Treatment considerations in actinic keratosis.
The chronic skin condition actinic keratosis (AK) is characterized by the formation of keratotic lesions of variable thickness that are poorly delimited. AK occurs on areas of the skin that have had long-term exposure to the sun or UV radiation. Although AKs may regress, they usually persist and can progress to squamous cell carcinoma (SCC). Clinicians are unable to predict which AKs will progress; therefore, both clinically visible lesions and subclinical, non-visible (i.e. the entire area affected by AK/field cancerization) should be treated. AK treatment options include lesion-directed therapies that target specific AK lesions and field-directed therapies that target multiple clinical lesions and the underlying field damage. This article reviews currently available treatment options in AK, with a focus on patient-applied field therapies, and their suitability according to specific disease characteristics and patient needs. Choice of treatment in AK depends on lesion-, patient- and treatment-related factors and should be individualized. Considerations when choosing a therapy include site of application, treatment duration, surface area of application, tolerability profiles and implications on adherence. Field-directed therapies treat clinical and subclinical damage (i.e. the entire area affected by AK), achieve high rates of sustained clearance of AKs and may reduce the risk of progression to SCC. There is a clear need for field therapies with short duration of treatment and predictable, short-lived, mild local skin reactions that can be used over a large surface area. Therapies with shorter and simpler treatment courses are often associated with better adherence than treatments with longer courses. These may, therefore, represent more appropriate choices in patients for whom convenience and/or adherence are an issue.


A stable, label-free optical interferometric biosensor based on TiO2 nanotube arrays.
Optical interferometry of a thin film array of titanium dioxide (TiO2) nanotubes allows the label-free sensing of rabbit immunoglobulin G (IgG). A protein A capture probe is used, which is immobilized on the inner pore walls of the nanotubes by electrostatic adsorption. Control experiments using IgG from chicken (which does not bind to protein A) confirms the specificity of the protein A-modified TiO2 nanotube array sensor. The aqueous stability of the TiO2 nanotube array was examined and compared with porous silica (SiO2), a more extensively studied thin film optical biosensor. The TiO2 nanotube array is stable in the pH range 2 to 12, whereas the porous SiO2 sensor displays significant degradation at pH > 8.


[Effects of intra-articular injection of p38 mitogen-activated protein kinase inhibitor on matrix metalloproteinase in articular cartilage of a rat model of osteoarthritis].
To observe the effect of intra-articular injection of SB203580, a selective p38 mitogen-activated protein kinase inhibitor, on the expression of matrix metalloproteinase (MMP)-3, MMP-13 in a rat model of osteoarthritis (OA) and to explore the relationship between the MMP-3/MMP-13 expressions and the severity of OA. Fourty SD rats underwent unilateral anterior cruciate ligament transection (ACLT) and then randomly divided into four groups, with 10 rats in each group. Group A received 0.1 ml intra-articular injection of SB203580 at a high concentration of 100 micromol/L (once a week) immediately after surgery, and group B were treated under the same condition using SB203580 with a low concentration of 10 micromol/ L Group C received 0.1 ml intra-articular normal saline, and group D were not injected as controls after ACLT. All rats were sacrificed seven weeks after the surgery. Macroscopic and immunohistochemical studies were performed on the cartilage. Protein expressions of MMP-3 and MMP-13 were determined by Western blot. RESULTS Cartilage degradation was significantly milder in group A and group B than in the control groups, as shown by morphological studies (P < 0. 05) and immunohistochemical studies (P < 0. 05). The protein expressions of MMP-3 and MMP-13 in cartilage were significantly lower in groups A and B than in groups C and D (P < 0.01). SB203580 can inhibit the expressions of MMP-3 and MMP-13 and thus protect the cartilage.


Design, production, and characterization of recombinant neocarzinostatin apoprotein in Escherichia coli.
Neocarzinostatin (NCS) is the first discovered anti-tumor antibiotic having an enediyne-containing chromophore and an apoprotein with a 1:1 complex. An artificial gene library for NCS apoprotein (apo-NCS) production in Escherichia coli was designed and constructed on a phage-display vector, pJuFo. The recombinant phages expressing pre-apo-NCS protein were enriched with a mouse anti-apo-NCS monoclonal antibody, 1C7D4. The apo-NCS gene (encsA) for E. coli was successfully cloned, and then re-cloned into the pRSET A vector. After the his-tagged apo-NCS protein had been purified and cleaved with enterokinase, the binding properties of the recombinant protein as to ethidium bromide (EtBr) were studied by monitoring of total fluorescence intensity and fluorescence polarization with a BEACON 2000 system and GraphPad Prism software. A dissociation constant of 4.4 +/- 0.3 microM was obtained for recombinant apo-NCS in the fluorescence polarization study. This suggests that fluorescence polarization monitoring with EtBr as a chromophore mimic may be a simplified method for the characterization of recombinant apo-NCS binding to the NCS chromophore. When Phe78 on apo-NCS was substituted with Trp78 by site-directed mutagenesis using a two stage megaprimer polymerase chain reaction, the association of the apo-NCS mutant and EtBr observed on fluorescence polarization analysis was of the same degree as in the case of the wild type, although the calculated maximum change (DeltaIT(max)) in total fluorescence intensity decreased from 113.9 to 31.3. It was suggested that an environmental change of the bound EtBr molecule on F78W might have dramatically occurred as compared with in the case of wild type apo-NCS. This combination of monitoring of fluorescence polarization and total fluorescence intensity will be applicable for determination and prediction of the ligand state bound or associated with the target protein. The histone-specific proteolytic activity was also re-investigated using this recombinant apo-NCS preparation, and calf thymus histone H1, H2A, H2B, H3, and H4. The recombinant apo-NCS does not act as a histone protease because a noticeable difference was not observed between the incubation mixtures with and without apo-NCS under our experimental conditions.


Exercise-induced deep vein thrombosis in the subclavian vein in an elite female athlete.
An adolescent female presented to the emergency room with pain, swelling and a palpable lump in the right axilla following activity on a rowing ergometer. The differential diagnosis at the time of presentation was deep vein thrombosis, mass compression and cellulitis. An ultrasound scan revealed an occlusive thrombus of the right axillary and subclavian veins, basilic vein and proximal cephalic vein. The patient underwent pharmacomechanical thrombolysis followed by catheter-directed thrombolysis. Dynamic venogram testing revealed venous thoracic outlet syndrome (VTOS) and a transaxillary first rib resection was performed to decompress the costoclavicular space. Genetic testing revealed the patient was heterozygous for factor V Leiden. Two rounds of balloon dilatation plasty were performed to relieve recurring symptoms due to scarring and persisting compression, 1 and 3 years post rib resection. After extensive shared decision-making, the patient returned to sport, reporting only intermittent symptoms of post-thrombotic syndrome. This case sheds light on the importance of early diagnosis of VTOS for successful return to sport.


Modeling and analysis of a meso-hydraulic climbing robot with artificial muscle actuation.
This paper presents a fully coupled electro-hydraulic model of a bio-inspired climbing robot actuated by fluidic artificial muscles (FAMs). This analysis expands upon previous FAM literature by considering not only the force and contraction characteristics of the actuator, but the complete hydraulic and electromechanical circuits as well as the dynamics of the climbing robot. This analysis allows modeling of the time-varying applied pressure, electrical current, and actuator contraction for accurate prediction of the robot motion, energy consumption, and mechanical work output. The developed model is first validated against mechanical and electrical data collected from a proof-of-concept prototype robot. The model is then employed to study the system-level sensitivities of the robot locomotion efficiency and average climbing speed to several design and operating parameters. The results of this analysis demonstrate that considering only the transduction efficiency of the FAM actuators is insufficient to maximize the efficiency of the complete robot, and that a holistic approach can lead to significant improvements in performance.


Evidence of automatic processing in sequence learning using process-dissociation.
This paper proposes a way to apply process-dissociation to sequence learning in addition and extension to the approach used by Destrebecqz and Cleeremans (2001). Participants were trained on two sequences separated from each other by a short break. Following training, participants self-reported their knowledge of the sequences. A recognition test was then performed which required discrimination of two trained sequences, either under the instructions to call any sequence encountered in the experiment "old" (the inclusion condition), or only sequence fragments from one half of the experiment "old" (the exclusion condition). The recognition test elicited automatic and controlled process estimates using the process dissociation procedure, and suggested both processes were involved. Examining the underlying processes supporting performance may provide more information on the fundamental aspects of the implicit and explicit constructs than has been attainable through awareness testing.


Chronic splanchnic hemodynamic effects of spironolactone with unrestricted sodium diet in patients with compensated cirrhosis.
The purpose of this study is to determine the hemodynamic effects of spironolactone administration associated with an unrestricted sodium diet (salt 10 g) in patients with compensated cirrhosis and portal hypertension. We studied the hemodynamic changes following eight weeks of administration of either placebo (N = 6) or spironolactone (100 mg/day) (N = 6 Pugh-Child's A and 6 B). No significant changes were observed after the administration of the placebo. Spironolactone induced a significant reduction in the hepatic venous pressure gradient (HVPG) (-10.1 +/- 13.3%, P < 0.05), which was associated with a significant reduction of cardiac output (-11.5 +/- 9.3%, P < 0.01), plasma volume (-8.1 +/- 4.7%, P < 0.01), and wedged hepatic venous pressure (-10.5 +/- 11.6%, P < 0.05). There was no significant change in hepatic blood flow and there was no significant correlation between the change in the HVPG and the change in circulating plasma volume. A decrease in the HVPG greater than 10% was observed in eight of 12 patients (67%), defined as responders, at eight weeks. Six of six (100%) grade A patients and two of six (33%) grade B patients responded. This study demonstrated that spironolactone with an unrestricted sodium diet decreased the HVPG in grade A patients but did not significantly decrease the HVPG in grade B patients.


Lipid profile in rheumatoid arthritis and its relation to disease activity.
To ascertain whether--1. Serum lipids are altered in rheumatoid arthritis (RA) patients and 2. Disease activity has any role in altering lipid profile. Lipid profiles of 25 RA cases were compared with age and sex matched controls. Serum triglycerides (STG) and total cholesterol (TC) were found to be significantly lower in RA patients. In patients with very active disease, activity index (AI) > 80, STG, TC and low-density lipoprotein (LDL-C) were significantly lower as compared to controls. For TG 'r' value of -0.483 indicated negative correlation between disease activity and TG values, though the correlation is not significant (p > 0.05). For TC 'r' value (-0.0551) indicates negative correlation between disease activity and serum TC.


