Spinal atypical teratoid rhabdoid tumor-narrative review and report of a rare case managed with multimodality approach.
Spinal atypical teratoid rhabdoid tumor (AT/RT) is an extremely rare tumor and represents less than 2% of all AT/RTs. Available medical literature on spinal AT/RT in English was retrieved from PubMed and comprehensively reviewed. Clinical presentation, diagnosis, management, prognosis, and outcome in patients with spinal AT/RT have been elucidated by citing a case of extradural AT/RT of the cervicodorsal spine. The age at presentation is usually less than 3 years. The most common site is the cervicodorsal spine. The most frequent tumor location is intradural extramedullary. A contrast-enhanced magnetic resonance imaging (MRI) of the entire neuraxis is the imaging modality of choice. The incidence of leptomeningeal dissemination is high (15-30%). Histopathological examination shows an admixture of primitive neuroectodermal, mesenchymal, and epithelial elements along with rhabdoid cells. Loss of SMARCB1/INI1 is considered pathognomonic of AT/RT. Maximal safe resection of tumor is the initial management of choice. Thereafter focal radiotherapy for localized tumor or craniospinal irradiation for leptomeningeal dissemination should be considered. Post-operative intensive polychemotherapy including intrathecal and high-dose chemotherapy (with autologous stem cell rescue) is usually considered to optimize survival. Typically, the time to recurrence and overall survival are less than 6 and 12 months, respectively. However, with judicious multimodality management long-term survivors are increasingly being recognized. The illustrative patient was a 18-month-old girl diagnosed with extradural AT/RT of the cervicodorsal spine (C3-D1), who was managed with maximal safe resection of tumor, multiagent chemotherapy (ICE-ifosfamide, carboplatin, etoposide) and focal RT to the tumor bed-50.4 Gy/28 fractions/5.5 weeks. At the last follow-up visit, 30 months after surgery, she had complete clinicoradiological response. Multimodal treatment comprising maximal safe resection of tumor, multiagent chemotherapy (ICE), and focal RT can lead to successful outcome in patients with localized spinal AT/RT, under the age of 3 years.


Spectral Jaccard Similarity: A New Approach to Estimating Pairwise Sequence Alignments.
Pairwise sequence alignment is often a computational bottleneck in genomic analysis pipelines, particularly in the context of third-generation sequencing technologies. To speed up this process, the pairwise k-mer Jaccard similarity is sometimes used as a proxy for alignment size in order to filter pairs of reads, and min-hashes are employed to efficiently estimate these similarities. However, when the k-mer distribution of a dataset is significantly non-uniform (e.g., due to GC biases and repeats), Jaccard similarity is no longer a good proxy for alignment size. In this work, we introduce a min-hash-based approach for estimating alignment sizes called Spectral Jaccard Similarity, which naturally accounts for uneven k-mer distributions. The Spectral Jaccard Similarity is computed by performing a singular value decomposition on a min-hash collision matrix. We empirically show that this new metric provides significantly better estimates for alignment sizes, and we provide a computationally efficient estimator for these spectral similarity scores.


Interaction between smoking and PON2 Ser311Cys polymorphism as a determinant of the risk of myocardial infarction.
Increased oxidative stress is thought to play a role in the pathogenesis of the atherothrombotic process. Paraoxonases (PONs) are closely related antioxidant enzymes encoded by clustered genes on chromosome 7q. We evaluated three PON polymorphisms (PON1 Leu55Met and Gln192Arg; PON2 Ser311Cys) as possible risk factors for coronary atherosclerotic disease (CAD) and/or its main thrombotic complication, myocardial infarction (MI). We studied 890 subjects with angiographic documentation of coronary vessels (272=CAD-free; 618=CAD). In the CAD group, 341 subjects had a previous MI. Frequencies of various genotypes were not significantly different between CAD-free subjects and the entire CAD population. In the latter group, there were more carriers of the PON2 311Cys variation among those who had suffered a MI than among those who had not (P<0.01 by chi2). The adjusted OR for MI among PON2 311Cys carriers was 1.5 (95%CI, 1.03-2.19). A gene-environmental interaction was found between PON2 Ser311Cys and smoking. Smoking by itself was associated with an increased MI risk. Among smokers, however, the MI risk was related to PON2 genotype: Cys/Cys homozygotes (OR=5.3; 95%CI, 1.7-16.4) and Ser/Cys heterozygotes (OR=2.1; 95%CI, 1.3-3.6) were at greater risk than Ser/Ser subjects (OR=1.2; 95%CI, 0.8-1.8). The PON2 polymorphism did not influence the MI risk among nonsmokers. In CAD subjects, a proportion of the risk of MI may be influenced by the interaction between smoking and a polymorphism in the antioxidant enzyme PON2.


Staged pain or systemic crisis? Research on the employment effect of enterprise green transformation.
The green transformation is a necessary path for industrialization to reach the advanced stage. Currently, achieving a win-win situation between green transformation and stable employment for residents has become a common concern for theoretical researchers and policymakers. This paper analyzes the influence mechanism of enterprise green transformation on employment using the partial equilibrium model. Furthermore, the employment effect and mechanism of enterprise green transformation are empirically verified with panel data from companies listed on the Shanghai and Shenzhen stock exchanges. The results indicate a dynamic non-linear relationship between enterprise green transformation and employment. As the transformation deepens, its impact on employment changes from negative to positive. Mechanism analysis reveals that enterprise green transformation has the potential to induce output growth and employment virtuous cycle. Additionally, environmental protection investment and labor employment in the transformation have a factor complementary effect. There is heterogeneity in the employment impact of enterprise green transformation, especially for production personnel, low-skilled labor, non-state-owned, heavy-polluting, and medium-low-tech enterprises, which experience stronger employment deprivation.


Do silver-impregnated dressings limit infections after lumbar laminectomy with instrumented fusion?
Silver has been used to reduce infection for centuries. This study retrospectively analyzed whether the introduction of silver-impregnated dressing (SD; Silverlon, Argentum Medical, LLC, Lakefront, GA) rather than RD (iodine- or alcohol-based swab and dry 4 x 4 gauze) would reduce the risk of superficial or deep infection after lumbar laminectomy with instrumented fusion. The first 128 patients had RD applied postoperatively, whereas the second population of 106 patients received SD. These dressings were used for the first 2 weeks after surgery. Other clinical, surgical, and outcome data were comparable for both groups. Three of 128 patients who underwent multilevel laminectomies with instrumented fusions receiving RD developed deep postoperative wound infections (culture confirmed). All were successfully managed with 6 weeks of postoperative antibiotics, and none required secondary surgery. In addition, 11 patients who had RD developed superficial infection/irritation; 7 required oral antibiotics (7-10 days) alone, whereas 4 were referred to plastic surgeons for superficial wound revision. Alternatively, there were neither deep nor superficial wound infections/irritation among the 106 patients who received SD. Although the number of cases in each series was small, there appeared to be a positive trend toward a reduction in postoperative wound infection using SD. Use of SD for application on lumbar wounds after laminectomies with instrumented fusions appeared to limit/reduce the incidence of both postoperative deep and superficial wound infections.


Improving brain and vascular health at the population level: Lessons from the Norwegian success story.
Stroke, dementia and ischemic heart disease are a triple threat which combined are the leading causes of death and disability globally. Fortunately, the three diseases share similar risk factors along the vascular cascade which can be targeted for primordial and primary prevention. In Norway, during 1990-2019, the age-standardised incidence rates decreased significantly for dementia by -5.4%, ischemic heart disease by -30.0%, and stroke by -35.3%. This was possible because Norway ensured equitable income for her citizens, and committed sufficient funds to universal health coverage while implementing a semi-decentralized and responsive health system with robust primary health care. This included monitoring the burden of the triple threat and their cardinal risk factors; ensuring primordial, primary and secondary preventive interventions; implementing acute care for ischemic heart disease and stroke; and ensuring interdisciplinary rehabilitation and chronic care for the triple threat. Overall, all countries will need to develop national strategies for combating the triple threat within the context of sustainable development goals with adequate allocation and utilization of resources.


Erysipelothrix rhusiopathiae Endocarditis in a Patient With Severe Unicuspid Aortic Valve Damage Complicated With Acquired Ventricular Septal Defect.
Erysipelothrix rhusiopathiae, is an important animal pathogen, but rarely reported in humans. To date, only fa ew cases of infective E rhusiopathiae endocarditis of the aortic valve have been described. We introduce the first reported case of severe damage of the native unicuspid aortic valve complicated with acquired ventricular septal defect caused by E rhusiopathiae endocarditis. This case may provide a better understanding of the disease process and transmission and underscores the need to include this pathogen in the differential diagnosis of infective endocarditis.


Anatomical specificity of vascular endothelial growth factor expression in glioblastomas: a voxel-based mapping analysis.
The expression of vascular endothelial growth factor (VEGF) is a common genetic alteration in malignant gliomas and contributes to the angiogenesis of tumors. This study aimed to investigate the anatomical specificity of VEGF expression levels in glioblastomas using voxel-based neuroimaging analysis. Clinical information, MR scans, and immunohistochemistry stains of 209 patients with glioblastomas were reviewed. All tumor lesions were segmented manually and subsequently registered to standard brain space. Voxel-based regression analysis was performed to correlate the brain regions of tumor involvement with the level of VEGF expression. Brain regions identified as significantly associated with high or low VEGF expression were preserved following permutation correction. High VEGF expression was detected in 123 (58.9 %) of the 209 patients. Voxel-based statistical analysis demonstrated that high VEGF expression was more likely in tumors located in the left frontal lobe and the right caudate and low VEGF expression was more likely in tumors that occurred in the posterior region of the right lateral ventricle. Voxel-based neuroimaging analysis revealed the anatomic specificity of VEGF expression in glioblastoma, which may further our understanding of genetic heterogeneity during tumor origination. This finding provides primary theoretical support for potential future application of customized antiangiogenic therapy.


