A unifying hypothesis of sodium and water regulation in health and disease.
Sodium and water retention is characteristic of edematous disorders including cardiac failure, cirrhosis, nephrotic syndrome, and pregnancy. In recent years, the use of a sensitive radioimmunoassay for plasma vasopressin has implicated the role of nonosmotic vasopressin release in the water retention of these edematous disorders. In experimental studies and studies in man, it has been found that the nonosmotic release of vasopressin is consistently associated with the activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. Moreover, the sympathetic nervous system has been shown to be involved in the nonosmotic release of vasopressin (carotid and aortic baroreceptors) and in the activation of the renin-angiotensin system (renal beta-adrenergic receptors). These findings have led to our proposal that body fluid volume regulation involves the dynamic interaction between cardiac output and peripheral arterial resistance. In this context, neither total extracellular-fluid (ECF) volume nor blood volume are determinants of renal sodium and water excretion. Rather, renal sodium and water retention is initiated by either a fall in cardiac output (e.g. ECF volume depletion, low-output cardiac failure, pericardial tamponade, or hypovolemic nephrotic syndrome) or peripheral arterial vasodilation (e.g. high-output cardiac failure, cirrhosis, pregnancy, sepsis, arteriovenous fistulae, and pharmacologic vasodilators). With a decrease in effective arterial blood volume (EABV). initiated by either a fall in cardiac output or peripheral arterial vasodilation, the acute response involves vasoconstriction mediated by angiotensin, sympathetic mediators, and vasopressin. The slower response to restoring EABV involves vasopressin-mediated water retention and aldosterone-mediated sodium retention. The renal vasoconstriction which accompanies those states that decrease EABV, by either decreasing cardiac output or causing peripheral arterial vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)


Plasminogen activator inhibitor type 1: cell-specific and differentiation-induced expression and regulation in human cell lines, as determined by enzyme-linked immunosorbent assay.
We have performed a comparative study of the regulation by glucocorticoids and phorbol 12-myristate 13-acetate (PMA) of the production of type 1 plasminogen activator inhibitor (PAI-1) by 12 human cell lines. A sandwich-type enzyme-linked immunosorbent assay (ELISA) for PAI-1 that measures free PAI-1 as well as complexes between PAI-1 and both types of plasminogen activators has been used. Basal PAI-1 accumulation varied more than 5000-fold between the cell lines. No correlation was found between the PAI-1 level and other characteristics of the cell lines, except that three lines of SV40-transformed fibroblasts produced more PAI-1 than two non-transformed fibroblast cell lines. Three out of the 12 cell lines responded to glucocorticoids by an increased PAI-1 production. Four cell lines responded to PMA by an increased PAI-1 production. In addition, PMA-induced differentiation of the monocyte cell line U937 and the promyelocytic cell line HL-60 into macrophage-like cells was found to be correlated with an up to 100-fold increase in PAI-1 accumulation. The PMA-dependent differentiation of HL-60 cells led to acquisition of glucocorticoid inducibility of PAI-1. These findings provide information for future studies of the molecular mechanism of cell-specific expression and regulation of PAI-1.


Culture of rat retina pigmented epithelial cells.
Retinal pigment epithelium cells play a key role in maintaining the normal function of retina and can express several neurotrophic factors, which support the neurosensory retina and may also provide trophic signals to the host dopaminergic neurons. The following chapter describes a protocol for the purification and culture of retinal pigmented epithelial cells from postnatal rat.


Immune response induced by recombinant pres2/S-protein and a pres2-S-protein fused with a core 18-27 antigen fragment of hepatitis B virus compared to conventional HBV vaccine.
Although comprehensive vaccination is the cornerstone of public health programs to control hepatitis B virus (HBV) infections, 5% of people who receive the existing vaccine do not develop proper immunity against HBV. To overcome this challenge, researchers have tried using various protein fragments encoded by the virus genome to achieve better immunization rates. An important antigenic component of HBsAg called the preS2/S or M protein has also received much attention in this area. The gene sequences of preS2/S and Core18-27 peptide were extracted from the GenBank (NCBI). Final gene synthesis was conducted with pET28. Groups of BALB/c mice were immunized with 10 μg/ml of recombinant proteins and 1 μg/ml CPG7909 adjuvant. Serum levels of IF-γ, TNF-α, IL-2, IL-4, and IL-10 were measured by ELISA assay method on spleen cell cultures on day 45, and IgG1, IgG2a, and total IgG titers obtained from mice serum were quantified on days 14 and 45. Statistical analysis did not show any significant difference between the groups regarding IF-γ level. There were, however, significant differences in terms of IL-2 and IL-4 levels between the groups receiving preS2/S-C18-27 with and without adjuvant and the groups receiving both preS2/S and preS2/S-C18-27 (Plus Recomb-Plus Recomb: the group of mice that received both preS2/S and preS2/S-C18-27 simultaneously). The strongest total antibody production was induced by immunization with both recombinant proteins without CPG adjuvant. The groups that received both preS2/S and preS2/S-C18-27, whether with or without adjuvant, were significantly different from those that received the conventional vaccine considering most abundant interleukins. This difference suggested that higher levels of efficacy can be achieved by the use of multiple virus antigen fragments rather than using a single fragment.


Expression of gelatinase/type IV collagenase in tumor necrosis correlates with cell detachment and tumor invasion.
We have previously observed that acellular extracts from necrotic areas (NE) of the non-metastatic murine mammary adenocarcinoma M3, enhance in vitro cell detachment and spontaneous lung metastases. In the present study, using different proteinase inhibitors along with NE, only the calcium chelator EDTA could significantly abrogate the enhanced cell detachment from M3 produced by NE. The typical cleavage products of type IV collagenase were detected inside the tumor necrotic area, mainly in association with necrobiotic cells, as evaluated by Western blot analysis and immunohistochemical assays. Zymography revealed the presence of 72- and 92-kDa gelatinase/type IV collagenase in NE. Moreover, NE increased the in vitro invasive ability of cultured M3 cells. The use of specific antibodies against both 72- and 92-kDa type IV collagenases in the invasion assay showed that only the latter was able to revert the enhanced invasiveness to the baseline. It can be concluded that tumor necrosis is an important source of gelatinase/type IV collagenase, mainly in its 92 kDa form, and plays a major role in tumor invasion.


Heterogeneity of tau proteins in Alzheimer's disease. Evidence for increased expression of an isoform and preferential distribution of a phosphorylated isoform in neurites.
PHF-tau, a modified form of tau in Alzheimer diseased brains, is composed of proteins of molecular weight 68, 64, and 60 kd. The 68-kd PHF-tau has been reported to be encoded by a tau transcript containing both exons 2 and 3. The 64-kd protein contains exon 2, but not exon 3, and the 60-kd protein contains neither exons 2 nor 3. To study the proportion of different tau isoforms in PHF-tau and normal tau, we raised antibodies to exon 2 (E-2) and exon 3 (E-3). By immunoblots, about 74% of the PHF-tau contained exon 2, and 25% contained exon 3; whereas in normal tau, 82 to 90% contained exon 2, and no more than 5% contained exon 3. Enzyme-linked immunosorbent assays demonstrated that PHF-tau was 38% less reactive with E-2 and 79% more reactive with E-3 than normal tau. Alkaline phosphatase treatment increased the E-2 immunoreactivity of PHF-tau by 120% and normal tau by 38%, but it had no effect on E-3 immunoreactivity. The dephosphorylated PHF-tau and normal tau were similar in E-2 immunoreactivities. Phosphatase treatment of Alzheimer's diseased brain sections increased the number of E-2 immunoreactive neuropil threads and senile plaque neurites but had very little effect on the number of immunoreactive neurofibrillary tangles. The results suggest that PHF-tau contains proportionally more isoforms with E-3 than normal tau; that the E-2 epitope is more phosphorylated in PHF-tau than in normal tau; and that the phosphorylated E-2 epitope of PHF-tau is preferentially located in neurites.


Genomic sequence analysis and organization of BmKalphaTx11 and BmKalphaTx15 from Buthus martensii Karsch: molecular evolution of alpha-toxin genes.
Based on the reported cDNA sequences of BmKalphaTxs , the genes encoding toxin BmKalphaTx11 and BmKalphaTx15 were amplified by PCR from the Chinese scorpion Buthus martensii Karsch genomic DNA employing synthetic oligonucleotides. Sequences analysis of nucleotide showed that an intron about 500 bp length interrupts signal peptide coding regions of BmKalphaTx11 and BmKalphaTx15. Using cDNA sequence of BmKalphaTx11 as probe, southern hybridization of BmK genome total DNA was performed. The result indicates that BmKalphaTx11 is multicopy genes or belongs to multiple gene family with high homology genes. The similarity of BmKalpha-toxin gene sequences and southern hybridization revealed the evolution trace of BmKalpha-toxins: BmKalpha-toxin genes evolve from a common progenitor, and the genes diversity is associated with a process of locus duplication and gene divergence.


Ecological implication of variation in the secondary metabolites in Parmelioid lichens with respect to altitude.
Lichens are known to synthesize a variety of secondary metabolites having multifunctional activity in response to external environmental condition. Two common lichen extrolites, atranorin and salazinic acid, are known to afford antioxidant as well as photoprotectant nature depending on the abiotic/biotic stress. The present investigation aims to study the influence of altitudinal gradient on the quantitative profile of atranorin and salazinic acid in three lichen species, Bulbothrix setschwanensis (Zahlbr.) Hale, Everniastrum cirrhatum (Fr.) Hale and Parmotrema reticulatum (Taylor) Choisy, Parmeliaceae using liquid chromatography-mass spectrometry (LC-MS/MS) technique. Samples were collected from high-altitude area, usually considered as non-polluted sites of Garhwal Himalaya. Characterization and quantification of the lichen substances in samples were carried out comparing with the standards of atranorin and salazinic acid. Results indicated significant variation in the chemical content with the rising altitude. All the three lichen species showed higher quantities of chemical substances with the altitudinal rise, while among the three lichen species, E. cirrhatum showed the highest quantity of total lichen compounds. The higher abundance and frequency of E. cirrhatum with increasing altitude as compared to B. setschwanensis and P. reticulatum may be attributed due to the presence of higher quantity of photoprotecting/antioxidant chemicals especially salazinic acid. Thus, the present study shows the prominent role of secondary metabolite in wider ecological distribution of Parmelioid lichens at higher altitudes.


