Prevalence and Associated Factors of Sarcopenia and Frailty in Parkinson's Disease: A Cross-Sectional Study.
Sarcopenia and frailty are found in up to one-third of the general elderly population. Both are associated with major adverse health outcomes such as nursing home placement, disability, decreased quality of life, and death. Data on the frequency of both syndromes in Parkinson's disease (PD), however, are very limited. We aimed to screen for sarcopenia and frailty in PD patients and to assess potential associations of both geriatric syndromes with demographic and clinical parameters as well as quality of life. In this observational, cross-sectional study, we included 104 PD patients from a tertiary center and 330 non-PD controls from a population-based cohort aged > 65 years. All groups were screened for sarcopenia using the SARC-F score and for frailty using the Clinical Frailty Scale of the Canadian Study of Health and Aging (CSHA CFS). Prevalence rates of sarcopenia and frailty were also assessed in 18 PD patients from a population-based cohort aged > 65 years. Moreover, PD patients from the tertiary center were evaluated for motor and non-motor symptoms, quality of life, and dependency. The prevalence of sarcopenia was 55.8% (95% CI: 46.2-64.9%) in PD patients from the tertiary center and 8.2% (5.7-11.7%; p < 0.001) in non-PD controls. Frailty was detected in 35.6% (27.0-45.2%) and 5.2% (3.2-8.1%; p < 0.001). Prevalence rates for sarcopenia and frailty were 33.3% (16.1-56.4%; p = 0.004) and 22.2% (8.5-45.8%; p = 0.017) in the community-based PD sample. Both sarcopenia and frailty were significantly associated with longer disease duration, higher motor impairment, higher Hoehn and Yahr stages, decreased quality of life, higher frequency of falls, a higher non-motor symptom burden, institutionalization, and higher care levels in PD patients from a tertiary center compared to not affected PD patients (all p < 0.05). Both frailty and sarcopenia are more common in PD patients than in the general community and are associated with a more adverse course of the disease. Future studies should look into underlying risk factors for the occurrence of sarcopenia and frailty in PD patients and into adequate management to prevent and mitigate them.


An aeration energy model for an immersed membrane bioreactor.
A simple model for evaluating energy demand arising from aeration of an MBR is presented based on a combination of empirical data for the membrane aeration and biokinetic modelling for the biological aeration. The model assumes that aeration of the membrane provides a proportion of the dissolved oxygen demanded for the biotreatment. The model also assumes, based on literature information sources, a linear relationship between membrane permeability and membrane aeration up to a threshold value, beyond which permeability is unchanged with membrane aeration. The model was benchmarked against two full-scale plant to obtain the most appropriate and conservative value of the slope of the flux:aeration curve and the blower efficiency. Benchmarking in this way produced a match to within 20% of all key process plant operational parameters. The model demonstrated that significant reductions in aeration energy could be obtained through operation at lower flux and reducing the membrane aeration requirement accordingly, so-called "proportional aeration" at lower flows. Similarly, increasing oxygen transfer from membrane aeration would also be expected to decrease energy demand. A sensitivity analysis of some of the key parameters revealed that, of the key operating parameters, loading, SOTE and MLSS concentration remain the most critical in determining energy demand. It is suggested that a key parameter representing membrane aeration in MBRs is the mean in-module air upflow velocity U, since this gives a reasonable representation of the shear applied through membrane aeration. U was found to vary between 0.04 and 0.1m/s across a number of modern large pilot and full-scale plant. An analysis reveals that significant reductions in energy demand are attained through operating at lower MLSS levels and membrane fluxes. Evidence provided from recent controlled pilot trials implies that halving the flux can reduce the aeration is suggested whereby the number of membrane tanks on line and/or the membrane aeration intensity is adjusted according to the flow, and thus flux, so as to reduce the overall aeration energy demand.


Gonadotropinoma presenting as a case of pseudo-ovarian failure changing to macroprolactinoma.
To present the first gonadotropinoma presenting as pseudo-menopause in a teenager. Human menopausal gonadotropins (hMG) were given to a 37-year-old woman whose hypergonadotropic amenorrhea with estrogen deficiency as a teenager was changed to hypogonadotropic amenorrhea by the growth and prolactin secretion of a macroprolactinoma. The patient responded multiple times, and every time to stimulation with hMG and each time produced several dominant follicles. She delivered two babies including conception at age 40. The fact that this woman could respond consistently to hMG 20 years after the diagnosis of premature menopause, it is clear that initially the etiology of the extremely high LH and FSH levels in an estrogen-deficient 18-year-old was the presence of gonadotropinoma secreting inert LH and FSH. Since serum prolactin was measured the first time at age 37, it is not clear whether the endogenous biologically active gonadotropine were suppressed by replacement of the gonadotroph cells with tumor cells or suppression of endogenous gonadotropins by hyperprolactinoma.


Therapeutic Effect of Polaprezinc on Reflux Esophagitis in the Rat Model.
To explore the protective effects and therapeutic mechanism of Esomeprazole (PPI), polaprezinc granule (PZ), and PPI + PZ on reflux esophagitis (RE) in the rat model. Wistar rats were randomly divided into 9 groups, which contain the control group, the acid cessation group (0.7% HCl, Q3D × 4), and the acid persistence group (0.7% HCl, Q3D × 11). PPI was administered by gavage at 8 mg·kg-1 body weight and PZ was administered by gavage at 120 mg·kg-1 body weight once a day for 15 days. The gastric cardia tissue of the feeding tube was observed under the light microscope, and the levels of interleukin-8 (IL-8) and prostaglandin E2 (PGE2) were measured by ELISA. The expression of EGFR, Akt, p-Akt, and p-mTOR was detected by Western blot. The ELISA results showed that the levels of IL-8 and PGE2 were significantly increased in the model group, but decreased in all groups after treatment. In the acid cessation group, PZ treatment had the most significant effect on reducing IL-8 levels and PPI + PZ treatment had the most significant effect on reducing PGE2 levels. In the acid persistence group, the PPI treatment had the most significant effect on reducing the levels of IL-8 and PGE2, and the PZ treatment could also significantly reduce their levels, close to the normal value. Western blot results showed that the expression of PI3K/Akt/mTOR pathway protein was increased in the model group, while its expression was decreased after treatment. Polaprezinc has a significant therapeutic effect on RE in rats, which can reduce the levels of IL-8 and PGE2 and downregulate the expression of PI3K/Akt/mTOR signal pathway protein. The efficacy of polaprezinc in the treatment of reflux esophagitis is comparable to that of PPI, and the combination of them is more effective in the reflux esophagitis treatment.


Immediately loaded anterior single-tooth implants: two cases.
Immediate loading of implants into fresh extraction sockets has the advantage of decreasing the period of healing, reducing the resorption of the alveolar bone, and achieving optimal esthetic results. These cases reveal the clinical success of immediate loaded single-tooth implants placed in fresh extraction sites.


Swallowing difficulties with oral drugs among polypharmacy patients attending community pharmacies.
Swallowing difficulties are common and can affect patients' ability to take solid oral dosage forms, thus compromising medication adherence. Strategies developed by patients to overcome such difficulties while taking medicines have seldom been described. To determine prevalence and characteristics of swallowing difficulties among primary care patients attending their community pharmacies; to explore strategies developed by patients to overcome their difficulties, and health professionals' awareness of these problems. Prospective study with a semi-structured questionnaire in random community pharmacies located in two Swiss regions. In each pharmacy, an interviewer asked 16 questions to each consecutive patient (18 years and older) with a prescription for at least 3 different solid oral forms. Quantification of number of patients with swallowing difficulties and detailed description of difficulties. Among 122 pharmacies, 59 (48 %) accepted to join the study and 410 patients were enrolled. Thirty-seven patients (9.0 %) reported ongoing swallowing difficulties, while 55 patients (13.4 %) reported past difficulties. For the majority of patients, difficulties occurred at each single dose (83.7 %), with a single medication (59.8 %) and lasted for less than 12 months (53.8 %). Number of tablets was not the main trigger. Swallowing difficulties impaired extremely daily life in 12 % of the patients. Intentional non adherence (23 % of patients) and altering the oral dose formulation were the most common and potentially harmful strategies used by patients to overcome their swallowing difficulties. According to the patients, pharmacists and physicians rarely inquired about their swallowing difficulties. We report a fairly high prevalence of swallowing difficulties in polypharmacy patients attending their community pharmacies. Pharmacists have to interview patients on their swallowing difficulties in a more systematic way, support patients in finding solutions and refer them to their physician if necessary to ensure continuity in care.


Efficient and Accurate Quantitative Profiling of Alternative Splicing Patterns of Any Complexity on a Laptop.
Alternative splicing (AS) is a widespread process underlying the generation of transcriptomic and proteomic diversity and is frequently misregulated in human disease. Accordingly, an important goal of biomedical research is the development of tools capable of comprehensively, accurately, and efficiently profiling AS. Here, we describe Whippet, an easy-to-use RNA-seq analysis method that rapidly-with hardware requirements compatible with a laptop-models and quantifies AS events of any complexity without loss of accuracy. Using an entropic measure of splicing complexity, Whippet reveals that one-third of human protein coding genes produce transcripts with complex AS events involving co-expression of two or more principal splice isoforms. We observe that high-entropy AS events are more prevalent in tumor relative to matched normal tissues and correlate with increased expression of proto-oncogenic splicing factors. Whippet thus affords the rapid and accurate analysis of AS events of any complexity, and as such will facilitate future biomedical research.


Self-luminescent photodynamic therapy using breast cancer targeted proteins.
Despite the potential of photodynamic therapy (PDT), its comprehensive use in cancer treatment has not been achieved because of the nondegradable risks of photosensitizing drugs and limits of light penetration and instrumentation. Here, we present bioluminescence (BL)-induced proteinaceous PDT (BLiP-PDT), through the combination of luciferase and a reactive oxygen species (ROS)-generating protein (Luc-RGP), which is self-luminescent and degradable. After exposure to coelenterazine-h as a substrate for luciferase without external light irradiation, Luc-RGP fused with a small lead peptide-induced breast cancer cell death through the generation of BL-sensitive ROS in the plasma membrane. Even with extremely low light energy, BLiP-PDT exhibited targeted effects in primary breast cancer cells from patients and in in vivo tumor xenograft mouse models. These findings suggest that BLiP-PDT is immediately useful as a promising theranostic approach against various cancers.