Industry experiences with immune-mediated findings in biotherapeutic nonclinical toxicology studies.
With the growth of monoclonal antibodies and other proteins as major modalities in the pharmaceutical industry, there has been an increase in pharmacology and toxicity testing of biotherapeutics in animals. Animals frequently mount an immune response to human therapeutic proteins. This can result in asymptomatic anti-drug antibody formation, immune complexes that affect drug disposition and/or organ function such as kidney, cytokine release responses, fatal hypersensitivity, or a range of reactions in between. In addition, an increasing number of oncology therapeutics are being developed that enhance or directly stimulate immune responses by a variety of mechanisms, which could increase the risk of autoreactivity and an autoimmune-like syndrome in animals and humans. When evaluating the risk of biotherapeutics prior to entering the clinic, the nonclinical safety data may include any of these responses and it is critical to understand whether they represent a safety liability for humans. The DruSafe Leadership group of the IQ Consortium conducted a survey of industry to understand sponsors' experiences with these immune reactions in nonclinical studies related to both immunogenicity and pharmacologically-mediated immune perturbations. The survey covered what pathways were affected, how the immune responses were presented, how the company and health authorities interpreted the data and whether the immune responses were observed in the clinic. Additionally, the survey gathered information on association of these findings with anti-drug antibodies as well as sponsor's use of immunogenicity predictive tools. The data suggests that the ability of a biotherapeutic to activate the immune system, intended or not, plays a significant role on characteristics of the response and whether theys are translatable.


Grenfell Tower fire - a tragic case study in health inequalities.
At least 80 people died in the recent Grenfell Tower fire in Kensington and Chelsea, West London. This incident has provoked much anger, debate and reflection on how such a tragedy could happen in London, one of the richest cities in the world. Seen through a public health lens, this disaster is ultimately about social inequality in modern Britain. Kensington and Chelsea is a deeply divided community, where many billionaires and very wealthy people live cheek by jowl with poor and disenfranchised people struggling to make ends meet. It is therefore not a surprise that such a terrible incident should happen in this socially unequal setting where very stark health inequalities already exist. This paper explores some of the broader underlying factors that may have contributed to this tragedy, the political determinants of health. As these factors are linked to both general and oral health inequalities, the lessons learnt from this incident have direct relevance and salience to oral health professionals concerned about tackling social inequalities in contemporary society.


Rebamipide reduces indomethacin-induced gastric injury in mice via down-regulation of ICAM-1 expression.
Non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric mucosal injury occurs through subsequent events following free radical production derived from activated neutrophils. In this study, we hypothesized that rebamipide, a novel anti-ulcer agent, exerts a protective effect on NSAID-induced gastric injury through its antioxidant properties. The protective effect of rebamipide in a mouse model of indomethacin-induced gastric injury and mechanisms for this effect were investigated. Pre-treatment with rebamipide significantly inhibited indomethacin-induced gastric mucosal injury in mice. Gastric thiobarbituric acid reactive substances (TBARS) levels and myeloperoxidase (MPO) activity substantially increased 3 hr after indomethacin administration. These increases were significantly inhibited by pre-treatment with rebamipide. Furthermore, rebamipide pre-treatment notably decreased intercellular adhesion molecule-1 (ICAM-1) expression that was up-regulated in gastric tissue treated with indomethacin. Therefore, rebamipide may reduce indomethacin-induced gastric mucosal injuries through its antioxidant effect, which inhibits the neutrophil activation step following up-regulation of ICAM-1 expression on endothelial cells.


Chewing tobacco use among pregnant women in India: Analysis of national family health surveys.
India accounts for over 67% of chewing tobacco users globally and more than 50 million women in India chew tobacco. Chewing tobacco is documented to have negative effects on health of mother and foetus. This research was conducted to study the trends in chewing tobacco use among pregnant women in India, and identify factors associated with chewing tobacco use among pregnant women. We analyzed micro-data from two representative national surveys i.e., National Family Health Survey (NFHS)-4 (2015-16) & NFHS-5 (2019-21). A sample of 32,428 & 28,408 pregnant women were extracted from NFHS-4 & NFHS-5 respectively. Weighted prevalence and 95% confidence levels of chewing tobacco use were computed. State wide comparisons in chewing tobacco use were made. Employing binary logistic regression, adjusted odds ratios (AOR) were computed to identify factors associated with chewing tobacco use. From NFHS-4 to 5 the prevalence of chewing tobacco use among pregnant women decreased from 4.0%(95% CI = 3.9-4.0) to 2.3%(95% CI = 2.2-2.4) respectively indicating a relative reduction of 42.5%. The highest prevalence remains to be in north-eastern India at 13.0%. Belonging to north-eastern region AOR = 7.0(95 %CI = 6.2-7.9), no-education AOR = 13.2(95 %CI = 10.5-16.5), poorest wealth index AOR = 6.7(95 %CI = 5.6-8.0) and belonging to scheduled tribe AOR = 2.6(95 %CI = 2.4-2.9) was significantly associated with chewing tobacco use among pregnant women. From NFHS-4 to 5, chewing tobacco use during pregnancy has shifted more towards socio-economically vulnerable population. Targeted approaches with accessible and affordable tobacco cessation advice integrated to primary healthcare system are needed.


Real-time fiber-based fluorescence lifetime imaging with synchronous external illumination: A new path for clinical translation.
Time-correlated single photon counting is the "gold-standard" method for fluorescence lifetime measurements and has demonstrated potential for clinical deployment. However, the translation of the technology into clinic is hindered by the use of ultrasensitive detectors, which make the fluorescence acquisition impractical with bright lighting conditions such as in clinical settings. We address this limitation by interleaving periodic fluorescence detection with synchronous out-of-phase externally modulated light source, thus guaranteeing specimen illumination and a fluorescence signal free from bright background light upon temporal separation. Fluorescence lifetime maps are generated in real-time from single-point measurements by tracking a reference beam and using the phasor approach. We demonstrate the feasibility and practicality of this technique in a number of biological specimens, including real-time mapping of degraded articular cartilage. This method is compatible and can be integrated with existing clinical microscopic, endoscopic and robotic modalities, thus offering a new pathway towards label-free diagnostics and surgical guidance in a number of clinical applications.


Changes in cigarette smoking behavior among breast cancer and unaffected women - A prospective study in the MARIE cohort.
Smoking cessation after a cancer diagnosis can reduce adverse cancer treatment outcomes. Whether a breast cancer diagnosis, a cancer commonly seen as unrelated to smoking cigarettes, motivates changes in smoking behavior is not fully understood. We aimed to compare long-term changes at three follow-up times of cigarette smoking behavior in women with breast cancer and baseline age- and region-matched unaffected women. We used longitudinal data from the population-based case-control study MARIE (Mamma Carcinoma Risk Factor Investigation). Women with breast cancer (N = 3813) and unaffected women (N = 7341) aged 50-74 years were recruited from 2002 to 2005. Analyses on changes in smoking were based on data from those who also completed follow-up 1 in 2009-2012, follow-up 2 in 2014-2016 and follow-up 3 in 2020. Multinomial logistic regression for changes (quitting, stable, or start smoking) adjusted for age, study region, education, comorbidities, living situation, and follow-up time, was applied to examine the associations between breast cancer status and changes in smoking behavior. Women with breast cancer had significantly higher odds than unaffected women of quitting smoking (OR = 1.38, 95 % CI: 1.01-1.89) and lower odds of returning to smoking (OR = 0.29, 95 % CI: 0.09-0.94) at follow-up 1, but were more likely to start or return to smoking at follow-up 2 (OR = 2.11, 95 % CI 1.08-4.15). No significant group differences were found for changes in smoking behavior at follow-up 3. Our findings indicate that short-term changes in smoking behavior can be attributed to a breast cancer diagnosis, but that over time the effect diminishes and changes in smoking no longer differ between breast cancer and breast cancer-free women. To support smoking cessation and to prevent relapse, guidelines to address smoking in cancer care, as well as comprehensive tobacco treatment services, are needed.


An epidemiological model of rinderpest. II. Simulations of the behaviour of rinderpest virus in populations.
Fixed parameters for different hypothetical strains of rinderpest virus (RV) and different susceptible populations are described together with details of their derivation. Simulations were then carried out in a computer model to determine the effects that varying these parameters would have on the behaviour of RV in the different populations. The results indicated that virulent strains of RV are more likely to behave in epidemic fashion whereas milder strains tend towards persistence and the establishment of endemicity. High herd immunity levels prevent virus transmission and low herd immunity levels encourage epidemic transmission. Intermediate levels of immunity assist the establishment of endemicity. The virus is able to persist in large populations for longer than in small populations. Different vaccination strategies were also investigated. In areas where vaccination is inefficient annual vaccination of all stock may be the best policy for inducing high levels of herd immunity. In endemic areas and in herds recovering from epidemics the prevalence of clinically affected animals may be very low. In these situations veterinary officers are more likely to find clinical cases by examining cattle for mouth lesions rather than by checking for diarrhoea or high mortalities.


Korean Red Ginseng increases defective pol gene in peripheral blood mononuclear cells of HIV-1-infected patients; inhibition of its detection during ginseng-based combination therapy.
We have reported that defective nef and gag genes are induced in HIV-1-infected patients treated with Korean Red Ginseng (KRG). To investigate whether KRG treatment and highly active antiretroviral therapy (HAART) affect genetic defects in the pol gene, we amplified and sequenced a partial pol gene (p-pol) containing the integrase portion (1.2 kb) by nested PCR with sequential peripheral blood mononuclear cells over 20 years and compared it with those patients at baseline, in control patients, those taking ginseng-based combination therapy (GCT; KRG plus combinational antiretroviral therapy) and HAART alone. We also compared our findings to look for the full-length pol gene (pol) (3.0-kb). Twenty-patients infected with subtype B were treated with KRG for 116 ± 58 months in the absence of HAART. Internal deletion in the pol gene (Δpol) was significantly higher in the KRG group (11.9%) than in the control group and at baseline; its detection was significantly inhibited during GCT as much as during HAART. In addition, the Δpol in p-pol significantly depended on the duration of KRG treatment. In pol, the proportion of Δpol was significantly higher in the KRG group (38.7%) than in the control group, and it was significantly inhibited during GCT and HAART. In contrast, the proportion of stop codon appeared not to be affected by KRG treatment. The PCR success rate was significantly decreased with longer GCT. The proportion of Δpol depends on template size as well as KRG treatment. HAART decreases the detection of Δpol.


Endometrioma and oocyte retrieval-induced pelvic abscess: a clinical concern or an exceptional complication?
The authors evaluated the risk of developing a pelvic abscess in a series of 214 in vitro fertilization cycles that were performed in women with endometriomas. This complication was never recorded, indicating that its risk is very low (0.0; 95% confidence interval, 0.0-1.7%).


