Role of iron biomarkers and iron intakes in lung cancer risk: A systematic review and meta-analysis.
The role of iron biomarkers and iron intake in the susceptibility to lung cancer is unclear. The purpose of this study was to conduct a systematic review and meta-analysis, to assess the relationship between iron levels in the body or iron intake and the risk of lung cancer. This review is registered with PROSPERO (number CRD 42020199776). PubMed, Web of Science, Scopus, Embase and Cochrane were used to search for studies assessing the relationship between iron and lung cancer, up to July 15, 2021. Qualitative and quantitative analysis was carried out to determine if there was a correlation between iron biomarkers/intakes and the risk of lung cancer. Twenty articles were included. Pooled analyses demonstrated that serum ferritin concentrations and transferrin saturation (TSAT) were significantly higher in patients with lung cancer than in healthy controls (ferritin: standardized mean differences [SMD], 0.235, 95% confidence interval [CI], 0.129, 0.341, I2 = 32.1 %; TSAT: SMD, 0.07, 95 % CI, 0.018, 0.121, I2 = 0 %). In contrast, serum transferrin concentrations were significantly lower in patients with lung cancer than in healthy controls (SMD, -0.591, 95 % CI, -1.18, -0.003, I2 = 87.7 %). No significant effects of serum iron, lung tissue iron, bronchoalveolar lavage fluid (BALF) ferritin, or iron intake (total iron, dietary iron, heme iron, or non-heme iron) were found on lung cancer incidence. Among the different iron biomarkers analyzed, a trend in association was only detected with serum ferritin, TSAT and transferrin concentration and no associations were found between iron intakes and the risk of lung cancer. However, more prospective studies are needed to strengthen the current evidence.


Flexible and Thermally Induced Switchable Fire Alarm Fabric Based On Layer-by-Layer Self-Assembled Silver Sheet/Fe3O4 Nanowire Composite.
Textiles with fire detection will appeal for the interior decoration of houses and play a critical role in public security. Herein, we fabricated a sandwichlike fire alarm fabric (Ag@Fe3O4-MS) based on Fe3O4 nanowire (NW) arrays and fish-scale-like silver sheets, designed by in situ layer-by-layer assembly on the surface of polypropylene (PP) nonwoven fabric. The Ag@Fe3O4-MS sensor has fish-scale-like silver sheets as self-assembling electrode layers on the upper and lower sides of fabric, which can be tailored into various shapes and integrated into other flexible electronics. The sensor provides a real-time monitoring strategy for early warning fire detection (below 100 °C). At room temperature, the fabricated Ag@Fe3O4-MS sensor is electrically insulating, while it switches to an electrical conductor when exposed to flame. In view of its fast response time (2 s) and sustained working time (at least 15 min), the sensor with a connected alarm light can immediately alert people of house fires. More importantly, this sensor can provide additional real-time information on the fire location and reliable real-time monitoring of fire rekindling. The sensor was exposed to fire for successive cycles with an average response of I = 43 mA, confirming the reliable repeatability to detect fires. This ultralight, flexible Ag@Fe3O4-MS sensor could have broad applications in home safety. Moreover, the sandwichlike design provides a reliable strategy to modify household fabric items to provide a fire warning function.


Role of CD8+ T cell exhaustion in the progression and prognosis of acute respiratory distress syndrome induced by sepsis: a prospective observational study.
CD8+ T cells are important for protective immunity against intracellular pathogens. Excessive amounts of antigen and/or inflammatory signals often lead to the gradual deterioration of CD8+ T cell function, a state called "exhaustion". However, the association between CD8+ T cell exhaustion and acute respiratory distress syndrome (ARDS) has not been studied. This study was conducted to elucidate how CD8+ T cells and inhibitory receptors were related to the clinical prognosis of ARDS. A prospective observational study in an emergency department enrolled patients who were diagnosed with sepsis-associated ARDS according to the sepsis-3 criteria and Berlin definition. Peripheral blood samples were collected within 24 h post recruitment. CD8+ T cell count, proliferation ratio, cytokine secretion, and the expression of coinhibitory receptors were assayed. Sixty-two patients with ARDS met the inclusion criteria. CD8+ T cell counts and proliferation rates were dramatically decreased in non-surviving ARDS patients. Increasing programmed cell death 1 (PD-1) expression on the CD8+ T cell surface was seen in patients with worse organ function, while an increasing level of T cell immunoglobulin mucin-3 (Tim-3) was associated with a longer duration of the shock. Kaplan-Meier analysis showed that low CD8+ T cell percentages and increased inhibitory molecule expression were significantly associated with a worse survival rate. CD8+ T cells and coinhibitory receptors are promising independent prognostic markers of sepsis-induced ARDS, and increased CD8+ T cell exhaustion is significantly correlated with poor prognosis.


Polychlorinated biphenyls and its potential role in endometriosis.
With the progress of global industrialization and environmental deterioration, the relationship between human health and the living environment has become an increasing focus of attention. Polychlorinated biphenyls (PCBs, including dioxin-like polychlorinated biphenyls and non-dioxin-like polychlorinated biphenyls), as part of the organic chlorine contaminants, have been suspected as playing a role in the etiopathogenesis of endometriosis. Several population-based studies have proposed that exposure to PCBs may increase the risk of developing endometriosis, while some epidemiological studies have failed to find any association between PCBs and endometriosis. The purpose of this review is to discuss the potential pathophysiological relationship between endometriosis and PCBs with a focus on both dioxin-like polychlorinated biphenyls and non-dioxin-like polychlorinated biphenyls.


Phosphate transport by embryonic chick duodenum. Stimulation by vitamin D3.
Embryonic chick duodenum maintained in organ culture is a well-suited model for the study of vitamin D effects on inorganic phosphate (Pi) absorption. The system is sensitive to as little as 6.5 nM vitamin D3 (0.1.I.U./ml culture medium). Increased phosphate absorption is observed after 6--12 h of culture. Maximal response (133% of vitamin D-efficient control) is achieved at 24 h. Phosphate uptake by embryonic chick duodenum involves a saturable and a non-saturable component. The former displays characteristics of an active sodium-dependent transport mechanism and is also sensitive to vitamin D3. Presence of the sterol in culture medium raises the maximal velocity from 55 to 75 nmol Pi/min per g tissue. Km remains unchanged (0.5 mM Pi). Duodena cultured in presence of inhibitors of protein synthesis (actinomycin D, alpha-amanitin and cycloheximide) display reduced rates of phosphate absorption. This treatment also prevents vitamin D3 action on phosphate transport. It is concluded that the sterol affects phosphate transport by modulation of synthesis of proteins which are functional in the Pi absorptive process.


High-throughput screening for biocatalysts.
Recent progress in high-throughput enzyme assays includes new examples of fluorogenic and chromogenic substrates, fluorescence resonance energy transfer substrates, and applications of the pH and pM indicator methods. Recent developments of Horeau's pseudo-enantiomer derivatisation method to screen enantioselectivities in high-throughput have also been reported.


Clinical course and outcome of a nosocomial outbreak of hepatitis C in a urology ward.
This paper describes a prospective study of the clinical course and outcome of a nosocomial outbreak of hepatitis C virus (HCV) infection in six male urology patients at a hospital in Stara Zagora, Bulgaria. These patients had been previously hospitalised in the urology ward, during which all had received intravenous therapy. Approximately three weeks later, all six were admitted to the infectious diseases unit with acute hepatitis, shown to be caused by HCV genotype 1b. The diagnosis was confirmed by polymerase chain reaction during the first week of their hospital stay. Infected patients were followed up for 30 months following diagnosis and 54 potential contacts for 6 months post-exposure. Four patients recovered completely; one developed chronic HCV infection and one died. The latter already had cirrhosis due to co-infection with hepatitis B virus. The investigation established the index case as a patient with chronic hepatitis C, who had been an in-patient on the same ward at the same time. The most likely route of transmission was intravenous heparin flushes administered with a common syringe. Contrary to the common assumption that acute HCV infection often leads to chronic disease, only one chronic case was observed during the 30-month period of investigation.


COVID-19 mortality and deprivation: pandemic, syndemic, and endemic health inequalities.
COVID-19 has exacerbated endemic health inequalities resulting in a syndemic pandemic of higher mortality and morbidity rates among the most socially disadvantaged. We did a scoping review to identify and synthesise published evidence on geographical inequalities in COVID-19 mortality rates globally. We included peer-reviewed studies, from any country, written in English that showed any area-level (eg, neighbourhood, town, city, municipality, or region) inequalities in mortality by socioeconomic deprivation (ie, measured via indices of multiple deprivation: the percentage of people living in poverty or proxy factors including the Gini coefficient, employment rates, or housing tenure). 95 papers from five WHO global regions were included in the final synthesis. A large majority of the studies (n=86) found that COVID-19 mortality rates were higher in areas of socioeconomic disadvantage than in affluent areas. The subsequent discussion reflects on how the unequal nature of the pandemic has resulted from a syndemic of COVID-19 and endemic inequalities in chronic disease burden.


Recharging cognition with DC brain polarization.
Electrical direct current (DC) has been applied to the human head throughout history for various reasons and with claims of behavioral effects and clinical benefits. This technique has recently been rediscovered and its effects validated with modern quantitative techniques and experimental designs. Despite the very weak current used, DC polarization applied to specific brain areas can alter verbal fluency, motor learning and perceptual thresholds, and can be used in conjunction with transcranial magnetic stimulation. Compact and safe, this old technique seems poised to allow major advances cognitive science and therapy.


Genomic insights into the taxonomic status of the Bacillus cereus group.
The identification and phylogenetic relationships of bacteria within the Bacillus cereus group are controversial. This study aimed at determining the taxonomic affiliations of these strains using the whole-genome sequence-based Genome BLAST Distance Phylogeny (GBDP) approach. The GBDP analysis clearly separated 224 strains into 30 clusters, representing eleven known, partially merged species and accordingly 19-20 putative novel species. Additionally, 16S rRNA gene analysis, a novel variant of multi-locus sequence analysis (nMLSA) and screening of virulence genes were performed. The 16S rRNA gene sequence was not sufficient to differentiate the bacteria within this group due to its high conservation. The nMLSA results were consistent with GBDP. Moreover, a fast typing method was proposed using the pycA gene, and where necessary, the ccpA gene. The pXO plasmids and cry genes were widely distributed, suggesting little correlation with the phylogenetic positions of the host bacteria. This might explain why classifications based on virulence characteristics proved unsatisfactory in the past. In summary, this is the first large-scale and systematic study of the taxonomic status of the bacteria within the B. cereus group using whole-genome sequences, and is likely to contribute to further insights into their pathogenicity, phylogeny and adaptation to diverse environments.


