Patients Undergoing Primary, Cementless TKA had Similar Pain, Opioid Utilization, and Functional Outcomes Compared to Matched Patients With Cemented Fixation.
Despite renewed interest in cementless fixation of total knee implants, many surgeons have anecdotal concerns about slower recovery and higher early pain scores. We sought to analyze 90-day opioid utilizations, inhospital pain scores, and patient-reported outcome measures (PROMs) in patients undergoing primary cemented versus cementless total knee arthroplasty (TKA). We retrospectively identified a cohort of opioid naïve patients undergoing primary TKA for osteoarthritis. There were 186 patients who had cementless TKAs matched 1:6 with 1,116 who received a cemented TKAs based on age (±6 years), body mass index (BMI) (±5), and sex. We compared inhospital pain scores, 90-day opioid utilizations in morphine milligram equivalents (MMEs), and early postoperative PROMs. The cemented and cementless cohorts had similar lowest (0.09 versus 0.08), highest (7.36 versus 7.34), and average (3.26 versus 3.27) pain scores using numeric rating scale (P > .05). They received similar inhospital (90 versus 102, P = .176), discharge (315 versus 315, P = .483), and total (687 versus 720, P = .547) MMEs. They had similar average inpatient hourly opioid consumption (2.5 versus 2.5 MMEs/hour, P = .965). Average refills 90 days postoperatively were similar in both cohorts (1.5 versus 1.4 refills, P = .893). Also, preoperative, 6-week, 3-month, delta 6-week, and delta 3-month PROMs scores were similar between cemented and cementless cohorts (P > .05) CONCLUSION: This matched study demonstrated similar in-hospital pain scores and opioid utilization, total MMEs prescribed within 90 days, and PROMs at 6 weeks and 3 months postoperatively between cemented and cementless TKAs. III, retrospective cohort study.


Risk assessment of chemicals potentially affecting male fertility.
Male reproductive toxicity involves a broad range of targets and mechanisms such as direct effects on the seminiferous epithelium and/or on Leydig and Sertoli cells supporting spermatogenesis, epididymal sperm maturation as well as endocrine disruption. Direct effects on spermatogenesis may be adequately revealed through both reproduction and repeated-dose toxicity studies; however, more research is needed on early markers of effect and on long-term sequelae of short-term exposures. Endocrine-related mechanisms are particularly relevant to subtle, but persistent effects on reproductive development due to altered early programming; the two-generation study is the test of choice, whereas targeted studies on the prepubertal phase are also desirable. Studies using in vitro methods as well as toxicogenomics are increasing; although gaps exist and much validation work is needed, in perspective, such approaches may be important in order to select compound, understand mechanisms, as well identify biomarkers of potential use also in human studies.


Full-length sequence of the novel HLA-C*12:02:36 allele by next generation sequencing in a Chinese individual.
C*12:02:36 differs from C*12:02:02:01 by one nucleotide change at nucleotide 438 in exon 3 from T to C.


Poly(A) length, cytoplasmic adenylation and synthesis of poly(A)+ RNA in early mouse embryos.
The poly(A) content of early mouse embryos fluctuates widely: after a transient increase in the one-cell embryo, there is a 70% drop in the two-cell and an approximately fivefold increase between the two-cell and early blastocyst stages (L. Pikó and K. B. Clegg, 1982, Dev. Biol. 89, 362-378). To shed light on the significance of these changes, we analyzed the size distribution of total poly(A) from embryos at different stages of development by gel electrophoresis and hybridization with [3H]poly(U). The number-average size of poly(A) tracts varies only slightly, from 61 to 77 nucleotides, indicating that the changes in poly(A) content are due primarily to changes in the number of poly(A) sequences, i.e., the number of poly(A)+ mRNA. From these data, the number of poly(A)+ mRNA can be estimated as follows: ovulated egg, 1.7 x 10(7); one-cell embryo, 2.4 x 10(7); late two-cell, 0.7 x 10(7); late eight-cell, 1.3 x 10(7); and early blastocyst, 3.4 x 10(7). These results suggest the elimination of the bulk of maternal poly(A)+ mRNA at the two-cell stage, to be replaced by newly synthesized mRNA derived from the embryonic genome. To study the synthesis of poly(A)+ mRNA, we cultured mouse embryos in vitro with [3H]adenosine and analyzed the labeled poly(A)+ RNA as to molecular size, length of the poly(A) tail, and relative distribution of label in poly(A) vs internal locations. We observed an active incorporation of label into large-molecular-weight (average size about 2 kb) poly(A)+ RNA at all stages from the one-cell to the blastocyst. However, in the one-cell embryo, about 70% of the label was localized in the poly(A) tail, suggesting cytoplasmic polyadenylation, and only about 30% was localized in the remainder of the molecule, suggesting the complete new synthesis of a small amount of poly(A)+ RNA. Differences in the size distribution of the labeled poly(A) as compared with the total poly(A) in the one-cell embryo indicate that the labeling is not due to a general turnover of poly(A) tails, but rather to the polyadenylation of previously nonpolyadenylated, stored RNA. Significant new synthesis of poly(A)+ RNA is evident from the two-cell stage onward and most likely accounts for the sharp rise in the number of poly(A)+ RNA molecules by the early blastocyst stage.


Predictive scoring model of mortality after surgical or endovascular revascularization in patients with critical limb ischemia.
The latest guideline points to life expectancy of <2 years as the main determinant in revascularization modality selection (bypass surgery [BSX] or endovascular therapy [EVT]) in patients with critical limb ischemia (CLI). This study examined predictors and a predictive scoring model of 2-year mortality after revascularization. We performed Cox proportional hazards regression analysis of data in a retrospective database, the Bypass and Endovascular therapy Against Critical limb ischemia from Hyogo (BEACH) registry, of 459 consecutive CLI patients who underwent revascularization (396 EVT and 63 BSX cases between January 2007 and December 2011) to determine predictors of 2-year mortality. The predictive performance of the score was assessed with the area under the time-dependent receiver operating characteristic curve. Of 459 CLI patients (mean age, 72 ± 10 years; 64% male; 49% nonambulatory status, 68% diabetes mellitus, 47% on regular dialysis, and 18% rest pain and 82% tissue loss as treatment indication), 84 died within 2 years after revascularization. In a multivariate model, age >75 years (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.10-2.85), nonambulatory status (HR, 5.32; 95% CI, 2.96-9.56), regular dialysis (HR, 1.90; 95% CI, 1.10-3.26), and ejection fraction <50% (HR, 2.49; 95% CI, 1.48-4.20) were independent predictors of 2-year mortality. The area under the time-dependent receiver operating characteristic curve for the developed predictive BEACH score was 0.81 (95% CI, 0.76-0.86). Predictors of 2-year mortality after EVT or BSX in CLI patients included age >75 years, nonambulatory status, regular dialysis, and ejection fraction <50%. The BEACH score derived from these predictors allows risk stratification of CLI patients undergoing revascularization.


Evidence for the delayed expression of a brainstem abnormality in albino ferrets.
Previous reports have suggested that neurons of the medial superior olivary nucleus in albino cats and rabbits are smaller than those in normally pigmented strains. In this investigation, the mean cross-sectional areas of neuronal perikarya in the medial superior olivary nucleus of pigmented and albino ferrets were compared at juvenile (14 weeks) and adult (greater than six months) ages. The mean cross-sectional area of the perikarya in adult albino ferrets was found to be 45% smaller than that of adult pigmented ferrets, confirming observations in cat and rabbit. The same comparison in juvenile ferrets, however, showed no significant differences. These results suggest that the mechanisms producing the abnormality of the auditory pathways differ from those responsible for the production of abnormal retinofugal pathways in albinos.


Cytomegalovirus infection in solid organ transplantation.
Cytomegalovirus infection remains a serious threat to solid transplant recipients. Despite advances in this field, there are still difficulties in the diagnosis of the disease and there are questions about the best and most cost-effective strategy to prevent infection and its direct and indirect consequences in the short and long term. All these points are discussed and updated in this chapter.


Interobserver reliability of the Gehweiler classification and treatment strategies of isolated atlas fractures: an internet-based multicenter survey among spine surgeons.
Atlas (C1) fractures are commonly rated according to the Gehweiler classification, but literature on its reliability is scarce. In addition, evaluation of fracture stability and choosing the most appropriate treatment regime for C1-injuries are challenging. This study aimed to investigate the interobserver reliability of the Gehweiler classification and to identify whether evaluation of fracture stability as well as the treatment of C1-fractures are consistent among spine surgeons. Computed tomography images of 34 C1-fractures and case-specific information were presented to six experienced spine surgeons. C1-fractures were graded according to the Gehweiler classification, and the suggested treatment regime was recorded in a questionnaire. For data analyses, SPSS was used, and interobserver reliability was calculated using Fleiss' kappa (κ) statistics. We observed a moderate reliability for the Gehweiler classification (κ = 0.50), the evaluation of fracture stability (κ = 0.50), and whether a surgical or non-surgical therapy was indicated (κ = 0.53). Type 1, 2, 3a, and 5 fractures were rated stable and treated non-surgically. Type 3b fractures were rated unstable in 86.7% of cases and treated by surgery in 90% of cases. Atlas osteosynthesis was most frequently recommended (65.4%). Overall, 25.8% of type 4 fractures were rated unstable, and surgery was favoured in 25.8%. We found a moderate reliability for the Gehweiler classification and for the evaluation of fracture stability. In particular, diverging treatment strategies for type 3b fractures emphasise the necessity of further clinical and biomechanical investigations to determine the optimal treatment of unstable C1-fractures.


External genitalia gunshot wounds: a ten-year experience with fifty-six cases.
To determine the appropriate methods for the diagnosis and management of gunshot injuries to the external genitalia. Retrospective analysis. Fifty-six patients with gunshot wounds (GSWs) to the external genitalia were seen over the last 10 years. All patients underwent physical examination, radiographic staging, and surgical exploration, according to protocol. There were 25 testicular, 19 scrotal soft tissue, 14 penile, 4 epididymal, 4 urethral, 4 vasal, and 3 superficial scrotal skin injuries. When possible, all injuries, except for the vasal and 1 urethral injury, were primarily repaired with excellent long-term results. Orchiectomy was required in half of testes struck by gunshots. Associated injuries with single GSWs were mostly to the proximity soft tissue and were amenable to conservative management. Major associated injuries were present in patients with multiple GSWs. In the absence of a suspected major associated injury, genital GSWs required only two diagnostic studies, a retrograde urethrogram for suspected urethral injury and a routine abdominal radiograph. Gunshot injuries to the penis or perineum, blood at the penile meatus, or gross hematuria were highly suggestive of urethral injury. Successful management of genital GSWs is dependent upon prompt surgical exploration, conservative debridement, and primary repair.