Cannabis use among Canadian adults with cancer (2007-2016): results from a national survey.
Background: The current study aims to evaluate the rates and associations of cannabis use among Canadian adults with cancer (2007-2016).Methods: Canadian Community Health Survey (CCHS) (2007-2016) was accessed and adult participants who answered yes to the question "Do you have cancer?" and who have complete information about cannabis use were included. Multivariable logistic regression was used to identify factors associated with cannabis use.Results: A total of 4667 participants who currently have cancer were included in the current analysis. The rate of cannabis use increased throughout the study (34.4% in 2015-2016 versus 27.7% in 2007-2008). The following factors were associated with cannabis use: younger age (OR: 3.64; 95% CI: 2.27-5.86; P<0.01); male sex (OR: 2.11; 95% CI: 1.80-2.48; P<0.01); white race (OR: 2.02; 95% CI: 1.46-2.78; P<0.01); single status (OR for married versus single: 0.38; 95% CI: 0.29-0.50; P<0.01) and higher income (OR for income < 20,000 versus income ≥ 80,000: 00.74; 95% CI: 0.56-0.99; P=0.04).Conclusions: Within this study cohort of Canadian adults with current cancer diagnosis, cannabis use is not uncommon. A history of cannabis use is associated with younger age, male sex, white race, non-married status, and higher income.


Assessment of compliance with home cardiorespiratory monitoring in infants at risk of sudden infant death syndrome. Collaborative Home Infant Monitoring Evaluation (CHIME).
Documented monitoring was used to evaluate prospectively (1) the level of compliance among infants in whom cardiorespiratory monitoring was clinically indicated and (2) factors that might influence compliance: diagnosis, socioeconomic status, maternal age and education, and alarms. Sixty-seven infants (51% female, 49% term) were sequentially enrolled, and monitoring was prescribed for the following indications: siblings of sudden infant death syndrome victims (16%), apnea of prematurity (45%), and apparent life-threatening events or apnea of infancy (39%). Demographic data, alarm and event data, and a summary report of monitor use from the first monitor download were obtained. Maternal age, education, and insurance status did not differ significantly by indication for monitoring. The median number of monitor alarms per 10 hours of use was 0.7 for apnea or bradycardia and 0.6 for loose lead alarms. Monitors were available for use in the home from 2 to 106 days (median, 11 days). Median hours of monitor use per full day in the home was 15.5 hours. Of 67 infants, 58 used the monitor for at least part of every day in the home. The number of hours of monitor use per day did not differ significantly by diagnostic category, chronologic age, alarms, maternal age, education, or insurance type. This study population of infants at increased risk of sudden infant death syndrome had excellent compliance; 75% of the infants were monitored more than 10.5 hours per day, and 25% were monitored more than 21 hours per day. Documented monitoring provides an objective measure of compliance. These data provide a potential goal for level of compliance with home cardiorespiratory monitoring.


Evaluation of the corneal topographic characteristics of keratoconus with orbscan II in patients with and without atopy.
: To analyze the differences in corneal topography in keratoconus patients with and without atopy. : In the Beyoglu Eye Research and Training Hospital Refractive Surgery Department, corneal examination with the Orbscan II device (Bausch & Lomb) was done to all patients between May and June 2004 who were diagnosed as keratoconus with corneal topography findings and who did not have any surgical procedure. The atopy grading was done according to the criteria of the UK Atopy Study Group (1994). Patients were divided into 2 groups according to the presence of atopy. The Orbscan findings of the 2 groups were compared. : Among 70 keratoconus patients, 33 patients had partial or full atopy. Sixty-six eyes of the 33 patients were classified as the atopic group, whereas 74 eyes of the remaining 37 patients were classified as the control group. The mean age of the patients was 27.7 +/- 9.5 years in the atopic group and 26.9 +/- 9.5 years in the control group. The central corneal thickness was 428.5 +/- 37.1 mum in the atopic group and 491.8 +/- 56.3 mum in the control group. There was a statistically significant difference between the mean central and thinnest corneal pachymetric readings, the distance of thinnest point to corneal center, anterior and posterior elevation values, distances of the anterior and posterior elevation to the central cornea, and irregularity indexes in the 2 groups (P < 0.05). : This study shows that corneal topographic and pachymetric characteristics of keratoconus may be different in atopic eyes from those in nonatopic eyes. Atopic keratoconus patients could possibly be evaluated as a separate entity in keratoconus disease.


The karyotype of the glucocorticoid-sensitive, lymphoblastic human T-cell line CCRF-CEM shows a unique deleted and inverted chromosome 9.
Chromosome karyotypes were prepared from the highly glucocorticoid-sensitive clone C7 of the human acute lymphoblastic leukemia T-cell line CCRF-CEM. The modal number of chromosomes is 47, and one chromosome #9 has a pericentric inversion of the heterochromatin region (9qh) plus a deletion of the short arm. In most cells, there is an extra chromosome #20. All other chromosomes appear to be normal. Examination of the uncloned line CCRF-CEM (ATCC CCL 119), which was frozen away shortly after the line was originated and has undergone fewer passages than CEM C7, also revealed the same abnormality of chromosome #9. Each of 10 other clones isolated from CCRF-CEM in this laboratory also contained the abnormal chromosome #9.


The idiotypic network: internal images of rabbit immunoglobulin allotopes.
Internal recognition is a primordial concept in the idiotypic network hypothesis proposed by N. Jerne. The analysis of idiotypic recurrence in rabbit antiallotypic antibodies led us to propose the existence of antiidiotypic molecules Ab2 beta carrying idiotopes which are internal images of the original immunizing allotype. Using mouse monoclonal antibodies, we have shown that the internal image of b6 rabbit allotopes is associated with the internal image of kappa 1 isotypic determinants. The influence of interactions within the idiotypic network on the evolution of the immunological repertoire is discussed.


[Relation between the parameters of lipid peroxidation and the constant potential of the rat brain].
Studies were carried out of the relationship between the constant potential level (CPL) and the intensity of lipid peroxidation (LP) of the brain membranes in rats with different motor asymmetry. Strong correlation was found between CPL and the content of LP products (diene conjugates, hydroperoxides and Schiff bases) in the hemispheres of the brain (R = 0.7-0.8).


Negative staining characteristics of arrays of mitochondrial pore protein: use of correspondence analysis to classify different staining patterns.
Fourier-filtered images of negatively stained arrays of mitochondrial pore protein have been classified by correspondence analysis of their diffraction patterns. The most significant component of interpattern variation is an isotropic shift in reflection intensities between high- and low-order reflections. This corresponds in the images to the presence or absence of high resolution detail (stain minima). Experimentally the loss of detail in images correlates with the use of highly dissociated heavy metal salts as negative stains. It is proposed that such stains yield poorer negative-contrast images due to electrostatic binding of heavy-metal complex ions to fixed charge groups on the protein. Results with surface-modified protein arrays are consistent with this hypothesis.


Children's Avoidance of Interrupting Others' Activities in Requesting Help: Cultural Aspects of Considerateness.
To be able to collaborate skillfully, people need to coordinate well with others, taking into account how their actions fit with those of their partners. This is a key aspect of an approach to learning called Learning by Observing and Pitching In, hypothesized to be common in many Indigenous-heritage communities of the Americas. This chapter considers cultural values that emphasize considerateness and awareness of how one's actions impact others such as the Mexican cultural value of respeto and cultural differences in children's efforts to avoid interrupting others' activity. US Mexican-heritage children showed more evidence of avoiding interrupting the ongoing activity of an adult when they requested help, compared with European American children from families with extensive schooling experience. Most of the Mexican-heritage children's requests for help that gave evidence of avoiding interruption were made nonverbally, which may facilitate unobtrusive requests. There were no significant differences among children from two US Mexican-heritage backgrounds varying in experience with Western schooling and likely experience with Indigenous-American practices, suggesting that the Mexican cultural value of respeto and associated considerateness is widespread even among US Mexican-heritage families with extensive experience with Western schooling and life in the United States.


The interrelationship of morphine and the parasympathetic nervous system in digoxin-induced arrhythmias in the guinea-pig.
1. The role of the parasympathetic nervous system and the effect of morphine on cardiac arrhythmias induced by digitalis was assessed in guinea-pigs that had digitalis arrhythmias produced by digoxin 50 micrograms/kg intravenously plus 500 micrograms/kg per h. 2. Morphine produced a dose-dependent rightward shift in the relationship between digoxin dose and arrhythmias. Morphine 5 mg/kg subcutaneously (s.q.) was associated with significantly (P less than 0.05) higher digoxin doses both at the onset of ventricular arrhythmias and at development of fatal arrhythmias compared with the control group that received saline s.q. 3. Vagotomy and atropine prevented the effect of morphine so that the dose-response relationships and the mean digoxin dose at onset of ventricular arrhythmias and the development of fatal arrhythmias were not significantly different from the control group receiving saline. 4. These data indicate that morphine limits the development of digitalis arrhythmias and this effect is, at least in part, mediated through the parasympathetic nervous system.


Acute and chronic electrophysiologic changes surrounding radiofrequency lesions.
Arrhythmia recurrences may occur after acutely successful radiofrequency (RF) ablation, suggesting reversible electrophysiologic effects on myocardial tissue. The aim of this study was to examine the electrophysiologic changes occurring in myocardium surrounding acute and chronic RF lesions. RF lesions (60 degrees C for 30 sec) were produced on the epicardial left ventricular surface of 35 isolated perfused rabbit hearts. Microelectrode transmembrane action potential recordings were made at 0.25-mm intervals along the epicardial (n = 20) or intramural (n = 6) aspects of the lesions for up to 3.5 mm from the lesion edge at baseline and after acute RF lesion formation. In nine hearts, chronic lesions were studied with epicardial recordings made 22 +/- 13 days after RF lesion formation. In the acute hearts at 600-msec paced cycle length, action potential duration at 50% repolarization (APD50) and 90% repolarization (APD90) were reduced by up to 41% and 19%, respectively, within 2.5 mm from the lesion edge (all P < 0.05). Maximal action potential amplitude (APDmax) was reduced by 16% at 0.25 mm from the lesion edge (P = 0.009) but dV/dt was not changed. Conduction time (CT) from the outermost recording site to the lesion edge (3.5-mm distance) was reduced from 16 +/- 3 msec at baseline to 13 +/- 4 msec post ablation (P = 0.006). Qualitatively similar findings occurred at 200-msec cycle lengths. There were no changes in APD, CT, APDmax, or dV/dt surrounding the chronic lesions at 22 +/- 13 days after lesion formation. Acutely following RF energy delivery, APD, APDmax, and CT are reduced in the tissue surrounding the lesion. These electrophysiologic changes resolve within 22 +/- 13 days of lesion formation.


