Analgesic and anti-inflammatory activity of ethanolic extracts of leaf and fruit pulp of Aegle marmelos in albino rats

Background: To study the analgesic and anti-inflammatory activity of the ethanolic extracts of leaf (LE) and fruit pulp (FE) of Aegle marmelos in comparison with the standard drugs pentazocine and diclofenac in albino rats. 56 healthy wistar albino rats of either sex were randomly divided into 14 groups of 4 each (n=4), weighing about 150-200grams were selected for the study. All drugs i.e. 1ml of 1% Carboxy methyl cellulose (CMC), pentazocine 10mg/kg (intraperitoneal), diclofenac 10 mg/kg and LE and FE at doses of 100mg/kg and 200mg/kg in 1% CMC (vehicle) were administered per oral one hour before the experiment.Methods: Analgesic activity was assessed by Eddy’s hot plate method (latency time) and acetic acid induced writhing (number of writhings) method. Anti-inflammatory activity was assessed by carrageenan induced hind paw edema method using digital plethysmometer.Results: Test drugs at doses LE 200mg/kg and FE 200mg/kg have shown significant increase in mean latency time in Eddy’s hot plate (P 0.05).Conclusions: Leaf extract (LE) and fruit extract (FE) at doses 200mg/kg have shown significant analgesic action and no anti-inflammatory action

Acute Kidney Injury in Severe Trauma Patients; a Record-Based Retrospective Study

Introduction: Acute kidney injury (AKI) is a common and devastating clinical issue in the community associated with high rates of morbidity and mortality. Objective: We aimed at estimating the frequency and levels of severity of AKI in trauma patients requiring hospital admission using the RIFLE criteria and assess their outcome. Method: Our retrospective record based study enrolled data of 80 participants aged 18-59 years who presented to the emergency department of KIMS hospital following an acute traumatic event. Participants with pre-existing renal dysfunction, chronic heart failure and chronic liver disease were excluded. Tests of significance were Chi square and independent sample t test, a p<0.05 was considered statistically significant. Results: Participants with AKI had significantly lower age (p=0.02) and lower revised trauma score (RTS) (p=0.01). Significant association of AKI with hypotension (p=0.01) and Glasgow coma scale (GCS) (p=0.008) was observed. No association of AKI with gender was observed (p=0.6). None of the AKI patients required renal replacement therapy and all participants attained normal renal function at discharge. Significantly longer mean duration of hospital stay (14.4 days) was observed among AKI patients (p=0.02). Totally, 6.3 % mortality was observed among both participants with and without AKI. Conclusion: Forty percent of acute trauma patients had AKI (in risk and injury category); but none were in failure, loss or end stage renal disease. No association of AKI and mortality was observed. AKI was associated with age, RTS, hypotension and GCS

Application of a Novel Algorithm for Expanding Newborn Screening for Inherited Metabolic Disorders across Europe

Inherited metabolic disorders (IMDs) are mostly rare, have overlapping symptoms, and can be devastating and progressive. However, in many disorders, early intervention can improve long-term outcomes, and newborn screening (NBS) programmes can reduce caregiver stress in the journey to diagnosis and allow patients to receive early, and potentially pre-symptomatic, treatment. Across Europe there are vast discrepancies in the number of IMDs that are screened for and there is an imminent opportunity to accelerate the expansion of evidence-based screening programmes and reduce the disparities in screening programmes across Europe. A comprehensive list of IMDs was created for analysis. A novel NBS evaluation algorithm, described by Burlina et al. in 2021, was used to assess and prioritise IMDs for inclusion on expanded NBS programmes across Europe. Forty-eight IMDs, of which twenty-one were lysosomal storage disorders (LSDs), were identified and assessed with the novel NBS evaluation algorithm. Thirty-five disorders most strongly fulfil the Wilson and Jungner classic screening principles and should be considered for inclusion in NBS programmes across Europe. The recommended disorders should be evaluated at the national level to assess the economic, societal, and political aspects of potential screening programmes

Atomic Hole Doping of Graphene

Graphene is an excellent candidate for the next generation of electronic materials due to the strict two-dimensionality of its electronic structure as well as the extremely high carrier mobility. A prerequisite for the development of graphene based electronics is the reliable control of the type and density of the charge carriers by external (gate) and internal (doping) means. While gating has been successfully demonstrated for graphene flakes and epitaxial graphene on silicon carbide, the development of reliable chemical doping methods turns out to be a real challenge. In particular hole doping is an unsolved issue. So far it has only been achieved with reactive molecular adsorbates, which are largely incompatible with any device technology. Here we show by angle-resolved photoemission spectroscopy that atomic doping of an epitaxial graphene layer on a silicon carbide substrate with bismuth, antimony or gold presents effective means of p-type doping. Not only is the atomic doping the method of choice for the internal control of the carrier density. In combination with the intrinsic n-type character of epitaxial graphene on SiC, the charge carriers can be tuned from electrons to holes, without affecting the conical band structure