A multi-locus approach to barcoding in the Anopheles strodei subgroup (Diptera: Culicidae).
The ability to successfully identify and incriminate pathogen vectors is fundamental to effective pathogen control and management. This task is confounded by the existence of cryptic species complexes. Molecular markers can offer a highly effective means of species identification in such complexes and are routinely employed in the study of medical entomology. Here we evaluate a multi-locus system for the identification of potential malaria vectors in the Anopheles strodei subgroup. Larvae, pupae and adult mosquitoes (n = 61) from the An. strodei subgroup were collected from 21 localities in nine Brazilian states and sequenced for the COI, ITS2 and white gene. A Bayesian phylogenetic approach was used to describe the relationships in the Strodei Subgroup and the utility of COI and ITS2 barcodes was assessed using the neighbor joining tree and "best close match" approaches. Bayesian phylogenetic analysis of the COI, ITS2 and white gene found support for seven clades in the An. strodei subgroup. The COI and ITS2 barcodes were individually unsuccessful at resolving and identifying some species in the Subgroup. The COI barcode failed to resolve An. albertoi and An. strodei but successfully identified approximately 92% of all species queries, while the ITS2 barcode failed to resolve An. arthuri and successfully identified approximately 60% of all species queries. A multi-locus COI-ITS2 barcode, however, resolved all species in a neighbor joining tree and successfully identified all species queries using the "best close match" approach. Our study corroborates the existence of An. albertoi, An. CP Form and An. strodei in the An. strodei subgroup and identifies four species under An. arthuri informally named A-D herein. The use of a multi-locus barcode is proposed for species identification, which has potentially important utility for vector incrimination. Individuals previously found naturally infected with Plasmodium vivax in the southern Amazon basin and reported as An. strodei are likely to have been from An. arthuri C identified in this study.


Cloning of genomic sequences from the human Y chromosome after purification by dual beam flow sorting.
Human Y chromosomes were purified by dual beam flow sorting from a human X Chinese hamster cell line retaining the Y as the only free human chromosome. DNA was extracted from the Y fraction and cloned into lambda gtWES . lambda B vector arms. More than 100 recombinant clones carrying human inserts have been characterised by Benton-Davis plaque screening and Southern blotting or in situ hybridisation. Several repetitive sequences were found to be predominantly located on the Y, whereas the majority also cross-hybridised with autosomal DNA. One repetitive clone gave a specific hybridisation signal with the X and the Y chromosome but not with autosomes. Preliminary evidence indicates that many clones contain single copy as well as repetitive sequences. However, no Y-specific single copy sequence has yet been identified.


American College of Physicians Ethical Guidance for Electronic Patient-Physician Communication: Aligning Expectations.
Communication is critical to strong patient-physician relationships and high-quality health care. In recent years, advances in health information technology have altered how patients and doctors interact and communicate. Increasingly, e-communication outside of in-person clinical encounters occurs in many ways, including through e-mail, patient-portals, texting, and messaging applications. This American College of Physicians (ACP) position paper provides ethics and professionalism guidance for these forms of e-communication to help maintain trust in patient-physician relationships and the profession and alignment between patient and physician expectations.


Direct observation of the specific heat of Majorana quasiparticles in superfluid3He-B.
The existence of Majorana quasiparticles was predicted in the edge state in topological insulators, especially in the p-wave superfluid medium [Formula: see text]He-B. Due to its purity and coherent quantum state, [Formula: see text]He-B is an ideal platform for searching for Majorana fermions in condensed matter systems. In the limit of extremely low temperatures, the density of Bogolyubov quasiparticles and the heat capacity of [Formula: see text]He-B decrease exponentially. In this article, we present the first observation of the deviation of its heat capacity from exponential dependence in the limit of record low cooling. We found an additional heat capacity that more than doubled the heat capacity of bulk [Formula: see text]He-B and changes as T[Formula: see text]. The additional heat capacity is in good agreement with the predicted heat capacity of 2D gas of Majorana. This observation is a direct proof of the existence of Majorana quasiparticles in [Formula: see text]He-B.


Hereditary melanoma and the dysplastic nevus syndrome: the risk of cancers other than melanoma.
We analyzed the prospective occurrence of cancers other than malignant melanoma in fourteen kindreds with hereditary cutaneous malignant melanoma and the dysplastic nevus syndrome. No significant excess of nonmelanoma cancers was documented, suggesting that hereditary cutaneous malignant melanoma/dysplastic nevus syndrome is not pleiotropic for other tumor types.


Acute and prolonged toxicity to aquatic organisms of new and existing chemicals and pesticides.
The relation of acute to prolonged toxicity of existing and new chemicals and active ingredients of numerous pesticides in the aquatic environment have been compared with their physico-chemical properties. The data had been presented to the authorities in behalf of the pesticide registrations, the notification of new chemicals or research projects. The ecotoxicity ratios are expressed as acute to prolonged ratios (APR). They are determined for fish and crustacea with existing and new chemicals and pesticides. In the case of the pesticides the data are subsummarized into fungicides, herbicides, insecticides. The variability of the APR is evaluated. According to the statistic evaluation of the data it must be summarized, that the toxic effects are often extremely specific and depend not only on the substance, but also on the aquatic species, the duration of the exposure, and the endpoint of the test. In general, a factor of 100 between the EC/LC50 of acute toxicity and NOEC of prolonged toxicity is scientifically justified. The data indicate that there is no significant correlation between lipophilic properties (logPow) or water solubility and toxicity in aquatic organisms. For that reason structure-activity relationships based on lipophilic properties of the substance cannot lead to reasonable results. It must be stated, that the prolonged ecotoxicity can not be exactly extrapolated from acute toxicity data on the basis of physico-chemical properties.


Comparison of Depression and Anxiety Following Self-reported COVID-19-Like Symptoms vs SARS-CoV-2 Seropositivity in France.
The long-term consequences of COVID-19 on mental health are a critical issue given the number of people infected with SARS-CoV-2 worldwide since the beginning of the pandemic. To investigate the associations between self-reported COVID-19-like symptoms or SARS-CoV-2 seropositivity and subsequent depression or anxiety. This propensity score-matched cohort study began in May 2020, with follow-ups in November 2020 and July 2021. The study used data from a large, randomly selected, national population-based cohort from France, the EpiCoV (Epidémiologie et Conditions de Vie) study. Of 85 074 individuals 15 years or older who completed the questionnaires at the 3 collection times, 28 568 were excluded because they did not return a blood sample for serologic testing, 1994 because of missing data on outcomes or exposures, and 9252 to respect the temporal sequence (exposure must precede the outcome). Propensity scores based on various socioeconomic, lifestyle, and health variables were computed to match participants who experienced COVID-19-like symptoms between February and November 2020 or showed SARS-CoV-2 seropositivity in November 2020. Logistic regression models were used to estimate associations between these occurrences and depression or anxiety assessed in July 2021 using the Patient Health Questionnaire 9-item and Generalized Anxiety Disorder 7-item scales, respectively. Among the 45 260 included participants (mean [SD] age, 51.1 [18.9] years; 52.4% women; 8.0% with depression and 5.3% with anxiety in July 2021), COVID-19-like symptoms were associated with subsequent depression (adjusted odds ratio, 1.70; 95% CI, 1.45-1.99) and anxiety (adjusted OR, 1.57; 95% CI, 1.29-1.92), whereas SARS-CoV-2 seropositivity was not. Furthermore, COVID-19-like symptoms, but not anosmia or dysgeusia alone, were associated with subsequent depression and anxiety in both the seropositive and seronegative subgroups. In this cohort study of more than 45 000 individuals drawn from the French general population, SARS-CoV-2 infection was not found as a risk factor of subsequent depression or anxiety. Moreover, self-reported COVID-19-like symptoms were associated with depression and anxiety assessed at least 8 months later in both seropositive and seronegative subgroups, suggesting that factors other than SARS-CoV-2 infection are implied in this association.


Inpatient primary prophylaxis of cancer-associated thromboembolism (CAT).
Cancer-associated thrombosis (CAT) increases morbidity and mortality in oncology patients. The risk of CAT is increased with hospitalization for acute medical illness. The goal of this review will be to examine the available evidence for (1) risk assessment and (2) primary thromboprophylaxis, (3) international published guideline recommendations, and (4) future directions to manage oncology patients admitted for an acute medical illness. A review was performed for each subject to gather information on the available evidence and recommendations available for oncology patients hospitalized for an acute medical illness. Risk assessments for thrombosis are primarily developed and validated in the general population. There is not a risk assessment that has specifically been developed and validated in oncology patients hospitalized for an acute medical illness. Most evidence for thromboprophylaxis of oncology patients is from sub-group analysis of larger randomized-controlled trials in the general population. Evidence is conflicting and suggests an individualized approach evaluating the risk-benefit of thromboprophylaxis. The strength of recommendations of international guidelines is limited because of the available evidence. Guidelines usually recommend utilizing and/or offering thromboprophylaxis to oncology patients hospitalized for an acute medical illness barring contraindications. Future evidence needs to improve risk assessments and knowledge of the appropriate agent, dose, and duration of thromboprophylaxis if indicated. Evidence for risk assessments and primary prophylaxis for oncology patients hospitalized for acute medical illness appears limited, with many research opportunities available to improve understanding on management of this patient population.


Dominant social status facilitates the behavioral effects of serotonergic agonists.
The effects of dominance rank on the behavioral responses to drugs that enhance central serotonergic function were examined in 45 adult male vervet monkeys living in 15 stable social groups. Each group contained 3 adult males, 3 adult females, and their immature offspring. Dominance rank was assessed by measuring success in intermale agonistic encounters. In every group one male was clearly the dominant, or alpha male, and the other two males were subordinate. Males from 5 groups received 3 doses of the serotonin reuptake inhibitor fluoxetine (0.5, 1.0 and 2.0 mg/kg/day); those from a second set of 5 groups received 3 doses of the receptor agonist quipazine (0.25, 0.50 and 1.0 mg/kg/day); those from a third set of 5 groups received the serotonin precursor tryptophan (10, 20 and 40 mg/kg/day). The 3 drug treatments produced strikingly similar behavioral effects. Each produced dose-dependent increases in approaching, grooming, resting and eating and decreases in locomoting, avoiding, being vigilant and being solitary. Dominant males were significantly more responsive behaviorally to all 3 drugs than were subordinate males: the increase or decrease in each behavioral measure was larger in dominant than in subordinate males. In combination with previous studies, these data suggest that dominant and subordinate males differ in the drug sensitivity of their serotonergic systems.


