Synthesis and characterization of tyramine-derivatized (1-->4)-linked alpha-D-oligogalacturonides.
The reducing end C-1 of (1-->4)-linked alpha-D-oligogalacturonides (oligogalacturonides), with degrees of polymerization (dp) 3 and 13, was coupled to tyramine via reductive amination in the presence of sodium cyanoborohydride. These derivatives were purified in milligram quantities and structurally characterized. Tyramination of trigalacturonic acid proceeded to completion. The yield of apparently homogeneous tyraminated trigalacturonic acid after desalting was 35%. Derivatization of tridecagalacturonide with tyramine was incomplete. The tyraminated tridecagalacturonide was purified to apparent homogeneity using semipreparative high-performance anion-exchange chromatography (HPAEC) with a yield of 30%. The structures of the derivatized oligogalacturonides were established by 1H NMR spectroscopy and electrospray mass spectrometry.


Chitinase production by Bacillus thuringiensis and Bacillus licheniformis: their potential in antifungal biocontrol.
Thirty bacterial strains were isolated from the rhizosphere of plants collected from Egypt and screened for production of chitinase enzymes. Bacillus thuringiensis NM101-19 and Bacillus licheniformis NM120-17 had the highest chitinolytic activities amongst those investigated. The production of chitinase by B. thuringiensis and B. licheniformis was optimized using colloidal chitin medium amended with 1.5% colloidal chitin, with casein as a nitrogen source, at 30°C after five days of incubation. An enhancement of chitinase production by the two species was observed by addition of sugar substances and dried fungal mats to the colloidal chitin media. The optimal conditions for chitinase activity by B. thuringiensis and B. licheniformis were at 40°C, pH 7.0 and pH 8.0, respectively. Na(+), Mg(2+), Cu(2+), and Ca(2+) caused enhancement of enzyme activities whereas they were markedly inhibited by Zn(2+), Hg(2+), and Ag(+). In vitro, B. thuringiensis and B. licheniformis chitinases had potential for cell wall lysis of many phytopathogenic fungi tested. The addition of B. thuringiensis chitinase was more effective than that of B. licheniformis in increasing the germination of soybean seeds infected with various phytopathogenic fungi.


Emerging Spotted Fever Rickettsioses in the United States.
Spotted fever rickettsioses are important causes of emerging infectious disease in the United States and elsewhere. Rocky Mountain Spotted Fever, caused by R. rickettsii causes a febrile, acute illness in dogs. Because it circulates in peripheral blood in low copy number and because of the acute nature of the disease, dogs may test PCR and seronegative at the time of presentation. Therefore, therapy with doxycycline must be initiated and continued based on the clinician's index of suspicion. Combining PCR with serologic testing, repeat testing of the same pre-antimicrobial blood sample, and testing convalescent samples for seroconversion facilitates diagnosis. The prognosis can be excellent if appropriate antimicrobial therapy is begun in a timely fashion. It is well established that dogs are sentinels for infection in people in households and communities. Whether R. rickettsii causes illness in cats is not well established. The role of other spotted fever group rickettsia in causing illness in dogs and cats is being elucidated. Veterinarians should keep in mind that novel and well characterized species of SFG Rickettsia are important causes of emerging infectious disease. Veterinarians can play an important role in detecting, defining, and preventing illness in their canine patients and their human companions.


Do minitransplants have minicosts? A cost comparison between myeloablative and nonmyeloablative allogeneic stem cell transplant in patients with acute myeloid leukemia.
Allogeneic hematopoietic stem cell transplantation (SCT) is a widely used, cost-intensive procedure. Although pretransplant nonmyeloablative (NMA) or reduced-intensity conditioning regimens appear very promising, prospective studies comparing this approach with the conventional myeloablative (MA) approach in specific hematologic diseases are necessary, especially in patients in whom the conventional approach is not contraindicated. Cost may be an important factor in the decision-making process. We compared the costs of MA and NMA transplants in patients with acute myeloid leukemia (AML). We estimated 1-year resource utilization in 12 consecutive MA patients (median age: 39 years) and in 11 consecutive NMA patients (median age: 58 years) who underwent HLA-identical sibling SCT for AML. Resources care expenses were valued using the average daily rate for personnel costs, supplies, and room costs. Other data were directly collected from the patients' charts. Despite a trend for lower costs in NMA patients during the first 6 months, costs during the 6-12-month period were significantly higher after NMA due to late complications and readmissions (P=0.03). Finally, mean 1-year costs were not different in MA and NMA patients (P=0.75). Prospective studies comparing conventional and NMA approaches in homogeneous populations should include economic items.


Comparison of several PCR procedures for detection of serum HCV-RNA using different regions of the HCV genome.
Different methods for the isolation of hepatitis C virus RNA and several sets of primers from the 5' untranslated, core, NS3, NS3/NS4 and NS5 regions of the hepatitis C virus genome were used for the detection of the viral genome by the polymerase chain reaction. Serum samples from 10 patients with chronic hepatitis C and 10 healthy controls were studied. The best method for the RNA extraction was with cold guanidinium isothiocyanate followed by a denaturation step prior to the polymerase chain reaction. Using this method, the percentage of positivity to hepatitis C virus sequences in serum depending on the region amplified were: 5' untranslated, 90%; Core, 20%; NS3, 80%; NS3/NS4, 60% and NS5, 60%.


Using modeling to help understand vaginal microbicide functionality and create better products.
A summary is presented of a range of mathematical models that relate to topical microbicidal molecules, applied vaginally to inhibit HIV transmission. These models contribute to the fundamental understanding of the functioning of those molecules, as introduced in different delivery systems. They also provide computational tools that can be employed in the practical design and evaluation of vaginal microbicide products. Mathematical modeling can be implemented, using stochastic principles, to understand the probability of infection by sexually transmitted HIV virions. This provides a frame of reference for the deterministic models of the various processes that underlie HIV transmission and its inhibition, including: the temporal and spatial history of HIV migration from semen to vaginal epithelial surfaces and thence to the underlying stroma; the time and spatial distribution of microbicidal drugs as delivered by various vehicles (e.g., gels, rings, films, and tablets)-this is central to understanding microbicide product pharmacokinetics; and the time and space history of the drug interactions with HIV directly and with host cells for HIV within the vaginal environment-this informs the understanding of microbicide pharmacodynamics. Models that characterize microbicide functionality and performance should and can interface with both in vitro and in vivo experimental studies. They can serve as a rapidly applied, inexpensive tool, to facilitate microbicide R&D, in advance of more costly and time consuming clinical trials.


Chromatographic studies on the binding, action and metabolism of (-)-deprenyl.
Serum binding, the effect on striatal dopamine release and the metabolism of (-)-deprenyl [N-methyl-N-propargyl(2-phenyl-1-methyl)ethylammonium chloride], TZ-650 [N-methyl-N-propargyl(2-phenyl)ethylammonium chloride] and J-508 [N-methyl-N-propargyl(indanyl)ammonium chloride] were investigated using various chromatographic methods. A strong interaction between (-)-deprenyl and macroglobulins was found. Deprenyl enhanced the dopamine release from striatal slices of the rat brain and also inhibited the dopamine-DOPAC conversion. Deprenyl analogues showed either smaller or no effect. Hydroxylation of (-)-deprenyl takes place in the para position, in addition to the usual oxidative N-dealkylations, which are known from various metabolic studies on N-substituted phenylalkylamines.


DNA secondary structure is influenced by genetic variation and alters susceptibility to de novo translocation.
Cumulative evidence suggests that DNA secondary structures impact DNA replication, transcription and genomic rearrangements. One of the best studied examples is the recurrent constitutional t(11;22) in humans that is mediated by potentially cruciform-forming sequences at the breakpoints, palindromic AT-rich repeats (PATRRs). We previously demonstrated that polymorphisms of PATRR sequences affect the frequency of de novo t(11;22)s in sperm samples from normal healthy males. These studies were designed to determine whether PATRR polymorphisms affect DNA secondary structure, thus leading to variation in translocation frequency. We studied the potential for DNA cruciform formation for several PATRR11 polymorphic alleles using mobility shift analysis in gel electrophoresis as well as by direct visualization of the DNA by atomic force microscopy. The structural data for various alleles were compared with the frequency of de novo t(11;22)s the allele produced. The data indicate that the propensity for DNA cruciform structure of each polymorphic allele correlates with the frequency of de novo t(11;22)s produced (r = 0.77, P = 0.01). Although indirect, our results strongly suggest that the PATRR adopts unstable cruciform structures during spermatogenesis that act as translocation hotspots in humans.


C-peptide measurement in the differentiation of type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus.
To determine whether individual subjects with Type 1 (insulin-dependent) diabetes or Type 2 (non-insulin-dependent) diabetes, who are treated with insulin, could be reliably distinguished, C-peptide concentrations and urinary C-peptide excretion were measured in 10 Caucasoids and 10 Pima Indians. All the subjects had developed diabetes before 21 years of age and were receiving insulin treatment. Fasting C-peptide concentrations were significantly higher in the Pima Indians (0.73 +/- 0.17 versus 0.02 +/- 0.01 nmol/l in Caucasoids; p less than 0.001), but there were slight overlaps in individual values. Urinary C-peptide excretion, an index of 24-h-insulin excretion, was also higher in the Pima Indian group (27.6 +/- 1.85 versus 0.72 +/- 0.18 pmol/min in Caucasoids; p less than 0.001) and there was no overlap in the individual values between the groups. The Pima Indians with early onset diabetes have been previously shown to have Type 2 diabetes, and the Caucasoids with an early onset are most likely to have Type 1 diabetes. These results suggest that distinction between these two major types of diabetes can be made effectively by using C-peptide measurements provided that overt renal disease is absent. This differentiation between insulin-treated patients will be useful for a variety of research applications and possibly in making clinical management decisions.


Combinatorial signaling pathways determine fibroblast proliferation and myofibroblast differentiation.
Fibroblast proliferation, differentiation into myofibroblasts, and increased collagen synthesis are key events during both normal wound repair and fibrotic lesion formation. Here we report that these biological responses to TGF-beta by fibroblasts are regulated via a CTGF-dependent pathway in concert with either EGF or IGF-2. Our studies indicate these responses to TGF-beta are mutually exclusive, and cells that are proliferating do not express alpha-SMA or elevated levels of collagen synthesis. Cells expressing alpha-SMA do not exhibit DNA synthesis but do coexpress higher levels of types I and III collagen mRNA. Thus, fibroblast proliferation and differentiation are controlled by combinatorial signaling pathways involving not only components of the TGF-beta/CTGF pathway, but also signaling events induced by EGF and IGF-2-activated receptors. Collectively, our studies indicate TGF-beta functions as a classic embryonic inducer, initiating a cascade that is controlled by other factors in the cellular environment. We propose a model for this process with regard to wound repair and fibrotic lesion formation that is likely applicable to other instances of CTGF action during embryogenesis.