Relationships between dental calcification stages and skeletal maturity indicators in Thai individuals.
The purpose of this study was to investigate the relationship between the stages of calcification of various teeth and skeletal maturity stages among Thai individuals. The study subjects consisted 139 male subjects and 222 female subjects ranging in age from 7 years to 19 years. A total of 361 hand-wrist and panoramic radiographs were obtained and analyzed. The tooth development of the mandibular canines, first and second premolars, and second and third molars were assessed according to the Demirjian's system. Skeletal age and skeletal maturity stages were determined from hand-wrist radiographs by using the method outlined in the atlas of Greulich and Pyle and the Fishman's system, respectively. The Spearman rank order correlation coefficient revealed significant relationships (r = 0.31-0.69, P < .01) between dental calcification stages and skeletal maturity stages. The second premolar was the tooth showing the highest correlation (r = 0.66 in male subjects, r = 0.69 female subjects). The third molar demonstrated the poorest correlation (r = 0.47 in male subjects, r = 0.31 in female subjects). The canine stage F for both sexes (63.2% for female subjects, 54.1% for male subjects) coincided with the MP3 stage. The second molar stage E for female subjects (51.4%) and stage G for male subjects (66.7%) were related to the S stage and the MP(3cap) stage, respectively. This suggests that tooth calcification stages from panoramic radiographs might be clinically useful as a maturity indicator of the pubertal growth period. However, further study is recommended in a larger sample size, and future studies should address development of the canines and second molars.


Long-Term Healthcare Cost Savings of a Pediatric Nephrotoxic Medication-Associated Acute Kidney Injury Reduction Program in a Simulated Sample.
Background: Nephrotoxic medication exposure is a common cause of acute kidney injury (AKI) in hospitalized children and is associated with chronic kidney disease (CKD). The pharmacist-reliant NINJA program reduced nephrotoxic medication exposure and associated AKI. Objectives: We assess potential healthcare cost savings from reduced CKD by preventing AKI with the NINJA program for a pediatric population through age 21. Methods: We simulated a cohort of 1000 hospitalized non-critically ill children. From the published literature, 310 develop AKI, 267 survive to 6 months, and 10-70% develop CKD, and NINJA implementation reduced AKI by 23.8%. Allowing for varying CKD rates, we estimated a range of NINJA's savings. We assumed an annual GFR decline of 1.2 (noHTN) ml/min/1.73 m2 for half the sample and 1.7 (HTN) ml/min/1.73 m2 for the other half to account for CKD progression without and with hypertension (HTN). We model attributable costs including CKD stage-related medications and outpatient visits/tests in 2018 dollars discounted at 3%. We subtract the cost of NINJA screening (daily serum creatinine and pharmacist time) from net savings. We exclude end-stage renal disease (ESRD) and hospitalization costs. Results: No intervention estimated CKD related costs are $761,852 to $5,735,027. Post-NINJA cost decreases to $616,086 to $4,312,183 (net savings: $145,766 to $1,422 183). Total savings, accounting for NINJA screening ($256,680) are -$110,914 to $1,1 165 503. The breakeven AKI to CKD conversion rate is 13-14% with growth hormone cost included, and 64-65% without. Conclusion: The NINJA program is likely cost beneficial, with greater savings into adulthood by avoiding/delaying ESRD and its costs.


Spectral sensitivity of the European ground squirrel (Citellus citellus L.).
The spectral sensitivity of the European ground squirrel was investigated by electroretinography (ERG) and visual-evoked cortical potentials. Using chromatic adaptation, two spectral systems were found, one peaking between 520 and 530 nm, the other at 465 nm. The blue system was characterized by a slower course of the potential, a lower threshold and the lack of a d wave in the ERG. However, its threshold is higher than the rod threshold and it was shown to be more resistant to adapting light stimuli than rod systems are. It is concluded that the second spectral system is a blue cone system which in its rod-like properties is comparable to the blue cones found in cat, monkey and man.


Cigarette smoke exposure as a model of inflammation associated with COPD.
Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation resulting from inflammation-driven pathologies in the lungs that are a consequence of smoking over many years. Given that the disease is increasing globally, understanding the mechanism by which cigarette smoke (CS) causes lung inflammation and exploiting that knowledge to develop effective treatments is urgently required. Animal models of CS exposure are commonly used to examine the inflammatory processes that may be involved in the development of COPD. The protocols described in this unit detail the development of preclinical models of CS-driven lung inflammation. These systems can be utilized to investigate the role of various biological pathways in CS-mediated inflammation and to assess the efficacy of new therapeutic strategies for treating COPD.


Piezosurgery versus Rotatory Osteotomy in Mandibular Impacted Third Molar Extraction.
The aim of this study is to compare piezoelectric surgery versus rotatory osteotomy technique in removal of mandibular impacted third molar. Sample size of 30 patients 18 males, 12 females with a mean age of 27.43 ± 5.27. Bilateral extractions were required in all patients. All the patients were randomly allocated to two groups in one group, namely control group, surgical extraction of mandibular third molar was done using conventional rotatory osteotomy and in the other group, namely test group, extraction of lower third molar was done using Piezotome. Parameters assessed in this study were - mouth opening (interincisal opening), pain (visual analog scale VAS score), swelling, incidence of dry socket, paresthesia and duration of surgery in both groups at baseline, 1st, 3rd, and 7th postoperative day. Comparing both groups pain scores with (P < 0.05) a statistically significant difference was found between two groups. Mean surgical time was longer for piezosurgery group (51.40 ± 17.9) minutes compared to the conventional rotatory group with a mean of (37.33 ± 15.5) minutes showing a statistically significant difference (P = 0.002). The main advantages of piezosurgery include soft tissue protection, optimal visibility in the surgical field, decreased blood loss, less vibration and noise, increased comfort for the patient, and protection of tooth structures. Therefore, the piezoelectric device was efficient in decreasing the short-term outcomes of pain and swelling although taking longer duration than conventional rotatory technique it significantly reduces the associated postoperative sequelae of third molar surgery.


[Radiation-induced intestinal fibrosis: pathological assessment and pharmacological prevention].
Although radiotherapy can improve the local control rate of tumors and prolong the survival period of patients, it can also lead to long-term adverse effects such as radiation-induced intestinal fibrosis. Radiation-induced intestinal fibrosis has a high incidence and poses significant challenges to treatment, severely impacting the quality of life of patients. Combining findings from domestic and international research, along with experiences of our center, this article mainly discusses the pathological changes of radiation-induced intestinal fibrosis, as well as the current status and challenges of pathological assessment and pharmacological prevention of this condition. At present, there is no definitive method to reverse the fibrotic pathological changes. Thus, the prevention of fibrosis is a crucial issue to be resolved. In the meantime, there is a lack of ideal assessment methods and effective preventive medications in clinical practice. It is necessary to enhance both basic and clinical research, thoroughly investigate the pathogenesis of the disease, and identify effective intervention targets to promote the diagnosis and treatment of radiation-induced intestinal fibrosis.


A variant of pulmonary alveolar microlithiasis in nackt mice.
Four adult mutant nackt mice, which demonstrate alopecia and CD4+ T-cell deficiency, and two outbred SENCAR mice (sentinels) were presented for routine health surveillance. Lesions were not observed at necropsy. Microscopically, all four nackt mice demonstrated multiple concretions that were 30-100 microm in diameter, irregularly rounded to oval, nonbirefringent, and amphophilic to basophilic. Many of the concretions appeared attached to or within the alveolar walls of all lung lobes. Approximately half of the concretions had irregular fracture lines. All concretions were periodic acid-Schiff positive, and Von Kassa staining revealed diffuse calcification. None of the concretions were associated with inflammatory cell infiltrates, and metaplastic ossification was not evident. A diagnosis of pulmonary alveolar microlithiasis, a rare disease in both humans and animals, was made based on the size and location of the concretions and the lack of an inflammatory response. This is the first report of a laboratory mouse demonstrating pulmonary alveolar microlithiasis.


Identification of G2607A mutation in EGFR gene with a significative rate in Moroccan patients with Bladder Cancer.
The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of bladder cancer. A total, 50 Moroccan patient specimens with bladder cancer and 48 healthy controls were analysed for EGFR mutations in the region delimiting exons 18-21 by PCR amplification and direct sequencing. Our results showed the absence of mutations in the EGFR kinase domain in these exons in all analysed specimens. However, sequence analysis of the EGFR-TK domain, revealed the presence of (G2607A) polymorphism at exon 20. Statistical analysis showed significant difference in the frequencies of G2607A polymorphism between cancer cases and healthy controls (p=0.0001) and the frequencies of the GG and GA/AA genotypes among the cancer cases were 28% and 72%, respectively. Moreover, allelic frequencies of G2607A polymorphism showed significant difference between cancer cases and healthy controls (p=0.0025). Data analysis showed no significant association between G2607A polymorphism and patients' age, clinical stage and tumor grade (p > 0.05). However, a significant difference was found between this polymorphism and patients' sex that could be a sampling bias due to the very limited number of women with bladder cancer. Our findings highlight that, mutations in EGFR kinase domain is a rare event in bladder cancer, suggesting, that treatment of bladder cancer patients with TKI may not be effective. However, the EGFR G2607A polymorphism in exon 20 is frequent in bladder cancer cases and must be further explored for its relevance in the treatment of this disease.