The effect of nitrogen and phosphorus addition on the growth, reproduction, and nutrient dynamics of two ericaceous shrubs.
Aboveground growth, reproduction, and foliar nitrogen and phosphorus contents of two ericaceous shrub species were compared over two seasons in (a) an undisturbed shrub bog (pocosin), and (b) a factorial fertilization design in which three levels each of nitrogen and phosphorus were added in all possible combinations. One species, Zenobia pulverulenta, is deciduous whereas the other species, Lyonia lucida, is evergreen. In the nutrient-poor undisturbed pocosin the two species exhibited similar foliar nitrogen and phosphorus concentrations and aboveground growth rates. Neither species flowered. In response to nutrient-addition Zenobia increased growth rates more than Lyonia. Foliar phosphorus concentrations of both species increased in response to enhanced phosphorus availability. in the first season neither species flowered in any treatment. In the second season Zenobia flowered only in the fertilized plots, with the most flowering in the high phosphorus treatments. I conclude that, by virtue of high growth rates and efficient use of nutrients and despite differences in leaf phenology and morphology, both Lyonia and Zenobia are successful in a competitive community under conditions of extremely low phosphorus availability. However, unlike Lyonia, Zenobia can take advantage of temporarily increased nutrient availability, which occurs following fire in the pocosin, to increase growth and reproduction.


Cardiovascular risk factors among youth with and without type 2 diabetes: differences and possible mechanisms.
To compare cardiovascular disease (CVD) risk factors among recently diagnosed youth with type 2 diabetes and nondiabetic youth and investigate whether demographic, behavioral, or metabolic factors might account for observed differences. Data from 106 type 2 diabetic and 189 nondiabetic multiethnic youth, aged 10-22 years, were analyzed. Prevalence of CVD risk factors were age and race/ethnicity adjusted using direct standardization. Multiple linear regression models were sequentially adjusted for demographic, behavioral (dietary saturated fat intake and physical activity), and metabolic (body adiposity and glycemia) factors to explore possible mechanisms associated with differences in CVD risk factors between the case and control groups. Compared with control subjects, youth with type 2 diabetes had a higher prevalence of elevated blood pressure, obesity, large waist circumference, low HDL cholesterol, high triglycerides, and high albumin-to-creatinine ratio (P < 0.05 for each risk factor). Type 2 diabetic youth also had higher levels of apolipoprotein B, fibrinogen, interleukin (IL)-6, C-reactive protein, and leptin; lower adiponectin levels; and denser LDL particles (P < 0.05 for each risk factor). Adjustment for BMI, waist circumference, and A1C substantially attenuated differences in the CVD risk factors between the case/control groups, except for fibrinogen and IL-6, which remained significantly higher in type 2 diabetic youth. Compared with control youth, type 2 diabetic youth have a less favorable CVD risk factor profile. Adiposity and glycemia are important contributors to differences in CVD risk profiles among type 2 diabetic and control youth. Inflammatory and prothrombotic factors may also play an important role.


Liver and kidney ultrasound elastography in children and young adults with hypertension or chronic kidney disease.
Ultrasound elastography is a research method increasingly used to measure tissue elasticity. The aim of the study was to assess its usability in pediatric patients with either chronic kidney disease (CKD) or hypertension. A total of 46 patients with CKD (group 1), 50 patients with hypertension (group 2), and 33 healthy participants as the control group were included. In all, we performed studies assessing their cardiovascular risk along with liver and kidney elastography. Liver elastography parameters were increased compared to those in the control group (1.49 m/s, p = 0.007, in group 1 and 1.52 m/s, p < 0.001, in group 2, vs. 1.41 m/s among controls). Kidney elastography parameters were significantly higher in group 2 (1.9 m/s, p = 0.001, and 1.9 m/s, p = 0.003, in each kidney) when compared to group 1 (1.79 m/s and 1.81 m/s). Additionally, all participants were divided according to overweight/obesity and normal weight status, where both liver (1.53 m/s vs. 1.45 m/s, p < 0.001) and kidney parameters (1.96 m/s and 1.92 m/s vs. 1.81 m/s and 1.84 m/s, p = 0.002) were significantly higher in the group of overweight/obese subjects. Ultrasound elastography of the liver and kidney is feasible in pediatric patients with either CKD or hypertension, showing increased liver stiffness parameters in both groups, further aggravated by obesity. In obese patients with CKD, kidney stiffness also increased indicating a negative effect of clustering cardiovascular risk factors leading to decreased kidney elasticity. Further research is warranted. A higher resolution version of the Graphical abstract is available as Supplementary information.


Double-bundle versus single-bundle anterior cruciate ligament reconstructions: a prospective, randomized study with 2-year follow-up.
This prospective, randomized study was conducted to compare the short-term results of arthroscopic double-bundle with single-bundle anterior cruciate ligament (ACL) reconstruction. One hundred and eight patients with a symptomatic ACL rupture were randomized to either double-bundle (Group DB) or single-bundle (Group SB) ACL reconstruction. Follow-up was conducted at 6, 12, 18 and 24 months postoperatively. At the 24-month follow-up, 94 of the 108 patients (87%) were available for evaluation. The rotational stability, as evaluated by pivot shift test, was significantly superior in the Group DB to that in the Group SB. No significant difference with regard to ACL revisions, total flexion work, mean peak flexion torque and extension work between the groups was detected. There was no significant difference between the groups in terms of the Tegner activity score, the knee injury and osteoarthritis outcome score, the Lysholm functional score, anterior knee pain or mobility, subjective knee function. In addition, no significant difference in laxity on the Lachman test or the KT-1000 maximum manual force test was investigated. All the results were significantly more satisfactory at each follow-up period than preoperatively, in both groups. Both SB- and DB-ACL reconstruction resulted in satisfactory subjective outcome and objective stability. Both these techniques can therefore be considered as suitable alternatives for ACL reconstruction. Moreover, as it seems to be according to the pivot shift test, the risk for the development of degenerative changes of the knee joint in a long run could be smaller in the Group DB.


Study the Effect of Tubotympanic Disease on Bone Conduction Threshold.
Tubo-tympanic disease of middle ear cleft can temporarily detoriate the bone conduction threshold specially in higher frequency in long standing cases. It mainly affects the inertial ossicular component of the bone conduction mechanism. (1) Study the effect of tubotympanic disease on bone conduction threshold (SN loss). (2) Study the duration of the disease on bone conduction threshold. 84 cases of tubotympanic disease were taken for the study. There pre-operative PTA was done and effect of the disease on the bone conduction threshold was noted. Results were analyzed by using analysis of variance. The significance level α was taken 0.05 as at marginally significant, 0.01 significant and 0.001 as highly significant. The bone conduction at all frequencies increased significantly P < 0.05 with duration of ear discharge. The differences in the bone conduction at all frequencies amongst normal ears were significantly lower as compared to the diseased ear. Duration of ear discharge and type of hearing loss reveals that in patients with ear discharge less than 11 years there were 24 (77.41%) subjects with conductive hearing loss, 1 (3.22%) subject with mixed hearing loss. As the duration increased 11-20 years, the cases of conductive hearing loss decreased 13 (56.52%) and cases of mixed hearing loss increased to 3 (13.04%). In patients with ear discharge of > 21 years conductive subjects were 19 (63.33%) and subjects with mixed hearing loss increased to 5 (33.33%) cases. The average hearing loss and the average bone conduction threshold increases as the duration of disease increases. In patients of safe CSOM who have poor BCT, it is the higher frequencies which are more affected.


The association between self-reported mobile phone usage with blood pressure and heart rate: evidence from a cross-sectional study.
With the advancement of technology, the rate of access and use of mobile phones in different communities has increased significantly. Mobile phones emit electromagnetic waves and therefore excessive use of them may have harmful effects on physical and mental health and especially on the cardiovascular system. This study aimed to investigate the association between self-reported mobile phone use duration and blood pressure and heart rate (HR) using data from Ravansar non-communicable diseases (RaNCD) cohort study. The present cross-sectional study was performed using the data of 8905 out of 10,065 participants in the RaNCD study in Iran. According to the mean self-reported duration of mobile phone usage (min/day) over the previous 12 months, all users were divided into four groups. The first and fourth groups had the least and most time using mobile phones respectively. The relationship between blood pressure and the duration of mobile phone use was determined using univariate and multiple linear regression. Of 8905 participants aged 35-65 years, 1515 (17.0%) of them didn't use mobile phones. The minimum, maximum, and mean duration of self-reported mobile phone use between users were 3.4, 50.4, and 19.5 min/day, respectively. A decrease in women's systolic and diastolic blood pressure (SBP and DBP) and HR was observed by increasing the duration of mobile phone use. With adjustment for effective confounding factors, there was a significant negative association between SBP [-2.52 (-4.11, -0.94)], DBP [-1.86 (-2.83, -0.89)], and duration of mobile use. In this study, a significant decreasing trend was found between SBP, DBP, and HR and higher mobile phone usage in women. Based on regression analysis, SBP, DBP, and duration of mobile phone use were associated negatively in those who used their phones for at least 8 h.


Clinical Review on the Utility of Fecal Microbiota Transplantation in Immunocompromised Patients.
Fecal microbiota transplantation (FMT) represents a promising management modality for Clostridium difficile infection (CDI). In immunocompromised patients, FMT is utilized for CDI as well as emerging non-CDI indications such as inflammatory bowel disease and graft versus host disease. PURPOSE OF REVIEW: This review aims to shed light on the safety and efficacy of FMT in immunocompromised patients, including patients suffering for human immunodeficiency virus infection, solid organ and hematopoietic stem cell transplant recipients, cancer patients, and patients on immunosuppressive therapies. RECENT FINDINGS: Though the body of evidence concerning the use of FMT in immunocompromised is growing, no clinical trials exist to date. Present literature weighs in favor of FMT in immunocompromised patients, with an acceptable adverse effect profile and minimal risk of infectious adverse events. Further large scale studies and randomized controlled trials to validate the utility of FMT in immunocompromised individuals will be a welcomed endeavor.