Selective capture of Salmonella enterica serovar typhi genes expressed in macrophages that are absent from the Salmonella enterica serovar Typhimurium genome.
Thirty-six Salmonella enterica serovar Typhi-specific genes, absent from the Salmonella enterica serovar Typhimurium genome, that were expressed in human macrophages were identified by selective capture of transcribed sequences. These genes are located on 15 unique loci of the serovar Typhi genome, including Salmonella pathogenicity islands (SPI-7, SPI-8, and SPI-10) and bacteriophages (ST15, ST18, and ST35).


Platelet transfusion reaction associated with interdonor HLA incompatibility.
An HLA-compatible platelet transfusion was followed by chills, fever, and severe respiratory distress in a multitransfused patient with chronic lymphocytic leukemia. During the previous 7 days the patient had received blood products without incident, including 8 units of red blood cells (RBC), 24 units of pooled random donor platelet concentrates, and five HLA-compatible platelet pheresis products. The patient had no demonstrable RBC, HLA lymphocytotoxic, platelet or granulocyte antibodies. The platelet donor, a multiparous female, had no granulocyte or RBC antibodies but had lymphocytotoxic antibodies against HLA-A2 CREG (cross-reacting group A2, A28, A23, A24) which reacted not with lymphocytes of the patient but with lymphocytes of the donor whose RBC were transfused 24 h prior to the platelet transfusion reaction and whose HLA type is A23, A24; B44, B57. No RBC donors had HLA lymphocytotoxic, granulocyte, or platelet antibodies against the platelet donor. The patient received three subsequent platelet transfusions from the same donor after removal of the antibody-laden plasma with no adverse reaction. These data suggest an interdonor reaction caused by the presence of cells from the RBC donor received by the patient 24 h prior to the transfusion of donor lymphocytotoxic antibody to HLA-A2 CREG antigens.


Perceptual asymmetry in schizophrenia and affective disorder: implications from a right hemisphere task.
The patterns of perceptual asymmetry exhibited by normal, schizophrenic, and affectively-disordered subjects on a dichotic tonal discrimination task, were compared. Affectively-disordered subjects' performances differed significantly from those of normal subjects, with normals demonstrating the expected left ear advantage, and affectively-disordered subjects showing no lateral advantage. The performance of the schizophrenic subjects fell between those of the normal and affective groups along a laterality continuum, with paranoid schizophrenic subjects tending to show a larger left ear advantage than non-paranoid schizophrenic subjects. The results do not support the hypothesis that schizophrenic subjects inappropriately transfer processing of right hemisphere stimuli to the left hemisphere, but do suggest that subgroup distinctions may be relevant to hypotheses of lateralized dysfunction in schizophrenia. Further, the performance of the affective group supports previous findings of right hemisphere abnormalities in affective disorder.


Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces the change of calcium mobilization via TRPC ion channels in cultured human corporal smooth muscle cells.
Hypercholesterolemia is a major risk factor for erectile dysfunction. To understand the mechanism(s) of hypercholesterolemia-induced erectile dysfunction, we studied the effect of lysophosphatidylcholine (LPC) on the membrane conductance of corporal smooth muscle cells. We used cultured human corporal smooth muscle cells. The intracelluar Ca2+ concentration ([Ca2+]i) and the influx of divalent cation was monitored by the ratio of fura-2 fluorescence (F(340/380)) and by the Mn2+-induced quenching rate of fura-2, respectively. The LPC-induced membrane current was characterized by the whole-cell patch-clamp technique and the molecular identity of suspected channels was probed by RT-PCR. LPC (20 microM) induced a statistically significant increase in F(340/380) to 119.9+/-3.9% of initial control (n=6) in corporal smooth muscle cells. The addition of 20 microM LPC accelerated the quenching rate of F360 by 59.5+/-11.8% (n=5). LPC activated nonselective cationic current (ILPC), similar to the known effects of phenylephrine in corporal myocytes. The size of ILPC at -60 mV was -55.3+/-6.3 pA (n=8). The transcript of transient receptor potential channel 6 (TRPC6) was detected in human corporal myocytes. We also found one splicing variant of TRPC6, TRPC6alpha. In conclusion, the present study suggests that the LPC, a major component of oxidized low-density lipoprotiens, increases calcium in corporal smooth muscle cells probably through activation of a TRPC6 channel and the increased [Ca2+]i by LPC via TRP channels is one of mechanisms for hypercholesterolemia-induced erectile dysfunction.


Cadralazine challenge in patients with previous hydralazine-induced lupus: a 6-month study.
The objective of this study was to investigate the effect of cadralazine in patients who had previously had hydralazine-induced lupus. There were 11 patients included in the study, 10 of whom were treated for 6 months with 15 or 20 mg cadralazine given once daily in combination with beta-blockers and diuretics. All patients had a history of hydralazine-induced lupus and were slow acetylators. None of the patients included in this study showed any current signs or symptoms of drug-induced lupus. No evidence of lupus-like symptoms or of immunologic laboratory abnormalities were found during the study period. Side effects associated with vasodilator therapy were noted in some patients but were transient and mild. We concluded that a cross-reaction between cadralazine and hydralazine does not seem likely to occur and that cadralazine, because of its chemical properties, probably will not give rise to drug-induced lupus.


Research on the drought index of irrigation district with multi-time scales.
The empirical mode decomposition method is applied to analyze fluctuating periods and local features of the annual drought index and the drought index in the irrigation and non-irrigation periods from 1956 to 2010 in the Yinchuan irrigation district. In order to understand the uncertainty between these variables, the set pair analysis method is used to present the identity, discrepancy, and contrary of the drought index with multi-time scales. The results reveal that the annual drought index and the drought index in the irrigation and non-irrigation periods have a complex relationship which may be related to El Niño, the air-sea intersection, and the long period of solar activity. The drought index in the irrigation and non-irrigation periods presents mainly the contrary and the discrepancy; the fluctuating shapes of the annual drought index and drought index in the irrigation period are the same on their different period levels. The original annual drought index and its intrinsic mode function components have a certain connection degree; they mainly present the discrepancy.


Overexpression of progesterone receptor membrane component 1: possible mechanism for increased breast cancer risk with norethisterone in hormone therapy.
Clinical trials have demonstrated an increased risk of breast cancer during estrogen/norethisterone (NET) therapy. With this in mind, the effects of estrogen/NET combination on the proliferation of breast cancer cells overexpressing the progesterone receptor membrane component 1 (PGRMC1) were examined. The same combination was used for the first time in a mouse xenograft model to determine its effects on tumor development. MCF-7 cells were stably transfected with PGRMC1 expression plasmid (WT-12 cells) or empty vector control (pcDNA-3HA). NET, medroxyprogesterone acetate (MPA), and progesterone were tested alone and sequentially and continuously combined with estradiol (E2). Six-week-old nude mice were inoculated with E2 pellets 24 hours before the injection of tumor cells into both flanks (n = 5-6 mice per group). After 8 days, animals were inoculated with a NET pellet or with placebo pellets, and tumor volumes were recorded twice a week. NET alone significantly increased the proliferation of WT-12 cells, MPA was effective only at the two highest concentrations, and progesterone had no effect. The twofold to threefold E2-induced increase (10 M) was not significantly influenced by the addition of the various progestogens. In contrast, 10 M E2 had no effect; however, addition of MPA and NET triggered a significant proliferative response. In vivo, a sequential combination of NET and E2 also significantly increased the tumor growth of WT-12 cells; empty vector cells did not respond to NET. We have demonstrated for the first time that an E2/NET combination increases the proliferation of PGRMC1-overexpressing breast cancer cells, both in vivo and in vitro. Our results suggest that undetected tumor cells overexpressing PGRMC1 may be more likely to develop into frank tumor cells in women undergoing E2/NET hormone therapy.


Comparison of amplitude recovery dynamics of two limit cycle oscillator models of the human circadian pacemaker.
At an organism level, the mammalian circadian pacemaker is a two-dimensional system. For these two dimensions, phase (relative timing) and amplitude of the circadian pacemaker are commonly used. Both the phase and the amplitude (A) of the human circadian pacemaker can be observed within multiple physiological measures--including plasma cortisol, plasma melatonin, and core body temperature (CBT)--all of which are also used as markers of the circadian system. Although most previous work has concentrated on changes in phase of the circadian system, critically timed light exposure can significantly reduce the amplitude of the pacemaker. The rate at which the amplitude recovers to its equilibrium level after reduction can have physiological significance. Two mathematical models that describe the phase and amplitude dynamics of the pacemaker have been reported. These models are essentially equivalent in predictions of phase and in predictions of amplitude recovery for small changes from an equilibrium value (A = 1), but are markedly different in the prediction of recovery rates when A < 0.6. To determine which dynamic model best describes the amplitude recovery observed in experimental data; both models were fit to CBT data using a maximum likelihood procedure and compared using Akaike's Information Criterion (AIC). For all subjects, the model with the lower recovery rate provided a better fit to data in terms of AIC, supporting evidence that the amplitude recovery of the endogenous pacemaker is slow at low amplitudes. Experiments derived from model predictions are proposed to test the influence of low amplitude recovery on the physiological and neurobehavioral functions.


A personal experience in comparing three nonoperative techniques for treating internal hemorrhoids.
Infrared photocoagulation therapy was used on a total of 302 patients. Approximately 20% of the patients experienced minor bleeding; however, two required surgery, and 30% of the patients experienced discomfort during a 14-day period following the procedure. Good results were obtained in patients with first- and second-degree hemorrhoids. Heater probe coagulation therapy was conducted in a total of 264 patients. Good results were achieved in 90% of patients with first- and second-degree hemorrhoids, minor pain and bleeding occurred in approximately 10% of these patients, and one patient with third-degree hemorrhoids who was treated with this technique failed to respond and required surgery. Ultroid d.c. current therapy was utilized in 192 patients, and follow-up results were good in 95% of these cases. Minor bleeding occurred in four patients. It is concluded that all three techniques, performed on an outpatient basis with little or no sedation, are effective modalities for first- and second-degree hemorrhoids, but that Ultroid d.c. current therapy is associated with less discomfort and fewer complications and that Ultroid therapy may yield good results in some patients with third- or even fourth-degree hemorrhoids.