Lactoferrin-Hexon Interactions Mediate CAR-Independent Adenovirus Infection of Human Respiratory Cells.
Virus entry into host cells is a complex process that is largely regulated by access to specific cellular receptors. Human adenoviruses (HAdVs) and many other viruses use cell adhesion molecules such as the coxsackievirus and adenovirus receptor (CAR) for attachment to and entry into target cells. These molecules are rarely expressed on the apical side of polarized epithelial cells, which raises the question of how adenoviruses-and other viruses that engage cell adhesion molecules-enter polarized cells from the apical side to initiate infection. We have previously shown that species C HAdVs utilize lactoferrin-a common innate immune component secreted to respiratory mucosa-for infection via unknown mechanisms. Using a series of biochemical, cellular, and molecular biology approaches, we mapped this effect to the proteolytically cleavable, positively charged, N-terminal 49 residues of human lactoferrin (hLF) known as human lactoferricin (hLfcin). Lactoferricin (Lfcin) binds to the hexon protein on the viral capsid and anchors the virus to an unknown receptor structure of target cells, resulting in infection. These findings suggest that HAdVs use distinct cell entry mechanisms at different stages of infection. To initiate infection, entry is likely to occur at the apical side of polarized epithelial cells, largely by means of hLF and hLfcin bridging HAdV capsids via hexons to as-yet-unknown receptors; when infection is established, progeny virions released from the basolateral side enter neighboring cells by means of hLF/hLfcin and CAR in parallel.IMPORTANCE Many viruses enter target cells using cell adhesion molecules as receptors. Paradoxically, these molecules are abundant on the lateral and basolateral side of intact, polarized, epithelial target cells, but absent on the apical side that must be penetrated by incoming viruses to initiate infection. Our study provides a model whereby viruses use different mechanisms to infect polarized epithelial cells depending on which side of the cell-apical or lateral/basolateral-is attacked. This study may also be useful to understand the biology of other viruses that use cell adhesion molecules as receptors.


Lung ventilation/perfusion SPECT in the artificially embolized pig.
Planar lung scintigraphy is a standard method used for the diagnosis of lung embolism, but it is hampered by the high incidence of nondiagnostic tests. Ventilation/perfusion SPECT may possibly improve this situation. The objective of this study was to compare planar lung scintigraphy with ventilation/perfusion SPECT using pigs with artificially engendered lung emboli labeled with (201)Tl. Sixteen anesthetized pigs were each injected with zero to 4 latex emboli. Cylindric emboli were used in the first 7 pigs and flat 3-tailed emboli were used in the remaining 9 pigs. The pigs spontaneously inhaled 30 MBq (99m)Tc-diethylenetriaminepentaacetic acid aerosol for ventilation scintigraphy. Planar scintigraphy and SPECT were performed using a double-head gamma camera in (99m)Tc and (201)Tl windows. Immediately thereafter, 100 MBq (99m)Tc-labeled macroaggregated albumin were injected intravenously followed by SPECT and, finally, planar scintigraphy. The ventilation background was subtracted from the perfusion tomograms for calculation of a normalized ventilation/perfusion (V/P) quotient image set. The cylindric emboli caused artifacts in the ventilation images; therefore, these were excluded from the final analysis. However, for the planar perfusion images of these pigs, sensitivity and specificity were 71% and 91%, respectively, whereas SPECT yielded 100% for both. For the 3-tailed emboli and ventilation/perfusion images, the sensitivity and specificity were 64% and 79%, respectively, for the planar modality, whereas SPECT yielded values of 91% and 87%, respectively. V/P SPECT may improve the diagnostic power of lung scintigraphy.


Non-pharmacological interventions for people living with young-onset dementia and their carers: A scoping review focussing on the support of participants' needs.
WHAT IS KNOWN ON THE SUBJECT?: Young-onset dementia (YOD) refers to a phenomenon in which dementia symptoms appear under age 65. Diagnosing YOD is difficult and its progression is fast. Furthermore, it limits the socio-economic careers of people living with YOD, regardless of their needs. People living with YOD and their carers have unstable occupational status and their dependents also have to face a high burden of care. They claim that existing social support for dementia is limited to the elderly and is not suitable for them. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The characteristics of non-pharmacological intervention studies for people living with YOD and/or their carers so far, and an analysis of the needs supported via the applied interventions. A theoretical basis and direction for the interventions to be studied in the future. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Research and intervention development should focus more on the needs of people living with YOD. In addition, it is necessary to understand and reflect on carers who directly care for people living with YOD. A multidisciplinary programme that supports wide area of the needs should be developed. INTRODUCTION: Young-onset dementia (YOD) is a highly influential disease that exerts force on the normal life of those who still have to continue social life. Research has been lacking in spite of its seriousness, which accounts for about 9% of all dementia cases. This study aimed to examine non-pharmacological interventions for people living with YOD and/or their carers, and to analyse how those interventions support their needs. A scoping review methodology was utilized to search the studies examining interventions for people living with YOD and/or their carers, and in English or Korean. The information was extracted, summarized and analysed in CANE categories. Sixteen studies were included in the review. Five types of interventions were drawn. 'Memory' was the most covered part of the needs by the interventions. This study found that interventions currently do not match the needs of people living with YOD and their carers. Multidisciplinary research would be eligible to cover the subjects' wide range of the needs as much as possible. We suggest the development of a specialized needs assessment tool and specialized interventions for people living with young-onset dementia and their carers.


Effect of Chronic Heart Rate Reduction by I(f) Current Inhibitor Ivabradine on Left Ventricular Remodeling and Systolic Performance in Middle-Aged Rats With Postmyocardial Infarction Heart Failure.
A large myocardial infarction (MI) initiates progressive cardiac remodeling that leads to systolic heart failure (HF). Long-term heart rate reduction (HRR) induced by the I f current inhibitor ivabradine (IVA) ameliorates left ventricular (LV) remodeling and improves systolic performance in young post-MI rats. However, the beneficial effects of chronic IVA treatment in middle-aged rats remain to be determined. A large MI was induced in 12-month-old rats by left coronary artery ligation. Rats were treated with IVA via osmotic pumps intraperitoneal in a dose of 10.5 mg/kg/d (MI + IVA) and compared with MI and sham-operated animals 12 weeks after MI. Heart rate in MI + IVA rats was on average 29% lower than that of rats in the MI group. Left ventricular remodeling was comparable between post-MI groups, although MI + IVA rats did not show the compensatory thickening of the noninfarcted myocardium. Chronic HRR had no effect on transverse cardiac myocyte size and capillary growth, but it reduced the collagen content in noninfarcted myocardium. Left ventricular systolic performance remained similarly impaired in MI and MI + IVA rats. Moreover, abrupt IVA withdrawal led to worsening HF and reduction of coronary reserve. Our data reveal that chronic IVA-induced HRR does not provide sustainable benefits for LV systolic performance in middle-aged rats with post-MI HF.


Negative regulation of type I interferon signaling by integrin-linked kinase permits dengue virus replication.
Dengue virus (DENV) infection can induce life-threatening dengue hemorrhagic fever/dengue shock syndrome in infected patients. DENV is a threat to global health due to its growing numbers and incidence of infection in the last 50 years. During infection, DENV expresses ten structural and nonstructural proteins modulating cell responses to benefit viral replication. However, the lack of knowledge regarding the cellular proteins and their functions in enhancing DENV pathogenesis impedes the development of antiviral drugs and therapies against fatal DENV infection. Here, we identified that integrin-linked kinase (ILK) is a novel enhancing factor for DENV infection by suppressing type I interferon (IFN) responses. Mechanistically, ILK binds DENV NS1 and NS3, activates Akt and Erk, and induces NF-κB-driven suppressor of cytokine signaling 3 (SOCS3) expression. Elevated SOCS3 in DENV-infected cells inhibits phosphorylation of STAT1/2 and expression of interferon-stimulated genes (ISGs). Inhibiting ILK, Akt, or Erk activation abrogates SOCS3 expression. In DENV-infected mice, the treatment of an ILK inhibitor significantly reduces viral loads in the brains, disease severity, and mortality rate. Collectively, our results show that ILK is a potential therapeutic target against DENV infection.


[Postcholecystectomy syndrome after simple cholecystectomy].
In a long-term follow-up, we were particularly interested in the incidence and cause of postoperative abdominal pain following simple cholecystectomy and in the incidence and etiology of reoperations of the biliary tract. For tat we analyzed 1539 patients who were operated by simple cholecystectomy between 1970 and 1979. Thereafter 875 (68.8%) were checked by us. We found 37.4% symptomatic patients, but in most cases no organic cause was detected. The major organic causes were scar problems and extrabiliary disorders; bilio-pancreatic disturbances were rare, but they needed a reintervention in most cases.


Effects of genomic context and chromatin structure on transcription-coupled and global genomic repair in mammalian cells.
It has been long recognized that in mammalian cells, DNA damage is preferentially repaired in the transcribed strand of transcriptionally active genes. However, recently, we found that in Chinese hamster ovary (CHO) cells, UV-induced cyclobutane pyrimidine dimers (CPDs) are preferentially repaired in both the transcribed and the non-transcribed strand of exon 1 of the dihydrofolate reductase (DHFR) gene. We mapped CPD repair at the nucleotide level in the transcriptionally active DHFR gene and the adjacent upstream OST gene, both of which have been translocated to two chromosomal positions that differ from their normal endogeneous positions. This allowed us to study the role of transcription, genomic context and chromatin structure on repair. We found that CPD repair in the transcribed strand is the same for endogenous and translocated DHFR genes, and the order of repair efficiency is exon 1 > exon 2 > exon 5. However, unlike the endogenous DHFR gene, efficient repair of CPDs in the non-transcribed strand of exon 1 is not observed in the translocated DHFR gene. CPDs are efficiently repaired in the transcribed strand in endogenous and translocated OST genes, which indicates that efficient repair in exon 1 of the non-transcribed strand of the endogenous DHFR gene is not due to the extension of transcription-coupled repair of the OST gene. Using micrococcal nuclease digestion, we probed the chromatin structure in the DHFR gene and found that chromatin structure in the exon 1 region of endogenous DHFR is much more open than at translocated loci. These results suggest that while transcription-coupled repair is transcription dependent, global genomic repair is greatly affected by chromatin structure.


Efficient catalytic conversion of concentrated cellulose feeds to hexitols with heteropoly acids and Ru on carbon.
A combination of heteropolyacids and Ru on carbon catalyzes the conversion of concentrated cellulose feeds into hexitols under H(2) pressure. Quantitative conversion of ball-milled cellulose was observed with remarkable hexitol volume productivity.