Actions of sulpiride and tiapride in a simple model of anxiety in mice.
A two-compartment activity box is described in which the actions of anxiolytic compounds may be readily detected. The box is designed with a partition which divides a dimly-lit black area and a brightly-illuminated white area. Free access to each section is enabled by means of a small opening in the partition. Measures of locomotion and rearing are recorded as well as transitions from black to white and vice versa. Time spent in each section is also measured. In this situation mice demonstrated a clear preference for the dim black section, a finding not inconsistent with the nocturnal nature of this species. By contrast, treatment with diazepam (0.125-5 mg/kg) or triazolam (0.01-0.1 mg/kg) produced a significant increase in activity in the white section. Locomotion and rearing in the black section showed a corresponding decrease. Sulpiride (0.5-20 mg/kg) and tiapride (0.5-40 mg/kg) had similar effects. These actions would appear to be independent of their effects on general activity, as amphetamine (1.25-2.5 mg/kg) increased and haloperidol (0.05-0.2 mg/kg) decreased overall exploratory behaviour in a non-selective manner. These data suggest the "two-compartment activity box" to be a model sensitive to the actions of clinically-active anxiolytics.


Markers of hypercoagulability in children with newly diagnosed acute lymphoblastic leukemia.
Venous thromboembolism (VTE) is a known complication for children with acute lymphoblastic leukemia (ALL). The aim of this study was to identify laboratory biomarkers that predict which children with ALL are at risk for VTE during induction chemotherapy. Newly diagnosed ALL patients admitted to Children's Hospital Los Angeles with a central venous catheter (CVC) were eligible to participate. Participants' blood samples (complete blood count [CBC], quantitative D-dimer, prothrombin fragment 1.2 [PTF 1.2], and thrombin-antithrombin complexes [TAT]) were collected at day 0 (baseline/prior to induction), day 7 (±2 days), day 14 (±2 days), day 21 (±2 days), and day 28 (±2 days) of induction chemotherapy or until participants presented with a symptomatic VTE. Seventy-five participants aged 1-21 years were enrolled and included in the final analysis. Twenty-six (35%) of the 75 participants were diagnosed with a CVC-associated VTE (22 asymptomatic and four symptomatic). There was a statistically significant difference between VTE and non-VTE participants for D-dimer (odds ratio [OR] 1.61, 95% confidence interval [CI]: 1.59-1.64), TAT (OR 1.34, 95% CI: 1.32-1.38), and PTF 1.2 (OR 1.31, 95% CI: 1.25-1.37) at all time points. Participants >10 years had a significantly higher risk of developing a VTE compared to participants <4 years (p = .007). Older children with ALL as well as those with an elevated TAT, PTF 1.2, or D-dimer showed an increased risk of VTE, which may hold potential for predicting VTE in future studies.


Pharmacists views on participating in New Zealand's community pharmacy anticoagulation management service: a mixed-methods study.
Background Optimal anticoagulation management is key for improving outcomes. The Community Pharmacy Anticoagulation Management Service (CPAMS) has beneficial effects on anticoagulant management. However, limited research exists on pharmacists' views of CPAMS provision, particularly the perspectives of pharmacists who do not provide CPAMS. Objectives To explore the experience and attitudes of pharmacists who do and do not provide CPAMS, and to identify factors that may influence further uptake of CPAMS. Setting CPAMS providing and non-providing pharmacies throughout New Zealand. Methods A mixed-methods study design was employed. Separate online surveys were conducted with CPAMS providers (N = 35) and non-providers (N = 73) to explore their views on the service. Twelve interviews were conducted with purposively selected participants, equally distributed between CPAMS providers and non-providers, to gain further insight into the issues surrounding CPAMS provision. Quantitative data were analysed using student's t-test and Mann Whitney U-test, and thematic analysis was used for qualitative data. Main outcome measure Experiences of and attitudes towards CPAMS. Results Our survey findings demonstrated that community pharmacists have high self-efficacy and motivation to providing CPAMS, and CPAMS had increased job satisfaction amongst providers. The overwhelming majority of CPAMS providers' survey participants believed that CPAMS improves the pharmacist-patient relationship, allowing them to assist patients with other aspects of their healthcare. Most non-provider survey participants also believed that their patients would benefit from CPAMS. The two most frequently reported barriers by non-providers survey participants were remuneration and staffing of pharmacists. The interview findings fell within five overarching themes: self-efficacy, CPAMS benefits to patients, barriers to providing CPAMS, the impact of CPAMS on pharmacist-patient and pharmacist-general practitioner relationships. Overall, the current funding model, the capping on the number of enrolled patients, and staffing were the main factors perceived by interview participants preventing the further uptake and implementation of CPAMS. CPAMS non-providers are willing to provide CPAMS; the main factor preventing this is availability of contracts. Conclusions Overall, pharmacists have favourable experiences of and attitudes towards CPAMS and strongly supported its wider implementation. Promoting the benefits and addressing the barriers highlighted in this study may lead to wider implementation of CPAMS.


Positive gallium-67 scintigraphy associated with pulmonary embolism.
A 54-year-old man presenting with symptoms and signs of pulmonary embolism demonstrated gallium-67 accumulation within the right lower lung field in the region of a pulmonary embolism with effusion. An associated infectious process was ruled out. This is contrary to the usual clinical experience and identifies a potential pitfall in the use of gallium-67 as an aid in the differential diagnosis of pulmonary embolism and pneumonitis.


Steady-state pharmacokinetics of rivastigmine in patients with mild to moderate Alzheimer's disease not affected by co-administration of memantine: an open-label, crossover, single-centre study.
It has been shown that combining memantine and a cholinesterase inhibitor, which each affect different neurotransmitter systems, may offer further improvements in efficacy over either treatment alone in patients with Alzheimer's disease. The present study was conducted to determine if memantine has any effects on the steady-state pharmacokinetics of rivastigmine in patients with mild to moderate Alzheimer's disease. Rivastigmine-treated Alzheimer's disease patients who had been maintained on a fixed regimen of twice-daily rivastigmine for >or=2 months were eligible to enter the study. Sixteen patients (seven males and nine females, age range 64-88 years, weight range 51.8-104 kg) were enrolled in this open-label, crossover study, which consisted of a 28-day screening period, a 36-hour baseline period, and a 35-day combination treatment phase. The patients spent the baseline period and day 35 at the study centre, where plasma samples for pharmacokinetic evaluation were taken at specified time intervals over a 10-hour time period. In addition, 10-hour (evening pre-dose) memantine plasma samples were taken on days 21, 34 and 35. The combination of memantine (10 mg twice daily) with rivastigmine (1.5-6 mg twice daily) was safe and well tolerated. At each dose level of rivastigmine, the area under the concentration-time curve (AUC) values of rivastigmine and its metabolite as well as the metabolite-to-parent AUC ratios were unaffected by co-administration of memantine, confirming the absence of a meaningful pharmacokinetic drug-drug interaction. Under the study conditions, the extent of systemic exposure to rivastigmine and its metabolite NAP226-90 at steady state did not appear to be affected by concomitant administration of memantine.


Comparison of the properties of CLCA1 generated currents and I(Cl(Ca)) in murine portal vein smooth muscle cells.
Calcium-activated chloride currents (I(Cl(Ca))) have been recorded in various smooth muscle cells but, to date, there has been no information as to the molecular nature of the channel underlying this conductance. We have characterised native I(Cl(Ca)) in freshly dispersed smooth muscle cells isolated from murine portal vein using whole-cell voltage clamp. I(Cl(Ca)) exhibited time-dependent activation at depolarised potentials and rapid deactivation upon repolarisation. The reversal potential of I(Cl(Ca)) was close to the theoretical equilibrium potential (E(Cl)) and was shifted by replacement of external Cl- by SCN- or isethionate. Dithiothreitol (DTT, 1 mM), a blocker of CLCA1, had no effect on the I(Cl(Ca)) current in myocytes. RT-PCR demonstrated the expression of mCLCA1 transcripts, but not mCLCA3 transcripts, in various murine smooth muscle cells including portal vein, as well as cardiomyocytes, and the levels of mCLCA1 transcriptional expression were quantified by real time quantitative RT-PCR. Stable transfection of HEK293 cells with the cDNA encoding mCLCA1 cloned from murine portal vein smooth muscle yielded a current with notable differences in Ca2+ sensitivity, channel kinetics and modulation by DTT from the native I(Cl(Ca)). However, there was some similarity in the pore properties and these data suggest that mCLCA1 alone does not comprise the Cl- channel in portal vein smooth muscle cells.


Structural studies of cell surface and secreted IgG in LPS-stimulated murine B cells.
We have characterized the cell surface IgG of LPS-stimulated B lymphocytes by surface iodination and specific immunoprecipitation. IgG3 was found to be the predominant IgG subclass expressed on the B cell surface after 5 days of stimulation with LPS. In contrast, IgG2b, IgG3, and IgG1 subclasses are all secreted. Cell surface IgG exhibits detergent binding characteristics not shown by secreted IgG and the gamma chains of the three subclasses of surface IgG examined have the apparent mol. wt of 64 Kd, some 9,000 larger than the H chains of secreted IgG.


Investigations of Shape Deformation Behaviors of the Ferromagnetic Ni-Mn-Ga Alloy/Porous Silicone Rubber Composite towards Actuator Applications.
Ferromagnetic shape memory alloys (FSMAs), which are potential candidates for future technologies (i.e., actuators in robots), have been paid much attention for their high work per volume and rapid response as external stimulation, such as a magnetic field, is imposed. Among all the FSMAs, the Ni-Mn-Ga-based alloys were considered promising materials due to their appropriate phase transformation temperatures and ferromagnetism. Nevertheless, their intrinsic embrittlement issue and sluggish twin motion due to the inhibition of grain boundaries restrict their practicability. This study took advantage of the single-crystal Ni-Mn-Ga cube/silicone rubber composite materials to solve the two aforementioned difficulties. The single-crystal Ni-Mn-Ga cube was prepared by using a high-temperature alloying procedure and a floating-zone (FZ) method, and the cubes were verified to be the near-{100}p Ni-Mn-Ga alloy. Various room temperature (RT) curing silicone rubbers were utilized as matrix materials. Furthermore, polystyrene foam particles (PFP) were used to provide pores, allowing a porous silicone rubber matrix. It was found that the elastic modulus of the silicone rubber was successfully reduced by introducing the PFP. Additionally, the magnetic field-induced martensite variant reorientation (MVR) was greatly enhanced by introducing a porous structure into the silicone rubber. The single-crystal Ni-Mn-Ga cube/porous silicone rubber composite materials are considered to be promising materials for applications in actuators.


