Transient salt wasting in POMC-deficiency due to infection induced stress.
Obesity is a multifactorial disorder influenced by genetic, behavioral, environmental and cultural factors. A twelve month old male patient was admitted to the hospital because of malaise, irritability, disquietness and obesity. His BMI was 19.8 kg/m (2) and BMI SDS was 1.38. Mental development was normal, and motor skills were mildly delayed most probably due to his obesity. His physical examination was totally normal except obesity and red hair. A history of hypoglycemia on the fourth day of life, which resolved after oral glucose administration, was reported. The child had been hyperphagic from the first weeks of life and had aggressive behavior when food was denied. The body weight of the patient increased dramatically during the first year of life. Based on the clinical features and laboratory findings (the overgrowth syndrome, red hair, hypoglycemia and hypocortisolism) the patient was diagnosed as POMC deficiency and the diagnosis was confirmed by genetic studies. Hypoglycemia and apnea episodes ceased as he was put on hydrocortisone but he developed relative mineralocorticoid deficiency during a urinary tract infection. In POMC deficiency, relative mineralocorticoid deficiency should be in mind in episodes of severe stress and therapy should be initiated.


A randomized, controlled trial of medical therapy versus endoscopic ligation for the prevention of variceal rebleeding in patients with cirrhosis.
Patients who have had one variceal bleed are at high risk of rebleeding. Since its introduction, endoscopic variceal banding has been shown to be superior to needle sclerotherapy. Banding has not been compared with hepatic venous pressure-guided medical therapy (beta-blockers and nitrates). One hundred two patients with cirrhosis and a recent esophageal variceal bleed were randomized to either endoscopic banding (51 patients) or medical therapy (51 patients). The hepatic venous pressure gradient was measured in all patients at baseline, at 3 months (drug therapy arm), and at yearly intervals (all patients). Primary end points were death or rebleeding. The 2 groups were well matched. Fifty-one percent were Pughs C, with a median Pughs score of 9.5. Nineteen patients rebled in the drug arm (median time, 24 days) and 27 patients in the banding arm (median time, 24 days). At 1 year, 43.7% of patients had bled in the drug arm compared with 53.8% in the banding arm (P = 0.25). Thirty-two percent of patients on medical therapy had died at 1 year, 22.5% on banding (P = 0.97). In the prevention of variceal rebleeding, beta-blockers +/- nitrates are as effective as endoscopic banding.


[Culture methods of human liver cells].
Attempts to isolate and cultivate human liver cells have been described. Many viable liver cells have been obtained when dissociated with collagenase followed by dispase. The morphology and differentiated functions have been maintained for more than 3 weeks when human fetal liver cells were cultured not only in medium containing 10(-3) M hydrocortisone, but also on collagen gel substrates with 5 x 10(-7) M hydrocortisone. The colony-forming capacity of primary cultured fetal human livers has also been described in the presence of conditioned medium.


SURGICAL STRATEGY FOR LARGE EXTRACEREBRAL SUBTENTORIAL TUMORS.
Radical surgery over large subtentorial tumors is associated with a high risk of postoperative complications. Despite significant development of imaging technology, intraoperative monitoring, and microsurgical treatment, problems one of tottal and safe large subtentorial tumors removal remain unsolved. The most critical problem relating to large tumors of this localization is postoperative edema. Also brainstem ischemic stroke is not rare and this would partly due to the tumors overgrowthing the vertebral and basilar arteries. Retrospective analysis of 59 patients with large (more than 3 cm) tumors to the posterior cranial fossa operated over 2015-2019 yy. There was gross total tumor removal in 49 (83%) patients; subtotal tumor removal in 5 (8,5%) patients; partial tumor removal in 5 (8,5%) cases. Complications occurred in 15 (25%) patients. The use of ventral craniobasal aprroaches and their combination with posterior-lateral approaches to the large subtentorial tumors allows rapid and early, effective brain stem decompression and subsequent safe and total tumor removal. Ventral decompression of the brain stem structures (endoscopic endonasal and transoral approaches, presigmoid approach, extreme lateral approach) prevents neurological complications thus early patients activation. Postoperative mortality of 3 (5.0%) out of 59 patients can be reduced by intensifying perioperative patient's management.


Adenylate energy pool and energy charge in maturing rape seeds.
A study of energy state and chemical composition of pod walls and seeds of maturing rape (Brassica napus L.) was conducted on two varieties, Victor and Gorczanski. Total adenosine phosphates, ATP, and adenylate energy charge increased with increasing cell number and cellular synthesis during the early stages, remained high at maximum dry weight accumulation and maximum substrate influx time, and decreased with ripening. A temporal control of energy supply and ATP concentration is evident in developing tissues with determined functions; whereas the association of a high energy charge and active cellular biosynthesis occurs only in tissues with a stabilized cell number.


Promoting Wellness in Orthopaedic Surgery Residency.
The challenges associated with surgical residency have been well documented and described. Despite implementation of work-hour restrictions, residency remains a balancing act between patient care, surgical and clinical education, medical record documentation, and research endeavors. The added challenge of balancing these duties with life outside of the hospital further complicates the situation. Multiple studies have documented the stress associated with residency training, highlighting the prevalence of emotional exhaustion, detachment from people both in and out of the hospital, and a concerning rate of clinical depression among residents. Moreover, this emotional exhaustion has been shown to directly correlate with residents' clinical performance and abilities to carry out academic duties. More recently, feelings of isolation and detachment have been exacerbated by the necessity of COVID-19 precautions and change in clinical duties. The Accreditation for Graduate Medical Education (ACGM) now requires all residencies to include programming that focuses on resident well-being. Programs have implemented various strategies in an effort to help their trainees cope with the stress associated with residency and beyond. Despite the variety in approaches of programs, these initiatives have the similar objective of teaching resilience and the ability to navigate stressors in a healthy and effective manner. The programming can also serve to promote resident interaction and develop camaraderie in an effort to minimize feelings of emotional exhaustion and isolation. In this article, we discuss the importance of sustained physician wellness and describe approaches from various professions that can be implemented into the wellness curriculum for residency programs across the country. By promoting a culture of wellness and incorporating effective wellness programming, our aim is that residents will be able to succeed not only in their training but also in their personal lives and professional endeavors after graduation.


Line focusing in micro-Raman spectroscopy.
In a microscope of a micro-Raman spectrometer a cylindrical lens is introduced to form a line-focus microprobe (LFMP). The dimensions of the LFMP are 0.66 x 167 microm. The lateral spatial resolution of Raman scattering with the LFMP is equal to the spatial resolution of the point-focus microprobe (PFMP). It is shown that the LFMP system enables measurements with a laser power density that is 320 times lower than the PFMP. For the same laser power density in both types of illumination, the LFMP Raman spectra give approximately radical320 or asymptotically equal to 18 times better signal-to-noise ratio.


Geometrical Scaling Effects in the Mechanical Properties of 3D-Printed Body-Centered Cubic (BCC) Lattice Structures.
This paper investigates size effects on the mechanical response of additively manufactured lattice structures based on a commercially available polylactic acid (PLA) polymer. Initial attention is focused on investigating geometrical effects in the mechanical properties of simple beams and cubes. Following this, a number of geometrically scaled lattice structures based on the body-centered cubic design were manufactured and tested in order to highlight size effects in their compression properties and failure modes. A finite element analysis was also conducted in order to compare the predicted modes of failure with those observed experimentally. Scaling effects were observed in the compression response of the PLA cubes, with the compression strength increasing by approximately 19% over the range of scale sizes investigated. Similar size-related effects were observed in the flexural samples, where a brittle mode of failure was observed at all scale sizes. Here, the flexural strength increased by approximately 18% when passing from the quarter size sample to its full-scale counterpart. Significant size effects were observed following the compression tests on the scaled lattice structures. Here, the compression strength increased by approximately 60% over the four sample sizes, in spite of the fact that similar failure modes were observed in all samples. Finally, reasonably good agreement was observed between the predicted failure modes and those observed experimentally. However, the FE models tended to over-estimate the mechanical properties of the lattice structures, probably as a result of the fact that the models were assumed to be defect free.


Cellular localization and up-regulation of multidrug resistance-associated protein 3 in hepatocytes and cholangiocytes during obstructive cholestasis in rat liver.
The hepatic expression of the ATP-dependent conjugate export pump multidrug resistance-associated protein 2 (Mrp2) is diminished in experimentally induced models of cholestasis. In this study we have examined the localization and expression of Mrp3, another member of the multidrug resistance-associated protein family, in normal liver and after obstructive cholestasis in the rat. Indirect immunofluorescence and confocal microscopy were used to determine the tissue localization and Western blot analysis was performed to quantitate the expression. In normal rat liver Mrp3 was found on the basolateral membrane of cholangiocytes and a single layer of hepatocytes surrounding the central vein. Three and 7 days after bile duct ligation Mrp3 expression was significantly increased, predominantly in hepatocytes in the pericentral region. By 14 days all hepatocytes showed basolateral membrane labeling for Mrp3 at a time when apical Mrp2 staining was significantly diminished. Proliferating bile ducts continued to stain positive, although the intensity of staining did not seem to vary. After 14 days Western blot quantitation showed that Mrp3 had increased approximately 30-fold in total liver membranes. Quantitation of Mrp3 in membranes from isolated hepatocytes of livers of sham and common bile duct-ligated (CBDL) animals showed a significant up-regulation beginning at 1 day and continuing to increase through 14 days postligation. This was in contrast to the progressive decrease in Mrp2 protein. Because Mrp3 is capable of transporting toxic bile acids, up-regulation of Mrp3 may compensate for the down-regulation of Mrp2 in obstructive cholestasis.


Pharmacokinetics of rapamycin.
Based on the present findings, a number of preliminary conclusions can be made regarding the distribution, pharmacokinetics, and therapeutic range investigations with RAPA: (a) the majority of the drug is sequestered in erythrocytes, resulting in whole blood concentrations; (b) the drug has a relatively long half-life in both humans and animals with 24-hour trough concentrations being within the analytical range of HPLC when immunosuppressive doses are administered; (c) the drug exhibits a proportionality between trough concentrations and dose; (d) trough concentrations of the drug appear to be related to immunosuppressive efficacy and drug-related side effects. The studies described here should provide a basis for the establishment of therapeutic monitoring protocols for RAPA.


