preloaded with calcium, a steady state of bound calcium is reached when the ATP is exhausted. Calcium is released under these conditions by prostaglandins E2 and F2alpha, but not by PGF1beta. The antibiotic ionophores X537A and A23187, as well as oxytocin, also release calcium previously accumulated under ATP stimulation. None of these agents, with the exception of oxytocin, release intrinsic calcium. Thus, the effect of prostaglandins resembles that of the ionophores, suggesting an ionophoretic action of these prostaglandins. The release of calcium conforms with the in vivo smooth muscle contracting action of these agents.


A giant choledochal cyst: A case reported from Tanzania.
Choledochal cyst is a rare common bile duct malformation that usually presents in the pediatric group with abdominal pain, distension, and jaundice. The pathophysiology remains unclear for the cause, and surgery aims to restore biliary enteric drainage. We present a six-year-old female who presented with gradual abdominal distention associated with jaundice. Abdominal ultrasound was suggestive of choledochal cyst, and CT-scan confirmed the diagnosis. She was operated on successfully and fared well. Choledochal cysts are a rare entity of common bile duct malformations and should be considered as a differential diagnosis in the pediatric age group. Diagnosis can be easily made by non-invasive and in-expensive radiologic modalities like ultrasonography in resource-limited settings.


Radioiodination of human growth hormone with characterization and minimization of the commonly defined "damaged products".
The radioiodination and chromatographic purification of human growth hormone (hGH) has been studied in order to better define and control the so-called "preparation damage", which is often a cause of interferences, loss in specific activity and sensitivity, misclassification errors in radioligand assays, and a source of misinterpretation when the tracer is used in receptors or in vivo studies. A series of labelings and false labelings, with and without protein carrier in the buffer used for Sephadex purification, indicate that the "preparation damage" peak is made up of two components: aggregated 125I-hGH and BSA-carried radioactivity. The former can be minimized by the use of recently extracted non-lyophilized hGH, and the latter by enzymatic labeling. Both components can be better resolved, and thus eliminated, when Sephadex G-100 is employed rather than G-75.


Structural basis of efficient electron transport between photosynthetic membrane proteins and plastocyanin in spinach revealed using nuclear magnetic resonance.
In the photosynthetic light reactions of plants and cyanobacteria, plastocyanin (Pc) plays a crucial role as an electron carrier and shuttle protein between two membrane protein complexes: cytochrome b(6)f (cyt b(6)f) and photosystem I (PSI). The rapid turnover of Pc between cyt b(6)f and PSI enables the efficient use of light energy. In the Pc-cyt b(6)f and Pc-PSI electron transfer complexes, the electron transfer reactions are accomplished within <10(-4) s. However, the mechanisms enabling the rapid association and dissociation of Pc are still unclear because of the lack of an appropriate method to study huge complexes with short lifetimes. Here, using the transferred cross-saturation method, we investigated the residues of spinach (Spinacia oleracea) Pc in close proximity to spinach PSI and cyt b(6)f, in both the thylakoid vesicle-embedded and solubilized states. We demonstrated that the hydrophobic patch residues of Pc are in close proximity to PSI and cyt b(6)f, whereas the acidic patch residues of Pc do not form stable salt bridges with either PSI or cyt b(6)f, in the electron transfer complexes. The transient characteristics of the interactions on the acidic patch facilitate the rapid association and dissociation of Pc.


Development of a dosimetry inter-comparison for IMRT as part of site credentialing for a TROG multi-centre clinical trial for prostate cancer.
A methodology has been developed for a dosimetry inter-comparison of intensity modulated radiation therapy (IMRT) delivery in Australasia. The inter-comparison is part of site credentialing for those sites participating in the prostate fractionated irradiation trial (PROFIT) for intermediate-risk prostate patients developed by the Ontario Clinical Oncology Group and coordinated in Australasia by the Trans Tasman Radiation Oncology Group. Features of the dosimetry inter-comparison design included the use of a dedicated pelvic anthropomorphic phantom, the use of a single CT data set of the phantom including contours and the use of radiochromic film as a dosimeter. Action levels for agreement between measured dose and treatment planning system dose have been proposed based on measurement uncertainty and international experience. A trial run of the dosimetry procedure at the reference centre gave results within the predefined action levels.