MCL1 provides a window on the role of the BCL2 family in cell proliferation, differentiation and tumorigenesis.
The MCL1 gene (myeloid cell leukemia-1) was discovered serendipitously about a decade ago and proved to be a member of the emerging BCL2 gene family. Ongoing studies of this gene provide an interesting perspective on the role of the BCL2 family in transitions in cell phenotype. Specifically, gene products that influence cell viability as a major effect (eg MCL1, BCL2 and other family members) can act as key determinants in cell proliferation, differentiation and tumorigenesis. Although they do not have a direct role in proliferation/differentiation programs, these genes can either permit these programs to proceed or prevent them. Through such effects, the BCL2 family regulates the normal flow of cells through cycles of proliferation and along various pathways of differentiation. A model is presented suggesting that this is accomplished by sustaining or inhibiting viability at critical points in the cell lifecycle. These critical points represent windows of time during which cell fate transitions are effected. They can also be visualized as windows that open or close to promote or prevent continued progression along various cell fate pathways. The pattern of BCL2 family expression at these points allows for the proliferation differentiation, and continued viability of cell types that are needed, while aborting these processes for cells that are overabundant or no longer needed. The combined action of the various family members can therefore control the fate of cells, tissues and even the organism. This mechanism involving apoptosis-related genes is readily executable, and is poised to respond to external signals through the differential regulation of BCL2 family members. As such, it plays an important role in the maintenance of tissue homeostasis and function. Alterations that affect the BCL2 family impair the capacity to control the flow of cells through these critical points, and thereby 'leave the window open' for cell immortalization and cancer. Targeting this family may thus provide a means of inhibiting cancer development and inducing apoptosis in tumor cells.


Does stronger pollen competition improve offspring fitness when pollen load does not vary?
Competition among pollen grains from a single donor is expected to increase the quality of the offspring produced because of the recessive deleterious alleles expressed during pollen-tube growth. However, evidence for such an effect is inconclusive; a large number of studies suffer from confounding variation in pollen competition with variation in pollen load. In this study, we tested the effect of pollen competition on offspring performance independently of pollen-load variation. We compared seed mass and early seedling performance in Dalechampia scandens (Euphorbiaceae) between crosses in which variation in pollen competition was achieved, without variation in pollen load, by manipulating the dispersion of pollen grains on the stigmas. Despite a large sample size (211 crosses on 20 maternal plants), we failed to find an effect of pollen competition on seed characteristics or early seedling performance. Paternal effects were always limited, and pollen competition never reduced the within-father (residual) variance. These results suggest that limited within-donor variation in genetic quality of pollen grains reduces the potential benefits of pollen competition in the study population. The lack of paternal effects on early sporophyte performance further suggests that benefits of pollen competition among pollen from multiple donors should be limited as well, and it raises questions about the significance of pollen competition as a mechanism of sexual selection.


"My critical filter buffers your app filter": Social media literacy as a protective factor for body image.
Exposure to idealized appearance images on social media is recognized as having a damaging effect on body image. Identifying and harnessing protective factors are, therefore, important research foci. Building on traditional media literacy concepts, one proposed protective factor is social media literacy, that is, the application of a critical analysis of motivations behind social media posts and the constructed, generally unrealistic nature of images, when viewing appearance-focused images on social media. This article describes theoretical models of social media literacy and current measurement approaches. In addition, it examines empirical support for a protective role for social media literacy, before considering directions for future research. It was concluded that, although there is still much that needs to be understood, there is modest preliminary support for a protective role for social media literacy, especially in girls and young women.


Role of epidermal growth factor and its receptor in mechanical stress-induced differentiation of human periodontal ligament cells in vitro.
The periodontal ligament (PDL) contains precursor cells for osteoblasts and cementoblasts. It has been shown that epidermal growth factor (EGF) inhibits dexamethasone-induced differentiation and up-regulates EGF-receptor (EGF-R) expression, whereas EGF-R is down-regulated in the course of differentiation. Thus it was suggested that EGF and its receptors act as a negative regulator of osteoblastic differentiation in PDL cells. In order to investigate further this hypothesis, human PDL cells were now used to elucidate the role of EGF and EGF-R in their proliferation and differentiation under mechanical stress-loaded conditions in vitro, as the PDL regularly receives mechanical stress from occlusal forces. As a model of mechanical stress, a cyclic stretch of 9 or 18% elongation was applied to the cells with a Flexercell cell-strain unit system. Alkaline phosphatase activity and osteocalcin mRNA expression were significantly induced by loading cyclic stretch for more than 4 days, whereas stretch slightly inhibited cell proliferation. Visualization of the actin stress fibres of the cells by rhodamine phalloidin revealed that approx. 10% of the total number of cells had become aligned perpendicularly to the direction of the stretch. The effects of stretch on alkaline phosphatase activity and cell proliferation were totally abolished by the presence of 10 ng/ml EGF. Western blotting of EGF-R protein demonstrated that stretch-induced differentiation accompanied the decreased expression of EGF-R protein in the cells. However, the amount of tyrosine-phosphorylated EGF-R upon EGF stimulation was restored to the control level in stretched cells. These results suggest that the EGF/EGF-R system acts as a negative regulator of differentiation of PDL cells regardless of the type of differentiation stimuli. Also, interaction between mechanical stress and the EGF/EGF-R system may participate in the osteoblastic differentiation of PDL cells and thereby regulate the source of cementoblasts and osteoblasts.


Moderate hypothermia alters interleukin-6 and interleukin-1alpha reactions in ischemic brain in mice.
Female C57BL/6 mice were decapitated and their brains were removed and cultured at either 37 or 33 degrees C for 48 h to investigate whether or not moderate hypothermia alters the cytokine reactions in the ischemic brain. The interleukin-6 and interleukin-1alpha levels in the culture media were significantly elevated in a time-dependent manner. The interleukin-6 levels after the incubation at 33 degrees C were significantly lower than those at 37 degrees C. The interleukin-1alpha levels at 33 degrees C were significantly higher than those at 37 degrees C. The interleukin-1alpha levels incubated with interleukin-6 antibody were significantly higher than those without IL-6 antibody. At 37 degrees C, the mRNA expression of interleukin-6 was observed from 2 to 48 h after incubation, but the same expression of interleukin-1alpha was only detected until 12 h. Accordingly, the ischemic brain incubated at 33 degrees C showed a decreased interleukin-6 production in comparison with that at 37 degrees C and the level of interleukin-6 showed negative feedback for the production of interleukin-1alpha. The temperature should, therefore, be carefully considered when evaluating the cytokine reaction for cerebral ischemia.


Anti-diabetic activity of a sulfated galactoarabinan with unique structural characteristics from Cladophora oligoclada (Chlorophyta).
The polysaccharide from green alga Cladophora oligoclada, OHSS2, was a sulfated galactoarabinan which was constituted by a backbone of (1 → 4)-β-l-arabinopyranose units with partial sulfate at C-3 of (1 → 4)-β-l-arabinopyranose units. The side chains containing (1 → 4)-β-l-arabinopyranose, (1 → 4)-β-d-galactopyranose and/or (1 → 4,6)-β-d-galactopyranose units were in C-2/C-3 of (1 → 4)-β-l-arabinopyranose units. OHSS2 had strong anti-diabetic activity in vitro assessed by inhibition of human islet amyloid polypeptide (hIAPP) aggregation. The mechanism analysis of anti-diabetic activity showed that OHSS2 diminished the production of intracellular reactive oxygen species and alleviated hIAPP aggregation-induced oxidative stress in NIT-1 cells. OHSS2 stabilized mitochondrial membrane potential, and enhanced the mitochondrial complex I, II or III activity and ATP level. Thus, OHSS2 effectively protected mitochondria from hIAPP aggregation-induced damage. Furthermore, OHSS2 was co-localized with mitochondria and could have a direct influence on mitochondrial function. These results revealed that OHSS2 had potential as a novel anti-diabetic agent.


Usefulness and Safety Evaluation of Chemotherapy Administration Device for Nurses: Experimental Study.
Antineoplastic drugs are considered high risk, and computerized systems favor safe administration. The objective of the study was to test the usefulness and safety of a new mobile device compared to the standard device for administering these antineoplastic treatments. This multicenter, quasi-experimental pre-post study assessed an intervention in two cancer centers in June and July 2020. Nineteen nurses participated by completing 57 questionnaires. The outcome variables were usefulness, ease of use, efficiency, safety, attitudes, and satisfaction with the new mobile device; they were measured by means of the USE questionnaire (Usefulness, Satisfaction, and Ease of use) and the Technology Attitude Survey (TAS). Professionals rated the new device higher than the standard device and showed a favorable attitude toward technology. The tested device was useful, effective, safe, and specific to the antineoplastic treatment administration process, garnering greater satisfaction among professionals than the standard. As new technologies can improve care for patients with cancer, it is essential to develop strategies to improve the experience of professionals for optimal implementation.


Using 3dRNA/DNA for RNA and DNA 3D Structure Prediction and Evaluation.
This article describes how to use 3dRNA/DNA to predict RNA and DNA 3D structures from their sequences and secondary (2D) structures. The predicted RNA and DNA 3D structures can be used to predict or understand their functions and can also be used to find the interactions between the RNA/DNA and other molecules. © 2023 Wiley Periodicals LLC. Basic Protocol: RNA/DNA 3D structure prediction using 3dRNA/DNA web server Alternate Protocol: Using 3dRNA/DNA and 3dRNAscore locally Support Protocol: Installing NSP.


Dysregulated T-Helper Type 1 (Th1):Th2 Cytokine Profile and Poor Immune Response in Pregnant Ferrets Infected With 2009 Pandemic Influenza A(H1N1) Virus.
Pregnancy has been associated with severe influenza, an association highlighted during the 2009 pandemic of influenza A(H1N1) virus (A[H1N1]pdm09) infection. To assess the underlying mechanism, we infected pregnant and non-pregnant ferrets with A(H1N1) pdm09 virus. A(H1N1)pdm09-infected pregnant ferrets also had higher levels of inflammatory cytokines in their pulmonary tracts. Systemically, total CD8+ T cell counts and A(H1N1)pdm09-specific B-cell responses in blood were significantly lower in pregnant ferrets. This model predicts that the poorer outcome for pregnant women during the A(H1N1)pdm09 pandemic was due to an elevated level of viral replication and to a cytokine imbalance that led to a less effective immune response.