Concurrent Chemoradiation Therapy Followed by Consolidation Chemotherapy for Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type.
To evaluate the effectiveness of concurrent chemoradiation therapy (CCRT) with 40 Gy followed by consolidation chemotherapy for localized extranodal natural killer (NK)/T-cell lymphoma (ENKTL), nasal type. From August 2004 to August 2012, 62 patients with newly diagnosed stage IE to IIE ENKTL underwent CCRT followed by consolidation chemotherapy. The median RT dose was 40 Gy. Cisplatin, 30 mg/m(2), was administered weekly during the RT course. Responders to CCRT were encouraged to undergo consolidation chemotherapy. Three different consolidation chemotherapy regimens were used consecutively: VIPD (etoposide, ifosfamide, cisplatin, and dexamethasone); VIDL (etoposide, ifosfamide, and dexamethasone followed by intramuscular injection of l-asparaginase); and MIDLE (methotrexate, etoposide, ifosfamide, mesna, and l-asparaginase). The median follow-up period was 49 months (range 8-112). After completion of CCRT, 56 patients (90.3%) had a complete response, 4 (6.4%) had a partial response, 1 (1.6%) had stable disease, and 1 patient (1.6%) had progressive disease (PD). Consolidation chemotherapy was recommended to 61 patients, after excluding the patient with PD, but was actually delivered to 58. Of these 58 patients, 56 (96.5%) had a complete response and 2 (3.5%) had PD. During the follow-up period, 17 patients (including 3 with PD) experienced progression. The median interval to progression was 11 months (range 1-61). Local failure developed in 6 patients, of whom, 2 had developed progression outside the RT field. For all patients, the 3-year overall survival, progression-free survival, and local control rates were 83.1%, 77.1%, and 92.4%, respectively. Grade ≥3 nonhematologic toxicity developed in only 3 patients (4.8%). Excellent clinical outcomes were achieved using CCRT with 40 Gy followed by consolidation chemotherapy. Additional investigation, however, is warranted to confirm our findings.


A bivalent single-chain Fv fragment against CD47 induces apoptosis for leukemic cells.
We constructed a single-chain antibody fragment (scFv) of murine monoclonal antibody, MABL, which specifically bound to human CD47 (hCD47) and induced apoptosis of the leukemic cells. The scFv of MABL antibody with a 15-residue linker (MABL scFv-15) formed both dimer (Mr 50 kDa) and monomer (Mr 25 kDa). Both MABL scFv-15 dimer and monomer had binding activity for hCD47. MABL scFv-15 dimer strongly induced apoptosis of hCD47-introduced mouse leukemic cells in vitro and exhibited anti-tumor effect in a myeloma transplanted mice model. However, MABL scFv-15 monomer scarcely exhibited these activities. These results strongly demonstrate that the ligation of CD47 antigen by two antigen-binding sites of MABL dimer is needed for inducing apoptosis. The parent MABL antibody caused hemagglutination due to the CD47 expressed on erythrocytes. Interestingly, MABL scFv-15 dimer did not cause hemagglutination. This apoptosis-inducing dimer appears to be a lead candidate for novel leukemic therapy.


One artificial insemination per cycle with donor sperm is as efficacious as two inseminations.
To compare pregnancy rates per treatment cycle of artificial inseminations with donor sperm in patients receiving one versus two inseminations. Retrospective cross-sectioned analysis of 167 patients who underwent 869 cycles receiving one or two donor inseminations were reviewed from 1987 through 1993 at our institution. A total of 256 cycles with one donor insemination per cycle resulted in 21 pregnancies and a cycle of fecundity of 8.2%, and 613 cycles with two donor inseminations resulted in 35 pregnancies and a cycle fecundity of 5.7%. Life table and logistic cumulative probability analysis of pregnancy occurrence showed no difference between treatment groups. These data suggest there are no important clinical differences of cycle fecundity or cure rate in one versus two inseminations with donor sperm. Economic costs of two inseminations may not be justified.


A UV-vis study of the effects of alcohols on formation and stability of Mn(por)(O)(OAc) complexes.
Interactions of three different (acetato) (tetraarylporphyrinato) manganese (III) Mn(III)(por) with tetra-n-butylammonium hydrogen monopersulfate (n-Bu(4)NHSO(5)), in the presence of excess tetra-n-butylammonium acetate (n-Bu(4)NOAc) and in the absence or presence of various alcohols (alcohols=CH(3)OH, C(2)H(5)OH, i-C(3)H(7)OH, t-C(4)H(9)OH) in CH(2)Cl(2), were monitored by their UV-vis spectral changes, under identical conditions, at room temperature. (Acetato) (tetrakispentafluorophenylporphyrinato) manganese (III) Mn(III)(tpfpp)(OAc) and (acetato) (tetramesitylporphyrinato) manganese (III) Mn(III)(tmp)(OAc) produced their corresponding high valent Mn(tpfpp)(O)(OAc) and Mn(tmp)(O)(OAc) both in the absence or presence of alcohols. Whereas, (acetato) (tetraphenylporphyrinato) manganese (III) Mn(III)(tpp)(OAc) only generated Mn(tpp)(O)(OAc) in the presence of less bulky alcohols. In the absence of alcohols or in the presence of t-C(4)H(9)OH, the UV-vis spectra displayed a very weak sign of formation of Mn(tpp)(O)(OAc) complex. It was observed that alcohols generally increased the rate of formation of Mn-oxo species in accordance with their acidity or hydrogen bonding strength, and enhanced the stability of Mn-oxo complexes, as their size increases. Attempts are made to explain these effects. A mechanistic scheme is also suggested for the decomposition of HSO(5)(-) to O(2) and HSO(4)(-), through the formation and dimerization of Mn-oxo species.


Basic amphipathic helical peptides induce destabilization and fusion of acidic and neutral liposomes.
We have studied the fusion of small unilamellar vesicles composed of egg PC and of a mixture of egg PC plus egg PA using various basic amphipathic peptides. Fusion was monitored by carboxyfluorescein leakage assay, light scattering, membrane intermixing assay, contents mixing assay and electron microscopy. Ac-(L-Leu-L-Ala-L-Arg-L-Leu)3-NHCH3 (peptide 4(3] and Ac-(L-Leu-L-Ala-L-Lys-L-Leu)3-NHCH3 (peptide 4'3), which have high hydrophobic moments, caused transformation of small unilamellar vesicles into larger and relatively homogeneous ones. Ac-(L-Leu-L-Leu-L-Ala-L-Arg-L-Leu)2-NHCH3 (5(2], which has medium hydrophobic moment, induced weak but appreciable fusion, while Ac-(L-Ala-L-Arg-L-Leu)3-NHCH3 (3(3] which has no helical structure did not show any fusion. However, peptides 4(3), 4'3 and 5(2) caused massive leakage of the contents from small unilamellar vesicles. These results indicated that interaction of the peptides with artificial membranes caused extensive perturbation of the lipid bilayer, followed by fusion. The fusogenic capacity of model basic peptides was correlated with the hydrophobic moment of each peptide when the peptides adopted an alpha-helical structure in the presence of acidic liposomes. Peptides 4(3) and 4'3 also showed weak fusogenic ability for neutral liposomes, while 5(2) and 3(3) showed no ability, suggesting that highly amphipathic peptides, such as 4(3), interact weakly but distinctly with neutral liposomes to fuse them.


An Overview of Principles and New Techniques for Facial Fat Grafting.
Facial fat grafting is a small-volume procedure and is primarily performed for facial rejuvenation, contouring, or regenerative surgery. The unsatisfying retention rate after fat grafting, however, led to unpredictable outcomes, subsequent multiple procedures, and even some complications. A variety of methods have been proposed to enhance the results of facial fat grafting, including several established surgical principles and many possible new techniques. Adding stem cells, fat preparations, and platelet concentrates may improve the survival after fat grafting but randomized controlled clinical studies are needed to determine their safety and efficacy as well as clinical indications for each technique.


X chromosome inactivation, differentiation, and DNA methylation revisited, with a tribute to Susumu Ohno.
X chromosome inactivation and DNA methylation are reviewed, with emphasis on the contributions of Susumu Ohno and the predictions made in my 1975 paper (Riggs, 1975), in which I proposed the "maintenance methylase" model for somatic inheritance of methylation patterns and suggested that DNA methylation would be involved in mammalian X chromosome inactivation and development. The maintenance methylase model is discussed and updated to consider methylation patterns in cell populations that have occasional, stochastic methylation changes by de novo methylation or demethylation, either active or passive. The "way station" model for the spread of X inactivation by LINE-1 elements is also considered, and some recent results from my laboratory are briefly reviewed.


Topical therapy for regression and melanoma prevention of congenital giant nevi.
Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.


Anxiety in synucleinopathies: neuronal circuitry, underlying pathomechanisms and current therapeutic strategies.
Synucleinopathies are neurodegenerative disorders characterized by alpha-synuclein (αSyn) accumulation in neurons or glial cells, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). αSyn-related pathology plays a critical role in the pathogenesis of synucleinopathies leading to the progressive loss of neuronal populations in specific brain regions and the development of motor and non-motor symptoms. Anxiety is among the most frequent non-motor symptoms in patients with PD, but it remains underrecognized and undertreated, which significantly reduces the quality of life for patients. Anxiety is defined as a neuropsychiatric complication with characteristics such as nervousness, loss of concentration, and sweating due to the anticipation of impending danger. In patients with PD, neuropathology in the amygdala, a central region in the anxiety and fear circuitry, may contribute to the high prevalence of anxiety. Studies in animal models reported αSyn pathology in the amygdala together with alteration of anxiety or fear learning response. Therefore, understanding the progression, extent, and specifics of pathology in the anxiety and fear circuitry in synucleinopathies will suggest novel approaches to the diagnosis and treatment of neuropsychiatric symptoms. Here, we provide an overview of studies that address neuropsychiatric symptoms in synucleinopathies. We offer insights into anxiety and fear circuitry in animal models and the current implications for therapeutic intervention. In summary, it is apparent that anxiety is not a bystander symptom in these disorders but reflects early pathogenic mechanisms in the cortico-limbic system which may even contribute as a driver to disease progression.