Analgesic and anti-inflammatory activities of Piper nigrum L.
To evaluate and compare the analgesic and anti-inflammatory activity of pure compound, piperine along with hexane and ethanol extracts of Piper nigrum L. fruit in mice and rats. The analgesic activity was determined by tail immersion method, analgesy-meter, hot plate and acetic acid induced writhing test. While the anti-inflammatory activity was evaluated by carrageenan-induced paw inflammation in rats. Piperine at a dose of 5 mg/kg and ethanol extract at a dose of 15 mg/kg after 120 min and hexane extract at a dose of 10 mg/kg after 60 min exhibited significant (P<0.05) analgesic activity by tail immersion method, in comparison to ethanol extract at a dose of 10 mg/kg using analgesy-meter in rats. However, with hotplate method, piperine produced significant (P<0.05) analgesic activity at lower doses (5 and 10 mg/kg) after 120 min. A similar analgesic activity was noted with hexane extract at 15 mg/kg. However, in writhing test, ethanol extract significantly (P<0.05) stopped the number of writhes at a dose of 15 mg/kg, while piperine at a dose of 10 mg/kg completely terminated the writhes in mice. In the evaluation of anti-inflammatory effect using plethysmometer, piperine at doses of 10 and 15 mg/kg started producing anti-inflammatory effect after 30 min, which lasted till 60 min, whereas hexane and ethanol extracts also produced a similar activity at a slightly low dose (10 mg/kg) but lasted for 120 min. It is concluded from the present study that Piper nigrum L possesses potent analgesic and anti-inflammatory activities.


Routine cerebrospinal fluid enterovirus polymerase chain reaction testing reduces hospitalization and antibiotic use for infants 90 days of age or younger.
The goal was to evaluate the impact of cerebrospinal fluid enterovirus polymerase chain reaction testing on the length of hospitalization and the duration of antibiotic use for infants < or = 90 days of age with suspected aseptic meningitis. This retrospective cohort study was conducted at an urban, tertiary-care children's hospital. Data were collected for 478 patients < or = 90 days of age for whom cerebrospinal fluid enterovirus polymerase chain reaction testing was performed during the enteroviral seasons of 2000 to 2006. The length of hospitalization and the duration of antibiotic use were assessed. Cerebrospinal fluid enterovirus polymerase chain reaction test results were positive for 154 patients (34.8%). The mean length of stay was 3.65 days. The median polymerase chain reaction turnaround time was 23 hours. In multivariate analysis, having a positive cerebrospinal fluid enterovirus polymerase chain reaction result was associated with a 1.54-day decrease in the length of stay and a 33.7% shorter duration of antibiotic use. When patients were stratified according to the presence or absence of pleocytosis, both groups demonstrated significant reductions in the length of stay with positive cerebrospinal fluid enterovirus polymerase chain reaction results (1.32 and 1.38 days, respectively). Furthermore, increasing the polymerase chain reaction turnaround time by 24 hours increased the length of stay by 13.6% for patients with positive cerebrospinal fluid enterovirus polymerase chain reaction results. Having positive cerebrospinal fluid enterovirus polymerase chain reaction results decreases the length of hospitalization and the duration of antibiotic use for young infants. These results support the routine use of this test during periods of peak enterovirus prevalence.


Evaluation and management of urinary tract infections in the neonate.
The prevalence of urinary tract infections (UTIs) among full-term neonates has been reported to be up to 1.1%, increasing up to 7% among those with fever. UTI in neonates may be the first indicator of underlying abnormalities of kidneys and the urinary tract. Early recognition and therapy of UTI and detection of risk factors offer chances for applying strategies to avoid renal damage and recurrences. However, established diagnostic strategies and prophylactic concepts today are under debate. Currently, the main focus has been on renal changes as indicators for underlying risk factors like vesicoureteral reflux, attaching much importance to dimercaptosuccinyl acid scans. Serum and urine markers will probably allow more restrictive diagnostic imaging. Prenatal and postnatal ultrasound screenings provide additional opportunities for prophylactic measures. Main objectives in the management of neonatal UTIs are the prevention of acute infection-related complications and renal damage. Neonates and very young infants with suspicious pyelonephritis should obligatorily be treated with a combination of parenterally administered antibiotics. As far as possible, diagnostic imaging should be risk-oriented and restricted to noninvasive, nonstressful procedures. The strategies of antibacterial prophylaxis for the prevention of recurrent UTIs are changing. In infants at risk, its benefits have not yet been proven by evident data.


Palmitic acid induces intestinal lipid metabolism disorder, endoplasmic reticulum stress and inflammation by affecting phosphatidylethanolamine content in large yellow croaker Larimichthys crocea.
In the 21st century, intestinal homeostatic imbalance has emerged as a growing health challenge worldwide. Accumulating evidence reveals that excessive intake of saturated fatty acid (SFA) induces intestinal homeostatic imbalance. However, the potential molecular mechanism is still unclear. In the present study, we found that palm oil or palmitic acid (PA) treatment disturbed lipid metabolism homeostasis and triggered endoplasmic reticulum (ER) stress and inflammation in the intestine or intestinal cells of large yellow croaker (Larimichthys crocea). Interestingly, PA treatment significantly decreased phosphatidylethanolamine (PE) content in the intestinal cells. PE supplementation decreased triglyceride content in the intestinal cells induced by PA treatment by inhibiting fatty acid uptake and lipogenesis. PE supplementation suppressed ER stress. Meanwhile, PE supplementation alleviated inflammatory response through p38 MAPK-p65 pathway, reducing the damage of intestinal cells caused by PA treatment to some extent. Our work revealed that intestinal homeostatic imbalance caused by PA treatment was partly due to the decrease of PE content. PE consumption might be a nutritional strategy to regulate intestinal homeostasis in fish and even human beings.


Healthcare Providers' Perspectives and Role in Improving Patient Engagement in HIV Treatment and Care in Almaty, Kazakhstan.
The HIV epidemic continues to grow in Eastern Europe and Central Asia. At the same time, there are major gaps in engagement in HIV treatment and care among people living with HIV (PLHIV) in the region, including Kazakhstan. Healthcare providers may have the potential to improve patients' initiation of and adherence to HIV treatment; however, their perspectives and experiences are often overlooked in the research from Kazakhstan. The purpose of our study was to gain an in-depth understanding of how providers perceive the factors influencing PLHIV's engagement in HIV treatment and care and to identify opportunities for expanding the role that providers can have in improving patient initiation and adherence to treatment in Kazakhstan. Through purposive sampling, we conducted in-depth interviews with 14 healthcare providers at the City AIDS Center in Almaty. We used team-based coding and thematic analysis in order to analyze the data. Quotes from providers were translated from Kazakh and Russian to English to illustrate the themes. Our results show that providers currently view their role as the need to break down myths around ART medications, and to educate and motivate patients to accept their diagnosis and learn to live with HIV. The need to address stigma and social isolation among PLHIV, the risk of overworked providers, and the need to improve patient-provider communication strategies are areas to consider for further interventions. Patient-provider communication interventions are needed in Kazakhstan in order to help meet the country's 90-90-90 HIV targets.


Unexpected lack of reactivity of allogeneic anti-Ia monoclonal antibodies with MHC class II molecules expressed by mouse intestinal epithelial cells.
We have examined MHC class II molecules expression by murine gut epithelial cells using a large panel of anti-Ia antibodies. In contrast to conventional APC (i.e., B cells and macrophages), only two anti-Ia antibodies reacted with enterocytes: a xenogeneic rat anti-Ia mAb (CD311) directed against a monomorphic class II determinant, and a polyclonal antiserum directed against both I-A and I-E heterodimers. In contrast, allogeneic anti-Ia mAb were either unreactive (17 of 20) or reacted weakly (3 of 20) with enterocytes, even after in vivo treatment with IFN-gamma. This pattern of Ia reactivity of epithelial cells was tissue specific (restricted to gut mucosa) and cell specific (restricted to gut epithelial cells). Biochemical and molecular studies confirmed that enterocytes expressed I-A and I-E isotypes on their cell surface and contained mRNA of both subregion loci. Interestingly, enterocytes appeared deficient in expression of the MHC class II-associated invariant chain, and are not able to stimulate allogeneic T cells. These data suggest that gut epithelial cells express a conformation of class II molecules, antigenically distinct from that expressed on conventional APC.


Clinical significance of positive immunoblotting but negative immunofluorescence for antimitochondrial antibodies in patients with liver diseases other than primary biliary cirrhosis.
The serum reaction to anti-2-oxo-acid dehydrogenase complex (2-OADC) enzymes, the antigens recognized by antimitochondrial antibodies (AMA), can be detected by immunoblotting in patients with liver diseases other than primary biliary cirrhosis (PBC), who are negative for AMA by conventional indirect immunofluorescence. Whether the presence of anti-2-OADC is related to PBC or represents preclinical PBC in such patients is obscure at present. We examined the immunoreactivity of AMA by immunofluorescense, immunoblotting, and enzyme inhibition assay in serum samples from 59 patients with liver diseases other than PBC and 71 healthy subjects. We also examined the clinical course of the patients in whom a positive result was obtained to elucidate whether such reaction was a "true" or "false" phenomenon. None of the 130 sera was positive for AMA by indirect immunofluorescence or for anti-pyruvate dehydrogenase complex (PDC) by enzyme inhibition assay. However, seven of 71 (10%) sera from healthy subjects contained weak IgG class antibody to PDC-E2 (four sera) or E2 subunit of branched-chain oxo-acid dehydrogenase complex (BCOADC-E2) (three sera). Of the 59 sera from patients with liver diseases other than PBC, four (7%) reacted against 2-OADC by immunoblotting. Of these, three sera were from patients with chronic hepatitis C virus (HCV) infection, and contained IgG class autoantibody to BCOADC-E2. The serum reactivity to BCOADC-E2 detected by immunoblotting in these three patients diminished after absorption with recombinant BCOADC-E2 fusion protein. During the 3-5 year follow-up period, AMA by immunofluorescence and anti-PDC activity by enzyme inhibition assay were always negative in these three patients. The other one serum was from patient with alcoholic cirrhosis, and contained IgM class autoantibody to E3 binding protein (E3-BP). This patient did not develop PBC during the following 2 years. Our results showed that anti-2-OADC antibodies could be detected in some patients with liver diseases other than PBC, and even in healthy individuals. The clinical significance of the presence of these serum reactions is obscure at this stage, but the production of anti-BCOADC-E2 may be linked to the presence of HCV in certain patients. Further prospective studies of larger population should clarify whether anti-2-OADC reaction can precede the clinical development of PBC.