[Hemostasis in burn patients and treatment with heparin. Relation to prognosis and infection. Pattern of blood levels of prekallikrein, alpha-2-macroglobulin, antithrombin III, plasminogen and alpha-2-antiplasmin].
In burnt patients with a fatal prognosis, the level of prekallikrein is initially low and further diminished. In burnt patients who survive, the initial decrease of the prekallikrein level is less pronounced and is progressively overcome, significantly by the sixth day. Moreover the decrease of the prekallikrein level occurs before and during clinical infection. In good prognosis patients, the level of alpha-2-macroglobulin remains low until day 20 and then increases in the noninfected patients while in fatal prognosis patients the level decreases. The level of antithrombin III and plasminogen is lower in fatal prognosis patients. These is no correlation between the level of antiplasmin and the outcome of burn injuries.


Topical versus oral antibiotics, with or without corticosteroids, in the treatment of tympanostomy tube otorrhea.
Antibiotic treatment is the standard of care for tympanostomy tube otorrhea. This meta-analysis aims to evaluate the efficacy of topical antibiotics with or without corticosteroids versus oral antibiotics in the treatment of tube otorrhea in children. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and ProQuest. The above databases were searched using a search strategy for randomized controlled trials for optimal treatment of tube otorrhea in the pediatric population. PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines were followed. Primary outcome was cure (i.e. clearance of otorrhea) at 2-3 weeks. Secondary outcomes were microbiological eradication and complications such as dermatitis and diarrhea. The incidence of these events was defined as dichotomous variables and expressed as a risk ratio (RR) and number needed to benefit (NNTB) in a random-effects model. We identified 1491 articles and selected 4 randomized controlled trials which met our inclusion criteria. Topical treatment had better cure (NNTB = 4.7, pooled RR = 1.35, p < 0.001) and microbiological eradication (NNTB = 3.5, pooled RR = 1.47, p < 0.001 among 3 of the studies) than oral antibiotics. Oral antibiotics had higher risk of diarrhea (pooled RR = 21.5, 95% CI 8.00-58.0, p < 0.001, Number needed to harm (NNTH) = 5.4) and dermatitis (pooled RR = 3.14, 95% CI 1.20-8.20, p = 0.019, NNTH = 32). The use of topical steroids in addition to topical antibiotics was associated with a higher cure rate (pooled RR = 1.59, p < 0.001 vs pooled RR = 1.57, p = 0.293). Topical antibiotics should be the recommended treatment for management of tympanostomy tube otorrhea in view of its significantly improved clinical and microbiological efficacy with lower risk of systemic toxicity as compared to oral antibiotics. Further research is necessary to confirm the benefits of topical corticosteroids as an adjunct to topical antibiotics.


Cerebral lateralization of haptic perception: interaction of responses to Braille and music reveals a functional basis.
Normally, haptic perception of the left hand surpasses that of the right. But simultaneously playing music into the left (but not the right) ear reverses this superiority. This suggests that the left cerebral hemisphere has full haptic perceptual capability, which is subject to right hemisphere interference unless the latter's attentional mechanisms are engaged by contralateral peripheral stimulation.


DIEER: Delay-Intolerant Energy-Efficient Routing with Sink Mobility in Underwater Wireless Sensor Networks.
Underwater Wireless Sensor Networks (UWSNs) are an enabling technology for many applications in commercial, military, and scientific domains. In some emergency response applications of UWSN, data dissemination is more important, therefore these applications are handled differently as compared to energy-focused approaches, which is only possible when propagation delay is minimized and packet delivery at surface sinks is assured. Packet delivery underwater is a serious concern because of harsh underwater environments and the dense deployment of nodes, which causes collisions and packet loss. Resultantly, re-transmission causes energy loss and increases end-to-end delay ( D E 2 E ). In this work, we devise a framework for the joint optimization of sink mobility, hold and forward mechanisms, adoptive depth threshold ( d t h ) and data aggregation with pattern matching for reducing nodal propagation delay, maximizing throughput, improving network lifetime, and minimizing energy consumption. To evaluate our technique, we simulate the three-dimensional (3-D) underwater network environment with mobile sink and dense deployments of sensor nodes with varying communication radii. We carry out scalability analysis of the proposed framework in terms of network lifetime, throughput, and packet drop. We also compare our framework to existing techniques, i.e., Mobicast and iAMCTD protocols. We note that adapting varying d t h based on node density in a range of network deployment scenarios results in a reduced number of re-transmissions, good energy conservation, and enhanced throughput. Furthermore, results from extensive simulations show that our proposed framework achieves better performance over existing approaches for real-time delay-intolerant applications.


Acute intestinal pseudo-obstruction (Ogilvie's syndrome) complicating radical retropubic prostatectomy.
We report 3 cases of acute colonic pseudo-obstruction in the immediate post-radical retropubic prostatectomy patient. We have not found this syndrome reported in this clinical setting, and suggest that it results from an imbalance in the autonomic innervation of the distal colon secondary to noxious afferent parasympathetic stimulation from the region of the prostate gland. Treatment guidelines are summarized stressing early recognition and conservative management of this potentially fatal complication.


⁹⁹mTc-(Me)FGCDEVD, a potential tracer for apoptosis detection.
(Me)FGC(Bz)DEVD was radiolabeled with technetium-99m in high yield. This tracer was preferentially accumulated in apoptotic cells in the in vitro studies. Tumor uptake occurred in vivo after cisplatin injection due to the apoptosis induction, which not observed in the untreated tumors. Therefore, (99m)Tc-(Me)FGCDEVD is a potential tracer for apoptosis detection.


Ultra-late antibody-mediated rejection 30 years after a living-related renal allograft.
Antibody-mediated renal allograft rejection has become increasingly recognized and more clearly defined through the use of flow cytometry cross-matching and the deposition of C4d in renal allograft biopsies. All of the cases reported thus far have developed an antibody within 10 years of transplantation, and many lacked HLA and/or donor specificity. The present patient developed an anti-HLA donor-specific antibody between the 22nd and 30th year after a living-related renal transplant. At the 30th year post-transplantation, she experienced a rise in the serum creatinine from 0.7 to 1.9 mg/dL associated with transplant biopsy C4d deposition in peritubular capillaries and glomeruli. After the replacement of azathioprine with mycophenolate mofetil, and six apheresis treatments followed by two infusions of IVIG, the renal function stabilized at 1.9 mg/dL, 33 years after transplantation. Antibody-mediated rejection must be considered as a possible cause or renal allograft dysfunction at all time periods after transplantation.


Critical appraisal of intra-articular glucocorticoid injections for symptomatic osteoarthritis of the knee.
Intra-articular (IA) injections of glucocorticoids (GCs) have been shown to decrease pain, increase mobility, and improve quality of life in patients with osteoarthritis (OA) of the knee. Concerns about cartilage loss with IA GCs have prompted reconsideration of their use in knee OA. This review has three objectives: 1) critically review the clinical, molecular, and structural effects of IA GCs in knee OA; 2) provide a design for a clinical trial aimed at improving our understanding of the long-term consequences of IA GCs; and 3) provide practical guidance on the use of IA GCs in patients with knee OA based on current information. A narrative review of current literature on the use of IA GCs for OA of the knee. Important questions remain to be fully answered with respect to IA GCs, including long-term effects on all aspects of the structural and molecular environment of the knee, and identification of factors that can reliably predict a positive or negative response to IA GCs. While awaiting results from an appropriately designed study, several provisional statements regarding IA GCs can be put forward: 1) IA GCs appear to be a relatively safe option that is effective in specific patients with symptomatic knee OA; 2) there is no definitive evidence that IA GCs accelerate joint deterioration to an important extent or hastens the requirement for knee replacement; and 3) there are few contraindications to IA GCs and injection-associated complications are rare when IA GCs are delivered with proper technique.


Structural investigation of the antibiotic ristomycin A. 13C-NMR spectral analysis of the interglycosidic linkages of the heterotetrasaccharide side-chain.
By 13C-NMR studies on Ia, IIa, IIb and IVa obtained by the chemical degradation of ristomycin A and on several synthetic model compounds it has been proved that an O-beta-D-arabinopyranosyl-(1 leads to 2)-O-alpha-D-mannopyranosyl-(1 leads to 2)-O-[alpha-L-rhamnopyranosyl-(1 leads to 6)]-D-glucopyranosyl heterotetrasaccharide moiety is connected to the aglycone of the antibiotic.


Anaerobic digestion of wheat straw--performance of continuous solid-state digestion.
In this study the upflow anaerobic solid-state (UASS) reactor was operated at various conditions to optimize the process parameters for anaerobically digesting wheat straw in a continuous process. Additionally, particle size effects have been studied in the operation at 55 and 60°C. Moreover, the incremental effect of the organic loading rate (OLR) to the system was examined from 2.5 to 8 gVS L(-1) d(-1). It was found that the UASS operating at 60 °C with a small OLR yields highest methane production, but the advantage over thermophilic operation is negligible. The rise in OLR reduces the systems yields, as expected. From OLR=8 gVS L(-1) d(-1) a second stage is necessary to circumvent volatile fatty acids accumulation.


Refractory atypical trigeminal neuralgia associated with reactivated herpesvirus infection: pathogenetic link and efficacy of combination antiviral therapy.
The purpose of this study is to diagnose herpesvirus infections in refractory atypical trigeminal neuralgia, to assess pathogenetic links, and to explore the efficacy of antiviral treatment. In a prospective controlled study, 95 patients with trigeminal neuralgia received antiviral therapy (valacyclovir + alpha2b-interferon) (experimental group, EG). Other patients refused to receive treatment (control group 1 (CG1), n = 31). Control group 2 (CG2) included 32 healthy individuals of the same age and sex. Herpesvirus infection was diagnosed in blood leukocytes by PCR (Biocom, Russian Federation). Serum concentrations of IgM, IgA and IgG to HSV-1/2, VZV (ELISA, Vector-Best, Russian Federation) were determined. Reactivation of herpesvirus infections was observed in the EG in 87% of cases. The heterogeneity of herpesvirus-associated damage of trigeminal nerves and anatomically related areas of the central nervous system (CNS) has been demonstrated. The treatment applied was effective for herpesvirus infection (77%) and pain (61%) and ineffective for immunity correction (26% of cases). Atypical refractory trigeminal neuralgia is associated with herpesvirus infections that reactivate due to minor immunodeficiencies. Antiviral treatment suppresses herpesviruses and reduces the intensity of pain. The online version contains supplementary material available at 10.1007/s13337-022-00769-9.