The use of a ditopic Gd(III) paramagnetic probe for investigating α-bungarotoxin surface accessibility.
Protein surface accessibility is a critical parameter which drives all intermolecular interaction processes. In this respect a big deal of information has been derived by analyzing paramagnetic perturbation profiles obtained from NMR protein spectra, particularly in the case that the effects due to different soluble paramagnets can be compared. Here Gd(2)L7, a neutral ditopic paramagnetic NMR probe, has been characterized in terms of structure and relaxivity and its paramagnetic perturbations on α-bungarotoxin CαH signals in ((1))H-((13))C HSQC (heteronuclear single quantum coherence) spectra have been analyzed. Then, these signal attenuations have been compared with the ones previously obtained in the presence of GdDTPA-BMA (gadolinium(III) diethylenetriamine-N,N,N',N'",N"-pentaacetate-bis(methylamide)). In spite of the different molecular size and shape, for the two probes a common pathway of approach to the α-bungarotoxin surface can be observed with an equally enhanced access of both GdDTPA-BMA and Gd(2)L7 toward the protein surface side where residues involved in the receptor binding are located. The different residence times of the water molecule directly coordinated by the Gd(III) ion measured for the two paramagnets account for the reduced broadening of water signal in the presence of the ditopic probe at equivalent gadolinium concentration. These features make Gd(2)L7 a very suitable probe for investigating protein surface accessibility of complex protein systems.


Impact of timing on in-patient outcomes of complete repair of tetralogy of Fallot in infancy: an analysis of the United States National Inpatient 2005-2011 database.
This study aimed to investigate whether age at complete repair of tetralogy of Fallot (TOF) impacts postoperative morbidity and length of hospital stay in infants less than 365 days of age. The United States Nationwide Inpatient Sample was searched for infants 0-365 days of age that underwent complete repair of TOF between 2005 and 2011. Patients were categorized based on age at time of repair: 0-30 days; 31-90 days; 91-180 days; > 180 days. A total of 1112 infants were included in the study. Multivariate analysis showed the risk of postoperative complications was 40% lower in infants ≥91 days old at the time of repair as compared to those ≤30 days old. In addition, children > 30 days old at the time of repair had a significantly shorter length of hospital stay than those aged ≤30 days. In the subgroup with elective repair, older age was associated with a shorter length of hospital stay as compared to those ≤30 days old at repair, while association between age at complete repair of TOF and postoperative complication was not significant among the groups after adjusting for confounders. In children < 1 year old, postoperative complications and length of hospital stay are affected by the timing of complete repair of TOF.


Improved reliability of wear performance for a fluorapatite veneering porcelain by ion-exchange strengthening and toughening.
Purpose of the present study was to explore the improvement of wear performance for a nano fluorapatite veneering porcelain by ion-exchange. Bar and disk specimens were prepared by IPS e.max Ceram as the nano fluorapatite veneering porcelain. Ion-exchange was performed in a melted KNO3 bath at two temperatures for different time-periods. After the ion-exchange, the bars were tested for flexural strength, surface Vickers hardness and HIF toughness, the disks were tested for wear performance paired with zirconia antagonist using a pin-on-disk tribometer with 10 N for 70✕104 wear cycles in artificial saliva. Wear analysis of the porcelain and zirconia was performed with a 3D profilometer. The microstructure and worn surface morphology were examined with scanning electron microscopy. One-way analysis of variance and Tukey's post-hoc pairwise comparison were used to analyse the wear data. The nano fluorapatite veneering porcelain before ion-exchange presented strong time-dependent wear behavior. Furthermore, wear rate of the original porcelain exhibited a very large standard deviation in the running-in wear stage, which was correlated with highly inhomogeneous distribution of the characteristic fluorapatite crystals in the microstructure. After ion-exchange at 350 °C and 380 °C, especially after the processing at 350 °C for 128 h, the wear rates of both running-in and steady wear stages could be significantly decreased. More importantly, the standard deviation of wear rate in the running-in wear stage could be remarkably reduced after the treatment. The improved reliability of wear performance was attributed to the strengthening and toughening effects of the ion-exchange processing. For the fluorapatite veneering porcelain, the ion-exchange protocol to obtain an ion-exchange layer with less stress relaxation and a considerable depth could strengthen and toughen the porcelain; as a result, the reliability of wear performance could be remarkably improved.


SAF-189s, a potent new-generation ROS1 inhibitor, is active against crizotinib-resistant ROS1 mutant-driven tumors.
The ROS1 fusion kinase is an attractive antitumor target. Though with significant clinical efficacy, the well-known first-generation ROS1 inhibitor (ROS1i) crizotinib inevitably developed acquired resistance due to secondary point mutations in the ROS1 kinase. Novel ROS1is effective against mutations conferring secondary crizotinib resistance, especially G2032R, are urgently needed. In the present study, we evaluated the antitumor efficacy of SAF-189s, the new-generation ROS1/ALK inhibitor, against ROS1 fusion wild-type and crizotinib-resistant mutants. We showed that SAF-189s potently inhibited ROS1 kinase and its known acquired clinically resistant mutants, including the highly resistant G2032R mutant. SAF-189s displayed subnanomolar to nanomolar IC50 values against ROS1 wild-type and mutant kinase activity and a selectivity vs. other 288 protein kinases tested. SAF-189s blocked cellular ROS1 signaling, and in turn potently inhibited the cell proliferation in HCC78 cells and BaF3 cells expressing ROS1 fusion wild-type and resistance mutants. In nude mice bearing BaF3/CD74-ROS1 or BaF3/CD74-ROS1G2032R xenografts, oral administration of SAF-189s dose dependently suppressed the growth of both ROS1 wild-type- and G2032R mutant-driven tumors. In a patient-derived xenograft model of SDC4-ROS1 fusion NSCLC, oral administration of SAF-189s (20 mg/kg every day) induced tumor regression and exhibited notable prolonged and durable efficacy. In addition, SAF-189s was more potent than crizotinib and comparable to lorlatinib, the most advanced ROS1i known against the ROS1G2032R. Collectively, these results suggest the promising potential of SAF-189s for the treatment of patients with the ROS1 fusion G2032R mutation who relapse on crizotinib. It is now recruiting both crizotinib-relapsed and naive ROS1-positive NSCLC patients in a multicenter phase II trial (ClinicalTrials.gov Identifier: NCT04237805).


Adverse effects of vagotomy on ethanol-induced gastric injury in the rat. Absence of a role for glutathione redox cycle.
Truncal vagotomy is known to aggravate the damaging effects of alcohol-induced gastric injury and prevent the occurrence of adaptive cytoprotection against such injury by a mild irritant. This study was undertaken to determine whether aberrations in glutathione (GSH) metabolism were responsible for these vagotomy-induced effects. Fasted rats (6-8/group) were subjected to truncal vagotomy and pyloroplasty or sham vagotomy and pyloroplasty. One week later they were given 2 ml of oral saline or the mild irritant, 25% ethanol (EtOH). Thirty minutes following such treatment, animals were either sacrificed or orally received 2 ml of 100% EtOH and then were sacrificed 5 min later. At sacrifice, in each experimental group, stomachs were removed and either evaluated macroscopically for the degree of injury involving the glandular gastric epithelium or samples of the mucosa were prepared for measurement of total GSH levels or GSH peroxidase (GPX) and GSH reductase (GRT) activity. In nonvagotomized animals, saline treatment prior to 100% EtOH exposure resulted in injury to the glandular epithelium involving approximately 18%. Treatment with 25% EtOH prior to 100% EtOH exposure virtually abolished this injury. In vagotomized animals, 100% EtOH elicited almost three times the amount of injury observed in the nonvagotomized state and the protective effect of 25% EtOH pretreatment was prevented. Effects of the various treatment modalities on GPX and GRT activity were not significantly different from control values. When mucosal GSH results were plotted against the presence or absence of gastric injury among the various groups studied, no significant correlation was apparent.(ABSTRACT TRUNCATED AT 250 WORDS)


Iatrogenic Creutzfeldt-Jakob disease in Australia: time to amend infection control measures for pituitary hormone recipients?
From 1967, the Australian Human Pituitary Hormone Program offered treatment for short stature and infertility using human cadaver-acquired pituitary hormones (human growth hormone [hGH] and human pituitary gonadotrophin [hPG]). The program was suspended in 1985 when a growth-hormone recipient in the United States developed Creutzfeldt-Jakob disease (CJD), an incurable and rapidly progressive neurodegenerative disorder. Since this time, recipients have lived with the significant anxiety that they have an elevated risk of developing CJD. Furthermore, additional CJD infection control measures are required when recipients undergo some types of surgery. As it is 20 years since the last Australian pituitary hormone recipient developed CJD, we evaluated the risk for Australian recipients of developing iatrogenic CJD, and compared Australian data with data from New Zealand and selected other countries who had pituitary hormone programs. Our evaluation indicates that pituitary hormone recipients in Australia have the lowest risk of developing iatrogenic CJD, and that Australia is the only country not to have experienced ongoing CJD-related deaths. Thus, we believe that: in the Australian hGH recipient cohort, the risk of developing CJD is sufficiently low for this cohort to no longer require additional infection control measures in the health care setting; and in the Australian hPG recipient cohort, if another 5 years elapses with no further occurrence of CJD in this group, the hPG recipient cohort could also be considered as not requiring additional infection control measures in the health care setting. These recommendations should not be misunderstood as implying that there is no ongoing risk, but that the risk is acceptably low and generally in keeping with guidelines that stratify the risk.


Many reptiles under threat of extinction.
Georgina Mills reports on new research that assessed the risk of extinction for more than 10,000 reptile species.


Production efficiency in small mammal populations.
The data used to analyse the relationship between production (P) and respiration (R) in small mammals (Grodziński and French 1983) are reanalysed and different conclusions are drawn. Differences in production efficiency cannot be attributed to any particular trophic classe, but in the higher taxonomic categories the murids have higher production effeciency than the rest. However examination of numerous populations of the same species shows that production efficiencies of congeneric species sometimes differ significantly and show differences which exceed those between higher taxa. The same applies to trophic classes. The low slope described for the regression of P on R for Insectivora is due to an aberrant set of data for Sorex araneus. Production efficiency is directly related to litter size in rodents and inversely to survival of adults. This result conflicts with much earlier work and is discussed at length.