The effect of shortening incisor teeth on the eruption rates and lengths of the other incisors in the rat.
The eruption rates and lengths of all four incisor teeth in rats were measured by recording the position of marks on their labial surfaces at 2-day intervals, using calibrated graticules in microscope eyepieces and ether anaesthesia. When one lower incisor, or both a lower and upper incisor, were unimpeded, the other lower incisor shortened markedly before the next measurement and the uppers slowly lengthened, so that the sum of the lengths of the lower and upper impeded incisors temporarily fell, then returned to control levels. The lower and upper impeded incisors showed temporary accelerations of their eruption when the other incisors were unimpeded. When an upper incisor was unimpeded, the lower incisors lengthened, increasing the sum of the lengths of the lower and upper impeded incisors, and the eruption of the lower and upper impeded incisors was slowed. When there were two impeded incisors in one jaw and only one (left) impeded incisor in the other jaw, the unopposed right impeded incisor tended to be slower and longer than its neighbour and there were significant correlations between the differences in eruption rates and differences in tooth lengths. In all these cases, there are negative relations between eruption and length; increases in length occur with decreases in eruption rate. The simplest explanation for this is that the length changes arise partly from the voluntary behaviour of the rat and also from mechanical problems due to having one impeded incisor in one jaw and two in the other jaw; the length changes cause the eruption-rate changes.


Safety issues in the pharmacologic management of chronic pain in the elderly.
Chronic pain is commonly encountered in elderly patients. About 20-50% of community-dwelling elderly experience it, and 45-80% of nursing home residents may be affected. Selection of pharmacologic therapy for the management of chronic pain must take into consideration the increased potential for adverse effects in this population. Major classes of drugs used to treat chronic pain (nonsteroidal antiinflammatory drugs, opioids, antidepressants) have adverse effects that occur more frequently in elderly than in younger patients. Given the often prolonged duration of therapy, optimal management requires minimizing the risk of adverse reactions.


Identifying care problem clusters and core care problems of older adults with dementia for caregivers: a network analysis.
A shift in research interest from separate care problem to care problem clusters among caregivers of people living with dementia may contribute to a better understanding of dementia care. However, the care problems network among caregivers of people living with dementia are still unknown. This study aimed to identify care problem clusters and core care problems, and explore demographic variables associated with these care problem clusters among caregivers of people living with dementia. Participants were recruited through memory clinics and WeChat groups. The principal component analysis was applied to identify care problem clusters. The network analysis was conducted to describe the relationships among care problems and clusters. Multiple linear models were used to explore the associated factors for the occurrence of the overall care problems and top three central care problem clusters. A total of 1,012 carer-patient pairs were included in the analysis. Nine care problem clusters were identified. In the entire care problem network, "deterioration in activities of daily living" was the most core care problem cluster across the three centrality indices, followed by "verbal and nonverbal aggression" and "loss of activities of daily living." Variables including marital status, years of dementia diagnosis, number of dementia medication type, and caregiver's educational attainment were associated with the prevalence of these three care problem clusters. Our study suggests that there is a need to evaluate care problem clusters for the improvement of care problem management among people living with dementia. It is particularly important to include assessment and treatment of core care problem as an essential component of the dementia care.


Integrating human iPSC-derived macrophage progenitors into retinal organoids to generate a mature retinal microglial niche.
In the retina, microglia are resident immune cells that are essential for development and function. Retinal microglia play a central role in mediating pathological degeneration in diseases such as glaucoma, retinitis pigmentosa, age-related neurodegeneration, ischemic retinopathy, and diabetic retinopathy. Current models of mature human retinal organoids (ROs) derived from iPS cell (hiPSC) do not contain resident microglia integrated into retinal layers. Increasing cellular diversity in ROs by including resident microglia would more accurately represent the native retina and better model diseases in which microglia play a key role. In this study, we develop a new 3D in vitro tissue model of microglia-containing retinal organoids by co-culturing ROs and hiPSC-derived macrophage precursor cells (MPCs). We optimized the parameters for successful integration of MPCs into retinal organoids. We show that while in the ROs, MPCs migrate to the equivalent of the outer plexiform layer where retinal microglia cells reside in healthy retinal tissue. While there, they develop a mature morphology characterized by small cell bodies and long branching processes which is only observed in vivo. During this maturation process these MPCs cycle through an activated phase followed by a stable mature microglial phase as seen by the down regulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. Finally, we characterized mature ROs with integrated MPCs using RNAseq showing an enrichment of cell-type specific microglia markers. We propose that this co-culture system may be useful for understanding the pathogenesis of retinal diseases involving retinal microglia and for drug discovery directly in human tissue.


Adoption and utilization of device-assisted telemedicine.
We estimate the effect of adopting a digital device for performing medical exams at home during telehealth visits. We match visits of adopters and non-adopters who used the same virtual care clinic but without the device and compare healthcare utilization after the matched visits. We find that device adoption, partially offset by decreased use of other primary care modalities, results in a 12% higher utilization rate of primary care and increased use of antibiotics. But - particularly among adults - adoption lowers the use of urgent care, the emergency room, and hospital care, resulting in no increase in total cost.


Blunted effect of the Kv channel inhibitor on pulmonary circulation in Tibetan sheep: a model for studying hypoxia and pulmonary artery pressure regulation.
The aim of this study was to assess the effect of 4-aminopyridine, a Kv channel inhibitor, on the pulmonary circulation of Tibetan sheep. It has been reported that chronic hypoxia downregulates the 4-aminopyridine (4AP)-sensitive Kv channel (which governs the membrane potential (Em) of pulmonary vascular smooth muscle cells in pulmonary vessels) without a change in 4AP sensitivity. Pulmonary haemodynamic indices and blood gas analyses were measured in six young male animals in an altitude chamber that was adjusted to simulated altitudes of 0 m, 2260 m, and 4500 m. Drip infusion of 4AP, 10 mg/h for 3 h, was started and continued during the study. With the increase in altitude mean pulmonary artery pressure increased and mean PaO(2) decreased. 4AP had no effect on the levels of mean PPA, mean pulmonary artery wedge pressure, cardiac output, and mean PaO(2), mean PaCO(2), and mean pH at any altitude but tended to alter heart rate and mean arterial pressure at altitudes of 2260 m and 4500 m. It is concluded that the 4AP-sensitive Kv channel does not play a role in pulmonary vascular tone in high-altitude active Tibetan sheep. Their pulmonary vascular oxygen sensing appears not to involve Kv channels.


Discrimination of geographical origin of cultivated Polygala tenuifolia based on multi-element fingerprinting by inductively coupled plasma mass spectrometry.
Inorganic elements are important components of medicinal herbs, and provide valuable experimental evidence for the quality evaluation and control of traditional Chinese medicine (TCM). In this study, to investigate the relationship between the inorganic elemental fingerprint and geographical origin identification of cultivated Polygala tenuifolia, 41 elemental fingerprints of P. tenuifolia from four major polygala-producing regions (Shanxi, Hebei, Henan, and Shaanxi) were evaluated to determine the importance of inorganic elements to cultivated P. tenuifolia. A total of 15 elemental (B, Ca, Cl, Cu, Fe, K, Mg, Mn, Na, N, Mo, S, Sr, P, and Zn) concentrations of cultivated P. tenuifolia were measured using inductively coupled plasma mass spectroscopy (ICP-MS). The element composition samples were classified by radar plot, elemental fingerprint, and multivariate data analyses, such as hierarchical cluster analysis (HCA), principle component analysis (PCA), and discriminant analysis (DA). This study shows that radar plots and multivariate data analysis can satisfactorily distinguish the geographical origin of cultivated P. tenuifolia. Furthermore, PCA results revealed that N, Cu, K, Mo, Sr, Ca, and Zn are the characteristic elements of cultivated P. tenuifolia. Therefore, multi-element fingerprinting coupled with multivariate statistical techniques can be considered an effective tool to discriminate geographical origin of cultivated P. tenuifolia.


Nuclearly translocated insulin-like growth factor 1 receptor phosphorylates histone H3 at tyrosine 41 and induces SNAI2 expression via Brg1 chromatin remodeling protein.
The insulin-like growth factor-1 receptor (IGF-1R) is a receptor tyrosine kinase that has crucial roles in cell proliferation and protection from apoptosis. It is therefore not surprising that IGF-1R is often found overexpressed in many types of tumors. This has made IGF-1R a prominent target molecule for pharmacological companies to develop new anti-cancer agents. However, several clinical trials during the last 5 years using IGF-1R specific antibodies have shown disappointing results. We have previously shown that upon IGF-1 stimulation, the receptor becomes SUMOylated and translocates into the nucleus of cancer cells to act as a transcription co-factor. Soon after our original study, several others have reported nuclear IGF-1R (nIGF-1R) as well, and some of them have demonstrated a prognostic value of nIGF-1R expression in cancer. In the current study we demonstrate that nIGF-1R binds to and phosphorylates histone H3 at tyrosine 41 (H3Y41) in HeLa cells. Furthermore, our results suggest that phosphorylation of H3Y41 by nIGF-1R, stabilizes the binding of Brg1 chromatin remodeling protein to Histone H3. Our findings suggest that phosphorylated nIGF-1R, rather than total nIGF-1R, plays a superior role in these contexts. We identified SNAI2 oncogene as a target gene for nIGF-1R and its expression was decreased upon mutation of H3Y41 or by Brg1 knockdown. Furthermore, we demonstrate that both IGF-1R and Brg1 binds to the SNAI2 promoter. As SNAI2 protein is implicated in e.g. cancer invasion and metastasis, the nIGF-1R-mediated effects shown in this study may influence such important tumor phenotypic actions.


Heterotopic brain tissue in the lung causing acute respiratory distress in an infant.
A three month male infant with a 24 hour history of cyanotic attacks was found to have heterotopic brain tissue at thoracotomy. He has remained well over 20 years of follow up. The pathogenesis of the condition is discussed.


Neuronal synchronicity in the pigeon "prefrontal cortex" during learning.
In general electrophysiological studies focus on the investigation of changes in discharge rate of neuronal responses which are related to sensory or behavioral events. However, equally important for explanation of higher cognitive functions, learning, memory storage and complex behavior is the interaction between neurons that are connected in cell assemblies. Synchronized inputs onto a neuron are much more effective at eliciting the following activity than uncorrelated inputs. The goal of the present study was to determine either the changes in discharge rate of neurons in the pigeon nidopallium caudolaterale as well as the synchronicity of these neurons during a discriminatory learning task. We found rate modulation effects as well as modulation of synchronization during the learning process.