Ectopic adrenal cortex tissue: an incidental finding during inguinoscrotal operations in pediatric patients.
The aim of the present study was to assess the occurrence of ectopic remnants of adrenal cortex tissue encountered in pediatric patients who underwent groin surgical explorations. We studied 1,862 patients with groin surgical explorations during a period of 12 consecutive years (1995-2006). Nodules resembling ectopic adrenal tissue were removed and the histopathological examination was performed using hematoxylin and eosin staining. We found ectopic adrenal cortex tissue along the spermatic cord in 31 patients in 1,862 groin surgical explorations, an overall incidence of 1.66%. None were found in females. Of the 31 cases, 20 were diagnosed as having undescended testes, 8 communicating hydrocele, and 3 inguinal hernia. Median age at diagnosis was 6.5 years (range 2-14). The nodules were found located along the spermatic cord, in the apex of the hernial sac, and between the testis and epididymis. Macroscopically, the nodules were round to oval in shape, 2-6 mm in diameter, and bright yellow to orange in color. Microscopically, they had three well-defined layers of adrenal cortex, with predominance of the zona fasciculata, surrounded by a fibrous capsule and none contained any medulla. Ectopic adrenal cortical tissue is a benign lesion. Although a routine search for this lesion is not indicated, it should be resected for histological analysis and differential diagnosis when it is found during a surgical procedure in this area.


Illusory sound shifts induced by the ventriloquist illusion evoke the mismatch negativity.
The ventriloquist illusion arises when sounds are mislocated towards a synchronous but spatially discrepant visual event. Here, we investigated the ventriloquist illusion at a neurophysiological level. The question was whether an illusory shift in sound location was reflected in the auditory mismatch negativity (MMN). An 'oddball' paradigm was used whereby simultaneously presented sounds and flashes coming from the same location served as standard. The deviant consisted of a sound originating from the same source as the standard together with a flash at 20 degrees spatial separation, which evoked an illusory sound shift. This illusory sound shift evoked an MMN closely resembling the MMN evoked by an actual sound shift. A visual-only control condition ruled out that the illusory-evoked MMN was confounded by the visual part of the audiovisual deviant. These results indicate that the crossmodal interaction on which the ventriloquist illusion is based takes place automatically at an early processing stage, within 200 ms after stimulus onset.


Harnessing progress: Gender, sexuality, and positive self-perceptions of aging in midlife.
Drawing on interviews, this article analyzes how lesbians, gay men, straight women, and straight men construct positive views of aging during midlife, a life course period when negative perceptions of aging are salient. Interviewees engaged in harnessing progress-a process of crafting personal aging narratives that emphasize growth and improvement-which helped them to feel positively about their own aging. All interviewees shared these progress narratives, but reports differed across gender and sexuality groups. Men's narratives focused on the wisdom they gained and how that made them more relevant to older and younger generations. Regarding the latter, straight men viewed their children as beneficiaries of their progress and gay men viewed younger LGBTQ people as beneficiaries. Women's progress narratives focused on self-improvement. Whereas straight women described becoming more self-reliant with age, lesbians described learning to stand up for themselves. Overall, findings reveal how gender and sexual identities-and the lifelong benefits and burdens that accompany those identities-influence how people create positive perceptions of aging.


Omega-3 fatty acid supplementation decreases DNA damage in brain of rats subjected to a chemically induced chronic model of Tyrosinemia type II.
Tyrosinemia type II is an inborn error of metabolism caused by a mutation in a gene encoding the enzyme tyrosine aminotransferase leading to an accumulation of tyrosine in the body, and is associated with neurologic and development difficulties in numerous patients. Because the accumulation of tyrosine promotes oxidative stress and DNA damage, the main aim of this study was to investigate the possible antioxidant and neuroprotective effects of omega-3 treatment in a chemically-induced model of Tyrosinemia type II in hippocampus, striatum and cerebral cortex of rats. Our results showed chronic administration of L-tyrosine increased the frequency and the index of DNA damage, as well as the 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the hippocampus, striatum and cerebral cortex. Moreover, omega-3 fatty acid treatment totally prevented increased DNA damage in the striatum and hippocampus, and partially prevented in the cerebral cortex, whereas the increase in 8-OHdG levels was totally prevented by omega-3 fatty acid treatment in hippocampus, striatum and cerebral cortex. In conclusion, the present study demonstrated that the main accumulating metabolite in Tyrosinemia type II induce DNA damage in hippocampus, striatum and cerebral cortex, possibly mediated by free radical production, and the supplementation with omega-3 fatty acids was able to prevent this damage, suggesting that could be involved in the prevention of oxidative damage to DNA in this disease. Thus, omega-3 fatty acids supplementation to Tyrosinemia type II patients may represent a new therapeutic approach and a possible adjuvant to the curren t treatment of this disease.


Review of human genetic and clinical studies directly relevant to GnRH signalling.
GnRH is the pivotal hormone in controlling the hypothalamic-pituitary gonadal (HPG) axis in humans and other mammalian species. GnRH function is influenced by a multitude of known and still unknown environmental and genetic factors. Molecular genetic studies on human families with hypogonadotropic hypogonadism over the past two decades have been instrumental in delineating the kisspeptin and neurokinin B signalling, which integrally modulates GnRH release from the hypothalamus. The identification of kisspeptin and neurokinin B ligand-receptor gene pair mutations in patients with absent puberty have paved the way to a greater understanding of the central regulation of the HPG cascade. In this article, we aim to review the literature on the genetic and clinical aspects of GnRH and its receptor, as well as the two ligand-receptor sets directly pertinent to the function of GnRH hormone signalling, kisspeptin/ kisspeptin receptor and NKB/NK3R.


A lot in a little: Assessment of skills laboratory course structures and faculty workloads.
Pharmacy skills development is essential to pharmacy programs to ensure "practice-ready" graduates. The objective was to describe the landscape of skills laboratory (lab) courses and faculty workload across United States schools and colleges of pharmacy (S/COP). The American Association of Colleges of Pharmacy Laboratory Instructors Special Interest Group disseminated an anonymous questionnaire to collect faculty demographics, skills lab format, faculty workload, and job satisfaction. Descriptive statistics were generated, and paired t-tests were used to assess changes before and during COVID-19. Faculty from 44 of 142 S/COP responded. Participants (n = 45) were more frequently assistant professors (49%), non-tenure track (80%), and female (98%). A mean of 103 students per class, with a mean of two lab courses in both the first and second years and 1.6 in the third year were reported. Courses had a mean 1.6 lab coordinators each. Many institutions leverage non-lab faculty, pharmacy volunteers, post-graduate trainees, and senior professional students to assist. Faculty reported a mean 28.2 hours per week related to lab activities. The mean assigned percent effort was 44% for teaching in the skills lab, demonstrating consistency with effort calculations. Job satisfaction (scale 1-10) decreased from 7.6 before COVID-19 to 6.4 during COVID-19 (P < .01), with satisfaction specifically with their lab role decreasing from 7.5 to 6.6 (P = .003). Skills lab faculty reported significant time coordinating labs and identified the need for additional support. S/COP should ensure appropriate personnel resources are available to provide quality clinical skills training.


The medulloblastoma cell line DAOY but not eleven other tumor cell lines expresses minichromosome maintenance protein 4.
Minichromosome maintenance proteins (MCM) are required for initiation and elongation of chromosomal DNA, ensuring that DNA replication takes place only once. Although MCMs are considered of utmost importance in tumor biology and as potential marker proteins, they were not unambiguously identified at the protein level and we therefore aimed to characterize MCM 4 in a medulloblastoma cell line and provide a protein chemical analytical tool. In addition, we searched for this protein in twelve tumor cell lines and a series of non-tumor cells. The DAOY medulloblastoma cell line was cultivated, lysed, proteins extracted and run on two-dimensional gel electrophoresis with subsequent in-gel digestion and mass spectrometrical (MS/MS) analysis of protein spots. One spot at pI 6.2 with an observed molecular weight of 98 kDa was identified as minichromosome maintenance protein 4 by peptide fingerprinting. Sequence coverage of 35% along with 25 matched peptides and MS/MS analyses of three matching peptides warranted unambiguous identification. The use of mass spectrometrical identification unequivocally allowed determination of MCM 4 expression in a medulloblastoma cell line exclusively. Given the biological and probable clinical importance of this molecule as a tentative marker protein, a fair analytical tool, independent of antibody availability and specificity is mandatory and determinations at the transcriptional level cannot be extrapolated to protein levels per se, as there is a long and unpredictable way from mRNA to protein.


Agrochemical poisoning in Sri Lanka.
Mortality resulting from agrochemicals met within the Office of the Judicial Medical Officer, Colombo, which is the premier Medico-legal Institute in Sri Lanka, are analysed over a 3-year period and the morbidity and mortality rates of the entire country are examined over a 10-year period. The number of patients admitted to hospitals in Sri Lanka during the period 1975-1983, stood at around 11,000-15,000 each year, with the year 1983 recording 16,649 admissions. The number of deaths during the same period varied from 900 to 1500 each year, while the year 1983 recording 1521 deaths. About 75% of such cases of poisoning were due to self ingestion while accidental and occupational poisoning formed the balance. Principal agricultural districts like Kurunegala, Jaffna, Vavuniya, Nuwara-Eliya and Badulla recorded the highest incidence of poisoning. The mortality figures of the Office of the J.M.O., Colombo, indicated that 4% of all bodies subjected to autopsy were those of agrochemical poisoning. The male/female ratio was 2:1. Seventy-five percent of deaths from agrochemical poisoning were recorded in the 15-39 year age group, while 33% of deaths belonged to the 20-24 age group. One third of cases of agrochemical poisoning were dead on being brought to hospital, while 50% were dead within 2 h and 60% dead within 24 h. Organophosphates accounted for 57.6% of all cases of agrochemical poisoning, while paraquat accounted for 21.2% of cases. Deaths were also reported from what are called safe chemicals like Carbamates and Pyrethrums due to their lethal additives.