Fatty infiltration of the minor salivary glands is a selective feature of aging but not Sjögren's syndrome.
Determine the presence and assess the extent of fatty infiltration of the minor salivary glands (SG) of primary SS patients (pSS) as compared to those with non-SS sicca (nSS). Minor SG biopsy samples from 134 subjects with pSS (n = 72) or nSS (n = 62) were imaged. Total area and fatty replacement area for each glandular cross-section (n = 4-6 cross-sections per subject) were measured using Image J (National Institutes of Health, Bethesda, MD). The observer was blinded to subject classification status. The average area of fatty infiltration calculated per subject was evaluated by logistic regression and general linearized models (GLM) to assess relationships between fatty infiltration and clinical exam results, extent of fibrosis and age. The average area of fatty infiltration for subjects with pSS (median% (range) 4.97 (0.05-30.2)) was not significantly different from that of those with nSS (3.75 (0.087-41.9). Infiltration severity varied widely, and subjects with fatty replacement greater than 6% were equivalently distributed between pSS and nSS participants (χ2 p = .50). Age accounted for all apparent relationships between fatty infiltration and fibrosis or reduced saliva flow. The all-inclusive GLM for prediction of pSS versus non-SS classification including fibrosis, age, fatty replacement, and focus score was not significantly different from any desaturated model. In no iteration of the model did fatty replacement exert a significant effect on the capacity to predict pSS classification. Fatty infiltration is an age-associated phenomenon and not a selective feature of Sjögren's syndrome. Sicca patients who do not fulfil pSS criteria have similar rates of fatty infiltration of the minor SG.


Converse magneto-electric effects in a core-shell multiferroic nanofiber by electric field tuning of ferromagnetic resonance.
This report is on studies directed at the nature of magneto-electric (ME) coupling by ferromagnetic resonance (FMR) under an electric field in a coaxial nanofiber of nickel ferrite (NFO) and lead zirconate titanate (PZT). Fibers with ferrite cores and PZT shells were prepared by electrospinning. The core-shell structure of annealed fibers was confirmed by electron- and scanning probe microscopy. For studies on converse ME effects, i.e., the magnetic response of the fibers to an applied electric field, FMR measurements were done on a single fiber with a near-field scanning microwave microscope (NSMM) at 5-10 GHz by obtaining profiles of both amplitude and phase of the complex scattering parameter S11 as a function of bias magnetic field. The strength of the voltage-ME coupling Av was determined from the shift in the resonance field Hr for bias voltage of V = 0-7 V applied to the fiber. The coefficient Av for the NFO core/PZT shell structure was estimated to be - 1.92 kA/Vm (- 24 Oe/V). A model was developed for the converse ME effects in the fibers and the theoretical estimates are in good agreement with the data.


Improvement in the bioreactor specific productivity by coupling continuous reactor with repeated fed-batch reactor for acetone-butanol-ethanol production.
In comparison to the different fermentation modes for the production of acetone, butanol and ethanol (ABE) researched to date, the continuous fermentation is the most economically favored. Continuous fermentation with two or more reactor cascade is reported to be the most efficient as it results in a more stable solvent production process. In this work, it is shown that a continuous (first-stage) reactor coupled to a repeated fed-batch (second stage) is superior to batch and fed-batch fermentations, including two-stage continuous fermentation. This is due to the efficient catalyst use, reported through the specific product rate and rapid glucose consumption rate. High solvents are produced at 19.4 g(ABE) l⁻¹, with volumetric productivities of 0.92 g(butanol) l⁻¹ h⁻¹ and 1.47 g(ABE) l ⁻¹ h⁻¹. The bioreactor specific productivities of 0.62 and 0.39 g g⁻¹(cdw) h⁻¹ obtained show a high catalyst activity. This new process mode has not been reported before in the development of ABE fermentation and it shows great potential and superiority to the existing fermentation methods.


Delirium Associated with Salicylate and Acetaminophen Overdose in a Patient with COVID-19: A Case Report.
The coronavirus disease 2019 (COVID-19) pandemic has created numerous clinical challenges for physicians, in part due to its wide range of clinical manifestations and associated complications. Here we present the case of a 69-year-old man who was admitted to the emergency department with fever, dyspnea, and altered mental status. We believe the patient's condition was precipitated by a COVID-19 infection-induced delirium, a setting in which he ingested aspirin and acetaminophen in overdose that required lifesaving interventions. This case illustrates the potential for neuropsychiatric effects in COVID-19 patients due to both direct viral central nervous system pathology and pandemic-related psychosocial stressors.


Lymph Node Subcapsular Sinus Microenvironment-On-A-Chip Modeling Shear Flow Relevant to Lymphatic Metastasis and Immune Cell Homing.
A lymph node sinus-on-a-chip adhesion microfluidic platform that recapitulates the hydrodynamic microenvironment of the lymph node subcapsular sinus was engineered. This device was used to interrogate the effects of lymph node remodeling on cellular adhesion in fluid flow relevant to lymphatic metastasis. Wall shear stress levels analytically estimated and modeled after quiescent and diseased/inflamed lymph nodes were experimentally recapitulated using a flow-based microfluidic perfusion system to assess the effects of physiological flow fields on human metastatic cancer cell adhesion. Results suggest that both altered fluid flow profiles and presentation of adhesive ligands, which are predicted to manifest within the lymph node subcapsular sinus as a result of inflammation-induced remodeling, and the presence of lymph-borne monocytic cells may synergistically contribute to the dynamic extent of cell adhesion in flow relevant to lymph node invasion by cancer and monocytic immune cells during lymphatic metastasis.


Clinical trials with aldose reductase inhibitors.
Following the identification of potent, orally active inhibitors of aldose reductase, the next challenge comes in demonstrating clinical utility in the treatment of diabetic complications. It is not feasible to conduct pivotal studies in all indications within the same trial and neuropathy evolved as the lead indication. There was little precedent for clinical trials in any diabetic complication and one of the challenges has been the derivation of standardized methodology for quantifying changes. In order to establish the value of any intervention in a chronic disease, it is necessary to demonstrate sustained benefit in long-term trials. This has been complicated by the absence of quantitative prospective data on the natural history of the disease process. In well-controlled clinical trials, patients are likely to improve their diabetic control which will have an additional effect over and above the usual placebo effect seen in any trial. In the absence of any standard therapy, the definition of clinical as opposed to statistical significance of any effect needs to be established. In the case of neuropathy this is further complicated by the heterogeneity of the disease and questions over the relevance of small changes in electrophysiology as an index of improvement in histopathology. The majority of the animal studies have concentrated on prevention of changes rather than reversal. However, in diabetics, complications develop slowly and significant tissue damage has occurred before clinical signs can be detected. To date, all clinical studies have concentrated on treatment of complications. The dose of ARI chosen for such studies has been based on the surrogate of erythrocyte aldose reductase activity confirmed by short-term studies on disease reversal.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of myocardial sheetlet sliding on left ventricular function.
Left ventricle myocardium has a complex micro-architecture, which was revealed to consist of myocyte bundles arranged in a series of laminar sheetlets. Recent imaging studies demonstrated that these sheetlets re-orientated and likely slided over each other during the deformations between systole and diastole, and that sheetlet dynamics were altered during cardiomyopathy. However, the biomechanical effect of sheetlet sliding is not well-understood, which is the focus here. We conducted finite element simulations of the left ventricle (LV) coupled with a windkessel lumped parameter model to study sheetlet sliding, based on cardiac MRI of a healthy human subject, and modifications to account for hypertrophic and dilated geometric changes during cardiomyopathy remodeling. We modeled sheetlet sliding as a reduced shear stiffness in the sheet-normal direction and observed that (1) the diastolic sheetlet orientations must depart from alignment with the LV wall plane in order for sheetlet sliding to have an effect on cardiac function, that (2) sheetlet sliding modestly aided cardiac function of the healthy and dilated hearts, in terms of ejection fraction, stroke volume, and systolic pressure generation, but its effects were amplified during hypertrophic cardiomyopathy and diminished during dilated cardiomyopathy due to both sheetlet angle configuration and geometry, and that (3) where sheetlet sliding aided cardiac function, it increased tissue stresses, particularly in the myofibre direction. We speculate that sheetlet sliding is a tissue architectural adaptation to allow easier deformations of the LV walls so that LV wall stiffness will not hinder function, and to provide a balance between function and tissue stresses. A limitation here is that sheetlet sliding is modeled as a simple reduction in shear stiffness, without consideration of micro-scale sheetlet mechanics and dynamics.


Abnormal auditory evoked potentials in hereditary motor-sensory neuropathy.
From a kinship with a dominantly inherited motor-sensory neuropathy, we studied 2 brothers with brainstem auditory evoked potentials and behavioral audiometric tests. They had abnormal prolongation of I-III interpeak intervals. Wave V was poorly developed. Conventional audiometric tests did not reveal a peripheral hearing loss. It is probable that their auditory nerves and spiral ganglia are undergoing a pathophysiological process analogous to that of their peripheral nerves.


Use of PRKO mice to study the role of progesterone in mammary gland development.
To better understand the distinct physiological roles played by progesterone and estrogen receptors (PR and ER) as well as to study directly PR function in an in vivo context, a novel mutant mouse strain, the PR knockout (PRKO) mouse, was generated carrying a germline loss of function mutation at the PR locus. Mouse mammary gland development has been examined in PRKO mice using reciprocal transplantation experiments to investigate the effects of the stromal and epithelial PRs on ductal and lobuloalveolar development. The absence of PR in transplanted donor epithelium, but not in recipient stroma, prevented normal lobuloalveolar development in response to estrogen and progesterone treatment. Conversely, the presence of PR in the transplanted donor epithelium, but not in the recipient stroma, revealed that PR in the stroma may be necessary for ductal development. Stimulation of ductal development by the PR may, therefore, be mediated by an unknown secondary signaling molecule, possibly a growth factor. The continued stimulation of the stromal PR appears to be dependent on reciprocal signal(s) from the epithelium. Thus, the combination of gene knockout and reciprocal transplantation technologies has provided some new insights into the role of stromal-epithelial interactions and steroid hormones in mammary gland development.