Correction: Comparative Developmental Transcriptomics Reveals Rewiring of a Highly Conserved Gene Regulatory Network during a Major Life History Switch in the Sea Urchin Genus Heliocidaris.
[This corrects the article DOI: 10.1371/journal.pbio.1002391.].


An Integrative Review of Mechanotransduction in Endothelial, Epithelial (Renal) and Dendritic Cells (Osteocytes).
In this review we will examine from a biomechanical and ultrastructural viewpoint how the cytoskeletal specialization of three basic cell types, endothelial cells (ECs), epithelial cells (renal tubule) and dendritic cells (osteocytes), enables the mechano-sensing of fluid flow in both their native in vivo environment and in culture, and the downstream signaling that is initiated at the molecular level in response to fluid flow. These cellular responses will be discussed in terms of basic mysteries and paradoxes encountered by each cell type. In ECs fluid shear stress (FSS) is nearly entirely attenuated by the endothelial glycocalyx that covers their apical membrane and yet FSS is communicated to both intracellular and junctional molecular components in activating a wide variety of signaling pathways. The same is true in proximal tubule (PT) cells where a dense brush border of microvilli covers the apical surface and the flow at the apical membrane is negligible. A four decade old unexplained mystery is the ability of PT epithelia to reliably reabsorb 60% of the flow entering the tubule regardless of the glomerular filtration rate. In the cortical collecting duct (CCD) the flow rates are so low that a special sensing apparatus, a primary cilia is needed to detect very small variations in tubular flow. In bone it has been a century old mystery as to how osteocytes embedded in a stiff mineralized tissue are able to sense miniscule whole tissue strains that are far smaller than the cellular level strains required to activate osteocytes in vitro.


Prognostic factors in patients with vulvar cancer treated with primary surgery: a single-center experience.
Vulvar cancer is a relatively rare disease. The aim of this study was to investigate prognostic factors in vulvar squamous cell carcinoma patients treated with primary surgery. Forty cases of vulvar squamous cell carcinoma treated with primary surgery were retrospectively analyzed. Overall survival (OS) and disease-specific survival (DSS) were calculated using the Kaplan-Meier method and prognostic factors were analyzed by multivariate analyses. The median age was 68 years. The FIGO stage distribution was as follows: 18 cases (45.0 %) in stage I, four cases (10.0 %) in stage II, 15 cases (37.5 %) in stage III, and three cases (7.5 %) in stage IV. A radical local excision was performed in 15 patients, and radical vulvectomy in 25 patients, and seven of these patients were treated with postoperative RT. The 5-year DSS rate was 72.6 %, and the 5-year OS rate was 70.3 %. Age and surgical margin ≤5 mm were independent prognostic factors for OS, and positive inguinal LN metastasis and surgical margin ≤5 mm were identified as independent prognostic factors for DSS. Complete radical excision is important regardless of operation mode. Adjuvant treatment should be considered for inguinal LN positive patients.


Replantation of thumb avulsion injuries.
To point out detailed technical considerations and tactical modifications within the experience of 59 replantations of thumb avulsion injuries, to clarify the indications of replantation, and to evaluate the long-term results. Seventy-two thumb avulsions of 510 thumb amputations were treated at our centre between 1986 - 2002. Sixty-two of them were male and 10 were female. The average age of the patients was 27 years. Fifty-nine avulsed thumbs were replanted, and 13 were considered as "not replantable" and operated using other reconstructive procedures. Since the main goal of thumb replantation is survival with sensitivity and good function, all the injured tissues were repaired or primarily reconstructed. As a main principle, we always aimed for a one-stage reconstruction including vein grafts for the arterial injury, direct vein repair or vein transfer to establish venous outflow, tendon transfers to restore movement, and nerve transfer to restore sensation. Overall survival rate was 84.7 %. The average follow-up time was 65.2 months. 80 percent of the patients returned to their original work within an average of 4 months after replantation. The patients were generally satisfied with the outcome and ability to use their thumb. The average range of movement of the interphalangeal joint was 75 % of the normal side. On average, key pinch strength was 65 % of contralateral hand. Two-point discrimination was less than 10 mm in 60 % of the cases. Semmes-Weinstein monofilament testing evaluation showed 2.83 in 35 patients, 3.61 in 20, and 6.68 in 4 patients. In replantation of avulsion amputation of the thumb, functional success depends on repair or reconstruction of all damaged tissues, if necessary, using nerve transfers and tendon transfers. If these could be done primarily as a one-stage reconstruction, the costs would be less, the patients would return to their work when the one-stage treatment and rehabilitation is finished, and would also eliminate the technical difficulties encountered in secondary reconstructions.


Irreversible Cabozantinib-induced left ventricular systolic dysfunction, a potentially novel observation.
The case report describes the presentation of incident heart failure with reduced ejection fraction, following Cabozantinib chemotherapy. In contrast to previous cases, despite maximal medical therapy for this gentleman it became irreversible and contributed to his death. Hence the case illustrates the potential cardiotoxicity of Cabozantinib and reinforces the need for co-ordinated multi-disciplinary team care for such patients. Within existing cardio-oncology infrastructure, it may mean that such patients require enhanced echocardiographic surveillance.


Leukotriene C4 binding to rat lung membranes.
A high affinity binding site for leukotriene C4 (LTC4), one component of slow reacting substance of anaphylaxis, has been identified in a membrane preparation from rat lung. As measured by a filtration technique, [3H]LTC4 binding was saturable, specific, reversible, and heat-sensitive. In the presence of 20 mM CaCl2, the dissociation constant (KD) was 41 +/- 9 nM and the maximum number of binding sites (Bmax) was 31 +/- 10 pmol/mg of protein. Specificity was demonstrated by competition studies in which LTC4 had a Ki of 40 nM against specifically bound [3H]LTC4, whereas leukotriene D4 (LTD4) had a Ki of 4 microM. The stereoisomers (5R, 6R) LTC4, (5S, 6S) LTC4, and (5R, 6S) LTC4 had Ki values 3-, 15-, and 25-fold higher than that of natural (5S, 6R) LTC4. Leukotrienes E4 and B4, several prostaglandins and fatty acids, glutathione, and platelet activating factor were even less effective with Ki values above 10 microM. A slow reacting substance of anaphylaxis antagonist, FPL 55712, which, in some systems, distinguishes LTC4- from LTD4-induced contractions, was a weak competitor with a Ki of 16 microM. Serine-borate complex which inhibits gamma-glutamyl transpeptidase, an enzyme responsible for LTC4 metabolism, did not alter binding. In addition, 100 microM FPL 55712 did not reduce metabolism. These observations suggest that the binding observed for LTC4 may represent association with a physiological receptor for this molecule which has a relatively low affinity for LTD4.


Adherence to NCCN Guidelines for Genetic Testing in Breast Cancer Patients: Who Are We Missing?
Genetic predisposition accounts for 5-10% of all breast cancers (BC) diagnosed. NCCN guidelines help providers identify appropriate candidates for counseling and testing. Concerns about underutilization of genetic testing have spurred interest in broader peri-diagnostic testing. We evaluated surgeon adherence to NCCN guidelines and studied patterns of testing in newly diagnosed BC patients. A total of 397 patients were identified with newly diagnosed BC treated at our institution between 2016 and 2017 with no prior genetic testing. Eligibility for genetic testing based on NCCN criteria, referral, and patient compliance were recorded. In total, 212 of 397 (53%) met NCCN testing criteria. Fifty-nine of 212 (28%) patients went untested despite meeting one or more criteria. Fourteen of 59 (24%) of these were referred but did not comply. Most common criteria for meeting eligibility for testing both in the overall cohort and among missed patients were family history-based. Age > 45 years old and non-Ashkenazi Jewish descent were predictive of missed referral (p < 0.01). We identified pathogenic mutations in 16 of 153 (10%) patients who did undergo testing (11 (7%) BRCA1 or 2 and 5 (3%) with other predisposition gene mutations) or 16 of 397 (4%) among the overall group. Our data highlight the underutilization of genetic testing. Even in the setting of a full-service breast center with readily available genetic counseling, there is a substantial miss rate for identifying eligible patients, related to assessment of family history, patient age, and ethnicity, as well as patient compliance. Broader peri-diagnostic testing should be considered, and higher compliance rates with patients referred should be sought.


Endovascular Treatment of Ruptured Vertebrobasilar Dissecting Aneurysms Using Flow Diversion Embolization Devices: Single-Institution Experience.
Treatment of ruptured posterior circulation dissecting aneurysms is technically challenging with potentially high morbidity and mortality. We sought to assess the safety and feasibility of using a flow-diversion device (FDD) and a specific acute antiplatelet aggregation protocol in the management of ruptured dissecting aneurysms. Subjects with ruptured dissecting aneurysms treated during a 3-year period were retrospectively identified from a prospective registry. Intraoperative complications, morbidity, and mortality were recorded. Tirofiban maintenance infusion without bolus was administered intravenously immediately after deployment of the FDD, and almost all patients were loaded with dual antiplatelet (aspirin and clopidogrel) post procedure. Clinical follow-up evaluation and modified Rankin Scale were assessed. Nine subjects with ruptured posterior circulation dissecting aneurysms were treated with an FDD: 5 vertebral artery, 2 basilar artery, and 2 posterior inferior cerebellar artery aneurysms. Average World Federation of Neurosurgical Societies score was 2 (range 1-5). Seven patients had external ventricular drain placed acutely for hydrocephalus. Eight patients received tirofiban infusion without bolus after FDD. No intraoperative complications occurred. Two subjects developed asymptomatic intraparenchymal hemorrhage found on surveillance noncontrast computed tomography. One subject suffered a major intraparenchymal hemorrhage and died a few days post intervention after additional anticoagulation was started for a left ventricular assist device. Follow-up modified Rankin Scale within 12 months was 0 in 3 subjects, 1 in 3 subjects, 2 in 1 subject, and 4 in 1. Treatment of dissecting posterior circulation aneurysms with FDDs is feasible and a potential alternative to deconstructive techniques.


Adenosine analogs inhibit fighting in isolated male mice.
The potent adenosine analogs N-ethylcarboxamide adenosine (NECA) and phenylisopropyladenosine (PIA) inhibit fighting and associated agonistic behaviors in isolated male mice. These effects are reversed by methylxanthines; moderate doses of NECA which inhibit fighting have minimal effects on spontaneous locomotor activity. At very low doses, both NECA and PIA increase fighting in parallel with previously reported increases of motor activity. Brain levels of [3H]-NECA and [3H]-PIA achieved at behaviorally effective doses suggest an involvement of adenosine receptors. The biochemical mechanism of adenosine receptor action with respect to fighting is unknown, but may include neuromodulatory effects on the release of other, more classical neurotransmitters.