IFN-α with dasatinib broadens the immune repertoire in patients with chronic-phase chronic myeloid leukemia.
In chronic myeloid leukemia (CML), combination therapies with tyrosine kinase inhibitors (TKIs) aim to improve the achievement of deep molecular remission that would allow therapy discontinuation. IFN-α is one promising candidate, as it has long-lasting effects on both malignant and immune cells. In connection with a multicenter clinical trial combining dasatinib with IFN-α in 40 patients with chronic-phase CML (NordCML007, NCT01725204), we performed immune monitoring with single-cell RNA and T cell receptor (TCR) sequencing (n = 4, 12 samples), bulk TCRβ sequencing (n = 13, 26 samples), flow cytometry (n = 40, 106 samples), cytokine analyses (n = 17, 80 samples), and ex vivo functional studies (n = 39, 80 samples). Dasatinib drove the immune repertoire toward terminally differentiated NK and CD8+ T cells with dampened functional capabilities. Patients with dasatinib-associated pleural effusions had increased numbers of CD8+ recently activated effector memory T (Temra) cells. In vitro, dasatinib prevented CD3-induced cell death by blocking TCR signaling. The addition of IFN-α reversed the terminally differentiated phenotypes and increased the number of costimulatory intercellular interactions and the number of unique putative epitope-specific TCR clusters. In vitro IFN-α had costimulatory effects on TCR signaling. Our work supports the combination of IFN-α with TKI therapy, as IFN-α broadens the immune repertoire and restores immunological function.


The cost of pursuing a medical career in the military: a tale of five specialties.
The physician payment system is a focus of potential reform in the United States. The authors explored the effects of the military's method of physician payment on physicians' returns on educational investment for several specialties. This retrospective, observational study used national data from 2003 and standard financial techniques to calculate the net present value-the current value of an expected stream of cash flows at a particular rate of interest-of the educational investments of medical students in ten 30-year career paths: either military or civilian careers in internal medicine, psychiatry, gastroenterology, general surgery, or orthopedics. At a 5% discount rate, in the civilian world, the lowest return on an educational investment accrued to psychiatrists ($1.136 million) and the highest to orthopedists ($2.489 million), a range of $1.354 million. In the military, the lowest returns accrued to internists ($1.377 million) and the highest to orthopedists ($1.604 million); however, the range was only $0.227 million, one-sixth that found in the civilian sector. The authors also found that most military physicians do not remain in the military for their full careers. Choosing a military career substantially decreases the net present value of an educational investment for interventionalists, but it does so only modestly for primary care physicians. Further, a military career path markedly diminishes specialty-specific variation in the net present values of educational investment. Adopting a military structure for engaging medical students might help reverse the current trend of declining interest in primary care.


Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation.
Hypertension is a cardiovascular disease that needs long-term medication. Oral delivery is the most common route for the administration of drugs. The present research is to develop piperine self-nanoemulsifying drug delivery system (PE-SNEDDS) using glyceryl monolinoleate (GML), poloxamer 188, and transcutol HP as oil, surfactant, and co-surfactant, respectively. The formulation was optimized by three-factor, three-level Box-Behnken design. PE-SNEDDs were characterized for globule size, emulsification time, stability, in-vitro release, and ex-vivo intestinal permeation study. The optimized PE-SNEDDS (OF3) showed the globule size of 70.34 ± 3.27 nm, percentage transmittance of 99.02 ± 2.02%, and emulsification time of 53 ± 2 s Finally, the formulation OF3 was transformed into solid PE-SNEDDS (S-PE-SNEDDS) using avicel PH-101 as adsorbent. The reconstituted SOF3 showed a globule size of 73.56 ± 3.54 nm, PDI of 0.35 ± 0.03, and zeta potential of -28.12 ± 2.54 mV. SEM image exhibited the PE-SNEDDS completely adsorbed on avicel. Thermal analysis showed the drug was solubilized in oil, surfactant, and co-surfactant. S-PE-SNEDDS formulation showed a more significant (p < 0.05) release (97.87 ± 4.89% in 1 h) than pure PE (27.87 ± 2.65% in 1 h). It also exhibited better antimicrobial activity against S. aureus and P. aeruginosa and antioxidant activity as compared to PE dispersion. The in vivo activity in rats exhibited better (p < 0.05) antihypertensive activity as well as 4.92-fold higher relative bioavailability than pure PE dispersion. Finally, from the results it can be concluded that S-PE-SNEDDS might be a better approach for the oral delivery to improve the absorption and therapeutic activity.


The Y chromosomes of Drosophila simulans are highly polymorphic for their ability to suppress sex-ratio drive.
The sex-ratio trait, known in several species of Drosophila including D. simulans, results from meiotic drive of the X chromosome against the Y. Males that carry a sex-ratio X chromosome produce strongly female-biased progeny. In D. simulans, drive suppressors have evolved on the Y chromosome and on the autosomes. Both the frequency of sex-ratio X and the strength of the total drive suppression (Y-linked and autosomal) vary widely among geographic populations of this worldwide species. We have investigated the pattern of Y-linked drive suppression in six natural populations representative of this variability. Y-linked suppressors were found to be a regular component of the suppression, with large differences between populations in the mean level of suppression. These variations did not correspond to differences in frequency of discrete types of Y chromosomes, but to a more or less wide continuum of phenotypes, from nonsuppressor to partial or total suppressor. We concluded that a large diversity of Y-linked suppressor alleles exists in D. simulans and that some populations are highly polymorphic. Our results support the hypothesis that a Y-chromosome polymorphism can be easily maintained by a balance between meiotic drive and the cost of drive suppression.


Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages.
Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been implicated in promoting colon cancer; however, the mechanisms behind this effect are poorly understood. We have previously demonstrated that deficiency of CCR6 is associated with decreased tumor macrophage accumulation in a model of sporadic intestinal tumorigenesis. In this study, we aimed to determine the role of stromal CCR6 expression in a murine syngeneic transplantable colon cancer model. We show that deficiency of host CCR6 is associated with decreased growth of syngeneic CCR6-expressing colon cancers. Colon cancers adoptively transplanted into CCR6-deficient mice have decreased tumor-associated macrophages without alterations in the number of monocytes in blood or bone marrow. CCL20, the unique ligand for CCR6, promotes migration of monocytes in vitro and promotes accumulation of macrophages in vivo. Depletion of tumor-associated macrophages decreases the growth of tumors in the transplantable tumor model. Macrophages infiltrating the colon cancers in this model secrete the inflammatory mediators CCL2, IL-1α, IL-6 and TNFα. Ccl2, Il1α and Il6 are consequently downregulated in tumors from CCR6-deficient mice. CCL2, IL-1α and IL-6 also promote proliferation of colon cancer cells, linking the decreased macrophage migration into tumors mediated by CCL20-CCR6 interactions to the delay in tumor growth in CCR6-deficient hosts. The relevance of these findings in human colon cancer is demonstrated through correlation of CCR6 expression with that of the macrophage marker CD163 as well as that of CCL2, IL1α and TNFα. Our findings support the exploration of targeting the CCL20-CCR6 pathway for the treatment of colon cancer.


Theoretical prediction on the thermal stability of cyclic ozone and strong oxygen tunneling.
Dual-level dynamics calculation with variational transition state theory including multidimensional tunneling has been performed on the isomerization reaction of cyclic ozone → normal (open) ozone, which was believed to be the stability-determining reaction of the elusive cyclic ozone molecule under thermal condition. The high-level potential energy surface data were obtained from the calculation using the MRCISD+Q theory with the aug-cc-pVQZ basis set, while the low-level reaction path information was obtained using the hybrid density functional theory B3LYP with the cc-pVTZ basis set. The calculated results showed very significant tunneling effects below 300 K (a factor of ∼200 at 300 K and over 10(7) at 200 K). Because of the strong tunneling effects and the potential energy surface crossing of the 1A(1) and 1A(2) states, the isomerization reactions were found to be significantly faster than previously believed. The half-life of the cyclic ozone was estimated only ∼10 s at 200 K and ∼70 s below 100 K, which might partly explain the unsuccessful attempts for its experimental identification. The kinetic isotope effects (KIEs) for various (18)O substitution reactions were also calculated as a function of temperature and were as high as 10 at very low temperature. Because of the large KIEs, the experimental identification of the cyclic (18)O(3) seems more promising.


Contribution of radioiodine uptake measurement and thyroid scintigraphy to the differential diagnosis of thyrotoxicosis.
Both clinical and subclinical thyrotoxicosis can result from a wide range of disorders. Establishing the correct etiology underlying thyrotoxicosis is essential to direct treatment towards its specific pathophysiologic process. Based on clinical experience and guideline recommendations, radioiodine iodine uptake (RAIU) measurement and scintigraphy are often requested as the first-line investigation in thyrotoxic patients; however, their specific individual contribution to the differential diagnosis of thyrotoxicosis has not been previously investigated. In our study we aimed at evaluating the diagnostic role of RAIU measurement and scintigraphy in the management of thyrotoxicosis. A total of 108 patients with clinical and 42 patients with subclinical thyrotoxicosis were included in this retrospective study. All patients had RAIU measured at 24 hours after (131)I-iodide administration, followed by thyroid scintigraphy. Based on the combination of RAIU and scintigraphy, patients were classified as having diffuse toxic goiter (DTG) in 44% (the most common diagnosis), toxic adenoma in 15.9%, thyroiditis in 14%, and toxic multinodular goiter in 2.7%, while the pattern was inconclusive in 22.7% of all patients. When considering only patients with clinical thyrotoxicosis, the scan was inconclusive in 12.9% of patients whereas it was inconclusive in 47.6% of patients with subclinical thyrotoxicosis. There was a highly significant association between thyrotoxic status and scan result, with a statistically significant better performance of RAIU and scintigraphy in patients with clinical thyrotoxicosis when compared to patients with subclinical thyrotoxicosis considered as a whole (P<0.001). Instead, no statistically significant difference was observed between patients with subclinical thyrotoxicosis and TSH <0.1 mU/L and patients with TSH between 0.1 mU/L and 0.4 mU/L (P=0.191). In conclusion, we confirm the key role of RAIU and scintigraphy in the management of thyrotoxicosis and document its better performance in patients with clinical thyrotoxic status.