Impact of type 2 diabetes mellitus on left ventricular deformation in non-ischemic dilated cardiomyopathy patients assessed by cardiac magnetic resonance imaging.
Type 2 diabetes mellitus (T2DM) increases the risk of worse long-term outcomes in patients with non-ischemic dilated cardiomyopathy (NIDCM). However, the additive effects of T2DM on left ventricular (LV) function in NIDCM remain unclear. Accordingly, we aimed to investigate the impact of comorbid T2DM on LV deformation in NIDCM individuals. Three hundred forty-two NIDCM patients without T2DM [NIDCM (T2DM-)], 93 with T2DM [NIDCM (T2DM+)] and 80 age- and sex-matched normal controls who underwent cardiac magnetic resonance scanning were included. LV geometry, function, and LV global strains, including peak strain (PS), peak systolic strain rate (PSSR) and peak diastolic strain rate (PDSR) in the radial, circumferential and longitudinal directions, were measured. NIDCM (T2DM+) patients were divided into two subgroups based on the HbA1c level (< 7.0% and ≥ 7.0%). The determinants of reduced LV myocardial strain for all NIDCM individuals and NIDCM (T2DM+) patients were assessed using multivariable linear regression analyses. Compared with normal controls, both NIDCM (T2DM -) and NIDCM (T2DM+) patients exhibited increased LV end-diastolic and end-systolic volume index and decreased LV ejection fraction. LV global strains progressively declined from the normal controls to the NIDCM (T2DM-) group to the NIDCM (T2DM+) group (all p < 0.017), except for radial PDSR and PSSR. Subgroup analysis showed that LV global radial PS and longitudinal PS, PSSR-L and PDSR-L were worse in NIDCM patients with poor glycemic control than in those with good glycemic control (p < 0.017). T2DM was an independent determinant of reduced LV global circumferential PS and longitudinal PS in patients with NIDCM (both p < 0.05). An increased HbA1c level was independently associated with a decreased global radial PS (β = - 0.285, p < 0.01) and longitudinal PS (β = 0.320, p < 0.01) in NIDCM (T2DM+) patients. T2DM has an additive deleterious effect on LV systolic and diastolic function in NIDCM patients. Among NIDCM patients with T2DM, HbA1c was found to be associated with reduced LV myocardial strain.


Psychotic-like reaction to procaine penicillin G.
A patient developed a psychotic-like reaction immediately after receiving an intramuscular injection of procaine penicillin G. The patient complained of a metallic taste, dizziness, ringing of the ears, and the fear of imminent death. No cardiovascular or pulmonary disturbances were noted. The reaction and all symptoms resolved within 15 minutes, and the patient has reported no further episodes. The case and a review of the literature are presented.


Identification and Expressional Analysis of Putative PRDI-BF1 and RIZ Homology Domain-Containing Transcription Factors in Mulinia lateralis.
Mollusca represents one of the ancient bilaterian groups with high morphological diversity, while the formation mechanisms of the precursors of all germ cells, primordial germ cells (PGCs), have not yet been clarified in mollusks. PRDI-BF1 and RIZ homology domain-containing proteins (PRDMs) are a group of transcriptional repressors, and PRDM1 (also known as BLIMP1) and PRDM14 have been reported to be essential for the formation of PGCs. In the present study, we performed a genome-wide retrieval in Mulinia lateralis and identified 11 putative PRDMs, all of which possessed an N-terminal PR domain. Expressional profiles revealed that all these prdm genes showed specifically high expression levels in the given stages, implying that all PRDMs played important roles during early development stages. Specifically, Ml-prdm1 was highly expressed at the gastrula stage, the key period when PGCs arise, and was specifically localized in the cytoplasm of two or three cells of blastula, gastrula, or trochophore larvae, matching the typical characteristics of PGCs. These results suggested that Ml-prdm1-positive cells may be PGCs and that Ml-prdm1 could be a candidate marker for tracing the formation of PGCs in M. lateralis. In addition, the expression profiles of Ml-prdm14 hinted that it may not be associated with PGCs of M. lateralis. The present study provides insights into the evolution of the PRDM family in mollusks and offers a better understanding of the formation of PGCs in mollusks.


Management of Pyogenic Spinal Infection, review of literature.
To evaluate the available evidence for the management of Pyogenic Spinal Infection (PSI). A comprehensive search for the relevant literature published between 1990 and 2018 to evaluate the management of PSI was conducted.Nonoperative management of carefully selected patients for an adequate duration of antibiotics can result in satisfactory outcomes with low recurrence rate. When there is an indication for surgery, posterior approach, with or without debridement of infected tissue reported to be associated with good outcomes. Studies with larger sample sizes and longer duration of follow up are recommended to formulate more comprehensive evidence.


Nonpenetrating glaucoma surgery.
Nonpenetrating glaucoma surgery continues to evolve and improve. New technical refinements and increased experience among its practitioners have led to improved efficacy and longer duration of filter survival. These refinements include the use of intraoperative and postoperative antimetabolites, adjunctive space-maintaining devices, and postoperative yttrium-aluminum-garnet laser goniopuncture. Deep sclerectomy and viscocanalostomy vary significantly in their surgical approaches and mechanisms of aqueous outflow. An understanding of the microanatomy of the aqueous outflow structures is necessary to gain surgical access to Schlemm's canal and to augment aqueous outflow surgically through the trabecular meshwork. Indications and contraindications for nonpenetrating glaucoma surgery are discussed.


Determining approximate size of maxillary anterior artificial teeth when mandibular anterior teeth are present. Part I: Size relationship.
Three methods were used to obtain a ratio of the maxillary to the mandibular anterior teeth, with results of 1.29, 1.30, and 1.31. It can be concluded that a ratio of 1.30 is sufficient to determine the approximate width of the six maxillary anterior teeth when given the size of the mandibular natural anterior teeth. This ratio should be valid to select a maxillary denture mold of sufficient width mesiodistally to obtain a Class I canine relationship. However, the ratio may need a slight adjustment to compensate for the intentional disocclusion of the maxillary denture teeth with the natural mandibular teeth. In Fig. 1 the canine to canine measurement of the mandibular anterior teeth was 35 mm; when multiplied by a factor of 1.30, a maxillary measurement of 45.5 mm is obtained. The denture teeth were to be set with approximately 1 mm of horizontal overjet and 1 mm of vertical overlap (Fig. 2), therefore a slightly larger mold of 48.5 mm was chosen (Fig. 3). This maxillary mold produced a Class I canine relationship (Fig. 4). The 48.5 mm ratio of the chosen maxillary mold to the mandibular measurement of 35 mm yielded a ratio of 1.38. When this ratio of 1.38 is applied, the desired prosthetic mold is not always available. There is a range of acceptability above and below the desired ratio.(ABSTRACT TRUNCATED AT 250 WORDS)


Association between elastography findings of the levator ani and stress urinary incontinence.
To investigate the elasticity of the levator ani musle (LAM) with the patients suffering from stress urinary incontinence (SUI) by transperineal elastography. Conventional transperineal ultrasound and elastography were performed in the patients with SUI on quiescent condition and maximal Valsalva. Transperineal ultrasound and elastography were repeated after Kegel exercises. The scoring system and strain ratio (SR) values were recorded and analyzed. After Kegel exercises, the ratio of subjective improvement or cure was 81 % (102/126). Mean elasticity score (ES) and SR of LAM were significantly higher than the value before on maximal Valsalva, respectively. Mean ES and SR of LAM after Kegel exercises were similar with the value before on quiescent condition, respectively. The improvement of SUI was associated with the stiffer LAM assessed by elastography. Women with SUI who have softer LAM were more likely to have symptoms of SUI and Kegel exercise could strengthen the stiffness of LAM. The improvement of SUI was associated with the stiffer LAM assessed by elastography.


Effects of a Subanesthetic Ketamine Infusion on Inflammatory and Behavioral Outcomes after Closed Head Injury in Rats.
Traumatic brain injury (TBI) affects millions of people annually, and most cases are classified as mild TBI (mTBI). Ketamine is a potent trauma analgesic and anesthetic with anti-inflammatory properties. However, ketamine's effects on post-mTBI outcomes are not well characterized. For the current study, we used the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA), which replicates the biomechanics of a closed-head impact with resulting free head movement. Adult male Sprague-Dawley rats sustained a single-session, repeated-impacts CHIMERA injury. An hour after the injury, rats received an intravenous ketamine infusion (0, 10, or 20 mg/kg, 2 h period), during which locomotor activity was monitored. Catheter blood samples were collected at 1, 3, 5, and 24 h after the CHIMERA injury for plasma cytokine assays. Behavioral assays were conducted on post-injury days (PID) 1 to 4 and included rotarod, locomotor activity, acoustic startle reflex (ASR), and pre-pulse inhibition (PPI). Brain tissue samples were collected at PID 4 and processed for GFAP (astrocytes), Iba-1 (microglia), and silver staining (axonal injury). Ketamine dose-dependently altered locomotor activity during the infusion and reduced KC/GRO, TNF-α, and IL-1β levels after the infusion. CHIMERA produced a delayed deficit in rotarod performance (PID 3) and significant axonal damage in the optic tract (PID 4), without significant changes in other behavioral or histological measures. Notably, subanesthetic doses of intravenous ketamine infusion after mTBI did not produce adverse effects on behavioral outcomes in PID 1-4 or neuroinflammation on PID 4. A further study is warranted to thoroughly investigate beneficial effects of IV ketamine on mTBI given multi-modal properties of ketamine in traumatic injury and stress.


Axon Guidance Studies Using a Microfluidics-Based Chemotropic Gradient Generator.
Microfluidics can be used to generate flow-driven gradients of chemotropic guidance cues with precisely controlled steepnesses for indefinite lengths of time. Neuronal cells grown in the presence of these gradients can be studied for their response to the effects exerted by the cues. Here we describe a polydimethylsiloxane (PDMS) microfluidics chamber capable of producing linear gradients of soluble factors, stable for at least 18 h, suitable for axon guidance studies. Using this device we demonstrate turning of superior cervical ganglion axons by gradients of nerve growth factor (NGF). The chamber produces robust gradients, is inexpensive to mass produce, can be mounted on a tissue culture dish or glass coverslip for long term time-lapse microscopy imaging, and is suitable for immunostaining.


Selective binding of CD4 and CD8 T-cells to antigen presenting cells for enrichment of CMV and HIV specific T-lymphocytes.
Adherent antigen presenting cells (APC) pulsed with protein or peptide antigens were used to capture specific CD4 or CD8 T-cells derived from established T-cell lines or from PBMC of immune subjects based on physiological interaction between TCR and MHC-peptide complex. This method could be applied independently of epitope specificity, HLA restriction alleles, activation markers and secreted cytokines, parameters required by other methods for selection of specific T cells. Non specific T-cells were removed by applying a 1g force that did not affect binding of specific T-lymphocytes. Lymphocyte selection was specific and the average recovery was 36% for CD4 T-cells. CD8 T-cells proved trickier to purify, since solid phase APC were recognized as targets for cytotoxicity. Specificity was comparable to CD4 cells, but the average recovery for CD8 cells was 26%. No residual alloreactivity was detected in expanded T-cells. Frequency and recovery of specific T-cells were comparable to other current technologies, such as generation of T-cell lines and cytokine capture method. Since antigen and IL2 are the only reagents added to the cultures, this physiological procedure can be proposed for selection and expansion of pathogen specific T-cells not only for research purposes, but also for adoptive reconstitution of immunocompromised subjects if performed under GMP conditions.