Socioeconomic determinants of China's growing CH4 emissions.
Reducing CH4 emissions is a major global challenge, owing to the world-wide rise in emissions and concentration of CH4 in the atmosphere, especially in the past decade. China has been the greatest contributor to global anthropogenic CH4 emissions for a long time, but current understanding towards its growing emissions is insufficient. This paper aims to link China's CH4 emissions during 2005-2012 to their socioeconomic determinants by combining input-output models with structural decomposition analysis from both the consumption and income perspectives. Results show that changes in household consumption and income were the leading drivers of the CH4 growth in China, while changes in efficiency remained the strongest factor offsetting CH4 emissions. After 2007, with the global financial crisis and economic stimulus plans, embodied emissions from exports plunged but those from capital formation increased rapidly. The enabled emissions in employee compensation increased steadily over time, whereas emissions induced from firms' net surplus decreased gradually, reflecting the reform on income distribution. In addition, at the sectoral level, consumption and capital formation respectively were the greatest drivers of embodied CH4 emission changes from agriculture and manufacturing, while employee compensation largely determined the enabled emission changes across all industrial sectors. The growth of CH4 emissions in China was profoundly affected by the macroeconomic situation and the changes of economic structure. Examining economic drivers of anthropogenic CH4 emissions can help formulate comprehensive mitigation policies and actions associated with economic production, supply and consumption.


Systolic time intervals in chronic anemia.
Systolic time intervals were measured noninvasively in 12 healthy control subjects (hemoglobin 12 to 15 Gm. per cent) and 32 cases of chronic anemia without underlying cardiovascular disease. It was found that in mild anemia (hemoglobin above 7 Gm. per cent), where cardiac output is known to be normal, the systolic time intervals were also normal. In severe anemia (hemoglobin below 7 Gm. per cent), where cardiac output is known to be high, the systolic time intervals showed the pattern usually associated with high cardiac output, i.e., increased left ventricular ejection time (LVET) and decreased pre-ejection period (PEP) and PEP/LVET ratio, only when congestive failure was absent. In severe anemia with congestive failure, the LVET was decreased, and PEP and PEP/LVET ratio were increased--the pattern associated with impaired myocardial performance, even though cardiac output is known to be high in such cases also.


Habitat overlap/niche segregation in two Umbilicaria lichens: a possible mechanism.
Umbilicaria muhlenbergii and Umbilicaria papulosa are two similar lichens which show extensive habitat overlap. Current theory predicts that for those resources that are limited, and of critical importance to both species, segregation is demand for or use of those resources ought to be present. Controlled experiments showed that the upper and lower cortical surfaces of the two species functioned in very different ways so that U. muhlenbergii is wetted most rapidly by runoff and mist-like precipitation whereas U. papulosa is wetted most rapidly by large raindrops. An analysis of the meteorological conditions in the natural habitat for the two lichens shows that the four months providing significant productivity in U. papulosa are the same months with a very high frequency of thunderstorms (which produce large drops). Conversely, the months which produce the greatest production in U. muhlenbergii are spread out over most of the year. When water is supplied after periods of dryness, the two species absorb it at different times and from different sources. This difference supports current ideas about niche segregation in plants but represents the first time it has been demonstrated for lichens.


Benefits of environmental information disclosure in managing water pollution: evidence from a quasi-natural experiment in China.
Environmental information disclosure (EID) is playing an increasingly important role in water pollution management. However, since EID is hard to measure and other endogeneity problems, it is difficult to capture the causal inference between the two. Using the difference-in-difference method, this paper takes advantage of the Pollution Source Regulatory Information Disclosure Index (PITI) program promulgated by China in 2008 as a quasi-natural experiment to empirically capture the net effect of EID on water pollution management and its impact mechanism. The results show that from the average treatment effects perspective, the PITI strongly promote water pollution management. However, the dynamic effects of PITI present a decreasing and weakening trend over time. Further mechanism analysis reveals that PITI improves water pollution management mainly through the technological innovation effect. Several robustness checks justify our findings. Heterogeneity analysis shows that the PITI has a greater positive impact on water pollution management in cities located in the southern areas and with high economic levels and with a larger population.


Image findings of cranial nerve pathology on [18F]-2- deoxy-D-glucose (FDG) positron emission tomography with computerized tomography (PET/CT): a pictorial essay.
This article aims to increase awareness about the utility of (18)F -FDG-PET/CT in the evaluation of cranial nerve (CN) pathology. We discuss the clinical implication of detecting perineural tumor spread, emphasize the primary and secondary (18)F -FDG-PET/CT findings of CN pathology, and illustrate the individual (18)F -FDG-PET/CT CN anatomy and pathology of 11 of the 12 CNs.


Open Versus Laparoscopic Surgery in the Management of Adrenocortical Carcinoma: A Systematic Review and Meta-analysis.
Laparoscopic surgery is considered a standard treatment for benign adrenal tumors; however, no consensus has been reached on the optimal resection technique for adrenocortical carcinomas. This study aims to evaluate the safety and efficacy of laparoscopic surgery and open surgery in the management of adrenocortical carcinoma. The Cochrane, Embase, PubMed, Scopus, and Web of Science databases were searched for articles from inception to May 2022, by two independent reviewers using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. The review was registered prospectively on the PROSPERO database (CRD42022316050). From 183 studies screened, 11 studies met the eligibility criteria, with a total of 1617 patients with adrenocortical carcinoma undergoing either laparoscopic surgery (n = 472) or open surgery (n = 1145). Open surgery demonstrated a lower rate of positive resection margin compared with laparoscopic surgery (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.10-2.10; I2 = 0%). Additionally, open surgery had more favorable overall survival (OR 0.56, 95% CI 0.44-0.72; I2 = 0%) and recurrence-free rates (OR 0.60, 95% CI 0.42-0.85; I2 = 38%) than laparoscopic surgery at 3 years. Hospital stay was shorter for laparoscopic surgery than open surgery (mean difference - 2.49 days, 95% CI - 2.95 to - 2.04; I2 = 45%). Open surgery should still be considered the standard operative approach; however, laparoscopic surgery could be regarded as an effective and safe operation for selected adrenocortical carcinoma cases with appropriate laparoscopic expertise. Further randomized controlled studies with tumor stage- and resection margin-dependent survival analysis are necessary to ascertain the safety and efficacy of the treatment.


Amyloid-β oligomers induce differential gene expression in adult human brain slices.
Cognitive decline in Alzheimer disease (AD) is increasingly attributed to the neuronal impact of soluble oligomers of the amyloid-β peptide (AβOs). Current knowledge on the molecular and cellular mechanisms underlying the toxicity of AβOs stems largely from rodent-derived cell/tissue culture experiments or from transgenic models of AD, which do not necessarily recapitulate the complexity of the human disease. Here, we used DNA microarray and RT-PCR to investigate changes in transcription in adult human cortical slices exposed to sublethal doses of AβOs. The results revealed a set of 27 genes that showed consistent differential expression upon exposure of slices from three different donors to AβOs. Functional classification of differentially expressed genes revealed that AβOs impact pathways important for neuronal physiology and known to be dysregulated in AD, including vesicle trafficking, cell adhesion, actin cytoskeleton dynamics, and insulin signaling. Most genes (70%) were down-regulated by AβO treatment, suggesting a predominantly inhibitory effect on the corresponding pathways. Significantly, AβOs induced down-regulation of synaptophysin, a presynaptic vesicle membrane protein, suggesting a mechanism by which oligomers cause synapse failure. The results provide insight into early mechanisms of pathogenesis of AD and suggest that the neuronal pathways affected by AβOs may be targets for the development of novel diagnostic or therapeutic approaches.


Radiation Facility Volume and Survival for Men With Very High-Risk Prostate Cancer Treated with Radiation and Androgen Deprivation Therapy.
Very high-risk (VHR) prostate cancer is an aggressive substratum of high-risk prostate cancer, characterized by high prostate-specific antigen levels, high Gleason score, and/or advanced T category. Contemporary management paradigms involve advanced molecular imaging and multimodal treatment with intensified prostate-directed or systemic treatment-resources more readily available at high-volume centers. To examine radiation facility case volume and overall survival (OS) in men with VHR prostate cancer. A retrospective cohort study was performed from November 11, 2022, to March 4, 2023, analyzing data from US facilities reporting to the National Cancer Database. Patients included men diagnosed with nonmetastatic VHR prostate cancer by National Comprehensive Cancer Network criteria (clinical T3b-T4 category, primary Gleason pattern 5, >4 cores with grade group 4-5, and/or 2-3 high-risk features) and treated with curative-intent radiotherapy and androgen deprivation therapy between January 1, 2004, to December 31, 2016. Treatment at high- vs low-average cumulative facility volume (ACFV), defined as the total number of prostate radiotherapy cases at an individual patient's treatment facility from 2004 until the year of their diagnosis. The nonlinear association between a continuous ACFV and OS was examined through a Martingale residual plot; an optimal ACFV cutoff was identified that maximized the separation between high vs low ACFV via a bias-adjusted log rank test. Overall survival was assessed between high vs low ACFV using Kaplan-Meier analysis with and without inverse probability score weighted adjustment and multivariable Cox proportional hazards. A total of 25 219 men (median age, 71 [IQR, 64-76] years; 78.7% White) with VHR prostate cancer were identified, 6438 (25.5%) of whom were treated at high ACFV facilities. Median follow-up was 57.4 (95% CI, 56.7-58.1) months. Median OS for patients treated at high ACFV centers was 123.4 (95% CI, 116.6-127.4) months vs 109.0 (95% CI, 106.5-111.2) months at low ACFV centers (P < .001). On multivariable analysis, treatment at a high ACFV center was associated with lower risk of death (hazard ratio, 0.89; 95% CI, 0.84-0.95; P < .001). These results were also significant after inverse probability score weighted-based adjustment. In this cohort study of patients with VHR prostate cancer who underwent definitive radiotherapy and androgen deprivation therapy, facility case volume was independently associated with longer OS. Further studies are needed to identify which factors unique to high-volume centers may be responsible for this benefit.