Single-cell electroporation.
Using modified patch-clamp methodology, we demonstrated that it is possible to insert genes or other compounds routinely into single cells by electroporation. When the cell is indented by a small-tipped microelectrode, a voltage of 10 V or less in the pipette is divided by the pipette resistance and the series resistance of the cleft between the pipette tip and the cell surface. The voltage at the cell membrane can be high enough to cause localized dielectric breakdown of the membrane and create pores that allow compounds in the pipette to enter the cell. Rectangular pulses from 20 micros to more than 300 ms are effective, as are frequencies from DC to 5 kHz. The most significant parameter was the total time for which the voltage was applied. Pipette voltages of 2-10 V were required, with larger genes requiring larger voltages. With optimal parameters, transfection rates in excess of 80% were also possible routinely. This approach offers an effective alternative to intracellular pressure injection and iontophoresis for placing genes, drugs, and other compounds in cells. Because of the small size of the electrode tips, substances can be inserted in cells from almost any location on their surfaces. In addition, the small tips electroporated only a limited area and so did little cell damage.


[Epidemiological studies on giardiosis in inhabitants of Szczecin].
The aim of the studies was to establish the prevalence of Giardia intestinalis in Szczecin population. The studies were carried out in 1991 - 1996. In this period 46,584 persons--22,371 adults and 24,213 children were examined. Faecal samples were examined with two methods--coprological and immunoenzymatic (ELISA) test. A total of 356 persons (0.78%) were found to be infected with G. intestinalis. No statistically significant differences between the infection rate of adults and children were observed. The adults were infected in 0.73% and the children in 0.80%. The analysis of the annual dynamics of G. intestinalis infection shows twice as large infection rate in September - October (1.18%) as in the remaining months (0.66%).


Roundtable Discussion: Making Sense of Current Liposuction Technologies.
Suction-assisted lipectomy (or "liposuction") is a fundamental technique for all plastic surgeons, and like many procedures in aesthetic surgery, its applications are continuing to evolve. With the rapid introduction of new technologies, many plastic surgeons are left with questions about how these new devices work, what results to expect, and how to best apply these technologies in their practice. We recognized that there is a need for unbiased recommendations to guide surgeons on how to approach current liposuction devices (as well as their adjuncts) and how to use them effectively for their patients. Using available literature and personal experience, we answer the most common questions that we hear from our plastic surgery colleagues.


Correlation of Mercury Occurrence with Age, Elemental Composition, and Life History in Sea-Run Food Fish from the Canadian Arctic Archipelago's Lower Northwest Passage.
As mercury emissions continue and climate-mediated permafrost thaw increases the burden of this contaminant in northern waters, Inuit from a Northwest passage community in the Canadian Arctic Archipelago pressed for an assessment of their subsistence catches. Sea-run salmonids (n = 537) comprising Arctic char (Salvelinus alpinus), lake trout (S. namaycush), lake whitefish (Coregonus clupeaformis), and cisco (C. autumnalis, C. sardinella) were analyzed for muscle mercury. Methylmercury is a neurotoxin and bioaccumulated with fish age, but other factors including selenium and other elements, diet and trophic level as assessed by stable isotopes of nitrogen (δ15N) and carbon (δ13C), as well as growth rate, condition, and geographic origin, also contributed depending on the species, even though all the fish shared a similar anadromous or sea-run life history. Although mean mercury concentrations for most of the species were ~0.09 µg·g-1 wet weight (ww), below the levels described in several jurisdictions for subsistence fisheries (0.2 µg·g-1 ww), 70% of lake trout were above this guideline (0.35 µg·g-1 ww), and 19% exceeded the 2.5-fold higher levels for commercial sale. We thus urge the development of consumption advisories for lake trout for the protection of pregnant women and young children and that additionally, periodic community-based monitoring be initiated.


Clinical Characteristics and Prognosis of Adult Orbital Cellulitis in a Tertiary General Hospital.
Adult orbital cellulitis (OC) occurs relatively rarely, and comprehensive studies that retrospectively evaluate OC are lacking. Here, we aimed to examine the clinical characteristics and prognosis of OC in a tertiary general hospital. Between October 2010 and May 2019, patients presenting with clinical symptoms of OC in a tertiary general hospital were analyzed in this retrospective study. Twenty-six cases were identified for a detailed review. In these cases, 16 males and 10 females were diagnosed with orbital cellulitis by clinical characteristics and multimodal examinations. We divided patients into three groups: (1) patients secondary to rhinosinusitis, (2) patients secondary to endogenous infection(s) without endophthalmitis, and (3) patients secondary to endophthalmitis. For each group, age, gender, eye type, combined systemic diseases, clinical presentation, leukocyte count, blood culture, diagnostic imaging, therapeutic methods, length of stay, time of postoperation, and patient prognosis were analyzed in detail. There were no significant differences regarding age, gender, preoperative leukocyte count, exophthalmia, blood culture, treatment, or visual changes within the three groups (P < 0.05). There were significant differences, however, in postoperative leukocyte count and ophthalmoplegia between the three groups (P < 0.05). The preoperative and postoperative logarithms of the minimum resolution angle scored by the best-corrected visual acuity (LogMAR BCVA) of group 3 were statistically significant compared to group 1 and group 2 (P < 0.05). We confirmed that the prognosis of OC patients combined with systemic diseases was poor. Patients with OC secondary to endophthalmitis infrequently experience ophthalmoplegia; however, these patients still have poor visual outcomes. Patients cultured positive for Klebsiella pneumoniae infection may not be associated with liver abscess. The level of leukocytes may indicate the condition of the disease.


Myricitrin ameliorates ethanol-induced steatosis in mouse AML12 liver cells by activating AMPK, and reducing oxidative stress and expression of inflammatory cytokines.
It is necessary to identify compounds that may provide protection against alcoholic liver disease. To the best of our knowledge, the effect of myricitrin on the development of ethanol‑induced liver disease has not been previously investigated. The present study aimed to determine the effect of myricitrin on ethanol‑induced steatosis in AML12 mouse liver cells and to identify the underlying molecular mechanisms. Ethanol‑treated AML12 cells exhibited significant improvement in viability following treatment with myricitrin. Oil red O staining indicated that myricitrin ameliorated ethanol‑induced lipid accumulation in cells. Furthermore, following treatment with myricitrin, improvement in ethanol‑induced steatosis and decrease in the levels of reactive oxygen species and lipoperoxides were observed in ethanol‑stimulated cells. Myricitrin suppressed mRNA and protein expression of tumor necrosis factor‑α, interleukin‑6 and transforming growth factor‑β1 in ethanol‑stimulated AML12 cells. Myricitrin markedly increased phosphorylation of adenosine monophosphate‑activated protein kinase (AMPK) and significantly reduced mRNA expression of sterol‑regulatory element‑binding protein‑1c (SREBP‑1c) and fatty acid synthase in ethanol‑stimulated AML12 cells. The results of the present study indicate that myricitrin ameliorates ethanol‑induced steatosis in AML12 cells by attenuating oxidative stress, suppressing expression of certain inflammatory cytokines and modulating the AMPK/SREBP-1c pathway.


SAR studies for a new class of antibacterial NAD biosynthesis inhibitors.
A new lead class of antibacterial drug-like NAD synthetase (NADs) inhibitors was previously identified from a virtual screening study. Here a solution-phase synthetic library of 76 compounds, analogs of the urea-sulfonamide 5838, was synthesized in parallel to explore SAR on the sulfonamide aryl group. All library members were tested for enzyme inhibition against NADs and nicotinic acid mononucleotide adenylyltransferase (NaMNAT), the last two enzymes in the biosynthesis of NAD, and for growth inhibition in a Bacillus anthracis antibacterial assay. Most compounds that inhibited bacterial growth also showed inhibition against one of the enzymes tested. While only modest enhancements in the enzyme inhibition potency against NADs were observed, of significance was the observation that the antibacterial urea-sulfonamides more consistently inhibited NaMNAT.


[Implication of the measurement of central corneal thickness in management of glaucoma patients].
Intraocular pressure (IOP) is a elementary data in diagnosis and therapy of glaucoma. Many studies have confirmed that most tonometry, including Goldmann applanation tonometry, are influenced by central corneal thickness (CCT) and CCT varies greatly among the general population. As a result, the measurement of CCT has a great implication in management of glaucoma. Further, CCT is confirmed a risk factor for progression from ocular hypertension to primary open angle glaucoma. The idea of that CCT may bear an inverse relation with the risk for developing glaucoma damage is in debating. Many specialists bring forward that CCT measurement should be one of the regular examinations in treatment of glaucoma patients.


The expression of Platelet-derived Growth factor receptors (PDGFRs) and their correlation with overall survival of patients with ovarian cancer.
The main aim of the study was to investigate the expression of Platelet-Derived Growth Factor Receptors alpha (PDGFR-alpha) and beta (PDGFR-beta) in malignant and benign ovarian tumors. We performed an analysis of the correlation of PDGFRs expression and stage of the disease, tumor grade and histopathological type of epithelial ovarian cancer (EOC). Additionally, we evaluated patient prognosis according to PDGFR expression. Our study group was composed of 52 samples of EOCs, 35 samples of benign ovarian tumors (BOTs), and 21 samples of unchanged ovaries (UOs). The samples were collected from patients who had been operated on in the Division of Gynecological Surgery of the Poznan University of Medical Sciences. PDGFR-alpha was found to be expressed more frequently in cancer cells of EOCs, when compared with tumor cells of BOTs and epithelium of UOs. On the other hand, PDGFR-alpha receptors were present less frequently in the stroma of EOCs, when compared with the stroma of BOTs and UOs. Comparing the studied groups, there were no statistically significant differences in the expression of PDGFR-beta. The expression of both PDGFRs was not related to the FIGO stage, grade or histopathological type of EOCs. The expression of the PDGFR-beta receptor in cancer cells was associated with an improved overall survival among patients with EOCs. Patient prognosis was not affected by either PDGFR-alpha expres- sion or by PDGFR-beta tumor stroma expression. The expression of PDGFR-alpha is significantly different when comparing EOCs, BOTs and UOs. However, the prognosis of EOC only seems to be affected by PDGFR-beta expression in cancer cells.


