Impaired micturition reflex caused by acute selective dorsal or ventral root(s) rhizotomy in anesthetized rats.
To clarify the contributions of parasympathetic inputs and outputs to the micturition reflex. Intra-vesical pressure (IVP), external urethral sphincter electromyogram (EMG), pelvic afferent nerve activities (PANA), and pelvic efferent nerve activities (PENA) as well as the time-derived IVP (dIVP, an index of bladder contractility) were evaluated in intact and acute dorsal or ventral root(s) rhizotomized (DRX and VRX, respectively) rats. In DRX rats, when compared with that in intact stage, the voiding frequency was decreased (75 +/- 15% of intact, P < 0.05, n = 8), while the threshold pressure to trigger voiding contractions was significantly increased (187 +/- 75% of intact, P < 0.05, n = 8). In addition, several insufficient contractions (5.3 +/- 3.5 contractions/voiding, P < 0.05, n = 8) occurred in ahead of each voiding contraction. On the other hand, in VRX rats, the peak and rebound IVP were significantly decreased (90 +/- 3.5% and 75 +/- 11.3% of intact, P < 0.01, n = 8), while the threshold pressure was not affected (102 +/- 11% of intact, P = NS, n = 8). The time-derived parameters were significantly decreased in VRX (peak dIVP, 78 +/- 10.2%, rebound dIVP, 75 +/- 15.6%, minimal dIVP, 68 +/- 14% of intact, P < 0.01, n = 8) but only peak dIVP was decreased (85 +/- 11% of intact, P < 0.01, n = 8) in DRX rats. Acute selective DRX and VRX rat can be an animal model to investigate peripheral neural control in micturition functions.


Subaortic stenosis and sudden death.
An obese white boy, 16 years old, collapsed and suddenly died while walking with friends. Since early childhood he had been known to have mild subaortic stenosis. At age 6 he exhibited first-degree heart block during an electrocardiographic exercise test. Neither then nor thereafter was he known to have any unusual symptoms until his death. Postmortem examination revealed marked cardiac enlargement without asymmetry or much dilatation. There was mild subaortic stenosis, but the heart was otherwise grossly normal. Special studies of his cardiac conduction system demonstrated fibrotic obliteration of the His bundle and proximal portions of both bundle branches. The same region had a much thickened central fibrous body from which the subaortic stenosis ridge protruded. Small arteries in the vicinity of the atrioventricular node were markedly narrowed. Because those vessels provide some of the blood supply to the His bundle region, their narrowing may have contributed to the fibrotic abnormalities observed. The extent of destruction of the His bundle makes a lethal failure of atrioventricular conduction the most likely terminal event.


Retrospective evaluation of a topology preserving non-rigid registration method.
This paper proposes a comprehensive evaluation of a monomodal B-spline-based non-rigid registration algorithm allowing topology preservation in 3-D. This article is to be considered as the companion of [Noblet, V., Heinrich, C., Heitz, F., Armspach, J.-P., 2005. 3-D deformable image registration: a topology preservation scheme based on hierarchical deformation models and interval analysis optimization. IEEE Transactions on Image Processing, 14 (5), 553-566] where this algorithm, based on the minimization of an objective function, was introduced and detailed. Overall assessment is based on the estimation of synthetic deformation fields, on average brain construction, on atlas-based segmentation and on landmark mapping. The influence of the model parameters is characterized. Comparison between several objective functions is carried out and impact of their symmetrization is pointed out. An original intensity normalization scheme is also introduced, leading to significant improvements of the registration quality. The comparison benchmark is the popular demons algorithm [Thirion, J.-P., 1998. Image matching as a diffusion process: an analogy with Maxwell's demons. Medical Image Analysis, 2 (3), 243-260], that exhibited best results in a recent comparison between several non-rigid 3-D registration methods [Hellier, P., Barillot, C., Corouge, I., Gibaud, B., Le Goualher, G., Collins, D.L., Evans, A., Malandain, G., Ayache, N., Christensen, G.E., Johnson, H.J., 2003. Retrospective evaluation of intersubject brain registration. IEEE Transactions on Medical Imaging, 22 (9), 1120-1130]. The topology preserving B-spline-based method proved to outperform the commonly available ITK implementation of the demons algorithms on many points. Some limits of intensity-based registration methods are also highlighted through this work.


Association of patient factors with time to treatment for breast cancer.
Studies have shown that in the United States, there is an increasing time from breast cancer diagnosis to first treatment (time to treatment or "TTT"), with concern that such delays may worsen oncologic outcomes. A component of TTT is the time from the initial diagnosis to initial surgical consultation (SC). We sought to identify patient-related factors associated with time to initial SC, and evaluate how this interval is associated with overall total time to treatment (TTT). A prospective database of women diagnosed with breast cancer at our institution from 2015 to 2016 was reviewed. Time from initial breast cancer diagnosis to SC and overall TTT was collected from the electronic medical record. Documented patient-identified preferences regarding scheduling the first surgical appointment were reviewed. A multivariate analysis was performed to determine clinical and patient factors associated with TTT. Of 553 breast cancer patients included in the study, 27% of women opted for the earliest appointment while 73% chose a later date. The median time from diagnosis to SC was 8.5 ± 4.7 days. Patients who accepted a first available SC waited an average of 5.6 ± 3.4 days, while those who deferred waited 9.5 ± 4.6 days (P < .001). Patients who deferred the earliest available SC were older, with a median age of 67 versus 63 years, (P = .018), and had a preference for a specific location in the geographical hospital region (P = .003). Patients who deferred the first available SC also had a longer TTT (33 vs. 28 days, P = .027). Among newly diagnosed breast cancer patients, there is a substantial population that defers the first available SC. These patients are also more likely to have a prolonged TTT. Future follow-up of this cohort is necessary to determine the delays on TTT affect cancer outcomes and overall survival.


The blood flow velocity waveform index in the fetal thoracic aorta and its ability to detect fetal compromise in the small for gestational age fetus.
In a prospective longitudinal study of 96 patients, mean values of blood velocity waveform indices of the fetal thoracic aorta are established with a combined linear array real-time and pulsed Doppler transducer. The course of the various blood velocity waveforms is elucidated. The most striking finding is the restricted variability of the pulsatility index (PI), resistance index (RI), A/B ratio, acceleration time (AcT) and acceleration time percentage (AcTP) during the last trimester of pregnancy. In 17 proven and evaluable SGA infants the various blood velocity waveform indices were compared with the established mean values. Fourteen of these 17 (82%) infants were proven to be intrauterine growth-retarded (IUGR). Only 3 of these 14 (21%) showed a significant increase in PI values.


Proliferative effect of PGD2 on osteoblast-like cells; independent activation of pertussis toxin-sensitive GTP-binding protein from PGE2 or PGF2 alpha.
PGD2 stimulated DNA synthesis and decreased alkaline phosphatase activity dose-dependently between 10 nM and 10 microM in osteoblast-like MC3T3-E1 cells. PGD2 had little effect on cAMP production, but caused very rapid enhancement of phosphoinositide (PI) hydrolysis dose-dependently between 10 nM and 10 microM. The formation of inositol trisphosphate (IP3) induced by PGD2 reached the peak within 1 min and decreased thereafter, which is more rapid than that induced by PGE2 or PGF2 alpha and both PGE2 and PGF2 alpha affected PGD2-induced IP3 formation additively. Pertussis toxin (PTX) inhibited both PGD2-induced formation of inositol phosphates and DNA synthesis. The degree of these PTX (1 micrograms/ml)-induced inhibitions was similar. In addition, neomycin, a phospholipase C inhibitor, inhibited PGD2-induced DNA synthesis as well as the formation of IP3, and the patterns of both inhibitions were similar. In the cell membranes, PTX-catalyzed ADP-ribosylation of a 40-kDa protein was significantly attenuated by pretreatment of PGD2. Time course of the attenuation of PTX-catalyzed ADP-ribosylation by PGD2 was apparently different from that by PGE2 or PGF2 alpha. These results indicate that PGD2 activates PTX-sensitive GTP-binding protein independently from PGE2 or PGF2 alpha and stimulates PI hydrolysis resulting in proliferation of osteoblast-like cells.


Effect of antibiotic prophylaxis for preventing infectious complications following impacted mandibular third molar surgery. A randomized controlled trial.
The objective of this study was to determine the effect of antibiotic prophylaxis in preventing postoperative infections after extraction of impacted mandibular third molars. A Parallel-group, randomized, blind, placebo-controlled trial was performed. 154 patients were randomly allocated to 2 groups; experimental (n=77) receiving 2g amoxicillin 1 hour prior to surgery and control (n=77) receiving placebo. Primary outcome was postoperative infections and secondary outcome was the need for rescue analgesia. 4.5% of patients developed postoperative infections, five patients of the control group (4 alveolar osteitis, 1 surgical site infection) and two of the experimental group (1 alveolar osteitis, 1 surgical site infection). Difference between groups was not statistically significant, RR=0.4 (95%CI 0.08-1.99, 𝘱=0.41) NNTB=26. Rescue analgesia intake was significantly higher in the control group (41 vs 18 patients of experimental group) RR=0.49 (95%CI 0.32-0.75, 𝘱<0.05) NNTB=3. The use of 2g amoxicillin 1 hour before surgery was not effective in significantly reducing the risk of postoperative infections from impacted mandibular third molars extraction, when compared to placebo. Nevertheless, antibiotic prophylaxis was associated with a reduced need for rescue analgesia.


Central angiotensinergic mechanisms associated with hypertension.
Following its generation by both systemic and tissue-based renin-angiotensin systems, angiotensin II interacts with specific, G-protein coupled receptors to modulate multiple physiological systems, including the cardiovascular system. Genetic models in which the different components of the renin-angiotensin system have been deleted show large changes in resting blood pressure. Interruption of the generation of angiotensin II, or its interaction with these receptors, decreases blood pressure in hypertensive humans and experimental animal models of hypertension. Whilst the interaction of angiotensin II with the kidney is pivotal in this modulation of blood pressure, an involvement of the system in other tissues is important. Both systemic angiotensins, acting via the blood-brain barrier deficient circumventricular organs, and centrally-generated angiotensin modulate cardiovascular control by regulating fluid and electrolyte ingestion, autonomic activity and neuroendocrine function. This review discusses the pathways in the brain that are involved in this regulation of blood pressure as well as examining the sites in which altered angiotensin function might contribute to the development and maintenance of high blood pressure.