Ventricular ectopic beats with exit block: a retrospective Holter monitor study.
A retrospective study was conducted to define the incidence of ventricular ectopic beats with exit block (concealed extrasystoles). Of 904 Holter recordings, 92 were admitted for study on the basis of sufficient ventricular ectopic beats on rhythm strips. Concealed bigeminy conforming to the equation of S = 2n - 1 (where S = the interectopic sinus beat and N = any interger) was the most common and occurred in 42 of 92 (46%) Holters included in this study. Concealed trigeminy was observed in 12 of 92 (13%) studies. These Holters also showed ventricular ectopic beats strongly suggestive of parasystole with entrainment. Of 53 Holters reviewed for parasystole 12 were suggestive of, and five indicated this dysrhythmia. We conclude that: 1. Concealed extrasystoles are more common than previously appreciated. 2. Concealed bigeminy and trigeminy appear together and conversion may not always be associated with a change in heart rate. 3. Recognition of this dysrhythmia is uncommon mostly because of inadequate lengths of rhythm strips. 4. Parasystole with entrainment is suggested as a common dysrhythmia when frequent extrasystoles are present.


Automation of diphenylhydantoin and phenobarbital measurements using the ABA-100 with emit reagents.
1. The EMIT-AED procedures for phenobarbital and diphenylhydantoin have been adapted for use on the ABA-100. 2. A basic language computer program has been developed for data reduction and quality control. 3. Within-run and run-to-run coefficients of variations were, in general, less than 8% across the concentration range tested. 4. Performance data on agreement of duplicates and recovery from "spiked" samples were aceptable. 5. The automated procedure provides a two-thirds savings in reagents.


Detection of mumps virus genotype H in two previously vaccinated patients from Mexico City.
Infections caused by mumps virus (MuV) have been successfully prevented through vaccination; however, in recent years, an increasing number of mumps outbreaks have been reported within vaccinated populations. In this study, MuV was genotyped for the first time in Mexico. Saliva samples were obtained from two previously vaccinated patients in Mexico City who had developed parotitis. Viral isolation was carried out in Vero cells, and the SH and HN genes were amplified by RT-PCR. Amplicons were sequenced and compared to a set of reference sequences to identify the MuV genotype.


Intercommunity variations in the association between social ties and mortality in the elderly. A comparative analysis of three communities.
Identical measures of social ties obtained from three community-based cohorts aged 65 and over from East Boston, MA; New Haven, CT; and two rural counties in Iowa permit the first direct cross-community comparison of the hypothesis that social isolation increases 5-year mortality risks (1982 to 1987) for older men and women. In sex-specific proportional hazards analyses, social ties were significantly and inversely related to mortality independently of age in all three cohorts (e.g., relative hazard (RH) = 1.97 to 3.06 for men and women, comparing those with no ties to those with four types of ties). After controlling for age, pack-years of smoking, body mass, chronic conditions, angina, and physical and cognitive disability, social ties remain significant predictors of mortality risk for the men and women in New Haven (RH = 2.4 and 1.8) and for women in Iowa (RH = 1.9). For the men in Iowa (RH = 1.4) and the men and women in East Boston (RH = 1.0 and 1.3), the associations are weaker and nonsignificant.


Evaluation of in vitro and in vivo potential of Bacillus subtilis MBTDCMFRI Ba37 as a candidate probiont in fish health management.
Bacillus subtilis MBTDCMFRI Ba37 (B. subtilis Ba37), an antibacterial strain isolated from the tropical estuarine habitats of Cochin, was evaluated for in vitro and in vivo potential, and its application as a candidate probiont in fish health management. B. subtilis Ba37 was characterized using their morphological and biochemical properties. It exhibited exoenzymatic activities, tolerance to various physiological conditions and a wide spectrum of antibacterial activity against aquaculture pathogens such as Vibrio and Aeromonas. In co-culture assay, B. subtilis Ba37 inhibited Vibrio anguillarum O1 (V. anguillarum O1) even with the initial cell count of 104 CFUmL-1. Cytotoxicity assay performed using the cell free supernatant (CFS) of B. subtilis Ba37 revealed its non toxic nature. A twenty one days of feeding trial was conducted in juveniles of Etroplus suratensis (E.suratensis) by administrating B. subtilis Ba37 to evaluate its efficacy on growth, immune parameters and antioxidant enzyme activities. Overall the supplementation of B. subtilis Ba37 enhanced significantly (P < 0.05) the survival rate, weight gain, specific growth (SGR), feed conversion ratio (FCR), protein efficiency ratio (PER), and feed efficiency (FE) of the fed animals as compared with the control. The immune parameters and antioxidant activities such as total protein, alkaline phosphatase (ALP), superoxide dismutase (SOD) and catalase were also improved significantly (P < 0.05) while serum alanine aminotransferase (SGOT) and serum aspartate aminotransferase (SGPT) activities were decreased slightly than the control. After fifteen days of challenge test, the fish fed with B. subtilis Ba37 showed higher relative percentage survival (RPS) than the control. Thus the study indicated the advantages of B. subtilis Ba37 to be used as a candidate probiont, which could be effectively utilized in managing diseases in aquaculture systems and to improve the health of the host.


Methamphetamine-induced behavioral sensitization in mice: alterations in mu-opioid receptor.
We had previously demonstrated that opioid receptors contribute to the induction and expression of behavioral sensitization induced by repeated daily injection with 2.5 mg/kg of methamphetamine for 7 days. Using the same regimen, the present study investigated the alterations in mu-opioid receptor during the induction (on days 2, 5, and 8) and expression (on days 11 and 21) periods of behavioral sensitization. Radioligand binding revealed that the maximal binding of mu-opioid receptor was not changed on days 2 and 5, but down-regulated on day 8. After cessation of drug treatment, the maximal binding of mu-opioid receptor gradually and time-dependently returned to normal level on day 11 and up-regulated on day 21. In contrast, no changes in delta- and kappa-opioid receptors were detectable on any given day examined. The potency of DAMGO for [(35)S]-GTPgammaS coupling was enhanced on days 2, 5, 11, and 21. Moreover, 1 muM of naltrexone or beta-chlornaltrexamine significantly suppressed the basal [(35)S]-GTPgammaS coupling on days 2, 11, and 21. These findings indicate enhanced responsiveness and elevated constitutive activity of mu-opioid receptor. In summary, our data clearly demonstrate that alterations in mu-opioid receptor are involved in and may contribute to the sensitization to locomotor stimulating effect of methamphetamine.


Exaggerated arsenic nephrotoxicity in female mice through estrogen-dependent impairments in the autophagic flux.
Gender is one of the essential factors in the development of various diseases and poisoning. Therefore, we herein examined gender differences in sodium arsenite (NaAsO2)-induced acute renal dysfunction. When male and female BALB/c mice were subcutaneously injected with NaAsO2 (12.5mg/kg), serum and urinary markers for proximal tubular injury were significantly higher in female mice than in male ones. NaAsO2-induced histopathological alterations were consistently more evident in females than in males. Ovariectomy, but not orchiectomy significantly attenuated NaAsO2-induced renal injury. These results imply that the hypersusceptibility of female mice is attributed to estrogen signals. NaAsO2 suppressed the autophagic flux in tubular cells through the activation of ERK. Enhancements in the activation of ERK were significantly greater in females than in males, with the eventual accumulation of LC3-II and P62 in the kidneys, implying that the autophagic flux is impaired in females. The IL-6/STAT3 signaling pathway had protective roles in NaAsO2-induced nephrotoxicity through the suppression of ERK activation. Despite the absence of differences in intrarenal IL-6 expression between male and female mice, STAT3 was less activated with enhanced SOCS3 expression in females than in males. An in vitro study using mProx24 cells revealed that the estrogen treatment induced SOCS3 expression, and eventually suppressed the autophagic flux, as evidenced by greater increases in the accumulation of LC3-II and p62 with ERK activation, which was canceled by the knockdown of Socs3. Collectively, these results indicate that estrogen has a negative impact on the development of NaAsO2 nephrotoxicity through its suppression of the autophagic flux.


Attitude of Italian dental practitioners toward bruxism assessment and management: A survey-based study.
Bruxism is a spectrum of masticatory muscles activities. According to the recent evidence and international consensus, there is no indication to treat bruxism unless clinical consequences are present. The aim of the present study was to investigate the approach of Italian dentists to bruxism in their clinical practice. An anonymous online survey was developed, composed by 26 items grouped into five sections: (1) Characteristics of the respondent (Q1-Q6); (2) Bruxism frequencies (Q7-Q11); (3) Bruxism assessment (Q12-Q15); (4) Bruxism management (Q16-Q20); (5) Occlusal splints therapy (Q21-Q26). A total of 384 practitioners, including specialists and non-specialists, participated in this survey. The majority of the respondents reported that 1-3 out of ten patients presented with bruxism. The diagnosis is mainly performed with non-instrumental methods, and facial pain and dental wear are the major clinical consequence associated with bruxism. Almost the entire sample of respondents report to offer occlusal splints to bruxism patients, and 41% refer to perform occlusal adjustments. Almost half of the respondents have never proposed any form of cognitive-behavioural therapy. The results of the current survey highlighted several inconsistencies in Italian dentists' approaches to bruxism, suggesting the need for better education of practitioners and for the development of a standardized protocol to assess and manage bruxism in dental practices.


Biogerontology research in Spain.
The article describes the features of biogerontology research in Spain and outlines the research in the biology of ageing, covering a wide spectrum of areas and topics. Research in biogerontology has expanded notably in quality and quantity in the last decades with the development of internationally recognized research groups actively working in the analysis of the complex process of ageing. In the last few years research in ageing has become a priority area in the National Program of Research which has substantially increased funds specifically allocated to biogerontology and biological research on senescence. Despite these improvements, special efforts have to be made not only to consolidate the existing groups but also to facilitate the initiation and development of new research groups in Universities, Hospitals and research institutions with capacity to incorporate trained researchers in this area. It would promote the continuous incorporation of technical and scientific advances in other disciplines to the understanding the biology of ageing and the molecular basis of cellular senescence, that will benefit actual and future ageing population.


