Aripiprazole therapy in 20 older adults with bipolar disorder: a 12-week, open-label trial.
Bipolar disorder in older adult populations has gained increasing attention due to the growing proportion of elderly in the United States and worldwide. A continuing unmet need is the identification of agents that are generally well-tolerated and effective in later life bipolar disorder. Aripiprazole is an atypical antipsychotic compound that is approved by the U.S. Food and Drug Administration for the treatment of bipolar mania and for the long-term treatment of bipolar disorder. This study is an open-label, prospective trial of aripiprazole therapy in 20 older adult patients with bipolar disorder. Older adults with bipolar I disorder (confirmed by the Mini-International Neuropsychiatric Interview) who were currently suboptimally responsive to their prescribed medication treatments received 12 weeks of open-label aripiprazole added on to existing mood stabilizer medication treatment. Aripiprazole was initiated at 5 mg daily and increased as tolerated. Efficacy outcomes included psychopathology measures (the Young Mania Rating Scale [YMRS] and the Hamilton Rating Scale for Depression [HAM-D]), extrapyramidal symptoms, and a level of functioning measure (the Global Assessment Scale [GAS]). The study was conducted from April 2004 to June 2005. Twenty older adults (mean age = 59.6 years, range 50-83 years) received aripiprazole therapy. Compared to baseline, individuals had significant reductions in mean depression scores (HAM-D baseline = 13.8, HAM-D end point = 6.1, p < .001), as well as mania scores (YMRS baseline = 8.6, YMRS end point = 3.9, p < .03). There were also significant improvements in functional status as measured by the GAS (p < .001). The mean +/- SD daily dose of aripiprazole was 10.26 +/- 4.9 mg/day. Overall, aripiprazole was adequately tolerated in this older adult population. Aripiprazole therapy may reduce symptoms in bipolar older adults, and it appears to be reasonably tolerated. However, larger, controlled trials are needed to confirm these preliminary findings.


Identification of phage-displayed peptides which bind to the human HnRNPA1 protein-specific monoclonal antibody.
We have screened a peptide phage display library to examine if monoclonal antibody-binding phages could be isolated from the library and thereby predict the antigenic epitopes of the antibodies from the isolated phages. The library was screened for high-avidity binding to monoclonal antibodies by an affinity purification technique called biopanning. Among the monoclonal antibodies examined, the human hnRNPA1 protein-specific monoclonal antibody 9H10 showed selective binding of phages. After two rounds of the biopanning, twelve clones of high-avidity-binding phages were chosen and their inserts were sequenced. Nucleotide sequence comparison of the 12 clones showed that there were 5 different species, with two species containing four members, implying that they were predominantly selected by the biopanning. The amino acid sequences of the inserts of the 12 clones were compared with that of the human hnRNPA1 protein in order to find the putative epitope of the human hnRNPA1 protein for 9H10. The C-terminal region of the human hnRNPA1 protein shows significant homology with the peptide sequences of the selected phage clones. These results show that this peptide phage display library can be useful in defining the epitope of some monoclonal antibodies.


Using pharmacogenetics to structure individual pain management protocols in total knee arthroplasty.
The purpose of this study was to use pharmacogenetics to determine the frequency of genetic variants in our total knee arthroplasty (TKA) patients that could affect postoperative pain medications. Pharmacogenetic testing evaluates patient DNA to determine if a drug is expected to have a normal clinical effect, heightened effect, or no effect at all on the patient. It also predicts whether patients are likely to experience side effects from medicine. We further sought to determine if changing the multimodal programme based on these results would improve pain control or reduce side effects. In this pilot study, buccal samples were collected from 31 primary TKA patients. Pharmacogenetics testing examined genetic variants in genes OPRM1, CYP1A2, CYP2B6, CYP2C19, CYP3A4, CYP2C9, and CYP2D6. These genes affect the pharmacodynamics and pharmacokinetics of non-steroidal anti-inflammatory drugs and opioids. We examined the frequency of genetic variants to any of the medications we prescribed including celecoxib, hydrocodone, and tramadol. Patients were randomized to one of two groups: the control group received the standard postoperative pain regimen, and the study group received a customized regimen based on the pharmacogenetic results. For the first ten postoperative days, patients recorded pain scores, medication, and side effects. Genetic variants involving one or more medications in the multimodal pain protocol occurred in 13 of the 31 patients (42%). In total, eight patients (26%) had variants affecting more than one of the medications. For the 25 patients who recorded pain and medication logs, the mean pain levels and morphine equivalents (MEQs) consumed in the first ten days were higher in the control group than in the custom-guided group (p = 0.019 for pain and p = 0.655 for MEQ). Overall, 42% of patients had a variant involving one of the pain medications prescribed in our perioperative pain program for TKA. Ongoing research will help determine if using these data to modify a patient's medication will improve outcomes. Cite this article: Bone Joint J 2020;102-B(6 Supple A):73-78.


Assessment of performance of selected serological tests for diagnosing brucellosis in pigs.
Swine brucellosis due to Brucella suis is considered an emerging zoonotic disease whose control is based on serological testing and the subsequent culling of seropositive animals or the full depopulation of affected flocks. Here we assessed the performance of several serological tests (Rose Bengal Test [RBT], indirect ELISA [i-ELISA], blocking ELISA [b-ELISA], and two competitive ELISAs [c-ELISA]) for diagnosing swine brucellosis caused by B. suis biovar 2. Both frequentistic and Bayesian statistical inference were used. A frequentistic analysis, using sera from known gold standard (GS) populations (i.e., from truly infected or brucellosis free animals), resulted in maximum (100%) diagnostic sensitivity (Se) and specificity (Sp) in the RBT, i-ELISA and b-ELISA tests. However, c-ELISAs resulted in lower diagnostic Se (ranging from 68.5% to 92.6%, according to the different cut-offs selected). A Bayesian analysis of tests yielding the best diagnostic performance with GS sera (RBT, i-ELISA and b-ELISA), but using a large collection of field sera, resulted in similar Se among tests but markedly lower (≈ 80%) than that resulting from the frequentistic analysis using the GS serum populations. By contrast, the estimated Sp in the Bayesian analysis was only slightly lower than 100%, thus similar to that obtained frequentistically. Our results show that adequate diagnostic tests for brucellosis in swine are available, but also emphasize the need for more extensive validation studies before applying these tests under field conditions.


[Acute appendicitis in patients with salmonellosis and dysentery].
Results of 214 appendectomies in patients with acute intestinal diseases were analyzed. The clinical course and results of treatment of acute appendicitis against the background of salmonellosis and dysentery were discussed. It was shown that the theory of infectious nature of acute appendicitis is rightful and that valuable etiotropic therapy is necessary for prevention of chronicity of the intestinal infection.


GC-MS Fingerprinting Combined with Chemical Pattern-Recognition Analysis Reveals Novel Chemical Markers of the Medicinal Seahorse.
Seahorse is a valuable marine-animal drug widely used in traditional Chinese medicine (TCM), and which was first documented in the "Ben Cao Jing Ji Zhu" during the Liang Dynasty. Hippocampus kelloggi (HK) is the most common seahorse species in the medicinal material market and is one of the genuine sources of medicinal seahorse documented in the Chinese pharmacopeia. It is mainly cultivated in the Shandong, Fujian, and Guangxi Provinces in China. However, pseudo-HK, represented by Hippocampus ingens (HI) due to its similar appearance and traits, is often found in the market, compromising the safety and efficacy of clinical use. Currently, there is a lack of reliable methods for identifying these species based on their chemical composition. In this study, we employed, for the first time, a strategy combining gas chromatography-mass spectrometry (GC-MS) fingerprints and chemical patterns in order to identify HK and HI; it is also the first metabolomic study to date of HI as to chemical components. The obtained results revealed remarkable similarities in the chemical fingerprints, while significant differences were also observed. By employing hierarchical cluster analysis (HCA) and principal component analysis (PCA), based on the relative contents of their characteristic peaks, all 34 samples were successfully differentiated according to their species of origin, with samples from the same species forming distinct clusters. Moreover, nonadecanoic acid and behenic acid were exclusively detected in HK samples, further distinguishing them from HI samples. Additionally, the relative contents of lauric acid, tetradecanoic acid, pentadecanoic acid, n-hexadecanoic acid, palmitoleic acid, margaric acid, oleic acid, fenozan acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) exhibited significant differences between HK and HI (p < 0.0001), as determined by an unpaired t-test. Orthogonal partial least squares discriminant analysis (OPLS-DA) identified seven components (DHA, EPA, n-hexadecanoic acid, tetradecanoic acid, palmitoleic acid, octadecanoic acid, and margaric acid) with high discriminatory value (VIP value > 1). Thus, nonadecanoic acid, behenic acid, and these seven compounds can be utilized as chemical markers for distinguishing HK from HI. In conclusion, our study successfully developed a combined strategy of GC-MS fingerprinting and chemical pattern recognition for the identification of HK and HI, and we also discovered chemical markers that can directly differentiate between the two species. This study can provide a foundation for the authentication of Hippocampus and holds significant importance for the conservation of wild seahorse resources.


High glucose-induced expression of inflammatory cytokines and reactive oxygen species in cultured astrocytes.
Astrocyte activation plays important roles both in physiological and pathological process in the CNS. In the latter, the process is further aggravated by hyperglycemia, leading to diabetes complications of CNS. We report here that high glucose (HG) treatment stimulated astrocytic morphological alteration coupled with changes in glial fibrillary acidic protein (GFAP) and vimentin expression. Additionally, HG upregulated the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-4 (IL-4), and vascular endothelial growth factor (VEGF); however, its effects on transforming growth factor-β (TGF-β) expression were not evident. HG treatment induced increased production of reactive oxygen species (ROS) as well as activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and signal transducer and activator transcription 3 (STAT 3). HG-induced expression of TNF-α, IL-6, IL-1β, IL-4, and VEGF was blocked by ROS scavenger and inhibitors specific for NF-κB and STAT 3, respectively. The results suggest that the aforementioned multiple inflammatory cytokines and mediators that may be linked to the pathogenesis of the diabetes complications of CNS are induced by HG via the key signaling pathways.