Chemoprevention in head and neck cancer: basic science and clinical application.
The concept of field cancerization and the multistep carcinogenesis theory are the premises on which the development of chemoprevention efforts has been based. The first concept underlies the fact that patients who have been cured of a cancer in the aerodigestive tract are still at risk of developing additional primary tumors in the same field, and the multistep carcinogenesis theory implies that the conceivable arrest of one of the steps by chemoprevention might be enough to impede the development of cancer. There is ongoing research for development of new candidate-chemopreventive substances in most areas of oncology. Most of the clinical experience in chemoprevention of head and neck cancer is based on the use of retinoids. Retinoids in high doses have demonstrated activity in treating oral premalignant lesions (OPLs) but with frequent side effects and early relapse after cessation of therapy. Subsequent trials showed better tolerability of retinoids in lower doses. Ongoing trials are currently evaluating whether chemoprevention over 3 years might have longer-lasting effect both on OPLs and in the prevention of second primary tumors.


Possible underlying mechanisms of sexual dimorphism in the immune response, fact and hypothesis.
It is a confirmed fact that in females both the humoral and cell mediated immune response is more active than in males. A large amount of information supports the view that hormones of the endocrine system are intimately involved in this immunological dimorphism. Such hormones include the gonadal steroids, the adrenal glucocorticoids, growth hormone (GH) and prolactin (Prl) from the pituitary, thymic hormones, and substances generated by activated lymphocytes. It is suggested that a complex medley of these hormonal interactions effect both developing lymphocytes within the microenvironment and regulate adult effector cells. The most important of these hormonal interactions leading to immunological dimorphism are the effects elicited by estrogen (E) elaborated at elevated levels from the female ovary after puberty. Elevated E leads to basal GH secretion, increased Prl, and increased thymosin release, all of which are hypothesized to effect lymphocyte development and stimulate adult T- and B-cell function in females. Interactions of hormonal regulatory axes involving the hypothalamus, pituitary, gonads, adrenals, and thymus are also thought to be involved. Factors elaborated by activated immune cells including IL-1 and IL-2 may also play a role in down regulation of these responses. Finally, genetic components are also considered pertinent especially under conditions of pathological disequilibrium leading to autoimmune disease. While the benefits provided by immunological dimorphism are still not entirely clarified, since sex hormones are intimately involved in immunological regulation it is quite possible that the increased immune response in females allows them to compensate for the increased physiological stress which accompanies reproduction. The final outcome would thus be the assurance of reproductive success of the species.


Implications from aphasia for the syntax of null-subject sentences: underlying subject slots in Bulgarian.
Evidence for the existence of an underlying sentence-initial subject slot for Bulgarian null-subject personal constructions can be found in two aberrant tendencies by a Bulgarian patient with aphasia. In response to test sentences consisting of personal constructions that contained an object pronominal clitic and no lexical subject, the patient tended either to insert a superfluous sentence-initial pronominal subject, or to place the object pronominal clitic left-adjacent to the verb, in the position that it would have occupied had a sentence-initial overt subject been present.


A review of thirty-three cases of ovarian dysgerminoma emphasising the role of radiotherapy.
The records of 33 cases of ovarian dysgerminoma seen in Manchester between 1943 and 1977 are reviewed, including details of presenting features, age distribution, treatment and survival. The five-year survival rate is 85%. All the Stage I cases and all patients under the age of 20 years at presentation have survived. The cases of the five patients who died are analysed in detail. From this series and review of other series it is concluded that young patients with unilateral Stage I desease who have had a total resection should be carefully followed and radiotherapy reserved for recurrent disease. This does not appear to affect their high chance of cure and enable patients who remain disease-free to retain one functioning ovary. All other patients should have surgery followed by radiotherapy to the whole abdomen. Analysis of the five deaths suggested that, even in Stage III disease a surgical attempt should be made to remove the bulk of the tumour and that the abdominal radiotherapy dose should not be less than 3000 rad in 20 treatments in 28 days.


High-Yield Ti3 C2 Tx MXene-MoS2 Integrated Circuits.
It is very challenging to employ solution-processed conducting films in large-area ultrathin nanoelectronics. Here, spray-coated Ti3 C2 Tx MXene films as metal contacts are successfully integrated into sub-10 nm gate oxide 2D MoS2 transistor circuits. Ti3 C2 Tx films are spray coated on glass substrates followed by vacuum annealing. Compared to the as-prepared sample, vacuum annealed films exhibit a higher conductivity (≈11 000 S cm-1 ) and a lower work function (≈4.5 eV). Besides, the annealed Ti3 C2 Tx film can be patterned through a standard cleanroom process without peeling off. The annealed Ti3 C2 Tx film shows a better band alignment for n-type transport in MoS2 channel with small work function mismatch of 0.06 eV. The MoS2 film can be uniformly transferred on the patterned Ti3 C2 Tx surface and then readily processed through the cleanroom process. A large-area array of Ti3 C2 Tx MXene-MoS2 transistors is fabricated using different dielectric thicknesses and semiconducting channel sizes. High yield and stable performance for these transistor arrays even with an 8 nm-thick dielectric layer are demonstrated. Besides, several circuits are demonstrated, including rectifiers, negative-channel metal-oxide-semiconductor (NMOS) inverters, and voltage-shift NMOS inverters. Overall, this work indicates the tremendous potential for solution-processed Ti3 C2 Tx MXene films in large-area 2D nanoelectronics.


Intrathoracic goitre: a cause of the superior vena cava syndrome.
Benign lesions of the mediastinum rarely produce obstruction of the innominate vessels. Two patients with intrathoracic goitre are described who presented with the superior vena cava syndrome. Venography in each case demonstrated the extent of obstruction and degree of collateral circulation. Early recognition of the association of intrathoracic goitre and superior vena caval obstruction may lead to clinical improvement with surgical treatment.


Prevention of drowning in infants, children, and adolescents.
Drowning is a leading cause of injury-related death in children. In 2000, more than 1400 US children younger than 20 years drowned. A number of strategies are available to prevent these tragedies. Pediatricians play an important role in prevention of drownings as educators and advocates.


Mitoxantrone: an overview of safety and toxicity.
Mitoxantrone (Novantrone), is an anthracenedione which in preclinical studies demonstrated a spectrum of antitumor activity similar to the anthracyclines, but with less cardiotoxicity. Novantrone is a cytotoxic agent that produces dose-dependent myelosuppression. When administered to patients intravenously every three weeks, white blood cell (WBC) and platelet nadirs occurred between days 8 and 15 with hematologic recovery by day 22. In multiple clinical trials in over 4450 patients, including 372 patients in randomized trials against Adriamycin, Novantrone was consistently associated with a reduced incidence of moderate and severe acute side-effects. In four randomized trials the adverse experience profile associated with Novantrone was superior to that of Adriamycin with statistically significant lower incidences of mucositis/stomatitis, nausea, vomiting and alopecia. Novantrone was less cardiotoxic than Adriamycin and cardiac events were rare in patients without predisposing risk factors. The high level of activity combined with improved patient tolerance and decreased toxicity make Novantrone a promising agent for patients requiring cytotoxic chemotherapy.


Evaluation of urinary selenium as a biomarker of human occupational exposure to elemental and inorganic selenium.
Selenium (Se) is an essential trace element, which however, exhibits a narrow safe range of intake. Selenium also occurs at several workplaces, which results in an inhalative selenium exposure of the employees. Thus, an efficient exposure assessment strategy is demanded. The most established parameter, selenium in plasma, mostly consists of protein-bound selenium. This study aimed to investigate urinary total selenium (Se-U) as an additional biomarker of recent human occupational exposure to elemental and inorganic selenium. Pre- and post-shift urine samples from employees with exposure to selenium-containing dust were analyzed to total selenium and compared with Se levels in urine samples from controls without occupational exposure to selenium as well as correlated with the recent ambient Se exposure by personal air monitoring. Se-U in post-shift samples was considerably increased compared to the levels in pre-shift samples as well as to the controls. However, Se-U in pre-shift urine was elevated compared to the Se-U in controls too. Se-U in post-shift urine and even better the shift increment in Se-U correlated with the air exposure of the present shift. A rough estimation by Se-U shift increment and external exposure accounted for an inhalative resorption rate of about 1%. Our data indicate that Se-U can display the exposure. Pre-shift Se-U levels may be based on previous exposure and indicate a slow urinary elimination kinetics. The results hint for a rather low resorption rate of selenium and inorganic selenium compounds via the lung.


Chemoprophylaxis of trypanosomiasis, due to Trypanosoma (Nannomonas) congolense, in rabbits using a slow release device containing homidium bromide.
The prophylactic activity of a subcutaneously implanted slow release device, containing homidium bromide, was assessed in rabbits, challenged with different stocks of T. congolense, and compared with the classical treatment of 1 mg homidium bromide/kg b.w. intramuscularly. The prophylactic activity of the intramuscular injection was less than a month, while the slow release device protected the rabbits against seven challenges with T. congolense during a period of more than 300 days.


Partial trypsin digestion as an indicator of mis-folding of mutant alanine:glyoxylate aminotransferase and chaperone effects of specific ligands. Study of a spectrum of missense mutants.
Alanine:glyoxylate aminotransferase (AGT) is a liver peroxisomal enzyme whose deficiency results in primary hyperoxaluria type 1 (PH1). More than 75 PH1 mutations are now documented in the AGT gene (AGXT), of which about 50% are missense. We have previously demonstrated that many such mutants expressed by transcription/translation are subject to generalized degradation by the proteasome and a specific limited trimming by an endogenous ATP-independent protease activity. Here, we report the results of partial digestion using trypsin as a mimic for the endogenous non-proteasomal protease and the use of N-terminal protein sequencing to determine the sensitive site. Partial trypsin digestion also provided an indicator of proper folding of the mutant enzyme. For selected mutations the sensitivity to trypsin could be ameliorated by addition of pyridoxal phosphate or aminooxy acetic acid as specific pharmacological chaperones.