Stereotactic techniques in managing pediatric brain tumors.
Stereotactic techniques available for managing pediatric brain tumors include not only stereotactic biopsy but also stereotactic craniotomy, brachytherapy, and stereotactic radiosurgery. This paper illustrates the use of these techniques in brain tumors in children over a 2-year period at Children's Hospital, Boston. Stereotactic biopsy was used in six cases of deep-seated tumor, with successful tissue diagnosis in all six. Stereotactic craniotomy, in which excision of a mass was done in the stereotactic frame with computed tomography-guided localization and control, was employed in three children. Interstitial radiation using implanted 125I seeds was carried out in two children with malignant astrocytomas: in both it provided good local control but there was later distant recurrence. Stereotactic radiosurgery with a modified linear accelerator was used in eight children as adjunctive therapy for local control. These cases illustrate the versatility of stereotactic techniques involved in a comprehensive approach to pediatric brain tumors.


Effect of Au substrate and coating on the lasing characteristics of GaAs nanowires.
Optically pumped lasing from highly Zn-doped GaAs nanowires lying on an Au film substrate and from Au-coated nanowires has been demonstrated up to room temperature. The conically shaped GaAs nanowires were first coated with a 5 nm thick Al2O3 shell to suppress atmospheric oxidation and band-bending effects. Doping with a high Zn concentration increases both the radiative efficiency and the material gain and leads to lasing up to room temperature. A detailed analysis of the observed lasing behavior, using finite-difference time domain simulations, reveals that the lasing occurs from low loss hybrid modes with predominately photonic character combined with electric field enhancement effects. Achieving low loss lasing from NWs on an Au film and from Au coated nanowires opens new prospects for on-chip integration of nanolasers with new functionalities including electro-optical modulation, conductive shielding, and polarization control.


Pretransplant dyslipidaemia determines outcome in lung transplant recipients.
There is little knowledge about the effect of dyslipidaemia on the outcome after lung transplantation. Thus, the aim of this retrospective single centre study was to analyse the impact of the plasma lipid profile on mortality in lung transplant recipients. From January 2000 to December 2008 the charts of 172 consecutive lung transplantation recipients were analysed. At baseline and after one year lipid profiles were routinely collected. During the follow-up major cardiovascular events (MCE; beginning of dialysis, cerebrovascular insult or myocardial infarction) were recorded. The follow-up period ended December 2010. Over all total cholesterol (4.3 ± 1.6 vs. 5.4 ± 1.3 mmol/l, p < 0.0001), triglycerides (1.2 ± 0.7 vs. 2.4 ± 1.3 mmol/l, p < 0.0001), HDL (1.5 ± 0.6 vs. 1.7 ± 0.6 mmol/l, p = 0.003) and TC/HDL ratio (3.0 ± 1.0 vs. 3.6 ± 1.2, p = 0.002) increased significantly after 1 year.During the observational period 6.9% (10 patients) suffered a major cardiac event. In univariate analysis MCE was associated with baseline TC: on average the event-group had a 33% higher baseline TC (5.6 vs. 4.2 mmol/l, OR 1.6, CI 1.1 - 2.2, p = 0.02). The total mortality in the observational period was 25% (36 patients overall). In univariate analysis mortality was associated with increased TC/HDL ratio. The non-survivors had on average a 22% higher baseline TC/HDL ratio (3.6 vs. 2.8, HR 2.8, CI 1.2 - 3.5, p = 0.001). There was no association between mortality and TC (p = 0.33), triglycerides (p = 0.34), HDL (p = 0.78) and creatinine (p = 0.73). In a multivariate model the hazard ratio was 1.5 (1.2 - 1.9, p = 0.001) per increase of 0.4 TC/HDL ratio. This study shows that the total cholesterol before transplantation is associated with the incidence of MCE and the cholesterol/HDL ratio with mortality in lung transplanted recipients.


Lymphatic and portal absorption of vitamin E in aging rats.
We studied the intestinal absorption and lymphatic versus portal distribution of vitamin E and its metabolites in vivo in young (4 month), "middle-aged" (14 month), and old (24 month) male Sprague-Dawley rats. Twenty-four hours after its surgical preparation, the rat's jejunum was infused with a physiological micellar solution containing 200 nM alpha-tocopherol. Its transport rate into lymph and bile as well as its accumulation in liver and intestinal tissues was measured. Lymphatic transport of vitamin E increased from 92 to 269 pmol/5 hr and bile appearance of vitamin E and its polar metabolites increased from 230 to 298 pmol/5 hr as rats aged. Tissue accumulation of the vitamin in the small intestine and liver increased significantly with aging (P less than 0.05). Total absorption of the vitamin and its intestinal metabolites increased from 5912 pmol/5 hr in young rats to 16,467 pmol/5 hr in old rats (P less than 0.01). Absorption expressed as a percentage of infused alpha-tocopherol increased from 19.7% at 4 months to 54.9% at 24 months. These studies demonstrate an aging-associated increase in the total amount of vitamin E absorbed and a shift from portal to lymphatic transport. These changes may represent a salutary adaptive increase in the systemic availability of vitamin E with aging.


Value of fiberoptic bronchoscopy and angiography for diagnosis of the bleeding site in hemoptysis.
We evaluated 36 patients during active hemoptysis and compared the diagnostic yield of different procedures. Twenty-seven patients (75%) had one or more previous episodes of hemoptysis, most of which were not massive. Fiberoptic bronchoscopy was performed in 25 patients, and the bleeding site was identified in 17 (68%). The likelihood of localizing the bleeding site was significantly higher with early versus delayed fiberoptic bronchoscopy (91% versus 50%). Bronchial arteriography was performed in all 36 patients; positive arteriographies were observed in 20 cases (55.5%). Arteriography was positive in only 2 of the 8 cases in which fiberoptic bronchoscopy did not localize the site of bleeding. Bronchial artery embolization was successfully performed in 10 patients. However, the bleeding recurred within the first week after embolization in 2 patients, and 1 of them died.


Fourier analysis of broad spectral EEG from a fluctuation point of view.
It is believed that the EEG is the most reliable method of evaluating brain function, but neither quantitative nor qualitative studies of the EEG have been carried out over the entire range of frequencies. Analysis of limited frequency bands of the EEG has not disclosed the whole of neuronal activity. The aim of this study is to clarify the upper limit of EEG frequency. Our EEG analytic system is composed of a high fiedlity preamplifier and signal processor with a frequency response within -3 dB below 20 kHz. Thirty adult cats were used for these experiments. The upper limit of the frequency varied in different structures: 6.9 +/- 0.8 kHz (+/- SEM) in motor cortex, 4.1 +/- 0.3 kHz in the hippocampus, 2.9 +/- 0.5 kHz in the amygdala, 9.3 +/- 0.6 kHz in the ventrolateral nucleus of the thalamus, and 9.9 +/- 0.5 kHz in the midbrain reticular formation. Three different types of amplitude spectra were characterized in bilogarithmic graphs. These types are named types f, f + L, and L corresponding to 1/f or Lorentzian fluctuation. In conclusion, the upper limit of frequency and the spectral types correspond to the neuronal specificity of different brain regions. Their physioanatomic significance is discussed.


Association of Uric Acid-Lowering Therapy With Incident Chronic Kidney Disease.
Uric acid is a waste metabolite produced from the breakdown of purines, and elevated serum uric acid levels are associated with higher risk of hypertension, cardiovascular disease, and mortality and progression of chronic kidney disease (CKD). Treatment of hyperuricemia in patients with preexisting CKD has not been shown to improve kidney outcomes, but the associations of uric acid-lowering therapies with the development of new-onset kidney disease in patients with estimated glomerular filtration rate (eGFR) within reference range and no albuminuria is unclear. To examine the association of initiating uric acid-lowering therapy with the incidence of CKD. This cohort study included patients with eGFR of 60 mL/min/1.73 m2 or greater and no albuminuria treated at US Department of Veterans Affairs health care facilities from 2004 to 2019. Clinical trial emulation methods, including propensity score weighting, were used to minimize confounding. Data were analyzed from 2020 to 2022. Newly started uric acid-lowering therapy. The main outcomes were incidences of eGFR less than 60 mL/min/1.73 m2, new-onset albuminuria, and end-stage kidney disease. A total of 269 651 patients were assessed (mean [SD] age, 57.4 [12.5] years; 252 171 [94%] men). Among these, 29 501 patients (10.9%) started uric acid-lowering therapy, and 240 150 patients (89.1%) did not. Baseline characteristics, including serum uric acid level, were similar among treated and untreated patients after propensity score weighting. In the overall cohort, uric acid-lowering therapy was associated with higher risk of both incident eGFR less than 60 mL/min/1.73 m2 (weighted subhazard ratio [SHR], 1.15 [95% CI, 1.10-1.20; P < .001) and incident albuminuria (SHR, 1.05 [95% CI, 1.01-1.09; P < .001) but was not associated with the risk of end-stage kidney disease (SHR, 0.96 [95% CI, 0.62-1.50]; P = .87). In subgroup analyses, the association of uric acid-lowering therapy with worse kidney outcomes was limited to patients with baseline serum uric acid levels of 8 mg/dL or less. These findings suggest that in patients with kidney function within reference range, uric acid-lowering therapy was not associated with beneficial kidney outcomes and may be associated with potential harm in patients with less severely elevated serum uric acid levels.