The {Cu2I2} cluster bearing metal organic frameworks: crystal structures and fluorescence detecting performances towards cysteine and explosive molecules.
Two {Cu2I2} cluster-bearing metal organic frameworks (MOFs) of {[Eu(CuI)2(INA)3DMF]·0.95DMF}n (Eu-CuI-INA) and {K[(CH3)2NH2]Sr4(INA)2(DMF)2{(Cu2I2)2(INA)8}·2H2O}n (Sr-K-CuI-INA, HINA = isonicotinic acid, DMF = N,N-dimethyl formamide) were prepared and characterized in this work. Both materials feature a three-dimensional (3-D) structure, in which the {Cu2I2} clusters and Eu3+ (or Sr2+) metal ions are coordinated by INA- ligands with pyridine and carboxylic groups, respectively. Impressively, Sr-K-CuI-INA exhibits sensitive fluorescence sensing behaviors towards cysteine and nitro-bearing molecules, demonstrating potential FL sensing applications for bio and explosive molecules. This work would provide a good reference for designing fluorescent MOF probes containing CuI molecules.


Profiling police presentations of mental health consumers to an emergency department.
Public mental health systems have been called on to better meet the needs of consumers presenting to health services with the police, yet few studies have examined police presentations among mental health consumers in large public mental health systems. This study was designed to determine the frequency profile and characteristics of consumers of mental health services brought in by police to an emergency department (ED) in Sydney, Australia. Using data from the emergency department information system and obtaining the psychiatric assessment from the medical record, we have examined trends and characteristics in mental health presentations brought in by the police to a general ED between 2003 and 2005. The sample consisted of 542 consumers with a mental health problem brought in by the police to the ED of a 350-bed community hospital. The characteristics of this group were compared with those of all mental health related ED presentations for the same period using logistic regression. Results indicated that police presentations are likely to be young males who are unemployed, have past and present alcohol and other drugs use, present after hours, and are admitted to hospital as a result of their presentation. These consumers are likely to have a presenting problem of a psychotic disorder, less likely to have a presenting problem of depression and/or anxiety, and given a triage code of three or higher. The study results highlight the importance of the availability of 24-hour access to mental health care to ensure a quick care delivery response. Police presentations to EDs with mental health issues are an indicator of significant impact on health services, especially with the current overcrowding of EDs and the associated long waiting times. Systems need to be developed that facilitate collaboration between EDs, hospital security, police services, mental health, and ambulance services.


Characteristics and outcomes of older people on antiretroviral therapy in Tlokwe Clinics, South Africa.
South Africa (SA) has a large human immunodeficiency virus (HIV) epidemic but little is known of its effect on those ≥ 60 years of age viz. 'older-persons' living with HIV (OPLWH). Numbers in this age group are increasing and are expected to place a greater strain on existing resources. To describe the demographic features and the co-morbidities of OPLWH in Tlokwe. This included an assessment of viral load (VL) suppression and the identification of associations between patient characteristics and clinical outcomes. A retrospective file review was undertaken to cover the period 01 May 2017 to 30 April 2018. Descriptive statistics were applied to demographic and clinical data and to treatment outcomes. Statistically significant associations were subjected to logistic regression analysis. Of the 191 participants, 111/191 (58.1%) were female and 167/191 (87.4%) were 60 -70 years of age. Of the participants, 154/191 (81.9%) were virally suppressed (< 400 copies/mL). Hypertension (n = 106/191, 55.5%) was the most frequently identified co-morbidity. A CD4 cell count of ≥ 350 cells/mm3 at last assessment correlated positively with VL suppression (odds ratio 2.3, confidence interval 1.05-5.02, p = 0.037). Although the level of VL suppression in this cohort was high, greater effort is required to bring this in line with the Joint United Nations Programme on HIV/AIDS (UNAIDS) recommendations viz. 90% viral suppression in PLWH by 2030. Further research is needed to define the evolving long-term needs of OPLWH and to facilitate entry into care of those currently not in care.


Immunohistochemical study for the expression of leukocyte adhesion molecules, and FGF23 and ACE2 in P. gingivalis LPS-induced diabetic nephropathy.
The present study aims to examine the expression of leukocyte adhesion molecules and renal metabolic factors in diabetic mouse kidneys with periodontal pathogen Pg-LPS-induced nephropathy. We recently reported that the glomerular endothelium expresses toll-like receptor (TLR)2 and TLR4 in diabetic environments and TLR2/4 ligand Porphyromonas (P.) gingivalis lipopolysaccharides (Pg-LPS) induce nephropathy in diabetic mice. It is thought that Pg-LPS promotes the chronic inflammation with the overexpression of leukocyte adhesion molecules and renal-specific metabolic enzymes by the recognition of Pg-LPS via TLR in the diabetic kidneys. There have been no reports of the effects of periodontopathic bacteria on the expression of leukocyte adhesion molecules and the accumulation of physiologically active substances in the kidney. The immunohistochemical investigation was performed on diabetic mouse kidney with Pg-LPS-induced nephropathy with glomerulosclerosis in glomeruli. There were no vessels which expressed vascular cell adhesion molecule-1 (VCAM-1), E-selectin, or fibroblast growth factor (FGF) 23 in streptozotocin (STZ)-induced diabetic ICR mice (STZ-ICR), or in healthy ICR mice administered Pg-LPS (LPS-ICR). However, in diabetic ICR mouse kidneys with Pg-LPS-induced nephropathy (LPS-STZ) the expression of VCAM-1 and the accumulation of FGF23 were observed in renal tubules and glomeruli, and the expression of E-selectin was observed in renal parenchyma and glomeruli. The angiotensin-converting enzyme 2 (ACE2) was detected in the proximal tubules but not in other regions of ICR, STZ-ICR, or LPS-ICR. In LPS-STZ ACE2 was detected both in renal tubules as well as in glomeruli. The Mac-1 and podoplanin-positive cells increased in the renal parenchyma with diabetic condition and there was the distribution of a large number of Mac-1-positive cells in LPS-STZ. The Pg-LPS may induce diabetic renal inflammation such as glomerulosclerosis and tubulitis with infiltration of Mac-1/podoplanin positive macrophages via glomerular overexpression of VCAM-1 and E-selectin, resulting in accumulation of both ACE2 and FGF23 which were unmetabolized with the inflammation-induced kidney damage under the diabetic condition. Periodontitis may be a critical factor in the progress of nephropathy in diabetic patients.


Mechanism-based Pharmacovigilance over the Life Sciences Linked Open Data Cloud.
Adverse drug reactions (ADR) result in significant morbidity and mortality in patients, and a substantial proportion of these ADRs are caused by drug-drug interactions (DDIs). Pharmacovigilance methods are used to detect unanticipated DDIs and ADRs by mining Spontaneous Reporting Systems, such as the US FDA Adverse Event Reporting System (FAERS). However, these methods do not provide mechanistic explanations for the discovered drug-ADR associations in a systematic manner. In this paper, we present a systems pharmacology-based approach to perform mechanism-based pharmacovigilance. We integrate data and knowledge from four different sources using Semantic Web Technologies and Linked Data principles to generate a systems network. We present a network-based Apriori algorithm for association mining in FAERS reports. We evaluate our method against existing pharmacovigilance methods for three different validation sets. Our method has AUROC statistics of 0.7-0.8, similar to current methods, and event-specific thresholds generate AUROC statistics greater than 0.75 for certain ADRs. Finally, we discuss the benefits of using Semantic Web technologies to attain the objectives for mechanism-based pharmacovigilance.


Assessing the accuracy and feasibility of a refractive error screening program conducted by school teachers in pre-primary and primary schools in Thailand.
As part of the development of a system for the screening of refractive error in Thai children, this study describes the accuracy and feasibility of establishing a program conducted by teachers. To assess the accuracy and feasibility of screening by teachers. A cross-sectional descriptive and analytical study was conducted in 17 schools in four provinces representing four geographic regions in Thailand. A two-staged cluster sampling was employed to compare the detection rate of refractive error among eligible students between trained teachers and health professionals. Serial focus group discussions were held for teachers and parents in order to understand their attitude towards refractive error screening at schools and the potential success factors and barriers. The detection rate of refractive error screening by teachers among pre-primary school children is relatively low (21%) for mild visual impairment but higher for moderate visual impairment (44%). The detection rate for primary school children is high for both levels of visual impairment (52% for mild and 74% for moderate). The focus group discussions reveal that both teachers and parents would benefit from further education regarding refractive errors and that the vast majority of teachers are willing to conduct a school-based screening program. Refractive error screening by health professionals in pre-primary and primary school children is not currently implemented in Thailand due to resource limitations. However, evidence suggests that a refractive error screening program conducted in schools by teachers in the country is reasonable and feasible because the detection and treatment of refractive error in very young generations is important and the screening program can be implemented and conducted with relatively low costs.


[Are we controlling the sedation in ICU? A multicenter study results].
The aim of this study is to evaluate the issues of sedation and analgesia in all-purpose ICUs in Russia. To obtain that, a single-day observational survey was performed in 55 ICUs of Ural and Siberia regions. This work enabled to describe the targets, instruments of control and patterns of sedative and analgetics and sedatives prescription, as well as to make conclusions about issues in this area and possibilities of creation and necessity of analgesia and sedation standards. The study has shown a decent percentage of use of standardized scales evaluating pain in ICU and predominance of effectivae drugs and analgesia patterns, which leads to "formalization" of analgesia and decrease of it's effectiveness. Sedation indications do not satisfy the modern concept, sedation level evaluation scores are used only in 13%, schemes and drugs are traditional. The results of this study may serve as a reason for discussion of necessity of introducing of sedative and analgetic therapy in ICU standarts.


Pulse oximetry: an alternative method for the assessment of oxygenation in newborn infants.
Continuous monitoring of oxygenation in sick newborns is vitally important. However, transcutaneous PO2 measurements have a number of limitations. Therefore, we report the use of the pulse oximeter for arterial oxygen saturation (SaO2) determination in 26 infants (birth weights 725 to 4,000 g, gestational ages 24 to 40 weeks, and postnatal ages one to 49 days). Fetal hemoglobin determinations were made on all infants and were repeated following transfusion. SaO2 readings from the pulse oximeter were compared with the SaO2 measured in vitro on simultaneously obtained arterial blood samples. The linear regression equation for 177 paired measurements was: y = 0.7x + 27.2; r = .9. However, the differences between measured SaO2 and the pulse oximeter SaO2 were significantly greater in samples with greater than 50% fetal hemoglobin when compared with samples with less than 25% fetal hemoglobin (P less than .001). The pulse oximeter was easy to use, recorded trends in oxygenation instantaneously, and was not associated with skin injury. We conclude that pulse oximetry is a reliable technique for the continuous, noninvasive monitoring of oxygenation in newborn infants.