[Conjunctival provocation test: recommendations].
The diagnosis of ocular allergy, which has become a real public health problem occurring in 25% of the general population and continues to rise, requires allergic testing. Skin and blood tests combined with interviewing the patient demonstrate sensitivity to one or more antigens. However, while allergic testing and interviews generally reveal the cause of the symptoms, only the conjunctival provocation test (CPT) provides clear evidence of a functional relation between the conjunctival pathology and exposure to the antigen. Since there is still no validated consensus regarding the criteria for positivity of the CPT in routine practice, the working group attempted to establish the major guidelines for conducting the test, to standardize approaches and pinpoint areas of uncertainty. The group established a consensus regarding the conditions for using the test (patient selection, allergens to be tested, usable concentrations, the test protocol, the signs and symptoms to be assessed, interpretation of results, follow-up) and identified two distinct patient groups (outpatients and hospitalized patients) in whom test-taking conditions are different. The outpatient group includes patients suffering from benign forms of conjunctivitis (acute, seasonal, or chronic) and those sensitive to the usual allergens (mainly domestic and airborne). In these cases, the test is given in a medical setting with an allergologist or an ophthalmologist who instills the drops relatively rapidly. The criterion for positivity is the extent of the pruritus. On the other hand, in the hospital population, which is composed of patients suffering from vernal conjunctivitis, the attempt to establish the triggering factor requires a more elaborate protocol carried out in an ophthalmologic setting and based on the association of a range of clinical and biological factors. The deliberations of the working group should lead to the standardization of the CPT procedure for diagnostic purposes.


Rapid clearance of cytomegalovirus-specific IgG after repeated intravenous infusions of human immunoglobulin into allogeneic bone marrow transplant recipients.
We studied the kinetics of the disappearance of CMV-specific IgG from the serum of 18 allogeneic bone marrow transplant recipients who were receiving repeated intravenous infusions of immunoglobulin. Peak serum titers occurred 24-48 hr after infusion. The mean half-life of IgG to CMV varied from 30 to 70 hr. Additional studies showed that this unexpectedly short half-life was not specific for either the preparation used or the type of patient studied. Repeated treatment did not prevent patients from developing CMV infections (incidence, 50%); however, none of the patients developed CMV interstitial pneumonitis. Treatment had to be discontinued for one patient because of a serum sickness-like syndrome. Our results suggest that rational, time-sequential passive immunization regimens should be developed.


[COVID-19-associated anosmia].
The article is a systematic review of the literature data summarizes to date on the issue of COVID-19-associated anosmia. We mainly used full-text and abstract electronic databases (PubMed, Scopus and Web of Science). The paper discusses hypothetical mechanisms of development, clinical features, as well as methods of diagnosis and treatment of COVID-19-associated anosmia.


Linear systems analysis of the ciliary steering behavior associated with negative-phototaxis in Chlamydomonas reinhardtii.
In response to light stimulation Chlamydomonas reinhardtii changes the beating frequency, beating pattern, and beating synchrony of the trans and cis cilia to steer the freely-swimming cell relative to light sources. To understand the cell steering behavior the impulse responses of the beating frequency and stroke velocity of each cilium have been obtained with high temporal resolution on cells held with a micropipette. Interestingly the response of each cilium is quite different. The trans cilium responds with less delay than the cis cilium for both beating frequency and stroke velocity. For light stimulation at 2 Hz, the critical cell-rotation frequency, both responses of the trans and cis cilia are about 180 degrees out of phase. The trans-cilium beating frequency response peaks at a stimulus frequency of 5-6 Hz, higher than the cis at 1-2 Hz. The stroke velocities of the trans and cis cilia have the same stimulus-frequency response (2 Hz), but the trans cilium has a shorter delay than the cis. The times to maximum response are much shorter than the time for a rotation of the cell. The use of two different approaches that enable the trans cilium to respond ahead of the cis for both the beating frequency and stroke velocity responses suggests the importance of both responses to phototaxis. Internal cell processing responsible for the time course of the responses is proposed.


Salt stress response and proline accumulation in Brachiaria humidicola plants with and without mycorrhizal inoculation.
The work was carried out to investigate the effects of different concentrations of NaCl on Brachiaria humidicola Rendle in the presence and absence of Glomus etunicatum Becker and Gerdemann, as well as to evaluate some growth parameters and the accumulation of free proline in the plant leaves. The soil used was a Neosoil Fluvic Eutrophic with pH of 6.5, organic matter, 12.8 g kg-1 and soil texture, sandy loam, in which Brachiaria humidicola Rendle cv. 409 was grown. Five NaCl concentrations were tested 0; 0.22; 1.09; 1.96 and 2.84 g. kg-1 of soil, whose electrical conductivity (EC) were 2.22; 4.00; 8.13; 12.53 and 16.50 dS m-1, respectively. Brachiaria humidicola showed salt tolerance when submitted to an EC of 4 dS m-1. There was a reduction of leaf area, dry matter of shoots and roots for the soil treatments beyond EC at 8 dS m-1. Free proline content in the leaves increased together with the increase in soil salinity (EC at 8 dS m-1) demonstrating that plants submitted to EC of 2 and 4 dS m-1 were less affected by salt stress, and consequently accumulated less proline in the leaves. Root colonization was not affected by the increase of NaCl dosage in the soil.


Automatic identification of suicide notes with a transformer-based deep learning model.
Suicide is one of the leading causes of death worldwide. At the same time, the widespread use of social media has led to an increase in people posting their suicide notes online. Therefore, designing a learning model that can aid the detection of suicide notes online is of great importance. However, current methods cannot capture both local and global semantic features. In this paper, we propose a transformer-based model named TransformerRNN, which can effectively extract contextual and long-term dependency information by using a transformer encoder and a Bi-directional Long Short-Term Memory (BiLSTM) structure. We evaluate our model with baseline approaches on a dataset collected from online sources (including 659 suicide notes, 431 last statements, and 2000 neutral posts). Our proposed TransformerRNN achieves 95.0%, 94.9% and 94.9% performance in P, R and F1-score metrics respectively and therefore outperforms comparable machine learning and state-of-the-art deep learning models. The proposed model is effective for classifying suicide notes, which in turn, may help to develop suicide prevention technologies for social media.


Cloning of the bovine antiapoptotic regulator, BCL2-related protein A1, and its expression in trophoblastic binucleate cells of bovine placenta.
This report studied the identification and sequence of a full-length cDNA for the bovine BCL2 antiapoptotic family member, BCL2-related protein A1 (BCL2A1), and its localized and quantitative expression in the placenta to clarify the regulatory mechanism of trophoblast cell proliferation and differentiation during implantation and placental development. We cloned a full-length bovine BCL2A1 cDNA with 725 nucleotides and an open-reading frame corresponding to a protein of 175 amino acids. The predicted amino acid sequence shared 78% homology with human BCL2A1. All BCL2 homology domains (BH1, BH2, BH3, and BH4) in bovine BCL2A1 were conserved as well as in other mammalian BCL2A1. In the placentomes, in situ hybridization demonstrated that the BCL2A1 was limited in binucleate cells expressing various pregnancy-specific molecules like placental lactogen. BCL2-associated X protein (BAX) was also expressed in binucleate cells. Quantitative real-time RT-PCR detection exhibited a high-level expression of BCL2A1 in the conceptus at Day 21 of gestation, and it was expressed and increased in the extraembryonic membrane, cotyledon, and intercotyledon from implantation to term. BAX expression intensity increased with progression of gestation and remained elevated in postpartum. Caspase-3 protein (CASP3) and mRNA (CASP3) were detected from late gestation to postpartum in placenta as well as in the results of TUNEL detection. We believe that the apoptosis of binucleate cells may be regulated by the balance of the BCL2A1 and BAX. BCL2A1 genes produced a BCL2A1 protein in the mammalian cell-expression system. This molecule is a new candidate for antiapoptotic maintenance of the binucleate cells that support placental functions throughout gestation in bovine.


[Typification of opisthorchiasis foci in the Orenburg Region].
On making expedition and studying the functioning of opisthorchiasis foci in the Orenburg Region, the authors have districted the region and identified 3 types of districts according to the pattern of Opisthorchis transmission: 1) areas lacking the conditions for forming an invasion foci; 2) those having all links of the focus, but lacking pathogen circulation; and 3) those having all conditions for pathogen circulation and the human beings are infected from the local infested fish--Type C. By studying opisthorchiasis in the Orenburg Region, the authors have established the rate of morbidity growth and their nonuniform distribution in this region. The findings have formed the basis of dividing the Orenburg Region by the endemicity of opisthorchiasis into 4 types of areas: non-endemic, low, moderate, and high endemic. The results of districting the region by the endemicity of areas, the nature of foci, and the social and natural factors determining an epidemiological process have formed the basis of a differential package of preventive measures against opisthorchiasis in the Orenburg Region.


Measures of native and non-native rhythm in a quantity language.
The traditional phonetic classification of language rhythm as stress-timed or syllable-timed is attributed to Pike. Recently, two different proposals have been offered for describing the rhythmic structure of languages from acoustic-phonetic measurements. Ramus has suggested a metric based on the proportion of vocalic intervals and the variability (SD) of consonantal intervals. Grabe has proposed Pairwise Variability Indices (nPVI, rPVI) calculated from the differences in vocalic and consonantal durations between successive syllables. We have calculated both the Ramus and Grabe metrics for Latvian, traditionally considered a syllable rhythm language, and for Latvian as spoken by Russian learners. Native speakers and proficient learners were very similar whereas low-proficiency learners showed high variability on some properties. The metrics did not provide an unambiguous classification of Latvian.


[The fetal systolic time intervals as an indicator of fetal hemodynamics--physiologic changes of the fetal systolic time intervals with fetal growth].
The fetal systolic time intervals (fetal STIs) with advancing fetal age were analysed in normal fetuses by means of the fetal STIs monitoring system which we had devised. The following results were obtained: The electro-mechanical delay (EMD), isometric contraction time (ICT) and pre-ejection period (PEP) were gradually prolonged during gestation; they were markedly prolonged after 32 weeks' gestation. The ventricular ejection time (VET) and VET corrected by heart rate (VET425) were shortened with advancing fetal age. The ejection index (PEP/VET425) and %PEP were increased, especially after 32 weeks' gestation. The PEP showed a high correlation with the ICT. The VET had a negative correlation with fetal heart rate between 36 and 40 weeks' gestation. The mean values (+/- S.D.) of these parameters between 36 and 40 weeks' gestation were as follows: EMD = 43.0 +/- 1.3 msec, ICT = 29.2 +/- 3.0 msec, PEP = 72.4 +/- 3.6 msec, %PEP = 17.1 +/- 1.4%, VET425 = 177.1 +/- 3.9 msec and PEP/VET425 = 0.407 +/- 0.022. The parameters were not correlated with birth weight. These results suggest marked fetal hemodynamic changes after 32 weeks' gestation, and these parameters may be used to indicate functional adaptation of the cardiovascular system with fetal growth.