(Poly)phenol toxicity in vivo following oral administration: A targeted narrative review of (poly)phenols from green tea, grape, and anthocyanin-rich extracts.
Fruit- and vegetable-derived (poly)phenols are secondary plant metabolites that may have beneficial effects on human health when consumed regularly. Recent years have seen rapid growth in both consumer demand for and research interest in (poly)phenol-rich dietary supplements, natural colorants, and functional foods. As these products continue to enter the marketplace and (poly)phenol intake patterns change from traditional food products to these sources, attention must be paid to the potential for toxicity from consuming elevated doses of (poly)phenols. To date, much remains unknown regarding the safety of high doses of (poly)phenols, especially in vivo. In this targeted narrative review, we summarize evidence from in vivo investigations of (poly)phenol toxicity after oral administration of green tea extracts, grape-derived phenolics, and anthocyanin-rich extracts. There is limited evidence of overt toxicity from oral ingestion of these (poly)phenol-rich sources, though more research on the safety of high doses-as well as defining what constitutes a "high" dose of both individual and complex mixtures of (poly)phenols-is needed before these observations can be used to create dietary guidance for consumers.


Sister chromatid exchange and cell cycle patterns of normal human bone marrow cells after in vitro exposure to cytostatic drugs.
The effect of different cytostatic chemotherapeutic drugs on the frequency of sister chromatid exchanges and growth kinetics of the bone marrow cells in normal adults was studied by means of an in vitro bromodeoxyuridine chromosome labeling method. Cytosine arabinoside, harringtonine, methotrexate, vincristine, and 6-mercaptopurine were tested. Three of these agents induced significantly high frequency of sister chromatid exchange (p less than 0.01 or p less than 0.05). The sister chromatid exchange frequency induced by cytosine arabinoside and that induced by 6-mercaptopurine were higher than those of the control group. The increased frequency of sister chromatid exchange predominated in C and A group chromosomes. At the concentration adopted by the authors, the growth kinetics were little influenced by these drugs.


The role of estrogen as a parahormone in brain and pituitary.
Where aromatase and estrogen receptors are co-localized in brain and pituitary, estrogen functions as a parahormone, and estrogen levels which determine the occurrence or magnitude of a response are those in close proximity to targets. Teleost fish, a vertebrate group characterized by exceptionally high aromatase in neuroendocrine tissues, are technically advantageous animal models for studying the cellular location of aromatase, natural changes correlated with seasonal reproductive cycles, substrate-dependence of the reaction, steroid induction of enzyme activity, and possible non-genomic actions of estrogen on cultured neurons. In addition, characterization of steroid receptors reveals that the androgen receptor, like aromatase, is present in unusually high concentrations (10- to 100-fold higher than in mammalian brain). Since androgen receptors and aromatase both utilize testosterone as a ligand, their high abundance in teleost brain may be the consequence of a functional interdependence during evolution, although the primary causal factor is unknown. These studies illustrate the usefulness of unconventional species and a comparative approach for obtaining new insights into brain-steroid interactions.


Zebrafish Neuroscience: Using Artificial Neural Networks to Help Understand Brains.
Brains are notoriously hard to understand, and neuroscientists need all the tools they can get their hands on to have a realistic shot at it. Advances in machine learning are proving instrumental, illustrated by their recent use to shed light on navigational strategies implemented by zebrafish brains.


Assessment of graduate public health education in Nepal and perceived needs of faculty and students.
Despite the large body of evidence suggesting that effective public health infrastructure is vital to improving the health status of populations, many universities in developing countries offer minimal opportunities for graduate training in public health. In Nepal, for example, only two institutions currently offer a graduate public health degree. Both institutions confer only a general Masters in Public Health (MPH), and together produce 30 graduates per year. The objective of this assessment was to identify challenges in graduate public health education in Nepal, and explore ways to address these challenges. The assessment included in-person school visits and data collection through semi-structured in-depth interviews with primary stakeholders of Nepal's public health academic sector. The 72 participants included faculty, students, alumni, and leaders of institutions that offered MPH programs, and the leadership of one government-funded institution that is currently developing an MPH program. Data were analyzed through content analysis to identify major themes. Six themes characterizing the challenges of expanding and improving graduate public health training were identified: 1) a shortage of trained public health faculty, with consequent reliance on the internet to compensate for inadequate teaching resources; 2) teaching/learning cultures and bureaucratic traditions that are not optimal for graduate education; 3) within-institution dominance of clinical medicine over public health; 4) a desire for practice-oriented, contextually relevant training opportunities; 5) a demand for degree options in public health specialties (for example, epidemiology); and 6) a strong interest in international academic collaboration. Despite an enormous need for trained public health professionals, Nepal's educational institutions face barriers to developing effective graduate programs. Overcoming these barriers will require: 1) increasing the investment in public health education and 2) improving the academic environment of educational institutions. Long term, committed academic collaborations with international universities may be a realistic way to: 1) redress immediate inadequacies in resources, including teachers; 2) encourage learning environments that promote inquiry, creativity, problem-solving, and critical thinking; and 3) support development of the in-country capacity of local institutions to produce a cadre of competent, well-trained public health practitioners, researchers, teachers, and leaders.


Custom zinc-finger nucleases for use in human cells.
Genome engineering through homologous recombination (HR) is a powerful instrument for studying biological pathways or creating treatment options for genetic disorders. In mammalian cells HR is rare but the creation of targeted DNA double-strand breaks stimulates HR significantly. Here, we present a method to generate, evaluate, and optimize rationally designed endonucleases that promote HR. The DNA-binding domains were synthesized by assembling predefined zinc-finger modules selected by phage display. Attachment of a transcriptional activation domain allowed assessment of DNA binding in reporter assays, while fusion with an endonuclease domain created custom nucleases that were tested for their ability to stimulate HR in episomal and chromosomal gene repair assays. We demonstrate that specificity, expression kinetics, and protein design are crucial parameters for efficient gene repair and that our two-step assay allows one to go quickly from design to testing to successful employment of the custom nucleases in human cells.


The in vivo pattern of firefly luciferase expression in transgenic plants.
Expression of the firefly luciferase gene in transgenic plants produces light emission patterns when the plants are supplied with luciferin. We explored whether in in vivo pattern of light emission truly reveals the pattern of luciferase gene expression or whether it reflects other parameters such as the availability of the substrate, luciferin, or the tissue-specific distribution of organelles in which luciferase was localized. The tissue-specific distribution of luciferase activity and the in vivo pattern of light were examined when the luciferase gene was driven by different promoters and when luciferase was was redirected from the peroxisome, where it is normally targeted, to the chloroplast compartment. It was found that the distribution of luciferase activity closely correlated with the tissue-specific pattern of luciferase mRNA. However, the in vivo light pattern appeared to reflect not only tissue-specific distribution of luciferase activity, but also the pattern of luciferin uptake.


Letrozole versus clomiphene citrate for ovulation induction in anovulatory women with polycystic ovarian syndrome: A randomized controlled trial.
To compare the efficacy of letrozole and clomiphene citrate (CC) for ovulation induction in infertile women with polycystic ovarian syndrome (PCOS). In this assessor blind, randomized controlled trial, 90 infertile women with PCOS were randomized to receive either letrozole or CC for ovulation induction in incremental doses for a maximum of three cycles. Main outcome measures studied were endometrial thickness, ovulation rate, pregnancy rate, rate of monofollicular development, and time to conception. Mean endometrial thicknesses were 9.86 ± 2.32 mm and 9.39 ± 2.06 mm with letrozole and CC, respectively (P=0.751). Cumulative ovulation rates were 86.7% and 85.2% with letrozole and CC, respectively (P=0.751). Pregnancy was achieved in 42.2% of women in the letrozole group and 20.0% of women in the CC group (P=0.04). Monofollicular development was seen in 68.4% of ovulatory cycles in the letrozole group compared with 44.8% in the CC group (P=0.000). Mean time to achieve pregnancy was significantly shorter (log rank P=0.042) with letrozole (9.65 weeks) than with CC (11.07 weeks). Letrozole is a better alternative for ovulation induction in anovulatory women with PCOS as pregnancy rates are higher, time to pregnancy is shorter, and chances of multiple pregnancy are less because of high monofollicular growth.


Preparation and Evaluation of Andrographolide Solid Dispersion Vectored by Silicon Dioxide.
Andrographolide (Andro) is a "natural antibiotic" as well as a typical insoluble drug. The purpose of this study was to investigate the feasibility of commercially available silica (SiO2) as a carrier of solid dispersion to enhance the dissolution of Andro. The solvent evaporation method was adopted, and a series of process parameters were studied to prepare a solid dispersion. Andro, SiO2, physical mixture, and solid dispersion were characterized with respect to particle size distribution, special surface area, pore volume, and scanning electron microscopy, Fourier transform infrared spectroscopy, and X-ray diffraction studies. Single factor test suggested the best preparation of solid dispersion was the drug and carrier (SiO2B) ratio of 1:8, with tetrahydrofuran as the solvent, and a recovery temperature of 50°C. Compared to crude drug and mixture, solid dispersion was found to form a unique structure to disperse the drug and displayed superior performance in rapid dissolution. The present study signifies the commercially available SiO2 is an excellent but cheap carrier to improve the dissolution of Andro. Our results provide a highly operability approach for improving the dissolution of insoluble natural products and are beneficial for the clinical effects improvement. The potential of commercially available silica as a carrier for enhancing the insoluble drug dissolution was investigatedFactors affecting the dissolution of solid dispersion were investigatedSolid dispersion formed a unique structure to disperse the drug and release drug rapidlyCommercially available silica is an excellent but cheap carrier to improve the dissolution of Andro. Abbreviation used: Andro: Andrographolide, BCS: Biopharmaceutics Classification System, SDS: Tetrahydrofuran and Sodium dodecyl sulfate, HPLC: High Performance Liquid Chromatography, SEM: Scanning Electron Microscope, BET: Brumauer-Emmett-Teller, FTIR: Fourier Transform Infrared Spectroscopy, XRD: X-ray Diffraction.


A rational approach to single, dual and triple therapy in COPD.
The complexity of COPD treatment has increased over the last 5 years mainly because of the proliferation of drugs and delivery devices. In this paper, we will focus on currently available therapy used for maintaining patient well-being rather than acute relief of symptoms. We propose a series of principles for rational therapy, and following a review of how currently available treatments perform in isolation and when compared with each other, we suggest an approach to aid the rational selection of the most appropriate treatment based on current evidence.