Berberine Protects Against Simulated Ischemia/Reperfusion Injury-Induced H9C2 Cardiomyocytes Apoptosis In Vitro and Myocardial Ischemia/Reperfusion-Induced Apoptosis In Vivo by Regulating the Mitophagy-Mediated HIF-1α/BNIP3 Pathway.
Berberine (BBR) has a variety of pharmacological activities and is widely used in Asian countries. However, the clinical application of BBR still lacks scientific basis, what protective mechanism of BBR against myocardial ischemia-reperfusion injury (MIRI). In vitro experiments, BBR pretreatment regulated autophagy-related protein expression, induced cell proliferation and autophagosome formation, and reduced the mitochondrial membrane potential (ΔΨm) increase in H9C2 cells. In vivo experiments, BBR reduced the myocardial infarct size, decreased cardiomyocyte apoptosis, and markedly decreased myocardial enzyme (CK-MB, LDH, and AST) activity-induced I/R. In addition, upon BNIP3 knockdown, the regulatory effects of BBR on the above indicators were weakened both in H9C2 cells and in vivo. Luciferase reporter and ChIP assays indicated that BBR mediated BNIP3 expression by enhancing the binding of HIF-1α to the BNIP3 promoter. BBR protects against myocardial I/R injury by inducing cardiomyocytes proliferation, inhibiting cardiomyocytes apoptosis, and inducing the mitophagy-mediated HIF-1α/BNIP3 pathway. Thus, BBR may serve as a novel therapeutic drug for myocardial I/R injury.


The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls.
Although the pathogenesis of hidradenitis suppurativa (HS) remains enigmatic, several factors point to potential involvement of the cutaneous microbiome. Insight into the cutaneous microbiome in HS using next-generation sequencing may provide novel data on the microbiological diversity of the skin. To investigate the follicular skin microbiome in patients with HS and in healthy controls. This case-control study obtained punch biopsy specimens from patients with HS (lesional and nonlesional) and healthy controls between October 1, 2014, and August 1, 2016. Data were analyzed from March to November 2016. Patients with HS were recruited from the Department of Dermatology, Zealand University Hospital, Roskilde, Denmark. Biopsy specimens were analyzed at the Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark. None of the participants received any antibiotics (systemic or topical therapy) within 1 month before the study. In patients with HS, biopsy specimens were obtained from lesional skin (axilla or groin) and nonlesional skin. Only nodules containing at least 1 visible hair follicle were biopsied. Biopsy specimens from healthy controls were obtained from the axilla only. The different microbiomes were investigated using next-generation sequencing targeting 16S and 18S ribosomal RNA. The skin microbiome was characterized in 30 patients with HS (mean [SD] age, 46.9 [14.0] years; 19 [63% female]) and 24 healthy controls (mean [SD] age, 32.2 [12.0] years; 13 [54% female]). The next-generation sequencing data provided a previously unreported (to our knowledge) characterization of the skin microbiome in HS. The study demonstrated that the microbiome in HS differs significantly from that in healthy controls in lesional and nonlesional skin. Overall, the following 5 microbiome types were identified: Corynebacterium species (type I), Acinetobacter and Moraxella species (type II), Staphylococcus epidermidis (type III), Porphyromonas and Peptoniphilus species (type IV), and Propionibacterium acnes (type V). In lesional skin, microbiome types consisted predominantly of type I or type IV. Microbiome type IV was not detected in healthy controls. Several taxa, including Propionibacterium, showed a significantly higher relative abundance in healthy controls vs HS skin, indicating that Propionibacterium may be part of the pathogenesis in HS. The study findings suggest a link between a dysbiotic cutaneous microbiome and HS.


Adherence tool for prophylactic haemophilia treatment in adult and adolescent patients: A systematic review and meta-analysis protocol.
Hemophilia is a congenital bleeding disorder resulting from a low level or deficiency of clotting factors. It is an x-linked recessive disease and happens almost exclusively in males whereas females are the carrier of the affected gene. The most common types of hemophilia are hemophilia A and Hemophilia B. Hemophilia is classified into mild, moderate and severe. Prophylaxis treatment has more advantages clinically compare to on-demand therapy. It may reduce the bleeding frequency, gives protection from joint damage, may lower the number of total bleeding episodes per year, and may reduce annualised spontaneous and trauma related bleeding events. However, prophylaxis treatment needs regular weekly infusions therefore it is painful to administer especially if the vein is difficult to access. It may cause pain at the site of injections and may lead to non-adherence to treatment. Non-adherence to a regimen will result in insufficient clotting factor levels in the body. The efficacy of the medication is reduced and may lead to a high bleeding tendency. Thus far, the study on adult haemophilic patient adherence tool is scarce and limited; and therefore this review is warranted. The study protocol is conducted as per the PRISMA-P guideline. There are 4 concepts in this systematic review which are Haemophilia, adult and adolescence, preventive treatment and adherence. Articles will be sought from electronic databases PUBMED, Ovid EMBASE, CINAHL, and SCOPUS using the MeSH term, synonym free-text word, truncation, and proximity operators as per each database. The proposed keywords within each concept will be joined using the Boolean operator "OR "and the 4 different concepts combined using the Boolean operator "AND". Search will be limited to Human, English language, and publication until 2022. Studies will be included if they meet the study inclusion criteria. The quality of the studies will be appraised using the Newcastle-Ottawa quality assessment scale (NOS) for observation-based studies. This systematic review does not require formal ethical approval as data will be extracted from selected published studies. The results will be disseminated through a peer-reviewed publication and relevant conference presentations.(PROSPERO registration CRD42021273813).


Metatranscriptomic virome assessment of Rhipicephalus microplus from Colombia.
Ticks (Ixodida) are hematophagous ectoparasites that harbor and transmit diverse species of viruses, some of which cause serious diseases with worldwide veterinary and human health consequences. Rhipicephalus microplus is an important cattle tick in Colombia, where it causes significant economic losses. Despite the importance of this tick, its viral profile is unknown. RNA sequencing was used in this study as a surveillance method for virus detection in R. microplus. Most of the viral origin contigs were assigned to two putative viruses: one chuvirus (Wuhan tick virus 2) and one phlebovirus-like (Lihan tick virus). In addition, viral contigs corresponding to two jingmenviruses previously reported in R. microplus from China and Brazil were detected, as well as a novel putative tymovirus, named here as Antioquia tymovirus-like 1 (ATV-like 1). The presence of some of these viruses across numerous regions in the world could have several explanations, including i) a long-term association between those viruses and R. microplus and ii) a consequence of livestock historical trade. Our results shed new light on the virus diversity of this tick species and provide a basis for further studies on the evolutionary history and pathogenic potential of these interesting viruses.


Role of cystic fibrosis transmembrane conductance regulator in patients with chronic sinopulmonary disease.
Previous studies report a high frequency of mutations in the cystic fibrosis (CF) transmembrane conductance regulator gene (CFTR) in patients with idiopathic bronchiectasis. However, most studies have based their findings on preselected patient groups or have performed limited testing for CF transmembrane conductance regulator (CFTR) dysfunction. The objective of our study was to evaluate the prevalence of CFTR gene mutations and/or CFTR-related ion channel abnormalities among subjects with idiopathic chronic sinopulmonary disease and the prevalence of CF or a CFTR-related disorder in this population. We evaluated 72 prospectively enrolled patients from 1995 to 2005 at the Hospital for Sick Children and St. Michael's Hospital with idiopathic chronic sinopulmonary disease for evidence of CFTR-mediated abnormalities. We performed CFTR genotyping and assessed CFTR function using sweat testing and nasal potential difference testing. The results were compared with data from healthy control subjects, CF heterozygotes, and patients with CF. The CFTR functional tests in idiopathic sinopulmonary patients showed a continuous spectrum, ranging from normal to values typically seen in individuals with CF. Forty-eight patients (66%) demonstrated CFTR mutations and/or abnormalities of CFTR function. Twenty-two (31%) fulfilled criteria for a diagnosis of CF and 26 (36%) for a CFTR-related disorder with a strong female preponderance. Functional tests, more than genotyping, were instrumental in establishing a CF diagnosis. Clinical features failed to distinguish subjects with CF from those with CFTR-related or idiopathic disease. The high prevalence of CF and CFTR dysfunction among patients with idiopathic chronic sinopulmonary disease underscores the need for extensive diagnostic evaluation for CF.


Oscillatory multiplexing of population codes for selective communication in the mammalian brain.
Mammalian brains exhibit population oscillations, the structures of which vary in time and space according to behavioural state. A proposed function of these oscillations is to control the flow of signals among anatomically connected networks. However, the nature of neural coding that may support selective communication that depends on oscillations has received relatively little attention. Here, we consider the role of multiplexing, whereby multiple information streams share a common neural substrate. We suggest that multiplexing implemented through periodic modulation of firing-rate population codes enables flexible reconfiguration of effective connectivity among brain areas.