[Etiology and evolution of the osteoarticular infections. 2009-2015: Pediatric Hospital Pereira Rossell Uruguay].
The most frequent osteoarticular infections (OAI) etiological agent is Staphylococcus aureus. The prevalence of other microorganisms has changed after the introduction of new vaccines. To describe the etiology and evolution of the OAIs in children hospitalized in Pediatric Hospital Pereira Rossell between 2009 and 2015. Joint fluid and bone puncture studies of hospitalized children suspected of OAI. Epidemiological characteristics, isolated microorganisms, complementary tests, initial treatment, complications, and days of hospitalization were analyzed. 335 patients; the etiology was established in 113. Clinical data could be analyzed in 87 cases. The average age was 6.1 years. They corresponded to: methicillin-sensitive S. aureus (n: 47), community-acquired methicillin-resistant S. aureus (CA-MRSA) (n: 11), Streptococcus pyogenes (n: 6), Streptococcus pneumoniae (n: 1), Haemophilus influenzae type b (n: 2), Gram-negative bacilli (n: 9), Kingella kingae (n: 1) others (n: 6). In 4 cases, more than one microorganism was isolated. CA-MRSA infections were more serious. A decrease is observed in the number of CA-MRSA isolates. A fact to be highlighted is the impact of universal vaccination against S. pneumoniae and H. influenzae type b. It is a finding to be monitored the increasing number of Gram-negative bacilli isolates.


Age-related changes in hemispheric asymmetry depend on sex.
A total of 92 participants, 50 younger (mean age 26.3 years) and 42 older (mean age 63.8 years), were tested for visual-field asymmetries. On a word-matching task, a right-visual-field (RVF) advantage increased with age, consistent with the theory that right-hemispheric function shows relatively greater decline with age than left-hemispheric function. On a figural-comparison task, a left-visual-field (LVF) advantage was marginally decreased with age in the men, but significantly increased in the women, probably because age-related changes in hormonal levels are more pronounced in women. This increase in LVF advantage is contrary to both the HAROLD theory that hemispheric asymmetry declines with age, and the theory of relative right-hemispheric decline.


Effect of formulation and process variables on the release behavior of amoxicillin matrix tablets.
The sustained release of amoxicillin is desired to be confined to the upper gastrointestinal tract to treat certain kind of infections. In vitro dissolution, at pH 1.2, of amoxicillin sustained release tablets has been studied varying the proportion of Carbopol 971P NF and sodium alginate as well as the ethanol/water proportion in the granulation fluid. M(t), the amount of drug released at time (t) and defined in terms of the total drug released over a long time period (M(inf), was described by M(t)/M(inf) = kt(n). Matrices with increasing proportions of sodium alginate showed increasing values of the exponent indicative of the release mechanism (n) and increasing release constant values (k). This is attributed to a drop in the coherence of the polymeric matrix with increasing alginate proportions that produces an increasing polymer relaxation and erosion. Decreasing Carbopol 971P NF proportions reduce the amount of dissolved polymer during granulation, producing a lesser obstruction of amoxicillin dissolution. Alginate proportions of 80% produce near zero order release profiles. Granules obtained with increasing ethanol proportions showed increasing release constant values and a minor change in the exponent (n) values. This is considered a result of lower polymer dissolution during granulation that allows a lesser matrix coherence and a greater amoxicillin dissolution. Alginate matrices granulated with different ethanol/water proportions showed no significant changes in the amoxicillin release profile. There is a trend toward increasing floating times with increasing Carbopol 971P NF proportions.


Presynaptic long-term plasticity.
Long-term synaptic plasticity is a major cellular substrate for learning, memory, and behavioral adaptation. Although early examples of long-term synaptic plasticity described a mechanism by which postsynaptic signal transduction was potentiated, it is now apparent that there is a vast array of mechanisms for long-term synaptic plasticity that involve modifications to either or both the presynaptic terminal and postsynaptic site. In this article, we discuss current and evolving approaches to identify presynaptic mechanisms as well as discuss their limitations. We next provide examples of the diverse circuits in which presynaptic forms of long-term synaptic plasticity have been described and discuss the potential contribution this form of plasticity might add to circuit function. Finally, we examine the present evidence for the molecular pathways and cellular events underlying presynaptic long-term synaptic plasticity.


Monitoring biosecurity in poultry production: an overview of databases reporting biosecurity compliance from seven European countries.
Compliance with required on-farm biosecurity practices reduces the risk of contamination and spread of zoonotic and economically important diseases. With repeating avian influenza epidemics in the poultry industry, the need to monitor and improve the overall level of biosecurity is increasing. In practice, biosecurity compliance is assessed by various actors (e.g., academic, private and public institutions), and the results of such assessments may be recorded and gathered in databases which are seldom shared or thoroughly analyzed. This study aimed to provide an inventory of databases related to the assessment of biosecurity in poultry farms in seven major poultry-producing European countries to highlight challenges and opportunities associated with biosecurity data collection, sharing, and use. The institutions in charge of these databases were contacted and interviewed using a structured questionnaire to gather information on the main characteristics of the databases and the context of their implementation. A total of 20 databases were identified, covering the gamut of poultry species and production types. Most databases were linked to veterinary health authorities or academia, and to a lesser extent interbranch organizations. Depending on the institutions in charge, the databases serve various purposes, from providing advice to enforcing regulations. The quality of the biosecurity data collected is believed to be quite reliable, as biosecurity is mostly assessed by trained farm advisors or official veterinarians and during a farm visit. Some of the databases are difficult to analyze and/or do not offer information concerning which biosecurity measures are most or least respected. Moreover, some key biosecurity practices are sometimes absent from certain databases. Although the databases serve a variety of purposes and cover different production types, each with specific biosecurity features, their analysis should help to improve the surveillance of biosecurity in the poultry sector and provide evidence on the benefits of biosecurity.


REG4, NEIL2, and BIRC5 gene expression correlates with gamma-radiation sensitivity in patients with rectal cancer receiving radiotherapy.
The present study aimed to identify genes that influence the susceptibility of cancer cells to radiation. The sensitivities of eight colorectal cancer cell lines to gamma radiation were tested. Microarray data and cells with stable overexpression were used to identify candidate genes. Candidate genes correlating with radioresistance were validated with the use of 22 clinical specimens obtained before preoperative radiotherapy from patients with rectal cancer. Regenerating islet-derived protein 4 (REG4) gene expression was 12-fold higher in radioresistant cells. REG4-overexpressing cells had higher survival rates and fewer DNA strand breaks after gamma irradiation. Expression of the antiapoptotic gene baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and base excision-repair pathway gene nei endonuclease VIII-like 2 (NEIL2) in REG4-overexpressing cells, was also three to four times higher than that of the parental cell lines. REG4, BIRC5 and NEIL2 expression levels were significantly higher in non-responding patients (n=14) than in responders (n=8). The REG4, BIRC5 and NEIL2 genes might be useful predictors of the sensitivity of cancer patients to radiotherapy.


Recommendations implicit in policy defaults.
Should people be considered organ donors after their death unless they request not to be, or should they not be considered donors unless they request to be? Because people tend to stay with the default in a variety of domains, policymakers' choice of default has large and often important effects. In the United States, where the organ-donation policy default is "not a donor," about 5,000 people die every year because there are too few donors. Four experiments examined two domains-being an organ donor and saving for retirement-where default effects occur and have important implications. The results indicate that default effects occur in part because policymakers' attitudes can be revealed through their choice of default, and people perceive the default as indicating the recommended course of action. Policymakers need to be aware of the implicit messages conveyed by their choice of default.


Coronary flow velocity pattern immediately after percutaneous coronary intervention as a predictor of complications and in-hospital survival after acute myocardial infarction.
Recently, it was reported that the degree of microvascular injury and left ventricular functional recovery during the chronic period can be predicted after treatment of the infarct-related artery based on the coronary flow velocity (CFV) pattern assessed using a Doppler guidewire. The aim of this prospective study was to examine whether the CFV pattern may predict complications and in-hospital survival after acute myocardial infarction (AMI). The study population consisted of 169 consecutive patients with a first anterior AMI successfully treated with percutaneous coronary intervention (PCI). We examined the CFV pattern immediately after PCI using a Doppler guidewire. In accordance with previous findings, we defined severe microvascular injury as a diastolic deceleration time < or =600 ms and the presence of systolic flow reversal. Patients were divided into two groups: those without severe microvascular injury (n=118; group 1) and those with severe microvascular injury (n=51; group 2). All of the patients who had cardiac rupture were in group 2. Congestive heart failure (CHF) was observed more frequently in group 2 than in group 1 (53% versus 8%, P<0.001). The in-hospital cardiac mortality rate was significantly higher in group 2 than in group 1 (18% versus 0%, P<0.001). Nine patients in group 2 died, 5 patients because of CHF and 4 patients because of cardiac rupture. These findings suggest that the CFV pattern is an accurate predictor of the presence or absence of complications and of in-hospital survival after AMI.


Hydration status substantially affects chronic cerebrospinal venous insufficiency assessments.
We sought to determine the effect of hydration on the criteria for chronic cerebrospinal venous insufficiency (CCSVI), a proposed hypothesis for the etiology of multiple sclerosis (MS). Sixteen subjects (11 MS and 5 controls) were asked to fast overnight. The following morning, 2 CCSVI ultrasound examinations were performed: 1 in the mildly dehydrated state, and another 30-45 minutes after rehydrating with 1.5 L of Gatorade. Seven subjects fulfilled CCSVI criteria in the dehydrated state. Of these, 5 (71%) no longer fulfilled CCSVI criteria after rehydration. One additional subject met CCSVI criteria only after rehydration. Hydration status has a substantial effect on CCSVI criteria, suggesting that the sonographic findings of CCSVI may represent a physiologic rather than pathologic state.


Does orthodontic treatment provide a real functional improvement? a case control study.
Electromyographic analysis of the masticatory muscles provides useful data on the behavior of these muscles during stomatognathic system functioning and allows a functional assessment of orthodontic treatments. This study was undertaken to verify if achieving an Angle Class I bite through orthodontic treatment can lead to neuromuscular balance. This study enrolled 30 patients (20 females, 10 males, mean age: 15.78 years) with an Angle Class II, division 1 malocclusion that was orthodontically treated. A group of 30 subjects (19 females, 11 males; mean age: 16.15 years), randomly selected among subjects with an Angle Class II, division 1 malocclusion that had not been orthodontically treated served as the Control group. Both groups were subjected to electromyography to study their neuromuscular characteristics. The Shapiro-Wilk's test revealed a non normal distribution, therefore we used a Friedman two way ANOVA by ranks test to compare differences of surface electromyography values between treated and untreated subjects at closed and open eyes condition. A statistically significant interaction between orthodontic treatment and open eyes conditions was detected for anterior temporal muscles. A significant imbalance of the anterior temporal muscles, which is indicative of an asymmetric electromyographic pattern, was also found. The present data indicate that achieving a correct occlusal target does not necessarily correspond to a neuromuscular balance.