Chemical-potential-based lattice Boltzmann method for nonideal fluids.
Chemical potential, as an important thermodynamic quantity, has been popularly used in thermodynamic modeling for complex systems, especially for those involving the phase transitions and chemical reactions. Here we present a chemical-potential-based multiphase lattice Boltzmann model, in which the nonideal force is directly evaluated by a chemical potential. The numerical computation is more efficient than the pressure-tensor-based model [Wen et al. Europhys. Lett. 112, 44002 (2015)10.1209/0295-5075/112/44002] because the calculations of the pressure tensor and its divergence are avoided. We have derived several chemical potentials of the popular equations of state from the free-energy density function. The theoretical analyses and numerical results support that the present model satisfies thermodynamics and Galilean invariance. An effective chemical-potential boundary condition is also implemented to investigate the wettability of a solid surface, and the contact angle can be linearly tuned by the surface chemical potential.


Pulmonary function tests.
The clinical significance of pulmonary function tests (including blood gas analysis) lies in their sensitivity for detecting PCP. PCP has most consistently been found to cause abnormalities in the DLCO and the exercise arterial blood gas; both are highly sensitive for the presence of Pneumocystis infection. These tests are more sensitive for the detection of PCP than are the resting arterial blood gas and chest x-ray. Therefore, measuring these values can be especially helpful in evaluating HIV-infected individuals who have pulmonary symptoms but whose resting arterial blood gas and/or chest radiograph are normal. The advantage of performing the exercise test over measuring the DLCO is that the exercise test is simple. It can be done without pulmonary function equipment and without a technologist. Furthermore, since many AIDS patients with non-PCP pulmonary disorders maintain "normal" exercise tests despite abnormal DLCO, it can be useful in evaluating patients for PCP who have known underlying lung disease with progressive symptoms. Measurement of lung volumes and spirometry lacks both sensitivity and specificity for detecting pulmonary disease in general and PCP in particular. Spirometry is helpful in detecting airways obstruction, which is not an uncommon finding in AIDS patients. The etiology, clinical significance, and treatment of obstructive ventilatory defects in the AIDS population remains unclear.


Improving Adolescent Judgment and Decision Making.
Human judgment and decision making (JDM) has substantial room for improvement, especially among adolescents. Increased technological and social complexity "ups the ante" for developing impactful JDM interventions and aids. Current explanatory advances in this field emphasize dual processing models that incorporate both experiential and analytic processing systems. According to these models, judgment and decisions based on the experiential system are rapid and stem from automatic reference to previously stored episodes. Those based on the analytic system are viewed as slower and consciously developed. These models also hypothesize that metacognitive (self-monitoring) activities embedded in the analytic system influence how and when the two systems are used. What is not included in these models is the development of an intersection between the two systems. Because such an intersection is strongly suggested by memory and educational research as the basis of wisdom/expertise, the present paper describes an Integrated Judgment and Decision-Making Model (IJDM) that incorporates this component. Wisdom/expertise is hypothesized to contain a collection of schematic structures that can emerge from the accumulation of similar episodes or repeated analytic practice. As will be argued, in comparisons to dual system models, the addition of this component provides a broader basis for selecting and designing interventions to improve adolescent JDM. Its development also has implications for generally enhancing cognitive interventions by adopting principles from athletic training to create automated, expert behaviors.


Early Recurrence of Neuroendocrine Liver Metastasis After Curative Hepatectomy: Risk Factors, Prognosis, and Treatment.
Early tumor recurrence after curative resection typically indicates a poor prognosis. The objective of the current study was to investigate the risk factors, treatment, and prognosis of early recurrence of neuroendocrine tumor (NET) liver metastasis (NELM) after hepatic resection. A total of 481 patients who underwent curative-intent resection for NELM were identified from a multi-institutional database. Data on clinicopathological characteristics, intraoperative details, and outcomes were documented. The optimal cutoff value to differentiate early and late recurrence was determined to be 3 years based on linear regression. With a median follow-up of 60 months, 223 (46.4%) patients developed a recurrence, including 158 (70.9%) early and 65 (29.1%) late recurrences. On multivariable analysis, pancreatic NET, primary tumor lymph node metastasis, and a microscopic positive surgical margin were independent risk factors for early intrahepatic recurrence. While recurrence patterns and treatments were comparable among patients with early and late recurrences, early recurrence was associated with worse disease-specific survival than late recurrences (10-year NELM-specific survival, 44.5 vs 75.8%, p < 0.001). Among the 34 (21.5%) patients who underwent curative treatment for early recurrence, post-recurrence disease-specific survival was better than non-curatively treated patients (10-year NELM-specific survival, 54.2 vs 26.3%, p = 0.028), yet similar to patients with late recurrences treated with curative intent (10-year NELM-specific survival, 54.2 vs 37.4%, p = 0.519). Early recurrence after surgery for NELM was associated with the pancreatic type, primary lymph node metastasis, and extrahepatic disease. Re-treatment with curative intent prolonged survival after recurrence, and therefore, operative intervention even for early recurrences of NELM should be considered.


Degeneration and regeneration of the olfactory epithelium after olfactory bulb ablation in the pig: a morphological and electrophysiological study.
The olfactory bulbs were removed surgically from Large White male and female pigs, 10--12 weeks of age. At intervals of 3, 7, 14, 42 and 84 d after bulbectomy, the pigs were sacrificed and portions of olfactory mucosa were removed from the ethmoturbinate and septum regions of the nasal cavity; olfactory mucosa was also removed from unoperated pigs. A piece of each tissue sample was processed for light microscopy. The remaining tissue was placed in Ringer-Locke solution, saturated with O2/CO2 at room temperature, and the electrical activity of the olfactory epithelium was investigated in vitro by passing a stimulus of butyl acetate vapour over the epithelium. Slow negative potential changes (electro-olfactogram, e.o.g.) induced by butyl acetate were recorded. During the first two weeks after bulbectomy there was a rapid decrease in the height of the olfactory epithelium associated with the disappearance of the e.o.g. response. However by 42 and 84 d after bulbectomy, partial recovery of the height and some electrical activity of the olfactory mucosa had occurred. In some pigs, the insertion of a stainless steel lining over the cribriform plate to prevent any association of regenerating axons with forebrain tissue had no effect on the regenerative characteristics studied.


[Clinicopathological characteristics of micropapillary variant of urinary bladder carcinoma].
Micropapillary urothelial carcinoma (MUC) is a rare variant of urinary bladder carcinoma associated with highly aggressive behaviour. The aim of this study was to analyse clinicopathological features of MUC particularly a relationship between pathological stage at presentation and proportion of micropapillary component (MPC) in 10 patients with MUC. In the examined period (January 1st 2004 - June 30th, 2007) there were 610 patients with urinary bladder cancer (M:F = 456:154), while 10 (1.6%) of them were patients with MUC. All MUC were invasive at the time of diagnosis. Stage distribution at presentation was 4 T1(40%) and 6 T2 (60%) and the percentage of MPC correlated with pathological stage: 3 of 4 (75%) tumors staged T1 had less than 10% of MPC and 5 of 6 (83,3%) tumors staged T2 had more than 50% of MPC. MUC is an aggressive tumor, often in advanced stage of disease at the time of diagnosis, in which the pathological stage is related to the proportion of MPC.


An Evaluation of Real-world Smart Sock-Based Temperature Monitoring Data as a Physiological Indicator of Early Diabetic Foot Injury: Case-Control Study.
Lower extremity complications of diabetes represent major health care complications both in terms of cost and impact to quality of life for patients with diabetic peripheral neuropathy. Temperature monitoring has been shown in previous studies to provide a useful signal of inflammation that may indicate the early presence of a foot injury. In this study, we evaluated the temperature data for patients that presented with a diabetic foot injury while using a sock-based remote temperature monitoring device. The study abstracted data from patients who were enrolled in a remote temperature monitoring program (2020-2021) using a smart sock (Siren Care). In the study cohort, a total of 5 participants with a diabetes-related lower extremity injury during the study period were identified. In the second comparison cohort, a total of 26 patients met the criteria for monitoring by the same methods but did not present with a diabetes-related podiatric lower extremity injury during the same period. The 15-day temperature differential between 6 defined locations on each foot was the primary outcome measure among subjects who presented with a diagnosed foot injury. Paired t tests were used to compare the differences between the two groups. A significant difference in temperature differential (temperature measured in °F) was observed in the group that presented with a podiatric injury over the course of evaluation versus the comparator group that did not present with a podiatric injury. The average difference from all 6 measured points was 1.4 °F between the injury group (mean 3.6, SD 3.0) and the comparator group (mean 2.2, SD 2.5, t=-71.4, df=39; P<.001). The results of this study suggest temperature monitoring in a sock form factor could be used to predict a developing foot injury. The continuous temperature monitoring system employed has implications for further algorithm development to enable early detection. The study was limited by a nonrandomized, observational design with limited injuries present in the study period. We look forward to further studies that will refine the predictive potential and confirm or refute the current promising data.


Kill kinetics of the cephalosporin antibiotics cephalexin and cefuroxime against bacteria of veterinary importance.
Kill kinetic studies for two cephalosporin antibiotics, cephalexin and cefuroxime were carried out against veterinary strains of Escherichia coli, Pasteurella multocida, Streptococcus suis, Erysipelothrix rhusiopathiae and a laboratory culture of Staphylococcus aureus. In more than 90 per cent of cases a kill of more than 99 per cent was achieved within four hours of antibiotic treatment at concentrations of 2 or 4 micrograms/ml. Although cefuroxime was effective at lower concentrations than cephalexin the rates of kill of the two antibiotics were comparable. The results are discussed in relation to in vivo dosage regimens.