Guideline for the management of chronic asthma in children--2000 update. Allergy Society of South Africa Working Group.
To increase awareness of asthma and diagnose asthma early in children. To make recommendations regarding management of chronic childhood asthma in a country with diverse cultural, socio-economic and educational characteristics. The guideline should be used by health professionals involved in the treatment of asthma at all levels of care. Various management options were considered. Ideal treatment includes use of the new generation inhaled corticosteroids (fluticasone, budesonide), housedust mite intervention for asthma control using impermeable covers for pillows and mattresses, and if needed use of inhaled long-acting beta 2 agonists (LABAs) and leukotriene receptor antagonists (LRAs). Alternative therapeutic approaches for situations where resources are limited include simple housedust mite control measures (e.g. airing mattresses and bedding), avoidance of exposure to passive smoking, use of lower doses of beclomethasone than recommended by other guideline documents and/or sustained-release (SR) theophylline as preventer treatment and use of plastic bottles as cheap spacer devices. The main potential outcomes considered were: to reduce morbidity and mortality by correct diagnosis of asthma, to achieve the best quality of life for the child with asthma, to minimise side-effects from medication and to prevent development of permanently abnormal lung function. Current international guideline documents for diagnosis and management of childhood asthma were evaluated. Clinical studies before 1998 pertaining to the various aspects of management of childhood asthma were reviewed, including controlled studies on the use of inhaled corticosteroids in children with asthma, randomised controlled trials on the use of LRAs and two studies evaluating the efficacy of LABAs. Current data on the anti-inflammatory effects of SR theophylline were also reviewed as well as a randomised controlled trial on the benefits of SR theophylline as adjunct treatment in childhood asthma. The benefit of simple spacer devices, based on well-conducted local studies (published in an international peer-reviewed journal) was also considered. The South African Childhood Asthma Working Group (SACAWG) committee members, appointed by the Allergy Society of South Africa (ALLSA), were selected to represent the interests of health professionals involved in the care of childhood asthma and to co-opt other colleagues with expertise relevant to the guideline. The committee was divided into six task groups headed by a chairperson--each task group had to review critically the previous SACAWG guideline (for deficiencies and obstacles to implementation), review current trends in asthma management (evidence-based where available) and submit proposals and recommendations to their respective chairperson. The chairperson then compiled a report for discussion by the SACAWG executive committee. The executive group convened a meeting to discuss the recommendations and obtain consensus. An editorial board was appointed to compile the final report. Cultural factors, patient preferences, cost, availability and education were considered important. Proper treatment should enable most children with asthma to lead normal or near-normal lives. The guideline could be implementable at all levels of care. The risk of systemic effects due to inhaled corticosteroids should be minimised in children with mild to moderate persistent asthma (risk of systemic effects is more likely at daily beclomethasone doses exceeding 400 micrograms or the equivalent dose of other inhaled corticosteroids). Promotion of simple environmental control measures and use of inhaled beclomethasone and/or SR theophylline should make treatment more widely available and more affordable and improve adherence to treatment. Alternative cheap plastic bottle spacer devices will increase availability and assist with overcoming the problem of incorrect inha


Analysis of joint force and torque for the human and non-human ape foot during bipedal walking with implications for the evolution of the foot.
The feet of apes have a different morphology from those of humans. Until now, it has merely been assumed that the morphology seen in humans must be adaptive for habitual bipedal walking, as the habitual use of bipedal walking is generally regarded as one of the most clear-cut differences between humans and apes. This study asks simply whether human skeletal proportions do actually enhance foot performance during human-like bipedalism, by examining the influence of foot proportions on force, torque and work in the foot joints during simulated bipedal walking. Skeletons of the common chimpanzee, orangutan, gorilla and human were represented by multi-rigid-body models, where the components of the foot make external contact via finite element surfaces. The models were driven by identical joint motion functions collected from experiments on human walking. Simulated contact forces between the ground and the foot were found to be reasonably comparable with measurements made during human walking using pressure- and force-platforms. Joint force, torque and work in the foot were then predicted. Within the limitations of our model, the results show that during simulated human-like bipedal walking, (1) the human and non-human ape (NHA) feet carry similar joint forces, although the distributions of the forces differ; (2) the NHA foot incurs larger joint torques than does the human foot, although the human foot has higher values in the first tarso-metatarsal and metatarso-phalangeal joints, whereas the NHA foot incurs higher values in the lateral digits; and (3) total work in the metatarso-phalangeal joints is lower in the human foot than in the NHA foot. The results indicate that human foot proportions are indeed well suited to performance in normal human walking.


FosB gene products trigger cell proliferation and morphological alteration with an increased expression of a novel processed form of galectin-1 in the rat 3Y1 embryo cell line.
In this study, we established rat 3Y1 embryo cell lines expressing FosB and DeltaFosB as fusion proteins (ER-FosB, ER-DeltaFosB) with the ligand-binding domain of human estrogen receptor (ER). The binding of estrogen to the fusion proteins resulted in their nuclear translocation. After estrogen administration, exponentially growing cells expressing ER-DeltaFosB, and to a lesser extent ER-FosB, underwent morphological alteration from the flat fibroblastic shape to an extended bipolar shape, and ceased proliferating. Such morphological alteration was also induced in quiescent cells expressing ER-DeltaFosB and ER-FosB after one round of cell division triggered by estrogen administration. The cells expressing ER-DeltaFosB changed shape frequently, and the content of F-actin in the cytoplasm detected by binding of Alexa 488-phalloidin significantly decreased after the morphological alteration. By two-dimensional gel electrophoresis analysis of cellular proteins from the cells expressing ER-DeltaFosB, we identified several proteins whose expression either increased or decreased after estrogen administration. Two of these proteins were identified from their amino acid sequences as novel processed form of galectin-1.


[Sclerosing perineurioma: case report and literature review].
Sclerosing perineurioma is a rare benign neoplasm composed exclusively of perineural differentiation cells spread in a dense fibrous stroma. It affects primarily the skin of fingers and that of the palm of the hands. It appears as a hard papule or nodule, normochromic and asymptomatic. A case of sclerosing perineurioma in the left palm of a 16-year-old female is described, with detailed demonstration of clinical aspects, histopathology and literature review published in the English language.


Suppression of Sympathetic Nerve Sprouting by Local Administration of an α-antagonist Around the Dorsal Root Ganglion in a Lumbar Radiculopathy Model.
Animal experimental study with intervention. The purpose of this study was to elucidate whether local administration of an α-antagonist around the dorsal root ganglion (DRG) suppressed sympathetic nerve sprouting, from the acute to the chronic pain development phase, in a lumbar radiculopathy model using immunohistochemical methods. The abnormal sympathetic-somatosensory interaction may underlie some forms of neuropathic pain. There were several reports suggesting α-antagonists are effective to treat neuropathic pain. However, its pathophysiological mechanisms remain obscure. We used 70 male Sprague-Dawley rats. After root constriction (RC), rats received a series of three local injections of the nonselective α-antagonist phentolamine around the DRG for 3 days. There were three groups of rats: those that were injected from the day of surgery and those injected from day 4 and third group injected from day 11. The control rats were subjected to RC but equal-volume normal saline injections, and the naïve rats were not subjected to any surgical procedures. At the 14th postoperative day, the left L5 DRG was removed, embedded in paraffin, and sectioned. Sections were then immunostained with antibodies to tyrosine hydroxylase (TH). To quantify the extent of the presence of sympathetic nerve fibers, we counted TH-immunoreactive fibers in the DRG using a light microscope equipped with a micrometer graticule. We counted the squares of the graticule, which contained TH-immunoreactive fibers for each of five randomly selected sections of the DRG. In the naïve group, TH-immunoreactive fibers were scarce in the DRG. α-antagonist injections from postoperative day 0 and 4 suppressed sympathetic nerve sprouting compared with the control group. α-antagonist injections from postoperative day 11 had no suppressant effect compared with the control group. The α-antagonist administered around the DRG could suppress neural plastic changes in the early phase after nerve injury. N/A.


Mechanistic comparison of blood undergoing laser photocoagulation at 532 and 1,064 nm.
We seek to compare and contrast the mechanisms of blood photocoagulation under 532 and 1,064 nm laser irradiation in vitro in order to better understand the in vivo observations. We also seek to validate a finite element model (FEM) developed to study the thermodynamics of coagulation. We study the photocoagulation of whole blood in vitro at 532 and 1,064 nm using time-domain spectroscopic and optical coherence tomography (OCT)-based imaging techniques. We model the coagulation using an FEM program that includes the latent heat of vaporization (LHV) of water, consideration of the pulse shape of the laser, and the bathochromic shift in the hemoglobin absorption spectrum. We find significant similarities in the spectroscopic, chemical, and structural changes occurring in hemoglobin and in the blood matrix during photocoagulation despite the very large difference in the absorption coefficients. The more uniform temperature profile developed by the deeper-penetrating 1,064 nm laser allows us to resolve the structural phase transition in the red blood cells (going from biconcave disc to spherocyte) and the chemical transition creating met-hemoglobin. We find that the RBC morphology transition happens first, and that the met-Hb transition happens at a much higher temperature ( > 90 degrees C) than is found in slow bath heating. The FEM analysis with the LHV constraint and bathochromic shift predicts accurately the imaging results in both cases, and can be used to show that at 1,064 nm there is the potential for a runaway increase in absorption during the laser pulse. Photothermally mediated processes dominate the in vitro coagulation dynamics in both regimes despite the difference in absorption coefficients. There is a significant risk under 1,064 nm irradiation of vascular lesions in vivo that the dynamic optical properties of blood will cause runaway absorption and heating. This may in turn explain some recent results at this wavelength where full-thickness burns resulted from laser treatment.


Pacing therapy in children with isolated complete atrioventricular block: a retrospective study of pacing system survival and pacing-related complications in a national cohort.
To evaluate pacing system survival and complications to pacemaker (PM) therapy in children with isolated complete atrioventricular block (CAVB). We performed a nationwide retrospective study of children diagnosed before 15 years of age with isolated CAVB and PM treatment. Between 1983 and 2012, 127 patients underwent PM-implantations at 3.2 (0-17) [median (range)] years and were followed for 11 (0.6-19) years. An endocardial or epicardial PM system was implanted in 72 and 55 patients, respectively. A total of 306 pacing leads (76% steroid-eluting) were implanted. Pacing system survival was significantly affected by age, with a higher risk of a new intervention for children aged <1 month at first implantation. Lead survival of the steroid-eluting leads at 5 and 10 years was 90 and 81%, respectively, with no difference between epicardial and endocardial systems. Complications leading to revision of the pacing system occurred in 24% of the patients. Patients aged <1 month at first PM implantation had a five-fold increased risk for a complication to occur. Dividing the cohort according to year of first procedure showed that those who had their first implantation ≥2002 had fewer complications and also lead- and pacing system survival was better in the later cohort. Pacing system survival and complications to PM therapy in young patients with isolated CAVB were significantly affected by age, with low age at PM implantation constituting a risk factor. Endocardial and epicardial pacing systems showed no significant differences in performance.


Heterogeneity of nucleotide frequencies among evolutionary lineages and phylogenetic inference.
A major assumption of many molecular phylogenetic methods is the homogeneity of nucleotide frequencies among taxa, which refers to the equality of the nucleotide frequency bias among species. Changes in nucleotide frequency among different lineages in a data set are thought to lead to erroneous phylogenetic inference because unrelated clades may appear similar because of evolutionarily unrelated similarities in nucleotide frequencies. We tested the effects of the heterogeneity of nucleotide frequency bias on phylogenetic inference, along with the interaction between this heterogeneity and stratified taxon sampling, by means of computer simulations using evolutionary parameters derived from genomic databases. We found that the phylogenetic trees inferred from data sets simulated under realistic, observed levels of heterogeneity for mammalian genes were reconstructed with accuracy comparable to those simulated with homogeneous nucleotide frequencies; the results hold for Neighbor-Joining, minimum evolution, maximum parsimony, and maximum-likelihood methods. The LogDet distance method, specifically designed to deal with heterogeneous nucleotide frequencies, does not perform better than distance methods that assume substitution pattern homogeneity among sequences. In these specific simulation conditions, we did not find a significant interaction between phylogenetic accuracy and substitution pattern heterogeneity among lineages, even when the taxon sampling is increased.