Schwannoma of the descending loop of the hypoglossal nerve: Case report.
Schwannomas of the descending loop of the hypoglossal nerve are very rare. They are slow-growing tumors that may masquerade a carotid body tumor. A 60-year-old female was referred for a latero-cervical mass appearing as a chemodectoma at CT-scan. At operation, a 2cm mass arising from the descending loop of the hypoglossal nerve was resected en bloc with the loop itself and a functional lymphadenectomy was associated. Post-operative course was uneventful and the patient is free from disease recurrence at one year follow-up. En bloc resection remains the real curative treatment of Schwannomas, ensuring unlimited freedom from disease, although causing functional impairment which may be significant. Nonetheless recurrence should be prevented as, beside requiring reintervention, it may harbor a malignant evolution towards sarcoma. Schwannomas of the descending lop of the hypoglossal nerve may masquerade a chemodectoma of the carotid bifurcation and can be curatively resected without any functional impairment.


Selective killing of circulating tumor cells prevents metastasis and extends survival.
Distant metastasis is initiated by circulating tumor cells (CTCs), which are considered to be a determining factor for the degree of metastasis and the survival of cancer patients. Although CTC-based diagnostic approaches are being rapidly developed, limited studies have proven the benefits of CTC elimination, with most studies providing only hypothetical inference because of the technical difficulty in examining the effects of CTC elimination in vivo. We modified photodynamic therapy to specifically eliminate green fluorescent protein (GFP)-expressing CTCs and evaluated the therapeutic efficacy of CTC elimination. When circulating blood is illuminated with a blue laser (λ = 473 nm), the combination of GFP and photosensitizers induces a selective elimination of GFP-expressing CTCs, with limited effect on normal cells. In GFP-expressing cancer cell-infused or transplanted mice models, the treatment suppressed distant metastasis and extended the survival of the tumor-bearing mice. Taken together, CTCs are a core seed to be metastasized into secondary organs and elimination of CTCs may improve the survival of cancer patients.


Climate warming increases the proportions of specific antibiotic resistance genes in natural soil ecosystems.
Understanding the future distribution of antibiotic resistance in natural soil ecosystems is important to forecast their impacts on ecosystem and human health under projected climate change scenarios. Therefore, it is critical and timely to decipher the links between climate warming and antibiotic resistance, two of Earth's most imminent problems. Here, we explored the role of five-year simulated climate warming (+ 4 °C) on the diversity and proportions of soil antibiotic resistance genes (ARGs) across three seasons in both plantation and natural forest ecosystems. We found that the positive effects of warming on the number and proportions of ARGs were dependent on the sampling seasons (summer, autumn and winter), and seasonality was a key factor driving the patterns of ARG compositions in forest soils. Fifteen ARGs, conferring resistance to common antibiotics including aminoglycoside, beta-lactam, macrolide-lincosamide-streptogramin B, multidrug, sulfonamide, and tetracycline, were significantly enriched in the warming treatment. We showed that changes in soil properties and community compositions of bacteria, fungi and protists can explain the changes in soil ARGs under climate warming. Taken together, these findings advance our understanding of environmental ARGs under the context of future climate change and suggest that elevated temperature may promote the abundance of specific soil ARGs, with important implications for ecosystem and human health.


Protease Substrate Profiling by N-Terminal COFRADIC.
Detection of (neo-)N-terminal peptides is essential for identifying protease cleavage sites . We here present an update of a well-established and efficient selection method for enriching N-terminal peptides out of peptide mixtures: N-terminal COFRADIC (COmbined FRActional DIagonal Chromatography). This method is based on the old concept of diagonal chromatography, which involves a peptide modification step in between otherwise identical chromatographic separations, with this modification step finally allowing for the isolation of N-terminal peptides by longer retention of non-N-terminal peptides on the resin. N-terminal COFRADIC has been successfully applied in many protease-centric studies, as well as for studies on protein alpha-N-acetylation and on characterizing alternative translation initiation events.


Antibody raised against extracellular proteinases of Sporothrix schenckii in S. schenckii inoculated hairless mice.
Sporothrix schenckii produces two extracellular proteinases, namely proteinase I and II. Proteinase I is a serine proteinase, inhibited by chymostatin, while proteinase II is an aspartic proteinase, inhibited by pepstatin. Studies on substrate specificity and the effect of proteinase inhibitors on cell growth suggest an important role for these proteinases in terms of fungal invasion and growth. There has, however, been no evidence presented demonstrating that S. schenckii produces 2 extracellular proteinases in vivo. In order to substantiate the in vivo production of proteinases and to attempt a preliminary serodiagnosis of sporotrichosis, serum antibodies against 2 proteinases were assayed using S. schenckii inoculated hairless mice. Subsequent to an intracutaneous injection of S. schenckii to the mouse skin, nodules spontaneously formed and disappeared for a period of 4 weeks. Histopathological examination results were in accordance with the microscopic observations. Micro-organisms disappeared during the fourth week. Serum antibody titers against purified proteinases I and II were measured weekly, using enzyme-linked immunosorbent assay (EIA). As a result, the time course of the antibody titers to both proteinases I and II were parallel to that of macroscopic and microscopic observations in an experimental mouse sporotrichosis model. These results suggest that S. schenckii produces both proteinases I and II in vivo. Moreover, the detection of antibodies against these proteinases can contribute to a serodiagnosis of sporotrichosis.


Dataset of long-term compressive strength of concrete with manufactured sand.
This paper presents 186 groups compressive strength tests data of concrete with manufactured sand (MSC) in different curing age and 262 groups compressive strength tests data of MSC at 28 days collected from authors' experiments and other researches in China. Further interpretation and discussion were described in this issues.


Preliminary outcomes of arthroscopic biceps rerouting for the treatment of large to massive rotator cuff tears.
We aimed to evaluate the short-term outcomes of arthroscopic biceps rerouting (ABR) for the treatment of large to massive rotator cuff tears (LMRCTs). A prospective evaluation of patients treated with ABR for the repair of LMRCTs was performed, with a minimum follow-up period of 18 months. Range of motion and functional outcomes (visual analog scale pain score, American Shoulder and Elbow Surgeons score, and Korean Shoulder Scale score) were assessed preoperatively and at final follow-up. Radiographs were used to evaluate the acromiohumeral interval (AHI). Magnetic resonance imaging was performed at 2 and 12 months postoperatively to examine the integrity of the repaired rotator cuff tendons. Eighty patients who met the study criteria underwent ABR from March 2017 to January 2019 in our hospital. Of these patients, 61 could be evaluated ≥18 months after surgery. The average age of the enrolled patients was 64.5 years. The visual analog scale pain score decreased from 3.7 preoperatively to 1.6 at final follow-up (P = .019), the American Shoulder and Elbow Surgeons score improved from 60.0 to 85.2 (P < .001), and the Korean Shoulder Scale score improved from 64.3 to 85.3 (P = .001). Assessment of range of motion showed significant improvement in forward flexion (from 138° to 146°, P < .001), external rotation at 90° of abduction (from 80° to 85°, P = .037), and internal rotation (from spinal level 9 to spinal level 10, P = .015) from preoperatively to last follow-up. The AHI was 7.1 mm at baseline and improved significantly to 9.7 mm at 3 months postoperatively (P < .001). The mean AHI at last follow-up was only 9 mm, but this was still significantly better than the mean preoperative AHI (P < .001). Of the patients, 16 (26%) exhibited a retear of the repaired rotator cuff on magnetic resonance imaging at 12 months postoperatively. Male sex was the only significant risk factor for retear (P = .037). ABR improved the functional and radiologic outcomes of patients with LMRCTs. The ABR technique can be a useful treatment option for LMRCTs.


The ancient Thracian endemic plant Haberlea rhodopensis Friv. and related species: A review.
Haberlea rhodopensis (HR) use dates back to the Thracian and Roman periods. Bulgarians call it Orpheus flower and exploit its leaves for making tea and extracts with detoxifying, tonic, restorative and rejuvenating effects. HR was traditionally applied in wound healing and treatment of cattle diseases. The general aim of the review was to analyze the progress of phytochemical and pharmacological studies on HR, focusing on its radioprotective and immunomodulating effects. The main source material for the review was collected using several global search engines with the phrase: Haberlea rhodopensis, as well as Bulgarian books and dissertations. HR metabolite profile includes large amounts of free sugars, polyols, polysaccharides (PS), flavonoids, phenolic acids and carotenoids. The radioprotective effect of 70% ethanolic leaf extract (70HREE) is explained by preservation of lymphocytes, other blood cells and testicular tissue from aberration under γ-radiation via stimulation of antioxidant enzymes and neutralization of free radicals. The extract immunomodulating activity results from raised antibody response, stem and neutrophil cell count, complement system activation, anti-tumour and anti-inflammatory effects. The detoxifying, restorative, rejuvenating and wound healing plant properties known to ethnomedicine were supported by radioprotective and immunomodulating studies. Metabolites of phenolic origin involved in HR resurrection are supposed to contribute to its radioprotective, immunomodulatory, anti-mutagenic and anti-aging effects. However, there is no chemical characterization of 70HREE in the investigations with humans and animals. Structure-activity relationship studies on HR immunomodulating and radioprotective compounds, and on their mode of action are required. They should include not only phenols but PS and other unexplored molecules. The metabolic activity of phagocytes, platelets and lymphocytes triggered by HR extracts has to be examined to elucidate their immunostimulatory potential. HR formulations can be tested in cosmetic, food and medical products as adjuvants to treat infectious, chronic inflammatory and tumour diseases, and especially in patients undergoing radiotherapy.


Team-based primary care program for disabled people and changes in rate of unmet health care needs.
Few studies have been conducted on the application of specific and practical methods, such as interventions, for reducing the unmet health care needs (UHCN) of disabled people. The study aims to evaluate the impact of the team-based primary care program (TPCP) for disabled people on UHCN. In 2017, we surveyed 696 disabled people who were enrolled in the TPCP at one of the 11 institutions belonging to the Korea Health Welfare Social Cooperative Federation from 2015 to 2017 to assess their unmet needs before and after enrolment. We conducted a logistic regression analysis before and after the program to evaluate the relationship between participation period and unmet needs after adjusting for physician type, gender, age, drinking, monthly income, disability type, personal assistance services and living alone. After using the service, the proportion of disabled people with unmet needs decreased from 42.9% to 20.4% for a medical doctor and 43.6% to 18.6% for a Korean medical (KM) doctor. After adjusting for related factors and stratifying with type of physician, the proportion of disabled people with unmet needs decreased significantly in response to the participation period for the medical doctor-involved program (P-trend < 0.001); this was not observed in the KM counterpart (P-trend = 0.6). The TPCP for disabled people provides disease prevention, health care and health promotion activities and is crucial for solving the unmet needs.