Poststroke epilepsy: occurrence and predictors--a long-term prospective controlled study (Akershus Stroke Study).
The aims of the study were to assess the occurrence of poststroke epilepsy (PSE) in patients with ischemic strokes, to identify predictors, and to investigate whether treatment in a stroke unit (SU) influenced the long-term outcomes of epilepsy. Patients with PSE, defined as those having two ore more unprovoked epileptic seizures > or = 1 week after an ischemic stroke, were identified from a cohort of 484 patients with ischemic strokes. The patients were prospectively assessed 7-8 years after stroke or until death. Different variables were studied to look for possible predictors. From 484 patients with ischemic strokes, PSE developed in 12 (2.5%) and 15 (3.1%) patients during the first year and 7-8 years after stroke, respectively. Eight (53%) of these patients were treated in a stroke unit (SU), and seven (47%) were treated in a general medical ward (GMW). The mean age of those who developed PSE and those who did not was 74.3 years and 76.3 years, respectively. In a multivariate analysis, a Scandinavian Stroke Scale (SSS) score < 30 on admission was a significant predictor for developing PSE [odds ratio (OR), 4.9; p = 0.004). The prevalence of PSE, 7 to 8 years after an ischemic stroke, was 3.1%. SSS scores < 30 on admission were a significant predictor for PSE. Neither treatment in SU versus GMW, cortical location, nor age at onset of stroke seemed to influence the risk of developing PSE.


Axotomy-induced motoneuron death is delayed in mice overexpressing PrPc.
The normal function of the cellular prion protein, PrP(c), remains largely unknown. Recently, PrP(c) has been implicated in the regulation of neuronal survival and was shown to confer neuroprotection in the brain. To pursue investigation of the role of PrP(c) in the CNS, we used the facial nerve section, a well-established experimental model of motoneuronal stress. Nerve sections were performed in 2- and 7-day-old newborn mice and in 2 month-old adult mice expressing different levels of PrP(c). We observed no differences in motoneuronal death triggered by facial nerve section between Prnp-/- and wild-type mice, whether in neonatal or adult mice. By contrast, overexpression of PrP(c) in Tga20 newborn mice was correlated with a better survival of motoneurons in the few days following axotomy. The protection was, however transient since motoneuron number in lesioned facial nuclei of Tga20 mice became identical to that of wild-type mice 7 days and 14 days following the lesion when performed in 2- and 7-day-old mice respectively. In Tga20 adult mice, no protection was observed 2 months after the lesion, a time with a significant degree of motoneuron death in adult control mice. These results, while providing further evidence that PrP(c) is endowed with neuroprotective capacity in vivo, also suggest that PrP(c) does not play a physiological role in the regulation of motoneuronal survival.


Bilateral complete ureteral obstruction and renal insufficiency secondary to granulomatous disease.
Chronic granulomatous disease is a rare disorder of neutrophil function that impairs the ability of phagocytes to react to infection and produces inflammatory lesions that may involve many organ systems. A young man recently presented with bilateral mid ureteral obstruction and renal insufficiency secondary to inflammation due to chronic granulomatous disease. To our knowledge, we believe this to be the only case of complete bilateral ureteral obstruction due to chronic granulomatous disease reported to date. A review of the disease, its pathogenesis and potential involvement of the urinary tract is presented.


Phenotypic correlates of male reproductive success in western gorillas.
Sexual selection is thought to drive the evolution of sexually dimorphic traits that increase male reproductive success. Despite a large degree of sexual dimorphism among haplorhine primates, phenotypic traits that may influence the reproductive success of males are largely unstudied due to long life spans and the difficulties in quantifying such traits non-invasively. Here we employ digital photogrammetry of body length and crest size, as well as ranking of the gluteal muscle size, to test whether these sexually dimorphic traits are associated with long-term measures of male reproductive success in western gorillas. Among 19 adult male gorillas monitored for up to 12.5 years, we found that all three phenotypic traits were positively correlated with the average number of mates per male, but only crest size and gluteal muscle size were significantly correlated with offspring survival and the annual rate of siring offspring that survive to weaning age. We discuss why such sexually dimorphic traits might be under ongoing selection in gorillas and other species.


Diabetic control and atypical antipsychotics: a case report.
People with schizophrenia are at increased risk of developing metabolic disturbances. This risk may be further exacerbated by the use of antipsychotic agents. Research is still ongoing to determine the metabolic impact of antipsychotics on glucose regulation. In this case report we review some of the possible mechanisms of action of antipsychotic medication on glucose regulation. We present the case of a 50-year-old man diagnosed with paranoid schizophrenia who developed type 2 diabetes mellitus whilst on treatment with second generation antipsychotics (SGA). His diabetes was controlled by a combination of antidiabetic drugs that were associated with his psychotropic treatment. Due to deterioration in his mental state, the patient was admitted on two occasions to a psychiatric unit during which his prescribed medication (olanzapine and risperidone) was discontinued and changed to aripiprazole. On both occasions, the patient suffered hypoglycaemic episodes and his antidiabetic treatment had to be adjusted accordingly. The patient did not require any antidiabetic treatment whilst on aripiprazole during the follow up period. Clinicians face regular dilemmas in trying to find the right balance between achieving control over a patient's mental illness and reducing any adverse effects associated with the prescribed medication. In patients receiving concomitant antidiabetic therapy, caution should be exercised when changing from one SGA to another. Whilst more longitudinal data are required, a trial of alternative SGAs, including aripiprazole in those developing type 2 diabetes and impaired glucose tolerance may be a worthwhile therapeutic option.


Structure of an archaeal homolog of the human protein complex Rpp21-Rpp29 that is a key core component for the assembly of active ribonuclease P.
Ribonuclease P (RNase P) is a ribonucleoprotein complex involved in the processing of the 5'-leader sequence of precursor tRNA. Human RNase P protein subunits Rpp21 and Rpp29, which bind to each other, with catalytic RNA (H1 RNA) are sufficient for activating endonucleolytic cleavage of precursor tRNA. Here we have determined the crystal structure of the complex between the Pyrococcus horikoshii RNase P proteins PhoRpp21 and PhoRpp29, the archaeal homologs of Rpp21 and Rpp29, respectively. PhoRpp21 and PhoRpp29 form a heterodimeric structure where the two N-terminal helices (alpha1 and alpha2) in PhoRpp21 predominantly interact with the N-terminal extended structure, the beta-strand (beta2), and the C-terminal helix (alpha3) in PhoRpp29. The interface is dominated by hydrogen bonds and several salt bridges, rather than hydrophobic interactions. The electrostatic potential on the surface of the heterodimer shows a positively charged cluster on one face, suggesting a possible RNA-binding surface of the PhoRpp21-PhoRpp29 complex. The present structure, along with the result of a mutational analysis, suggests that heterodimerization between PhoRpp21 and PhoRpp29 plays an important role in the function of P. horikoshii RNase P.


Fouling, performance and cost analysis of membrane-based water desalination technologies: A critical review.
While water is a key resource required to sustain life, freshwater sources and aquifers are being depleted at an alarming rate. As a mitigation strategy, saline water desalination is commonly used to supplement the available water resources beyond direct water supply. This is achieved through effective advanced water purification processes enabled to handle complex matrix of saline wastewater. Membrane technology has been extensively evaluated for water desalination. This includes the use of reverse osmosis (RO) (the most mature membrane technology for desalination), pervaporation (PV), electrodialysis (ED), membrane distillation (MD), and membrane crystallization (MCr). Though nanofiltration (NF) is not mainly applied for desalination purposes, it is included in the reviewed processes because of its ability to reach 90% salt rejection efficiency for water softening. However, its comparison with other technologies is not provided since NF cannot be used for removal of NaCl during desalination. Remarkably, membrane processes remain critically affected by several challenges including membrane fouling. Moreover, capital expenditure (CAPEX) and operating expenditure (OPEX) are the key factors influencing the establishment of water desalination processes. Therefore, this paper provides a concise and yet comprehensive review of the membrane processes used to desalt saline water. Furthermore, the successes and failures of each process are critically reviewed. Finally, the CAPEX and OPEX of these water desalination processes are reviewed and compared. Based on the findings of this review, MD is relatively comparable to RO in terms of process performance achieving 99% salt rejections. Also, high salt rejections are reported on ED and PV. The operation and maintenance (O&M) costs remain lower in ED. Notably, the small-scale MD OPEX falls below that of RO. However, the large-scale O&M in MD is rarely reported due to its slow industrial growth, thus making RO the most preferred in the current water desalination markets.


A new formula to predict the size and insertion depth of cuffed nasotracheal tube in children receiving dental surgery: a retrospective study.
This retrospective study aimed to develop a new formula for selecting the appropriate size and determining the depth of the cuffed nasotracheal intubation (NTI) for a cuffed endotracheal tube (cETT) in pediatric patients undergoing dental surgery. In addition, the clinical data on cETT (i.e., the size and depth of insertion) was compared with those calculated with age-based formulas to evaluate their correlation. A total number of 684 patients who received NTI were enrolled (healthy group, n = 607; special-need group, n = 77). The ETT size used in real-world scenarios was smaller (i.e., about 0.5 and 0.94 mm) than the age-based formula, while the ETT depth was greater (i.e., about 1.5 cm) than the age-based formula in both groups. In the healthy group, age, gender, and body weight were identified as predictors of ETT size and depth through multiple linear regression analysis, while only age and body weight were predictors in the special-needs group. New formulas were developed based on these findings, with ETT size = 3.98 + 0.052 × age + 0.048 × gender (male = 1, female = 0) + 0.023 × body weight (kg) and ETT depth = 15.1 + 0.43 × age + 0.300 × gender (male = 1, female = 0) + 0.007 × body weight (kg). The new formula could be useful for both healthy and special-need pediatric populations undergoing dental procedures.


The use of exploratory factor analysis in evaluating midwives' attitudes and stereotypical myths related to the identification and management of domestic violence in practice.
to investigate the suitability of the 'Midwives' Attitudes to Domestic Violence Scale' for evaluating midwives' attitudes and stereotypical myths related to the identification and management of domestic violence in practice. Other objectives were to assess midwives' perceived role and experience of raising the issue of domestic violence with their clients, and to assess their perceived prevalence of domestic violence in their current practice. survey using a postal quesnionnaire. The questionnaire included a scale on attitudes to, and stereotypical myths surrounding, domestic violence within maternity care, and assessed demographic details. Northern Ireland. 861 hospital and community midwives. 488 midwives returned a completed questionnaire leading to a 57% response rate. Exploratory factor analysis of the 22-item attitude questionnaire produced three factors that accounted for 36% of the variance: namely, factor 1: non-susceptible to myths; factor 2: training and information; and factor 3: confidence. In general, as indicated by the mean summary score, most of the midwives (82%) did not subscribe to the numerous stereotypical myths surrounding domestic violence. Similarly, there was general agreement with issues associated with factor 2: training and information (mean summary score 74%). Importantly, however, factor 3, associated with confidence levels, indicated that, in general, midwives lacked confidence in dealing with the issues addressing domestic violence (mean summary score 33%). the measure provides a reliable method for assessing midwives' attitudes and training needs for identifying and dealing with domestic abuse. It may also serve to evaluate training and policy interventions in domestic violence.