Multifunctional hybrid functionalization of cellulose fabrics with AgNWs and TiO2.
A study on the hybrid functionalization of cotton and viscose fabrics using silver nanowires (AgNWs) colloid and titanium dioxide (TiO2) sol prepared in sol-gel technique was carried out. The microwave treatment was applied to change amorphous form of TiO2 to anatase. The photocatalytic activity of both cellulose fabrics was evaluated by decomposition of nicotine using new method on the basis of infrared spectroscopy. The AgNWs/TiO2 modification caused 3 and 4 times (cotton fabric) and 1.8 and 1.5 (viscose fabric) faster decomposition of nicotine under respectively UV and VIS light than for unmodified fabrics. The AgNWs/TiO2 modified cotton showed the surface resistance 1.5×103Ω and antibacterial effect against Staphylococcus aureus and Klebsiella pneumoniae bacteria. The same modification method gives various effects for cotton and viscose fabrics. Our study demonstrates that AgNWs/TiO2 modified cotton fabric with protective properties against bacteria can be used as conductive and air purifying materials.


Identification of novel hypermethylated or hypomethylated CpG sites and genes associated with anthracycline-induced cardiomyopathy.
Anthracycline-induced cardiomyopathy is a leading cause of late morbidity in childhood cancer survivors. Aberrant DNA methylation plays a role in de novo cardiovascular disease. Epigenetic processes could play a role in anthracycline-induced cardiomyopathy but remain unstudied. We sought to examine if genome-wide differential methylation at 'CpG' sites in peripheral blood DNA is associated with anthracycline-induced cardiomyopathy. This report used participants from a matched case-control study; 52 non-Hispanic White, anthracycline-exposed childhood cancer survivors with cardiomyopathy were matched 1:1 with 52 survivors with no cardiomyopathy. Paired ChAMP (Chip Analysis Methylation Pipeline) with integrated reference-based deconvolution of adult peripheral blood DNA methylation was used to analyze data from Illumina HumanMethylation EPIC BeadChip arrays. An epigenome-wide association study (EWAS) was performed, and the model was adjusted for GrimAge, sex, interaction terms of age at enrollment, chest radiation, age at diagnosis squared, and cardiovascular risk factors (CVRFs: diabetes, hypertension, dyslipidemia). Prioritized genes were functionally validated by gene knockout in human induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) using CRISPR/Cas9 technology. DNA-methylation EPIC array analyses identified 32 differentially methylated probes (DMP: 15 hyper-methylated and 17 hypo-methylated probes) that overlap with 23 genes and 9 intergenic regions. Three hundred and fifty-four differential methylated regions (DMRs) were also identified. Several of these genes are associated with cardiac dysfunction. Knockout of genes EXO6CB, FCHSD2, NIPAL2, and SYNPO2 in hiPSC-CMs increased sensitivity to doxorubicin. In addition, EWAS analysis identified hypo-methylation of probe 'cg15939386' in gene RORA to be significantly associated with anthracycline-induced cardiomyopathy. In this genome-wide DNA methylation profile study, we observed significant differences in DNA methylation at the CpG level between anthracycline-exposed childhood cancer survivors with and without cardiomyopathy, implicating differential DNA methylation of certain genes could play a role in pathogenesis of anthracycline-induced cardiomyopathy.


Diode laser cyclophotocoagulation paves way to a safer trabeculectomy in eyes with medically uncontrollable intraocular pressure.
High intraocular pressure (IOP) not responding to systemic and topical anti-glaucoma medications renders the eye at risk for both intra- and post-operative complications of glaucoma filtration surgery. Laser cyclophotocoagulation is able to lower IOP in such refractory glaucoma eyes and may make the surgical event safer. This study assessed diode laser cyclophotocoagulation (DLCP) when used as a temporary measure for lowering IOP prior to performing trabeculectomy. This study is a retrospective analysis of cases planned for trabeculectomy surgery, uncontrolled on maximally tolerable systemic anti-glaucoma medications. They were analysed for response to DLCP in terms of IOP control, vision-related complications, increased inflammation, post-trabeculectomy hypotony and chances of phthisis and ciliary shutdown. Twelve eyes of ten patients aged 35-65 years were identified and all followed up for at least 2 years. One week following DLCP, the IOP (mean ± SD) declined by 51 % from 46.8 ± 5.4 to 22.8 ± 3.3 mmHg. The IOP was further reduced to 15.4 ± 2.7 mmHg at 4 weeks after trabeculectomy; it remained in the mid-teens for a minimum of 2 years in all cases. The mean (±SD) visual acuity improved from 1.4 ± 0.4 to 0.8 ± 0.4 LogMAR equivalents following trabeculectomy. In four eyes, phacoemulsification was performed 5-7 months after trabeculectomy with improvement in best-corrected visual acuity. One patient developed transient hypotony, post-trabeculectomy, which resolved by 6 days. There were no other complications like increased inflammation, prolonged hypotony or suprachoroidal haemorrhage. DLCP is, thus, effective and safe for temporarily controlling IOP; thereby trabeculectomy can be performed in a quieter ocular milieu.


Lewis Acid Assisted Brønsted Acid Catalysed Decarbonylation of Isocyanates: A Combined DFT and Experimental Study.
An efficient and mild reaction protocol for the decarbonylation of isocyanates has been developed using catalytic amounts of Lewis acidic boranes. The electronic nature (electron withdrawing, electron neutral, and electron donating) and the position of the substituents (ortho/meta/para) bound to isocyanate controls the chain length and composition of the products formed in the reaction. Detailed DFT studies were undertaken to account for the formation of the mono/di-carboxamidation products and benzoxazolone compounds.


Capillarity and diffusion distances in skeletal muscles in birds.
Tissue capillarity and diffusion distances were determined for red and white skeletal muscles of adult birds ranging in mass from 10.8 to 6200 g. In addition, literature values for capillarity and diffusion distances in skeletal muscles of mammals were incorporated into the data set. Muscle mass was closely coupled to body mass. However, no significant allometric relations were found for any of the other variables measured. Number of capillaries per fiber was not correlated with cross sectional area of individual muscle fibers. Thus, capillary density decreased in a hyperbolic manner against fiber area and diffusion distance decreased in a hyperbolic manner against the number of capillaries per muscle fiber. Red muscles had significantly higher numbers of capillaries per fiber and significantly shorter diffusion distances than did white muscles. The patterns for tissue capillarity and diffusion distances in avian muscle reported here are similar to values reported previously for mammalian muscles. In both taxonomic groups capillarity and diffusion distances are independent of body mass. In addition, diffusion distances are characteristic of capillaries distributed in random arrays through the muscle cross section.


Radiofrequency ablation of parathyroid adenoma in primary hyperparathyroidism.
We present a case of a 32-year-old woman with hyperparathyroidism, treated with ultrasound-guided percutaneous radiofrequency ablation (RFA). RFA, assisted by saline injection inferomedial to the parathyroid, is a safe technique that prevents burn injury to the nerve. The saline injection technique shifted the parathyroid gland laterally, so that the distance between the nerve and the parathyroid gland was sufficient to prevent burn injury. The completeness of tissue ablation was evaluated based on Doppler ultrasound imaging and serum intact parathyroid hormone (iPTH) level immediately after RFA. There were no complications associated with RFA. Serum iPTH levels normalized during follow-up for 20 months. It was possible to perform RFA for primary parathyroid adenoma safely using a saline injection technique.


An optimized test bolus for computed tomography pulmonary angiography and its application at 80 kV with 10 ml contrast agent.
Computed tomography pulmonary angiography (CTPA) is usually used for pulmonary embolism (PE) detection. However, the determination of scan timing remains a challenge due to the short scan duration of CTPA. We aimed to develop an optimized test bolus to determine scan delay in CTPA. The time-enhancement curves were obtained by measuring the enhancement within a region of interest in the main pulmonary artery and vein. A total of 70 patients were randomly divided into two groups (n = 35 each): the control group underwent CTPA using the test bolus approach and the test group underwent CTPA using the biphasic time-enhancement curves approach. Tube voltages of 100 kVp and 80 kVp and 20 ml and 10 ml contrast agent were adopted in the control and test groups, respectively. The CT numbers, image quality, PE detection was evaluated. There was a point of intersection between the pulmonary artery and vein test bolus enhancement curves. The scan delay time (TDELAY) was obtained based on the time at intersection (TCROSS) and the scan duration (TSD): TDELAY = TCROSS - TSD. The mean CT numbers for pulmonary vein in the control were higher than those in the test group (all p < 0.001). The image quality for the pulmonary arteries in the test group was better than that in the control group (p < 0.01), with artifact reduction in the superior vena cava. Segmental PE could be detected using the optimized protocol. The radiation dose and iodine load in the test group were all lower than those in the control (p < 0.01). We established an approach to calculate the scan delay of CTPA, and this approach could be used for CTPA at 80 kVp with 10 ml contrast agent.


Keratitis associated with the multiple endocrine deficiency, autoimmune disease, and candidiasis syndrome.
Optimal management of the ocular and systemic components of the multiple endocrine deficiency, autoimmune disease, candidiasis syndrome requires early identification of affected individuals. This autosomal recessive syndrome is characterized by hypoparathyroidism, Addison's disease, and chronic mucocutaneous candidiasis among other endocrinopathies and immune disorders. We retrospectively reviewed 16 patients, 14 with the full syndrome and two with the syndrome partially manifested. Four of these patients manifested a self-limited, bilateral keratitis in which the age of onset ranged from 2 to 9 years. Keratitis preceded the onset of any endocrinopathy in two of four patients and was among the first signs of the syndrome. The keratitis was not caused by hypoparathyroidism or candidiasis. The anterior stromal vascularization and scarring resulted in a visual acuity of 20/50 or worse in four of eight affected eyes. We recommend medical management of the corneal disease without surgical intervention.