Age at onset and long-term metabolic control affect height in type-1 diabetes mellitus.
Reduced height as a consequence of type-I-diabetes mellitus in childhood has been reported in many studies. However, it is still debated whether good metabolic control can normalize the growth rate. A total of 436 children (204 boys, 232 girls, mean age at diagnosis of diabetes 8.2+/-0.2 years) were followed at our outpatient diabetes centre. Z-scores for height were evaluated in relation to duration of diabetes, age at onset and long-term metabolic control. At diagnosis, height in children with diabetes was significantly above the reference population (+0.43+/-0.09). Standardized height decreased during the subsequent course of diabetes. This likely represents a delay of growth, as the final height (chronological age > 18 years, n = 144) was +0.27+/-0.09. Growth reduction was more pronounced in patients diagnosed before the onset of puberty and final height in patients with a prepubertal onset of diabetes was significantly lower (+0.10+/-0.13) compared to patients with a pubertal/postpubertal onset (+0.52+/-0.14). Among patients with a prepubertal onset, the subgroup with "poor" metabolic control (long-term median HbA(Ic) >7%) lost significantly more height compared to patients with "good" metabolic control. Despite modern treatment regimens, reduced longitudinal growth can still be demonstrated in type-I diabetes. This parameter therefore provides a valuable endpoint for quality control in paediatric diabetology.


Severe respiratory syncytial virus pneumonia associated with primary Epstein-Barr virus infection.
This is a case report of a child with severe respiratory syncytial virus (RSV) pneumonia and concurrent infection with Epstein-Barr virus. We hypothesize that immunosuppression due to EBV may have contributed to the severity of his RSV infection. The diagnosis of RSV infection was facilitated by bronchoalveolar lavage.


Fifty-one Kaposi sarcoma patients.
Kaposi sarcoma (KS) is a mesenchymal tumor originating from lymphatic endothelial cells. Immunosuppressive patients have higher risk for KS. HHV-8 has a role in immunopathogenesis of KS. Aim Evaluation of demographical properties with tumor characteristics and treatment modalities of KS. Histopathologically documented KS patients were evaluated retrospectively. Anti-HIV seroprevalence was also evaluated with patient and tumor characteristics besides treatment regimens. Fifty-one patients were included between September 1998 and February 2009. Male/female ratio was 3.25 (39/12). Median age was 68 (31-94). Lower extremity was the most common site whereas excisional biopsy was the most common diagnostic procedure. Smoking rate was 42.8%. Twenty percent had family history for cancer. Anti- HIV seropositivity rate was 1.9%. Thirty eight percent had local monotherapy, and radiotherapy was most common (26%). Multidisciplinary approach rate was 44%. Most of them had surgery and radiotherapy combination. Two-third of the patients had radiotherapy alone or with other modalities. Rates were as 12% for chemotherapy and 6% for interferon. Vincristine-bleomycin-doxorubicin combination was the most preferred regimen (60%). Male patients in the sixth decade seem to have higher risk for KS. Smoking rate was almost as high. Local therapy might be sufficient in most of the patients. However, we may also consider systemic chemotherapy for selected patients, including vincristine, bleomycin and doxorubicin.


Effect of analytically measured fiber and resistant starch from gluten-free products on the diets of individuals with celiac disease.
The aim of the present work was to assess the content of fiber and resistant starch (RS) in several gluten-free products (GFPs), compare them with their gluten-containing analogs (GCP) analytically and with label data, and measure the contribution of these foodstuffs to the fiber content of a gluten-free diet. Total dietary fiber and RS content in a large amount of GFP (n = 55) and their counterparts (n = 55) were measured by analytical techniques based on AOAC methods. Dietary assessment was carried out with a sample of 141 individuals (pediatric and adult patients with celiac disease) submitted to a food frequency questionnaire and a 24-h recall survey (three times on different days). In general terms, GFP and GCP showed similar fiber and RS content, with the exception of breads, which revealed a higher percentage of both in GFPs. This food group was the main contributor to fiber intake in both groups of patients. Even if GFPs were to be blamed for being nutritionally poorer than GCPs, this was not the case for fiber. The fiber and RS content were not different in the studied samples, except for the bread. It is noteworthy that label information can underestimate fiber consumption among those with celiac disease, and this must be considered for future database revision. Additionally, we demonstrated a significant effect on the fiber intake of children and adults due to GFPs, and especially to bread, a widely consumed basic product.


Dietary niche breadth in a local community of passerine birds: an analysis using phylogenetic contrasts.
The analysis of a local community of forest passerines (13 species) using phylogenetic contrasts shows a correlation between body size of bird species and mean prey size, minimum prey size, maximum prey size and the size range of dietary items. This suggests that larger birds drop small prey taxa from their prey list, because of the difficulty of capturing very small prey, for energetic reasons or because of microhabitat usage. We find some support for the third hypothesis. Dietary niche breadth calculated across prey taxa is not related to body size. Dietary niche breadth, however, is correlated with size-corrected measurements of the bill and locomotor apparatus. Long and slender bills increase the dietary niche breadth. Thus subtle differences constrain foraging and the techniques of extracting certain prey taxa form crevices. Dietary niche breadth and foraging diversity are positively correlated with population density: at least locally dietary generalists occur at higher breeding densities than specialists.


Exosomal noncoding RNAs in prostate cancer.
Prostate cancer (PCa) is the second most common cancer and the fifth leading cause of mortality among men. The recurrent reports of false-positive results of common PCa biomarkers have led to the introduction of some promising biomarkers for PCa, such as exosomal non-coding RNAs (ncRNAs). Exosomes contain various components, such as several ncRNAs (miRNAs and lncRNAs), which are important in the initiation and progression of PCa. These ncRNAs also reflect the state of the origin cell. In this article, we reviewed research on the importance and roles of ncRNAs in PCa, focusing on exosomal ncRNAs. We highlighted plasma exosomal miRNAs (8 miRNAs), urine exosomal miRNAs (19miRNAs), serum miRNAs (2 miRNAs), and five miRNAs in semen used for PCa diagnosis. Also, four exosomal lncRNAs in plasma and urine can be used as biomarkers for PCa diagnosis.


Complex Network Analysis in Microbial Systems: Theory and Examples.
A central driver for the field of systems biology is to develop an understanding of how interactions between components affect the functioning of a system as a whole. Network analysis is an approach that is uniquely suited to uncover patterns and organizing principles in a wide variety of complex systems. In this chapter, we will give a detailed description of basic concepts for characterizing empirical networks, frequently used random network models, and how to compute properties of networks using Python packages. We will demonstrate the application of network analysis by investigating several biological networks.


Facile synthesis of glucose-sensitive chitosan-poly(vinyl alcohol) hydrogel: Drug release optimization and swelling properties.
The study describes the development of glucose-sensitive hydrogel and optimization of bovine serum albumin release profile from the hydrogel. To enhance the glucose sensitivity and improve the swelling behaviors of the hydrogel system, boric acid crosslinking, and freeze-thawing cycle techniques were used to prepare chitosan-poly(vinyl alcohol) hydrogel. The structure of the resultant hydrogel was confirmed by scanning electron microscopy and Fourier transform infrared spectroscopy. The experimental results revealed that the swelling of the hydrogel was influenced by the pH of the medium, and the hydrogel displayed explicit glucose-sensitivity under physiological conditions. The values of the diffusion exponent range between 0.34 and 0.44 and the diffusion of water into the gel system are assumed to be pseudo-Fickian in nature. Under optimized conditions, the cumulative Bovine serum albumin (BSA) drug releases ranged between 69.33±1.95% and 86.45±1.16% at 37°C in the presence of glucose and pH 7.4, respectively.


Evaluation of a new strategy for detection of thyroid dysfunction in the routine laboratory.
We assessed the use of a new strategy for detecting thyroid disorders, utilizing a sensitive assay for concentrations of thyrotropin (TSH) and free thyroid hormone in serum as follow-up tests. Of 1279 patients who were not on thyroxin (T4) replacement treatment, 82% could be classified as euthyroid and would require no further tests. In patients who were on T4 replacement, 41% fell into the euthyroid category and would require no further tests. Using this strategy to replace our existing strategy of free thyroxin as a "first-line" test would reduce the proportion of patients who would require one or more follow-up tests from 49% to 24%.


Orbicular muscle akinesia in regional ophthalmic anaesthesia with pH-adjusted bupivacaine: effects of hyaluronidase and epinephrine.
The success rate and duration of lid akinesia after adding hyaluronidase and/or epinephrine to pH-adjusted bupivacaine was examined in a double-blind fashion in patients undergoing cataract surgery under local anaesthesia. A two-injection-site technique was used. For globe akinesia all patients (n = 120) received an inferolateral intraconal injection (3 ml) of pH-adjusted bupivacaine 0.75% and hyaluronidase. Lid akinesia was obtained with a medial extraconal injection (3.5 ml) of alkalinized bupivacaine with or without an adjunct. The patients were randomized to four groups as follows: a medial injection of plain bupivacaine (n = 31), with added hyaluronidase (n = 30), with added epinephrine (n = 29) or with both epinephrine and hyaluronidase (n = 30). The final solutions had a pH of 6.7. Lid akinesia was supplemented with periosteal injections if needed. The degree of akinesia from clinical assessment was graded from 0-2 and also measured with electromyography at ten minute intervals for 30 min after surgery, and three hours after the block. The least satisfactory result (P < 0.01) and shortest duration of the lid block (P < 0.05) was obtained with plain pH-adjusted bupivacaine. No differences in the success rate or duration of the block among the other groups were seen. The duration of the block was longer in the epinephrine groups than in the two other groups (P < 0.01) and longer in the epinephrine and hyaluronidase group than in the group receiving only hyaluronidase (P < 0.05). We conclude that the best initial results and longest duration of blocks were shown in the groups receiving epinephrine or epinephrine and hyaluronidase.


Allometric versus ratiometric normalization of left ventricular stroke volume by Doppler-echocardiography for outcome prediction in severe aortic stenosis with preserved ejection fraction.
Appropriate normalization methods to scale Doppler-derived stroke volume (SV) to body size in patients with aortic stenosis (AS) are poorly defined and reference values are lacking. We aim to establish reference values of normalized SV in adults, and to compare the prognostic value of SV normalized by different methods in AS patients. In 2781 normotensive, non-obese adults without cardiovascular disease we defined normal relationships between SV and body size by nonlinear regression. Reference SV values were calculated by quantile regression. We subsequently analyzed by Cox analysis the prognostic performance of ratiometric and allometric normalized SV in 1450 patients with severe AS and preserved LVEF under medical and surgical management. Unlike ratiometric normalization, allometric indexation eliminated the residual relationships between normalized SV and body size. The allometric exponents that adequately described the SV-height (H) and SV-body surface area (BSA) relationships were 1.32, and respectively 0.88. In males, low-flow (LF) reference values were: <28 ml/m2, <30 ml/m, <30ml/(m2)0.88, and, respectively, <26 ml/m1.32, and in females <27 ml/m2, <28 ml/m, <29ml/(m2)0.88, and, respectively, <24 ml/m1.32. In patients with severe AS, SV/H1.32 was most consistently associated with mortality and showed better prognostic performance than other normalized SV parameters (adjusted hazard ratios: 1.86 for SV/H1.32, 1.72 for SV/H, 1.64 for SV/BSA, and 1.61 for SV/BSA0.88). Compared to H-normalization, BSA-normalization markedly overestimated the frequency of LF (3% vs. 9%). We provide normative reference values and appropriate normalization methods for SV by Doppler-echocardiography. In severe AS, SV/H1.32 seems the most appropriate indexation method, especially in obese individuals.