Imaging of acute pancreatitis and its complications.
Patients with acute pancreatitis may present with mild or severe disease, the latter comprising a minority of cases but accounting for most of the morbidity and mortality associated with this disease. Contrast-enhanced computed tomography is the mainstay of imaging patients with acute pancreatitis and is widely used in both the community and academic settings. A variety of retroperitoneal morphologic changes are readily depicted, and the correct assessment of these abnormalities is imperative for management. The purpose of this review is to describe the imaging evaluation of patients with acute pancreatitis by using the 1992 Atlanta Symposium classification and definitions to describe local complications depicted on contrast-enhanced computed tomography. Correlation with the proposed revision of Atlanta Symposium definitions set forth by the Acute Pancreatitis Working Group will be discussed.


Lipid nanoparticle-mediated drug delivery to the brain.
Lipid nanoparticles (LNPs) have revolutionized the field of drug delivery through their applications in siRNA delivery to the liver (Onpattro) and their use in the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines. While LNPs have been extensively studied for the delivery of RNA drugs to muscle and liver targets, their potential to deliver drugs to challenging tissue targets such as the brain remains underexplored. Multiple brain disorders currently lack safe and effective therapies and therefore repurposing LNPs could potentially be a game changer for improving drug delivery to cellular targets both at and across the blood-brain barrier (BBB). In this review, we will discuss (1) the rationale and factors involved in optimizing LNPs for brain delivery, (2) ionic liquid-coated LNPs as a potential approach for increasing LNP accumulation in the brain tissue and (3) considerations, open questions and potential opportunities in the development of LNPs for delivery to the brain.


Clinical determinants of migraine preventive treatment: contribution of SMILE, an observational survey of primary care migraine management in France.
SMILE was an observational study carried out in France among office-based general practitioners (GPs) and neurologists from November 2005 to July 2006 to assess the determinants of prescription of migraine preventive therapy in primary care medicine. A total of 1467 GPs and 83 neurologists were included, treating 5417 and 248 migraine sufferers, respectively. The main factors leading physicians to deem a patient eligible for preventive treatment were perceived medication overuse and frequency of headaches, and secondarily, severity of headaches and functional impact. On the other hand, patient satisfaction with the acute treatment of attacks and triptan use, and secondarily, a long migraine history were found to influence patient eligibility negatively. Noticeably, psychiatric disorders (anxiety, stress) did not appear, aside from somatic factors, among the determinants that significantly influence physicians' judgment about the option of establishing a preventive treatment. However, they are important features of migraine condition and should be listed among the factors guiding choices about migraine preventive therapy.


Barriers to screening for cancer of the cervix.
Despite the widespread availability and demonstrated efficacy of screening with the Papanicolaou smear, many women are screened irregularly or not at all. This study was designed to identify the barriers that prevent those women at risk for cervical cancer from being screened. Complete cervical cytology screening histories were taken during a population-based case-control study of invasive squamous cell carcinoma of the cervix involving 200 patients and their matched neighborhood controls. Smears taken during the previous 5 years were verified whenever possible. Ordinal logistic regression analysis was used to identify seven factors that significantly (P less than 0.05) and independently predicted regular recent screening among both cases and controls [failure to understand the importance and screening nature of cervical smears (-), expressed fears of embarrassment (-), having had a urogenital infection (+), number of pregnancies during the last 5 years (+), the number of pregnancies for which no prenatal care was sought (-), and knowledge of the recommended screening interval (+)], two variables that predicted screening among cases but not controls [age (-) and number of years of oral contraceptives use (+)], and one that predicted screening only among controls [years of living in the United States (+)]. Education, income, Latin heritage, being married, having a regular physician for one's medical care, and all other methods of birth control were significant predictors of screening in the univariate analyses, but were explained by the other more powerful predictors in the multivariate analysis.


Axonal transport and the cytoskeleton.
Great advances in the field of axonal transport have been made in the past year, including the identification of new molecular motors associated with microtubules and actin. In addition, studies on the mechanisms of bidirectional fast axonal transport have clarified new aspects of this process, such as the isolation of a kinesin-binding protein, kinectin, and the finding that phosphorylation regulates kinesin's dissociation from membranous organelles. New approaches to studying slow transport of cytoskeletal proteins have provided further evidence that the axonal cytoskeleton in mammalian systems is largely stationary, although a dynamic exchange occurs between polymers and a small pool of moving subunits.


Effect of human serum on alkaline phosphatase induction in cultured human tumor cells.
The continuous cell lines T 24 and HT-29, derived from human bladder and colon carcinomas, produce term-placental and intestinal alkaline phosphatase, respectively. Growth in hyperosmolar medium or exposure to prednisolone or sodium butyrate induces increased enzyme levels, and combinations of inducers elicit synergistic activity increases. The effect of the inducing agents is strikingly diminished when cells are grown in the presence of high concentrations of human serum, and the synergistic increases are essentially abolished. Major human serum protein fractions do not affect alkaline phosphatase induction.


Innovating the conservative management of isolated cervical aplasia.
Isolated cervical aplasia (ESHRE/ESGE U0C4V0) is a rare condition with an incidence of approximately 1:100,000 births.This congenital malformation of the female genital tract represents an impairment of the outflow tract and is an inevitable cause of infertility. Patients usually present with pelvic pain or haematometra and surgical treatment is needed. Conservative management is the first line of approach, allowing for future fertility. However, complications are not negligible. Choosing the best surgical technique remains controversial as few follow-up studies have been published.We describe a case report of isolated cervical aplasia diagnosed in a 16-year-old patient, managed by a canalisation procedure using a Foley catheter. Following failure of this approach, a levonorgestrel intrauterine system was inserted, which remained efficient after 4 years.This case adds to the few reports of success in the management of this challenging clinical entity and might guide clinicians to avoid non-conservative approaches in young patients.


Effect of supplementation with leucine alone, with other nutrients or with physical exercise in older people with sarcopenia: a systematic review.
Older adults are at a greater risk of developing sarcopenia as a result of reduced mobility, malnutrition, dietary changes and certain diseases. There are no systematic reviews in the literature analysing the effects of supplementation with leucine alone or as part of a supplement, and with or without physical exercise in older people with sarcopenia. We aimed to systematically review the evidence in intervention studies on the effects of supplementation with leucine, either alone, combined with other supplements, or combined with other supplements and physical exercise in older people with sarcopenia. Literature searches related to the topic were conducted in three databases (Pubmed/Medline, Cochrane and SciELO) looking for articles published prior to December 2020. This review includes intervention studies in older adults over 60 years of age with a history of sarcopenia where researchers reported on the effects of leucine supplementation, with or without physical exercise, related to the disease's treatments or outcomes. The systematic review identified three intervention studies examining the effect of leucine without physical exercise, one on leucine with physical exercise, seven on leucine paired with another nutrient and without physical exercise, and twelve on leucine paired with another nutrient and physical exercise. The results revealed that leucine supplementation alone and without physical exercise did not improve markers of sarcopenia, whereas interventions pairing leucine with supplements, particularly leucine-enriched protein supplements, are a promising treatment for the improvement of sarcopenic markers, whether with or without physical exercise. Leucine supplementation, specifically paired with protein supplements, both with and without physical exercise, was found to be an effective dietary intervention for the improvement of sarcopenia. Further dietary interventions are necessary to calculate effective dosage quantities for both leucine and nutrient supplementation as an integral part of the treatment.


Identification of a series of 1,2,3,4-tetrahydroisoquinolinyl-benzamides with potential anticonvulsant activity.
A series of N-(tetrahydroisoquinolinyl)-2-methoxybenzamides was identified by high-throughput screening at the novel SB-204269 binding site. SAR studies have provided compounds 4 and 14 with high affinity and good anticonvulsant activity in animal models.


First-trimester screening for chromosomal abnormalities by fetal nuchal translucency in a Brazilian population.
To examine the detection rate of chromosomal abnormalities using nuchal translucency (NT) thickness in a Brazilian population. This was a prospective study of 2996 singleton pregnancies with a live fetus at 10-14 weeks of gestation attending for routine antenatal care in a teaching hospital in Brazil. Fetal crown-rump length (CRL) and NT thickness were measured and the risks for trisomy 21 were calculated by a combination of maternal age and fetal NT with the use of software provided by The Fetal Medicine Foundation. Sensitivity and positive predictive values for different risk cut-offs were calculated. Chromosomal defects were diagnosed in 22 cases, including 10 cases of trisomy 21. The estimated risk based on maternal age and fetal NT was 1 in 300 or greater in 222 (7.4%) cases and these included nine of 10 (90.0%) pregnancies with trisomy 21 and nine of 12 (75.0%) pregnancies with other chromosomal defects. The NT was above the 95th centile in 5.8% of cases and this group included 70% of the trisomy 21 cases. A combination of maternal age and fetal NT provides an effective method of screening for chromosomal defects. The performance of the test in a Brazilian population is similar to that in Britain.


Network-based analysis of calcium-binding protein genes identifies Grp94 as a target in human oral carcinogenesis.
To characterise Ca(2+) -binding protein gene expression changes in oral squamous cell carcinomas (OSCCs), we compared the gene expression profiles in OSCC-derived cell lines with normal oral tissues. One hundred Ca(2+) -binding protein genes differentially expressed in OSCCs were identified, and genetic pathways associated with expression changes were generated. Among genes mapped to the network with the highest significance, glucose-regulated protein 94 kDa (Grp94) was evaluated further for mRNA and protein expression in the OSCC cell lines, primary OSCCs, and oral premalignant lesions (OPLs). A significant (P<0.001) overexpression of Grp94 protein was observed in all cell lines compared to normal oral epithelium. Immunohistochemical analysis showed highly expressed Grp94 in primary OSCCs and OPLs, whereas most of the corresponding normal tissues had no protein immunoreaction. Real-time quantitative reverse transcriptase-PCR data agreed with the protein expression status. Moreover, overexpression of Grp94 in primary tumours was significantly (P<0.001) correlated with poor disease-free survival. The results suggested that Grp94 may have potential clinical application as a novel diagnosis and prognostic biomarker for human OSCCs.