Health inequities in dialysis care: A scoping review.
We aim to look at potential gaps in current dialysis literature on inequities and explore future research that could contribute to more equitable care. Following guidelines from the Joanna Briggs Institute (JBI) and the Preferred Reporting Items for Systematic reviews and Meta Analyses extension for Scoping Reviews (PRISMA-ScR), we conducted a scoping review of health inequities in dialysis. PubMed and Ovid Embase were searched in July 2022 for articles published between 2016 and 2022 that examined at least one of the following NIH defined health inequities: race/ethnicity, sex/gender, LGBTQ+ identity, underserved rural populations, education level, income, and occupation status. Frequencies of each health inequity as well as trends over time of the four most examined inequities were analyzed. In our sample of 69 included studies, gaps were identified in LGBTQ+ identity and patient education. Inequities pertaining to race/ethnicity, sex/gender, underserved rural populations, and income were sufficiently reported. No trends between inequities investigated over time were identified. Our scoping review examined current literature on health inequities pertaining to dialysis and found gaps concerning LGBTQ+ and patients with lower levels of education. To help fill these gaps, and possibly alleviate additional burden to these patients, we recommend cultural competency training for providers and dialysis center staff as well as community-based educational programs to improve dialysis patients' health literacy.


Direct-write piezoelectric polymeric nanogenerator with high energy conversion efficiency.
Nanogenerators capable of converting energy from mechanical sources to electricity with high effective efficiency using low-cost, nonsemiconducting, organic nanomaterials are attractive for many applications, including energy harvesters. In this work, near-field electrospinning is used to direct-write poly(vinylidene fluoride) (PVDF) nanofibers with in situ mechanical stretch and electrical poling characteristics to produce piezoelectric properties. Under mechanical stretching, nanogenerators have shown repeatable and consistent electrical outputs with energy conversion efficiency an order of magnitude higher than those made of PVDF thin films. The early onset of the nonlinear domain wall motions behavior has been identified as one mechanism responsible for the apparent high piezoelectricity in nanofibers, rendering them potentially advantageous for sensing and actuation applications.


The implications of clinical risk factors, CAR index, and compositional changes of immune cells on hyperprogressive disease in non-small cell lung cancer patients receiving immunotherapy.
Immune checkpoint blockades (ICBs) are characterized by a durable clinical response and better tolerability in patients with a variety of advanced solid tumors. However, we not infrequently encounter patients with hyperprogressive disease (HPD) exhibiting paradoxically accelerated tumor growth with poor clinical outcomes. This study aimed to investigate implications of clinical factors and immune cell composition on different tumor responses to immunotherapy in patients with non-small cell lung cancer (NSCLC). This study evaluated 231 NSCLC patients receiving ICBs between January 2014 and May 2018. HPD was defined as a > 2-fold tumor growth kinetics ratio during ICB therapy and time-to-treatment failure of ≤2 months. We analyzed clinical data, imaging studies, periodic serologic indexes, and immune cell compositions in tumors and stromata using multiplex immunohistochemistry. Of 231 NSCLC patients, PR/CR and SD were observed in 50 (21.6%) and 79 (34.2%) patients, respectively and 26 (11.3%) patients met the criteria for HPD. Median overall survival in poor response groups (HPD and non-HPD PD) was extremely shorter than disease-controlled group (SD and PR/CR) (5.5 and 6.1 months vs. 16.2 and 18.3 months, respectively, P = 0.000). In multivariate analysis, HPD were significantly associated with heavy smoker (p = 0.0072), PD-L1 expression ≤1% (p = 0.0355), and number of metastatic site ≥3 (p = 0.0297). Among the serologic indexes including NLR, PLR, CAR, and LDH, only CAR had constantly significant correlations with HPD at the beginning of prior treatment and immunotherapy, and at the 1st tumor assessment. The number of CD4+ effector T cells and CD8+ cytotoxic T cells, and CD8+/PD-1+ tumor-infiltrating lymphocytes (TIL) tended to be smaller, especially in stromata of HPD group. More M2-type macrophages expressing CD14, CD68 and CD163 in the stromal area and markedly fewer CD56+ NK cells in the intratumoral area were observed in HPD group. Our study suggests that not only clinical factors including heavy smoker, very low PD-L1 expression, multiple metastasis, and CAR index, but also fewer CD8+/PD-1+ TIL and more M2 macrophages in the tumor microenvironment are significantly associated with the occurrence of HPD in the patients with advanced/metastatic NSCLC receiving immunotherapy.


Oral mucormycosis in children with leukemia: report of 2 cases.
Mucormycosis is a rare acute opportunistic infection caused by a saprophytic fungus, which belongs to the order Mucorales. This report describes intraoral mucormycosis in 2 children with acute leukemia who were undergoing chemotherapy and had febrile neutropenia. A 7-year-old boy with acute myeloid leukemia and a 9-year-old boy with acute lymphoblastic leukemia were referred to the Department of Pediatric Dentistry at Cukurova University for their intraoral soft tissue lesions, which were diagnosed as mucormycosis by histologic examination. While, for the first case, the lesion was debrided under general anesthesia and medical antifungal therapy was performed, only medical management was done, without any debridement, for the second case. Early recognition of mucormycosis is necessary to limit the spread of infection, which can lead to high morbidity and mortality. Therefore, health practitioners should be familiar with the signs and symptoms of the disease.


How Much Does Lead Shielding during Fluoroscopy Reduce Radiation Dose to Out-of-Field Body Parts?
Fluoroscopy technologists routinely place a lead shield between the x-ray table and the patient's gonads, even if the gonads are not directly in the x-ray field. Internal scatter radiation is the greatest source of radiation to out-of-field body parts, but a shield placed between the patient and the x-ray source will not block internal scatter. Prior nonfluoroscopy research has shown that there is a small reduction in radiation dose when shielding the leakage radiation that penetrates through the collimator shutters. The goal of this in vitro study was to determine if there was any radiation dose reduction when shielding leakage radiation during fluoroscopy. This was an in vitro comparison study of radiation doses using different collimation and shielding strategies during fluoroscopy. Ionization chamber measurements were obtained during fluoroscopy of an acrylic block with and without collimation and shielding. Ionization chamber readings were taken in-field at 0 cm and out-of-field at 7.5, 10, and 12.5 cm from beam center. Collimation reduced 87% of the out-of-field radiation dose, and the remaining measurable dose was because of internal scatter. The radiation dose contribution from leakage radiation was negligible, as there was not any measurable radiation dose difference when shielding leakage radiation, with P value of .48. These results call into question the clinical utility of routinely shielding out-of-field body parts during fluoroscopy.


Surface polymers of the nematode-trapping fungus Arthrobotrys oligospora.
The nematophagous fungus Arthrobotrys oligospora captures nematodes using adhesive polymers present on special hyphae (traps) which form a three-dimensional network. To understand further the adhesion mechanisms, A. oligospora surface polymers were visualized by transmission electron microscopy and characterized by chemical methods. Both traps and hyphae were surrounded by a fibrillar layer of extracellular polymers which stained with ruthenium red. The polymer layer was resistant to most of the chemicals and enzymes tested. However, part of the layer was removed by sonication in a Tris-buffer or by extraction in a chaotropic salt solution (LiCl), and the structure of the polymers was modified by treatment with Pronase E. Chemical analysis showed that the crude extracts of surface polymers removed by sonication or LiCl solution contained neutral sugars, uronic acids and proteins. Gel chromatography of the extracts revealed that the major carbohydrate-containing polymer(s) had a molecular mass of at least 100 kDa, containing neutral sugars (75% by weight, including glucose, mannose and galactose), uronic acids (6%) and proteins (19%). There was more polymer in mycelium containing trap-bearing cells than in vegetative hyphae. SDS-PAGE of the extracted polymers showed that the trap-forming cells contained at least one protein, with a molecular mass of approx. 32 kDa, not present on vegetative hyphae. Examining the capture of nematodes by traps of A. oligospora in which the layer of surface polymers was modified, or removed by chemical or enzymic treatments, showed that both proteins and carbohydrate surface polymers were involved in the adhesion process.


Geo-Spatial Economic Assessment of the Potential Development of Bioenergy Combined with Direct Air Carbon Capture (BEDAC) in the USA.
This study presents a geo-spatial and economic framework to localize future bioenergy power plants combined with direct air capture (BEDAC). This framework is applied to two regions in the USA to assess the optimal use of forest biomass and in situ carbon sequestration under three specific short-term sequestration targets. Results show that there are many locations that have both the necessary biomass and geology required for storage. The Southeast has greater potential for forestry biomass due to both the rate of growth and forested areas, but the sequestration potential is mostly limited to a CO2 solution in saline aquifers. The Pacific Northwest has more sequestration potential than the Southeast given the location of managed forests and storage sites in carbonate mineralization in bedrock. The two combined regions have a total potential sequestration of 9.3 GtCO2 for the next 20 years that can be achieved under an implicit carbon value of $249/tCO2.


Bioengineered hyaluronic acid elicited a nonantigenic T cell activation: implications from cosmetic medicine and surgery to nanomedicine.
Hyaluronan is known to act as a filling material of extracellular matrices and as an adhesive substrate for cellular migration. Consequently, it is widely used in aesthetic medicine and surgery, and it would be expected to be used in nanomedicine. Previous clinical case reports associated hyaluronic acid implants to delayed immune-mediated adverse effects. A series of experiments to evaluate immune cell activation supported by this dermal filler and nanomedical biomaterial were performed. The study comprised a total of 12 individuals. Four healthy individuals, none with cosmetically injected dermal filler, were considered as control. Five individuals carried injections of hyaluronic acid dermal filler. Three individuals carried injections of hyaluronic acid dermal filler and presented delayed adverse effects related to the dermal filler. Hyaluronic acid-stimulated peripheral blood mononuclear cells (PBMC) produced low levels of pro-inflammatory cytokines. Phytohemagglutinine (PHA)-stimulated PBMC from patients with hyaluronic implants presenting adverse effects showed a slight increase in the production of interferon (IFN)-gamma and higher expression of CD25, CD69, or CD71. In conclusion, hyaluronic acid administration elicited a laboratory evidence of immune cell activation. Production of low levels of proinflammatory cytokines in vitro could be an observation for low-grade inflammation in vivo resulting in T cell activation.