Lumbar epidural analgesia with bupivacaine in labor. Determination of drug concentration and pH in fetal scalp blood, and continuous fetal heart rate monitoring.
Lumbar epiduval analgesia with bupivacaine was given to 37 women for uncomplicated labor. After the blcokade serial determinations of pH and bupivacaine concentration were made in fetal scalp blood and maternal venous blood and there was continuous monitoring of the fetal heart rate. Fetal scalp blood pH was within normal limits and no pathologic FHR tracings were elicited by the blockade, although a temporary decrease of the baseline fetal heart rate irregularity was seen in about one-fifth of the cases. Fetal drug concentrations were low and about one-fourth of corresponding maternal values. After reinjection of bupivacaine the degree of drug accumulation was fairly similar in fetal and maternal blood.


Use of labor analgesia in trials of labor after previous cesarean section: A nationwide register-based analysis in Finland.
The literature concerning the overall use of labor analgesia among women with trials of labor after cesarean section (TOLAC) is lacking. The primary aim of this study is to report the rate of different labor analgesia methods among women with TOLAC. The secondary aim was to compare the use of labor analgesia between women with the first TOLAC and control group consisting of nulliparous women. Data from the National Medical Birth Register was used to evaluate the usage of labor analgesia in TOLACs. The use of labor analgesia in the first TOLAC is compared to the pregnancies of nulliparous women. The analgesia methods were stratified into neuraxial analgesia, pudendal, paracervical, nitrous oxide, other medical, other non-medical, and no analgesia. These are analyzed as categorized dichotomy (yes or no) variables. A total of 38 596 TOLACs as second pregnancy of the mother was found during our study period. The control group consisted of a total of 327 464 pregnancies of nulliparous women. Epidural analgesia (61.6% vs 67.1%), nitrous oxide (56.1% vs 62.0%), and non-medical analgesia (30.1% vs 35.0%) were less consumed among women with TOLAC. The rate of spinal analgesia was higher among women with TOLAC (10.1% vs 7.6%) when compared to the control group. However, when only vaginal deliveries were included, the rate of labor analgesia increased especially in the TOLAC group. The main finding of this study is that women with TOLAC had a generally lower rate of labor analgesia. However, the rate of spinal analgesia was higher among women with TOLAC when compared to the control group, however. The results of this study inform midwives, obstetricians, and anesthesiologists on current practices and how to improve the analgetic treatment in TOLAC.


Sub-population analysis of patients with plaque psoriasis treated with calcipotriol/betamethasone aerosol foam; effectiveness and patient satisfaction, according to baseline disease severity and prior psoriasis treatment experience, in a Greek population.
Fixed combination calcipotriol/betamethasone (Cal/BD) aerosol foam has been shown to be effective in psoriasis treatment in clinical trials, but real-world evidence is currently sparse. The real-world CELSUS study in Greece found that Cal/BD aerosol foam treatment was effective and associated with satisfaction in psoriasis patients. Patients from the CELSUS study (N = 400) were stratified by baseline disease severity according to physician's global assessment (PGA) score (mild vs. moderate vs. severe) and by previous psoriasis treatment (naïve vs. treatment-experienced). Proportions of patients achieving treatment success (clear/almost clear [PGA 0/1]) after 4 weeks' treatment with Cal/BD aerosol foam were reported for each subgroup. Psoriasis area and severity index (PASI) and patient-reported itch, itch-related sleep loss, scaling, dry skin, and erythema numerical rating scores were reported by subgroup. At baseline, 216 (54%) patients were systemic-or-topical psoriasis treatment-naïve and 184 (46%) were treatment experienced. By disease severity, there were 135 versus 89 patients with mild, 69 versus 83 with moderate and 12 versus 12 with severe disease in the treatment-naïve versus treatment-experienced groups, respectively. In the treatment-naïve group, treatment success was achieved by 72.6%, 56.5%, and 66.7% of patients with mild, moderate, and severe disease, respectively, while the proportions in the treatment-experienced group were 60.7%, 42.2%, and 25%, respectively. Reduction from baseline in psoriasis symptoms was observed in all patient groups. The greatest reductions were observed in treatment-naïve patients with severe disease. Clinically relevant benefits were observed with Cal/BD aerosol foam in psoriasis patients, regardless of prior treatment-experience and disease severity at baseline.


[Clinical evaluation of chemotherapy with irinotecan (CPT-11), l-leucovorin (l-LV), 5-fluorouracil (5-FU), and UFT for metastatic or recurrent colorectal cancer].
A clinical study has been conducted since August 2001 to investigate whether chemotherapy with CPT-11/l-LV/ 5-FU/UFT could be an effective regimen for advanced or recurrent colorectal cancer. The chemotherapy consisted of CPT-11 30 mg/m2 iv, as a 120-minute infusion, followed by l-LV 30 mg/m2, as a 60-minute infusion, followed by 5-FU 300 mg/m2, as a 120-minute infusion. This treatment was administered weekly for 6 weeks followed by a 2-week rest period and repeated every 8 weeks. UFT (250 mg/m2/day) was orally administered daily. All patients were evaluable for efficacy, 2 CR, 5 PR, 3 SD and 7 PD. The overall response rate was 41.1% with a median time to progression of 7.1 months and a median survival time of 12.0 months. No grade 3/4 toxicities were observed. The present study suggests that combination chemotherapy with CPT-11, l-LV, 5-FU, and UFT is well tolerated and might be a promising regimen for advanced or recurrent colorectal cancer.


Molecular similarity analysis between insect juvenile hormone and N, N-diethyl-m-toluamide (DEET) analogs may aid design of novel insect repellents.
Molecular similarity analysis of stereoelectronic properties between natural insect juvenile hormone (JH), -a synthetic insect juvenile hormone mimic (JH-mimic, undecen-2-yl carbamate), and N, N-diethyl-m-toluamide (DEET) and its analogs reveals similarities that may aid the design of more efficacious insect repellents and give a better insight into the mechanism of repellent action. The study involves quantum chemical calculations using the AM1 semi-empirical computational method enabling a conformational search for the lowest and most abundant energy conformers of JH, JH-mimic, and 15 DEET compounds, followed by complete geometry optimization of the conformers. Similarity analyses of stereoelectronic properties such as structural parameters, atomic charges, dipole moments, molecular electrostatic potentials, and highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were performed on JH, JH-mimic and the DEET compounds. The similarity of stereoelectronic attributes of the amide/ester moiety, the negative electrostatic potential regions beyond the van der Waals surface, and the large distribution of hydrophobic regions in the compounds appear to be the three important factors leading to a similar interaction with the JH receptor. The similarity of electrostatic profiles beyond the van der Waals surface is likely to play a crucial role in molecular recognition interaction with the JH receptor from a distance. This also suggests electrostatic bioisosterism of the amide group of the DEET compounds and JH-mimic and, thus, a model for molecular recognition at the JH receptor. The insect repellent property of the DEET analogs may thus be attributed to a conflict of complementarity for the JH receptor binding sites.


Axonal rearrangement without reexpression of a growth associated marker: evidence from the compression of the retinotectal system in adult goldfish.
Growing axons express a number of proteins associated with axonal growth which are thought to be critical for regeneration and sprouting. Whether these proteins are expressed during injury-induced axonal remodeling is tested in this paper. The posterior half of the adult goldfish tectum was removed leaving the anterior half intact. This causes optic fibers from nasal retina, which project to posterior tectum, to displace temporal fibers from the anterior remnant and form a compressed retinotopic projection of the entire retina onto the anterior tectum. Immunohistochemistry using an antibody shown here to recognize growing and regenerating fibers in goldfish was used to monitor optic fibers. As expected, surgery induced reactivity in the axotomized nasal axons peaking at 1 month which returned to normal at 2 months when compression was completed. Unexpectedly, axons from temporal retina showed no detectable reactivity even though they were induced to grow anteriorly by the invading nasal fibers. Extensive axonal remodeling and synaptic rearrangement can occur without reentering the growth state associated with axonal growth and regeneration.


The changes of expressive levels of IL-17A, STAT3, and RORγt in different invasive pulmonary aspergillosis mice.
T helper 17 (Th17) lymphocytes play an important role in Aspergillus adaptive immune response against Aspergillus fumigatus, but there is little attention focused on the different types of immunosuppressive models in which invasive pulmonary aspergillosis (IPA) develops. In addition, the expression levels of signal transducer and activator of transcription 3 (STAT3)/retinoic acid-related orphan nuclear receptor gamma (RORγt)/interleukin (IL)-17A signaling pathway, which is involved in the regulation of Th17 cells, as well as whether there are differences between two types of IPA mice models, remain unknown. Six to eight weeks old female BALB/c mice were treated with cortisone acetate or cyclophosphamide to establish the immunosuppressive mice models, and then, A. fumigatus inoculum was injected to form the IPA groups and sterile saline was injected to form the control groups. Flow cytometry was performed to measure the proportion of Th17 cells in CD4+ T cells in the peripheral blood, spleen, and lung of the mice. The expression of IL-17A, RORγt, and STAT3 mRNA was detected by real-time polymerase chain reaction. Concentrations of IL-6 in the plasma and bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay. The proportion of Th17 in the peripheral blood and lung tissue in neutropenic IPA mice showed a more significant increase than in non-neutropenic IPA mice (P<0.01). The IL-6 protein also showed the same trend in plasma and bronchoalveolar lavage fluid (P<0.01). Compared with the control groups, the expression of IL-17A at mRNA level in the lung was significantly increased, while RORγt/STAT3 mRNA was significantly decreased in the IPA groups (P<0.01). The expression of RORγt and STAT3 mRNA in the lung tissue in both groups was significantly decreased. IL-17 may play a negative role in the defense against Aspergillus through uprating IL-6.


Atypical Presentation of Cystic Fibrosis in An Infant.
Dermatitis as an initial manifestation of cystic fibrosis (CF) is unusual. The eruption is usually first noted in the perineum anywhere from several days to few months after birth. It subsequently spreads to the extremities and trunk. We report a 2-month-old male baby who presented with failure to thrive, hypoproteinemia, anemia, and a cutaneous eruption resembling acrodermatitis enteropathica. Oral zinc supplementation resulted in temporary resolution of the dermatitis. A further workup revealed the diagnosis of CF. The rash was responsive to nutritional and pancreatic enzyme supplementation.