Fostering a faster post-operative wound healing process with hyperbaric oxygen therapy in a rare case of squamous odontogenic tumor.
The surgical removal of an intraoral tumor and preventing intraoral wound dehiscence are constant challenges faced by surgeons today. Hyperbaric oxygen therapy (HBOT), the inhalation of 100% oxygen at a greater atmospheric pressure, is often used in cases of wounds to induce a faster wound healing process, alongside other treatment modalities. We report a rare case of squamous odontogenic tumor (SOT) treated with HBOT after being surgically removed to foster an accelerated wound recovery. A 39-year-old Asian male presented with an intraoral 3 × 4 cm tumor, accompanied by acute pain on the maxillary region. Biopsy results showed a solid, brown parenchyma with islands of mature squamous epithelial cells, confirming the diagnosis of an SOT. An intraoral surgical approach was performed to remove the tumor. The patient was then treated with prophylactic antibiotics and 5 consecutive, daily sessions of HBOT at 2.0 ATA as an adjuvant therapy. No further complaints and no abnormalities were found at the 2-week follow-up evaluation. In our case of SOT, HBOT plays a role to inhibiting the bacterial growth which could lead to post-operative wound infections. A number of studies have incorporated HBOT as an adjuvant therapy for post-operative intra oral wounds which has resulted in minimal wound complications. The use of HBOT as an adjunctive therapy in managing possible wound complications after the resection of an intraoral tumor enables a faster angiogenesis process, reduces tissue hypoxia and minimizes the risk of post-operative wound infections; hence fostering the wound healing process.


Evaluation of chemotherapeutic effects on gastric cancer in relation to the histological pattern.
A combination of MFC (Mitomycin-C, 5-FU and Cytosine arabinoside) was administered to 32 gastric cancer patients and study was made of the therapeutic efficacy in relation to the histological pattern. In evaluation based on the degree of cancer cell infiltration (INF), chemotherapy was more effective in cases with INF alpha and beta than those with INF gamma. As for the grade of follicular hyperplasia in regional lymph nodes of gastric cancer, the higher was the grade, the more effective was the chemotherapy. However, a significant relationship could not be observed between histological pattern of stromal reaction of the gastric cancer and clinical effects of chemotherapy. The grade of lymphocyte infiltration or connective tissue reaction in the stroma was not related with the therapeutic effects. No relationship was also obtained between the grade of sinus histiocytosis of lymphoid reaction in the lymph nodes and therapeutic effects.


Salinity-induced modulation of growth and antioxidant activity in the callus cultures of miswak (Salvadora persica).
Miswak (Salvadora persica Linn.) is a medium-sized tree, desert facultative halophytic plant. Besides edible fruits and non-edible seed oil, the plant contains several bioactive compounds like alkaloids, tannins, saponins and sterols related to food and cosmetic industries. In the present study, physiological responses and antioxidant potential under salinity stress were investigated in callus cultures of S. persica to evaluate its use as a source of antioxidant. The callus cultures were grown on MS medium supplemented with 0.5 mg/l each of 2,4,5-T and BAP, which could be established successfully by regular subcultures of slow growing callus on this medium for several months. Increased dry weight, soluble proteins, proline, soluble carbohydrates and CAT activity were recorded under NaCl stress in comparison to control cultures. The DPPH and FRAP antioxidant activities were gradually elevated in NaCl-treated callus, whereas SOD quenching was recorded maximum at 200 mM. A significant correlation between antioxidant capacity and phenol content was observed, indicating that phenolic compounds are the major contributors to the antioxidant potential in S. persica. These findings suggest that increased salinity stress caused elevated antioxidant potentials and the plants grown in such conditions may serve as potential source of antioxidant.


HIV prevention and HIV care among transgender and gender diverse youth: design and implementation of a multisite mixed-methods study protocol in the U.S.
In the U.S., transgender and gender diverse (TGD) populations face structural, interpersonal, and individual barriers to healthcare. Less is known, however, about the HIV prevention and treatment experiences of TGD youth in the U.S. The current study was developed to fill this research gap. This article describes the research protocol for a multi-site, U.S.-based mixed-methods study that sought to identify the multi-level facilitators and barriers that influence participation of TGD youth in various stages of the HIV prevention (e.g., pre-exposure prophylaxis uptake) and care continua. A sample of diverse TGD youth ages 16-24 was recruited from 14 U.S. sites. TGD youth participants completed a one-time, in-person visit that included an informed consent process, computer-based quantitative survey, and in-depth qualitative interview assessing experiences accessing HIV prevention and/or care services. Providers serving TGD youth were recruited from the same 14 sites and completed a one-time visit via phone that included informed consent, demographic questionnaire, and in-depth qualitative interview assessing their experiences providing HIV prevention or treatment services to TGD youth. Overall, 186 TGD youth ages 16-24 and 59 providers serving TGD youth were recruited and enrolled from across the 14 U.S. sites. TGD youth participants had a mean age of 20.69; 77.3% youth of color; 59.7% trans-feminine; 15.5% trans-masculine; 24.9% non-binary; 53.6% family income under poverty level. Providers included medical and mental health providers as well as case manager/care coordinators, HIV test counselors, and health educators/outreach workers. Providers were 81.3% cisgender and 30.5% people of color. Successes with community-engagement strategies and gender-affirming research methods are reported. This study addresses critical gaps in current knowledge about the HIV prevention and care experiences of TGD youth. Findings have implications for the development of HIV interventions across levels to support the health and well-being of TGD youth. Future research is warranted to replicate and expand on lessons learned regarding recruitment and engagement of communities of TGD youth, including longitudinal designs to assess engagement across their developmental stages. Lessons learned working with TGD youth through developing and implementing the study protocol are shared. Registered on ClinicalTrials.gov on 05/20/2015 (NCT02449629).


Polysaccharide/mesoporous silica nanoparticle-based drug delivery systems: A review.
Mesoporous silica nanoparticles (MSNs) have been well-researched in the design and fabrication of advanced drug delivery systems (DDSs) due to their advantages such as good biocompatibility, large specific surface area and pore volume for drug loading, easily surface modification, adjusted size and good thermal/chemical stability. For MSN-based DDSs, gate materials are also necessary. And natural polysaccharides, one kind of the most abundant natural resource, have been widely applied as the "gatekeepers" in MSN-based DDSs. Polysaccharides are cheap and rich in sources with good biocompatibility, and some of them have important biological functions. In this review article, polysaccharides including chitosan, hyaluronic acid, sodium alginate and dextran, et al. are briefly introduced. And the preparation processes and properties such as controlled drug release, cancer targeting and disease diagnosis of functional polysaccharide/MSN-based DDSs are discussed.


Beyond the Black Queen Hypothesis.
The Black Queen Hypothesis, recently proposed to explain an evolution of dependency based on gene loss, is gaining ground. This paper focuses on how the evolution of dependency transforms interactions and the community. Using agent-based modeling we suggest that species specializing in the consumption of a common good escape competition and therefore favor coexistence. This evolutionary trajectory could open the way for novel long-lasting interactions and a need to revisit the classically accepted assembly rules. Such evolutionary events also reshape the structure and dynamics of communities, depending on the spatial heterogeneity of the common good production. Let Black be the new black!


Self-report of Nurse Professionalism and Factors Affecting It: A Cross-sectional Study.
To evaluate the perception of professionalism by nurses and identify factors that affect the evaluation of professionalism. Professionalism is conceptualized as the set of beliefs related to the autonomy of the profession. Lack of professional respect, a disruptive work environment, and suppression of progressivism in the profession are identified as factors that lead to leaving the profession. The study was carried out according to the CHEERIES (Checklist for Reporting Results of Internet E-Surveys) checklist and included 250 RNs. The Nurses' Professionalism Inventory (NPI) was used. The mean composite score of the NPI indicates a positive reflection of the professionalism of the nurse. Nurse education and job position were the most significant factors that affected perception of professionalism (P < 0.05). The results show the need to examine the issue of professionalism in nursing to a greater extent and implement the findings of research on innovations at all levels of nursing education.


Incidence, radiographic predictors, and clinical outcome of acromial stress reaction and acromial fractures in reverse total shoulder arthroplasty.
Acromial and scapular spine fractures (ASFs) are known complications following implantation of reverse total shoulder arthroplasty (RTSA). The entity of acromial stress reaction (ASR) without fracture has recently been described. The purpose of this study was to analyze the incidence, radiographic predictors, treatment options, healing rates, and clinical outcomes of ASF and ASR compared with a control group. A total of 854 primary RTSAs were implanted between 2005 and 2018 in a single shoulder unit of a tertiary referral hospital and retrospectively reviewed for the incidence of ASF and ASR. ASR was defined as pain at the acromion or scapular spine after fracture exclusion on computed tomography scans. The ASF group was matched to a control group. Preoperative and postoperative radiographs were analyzed for radiographic predictors of ASF or ASR. The impact of ASF and ASR, operative vs. nonoperative treatment, and fracture union on clinical outcomes (Constant-Murley score [CS], Subjective Shoulder Value [SSV], and range of motion) with a minimum follow-up period of 2 years was analyzed. A total of 46 ASFs (5.4%) in 44 patients and 44 ASRs (5.2%) in 43 patients were detected at a mean of 16 ± 24 months and 20 ± 23 months postoperatively, respectively. Predictive radiographic factors were an increased critical shoulder angle and lateralization shoulder angle. The overall union rate was 55% (22 of 40) but was significantly higher following operative treatment (9 of 11, 82%) compared with nonoperative treatment (13 of 29, 45%). Patients with ASF or ASR demonstrated inferior clinical outcomes (CS, 44 ± 21 and 48 ± 18; SSV, 52% ± 25% and 57% ± 27%) compared with the control group (CS, 66 ± 14; SSV, 82% ± 22%) independent of bony union or treatment at a mean of 59 ± 33 months (ASF) and 61 ± 38 months (ASR). ASF and ASR are frequent complications following RTSA implantation with similar poor clinical outcome measures. The healing rate was shown to be much higher with a surgical approach. Nevertheless, fracture consolidation does not result in better clinical outcomes compared with nonunion.


Estimated Changes in Insulin Prices and Discounts After Entry of New Insulin Products, 2012-2019.
Despite the political salience of insulin prices, no study to date has quantified trends in insulin prices that account for manufacturer discounts (net prices). To describe trends in insulin list prices and net prices faced by payers from 2012 to 2019 and estimate changes in net prices after the 2015 to 2017 entry of new insulin products. This longitudinal study included an analysis of Medicare, Medicaid, and SSR Health drug pricing data from January 1, 2012, to December 31, 2019. Data analyses were performed from June 1, 2022, to October 31, 2022. US sales of insulin products. Net prices faced by payers were estimated for insulin products as list prices minus manufacturer discounts negotiated in commercial and Medicare Part D markets (ie, commercial discounts). Trends in net prices were evaluated before and after the entry of new insulin products. Net prices of long-acting insulin products increased at an annual rate of 23.6% from 2012 to 2014 but decreased at an annual rate of 8.3% after the introduction of insulin glargine (Toujeo and Basaglar) and degludec (Tresiba) in 2015. Net prices of short-acting insulin increased at an annual rate of 5.6% from 2012 to 2017 but then decreased from 2018 to 2019 after the introduction of insulin aspart (Fiasp) and lispro (Admelog). For human insulin products, which did not experience entry of new products, net prices increased at an annual rate of 9.2% from 2012 to 2019. From 2012 to 2019, commercial discounts increased from 22.7% to 64.8% for long-acting insulin products, from 37.9% to 66.1% for short-acting insulin products, and from 54.9% to 63.1% for human insulin products. In this longitudinal study of US insulin products, results suggest that insulin prices substantially increased from 2012 to 2015, even after accounting for discounts. The introduction of new insulin products was followed by substantial discounting practices that lowered net prices faced by payers.