The Struggle with Rheumatism through Dracunculus vulgaris Schott: In the Light of Ethnobotanical Information.
The fruits with the seeds of Dracunculus vulgaris Schott. (Araceae) are used against inflammatory diseases in Turkey. The present study was designed to justify this folkloric usage of the plant. Therefore, the aim of this study was to investigate the anti-inflammatory activity of D. vulgaris. Petroleum ether, ethyl acetate and methanol extracts were prepared from the fruits, successively. Carrageenan-, serotonin-, and prostaglandin E2-induced hind paw edema; acetic acid-induced capillary permeability and 12-O-tetradecanoyl-phorbol-13-acetate-induced mouse ear edema models were used to assess the anti-inflammatory activity of the extracts. The analgesic activity was observed by using p-benzoquinone-induced abdominal constriction test. The petroleum ether extract displayed the highest activities in all of the used test models compared with the control group. Therefore, the constituents of this extract were determined by using gas chromatography-mass spectroscopy (GC-MS). Linoleic acid was found to be the major constituent of the petroleum ether extract of D. Vulgaris. This study has provided some justification for the folkloric use of the plant.


Dynamics of Phosphorus and Biostimulants on Agro-Morphology, Yield, and Essential Oil Profile of German Chamomile (Matricaria chamomilla L.) Under Acidic Soil Conditions of the Western Himalaya.
German chamomile (Matricaria chamomilla L.) is a promising and easy to cultivate crop under suitable nutrient supply conditions, but acidic soils of Indian western Himalayas limit the availability of phosphorus to the plant and reduce flower production. Thus, a field experiment was conducted for two consecutive seasons (2018-2019 and 2019-2020) to study the effect of phosphorus dynamics and biostimulant application on the agro-morphological traits, essential oil (EO) yield, and chemical constituents of German chamomile in the mid hills of the western Himalayan region. The experiment consisted of 12 treatments, four phosphorus fertilizer levels (0, 30, 60 and 90 kg ha-1) and three biostimulants levels (control, amino acid at 5 mL L-1, and humic acid at 10 mL L-1). The experiment was replicated three times in a factorial complete randomized block design (FRBD). Agro-morphological and yield characteristics were significantly higher in phosphorus at 90 kg ha-1 and humic acid application compared to the control. Dry flower and EO yield was 17.87 and 26.76% higher with the 90 kg ha-1 phosphorus application while 2.45 and 5.79% higher in humic acid at 10 mL L-1 compared to the control. The EO constituents viz., chamazulene was 12.04 and 8.85% higher in phosphorus at 90 kg ha-1 and humic acid at 10 mL L-1 application compared to the control. On the other hand, α-bisabolol oxide B and α-bisabolol oxide A were decreased with increase in phosphorus application. This study presents novel facts, elucidation, and explanation for farmers and industrialists to produce German chamomile in acidic soils by integrating biostimulants with phosphorus fertilization and getting maximum yield and quality EO.


Synthesis and biodistribution of [18F]FE@CIT, a new potential tracer for the dopamine transporter.
In the last decade radiolabeled tropane analogs based on beta-CIT have proven indispensable for the imaging of the dopamine transporter. However, further improvements in their pharmacodynamic and pharmacokinetic features are desirable. An important improvement, yielding in higher affinity to the dopamine transporter (DAT) vs. serotonin transporter (SERT), can be achieved by a simple replacement of the carboxylic methyl ester group in beta-CIT by a fluoroethyl ester. The preparation and ex vivo evaluation of this new beta-CIT-analog ([18F]FE@CIT) is presented here. Precursor and standard were prepared from beta-CIT and analyzed by spectroscopic methods. Yields of precursor and standard preparation were 61% and 42%, respectively. [18F]FE@CIT was prepared by distillation of [18F]bromofluoroethane ([18F]BFE) and reaction with (1R-2-exo-3-exo)8-methyl-3-(4-iodo-phenyl)-8-azabicyclo[3.2.1] octane-2-carboxylic acid. After 10 min at 150 degrees C the product was purified using a C-18 SepPak. The radiosynthesis evinced radiochemical yields of >90% (based on [18F]BFE), the specific radioactivity was >416 GBq/micromol. An average 30 microAh cyclotron irradiation yielded more than 2.5 GBq [18F]FE@CIT. For the ex vivo bioevaluation, 20 male Sprague-Dawley rats were sacrificed at 5, 15, 30, 60, and 120 min after injection. Organs were removed, weighed, and counted. For autoradiographic experiments, transverse brain slices of about 100 microm were prepared. The ex vivo evaluation showed highest brain uptake in striatal regions, followed by thalamus and cerebellum. The highest striatum to cerebellum ratio was 3.73 and the highest thalamus to cerebellum ratio was 1.65. Autoradiographic images showed a good and differentiated uptake in striatal regions with a good target-to-background ratio.