[Ganglion Cell Complex Map for Detecting Early Damage in High Tension and Normal Tension Glaucoma].
Glaucoma is one of the leading causes of irreversible blindness worldwide. We aimed to compare the findings of a ganglion cell complex (GCC) test with a test of the retinal nerve fibre layer (RNFL) in high and normal tension glaucoma patients. Sixty-two patients were enrolled in the study: 12 glaucoma suspects, 30 with diagnosed glaucoma and 20 with normal tension glaucoma. All subjects had visual acuity testing, tonometry, computer perimetry (Humphrey) and optical coherence tomography (OCT) with an OCT RTvue (RNFL 3.45, NHM4 and GCC). In 58 % of the glaucoma suspects, there were no changes in the perimetry results, as well as with OCT. In 42 % of the subjects, pathological changes in the GCC map preceded those of the RNFL. In patients with HTG, an almost linear correlation was found between the RNFL changes and GCC alterations. Statistical analysis showed that, in glaucoma suspects, the diagnostic value of the average GCC thickness was more significant than the average NFL thickness (0.90 [0.02] to 0.78 [0.02] µm). In 56 % of normal tension glaucoma patients, changes in the RNFL prevailed over those in the GCC. OCT diagnosis is an important tool for detecting early glaucoma changes. In glaucoma suspects, however, GCC changes can be more sensitive. In NTG, the results are still considered controversial. Nevertheless, in the majority of subjects, the RNFL changes prevailed over the GCC changes. The findings in NTG are similar to those in neurological diseases such as multiple sclerosis and Alzheimer's disease.


The effect of monoamine oxidase-B inhibitors on the alleviation of depressive symptoms in Parkinson's disease: meta-analysis of randomized controlled trials.
Depression is a major nonmotor symptom of Parkinson's disease (PD). However, few treatments exist for PD depression. Monoamine oxidase-B inhibitors (MAOB-Is) provide symptomatic relief for the motor symptoms of PD and exert antidepressive effects. The present meta-analysis of randomized controlled trials (RCTs) investigated the effects of MAOB-Is on depressive symptoms in patients with PD. Articles on PD-management-related RCTs using one of three MAOB-Is approved by the US Food and Drug Administration, that is, selegiline, rasagiline, and safinamide, were identified. The primary outcomes were the benefits of MAOB-Is for depressive symptoms. Subgroup analysis included the effects of MAOB-Is on patients in the early versus middle-to-late stages of PD and the effect of short-term versus long-term treatment. Overall, six studies were included, four of which were conducted on patients with early stage PD. Overall, MAOB-Is significantly reduced the severity of depressive symptoms [standardized mean difference (SMD): -0.14, 95% confidence interval (CI): -0.21 to -0.06, p < 0.001]. Subgroup analysis indicated that the positive effect of MAOB-Is was significant in patients with early stage PD (SMD: -0.20, 95% CI: -0.31 to -0.09, p < 0.001), but not in those with middle-to-late-stage PD (SMD: -0.07, 95% CI: -0.17 to 0.03, p = 0.18). The antidepressive effect was significant for short-term treatment, that is, 90-120 days (SMD: -0.23, 95% CI: -0.35 to -0.10, p < 0.001), but not long-term treatment, that is, 24 weeks to 18 months (SMD: -0.08, 95% CI: -0.18 to 0.01, p = 0.09). In addition to the treatment of PD motor symptoms, MAOB-Is may help reduce the severity of depressive symptoms in PD, especially in patients with early stage PD. Considering the tolerability and simultaneous benefits of MAOB-Is, further RCTs are warranted to confirm their therapeutic effects in moderate-to-severe PD depression.


One-step synthesis of the nanostructured AgI/BiOI composites with highly enhanced visible-light photocatalytic performances.
The nanostructured AgI/BiOI composites were prepared by a facile, one-step, and low temperature chemical bath method with Bi(NO(3))(3), AgNO(3), and KI. Several characterization tools, such as X-ray powder diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), the Brunauer-Emmett-Teller (BET) surface area, photoluminescence (PL) spectra, and UV-vis diffuse reflectance spectroscopy, were employed to study the phase structures, morphologies, and optical properties of the samples. The PL intensity of AgI was greatly decreased when combined with BiOI, indicating the corresponding decreased recombination of the carriers. The photocatalytic properties of the as-prepared products were measured with the degradation of methyl orange and phenol at room temperature under visible light irradiation. The AgI/BiOI composites showed much higher photocatalytic performances over BiOI as well as AgI. It was also found that the AgI amount in the AgI/BiOI composites played an important role in the corresponding photocatalytic properties and the optimized ratio was obtained at 20%. The dramatic enhancement in the visible light photocatalytic performance of the AgI/BiOI composites could be attributed to the effective electron-hole separations at the interfaces of the two semiconductors, which facilitate the transfer of the photoinduced carriers. By the detection of hydroxyl radicals through a fluorescence technique, the photoinduced holes (h(VB)(+)) were considered to be the dominant active species in the photodegradation process, which was also deduced from the theoretical speculations. The photocatalytic performances of the AgI/BiOI composites were maintained for the cycling experiments. In addition, based on the XRD and XPS patterns of the AgI/BiOI composites before and after reaction, AgI was stable in the composites under visible irradiation, indicating that AgI/BiOI composites could be used as stable and efficient visible-light-induced photocatalysts.


[Diagnostic difficulties and remission criteria of autoimmune pancreatitis].
The paper describes a clinical case in a 56-year-old female patient who has been suffering from chronic autoimmune pancreatitis, chronic recurrent cholangitis for 3 years. It demonstrates diagnostic difficulties at the early stage of the disease, the specific features of its course, the sequence of treatment in the patient, and problems in choosing a therapy option to achieve a remission.


A Comprehensive Review of Transesophageal Echocardiography During Orthotopic Liver Transplantation.
Orthotopic liver transplantation (OLT) is characterized by significant hemodynamic disturbances and anesthetic challenges. Intraoperative transesophageal echocardiography (TEE) can be used to guide management during these procedures. This review examines the role of echocardiography during OLT, presents common TEE findings during each phase of OLT, and discusses the benefits demonstrated with TEE use and the safety of TEE in this patient population. Finally, the authors propose an algorithm for the safe use of TEE during OLT.


Outcome after fractures of the femur in Paget's disease.
We reviewed ninety-three patients who had one hundred and seven complete fractures of the femur between them and were treated over a twenty-five year period in Western Australia and South Australia. Operative surgical management of complete fractures in the middle and distal thirds was usually successful. In contrast, fractures proximal to the middle third were regularly associated with non-union, implant failure and requirement for revision surgery. In view of this significant difference in outcome after fracture of the pagetic femur in different sites, a comprehensive surgical management strategy is recommended in order to avoid complications.


B lymphocyte-induced maturation protein (Blimp)-1, IFN regulatory factor (IRF)-1, and IRF-2 can bind to the same regulatory sites.
The transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) is expressed in some differentiated cells and is required for terminal differentiation of B cells. To facilitate identification of Blimp-1 target genes, we have determined the optimal DNA recognition sequence for Blimp-1. The consensus is very similar to a subset of sites recognized by IFN regulatory factors (IRFs) that contain the sequence GAAAG. By binding competition and determination of equilibrium dissociation constants, we show that Blimp-1, IRF-1, and IRF-2 have similar binding affinities for functionally important regulatory sites containing this sequence. However, Blimp-1 does not bind to all IRF sites, and specifically does not recognize IRF-4/PU.1 or IRF-8 sites lacking the GAAAG sequence. Chromatin immunoprecipitation studies showed that Blimp-1, IRF-1, and IRF-2 all bind the IFN-beta promoter in vivo, as predicted by the in vitro binding parameters, and in cotransfections Blimp-1 inhibits IRF-1-dependent activation of the IFN-beta promoter. Thus, our data suggest that Blimp-1 competes in vivo with a subset of IRF proteins and help predict the sites and IRF family members that may be affected.


Rehabilitation that works--vocational outcomes following rehabilitation for occupational musculoskeletal pain.
To describe the short term vocational outcome for accident compensation claimaints with disabling musculoskeletal pain following a comprehensive, interdisciplinary rehabilitation programme. A telephone follow-up audit of clients who had undertaken a rehabilitation programme characterised by a cognitive-behavioural approach with self-management, reconditioning, vocational rehabilitation and psychological pain management. Of 62 clients who had undergone a rehabilitation programme, we obtained follow-up information on 49 (79%). These were predominantly male, aged in their mid 30s, manual workers with low back pain and a median sick leave of twelve months. At a median of five months a vocational success was achieved in 75%: working full time (47%), part time (12%) or actively looking for work (16%). Of those in work, 48% went back to the same job, 7% went back to the same job but with a different employer and 15% went to a different job that used the same skills. Logistic regression analysis showed that duration of work disability was the major predictor of vocational success (OR 0.36, 95% CI 0.18 to 0.78, for a difference of twelve months). Despite the uncontrolled nature of these results, it is likely that the rehabilitation programme had a significant impact in getting compensation claimants back to work. Only a minority require substantive retraining and early intervention is associated with a better outcome.


[Biliary lesions after laparoscopic cholecystectomy].
Laparoscopic cholecystectomy is the suitable treatment for symptomatic cholelithiasis, even if the incidence of biliary lesions following this procedure may be up to threefold higher than that of open cholecystectomy. We report our experience concerning the incidence, aetiopathogenesis, diagnosis and treatment of complications in a homogeneous group of laparoscopic cholecystectomies. In a total of 492 laparoscopic cholecystectomies only three bile duct lesions were observed (0.6%); they were classified according to Bismuth and re-assessed according to Strasberg. They consisted in two biliary leakages and one bile duct stricture. All patients were evaluated by full blood test, ultrasonography and endoscopic retrograde cholangiopancreatography. Endoscopic treatment was successful in the two patients with biliary leakage, while the patient with a stricture required surgical therapy. In conclusion, we suggest that a correct knowledge of the aetiopathogenesis together with a multidisciplinary approach to the diagnosis appear to be the best method for the detection, complete classification and most suitable treatment of symptomatic cholelithiasis.