Alpha1-adrenoceptors mediate dihydroxyphenylalanine-induced activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaques.
The mechanisms underlying actions of dihydroxyphenylalanine (L-DOPA) in Parkinson's disease remain to be fully elucidated. Noradrenaline formed from L-DOPA may stimulate alpha(1)-adrenoceptors. We assessed the involvement of alpha(1)-adrenoceptors in actions of L-DOPA in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaques. In each animal, the minimal dose of L-DOPA required to alleviate parkinsonian symptoms was defined (12.5-25 mg/kg p.o.). The effects of coadministration of the alpha(1)-adrenoceptor antagonist prazosin ([4-(4-amino-6,7-dimethoxy-quinazolin-2-yl) piperazin-1-yl]-(2-furyl)methanone) on motor activity, parkinsonism, and dyskinesia were assessed. Antiparkinsonian benefit was accompanied by mild dyskinesia. L-DOPA also elicited hyperactivity, i.e., activity greater than that seen in normal animals. Coadministration of prazosin (0.16-0.63 mg/kg p.o.) with L-DOPA did not significantly affect either its antiparkinsonian actions or dyskinesia. However, prazosin significantly and dose-dependently attenuated L-DOPA-induced activity, reducing it to a level equivalent to that of normal animals. More specifically, during periods of pronounced L-DOPA-induced activity, prazosin attenuated the total and duration of activity by 80 and 76%, respectively. These actions of prazosin were expressed in the absence of sedation. Although activation of alpha(1)-adrenoceptors plays no major role in the antiparkinsonian and dyskinetic effects of L-DOPA per se, it does contribute to the induction of hyperactivity. alpha(1)-Adrenoceptors may be involved in pathological responses to L-DOPA treatment, including the dopamine dysregulation syndrome.


[Chronification of neuroses--on the critical phase of the inpatient-ambulatory care transition].
The contribution deals with the critical transition from ward treatment and follow-up care as an outpatient. Patients with primary psychic maldevelopment are compared with those of a secondary psychic development. Changes in symptoms and personality were measured with a battery of tests during a pre-post follow-up study (intervals of eight weeks between tests). Special attention is paid to changes after discharge from hospital and deterioration, which was common among the patients with secondary psychic maldevelopment, is discussed.


Assessing the performance of a sequencing batch biofilm reactor bioaugmented with P. stutzeri strain XL-2 treating ammonium-rich wastewater.
Pseudomonas stutzeri XL-2, with the capability of heterotrophic nitrification-aerobic denitrification and biofilm-forming, was applied in a sequencing batch biofilm reactor (SBBR) for bioaugmented treatment of ammonium-rich wastewater. The bioaugmented system SBBR 1 showed a rapid development of biofilm and relatively shorter time for biofilm hanging compared with the control system SBBR 2 without strain XL-2 inoculation. At different NH4+-N loads of 100, 200 and 300 mg/L, the effluent TN removal ratios ranged in 88.7-97.0%, 85.1-93.5% and 87.8-92.5% respectively in SBBR 1, while only ranged in 77.4-85.4%, 77.1-84.3% and 79.8-85.0% in SBBR 2. Less accumulation of NO2--N and NO3--N resulted in the better performance on TN removal in SBBR 1. Microbial community structure analysis revealed that strain XL-2 successfully proliferated in SBBR 1 and contributed to the less accumulation of NO2--N and NO3--N as well as biofilm formation.


Is maxillary expansion effective in treatment of obstructive sleep apnoea syndrome? A systematic review of systematic reviews.
Background Maxillary expansion (ME) might be beneficial in improving airway dimensions and obstructive sleep apnoea syndrome (OSAS) in patients with constricted maxillae. The aim of this overview is to present clinicians with a summary of the evidence. Data from systematic reviews and meta-analyses were evaluated to investigate the effect of ME on OSAS.Methods An electronic search was commenced in five databases, in addition to a manual search until July 2021. Screening of articles started with title and abstract followed by full-text assessment. Systematic reviews with/without meta-analyses were included. Critical appraisal was done using A Measurement Tool to Assess Systematic Reviews (AMSTAR) 2, Level of Research Design scoring and criteria of body of evidence scores. The search, study selection and critical appraisal were completed by three reviewers.Results In total, 14 systematic reviews with/without meta-analyses were included. The quality of available evidence ranged between low to high, based on the overall quality evaluation.Conclusions Based on the available evidence, maxillary expansion might be able to improve the nasal airway volume and OSAS in both growing and adult patients in the short term. ME can be considered as one of the treatment options in cases with OSAS.


Age-dependent changes of enzyme activities in the different fibre types of rat extensor digitorum longus and gastrocnemius muscles.
The age-dependent change of metabolic profiles of SO (slow-oxidative), FOG (fast-oxidative glycolytic) and FG (fast-glycolytic) fibres of muscles digitorum longus and musculus gastrocnemius of rat from 14 days to 370 days was measured cytophotometrically. Fibres were classified visually and using cytophotometrical data from staining reactions for myofibrillar adenosinetriphosphatase (ATPase), succinate dehydrogenase (SDH) and alpha-glycerophosphate dehydrogenase (alpha-GPDH) in the same fibre. The fibre type population as percentage was estimated at different ages. The age-dependent change of enzyme activities was demonstrated in each fibre type. SDH-heterogeneity of FOG-fibres and consequently an overlap with SO-fibres was detected. The alpha-GPDH/SDH-activity quotient allowed to distinguish SO-, FOG- and FG-fibres, and the age-dependent change of activity quotient characterized the change of metabolic properties in the concerned fibre types. Whereas in gastrocnemius muscle the metabolic profile of FOG-fibres was similar to that of SO-fibres, in extensor digitorum longus muscle the metabolism of FOG-fibres was similar to that of FG-fibres. Between the two muscles differences were also shown for the fibre type responsible for changes of enzyme activities in the whole muscle, measured biochemically.


The frequency of aneuploidy in prenatally diagnosed congenital heart disease: an indication for fetal karyotyping.
The frequency of chromosomal abnormalities in infants with congenital heart disease has been estimated from postnatal clinic data to be 5% to 10%. Over an 18-month period we performed fetal echocardiograms on 502 fetuses and found cardiac anomalies in 34. Eleven of these fetuses (32%) had abnormal chromosomes. This marked discrepancy from the data found in the pediatric literature may relate to nonviable fetuses identified in utero, who escape pediatric case identification. We conclude that in cases of fetal heart disease the workup should include either amniocentesis or fetal blood sampling for chromosome analysis. The information can be used for complete parental counseling and for managing delivery and neonatal care.


Oral lesions in HIV infected individuals from Ribeirão Preto, Brazil.
The aim of this study was to diagnosis oral lesions related to HIV infection in individuals followed in the General Hospital of the School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. The presence of oral lesions was correlated with gender, age, smoking habit, levels of CD4 lymphocytes, HIV load, time of HIV seropositivity, AIDS condition, use of removable dental prosthesis, and use of HAART. 340 HIV infected individuals were selected for this study, all participants of the study were examined by only one practiced dentist which performed anamnesis, peribuccal and oral examination. Oral lesions were observed in 113 of 340 (33.2%) HIV infected individuals. These oral lesions included: oral candidiasis (17.7%) of pseudomembranous (10.8%) and of erythematous types (6.9%), angular cheilitis (13.9%), hairy leukoplakia (11.8%), and oral ulcers (2.1%). Oral candidiasis lesions were more frequently observed in women (p.033). Smoking addict participants presented a high frequency of tongue hairy leukoplakia (p.038) and a reduced frequency of oral ulcers (p.018). Hairy leukoplakia and pseudomembranous candidiasis were inversely correlated to CD4+L levels and directly correlated with HIV load, behaving as immune depression markers. Hairy leukoplakia and pseudomembranous candidiasis also showed an inverse correlation with HAART use (p<.0001). Patients using mobile dental prosthesis presented a high frequency of erythematous candidiasis (p.003). The inverse correlation with CD4+L level and the direct correlation with HIV load suggest that oral lesions could be used as alternative clinical markers for poor immune condition in HIV infected individuals.


Deafness mutation mining using regular expression based pattern matching.
While keyword based queries of databases such as Pubmed are frequently of great utility, the ability to use regular expressions in place of a keyword can often improve the results output by such databases. Regular expressions can allow for the identification of element types that cannot be readily specified by a single keyword and can allow for different words with similar character sequences to be distinguished. A Perl based utility was developed to allow the use of regular expressions in Pubmed searches, thereby improving the accuracy of the searches. This utility was then utilized to create a comprehensive listing of all DFN deafness mutations discussed in Pubmed records containing the keywords "human ear".


Auscultatory, echocardiographic, biochemical, nutritional, and environmental characteristics of mitral valve disease in Norfolk terriers.
In order to more fully understand degenerative mitral valve disease (DMVD) in the Norfolk terrier, we sought to characterize findings from the physical and echocardiographic examination; biochemical, biomarker, and nutritional profiles; and select environmental variables from a cohort of apparently healthy Norfolk terriers. Overtly healthy Norfolk terriers ≥ 6 yrs old were recruited by 3 different veterinary hospitals and underwent historical, physical, electrocardiographic (ECG), and 2D/color-flow Doppler echocardiographic examinations. Anterior mitral valve leaflet length, maximal thickness, area, and degree of prolapse were measured or calculated from two-dimensional images. Blood samples were obtained for serum biochemistry, serum serotonin, plasma NT-proBNP, amino acid profile, C-reactive protein, and cardiac troponin I. Of the 48 dogs entered into the study, 23 (48%) had murmurs, 2 (4%) had mid-systolic clicks, 11 (23%) had ECG P pulmonale, and 41 (85%) were deemed to have echocardiographic evidence of DMVD, including 18 Norfolk terriers without a murmur. Seven (15%), 28 (58%), and 13 (27%) dogs were classified as normal (stage 0), International Small Animal Cardiac Health Council (ISACHC) stage 1a, and 1b, respectively. Mean indexed echocardiographic mitral leaflet thickness (P = 0.017), area (P = 0.0002), prolapse (P = 0.0004), and left atrial to aortic diameter (P = 0.01) were significantly different between ISACHC 0, 1a, and 1b. DMVD is relatively common in Norfolk terriers and echocardiographic changes consistent with mild DMVD can be seen in dogs without a heart murmur.