The prognostic value of peri-operative neurological performance in glioblastoma patients.
IDH-wild-type glioblastoma (GBM) is a disease with devastating prognosis. First-line therapy consists of gross total resection and adjuvant radiotherapy with concomitant temozolomide. Several clinical parameters have been identified to provide prognostic value. We investigated whether peri-operative overall neurological performance could also be used to evaluate patients' prognosis. All patients with histologically diagnosed GBM between 2014 and 2017 over 18 years and MRI within 72 h after surgery were reviewed. To quantify neurological performance, the medical research council neurological performance score (MRC-NPS) was used. Univariate analysis with Kaplan-Meier estimate and log-rank test was performed. Survival prediction and multivariate analysis were performed employing Cox proportional hazard regression. One hundred thirty-nine patients were included. In univariate analysis, survival decreased with increasing post-operative MRC-NPS scale. Moreover, post-operative MRC-NPS of 4 was statistically significant associated with reduced overall survival when analyzed for complete (p = 0.027) and partial resection (p = 0.002) as well as unilobar (p = 0.003) and multilobar tumor location (p < 0.0005). In multivariate analysis, extent of resection (hazard ratio (HR) 3.142), adjuvant therapy regimen (HR 3.001), tumor location (HR 2.005), and post-operative MRC-NPS (HR 2.310) had significant influence on overall survival. We propose the post-operative neurological performance as an independent prognostic factor for GBM patients.


Diffusion of dye after perineural injection of the palmar/plantar nerves in two different sites in horses: an ex-vivo study.
This study aimed to evaluate the distribution of dye at two perineural injection sites of the palmar/plantar nerves and describe their anatomical variations of positioning at the level of the distal metacarpus/metatarsus in horses. Two ml of 1% methylene blue solution was injected in 24 limbs (12 forelimbs and 12 hindlimbs) of horse cadavers at two different points: Group 1: between the branch of the suspensory ligament and deep digital flexor tendon, and Group 2: between the deep and superficial digital flexor tendons. This was followed by dissection and evaluation of the solution diffusion. A photographic record and description of the anatomical position of the palmar/plantar nerve were performed. A comparison of diffusion directions in each portion (medial or lateral) between groups showed no statistical difference (P > 0.05), except in the dorsal direction on the medial portion of hindlimbs, which was higher in Group 2 (P = 0.025). The digital flexor tendon sheath was inadvertently injected four times into the forelimbs of Group 2. Both injection sites offered good dye contact with the palmar/plantar nerves, with the position between the deep digital flexor tendon and suspensory ligament branch having a higher contact area, regardless of the limb portion. The anatomical position of the palmar/plantar nerve in the cadaver specimens was similar between the same limb portions.


Convolutional neuronal networks combined with X-ray phase-contrast imaging for a fast and observer-independent discrimination of cartilage and liver diseases stages.
We applied transfer learning using Convolutional Neuronal Networks to high resolution X-ray phase contrast computed tomography datasets and tested the potential of the systems to accurately classify Computed Tomography images of different stages of two diseases, i.e. osteoarthritis and liver fibrosis. The purpose is to identify a time-effective and observer-independent methodology to identify pathological conditions. Propagation-based X-ray phase contrast imaging WAS used with polychromatic X-rays to obtain a 3D visualization of 4 human cartilage plugs and 6 rat liver samples with a voxel size of 0.7 × 0.7 × 0.7 µm3 and 2.2 × 2.2 × 2.2 µm3, respectively. Images with a size of 224 × 224 pixels are used to train three pre-trained convolutional neuronal networks for data classification, which are the VGG16, the Inception V3, and the Xception networks. We evaluated the performance of the three systems in terms of classification accuracy and studied the effect of the variation of the number of inputs, training images and of iterations. The VGG16 network provides the highest classification accuracy when the training and the validation-test of the network are performed using data from the same samples for both the cartilage (99.8%) and the liver (95.5%) datasets. The Inception V3 and Xception networks achieve an accuracy of 84.7% (43.1%) and of 72.6% (53.7%), respectively, for the cartilage (liver) images. By using data from different samples for the training and validation-test processes, the Xception network provided the highest test accuracy for the cartilage dataset (75.7%), while for the liver dataset the VGG16 network gave the best results (75.4%). By using convolutional neuronal networks we show that it is possible to classify large datasets of biomedical images in less than 25 min on a 8 CPU processor machine providing a precise, robust, fast and observer-independent method for the discrimination/classification of different stages of osteoarthritis and liver diseases.


Stem Cells and Spinal Fusion.
There are a number of bone regeneration therapeutics available to aid spinal fusion; however, many are associated with pseudarthrosis, inflammation, and other complications. Mesenchymal stem cells for fusion has been promoted to mitigate these risks and achieve successful bony fusion. This article reviews the clinical studies available with use in spinal fusion. Preliminary results demonstrate that stem cells can provide high rates of fusion, comparable to autograft, without associated morbidity. Autologous and allogeneic stem cell sources showed similar rates of fusion in this review. Further research is required to evaluate which clinical situations are the optimum for stem cell use.


Automatic generation of pseudoknotted RNAs taxonomy.
The ability to compare RNA secondary structures is important in understanding their biological function and for grouping similar organisms into families by looking at evolutionarily conserved sequences such as 16S rRNA. Most comparison methods and benchmarks in the literature focus on pseudoknot-free structures due to the difficulty of mapping pseudoknots in classical tree representations. Some approaches exist that permit to cluster pseudoknotted RNAs but there is not a general framework for evaluating their performance. We introduce an evaluation framework based on a similarity/dissimilarity measure obtained by a comparison method and agglomerative clustering. Their combination automatically partition a set of molecules into groups. To illustrate the framework we define and make available a benchmark of pseudoknotted (16S and 23S) and pseudoknot-free (5S) rRNA secondary structures belonging to Archaea, Bacteria and Eukaryota. We also consider five different comparison methods from the literature that are able to manage pseudoknots. For each method we clusterize the molecules in the benchmark to obtain the taxa at the rank phylum according to the European Nucleotide Archive curated taxonomy. We compute appropriate metrics for each method and we compare their suitability to reconstruct the taxa.


Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses.
The number of naive T cells decreases and susceptibility to new microbial infections increases with age. Here we describe a previously unknown subset of phenotypically naive human CD8(+) T cells that rapidly secreted multiple cytokines in response to persistent viral antigens but differed transcriptionally from memory and effector T cells. The frequency of these CD8(+) T cells, called 'memory T cells with a naive phenotype' (TMNP cells), increased with age and after severe acute infection and inversely correlated with the residual capacity of the immune system to respond to new infections with age. CD8(+) TMNP cells represent a potential new target for the immunotherapy of persistent infections and should be accounted for and subtracted from the naive pool if truly naive T cells are needed to respond to antigens.


Carbon dioxide laser trabeculostomy for the treatment of neovascular glaucoma.
During the past 24 months, 23 cases of advanced neovascular glaucoma, unresponsive to medical therapy, have been treated by a trabeculostomy procedure using a carbon dioxide laser. This procedure entails surgical entry into the anterior chamber from beneath either a conjunctival or scleral flap in such a way as to completely cauterize any neovascular tissue in the corneoscleral angle and to permit adequate drainage of the aqueous in fluid from the anterior chamber to the periocular space. The average intraocular pressure prior to carbon dioxide laser trabeculostomy was 54 mmHg and these pressures were lowered below 18 mmHg in over 70% of the cases followed for longer than six months postlaser therapy. Treatment was considered a failure in 16% of the cases where the intraocular pressure was not lowered substantially. Fourteen percent of the treated eyes sustained a pressure decrease to within the 26-35 mmHg range. Carbon dioxide laser trabeculostomy provides a new method of lowering the intraocular pressure in severe cases of neovascular glaucoma without the hazard of intraocular hemorrhage common with other filtration procedures or the ciliary destruction present with the cyclocautery operations. The indications, surgical technique, and complications will be discussed.


Validation of a non-contact technique for local skin temperature measurements.
Here we propose to quantify local temperature variations using thermal imaging to assess the effect of dermatological lasers. To quantify the temperature raise induced by laser application and to differentiate the effects of a potassium titanyl phosphate (KTP) laser and an intense pulsed light (IPL). A randomized comparative study was performed on 10 adult volunteers with symmetrical rosacea treated by KTP laser or IPL. Skin temperature measurements were performed on inclusion, immediately after laser treatment and 3 min after thermal water application, using a high-resolution (0.08 degrees C) infrared thermal video camera. KTP laser treatment induced a significant rise in local skin temperature whereas no significant change was revealed by the IPL treatment. The infrared camera is a reliable and reproducible technique that allows a follow-up of skin temperature without skin contact. Thermography using an infrared camera could potentially be applied in clinical pharmacology for inflammatory reactions or scarring processes.


Lumbar spinal fusion of low-grade degenerative spondylolisthesis (Meyerding grade I and II): Do reduction and correction of the radiological sagittal parameters correlate with better clinical outcome?
Lumbar and lumbosacral spinal fusion is an established procedure for the treatment of degenerative spondylolisthesis. However, the impact of reduction in the affected segment and of improvement in the radiological sagittal parameters on the clinical outcome remains unclear. Purpose of the study is to analyze the correlation between the radiological sagittal parameters and clinical outcome after lumbar spinal fusion in low-grade degenerative spondylolisthesis. In a monocentric prospective, clinical study, patients with low-grade degenerative spondylolisthesis of a single lumbar segment have been included. All patients received a lumbar spinal fusion according to the pathology of the treated segment. Patients attended clinical and radiological follow-up examination 1 and 2 years postoperatively. Clinical outcome was assessed using the Core Outcome Measurement Index (COMI), the Oswestry Disability Index (ODI) and the EuroQol 5D. The sagittal spinopelvic radiological parameters, sagittal rotation and anterior displacement of the affected segment and lumbar lordosis were assessed. The correlation between the sagittal radiological parameters and clinical outcome was analyzed using Spearman-Rho bi-serial test. Sixty-two patients (35 female and 27 male) with an average age of 59.3 years were included in the study. All patients completed the follow-up examinations. Significant improvement in COMI, ODI and EuroQol 5D scores was shown in all follow-up examinations. Significant reduction in the anterior displacement was measured postoperatively, which was preserved during the follow-up. However, no correlation could be demonstrated between reduction in anterior displacement and improvement in clinical outcome. Nonetheless, correlation between correction of sagittal rotation and clinical outcome was shown. Reduction in anterior displacement of the affected segment in the surgical treatment of low-grade degenerative spondylolisthesis does not have an impact on the clinical outcome.


