Possible role of the gut microbiome in mediating the beneficial effects of the six-herbal formulation STW 5-II on digestive health.

BACKGROUND: STW 5-II is a combination of six herbal extracts with clinically proven efficacy in functional dyspepsia (FD) and irritable bowel syndrome (IBS). STW 5-II contains a wide variety of secondary plant constituents that may interact with the human gut microbiome. In addition to complex carbohydrates, secondary plant metabolites, such as polyphenols, are known to exert prebiotic-like effects. PURPOSE: This study aimed to assess the bidirectional interactions between STW 5-II and the human gut microbiome. METHODS: STW 5-II was incubated with human fecal microbiota in a short-term colonic model. In the samples, the impact of STW 5-II on microbial fermentation capacity (pH, gas production), short chain fatty acid (SCFA) production, and microbial composition (Illumina 16S rRNA gene sequencing) was analyzed. In addition, the biotransformation of STW 5-II constituents by the fecal microbiota was assessed by UHPLCHRMS-based metabolite profiling. Furthermore, Caco-2/THP1 co-culture assay was used to explore the effect on gut barrier integrity and inflammatory markers. RESULTS: Fermentation of STW 5-II by fecal microbiota led to consistent changes in pH and gas production and increased production of SCFAs (acetate, propionate, and butyrate). STW 5-II promoted the enrichment of Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, and Eggerthellaceae and suppressed the growth of pathogenic species from the Enterobacteriaceae family. In Caco2/THP1 culture, treatment with STW 5-II-incubated samples resulted in significantly increased transepithelial electrical resistance, indicating enhanced barrier function. Among inflammatory markers, STW 5-II-incubated samples increased LPS-induced secretion of the anti-inflammatory cytokine IL-10, as well as NF-κB activity, and significantly decreased the secretion of the pro-inflammatory chemokine MCP-1. UHPLCHRMS analysis identified 110 constituents of STW 5-II with changed levels during incubation with fecal microbiota: 63 constituents that were metabolized, 22 intermittently increased metabolites, and 25 final metabolites, including compounds with established anti-inflammatory activity, such as 18ß-glycyrrhetinic acid. CONCLUSION: These findings indicate a microbiome-mediated digestive health-promoting effect of STW 5-II via three different routes, namely enhanced microbial SCFA production, microbial production of potentially bioactive metabolites from STW 5-II constituents, and prebiotic-like action by promoting the proliferation/growth of beneficial bacteria.

Kinetics of growth, development and absorption of nutrients in stone pine (Pinus pinea L.) cultivated in the presence of NaCl.

The aim of the present work was to evaluate and analyze the growth and mineral nutrition response of stone pine (Pinus pinea L.) seedlings, an economically important forest species. We analyzed the salinity effects on the kinetics of growth, development, and absorption of nutrients of plants cultivated under controlled conditions on a solid organic substrate. Pinus pinea plants were able to tolerate 25 mM NaCl concentration without reduced growth compared to the non-saline control. However, the salt concentration of 50 mM significantly affected the seedling growth after two weeks of treatment. Root growth activity was decreased more than the aerial parts at applied NaCl concentrations. On the other hand, seedlings restricted the transport of Na+ ions to the aerial parts and were strongly selective in favour of K+ ions. The presence of NaCl in the culture medium decreased the absorption rate and the export of K+ and Na+ ions to the aerial parts. This was reflected in the accumulation way of these two ions in the whole plant.

Dual opposing actions of STW 5 on TRP receptors mediate neuronal desensitisation in vitro.

AIMS: STW 5 is an herbal drug combination used for the treatment of functional gastrointestinal disorders (FGIDs) with visceral hypersensitivity as the therapy-resistant hallmark. STW 5 has been clinically proven to alleviate visceral hypersensitivity-related symptoms, including abdominal pain, bloating, nausea, and early satiety. However, the molecular and cellular mechanisms underlying the antinociceptive action of STW 5 remain unknown. Here, we investigate the role of STW 5 in the calcium mobilisation of dorsal root ganglion (DRG) sensory neurons. MAIN METHODS: Calcium imaging experiments were performed with freshly dissociated cultured murine DRG neurons isolated from mice by microfluorometry. TRPA1-deficient DRGs, TRPV1-deficient DRGs, TRPA1/V1 double-deficient DRGs, and wild-type DRGs have been used to investigate the role of TRPs ion channels in mediating STW 5 action. KEY FINDINGS: STW 5 (1.74 and 5.8 mg/ml) induced calcium ion influx into DRG neurons in a concentration-dependent manner. Calcium transients were desensitised during repeated exposure to STW 5, an effect that was facilitated in TRPA1-deficient DRGs and less pronounced in TRPV1-deficient DRGs compared to wild-type (WT) DRGs. SIGNIFICANCE: Repeated exposure to STW 5 induced desensitisation of sensory neurons and may ultimately contribute to its proven clinical efficacy against sensory-related symptoms in patients with FGID, including abdominal pain, bloating, nausea, and early satiety. This effect is modulated by the two prominent irritant sensors in nociceptors, TRPA1 and TRPV1.

Eosinophil counts in colonic tissue eosinophilia: Investigating specificity and sensitivity of cutoff points and comparing two counting methods.

BACKGROUND/AIMS: The aim of this study was to investigate the specificity and sensitivity of eosinophil cutoff points defining the colonic tissue eosinophilia (TE) and compare the yield of reporting the highest count versus the mean of five high-power fields (HPFs). MATERIALS AND METHODS: One hundred and seventy-one cases of colonic TE, including 22 primary eosinophilic colitis (PEC) cases, were compared to one hundred and twenty-one normal controls in the University of Jordan. The highest eosinophil count (EC) and the mean of five HPFs were recorded. The receiver operating characteristic curve (ROC) analysis was used to find the cutoff point with the best sensitivity and specificity. RESULTS: There was no significant advantage of counting five fields over counting the most densely populated HPF. Using 30 eosinophils per HPF achieved 80% sensitivity and 65% specificity. This point is close to the mean in normal controls plus one standard deviation (SD) (29 per HPF). However, there was overlap between normal counts and TE, using 30 as a cutoff point resulted in 35% false-positive rate. There was no reliable cutoff point to differentiate PEC from secondary TE. CONCLUSION: We recommend reporting the highest EC in colonic biopsies and using 30 as a cutoff point, bearing in mind the overlap with normal and correlating with the clinical team to not treat asymptomatic patients. Clinicopathological correlation is essential to separate PEC from secondary TE.

Value of troponin levels in the diagnosis of cardiac dysfunction in moderate scorpion envenomation.

CONTEXT: Cardiac dysfunction is one of the most serious consequences of scorpion envenomation. The best tool to evaluate cardiac function is echocardiography, but it is not available at all emergency departments. Many studies aimed to describe biological predictive factors of cardiac dysfunction in scorpion envenomation. Troponin is one of these biomarkers but its correlation with myocarditis is not well established. The aim of this study was to evaluate correlation between troponin levels and cardiac dysfunction in moderate scorpion envenomation. METHODS: A retrospective monocentric study including patients admitted in the emergency department for moderate scorpion envenomation with troponin measurement during their early management. On arrival, an electrocardiogram and a chest X-ray were realized for all patients. RESULTS: We enrolled 132 patients with a mean age at 31.3 ± 24.4 years and a 1.35 sex-ratio. All patients had moderate systemic manifestations. There were 28 patients with clinical manifestations of cardiac dysfunction without life-threatening troubles (21.2%). Troponin was undetectable in 69 patients (56%). The mean value of troponin level (pg/ml) was higher in patients with clinical manifestations of left ventricular dysfunction (1.80 ± 3.8 vs. 0.11 ± 0.5; p = 0.02). Troponin levels were significantly higher in patients with positive T wave on electrocardiogram. CONCLUSION: In patients with moderate scorpion envenomation with positive T wave, high values of troponin suggest the presence of cardiac dysfunction.

Routine Postoperative Laboratory Tests Are Unnecessary After Partial Knee Arthroplasty.

BACKGROUND: While partial knee arthroplasty (PKA) is increasingly performed on an outpatient basis, many surgeons still admit patients overnight and obtain laboratory studies on the first postoperative day. The purpose of this study was to investigate the utility and cost effectiveness of routine postoperative laboratory studies after PKA. METHODS: This is a retrospective review of 322 consecutive unilateral or bilateral simultaneous PKAs (unicompartmental, patellofemoral, and modular bicompartmental knee arthroplasty) performed by a single surgeon. There were 408 complete blood counts and basic metabolic panels ordered. RESULTS: Despite a large number of laboratory studies ordered and abnormalities detected, there was a 1.6% rate of laboratory-associated interventions (for either hypokalemia or hyperglycemia in 5 patients) and no red blood cell transfusions. Hospital charges associated with laboratory studies totaled $85,413. There were no 90-day postoperative hospital readmissions or emergency department evaluations related to abnormal postoperative laboratory values. CONCLUSION: With an increasing emphasis placed on cost containment, the low rate of laboratory-associated interventions after PKA suggests that routinely obtaining laboratory studies are neither necessary nor cost effective.

Simvastatin Use in Patients with Type 2 Diabetes Mellitus: The Effects on Oxidative Stress.

OBJECTIVES: Studies have shown that people with type 2 diabetes mellitus (T2DM) may develop atherosclerosis due to the disturbance in oxidative control and progressive dyslipidemia. Our study aimed to highlight the benefits of simvastatin treatment in improving serum lipids and reducing oxidative damage in patients with T2DM. METHODS: Our randomized control trial included 56 patients with T2DM and dyslipidemia. The participants were on glibenclamide (5mg/day) during the period of the study. The patients were divided into two study groups (groups 1 and 2). Group 1 was the control group and consisted of 31 patients. Group 2 consisted of 25 participants, who were given simvastatin 20mg tablet once daily for 12 weeks. The control group did not receive simvastatin. Both groups were followed-up for measurement of blood pressure, pulse rate, serum lipids, and parameters of oxidative stress. RESULTS: The simvastatin treated group showed a significant improvement with reduced erythrocyte glutathione compared to the control group (p<0.001). This was also associated with a significant reduction in erythrocyte malondialdehyde in the simvastatin treated group compared to the control group (p<0.001). Serum lipids reflected a similar improvement in the levels of erythrocyte malondialdehyde. CONCLUSION: Our study highlights the beneficial role of simvastatin in improving the degree of oxidative stress in patients with T2DM through its effects on serum lipids and lipid peroxidation.

Family medicine training in Saudi Arabia: Are there any variations among different regions?

AIMS: The aim was to compare Eastern, Makkah, and Asir regions in term of residents' perception of the achievement of training objectives, and to assess various rotations based on residents' perception. SETTINGS AND DESIGN: This cross-sectional study was done among family medicine residents in the Eastern, Makkah, and Asir regions. METHODOLOGY: A questionnaire was developed by the investigator and validated by two experts. All residents, except R1 residents, were included. All data were collected by the investigator by direct contact with the residents. STATISTICAL ANALYSIS USED: Cronbach's alpha, analysis of variance, t-test, and univariate regression model as appropriate, were used. RESULTS: Reliability of the questionnaire was found to be 75.4%. One hundred and seven (response rate: 83.6%) residents completed the questionnaire. There were 51 (47.7%), 27 (25.2%), and 29 (27.1%) residents in the program in the Eastern region, Makkah, and Asir, respectively. The mean age was 29.1 ± 2.5 years; half of the residents were male, most of (83.2%) were married, and more than half (54.2%) of had worked in primary health care before joining the program. Overall, 45% of the residents perceived that they had achieved the training objectives. The highest rotations as perceived by the residents were psychiatry and otolaryngology while the lowest were orthopedics and ophthalmology. There were significant differences among the study regions with regard to the rotations in family medicine, internal medicine, orthopedics, general surgery, and emergency medicine. CONCLUSIONS: Overall, a good percentage of the residents perceived that they had achieved the training objectives. The rotations differed in the studied regions. Psychiatry and otolaryngology had the highest percentage of family medicine residents who perceived that they had achieved the training objectives while lowest was in internal medicine and obstetrics and gynecology. The highest rotations as perceived by the family medicine residents were psychiatry and otolaryngology while lowest were orthopedics and ophthalmology. Sharing of experience and further studies are needed to improve the program rotations.

Osteonecrosis of the knee: review.

Osteonecrosis is a devastating disease that can lead to end-stage arthritis of various joint including the knee. There are three categories of osteonecrosis that affect the knee: spontaneous osteonecrosis of the knee (SONK), secondary, and post-arthroscopic. Regardless of osteonecrosis categories, the treatment of this disease aims to halt further progression or delay the onset of end-stage arthritis of the knee. However, once substantial joint surface collapse has occurred or there are sign of degenerative arthritis, joint arthroplasty is the most appropriate treatment option. Currently, the non-operative treatment options consist of observation, non-steroidal anti-inflammatory drugs (NSAIDs), protected weight bearing, and analgesia as needed. Operative interventions include joint preserving surgery, unilateral knee arthroplasty (UKA), or total knee arthroplasty (TKA) depending on the extent and type of disease. Joint preserving procedures (i.e., arthroscopy, core decompression, osteochondral autograft, and bone grafting) are usually attempted in pre-collapse and some post-collapse lesions, when the articular cartilage is generally intact with only the underlying subchondral bone being affected. Conversely, after severe subchondral collapse has occurred, procedures that attempt to salvage the joint are rarely successful and joint arthroplasty are necessary to relieve pain. The purpose of this article is to highlight the recent evidence concerning the treatment options across the spectrum of management of osteonecrosis of the knee including lesion observation, medications, joint preserving techniques, and total joint arthroplasties.

[Rhinocerebral mucormycosis complicated by hemophagocytic lymphohistiocytosis: case report from Tunisia]. / Mucormycose rhinocérébrale compliquée d'un syndrome d'activation macrophagique: une observation Tunisienne.

Mucormycosis is a rare and often fatal fungal infection caused by fungi of the Mucorales order. It is mostly seen in people with weakened immune systems or with uncontrolled diabetes, and can cause extensive soft tissue damage and decay. Hemophagocytic lymphohistiocytosis has been reported only rarely and never described in an intensive care or emergency department setting. The purpose of this report is to describe a fatal case of sinonasal mucormycosis complicated by hemophagocytic lymphohistiocytosis in a diabetic child.

Anti-genotoxic and free-radical scavenging activities of extracts from (Tunisian) Myrtus communis.

The effect of extracts from leaves of Myrtus communis on the SOS reponse induced by Aflatoxin B1 (AFB1) and Nifuroxazide was investigated in a bacterial assay system, i.e. the SOS chromotest with Escherichia coli PQ37. Aqueous extract, the total flavonoids oligomer fraction (TOF), hexane, chloroform, ethyl acetate and methanol extracts and essential oil obtained from M. communis significantly decreased the SOS response induced by AFB1 (10 microg/assay) and Nifuroxazide (20 microg/assay). Ethyl acetate and methanol extracts showed the strongest inhibition of the induction of the SOS response by the indirectly genotoxic AFB1. The methanol and aqueous extracts exhibited the highest level of protection towards the SOS-induced response by the directly genotoxic Nifuroxazide. In addition to anti-genotoxic activity, the aqueous extract, the TOF, and the ethyl acetate and methanol extracts showed an important free-radical scavenging activity towards the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. These results suggest the future utilization of these extracts as additives in chemoprevention studies.

Measurement of B(D+-->K(*0)l(+)nu(l)).

Using 13.53 fb(-1) of CLEO data, we have measured the ratios of the branching fractions R(+)(e),R(+)(mu) and the combined branching fraction ratio R(+)(l), defined by R(+)(l)=[B(D+-->K(*0)l(+)nu(l))]/[B(D+-->K-pi(+)pi(+))]. We find R(+)(e)=0.74+/-0.04+/-0.05, R(+)(mu)=0.72+/-0.10+/-0.05, and R(+)(l)=0.74+/-0.04+/-0.05, where the first and second errors are statistical and systematic, respectively. The known branching fraction B(D+-->K-pi(+)pi(+)) leads to B(D+-->K(*0)e(+)nu(e))=(6.7+/-0.4+/-0.5+/-0.4)%, B(D+-->K(*0)mu(+)nu(mu))=(6.5+/-0.9+/-0.5+/-0.4)%, and B(D+-->K(*0)l(+)nu(l))=(6.7+/-0.4+/-0.5+/-0.4)%, where the third error is due to the uncertainty in B(D+-->K-pi(+)pi(+)).

Observation of the decay Omega(0)(c)-->Omega(-)e(+)nu(e).

Using the CLEO detector at the Cornell Electron Storage Ring we have observed the Omega(0)(c) (css ground state) in the decay Omega(0)(c)-->Omega(-)e(+)nu(e). We find a signal of 11.4+/-3.8(stat) events. The probability that we have observed a background fluctuation is 7.6x10(-5). We measure B(Omega(0)(c)-->Omega(-)e(+)nu(e)).sigma(e(+)e(-)-->Omega(0)(c)X)=(42.2+/-14.1(stat)+/-5.7(syst)) fb and R=[Gamma(Omega(0)(c)-->Omega(-)pi(+))]/[Gamma(Omega(0)(c)-->Omega(-)enu(e))]=00.41+/-0.19(stat)+/-0.04(syst). This is the first statistically significant observation of an individual decay mode of the Omega(0)(c) in e(+)e(-) annihilation and the first example of a baryon decaying via beta emission, where no quarks from the first generation participate in the reaction.

Experimental investigation of the two-photon widths of the chi(c0) and the chi(c2) mesons.

Using 12.7 fb(-1) of data collected with the CLEO detector at CESR, we observed two-photon production of the cc states chi(c0) and chi(c2) in their decay to pi(+)pi(-)pi(+)pi(-). We measured gamma(gammagamma)(chi(c))xB(chi(c)-->pi(+)pi(-)pi(+)pi(-)) to be 75+/-13(stat)+/-8(syst) eV for the chi(c0) and 6.4+/-1.8(stat)+/-0.8(syst) eV for the chi(c2), implying gamma(gammagamma)(chi(c0)) = 3.76+/-0.65(stat)+/-0.41(syst)+/-1.69(br) keV and gamma(gammagamma)(chi(c2)) = 0.53+/-0.15(stat)+/-0.06(syst)+/-0.22(br) keV. Also, cancellation of dominant experimental and theoretical uncertainties permits a precise comparison of gamma(gammagamma)(chi(c0))/gamma(gammagamma)(chi(c2)), evaluated to be 7.4+/-2.4(stat)+/-0.5(syst)+/-0.9(br), with QCD-based predictions.

Rate measurement of D(0)-->K+pi(-)pi(0) and constraints on D(0) -- D(0) mixing.

We present an observation and time-integrated rate measurement of the decay D(0)-->K(+)pi(-)pi(0) produced in 9 fb(-1) of e(+)e(-) collisions near the Upsilon(4S) resonance. The signal is inconsistent with an upward fluctuation of the background by 4.9 standard deviations. We measured the time-integrated rate of D(0)-->K(+)pi(-)pi(0) normalized to the rate of D(0)-->K(+)pi(-)pi(0) to be 0.0043(+0.0011)(-0.0010) (stat)+/-0.0007 (syst). This decay can be produced by doubly Cabibbo-suppressed decays or by the D(0) evolving into a D(0) through mixing, followed by a Cabibbo-favored decay to K(+)pi(-)pi(0). We also found the CP asymmetry A = (9(+25)(-22))% be consistent with zero.

An evaluation of the change in electrocardiographic P-wave variables after acute caffeine ingestion in normal volunteers.

BACKGROUND: Caffeine's effect on supraventricular dysrhythmias is poorly understood, and establishing a marker to predict atrial fibrillation may help to explain supraventricular dysrhythmias caused by caffeine. OBJECTIVE: To evaluate the effects of caffeine (mean 6.1 mg/kg) on maximum P-wave duration and P-wave dispersion in normal volunteers. METHOD: A randomised, double-blind, placebo-controlled, crossover study in 10 healthy volunteers at least 17 years of age at the University of Connecticut. Participants abstained from caffeinated products for at least 2 days before study initiation and were randomly allocated on different days to receive placebo or caffeine 400 mg. For each of the study phases, a baseline 12-lead electrocardiogram (ECG) was performed and a subsequent 12-lead ECG was performed 3 h after ingesting the study drug. RESULTS: No significant changes were found within intra- or intergroup comparisons for any P-wave variables measured. CONCLUSION: Single dose caffeine (400 mg) does not affect average P-wave duration, maximum P-wave duration or P-wave dispersion in normal individuals.

Evaluation of electrocardiographic and hemodynamic effects of caffeine with acute dosing in healthy volunteers.

STUDY OBJECTIVE: To evaluate the effects of moderate, single-dose caffeine consumption on electrocardiographic variables: PR, QRS, QT, QTc, and RR intervals, and QT and QTc interval dispersion. Effects of caffeine on blood pressure and heart rate also were evaluated. DESIGN: Randomized, double-blind, placebo-controlled, crossover study. SETTING: University school of pharmacy. PATIENTS: Ten healthy volunteers aged 17 years or older. INTERVENTION: Participants abstained from caffeinated products for at least 2 days before the study began and were randomly designated to receive placebo or caffeine 400 mg on various days. For each of the study phases, a baseline 12-lead electrocardiogram (ECG) was performed and a subsequent 12-lead ECG performed 3 hours after ingesting the study drug. Blood pressure readings were taken with each ECG. MEASUREMENTS AND MAIN RESULTS: No significant changes in any intragroup or intergroup electrocardiographic variables occurred. Caffeine increased blood pressure (systolic blood pressure [SBP]/diastolic blood pressure [DBP]) from 118+/-5/75+/-6 mm Hg to 128+/-8/77+/-7 mm Hg versus baseline (p=0.0022 and p=0.0368 for SBP and DBP, respectively). After drug dosing, SBP in the caffeine group was significantly higher than in the placebo group (128+/-8 mm Hg versus 119+/-7 mm Hg, p=0.0174). CONCLUSION: Moderate caffeine consumption by healthy young adults does not acutely affect PR, QRS, QT, QTc, and RR intervals, or QT and QTc interval dispersion. Caffeine-naive subjects experienced persistent elevations in SBP and DBP 3 hours after caffeine ingestion, indicating that longer caffeine abstinence than that which is recommended is necessary for blood pressure determination in the clinical setting.

Search for B --> tau(nu) and B --> K(nu)nu.

We report results of a search for B-->tau(nu) in a sample of 9.7 x 10(6) charged B meson decays. We exclusively reconstruct the companion B decay to suppress background. We set an upper limit on the branching fraction B(B-->tau(nu))<8.4 x 10(-4) at 90% confidence level. We also establish B(B+/--->K+/-nu(nu))<2.4 x 10(-4) at 90% confidence level.

First observation of the sigma(*+)(c) baryon and a new measurement of the sigma(*+)(c) mass.

Using data recorded with the CLEO II and CLEO II.V detector configurations at the Cornell Electron Storage Rings, we report the first observation and mass measurement of the Sigma(*+)(c) charmed baryon, and an updated measurement of the mass of the Sigma(+)(c) baryon. We find M(Sigma(*+)(c))-M(Lambda(+)(c)) = (231.0+/-1.1+/-2.0) MeV, and M(Sigma(+)(c))-M(Lambda(+)(c)) = (166.4+/-0.2+/-0.3) MeV, where the errors are statistical and systematic, respectively.