Low Malignancy Rates in Fine-Needle Aspiration Cytologies in a Primary Care Setting in Germany.
Reported results for thyroid nodule fine-needle aspiration (FNA) cytology mainly originate from tertiary centers. However, thyroid nodule FNA cytology is mainly performed in primary care settings for which the distribution of FNA Bethesda categories and their respective malignancy rates are largely unknown. Therefore, this study investigated FNA cytology malignancy rates of a large primary care setting to determine to what extent current evidence-based strategies for the malignancy risk stratification of thyroid nodules are applied and applicable in such primary care settings. In a primary care setting, 9460 FNAs of thyroid nodules were retrospectively analyzed from 8380 patients evaluated by one cytologist (I.R.) during a period of two years. The 8380 FNA cytologies were performed by 64 physicians in different private practices throughout Germany in primary care settings. The cytopathologic results were classified according to the Bethesda System as non-diagnostic in 19%, cyst/cystic nodule in 21%, benign (including thyroiditis) in 48%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 6%, follicular neoplasms/suspicious for follicular neoplasm (FN/SFN) in 4%, suspicious for malignancy (SFM) in 1%, and malignant in 1%. The proportion of patients proceeding to surgery or with a follow-up of at least one year and the observed risks of malignancy were 22%/8% for AUS/FLUS, 69%/17% for FN/SFN, 78%/86% for SFM, and 71%/98% for malignant. For 112 cytologically suspicious and malignant FNAs, there were 102 true positives and 10 false positives, considering histology as gold standard. At variance with other data mostly originating from tertiary centers, these data demonstrate low percentages for malignant, SFM, FN/SFN, and AUS/FLUS, and high percentages for cysts/cystic nodules in this primary care setting in Germany. The risks of malignancy for malignant, SFM, AUS/FLUS, and FN/SFN FNA cytologies are according to Bethesda recommendations.


An Iodine Balance Study in Chinese School-age Children.
Few iodine balance studies have been conducted in school-age children. This study aimed to conduct an iodine balance study in school-age children. We measured daily iodine intake, excretion, and retention for 3 consecutive days without any dietary interventions in school-age children. Linear mixed-effects models were used to fit the relationship between total iodine intake and iodine retention. 29 children aged 7-12 years (mean age 10.2 ± 1.4 years) with normal thyroid function and thyroid volume were recruited. The 0 balance value (iodine intake = iodine excretion, iodine retention = 0 μg/day) shifted with iodine intake in an iodine sufficient population. The 0 balance value for school-age children with an iodine intake of 235 (133, 401) μg/day is 164 μg/day. Children aged 7-12 years with iodine intake >400 μg/day were almost all in a positive iodine state. An iodine intake of 235 (133, 401) μg/day for children aged 7-10 years achieved a 0 balance value of 164 μg/day. Long-term iodine intake of >400 μg/day is not recommended.


To What Extent Do Erotic Images Elicit Visuospatial versus Cognitive Attentional Processes? Consistent Support for a (Non-Spatial) Sexual Content-Induced Delay.
It is almost a cultural truism that erotic images attract our attention, presumably because paying attention to erotic stimuli provided our ancestors with mating benefits. Attention, however, can be narrowly defined as visuospatial attention (keeping such stimuli in view) or more broadly as cognitive attention (such stimuli taking up one's thoughts). We present four independent studies aiming to test the extent to which erotic images have priority in capturing visuospatial versus cognitive attention. Whereas the former would show in quicker reactions to stimuli presented in locations where erotic images appeared previously, the latter causes delayed responding after erotic images, independent of their location). To this end, we specifically modified spatial cueing tasks to disentangle visuospatial attention capture from general sexual content-induced delay (SCID) effects-a major drawback in the previous literature. Consistently across all studies (total N = 399), we found no evidence in support of visuospatial attention capture but reliably observed an unspecific delay of responding for trials in which erotic images appeared (irrespective of cue location). This SCID is equally large for heterosexual men and women and reliably associated with their self-reported sexual excitability.


[The use of preserved photomodified autoblood for the prevention of thromboembolic complications in surgical interventions on the small pelvis].
The method of UV irradiation of autoblood followed by infusion in the early postoperative period was used in 109 patients subjected to various operative interventions on the small pelvis organs. It was established that the infusion of autologous photomodified blood allowed to avoid postoperative thromboembolic complications.


Consequence of solubility alteration by salt effect on dissolution enhancement and biological response of a solid dispersion of an experimental antianginal drug.
Improvement of dissolution of a poorly water-soluble experimental antianginal drug has been obtained by solid dispersion preparation. Its solubility decreased with rising chloride ion concentration and biological responses in dogs varied with the gastrointestinal administration site. A correlation seemed to exist between the apparent solubility and the heart rate activity.


Effects of noise and harmonic excitation on the growth of Bacillus subtilis biofilm.
We study the dynamic growth behaviors of Bacillus subtilis biofilms by using a stochastic delay differential equation similar to the Mackey-Glass equation. We observe a wealth of dynamic behavior from a mathematical perspective. Firstly, the change of the time delay (i.e. the time that the growth state of the periphery to affect the stress of the interior cells needs and the time required for the stress signal coming from the interior to reach the peripheral cells) and the external excitation (i.e. the change in temperature) frequency will influence the size of Bacillus subtilis biofilm and the collective growth of the cell community. We also found the resonance phenomena in mathematics, which is of great help in understanding the behavior of stress levels in the biofilm periphery. Secondly, the direction of the Hopf bifurcation and the stability of the bifurcating periodic solutions are derived by using the normal form theory and the center manifold reduction. Numerical simulations are carried out to ensure theoretical results. Finally, the effects of noise on stress levels in the biofilm periphery are analyzed and reveal more complex dynamics of the system.


5-substituted 2-bromoindolo[3,2-b]quinoxalines. A class of potential antitumor agents with cdc25 phosphatase inhibitory properties.
Several derivatives of 5-substituted 2-bromoindolo[3,2-b]quinoxaline were synthesized and characterized. The synthesized compounds were evaluated for their antitumor activity using the National Cancer Institute-in vitro-disease oriented antitumor screen and two biochemical mechanism-based screens (cdc2 kinase and cdc25 phosphatase). Compound 19 showed broad spectrum antitumor activity with full panel (MG-MID) GI50. TGI, and LC50 of 14.2, 31.6- and 66.2 microM, respectively. In addition it inhibited cdc2 kinase and cdc25 phosphatase with IC50's of 70 and 25 microM, respectively. Thus, compound 19 represents a model for compounds with potential antitumor activity and cdc25 phosphatase inhibitory properties.


Impact of first-line cryoablation for atrial fibrillation on healthcare utilization, arrhythmia disease burden and efficacy outcomes: real-world evidence from the Cryo Global Registry.
Cryoballoon ablation (CBA) is an effective first-line treatment for symptomatic atrial fibrillation (AF), as recently demonstrated by three randomized trials. This sub-analysis of the Cryo Global Registry aims to examine current clinical practices of first-line CBA. AF patients treated with first-line CBA were compared to CBA in antiarrhythmic drug (AAD)-refractory patients at 12 months. Efficacy was examined using time-to-first atrial arrhythmia recurrence following a 90-day blanking period. Healthcare utilization was evaluated by repeat ablations and hospitalizations. Disease burden was examined by assessing quality of life (QOL) and patients' reporting of symptoms. Of 1394 patients, 433 (31.1%) were treated with first-line CBA, which was more frequent in high-volume centers. Serious procedure-related adverse event rates were similar. Efficacy at 12 months was higher in the first-line group (87.8 vs. 81.6%, HRunadj 0.64 (95% CI 0.47-0.88); p < 0.01) regardless of the centers' CBA experience; when controlling for baseline characteristics, the difference was not significant (HRadj 0.87 (95% CI 0.56-1.37); p = 0.55). No difference was observed in repeat ablations and hospitalizations between cohorts. First-line patients experienced a larger mean reduction in symptoms and were prescribed AADs at a lower rate at 12-month follow-up (9.7 vs. 29.9%). QOL improved in both cohorts from baseline to 12 months with no significant difference between groups (p = 0.29). In this global real-world experience, first-line CBA in patients with symptomatic AF is effective, with a larger symptom reduction compared with CBA after AAD failure and without a difference in healthcare utilization at mid-term follow-up. https://clinicaltrials.gov/ct2/show/NCT02752737.


Lateral retinacular release in concordance with medial patellofemoral ligament reconstruction in patients with recurrent patellar instability: A computational model.
The aim of this study was to develop and validate a finite element (FE) model of the patellofemoral joint to analyze the biomechanics of lateral retinacular release after medial patellofemoral ligament (MPFL) reconstruction in patellar malalignment (increased tibial tubercle-trochlear groove distance (TT-TG)). We hypothesized that lateral retinacular release is not appropriate in patellar instability addressed by MPFL reconstruction due to decreased lateral stability and inappropriate adjustment in patellofemoral contact pressures. A FE in-silico model of the patellofemoral joint was developed and validated. The model was used analyze the effect of lateral retinacular release in association with MPFL reconstruction on patellofemoral contact pressures, contact area, and lateral patellar displacement during knee flexion. MPFL reconstruction alone results in restoration of patellofemoral contact pressures throughout the entire range of motion (0-90°), mimicking the results from healthy condition. The addition of the lateral retinacular release to the MPFL reconstruction resulted in significant reductions in both patellofemoral contact pressure and contact area. Lateral retinacular release resulted in more lateral patellar displacement during the mid-flexion knee range of motion. Combination of lateral retinacular release with MPFL reconstruction in patients with increased TT-TG is not recommended as MPFL reconstruction alone for first-line management of recurrent patellar instability offers a greater biomechanical advantage and restoration of contact forces to resemble that of the healthy knee. The presented biomechanical data outlines the effect of concomitant MPFL reconstruction and lateral retinacular release to help guide surgical planning for patients with recurrent patellar instability due to malalignment.