Central neurocytoma: a clinico-pathological study of eight cases.
Central neurocytomas are benign neuronal tumours generally found in the lateral or third ventricles. They are rare, comprising < 1% of all brain tumours. It is frequently confused with other tumours of the central nervous system particularly oligodendroglioma. The present study was done to analyse the histopathological features including immunohistochemical profile of these rare tumours. Eight cases were taken up for the study. Seven of the cases had an intraventricular location and one was located outside the ventricles. Increased intracranial pressure was the most common presenting symptom. Microscopically all tumours were composed of small uniform cells with perinuclear halos and regular round nuclei. The tumour in extraventricular location showed atypical features. Immunohistochemistry showed positivity for neuronal markers. The present series highlights the characteristic clinical and pathological findings of this rare brain tumour. Immunostaining for neuronal markers are essential for distinguishing them from other small round cell tumours of the brain.


Adenylylcyclase gene transfer increases function of the failing heart.
A persistent question in cardiovascular gene transfer concerns whether an exogenously delivered gene can increase function of the failing heart. Here we test the hypothesis that intracoronary delivery of adenovirus encoding adenylylcyclase type VI (Ad.ACVI) in the setting of active heart failure will increase function of the failing heart. As a model of heart failure, we used transgenic mice with dilated and poorly functioning hearts resulting from cardiac-directed expression of Galphaq.Galphaq mice with equivalent pretreatment impairment in left ventricular (LV) function (echocardiography) received 2.5x1010 viral particles of Ad.ACVI or Ad.EGFP (enhanced green fluorescent protein), or saline, by indirect intracoronary delivery. Serial echocardiograms obtained before and 14 days after gene transfer showed that Ad.ACVI increased LV ejection fraction (p<0.01) and velocity of circumferential fiber shortening (p<0.03). Detailed measurements in isolated hearts showed that ACVI gene transfer increased LV positive dP/dt (p=0.02) and LV negative dP/dt (p=0.01). Gene transfer was confirmed by polymerase chain reaction. These data show that, in an animal model that mimics key aspects of clinical congestive heart failure, cardiac gene transfer of ACVI increases function of the failing heart.


Epidemiological study of gastric Helicobacter spp. in dogs with gastrointestinal disease in Japan and diversity of Helicobacter heilmannii sensu stricto.
Epidemiological and pathological studies of Helicobacter spp. in canine stomachs in Japan were performed to investigate strain specific pathogenicity. Gastric biopsies from 144 dogs with gastrointestinal diseases were evaluated for the presence of Helicobacter spp. using genus and species specific PCRs for Helicobacter felis, Helicobacter bizzozeronii, Helicobacter heilmannii sensu stricto (s.s.) and Helicobacter pylori. PCR indicated that 50/144 (34.7%) dogs were infected with Helicobacter spp. Of the genus positive samples, 21/50 could not be amplified by any of the species specific PCRs. To investigate Helicobacter at the species level, partial ureAB gene sequences from 48/50 genus positive samples were determined; 47 strains were identified. Thirty-five strains from 45 cases were closely related to H. heilmannii s.s. (89-99% sequence similarity), seven strains from seven cases were closely related to H. bizzozeronii (95-99% sequence similarity), three strains from three cases were closely related to Helicobacter felis (86%, 98% and 99% sequence similarity), one strain from one case was closely related to Helicobacter salomonis (99% sequence similarity) and one strain from one case was closely related to H. pylori (99% sequence similarity). Dogs infected with Helicobacter spp. most similar to H. heilmannii s.s. had a higher frequency of moderate to severe gastritis than dogs negative for Helicobacter spp. (P=0.044). In conclusion, the predominant Helicobacter spp. detected in canine stomachs in our study were most closely related to H. heilmannii s.s. and displayed substantial genetic diversity. Infection with Helicobacter spp. may be associated with more severe gastritis in dogs.


[Early therapy with immunoglobulins after extensive abdominal operations. A random study (author's transl)].
A random study with 100 patients was conducted to show whether the immunoglogulin Gamma Venin, when given after rectum extirpation, has an effect on wound healing and other infections. The patients in the test group received 10 g of Gamma Venin within the first 48 h after surgery. The number of days with purulent wound secretion were reduced to 0.71 (test group) as opposed to 7.61 (control) with statistical significance. Primary wound healing was 37% in the test group and 9% in the control group (P < 0.01). Other infections occurred in a similar range. The time of hospitalization was 3.44 days less than in the test group (P < 0.01).


Severe Pediatric COVID-19 Presenting With Respiratory Failure and Severe Thrombocytopenia.
The novel severe acute respiratory syndrome coronavirus 2 is a worldwide pandemic. The severe morbidity and mortality associated with coronavirus disease 2019 has mostly affected the elderly or those with underlying medical conditions. We present a case of a 12-year-old girl with no past medical history who presented with fever, cough, and vomiting. Laboratory evaluation revealed severe thrombocytopenia and elevated markers of inflammation. The patient progressed to respiratory failure, and testing results for the severe acute respiratory syndrome coronavirus 2 returned positive. Because of the severity of her thrombocytopenia, she was treated with intravenous immunoglobulin and steroids with prompt improvement in platelets. The patient's severe acute respiratory distress syndrome was managed with mechanical ventilation, inhaled nitric oxide, and then airway pressure release ventilation. After azithromycin and hydroxychloroquine were given without improvement, our patient received tocilizumab, an anti-interleukin-6 receptor antibody, and remdesivir, a broad antiviral agent, with significant clinical benefit soon afterward. Given that severe pediatric coronavirus disease 2019 is rare, we hope to inform pediatric providers on the clinical course and management considerations as this pandemic continues to spread.


[Uroflowmetry in examination of the female with stress urinary incontinence].
Show the ability of uroflowmetry to record episodes of involuntary loss of urine at an altitude cough bursts. A total of 49 women with a genital prolapse and stress urinary incontinence. The study was conducted during bladder filling 150-300 ml of urine. A patient chair being Uroflowmeter three times at intervals of 3-5 coughs seconds. Episodes of involuntary discharge of urine at an altitude cough shocks on uroflowgramme recorded as separate trapezoidal or triangular peaks. The same procedure was carried out and after surgery. All women graphically documented episodes of involuntary discharge of urine at an altitude cough shocks before operation. Uroflowmetry after surgery confirmed the fact of continence. The study is simple, not cumbersome for the patient. The opportunity to document the diagnosis stress urinary incontinence. The proposed method of uroflowmetry in examining women with stress urinary incontinence allows not only to estimate the total evacuation function of the bladder and urethra, but also graphically record the episodes of involuntary loss of urine during coughing.


[A quantitative pharmaco-EEG study on psychotropic properties of cerebral metabolic enhancers: comparison between young and elderly healthy volunteers].
In order to investigate psychotropic properties of cerebral metabolic enhancers (CMEs), the author carried out two identical quantitative pharmaco-EEG studies in different age groups of healthy volunteers; the young group (group-Y) consisted of six males between the ages of 21-26 years and elderly group (group-E) consisted of six males between the ages of 60-66 years. The drugs tested were five CMEs, dihydroergotoxine mesylate (DHE), propentofylline (PPF), nicergoline (NCG), lisuride maleate (LIS) and ibudilast (IDL). Each volunteer received either of the five test drugs or inert placebo in six one-day weekly sessions' according to single-blind, randomized crossover design. In each session, a single oral dose, equivalent to the clinically recommended daily dose, of either drug or placebo was administered and EEGs were recorded before and 1.3 and 6 hours after the drug administration. Firstly, the background EEGs before the drug administration were compared between the two groups. Group-E showed less slow activities and more alpha and fast activities than group -Y. This difference in background EEG profiles between two groups are considered to be due to physiological aging process. Secondly, drug effects on EEGs in two groups were compared. There were discrepancies in drug-induced EEG changes between the groups. In group-Y, any of the five tested CMEs did not induce EEG changes that were significantly different from placebo, whereas, in group-E, drug-induced EEG changes were more apparent. In group-E, DHE and PPF induced similar EEG changes, which were characterized by a decrease of alpha activity associated with marked decreases of slow and fast activities, the EEG profile similar to thymoleptics with sedative effects. LIS and IDL induced a decrease of alpha activity and an increase of fast activities, the profile close to thymoleptics with mood-elevating (stimulant) effects. NCG induced an increase of slow activities, the profile close to central depressants. These results in this study coincided with the experimental and subjective classification of the clinical effects of CMEs. Further analysis of EEG profiles based on principal component analysis indicated that there were two major components in background EEGs. There were discrepancies in the response to CMEs between two groups. In group-Y, CME-induced changes were seen mainly in the second principal component, while in group-E, the changes were seen mainly in the first principal component. These results suggested CMEs provoked thymoleptic effects by affecting the essential component of the EEG basic rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)


A mathematical model for treatment-resistant mutations of hiv.
In this paper, we propose and analyze a mathematical model, in the form of a system of ordinary differential equations, governing mutated strains of human immunodeficiency virus (HIV) and their interactions with the immune system and treatments. Our model incorporates two types of resistant mutations: strains that are not responsive to protease inhibitors, and strains that are not responsive to reverse transcriptase inhibitors. It also includes strains that do not have either of these two types of resistance (wild- type virus) and strains that have both types. We perform our analysis by changing the system of ordinary differential equations (ODEs) to a simple single-variable ODE, then identifying equilibria and determining stability. We carry out numerical calculations that illustrate the behavior of the system. We also examine the effects of various treatment regimens on the development of treatment-resistant mutations of HIV in this model.


The history of introduction of the African baobab (Adansonia digitata, Malvaceae: Bombacoideae) in the Indian subcontinent.
To investigate the pathways of introduction of the African baobab, Adansonia digitata, to the Indian subcontinent, we examined 10 microsatellite loci in individuals from Africa, India, the Mascarenes and Malaysia, and matched this with historical evidence of human interactions between source and destination regions. Genetic analysis showed broad congruence of African clusters with biogeographic regions except along the Zambezi (Mozambique) and Kilwa (Tanzania), where populations included a mixture of individuals assigned to at least two different clusters. Individuals from West Africa, the Mascarenes, southeast India and Malaysia shared a cluster. Baobabs from western and central India clustered separately from Africa. Genetic diversity was lower in populations from the Indian subcontinent than in African populations, but the former contained private alleles. Phylogenetic analysis showed Indian populations were closest to those from the Mombasa-Dar es Salaam coast. The genetic results provide evidence of multiple introductions of African baobabs to the Indian subcontinent over a longer time period than previously assumed. Individuals belonging to different genetic clusters in Zambezi and Kilwa may reflect the history of trafficking captives from inland areas to supply the slave trade between the fifteenth and nineteenth centuries. Baobabs in the Mascarenes, southeast India and Malaysia indicate introduction from West Africa through eighteenth and nineteenth century European colonial networks.