Finite-time and fixed-time stabilization of multiple memristive neural networks with nonlinear coupling.
This brief presents the finite-time stabilization and fixed-time stabilization of multiple memristor-based neural networks (MMNNs) with nonlinear coupling. Under the retarded memristive theory, the generalized Lyapunov functional method, extended Filippov-framework and Laplacian matrix theory, we can realize both the finite-time stabilization and fixed-time stabilization problem of MMNNs by designing novel state-feedback controller and the corresponding adaptive controller with regulate parameters. Moreover, we assess the bounds of settling time for the both two kinds of stabilization respectively, and we deeply analyze the influence of initial desiring values and the linear growth condition of the controller on the system. Finally, the benefits of the proposed approach and the experimental analysis are demonstrated by numerical examples.


Evolution of a human Y chromosome-specific repeated sequence.
The structure and evolution of a repetitive sequence on the human Y chromosome has been studied by restriction enzyme analysis of both total DNA and the isolated sequence. The sequence is shown to cross-hybridize to sequences in female DNA forming unstable duplexes. Mouse/human cell hybrids have been used to investigate the pattern of sequence homology on the X chromosome and some autosomes. We conclude that this sequence is related to human satellite III, but shows considerable differences in structure.


Electrically controlled spin polarized current in Dirac semimetals.
We propose a highly tunable [Formula: see text] spin-polarized current generated in a spintronic device based on a Dirac semimetal (DSM) under a magnetic field, which can be achieved merely by controlling electrical parameters, i.e. the gate voltage, the chemical potential in the lead and the coupling strength between the leads and the DSM. These parameters are all related to the special properties of a semimetal. The spin polarized current generated by gate voltage is guaranteed by its semimetallic feature, because of which the density of state vanishes near Dirac nodes. The barrier controlled current results from the different distance of Weyl nodes generated by the Zeeman field. And the coupling strength controlled spin polarized current originates from the surface Fermi arcs. This DSM-based spintronic device is expected to be realized in [Formula: see text] experimentally.


3-Hydroxy-3-methylglutaryl coenzyme A reductase in the sea urchin embryo is developmentally regulated.
The activity of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, an enzyme which plays a regulatory role in the synthesis of cholesterol, dolichol, and coenzyme Q, has been measured in the developing embryo of the sea urchin. Enzyme activity increased at least 200-fold during development from the unfertilized egg to the pluteus stage embryo. Mixing experiments suggested that the low level of enzyme activity found at early stages was not due to the presence of inhibitor(s) in the egg or zygote. The enzyme in the sea urchin embryo exhibited properties different from that found in mammals: only a fraction of the activity could be solubilized from microsomes, and mild trypsinization inactivated the enzyme without releasing any of it from the microsomes in soluble form. To further study the sea urchin HMG-CoA reductase, a genomic clone was identified by hybridization to a cDNA encoding hamster HMG-CoA reductase. Sequence analysis of this clone revealed a coding region that shares a high degree of homology with the carboxyl-terminal domain of hamster HMG-CoA reductase. Analysis of sea urchin embryo HMG-CoA reductase mRNA levels using a restriction fragment derived from the genomic clone revealed a 5.5-kilobase poly(A)+ mRNA that increased 15-fold during development from the egg to the gastrula stage and then decreased 1.5-fold at the pluteus stage. Since the relative increase in HMG-CoA reductase mRNA was less than the increase in enzyme activity (15-fold versus 200-fold) factors in addition to the level of mRNA may control the activity of this enzyme during embryogenesis.


The role of calcium and vitamin D dietary intake on risk of colorectal cancer: systematic review and meta-analysis of case-control studies.
The aim of this study is to analyze the current evidence about the relationships between calcium/vitamin D and CRC based on case-control studies according to sex, tumor location and continental region to complement the information obtained in meta-analyses of other designs. The articles were located in three databases (PUBMED, EMBASE and SCOPUS), they should be written in English language, with a case and control design and published between 1 January 1970 and 31 October 2019. There were 37 selected studies, 32 for intake of calcium, that involved 24,353 CRC cases and 30,650 controls, and 23 for that of VIT D, with a total of 19,076 cases and 36.746 controls included. For dietary calcium intake, the overall OR was 0.94 (95% CI 0.92-0.97), suggesting a reducing effect with a 6% decrease in CRC risk for every 300 mg of calcium ingested daily. Regarding vitamin D intake a global OR of 0.96 (95% CI 0.93-0.98) was observed, what means a 4% decrease in the risk of CRC per 100 IU/day of vitamin D. Higher dietary intakes of calcium and vitamin D are associated to a decreased risk of CRC.


COVID-19 disruptions to elective postoperative care did not adversely affect early complications or patient reported outcomes of primary TKA.
Elective orthopedic care, including in-person office visits and physical therapy (PT), was halted on March 16, 2020, at a large, urban hospital at the onset of the local COVID-19 surge. Post-discharge care was provided predominantly through a virtual format. The purpose of this study was to assess the impact of postoperative care disruptions on early total knee arthroplasty (TKA) outcomes, specifically 90-day complications, 120-day rate of manipulation under anesthesia (MUA) and 1-year patient-reported outcome measures (PROMs). Institutional records were queried to identify 624 patients who underwent primary, unilateral TKA for osteoarthritis and who were discharged home between 1/1/20 and 3/15/20. These patients were compared to 558 controls discharged between 1/1/19 and 3/15/2019. Cohort demographics and in-hospital characteristics were equivalent apart from inpatient morphine milligram equivalent (MME) consumption. Patient-reported access to PT (p < 0.001) and post-discharge care (p < 0.001) were worse among study patients. Study patients were prescribed fewer post-discharge PT sessions (19.8 vs. 23.5; p < 0.001) and utilized telehealth more frequently (p < 0.001). Mann-Whitney U, T, Fisher's Exact, and chi-squared tests were used to compare outcomes. Ninety-day CMS complications were lower among study patients (3.5% vs. 5.9%; p = 0.05). Rates of MUA were similar between groups. Study patients reported similar PROMs and marginally inferior VR-12 mental and LEAS functional outcomes at 1 year. Disruptions to elective orthopedic care in March 2020 seemed to have had no major consequences on clinical outcomes for TKA patients. Our findings question the usefulness of pre-pandemic post-discharge protocols, which may over-emphasize in-person visits and PT.


Robot assisted laparoscopic partial cystectomy for inflammatory myofibroblastic tumor with simultaneous intraoperative flexible cystoscopy for tumor mapping.
Bladder masses are an infrequent occurrence rarely suspected in cases of pediatric hematuria. Inflammatory myofibroblastic tumors represent one differential diagnosis that is difficult to characterize as purely benign and should therefore be given special consideration. Although uncommon, this is an important entity to recognize for potential bladder sparing and minimally invasive surgical approaches.


NMR evidence of a valinomycin-proton complex.
In addition to the well-known complexes of valinomycin with alkali metal cations, an equimolar complex of the same compound with proton was found to be formed in nitrobenzene. Hydrogen bis(1,2-dicarbollylide) cobaltate (HDCC) was used as a proton source. According to NMR spectra, the complex formation is quantitative at proton/valinomycin molar ratios up to 1:1 but there is fast exchange of protons between coordinated and uncoordinated valinomycin molecules at lower ratios. 1H and 13C NMR spectra show a dramatic change in the valinomycin conformation during its coordination with protons, probably from a propeller-like to a bracelet-like form. As valinomycin is one of the well-known ion-carrying ionophores facilitating especially the K+ ion transport across a biological membrane, the existence of the valinomycin-proton complex could be important in biochemistry and biology.


Comprehensive assessment of biorefinery potential for biofuels production from macroalgal biomass: Towards a sustainable circular bioeconomy and greener future.
Marine macroalgae have attracted significant interest as a viable resource for biofuel and value-added chemical production due to their abundant availability, low production costs, and high carbohydrate and lipid content. The growing awareness of socio-economic factors worldwide has led to a greater consideration of marine macroalgae as a sustainable source for biofuel production and the generation of valuable products. The integration of biorefinery techniques into biofuel production processes holds immense potential for fostering the development of a circular bioeconomy on a broad scale. Extensive research was focused on the technoeconomic and environmental impact analysis of biofuel production from macroalgal biomass. The integrated biorefinery processes offers valuable pathways for the practical implementation of macroalgae in diverse conversion technologies. These studies provided crucial insights into the large-scale industrial production of biofuels and associated by-products. This review explores the utilization of marine macroalgal biomass for the production of biofuels and biochemicals. It examines the application of assessment tools for evaluating the sustainability of biorefinery processes, including process integration and optimization, life cycle assessment, techno-economic analysis, socio-economic analysis, and multi-criteria decision analysis. The review also discusses the limitations, bottlenecks, challenges, and future perspectives associated with utilizing macroalgal biomass for the production of biofuels and value-added chemicals.


Postoperative opioid administration and post-traumatic stress symptoms in preschool children after cardiac surgery.
The purpose of this study was to explore relationships between postoperative opioid administration and posttraumatic stress symptoms (PTSS) in preschool-aged children surviving cardiac surgery. This was a cross-sectional, descriptive study using survey administration and medical chart review. Primary caregivers of children aged three to six years who underwent cardiac surgery at our institution between 2018 and 2020 were invited to participate. Opioid administration was calculated according to morphine milligram equivalents and indexed to the child's body weight. Caregivers completed the Young Child Posttraumatic Stress Disorder Checklist to explore child PTSS. We used correlational methods to assess the strength and direction of relationships between postoperative opioid administration and child PTSS. We did not find a statistically significant relationship between total postoperative opioid administration and child PTSS. When analyzing individual opioid agents, morphine did show a significant inverse relationship to YCPC scores (rs = -.57, p = .017) in children with single ventricle physiology. Total postoperative opioid administration was not statistically significantly related to child PTSS in our sample. Differing patterns of association were noted among children with single- versus bi-ventricular physiology. Postoperative morphine administration was favorably associated with PTSS in children with single-ventricle physiology. Nurses caring for preschool children who undergo cardiac surgery should anticipate the potential development of PTSS in their patients. Studies using larger sample sizes and longitudinal design are needed to replicate the significant relationship between morphine administration and PTSS in preschoolers with single-ventricle physiology.