Chemical characterization of pterosaur melanin challenges color inferences in extinct animals.
Melanosomes (melanin-bearing organelles) are common in the fossil record occurring as dense packs of globular microbodies. The organic component comprising the melanosome, melanin, is often preserved in fossils, allowing identification of the chemical nature of the constituent pigment. In present-day vertebrates, melanosome morphology correlates with their pigment content in selected melanin-containing structures, and this interdependency is employed in the color reconstruction of extinct animals. The lack of analyses integrating the morphology of fossil melanosomes with the chemical identification of pigments, however, makes these inferences tentative. Here, we chemically characterize the melanin content of the soft tissue headcrest of the pterosaur Tupandactylus imperator by alkaline hydrogen peroxide oxidation followed by high-performance liquid chromatography. Our results demonstrate the unequivocal presence of eumelanin in T. imperator headcrest. Scanning electron microscopy followed by statistical analyses, however, reveal that preserved melanosomes containing eumelanin are undistinguishable to pheomelanin-bearing organelles of extant vertebrates. Based on these new findings, straightforward color inferences based on melanosome morphology may not be valid for all fossil vertebrates, and color reconstructions based on ultrastructure alone should be regarded with caution.


Augmentation of ECG QRS complexes after fluid removal via a mechanical ultrafiltration pump in patients with congestive heart failure.
Augmentation of the amplitude of ECG QRS complexes, correlating with loss of weight or fluid volume removed, has been documented in patients with congestive heart failure (CHF). We investigated the effect of an ultrafiltration (UF) pump on the fluid removal and the amplitude of ECG QRS complexes in patients with CHF. Nine patients aged 48.3 +/- 10.4 years with CHF were treated with an UF system, and weights, fluid removed, and sums of the amplitude of QRS complexes (SigmaQRS), were inter-correlated. UF resulted in removal of 4.62 +/- 1.82 L of fluid, 5.0 +/- 2.9% decrease in the weights (P = 0.002) and 18.1 +/- 16.8% increase in the SigmaQRS (P = 0.012). There was a moderate correlation of % increase in the SigmaQRS and net fluid volume losses (UF + urine - oral intake), (r = 0.67, P = 0.0471, and a poor correlation between % increase in the SigmaQRS and % decrease in weights (r = 0.11, P = 0.77). Correlations of the change in weights after UF with the fluid removed by UF, or with the volume of total fluid loss (including insensible losses) were moderate but barely statistically significant (r = 0.65, P = 0.0559), and (r = 0.65, P = 0.0577), correspondingly. Augmentation of the amplitude of QRS complexes correlates well with net fluid loss in response to UF in patients with CHF, and can be employed as an index of effectiveness of therapy. Also, a model of fluid losses in patients treated for CHF is being proposed.


Drug resistance pattern of mycobacterial isolates in HIV and non-HIV population in South India.
Emergence of drug resistance has complicated the treatment of tuberculosis (TB). WHO reports India to be one among 27 "high burden" multidrug-resistant (MDR) TB countries. To diagnose TB and detect drug resistance of mycobacterial isolates in acid-fast bacilli (AFB) smear negative HIV reactive patients (Group A) and compare them with HIV seropositive AFB smear positive (Group B) and HIV-seronegative AFB positive cases (Group C). Clinical specimens collected in all groups were processed as per the standard protocol except blood, which was processed by lysis centrifugation technique. They were then inoculated with Lowenstein-Jensen media and the isolates obtained were subjected to drug susceptibility test (DST) by proportion method and genotype MTBDR plus assay. In Group A, 162 patients were included. Of the 443 clinical samples collected, 76 mycobacterial strains were obtained from 67 (41%) patients. Of these, 50 (65.8%) were sensitive to all drugs and 26 (34.2%) resistant to one or more anti-tubercular drugs. Antibiogram of Group A when compared with Group B and C showed that the MDR rate 6.6%, 6.7% and 8% respectively) did not differ much; but resistance to at least single drug was (26 [34.2%], 3 [10%], and 8 [16%]), respectively. Our study suggests that HIV has no influence on the anti-tubercular resistance pattern, but increased MDR rate along with HIV in high TB burden setting stresses the need for early diagnosis and DST in providing proper regimens and improve prognosis.


Associated Factors for Asthma Severity in Korean Children: A Korean Childhood Asthma Study.
Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. This study was performed on 667 children aged 5-15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.


Structural determinants of metal selectivity in prokaryotic metal-responsive transcriptional regulators.
Metal ion homeostasis in prokaryotes is maintained by metal-responsive transcriptional regulatory proteins that regulate the transcription of genes encoding proteins responsible for metal detoxification, sequestration, efflux and uptake. These metalloregulatory, or metal sensor proteins, bind a wide range of specific metal ions directly; this in turn, allosterically regulates (enhances or decreases) operator/promoter binding affinity or promoter structure. Recent structural studies reveal five distinct families of metal sensor proteins. The MerR and ArsR/SmtB families regulate the expression of genes required for metal ion detoxification, efflux and sequestration; here, metal binding leads to activation (MerR) or derepression (ArsR/SmtB) of the resistance operon. In contrast, the DtxR, Fur, and NikR families regulate genes encoding proteins involved in metal ion uptake; in these cases, the metal ion functions as a co-repressor in turning off uptake genes under metal-replete conditions. Inspection of the structures of representative members from each metal sensor family reveals several common characteristics: (1) they function as homo-oligomers (either dimers or tetramers); (2) metal-binding ligands are found at subunit interfaces, with ligands derived from more than one protomer; this likely helps drive quaternary structural changes that mediate allosteric coupling between the metal and DNA binding sites; and (3) the primary determinant of metal ion selectivity within each protein family is dictated by the coordination geometry of the metal chelate, with trends consistent with expectations from fundamental inorganic chemistry. This review highlights recent efforts to elucidate the structure of metal sensing chelates and the molecular mechanisms of allosteric coupling in metal sensor proteins.


Equipping clinical leaders for system and service improvements in quality and safety: an Australian experience.
To develop clinical leadership among health professionals working in public sector organisations to improve their skills in ensuring high quality and safe health services. A longitudinal pre-post-intervention mixed methods study that included 60 health professionals working in one state in Australia. The program was successful in the development of clinical leaders. An interdisciplinary, inter-sectoral leadership development program involving health professionals from metropolitan, regional and rural areas can be successful in developing knowledge, skills and competencies among these health professionals in health service quality and safety. Health professionals can participate in a development program to enhance their clinical leadership skills. While this was a post-qualification course, targeting experienced health professionals, the learnings could be applied to pre-qualification education of health professionals.


In vitro fertilization treatments with the use of clomiphene citrate or letrozole.
There has been increasing interest in combining the oral agents clomiphene citrate (CC) and letrozole with gonadotropins in IVF: for poor responders to reduce the amount of gonadotropins used, and in normal responders to reduce the incidence of ovarian hyperstimulation (OHSS). In normal responders, mild stimulation with the use of CC and gonadotropins was found to decrease the number of oocytes retrieved and result in good pregnancy rates, but in most studies the cumulative pregnancy rate was lower compared with conventional ovarian stimulation when frozen embryo transfers were considered. Coadministration of letrozole and gonadotropins has mainly been used in patients with breast cancer to prevent the massive elevation of serum E2 concentrations with the use of standard controlled ovarian hyperstimulation. CC and letrozole have both been used with gonadotropins in poor responders and have been shown to reduce the amount of gonadotropin used without reducing the pregnancy rate. Letrozole use with gonadotropins in IVF cycles may increase endometrial receptivity by increasing integrin expression in the endometrium and by lowering estrogen concentrations to more physiologic levels.


CIN or not: An approach to the evaluation and management of chronic idiopathic neutrophilia.
Neutrophilia refers to an increase in the number of circulating neutrophils in the peripheral blood. Some common etiologies include infection, inflammatory conditions, myeloproliferative disorders, malignancies, endocrinopathies, drugs, and anemia. Rare disorders such as leukocyte adhesion deficiency can also cause neutrophilia. In many cases, there is an elevation of neutrophil count that persists for months or even years with no clear underlying cause in an otherwise asymptomatic patient. This is referred to as chronic idiopathic neutrophilia (CIN). Despite being a condition encountered by many physicians, there is a paucity of literature addressing CIN. Certain conditions such as stress, exercise, smoking, obesity, and obstructive sleep apnea have been associated with CIN and may provide explanations for neutrophilia previously thought to be idiopathic. Herein, we present a review of the literature on CIN and propose a systematic approach to this commonly encountered clinical condition.


Management of hepatocellular carcinoma patients with portal vein tumor thrombosis: A narrative review.
Hepatocellular carcinoma (HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis (PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. We have reviewed literature from PubMed on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can benefit from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also beneficial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classification models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival. HCC with PVTT is still a thorny problem, and effective therapeutics need to be explored.


pH-Responsive strips integrated with resazurin and carbon dots for monitoring shrimp freshness.
Carbon dots (CDs) were synthesized via a one-step hydrothermal approach using tangerine peel (Tan) and resazurin (Res) to fabricate biocompatible indicators for food freshness. The CDs' pH-responsive mechanism, morphology, zeta potential, XPS, and optical and fluorescence analysis were investigated. The as-prepared tangerine peel/resazurin carbon dots (Tan/Res CDs) exhibited pH-responsive emission that changed from yellow to orange as the pH value increased. The Tan/Res CDs showed the sensing ability of ammonia with a detection limit of 0.84 μM by proportionally losing fluorescence intensity as the concentration increased from 1 to 100 μM. The CDs were coated onto paper strips to impart biogenic amine (BAs) detection for pH-responsive intelligent monitoring of packaged foods. The Tan/Res CDs paper-based indicator exhibited an impressive color change from yellow to brown during the detection of ammonia vapor. The indicator also showed the ability to detect BAs through a color change, demonstrating the ability to monitor the freshness of shrimp in situ. Additionally, the efficacy of the Tan/Res CDs indicator is validated by total volatile basic nitrogen (TVB-N), providing customers and suppliers with a simple, inexpensive, and portable tool to monitor the freshness of seafood in real-time.