Controlling Epithelial Polarity: A Human Enteroid Model for Host-Pathogen Interactions.
Human enteroids-epithelial spheroids derived from primary gastrointestinal tissue-are a promising model to study pathogen-epithelial interactions. However, accessing the apical enteroid surface is challenging because it is enclosed within the spheroid. We developed a technique to reverse enteroid polarity such that the apical surface everts to face the media. Apical-out enteroids maintain proper polarity and barrier function, differentiate into the major intestinal epithelial cell (IEC) types, and exhibit polarized absorption of nutrients. We used this model to study host-pathogen interactions and identified distinct polarity-specific patterns of infection by invasive enteropathogens. Salmonella enterica serovar Typhimurium targets IEC apical surfaces for invasion via cytoskeletal rearrangements, and Listeria monocytogenes, which binds to basolateral receptors, invade apical surfaces at sites of cell extrusion. Despite different modes of entry, both pathogens exit the epithelium within apically extruding enteroid cells. This model will enable further examination of IECs in health and disease.


How to Improve the Outcomes of Anterior Septal Perforations Repair With Combined Flaps.
The combination of a partial inverted edges with an either extended anterior ethmoidal flap or greater palatine artery flap, in which the anterior incision includes contralateral mucosa (ZigZag anterior flap-incision). Laryngoscope, 133:1614-1617, 2023.


Brain Volume Loss During the First Year of Interferon-Beta Treatment in Multiple Sclerosis: Baseline Inflammation and Regional Brain Volume Dynamics.
A pseudoatrophy effect, mostly affecting white matter, can be observed in patients with multiple sclerosis (MS) early on natalizumab therapy. We aimed to investigate whether a similar pattern could be found after interferon-beta treatment onset. From a prospective, ongoing cohort, 123 patients treated with interferon-beta were included. A brain MRI was performed at baseline (3 months prior) and 12 months after therapy onset in all patients. SPM8 software was used for volumetric analysis. Brain parenchymal, gray and white matter volumes at baseline and follow-up were obtained, allowing calculation of percentage of volume changes (BVc, GMVc, and WMVc, respectively). Descriptive statistics and linear regression models were performed. Eighty-four patients were analyzed (39 patients were excluded mostly due to incomplete MRI protocol or segmentation errors); baseline mean age was 33.6 years (SD 8.7), median disease duration was 2.8 years (.3-14), and median EDSS was 1.5 (0-6). Forty-nine patients (58.3%) had baseline gadolinium-enhancing (Gd+) lesions with a median number of 1 (0-18). The regression analysis (adjusted by the number of Gd+ at follow-up MRI, age, disease duration, and baseline EDSS) showed that a higher baseline number of Gd+ lesions was predictive of larger decreases in BVc and WMVc (P = .013 and P = .003, respectively) but not GMVc (P = .777). Concurrent inflammation has an impact on brain volume measurements (especially white matter) during the first year of interferon-beta therapy, and should be taken into account when interpreting early brain volume changes on therapy.


Exposure to morphine affects the expression of endocannabinoid receptors and immune functions.
Compared with control rats, rats under morphine exposure exhibited cannabinoid receptor 2 (CB2-R) upregulation in the spleen and periphery blood mononuclear cells (PBMCs). IgG and IgM values in the plasma were also altered. In morphine abusers, cannabinoid receptors were upregulated in the PBMCs, and the expression of IL-4 mRNA in the PBMCs as well as the IgG and IgM values in the plasma were higher compared with those in healthy people. The expression of cannabinoid receptor 1 and CB2-R in culture cells was directly affected by morphine treatment. These findings indicate that the alteration in cannabinoid receptor expression could be disturbed by morphine exposure, and it may be involved in abnormal immune function.


A putative G protein-coupled receptor involved in innate immune defense of Procambarus clarkii against bacterial infection.
The immune functions of G protein-coupled receptor (GPCR) were widely investigated in mammals. However, limited researches on immune function of GPCRs were reported in invertebrates. In the present study, the immune functions of HP1R gene, a putative GPCR identified from red swamp crayfish Procambarus clarkii were reported. Expression of HP1R gene was significant up-regulated in response to heat-killed Aeromonas hydrophila challenge. HP1R gene silencing mediated by RNA interference significantly enhanced the susceptibility of red swamp crayfish to A. hydrophila and Vibrio alginolyticus, indicating that HP1R was required for red swamp crayfish to defend against bacterial challenge. In HP1R-silenced crayfish, increased bacterial burden and decreased THC in response to bacterial challenge were observed when compared with control crayfish. No significant difference of proPO gene expression was observed between HP1R-silenced and control crayfish after challenge with heat-killed A. hydrophila. However, PO activity in response to bacterial challenge was significantly reduced in HP1R-silenced crayfish. The results collectively indicated that HP1R was an important immune molecule which was required for red swamp crayfish to defend against bacterial infection.


Identification of novel antioxidant peptides from snakehead (Channa argus) soup generated during gastrointestinal digestion and insights into the anti-oxidation mechanisms.
Antioxidant peptides obtained from snakehead (Channa argus) soup (SHS) after simulated gastrointestinal (GI) digestion were separated, identified and characterized. Results showed that the fraction with MW < 3 kDa had the highest antioxidant capacity. Four novel antioxidant peptides were identified after RP-HPLC and UPLC-MS/MS. PGMLGGSPPGLLGGSPP and SDGSNIHFPN had the highest DPPH radical scavenging activity (IC50 = 1.39 mM) and Fe2+ chelating ability (IC50 = 4.60 mM), respectively. Structures in silico for IVLPDEGK, PGMLGGSPPGLLGGSPP and SDGSNIHFPN suggest at least one β-turn and/or α-helix, which are associated with antioxidant activity. Moreover, our results showed that these three peptides docked with a recombinant Kelch-like ECH-associated protein 1 (Keap1) with a binding score greater than TX6, a good ligand of Keap1. The cell viability assay also showed significant cytoprotective effects against H2O2-induced cellular oxidative damage. This information implies that antioxidant mechanisms of novel SHS peptides occurred via activation of cellular anti-oxidation Keap1-Nrf2 signaling pathway.


Protective effect of histidine on MPP+-induced hydroxyl radical generation in rat striatum.
We investigated the efficacy of histidine on MPP+-induced hydroxyl radical (.OH) formation in extracellular fluid of rat striatum. Rats were anesthetized and sodium salicylate in Ringer's solution (0.5 nmol microl-1 min-1) was infused through a microdialysis probe to detect the generation of.OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. MPP+ (5 mM) clearly produced an increase in.OH formation. However, histidine (25 mM) reduced the.OH formation by the action of MPP+. These results indicate that histidine protects MPP+-induced.OH formation in rat striatum.


Covalent immobilization of alpha-galactosidase from Penicillium griseoroseum and its application in oligosaccharides hydrolysis.
Partially purified alpha-Galactosidase from Penicillium griseoroseum was immobilized onto modified silica using glutaraldehyde linkages. The effective activity of immobilized enzyme was 33%. Free and immobilized alpha-galactosidase showed optimal activity at 45 degrees C and pH values of 5 and 4, respectively. Immobilized alpha-galactosidase was more stable at higher temperatures and pH values. Immobilized alpha-galactosidase from P. griseoroseum maintained 100% activity after 24 h of incubation at 40 degrees C, while free enzyme showed only 32% activity under the same incubation conditions. Defatted soybean flour was treated with free and immobilized alpha-galactosidase in batch reactors. After 8 h of incubation, stachyose was completely hydrolyzed in both treatments. After 8 h of incubation, 39% and 70% of raffinose was hydrolyzed with free and immobilized alpha-galactosidase respectively. Immobilized alpha-galactosidase was reutilized eight times without any decrease in its activity.


Acute and subchronic exposure of cyadox induced metabolic and transcriptomic disturbances in Wistar rats.
Cyadox, a potential antimicrobial growth promoter, has been widely studied and prospected to be used as an additive in livestock and poultry feed. Although high cyadox exposure has been reported to cause toxicity, the exact metabolic effects are not fully understood. Our study aim is to evaluate the metabolic effects of cyadox using comprehensive methods including serum clinical chemical test, histopathology analysis, metabolomics, and transcriptomics profile analysis. One single acute dosage over 7-day course and one subchronic 90-day dietary ingestion of cyadox intervention were conducted on the Wistar rats separately. Dose-dependent alterations were shown in the metabolism of the urine, kidney, plasma, and liver by metabolomics analysis. We further investigated gene expressions of the liver administered with high dose of cyadox for 12 weeks. Top sixty-six differentially expressed genes involved in the pathways, including xenobiotic (cyadox) metabolism, lipid metabolism, energy metabolism, nucleic acid metabolic process, inflammatory response, and response to the oxidative stress, which were in concordance with these metabolic alternations. Our study provided a comprehensive information on how cyadox modulates the metabolism and gene expressions, which is vital when considering the safe application of cyadox.


Evaluation of sliding window correlation performance for characterizing dynamic functional connectivity and brain states.
A promising recent development in the study of brain function is the dynamic analysis of resting-state functional MRI scans, which can enhance understanding of normal cognition and alterations that result from brain disorders. One widely used method of capturing the dynamics of functional connectivity is sliding window correlation (SWC). However, in the absence of a "gold standard" for comparison, evaluating the performance of the SWC in typical resting-state data is challenging. This study uses simulated networks (SNs) with known transitions to examine the effects of parameters such as window length, window offset, window type, noise, filtering, and sampling rate on the SWC performance. The SWC time course was calculated for all node pairs of each SN and then clustered using the k-means algorithm to determine how resulting brain states match known configurations and transitions in the SNs. The outcomes show that the detection of state transitions and durations in the SWC is most strongly influenced by the window length and offset, followed by noise and filtering parameters. The effect of the image sampling rate was relatively insignificant. Tapered windows provide less sensitivity to state transitions than rectangular windows, which could be the result of the sharp transitions in the SNs. Overall, the SWC gave poor estimates of correlation for each brain state. Clustering based on the SWC time course did not reliably reflect the underlying state transitions unless the window length was comparable to the state duration, highlighting the need for new adaptive window analysis techniques.