Hepatitis B virus large surface protein is not secreted but is immunogenic when selectively expressed by recombinant vaccinia virus.
The envelope region of the hepatitis B virus (HBV) genome contains an open reading frame that begins upstream of the major surface protein gene. The two minor proteins that are initiated within this pre-s segment are immunogenic and may be involved in virus attachment to hepatocytes. We have constructed a recombinant vaccinia virus that contains the predicted coding segment for the large surface protein (LS) under control of a vaccinia virus that contains the predicted coding segment for the large surface protein (LS) under control of a vaccinia virus promoter. Cells infected with the recombinant virus synthesized HBV polypeptides of 39 and 42 kilodaltons, corresponding to the unglycosylated and glycosylated forms of LS, respectively. The presence of pre-s epitopes in the 39- and 42-kilodalton polypeptides was demonstrated by binding of antibody prepared against a synthetic peptide. Synthesis of the 42-kilodalton species was specifically inhibited by tunicamycin, suggesting that it is N-glycosylated. Despite apparent glycosylation, LS was not secreted into the medium of infected cells. Nevertheless, rabbits vaccinated with the purified recombinant virus made antibodies that recognized s and pre-s epitopes. Antibody to the NH2 terminus of LS appeared before or simultaneously with antibody that bound to the major surface protein. The additional immunogenicity provided by expression of LS may be advantageous for the development of an HBV vaccine.


Galectins in Protozoan Parasitic Diseases: Potential Applications in Diagnostics and Therapeutics.
Neglected tropical diseases (NTDs) constitute a group of diseases that generally develop in tropical or subtropical climatic conditions and are related to poverty. Within the spectrum of NTDs, diseases caused by protozoa such as malaria, Chagas disease, and leishmaniasis exhibit elevated mortality rates, thereby constituting a substantial public health concern. Beyond their protozoan etiology, these NTDs share other similarities, such as the challenge of control and the lack of affordable, safe, and effective drugs. In view of the above, the need to explore novel diagnostic predictors and therapeutic targets for the treatment of these parasitic diseases is evident. In this context, galectins are attractive because they are a set of lectins bound to β-galactosides that play key roles in a variety of cellular processes, including host-parasite interaction such as adhesion and entry of parasites into the host cells, and participate in antiparasitic immunity in either a stimulatory or inhibitory manner, especially the galectins-1, -2, -3, and -9. These functions bestow upon galectins significant therapeutic prospects in the context of managing and diagnosing NTDs. Thus, the present review aims to elucidate the potential role of galectins in the diagnosis and treatment of malaria, leishmaniasis, and Chagas disease.


Painful jerk test: a predictor of success in nonoperative treatment of posteroinferior instability of the shoulder.
The jerk test has been used as a diagnostic test of the posteroinferior instability of the shoulder. Pain may or may not be associated with posterior clunking during the jerk test. To evaluate the presence or absence of pain with the jerk test as a predictor of the success of nonoperative treatment for posteroinferior instability of the shoulder and to identify the pathologic lesion responsible for the pain in the jerk test. Retrospective review of prospectively collected data. Eighty-one patients (89 shoulders) who had posteroinferior instability with a positive posterior clunk in their shoulders during the jerk test were nonoperatively treated. The patients were divided into 2 groups with respect to the presence of pain in the jerk test: the painless jerk group (54 shoulders) and the painful jerk group (35 shoulders). Response to the nonoperative treatment was evaluated after at least a 6-month rehabilitation program. Patients who did not respond to the rehabilitation underwent arthroscopic examination to identify any pathologic lesions. The painful jerk group had a higher failure rate with nonoperative treatment (P < .001). In the painless jerk group, 50 shoulders (93%) responded to the rehabilitation program after a mean of 4 months. Four shoulders (7%) were unresponsive to the rehabilitation. In the painful jerk group, 5 shoulders (16%) were successful with the rehabilitation, whereas the other 30 shoulders (84%) failed. All 34 shoulders that were unresponsive to the rehabilitation had a variable degree of posteroinferior labral lesions. The jerk test is a hallmark for predicting the prognosis of nonoperative treatment for posteroinferior instability. Shoulders with symptomatic posteroinferior instability and a painful jerk test have posteroinferior labral lesions.


Inflammatory mediators and modulators released in organ culture from rabbit skin lesions produced in vivo by sulfur mustard. I. Quantitative histopathology; PMN, basophil, and mononuclear cell survival; and unbound (serum) protein content.
When applied topically to the skin of rabbits in vivo, sulfur mustard (SM), the vesicant used in World War I, produced a slowly developing inflammatory response, which peaked in size at 1 and 2 days, ulcerated within 3 days, and reepithelialized by 10 days. Histologically, basophils and polymorphonuclear leukocytes (PMNs) were common in both early and late lesions, and the crust over the ulcers was composed of dead epidermal cells, fibrin, and large numbers of PMNs. Healing occurred under the crust by migration of epidermal cells from the margins of the lesions and from the hair follicles. In organ culture, the lesion explants survived well, and reepithelialization even took place. Their excellent survival enabled us to compare the life spans of the infiltrating leukocytes within an inflammatory site. PMNs within the explants began disappearing during the first day of culture, and almost all had disappeared by 3 days. In contrast, over half of the basophils and the mononuclear cells within the explants were still present after 3 days of culture. The 1-, 2-, 3-, 6-, and 10-day (1.0-sq cm) SM lesion biopsies showed a 30-45% increase in weight (when compared with normal skin), presumably due to the extravasation of serum proteins and the fluids retained by them. When the biopsies were organ-cultured for 3 days, the 1-, 2-, and 3-day lesions lost weight, and the 6- and 10-day lesions (and normal skin) gained weight. These weight differences were not due to the amount of unbound protein extractable into the culture fluids, because both the early lesions and the late lesions contained about the same amount of unbound protein. The most likely explanation for these weight differences is that the newly formed ground substances of late lesions absorbed culture fluid, because the ground substance had changed from the sol state of acute inflammation (in which it was extractable) back to its normal gel state (in which it was not extractable). The unbound protein extractable into the culture fluids was mostly of serum origin. This protein averaged 1.9 mg for 1.0 sq cm normal skin explants (with a mean weight of 215 mg), and 6.4 mg for 1-day SM lesions (with a mean weight of 313 mg). Because rabbit serum contains about 60 mg protein/ml, these figures indicate that normal skin contained about 15% (unbound) serum by weight.(ABSTRACT TRUNCATED AT 400 WORDS)


Increased von Willebrand factor levels in patients with systemic lupus erythematosus reflect inflammation rather than increased propensity for platelet activation.
von Willebrand factor (VWF) is involved in platelet plug formation and protein transport. Increased VWF levels in systemic lupus erythematous (SLE) are considered risk factors for vascular events. VWF protein levels, however, do not accurately reflect its platelet-aggregating function, which has not been examined in SLE. Cross-sectional study with clinical and laboratory data obtained in patients with SLE (n=92) from a regional lupus registry. VWF function was determined by ristocetin-induced platelet aggregation (VWF ristocetin cofactor, VWF:RCo) and VWF levels by turbidimetric assay (VWF antigen, VWF:Ag). The platelet-aggregating activity per VWF unit was estimated by the VWF RCo/Ag ratio. Healthy controls served as comparators and associations were evaluated by non-parametric methods. VWF:Ag (142% vs 107%, p=0.001) and VWF:RCo levels (123% vs 78%, p<0.041) were increased in patients with SLE, but VWF RCo/Ag ratio was similar as in controls (0.83 vs 0.82, p=0.8). VWF:Ag levels were higher in patients experiencing serositis but unrelated to other manifestations, thrombotic disease, Systemic Lupus Erythematous Disease Activity Index 2000 or Systemic Lupus International Collaborative Clinics-Damage Index. VWF:Ag levels correlated significantly with VWF:RCo levels (Rs 0.8, p<0.001), erythrocyte sedimentation rate (ESR) (Rs 0.32, p<0.01), anti-dsDNA Ab (Rs 0.27, p<0.01), total IgG (Rs 0.33 p<0.01), fibrinogen (Rs 0.28, p<0.01) and ceruloplasmin (Rs 0.367, p<0.01) levels. VWF:RCo levels were not related to clinical findings but were correlated with ESR, anti-dsDNA and transferrin levels. No serological associations existed for VWF RCo/Ag ratio (all p>0.2). In this SLE cohort, VWF:Ag behaved similarly to acute-phase reactants, but VWF:Ag increases were not matched by increases in functional activity per unit of VWF. Thus, more VWF did not increase the propensity for platelet aggregation in SLE.


[Spectroscopic study of the mechanism of cholesterol interaction with apolipoproteins: a model of cholesterol-synthetic apolipoprotein A-I fragment].
To investigate the mechanism of cholesterol binding to apolipoproteins, a fragment of human apolipoprotein A-I involving its amino acid residues 144-164 has been synthesized. The interaction of this peptide (both native and having modified functional groups) with cholesterol in a water-alcohol medium has been studied, using fluorescence and circular dichroism techniques as well as NMR NOE spectroscopy. It has been found that the oligopeptide is able to form complexes with one and two cholesterol molecules, the association constant being as high as 10(8) M-1. The interaction involves hydrogen bonds formed by the cholesterol OH-group as well as hydrophobic interaction of the nonpolar groups of cholesterol and the peptide. The latter requires a specific conformation, i.e., the formation in the peptide molecule of a "cavity" at the expense of ionic coupling between the carboxylate groups in Asp or Glu side chains and the guanidinium groups of the protein. At pH 6.3, the OH-group of cholesterol becomes involved in the H-bond system which includes a COOH-group of Asp and two imidazole groups of His, one of which is in a neutral and the other one in a protonated from.