Effects of platelet-rich plasma in the treatment of plantar fasciitis: A meta-analysis of randomized controlled trials.
Plantar fasciitis is a common cause of heel pain, which often results in significant morbidity. There have been several treatment options that are used for plantar fasciitis, including nonsteroidal anti-inflammatory drugs, orthoses, physical therapy, and steroid injections. The aim of this meta-analysis was to compare the effects of platelet-rich plasma (PRP) and other treatments in patients with plantar fasciitis. Medline, Web of Science, and Embase were systematically searched to identify relevant trials. Randomized controlled trials (RCTs) that compared the effects of PRP and other treatments on plantar fasciitis were included. The main outcomes included changes from baseline in visual analog scale (VAS) score, American Orthopaedic Foot and Ankle Society Score (AOFAS), and Roles-Maudsley score (RMS). Results were expressed as weight mean difference (WMD) with 95% confidence interval (95% CI). The meta-analysis was performed using a fixed-effects or random-effects model according to heterogeneity. Ten RCTs involving a total of 445 patients with plantar fasciitis were included. Among these studies, 9 compared PRP with steroid, and 1 compared PRP with whole blood.Four studies were categorized as being at low risk of bias, and the remaining 6 as being at unclear risk of bias.Pooled estimates suggested that PRP had greater changes in VAS and AOFAS scores than other treatments. However, it had no benefit effect in the RMS.Subgroup analysis for VAS and AOFAS showed that PRP had superior effect than other treatments at 12 months, but not at the 1, 3, 6 months.Subgroup analysis based on treatment regimens demonstrated that PRP was more effective than steroid in the change from baseline in AOFAS, but not in VAS and RMS scores. PRP was as effective as other treatments in reducing pain and improving function in patients with plantar fasciitis. Subgroup analysis indicated that PRP had better effect than steroid in AOFAS Score and its effect was durable in a long term. However, considering the potential limitations in this study, more large-scale RCTs are needed to confirm the current findings.


Photodegradation of organic contamination in wastewaters by bonding TiO2/single-walled carbon nanotube composites with enhanced photocatalytic activity.
Bonding TiO(2)/single-walled carbon nanotube (SWCNT) composites have been successfully synthesized through a facile sol-solvothermal technique. The obtained materials were characterized in detail by XRD, FT-IR, Raman and TEM. The results revealed that TiO(2) and SWNCT linked compactly through ester bonds and thus improved their interfaces. Therefore, the recombination of photogenerated electron-hole pairs was inhibited efficiently, which improved the photocatalytic activity. A reasonable mechanism was proposed to explain its formation. The photocatalytic activity was investigated utilizing rhodamine B and nitrobenzene (NB) as models for organic contamination in wastewaters. Experimental results indicated that this bonding composite exhibited higher photocatalytic activity than that of Degussa P25. The excellent photocatalytic activity could be attributed to larger surface area, smaller crystalline size, and especially the ester bonds, which was further confirmed by surface photovoltage spectroscopy. Furthermore, by adding ()OH scavenger tert-butanol, the obvious decrease of NB photodegradation indicated that NB was oxidized primarily by ()OH. The photodegradation products were identified by GC/MS, further indicating that the degradation proceeded via ()OH oxidation. A possible reaction pathway for the degradation of NB was suggested by the evidence presented in this study.


Heterogeneity of schizoaffective disorder compared with schizophrenia and bipolar disorder.
Low diagnostic reliability, the need to meet criteria of two disorders, and its status as residual diagnosis in clinical practice led us to hypothesize that schizoaffective disorder (SAD) is characterized by considerable heterogeneity, particularly in comparison with schizophrenia (SZ) and bipolar disorder (BD). As this has not been investigated the aim of this study is to test whether heterogeneity is larger in SAD than in SZ and BD. Systematic search for studies simultaneously comparing all three diagnoses regarding demographic, clinical, psychometric (clinical rating scales and IQ tests), and biological parameters; comparison of heterogeneity as measured by standard deviation (SD). Standard deviation of SAD samples (N = 47) was smaller than in both differential diagnoses. SDs were 7% higher in BD than in SAD (SZ: 2% higher); in studies employing DSM-IIIR/-IV pooled SD was 4% higher in BD (8% lower in SZ). Differences between diagnoses were limited to the comparison of SAD and BD, and became smaller when only psychotic BD was considered. Heterogeneity of SZ and BD is not smaller than that of SAD. SAD seems not to be more diverse than other functional psychoses. Results are preliminary because of the novelty of the approach and to the small number of studies.


Careers in medicine or what do you want when you grow up?
This paper is in the form of a letter to a medical student advising her/him on how to choose his/her future specialty.


Viruses that ride on the coat-tails of actin nucleation.
Actin nucleation drives a diversity of critical cellular processes and the motility of a select group of viral pathogens. Vaccinia virus and baculovirus, Autographa californica multiple nucleopolyhedrovirus, recruit and activate the cellular actin nucleator, the Arp2/3 complex, at the surface of virus particles thereby instigating highly localized actin nucleation. The extension of these filaments provides a mechanical force that bestows the ability to navigate the intracellular environment and promote their infectious cycles. This review outlines the viral and cellular proteins that initiate and regulate the signalling networks leading to viral modification of the actin cytoskeleton and summarizes recent insights into the role of actin-based virus transport.


Perinatal changes of 2,3-diphosphoglycerate and oxygen affinity in mammals not having fetal type hemoglobins.
The interrelationship of 2,3-diphosphoglycerate (2,3-DPG) and P50 levels during the fetal and postnatal life were determined in two mammalian species which do not have a switchover of hemoglobin type at the end of their fetal development. In the guinea pig and rabbit, the 2,3-DPG levels remain low during fetal life and increase only after birth remaining elevated throughout adult life. The adult levels were reached at 2 days of age in the guinea pig and the 20th day in rabbit. Fetal P50 values increased only after birth, paralleling the rise in the 2,3-DPG. The rapidity of the postnatal rise in 2,3-DPG and decrease in P50 appears related to the maturity of the newborn animal at birth in these species.


Activation of membrane receptors by neurotransmitter released from temperature-sensitive hydrogels.
The present paper describes the design, construction and testing of a temperature-sensitive N-isopropylacrylamide hydrogel device for studying the controlled presentation of gamma-aminobutyric acid (GABA) to GABA(C) membrane receptors expressed in Xenopus laevis oocytes. Upon temperature lowering, the GABA-loaded hydrogel positioned near the surface of the GABA(C)-expressing oocyte elicits a membrane current response resembling that induced by superfusion of the oocyte with free GABA. The response to cooling is not observed when GABA is omitted from the hydrogel loading solution. In addition, picrotoxin, a known GABA(C) receptor antagonist, inhibits the oocyte membrane current response associated with temperature lowering of GABA-loaded hydrogels. The data indicate that the present system affords a temperature-regulated release of GABA from the hydrogel and a resulting activation of the expressed GABA(C) receptors.


Presence of hemagglutination inhibition and neutralization antibodies to Japanese encephalitis virus in wild pigs on an offshore island in Singapore.
A study was conducted to determine the presence of hemagglutination inhibition (HI) and neutralization antibodies against Japanese encephalitis virus (JEV) in wild pigs on an offshore island in Singapore. Blood samples were collected from 28 wild pigs on the island. All the sera tested with HI assay and plaque reduction neutralization tests were found to be positive for antibodies against JEV. Our results indicate that the wild pigs have been infected with JEV on the offshore island and there is JEV transmission.


Maternal mortality in a rural Tanzanian hospital: fatal Jarisch-Herxheimer reaction in a case of relapsing fever in pregnancy.
Relapsing fever is a disease caused by one of the species of Borrelia. It is often misdiagnosed as malaria and can have fatal complications such as the Jarisch-Herxheimer reaction (JHR) after the commencement of treatment with antibiotics. A 19-year-old Tanzanian woman was admitted after a term home delivery that day. She presented with a 2 day history of fever, headache, general body malaise and vomiting. She was misdiagnosed as having severe malaria and was treated with quinine. The blood slide showed Borrelia duttoni. The patient continued treatment with procaine penicillin fortified for relapsing fever. Several hours later the woman died, probably due to JHR. This case of a patient with relapsing fever who died from a JHR stresses the importance of adequate diagnosis and treatment which should include careful monitoring, especially for the first hours after starting antibiotics.


Calcium, phosphoinositide, and 1,2-diacylglycerol responses of blood vessels of deoxycorticosterone acetate-salt hypertensive rats to endothelin-1.
In previous studies a decreased responsiveness to endothelin-1 (ET-1) of conduit arteries and resistance vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats was found in comparison with uninephrectomized controls. Decreased isometric force, number of receptors, and inositol phosphate accumulation were reported in the DOCA-salt animals. In the present study effects of ET-1 on cytosolic free calcium, inositol phosphates, and 1,2-diacylglycerol were investigated in blood vessels of DOCA-salt hypertensive rats. Basal cytosolic free calcium, measured with the fluorescent dye fura-2, was 201 +/- 41 nmol/l in mesenteric arteries of DOCA-salt rats and 45 +/- 9 nmol/l in uninephrectomized controls (p less than 0.01). The maximal response of cytosolic free calcium (to 30 nmol/l ET-1) was 176 +/- 22% of the basal value for DOCA-salt and 242 +/- 6% for uninephrectomized rats (p less than 0.05). The concentration giving 50% of the maximum response was 9.0 and 6.5 nmol/l for DOCA-salt rats and controls, respectively. Inositol phosphate production after stimulation with 100 nmol/l ET-1 in the presence of LiCl was lower by at least 30% (p less than 0.01) in both aorta and mesenteric arteries of DOCA-salt hypertensive versus control rats. Basal levels of diacylglycerol in aorta were similar in DOCA-salt rats and in controls and did not respond to a 100 nmol/l ET-1 stimulation in the DOCA-salt rats, in contrast to the increase found in the control uninephrectomized rats (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Kinase-negative mutants of S49 mouse lymphoma cells carry a trans-dominant mutation affecting expression of cAMP-dependent protein kinase.
Kinase-negative mutants of S49 mouse lymphoma cells are pleiotropically negative for all known cAMP-mediated responses of S49 cells and yield cell extracts which are deficient in cAMP binding activity and devoid of cAMP-dependent protein kinase activity. In hybrids between kinase-negative and wild-type cells, the mutant phenotype is dominant: the tetraploid hybrids have reduced cAMP-binding activity and undetectable cAMP-dependent kinase activity. The mutant phenotype is attributable to neither a soluble inhibitor of kinase catalytic subunit, nor a defective kinase regulatory subunit acting as an inhibitor, nor a defective catalytic subunit which sequesters regulatory subunits in inactive complexes. We propose that these mutants carry trans-dominant lesions in a regulatory locus responsible for setting intracellular levels of kinase expression.