Effects of an online mindfulness-based intervention on Fear of Cancer Recurrence and quality of life among Chinese breast cancer survivors.
Mindfulness-based interventions (MBIs) targeting cancer-related emotions and quality of life have attracted extensive attention in recent years. The purpose of the current study was to assess the feasibility and acceptability of an online mindfulness-based intervention and examine its effects on Chinese breast cancer survivors. Sixty-five breast cancer survivors were randomized to either an online MBI or to wait for the next available program. The control group received usual care, while the intervention group also received six weeks of online MBI training. Participants completed the Short Form of the Fear of Cancer Recurrence Inventory (FCRI-SF), Five Facet Mindfulness Questionnaire (FFMQ) and European Organization for Research and Treatment of Cancer questionnaire (EORTC-QLQ-C30) at baseline (T1), immediately after the intervention (postintervention: T2) and 1 month later (1-month postintervention: T3). In addition, answers provided to questions about the experience of participating in the course were analyzed. Compared with the control group, the mindfulness, emotional and cognitive function of the MBI group was significantly improved after the intervention, and the FCR of breast cancer survivors was significantly alleviated. These effects were still significant 1 month after the end of the intervention. Additionally, participants were satisfied with the online MBI through the qualitative survey. This online MBI showed promise for Chinese breast cancer survivors, facilitating a reduction in FCR and improving their quality of life. The results of our study indicated that online MBI treatment could offer a scalable approach to manage FCR and maintain mental health for breast cancer survivors.


Responses of spinothalamic tract cells in the superficial dorsal horn of the primate lumbar spinal cord.
1. The responses of thirty-five spinothalamic tract (s.t.t.) cells in or near lamina I of the dorsal horn were examined in chloralose- and barbiturate-anaesthetized monkeys (Macaca fascicularis). Many of the cells could be classified on the basis of receptive field properties as either wide dynamic range (w.d.r.) cells or as high-threshold (h.t.) cells. 2. Thalamic stimulation sites for antidromic activation of the s.t.t. cells were in or around the ventral posterior lateral nucleus. Axons of the s.t.t. cells had a mean conduction velocity of 17 m/s (33 and 14 m/s for w.d.r. and h.t. cells, respectively). Mean minimum afferent conduction velocity averaged 37 m/s (52 and 23 m/s for w.d.r. and h.t. cells, respectively). Background activity was low (mean of 2.3 impulses/s). 3. An alternative classification of the cells was based on a kappa means cluster analysis of the responses to a series of mechanical stimuli. The response profiles for a given cell were normalized, and those of the s.t.t. cells in or near lamina I were analysed along with the responses of a population of s.t.t. cells, largely in laminae IV-VI, that had been described previously. S.t.t. cells in or near lamina I were distributed amongst three of the four groups of cells determined by the cluster analysis (types 2-4). 4. Vibratory stimuli excited most of the w.d.r. but none of the h.t. cells tested. Best frequencies were 5-10 Hz (at 100 and 500 microns indentations). 5. Most w.d.r. but few h.t. cells responded to cutaneous cooling. All of the cells responded to noxious heating, but w.d.r. cells had steeper stimulus-response curves. 6. After a series of noxious heat stimuli, the thresholds for noxious heat were lowered and responses to lower-intensity noxious heat stimuli were enhanced (sensitization). However, responses to more intense stimuli were reduced (inactivation). Similar changes were seen in the responses to graded mechanical stimuli. 7. It is concluded that s.t.t. cells in or near lamina I can signal noxious cutaneous stimuli but have poor coding abilities for innocuous mechanical stimuli. Some of these cells respond to innocuous thermal stimuli, but their role in thermoreception is unclear. The small receptive fields suggest that these cells could contribute to stimulus localization.


Positive impact on heat loss and patient experience of preheated skin disinfection: a randomised controlled trial.
The aim of this study was to compare the effect of preheated (36 °C) and room-temperature (20 °C) skin disinfectant solution on skin temperature and patients' experience of the skin disinfection process. To prevent surgical site infections, it is important to disinfect skin prior to invasive surgery. In clinical practice, conscious patients often comment on the coldness of the preoperative skin disinfection solution. Evidence is lacking, as to whether preheated skin disinfectant has any positive effects during preoperative skin disinfection. Randomised controlled trial. A total of 220 patients undergoing pacemaker, implantable cardioverter-defibrillator, or cardiac resynchronisation therapy under local anaesthesia were included and randomly allocated to preheated or room-temperature skin disinfection. Skin temperature was assessed before and after skin disinfection at the planned incision site; in addition, three study-specific questions were used to assess how patients experienced the temperature. Patients experienced the skin disinfection process with preheated disinfectant as significantly more pleasant. They felt less cold and reported increased satisfaction with the temperature of the solution compared to patients who were disinfected with room-temperature solution. Skin disinfection with preheated solution also yielded a significantly higher mean skin temperature compared to room-temperature solution. Preoperative skin disinfection with preheated disinfectant may prevent heat loss and contributes to a more pleasant experience for patients. Skin disinfection with preheated skin disinfectant is an easy and inexpensive nursing intervention that has a positive impact on heat loss and on patients' experience of the disinfection process.


RAGE and glyoxalase in kidney disease.
Glycation is an important reaction in the regulation of physiological state. When poorly controlled, however, glycation can also result in the accumulation of glycated proteins (advanced glycation endproducts; AGEs) in the body. This AGE accumulation is termed glycative stress, and is an established pathological factor: to date, glycative stress has been closely associated with not only kidney diseases, but also kidney aging. Accumulating evidence demonstrates that the progression of renal tubular damage and tubular aging are often correlated with activation of the receptor for the AGE (RAGE)-AGE pathway or decreased activity of glyoxalase 1, which is an anti-glycation enzyme to lower glycative stress. Further, glycative stress exacerbates the derangement of protein homeostasis: the posttranslationally modified proteins by glycation often lose or gain their functions. Such deranged protein homeostasis leads to endoplasmic reticulum (ER) stress, a state of ER dysfunction in which the quality control of proteins is defective, as well as to induction of its stress signal, the unfolded protein response (UPR), in the kidney. The lowering of glycative stress via modulation of RAGE-AGE axis or glyoxalase 1 activity is beneficial for tubular homeostasis and the subsequent prevention and treatment of kidney disease, suggesting the possibility of novel therapeutic approaches which target glycative stress. In this review, we focused on the impact of glycative stress in the kidney, especially the role of RAGE and glyoxalase 1. Further we also discuss the crosstalk between glycative stress and ER stress in their effect on protein homeostasis.


The initiation and maintenance of bradycardia in a diving mammal, the muskrat, Ondatra zibethica.
1. The cardiac and respiratory responses shown by muskrats in both unrestrained and restrained dives have been compared with responses elicited by stimulation of a number of cardio-depressant receptor inputs, in an attempt to determine which are most important in initiating and maintaining diving bradycardia. 2. In unrestrained voluntary dives heart rate fell from 310 +/- 3 to 54 +/- 3 beats min-1 in 1 to 2 sec, which was significantly below that seen in dives by restrained unanaesthetized or anaesthetized animals. 3. Pouring water on the external nares during maintained artificial ventilation caused heart rate to decline to 76 +/- 12 beats min-1 after 1 sec. Flowing water through the internal nares caused apnoea, in the expiratory position, and bradycardia within one third of a second. Heart rate fell to 20 +/- 2 beats min-1, 1 sec after the start of water flow. Substituting saline for water reduced both the apnoeic and cardiac responses. Bilateral section of the maxillary branch of V and the inferior laryngeal (X) nerves completely abolished the cardiac and respiratory response to water flow. 4. Artificial ventilation throughout periods of nasal stimulation with water or saline reduced the bradycardia, although even the saline driven response could not be completely abolished. Lung deafferentation eliminated any direct effect of artificial ventilation on heart rate during nasal stimulation. 5. Lung deflation caused bradycardia within 0.97 +/- 0.17 sec, heart rate falling from 268 +/- 7 to 59 +/- 4 beats min-1. Bradycardia also occurred during maintained lung inflation but it was delayed for a period which varied from 6.8 +/- 1.8 sec at an inflation pressure of 0.5 kPa to 35 +/- 7 sec at 1.5 kPa. 6. Bradycardia caused by nasal water flow or lung deflation was unaffected by bilateral section of the sinus nerve. 7. Artificial ventilation of paralysed muskrats with 5% CO2 in N2 caused bradycardia when Pa, O2 reached 8.4 +/- 0.8 kPa and heart rate declined to 76 +/- 7 beats min-1 at 4 kPa. Bilateral section of the sinus nerve delayed bradycardia until Pa, O2 reached 4.5 +/- 0.5 kPa. 8. These results suggest that the cardiac response to submergence could be the expression of input from three groups of receptors, nasal, lung and carotid chemoreceptors, although it is not clear how they interact with one another to generate the cardiac responses displayed by unrestrained animals during submergence.


[Cardiogenic shock after acute myocardial infarction].
Cardiogenic shock remains the major cause of death among patients with acute myocardial infarction. Besides supportive therapy there is clear evidence that revascularization of the infarct related artery should be performed as soon as possible with percutaneous transluminal coronary angioplasty. Placement of coronary stents and administration of platelet glycoprotein IIb/IIIa antagonists may further improve outcome. Intra-aortic balloon pumping should be integral part of this treatment strategy but is unfortunately underused in clinical practice. Routine bypass surgery for cardiogenic shock patients is deferred and restricted to selected patients.


Efficient production of L-lactic acid with high optical purity by alkaliphilic Bacillus sp. WL-S20.
Highly efficient polymer-grade L-lactic acid production was achieved by an alkaliphilic strain Bacillus sp. WL-S20 using inexpensive peanut meal as nitrogen source and sodium hydroxide as neutralizing agent. In multi-pulse fed-batch fermentation of Bacillus sp. WL-S20, a L-lactic acid concentration of 225 g/l with a yield of 99.3% was obtained. In single-pulse fed-batch fermentation, a concentration of 180 g/l was obtained with a yield of 98.6%. No D-isomers of lactic acid were detected. The production of a high concentration of optically pure L-lactic acid by alkaliphilic Bacillus sp. WL-S20, combined with a low-cost nutrient and environment-friendly NaOH-based process, represent a potentially novel way for L-lactic acid production at an industrial scale.