Estrogens and progesterone as neuroprotectants: what animal models teach us.
Estradiol and progesterone are two steroid hormones that target a variety of organ systems, including the heart, the bone and the brain. With respect to the latter, a large volume of basic science studies support the neuroprotective role of estradiol and/or progesterone. In fact, the results of such studies prompted the assessment of these hormones as protective agents against such disorders as Alzheimer's disease, stroke and traumatic brain injury. Interestingly, results from the Women's Health Initiative (WHI) yielded results that appeared to be inconsistent with the data derived from in vitro and in vivo models. However, we argue that the results from the basic science studies were not inconsistent with the clinical trials, but rather, are consistent with, and may even have predicted, the results from the WHI. To illustrate this point, we review here certain in vivo paradigms that have been used to assess the protective effects of estrogens and progesterone, and describe how the results from these animal models point to the importance of the type of hormone, the age of the subjects and the method of hormone administration, in determining whether or not hormones are neuroprotective.


Etiology of immune stromal (interstitial) keratitis.
We compared the etiologies of immune stromal keratitis (ISK), also known as interstitial keratitis (IK), in a recent group of patients with active and inactive ISK. We reviewed the charts of 97 patients seen in the cornea clinic at the University of Minnesota from 1985 through 1994. Fifty-five patients were classified as having active ISK, defined by stromal inflammation without ulceration within 1 year of presentation. Forty-two patients were identified as having inactive ISK, defined by evidence of past stromal inflammation including stromal scarring, stromal thinning, ghost vessels, and reduplication of Descemet's membrane without active inflammation for the 1 year before presentation. We determined the etiology of the ISK by careful review of the patient's ocular examination, as well as medical and laboratory workup. Patients were labeled with the diagnosis of idiopathic ISK if no identifiable etiology was found. Herpes simplex virus (HSV) accounted for 71.4% of unilateral active ISK. Idiopathic accounted for 14.3%, and varicella-zoster virus accounted for 8.6% in this group. HSV was the etiologic factor of 50.0% of inactive unilateral cases, whereas 33.3% were idiopathic. Sixty percent of cases of bilateral, active ISK were from idiopathic causes. Syphilis was the cause of 48.5% of bilateral inactive cases. In this group, 33.3% were from idiopathic causes. Although syphilis has been recognized for many years as the cause of 90% of cases of ISK, this is no longer true. We demonstrated that active ISK is most commonly caused by HSV or is idiopathic and that, although syphilis is the leading cause of inactive, bilateral ISK, it is responsible for only 18.6% of total cases.


Lissencephaly-pachygyria spectrum in a North Indian boy with Wolcott-Rallison syndrome due to homozygous deletion of exon 1 in the EIF2AK3 gene.
Wolcott-Rallison syndrome (WRS) is a rare autosomal recessive disorder characterized by neonatal diabetes mellitus (NDM), epiphyseal dysplasia, and hepatic and renal dysfunction. Although neuro-psychological features are common in patients with WRS, malformations of cortical development (MCDs) are rarely reported. A 3-month-old boy, born to non-consanguineous parents, presented with right focal seizures since two months of age and recently detected diabetes mellitus. He also had a small head and lissencephaly-pachygyria spectrum on brain imaging. Genetic testing confirmed the diagnosis of WRS by identifying a biallelic homozygous deletion of exon 1 in the EIF2AK3 gene. The child achieved reasonable glycemic control on the basal-bolus insulin regimen. Presentation of WRS may occur with neurological manifestations such as lissencephaly-pachygyria spectrum. Early confirmation of the genetic diagnosis of WRS by screening for pathogenic variants in the EIF2AK3 gene is important in children with NDM and associated syndromic features. Establishing the diagnosis of WRS helps in predicting the development of subsequent clinical features, guides management, and may improve patient outcomes.


New Trends in the Treatment of Schizophrenia.
This article are to describe current trends in the treatment of schizophrenia and the most interesting new approaches to optimizing outcome and fostering the development of new schizophrenia treatments. Increasing utilization of diverse types of atypical antipsychotic drugs (AAPDs), e.g. clozapine- type serotonin (5-HT)2A and weak dopamine (DA) D2 antagonist, amisulpride, a D2/D3/5-HT7 antagonist, and cariprazine, a D3 partial agonist with additional neurotransmitter targets, is occurring as their advantages in efficacy, especially for cognitive impairment and mood symptoms, and side effects are becoming appreciated. Typical APDs, e.g. haloperidol, are diminishing in favor because of their EPS, especially, tardive dyskinesia (T D) and appreciation that reducing D2 receptor stimulation is not the only means to treat psychosis. Some of the mechanisms inherent in various AAPDs, e.g. 5-HT2A inverse agonism, and D3 receptor partial agonism, are now recognized as effective treatments for psychosis. A new focus on treating the cognitive impairment associated with schizophrenia (CIAS) has emerged via mechanisms such as stimulation of acetyldraline receptor with muscarinic and nicotinic receptor agonists, but demonstrating their efficacy in trials is proving elusive. Pharmacogenetic strategies which may lead to personalized treatment of schizophrenia are emerging but have not yet succeeded in being widely reimbursable. Transcranial stimulation and cognitive enhancement therapy are more common but more evidence for their efficacy is needed. The heterogeneity of the pathophysiology of the various domains of schizophrenia requires a diversity of treatments that are best met by the expert use of AAPDs at the current time. Pharmacogenetic efforts are consistent with new evidence that multiple genes are involved in the risk for schizophrenia and the effectiveness of AAPDs.


Analysis of Butyrophilin-Mediated Activation of γδ T Cells from Human Spleen.
There is considerable interest in therapeutically engaging human γδ T cells. However, due to the unique TCRs of human γδ T cells, studies from animal models have provided limited directly applicable insights, and human γδ T cells from key immunological tissues remain poorly characterized. In this study, we investigated γδ T cells from human spleen tissue. Compared to blood, where Vδ2+Vγ9+ T cells are the dominant subset, splenic γδ T cells included a variety of TCR types, with Vδ1+ T cells typically being the most frequent. Intracellular cytokine staining revealed that IFN-γ was produced by a substantial fraction of splenic γδ T cells, IL-17A by a small fraction, and IL-4 was minimal. Primary splenic γδ T cells frequently expressed NKG2D (NK group 2 member D) and CD16, whereas expression of DNAM-1 (DNAX accessory molecule 1) , CD28, PD-1, TIGIT, and CD94 varied according to subset, and there was generally little expression of natural cytotoxicity receptors, TIM-3, LAG-3, or killer Ig-like receptors. In vitro expansion was associated with marked changes in expression of these activating and inhibitory receptors. Analysis of functional responses of spleen-derived Vδ2+Vγ9+, Vδ1+Vγ9+, and Vδ1+Vγ9- T cell lines to recombinant butyrophilin BTN2A1 and BTN3A1 demonstrated that both Vδ2+Vγ9+ and Vδ1+Vγ9+ T cells were capable of responding to the extracellular domain of BTN2A1, whereas the addition of BTN3A1 only markedly enhanced the responses of Vδ2+Vγ9+ T cells. Conversely, Vδ1+Vγ9+ T cells appeared more responsive than Vδ2+Vγ9+ T cells to TCR-independent NKG2D stimulation. Thus, despite shared recognition of BTN2A1, differential effects of BTN3A1 and coreceptors may segregate target cell responses of Vδ2+Vγ9+ and Vδ1+Vγ9+ T cells.


Analog integrated circuits for the Lotka-Volterra competitive neural networks.
A subthreshold MOS integrated circuit (IC) is designed and fabricated for implementing a competitive neural network of the Lotka-Volterra (LV) type which is derived from conventional membrane dynamics of neurons and is used for the selection of external inputs. The steady-state solutions to the LV equation can be classified into three types, each of which represents qualitatively different selection behavior. Among the solutions, the winners-share-all (WSA) solution in which a certain number of neurons remain activated in steady states is particularly useful owing to robustness in the selection of inputs from a noisy environment. The measured results of the fabricated LV IC's agree well with the theoretical prediction as long as the influence of device mismatches is small. Furthermore, results of extensive circuit simulations prove that the large-scale LV circuit producing the WSA solution does exhibit a reliable selection compared with winner-take-all circuits, in the possible presence of device mismatches.


Complex genetic predisposition to cancer in an extended HNPCC family with an ancestral hMLH1 mutation.
Hereditary non-polyposis colorectal cancer (HNPCC) is characterised by a genetic predisposition to develop colorectal cancer at an early age and, to a lesser degree, cancer of the endometrium, ovaries, urinary tract, and organs of the gastrointestinal tract other than the colon. In the majority of families the disease is linked to mutations in one of the two mismatch repair genes, hMSH2 or hMLH1. We have found a novel hMLH1 nonsense mutation in a Swiss family with Lynch syndrome, which has been transmitted through at least nine generations. A different tumour spectrum of neoplasms of the skin, soft palate, breast, duodenum, and pancreas was observed in three branches of this family, where there was a virtual absence of colonic tumours. The hMLH1 mutation could not be detected in members of these branches suggesting that at least a second genetic defect predisposing to cancer is segregating in part of the kindred.


Mean heart dose variation over a course of breath-holding breast cancer radiotherapy.
The purpose of the work was to estimate the dose received by the heart throughout a course of breath-holding breast radiotherapy. 113 cone-beam CT (CBCT) scans were acquired for 20 patients treated within the HeartSpare 1A study, in which both an active breathing control (ABC) device and a voluntary breath-hold (VBH) method were used. Predicted mean heart doses were obtained from treatment plans. CBCT scans were imported into a treatment planning system, heart outlines defined, images registered to the CT planning scan and mean heart dose recorded. Two observers outlined two cases three times each to assess interobserver and intraobserver variation. There were no statistically significant differences between ABC and VBH heart dose data from CT planning scans, or in the CBCT-based estimates of heart dose, and no effect from the order of the breath-hold method. Variation in mean heart dose per fraction over the three imaged fractions was <6 cGy without setup correction, decreasing to 3.3 cGy with setup correction. If scaled to 15 fractions, all differences between predicted and estimated mean heart doses were <0.5 Gy and in 80% of cases, they were <0.25 Gy. Variation in mean heart dose was at an acceptable level over the duration of breath-holding radiotherapy and was well predicted by the planning system. Advances in knowledge: Mean heart dose was not adversely affected by fraction-to-fraction variations throughout a course of heart-sparing radiotherapy using two well-established breath-holding methods.