Genetic contributors toward increased risk for ischemic heart disease.
Cardiovascular disease is a leading cause of mortality in the United States, and is a significant cause of death worldwide. In 2002, it accounted for 38.0% of all deaths in the US, and approximately one-third of all global deaths. It has a significant economic impact, with an estimated cost in the US of 393.5 billion US dollars for 2005. The most common form of heart disease is coronary heart disease (CHD)(1)/coronary artery disease (CAD) resulting from atherosclerosis. Thirteen million Americans are affected by CHD annually, with 7.1 million of these experiencing a myocardial infarction (MI). Five to ten percent of new MI's occur in individuals younger than age 50, and the lifetime risk of developing CAD after age 40 ranges from 32% in women to 49% in men. Because of its major impact on morbidity and mortality, as well as its contribution to annual health care costs, it is of the utmost importance that improved strategies for preventing and treating CAD be developed. A promising, but inherently difficult, area of study is the identification of genes that predispose to or directly cause CAD. The identification of these genes may lead to screening tests that will allow persons at risk for developing CAD to be identified early enough that prevention/intervention strategies can be implemented to prevent or ameliorate the disease process, and may also lead to the development of gene therapy mechanisms useful in the treatment of ischemic heart disease (IHD). Because an exhaustive review of all the genes being studied in relation to CAD and MI is difficult within the confines of a review article, this review will focus on describing representative studies investigating the genes considered most likely to potentially contribute toward an increased risk for CAD and MI. Genes resulting in inherited disorders with which an increased risk of CAD and MI is associated will be discussed, as well as a number of candidate genes that may play a role in the multifactorial inheritance of CHD risk.


Botulinum Injections for Idiopathic Cervical Dystonia: a Longitudinal Study.
Botulinum toxin (BT) injections into the cervical muscles are an effective and commonly practiced treatment approach for cervical dystonia. In this retrospective longitudinal study, we collected data from the Sheba electronic medical records on consecutive patients with idiopathic cervical dystonia (ICD), treated regularly with periodic BT injections between the years 2008-2020. All treatment visits were analyzed regarding type of toxin, dose injected, and clinical outcomes. The vast majority of patients were treated with abobotulinum toxin A. Sixty-four ICD patients (51 (79.7%) females, onset at age 45.8 ± 13.7 years) were treated over 17.1 ± 13.9 (range 3 to 49) visits per patient; BT treatment efficacy increased gradually from initial treatment sessions to visit 13, when it achieved a steady state. While the subjective report of percentage improvement and its duration were around 78.9 ± 17.1% for 2.8 ± 1.0 months, respectively, the dose of BT increased significantly over the years (p = 0.006). Side effects (SE) were not rare, and commonly recurred after subsequent sessions and were usually mild and short-lasting, with dysphagia being the most common (~17.5%), followed by neck/arm weakness (11.9%) and cervical pain (8.9%). Repeated injections of BT for ICD remain beneficial for patients over several years of therapy, and despite mild SE, patients tend to adhere to a 3-4 months interval schedule.


Pitfalls and valid approaches to pharmacokinetic analysis of mean concentration data following intravenous administration.
Pharmacokinetic analysis fo arithmetic mean concentration data can lead us to selection of an inappropriate deterministic compartmental model and biased pharmacokinetic parameter estimates. The terminal phase disposition rate constant estimated by fitting a deterministic model to mean data is in all cases an underestimate of the expected value of this rate constant. The area under the mean data curve calculated via the linear trapezoidal rule from time zero to the last detectable concentration sampling point is equal to the mean of the individual subject areas under the curve for the same time span. This equality supports the use of mean data for determination of model-independent pharmacokinetic parameters.


macho-1-Related genes in Ciona embryos.
In ascidians, maternal factor(s) localized in the myoplasm of the egg are essential for specification and subsequent differentiation of larval muscle cells. The macho-1 gene of Halocynthia roretzi encodes a zinc-finger protein: the gene is only expressed maternally, the resultant maternal mRNA is localized to the myoplasm, and the gene function is essential for muscle cell differentiation. Here we have characterized macho-1 homologues, Ci-macho1 of Ciona intestinalis and Cs-macho1 of Ciona savignyi. Interestingly, we found that the Ciona macho-1 genes are expressed both maternally and zygotically: their maternal transcript is localized to the myoplasm while their zygotic expression is seen after neurulation in cells of the central nervous system. Functional suppression of Cs-macho1 with morpholino antisense oligonucleotide resulted in inhibition of the initiation of zygotic expression of a muscle-specific actin gene. We propose a possible evolutionary scenario in which an ancestral Zic-related gene gave rise to both the macho-1-like muscle determinant gene as well as neuronal Zic genes.


The immunosuppressant drug FK506 prevents Fas-induced apoptosis in human hepatocytes.
FK506 is a potent immunosuppressive drug used for the prevention of graft rejection in organ transplantation. Experimental and clinical studies have shown correlations between apoptosis and graft rejection, and apoptosis also plays a role in cell death after ischemia-reperfusion injury in the rat liver. Fas-mediated apoptosis is very likely involved in allograft rejection and experimental evidence has shown a decrease of FasR expression in mouse hepatocytes produced by the drugs. On the basis of these findings we have investigated the protective effect of FK506 in comparison with cyclosporine A (CsA) on Fas-induced apoptosis, by analysing the activation of downstream effector caspases in human hepatocytes. Apoptosis was induced by treatment with agonistic antibodies against FasR, which resulted in a significant activation of caspase-3 after 12 h. Prevention of the downstream activation of the caspase cascade and apoptosis was observed when hepatocytes were pre-treated for 3 h with immunosuppressant drugs. A significant reduction (ca. 30-40%) of caspase-3 activation by 5 microM FK506 and CsA was observed. Along with less activation of caspase-3 a decrease of apoptotic DNA fragmentation was found. In addition, FK506 significantly reduced not only caspase-8 but also caspase-9 activation, to a similar extent as CsA, thus suggesting a protective effect at the mitochondrial level of this drug, as has already been reported for CsA. These effects of FK506 help to explain its strong anti-rejection properties and suggest promising benefits of pharmacological preconditioning on ischemia-reperfusion injury following liver transplantation.


Gate-tuned Josephson effect on the surface of a topological insulator.
In the study, we investigate the Josephson supercurrent of a superconductor/normal metal/superconductor junction on the surface of a topological insulator, where a gate electrode is attached to the normal metal. It is shown that the Josephson supercurrent not only can be tuned largely by the temperature but also is related to the potential and the length of the weak-link region. Especially, the asymmetry excess critical supercurrent, oscillatory character, and plateau-like structure have been revealed. We except those phenomena that can be observed in the recent experiment.


Sediment from lake with missing egg bank is toxic to hatchlings of model zooplankton: A reason to consider obligate dormancy in toxicological assessment.
Over the last 60 years, valuable progress was made in the standardization of environmental monitoring with model zooplankton. However, obligate dormancy in zooplankton life cycles is not yet considered in standardized toxicology methods. Most zooplankton from coastal and inland waters use dormancy as a critical ecological strategy, and exposure to toxicants during dormancy or resurrection from dormancy alters developmental patterning and hatching success. The present study accounts for this by using both standardized and novel toxicology assays to assess the impacts of coal ash contaminated sediments and water on development, hatching, and survivorship of model zooplankton. The results demonstrate that standardized assays with rotifer and cladoceran models detect no toxicity in surface water and sediment pore water from Lake Sutton, North Carolina, USA. By contrast, novel toxicity assays with cladoceran and anostracan models demonstrate that development and larval survivorship are negatively impacted by Lake Sutton water and sediment. Embryos of Artemia franciscana display developmental patterning and hatching aberrations that match those observed in previous studies with metals when hatched in filtered surface water or pore water after a period of anoxia-induced dormancy. Larval survivorship in Daphnia magna and A. franciscana also decreases when post-diapause embryos are hatched in the presence of sediment. The effects of whole sediment on larval survivorship are not explained by coal ash impacts on water pH. These data provide an explanation for the missing egg bank and historic community restructure in Lake Sutton. The data also demonstrate a need for standardized assays that include dormant life stages.


Disagreement between self-reported and clinician-ascertained suicidal ideation and its correlation with depression and anxiety severity in patients with major depressive disorder or bipolar disorder.
To study the disagreement between self-reported suicidal ideation (SR-SI) and clinician-ascertained suicidal ideation (CA-SI) and its correlation with depression and anxiety severity in patients with major depressive disorder (MDD) or bipolar disorder (BPD). Routine clinical outpatients were diagnosed with the MINI-STEP-BD version. SR-SI was extracted from the 16 Item Quick Inventory of Depression Symptomatology Self-Report (QIDS-SR-16) item 12. CA-SI was extracted from a modified Suicide Assessment module of the MINI. Depression and anxiety severity were measured with the QIDS-SR-16 and Zung Self-Rating Anxiety Scale. Chi-square, Fisher exact, and bivariate linear logistic regression were used for analyses. Of 103 patients with MDD, 5.8% endorsed any CA-SI and 22.4% endorsed any SR-SI. Of the 147 patients with BPD, 18.4% endorsed any CA-SI and 35.9% endorsed any SR-SI. The agreement between any SR-SI and any CA-SI was 83.5% for MDD and 83.1% for BPD, with weighted Kappa of 0.30 and 0.43, respectively. QIDS-SR-16 score, female gender, and ≥4 year college education were associated with increased risk for disagreement, 15.44 ± 4.52 versus 18.39 ± 3.49 points (p = 0.0026), 67% versus 46% (p = 0.0783), and 61% versus 29% (p = 0.0096). The disagreement was positively correlated to depression severity in both MDD and BPD with a correlation coefficient R(2) = 0.40 and 0.79, respectively, but was only positively correlated to anxiety severity in BPD with a R(2) = 0.46. Self-reported questionnaire was more likely to reveal higher frequency and severity of SI than clinician-ascertained, suggesting that a combination of self-reported and clinical-ascertained suicidal risk assessment with measuring depression and anxiety severity may be necessary for suicide prevention.


BEYOND KRAS: Other markers and potential treatment strategies for KRAS mutant and wild-type patients.
Despite the advances and new drug discoveries, the best drug in metastatic colorectal cancer (mcrc) is 5-fluorouracil. This drug is the backbone of FOLFOX and FOLFIRI which are the standard first line cytotoxic regimens in the metastatic setting. The efficacies of these two regimens are equivalent, and the selection of one over the other is largely based on the side effect profile. Bevacizumab is commonly added to each of these regimes in the first line setting. When a patient develops progression of disease on FOLFOX, then treatment with either single agent irinotecan, or FOLFIRI is a typical approach. If FOLFIRI-BEV is used in first line, the FOLFOX is typically given in second line. All patients with metastatic colorectal cancer have their tumor tested for the KRAS mutation in exon 2. If the tumor is KRAS wild-type then either cetuximab or panitumumab, with or without continued irinotecan, may be used. In patients whose tumors are symptomatic, and so requiring a rapid response, cetuximab or panitumumab may be incorporated into second line therapy instead of third line. There are no data supporting the use of cetuximab after progression on panitumumab or vice versa and use of one of these agents after failure on the other is not appropriate. Upon progression on the standard chemotherapies outlined above appropriate patients may be offered participation in a clinical trial. For patients whose tumors are KRAS mutant a clinical trial should be considered upon progression on oxaliplatin and irinotecan-based regimens. New agents and combinations of targeted therapies described below offer promising therapies for patients with both KRAS wild type and mutant tumors. As our molecular knowledge of mcrc advances future therapies will likely tailor an individualized approach based on tumor specific molecular markers.


Functionally relevant microsatellites in sugarcane unigenes.
Unigene sequences constitute a rich source of functionally relevant microsatellites. The present study was undertaken to mine the microsatellites in the available unigene sequences of sugarcane for understanding their constitution in the expressed genic component of its complex polyploid/aneuploid genome, assessing their functional significance in silico, determining the extent of allelic diversity at the microsatellite loci and for evaluating their utility in large-scale genotyping applications in sugarcane. The average frequency of perfect microsatellite was 1/10.9 kb, while it was 1/44.3 kb for the long and hypervariable class I repeats. GC-rich trinucleotides coding for alanine and the GA-rich dinucleotides were the most abundant microsatellite classes. Out of 15,594 unigenes mined in the study, 767 contained microsatellite repeats and for 672 of these putative functions were determined in silico. The microsatellite repeats were found in the functional domains of proteins encoded by 364 unigenes. Its significance was assessed by establishing the structure-function relationship for the beta-amylase and protein kinase encoding unigenes having repeats in the catalytic domains. A total of 726 allelic variants (7.42 alleles per locus) with different repeat lengths were captured precisely for a set of 47 fluorescent dye labeled primers in 36 sugarcane genotypes and five cereal species using the automated fragment analysis system, which suggested the utility of designed primers for rapid, large-scale and high-throughput genotyping applications in sugarcane. Pair-wise similarity ranging from 0.33 to 0.84 with an average of 0.40 revealed a broad genetic base of the Indian varieties in respect of functionally relevant regions of the large and complex sugarcane genome. Microsatellite repeats were present in 4.92% of sugarcane unigenes, for most (87.6%) of which functions were determined in silico. High level of allelic diversity in repeats including those present in the functional domains of proteins encoded by the unigenes demonstrated their use in assay of useful variation in the genic component of complex polyploid sugarcane genome.


Acute onset of ovarian dysfunction in young females after start of cancer treatment.
Female childhood cancer survivors are at risk of ovarian failure and premature ovarian insufficiency. We hereby present an interim analysis of a prospective observational study of ovarian function during cancer treatment of young females in relation to clinical factors. Thirty-four consecutive female cancer patients aged 0-18 year were included after informed consent. Serum/Plasma levels of anti-Müllerian hormone (AMH), inhibin B, FSH, LH, and oestradiol (E2) were measured at diagnosis and every 3-4 months during and after treatment. All patients had detectable AMH levels at diagnosis. Eleven patients had reached menarche (mean age 14½ years) and the remaining patients had a mean age of 6½ years. They all showed a rapid decline in AMH after 3 months of treatment, regardless of AMH at diagnosis, age, menarche, or treatment given. Those given radiotherapy below the diaphragm and/or stem cell transplantation (SCT) (n = 9) had no ovarian recovery during or 1½-year after treatment. However, recovery was observed in those given standard treatment for acute lymphatic leukemia (n = 7) already during maintenance chemotherapy. For the remaining patients, longer follow-up is required for analysis of ovarian recovery after treatment. Rapid ovarian dysfunction is observed in all females after initiation of cancer treatment as measured by AMH and inhibin B. Our data regarding those who require abdominal radiotherapy and/or SCT confirms the recommendations in the Nordic countries where these patients are eligible for cryopreservation of ovarian cortical tissue before start of cancer treatment.


MRI appearance of a cerebral cavernous malformation in the caudate nucleus before and after chorea onset.
Movement disorders associated with cerebral cavernous malformations (CM) are seldom reported, and chorea, in particular, is rarely associated with a CM located in the caudate nucleus. Here we report a 78-year-old female patient with chorea, who presented with choreiform movements due to a CM in the contralateral caudate nucleus. A brain MRI was obtained and compared with that obtained before the onset of chorea. The new images did not reveal further extralesional hemorrhage from the CM when compared with the previous images. The choreiform movements showed spontaneous improvement and then disappeared completely. We reviewed previous reports of patients with chorea associated with a CM, and conclude that CM located in the caudate nucleus can cause chorea.


Gender difference in accumulation of calcium and phosphorus in the left coronary arteries of Thais.
To examine whether there were gender differences in compositional changes of the coronary artery with aging, the authors investigated the gender difference in age-related changes of elements in the left coronary arteries of Thais by direct chemical analysis. After ordinary dissections by students at Chiang Mai University were finished, the left coronary arteries were resected from Thai subjects. The Thai subjects consisted of 69 men and 34 women. The ages of the male subjects ranged from 25 to 87 years (average age = 62.6 ± 11.4 years) and of the female subjects from 24 to 86 years (average age = 59.4 ± 14.6 years). After incinerating the arteries with nitric acid and perchloric acid, the element content was determined by inductively coupled plasma-atomic emission spectrometry. The Ca and P contents tended to increase in the left coronary arteries of men with age, but the increases were not statistically significant. In the left coronary arteries of women, the Ca and P contents increased significantly and progressively with aging. In addition, the Na content increased significantly in the left coronary arteries of both men and women with aging. The differences in the average contents of Ca and P by age group were observed between the left coronary arteries of men and women. With Student's t test, significant gender differences in the average contents of Ca and P were found in both the 40s and the 70s. The Ca and P contents of the left coronary arteries in the 40s were significantly higher in men than in women. In contrast, the Ca and P contents in the 70s were significantly higher in women than in men. These results indicated that the accumulation of Ca and P in the left coronary arteries of Thais occurred at least 10 years earlier in men than in women, but a higher accumulation of Ca and P in old age occurred in the left coronary arteries of women compared with those of men. The present study revealed that there were significant gender differences in the left coronary arteries with regard to the accumulation of Ca and P with aging. It is reasonable to presume that taking clinical findings into consideration, the gender differences in the left coronary arteries may result from hormonal and/or genetic factors rather than lifestyle factors.


CDC releases detailed guidelines for PEP use. Agency focuses on nonoccupational exposure.
While post-exposure prophylaxis has been available to medical employees and first responders for years, public health officials routinely have dismissed the possibility of extending PEP to the general public, citing the inefficiency of its use. That philosophy has changed. For the first time, the CDC has provided a detailed blueprint for how clinicians might recommend nPEP among patients who might have been exposed to HIV within the previous 72 hours.


Indoor radon measurements in the city of Valencia.
The indoor radon risk in Valencia (Spain) was studied more than twenty years ago in two surveys using different methodologies and leading to contradictory results. We report here on new indoor radon measurements with the charcoal canister technique, which confirm the low average level of indoor radon in the city, with a geometrical mean of 24 Bq/m(3) and an arithmetic mean of 27 Bq/m(3).


Autoantibodies production and immunological abnormalities after bariatric surgery.
Bariatric surgery is a widely used procedure for the treatment of obesity. Our aim is to describe the main immunological changes in patients who undergo bariatric surgery. A prospective study was conducted within a cohort of patients undergoing bariatric surgery and without previous evidence of systemic or organ-specific autoimmune diseases in whom 3 blood samples were collected - one day before surgery (Time 0), and 5 (Time 1) and 10 months (Time 2) after surgery. Thirty four obese patients underwent surgery (Time 0):30(88.24%) were women, mean age 38.3 years. When comparing Time 0 and Time 2, there were statistically significant changes in CD4+T cell count, with an increase from 1074/mL(IQR:860-1316) to 1217.5/mL(IQR:838-1510),p = 0.0002. The CD4/CD8 ratio increased from 2.2(IQR: 1.7-2.7) to 2.4(1.8-2.8), p = 0.0001. As for humoral variables, the C3 fraction of complement decreased from 164 ± 40.6 mg/dL to 112.4 ± 31.4 mg/dL(p < 0.001) and C4 decreased from 29.3 ± 10.1 mg/dL to 22.5 ± 7.1(p = 0.0009) at Time 2. Four patients with negative ANAs at baseline, showed positive ANAs at Time 2.One patient developed anti-citrullinated peptide antibodies >200 IU/mL at Time 2. Patients undergoing bariatric surgery show immunological changes which might eventually lead to develop an autoimmune disease.


Genetic diversity and structure of Capparis spinosa L. in Iran as revealed by ISSR markers.
Capparis spinosa L. (caper bush) is an economically and ecologically important perennial shrub that grows across different regions of Iran. In this study, the genetic diversity and population structure of Iranian genepool of C. spinosa is evaluated using Inter Simple Sequence Repeat (ISSR) markers. Using 10 ISSR primers, 387 DNA fragments (bands) were amplified from the genomic DNA of 92 individuals belonging to twenty-one populations of C. spinosa, of which 378 (97.7%) were polymorphic. High level of genetic diversity (percentage of polymorphic loci = 98.2%, h = 0.1382, I = 0.243), high genetic differentiation (Gst = 0.5234) and low gene flow (Nm = 0.4553) among populations were observed. Caper bush populations were divided into 4 groups in the dendrogram, PCoA plot and Bayesian clustering results, mostly corresponded to their geographic regions. The results showed that there are value in sampling Iranian caper bush populations to look for valuable alleles for use in plant breeding programs.