The Saccharomyces cerevisiae Sae2 protein promotes resection and bridging of double strand break ends.
When eukaryotic chromosomes undergo double strand breaks (DSBs), several evolutionarily conserved proteins, among which the MRX complex, are recruited to the break site, leading to checkpoint activation and DNA repair. The function of the Saccharomyces cerevisiae Sae2 protein, which is known to work together with the MRX complex in meiotic DSB processing and in specific mitotic DSB repair events, is only beginning to be elucidated. Here we provide new insights into the role of Sae2 in mitotic DSB repair. We show that repair by single strand annealing of a single DSB, which is generated by the HO endonuclease between direct repeats, is defective both in the absence of Sae2 and in the presence of the hypomorphic rad50s allele altering the Rad50 subunit of MRX. Moreover, SAE2 overexpression partially suppresses the rad50s single strand annealing repair defects, suggesting that the latter might arise from defective MRX-Sae2 interactions. Finally, SAE2 deletion slows down resection of an HO-induced DSB and impairs DSB end bridging. Thus, Sae2 participates in DSB single strand annealing repair by ensuring both resection and intrachromosomal association of the broken ends.


A Dynamic Task Allocation Framework in Mobile Crowd Sensing with D3QN.
With the coverage of sensor-rich smart devices (smartphones, iPads, etc.), combined with the need to collect large amounts of data, mobile crowd sensing (MCS) has gradually attracted the attention of academics in recent years. MCS is a new and promising model for mass perception and computational data collection. The main function is to recruit a large group of participants with mobile devices to perform sensing tasks in a given area. Task assignment is an important research topic in MCS systems, which aims to efficiently assign sensing tasks to recruited workers. Previous studies have focused on greedy or heuristic approaches, whereas the MCS task allocation problem is usually an NP-hard optimisation problem due to various resource and quality constraints, and traditional greedy or heuristic approaches usually suffer from performance loss to some extent. In addition, the platform-centric task allocation model usually considers the interests of the platform and ignores the feelings of other participants, to the detriment of the platform's development. Therefore, in this paper, deep reinforcement learning methods are used to find more efficient task assignment solutions, and a weighted approach is adopted to optimise multiple objectives. Specifically, we use a double deep Q network (D3QN) based on the dueling architecture to solve the task allocation problem. Since the maximum travel distance of the workers, the reward value, and the random arrival and time sensitivity of the sensing tasks are considered, this is a dynamic task allocation problem under multiple constraints. For dynamic problems, traditional heuristics (eg, pso, genetics) are often difficult to solve from a modeling and practical perspective. Reinforcement learning can obtain sub-optimal or optimal solutions in a limited time by means of sequential decision-making. Finally, we compare the proposed D3QN-based solution with the standard baseline solution, and experiments show that it outperforms the baseline solution in terms of platform profit, task completion rate, etc., the utility and attractiveness of the platform are enhanced.


Parkinsonism as a Complication of Bariatric Surgery.
The association between Parkinsonism and BS has already been reported in only three patients worldwide. We report a 39-years old Kuwaiti female who presented with parkinsonian features and mononeuropathy (carpal tunnel syndrome) 3 years after a vertical sleeve gastrectomy operation. We conclude that with the increasing popularity of bariatric surgery, clinicians will need to recognize and manage neurologic complications that may appear soon after or years to decades later. Thorough evaluation is essential for any patient who has undergone bariatric surgery and develops neurologic symptoms.


Sphingolipids as prognostic biomarkers of neurodegeneration, neuroinflammation, and psychiatric diseases and their emerging role in lipidomic investigation methods.
Lipids play an important role in neurodegeneration, neuroinflammation, and psychiatric disorders and an imbalance in sphingolipid levels is associated with disease. Although early diagnosis and intervention of these disorders would clearly have favorable long-term outcomes, no diagnostic tests currently exist that can accurately identify people at risk. Reliable prognostic biomarkers that are easily accessible would be beneficial to determine therapy and treatment response in clinical trials. Recent advances in lipidomic investigation methods have greatly progressed the knowledge of sphingolipids in neurodegenerative and psychiatric disorders over the past decades although more longitudinal studies are needed to understand its exact role in these disorders to be used as potential tools in the clinic. In this review, we give an overview of the current knowledge of sphingolipids in neurodegenerative and psychiatric disorders and explore recent advances in investigation methods. Finally, the potential of sphingolipid metabolism products and signaling molecules as potential biomarkers for diagnosis, prognostic, or surrogate markers of treatment response is discussed.


Adults' Experiences with Type 2 Diabetes in Rural Guatemala: A Qualitative Study.
Given that the diabetes burden is rising rapidly in low- and middle-income countries, it is critical to understand perspectives of people living with diabetes in these settings. This qualitative study examines perceptions of causality and treatment among adults with type 2 diabetes in rural Indigenous communities of Guatemala. We conducted semi-structured interviews with 29 people living with type 2 diabetes from a population survey in two majority Indigenous Guatemalan towns. Data were coded inductively and themes were elucidated by consensus. Participants emphasized strong emotional experiences and stress as perceived causes of diabetes, as well as diet and heritability. All participants took biopharmaceutical treatments, but many also endorsed diet, exercise, herbal remedies, and naturopathic products as important remedies. Perspectives from people living with diabetes in two rural Indigenous towns in Guatemala differ from the biomedical model of disease and have implications for clinical practice and program development.


Synthetic biology with surgical precision: targeted reengineering of signaling proteins.
The complexity of living systems exceeds everything else studied by natural sciences. Sophisticated networks of intimately intertwined signaling pathways coordinate cellular functions. Clear understanding how the integration of multiple inputs produces coherent behavior is one of the major challenges of cell biology. Integration via perfectly timed highly regulated protein-protein interactions and precise targeting of the "output" proteins to particular substrates is emerging as a common theme of signaling regulation. This often involves specialized scaffolding proteins, whose key function is to ensure that correct partners come together in an appropriate place at the right time. Defective or faulty signaling underlies many congenital and acquired human disorders. Several pioneering studies showed that ectopic expression of existing proteins or their elements can restore functions destroyed by mutations or normalize the signaling pushed out of balance by disease and/or current small molecule-based therapy. Several recent studies show that proteins with new functional modalities can be generated by mixing and matching existing domains, or via functional recalibration and fine-tuning of existing proteins by precisely targeted mutations. Using arrestins as an example, we describe how manipulation of individual functions yields signaling-biased proteins. Creative protein redesign generates novel tools valuable for unraveling the intricacies of cell biology. Engineered proteins with specific functional changes also have huge therapeutic potential in disorders associated with inherited or acquired signaling errors.


The acoustic startle reflex in stiff-man syndrome.
We studied the EMG response to loud noise in eight patients with stiff-man syndrome (SMS). Audiogenic muscle jerks originated in the acoustic startle reflex. Patients demonstrated excessive, poorly habituating motor activity predominantly in axial and leg muscles. Exaggerated startle in SMS probably reflects segmental hyperexcitability of axial and lumbar spinal motor neurons.


Mitochondrial genome characteristics of six Phylloscopus species and their phylogenetic implication.
The mitochondrial genomes of six Phylloscopus species-small insectivores belonging to the Phylloscopidae family-were obtained using the Illumina sequencing platform. The mitogenomes were closed circular molecules 16,922-17,007 bp in size, containing 13 protein-coding genes, 22 tRNA genes, two rRNA genes, and two control regions (CR1 and remnant CR2). The gene orders were conserved in 35 sampled Phylloscopus mitogenomes in the GenBank database, with a gene rearrangement of cytb-trnT-CR1-trnP-nad6-trnE-remnant CR2-trnF-rrnS. The average base compositions of the six Phylloscopus mitogenomes were 29.43% A, 32.75% C, 14.68% G, and 23.10% T, with the A+T content slightly higher than that of G+C. ATG and TAA were the most frequent initiating and terminating codons, respectively. Several conserved boxes were identified in CR1, including C-string in domain I; F, E, D, and C boxes, as well as bird similarity and B boxes, in domain II; and CSB1 in domain III. Tandem repeats were observed in remnant CR2 of the Phylloscopus fuscatus and Phylloscopus proregulus mitogenomes. A phylogenetic analysis with maximum likelihood (ML) and Bayesian inference (BI) methods, based on 13 protein-coding genes and two rRNA genes, indicated that the Phylloscopus species was divided into two larger clades, with a splitting time approximately 11.06 million years ago (mya). The taxa of Phylloscopus coronatus/Phylloscopus burkii and Phylloscopus inornatus/P. proregulus were located at the basal position of the different clades. The phylogenetic result of the cox1 gene showed that Seicercus was nested within Phylloscopus. The complete set of mitogenomes of the Phylloscopus species provides potentially useful resources for the further exploration of the taxonomic status and phylogenetic history of Phylloscopidae.


Platelet P2 receptors: old and new targets for antithrombotic drugs.
Platelets possess three P2 receptors for adenine nucleotides: P2Y1 and P2Y12, which interact with ADP, and P2X1, which interacts with ATP. The interaction of adenine nucleotides with their platelet receptors plays an important role in thrombogenesis. The thienopyridine ticlopidine, an antagonist of the platelet P2Y12 ADP receptor, reduces the incidence of vascular events in patients at risk, but it also has some important drawbacks: a relatively high incidence of toxic effects; delayed onset of action; high inter-individual variability in response. Another thienopyridine, clopidogrel, has superseded ticlopidine, because it is an efficacious antithrombotic drug and is less toxic than ticlopidine. However, the high inter-patient variability in response still remains an important issue. These drawbacks justify the continuing search for agents that can further improve the clinical outcome of patients with atherosclerosis through greater efficacy and/or safety. A new thienopyridyl compound prasugrel, which is characterized by higher potency and faster onset of action compared with clopidogrel, is currently under clinical evaluation. Two direct and reversible P2Y12 antagonists, cangrelor and AZD6140, have very rapid onset and reversal of platelet inhibition, which make them attractive alternatives to thienopyridines, especially when rapid inhibition of platelet aggregation or its quick reversal are required. Along with new P2Y12 antagonists, inhibitors of the other platelet receptor for ADP, P2Y1, and of the receptor for ATP, P2X1, are under development and may prove to be effective antithrombotic agents.