Transient excited singlet state absorption in Rhodamine 6G

Transient excited singlet state absorption (ESSA) has been studied in Rhodamine 6G in ethanol using a nitrogen laser and nitrogen laser-pumped dye laser. Broad absorption with several submaxima and possible shoulders, which represent the vibrational structure, has been observed in Rhodamine 6G in the region, 4175-4640 Å . The position of the lowest vibrational level of the first excited singlet state S 1 has been determined from the crossing point of the long and short wavelength spectral wings of absorption and fluorescence respectively. The energy level scheme of the molecule has been obtained with the help of the absorption and fluorescence spectra recorded. The observed structure in ESSA has been tentatively interpreted to be due to transitions from the different vibrational levels of S 1 to one or more vibrational levels of the upper singlet electronic state S4

KirBac1.1: It's an Inward Rectifying Potassium Channel

KirBac1.1 is a prokaryotic homologue of eukaryotic inward rectifier potassium (Kir) channels. The crystal structure of KirBac1.1 and related KirBac3.1 have now been used extensively to generate in silico models of eukaryotic Kir channels, but functional analysis has been limited to 86Rb+ flux experiments and bacteria or yeast complementation screens, and no voltage clamp analysis has been available. We have expressed pure full-length His-tagged KirBac1.1 protein in Escherichia coli and obtained voltage clamp recordings of recombinant channel activity in excised membrane patches from giant liposomes. Macroscopic currents of wild-type KirBac1.1 are K+ selective and spermine insensitive, but blocked by Ba2+, similar to “weakly rectifying” eukaryotic Kir1.1 and Kir6.2 channels. The introduction of a negative charge at a pore-lining residue, I138D, generates high spermine sensitivity, similar to that resulting from the introduction of a negative charge at the equivalent position in Kir1.1 or Kir6.2. KirBac1.1 currents are also inhibited by PIP2, consistent with 86Rb+ flux experiments, and reversibly inhibited by short-chain di-c8-PIP2. At the single-channel level, KirBac1.1 channels show numerous conductance states with two predominant conductances (15 pS and 32 pS at −100 mV) and marked variability in gating kinetics, similar to the behavior of KcsA in recombinant liposomes. The successful patch clamping of KirBac1.1 confirms that this prokaryotic channel behaves as a bona fide Kir channel and opens the way for combined biochemical, structural, and electrophysiological analysis of a tractable model Kir channel, as has been successfully achieved for the archetypal K+ channel KcsA

Water-Gated Charge Doping of Graphene Induced by Mica Substrates

We report on the existence of water-gated charge doping of graphene deposited on atomically flat mica substrates. Molecular films of water in units of ~0.4 nm-thick bilayers were found to be present in regions of the interface of graphene/mica hetero-stacks prepared by micromechanical exfoliation of kish graphite. The spectral variation of the G and 2D bands, as visualized by Raman mapping, shows that mica substrates induce strong p-type doping in graphene, with hole densities of $(9 \pm 2) \times 1012 cm${-2}$. The ultrathin water films, however, effectively block interfacial charge transfer, rendering graphene significantly less hole-doped. Scanning Kelvin probe microscopy independently confirmed a water-gated modulation of the Fermi level by 0.35 eV, in agreement with the optically determined hole density. The manipulation of the electronic properties of graphene demonstrated in this study should serve as a useful tool in realizing future graphene applications.Comment: 15 pages, 4 figures; Nano Letters, accepted (2012

Gating at the Mouth of the Acetylcholine Receptor Channel: Energetic Consequences of Mutations in the αM2-Cap

Gating of nicotinic acetylcholine receptors from a C(losed) to an O(pen) conformation is the initial event in the postsynaptic signaling cascade at the vertebrate nerve-muscle junction. Studies of receptor structure and function show that many residues in this large, five-subunit membrane protein contribute to the energy difference between C and O. Of special interest are amino acids located at the two transmitter binding sites and in the narrow region of the channel, where C↔O gating motions generate a low↔high change in the affinity for agonists and in the ionic conductance, respectively. We have measured the energy changes and relative timing of gating movements for residues that lie between these two locations, in the C-terminus of the pore-lining M2 helix of the α subunit (‘αM2-cap’). This region contains a binding site for non-competitive inhibitors and a charged ring that influences the conductance of the open pore. αM2-cap mutations have large effects on gating but much smaller effects on agonist binding, channel conductance, channel block and desensitization. Three αM2-cap residues (αI260, αP265 and αS268) appear to move at the outset of channel-opening, about at the same time as those at the transmitter binding site. The results suggest that the αM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance

Retrospective Review of Positive Newborn Screening Results for Isovaleric Acidemia and Development of a Strategy to Improve the Efficacy of Newborn Screening in the UK

\ua9 2024 by the authors.Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–>70) \ub5mol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) \ub5mol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 \ub5mol/L triggering urgent referral, and those >2.0 and <5.0 \ub5mol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder