Surgically removed adrenal metastasis from cancer of the rectum. Report of a case.
A woman was operated on for pulmonary metastasis four years after a radical resection of the rectum, and four years thereafter a solitary metastasis to the left adrenal was found. An elevated serum carcinoembryonic antigen (CEA) level indicated the lesion. Adrenalectomy was performed and the patient has been well with no further evidence of disease.


Repetitive monomorphic ventricular tachycardia associated with exercise--a case report.
The case of a 45-year-old man suffering from a catecholamine-sensitive ventricular tachycardia originating from the right ventricular outflow tract is reported. The authors describe a novel noninvasive treatment strategy for the management of this patient.


Conjugated linoleic acid and L-carnitine combination effects on obesity-related miRNAs in diet-induced obese rats.
Obesity is a major global health issue, resulting in significant costs and increased mortality rates. Finding effective treatments for obesity is therefore essential. This study investigated the combined effects of L-Carnitine (LC) and Conjugated Linoleic Acid (CLA) on weight loss and adipose tissue microRNA levels. Forty male Wistar rats weighing 150-200 g and about 8 weeks old were fed either a normal fat diet (NFD) or a high-fat diet (HFD) for 8 weeks. Afterwards, the HFD group was randomly divided into four subgroups: control, LC (200 mg kg-1), CLA (500 mg kg-1), and both (n = 8 in each group). The study lasted for an additional 4 weeks. The animals' weights were recorded regularly, and after 12 weeks, miRNAs were extracted from epididymal adipose tissue and analysed using real-time PCR. The miRNA expression levels of miR-27a and miR-143 were compared between groups using Kolmogorov-Smirnov and one-way ANOVA tests in SPSS software. At the end of the first 8 weeks, the HFD group weighed significantly more than the NFD group. LC significantly decreased weight gain (4.2%) compared to the control group, whereas CLA alone (3.5%) or in combination with LC (3.1%) did not significantly slow weight gain. Real-time PCR results showed that the HFD group had higher miR-143 levels and lower miR-27a levels compared to the NFD group. LC and CLA increased miR-27a expression after 4 weeks, but their combination decreased miR-27a expression. CLA alone reduced miR-143 expression, whereas LC had almost no effect. Their combination also reduced miR-143 expression. CLA and LC, which are considered weight loss supplements, can potentially regulate metabolism and cellular pathways. However, their combination did not show a synergistic effect on weight loss, possibly due to the reduction in miR-27a expression. Further studies are needed to evaluate the effects of combined fat burners on obesity treatment.


The "window" of slow pathway conduction after ablation and recurrence of atrioventricular nodal reentrant tachycardia.
Slow pathway (SP) conduction often persists following radiofrequency (RF) catheter ablation of atrioventricular nodal reentrant tachycardia (AVNRT). An association between persistent SP conduction, as evidenced by discontinuous AV nodal conduction curves, and recurrent tachycardia has not been established. Of note, the segment of the curve attributable to SP conduction (the "window" of SP conduction) varies. This study examined whether the maximal post-ablation SP conduction window length differs in patients who later have recurrent tachycardia when compared with those who do not recur. Electrophysiologic study data were compared in two groups who had undergone RF ablation of the SP for typical AVNRT at a single center from 1992-1998. The groups, consisting of seven known recurrences (Group A) and 50 non-recurrences confirmed through a follow-up survey and phone contact (Group B), were similar in gender proportion, age, baseline electrophysiologic data, and number of RF deliveries. Four patients (57%) from Group A and 26 (52%) from Group B exhibited discontinuous AV nodal conduction curves after ablation. The maximum post-ablation window lengths among patients with dual AV nodal physiology varied widely and similarly in the two groups, and the means did not significantly differ (53 +/- 47 msec in Group A vs. 36 +/- 31 msec in Group B; p=0.36). Persistent SP conduction post-ablation in this series was a common finding not predictive of recurrence. No difference in the maximum SP conduction window post-ablation was evident between recurrences and non-recurrences.


Newborn screening for cystic fibrosis in Wisconsin: nine-year experience with routine trypsinogen/DNA testing.
To describe the development and follow-up confirmatory results of the routine cystic fibrosis (CF) newborn screening (NBS) program in Wisconsin. CF NBS has been performed on a routine clinical basis in Wisconsin since July 1994. The 2-tiered immunoreactive trypsinogen (IRT)/DNA technique was used on dried blood on filter paper spots. From July 1994 to February 2002, mutation analysis was for the DeltaF508 allele. Beginning in March 2002, multimutation analysis of 25 CF mutations was performed. Infants with a positive result on NBS were seen in certified CF centers for sweat testing by means of quantitative pilocarpine iontophoresis, and families received genetic counseling. From July 1994 to February 2002, there were 120 cases of CF detected by means of NBS (509,794 infants screened), with 53 DeltaF508 homozygotes and 67 compound heterozygotes. There were 8 clinically diagnosed cases of CF (no DeltaF508 allele). The CF incidence was 1:3983 (95%CI, 1:3373-1:4774). From March 2002 to June 2003, multimutation analysis identified 21 cases of classic CF (90,142 infants screened). Sweat tests were successfully performed in infants younger than 1 month. Early diagnosis of CF through NBS was successfully performed, with an estimated sensitivity rate of 99% using the IRT/25 CFTR multimutation assay.


Association between onset and disappearance of pain and changes in physical activity among older adults - longitudinal evidence from the German Ageing Survey.
Physical activity (PA) is important for healthy ageing. Nonetheless, recommended PA guidelines from the World Health Organization are not met by many older adults. To increase PA, influencing factors have been investigated. But it is still unknown how the onset or disappearance of pain within an individual is associated with different PA intensities in older men and women. We used longitudinal data from the nationwide representative German Ageing Survey, waves 2014 and 2017 (analytical sample, n = 6194, 45% women). PA was assessed with questions on low, moderate, and vigorous PA per week and converted into metabolic equivalent of task (MET) values. Pain was dichotomized from a 5-point scale into no pain versus some pain. The association between the onset or disappearance of pain from 2014 to 2017 on total, vigorous, moderate, and low PA was investigated using sex stratified asymmetric fixed effects models. The onset of pain in older men (ß = 977.84, P = 0.041), and the disappearance of pain in older women (ß = 1531.69, P = 0.025), were associated with increased total PA. The results for men were driven by increases in vigorous (ß = 592.62, P = 0.035) PA, while the change in women was driven by low (ß = 242.16, P = 0.020) and moderate (ß = 496.48, P = 0.034) PA intensities. However, the observed differences between men and women were not statistically significant. The divergent associations between the onset and disappearance of pain and PA, driven by different PA intensities in men and women, suggest the existence of factors such as PA intensity influencing the association.


Adolescents in families adopting older children: implications for service.
Editor's Note: The study reported here is of necessarily limited scope and design because of the realistically small number of adoptions with families containing adolescents that are available for examination. The findings and conclusions of the authors are nonetheless useful for agencies involved in special-needs adoption.


Clustering behavior in microbial communities from acute endodontic infections.
Acute endodontic infections harbor heterogeneous microbial communities in both the root canal (RC) system and apical tissues. Data comparing the microbial structure and diversity in endodontic infections in related ecosystems, such as RC with necrotic pulp and acute apical abscess (AAA), are scarce in the literature. The aim of this study was to examine the presence of selected endodontic pathogens in paired samples from necrotic RC and AAA using polymerase chain reaction (PCR) followed by the construction of cluster profiles. Paired samples of RC and AAA exudates were collected from 20 subjects and analyzed by PCR for the presence of selected strict and facultative anaerobic strains. The frequency of species was compared between the RC and the AAA samples. A stringent neighboring clustering algorithm was applied to investigate the existence of similar high-order groups of samples. A dendrogram was constructed to show the arrangement of the sample groups produced by the hierarchical clustering. All samples harbored bacterial DNA. Porphyromonas endodontalis, Prevotella nigrescens, Filifactor alocis, and Tannerela forsythia were frequently detected in both RC and AAA samples. The selected anaerobic species were distributed in diverse small bacteria consortia. The samples of RC and AAA that presented at least one of the targeted microorganisms were grouped in small clusters. Anaerobic species were frequently detected in acute endodontic infections and heterogeneous microbial communities with low clustering behavior were observed in paired samples of RC and AAA.


Multiple active cobalt species embedded in microporous nitrogen-doped carbon network for the selective production of hydrogen peroxide.
To obtain excellent electrocatalysts for improving H2O2 yield and selectivity, we formulated a novel method for embedding cobalt catalytic active sites in porous two-dimensional nitrogen-doped carbon network (CNy) network and employed them as excellent two-electron oxygen reduction reaction (2e--ORR) electrocatalysts. The polymeric cobalt-based metal-organic framework (polyCo-MOF) and melamine-cyanuric acid-complex (MCA) hybrid (denoted as polyCo-MOF@MCA) was used as a precursor for preparing a series of electrocatalysts comprising multiple active sites such as metallic Co, CoOx, or Co-N, which are homogeneously embedded in the porous two-dimensional CNy network through pyrolysis at high temperatures (600 °C, 700 °C, and 800 °C) under N2 atmosphere. The obtained CoOx/Co@CNy,700 hybrid by pyrolyzing polyCo-MOF@MCA at 700 °C displayed remarkably high H2O2 production and large selectivity in an alkaline solution. The possible catalytic mechanism of CoOx/Co@CNy,700 toward 2e--ORR was identified by determining the catalytic kinetics and control experiments. The cathode assembled with the CoOx/Co@CNy,700 hybrid showed the maximum H2O2 production of 405 mmol L-1gcat.-1h-1 with a high Faradaic efficiency of 88.9 % at 0.65 V. The present work demonstrated a novel strategy for identifying excellent electrocatalysts with homogeneously dispersed multiple active sites and high production and selectivity for H2O2 synthesis, extending the applications of porous organic frameworks to the field of clean energy.


Is it feasible to rely on intraoperative X ray in correcting hallux valgus?
The aim of the study was to prove whether the intraoperatively taken fluoroscopy pictures compared to the X rays taken 8 weeks and 3 months postoperatively picture the achieved correction reliably. In a prospective study, the pre- and postoperative standing foot X rays as well as the intraoperatively taken fluoroscopy pictures of 31 patients were analysed. The intermetatarsal angle (IMA) and the hallux valgus angle (HVA) were measured. In all cases, a tarso-metatarsal joint I arthrodesis combined with a distal soft tissue release was performed. The mean age was 54 (17-73) years. There was no significant difference between the measured angles in intraoperative fluoroscopy and standing X rays postoperatively taken. Despite the consideration that fluoroscopic pictures lack the loading criteria, we found reliable results in IMA and HVA.


α-Synuclein and Parkinsonism: Updates and Future Perspectives.
Mutations in the SNCA gene, which encodes the α-synuclein protein, were the first discovered genetic causes of familial parkinsonism with Lewy pathology. To date, six different SNCA missense mutations as well as multiplications are known to cause parkinsonism. For this review, we performed a literature search to identify all published cases of SNCA-related parkinsonism to provide an updated summary of the clinical and neuropathological features of parkinsonism due to SNCA mutations. Familial parkinsonism associated with SNCA is rare, but α-synuclein aggregation is a core feature of sporadic parkinsonism, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Research into α-synuclein and parkinsonism has impacted how we define the pathology and understand the pathogenesis of Parkinson's disease and related neurodegenerative disorders. We briefly discuss some of the lessons we have learned from research into the physiological role of α-synuclein and its pathological links to neurodegeneration and parkinsonism.


Evaluation of loxoprofen and its alcohol metabolites for potency and selectivity of inhibition of cyclooxygenase-2.
Loxoprofen, its trans-alcohol and cis-alcohol metabolites were evaluated for selectivity of inhibition of COX-2 over COX-1. The (2S,1'R,2'S)-trans-alcohol derivative was found to be the most active metabolite and to be a potent and nonselective inhibitor of COX-2 and COX-1 in both enzyme and human whole blood assays.


Inhibition of T-antigen expression promoting glycogen synthase kinase 3 impairs merkel cell carcinoma cell growth.
Merkel cell carcinoma is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV). Since proliferation of MCPyV-positive MCC tumor cells strictly depends on expression of the virus-encoded T antigens (TA), these proteins theoretically represent ideal targets for different kinds of therapeutic approaches. Here we developed a cell-based assay to identify compounds which specifically inhibit growth of MCC cells by repressing TA expression. Applying this technique we screened a kinase inhibitor library and identified six compounds targeting glycogen synthase kinase 3 (GSK3) such as CHIR99021 as suppressors of TA transcription in MCC cells. Involvement of GSK3α and -β in the regulation of TA-expression was confirmed by combining GSK3A knockout with inducible GSK3B shRNA knockdown since double knockouts could not be generated. Finally, we demonstrate that CHIR99021 exhibits in vivo antitumor activity in an MCC xenograft mouse model suggesting GSK3 inhibitors as potential therapeutics for the treatment of MCC in the future.


Non-muscle myosin II isoforms orchestrate substrate stiffness sensing to promote cancer cell contractility and migration.
The stiffening of the extracellular matrix (ECM) during tumor progression results in an increase in cancer cell motility. In cell migration, two major isoforms of non-muscle myosin II (NMII), NMIIA and NMIIB, are expressed and assembled into the cytoskeleton. However, the isoform-specific regulatory roles of NMIIA and NMIIB as well as the underlying mechanisms in response to mechanical cues of the ECM are still elusive. Here, based on polyacrylamide (PAA) gels with tunable elastic modulus, we mimicked the mechanical properties of tumor tissue at different stages of breast cancer in vitro and investigated the distinct roles of NMII isoforms in the regulation of substrate stiffness. We demonstrate that NMIIA is engaged in establishing cell polarity by facilitating lamellipodia formation, focal adhesion turnover, and actin polymerization at the cell leading edge, while NMIIB is recruited to the cell perinuclear region and contributes to traction force generation and polarized distribution, both in a substrate stiffness-dependent manner. We further validated that substrate stiffness modulates the distribution and activation of NMII isoforms via the Rac1/p-PAK1/pS1916-NMIIA and PKCζ/pS1935-NMIIB signaling pathways in a site- and kinase-specific phosphoregulation manner. Our study is helpful for understanding the mechanotransduction of cancer cells and provides inspiration for molecular targets in antimetastatic therapy.


Lipids and stroke: neglect of a useful preventive measure?
The epidemiological studies linking lipid variables and stroke are reviewed. These studies indicate that serum total cholesterol (TC) levels are associated positively with thrombotic and negatively with haemorrhagic strokes. Relationships for other lipid fractions are not as clearly defined. The results of trials with lipid lowering drugs suggest that only statins effectively reduce the incidence of stroke. Differences between trial results may be due to variation in the extent of reduction of TC levels. Possible underlying mechanisms for benefit and the apparent superiority of statins are also discussed. The reduction in the risk of thrombotic stroke with statins is most evident through meta-analyses (p < 0.001) and less impressive in individual trials (p < 0.03). This difference is largely attributable to the small number of events in trials primarily aimed at evaluating ischaemic heart disease (IHD) reduction. This also means that benefit may be limited to those with established IHD. IHD and thrombotic stroke share common risk factors and patients with one condition are at high risk of developing the other. Therefore, one additional reason for using statins in these patients is that these drugs can effectively prevent IHD-related events including deaths.


[Impact of Enclosure Culture on Heavy Metal Content in Surface Sediments of Hongze Lake and Ecological Risk Assessment].
In order to explore the concentrations of heavy metals and the influence of fencing on Hongze lake, the content, source, and spatial distribution characteristics of heavy metals in surface sediments and ecological risks were analyzed in 2018 after part of the fence around Hongze Lake was removed. The results showed that the average contents of Cr, Ni, Cu, Zn, As, Cd, and Pb in the surface sediments in Hongze Lake were 66.78, 33.89, 25.35, 74.77, 16.55, 0.23, and 27.20 mg·kg-1, respectively. Cr, Ni, Cu, Zn, and Pb contents were at non-polluting levels, with As and Cd at the lowest level, based on the accumulation index evaluation. Except for Cd, all the elements showed low potential ecological risk. The results showed that the heavy metal content in the fenced, dismantled, and peripheral areas increased and accumulated towards the center of the lake. The removal of the fence did not significantly reduce the heavy metal content in the short-term. Overall, Hongze Lake presented a state of low ecological risk. In the future, environmental policies should include surface sediment accumulation areas and fencing culture in the north and northeast of Hongze Lake.


Operative management of intrauterine device complications: a case series report.
There is limited information about the number of intrauterine device (IUD) users requiring operative intervention for device-related complications. This is an evaluation of cases requiring in-hospital operative intervention for IUD perforations, removals and pregnancy-related complications. Large retrospective case series of patients who received operative management of IUD complications. Charts of patients from 15 hospitals in two health care systems from 2000 to 2007 were reviewed and outcomes of 276 women are reported. There were 95 operative IUD removals for perforations (including 60 levonorgestrel-releasing intrauterine systems), 157 operative procedures for inability to remove an IUD in the office, and 42 pregnancy-related complications that were managed in the operating room. Ectopic pregnancy was the most common diagnosis among pregnant women (23 of 42 pregnant women, 54.8%). The majority of operative procedures were performed for intrauterine IUDs, most of which were appropriately positioned IUDs with missing or short strings. In-office techniques for obtaining analgesia and dilation as well as appropriate devices for removal of T-shaped IUDs should make this practice rare.


[Functional anatomy of the feeding apparatus of the mallard (Anas platyrhynchos L.) structure, movement, electro-myography and electro-neurography (author's transl)].
A causal model for the functioning of the beakapparatus of the mallard during straining is formulated on a qualitative basis. The starting point for this model is an abstraction of the analysed structure of the muscle, bone, ligament system. The system was studied by electromyography and cinematography of the movements. It was attempted to quantify the model. Connections with neurography are shown.


Coumaric acid induces mitochondrial damage and oxidative-mediated cell death of human endothelial cells.
Evidence that higher natural antioxidants (NA) intake provides cardiovascular protection is contradictory. The endothelium plays a pivotal role in cardiovascular homeostasis, and for this reason, the molecular events resulting from the interaction of NA with endothelial cells (ECs) are actively investigated. Here, we show that moderately high doses of coumaric acid (CA) induced intracellular reactive oxygen species (ROS) production, mitochondrial membrane depolarization and ECs death. Treatment of ECs with cyclosporine A, a mitochondrial permeability transition pore inhibitor, prevented the oxidative-mediated cell damage indicating mitochondrial involvement in CA-induced ECs impairment. CA-induced intracellular ROS generation was counteracted by the specific cytochrome P450 (CYP) 2C9 inhibitor sulfaphenazole (SPZ). SPZ also prevented CA-induced mitochondrial membrane depolarization and ECs death, implicating CYP2C9 in mediating the cellular response upon CA treatment. Our results indicate that moderately high doses of CA can promote CYP2C9-mediated oxidative stress eliciting mitochondrial-dependent ECs death and may pave the way toward mechanistic insight into NA effects on cardiovascular cells.


Effect of fingolimod action on the release of monocyte-derived microvesicles in multiple sclerosis patients.
Recently, microvesicles (MVs) were considered as important mediators of intercellular communication, especially in pathological conditions as Multiple Sclerosis (MS). In myeloid cells, MV shedding is induced by the receptor P2X7 with the involvement of acid sphingomyelinase (A-SMase) and release of the IL-1β. In this study we evaluate how Fingolimod affects MVs production by the monocytes, as well as P2X7R, IL-1β expression and A-SMase activity. Treatment decreased MVs production and IL-1β expression. This effect was associated with the inhibition of A-SMase activity in BzATP-stimulated monocytes from MS patients. These evidences suggest monocyte MVs as a possible disease and drug-efficacy biomarkers.


Peak N160 of rat flash evoked potential: does it reflect habituation or sensitization?
Flash evoked potentials recorded from awake rats contain a negative peak occurring about 160 msec after the flash (N160). This peak has been associated with a specific level of arousal, and/or habituation by various authors. The current studies attempted to determine whether changes in N160 amplitude which accompany repeated testing reflect processes associated with sensitization or habituation. This paper describes experiments in Long-Evans hooded rats which demonstrate the effects of repeated testing, varying stimulus intensity, varying stimulus frequency, and discharging an alarm bell before and during a test session. Repeated testing produced increases in N160 amplitude which were greater at high than low stimulus intensities. Repeated exposure to the test chamber without flashing did not alter N160 amplitude, nor did altering stimulus rate within the range of 0.5 to 4.0 Hz. Discharging an alarm increased N160 amplitude. Taken together, the data suggest that amplitude of N160 more closely reflects sensitization to the stimulus than habituation to either the stimulus or any feature of the test situation.


Recurrent Atherosclerotic Cardiovascular Event Rates Differ Among Patients Meeting the Very High Risk Definition According to Age, Sex, Race/Ethnicity, and Socioeconomic Status.
Background The risk for atherosclerotic cardiovascular disease (ASCVD) events may differ by sociodemographic factors among patients meeting the definition of very high risk according to the 2018 American Heart Association/American College of Cardiology cholesterol guideline, leading to treatment disparities. We estimated the risk for recurrent ASCVD events among adults meeting the definition of very high risk by age, sex, race/ethnicity, and socioeconomic status in a US integrated healthcare system. Methods and Results The study cohort included Kaiser Permanente Southern California members aged ≥21 years with a history of clinical ASCVD on September 30, 2009. Very high risk for recurrent ASCVD was defined by a history of ≥2 major ASCVD events or a history of 1 major event along with ≥2 high-risk conditions. Patients were followed through 2015 for a first recurrent ASCVD event. Of 77 101 patients with ASCVD, 50.8% met the definition for very high risk. Among patients meeting the definition of very high risk, recurrent ASCVD rates were higher in older (>75 years) versus younger patients (21-40 years) (sex-adjusted hazard ratio [HR] [95% CI] 1.85; 1.23-2.79), non-Hispanic Black patients versus non-Hispanic White patients (age-, sex-adjusted HR, 1.32; 1.23-1.41), those who lived in neighborhoods with lower (<$35k) versus higher annual household income (≥$80k) (HR, 1.20; 1.11-1.30), or with lower (≥31.2%) versus higher education levels (<8.8% high school or lower) (HR, 1.26; 1.19-1.34). Conclusions Disparities in the risk for recurrent ASCVD events were present across sociodemographic factors among very high risk patients. The addition of sociodemographic factors to current definitions of very high risk could reduce health disparities.


Monte Carlo determination of radiation-induced cancer risks for prostate patients undergoing intensity- modulated radiation therapy.
The application of intensity-modulated radiation therapy (IMRT) has enabled the delivery of high doses to the target volume while sparing the surrounding normal tissues. The drawbacks of intensity modulation, as implemented using a computer controlled multileaf collimator (MLC), are the larger number of monitor units (MUs) and longer beam-on time as compared with conventional radiotherapy. Additionally, IMRT uses more beam directions--typically 5-- 9 for prostate treatment--to achieve highly conformal dose and normal-tissue sparing. In the present work, we study radiation-induced cancer risks attributable to IMRT delivery using MLC for prostate patients. Whole-body computed tomography scans were used in our study to calculate (according to report no. 116 from the National Council on Radiation Protection and Measurements) the effective dose equivalent received by individual organs. We used EGS4 and MCSIM to compute the dose for IMRT and three-dimensional conformal radiotherapy. The effects of collimator rotation, distance from the treatment field, and scatter and leakage contribution to the whole-body dose were investigated. We calculated the whole-body dose equivalent to estimate the increase in the risk of secondary malignancies. Our results showed an overall doubling in the risk of secondary malignancies from the application of IMRT as compared with conventional radiotherapy. This increase in the risk of secondary malignancies is not necessarily related to a relative increase in MUs. The whole-body dose equivalent was also affected by collimator rotation, field size, and the energy of the photon beam. Smaller field sizes of low energy photon beams (that is, 6 MV) with the MLC axis along the lateral axis of the patient resulted in the lowest whole-body dose. Our results can be used to evaluate the risk of secondary malignancies for prostate IMRT patients.


Effects of melatonin and epithalamin on the content of protein and lipid peroxidation products in rat cortex and hippocampus under conditions of acute hypoxia.
The effects of melatonin and epithalamin on the content of protein and lipid peroxidation products in the cortex and hippocampus of hypoxic rats were studied under conditions of acute hypobaric hypoxia equivalent to the altitude of 12,000 m. Pineal preparations reduced the intensity of free-radical processes in the brain exposed to acute hypoxia. Epithalamin more effectively than exogenous melatonin protected hippocampal neurons during acute hypoxia by reducing free-radical damage to lipids and proteins.


Decreased Pneumococcal Carriage Among Older Adults in Denmark During the COVID-19 Lockdown.
COVID-19 containment measures reduced the burden of invasive pneumococcal disease. Data on pneumococcal carriage rates among adults during the pandemic are scarce. Naso- and oropharyngeal swabs and questionnaires were collected during January 2019 to December 2021 from adults ≥64 years of age. Carriage was determined by lytA/piaB PCR. A total of 1556 participants provided paired naso- and oropharyngeal swabs. Their median age was 74 years (IQR, 70-79). Streptococcus pneumoniae DNA was detected in 146 (9.4%) oropharyngeal swabs and 34 (2.2%) nasopharyngeal. The carriage rate decreased from 12.9% (95% CI, 10.1%-16.1%, n = 66/511) prelockdown (January 2019-February 2020) to 4.2% (95% CI, 2.0%-7.5%, n = 10/240) during lockdown (March 2020-February 2021) and increased to 12.1% (95% CI, 9.8%-14.7%, n = 87/719) with the reopening of society (March 2021-December 2021; P = .0009). Pneumococcal carriage prevalence declined significantly during pandemic mitigation measures and rebounded to prepandemic levels as measures were lifted.


The 1933 Long Beach Earthquake (California, USA): Ground Motions and Rupture Scenario.
We present a synoptic analysis of the ground motions from the 11 March 1933 Mw 6.4 Long Beach, California, earthquake, the largest known earthquake within the central Los Angeles Basin region. Our inferred shaking intensity pattern supports the association of the earthquake with the Newport-Inglewood fault; it further illuminates the concentration of severe damage in the town of Compton, where accounts suggest vertical ground motions exceeding 1 g. We use a broadband simulation approach to develop a rupture scenario for this earthquake, informed by the damage distribution. The predicted shaking for a 25-km-long fault matches the intensity distribution, with an indication that non-linear site response on soft sediments in some near-field regions was stronger than predicted using a simple model to account for non-linearity. Our results suggest that the concentration of damage near Compton can be explained by a combination of local site amplification, source-controlled directivity, and three-dimensional basin effects whereby energy was channeled towards the deepest part of the Los Angeles Basin.


CYP1A1-mediated mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons.
Polycyclic aromatic hydrocarbons (PAHs) have been known to induce atherosclerosis. It has been reported that the metabolic activation of PAHs by cytochrome P450 (CYP) is an important step for PAH-induced atherosclerosis. We recently reported that PAHs down-regulated the liver X receptor (LXR) alpha-regulated genes via aryl hydrocarbon receptor (AHR) as one of the causes responsible for atherosclerosis induced by PAHs. Thus, the aim of this study was to clarify the role of CYP1A1 in the suppression of LXR-mediated signal transductions by 3-methlychoranthrene (MC), one of the PAHs. We found that LXR-mediated transactivation was inhibited by the PAH, but not by halogenated aromatic hydrocarbon, which is scarcely metabolized by CYP1A1. The repression of LXR-mediated signal transductions by MC was restored by co-treatment of HepG2 cells with a CYP1A1 inhibitor, alpha-naphthoflavone, and by the transfection of short interference RNA for CYP1A1. Based on these lines of evidence, we propose that the metabolic activation of PAHs by CYP1A1, but not the activation of AHR by PAHs, is a direct mechanism for atherosclerosis via the suppression of LXR-mediated signal transductions.


Antibiofilm properties of bioactive compounds from Actinomycetes against foodborne and fish pathogens.
In nature, bacteria can form biofilms, multi-layered structures that adhere microbial populations to solid surfaces by exopolysaccharides, proteins, and nucleic acids. In addition to causing foodborne infections, biofilms can be a major problem in aquaculture. Actinomycetes extracts have previously demonstrated antibiofilm activity against multiple foodborne and fish pathogens, and further characterization of these extracts is needed. In this study, we identified the chemical structures and antibiofilm properties of four extracts and determined the genetic similarity of the isolates to known Streptomyces isolates. We found that several extracts contained multiple antibiofilm compounds, and the antibiofilm activities of all extracts were most stable at pH 6. Furthermore, the antibiofilm inhibition and destruction activities of the isolates were stable at different temperatures. All of crude extracts demonstrated activity against biofilms formed by foodborne and fish pathogens on the surface of stainless-steel coupons as well as polystyrene that commonly used in industrial equipment. Using PCR 16S-rRNA gene and DNA sequencing analysis, the four Actinomycetes isolates were found to be 99% (1 AC), 97% (20 PM), 95% (16 PM), and 85% (18 PM) similar to Streptomyces. Biofilm structure were analyzed using Scanning Electron Microscopy coupled with Energy-Dispersive Spectrometry analysis. Coniine/(S)-2-propylpiperidine was the most active fraction of the crude extracts of the 1 AC, 20 PM, and 16 PM isolates, and piperidine, 2-(tetrahydro-2-furanyl) was most active in the 18 PM isolate.


The long non-coding RNA, MHM, plays a role in chicken embryonic development, including gonadogenesis.
MHM is a chicken Z chromosome-linked locus that is methylated and transcriptionally silent in male cells, but is hypomethylated and transcribed into a long non-coding RNA in female cells. MHM has been implicated in both localised dosage compensation and sex determination in the chicken embryo, but direct evidence is lacking. We investigated the potential role of MHM in chicken embryonic development, using expression analysis and retroviral-mediated mis-expression. At embryonic stages, MHM is only expressed in females. Northern blotting showed that both sense and antisense strands of the MHM locus are transcribed, with the sense strand being more abundant. Whole mount in situ hybridization confirmed that the sense RNA is present in developing female embryos, notably in gonads, limbs, heart, branchial arch and brain. Within these cells, the MHM RNA is localized to the nucleus. The antisense transcript is lowly expressed and has a cytoplasmic localization in cells. Mis-expression of MHM sense and antisense sequences results in overgrowth of tissues in which transcripts are predominantly expressed. This includes altered asymmetric ovarian development in females. In males, MHM mis-expression impairs gonadal expression of the testis gene, DMRT1. Both MHM sense and antisense mis-expression cause brain abnormalities, while MHM sense causes an increase in male-biased embryo mortality. These results indicate that MHM has a role in chicken normal embryonic development, including gonadal sex differentiation.


A study of the relationship between professional values and ethical climate and nurses' professional quality of life in Iran.
To explore the relationship between nursing professional values and ethical climate and nurses' professional quality of life. The present study is a descriptive, cross-sectional work in which 400 nurses from various wards of hospitals in the south-east of Iran were studied. Data were collected using a questionnaire consisting of four sections: demographics, Nurses' Professional Values Scale-Revised (NPVS-R), the Hospital Ethical Climate Survey (HECS), and the Professional Quality of Life Scale (ProQOL). The total mean scores for professional values were 105.29 ± 15.60. The total mean score for the ethical climate was 100.09 ± 17.11. The mean scores for the indexes of compassion satisfaction, burnout, and secondary traumatic stress were 45.29 ± 8.93, 34.38 ± 6.84, and 32.15 ± 7.02 respectively. The relationships between professional values and the indexes of compassion satisfaction (r = 0.56), burnout (r = 0.26), and secondary traumatic stress (r = 0.18) were found to be positive and significant (P < 0.001). Also, the relationships between ethical climate and the items of compassion satisfaction (r = 0.60, P < 0.001), burnout (r = 0.15, P = 0.002) were found to be positive and significant. An understanding of nurses' perception of professional values and improving the ethical climate at work can help nursing administrators identify more effective strategies toward increasing compassion satisfaction and lessening burnout and work-related stress.


Supporting and Protecting Residents Experiencing Homelessness in the Nation's Largest Cities During COVID-19.
Large urban health departments developed and implemented various approaches to prevent COVID-19 outbreaks and promote the health and well-being of individuals experiencing homelessness and housing insecurity throughout the pandemic. Reviewing the approaches of several large urban health departments, the most frequent practices included increasing housing options, on-the-ground outreach and resource allocation, and integrated communications. Key steps necessary to develop and implement these policies and procedures are discussed, and innovative approaches are highlighted.


Allergic skin testing: a clinical investigation.
Forty patients were administered a total of 2,395 skin tests in order to assess the effects of method, concentration, diluent, manufacturer, and mixtures on patient reaction to inhalant extract solutions. The prick method was found to be superior to the scratch method. The intracutaneous technique exhibited the greatest degree of specificity. Patients reacted at a higher level to higher concentrations of extract solution, descending to a lower level of reaction to lesser concentrations of extract solution. Patient reactions were variable to aqueous vs glycerin solutions. Clear differences in the potency of extract solutions produced by manufacturers A, B, and C were evident. Specifically, the products of manufacturer C were least potent. The results illustrate the possibility of a dilution factor existing in mixtures of extract solutions, producing a decrease in their potency when compared to the potency of their individually administered components. A technique with the potential for wide acceptance and clinical applicability is proposed.


Defective DNA repair and cell cycle arrest in cells expressing Merkel cell polyomavirus T antigen.
The pathways by which Merkel cell polyomavirus (MCV) infection contributes to the formation of Merkel cell carcinomas are important for understanding the pathogenesis of these cancers. We hypothesized that MCV T antigen suppresses normal responses to ultraviolet radiation (UVR)-induced DNA damage. An MCV-infected cell line (MKL-1) exhibited UVR hypersensitivity, impaired repair of DNA lesions and cell cycle arrest after UVR, as well as reduced levels of the DNA damage recognition protein, XPC. When ectopically expressed in uninfected UISO cells, mutant but not wild-type T antigen resulted in loss of repair of UVR-induced cyclobutane pyrimidine dimers and reductions in XPC, p53 and p21 levels, whereas both wild-type and mutant T antigen inhibited cell cycle arrest after UVR. Similarly, only mutant T antigen in normal fibroblasts inhibited DNA repair and XPC expression, while both mutant and wild-type T antigens produced cell cycle dysregulation. Wild-type T antigen expression produced large T, 57 kT and small T antigens while mutant T antigen was only detectable as a truncated large T antigen protein. Expression of wild-type large T antigen but not small T antigen inhibited the G1 checkpoint in UISO cells, but neither wild-type large T nor small T antigens affected DNA repair, suggesting that large T antigen generates cell cycle defects, and when mutated may also impair DNA repair. These results indicate that T antigen expression by MCV can inhibit key responses to UVR-induced DNA damage and suggest that progressive MCV-mediated abrogation of genomic stability may be involved in Merkel cell carcinogenesis.


The impact of organised screening programmes on the stage-specific incidence of breast cancer in some Italian areas.
The aim of this study was to examine the effects of mammographic screening programmes on stage-specific incidence of breast cancer. The study compared prescreening and screening periods in seven areas in Italy, primarily evaluating the first screening round. All 17617 breast cancers (16554 invasive, 1063 in situ) registered in women aged 40-79 years between 1988 and 1999 were analysed through age-standardised rates and Poisson regression models. For all areas, independent of the baseline rates, the introduction of screening increased incidence for invasive cancers overall and, more markedly, for early cancers (screening/prescreening ratio: range 1.07-1.47 and 1.23-1.82, respectively), modifying the pattern of age-specific rates. The multiple regression analysis showed that the percentage of cases diagnosed at screening explained most of the increase; a residual effect of diagnosis period (screening versus prescreening) suggested a role for 'spontaneous' early detection in ages outside of the screening programme. Advanced cases did not show consistent variations across the registries for those aged 40-79 years (range: 0.91-1.21), whereas a more coherent picture was observed for those aged 50-69 years. In one area, a moderate reduction in the number of 'advanced' cases in the second screening period was observed. For all stages, the age-specific incidence rates of cases diagnosed outside of the screening programme for the age groups 50-69 years were lower than the corresponding rates in the prescreening period, suggesting a shift from the usual clinical services to the screening programme. Our results confirmed the increase in early-stage cancers occurring at the start of screening, and substantially explained the rise in breast cancer incidence. In addition, our study confirms the importance of cancer registries in monitoring the effect of breast cancer screening and the validity, for this purpose, of the linkage between cancer registries and screening programme databases.


The effect of a single session submaximal aerobic exercise on premotor fraction of reaction time: an electromyographic study.
Numerous studies investigating the effect of exercise on reaction time have yielded contradictory results. Most of the studies use computer based methods to measure reaction time instead of electromyography, yielding total reaction time rather than premotor time. In this study, we aimed to investigate the effect of a single session aerobic exercise on premotor fraction of reaction time in sedentary healthy individuals. Twenty-two sedentary healthy subjects (11 subjects for the study group and 11 for the control group) enrolled in this study. Subjects in the exercise group performed a single session submaximal cycling exercise. Electromyographic reaction times were measured before and after the exercise session. In the control group, reaction time measurements were taken twice with an interval of 20 min. In the exercise group, premotor fraction of reaction time values decreased considerably (P=0.01) after the exercise session. A single bout of cycling exercise significantly improved premotor fraction of reaction time in healthy young sedentary subjects. Physical activity improves not only physical fitness but also cognitive functions. Electromyographic reaction time evaluations may be used in the sports medicine field where both aerobic fitness and short reaction time are indispensable demands.


Plasma-Enhanced Chemical-Vapor-Deposition Synthesis of Photoredox-Active Nitrogen-Doped Carbon from NH3 and CH4 Gases.
Earth's primordial atmosphere was rich in ammonia and methane. To understand the evolution of the atmosphere, these two gases were used to make photoredox-active nitrogen-doped carbon (NDC). Photocatalysts such as NDC might play an important role in the development of geological and atmospheric chemistry during the Archean era. This study describes the synthesis of NDC directly from NH3 and CH4 gases. The photocatalyst product can be used to selectively synthesize imines by photo-oxidization of amines, producing H2 O2 simultaneously in the photoreduction reaction. Our findings shed light on the chemical evolution of the Earth.


Donor specificity and regioselectivity in Lipolase mediated acylations of methyl α-D-glucopyranoside by vinyl esters of phenolic acids and their analogues.
Methyl α-D-glucopyranoside as a model acceptor was acylated by several phenolic and non-phenolic vinyl esters using immobilised Lipolase. Donor specificity and regioselectivity of reaction were investigated. Conversion and rate of acylation by structurally varied donors indicates that the synthetic reactivity of Lipolase corresponds to the hydrolytic activity of feruloyl esterase type A. Lipolase exhibited remarkable regioselectivity for primary position of methyl α-D-glucopyranoside. The acylation occurred exclusively at 6-O primary position when vinyl esters of phenolic acids (hydroxybenzoates, hydroxyphenylalkanoates and hydroxycinnamates) served as acyl donors (5-77%). In addition to the major 6-O-acyl products (52-79%), 2,6-di-O-acylated derivatives were isolated from reaction mixtures (2-13%) when non-phenolic donors were used (vinyl esters of fully methoxylated derivatives of phenolic acids, along with vinyl benzoates, cinnamates or some heterocyclic analogues).


Remediation of chlorinated aliphatic hydrocarbons (CAHs) contaminated site coupling groundwater recirculation well (IEG-GCW®) with a peripheral injection of soluble nutrient supplement (IEG-C-MIX) via multilevel-injection wells (IEG-MIW).
An innovative Groundwater Circulation Well (GCW) process was configured, installed, and tested for optimizing the distribution of a soluble nutrient supplement in a heterogeneous aquifer for reductive dehalogenation. This generated an in-situ bioreactor for the enhanced treatment of chlorinated aliphatic hydrocarbons (CAHs). At a site in Barcelona, Spain, trichloroethylene (TCE) concentration was found in the source area to a maximum value of up to 170 mg/L, while the degradation products like 1,2-dichloroethylene (1,2-DCE) and vinyl chloride (VC) were detected in significantly lower concentrations or were even absent. The novel system combined a vertical recirculation well (IEG-GCW®) and four multilevel injection wells (IEG-MIWs) to introduce the carbon solution into the aquifer. A 12 m deep IEG-GCW® equipped with 2 screened sections were located in the center of the 4 IEG-MIWs. The GCW induced flow moves the groundwater in an ellipsoidal recirculation cell to spread the supplements from the central GCW and from the peripheral MIWs in the aquifer body. Two multilevel sampling wells (IEG-MLSWs®) in the radius of influence (ROI) monitor the remediation process to capture hydrochemical variations along the vertical aquifer sections. A multi-source model harmonizes geological and hydrochemical information during different remediation stages, guiding the adaptation of the remediation strategy to physicochemical conditions and unmasking the decontamination mechanics induced by the remedial actions. Hydrochemical monitoring of MLWS and the stable carbon isotopic signature of cis-1,2-DCE and VC show the mobilization of secondary contamination sources triggered by recirculation during remediation, the stimulation of microbiological activity following nutrient supplement via GCW and MIWs, and the strong decrease of CAHs concentrations at different aquifer levels. Evidence from the first application at the field scale reveals a significant increase in the chloroethane biodegradation rate and short-term effectiveness of the innovative remediation strategy. GCW-MIWs synergy represents a promising strategy to degrade CAHs in a shorter period through the combination of a controllable hydraulic system, effective nutrient distribution, and the monitoring of the remediation process.


A ditopic calix[6]arene ligand with N-methylimidazole and 1,2,3-triazole substituents: synthesis and coordination with Zn(II) cations.
The first member of a new class of ditopic calix[6]arene has been synthesized, which is decorated with three N-methylimidazoles at the small rim and three 1,4-disubstituted-1,2,3-triazoles at the large rim. The coordination of a first Zn(II) cation selectively takes place at the small rim. Addition of a second equivalent results in the complexation of the three triazoles, providing a rare example of 1,2,3-triazole ligands embedded within a supramolecular system.


Cu(I)-catalyzed synthesis of imidazo[1,2-a]pyridines from aminopyridines and nitroolefins using air as the oxidant.
A copper-catalyzed method for the synthesis of imidazo[1,2-a]pyridines with aminopyridines and nitroolefins using air as oxidation agent in a one-pot procedure has been developed. In this process, the reaction appears to be very general and suitable for construction of a variety of imidazo[1,2-a]pyridines.


Prophylactic effect of angiotensin receptor blockers in children with genetic aortopathies: the early bird catches the worm.
In genetic aortopathies (GA) particular attention is paid to aortic root dilatation which has an impact on morbidity and mortality. This study focuses on the effects of therapy with angiotensin-II-receptor-blockers (ARB) or beta-blockers (BB) on aortic root growth and the question which therapy should be initiated at which dosage and at what age. Since 1998 we diagnosed 208 patients with GA (170 FBN-1). 81 patients between 5 months and 18 years receiving either ARB or BB therapy were included. We retrospectively analyzed the progression of the dilatation of Sinus Valsalva aortae (SV) using calculated z-scores before and after therapy initiation and compared BB and ARB treatment. Both ARB and BB (p < 0.05) therapy showed significant improvement in aortic root growth, while the effect is significantly more pronounced in ARB (p < 0.01) independent of age and genetic cause. A detailed comparison of the two drug groups showed a more sustained effect in limiting the progression of the dilatation of the aortic root in patients treated with ARB. Progression of dilatation of the SV was significantly lower in children treated with ARBs compared to BB (delta z-score, p < 0.05). In addition, ARBs were better tolerated and had a significantly lower discontinuation rate (3%) compared to BB (50%) (p < 0.01). Independently of age at initiation all children and adolescents were able to reach the target dose under ARB. We demonstrated a significant change in both treatment options, with the effect of ARB being more pronounced while being better tolerated throughout the treatment period.


Fetal echocardiography at 11 + 0 to 13 + 6 weeks using four-dimensional spatiotemporal image correlation telemedicine via an Internet link: a pilot study.
To assess whether spatiotemporal image correlation (STIC) volumes from fetuses at 11 + 0 to 13 + 6 weeks' gestation can be obtained by a non-expert and whether fetal echocardiography can be performed via a telemedicine link, providing a remote and reproducible diagnosis of the fetal heart condition. STIC volume datasets from 35 fetuses at 11 + 0 to 13 + 6 weeks were obtained prospectively by a general obstetrician, transmitted via the Internet and subsequently analyzed systematically by two different reviewers. Forty-nine pregnancies were initially enrolled into the study, but adequate volumes were not obtained for 14. Thirty-four datasets were obtained on transabdominal and one on transvaginal ultrasound examination. A checklist was used that included 18 structures and views relating to the fetal heart evaluation, and each reviewer assigned the variables as normal, abnormal or unsure. Cohen's kappa analysis was used to evaluate the agreement between reviewers and the reported findings were compared with the outcome where available. The mean gestational age was 12 + 3 weeks and the mean (range) crown-rump length was 68 (47-84) mm. The mean maternal age was 33 (range, 26-41) years; 12/35 (34%) were older than 35 years. The four-chamber view obtained was apical in 22/35 (63%) cases and lateral in 13 (37%). Volume datasets were obtained after 12 weeks' gestation in 30/35 fetuses. Three cases had nuchal translucency thickness above the 99(th) percentile, and two of these had an abnormal heart. Five cases had abnormal outcomes. A mean of 3 (range, 1-6) STIC datasets per patient were acquired. The kappa index obtained confirmed interobserver reliability, with good or very good concordance (kappa > 0.6) in 14/18 structures and views related to the heart. STIC volumes acquired between 11 + 0 and 13 + 6 weeks' gestation could be sent over the Internet and their analysis enabled recognition of most of the structures and views necessary to assess the small fetal cardiac anatomy, with a high degree of interobserver concordance.


Mapping the transcription start points of the Staphylococcus aureus eap, emp, and vwb promoters reveals a conserved octanucleotide sequence that is essential for expression of these genes.
Mapping the transcription start points of the eap, emp, and vwb promoters revealed a conserved octanucleotide sequence (COS). Deleting this sequence abolished the expression of eap, emp, and vwb. However, electrophoretic mobility shift assays gave no evidence that this sequence was a binding site for SarA or SaeR, known regulators of eap and emp.


Vegetation Classification and Distribution Patterns in the South Slope of Yarlung Zangbo Grand Canyon National Nature Reserve, Eastern Himalayas.
Yarlung Zangbo Grand Canyon National Nature Reserve has the most complete vertical vegetation belts in China. However, identification and distribution of vertical vegetation belts is still uncertain and in debate. To explore the above issues, 190 plots were surveyed within the reserve from 2019 to 2021. Based on the vegetation plot data, cluster analysis, ordination analysis, and biodiversity statistics were performed to reveal the structure of vertical vegetation belts-the driving factors of vegetation distribution-to describe the main biodiversity patterns. Five vertical vegetation belts were identified by clustering. NMDS ordination showed that the main factor of vegetation distribution is elevation. Based on the results of the analysis and previous literature, a new scheme of vertical vegetation belts in the south slope of the reserve was proposed. There was a lower montane seasonal rainforest belt (600-1100 m), a lower montane evergreen broadleaf forest belt (1100-1800 m), a middle montane semi-evergreen broadleaf forest belt (1800-2400 m), a subalpine evergreen needleleaf forest belt (2400-3800 m), a alpine shrubland and meadow belt (3800-4400 m), an alpine sparse vegetation belt (4400-4800 m), and a nival belt (4800-7782 m). Among them, the seasonal rainforest belts are the northernmost distribution of this type, and the semi-evergreen broadleaf forest belts exist only in the Eastern Himalayas. The study showed a unimodal pattern in plant species diversity, the peak of which is about 1900 m. The middle montane semi-evergreen broadleaf forest belt had the highest species diversity in the reserve. This study settled the issues regarding the vertical vegetation belts, the main drivers of vegetation and assessment of plant species diversity in the south slope of the Yarlung Zangbo Grand Canyon National Nature Reserve. It provides essential support for the management and conservation of these ecosystems in the reserve.


Pancreatic trypsin inhibitor. A new crystal form and its analysis.
Basic pancreatic trypsin inhibitor (Trasylol) was crystallized in a new crystal form with space group P212121 and lattice constants a = 74.1 A, b = 23.4 A, c = 28.9 A. Its structure was determined at 0.94 A resolution applying Patterson search techniques.


Modifiable risk factors for diphtheria: A systematic review and meta-analysis.
To identify modifiable risk factors for diphtheria and assess their strengths of association with the disease. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Electronic databases and grey literature were searched from inception until January 2023. Studies had to report on diphtheria cases and estimates of association for at least one potential risk factor or sufficient data to calculate these. The quality of non-ecological studies was assessed using the Newcastle-Ottawa Scale (NOS), while the quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. The search yielded 37,705 papers, of which 29 were ultimately included. All the non-ecological studies were of moderate to high quality. Meta-analysis of 20 studies identified three factors increasing the risk of diphtheria: incomplete vaccination (<3 doses) (pooled odds ratio (POR) = 2.2, 95% confidence interval (CI) = 1.4-3.4); contact with a person with skin lesions (POR = 4.8, 95% CI = 2.1-10.9); and low knowledge of diphtheria (POR = 2.4, 95% CI = 1.2-4.7). Contact with a case of diphtheria; sharing a bed or bedroom; sharing utensils, cups, and glasses; infrequent bathing; and low parental education were associated with diphtheria in multiple studies. Evidence for other factors was inconclusive. The quality of evidence was low or very low for all the risk factors. Findings from the review suggest that countries seeking to control diphtheria need to strengthen surveillance, improve vaccination coverage, and increase people's knowledge of the disease. Future research should focus on understudied or inconclusive risk factors.


Tails don't tell the whole story.
Before engaging G protein-coupled receptors (GPCRs) to transduce extracellular signals, heterotrimeric G proteins (Gαβγ) must fold properly with the help of chaperones. In this issue of Structure, Papasergi-Scott et al. (2023) unveil the molecular basis for how mammalian Ric-8 chaperones achieve selectivity for their respective Gα subunit clients.


Noradrenergic transmission in isolated guinea-pig intestine following in vivo administration of antibodies to dopamine beta-hydroxylase.
The effectiveness of transmission from noradrenergic nerves supplying the guinea-pig ileum was evaluated in normal preparations and in preparations taken from animals injected 18 h to 4 days previously with antiserum to dopamine beta-hydroxylase. Degeneration of the nerves following the antiserum was monitored histochemically in the same preparations. A decline in the effectiveness of transmission, which paralleled the degeneration of the nerves, was observed. The earliest effects were detected at 18 h and the greatest effect was found at 2-4 days following the administration of antiserum. Binding of the antibodies has been detected as early as 6 h after injection. It is therefore concluded that binding of the antibodies to the nerves, per se, does not significantly compromise transmission, and that histochemical evidence of degeneration can be used to indicate the onset of functional deterioration of noradrenergic nerves following their exposure to antibodies to dopamine beta-hydroxylase.


Waist-to-height ratio and dynapenic abdominal obesity in users of hemodialysis services.
Abdominal obesity and decreased muscle strength are risk factors for individuals on hemodialysis. Thus, the combination of these two factors known as dynapenic abdominal obesity acts as an important marker of the nutritional status of this population. Therefore, the objective of the work was to investigate the association between abdominal obesity, dynapenia, and sociodemographic, clinical, and nutritional factors in individuals with chronic kidney disease undergoing hemodialysis. Cross-sectional study with 940 individuals undergoing hemodialysis in southeastern Brazil. Dynapenic abdominal obesity was defined by the combination of the presence of abdominal obesity, indicated by the waist-to-height ratio, and the reduction in muscle strength, measured by handgrip strength. Binary logistic regression was performed to calculate the odds ratio (OR) and the respective confidence intervals (95% CI). Dynapenic abdominal obesity was present in 45.42% of the study population. We found that being 18-59 years (OR: 3.17; 95% CI 2.35-4.28; p < 0.001) and being overweight (OR: 2.58; 95% CI 1.92-3.47; p < 0.001) increased the chances for the presence of dynapenic abdominal obesity; however, the habit of consuming meals away from home (OR: 0.63; 95% CI 0.47-0.85; p = 0.003) and having preserved behavioral adductor muscle thickness (OR: 0.52; 95% CI 0.38-0.71; p < 0.001) are considered protective factors. Dynapenic abdominal obesity, present in individuals on hemodialysis, may represent a valid nutritional tool for assessing cardiovascular risk and mortality in this population, in order to implement the most effective preventive and/or therapeutic intervention possible.


The CUSUM statistic of change point under NA sequences.
In this paper, we investigate the CUSUM statistic of change point under the negatively associated (NA) sequences. By establishing the consistency estimators for mean and covariance functions respectively, the limit distribution of the CUSUM statistic is proved to be a standard Brownian bridge, which extends the results obtained under the case of an independent normal sample and the moving average processes. Finally, the finite sample properties of the CUSUM statistic are given to show the efficiency of the method by simulation studies and an application on a real data analysis.


User-Centered Design of the consideRATE Questions, a Measure of People's Experiences When They Are Seriously Ill.
No brief patient-reported experience measure focuses on the most significant concerns of seriously ill individuals. The objective of the study was to develop the consideRATE questions. This user-centered design study had three phases. We reviewed the literature and consulted stakeholders, including caregivers, clinicians, and researchers, to identify the elements of care most important to patients (Phase 1). We refined items based on cognitive interviews with patients, families, and clinicians (Phase 2). We piloted the measure with patients and families (Phase 3). Phase 1 resulted in seven questions addressing the following elements: 1) care team attention to patients' physical symptoms, 2) emotional symptoms, 3) environment of care, 4) respect for patients' priorities, 5) communication about future plans, 6) communication about financial and similar affairs, and 7) communication about illness trajectory. Phase 2 participants included eight patients, eight family members, and seven clinicians. We added an open-text comment option. We did not identify any other issues that were important enough to participants to include. Response choices ranged from one (very bad) to four (very good), with a not applicable option (does not apply). Phase 3 involved 15 patients and 16 family members and demonstrated the acceptability of the consideRATE questions. Most reported that the questions were not distressing, disruptive, or confusing. Completion time averaged 2.4 minutes (range 1-5). Our brief patient-reported serious illness experience measure is based on what matters most to patients, families, and clinicians. It was acceptable to patients and families in a regional sample. It has promise for use in clinical settings.


AR identification and spectral estimate applied to the R-R interval measurements.
The methods of identification and spectral estimate are applied to the tachogram, i.e. the time series constituted by the cycle-by-cycle R-R interval durations measured on the ECG signal from cardiological patients in ambulatory rehabilitation training after episodes of myocardial infarction or ischemic disease. The Batch Least Squares Method is applied to identify the series as an AR process of 5th order. The whiteness test and Rissanen's optimization criterion are also fulfilled. The clinical information is in this way highly compressed in the pole diagram and in the Maximum Entropy Spectrum (MES) estimated on the basis of the AR coefficients. The experimental results in a restricted set of patients confirm the feasibility of new instrumentation design criteria for non-conventional R-R intervals parametrisation, successive diagnostic classification and beat prediction. Finally, some preliminary considerations about the capabilities of the introduced methods put into evidence the role of computerized techniques in recognizing the fundamental patterns of physiopathological heart rate variability, which the usual conventional methods of ECG analysis are not able to detect in a reliable way.


Spontaneous retraction of indwelling catheters: previously unreported complications.
The development of totally implantable reservoir central venous access systems has been an important advance in patients requiring long-term central venous access. With lower rates of infection and thrombosis than those with external catheters, they have potential for greater longevity and patient acceptance. Complications such as subcutaneous prosthetic infection, infusate extravasation, and difficulty in locating and puncturing the port have been reported. We present two cases of catheter migration and withdrawal from the subclavian vein. This presumably occurred from the action of the underlying pectoralis muscle on the reservoir, as well as a "jetting effect" during flushing. We make suggestions for prevention of similar problems in the future.


Neurodevelopment in preterm infants with and without placenta-related intrauterine growth restriction and its relation to perinatal and postnatal factors.
Intrauterine-growth restriction is associated with impaired neurodevelopment. However, studies on early childhood neurodevelopment of premature infants with placenta-related intrauterine-growth restriction (IUGR) are scarce and heterogeneous. We aimed to analyze the impact of placenta-related IUGR on preschool age neurodevelopment in preterm infants, and to ascertain which prenatal and postnatal factors influence neurodevelopment in these infants. Prospective cohorts study: 48 placenta-related IUGR premature infants and 25 matched non-IUGR premature infants (mean gestational age: 31.4 and 31.6 weeks, respectively). Preschool neurodevelopment assessment with cognitive Bayley Scales III and with ASQ-III surveys (age interval: 34.07-42.50 months). Inter-cohort result comparison. Analysis of perinatal and environmental factors associated with impaired neurodevelopment in both cohorts. No statistically significant neurodevelopment differences were observed at preschool age between both preterm cohorts. Multivariate analysis of perinatal and environmental factors showed daycare, breastfeeding, higher parental educational level, and absence of severe neonatal morbidity to be associated with a lower risk of altered neurodevelopment at preschool age. Placenta-related IUGR does not have a significant impact on preschool neurodevelopment in our preterm patients. Instead, post-natal positive environmental factors such as parental educational level, breastfeeding, and daycare attendance make a difference towards an improvement in neurodevelopment in these infants.


Why very low density lipoprotein levels are normal in familial hyperchylomicronaemia.
The anomalous finding that very low density lipoprotein levels are relatively normal in patients with familial hyperchylomicronaemia has never been satisfactorily explained, particularly in view of the marked reduction or absence of peripheral lipoprotein lipase activity characteristic of this condition. I propose that the discrepancy between the plasma levels of the two triglyceride-rich lipoprotein fractions in these patients is due to the secretion by the liver of triglyceride in the form of chylomicron-like particles, rather than as very low density lipoprotein. The proposed "switch" in the spectrum of lipoproteins secreted by the liver is probably contingent upon the activity of the hepatic lipase present on the liver cell plasma membrane.


Anorectal symptoms before and after laparoscopic sacrocolpoperineopexy for pelvic organ prolapse.
To evaluate changes in anorectal symptoms before and after pelvic organ prolapse (POP) surgery, using laparoscopic sacrocolpoperineopexy. Preoperative and postoperative anorectal symptoms, colorectal-anal distress inventory (CRADI) and colorectal-anal impact questionnaire (CRAIQ) scores were prospectively compared from 90 consecutive women undergoing laparoscopic sacrocolpoperineopexy. After a median follow-up of 30.7 months, laparoscopic surgery significantly worsened CRADI (p = 0.02) with no effect on CRAIQ (p = 0.37) scores. Post-operative and de novo straining (27%) and the need for digital assistance (17%) were the most frequent anorectal symptoms. No correlation was found between laparoscopic surgery and anorectal symptoms after multivariate analysis (OR = 2.45[95% confidence interval 0.99-6.05], p = 0.05). Anorectal symptoms are not improved after POP surgery by laparoscopic sacrocolpoperineopexy.


Characterization of a nonhemagglutinating mutant of canine parvovirus.
A nonhemagglutinating mutant of a 1978 isolate of canine parvovirus (CPV) was derived after repeated passages in the NLFK feline kidney cell line. The mutant CPV was antigenically indistinguishable from wild-type virus when tested with 82 monoclonal antibodies, and it replicated in cat and dog cell lines in culture. Sequences of the VP-1 and VP-2 genes revealed two nucleotide and two predicted amino acid sequence differences at 77 and 88 genome map units in the mutant compared to hemagglutinating viruses. One or both of those two mutations must determine the difference in the ability of the virus to agglutinate erythrocytes.


Preservation of the temporal muscle during the frontotemporoparietal approach for decompressive craniectomy: technical note.
In patients undergoing decompressive craniectomy, resection and detachment of the temporal muscle produces esthetic and functional damage, due to atrophy of the frontal portion of the temporal muscle in the temporal fossa. We have performed en-block temporal muscle detachment in decompressive craniectomy patients to avoid esthetic and functional damage to the temporal muscle. Twenty-one patients underwent decompressive craniectomy using a frontotemporoparietal approach. Through a three-leaf clover flap skin incision, the temporal muscle was detached en-block and overturned antero-inferiorly conjoined with the frontal myocutaneous flap. A decompressive craniectomy and duraplasty were performed. A polyethylene sheet was added to prevent adherence of the temporal muscle to the dura mater. The decompressive craniectomy was effective in all patients. When subsequent cranioplasty was performed, the temporal muscle was easily repositioned. No complications resulted from the en-block temporal muscle detachment or the use of the polyethylene sheet. In 18 patients eligible for clinical and radiological follow-up, excellent (n = 4) or good (n = 14) esthetic results were detected. Chewing ability is considered normal by all patients. Although it requires that the patient undergo two surgical procedures, en-block detachment of the temporal muscle during decompressive craniectomy allows good esthetic and functional results.


In vivo biological effect of allogeneic cultured thymic epithelium on thymus-dependent immunity in athymic nude rats.
We have extended our previous study of induction of T-lymphocyte immunocompetence in athymic nude rats by cultured epithelium (CTE) of syngeneic origin to that by CTE of allogeneic origin. Immune responsiveness (IgG-class antibody and delayed-type hypersensitivity) after ovalbumin immunization is detectable by 4-6 weeks after transplantation. However, the antibody appears at a slower rate when compared with heterozygous immunocompetent littermates. Seven weeks after transplantation phytohaemagglutinin responsiveness of spleen cells is detectable, and in T-dependent areas of lymphoid organs lymphocytes with helper and non-helper T-cell phenotype are present, but at lower levels than those in heterozygous immunocompetent littermates. Levels comparable to that of immunocompetent rats are reached about 20 weeks after transplantation. Since CTE contains thymocytes, control experiments consisted of transplantation with high numbers of allogeneic freshly isolated thymocytes in athymic nude rats. These animals showed IgG-class antibody formation after ovalbumin immunization, but at lower levels than CTE-treated rats, and were almost negative in T-cell immunocompetence assessed in the other assays. We conclude that CTE of allogeneic origin induces T-cell immunocompetence in athymic nude rats to the level of heterozygous immunocompetent littermates. This study adds to the rationale of CTE transplantation applied in treatment of thymic dysfunction.


Co-expression of the toleragenic glycoprotein, CD200, with markers for cancer stem cells.
Tumor immunology fundamentals suggest immunological surveillance has the ability to recognize malignant cells and kill them before a tumor develops. However, cancer cells employ evasion mechanisms whereby the immune system may be actively suppressed or even tolerized to the tumor. Recently cancer stem cells were linked to tumor initiation and formation. However, no reports have addressed whether these cells participate in a tumor's ability to evade immune surveillance. Recently the glycoprotein CD200, expressed within the innate immune system and other tissues and cells, was shown to be involved in tolerance. Here we describe CD200 co-expression with stem cell markers found on prostate, breast, brain, and colon cancers. This is the first report describing an immunomodulatory molecule on epithelial cancer stem cells. This important finding suggests a mechanism by which a tumor might evades immune system detection.


Scotopic vision in colour-blinds.
Alleles causing colour-blindness are present in humans at non-negligible levels, and it is not yet understood how colour-blindness is maintained, since colour-vision probably provides a selective advantage, e.g. when foraging. We show that after dark-adaptation colour-blinds had lower light perception thresholds than colour-normals (0.44 log-units), which may give a selective advantage under scotopic conditions, which may offset the disadvantage that colour-blinds suffer during foraging.


Hierarchical nanostructures of Au@ZnO: antibacterial and antibiofilm agent.
The perpetual use of antibiotics against pathogens inadvertently altered their genes that have translated into an unprecedented resistance in microorganisms in the twenty-first century. Many researchers have formulated bactericidal and bacteriostatic inorganic nanoparticle-based antiseptics that may be linked to broad-spectrum activity and far lower propensity to induce microbial resistance than organic-based antibiotics. Based on this line, herein, we present observations on microbial abatement using gold-based zinc oxide nanostructures (Au@ZnO) which are synthesized using hydrothermal route. Inhibition of microbial growth and biofilm using Au@ZnO is a unique feature of our study. Furthermore, this study evinces antimicrobial and antibiofilm mechanisms of photo-eradiated Au@ZnO by disruption of cellular functions and biofilms via reactive oxygen species (ROS)-dependent generation of superoxide anion radical. The present study is significant as it introduces novel functionalities to Au@ZnO in the biomedical field which can be extended to other species of microbial pathogens.


Convergent succession of phytoplankton in microcosms with different inoculum species composition.
Different initial mixtures of phyto-and zooplankton from different lakes were grown under identical chemical and physical conditions in medium size (8-and 12-1) laboratory microcosm cultures until convergence of phytoplankton species composition was attained. Five such experiments with four (four experiments) or three (one experiment) microcosm cultures were run. Three experiments were performed with weak stirring which permitted sedimentary elimination of the diatoms. Two experiments were conducted with stronger stirring to prevent sedimentation. In the three "sedimentation intensive" experiments, the final phytoplankton community was composed of the filamentous chlorophyte Mougeotia thylespora together with a smaller biomass of nanoplanktic algae. In the two "sedimentation free" experiments the final phytoplankton community consisted of pennate diatoms. Both dissolved nutrient concentrations and the chemical composition of biomass suggested strong nutrient limitation of algal growth rates in the final phase of the experiments. The zooplankton communities at the end of the experiments were composed of species that were apparently unable to ingest the large, dominant algae and that presumably fed on the nanoplanktic "undergrowth" and the bacteria. There was a distinct sequence of events in all experiments: first, the large zooplankton species (Daphnia and Copepoda) were replaced by smaller ones (Chydorus, Bosmina, rotifers); second, all cultures within one experiment developed the same nutritional status (limitation by the same nutrient); and third, the taxonomic composition of phytoplankton of the different cultures within one experiment converged. The last took 7-9 weeks, with is about 2-3 times as long as the time needed in a phytoplankton competition experiment to reach the final outcome.


Neonatal small intestinal motility: motor responses to feeding in term and preterm infants.
To explore the possibility that the intestinal motor response to feeding is intact even in infants with immature fasting patterns, we performed low-compliance, continuous-infusion manometry in 13 term and 23 preterm infants during the first postnatal week. Babies were fed a standard formula intraduodenally at 4 ml/kg/2 hr by infusion pump. Small bowel motility responded to feeding; fasting patterns were replaced with long periods of persistent activity. During the infusion of formula, there was no significant difference in motor activity between preterm and term infants. Four characteristics of motor activity changed with feeding: motility index, the number of pressure peaks per 30-minute period, mean amplitude of pressure peaks, and duration of periods of quiescence. The number of pressure peaks per 30-minute period was the most sensitive index of the motor response to feeding, and it was used to characterize the fed pattern response. The start and duration of the fed response were similar in both groups of infants. Thus, despite the presence of immaturity in fasting patterns, the intestine of the preterm infant responds appropriately to feeding. These data help explain why preterm infants usually tolerate antral feedings, and support their use.


Preoperative home-based physical therapy versus usual care to improve functional health of frail older adults scheduled for elective total hip arthroplasty: a pilot randomized controlled trial.
To investigate the feasibility and preliminary effectiveness of a home-based intensive exercise program to improve physical health of frail elderly patients scheduled for elective total hip arthroplasty (THA). Single-blind pilot randomized controlled trial. Patients' homes and a general hospital in The Netherlands. Frail patients (N=30) older than 65 years. A preoperative, home-based program supervised by an experienced physical therapist to train functional activities and walking capacity. The control group received usual care consisting of 1 session of instructions. Feasibility was determined on the basis of adherence to treatment, patient satisfaction, adverse events, walking distance (measured with a pedometer), and intensity of exercise (evaluated with the Borg scale). Preliminary pre- and postoperative effectiveness was determined by the Timed Up & Go (TUG) test, 6-minute walk test (6MWT), Chair Rise Time, and self-reported measures of functions, activities, and participation. Patient satisfaction and adherence to the training were good (median=5 on a 5-point Likert scale) and no serious adverse events occurred. The Borg score during training was 14 (range, 13-16). Preoperative clinical relevant differences on the TUG test (2.9 s; 95% confidence interval [CI], -0.9 to 6.6) and significant differences on the 6MWT (41 m; 95% CI, 8 to 74) were found between groups. Intensive preoperative training at home is feasible for frail elderly patients waiting for THA and produces relevant changes in functional health. A larger multicenter randomized controlled trial is in progress to investigate the (cost-)effectiveness of preoperative training.


Overshadowing as a function of trial number: dynamics of first- and second-order comparator effects.
In two conditioned lick suppression experiments with rats, we examined the permanence of the overshadowing effect as a function of the number of compound reinforced training trials. In Experiment 1, robust overshadowing was observed following 4 compound-US pairings but dissipated with 36 pairings. Overshadowing decreased because responding to the overshadowed stimulus increased, not because responding by the control group decreased. This dissipation was stimulus specific and not attributable to a response ceiling. Experiment 2 extended the generality of the effect to a sensory preconditioning design and further demonstrated that overshadowing lost through many compound-US pairings was restored by posttraining extinction of the training context. The results are explicable in terms of the extended comparator hypothesis (Denniston, Savastano, & Miller, 2001) under the assumption that the impacts of first- and second-order comparator processes grow differentially as a function of number of trials.


LASER demarcation photocoagulation for rhegmatogenous retinal detachments.
to evaluate demarcation laser photocoagulation (DLP) for macula-sparing rhegmatogenous retinal detachments (RRD) with and without symptoms of posterior vitreous separation or progressive visual field defect. retrospective, interventional, single surgeon case series of consecutive patients with RRD treated with demarcation laser photocoagulation between March 1999 and February 2008 at an academic center. The null hypothesis was that there exists no difference in the rate of progression for retinal detachment irrespective of the presence ('symptomatic') or absence ('asymptomatic') of symptoms of posterior vitreous separation or visual field defect at presentation. a total of 27 eyes of 26 patients were included in the study. In all, 22 of the 27 eyes (81.4%) did not require additional treatment and remained attached during mean follow-up of 38.4 months. None of the 14 asymptomatic patients required surgery (0%) whereas 5 out of the 13 patients (38.5%) who were symptomatic at presentation required further intervention (p=0.016): one patient required additional laser only and four patients required scleral buckling or vitrectomy. Pre- and post- DLP logMAR visual acuity was 0.15 and 0.14, respectively. demarcation laser photocoagulation is an effective alternative to scleral buckling or vitrectomy for treating asymptomatic RRDs. It has a high failure rate among eyes with symptomatic RRD.


Probiotic use in irritable bowel syndrome.
Over the past several years, a number of studies have addressed the role of specific strains of bacteria, or combinations thereof, to alleviate certain symptoms of irritable bowel syndrome (IBS). More importantly, the precise factors that contribute to this therapeutic effect, such as modulations in cytokine levels and alterations in colonic motility, are being clarified. This review serves to summarize the evidence for the use of probiotics in the treatment of IBS and to place this information in clinical context. Potential future developments and areas of possible research are also discussed.


Guidelines for eye care in patients with diabetes mellitus. Results of a symposium. The Kentucky Diabetic Retinopathy Group.
A symposium was held in Lexington, Ky, that resulted in state-of-the-art current management recommendations or guidelines regarding eye care in patients with diabetes mellitus. These guidelines have been endorsed by the American Academy of Ophthalmology and are presented in a 10-point outline.


Improved in vitro antioxidant and antimicrobial capacities of polysaccharides isolated from Salicornia arabica.
A newly profiling of Salicornia arabica (SAPS) polysaccharides was investigated. The water-soluble polysaccharide extract extracted from the Tunisian halophyte (SA) contained sulfate (9.64 ± 0.003%), carbohydrate (86.33 ± 0.003%), protein (1.24%), and uronic acids (3.33 ± 0.37%). The analysis of the monosaccharide composition revealed the presence of arabinose, Glucopyranose galactose, Glucuronic acid and glucose. The identified polysaccharide was considered as heterogeneous and highly branched via gaz chromatography, Fourier Transform Infrared Spectrometer (FT-IR), Thin layer chromatography (TLC) analysis. It also displayed an important radical scavenging and reducer power as well it exhibited effective antimicrobial properties.