Regulatory roles of micro-RNAs in T cell autoimmunity.
MicroRNAs (miRNAs) are short conserved non-coding RNA molecules that have recently emerged as post-transcriptional gene expression regulators. miRNAs degrade or repress target mRNAs by targeting the 3' UTR region. miRNA-mediated gene regulation is crucial for regular biological processes such as immune cell lineage commitment, differentiation, maturation, and maintenance of immune homeostasis and regular function. Changes in miRNA expression patterns have been recorded in a wide range of human diseases, including autoimmunity, especially in T cell-related autoimmunity. This review discusses recent progress in miRNA-mediated regulation of T cell-related autoimmunity. Specifically, we discuss the modality of T cell-related autoimmunity regulation by miRNAs through affecting molecular and biological processes.


Outcome of duodenopancreatic resections in patients with multiple endocrine neoplasia type 1.
To evaluate the outcome of an aggressive surgical approach for duodenopancreatic neuroendocrine tumors (PETs) associated with multiple endocrine neoplasia type 1 (MEN1). The management of PETs is still controversial in the setting of the autosomal dominant inherited MEN1 syndrome. MEN1 patients that had either biochemical evidence of functioning PETs or visualized nonfunctioning PETs larger than 1 cm in size on imaging were operated. Since 1997, patients were followed annually by biochemical testing and imaging studies. Twenty-six genetically confirmed MEN1 patients underwent duodenopancreatic resection for functioning (n = 17) or nonfunctioning (n = 9) PETs. Ten (38%) patients had malignant PETs as characterized by the presence of lymph node (10 patients) and/or distant metastases (2 patients). The surgical approach was selected based on the type, location, and size of PETs. Four Zollinger-Ellison syndrome (ZES) patients required pylorus preserving pancreaticoduodenectomy (PPPD) as initial or redo procedure, 20 patients underwent other duodenopancreatic resections, and 2 patients had simple enucleations of PETs. After median 83 months (range, 5-241 months), 24 patients were alive and 2 patients died of an unrelated cause. All patients with insulinoma or vipoma and 7 of 11 patients with ZES were biochemically cured, including the ZES patients who underwent PPPD. However, 19 of 26 (73%) patients developed new small PETs (<1 cm) in the pancreatic remnant, but no patient had yet detectable metastases on imaging. Early and aggressive surgery of PETs in MEN1 patients prevents the development of liver metastases, which are the most life-threatening determinant. PPPD might be the procedure of choice for MEN1-ZES, which has to be proven in large scale studies.


Substance abuse disorders: a psychiatric priority. Group for the Advancement of Psychiatry Committee on Alcoholism and the Addictions.
The renewed public, governmental, and professional interest in addictive disorders should serve to encourage the interest of psychiatrists in this important and rapidly changing field. It is the view of the Group for the Advancement of Psychiatry (GAP) Committee on Alcoholism and the Addictions that all psychiatrists should possess expertise in the recognition, assessment, and treatment of substance use disorders. This position paper by the GAP committee reviews the role of the psychiatrist in the evaluation and treatment of patients with substance use disorders. It also notes some of the obstacles to full involvement in this field by medical practitioners in general and psychiatrists in particular. The psychiatrist has a critical role to play in the diagnosis and treatment of patients with substance use disorders. As biopsychosocial phenomena, substance abuse problems constitute a special and direct challenge to the psychiatrist, whose training, perspective, and competence should span all three domains. Psychiatrists must be willing to accept this challenge and fully participate in the development and application of treatment strategies adequate to cope with the enormous human suffering resulting from the abuse of alcohol and other psychoactive drugs.


Modulation of connexin43 alters expression of osteoblastic differentiation markers.
Gap junctional channels between cells provide a pathway for exchange of regulatory ions and small molecules. We previously demonstrated that expression of connexins and cell-to-cell communication parallel osteoblastic differentiation and that nonspecific pharmacological inhibitors of gap junctional communication inhibit alkaline phosphatase activity. In this study, we stably transfected connexin (Cx)43 antisense cDNA into the immortalized human fetal osteoblastic cell line hFOB 1.19 (hFOB/Cx43(-)). hFOB/Cx43(-) cells express lower levels of Cx43 protein and mRNA and display a 50% decrease in gap junctional intercellular communication relative to control [hFOB/plasmid vector control (pvc)]. This suggests that other connexins, such as Cx45, which is expressed to a similar degree in hFOB/Cx43(-) cells and hFOB/pvc cells, contribute to cell-to-cell communication in hFOB 1.19 cells. We observed almost total inhibition of alkaline phosphatase activity in hFOB/Cx43(-) cells despite only a 50% decrease in cell-to-cell communication. This suggests the intriguing possibility that Cx43 expression per se, independent of cell-to-cell communication, influences alkaline phosphatase activity and perhaps bone cell differentiation. Quantitative real-time RT-PCR revealed that mRNA levels for osteocalcin and core binding factor alpha1 (Cbfa1) increased as a function of time in hFOB/pvc but were inhibited in hFOB/Cx43(-). Osteopontin mRNA levels were increased in hFOB/Cx43(-) relative to hFOB/pvc and decreased as a function of time in both hFOB/Cx43(-) and hFOB/pvc. Transfection with Cx43 antisense did not affect expression of type I collagen in hFOB 1.19 cells. These results suggest that gap junctional intercellular communication and expression of Cx43 contribute to alkaline phosphatase activity, as well as osteocalcin, osteopontin, and Cbfa1 expression in osteoblastic cells.


HIV-1 protein expression from synthetic circles of DNA mimicking the extrachromosomal forms of viral DNA.
We have constructed circular forms of human immunodeficiency virus type 1 viral DNA in vitro that closely resemble the single and double long terminal repeat circular forms of unintegrated viral DNA formed in the nuclei of infected cells. We have analyzed viral protein expression after transient transfection of these circular DNAs into HeLa cells and compared it with expression from a transfected linearized plasmid containing an integrated provirus. Both circular forms are expressed, as judged by the appearance of extracellular p24, and expression is trans-activated by human immunodeficiency virus type 1 Tat. Viral p24 production, however, is approximately an order of magnitude lower than that obtained with transfected integrated viral DNA. Similar data were obtained when a luciferase reporter gene was substituted for the coding regions of the viral DNA. Positional effects of the transcriptional initiation and termination signals in the long terminal repeat appear to account for some of the low expression levels. These data suggest that unintegrated circular viral DNAs are transcriptionally active, although at low levels, and may contribute to overall viral replication in infected people under some conditions.


Increase of natural N enrichment of soybean nodules with mean nodule mass.
The (15)N abundance of soybean (Glycine max L. Merrill var Harosoy) nodules is usually greater than it is for other tissues or for atmospheric N(2). Results of experiments in which nodules were separated by size show that the magnitude of the (15)N enrichment is correlated with nodule mass. The results support the hypothesis that (15)N enrichment of nodules results from differential N isotopic fractionation for synthesis of nodule tissue versus synthesis of compounds for export from the nodule. The physiological significance of this hypothesis is that it requires that a substantial fraction of the N for nodule tissue synthesis in (15)N-enriched nodules be N recently fixed within the same nodule.


Screening for gonorrhoea using samples collected through the English national chlamydia screening programme and risk of false positives: a national survey of local authorities.
To investigate use of dual tests for Chlamydia trachomatis and Neisseria gonorrhoeae on samples collected through the National Chlamydia Screening Programme (NCSP) in England. During May-July 2013, we delivered an online survey to commissioners of sexual health services in the 152 upper-tier English Local Authorities (LAs) who were responsible for commissioning chlamydia screening in people aged 15-24 years. (1) The proportion of English LAs using dual tests on samples collected by the NCSP; (2) The estimated number of gonorrhoea tests and false positives from samples collected by the NCSP, calculated using national surveillance data on the number of chlamydia tests performed, assuming the gonorrhoea prevalence to range between 0.1% and 1%, and test sensitivity and specificity of 99.5%. 64% (98/152) of LAs responded to this national survey; over half (53% (52/98)) reported currently using dual tests in community settings. There was no significant difference between LAs using and not using dual tests by chlamydia positivity, chlamydia diagnosis rate or population screening coverage. Although positive gonorrhoea results were confirmed with supplementary tests in 93% (38/41) of LAs, this occurred after patients were notified about the initial positive result in 63% (26/41). Approximately 450-4500 confirmed gonorrhoea diagnoses and 2300 false-positive screens might occur through use of dual tests on NCSP samples each year. Under reasonable assumptions, the positive predictive value of the screening test is 17-67%. Over half of English LAs already commission dual tests for samples collected by the NCSP. Gonorrhoea screening has been introduced alongside chlamydia screening in many low prevalence settings without a national evidence review or change of policy. We question the public health benefit here, and suggest that robust testing algorithms and clinical management pathways, together with rigorous evaluation, be implemented wherever dual tests are deployed.


System for deep venous thrombosis detection using objective compression measures.
A system for objective vessel compression assessment for deep venous thrombosis characterization using ultrasound image data and a sensorized ultrasound probe is presented. Two new objective measures calculated from applied force and transverse vessel area are also presented and used to describe vessel compressibility. A modified star-Kalman algorithm is used for feature detection in acquired ultrasound images, and objective measures of vessel compressibility are calculated from the detected features and acquired force and location data from the sensorized probe. A three-dimensional shape model of the examined vessel that includes compressibility measures mapped as colors to its surface is presented on the user interface, as well as a virtual representation of the image plane. The compressibility measures were validated using expert segmentation of healthy and diseased vessels and compared using paired t-tests, which showed a significant difference between healthy and diseased cases for both measures. 100% sensitivity and specificity were obtained for both measures. The system was implemented in real-time (16 Hz) and evaluated using a tissue phantom and on healthy human subjects. Sensitivity was 100% and 60%, while specificity was 97% for both measures when implemented. The initial results for the system and its components are promising.