Supplemental Nutrition Assistance Program Emergency Allotments and Food Security, Hospitalizations, and Hospital Capacity.
Understanding how social policies shape health is a national priority, especially in the context of the COVID-19 pandemic. To understand the association between politically motivated changes to Nebraska's Supplemental Nutrition Assistance Program (SNAP) policy and public health measures during the COVID-19 pandemic. This cross-sectional study used synthetic control methods to estimate the association of Nebraska's decision to reject emergency allotments for the SNAP with food security and hospital capacity indicators. A counterfactual for Nebraska was created by weighting data from the rest of the US. State-level changes in Nebraska between March 2020 and March 2021 were included. Data were acquired from the Census Bureau's Household Pulse Survey on individual food security and mental health indicators and from the US Centers for Disease Control and Prevention on hospital-level capacity indicators. Data analysis occurred between October 2022 and June 2023. The rejection of additional SNAP funds for low-income households in Nebraska from August to November 2020. Food insecurity and inpatient bed use indicators (ie, inpatient beds filled, inpatient beds filled by patients with COVID-19, and inpatients with COVID-19). The survey data of 1 591 006 respondents from May 2020 to November 2020 was analyzed, and 24 869 (1.56%) lived in Nebraska. Nebraska's population was composed of proportionally more White individuals (mean [SD], 88.70% [0.29%] vs 78.28% [0.26%]; P < .001), fewer individuals who made more than $200 000 in 2019 (4.20% [0.45%] vs 5.22% [0.12%]; P < .001), and more households sized 1 to 3 (63.41% [2.29%] vs 61.13% [1.10%); P = .03) compared with other states. Nebraska's rejection of additional funding for SNAP recipients was associated with increases in food insecurity (raw mean [SD] difference 1.61% [1.30%]; relative difference, 19.63%; P = .02), percentage of inpatient beds filled by patients with COVID-19 (raw mean [SD] difference, 0.19% [1.55%]; relative difference, 3.90%; P = .02), and percentage of inpatient beds filled (raw mean [SD] difference, 2.35% [1.82%]; relative difference, 4.10%; P = .02). In this cross-sectional study, the association between social policy, food security, health, and public health resources was examined, and the rejection of emergency allotments in Nebraska was associated with increased food insecurity. Additionally, this intervention was associated with an increased rate of hospitalizations for COVID-19 and non-COVID-19 causes.


Trends and disparities in telehealth use among Louisiana Medicaid beneficiaries with type 2 diabetes.
To examine trends in telehealth use among Medicaid beneficiaries with type 2 diabetes (T2D) before and during the coronavirus disease 2019 (COVID-19) pandemic and identify factors related to telehealth use. We compared monthly proportions of outpatient visits delivered by telehealth by race/ethnicity, geography and age among Louisiana Medicaid beneficiaries with T2D using claims data from January 2018 to August 2021. We also examined the changes in provider types delivering telehealth. Multivariable logistic regression was conducted to identify individual level and zip code-level factors associated with telehealth use during the COVID-19 pandemic. The monthly proportion of outpatient visits delivered by telehealth was low (< 1%) before the pandemic, spiked in April 2020 (> 15%), then remained at approximately 5%. Telehealth use varied across different racial/ethnic groups, geography and age groups over years. Older beneficiaries were less probable to use telehealth during the pandemic (adjusted odds ratio [AOR] = 0.874, 95% confidence interval [CI]: 0.831-0.919). Females used more telehealth than males (AOR = 1.359, 95% CI: 1.298-1.423). Black beneficiaries used more telehealth than White beneficiaries (AOR = 1.067, 95% CI: 1.000-1.139). More telehealth services were used by Medicaid beneficiaries who were living in urban areas, with more primary care utilization, and with more chronic conditions at baseline. We found disparities in the uptake of telehealth during the COVID-19 pandemic, but they might have been narrowed for some groups (Hispanic and rural) among Louisiana Medicaid beneficiaries with T2D. Future studies should explore strategies to improve access to telehealth services and reduce related disparities for the low-income population.


Behçet's disease presenting with a hypopharyngeal ulcer.
A 40-year-old man presented with a single, major ulcer in the hypopharynx. Histopathological examination revealed necrosis and extensive vasculitis. Since the patient had recurrent oral ulcers and genital ulcers in his history and a positive pathergy test, a diagnosis of Behçet's disease was made, according to the 1992 international criteria. Behçet's disease should be kept in mind in differential diagnoses of hypopharyngeal ulcerous lesions, and detailed case histories should be taken.


The "multi-purge procedure" and its application for hydrophilic lens wearers utilizing preserved solutions.
The multi-purge procedure has been used to remove or dilute preservatives in chemical rinsing, storage or disinfecting solutions for soft lenses. It is used for patients who use preserved solutions and who develop eye reactions to these solutions.


Retracted: Gait Recognition Based on the Plantar Pressure Data of Ice and Snow Athletes.
[This retracts the article DOI: 10.1155/2022/2982894.].


Assessment of the efficiency of different chemical treatments and ultrasonic cleaning for defatting of cancellous bone samples.
Our study aimed to asses the defatting efficiency of different methods, which are commonly used and easily available in the laboratory in order to find a method that is effective, convenient, safe, and economical. Cylindrical cancellous bone specimens were obtained from fresh-frozen human cadaver femoral condyles, cut into multiple small specimens (Ø8 × 2 mm), and assigned to two groups that were treated with either chemical solvent soaking (Solvent group) or ultrasonic cleaning (Ultrasound group). Each group was divided into several subgroups based on different treatments. Digital photographs were taken of each specimen. The difference of material density (Δρb), apparent density (Δρapp), and porosity (ΔP) before and after treatment were used as evaluation indicators. For the solvent group, in Δρb, only the combination of 99% ethanol and detergent solution showed a significant difference before and after treatment (P = 0.00). There was no significant difference in ΔP among acetone, the mixture of 99% ethanol and acetone, and the combination of 99% ethanol and detergent solution (P = 0.93). For the ultrasound group, the median of all subgroups in Δρapp and ΔP were all lower than the solvent group. The combination of 99% ethanol and detergent solution (v/v = 1:20), as well as the mixture of 99% ethanol and acetone (v/v = 1:1), seem to be the optimal defatting methods for 2 mm thick cancellous bone slices due to their effectiveness, availability, low-cost and safety. Chemical soaking for 24 h is more effective than ultrasonic cleaning with 99% ethanol or acetone for 20 or 40 min.


Polypeptide structure of DNA primase from a yeast DNA polymerase-primase complex.
An immunoaffinity chromatographic procedure was developed to purify DNA polymerase-DNA primase complex from crude soluble extracts of yeast cells. The immunoabsorbent column is made of mouse monoclonal antibody to yeast DNA polymerase I covalently linked to Protein A-Sepharose. Purification of the complex involves binding of the complex to the immunoabsorbent column and elution with concentrated MgCl2 solutions. After rebinding to the monoclonal antibody column free primase activity is selectively eluted with a lower concentration of MgCl2. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate showed the presence of five major peptides, p180, p140, p74, p58, and p48 in the immunoaffinity-purified DNA polymerase-DNA primase complex. Free primase and free polymerase fractions obtained by fractionation on the immunoabsorbent column were analyzed on activity gels and immunoblots. These analyses showed that p180 and p140 are DNA polymerase peptides. Two polypeptides of 58 and 48 kDa co-fractionated with the free yeast DNA primase. From sucrose gradient analysis we estimate a molecular weight of 110 kDa for the native DNA primase.


Machine learning with in silico analysis markedly improves survival prediction modeling in colon cancer patients.
Predicting the survival of cancer patients provides prognostic information and therapeutic guidance. However, improved prediction models are needed for use in diagnosis and treatment. This study aimed to identify genomic prognostic biomarkers related to colon cancer (CC) based on computational data and to develop survival prediction models. We performed machine-learning (ML) analysis to screen pathogenic survival-related driver genes related to patient prognosis by integrating copy number variation and gene expression data. Moreover, in silico system analysis was performed to clinically assess data from ML analysis, and we identified RABGAP1L, MYH9, and DRD4 as candidate genes. These three genes and tumor stages were used to generate survival prediction models. Moreover, the genes were validated by experimental and clinical analyses, and the theranostic application of the survival prediction models was assessed. RABGAP1L, MYH9, and DRD4 were identified as survival-related candidate genes by ML and in silico system analysis. The survival prediction model using the expression of the three genes showed higher predictive performance when applied to predict the prognosis of CC patients. A series of functional analyses revealed that each knockdown of three genes reduced the protumor activity of CC cells. In particular, validation with an independent cohort of CC patients confirmed that the coexpression of MYH9 and DRD4 gene expression reflected poorer clinical outcomes in terms of overall survival and disease-free survival. Our survival prediction approach will contribute to providing information on patients and developing a therapeutic strategy for CC patients.


[Cogan syndrome].
Cogan's syndrome is a rare disorder of unknown origin characterized by inflammatory ocular disease (mainly interstitial keratitis) and audiovestibular symptoms (mainly acute-onset sensorineural hearing loss) in the setting of a negative work-up for syphilis. The diversity of the ocular and audiovestibular manifestations reported in the literature in atypical Cogan's syndrome should make one cautious before accepting the diagnosis as the disease may mimic various other systemic disorders. Systemic corticosteroids are always the most widely used and successful therapy. For patients requiring high and prolonged doses, additional immunosuppression is appropriate. Methotrexate is the first-line steroid sparing agent. However, patients without systemic disease or severe eye disease unmanageable by topical corticosteroids should not be subjected to protracted courses of corticosteroids or immunosuppressive agents, particularly when little gain in hearing is obtained with their use. The effect of TNF-alpha blockers was recently investigated. Infliximab might be an alternative therapy in cases of failure of corticosteroids and immunosuppressive therapy. However, treatment might be more effective when started at an early stage of the disease, when the lesions are still reversible.


Apparent effect of ascorbic acid medication on semen metal levels.
The apparent effect of ascorbic acid therapy for nonspecific spermagglutination on semen levels of ascorbic acid as well as macro- and micrometals was determined in 20 men (ages 25 to 38). Pretreatment diagnosis was based on infertility and relatively low ratings in sperm density, motility, motility index, and semen volume, and were associated with large numbers of abnormal sperm, sperm precursors, and leukocytes. The pretreatment levels of ascorbic acid, sodium, iron, potassium, zinc, manganese, lead, magnesium, and copper were measured in each patient's semen and compared with levels following 60 days of dietary vitamin C supplementation (1.0 gm/day). Analysis of the vitamin C preparation prescribed revealed that each subject was given an impure ascorbic acid medication to supplement a normal diet. Therefore, the significant increases in levels of ascorbic acid and metals in semen following therapy could not be attributed to ascorbic acid alone, nor, similarly, the improved physical parameters of each subject's semen following therapy; no apparent spermagglutination and restored fertility may be due to the interaction of ascorbic acid with cations found in semen.