Activation of peroxymonosulfate by ZIFs derived Fe/Cu encapsulated N-doped carbon for bisphenol A degradation: The role of N doping.
Bisphenol A (BPA) is a typical kind of endocrine disruption chemical, which has a negative effect on human health, and thus it is necessary to remove BPA from water. Herein, activation of peroxymonosulfate (PMS) by Fe, Cu-Coordinated ZIF-Derived Carbon Framework bifunctional catalyst (Fe/Cu@NC-x) fabricated via hydrothermal-calcination method for BPA removal. The physicochemical properties of Fe/Cu@NC-x were studied by X-ray diffraction, Transmission electron microscopy, Scanning electron microscopy, Raman Spectroscopy, Brunauer-Emmett Teller, and X-ray photoelectron spectroscopy. The effects of the Fe/Cu@NC-900 dosage and PMS concentration, initial pH, and co-existing anions on BPA degradation were evaluated. Under optimized factors (pH unadjusted, Fe/Cu@NC-900 = 0.2 g/L, and PMS = 0.75 g/L), the degradation efficiency of BPA can reach 98% after 30 min. In addition, the BPA degradation efficiency was different extents restrain by inorganic anions (SO42- > Cl- > HCO3- > NO3-). Furthermore, the free radicals (SO4-·, ·OH, and O2-·) and non-radical (1O2) contribute to rapid BPA degradation in Fe/Cu@NC-900/PMS system. This study presents a novel material with significant performance for the removal of organic pollutants.


Role for Prdx1 as a specific sensor in redox-regulated senescence in breast cancer.
Recent studies suggest that Peroxiredoxin 1 (Prdx1), in addition to its known H₂O₂-scavenging function, mediates cell signaling through redox-specific protein-protein interactions. Our data illustrate how Prdx1 specifically coordinates p38MAPK-induced signaling through regulating p38MAPKα phosphatases in an H₂O₂ dose-dependent manner. MAPK phosphatases (MKP-1 and/or MKP-5), which are known to dephosphorylate and deactivate the senescence-inducing MAPK p38α, belong to a group of redox-sensitive phosphatases (protein tyrosine phosphatases) characterized by a low pKa cysteine in their active sites. We found that Prdx1 bound to both MKP-1 and MKP-5, but dissociated from MKP-1 when the Prdx1 peroxidatic cysteine Cys52 was over-oxidized to sulfonic acid, which in turn resulted in MKP-1 oxidation-induced oligomerization and inactivity toward p38MAPKα. Conversely, over-oxidation of Prdx1-Cys52 was enhancing in the Prdx1:MKP-5 complex with increasing amounts of H₂O₂ concentrations and correlated with a protection from oxidation-induced oligomerization and inactivation of MKP-5 so that activation toward p38MAPK was maintained. Further examination of this Prdx1-specific mechanism in a model of reactive oxygen species-induced senescence of human breast epithelial cells revealed the specific activation of MKP-5, resulting in decreased p38MAPKα activity. Taken together, our data suggest that Prdx1 orchestrates redox signaling in an H₂O₂ dose-dependent manner through the oxidation status of its peroxidatic cysteine Cys52.


Primary mode of delivery and subsequent pregnancy.
To investigate the relationship between primary mode of delivery and subsequent pregnancy and to compare the findings with a previous study conducted on an earlier cohort from the same population. Population cohort. Aberdeen City, Scotland. Women who delivered their first singleton child in Aberdeen Maternity Hospital between 1980 and 1997. Population-based data relating to the index and next pregnancy event, if any, were obtained from the Aberdeen Maternity Neonatal Databank. Subsequent pregnancy was compared across the three modes of delivery groups using log rank tests and Cox proportional hazards regression models. First subsequent pregnancy following index delivery. Women who delivered by caesarean section (CS) were less likely to have a subsequent pregnancy compared with those who had a spontaneous vaginal delivery (SVD), hazard ratio = 0.91 (95% CI 0.87, 0.95). This confirmed the findings of a previous study conducted on an earlier cohort of the same population. The median time to next pregnancy following CS was 36.3 months, 31.8 months following instrumental vaginal delivery (IVD) and 30.4 months following SVD. In contrast to the earlier study where women who had an instrumental delivery were found to be an intermediate group, we found no difference in subsequent pregnancy following IVD compared with SVD, HR = 1.0 (95% CI 0.96, 1.03). Following an initial delivery by CS, fewer women went on to have another pregnancy compared with SVD. The incidence of subsequent pregnancy is similar following instrumental and SVD.


Ultrastructure and Phylogeny of Kirithra asteri gen. et sp. nov. (Ceratoperidiniaceae, Dinophyceae) - a Free-Living, Thin-Walled Marine Photosynthetic Dinoflagellate from Argentina.
A gymnodinioid photosynthetic dinoflagellate was isolated from Argentina and examined by light and electron microscopy and analysis of nuclear-encoded LSU rDNA. Kirithra asteri gen. et sp. nov. was proposed as morphology and molecular phylogeny separated this dinoflagellate from others within the family Ceratoperidiniaceae. Cells were surrounded by a hyaline amphiesma comprising polygonal vesicles. Each vesicle contained a honeycomb and a trilaminar structure. An anterior sulcal extension ending in a complete circle formed the apical structure complex (ASC), which characterizes Ceratoperidiniaceae. The ASC comprised three rows of vesicles. The nucleus was located in the hypocone, and several large, irregularly shaped vesicles were present in the epi- and hypocone. Chloroplasts were surrounded by three membranes, and grana-like arrangements of thylakoids were observed in one strain used for ultrastructural study. The cell centre contained 1-3 multiple-stalked pyrenoids and membrane-bound vesicles containing tile-like structures surrounded each pyrenoid. Two pusules with collecting chambers and associated vesicles branched off each of the flagellar canals. The flagellar apparatus featured a ventral connective between the amphiesma and the R1 root, and almost opposite basal bodies, rarely seen in dinoflagellates. This was the first ultrastructural study of a species within Ceratoperidiniaceae.


cFLIP regulation of lymphocyte activation and development.
Cellular caspase-8 (FLICE)-like inhibitory protein (cFLIP) was originally identified as an inhibitor of death-receptor signalling through competition with caspase-8 for recruitment to FAS-associated via death domain (FADD). More recently, it has been determined that both cFLIP and caspase-8 are required for the survival and proliferation of T cells following T-cell-receptor stimulation. This paradoxical finding launched new investigations of how these molecules might connect with signalling pathways that link to cell survival and growth following antigen-receptor activation. As discussed in this Review, insight gained from these studies indicates that cFLIP and caspase-8 form a heterodimer that ultimately links T-cell-receptor signalling to activation of nuclear factor-kappaB through a complex that includes B-cell lymphoma 10 (BCL-10), mucosa-associated-lymphoid-tissue lymphoma-translocation gene 1 (MALT1) and receptor-interacting protein 1 (RIP1).


Evidence of early beta-cell deficiency among children who show impaired fasting glucose: 10-yr cohort study (EarlyBird 56).
Impaired fasting glucose (IFG) is a predictor of future diabetes and is increasingly common in children, but the extent to which it results from excess insulin demand or failure of supply is unclear. Our aim was to compare the behaviour of insulin sensitivity and beta-cell function in children who developed IFG with those whose glucose levels remained within the normal range. We examined trends in fasting glucose, insulin sensitivity (HOMA-S) and beta-cell function (HOMA-B) in 327 healthy children annually from 5 to 15 yr, and the parents at baseline. Fifty-five children showed IFG, mostly after age 11 yr. Fasting glucose rose progressively and was higher throughout in those who developed IFG compared with those who did not (p < 0.001). Beta-cell function was lower from the age of 5 yr in those who developed IFG (p = 0.006), but there was no difference in BMI (p = 0.71). A difference in insulin sensitivity was revealed on adjustment for covariates (p = 0.03). Glucose was higher (p < 0.001), beta-cell function lower (p = 0.01), and insulin sensitivity the same (p = 0.86) in the mothers of children who showed IFG, compared with those who did not. IFG is common in contemporary children, and appears to be related to a defect in beta-cell function already present at 5 yr. Similar findings in the mothers of IFG children suggest that the beta-cell defect may be transmissible.


Determination of the bioavailability of intranasal elcatonin in humans: development of a sandwich transfer enzyme immunoassay for elcatonin.
A sandwich transfer enzyme immunoassay for elcatonin (ECT) and its usability for the pharmacokinetic study are described. The anti-salmon calcitonin (SCT) antibody was used for the present assay. The assay procedure consisted of the reaction of ECT with 2,4-dinitrophenylbiotinyl anti-SCT IgG and anti-SCT Fab'-beta-D-galactosidase conjugate, trapping onto (anti-2,4-dinitrophenyl bovine serum albumin) IgG-coated polystyrene balls, eluting with epsilonN-2,4-dinitrophenyl-L-lysine and transferring to streptavidin-coated polystyrene balls and fluorometric detection of beta-D-galactosidase activity. The practical detection limit of ECT was 0.15 pg (44 amol)/50 microl of sample and 3 pg/ml as the concentration. The application of this method has enabled us to directly estimate the bioavailability of ECT dosed intranasaly at a therapeutic level (100 IU, 17 microg) for its anti-osteoporotic effect as compared to an intramuscular dose (40 IU, 6.7 microg). The pharmacokinetic parameters of the intranasal ECT (n = 6) thus estimated were as follows: the area underthe serum concentration-time curve (AUC) = 2,570 +/- 1,650 (SD) pg x min/ml, and the maximal concentration (Cmax) = 60 +/- 25 (SD) pg/ml with the maximal time (Tmax) = 17.5 +/- 6.9 (SD) min, when the AUC for the intramuscular ECT (n = 9) = 9,460 +/- 5,870 (SD) pg x min/ml and the Cmax = 165 +/- 79 (SD) pg/ml with the Tmax = 16.1 +/- 4.2 (SD) min.