Primary amyloidosis of lower urinary tract.
Primary amyloidosis of the lower urinary tract is a rare condition with an excellent prognosis in most cases. Three patients with this condition are described. In the cases of localized amyloidosis of the urethra and urinary bladder, the clinical presentation mimicked cancer of the respective sites. This was also true in the case of primary systemic amyloidosis involving the bladder. If significant associated systemic or local disease can be excluded, management is symptomatic and expectant.


The Role of Metabolic Surgery in Non-alcoholic Steatohepatitis Improvement.
Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity and overweight. It has a broad spectrum of clinical and histological presentations, such as steatosis, inflammation (known as non-alcoholic steatohepatitis or NASH), fibrosis, and cirrhosis. There is increasing evidence that marked weight loss following bariatric surgery is associated with NASH resolution; however, little is known about the mechanisms that may lead to this beneficial condition and if it is due to weight loss alone. In this review, the authors present the latest data regarding NASH resolution following metabolic surgery and try to answer the following questions: is NASH resolution due to weight loss alone or is it related to weight-independent effects similarly to T2D? In such case, can NASH be considered as a sole criterion for metabolic surgery? Most data evaluating NAFLD and bariatric and metabolic surgery are derived from cohort studies. Available data are extremely variable, but in general show a dramatic regression of steatosis, inflammatory changes, and in some cases even fibrosis that is probably linked to major weight loss following surgery. There are no randomized controlled trials evaluating the effects of metabolic surgery over NASH vs. lifestyle modifications. To consider NASH a sole indication for metabolic surgery regardless of BMI, such studies are desperately needed and should be the primary focus of future research in metabolic surgery.


Long-term soil water limitation and previous tree vigor drive local variability of drought-induced crown dieback in Fagus sylvatica.
Ongoing climate warming is increasing evapotranspiration, a process that reduces plant-available water and aggravates the impact of extreme droughts during the growing season. Such an exceptional hot drought occurred in Central Europe in 2018 and caused widespread defoliation in mid-summer in European beech (Fagus sylvatica L.) forests. Here, we recorded crown damage in 2021 in nine mature even-aged beech-dominated stands in northwestern Switzerland along a crown damage severity gradient (low, medium, high) and analyzed tree-ring widths of 21 mature trees per stand. We aimed at identifying predisposing factors responsible for differences in crown damage across and within stands such as tree growth characteristics (average growth rates and year-to-year variability) and site-level variables (mean canopy height, soil properties). We found that stand-level crown damage severity was strongly related to soil water availability, inferred from tree canopy height and plant available soil water storage capacity (AWC). Trees were shorter in drier stands, had higher year-to-year variability in radial growth, and showed higher growth sensitivity to moisture conditions of previous late summer than trees growing on soils with sufficient AWC, indicating that radial growth in these forests is principally limited by soil water availability. Within-stand variation of post-drought crown damage corresponded to growth rate and tree size (diameter at breast height, DBH), i.e., smaller and slower-growing trees that face more competition, were associated with increased crown damage after the 2018 drought. These findings point to tree vigor before the extreme 2018 drought (long-term relative growth rate) as an important driver of damage severity within and across stands. Our results suggest that European beech is less likely to be able to cope with future climate change-induced extreme droughts on shallow soils with limited water retention capacity.


Regional heterogeneity in rat Peyer's patches through whole transcriptome analysis.
Peyer's patches are gut-associated lymphoid tissue located throughout the intestinal wall. Peyer's patches consist of highly organized ovoid-shaped follicles, classified as non-encapsulated lymphatic tissues, populated with B cells, T cells, macrophages, and dendritic cells and function as an organism's intestinal surveillance. Limited work compares the gene profiles of Peyer's patches derived from different intestinal regions. In the current study, we first performed whole transcriptome analysis using RNAseq to compare duodenal and ileal Peyer's patches obtained from the small intestine of Long Evans rats. Of the 12,300 genes that were highly expressed, 18.5% were significantly different between the duodenum and ileum. Using samples obtained from additional subjects (n = 10), we validated the novel gene expression patterns in Peyer's patches obtained from the three regions of the small intestine. Rats had a significantly reduced number of Peyer's patches in the duodenum in comparison to either the jejunum or ileum. Regional differences in structural, metabolic, and immune-related genes were validated. Genes such as alcohol dehydrogenase 1, gap junction protein beta 2, and serine peptidase inhibitor clade b, member 1a were significantly reduced in the ileum in comparison to other regions. On the other hand, genes such as complement C3d receptor type, lymphocyte cytosolic protein 1, and lysozyme C2 precursor were significantly lower in the duodenum. In summary, the gene expression pattern of Peyer's patches is influenced by intestinal location and may contribute to its role in that segment.


An unusual case report of pulmonary adenoid cystic carcinoma metastasis to the kidney. Case report and literature review.
Adenoid cystic carcinoma (ACC) is a malignant neoplasm, frequently affecting the salivary glands, and rarely occurring in other locations. ACC is characterized by slow growth, perineural invasion, local and late recurrence after original treatment. However, renal metastasis of ACC is very rare. To our best knowledge, only 11 cases of ACC metastasis to the kidney have been reported in the English literature to date. Herein, we presented a rare case of a 70-year-old man with renal metastasis from ACC of the right lung after 3 years of primary presentation. Our patient underwent right radical nephrectomy and histologically confirmed as Metastatic Adenoid Cystic Carcinoma.


Multifactor Dimensionality Reduction Analysis to Evaluate the Association of Dopamine Beta-Hydroxylase (DΒH) Polymorphisms with Susceptibility to Dementia (SADEM Study).
Dementia is a multifactorial disease in which environmental, lifestyle, and genetic factors intervene. Population studies have been used in looking for the susceptibility genes for this disease. Since the activity of dopamine b hydroxylase (DβH) is reduced in the hippocampus and neocortex in the brain, changes in the physiological status of dopamine have been reported in Alzheimer's disease (AD) induced by this enzyme. Therefore, DBH polymorphisms have been associated with susceptibility to some neurological diseases such as AD, but few studies have investigated the relationship between these polymorphisms with other types of dementia, especially in Mexican populations. The aim of this study was to evaluate the association between single-nucleotide polymorphism (SNP) in the dopamine b-hydroxylase (DBH gene (rs1611115) and their interactions with environmental factors and the dementia risk. We examined the genotype of the gene DBH (rs1611115) polymorphism in patients with dementia and healthy. The interaction and the impact of DBH (rs1611115) polymorphism on dementia were examined through multifactor dimensionality reduction (MDR) analysis, and the results were verified by the Chi-square test. Hardy-Weinberg equilibrium (HWE) was also checked by the Chi-square test. The relative risk was expressed by odds ratio (OR) and 95%. A total of 221 dementia patients and 534 controls met the inclusion criteria of MDR analyses. The results of the MDR analysis showed that the development of dementia was positively correlated with interaction between the TT genotype of the DBH1 locus rs1611115 TT and diabetes, hypertension, and alcohol consumption (OR = 6.5: 95% CI = 4.5-9.5), originating further cognitive damage. These findings provide insight into the positive correlation between the metabolism and cardiovascular disorders and the presence of the T allele by means of a recessive model of DBH rs1611115 polymorphism with the suspensibility of dementia.


[MSCT perfusion analysis of nasopharyngeal cancer].
To study MSCT perfusion imaging of nasopharyngeal cancer and its differentiated diagnosis. Thirty cases with nasopharyngeal cancer performed multi-detector CT perfusion examination. Among them, there were 6 cases of 25 post-radiotherapy patients performed perfusion imaging with CT scan. Nasopharynx perfusion parameters include blood flow (BF), blood volume (BV), mean transit time (MTT) and permeability surface (PS). Compared with normal region of nasopharynx, BF, BV and PS in nasopharyngeal cancer increased significantly, while MTT has not significant difference between these two areas. Nasopharynx perfusion parameters (BF, BV and PS) measured with CT were significantly altered in nasopharyngeal cancer. There was important appliance value in differentiated diagnosis of nasopharyngeal malignant neoplasms and evaluation of outcome of radiotherapy of nasopharyngeal cancer.


Saccharomycopsis oxydans sp. nov., a new non-fermentative member in the genus Saccharomycopsis isolated from a traditional dairy product of Iran.
A total of 21 yeast isolates were recovered as part of a research project on biodiversity of yeasts in traditional dairy products in Alborz province, Iran. Standard protocols were used to carry out phenotypic, biochemical, physiological characterization and the phylogenetic analysis of combined the D1/D2 domain of the large ribosomal subunit (26S or LSU) and ITS region sequences. Five strains represented a potential new ascomycetous yeast species. Ascospore formation was not observed in these strains, and they did not ferment the examined carbon sources. Phylogenetic analysis placed these isolates in a well-supported sub-clade in the genus Saccharomycopsis. Here, we describe this novel yeast as Saccharomycopsis oxydans sp. nov.


The early impact of genetics on our understanding of cell cycle regulation in Aspergillus nidulans.
The application of genetic analysis was crucial to the rapid progress that has been made in cell cycle research. Ron Morris, one of the first to apply genetics to cell cycle research, developed Aspergillus nidulans into an important model system for the analysis of many aspects of cell biology. Within the area of cell cycle research, Ron's laboratory is noted for development of novel cell biological and molecular genetic approaches as well as seminal insights regarding the regulation of mitosis, checkpoint regulation of the cell cycle, and the role of microtubule-based motors in chromosome segregation. In this special edition of FGB dedicated to Ron Morris, and in light of the recent progress in fungal genomics, we review the outstanding contributions his work made to our understanding of mitotic regulation. Indeed, his efforts have provided many mutants and experimental tools along with the conceptual framework for current and future studies of mitosis in A. nidulans.


Histopathology of chondronecrosis development in knee articular cartilage in a rat model of Kashin-Beck disease using T-2 toxin and selenium deficiency conditions.
The objective of this study is to observe pathogenic lesions of joint cartilages in rats fed with T-2 toxin under a selenium deficiency nutrition status in order to determine possible etiological factors causing Kashin-Beck disease (KBD). Sprague-Dawley rats were fed selenium-deficient or control diets for 4 weeks prior to their being exposed to T-2 toxin. Six dietary groups were formed and studied 4 weeks later, i.e., controls, selenium-deficient, low T-2 toxin, high T-2 toxin, selenium-deficient diet plus low T-2 toxin, and selenium-deficient diet plus high T-2 toxin. Selenium deficiencies were confirmed by the determination of glutathione peroxidase activity and selenium levels in serum. The morphology and pathology (chondronecrosis) of knee joint cartilage of experimental rats were observed using light microscopy and the expression of proteoglycans was determined by histochemical staining. Chondronecrosis in deep zone of articular cartilage of knee joints was seen in both the low and high T-2 toxin plus selenium-deficient diet groups, these chondronecrotic lesions being very similar to chondronecrosis observed in human KBD. However, the chondronecrosis observed in the rat epiphyseal growth plates of animals treated with T-2 toxin alone or T-2 toxin plus selenium-deficient diets were not similar to that found in human KBD. Our results indicate that the rat can be used as a suitable animal model for studying etiological factors contributing to the pathogenesis (chondronecrosis) observed in human KBD. However, those changes seen in epiphyseal growth plate differ from those seen in human KBD probably because of the absence of growth plate closure in the rat.