Gigantic undifferentiated pleomorphic sarcoma (UPS) of breast in a woman: A rare case report.
Undifferentiated pleomorphic sarcoma (UPS), also known as malignant fibrous histiocytoma, is a rare mesenchymal tumor that occurs mostly in the soft tissue of the limbs and retroperitoneum. UPS of the breast is extremely rare, with less than 20 cases reported in the literature. We present a case of UPS of the right breast in a 56-year-old female. The growth of tumor could not be impeded by chemotherapy and radiotherapy. Then, she underwent right modified radical mastectomy with axillary lymph node dissection. The patient died eventually due to severe respiratory failure. UPS of the breast is a rare and aggressive tumor that presents with a rapidly growing mass. It can be difficult to diagnose as it shows no specific histological features and can mimic other spindle cell tumors of the breast. Breast sarcomas are categorized in very rare malignancies, and the mortality of this type of cancers are significantly high as they often are not diagnosed in early stages. The treatment of UPS of the breast is mostly surgical, with adjuvant radiotherapy and chemotherapy depending on the tumor characteristics and response to neoadjuvant chemotherapy. Long-term follow-up is necessary as these tumors have a high rate of local recurrence and distant metastasis.


Challenges, experience and coping of health professionals in delivering healthcare in an urban slum in India during the first 40 days of COVID-19 crisis: a mixed method study.
To describe the initial dilemmas, mental stress, adaptive measures implemented and how the healthcare team collectively coped while providing healthcare services in a large slum in India, during the COVID-19 pandemic. Community Health Division, Bangalore Baptist Hospital, Bangalore. We used mixed methods research with a quantitative (QUAN) paradigm nested in the primary qualitative (QUAL) design. QUAL methods included ethnography research methods, in-depth interviews and focus group discussions. A healthcare team of doctors, nurses, paramedical and support staff. Out of 87 staff, 42 participated in the QUAL methods and 64 participated in the QUAN survey. Being cognizant of the extreme vulnerability of the slums, the health team struggled with conflicting thoughts of self-preservation and their moral obligation to the marginalised section of society. Majority (75%) of the staff experienced fear at some point in time. Distracting themselves with hobbies (20.3%) and spending more time with family (39.1%) were cited as a means of emotional regulation by the participants in the QUAN survey. In the QUAL interviews, fear of death, the guilt of disease transmission to their loved ones, anxiety about probable violence and stigma in the slums and exhaustion emerged as the major themes causing stress among healthcare professionals. With positive cognitive reappraisal, the health team collectively designed and implemented adaptive interventions to ensure continuity of care. They dealt with the new demands by positive reframing, peer support, distancing, information seeking, response efficacy, self-efficacy, existential goal pursuit, value adherence and religious coping. The novel threat of the COVID-19 pandemic threw insurmountable challenges potentiating disastrous consequences; slums becoming a threat to themselves, threat to the health providers and a threat for all. Perhaps, a lesson we could learn from this pandemic is to incorporate 'slum health' within universal healthcare.


Prenatal diagnosis of congenital anomalies requiring surgical correction. Implications for the future.
With the use of maternal ultrasonography, 22 infants had an anomaly identified before delivery. Nine had gastrochisis. In all, ultrasonography was performed because of an elevated maternal serum alpha 1 fetoprotein level. Ultrasonography for other indications identified three infants with omphaloceles, three with cystic adenomatoid malformation of the lung, two with duodenal atresia, two with posterior urethral valves, and one each with obstruction of the ureteropelvic junction, a retroperitoneal teratoma, and an ovarian cyst. Infants were delivered in a neonatal center able to provide total care from the time of birth, thus the risks of transport over long distances were avoided. One of the infants with cystic adenomatoid malformation was incorrectly diagnosed as having a congenital diaphragmatic hernia, and the complete posterior urethral valve bilateral hydronephrosis complex was not identified in this infant until after delivery. The ability to diagnose complex anomalies correctly places new responsibilities on the surgeon who must counsel the parents on his ability to successfully treat the identified anomaly. Improved diagnostic accuracy, increased case findings, careful counselling, and delivery of high-risk infants in regional centers must be major priorities to improve neonatal surgical care in the next decade.


Liquid Biopsies: Emerging role and clinical applications in solid tumours.
Late detection and lack of precision diagnostics are the major challenges in cancer prevention and management. Biomarker discovery in specific cancers, especially at the pre-invasive stage, is vital for early diagnosis, positive treatment response, and good disease prognosis. Traditional diagnostic measures require invasive procedures such as tissue excision using a needle, an endoscope, and/or surgical resection which can be unsafe, expensive, and painful. Additionally, the presence of comorbid conditions in individuals might render them ineligible for undertaking a tissue biopsy, and in some cases, it is difficult to access tumours depending on the site of occurrence. In this context, liquid biopsies are being explored for their clinical significance in solid malignancies management. These non-invasive or minimally invasive methods are being developed primarily for identification of biomarkers for early diagnosis and targeted therapeutics. In this review, we have summarised the use and importance of liquid biopsy as significant tool in diagnosis, prognosis prediction, and therapeutic development. We have also discussed the challenges that are encountered and future perspective.


Pre-treatment with ebselen and vitamin E modulate acetylcholinesterase activity: interaction with demyelinating agents.
The ethidium bromide (EB) demyelinating model was associated with vitamin E (Vit E) and ebselen (Ebs) treatment to evaluate acetylcholinesterase (AChE) activity in the striatum (ST), hippocampus (HP), cerebral cortex (CC) and erythrocytes. Rats were divided into seven groups: I-Control (saline), II-(canola); III-(Ebs), IV-(Vit E); V-(EB); VI-(EB+Ebs) and VII-(EB+Vit E). At 3 days after the EB injection, AChE activity in the CC and HC was significantly reduced in groups III, IV, V, VI and VII (p<0.05) and in the ST it was reduced in groups III and V (p<0.05) when compared to the control group. At 21 days after the EB injection, AChE activity in the CC was significantly reduced in groups III, IV and V, while in groups VI and VII a significant increase was observed when compared to the control group. In the HC and ST, AChE activity was significantly reduced in groups V, VI and VII when compared to the control group (p<0.05). In the erythrocytes, at 3 days after the EB injection, AChE activity was significantly reduced in groups III, IV, V, VI and VII and at 21 days there was a significant reduction only in groups VI and VII (p<0.05) when compared to the control group. In conclusion, this study demonstrated that Ebs and Vit E interfere with the cholinergic neurotransmission by altering AChE activity in the different brain regions and in the erythrocytes. Furthermore, treatment with Vit E and Ebs protected against the demyelination lesion caused by EB. In this context, we can suggest that ebselen and Vit E should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with demyelinating events.


Gulf War Era Veterans' perspectives on research: a qualitative study.
Many veterans of the 1990-1991 Gulf War Era (GWE) have experienced poorly understood health issues. In response to challenges recruiting this population for research, we conducted focus groups and semi-structured phone interviews with GWE veterans and subject matter experts (SMEs) to explore GWE veterans' perceptions about research. Transcribed discussions were content-analyzed. Participants discussed research-related motivators and barriers identified among other populations, and nuances that may be specific to GWE veterans. Examples of motivating factors included: seeking answers about causes of and treatment for health issues; helping oneself; and helping other veterans. Examples of barriers included: distrust and dissatisfaction with federal entities; lack of research follow-through; and concerns about privacy and confidentiality. Researchers can use this information to better address GWE veterans' concerns and motivate them to participate in research. Inclusion of GWE veterans in research will allow researchers and clinicians to better understand and address health issues affecting this population.


Discovery of small-molecule modulators of the secretin receptor: Purmorphamine as novel anti-hypertensive agent.
The Secretin/Secretin receptor (SCTR) axis is well-known for its important role in water/salt homeostasis and blood pressure control. Recent studies revealed that absence of Secretin could lead to hypertension in animals and the administration of external Secretin leads to a sharp drop in blood pressure. Therefore, Secretin receptor has emerged as a crucial drug target of interest. In this report, using structure based drug design strategy, we have identified a small compound-based Secretin receptor modulator (i.e. purmorphamine or KSD179019). The virtual docking of KSD179019 with SCTR crystal structure and homology models revealed similar binding interactions. Based on active pharmacophores of KSD179019, several derivatives were designed and sythesized. SAR studies revealed that KSD179019 is the most effective SCTR modulator and chosen for further biological evaluation, including drug like properties and anti-hypertensive effect. KSD179019 not only has a similar blood pressure lowering effect as SCT peptide, but more importantly, it has a much longer half-life (∼8 h) and can be taken orally. Preliminary preclinical studies revealed extended bioavailability and low toxicity of this compound.


Regulation of protein phosphorylation in ocular ciliary epithelial cells by A, C and Ca2+/calmodulin-dependent protein kinases.
We have studied protein phosphorylation events in a cell line (8-SVHCE) derived from the human ocular ciliary epithelium after transformation within Simian Virus-40. We have investigated the time-course and identification of intracellular phosphorylated protein substrates in response to isoproterenol, phorbol-12-myristate-13-acetate (PMA), and ionophore A23187, which are activators of protein kinase A, C and calcium/calmodulin-dependent protein kinase, respectively. Five major endogenous phosphoproteins were readily identified by two-dimensional polyacrylamide gel electrophoresis with the following molecular weights: 80, 57, 24 and 19 kDa. Tryptic peptide analysis and phosphoaminoacid composition were utilized to aid the identification of the phosphoproteins. From these studies we have observed the following: (a) the most prominent phosphorylation of the 80-kDa protein occurs rapidly (1 min) in response to PMA treatment and is potentiated by isoproterenol, (b) the phosphorylation of the 57-kDa substrate (vimentin) occurs preferentially with isoproterenol treatment and increases gradually from 1 to 30 min, (c) late phosphorylation (60 min) of the 80-kDa protein by PMA is potentiated by isoproterenol, and (d) late phosphorylation of 19-kDa and 24-kDa substrates occurs with PMA treatment and is potentiated by A21387. The desensitization of adenylate cyclase activity by PMA or isoproterenol in 8-SVHCE cells results in altered adenylate cyclase activity, which appears to be correlated with similar alterations in the phosphorylation of the 57-kDa substrate (vimentin).(ABSTRACT TRUNCATED AT 250 WORDS)