Platelet endothelial cell adhesion molecule-1 (PECAM1) plays a critical role in the maintenance of human vascular endothelial barrier function.
Cardiovascular endothelial barrier dysfunction is associated with a number of cardiovascular diseases. This study aims to investigate the role of platelet endothelial cell adhesion molecule-1 (PECAM1) in the maintenance of the vascular endothelial barrier integrate. Human umbilical vein endothelial cells (HUVECs) were cultured into monolayers using as an in vitro model to assess the endothelial barrier function. Knockdown of the gene of PECAM1 markedly reduced the transendothelial resistance and increased the permeability of the HUVEC monolayers. From the wild HUVECs, we detected a complex of PECAM1, claudin1, occluding and endothelial cell selective adhesion molecule (ESAM); such a complex was not detected in the PECAM1-deficient HUVECs. Knockdown of either claudin1, or occludin, or ESAM, did not affect the formation of the tight junction (TJ) complex. Exposure to recombinant interleukin (IL)-13 inhibited the expression of PECAM1 and down-regulated the HUVEC monolayer barrier function. PECAM1 plays an important role in the formation of TJ complex.


Nicotine-induced changes in the metabolism of specific brain proteins.
The effect of acute and chronic nicotine on the metabolism of specific brain proteins was examined by measuring incorporation of labeled valine into protein, with densitometric scanning of proteins resolved by gel electrophoresis. Acute and chronic administration of nicotine (0.4 mg/kg per 30 min for 2 hours, s.c., or 0.5 mg/kg per 30 min for 5 days (Alzet mini-pump implanted subcutaneously] reduced incorporation of [14C]valine administered by approximately 6-7%. The results with chronic nicotine administration indicated a lack of tolerance for this effect of nicotine. Mecamylamine, a nicotinic ganglionic antagonist, does not seem to block the inhibition of protein synthesis. Small increases in protein content were observed in a high- and a low-molecular-weight region of SDS-polyacrylamide gel, used to separate proteins from newborn brain. In adult brain after chronic nicotine administration, selective increases and a decrease were seen in selective bands. Results are consonant with selective effects of nicotine on the synthesis or degradation of specific brain proteins.


The effect of hypoxemia on muscle sympathetic nerve activity and cardiovascular function: a systematic review and meta-analysis.
We conducted a systematic review and meta-analysis to determine the effect of acute poikilocapnic, high-altitude, and acute isocapnia hypoxemia on muscle sympathetic nerve activity (MSNA) and cardiovascular function. A comprehensive search across electronic databases was performed until June 2021. All observational designs were included: population (healthy individuals); exposures (MSNA during hypoxemia); comparators (hypoxemia severity and duration); outcomes (MSNA; heart rate, HR; and mean arterial pressure, MAP). Sixty-one studies were included in the meta-analysis. MSNA burst frequency increased by a greater extent during high-altitude hypoxemia [P < 0.001; mean difference (MD), +22.5 bursts/min; confidence interval (CI) = -19.20 to 25.84] compared with acute poikilocapnic hypoxemia (P < 0.001; MD, +5.63 bursts/min; CI = -4.09 to 7.17) and isocapnic hypoxemia (P < 0.001; MD, +4.72 bursts/min; CI = -3.37 to 6.07). MSNA burst amplitude was only elevated during acute isocapnic hypoxemia (P = 0.03; standard MD, +0.46 au; CI = -0.03 to 0.90), and MSNA burst incidence was only elevated during high-altitude hypoxemia [P < 0.001; MD, 33.05 bursts/100 heartbeats; CI = -28.59 to 37.51]. Meta-regression analysis indicated a strong relationship between MSNA burst frequency and hypoxemia severity for acute isocapnic studies (P < 0.001) but not acute poikilocapnia (P = 0.098). HR increased by the same extent across each type of hypoxemia [P < 0.001; MD +13.81 heartbeats/min; 95% CI = 12.59-15.03]. MAP increased during high-altitude hypoxemia (P < 0.001; MD, +5.06 mmHg; CI = 3.14-6.99), and acute isocapnic hypoxemia (P < 0.001; MD, +1.91 mmHg; CI = 0.84-2.97), but not during acute poikilocapnic hypoxemia (P = 0.95). Both hypoxemia type and severity influenced sympathetic nerve and cardiovascular function. These data are important for the better understanding of healthy human adaptation to hypoxemia.


Biogenic amine-related enzymes and personality variations in normals.
Altered activities of biogenic amine-related enzymes have been reported in some studies of patients with affective disorders and chronic schizophrenia. To evaluate whether any relationship between personality variations, including non-diagnosed psychopathology, and these enzymes might occur in non-psychiatric patients, 95 young adult volunteers were studied. Higher MMPI and Zuckerman sensation--seeking scale scores were found in male, but not female, volunteers with lower platelet and plasma amine oxidase activities. Males generally exhibited negative correlations, while females had positive correlations between the psychological test scores and amine oxidase activities. In contrast to the amine oxidase results, no associations were observed between plasma dopamine beta-hydroxylase activities and the personality variables.


The detection and genetic characterization based on the S1 gene region of BCoVs from respiratory and enteric infections in Turkey.
We investigated bovine coronavirus (BCoV) as an etiological agent in cattle with clinical respiratory and digestive signs using 147 feces and 199 nasal swab samples. A total of 18 test samples (16 feces and 2 nasal swap samples) were detected positive by ELISA and/or RT-PCR targeting the BCoV N gene. The partial S1 gene regions of BCoVs (An-4 and An-11) detected in feces samples from two herd-mate dairy calves were compared. Virological and serological results indicated that BCoVs are widespread in Turkey and are likely etiological agents in diarrhea cases in calves.


Two-Dimensional (2D) materials in the detection of SARS-CoV-2.
The SARS-CoV-2 pandemic has resulted in a devastating effect on human health in the last three years. While tremendous effort has been devoted to the development of effective treatment and vaccines against SARS-CoV-2 and controlling the spread of it, collective health challenges have been encountered along with the concurrent serious economic impacts. Since the beginning of the pandemic, various detection methods like PCR-based methods, isothermal nucleic acid amplification-based (INAA) methods, serological methods or antibody tests, and evaluation of X-ray chest results have been exploited to diagnose SARS-CoV-2. PCR-based detection methods in these are considered gold standards in the current stage despite their drawbacks, including being high-cost and time-consuming procedures. Furthermore, the results obtained from the PCR tests are susceptible to sample collection methods and time. When the sample is not collected properly, obtaining a false result may be likely. The use of specialized lab equipment and the need for trained people for the experiments pose additional challenges in PCR-based testing methods. Also, similar problems are observed in other molecular and serological methods. Therefore, biosensor technologies are becoming advantageous with their quick response, high specificity and precision, and low-cost characteristics for SARS-CoV-2 detection. In this paper, we critically review the advances in the development of sensors for the detection of SARS-CoV-2 using two-dimensional (2D) materials. Since 2D materials including graphene and graphene-related materials, transition metal carbides, carbonitrides, and nitrides (MXenes), and transition metal dichalcogenides (TMDs) play key roles in the development of novel and high-performance electrochemical (bio)sensors, this review pushes the sensor technologies against SARS-CoV-2 detection forward and highlights the current trends. First, the basics of SARS-CoV-2 detection are described. Then the structure and the physicochemical properties of the 2D materials are explained, which is followed by the development of SARS-CoV-2 sensors by exploiting the exceptional properties of the 2D materials. This critical review covers most of the published papers in detail from the beginning of the outbreak.


Lactate measurements accurately predicts 1-week mortality in emergency department patients with acute kidney injury.
Studies on prognostic indicators in patients with acute kidney injury are limited. This study investigated 1-week mortality, laboratory and clinical parameters according to the lactate levels in patients with acute kidney injury. In this cross-sectional study, we compared the lactate levels on admission and follow-up in emergency department with vital findings, laboratory parameters, and 1-week mortality. Data of 3375 patients examined; 2681 patients excluded and 694 patients were included. Median lactate level on admission was 1.6 (1.1-2.5) mmol/L for patients who discharged from emergency department, 2.2 (1.3-3.4) mmol/L for patients admitted to the hospital wards, 3.7 (1.7-7.2) mmol/L for patients admitted to the intensive care unit and 4.4 (2.4-8.0) mmol/L for patients with mortality within 1-week of ED presentation. Mortality was 30.4% in patients with high lactate levels and 8.1% in patients with normal lactate levels on admission. (p < 0.001, odds ratio 5.0, 95% CI 3.2-7.7) Elevated lactate level was independent risk factor for 1-week-mortality. (p < 0.001, odds ratio 1.138, 95% CI 1.067-1.214) Patients with high lactate levels have low systolic blood pressure, diastolic blood pressure, oxygen saturation, pH, base deficit, and bicarbonate, and higher heart rate and respiratory rate. The mortality of patients with normal lactate levels on admission was 8.1%, while mortality rate increased to 19% if elevated lactate levels observed during emergency department follow-up. Elevated lactate level predicts 1-week mortality in patients presenting with acute kidney injury in emergency department. Elevated lactate level were associated with poorer vital signs and abnormal laboratory results.


Jojoba Seed Oil as Feed Additive for Sustainable Broiler Meat Production under Hot Climatic Conditions.
This study aimed to evaluate the impact of dietary addition of jojoba seed oil on productive performance, physicochemical attributes and carcass quality of broiler meat under tropical weather conditions. A total of 384 one-day-old Ross-308 were subdivided into four dietary treatments of jojoba seed oil: 0, 50, 100 and 150 mg/kg of control diet. Each treatment group included twelve replicates with eight birds each. The results showed that dietary supplementation of jojoba seed oil linearly increased (p < 0.01) feed intake, body weight gain and improved (p < 0.01) feed conversion ratio. Interestingly, diets supplemented with jojoba seed oil linearly (p < 0.05) improved the percentage of dressing and reduced abdominal fat percentage compared to the control group. Dietary supplementation of jojoba seed oil showed no effects (p ≥ 0.05) on the weight of internal organs, including liver, heart, gizzard, spleen and pancreas of broiler chickens. Increasing jojoba seed oil levels in the diet decreased (p < 0.001) percentages of cook and drip losses of breast and leg (drumstick and thigh) muscles of broilers. It was concluded that jojoba seed oil used as a feed additive up to 150 mg/kg improves growth performance and meat quality of broiler chickens in tropical weather conditions.