Extreme pluvial episodes: bacteriological vulnerability of some subtropical fluvial systems (Santa Fe, Argentina).
Bacteriological water monitoring carried out during extreme precipitation events can identify higher or lower vulnerability of hydric resources to bacterial contamination. This hypothesis was tested in nine lotic and lentic environments of the floodplain of the Paraná River, one of the largest rivers in the world, after the rainiest month of the century (November 2000; 338 mm). To measure this impact, the concentration of Escherichia coli was compared with that obtained during dry weather (220 samples). Aquatic environments far from urban areas were relatively less affected. In closer areas, in contrast, the concentration of E. coli was 200 to 350 times higher than the average (P<0.0001). The concentration of the faecal contamination indicator was 8 to 13 times higher than the average (P<0.0001) in the middle course of the Paraná River (31 degrees 42' 04"S; 60 degrees 29' 39"W), but lakes isolated from rivers and urban areas were not affected by the event (concentrations lower than the average).


Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies.
The O-antigen polysaccharide (O-PS) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies elicited by O-PS often confer protection against infection; therefore, O-PS glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. However, conventional methods for natural extraction or chemical synthesis of O-PS are technically demanding, inefficient, and expensive. Here, we describe an alternative methodology for producing glycoconjugate vaccines whereby recombinant O-PS biosynthesis is coordinated with vesiculation in laboratory strains of Escherichia coli to yield glycosylated outer membrane vesicles (glycOMVs) decorated with pathogen-mimetic glycotopes. Using this approach, glycOMVs corresponding to eight different pathogenic bacteria were generated. For example, expression of a 17-kb O-PS gene cluster from the highly virulent Francisella tularensis subsp. tularensis (type A) strain Schu S4 in hypervesiculating E. coli cells yielded glycOMVs that displayed F. tularensis O-PS. Immunization of BALB/c mice with glycOMVs elicited significant titers of O-PS-specific serum IgG antibodies as well as vaginal and bronchoalveolar IgA antibodies. Importantly, glycOMVs significantly prolonged survival upon subsequent challenge with F. tularensis Schu S4 and provided complete protection against challenge with two different F. tularensis subsp. holarctica (type B) live vaccine strains, thereby demonstrating the vaccine potential of glycOMVs. Given the ease with which recombinant glycotopes can be expressed on OMVs, the strategy described here could be readily adapted for developing vaccines against many other bacterial pathogens.


Synthesis and structure-activity relationships of a new model of arylpiperazines. 4. 1-[omega-(4-Arylpiperazin-1-yl)alkyl]-3-(diphenylmethylene) - 2, 5-pyrrolidinediones and -3-(9H-fluoren-9-ylidene)-2, 5-pyrrolidinediones: study of the steric requirements of the terminal amide fragment on 5-HT1A affinity/selectivity.
In the present paper, we report the synthesis and the binding profile on 5-HT1A, alpha1 and D2 receptors of a new series of 1-[omega-(4-arylpiperazin-1-yl)alkyl]-3-(diphenylmethylene)- 2, 5-pyrrolidinediones (III) (1-4) and -3-(9H-fluoren-9-ylidene)-2, 5-pyrrolidinediones (IV) (1-4), in which the alkyl linker contains 1-4 methylenes and the aryl group is variously substituted. The results obtained are compared to those previously reported for bicyclohydantoin (I) and the related bicyclic amine (II) series. A considerable part of the tested compounds 1-4 demonstrated moderate to high affinity for 5-HT1A and alpha1 receptor binding sites but had no affinity for D2 receptors. The study of the length of the alkyl chain and the imide substructure has allowed us to suggest some differences between the 5-HT1A and the alpha1-adrenergic receptors: (i) for III and IV, affinity for the 5-HT1A receptor as a function of the length of the methylene linker decreases in the order 4 > 1 >> 3 approximately 2, while for the alpha1 receptor affinity decreases in the order 3 approximately 4 > 1 approximately 2; (ii) the no-pharmacophoric steric pocket (receptor zone which does not hold the pharmacophore of the ligand but holds a nonessential fragment of the molecule) in the 5-HT1A receptor has less restriction than the corresponding pocket in the alpha1 receptor. Compounds 3a,e, which are highly selective for alpha1-adrenergic receptors, displayed antagonist activity. On the other hand, the best compromise between affinity and selectivity for 5-HT1A receptors is reached in these new series with n = 1, which is in agreement with our previous results for the bicyclohydantoin derivatives I. Two selected compounds (1d and 4e) retain agonist properties at postsynaptic 5-HT1A receptors. The same 5-HT1A agonist profile found in these compounds suggests the existence of two different no-pharmacophoric steric pockets in this receptor and a different interaction of compounds with n = 1 and n = 4. The information obtained from the interpretation of the energy minimization and 2D-NOESY experiments of compounds 1-4 together with the synthesis and binding data of new conformationally restrained analogues 4k-m is in good agreement with this working hypothesis.


Can the severity of root resorption be accurately judged by means of radiographs? A case report with histology.
Root resorption of lateral incisors caused by the pressure of erupting canines is a well-known but relatively rare problem in orthodontics and general dentistry. It is usually diagnosed on radiographs. The purpose of this article is to discuss some difficulties associated with evaluating root resorption from radiographs alone. A case report is presented as an example. Radiographs showed that an 11-year-old girl had marked root resorption of the maxillary lateral incisors, caused by the impacted permanent canines. The incisors were to be extracted. Several months before the extractions, a canine had been surgically exposed to remove pressure from the incisor root. The lateral incisors were analyzed histologically, and the histologic findings were compared with those of the patient's mandibular first premolars, which had been extracted. The resorption of the lateral incisors was more severe than expected from the radiographs. The resorption extended far into the pulp. Most, although not all, root resorption areas showed histologic evidence of repair, but the amount of repair was far from functional repair levels. The mandibular first premolars had no signs of resorption, thus excluding systemic causes. The severity of root resorption of lateral incisors cannot be accurately judged from radiographs alone.


Sigma-hole bonding between like atoms; a fallacy of atomic charges.
Covalently bonded atoms, at least in Groups V-VII, may have regions of both positive and negative electrostatic potentials on their surfaces. The positive regions tend to be along the extensions of the bonds to these atoms; the origin of this can be explained in terms of the sigma-hole concept. It is thus possible for such an atom in one molecule to interact electrostatically with its counterpart in a second, identical molecule, forming a highly directional noncovalent bond. Several examples are presented and discussed. Such "like-like" interactions could not be understood in terms of atomic charges assigned by any of the usual procedures, which view a bonded atom as being entirely positive or negative.


Effect of intravenous infusions on laboratory results in blood specimens drawn proximal to the insertion site of an intravenous canula.
Blood sampling contralateral to the insertion site of an intravenous line is always first choice. When blood must be drawn proximal to an i.v. insertion site, dilution and contamination by the infused substance can occur. To study the effects of obtaining blood specimens proximal to a discontinued intravenous line a clinical trial in a small community hospital was designed. Ten patients received an intravenous infusion with sodium chloride 0.45%/dextrose 2.5%. Bloodsamples were taken simultaneously from the i.v.-arm and the control-arm with the infusion running and 1, 3, and 5 min after shutting off the infusion. Between-arm differences are significant for all analytes while the infusion is running, but not after the infusion is discontinued. Wide ranges in differences in terms of percentage exist for many analytes 1 min after shutting off the infusion, and for glucose also 3 min after shutting off the infusion. A three minute interval is recommended when drawing blood proximal to a shut-off infusion. Longer intervals may be advisable for analytes present in the infused substance.


Formation and Stabilization of NiOOH by Introducing α-FeOOH in LDH: Composite Electrocatalyst for Oxygen Evolution and Urea Oxidation Reactions.
NiOOH is considered as the most active intermediate during electrochemical oxidation reaction, however, it is hard to directly synthesize due to high oxidation energy. Herein, theoretical calculations predict that α-FeOOH enables a decline in formation energy and an improvement in stabilization of NiOOH in NiFe-based layered double hydroxide (LDH). Inspiringly, a composite composed of α-FeOOH and LDH is well-designed and successfully fabricated in hydrothermal treatment by adding extra Fe3+ resource, and stable NiOOH is obtained by the following electro-oxidation method. Benefiting from strong electron-capturing capability of α-FeOOH, it efficiently promotes charge redistribution around the Ni/Fe sites and activates Ni atoms of LDH, verified by X-ray photoelectron spectra (XPS) and X-ray absorption spectra (XAS). The d-band center is optimized that balances the absorption and desorption energy, and thus Gibbs free energy barrier is lowered dramatically toward oxygen evolution reaction (OER) and urea oxidation reaction (UOR), and finally showing an outstanding overpotential of 195 mV and a potential of 1.35 V at 10 mA cm-2 , respectively. This study provides a novel strategy to construct highly efficient catalysts via the introduction of a new phase for complex multiple-electron reactions.


Insoluble "fibrin" in human aortic intima. Quantitative studies on the relationship between insoluble "fibrin", soluble fibrinogen and low density lipoprotein.
A quantitative assay for fibrin or other insoluble fibrin-like antigens ("fibrin") in small samples of intima is described. Tissue samples were subjected to electrophoresis directly from the intima into an antibody-containing gel to remove and measure fibrinogen and other soluble fibrin reactive antigens (FRA). The residual tissue was then exhaustively incubated with plasmin, and the soluble fragments generated from the insoluble "fibrin" were measured by quantitative immunoelectrophoresis. "Fibrin" accounted for about 2% of the tissue dry weight in normal intima and the ratio fibrinogen/"fibrin" was 1-1.5. In the gelatinous lesions, which seem to be the precursors of fibrous plaques, there was a small increase in "fibrin" but a substantial increase in fibrinogen and low density (LD)-lipoprotein, and the ratio fibrinogen/"fibrin" rose to about 3, which suggests that the increase in "fibrin" is secondary to increased permeation of fibrinogen. At the edges of large plaques there was also a threefold increase in fibrinogen, but "fibrin" increased fivefold, and accounted for 10% of the tissue dry weight. The same high concentration was found in the centres of large fibrous plaques with advanced atheroma lipid. Raised levels of "fibrin" were accompanied by raised levels of fibrinogen in most tissue samples. About 80% of the total soluble FRA could be clotted with thrombin; there was no significant difference between normal intima and lesions, and the proportion clotted was not related to "fibrin" content.