[Changes in the electromyographic potentials in cats poisoned with superlethal doses of phosdrin and treated with doline].
The authors carried out studies on 10 cats, anesthetized by urethane, under atropine protection and under the conditions of artificial respiration and examined the influence of therapeutic antidote of phosphorganic pesticides-Doline on the induced eletromyographic activity during total neuro-muscular block, induced by superlethal doses of phosphadrine. It was established that superlethal doses of phosphadrine induced total block of electropotentials in neuro-muscular conduction of the peripheral musculature, which was removed immediately after venous and muscular administration of the antidote Doline.


Fruit Flies (Diptera: Tephritoidea) and Parasitoids (Hymenoptera) Associated with Native Fruit Trees in the Chaco Biome.
Fruit flies (Diptera: Tephritoidea) are the main pests over important fruits and vegetables. In this research was evaluated the tritrophic interactions of fruit flies and their parasitoids occurring in native fruits in the Chaco Biome. Fruit sampling was carried out monthly in three areas of vegetation communities in Chaco Biome: Forested Steppic Savanna, Wooded Steppic Savanna, Park Steppic Savanna, Porto Murtinho-MS, Brazil, from April 3, 2017, to November 16, 2018 (totaling 20 samples). Fruits of 33 plant species were examined for fruit flies and parasitoids from these three Chaco locations. Sixteen species of fruit plants were infested by 11 species of fruit flies: five species of Anastrepha Schiner (Tephritidae): Anastrepha fraterculus (Wiedemann), Anastrepha obliqua (Macquart), Anastrepha sororcula Zucchi, Anastrepha turpiniae Stone, Anastrepha zenildae Zucchi, and six of Neosilba McAlpine (Lonchaeidae): Neosilba bifida Strikis and Prado, Neosilba certa (Walker), Neosilba glaberrima (Wiedemann), Neosilba inesperata Strikis and Prado, Neosilba pendula (Bezzi), Neosilba zadolicha McAlpine and Steyskal. Three species of parasitoids: Doryctobracon areolatus (Szepliget) and Utetes anastrephae (Viereck) (Braconidae) parasitized Anastrepha spp., and Aganaspis pelleranoi (Figitidae) parasitized Neosilba spp. All fruit flies and parasitoid species reported here are new records for the Chaco Biome. Furthermore, the following trophic associations are new records worldwide: Anastrepha obliqua in Sideroxylon obtusifolium; Anastrepha zenildae, Neosilba inesperata, and Neosilba zadolicha in Eugenia myrcianthes; Anastrepha fraterculus, Anastrepha sororcula, Neosilba pendula, and Neosilba inesperata in Campomanesia adamantium; Anastrepha spp. in Garcinia gardneriana and Agonandra brasiliensis.


Proliferative urocystica and adenoma in a guinea-pig.
Proliferative urocystica and adenoma occurred in the urothelium of one clinically normal guinea-pig in a group of nine fed with a diet containing shade-dried Christella dentata (Forssk) fern. It was concluded that the lesions were due to prolonged feeding (285 days) of the fern.


Limited English Proficiency as a Barrier to Inclusion in Emergency Medicine-Based Clinical Stroke Research.
Individuals with Limited English Proficiency (LEP) represent a growing percentage of the U.S. population yet face inequities in health outcomes and barriers to routine care. Despite these disparities, LEP populations are often excluded from clinical research studies. The aim of this study was to assess for the inclusion of LEP populations in published acute care stroke research in the U.S. A systematic review was conducted of publications from three databases using acute care and stroke specific Medical Subject Heading key terms. The primary outcome was whether language was used as inclusion or exclusion criteria for study participation and the secondary outcome was whether the study explored outcomes by language. A total of 167 studies were included. Twenty-two studies (13.2%) indicated the use of language as inclusion/exclusion criteria within the manuscript or dataset/registry and only 17 studies (10.2%) explicitly included LEP patients either in the study or dataset/registry. Only four papers (2%) include language as a primary variable. As LEP populations are not routinely incorporated in acute care stroke research, it is critical that researchers engage in language-inclusive research practices to ensure all patients are equitably represented in research studies and ultimately evidence-based practices.


Economic Hardship in Childhood: A Neglected Issue in ACE Studies?
Objectives Adverse childhood experiences (ACEs) have been linked with ill-health in adulthood, but ACE literature has focused on family disruption or dysfunction (e.g., child abuse, parental separation), with less attention to economic adversity. We examined whether a mother's economic hardship in childhood (EHC) was associated with women's hardships and health-risk behaviors during/just before pregnancy. Methods We analyzed population-based survey data on 27,102 postpartum California women. EHC included respondents' reports that during childhood they/their families experienced hunger because of inability to afford food or moved because of problems paying rent/mortgage and the frequency of difficulty paying for basic needs. We examined six maternal hardships/behaviors during/just before pregnancy, including four hardships (poverty, food insecurity, homelessness/no regular place to sleep, intimate partner violence) and two behaviors (smoking, binge drinking). Prevalence ratios (PRs) were calculated from sequential logistic regression models estimating associations between EHC (categorized by level of hardship) and each maternal hardship/behavior, first without adjustment, then adjusting for other childhood and current maternal factors, and finally adding family disruption/dysfunction. Results Before adjustment for family disruption/dysfunction, the highest and intermediate EHC levels were associated with each maternal hardship/behavior; after full adjustment, those associations persisted except with smoking. Higher EHC levels generally appeared associated with larger PRs, although confidence intervals overlapped. Conclusions for Policy/Practice These findings link childhood economic hardship with women's hardships, binge drinking, and possibly smoking around the time of pregnancy. Without establishing causality, they support previous research indicating that childhood economic adversity should be considered an ACE.


Search for alpha-helical propensity in the receptor-bound conformation of glucagon-like peptide-1.
To elucidate the receptor-bound conformation of glucagon-like peptide-1 (GLP-1), a series of conformationally constrained GLP-1 analogues were synthesized by introducing lactam bridges between Lys(i) and Glu(i)(+4) to form alpha-helices at various positions. The activity and affinity of these analogues to GLP-1 receptors suggested that the receptor-bound conformation comprises two alpha-helical segments between residues 11-21 and 23-34. It is notable that the N-terminal alpha-helix is extended to Thr(11), and that Gly(22) plays a pivotal role in arranging the two alpha-helices. Based on these findings, a highly potent bicyclic GLP-1 analogue was synthesized which is the most conformationally constrained GLP-1 analogue reported to date.


Immunolabelling patterns of gap junction connexins in the developing and mature rat heart.
The distribution of gap junctions in prenatal, postnatal, and adult rat hearts was studied by laser scanning confocal microscopy, using antiserum raised to a peptide (HJ) matching part of the sequence of connexin43 (a cardiac gap junction protein). Using digital reconstruction of optically-sectioned tissue volumes, a highly sensitive detection of immunolabelled gap junctions was achieved. The distribution of positive anti-HJ immunolabelling was regionalised in the prenatal heart from its first detection at 10 days post-coitus. High levels of immunopositive staining occurred in the trabeculae of the embryonic ventricles. Other zones of the early myocardium including early central conduction tissues had no detectable signal. The prenatal outflow tract, interventricular septum and a narrow zone of myocardium subjacent to the epicardial free wall also had low levels of immunopositive signal. During postnatal growth and in the adult rat heart, a marked distinction emerged between the central conducting tissues of the atria and ventricles. Whilst small immunostained gap junctions became detectable within the atrioventricular node on the atrial side of the junction, between the interatrial and interventricular septa, no immunolabelling was found within the ventricular branching bundle. This difference between the atrioventricular node and branching bundle is consistent with potential functional distinctions between these two structures, and is not consistent with the recent proposal that the His bundle and its branches act as an extended atrioventricular node in smaller mammals such as the rat. Ventricular Purkinje fibres, distal to the branching bundle, showed high levels of anti-HJ immunostaining. Organisation of gap junctions into intercalated disks within the ventricle proceeded late into intercalated disks within the ventricle proceeded late into the adolescent stages of heart growth. The distribution of a second connexin protein, MP70, not previously characterised in the heart, was studied using monoclonal antibodies. MP70 was transiently immunolabelled in the heart during the postnatal period, but only within valves. Previously, this protein has been reported only in the eye lens. MP70-containing gap junctions may represent a specialisation in avascular tissues, since blood vessels are not present in either the eye lens or the cusps of heart valves.


Two-stage weighted PROMETHEE II with results' visualization.
Multicriteria decision-making methods are widely spread and used to assist the decision-makers to resolve problems. Many of the methods are simple to deploy (WSA, TOPSIS), which is an advantage and because of the computer boom, there is no problem with calculations. However, more sophisticated methods are evolving. The modelling of preferences is improved (from linear in WSA to Gaussian in PROMETHEE), multilevel decision-making (such as AHP) is extended to modelling of dependencies between individual criteria (ANP). The presented method, two-stage weighted PROMETHEE, combines the advantages of generalized preferential functions in PROMETHEE methods, unambiguous arrangement (PROMETHEE II) and hierarchical approach (AHP). In addition, this paper demonstrates the application of the method to evaluate the order of 14 regions of the Czech Republic in regard to economic indices such as the unemployment rate, economic activity, average age, wages, free working places, income, consumption and investments. Data are taken from the Czech Statistical Office web and include the years 2012-2019. In the first stage, the position of each region is calculated; in the second stage, all years mentioned are considered, including the aspect of the weighted time series. Result visualization is made possible using the Visual PROMETHEE software.


Some properties of extrastriate visual units in the cortex of the rabbit.
Receptive fields and trigger properties of 306 units in the visual cortex of the rabbit have been examined in detail. Reconstruction of the electrode tracks revealed that 276 of these recordings were made from cells located in the striate cortex, whilst the remaining 30 were found to lie in cortex lateral to the striate field. These latter units have been termed 'extrastriate'. Five penetrations involved both striate and extrastriate units enabling a direct comparison of their properties to be made. The most outstanding feature of the extrastriate units was their huge receptive field sizes (up to 80 degrees X 130 degrees) and high rates of spontaneous activity (usually between 10 and 20 imp./sec). None of these cells responded well to stationary stimuli and most preferred moving targets. Responses could be elicited regardless of the nature of stimulus-to-background contrast and were constant over a wide range of stimulus sizes. No cells were found which were orientation selective. Approximately half the extrastriate units were direction selective, the majority preferred anterior movement in the visual field. Movement in the counter-preferred direction generally resulted in suppression of the spontaneous discharge. In contrast to this the receptive fields of cells in the striate cortex were small, and were often sensitive to features such as stimulus size, orientation, and contrast, in addition to movement and direction of movement. The similarity between one class of extrastriate unit, and units recently observed in the pretectum of the rabbit is pointed out.