The proximity of a highway increases CO2 respiration in forest soil and decreases the stability of soil organic matter.
Roadways traverse many forest areas and they often have harmful effects on forest soils, including the modified stability of soil organic matter (SOM). Soil CO2 respiration is an important indicator of SOM biological stability. The aim of this study was to test the hypotheses that a roadway will (1) modify the composition of the cation exchange capacity of adjacent forest soils, and (2) significantly decrease the stability of SOM. Two study sites were established in Scots pine and Silver fir stands, located close to the S7 highway in central Poland, which was opened to traffic in 1984. From each site, samples were taken at 2, 12 and 22 m from the forest edge. Soil CO2 respiration was determined using closed chamber incubation with an alkali trap. We also conducted a comprehensive analysis of soil chemical properties. The stoichiometric ratios of chosen chemical parameters to total carbon (Ct) were calculated. In both sites, we observed increased soil pH and CO2 respiration in the vicinity of the highway, as well as increased ratios of exchangeable calcium (Ca), magnesium (Mg) and sodium (Na) to Ct. In the fir site, the humic and fulvic acids, the dissolved organic carbon (DOC) content and aluminum (Al) to Ct ratio were depleted in close proximity to the highway. We suggest that the combined effect of Ca and Na ions, originating from winter de-icing, caused the depletion of Al and hydrogen (H) in the soil close to the forest edge and, therefore, resulted in lower SOM stability expressed as the decreased DOC and pyrophosphate-extractable carbon content, as well as the release of CO2. We conclude that the changes of SOM stability with distance were the effect of modification of ion-exchange relationships (particularly base cations versus Al3+ with H+) rather than forest stand species or intrinsic SOM properties (like functional groups, the recalcitrance of bindings etc.). Our work supports earlier studies, confirming the significant impact of Al and H on SOM stability.


War in Ukraine - Changing the Polish paediatric population as a consequence of forced migration (a preliminary study).
The study aimed to briefly analyse the basic anthropometric characteristics of Ukrainian adolescents against their Polish counterparts. The study was school-based, carried out April-June 2022 and followed a cross-sectional model. It included 642 children from Poland and Ukraine (aged 10-15) who attended ten randomly selected primary schools in Kraków (Poland). Noticeable differences between Polish and Ukrainian adolescents were observed. As the analysed characteristics included features such as the amount and distribution of body fat, they can be crucial in the indirect assessment of health status, particularly the risk of cardiovascular and metabolic diseases. This in turn, can help to properly accommodate the changing needs of the population.


Patient accounts for nonadherence: A critical window into the patient experience.
This paper explores patient use of excuses to better understand the patient experience during clinical interactions. A content analysis of 32 residents treating 99 different patients was used to reveal accounts of nonadherence. Using grounded theory, these accounts were coded into types and then reduced using a Q-sort. Analysis revealed 163 accounts of nonadherence. When questioned about their adherence to treatment, 68% of patients offered at least one account for nonadherence during the visit. These accounts were coded into fourteen types and then the Q-sort identified four types of accounts: healthcare system failures, treatment failure, situational exigencies, and self-directed. Of the accounts offered, 7% of the patients provided 6 or more accounts and 25% provided between 3 and 5 accounts. The examination of excuses provides a unique way to gain insight into how patients communicate with their physicians. Patient accounts ranged from those where patients indicated adherence was within their control (self-directed) and accounts outside their control (healthcare system failure, treatment failure, and situational exigency). The types of accounts of nonadherence patients could provide doctors insight into the patient experience. Recognizing these types could allow opportunities for doctors to develop communication strategies for encouraging patient adherence.


Femoral neck cortical geometry measured with magnetic resonance imaging is associated with proximal femur strength.
Magnetic resonance imaging (MRI) is a promising medical imaging technique that we used to assess femoral neck cortical geometry. Our primary objective was to assess whether cortical bone in the femoral neck assessed by MRI was associated with failure load in a simulated sideways fall, with and without adjustment for total bone size. Our secondary objective was to assess the reliability of the MRI measurements. We imaged 34 human cadaveric proximal femora using MRI and dual-energy X-ray absorptiometry (DXA). MRI measurements of cross-sectional geometry at the femoral neck were the cortical cross-sectional area (CoCSA(MRI)), second area moment of inertia (x axis; Ix(MRI)), and section modulus (x axis; Zx(MRI)). DXA images were analyzed with the standard Hologic protocol. From DXA, we report the areal bone mineral density (aBMD(DXA)) in the femoral neck and trochanteric subregions of interest. The femora were loaded to failure at 100 mm/s in a sideways fall configuration (15 degrees internal rotation, 10 degrees adduction). Failure load (N) was the primary outcome. We observed that the femoral neck CoCSA(MRI) and Ix(MRI) were strongly associated with failure load (r (2)=0.46 and 0.48, respectively). These associations were similar to those between femoral neck aBMD and failure load (r (2)=0.40), but lower than the associations between trochanteric aBMD and failure load (r (2)=0.70). We report that MRI holds considerable promise for measuring cortical bone geometry in the femoral neck and for predicting strength at the proximal femur.


Practices and challenges for hemophilia management under resource constraints in Thailand.
Hemophilia is an inherited bleeding disorder caused by deficiency of a specific coagulation factor. Factor VIII deficiency is responsible for hemophilia A while factor IX deficiency is responsible for hemophilia B. As per the 2020 annual global survey by the World Federation of Hemophilia, only 1828 Thai hemophiliacs have been registered to the national healthcare system. The reason for the low number is the underdiagnosis which is a major concern in the real-world practice among Asian countries. In Thailand, most hemophiliacs are diagnosed by general practitioners, pediatricians or internists at rural hospitals and are referred to hemophilia specialists at the Hemophilia Treatment Centers (HTCs). Despite the challenges pertaining to infrastructure and cost of treatment, Thailand has progressed substantially in providing the required hemophilia care, as evidenced by an evolution in acquiring and sharing knowledge as well as collaborative efforts among multiple stakeholders over the past three decades. In this letter-to-the-editor, the authors have summarized the practices for and challenges faced with hemophilia management in Thailand.


Experimental liver transplantation on pigs -- technical considerations.
The purpose was to improve and refine our technique for orthotopic liver transplantation. Experimental interventions were performed on pigs, 26 pairs. Orthotopic transplantation was performed after lavage of the donor pig liver by pressure gradient and transplantation was performed using portocavo- jugular shunt and veno-venous, arterio-arterial and choledocho-choledochal sutures in end-to-end manner. Immediate survival was 88.46%. Experimental transplant activity on pigs is of real value, contributing to a faster learning curve and at the same time improving handling, increasing the efficiency of sutures, as well as anesthetic and surgical team building.


STUDY OF THE MEDIAN AND ULNAR NERVOUS BRANKS TO KAPLAN'S LINE.
This study aims to present lines A1 and A2 in association with Kaplan's cardinal line (LCK), and relate them to the thenar motor branch of the median nerve (RMTNM) and to the deep branch of the ulnar nerve (RPNU). Ten hands of five adult cadavers were dissected. The RMTNM origin was positioned proximal to the LCK in all limbs. In two, the RMTNM was positioned exactly on the A1 line; in seven, it was on the ulnar side in relation to A1. In one, it was on the radial side relative to the A1. The origin of the RPNU was identified between the pisiform and the LCK in nine limbs; in one, the RPNU was positioned from the ulnar nerve in relation to A2; and in two, the A2 passed exactly at the point of division of the ulnar nerve into superficial branches and deep. We did not identify the positioning of the RPNU on the radial side of the A2 line. The impact of this study was to identify the anatomical trajectory of these nerves by detaching A1 and A2 along with the KCL, avoiding iatrogenic lesions during surgical procedures. Level of Evidence IV, Case Series.


The impact of adolescent stress experiences on neurobiological development.
Adolescence is considered a developmental period of heightened vulnerability to many psychological dysfunctions-primarily due to the high structural neuronal plasticity that accompanies the associated physical and cognitive gains, rendering an individual highly susceptible to environmental stressors during this time. Recently, interest has been generated in the study of neuronal and behavioral adaptation to adverse experiences during adolescence. This review will provide an overview of the principal neurobehavioral changes that occur during adolescence and describe what happens when the maturation of these functions is altered by stressful environmental stimuli.


Sublethal Exposure to Plasma-Activated Water Influences the Morphological Characteristics, Phagocytic Ability, and Virulence of Acanthamoeba castellanii.
This study aimed to examine the ultrastructure, cytotoxicity, phagocytosis, and antioxidant responses of Acanthamoeba castellanii trophozoites exposed to sublethal plasma-activated water. Trophozoites were exposed to a sublethal treatment of PAW and compared to untreated viable trophozoites via adhesion assays on macrophage monolayers, osmo- and thermotolerance tests. Bacterial uptake was assessed in treated cells to evaluate their phagocytic characteristics. Oxidative stress biomarkers and antioxidant activities were compared in treated and untreated trophozoites. Finally, the expression of the mannose-binding protein (MBP), cysteine protease 3 (CP3), and serine endopeptidase (SEP) genes was determined in cells. In PAW-treated trophozoites, cytopathic effects were more extensive and resulted in the detachment of macrophage monolayers. Treated trophozoites could not grow at high temperatures (43 °C). Moreover, they showed osmotolerance to 0.5 M D-mannitol but not to 1 M. Results demonstrated a higher bacterial uptake rate by PAW-treated trophozoites than untreated cells. Activities of superoxide dismutase and catalase and catalase were significantly greater in the treated trophozoites, and the glutathione and glutathione/glutathione disulfide were significantly lower in the PAW-treated cells. Exposure to PAW also significantly increased the malondialdehyde level and total antioxidant capacity. Treatment with PAW led to significantly higher expression of virulent genes like MBP, CP3, and SEP. PAW is a double-edged sword against A. castellanii. PAW is an effective antiamoebic agent in proper usage, whereas its sublethal exposure may reduce its effectiveness and increase amoebas' pathogenicity. An agent's adequate concentration and exposure time are essential to achieve optimum results.


The effect of dietary sesame oil and ginger oil as antioxidants in the adult rat dorsal root ganglia after peripheral nerve crush injury.
The purpose of this study was to investigate the effect of dietary sesame oil and ginger oil supplements on the dorsal root ganglia following a sciatic nerve crush model in male Wistar albino rats. Crush injury models have been done by means of graded forceps (50 Newton). The animals were given a daily sesame oil (4 ml/kg/day) and ginger oil (400 mg/kg/day) via oral gavage for a period of 28 days. Dorsal root ganglia from the L5 levels were harvested. Processing of tissues was done for electron microscopy and light microscopy. Immunohistochemical staining with active caspase-3 antibody and qualitative ultrastructural analyses of tissues were made by a light and a transmission electron microscope, respectively. The results showed that crush injury leads to remarkable ultrastructural changes in sensory neurons, such as swollen mitochondria, disruption of cristae structure, glial cell proliferation and, consequently, phagocytosis of the damaged neuron. These ultrastructural changes were less evident in the treated groups, and both natural compounds reduced the expression of activated caspase-3, which may also affect ultrastructural changes. The application of the natural products sesame oil and ginger oil may represent a supportive approach to the protection of sensory neurons against the destructive effects of peripheral nerve crush injury.