Simple 1-Step Ankle Arthroscopy Distraction.
Ankle arthroscopy has emerged as a viable treatment option for multiple ankle pathologies and continues to have expanding indications as technology and techniques improve. Historically, ankle arthroscopy used skeletal traction, and it has transitioned to noninvasive soft-tissue distraction because of high rates of iatrogenic complications. Although soft-tissue distraction has decreased complications, it continues to be both cumbersome and time-consuming. Thus we propose a 1-step simple ankle arthroscopy distraction technique that uses an external positioning arm to allow the surgeon to apply manual traction in multiple positions without the use of any reprocessed sterile equipment.


Impact of septoplasty on pulmonary artery pressure in patients with markedly deviated septum.
The nasal septal deviation (NSD) increases upper airway obstruction. This study aimed to measure the mean pulmonary arterial pressure (mPAP) of the patients with markedly deviated nasal septum and to determine the effect of septoplasty on the pulmonary arterial pressure. Fifty-one patients with NSD (mean age, 37.1 [SD, 8.6] years; 27 men and 24 women) were included in the study. Thirty-five of the patients (22 men, 13 women) aged between 21 and 55 years (mean, 35.1 [SD, 8.9] years) comprised the control group. Mean pulmonary arterial pressure was measured in the preoperative period and postoperative third month. The mean preoperative mPAP value (25.4 [SD, 5.3]) of the study group was statistically significantly higher than that of the control group (20.5 [SD, 2.8]) (P = 0.000). There was a significant decrease in mPAP after the operation (20.6 [SD, 3.8]) (P = 0.000). Twenty-two of 51 patients had pulmonary arterial hypertension. Markedly deviated nasal septum significantly affected mPAP. Septoplasty was efficient in the treatment of patients with NSD.


Understanding clinical decision-making during the COVID-19 pandemic: A cross-sectional worldwide survey.
The lack of evidence-based recommendations for therapeutic decisions during the early weeks of the COVID-19 pandemic creates a unique scenario of clinical decision making which is worth to analyze. We aim to identify the drivers of therapeutic aggressiveness during the first weeks of the COVID-19 pandemic. This cross-sectional worldwide survey (conducted April 12 to 19, 2020) was aimed at physicians who managed patients diagnosed with COVID-19. Treatment preferences were collected in five different clinical scenarios. We used multilevel mixed-effects ordered logistic regression to identify variables that were associated with the use of more aggressive therapies. The survey was completed by 852 physicians from 44 different specialties and 29 countries. The heterogeneity of therapeutic decisions increased as the clinical scenario worsened. Factors associated with aggressive therapeutic decisions were higher self-perceived expertise (high vs. null, OR 1.95, 95%CI 1.31-2.89), perceived quality of COVID-19 publications (high vs. null, OR 1.92, 95%CI 1.17-3.16), and female sex (OR 1.17, 95%CI 1.02-1.33). Conversely, Infectious Diseases specialty, Latin American and North American origin, lower confidence in the treatments chosen, and having published articles indexed in PubMed as the first-author were associated with the use of less aggressive therapies. Our study provides insight into the drivers of the decision-making process during a new and extreme health emergency. Different factors including the perceived expertise and quality of publications, gender, geographic origin, medical specialty and implication in medical research influenced this process. The clinical severity attenuated the physician's tolerance for uncertainty. No funding was required.


Advances in research on carcinogenic and genotoxic by-products of chlorine disinfection: chlorinated hydroxyfuranones and chlorinated acetic acids.
The introduction of chlorination of public drinking water in the early 1900's was a major factor in the fight against waterborne disease. In the 1970's it was discovered that chlorine reacted with naturally occurring organic constituents, particularly in surface water, to yield small quantities of chlorinated by-products such as chloroform for which regulations were subsequently developed. Since then there has been shown to be a substantial number of other by-products some in concentrations of a few nanograms/l and others similar concentrations to the THM. Of particular note are the potent bacterial mutagen MX and the chlorinated acetic acids. Current research into the significance of these for man is described and the key issues for risk assessment are identified.


Short-term weight changes in community-dwelling older adults: the Health, Aging, and Body Composition Weight Change Substudy.
The frequency and short-term natural history of weight loss in community-dwelling older adults have not been described. Unintentional weight loss may be more likely to continue than intentional weight loss. The present substudy described the frequency of a > or = 5% loss or gain in body weight in community-dwelling older adults at an annual examination of the Health, Aging, and Body Composition (Health ABC) Study and 6 mo later. The weight-management practices used by the participants were also described. A total of 522 older adults with either a > or = 5% weight gain (n = 116) or a > or = 5% weight loss (n = 171) in the previous year were compared with a random sample of weight-stable older adults (< 5% weight loss or gain, n = 235) at the fourth annual visit of the ongoing Health ABC Study. The participants' weight-loss intention and weight-management practices were assessed by an interview. The participants' weight was reassessed 6 mo later. Compared with the weight-stable participants, the participants who had lost or gained weight at the substudy baseline were more likely to have subsequent weight changes. The direction of the subsequent weight change, however, was more likely toward either maintenance of or recovery from the previous weight change. Only 4% of the participants who gained weight and 11% of those who lost weight continued to gain or lose weight, respectively. Continued weight loss was more common in the participants with unintentional weight loss than in those with intentional weight loss, but the difference was not significant. Weight changes were common, but most participants, including those who unintentionally lost weight, maintained their weight change or resolved their weight change in 6 mo. Unintentional weight loss appears less likely to resolve than other weight changes.


Shape-changing chains for morphometric analysis of 2D and 3D, open or closed outlines.
Morphometrics is a multivariate technique for shape analysis widely employed in biological, medical, and paleoanthropological applications. Commonly used morphometric methods require analyzing a huge amount of variables for problems involving a large number of specimens or complex shapes. Moreover, the analysis results are sometimes difficult to interpret and assess. This paper presents a methodology to synthesize a shape-changing chain for 2D or 3D curve fitting and to employ the chain parameters in stepwise discriminant analysis (DA). The shape-changing chain is comprised of three types of segments, including rigid segments that have fixed length and shape, scalable segments with a fixed shape, and extendible segments with constant curvature and torsion. Three examples are presented, including 2D mandible profiles of fossil hominin, 2D leaf outlines, and 3D suture curves on infant skulls. The results demonstrate that the shape-changing chain has several advantages over common morphometric methods. Specifically, it can be applied to a wide range of 2D or 3D profiles, including open or closed curves, and smooth or serrated curves. Additionally, the segmentation of profiles is a flexible and automatic protocol that can consider both biological and geometric features, the number of variables obtained from the fitting results for statistical analysis is modest, and the chain parameters that characterize the profiles can have physical meaning.


Mechanisms of protective functions of Escherichia coli polyamines against toxic effect of paraquat, which causes superoxide stress.
The toxic effect of paraquat, mainly caused by production of superoxide radicals, results in the induction of polyamine synthesizing enzymes and their products in cells of exponentially growing E. coli cultures. The activity of ornithine decarboxylase increases approximately twofold and the activity of lysine decarboxylase increases 1.4-fold. Unlike cadaverine, putrescine and spermidine stimulate expression of the soxRS regulon genes, and this depends on the polyamine concentration and is specific for different genes of the regulon. Of six genes studied, the maximum (to 130%), minimum (about 40%), and average (60-80%) stimulation was observed for the stress induction of nfo (endonuclease IV), sodA (superoxide dismutase), and the soxS gene of the transcriptional regulator, respectively. Addition of paraquat to exponentially growing E. coli culture results in oscillations of the topological state of DNA. Putrescine prevents the drop in the extent of DNA supercoiling caused by the damaging effect of free radicals during the first minutes of stress and increases it during the restoration (the peak of the transcriptional activity of the soxRS regulon genes). These effects are due to properties of putrescine as a DNA protector and modulator of its topological state. The ability of putrescine to decrease the mutation rate under conditions of superoxide stress induced by addition of paraquat is shown by the example of rifampicin resistance.


The investigation on the pressure-induced phase transition in linoleic acid by in situ Raman spectroscopy.
With diamond anvil cell as a high-pressure apparatus, the in situ Raman spectra of linoleic acid from normal pressure to 1.29 GPa were measured to investigate the effect of pressure on the structural changes. In the pressure ranges of 0.07-0.12 GPa and 0.31-0.53 GPa, the significant changes in Raman spectra show that linoleic acid undergoes two pressure-induced phase transitions. Spectral analysis indicates that the polymethylene chain of linoleic acid molecule transforms from the disordered gauche conformation to the ordered trans conformation in the range of 0.07-0.12 GPa. And the polymethylene chain of linoleic acid molecule remains the ordered trans conformation whereas the conformation of the olefin group significantly changes and the degree of conformational order increases in the range of 0.31-0.53 GPa. The pressure-induced phase transitions in linoleic acid are reversible.


Colour discrimination thresholds in Parkinson's disease: results obtained with a rapid computer-controlled colour vision test.
A dysfunction of dopaminergic retinal neurons is thought to occur in Parkinson's disease, manifesting itself in impaired performance on various visual discrimination tasks. We have investigated whether differences in colour discrimination could readily be detected between a normal group and a Parkinsonian group, using a computer-controlled test of colour vision. Although some individual Parkinsonian patients showed an abnormal elevation of colour discrimination thresholds, there was no significant difference between the normal group and the Parkinsonian group.


An enantioselective four-component reaction via assembling two reaction intermediates.
A reaction intermediate is a key molecular entity that has been used in explaining how starting materials converts into the final products in the reaction, and it is usually unstable, highly reactive, and short-lived. Extensive efforts have been devoted in identifying and characterizing such species via advanced physico-chemical analytical techniques. As an appealing alternative, trapping experiments are powerful tools in this field. This trapping strategy opens an opportunity to discover multicomponent reactions. In this work, we report various highly diastereoselective and enantioselective four-component reactions (containing alcohols, diazoesters, enamines/indoles and aldehydes) which involve the coupling of in situ generated intermediates (iminium and enol). The reaction conditions presented herein to produce over 100 examples of four-component reaction products proceed under mild reaction conditions and show high functional group tolerance to a broad range of substrates. Based on experimental and computational analyses, a plausible mechanism of this multicomponent reaction is proposed.