MHTP, a synthetic tetratetrahydroisoquinoline alkaloid, attenuates lipopolysaccharide-induced acute lung injury via p38MAPK/p65NF-κB signaling pathway-TLR4 dependent.
This study investigated the mechanism of action of a synthetic tetrahydroisoquinoline alkaloid, MHTP, in an experimental model of acute lung injury (ALI) in two distinct moments: 72 h and 10 days. To realize this study, 2.5 mg/kg of lipopolysaccharide (LPS) was intranasally administered in BALB/c mice, and nasal instillation of MHTP (1.25; 2.5; 5.0; 10 or 20 mg/kg) was administrated at 1, 24, and 48 h after LPS challenge. The data were statistically analyzed and p < 0.05 was considered statistically significant. MHTP treatment (2.5, 5.0, 10 or 20 mg/kg) significantly decreased neutrophil migration into the bronchoalveolar lavage fluid (BALF), tissue inflammatory cell infiltration, edema, and hemorrhage as well as collagen fiber deposition on the perialveolar regions at both moments. TNF-α and IL-6 levels were significantly diminished in the MHTP-treated animals at 72 h and maintained them, at a basal level, at 10-day observation. These effects of MHTP are due to downregulating p38MAPkinese/p65NFκB signaling pathway-TLR4 dependent. Also, the MHTP treatment promoted a survival rate at 100% and improved their body weights during the 10-day observation. Unlike, the LPS group (non-treated LPS challenged animals) presented less than 50% of surviving rate at 72 h and the animals that survived did not improve their physiological state at 10-day observation. These data showed for the first time the beneficial and effective activity of a nasal treatment with a synthetic tetrahydroisoquinoline alkaloid on an experimental model of ALI and pointed out the molecular mechanism related to it.


Arsenic in shallow aquifer in the eastern region of Bangladesh: insights from principal component analysis of groundwater compositions.
Probable sources and mechanisms of arsenic (As) release in shallow aquifer in eastern Bangladesh are evaluated using statistical analysis of groundwater compositions. Dissolved As in 39 samples ranged from 8.05 to 341.5 microg/L with an average of 95.14 microg/L. Ninety seven percent of wells exceed the WHO limit (10 microg/L) for safe drinking water. Principal component analysis is applied to reduce 16 measured compositional variables to five significant components (principal components--PCs) that explain 86.63% of the geochemical variance. Two component loadings, namely PC 1 and PC 2 (45.31% and 23.05%) indicate the natural processes within the aquifers in which organic matter is a key reactant in the weathering reactions. Four groups of wells are defined by the PCA and each group of wells represents distinct physicochemical characteristics. Among them, group III groundwater shows higher As concentration together with high concentrations of Fe, Mn, dissolved organic carbon, PO4(3-) and HCO3(-) than groups I and II. Speciation calculations suggest that only wells of group III are saturated with respect to siderite, and all groups of samples are supersaturated with respect of rhodochrosite. The relationship of As with these parameters in the different groups of wells of the study area suggests that reductive dissolution of Fe-Mn oxyhydroxides with microbially mediated degradation of organic matter is considered to be the dominant processes to release As in groundwater.


Systematic review and meta-analysis: Is there any role for antioxidant therapy for pain in chronic pancreatitis.
Chronic pancreatitis (CP) is an irreversible disease with increased oxidative stress. The therapeutic role of antioxidants for pain reduction in CP is debatable. A systematic review of articles in PubMed and Embase until February 2020 was performed. Only randomized controlled trials conducted on humans to evaluate the therapeutic effects of antioxidants for pain in CP were included. Studies of other design, nonhuman studies, and those that did not objectively assess pain were excluded. Twelve articles and four articles were eligible for qualitative and quantitative analysis, respectively. The four included studies had a total of 352 participants. Pain reduction as measured by a visual analog scale was not significantly different in the antioxidant group compared to placebo (standardized mean difference = -0.14 [95% confidence interval [CI] = -0.44 to 0.17]; P = 0.38). Number of pain-free participants was also similar (odds ratio [OR] = 1.59 [0.97-2.59]; P = 0.06). There was no difference in outcome when comparing different etiologies of CP or age group. The reduction in the number of analgesics used did not differ between both groups. Antioxidants were not associated with increased adverse events (OR = 2.59 [CI = 0.77-8.69]; P = 0.12). A qualitative analysis on the effect on quality of life did not suggest any significant improvement with antioxidants. There was no significant pain reduction or change in quality of life in CP patients with use of antioxidants. This makes their routine use in the management of CP questionable. However, further studies may identify a subgroup where they are more useful.