Folivory as a Constraint on Social Behaviour of Langurs in South India.
Folivory, being a dietary constraint, can affect the social time of colobines. In the present study, we compared food items and activity budgets of two closely related species of colobines inhabiting South India, i.e. the Hanuman langur (Semnopithecus hypoleucos) and Nilgiri langur (Semnopithecus johnii), to determine whether folivory had an impact on social time in these species. Our study established that Nilgiri langurs were more folivorous than Hanuman langurs. Nilgiri langurs spent much less time on social activities, but more time on resting, although the social organization of S. hypoleucos was similar to that of the Nilgiri langur. The enforced resting time for fermentation of leafy food items may have reduced the time available for social interactions, which in turn affected the social time in Nilgiri langurs. By comparing the data from previous studies on other Hanuman langur species, we found that S. hypoleucos spent a similar amount of time on social activities as Semnopithecus entellus. Hence, the social behaviour of S. entellus and S. hypoleucos is phylogenetically highly conservative.


New strategies in nonoperative management of meconium ileus.
The aim of this study was to develop new nonoperative strategies for the management of meconium ileus in an attempt to improve on the current unacceptable failure rate. Mice were constipated with subcutaneous morphine injection. Each then received an enema solution (perflubron, surfactant, Tween-80, Gastrografin, Golytely, DNase, N-Acetylcysteine, Viokase, or normal saline). After the enema solution was administered, stool output was quantitated. Histologic examination of the intestines was performed on a second group of mice that also received enemas. Finally, viscosity measurements were taken of human meconium at baseline and after variable incubation periods with each test solution. For relieving constipation in vivo, Gastrografin enema was most efficacious. All agents were equally benign to the intestinal mucosa. In vitro, only 4% N-Acetylcysteine and perflubron were less effective at decreasing meconium viscosity than normal saline at T = 0 hours, with N-Acetylcysteine producing greater reduction in viscosity than normal saline at T = 6 hours. Our results show that surfactant and Gastrografin are the most effective for the in vivo relief of constipation. This is accomplished without mucosal damage. These agents also significantly reduce viscosity in vitro, and we speculate that they may be beneficial in relieving constipation caused by meconium ileus in cystic fibrosis patients.


Abundant accumulation of the calcium-binding molecular chaperone calreticulin in specific floral tissues of Arabidopsis thaliana.
Calreticulin (CRT) is a calcium-binding protein in the endoplasmic reticulum (ER) with an established role as a molecular chaper-one. An additional function in signal transduction, specifically in calcium distribution, is suggested but not proven. We have analyzed the expression pattern of Arabidopsis thaliana CRTs for a comparison with these proposed roles. Three CRT genes were expressed, with identities of the encoded proteins ranging from 54 to 86%. Protein motifs with established functions found in CRTs of other species were conserved. CRT was found in all of the cells in low amounts, whereas three distinct floral tissues showed abundant expression: secreting nectaries, ovules early in development, and a set of subepidermal cells near the abaxial surface of the anther. Localization in the developing endosperm, which is characterized by high protein synthesis rates, can be reconciled with a specific chaperone function. Equally, nectar production and secretion, a developmental stage marked by abundant ER, may require abundant CRT to accommodate the traffic of secretory proteins through the ER. Localization of CRT in the anthers, which are degenerating at the time of maximum expression of CRT, cannot easily be reconciled with a chaperone function but may indicate a role for CRT in anther maturation or dehiscence.


Neem Derivatives Inhibits Tau Aggregation.
Tau is a phosphoprotein with natively unfolded conformation that functions to stabilize microtubules in axons. Alzheimer's disease pathology triggers several modifications in tau, which causes it to lose its affinity towards microtubule, thus, leading to microtubule disassembly and loss of axonal integrity. This elicit accumulation of tau as paired helical filaments is followed by stable neurofibrillary tangles formation. A large number of small molecules have been isolated from Azadirachta indica with varied medicinal applications. The intermediate and final limonoids, nimbin and salannin respectively, isolated from Azadirachta indica, were screened against tau aggregation. ThS and ANS fluorescence assay showed the role of intermediate and final limonoids in preventing heparin induced cross-β sheet formation and also decreased hydrophobicity, which are characteristic nature of tau aggregation. Transmission electron microscopy studies revealed that limonoids restricted the aggregation of tau to fibrils; in turn, limonoids led to the formation of short and fragile aggregates. Both the limonoids were non-toxic to HEK293T cells thus, substantiating limonoids as a potential lead in overcoming Alzheimer's disease.


Basaloid squamous cell carcinoma of the larynx: report of a case.
Basaloid squamous cell carcinoma is a variant of squamous cell carcinoma. This malignancy has a predilection for the upper aerodigestive tract, although it has been found in multiple other sites. The tumor is highly aggressive biologically, and the overall prognosis is poor despite intensive treatment. We describe a case of basaloid squamous cell carcinoma of the larynx that metastasized to the spine.


Successful treatment of florid cutaneous warts with intravenous cidofovir in an 11-year-old girl.
Cutaneous warts, commonly seen in children and the immunosuppressed are socially distressing and are often resistant to traditional treatments. Here, we report an 11-year-old girl with bilateral florid verrucous lesions on her hands, feet and chin, which were refractory to a number of standard treatments including cryotherapy, cantharidin preparations, topical salicylic acid, surgical debulking techniques, oral Cimetidine, and topical and intralesional Cidofovir. As the disfiguring lesions had a marked adverse effect on her quality of life, a trial of IV Cidofovir was instituted. We administered five cycles of IV Cidofovir with a 1-week interval between the first and second treatment, followed by 2-week intervals thereafter. This regime was well tolerated and we report dramatic resolution of the lesions with persistent clearance 6 months after completion of the fifth infusion. Resolution of recalcitrant warts with IV Cidofovir has been reported in a limited number of cases. Our experience supports its efficacy in this setting, and to the best of our knowledge this is the first report of successful treatment of cutaneous warts with IV Cidofovir in a pediatric case.


Decoding Intent With Control Theory: Comparing Muscle Versus Manual Interface Performance.
Manual device interaction requires precise coordination which may be difficult for users with motor impairments. Muscle interfaces provide alternative interaction methods that may enhance performance, but have not yet been evaluated for simple (eg. mouse tracking) and complex (eg. driving) continuous tasks. Control theory enables us to probe continuous task performance by separating user input into intent and error correction to quantify how motor impairments impact device interaction. We compared the effectiveness of a manual versus a muscle interface for eleven users without and three users with motor impairments performing continuous tasks. Both user groups preferred and performed better with the muscle versus the manual interface for the complex continuous task. These results suggest muscle interfaces and algorithms that can detect and augment user intent may be especially useful for future design of interfaces for continuous tasks.


Racial and ethnic differences in clinical outcomes among multiple myeloma patients treated with CAR T-cell therapy.
Idecabtagene vicleucel (ide-cel) was the first chimeric antigen receptor T-cell therapy to gain FDA approval for patients with relapsed/refractory multiple myeloma (RRMM). The clinical outcomes of standard of care (SOC) ide-cel in racially and ethnically diverse populations have been understudied. This study pooled data from 207 RRMM patients (28% racial and ethnic minority patients) treated with SOC ide-cel across 11 institutions to examine racial and ethnic differences in the incidence of toxicities and adverse events, response to ide-cel, and survival. This study included 22 (11%) Hispanic, 36 (17%) Non-Hispanic Black, and 149 (72%) Non-Hispanic White RRMM patients. Compared to Hispanic and Non-Hispanic White patients, Non-Hispanic Black patients had higher median levels of C-reactive protein (1.0, 0.8, and 3.5 mg/dL, respectively; P=0.02) and baseline ferritin (362.0 vs. 307.0 vs. 680.5, respectively; P=0.08) and were more likely to develop cytokine release syndrome (77%, 85%, and 97%, respectively; P=0.04). Although best overall response rate was lower among Hispanic patients (59%) compared to Non-Hispanic Black (86%) and White patients (86%; P=0.01), there were no racial and ethnic differences in progression-free or overall survival. We provide the first and largest investigation of clinical outcomes of SOC ide-cel by race and ethnicity. Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all RRMM patients. These findings should be confirmed in larger samples of diverse RRMM patients with longer follow-up time.


[Internal carotid artery dissection on arterial fibromuscular dysplasia causing a central retinal artery occlusion: a case report].
We report a case of a 66-year-old woman presenting a central retinal artery occlusion with no cardiovascular risk factor, with assessment using supra-aortic artery ultrasonography showing total internal carotid artery thrombosis. When vascular thrombosis risk factors are absent, more in-depth assessment such as a supra-aortic artery angioscan can provide the diagnosis of arterial dissection on arterial fibromuscular dysplasia. Central retinal artery occlusion is a rare but severe pathology. Therefore it is very important not to neglect the etiological assessment, because it can be the revealing element of a severe pathology.


Surface Decoration on Polymeric Gate Dielectrics for Flexible Organic Field-Effect Transistors via Hydroxylation and Subsequent Monolayer Self-Assembly.
A simple photochemical reaction based on confined photocatalytic oxidation (CPO) treatment and hydrolysis was employed to efficiently convert C-H bonds into C-OH groups on polymeric material surfaces, followed by investigation of monolayer self-assembly decoration on polymeric dielectrics via chemical bonding for the organic field-effect transistors (OFETs) applications. This method is a low temperature process and has negligible etching effect on polymeric dielectric layers. Various types of self-assembled monolayers have been tested and successfully attached onto the hydroxylated polymeric dielectric surfaces through chemical bonding, ensuring the stability of decorated functional films during the subsequent device fabrication consisting of solution processing of the polymer active layer. With the surface decoration of functional groups, both n-type and p-type polymers exhibit enhanced carrier mobilities in the unipolar OFETs. In addition, enhanced and balanced mobilities are obtained in the ambipolar OFETs with the blend of polymer semiconductors. The anchored self-assembled monolayers on the dielectric surfaces dramatically preclude the solvent effect, thus enabling an improvement of carrier mobility up to 2 orders of magnitude. Our study opens a way of targeted modifications of polymeric surfaces and related applications in organic electronics.