A Value-Critical Choice Analysis of a Policy to Prevent Suicide in Veterans and Service Members.
A few years after the advent of the Global War on Terror, veteran and service member suicide emerged on the national forefront as a public health issue of significant concern. This social policy analysis applies a value-critical choice model to the military suicide prevention provisions mandated by Section 2 of Exec. Order No. 13625 (2012): Improving Access to Mental Health Services for Veterans, Service Members, and Military Families. Results reveal that the suicide prevention provisions mandated by the order have not been fully and effectively implemented and the goal of reducing military suicide remains elusive.


Modeling the dynamics of COVID-19 in the presence of Delta and Omicron variants with vaccination and non-pharmaceutical interventions.
Since its inception in December 2019, many safe and effective vaccines have been invented and approved for use against COVID-19 along with various non-pharmaceutical interventions. But the emergence of numerous SARS-CoV-2 variants has put the effectiveness of these vaccines, and other intervention measures under threat. So it is important to understand the dynamics of COVID-19 in the presence of its variants of concern (VOC) in controlling the spread of the disease. To address these situations and to find a way out of this problem, a new mathematical model consisting of a system of non-linear differential equations considering the original COVID-19 strain with its two variants of concern (Delta and Omicron) has been proposed and formulated in this paper. We then analyzed the proposed model to study the transmission dynamics of this multi-strain model and to investigate the consequences of the emergence of multiple new SARS-CoV-2 variants which are more transmissible than the previous ones. The control reproduction number, an important threshold parameter, is then calculated using the next-generation matrix method. Further, we presented the discussion about the stability of the model equilibrium. It is shown that the disease-free equilibrium (DFE) of the model is locally asymptotic stable when the control reproduction is less than unity. It is also shown that the model has a unique endemic equilibrium (EEP) which is locally asymptotic stable when the control reproduction number is greater than unity. Using the Center Manifold theory it is shown that the model also exhibits the backward bifurcation phenomenon when the control reproduction number is less than unity. Again without considering the re-infection of the recovered individuals, it is proved that the disease-free equilibrium is globally asymptotically stable when the reproduction threshold is less than unity. Finally, numerical simulations are performed to verify the analytic results and to show the impact of multiple new SARS-CoV-2 variants in the population which are more contagious than the previous variants. Global uncertainty and sensitivity analysis has been done to identify which parameters have a greater impact on disease dynamics and control disease transmission. Numerical simulation suggests that the emergence of new variants of concern increases COVID-19 infection and related deaths. It also reveals that a combination of non-pharmaceutical interventions with vaccination programs of new more effective vaccines should be continued to control the disease outbreak. This study also suggests that more doses of vaccine should provide to combat new and deadly variants like Delta and Omicron.


Expressional and functional analysis of CYP15A1, a juvenile hormone epoxidase, in the red flour beetle Tribolium castaneum.
Juvenile hormone (JH) is synthesized and secreted by the corpora allata. In the final two steps of JH biosynthesis, farnesoic acid (FA) is converted to JH through methylation by JH acid O-methyltransferase (JHAMT) and epoxidation by the cytochrome P450 enzyme CYP15. In the present study, we identified a homolog of CYP15 from the red flour beetle Tribolium castaneum (TcCYP15A1), and analyzed its expression as well as its role in JH biosynthesis. Quantitative RT-PCR analysis showed that the level of TcCYP15A1 mRNA was high in the embryonic stage as well as in the middle of the final larval instar. In the embryonic stage, the transcript level of TcCYP15A1 started to increase 30h after egg laying (AEL), peaked 54-60h AEL, and was followed by an increase of TcJHAMT mRNA, suggesting that JH biosynthesis started at this time point. TcCYP15A1 mRNA was present, but not exclusively so in the larval corpora allata. The recombinant TcCYP15A1 protein epoxidized both FA and methyl farnesoate (MF) in highly stereo-specific manners. These results confirmed that TcCYP15A1 is involved in JH biosynthesis. The RNAi-mediated knockdown of TcCYP15A1 in the pre-final larval instar did not result in precocious metamorphosis to pupa, indicating that MF may exhibit JH-like activity in order to maintain the larval status. The double knockdown of TcJHAMT and TcCYP15A1 resulted in pupae and adults with shorter wings, suggesting that the precursors of JH, JH acid and MF, may be essential for wing expansion.


Pandemic H1N1 influenza-associated myocarditis in a patient with Castleman's disease.
We report on a patient with longstanding multicentric Castleman's disease, hyaline-vascular type, who presented with nearly-fatal myocarditis associated with a 2009 pandemic H1N1 influenza virus infection. This is the first case of such an association described in the literature.


Use of a p64 MW Flow Diverter with Hydrophilic Polymer Coating (HPC) and Prasugrel Single Antiplatelet Therapy for the Treatment of Unruptured Anterior Circulation Aneurysms: Safety Data and Short-term Occlusion Rates.
To assess the safety and short-term occlusion rates in procedures using the p64 MW hydrophilic polymer-coated (HPC) flow diverter (FD) with prasugrel single antiplatelet therapy (SAPT) for the treatment of anterior circulation saccular aneurysms. We retrospectively identified patients who underwent treatment of one or more intracranial anterior circulation saccular aneurysms between March 2020 and December 2021 with a p64 MW HPC FD and prasugrel SAPT with verified P2Y12 platelet receptor inhibition. Patients diagnosed with fusiform, dissecting, or recently ruptured aneurysms were excluded. Periprocedural and postprocedural complications, clinical outcomes, and angiographic follow-up results were evaluated. One hundred and two patients with 132 intracranial aneurysms met the inclusion criteria. Previous or concomitant treatments (e.g., coil occlusion) had been performed on 18 of these aneurysms. The technical success rate (i.e., implantation of the intended FD) was 100% with an average of 1.1 devices implanted per patient. Periprocedural and postprocedural complications occurred in 13.6% and 6.8% of these patients, respectively. No mortality or permanent clinical deterioration (i.e., modified Rankin scale score ≥ 3) were reported. Early follow-up digital subtraction angiography revealed aneurysmal occlusion rates of 72.6% and 83.8% at four and nine months, respectively. The implantation of a p64 MW HPC FD with prasugrel SAPT is safe and results in rapid, reliable and effective aneurysmal occlusion.


Foxo1-mediated inflammatory response after cerebral hemorrhage in rats.
The forkhead box O (Foxo) family of transcription factors plays a crucial role in cell apoptosis, immune regulation, and tissue development. Foxo1, as the foremost member of the Foxo family, regulates a wide range of molecular signals in many tissues, including tumor, liver, and brain. This study investigated Foxo1 expression at different time points and in different brain areas, and the role of Foxo1 in vivo in regulating inflammatory injury in a rat model of autologous blood-injected cerebral hemorrhage injury. We found that Foxo1 expression peaked at 12h post-intracerebral hemorrhage (ICH) and in the ipsilateral corpus striatum. Foxo1 knockdown by Foxo1 siRNA decreased ICH injury, improved neurological function, and decreased the expression of inflammatory factors downstream of the Foxo1 pathway, including TLR4, NF-κB, TNF-α, IL-1β, and IL-18. Foxo1 knockdown also decreased the expression and activity of myeloperoxidase, IL-1β, and IL-18. In conclusion, our findings demonstrate that Foxo1 is a key regulator of inflammatory injury in rats after ICH. By identifying the molecular mechanisms of Foxo1/TLR4/NF-κB signaling, we provide a novel rationale for therapeutic approaches to managing inflammatory injury after ICH.


Standardized reporting of histological diagnoses for non-neoplastic liver conditions in needle biopsies.
The importance of standardizing surgical pathology reports is emerging from the literature. The use of checklists has recently been proposed for diagnosing the major tumour types, but no attention has been given to non-neoplastic conditions. In this paper a checklist for standard reports of liver needle biopsies for non-neoplastic conditions is presented.


Cross-National Variation in Glycemic Control and Diabetes-Related Distress Among East Asian Patients Using Insulin: Results from the MOSAIc Study.
Guidelines recommend insulin progression for patients with type 2 diabetes (T2D) with inadequate glycemic control. The Multinational Observational Study Assessing Insulin use (MOSAIc [ClinicalTrials.gov identifier, NCT01400971]) study is a 2-year observational study, investigating factors that influence insulin progression in T2D patients. In this first of two reports, we describe baseline clinical and psychosocial characteristics of Chinese, Japanese, and South Korean patients who participated in MOSAIc. Insulin treatment, factors affecting progression, and outcomes will be reported separately. Patients with T2D using insulin for ≥3 months were eligible. Baseline demographic, clinical, and psychosocial data were collected from patients. Quality of life instruments, including the Diabetes Distress Scale (DDS), were used to assess patient's concerns about disease management, support, and emotional burden. The association between the DDS and the selected covariates was also assessed. A total of 373 patients in China, 157 in Japan, and 141 in South Korea were enrolled from July 2011 to July 2013. Mean ± standard deviation duration (years) of T2D differed across countries (China 11.4 ± 7.5; Japan 13.8 ± 8.7; South Korea 15.7 ± 8.8; P < 0.0001). Japanese patients used more noninsulin anti-hyperglycemic agents than did Chinese or South Korean patients (P < 0.0001). Exclusive use of basal insulin was most common in Japan and South Korea compared with China, whereas approximately 66.8% of Chinese patients used mixed insulin. Covariates associated with the DDS were younger age [P = 0.044 (Japan)], higher incidence of monthly hypoglycemia [P = 0.036 [China]; P = 0.021 (South Korea)], and male gender [P = 0.037 (South Korea)]. There were significant differences amongst East Asian patients with T2D treated with insulin, including in quality of life scores. Results from the MOSAIc longitudinal analyses will further investigate trends of insulin intensification and barriers to insulin progression. Eli Lilly and Company.