Selective retrieval of antibody-secreting hybridomas in cell arrays based on the dielectrophoresis.
A cascade of the formation of cell arrays, the discrimination of cells secreting specific molecules, and the selective retrieval of cells has been developed to harvest antibody-secreting hybridomas in heterogeneous cell populations simply and rapidly. The microwell array device consisted of three-dimensional microband electrodes by assembling both upper and lower substrates perpendicularly. Arrays of hybridomas secreting specific antibodies were prepared by aligning hybridomas in each microwell based on the attractive force of positive dielectrophoresis (p-DEP). Antibody secreted by the hybridomas in the microwells was recognized by the antigen immobilized on the microwells or the membrane surfaces of hybridomas to discriminate hybridomas with the secretion ability. Thereafter, a repulsive force of negative dielectrophoresis (n-DEP) was applied to release the target hybridomas from the microwell array. To harvest the target hybridoma, AC signals could be modulated in the n-DEP frequency region and applied to a pair of microband electrodes located above and below each microwell containing target hybridoma. Thus, the cell-based array system described in this study allowed selective retrieval of single target hybridomas by merely switching from p-DEP to n-DEP after selecting the antibody-secreting hybridomas trapped in each microwell. The development of this high-affinity device could be useful to recover hybridomas producing antibodies in large populations of cells rapidly and effectively.


Computed tomographic findings in cerebral hemiatrophy.
The clinical, plain skull radiographic, brain scan, and CT findings of four patients with cerebral hemiatrophy are described. CT scanning is the most innocuous and most sensitive diagnostic method available to confirm the clinical diagnosis when plain skull radiographic changes are not confirmatory.


Crohn's Disease Only Visible on Small Bowel Capsule Endoscopy: A New Entity.
In rare cases, the diagnosis of Crohn's disease (CD) can only be achieved using small bowel capsule endoscopy (SBCE). We investigate the characteristics of patients with CD only visible on SBCE and assess their disease course. Data of all adult patients with confirmed CD diagnosis based on SBCE with normal endoscopic and cross-sectional imaging findings were retrospectively collected in three tertiary-level hospitals from January 2014 to March 2020. Thirteen patients were included. Ten patients were females, and the mean age at diagnosis was 36 years. Ileum was mostly involved (85%), while duodenum and jejunum were affected in 23% and 38% of the cases, respectively. Nine patients had one segment involved, while four subjects had two or three segments affected. All patients had inflammatory behavior. First treatment consisted of steroids in all cases, and six patients were later treated with immunosuppressant or biologics. After a mean follow-up of 27.5 months, no change in disease behavior, hospitalization, or CD-related surgery was observed. CD only visible at SBCE is a rare condition with a more favorable disease course compared to general CD with a lower rate of complicated behavior, hospitalization, and surgery, despite a similar use of immunosuppressant or biologics.


Whether Letrozole could reduce the incidence of early ovary hyperstimulation syndrome after assisted reproductive technology? A systematic review and meta-analysis.
Letrozole can significantly decrease the estrogen level, and has been administrated to prevent the incidence of early ovary hyperstimulation syndrome (OHSS). However, the effect of Letrozole on prevention of OHSS reached to controversial conclusions. The present meta-analysis aim to examine whether Letrozole could reduce the incidence of early OHSS after assisted reproductive technology (ART). An exhaustive electronic literature search was conducted on MEDLINE, Google Scholar, CNKI and WANFANG MED ONLINE, from inception until May 2018. We include clinical trials that examined the effect of Letrozole on the prevention of early OHSS. The main outcome measures were the incidence of total early OHSS, mild early OHSS, moderate early OHSS, and severe early OHSS. Eight studies included in the review. Of these, five publications evaluated the effect of Letrozolel on the prevention of total, mild, moderate, and severe OHSS, respectively. The results indicated that there was a significantly decreased incidence of total OHSS with Letrozole compared with control group, and there were no significantly differences in the incidence of mild, moderate, and severe OHSS between study group with Letrozole and control group. Eight studies reported the incidence of moderate + severe OHSS. We found a significant decrease in incidence of moderate + severe OHSS in high-risk women with Letrozole. Letrozole has no beneficial effect on the prevention of mild, moderate, and severe OHSS, individually; Letrozole should not be considered as the first-line treatment for prevention of OHSS. Further cohort studies are required to explore the effect of Letrozole on the prevention of OHSS. This study aimed to examine whether Letrozole could reduce the incidence of early OHSS after assisted reproductive technology (ART). A meta-analysis including 8 studies was conducted. There were no significantly differences in the incidence of mild, moderate, and severe OHSS between study group with Letrozole and control group. Letrozole has no beneficial effect on the prevention of mild, moderate, and severe OHSS, individually.


CDCDB: A large and continuously updated drug combination database.
In recent years, due to the complementary action of drug combinations over mono-therapy, the multiple-drugs for multiple-targets paradigm has received increased attention to treat bacterial infections and complex diseases. Although new drug combinations screening has benefited from experimental tests like automated high throughput screening, it is limited due to the large number of possible drug combinations. The task of drug combination screening can be streamlined through computational methods and models. Such models require up-to-date databases; however, existing databases are static and consist of the data collected at the time of their creation. This paper introduces the Continuous Drug Combination Database (CDCDB), a continuously updated drug combination database. The CDCDB includes over 40,795 drug combinations, of which 17,107 are unique combinations consisting of more than 4,129 individual drugs, curated from ClinicalTrials.gov, the FDA Orange Book®, and patents. To create CDCDB, we use various methods, including natural language processing techniques, to improve the process of drug combination discovery, ensuring that our database can be used for drug synergy prediction. Website: https://icc.ise.bgu.ac.il/medical_ai/CDCDB/ .


An in vitro study of theaflavins extracted from black tea to neutralize bovine rotavirus and bovine coronavirus infections.
Crude theaflavin was extracted from black tea and then fractionated by HPLC into five components (initial peaks (IP), TF1, TF2A, TF2B, and TF3). The crude extract and the various fractions of theaflavin were collected and tested, individually and in combination, for antirotaviral activity. The mean effective concentration (EC50) was calculated and compared. Activity varied from the most active being the uncharacterized theaflavin-like initial peaks (IP) with an EC50 of 0.125 microgram/ml to the least active being theaflavin-3 monogallate (TF2A) with an EC50 of 251.39 micrograms/ ml. The combination of TF1 + TF2A + TF2B + TF3 was more active than the sum of the activities of these four fractions individually, indicating synergism among the peaks. Only the crude extract was assayed for activity against coronavirus; the EC50 was 34.7 micrograms/ml.


Limbic hyperreactivity in bipolar II disorder.
The authors' goal was to determine whether patients with bipolar II disorder had altered regional brain responses to novel motor sequences. Regional cerebral blood flow was measured with positron emission tomography in 13 patients with bipolar II disorder and 14 healthy comparison subjects. Participants performed a serial reaction time task in which they were visually cued to press one of four buttons at a time. The order of button presses was determined by a complex sequence that was changed in the latter half of the study. In the comparison subjects a spatial attention circuit in the superior parietal lobe and supplementary motor area was activated in response to the introduction of the new sequence. Patients did not display this activation pattern; instead, a widespread limbic network was activated in response to the new sequence. The attentional resources of patients with bipolar II disorder are not reallocated when they are confronted with a nonemotional motor task; rather, their performance is altered through activation of limbic circuitry.


Neuroprotective effects of glucagon-like peptide-1 (GLP-1) analogues in epilepsy and associated comorbidities.
Epilepsy is a common neurological condition induced by losing equilibrium of different pathway as well as neurotransmitters that affects over 50 million people globally. Furthermore, long-term administration of anti-seizure medications has been associated with psychological adverse effects. Also, epilepsy has been related to an increased prevalence of obesity and called type 2 diabetes mellitus. On the other hand, GLP-1 receptors are located throughout the brain, including the hippocampus, which have been associated to majority of neurological conditions, such as epilepsy and psychiatric disorders. Moreover, the impact of different GLP-1 analogues on diverse neurotransmitter systems and associated cellular and molecular pathways as a potential therapeutic target for epilepsy and associated comorbidities has piqued curiosity. In this regard, the anticonvulsant effects of GLP-1 analogues have been investigated in various animal models and promising results such as anticonvulsants as well as cognitive improvements have been observed. For instance, GLP-1 analogues like liraglutide in addition to their possible anticonvulsant benefits, could be utilized to alleviate mental cognitive problems caused by both epilepsy and anti-seizure medication side effects. In this review and growing protective function of GLP-1 in epilepsy induced by disturbed neurotransmitter pathways and the probable mechanisms of action of GLP-1 analogues as well as the GLP-1 receptor in these effects have been discussed.


Presumed adrenal insufficiency in neonates treated with corticosteroids for the prevention of bronchopulmonary dysplasia.
To determine if extremely preterm (EPT) neonates receiving dexamethasone for the prevention of BPD have a higher incidence of presumed adrenal insufficiency (PAI). Retrospective cohort study of neonates <28 weeks gestation examining PAI after dexamethasone use and PAI after intratracheal budesonide with surfactant administration. Of 332 neonates, 38% received dexamethasone. The incidence of PAI was higher in neonates who had received dexamethasone (20.8% vs 2.9%, p < 0.001). However, for intubated babies receiving surfactant, dexamethasone was not independently associated with increased PAI after adjusting for gestational age, birthweight, and race (aOR 2.92, 95% CI: 0.79-10.85). Dexamethasone was independently associated with increased PAI in infants previously receiving budesonide/surfactant treatment (aOR 5.38, 95% CI: 1.38-20.90). The use of dexamethasone alone was not associated with increased PAI, when adjusted for prematurity-related factors. The combination of budesonide with dexamethasone was significantly associated with increased PAI.