Characterization of the cyclic 3',5'-nucleotide phosphodiesterase actitivty associated with synaptosomal plasma membranes and synaptic junctions.
Some characteristics of the cyclic 3',5'-nucleotide phosphodiesterase (phosphodiesterase) activity associated with the synaptosomal plasma membrane (synaptic membrane) and the synaptic junction fractions of rat brain are reported. Kinetic analysis revealed that only one type of phosphodiesterase activity, with a Km of 2.10 19(-4) M for cyclic AMP, is associated with both fractions. The specific activities of the phosphodiesterase in synaptic membranes and synaptic junctions have been estimated at 23.4 nmol/min per mg protein and 22.5 nmol/min per mg protein, respectively. The synaptic junction-associated activity undergoes a 30% stimulation by Ca2+ while no Ca2+ sensitivity of the synaptic membrane-associated activity could be detected. Cytochemical studies performed on the synaptic membrane fraction demonstrated a predominant localization of phosphodiesterase activity over postsynaptic densities, while dense deposits were sometimes observed over the synaptic cleft region.


Efficacy of Jawarish Shahi a herbal formulation in irritable bowel syndrome: An open-labeled single-arm clinical trial.
Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders characterized by chronic recurrent abdominal pain related to a change in bowel habit or defecation frequency and commonly accompanied by anxiety and depression affecting about 10% population globally. Jawarish Shahi (JS) is a special dosage form prepared for gastrointestinal disorders in Unani medicine containing Phyllanthus emblica L., Terminalia chebula Retz., Coriandrum sativum L., Elettaria cardamomum (L.) Maton and Salix caprea L. Considering the antioxidant, immunomodulatory, antispasmodic analgesic, antidiarrheal, antisecretory, laxative, anti-inflammatory, anxiolytic, and antidepressant properties, the present study was aimed to evaluate the efficacy of JS in IBS. This single-arm open-labeled clinical trial was conducted on 26 male and female patients of IBS according to Rome IV criteria, aged 18-50 years with moderate symptoms. JS was given 7 g orally twice a day after meal with water for 45 days. IBS Severity Scoring Scale (IBS-SSS) was used for efficacy outcomes and the difference was analyzed from baseline to the subsequent follow-ups. Data analysis of subsequent followup showed a significant decrease in IBS-SSS scores except for 2nd followup, scores decreased from 229.50 ± 75.91 to 203.12 ± 71.71 (p < 0.1018), 150.61 ± 55.32 (p < 0.0001), and 123.76 ± 54.81 (p < 0.0001) at 0, 15th, 30th, 45th day of follow up respectively. The present study revealed that JS is safe and effective in reducing the overall symptoms of IBS in respect to its severity and impact on quality of life and can be used as an alternate as well as a complementary treatment in IBS.


Cervical spondylolisthesis C6-C7 in a young wrestler: case report.
We present both the clinical and radiographic data of a 15-year-old boy, suffering from a lytic spondylolisthesis C6-C7 and treated by circumferential fusion.


Rapid identification of flaviviruses based on conserved NS5 gene sequences.
Two conserved regions in the sequence of the NS5 gene of Flaviviruses were identified. Primers were designed from the consensus sequence of these regions and were used in a reverse transcription/polymerase chain reaction (RT/PCR) to amplify a region of the central european tick-borne encephalitis virus Kumlinge NS5 gene. The authenticity of the amplified fragment was confirmed by nucleotide sequencing. A band of the expected size was also obtained when this RT/PCR was applied to 13 other flaviviral RNAs. This method may be useful for characterisation of the NS5 genes of flaviviruses and as a potential pan-flavivirus diagnostic tool.


Timing of Mean Transit Time Maximization is Associated with Neurological Outcome After Subarachnoid Hemorrhage.
Computed tomography perfusion (CTP) has gained significant relevance for the radiological screening of patients at risk of developing delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Particularly, the impact of MTTPEAK, i.e., the maximal mean transit time value in a series of CTP measurements, for the prediction of long-term outcome has recently been demonstrated by our group. Complementing this recent work, the present study investigated how the timing of MTTPEAK affected the long-term outcome after aneurysmal subarachnoid hemorrhage. CTP examinations from 103 patients with clinical deterioration attributed to DCI after aSAH were retrospectively analyzed for time interval between SAH ictus and onset of MTTPEAK in association with modified Rankin Scale (mRS) 23.1 months after SAH. Patients with unfavorable outcome (mRS > = 2) suffered significant earlier MTTPEAK onsets than patients with favorable outcome (mRS = 0 and 1). MTTPEAK within the first week was associated with significantly higher mRS scores compared to later MTTPEAK. Timing of MTTPEAK together with the value of MTTPEAK and initial World Federation of Neurosurgical Societies (WFNS) grade was a significant predictor for an unfavorable outcome (mRS > = 2). The current findings suggest a presumably higher vulnerability of the brain to early microcirculatory impairments after aSAH and highlight that timing of MTT elevations could be considered for the identification of patients at increased risk for poor neurological outcome due to DCI.


Behavioral evidence for format-dependent processes in approximate numerosity representation.
A genuinely abstract number representation is thought to be capable of representing the numerosity of any set of discrete elements, whether they are sequentially or simultaneously presented. Recent neuroimaging studies, however, have demonstrated that different areas of intraparietal sulcus play a role in extracting numerosity across simultaneous or sequential presentation during a quantification process, suggesting the existence of a format-dependent numerical system. To test whether behavioral evidence exists for format-dependent numerical processing in adult humans, we measured the Weber fractions of numerosity discrimination for sequential stimuli, simultaneous stimuli, and cross-format stimuli with a carefully controlled experimental procedure. The results showed distinct differences between the performance in the simultaneous and sequential conditions, supporting the existence of format-dependent processes for numerosity representation. Moreover, the performance on cross-format trials differed among participants, with the exception that performance was always worse than in the simultaneous condition. Taken together, our findings suggest that numerical representation may involve a complex set of multiple stages.


Aclidinium: in chronic obstructive pulmonary disease.
Aclidinium, an inhaled, long-acting antimuscarinic agent, has been developed as a twice-daily maintenance treatment for chronic obstructive pulmonary disease (COPD). Treatment with the approved dosage of aclidinium (400 μg twice daily) statistically significantly improved bronchodilation, disease-specific health status, dyspnoea, night-time COPD symptoms and use of rescue medication compared with placebo in pivotal studies of 12 (ACCORD COPD I) or 24 (ATTAIN) weeks duration in patients with moderate to severe COPD. The improvements in bronchodilation, health status and dyspnoea were clinically meaningful compared with placebo after 24 weeks of treatment in ATTAIN; generally similar results were seen after 12 weeks of treatment in both trials. Aclidinium also statistically significantly reduced the incidence of COPD exacerbations compared with placebo in these studies (albeit neither trial was designed to assess exacerbation frequency). Inhaled aclidinium has a low systemic bioavailability; the approved dosage was generally well tolerated in clinical trials of up to 52 weeks duration. Aclidinium had an adverse event profile that was similar to that of placebo and characterized by low incidences of major adverse cardiovascular events and potential anticholinergic adverse events.


Nicotine effect on prepulse inhibition and prepulse facilitation in schizophrenia patients.
Acoustic prepulse inhibition (PPI) is considered an important biomarker in animal studies of psychosis and a number of psychiatric conditions. Nicotine has been shown to improve acoustic PPI in some animal strains and in humans. However, there is little data on effects of nicotine on acoustic PPI in schizophrenia patients using a double-blind, placebo-controlled study design. The primary aim of the current study was to test the effect of nicotine nasal spray on acoustic PPI in schizophrenia patients. The secondary aim was to test nicotine effect on prepulse facilitation (PPF). The study included 18 schizophrenia patient smokers and 12 healthy control smokers, tested in a double-blind, placebo-controlled, crossover, randomized design immediately after nicotine or saline placebo nasal sprays. PPI was tested using 120 ms prepulse-pulse interval. PPF was tested using 4500 ms prepulse-pulse interval. The results showed a significant main effect of drug on PPI in that nicotine improved PPI compared to placebo (p=0.008) with no drug by diagnosis interaction (p=0.90). Improvement in PPI in response to nicotine was significantly correlated with the baseline severity of clinical symptoms (r=0.59, p=0.02) in patients. There was no significant drug or drug by diagnosis interaction for the 4500 ms prepulse-pulse interval condition. However, nicotine improved inhibition in a subgroup of subjects exhibiting PPF (p=0.002). In conclusion, the findings confirmed that nicotine transiently improves acoustic PPI in schizophrenia patients. Additionally, schizophrenia patients with more clinical symptoms may have benefited more from nicotinic effect on PPI.


Evolution of total antioxidant status in a model of acute renal insufficiency in rats.
Accurate estimation of the Total Antioxidant Status (TAS) in the myoglobinuric acute renal failure (ARF) is necessary because its pathogenesis is believed to be mediated, at least in part, by the development of oxidative stress resulting from the generation of oxygen free radicals and reduced antioxidant defense system. The purpose of this study is to examine the TAS 24 and 72 h after glycerol injection in a model of myoglobinuric-ARF. The study was conduced in 28 Sprague-Dawley rats. In group 1 (n = 7) rats were placed into individual metabolic cages and deprived of water during 24 h. afterwards an intramuscular injection of glycerol was administrated (50% vol/vol in sterile saline) 10 mg/100 g of body weight and 24 h later blood samples were collected for biochemical measurements (urea, creatinine, creatine-kinase, and TAS levels). In group 2 (n = 7), rats followed the same conditions than group 1 ones but blood samples were collected 72 h after glycerol injection. In groups 3 (n = 7) and 4 (n = 7) rats didn't receive glycerol injection, and blood samples were collected within 24 and 72 h respectively after they were placed into metabolic cages. In groups 1 and 2 we observed a renal function decrease, with higher serum levels of urea and creatinine in group 2 (urea levels: 269 +/- 16 mg/dL vs. 586 +/- 147 mg/dL; p < 0.001. Creatinine levels: 2.8 +/- 0.2 mg/dL vs. 5.8 +/- 0.7 mg/dL; p < 0.001). TAS levels in groups 2, 3, and 4 were similar, but in group 1 was significantly lower (group 1: 0.81 +/- 0.2 mmol/L; group 2: 1.3 +/- 0.1 mmol/L; group 3: 1.2 +/- 0.3 mmol/L, and group 4: 1.2 +/- 0.2 mmol/L; p < 0.005). In the model of glycerol induced myoglobinuric-ARF we observed a decrease of serum TAS level within 24 h with spontaneous recuperation 72 h after.