Growth and hormonal profile from birth to adolescence of a girl with aromatase deficiency.
Aromatase deficiency is a rare autosomal recessive disorder caused by mutations in the CYP19A1 gene and characterized by lack of conversion of androgens to estrogens. It presents with virilization of pregnant mothers during the antenatal period, and virilization of female fetuses at birth. Affected subjects of either gender later manifest with features of estrogen deficiency and androgen excess. We describe the clinical course of an Indian girl with aromatase deficiency from birth to 16 years of age. Estrogen replacement was begun at age 13.5 years. The child's growth, hormonal, radiological, and metabolic parameters were monitored throughout the course of treatment. The child presented with obesity, tall stature, delayed bone age, osteoporosis, hyperinsulinemia with acanthosis nigricans, and hypergonadotropic hypogonadism with cystic ovaries. Estrogen replacement resulted in a plateauing of height, improvement of bone maturation, and pubertal progression with the disappearance of ovarian cysts. However, hyperinsulinemia and acanthosis nigricans persisted despite estrogen replacement and metformin. Genetic analysis revealed a homozygous arginine to cysteine substitution at codon 435 in exon 10 of CYP19A1. This is the first case of aromatase deficiency reported from India. This case highlights the role of estrogen in skeletal maturation and mineralization and the effect of estrogen deficiency and androgen excess over glucose metabolism in adolescent females.


Community Reintegration After Rehabilitation for Hip Fracture: A Systematic Review and Meta-analysis.
To investigate the effect of rehabilitation on the physical, social, and psychological dimensions of community reintegration after hip fracture. Electronic databases Embase, EMCare, MEDLINE, PsycINFO, Cumulative Index to Nursing and Allied Health, and SPORTDiscus were searched from the earliest date available to second June 2021. Searching identified 1844 potentially relevant articles. Twenty randomized controlled trials evaluating physical retraining, cognitive retraining, and model of care interventions on physical, social and psychological aspects of community reintegration for 3075 adults after hip fracture were included. Data were extracted using predetermined templates for participant characteristics, intervention type and setting, and outcomes related to community reintegration. Methodological quality was assessed using the Physiotherapy Evidence Database scale, and the Grading of Recommendations, Assessment, Development, and Evaluations approach was applied to each meta-analysis. Post intervention data were pooled to calculate risk ratios (RRs), mean differences, standardized mean differences, and 95% confidence intervals (CIs) using inverse variance methods and a random-effects model. Compared with usual care or no rehabilitation, there was moderate-quality evidence to suggest that physical retraining interventions improved outdoor mobility (RR, 1.45; 95% CI, 1.09-1.91; I2=0%) and moderate-quality evidence to suggest that physical retraining improved Nottingham Extended Activities of Daily Living Scale scores (physical and social reintegration) by a mean 3.5 units (95% CI, 0.99-6.01; I2=0%). Meta-analyses showed no significant effect for cognitive retraining and model of care interventions on any dimension of community reintegration. Preliminary evidence suggests that physical rehabilitation after hip fracture improves physical and social aspects of community reintegration. The effect of psychological and home-based interventions on community reintegration is currently unclear. Further research is needed to determine the effect of rehabilitation on community reintegration, using interventions and measures that encompass all dimensions of community reintegration.


Non-enzymatic glycation of antithrombin III in vitro.
Non-enzymatic glycation of antithrombin III (AT-III) has been proposed as a significant contributor to the increased incidence of thrombo-occlusive events in diabetics. AT-III, isolated from normal human plasma by means of heparin affinity and ion-exchange chromatography, was incubated with 0-0.5 M glucose in neutral phosphate buffer at 37 degrees C. The extent of non-enzymatic glycation could be monitored by uptake of radioactivity as well as by binding to a phenylboronate affinity resin, which effectively retards AT-III containing ketoamine-linked glucose. Non-enzymatically glycated AT-III (approx. 1 mol glucose/mol protein) bound heparin nearly as efficiently as non-glycated AT-III. The two AT-III preparations were equally active in inhibiting thrombin cleavage of chromogenic substrate. Following incubation with [14C]glucose, structural analyses of cyanogen-bromide-cleaved peptides of enzymatically glycated AT-III showed that the [14C]glucose adducts were distributed over many sites on the molecule. This lack of specificity contrasts with the restricted sites of modification on hemoglobin, albumin and ribonuclease A, and explains why non-enzymatic glycation of AT-III has little if any effect on its function.


Delorme's operation and sphincteroplasty for rectal prolapse and fecal incontinence.
Clinical and manometric results of Delorme's operation and sphincteroplasty were assessed retrospectively in patients undergoing this procedure for fecal incontinence and rectal prolapse. A series of 33 patients (11 males, 22 females; aged 18-83 years, mean 59) with external rectal prolapse were treated by Delorme's operation between 1989 and 1996. Mean follow-up was 39 months (range 7-84). Sphincteroplasty was associated in 12 cases with severe fecal incontinence due to striated muscle defects. Good results were achieved in 27 patients (79%); prolapse recurrence was observed in 6 (21%), the mean recurrence time being 9 months (range 1-24 months). There were no postoperative deaths. Minor complications occurred in 15 patients. Changes in preoperative and postoperative manometric patterns were as follows (mean +/- SEM): voluntary contraction from 59 +/- 6.9 to 66 +/- 7.1 mmHg (P = 0.05), resting tone from 33 +/- 5 to 32 +/- 4.3 mmHg, rectal sensation from 59 +/- 5 to 61 +/- 5.2 ml of air (n.s.). A solitary rectal ulcer syndrome was detected in five patients. The histological pattern demonstrated pathological changes in 40% of cases. Fecal incontinence was resolved in 6 of 20 cases (30%) and chronic constipation in 4 of 9 (44%). Failure (n = 3) was related primarily to postoperative sepsis. The incontinence score showed a mean improvement of 35% decreasing, from 4.5 +/- 0.39 to 2.9 +/- 0.44 after surgery (P < 0.01). In conclusion, Delorme's procedure did not lead to constipation and improved anal continence when associated with sphincteroplasty.


Monoclonal antibodies to intermediate filaments in chick muscle cell cultures.
Two monoclonal antibodies, FIFI and PHIL, have been prepared using detergent-washed myogenic cells as immunogen. On Western blots of total protein extracts of muscle cells, both antibodies bind to vimentin (52 kD) and its degradation products (major band at 42 kD), but do not bind to mouse proteins or to actin (42 kD). Specificity for a determinant common to vimentin and desmin was confirmed by 2-D gel electrophoresis of muscle cell extracts and purified desmin. Western blots with FIFI reveal particularly well the extreme sensitivity of intermediate filaments (IFs) to proteolysis, which was preventable in brain tissue only by boiling in 1% SDS, although it could be reduced in both brain and muscle by less extreme methods. Western blots suggest a large increase in IF content of differentiating myoblast cell cultures at the time of cell fusion and an increase of at least 4-fold is confirmed by a quantitative immunoassay using a direct ELISA method. Immunofluorescence microscopy shows that this increase is due to the appearance of high concentrations of the intermediate filament antigen at the ends of early myotubes, preceding the appearance of cross-striations in myofibrils. Furthermore, whereas the polar filaments detected by FIFI run right to the ends of the early myotubes and only sparingly penetrate the central area, cross-striated myofibrils (as detected by the monoclonal antibody, SAM) run the length of the myotube but do not reach the ends. Colcemid and colchicine cause the vimentin filaments in fibroblasts to collapse into perinuclear rings or caps, but do not have this effect on the polar fluorescence in early myotubes. Heat shock (2 h at 45 degrees C) has a similar differential effect. The results suggest that early in muscle differentiation intermediate filament proteins accumulate rapidly at myotube ends, where they are organized differently from those in fibroblasts.


Venetoclax imparts distinct cell death sensitivity and adaptivity patterns in T cells.
BH3 mimetics are increasingly used as anti-cancer therapeutics either alone or in conjunction with other chemotherapies. However, mounting evidence has also demonstrated that BH3 mimetics modulate varied amounts of apoptotic signaling in healthy immune populations. In order to maximize their clinical potential, it will be essential to understand how BH3 mimetics affect discrete immune populations and to determine how BH3 mimetic pressure causes immune system adaptation. Here we focus on the BCL-2 specific inhibitor venetoclax (ABT-199) and its effects following short-term and long-term BCL-2 blockade on T cell subsets. Seven day "short-term" ex vivo and in vivo BCL-2 inhibition led to divergent cell death sensitivity patterns in CD8+ T cells, CD4+ T cells, and Tregs resulting in shifting of global T cell populations towards a more memory T cell state with increased expression of BCL-2, BCL-XL, and MCL-1. However, twenty-eight day "long-term" BCL-2 blockade following T cell-depleted bone marrow transplantation did not lead to changes in the global T cell landscape. Despite the lack of changes in T cell proportions, animals treated with venetoclax developed CD8+ and CD4+ T cells with high levels of BCL-2 and were more resistant to apoptotic stimuli following expansion post-transplant. Further, we demonstrate through RNA profiling that T cells adapt while under BCL-2 blockade post-transplant and develop a more activated genotype. Taken together, these data emphasize the importance of evaluating how BH3 mimetics affect the immune system in different treatment modalities and disease contexts and suggest that venetoclax should be further explored as an immunomodulatory compound.


Overlap of allergic, eosinophilic and type 2 inflammatory subtypes in moderate-to-severe asthma.
Current biologic therapies target allergic, eosinophilic or type 2 inflammation phenotypic asthma. However, frequency and degree of overlap among these subtypes is unclear. To characterize overlap among allergic, eosinophilic and type 2 asthma phenotypes. Post hoc analyses of baseline data were performed in two adult populations: (a) not selected for any asthma subtype (N = 935) and (b) selected for allergic asthma (N = 1049). Degree of overlap was examined using commonly accepted phenotypic definitions to guide treatment for allergic asthma (skin prick-positive and/or positive serum-specific immunoglobulin E > 0.35 kU/L) and eosinophilic asthma (blood eosinophil high count ≥ 300 cells/µL; low cut-off ≥ 150 cells/µL). Consistent with previous studies, fractional exhaled nitric oxide high level of ≥ 35 ppb and low cut-off of ≥ 25 ppb were selected as local markers of type 2 inflammation and to prevent overlap with the systemic eosinophilic asthma definition. In the non-subtype-selected population, 78.0% had allergic asthma; of these, 39.5% had eosinophilic asthma and 29.5% had type 2 asthma. Within patients with eosinophilic asthma (40.6% of total), 75.8% had allergic asthma and 41.3% had type 2 asthma. Within patients with type 2 asthma (28.3% of total), 81.1% had allergic asthma and 59.2% had eosinophilic asthma. In the allergic asthma-selected population, 38.3% had eosinophilic asthma and 29.2% had type 2 asthma. Within patients with eosinophilic asthma, 46.3% had type 2 asthma. Within patients with type 2 asthma, 60.8% had eosinophilic asthma. Overlaps among subtypes increased at low cut-off values. In this post hoc analysis in adults with moderate-to-severe asthma, allergic asthma was the most prevalent phenotype, followed by eosinophilic and type 2 asthma. Despite observed overlaps, a considerable proportion of patients had only a predominantly allergic subtype. Understanding the degree of overlap across phenotypes will help patient management and guide treatment options.