A spheroid-based 3-D culture model for pancreatic cancer drug testing, using the acid phosphatase assay.
Current therapy for pancreatic cancer is multimodal, involving surgery and chemotherapy. However, development of pancreatic cancer therapies requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Compared to two-dimensional culture of cell monolayer, three-dimensional (3-D) models more closely mimic native tissues, since the tumor microenvironment established in 3-D models often plays a significant role in cancer progression and cellular responses to the drugs. Accumulating evidence has highlighted the benefits of 3-D in vitro models of various cancers. In the present study, we have developed a spheroid-based, 3-D culture of pancreatic cancer cell lines MIAPaCa-2 and PANC-1 for pancreatic drug testing, using the acid phosphatase assay. Drug efficacy testing showed that spheroids had much higher drug resistance than monolayers. This model, which is characteristically reproducible and easy and offers rapid handling, is the preferred choice for filling the gap between monolayer cell cultures and in vivo models in the process of drug development and testing for pancreatic cancer.


Predictive Mechanisms Are Not Involved the Same Way during Human-Human vs. Human-Machine Interactions: A Review.
Nowadays, interactions with others do not only involve human peers but also automated systems. Many studies suggest that the motor predictive systems that are engaged during action execution are also involved during joint actions with peers and during other human generated action observation. Indeed, the comparator model hypothesis suggests that the comparison between a predicted state and an estimated real state enables motor control, and by a similar functioning, understanding and anticipating observed actions. Such a mechanism allows making predictions about an ongoing action, and is essential to action regulation, especially during joint actions with peers. Interestingly, the same comparison process has been shown to be involved in the construction of an individual's sense of agency, both for self-generated and observed other human generated actions. However, the implication of such predictive mechanisms during interactions with machines is not consensual, probably due to the high heterogeneousness of the automata used in the experimentations, from very simplistic devices to full humanoid robots. The discrepancies that are observed during human/machine interactions could arise from the absence of action/observation matching abilities when interacting with traditional low-level automata. Consistently, the difficulties to build a joint agency with this kind of machines could stem from the same problem. In this context, we aim to review the studies investigating predictive mechanisms during social interactions with humans and with automated artificial systems. We will start by presenting human data that show the involvement of predictions in action control and in the sense of agency during social interactions. Thereafter, we will confront this literature with data from the robotic field. Finally, we will address the upcoming issues in the field of robotics related to automated systems aimed at acting as collaborative agents.


Investigating underlying human immunity genes, implicated diseases and their relationship to COVID-19.
Aim: A human immunogenetics variation study was conducted in samples collected from diverse COVID-19 populations. Materials & methods: Whole-genome and whole-exome sequencing (WGS/WES), data processing, analysis and visualization pipeline were applied to identify variants associated with genes of interest. Results: A total of 2886 mutations were found across the entire set of 13 genomes. Functional annotation of the gene variants revealed mutation type and protein change. Many variants were found to be biologically implicated in COVID-19. The involvement of these genes was also found in multiple other diseases. Conclusion: The analysis determined that ACE2, TMPRSS4, TMPRSS2, SLC6A20 and FYCOI had functional implications and TMPRSS4 was the gene most altered in virally infected patients.


QbD approach to investigate product and process variabilities for brain targeting liposomes.
Efficacy of central nervous system-acting medications is limited by its localization and ability to cross the blood-brain barrier (BBB); therefore, the crux is in designing delivery systems targeted to cross the BBB. Toward this objective, this study proposed pegylated and glycosylated citalopram hydrobromide (Cit-HBr) liposomes as a delivery approach for brain targeting. The multicomponent liposomes were evaluated for drug encapsulation, vesicular size, size distribution, conductivity and drug release characteristics. Moreover, the interaction among the employed components was evaluated by Fourier transform infrared, differential scanning calorimetric and X-ray diffraction analysis. Through a systematic screening design of formulation and process variables in the optimization phase, an improvement of Cit-HBr loading, fine vesicular size with narrow size distribution, greater stability and sustained release features were achieved. The compatibility studies unveiled a significant interaction between Cit-HBr and dicetyl phosphate to control drug encapsulation and release properties. The optimization process showed a minimal range of design space to achieve the preset desirability; more precisely dicetyl phosphate, polyethylene glycol, N-acetyl glucosamine and freeze-thaw cycles of 3%, 5%, 4% and 2 cycles, respectively, were used. Using brain endothelial cell models, the optimized formulations showed an acceptable cell viability with preserved monolayer integrity and an enhanced flux and permeability. Thus, this study has proposed an optimized pegylated and glycosylated vector that is a promising step for brain targeting.


Invasive cutaneous mucormycosis in a preterm neonate presenting as a vesicobullous lesion.
Mucormycosis is a relatively rare fungal infection seen in immunocompromised patients. Very few cases of invasive cutaneous mucormycosis occurring in neonates have been reported in literature. It is an aggressive disease with a mortality rate of around 64% in neonates, so a high index of suspicion is essential for rapid diagnosis and definitive treatment with broad-spectrum antifungals such as Amphotericin B. We present a case of a premature infant born at 25 weeks of gestation who developed vesicobullous lesions all over the body on day 5 of life. Biopsy from the vesicles confirmed the presence of angioinvasive fungal hyphae of mucormycosis which were highlighted on Periodic acid-Schiff and Grocott stain.


Sero-epidemiology of peste des petits ruminants in Oromia and Afar regional states of Ethiopia.
Peste des petits ruminants (PPR) is a severe non-zoonotic viral disease of small ruminants caused by a morbillivirus closely related to rinderpest virus (RPV). The disease is widespread in Africa, the Middle East and Southern Asia. It is one of the priority animal diseases whose control is considered important for poverty alleviation in those regions because of the associated high economic losses. A sero-epidemiological study of PPR was conducted in Oromia and Afar regional states of Ethiopia. A total of 800 serum samples from sheep and goats were collected between October 2015 and March 2016 in Afar and Oromia, where no vaccination history has been recorded. These two regions are known to have a large population of small ruminants. The levels of PPR antibodies obtained in the two regions using the competitive enzyme-linked immunosorbent assay (cELISA) ID Screen® PPR Competition from IDvet (Montpellier, France) were similar, at 12.7% and 13.0% for Afar and Oromia, respectively. A seroprevalence of 12.9% for the two regions was obtained. The study also linked seropositivity to risk factors such as sex, age and species with a p-value of less than 0.05 (p = 0.0001, p = 0.0001 and p = 0.004, respectively).


[Effects of Rap2b gene on foci formation and wound-healing of NIH3T3 cells].
To explore the effects on foci formation and wound-healing of NIH3T3 cells, and to provid the experimental evidence of its function. DNA from human lung cells was extracted and amplification of Rap2b gene was done by PCR. Eukaryotic expression vector pcDNA3. 1-Rap2b was constructed and was stable transfected into NIH3T3 cell followed with foci formation assay and wound-healing assay. The number of the foci formation of NIH3T3 cell transfected by eukaryotic expression vector pcDNA3. 1-Rap2b was increased remarkably in foci formation assay (P < 0.01) and NIH3T3 cells transfected by eukaryotic expression vector pcDNA3. 1-Rap2b were quickly heal up in wound-healing assay. The extrinsic expression of Rap2b could transform NIH3T3 cell using foci formation assay and wound-healing assay. Rap2b gene might play an oncogenic role in tumorigenesis.


Contraceptive use, prevalence and predictors of pregnancy planning among female sex workers in Uganda: a cross sectional study.
Unintended pregnancies are associated with negative consequences to both mother and baby. Female Sex Workers (FSWs) are at high risk of unintended/unplanned pregnancies. However, prevalence of pregnancy planning and its predictors among FSWs has not been comprehensively investigated. This study was designed to determine contraceptive use, the prevalence, and predictors of pregnancy planning among FSWs in Uganda. In this cross-sectional study, 819 FSWs attending most at risk populations initiative (MARPI) clinics were recruited using systematic sampling and interviewed with a pretested questionnaire that included collection of data on pregnancy intention using the London Measure of Unplanned Pregnancy (LMUP). Data were analysed using STATA version 14.0. Multinomial logistic regression model was used to identify predictors of pregnancy planning, RESULTS: Of the 819 study participants, only 90 (11.0%) had planned pregnancies. Overall, 462 (56.4%) were hazardous alcohol users and 335 (40.9%) abused drugs; 172 (21.0%) had been raped in the last 2 years and 70 (40.7%) of these accessed emergency contraception post-rape. Dual contraception use (condom and other modern method) was 58.0%. Having a non-emotional partner as a man who impregnated the FSW compared to emotional partner was significantly associated with less planned relative to unplanned pregnancy, (aRR = 0.15 95%Cl =0.08, 0.30), so was lack of reported social support compared to support from friends, (aRR = 0.44; 95% CI = 0.22-0.87), keeping all factors constant in the model. Being raped (aRR = 0.51; 95% CI = 0.31-0.84) or abuse of substances (aRR = 0.65; 95% CI = 0.45-0.93) were significantly associated with lower ambivalence relative to unplanned pregnancy but not with planned relative to unplanned pregnancy. Compared to women in the general population, pregnancy planning was low among FSWs amidst modest use of dual contraceptive. There is an urgent need to promote dual contraception among FSWs to prevent unplanned pregnancies especially with non-emotional partners, drug users, and post-rape.


Compton coincidence in silicon photon-counting CT detectors.
Purpose: Compton interactions amount to a significant fraction of the registered counts in a silicon detector. In a Compton interaction, only a part of the photon energy is deposited and a single incident photon can result in multiple counts unless tungsten shielding is used. Deep silicon has proved to be a competitive material for photon-counting CT detectors, but to improve the performance further, one possibility is to use coincidence techniques to identify Compton-scattered photons and reconstruct their incident energies. Approach: In a detector with no tungsten shielding, incident photons can interact through a series of interactions. Based on the position and energy of each interaction, probability-based methods can be used to estimate the incident photon energy. Here, we present a maximum likelihood estimation framework along with an alternative method to estimate the incident photon energy and position in a silicon detector. Results: Assuming one incident photon per time frame, we show that the incident photon energy can be estimated with a mean error of - 0.07 ± 0.03 keV and an RMS error of 3.36 ± 0.02 keV for a realistic case in which we assume a detector with limited energy and spatial resolution. The interaction position was estimated with a mean error of - 2 ± 11 μ m in x direction and 7 ± 11 μ m in y direction. Corresponding RMS errors of 1.09 ± 0.01 and 1.10 ± 0.01 mm were achieved in x and y , respectively. Conclusions: The presented results show the potential of using probability-based methods to improve the performance of silicon detectors for CT.