Rapid and Modular Assembly of Click Substrates To Assay Enzyme Activity in the Newborn Screening of Lysosomal Storage Disorders.
Synthetic substrates play a pivotal role in the development of enzyme assays for medical diagnostics. However, the preparation of these chemical tools often requires multistep synthetic procedures complicating structural optimization and limiting versatility. In particular, substrates for enzyme assays based on tandem mass spectrometry need to be designed and optimized to fulfill the requirements to finally enable the development of robust diagnostic assays. In addition, isotope-labeled standards need to be prepared to facilitate accurate quantification of enzyme assay products. Here we report the development of a building block strategy for rapid and modular assembly of enzyme substrates using click chemistry as a key step. These click substrates are made up of a sugar moiety as enzyme responsive unit, a linker that can easily be isotope-labeled for the synthesis of internal standards, and a modifier compound that can readily be exchanged for structural optimization and analytical/diagnostic tuning. Moreover, the building block assembly eliminates the need for extensive optimization of different glycosylation reactions as it enables the divergent synthesis of substrates using a clickable enzyme responsive unit. The outlined strategy has been applied to obtain a series of synthetic α-l-iduronates and sulfated β-d-galactosides as substrates for assaying α-l-iduronidase and N-acetylgalactosamine-6-sulfate sulfatase, enzymes related to the lysosomal storage disorders mucopolysaccharidosis type I and type IVa, respectively. Selected click substrates were finally shown to be suitable to assay enzyme activities in dried blood spot samples from affected patients and random newborns.


An empirical analysis of primary and secondary pharmaceutical patents in Chile.
We analyze the patent filing strategies of foreign pharmaceutical companies in Chile distinguishing between "primary" (active ingredient) and "secondary" patents (patents on modified compounds, formulations, dosages, particular medical uses, etc.). There is prior evidence that secondary patents are used by pharmaceutical originator companies in the U.S. and Europe to extend patent protection on drugs in length and breadth. Using a novel dataset that comprises all drugs registered in Chile between 1991 and 2010 as well as the corresponding patents and trademarks, we find evidence that foreign originator companies pursue similar strategies in Chile. We find a primary to secondary patents ratio of 1:4 at the drug-level, which is comparable to the available evidence for Europe; most secondary patents are filed over several years following the original primary patent and after the protected active ingredient has obtained market approval in Chile. This points toward effective patent term extensions through secondary patents. Secondary patents dominate "older" therapeutic classes like anti-ulcer and anti-depressants. In contrast, newer areas like anti-virals and anti-neoplastics (anti-cancer) have a much larger share of primary patents.


Does fasting during Ramadan increase the risk of the development of sialadenitis?
Ramadan is a month within the Islamic lunar calendar when Muslims are required to fast (abstain from food and drink) during the daytime (from sunrise to sunset) for the entire month. Due to the established connection between fasting and dehydration and acute sialadenitis, the aim of this study is to determine if there is a higher frequency of sialadenitis among the Muslim population during Ramadan than during other months of the year. We conducted a retrospective study using the medical records of 120 Muslim patients admitted to the emergency room (ER) and diagnosed with acute sialadenitis over a 5-year period at the Baruch Padeh Medical Center, Poriya, and St. Vincent de Paul (French) Hospital, Nazareth, both located in Israel. The study group were Muslim patients, with the aforementioned diagnosis, admitted during Ramadan, while the control group included patients diagnosed with sialadenitis during the rest of the year. We analyzed overall admission frequency as well as descriptive and diagnostic data, including age, sex, gland involved and several blood test results. During the month of Ramadan, the admission of Muslims with a diagnosis of acute sialadenitis was more than double that during the other months of the year - a difference that was found to be statistically significant (p = 0.001). Additionally, we found that Ramadan sialadenitis patients had significantly higher leukocyte numbers at admission (p = 0.0085) and, importantly, a significantly higher level of dehydration (blood urea nitrogen (BUN)/creatinine ratio) than non-Ramadan sialadenitis patients (p = 0.0001). There is evidence that fasting in Ramadan may increase the risk for the development of acute sialadenitis. Our results suggest that this may be the result of dehydration.


The effect of seeing a family physician on the level of glycosylated hemoglobin (HbA1c) in type 2 Diabetes Mellitus patients.
Glycosylated hemoglobin (HbA1c) in diabetic patients reflects the average blood glucose level, and will not be affected by variability in blood glucose in short time. Regular care of patients by medical staff could effectively control glycemic situation. The aim of this study was to assess the effect of medical care by general physicians on glycemic control by measuring of HbA1c. In order to assess the effectiveness of National program for diabetes control and prevention in Iran, we compare HbA1c, Fasting blood glucose (FBS), systolic and diastolic blood pressure in two groups of diabetic patients diagnosed in this program. The first group consisted of patients who received at least four visits by General Physician (GP) during one year after the diagnosis, and second group were patients who did not visited by GPs or received 1-3 visits. After one year, 24.1% of patients did not receive any care, while 57.9% examined at least once a year. Among visited patients, 23.5% received 1-3 times medical care and 23.5% received four or more visits. HbA1c was significantly lowered in patients with appropriate care (four and more) compared with the non cared patients and patients with less than four cares. Appropriate number of visits for each patient by GPs is an effective glycemic control in diabetic patients. Although this study provides a framework for medical care in diabetes, how to take care of these patients depends on specific situation of each patient and should be determined for each of them individually.


Physiological and proteomic responses of different willow clones (Salix fragilis x alba) exposed to dredged sediment contaminated by heavy metals.
High biomass producing species are considered as tools for remediation of contaminated soils. Willows (Salix spp.) are prominent study subjects in this regard. In this study, different willow clones (Salix fragilis x alba) were planted on heavy-metal polluted dredging sludge. A first objective was assessment of the biomass production for these clones. Using a Gupta statistic, four clones were identified as high biomass producers (HBP). For comparison, a group of four clones with lowest biomass production were selected (LBP). A second objective was to compare metal uptake as well as the physiological and proteomic responses of these two groups. All these complementary data's allow us to have a better picture of the health of the clones that would be used in phytoremediation programs. Cd, Zn, and Ni total uptake was higher in the HBPs but Pb total uptake was higher in LBPs. Our proteomic and physiological results showed that the LBPs were able to maintain cellular activity as much as the HBPs although the oxidative stress response was more pronounced in the LBPs. This could be due to the high Pb content found in this group although a combined effect of the other metals cannot be excluded.


[Indicators of nonspecific immunity in patients with hereditary hemochromatosis].
Parameters of nonspecific defence--complement protein function, circulating immune complex level, neutrophil phagocytic activity, completeness of the phagocytic reaction, C3c level, were evaluated in 162 carriers of hemochromatosis gene (114 homozygotes and 48 heterozygotes with respect to hereditary hemochromatosis) aged from 7 to 64 years. The analysis of the results obtained has permitted a conclusion that the suppression of the complement system function, according to the classic or alternative type, is associated with the disease pathogenesis--hyperferremia, and is caused by the damage of the immunocompetent organs and cells synthesizing individual proteins of the complement, as well as by infectious complications leading to hypocomplementemia with respect to separate components.


Diagnostic vitrectomy and uveitis.
When properly used, diagnostic vitrectomy can be an extremely helpful procedure for establishing the etiology of ocular inflammation. New instruments have enabled more expedient and safer surgery. Analytical assays continue to improve in quality and quantity as our understanding of ocular diseases grows. Though no single assay is completely sensitive, a combination of assays may improve the yield and accuracy of diagnostic vitreous biopsy (Table 5). Keeping abreast of these advances may aid ophthalmologists in obtaining earlier diagnosis and better outcomes for their patients.


Breast and cervical cancer screening among women with physical disabilities.
This article reports findings from the National Study of Women with Physical Disabilities about rates of screening for breast and cervical cancer and factors associated with regular screening in a large sample of women with a variety of physical disabilities and a comparison group of women without disabilities. Case-comparison study using written survey. Data were analyzed using measures of central tendency, chi 2 analysis, logistic regression, and risk using odds ratios. General community. A total of 843 women, 450 with disabilities and 393 of their able-bodied friends, aged 18 to 65, who completed the written questionnaire. The most common primary disability type was spinal cord injury (26%), followed by polio (18%), neuromuscular disorders (12%), cerebral palsy (10%), multiple sclerosis (10%), and joint and connective tissue disorders (8%). Twenty-two percent had severe functional limitations, 52% had moderate disabilities, and 26% had mild disabilities. Outcomes were measured in terms of frequency of pelvic exams and mammograms. Women with disabilities tend to be less likely than women without disabilities to receive pelvic exams on a regular basis, and women with more severe functional limitations are significantly less likely to do so. No significant difference was found between women with and without disabilities, regardless of severity of functional limitation, in receiving mammograms within the past 2 years. Perceived control emerged as a significant enhancement factor for mammograms and marginally for pelvic exams. Severity of disability was a significant risk factor for noncompliance with recommended pelvic exams, but not mammograms. Race was a significant risk factor for not receiving pelvic exams, but not mammograms. Household income and age did not reach significance as risk factors in either analysis. Women with physical disabilities are at a higher risk for delayed diagnosis of breast and cervical cancer, primarily for reasons of environmental, attitudinal, and information barriers. Future research should focus on the subpopulations that were not surveyed adequately in this study, women with disabilities who have low levels of education or income, or who are of minority status.


Absorbing one-dimensional planar photonic crystal for amorphous silicon solar cell.
We report on the absorption of a 100nm thick hydrogenated amorphous silicon layer patterned as a planar photonic crystal (PPC), using laser holography and reactive ion etching. Compared to an unpatterned layer, electromagnetic simulation and optical measurements both show a 50% increase of the absorption over the 0.38-0.75micron spectral range, in the case of a one-dimensional PPC. Such absorbing photonic crystals, combined with transparent and conductive layers, may be at the basis of new photovoltaic solar cells.


Tele-ICU "myth busters".
Tele-intensive care unit (ICU) technology has been proven to bridge the gap between available resources and quality care for many health care systems across the country. Tele-ICUs allow the standardization of care and provide a second set of eyes traditionally not available in the ICU. A growing body of literature supports the use of tele-ICUs based on improved outcomes and reduction in errors. To date, the literature has not effectively outlined the limitations of this technology related to response to changes in patient care, interventions, and interaction with the care team. This information can potentially have a profound impact on service expectations. Some misconceptions about tele-ICU technology include the following: tele-ICU is "watching" 24 hours a day, 7 days a week; tele-ICU is a telemetry unit; tele-ICU is a stand-alone crisis intervention tool; tele-ICU decreases staffing at the bedside; tele-ICU clinical roles are clearly defined and understood; and tele-ICUs are not cost-effective to operate. This article outlines the purpose of tele-ICU technology, reviews outcomes, and "busts" myths about tele-ICU technology.