Antibodies to surface IgM and IgD increase the expression of various class II antigens on human B cells.
Antibodies to surface IgM and IgD were found to induce increased expression of class II antigens on normal and neoplastic human B cells within 24 h of stimulation. Antigens associated with different class II sub-locus genes (DC, DR and SB) were all found to be increased as determined by monoclonal antibodies (Leu-10 and B 3/4 for DC, D 1/12 for DR and MHM4 for SB-associated antigens). The increased expression of class II antigens was selective as anti-immunoglobulins failed to increase expression of other surface antigens such as B1 and beta 2-microglobulin. The effect of anti-mu and anti-delta could be blocked specifically by corresponding myeloma proteins suggesting that antibodies to surface IgM and IgD, respectively, were responsible for the effect observed. Moreover, antibodies to another surface antigen (B1) failed to induce such changes. Increased class II antigen expression appeared to be dependent on protein synthesis, and early changes in ion fluxes, but could not be elicited by membrane depolarization as reported in murine systems.


Noralashinol A, a new norlignan from stem barks of Syringa pinnatifolia.
One new norlignan, namely noralashinol A (1), one known analogue (2), together with seven known lignans (3-9) were isolated from the stem barks of Syringa pinnatifolia. Their structures were elucidated extensively by spectroscopic methods, including mass spectrometry and 1D and 2D NMR spectroscopies. Compound 8 significantly inhibited NO production in LPS-induced BV-2 murine microglia cells with its IC50 value of 20.7 μM, compared to a positive control quercetin with its IC50 value of 15.3 μM.


Bright liver and alanine aminotransferase are associated with metabolic syndrome in adults.
The metabolic syndrome has become a significant health problem worldwide. In this study, we investigated the relationship between the metabolic syndrome, bright liver (BL) by ultrasonography (US), and plasma alanine aminotransferase (ALT) levels among apparently healthy adults. A total of 15,430 nonalcoholic healthy adults without hepatitis B or C were recruited from four nationwide MJ Health Screening Centers in Taiwan in 2000. Metabolic syndrome was defined using the National Cholesterol Education Panel (NCEP) metabolic syndrome criteria or modified NCEP criteria. Based on liver US, subjects were classified into either having BL or not. The relationship between the metabolic syndrome, BL, and ALT levels was examined using multivariate logistic regression analysis. The crude OR of the metabolic syndrome was 13.92 (12.19 using modified NCEP criteria), and the age-BMI-sex-adjusted OR was 3.77 (3.71 using modified NCEP criteria) in subjects with BL vs. subjects without BL, respectively. The ORs of the metabolic syndrome were significantly higher in subjects with elevated ALT levels than in those with normal ALT levels. After adjustment for age, sex, and BMI, BL and elevated ALT level were independently associated with increased risk of the metabolic syndrome. Presence of BL and elevated plasma ALT level was independently associated with increased risk of the metabolic syndrome in adults. These factors contribute to a list of well-known risk factors, including obesity, aging, and male sex, and thus can be applied as an additional evaluation for the metabolic syndrome in a clinical setting.


A distributional regression approach to income-related inequality of health in Australia.
Several studies have confirmed the existence of a significant positive relationship between income and health. Conventional regression techniques such as Ordinary Least Squares only help identify the effect of the covariates on the mean of the health variable. In this way, important information of the income-health relationship could be overlooked. As an alternative, we apply and compare unconventional regression techniques. We adopt a distributional approach because we want to allow the effect of income on health to vary according to people's health status. We start by analysing the income-health relationship using a distributional regression model that falls into the GAMLSS (Generalized Additive Models for Location, Scale and Shape) framework. We assume a gamma distribution to model the health variable and specify the parameters of this distribution as linear functions of a set of explanatory variables. For comparison, we also adopt a quantile regression analysis. Based on predicted health quantiles, we use both a parametric and a non-parametric approach to estimate the lower tail of the health distribution. Our data come from Wave 13 of the Household, Income and Labour Dynamics in Australia (HILDA) survey, collected in 2013-2014. According to GAMLSS, we find that the risk of ending up in poor, fair or average health is lower for those who have relatively high incomes ($80,000) than for those who have relatively low incomes ($20,000), for both smokers and non-smokers. In relative terms, the risk-lowering effect of income appears to be the largest for those who are in poor health, again for both smokers and non-smokers. The results obtained on the basis of quantile regression are to a large extent comparable to those obtained by means of GAMLSS regression. Both distributional regression techniques point in the direction of a non-uniform effect of income on health, and are therefore promising complements to conventional regression techniques as far as the analysis of the income-health relationship is concerned.


Big endothelin-1 as a tumour marker for canine haemangiosarcoma.
Haemangiosarcoma (HSA) is an important malignant neoplasm of dogs that originates from vascular endothelial cells. This study explored the suitability of using serum big endothelin-1 (ET-1) as a tumour marker for canine spontaneous HSA. Serum big ET-1 was measured in dogs with splenic HSA (n = 14), splenic malignant tumours other than HSA (n = 10), benign splenic lesions (n = 11) and normal healthy dogs (n = 17) by ELISA. Serum big ET-1 levels in dogs with HSA were significantly (P < 0.01) higher than in other dogs. High sensitivity (100%, 95% confidence interval 86-100%) and specificity (95%, 95% confidence interval 86-95%) for HSA diagnosis were obtained using a cut-off of 17 pg/mL according to receiver operating characteristic (ROC) curves (area under ROC curve 0.93). PPET1, ETA, VEGF and Hif1-α mRNA expression, measured by real-time PCR, were elevated in HSA compared with normal tissues. These findings suggest that elevated serum big ET-1 could be used as a diagnostic marker for canine HSA.


Predicting early breastfeeding attrition.
The Breastfeeding Attrition Prediction Tool (BAPT) is based on the theory of planned behavior, which explains behavior as a function of attitudes, subjective norm, and perceived control. The BAPT subscales are positive and negative attitudes toward breastfeeding, family and professional expectations, and perceived ability to be successful. The purpose of this study was to test the reliability and validity of the BAPT among 269 women who planned to breastfeed for at least 8 weeks. Subjects completed the BAPT in the hospital and during a telephone interview at 8 weeks. Based on factor analysis, several items were deleted. Using discriminant function analysis, the modified BAPT was an effective predictor of 78% of women who stopped breastfeeding before 8 weeks and 68% of those who were still breastfeeding. There is potential for the modified BAPT to be an adjunct for the clinician in identifying women at risk for early cessation of breastfeeding.


Diverse cloud and aerosol impacts on solar photovoltaic potential in southern China and northern India.
Cloud and aerosol are two important modulators that influence the solar radiation reaching the earth's surface. It is intriguing to find diverse impacts of clouds and aerosols over Southern China (SC) and Northern India (NI) which result in remarkable differences in the plane-of-array irradiance (POAI) that signifies the maximum available solar photovoltaic potential by combining the latest satellite retrieval results and modeling tools. By separating the impacts of cloud and aerosol on the POAI, it is found that clouds are responsible for the most reduction of POAI in the SC, while aerosols and clouds are equally important for the NI region. The frequent occurrences of low and middle level clouds with high optical depth in the SC, as compared with the much lower occurrences of all levels of clouds with lower optical depth in the NI, is regarded as the major reason for the differences in the POAI. The differences in the main compositions of aerosols in the SC (sulfate) and the NI (dust) could be essential to answer the question of why higher aerosol optical depth in the SC whereas leads to weaker reduction in the POAI than that in the NI. The mitigation measures targeting on the controls of different types of aerosols should be considered for different regions.


Brain-wide interactions during hippocampal sharp wave ripples.
During periods of disengagement from the environment, transient population bursts, known as sharp wave ripples (SPW-Rs), occur sporadically. While numerous experiments have characterized the bidirectional relationship between SPW-Rs and activity in chosen brain areas, the topographic relationship between different segments of the hippocampus and brain-wide target areas has not been studied at high temporal and spatial resolution. Yet, such knowledge is necessary to infer the direction of communication. We analyzed two publicly available datasets with simultaneous high-density silicon probe recordings from across the mouse forebrain. We found that SPW-Rs coincide with a transient brain-wide increase in functional connectivity. In addition, we show that the diversity in SPW-R features, such as their incidence, magnitude, and intrahippocampal topography in the septotemporal axis, are correlated with slower excitability fluctuations in cortical and subcortical areas. Further, variations in SPW-R features correlated with the timing, sign, and magnitude of downstream responses with large-amplitude SPW-Rs followed by transient silence in extrahippocampal structures. Our findings expand on previous results and demonstrate that the activity patterns in extrahippocampal structures depend both on the intrahippocampal topographic origin and magnitude of hippocampal SPW-Rs.


Experimental optimization of single-exposure dual-energy angiography with photon-counting x-ray detectors.
Photon-counting x-ray detectors may enable single-exposure dual-energy (DE) x-ray angiography. The purpose of this paper is to experimentally optimize the energy thresholds and tube voltage for single-exposure DE x-ray angiography. We optimized single-exposure DE x-ray angiography using the iodine signal-difference-to-noise ratio (SDNR) per root patient air kerma (κ) as a figure of merit. We measured the iodine SDNR by imaging an iodine stepwedge immersed in a water tank with a depth of 30 cm in the direction of x-ray propagation. The stepwedge was imaged using tube voltages ranging from 90 to 150 kV and a cadmium telluride (CdTe) x-ray detector with two energy bins and analog charge summing for charge sharing suppression. The energy threshold that separates the two energy bins was varied from approximately 35 keV to approximately 75% of the maximum energy of the x-ray beam. Curve fitting was used to determine the threshold that maximized SDNR / κ $\mathrm{SDNR}/\sqrt {\kappa }$ . The effect of scatter was determined from measurements of the scatter-to-primary ratios (SPRs) of the low-energy and high-energy images and a semi-empirical model of the relationship between SDNR and SPR. Using the optimal parameters, we imaged a phantom with vessel-simulating structures and background clutter. The optimal energy thresholds increased monotonically from ∼50 to ∼85 keV over the range of tube voltages considered. For tube voltages greater than 90 kV, the optimal energy thresholds consistently allocated approximately two thirds of all detected primary photons to the low energy bin; this ratio was preserved without scatter. Consistent with prior modeling studies, SDNR / κ $\mathrm{SDNR}/\sqrt {\kappa }$ increased monotonically with tube voltage from 90 to 150 kV; SDNR / κ $\mathrm{SDNR}/\sqrt {\kappa }$ at 150 kV was approximately 38% higher than that at 90 kV for an iodine area density of ∼50 mg/cm2 . Scatter reduced SDNR by approximately 25% for SPRs of ∼1 and 0.4 in low-energy and high-energy images, respectively. Achieving optimal image quality in single-exposure DE angiography with photon-counting x-ray detectors will require high tube voltages (i.e., >130 kV) and, for thick patients, energy thresholds that allocate approximately two thirds of all primary photons to the low-energy image. Future work will compare the image quality of singe-exposure photon-counting and kV-switching approaches to DE x-ray angiography.


Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence.
Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. Retrospective cohort study. Finnish healthcare registers. Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect.


Major depression treatment in Germany-descriptive analysis of health insurance fund routine data and assessment of guideline-adherence.
Guideline oriented treatment strategies of Major depressive disorder (MDD) improve treatment outcomes and reduce risks of chronicity and recurrence. Description of routine treatment reality and analysis of guideline fidelity in first episode MDD in Germany. Indicators: patients with severe or psychotic depression or severe psychiatric comorbidities' treatment by specialists, adequate antidepressant pharmacotherapy, permanent treatment with more than one antidepressant, long-term benzodiazepine treatment and provision of psychotherapy. Descriptive analysis of routine data of the German statutory health insurance fund Barmer GEK in the index year 2011 that covers a population of 7,501,110. 236,843 patients were diagnosed a depressive episode. 53.0% of the patients with severe depression, 34.4% with psychotic depression and 50.9% with severe psychiatric comorbidities were treated by specialists; of the patients treated by a general practitioner 48.1% with severe and 47.3% with psychotic depression received an antidepressant; 9.7% of all patients with MDD got two antidepressants simultaneously; 8.3% received longterm benzodiazepine prescriptions; 26.1% got psychotherapy. the analyses depends on the indicators definitions that cannot cope with the variety of individual treatment path; comparison with guidelines was complicated by a large fraction of patients with recurrent MDD that was wrongly diagnosed with first episode depression; due to the data structure, not all guideline recommendations could be examined Routine practice was oriented upon the guidelines recommendations. However some aspects could be identified that bear potential for improvements.


[Prevention and treatment of hemostatic disorders in patients with liver cirrhosis].
Disorders of the different links of the hemostatic system in patients with liver cirrhosis can be corrected by simultaneous prescription of minimal doses of heparin, vicasol and curantyl. As a result, treatment of liver cirrhosis, including cases with initial manifestations of the hemorrhagic syndrome, produced significant improvement of the hemostatic parameters and abatement of this syndrome. It is expedient to include this method in the combined treatment of this category of patients.


Development of high-throughput methods to quantify cysts of Toxoplasma gondii.
Toxplasma is a protozoan parasite, which forms persistent cysts in tissues of chronically infected animals and humans. Cysts can reactivate leading to severe pathologies. They also contribute to the transmission of Toxoplasma infection in humans by ingestion of undercooked meat. Classically, the quantification of cyst burden in tissues uses microscopy methods, which are laborious and time consuming. Here, we have developed automated protocols to quantify cysts, based on flow cytometry or high-throughput microscopy. Brains of rodents infected with cysts of Prugniaud strain were incubated with the FITC-Dolichos biflorus lectin and analyzed by flow cytometry and high-throughput epifluorescence microscopy. The comparison of cyst counts by manual epifluorescence microscopy to flow cytometry or to high-throughput epifluorescence microscopy revealed a good correlation (r = 0.934, r = 0.993, P < 0.001 respectively). High-throughput epifluorescence microscopy was found to be more specific and sensitive than flow cytometry and easier to use for large series of samples. This reliable and easy protocol allow the specific detection of Toxoplasma cysts in brain, even at low concentrations; it could be a new way to detect them in water and in contaminate food.


Laypeople's activity for seeking telephone number of EMS before and during the COVID-19 outbreak: An analysis of web search data.
To explore trends and patterns of laypeople's activity for seeking telephone number of emergency medical services (EMS) based on analysis of online search traffic, including changes of the search activity with onset of the coronavirus disease 2019 (COVID-19) outbreak, in five countries - the United States of America (USA), India, Brazil, the United Kingdom (UK) and Russia. Google Trends (GT) country-level data on weekly relative search volumes (RSV) for top queries to seek EMS number were examined for January 2018-October 2021, including a comparison of RSVs between pre-COVID-19 period (January 2018-October 2019) and COVID-19 period (January 2020-October 2021), and evaluation of temporal associations of RSVs with weekly numbers of new COVID-19 cases. The countries demonstrated diverse patterns of the search activity with significantly different mean RSVs (the USA 1.76, India 10.20, Brazil 2.51, the UK 6.42, Russia 56.79; p < 0.001). For all countries excepting the USA mean RSVs of the COVID-19 period were significantly higher compared with the pre-COVID-19 ones (India +74%, Brazil +148%, the UK +22%, Russia +9%; p ≤ 0.034), and exhibited positive correlations with numbers of new COVID-19 cases, more pronounced for 2021 (India rS = 0.538, Brazil 0.307, the UK 0.434, Russia 0.639; p ≤ 0.045). Laypeople's activity for seeking EMS telephone number greatly varies between countries. It clearly responds to the spread of COVID-19 and could be reflective of public need for obtaining emergency help. Further studies are required to establish the role of GT for conducting real-time surveillance of population demand for EMS.


Machine learning for multidimensional response and survival after cardiac resynchronization therapy using features from cardiac magnetic resonance.
Cardiac resynchronization therapy (CRT) response is complex, and better approaches are required to predict survival and need for advanced therapies. The objective was to use machine learning to characterize multidimensional CRT response and its relationship with long-term survival. Associations of 39 baseline features (including cardiac magnetic resonance [CMR] findings and clinical parameters such as glomerular filtration rate [GFR]) with a multidimensional CRT response vector (consisting of post-CRT left ventricular end-systolic volume index [LVESVI] fractional change, post-CRT B-type natriuretic peptide, and change in peak VO2) were evaluated. Machine learning generated response clusters, and cross-validation assessed associations of clusters with 4-year survival. Among 200 patients (median age 67.4 years, 27.0% women) with CRT and CMR, associations with more than 1 response parameter were noted for the CMR CURE-SVD dyssynchrony parameter (associated with post-CRT brain natriuretic peptide [BNP] and LVESVI fractional change) and GFR (associated with peak VO2 and post-CRT BNP). Machine learning defined 3 response clusters: cluster 1 (n = 123, 90.2% survival [best]), cluster 2 (n = 45, 60.0% survival [intermediate]), and cluster 3 (n = 32, 34.4% survival [worst]). Adding the 6-month response cluster to baseline features improved the area under the receiver operating characteristic curve for 4-year survival from 0.78 to 0.86 (P = .02). A web-based application was developed for cluster determination in future patients. Machine learning characterizes distinct CRT response clusters influenced by CMR features, kidney function, and other factors. These clusters have a strong and additive influence on long-term survival relative to baseline features.


Removal of intraocular lenses: explanation and/or lens exchange.
Removal of intraocular lenses are often performed without adequate reason. I attempted to clarify indications and describe certain methods to remove intraocular lenses safely. I also defined the terminology used in conjunction with intraocular lens removal. (Table).


Chromopynones are pseudo natural product glucose uptake inhibitors targeting glucose transporters GLUT-1 and -3.
The principles guiding the design and synthesis of bioactive compounds based on natural product (NP) structure, such as biology-oriented synthesis (BIOS), are limited by their partial coverage of the NP-like chemical space of existing NPs and retainment of bioactivity in the corresponding compound collections. Here we propose and validate a concept to overcome these limitations by de novo combination of NP-derived fragments to structurally unprecedented 'pseudo natural products'. Pseudo NPs inherit characteristic elements of NP structure yet enable the efficient exploration of areas of chemical space not covered by NP-derived chemotypes, and may possess novel bioactivities. We provide a proof of principle by designing, synthesizing and investigating the biological properties of chromopynone pseudo NPs that combine biosynthetically unrelated chromane- and tetrahydropyrimidinone NP fragments. We show that chromopynones define a glucose uptake inhibitor chemotype that selectively targets glucose transporters GLUT-1 and -3, inhibits cancer cell growth and promises to inspire new drug discovery programmes aimed at tumour metabolism.


Laser-cut-type versus braided-type covered self-expandable metallic stents for distal biliary obstruction caused by pancreatic carcinoma: a retrospective comparative cohort study.
Covered self-expandable metallic stents (CMSs) are widely used for malignant distal biliary obstructions (MDBOs) caused by pancreatic carcinoma. This study compared the efficacy and safety of the laser-cut-type and braided-type CMSs. To palliate MDBOs caused by pancreatic carcinoma, the laser-cut-type CMSs was used from April 2014 to March 2017, and the braided-type CMSs was used from April 2017 to March 2019. The tested self-expandable metallic stents were equipped with different anti-migration systems. In total, 47 patients received CMSs for MDBOs (24 laser-cut type, 23 braided-type). The time to recurrent biliary obstruction (TRBO) was significantly longer in the braided-type CMSs (p=0.0008), and the median time to stent dysfunction or patient death was 141 and 265 days in the laser-cut-type CMSs and braided-type CMSs, respectively (p=0.0023). Stent migration was the major cause of stent dysfunction in both groups, which occurred in 37.5% of the laser-cut-type CMSs and 13.0% of the braidedtype CMSs. There were no differences in the survival duration between the groups. The TRBO was significantly longer for the braided-type CMSs with an anti-migration system than for the laser-cuttype. Stent migration tended to be less frequent with the braided-type CMSs than with the laser-cut-type CMSs.


[Papillary and cystic tumor of pancreas--Frantz's tumor].
The aim of the authors is to introduce one rare known pathology which the Frantz's tumor is, his clinical characteristic, clinical signs, diagnostic and treatment. We have observed two separate cases of this illness in Clinic of Surgery (University Hospital "Queen Yoanna") in comparison with evidence of famous world surgeons. We have made an attempt to introduce one disease, which even though not often observed is significant by the fact that affect young women (girls) and only surgical resection is a treatment of choice.