Sex Differences in the Neural and Behavioral Effects of Acute High-Dose Edible Cannabis Consumption in Rats.

The consumption of Δ9-tetrahydrocannabinol (THC)- or cannabis-containing edibles has increased in recent years; however, the behavioral and neural circuit effects of such consumption remain unknown, especially in the context of ingestion of higher doses resulting in cannabis intoxication. We examined the neural and behavioral effects of acute high-dose edible cannabis consumption (AHDECC). Sprague-Dawley rats (six males, seven females) were implanted with electrodes in the prefrontal cortex (PFC), dorsal hippocampus (dHipp), cingulate cortex (Cg), and nucleus accumbens (NAc). Rats were provided access to a mixture of Nutella (6 g/kg) and THC-containing cannabis oil (20 mg/kg) for 10 minutes, during which they voluntarily consumed all of the provided Nutella and THC mixture. Cannabis tetrad and neural oscillations were examined 2, 4, 8, and 24 hours after exposure. In another cohort (16 males, 15 females), we examined the effects of AHDECC on learning and prepulse inhibition and serum and brain THC and 11-hydroxy-THC concentrations. AHDECC resulted in higher brain and serum THC and 11-hydroxy-THC levels in female rats over 24 hours. AHDECC also produced: 1) Cg, dHipp, and NAc gamma power suppression, with the suppression being greater in female rats, in a time-dependent manner; 2) hypolocomotion, hypothermia, and antinociception in a time-dependent manner; and 3) learning and prepulse inhibition impairments. Additionally, most neural activity and behavior changes appear 2 hours after ingestion, suggesting that interventions around this time might be effective in reversing/reducing the effects of AHDECC. SIGNIFICANCE STATEMENT: The effects of high-dose edible cannabis on behavior and neural circuitry are poorly understood. We found that the effects of acute high-dose edible cannabis consumption (AHDECC), which include decreased gamma power, hypothermia, hypolocomotion, analgesia, and learning and information processing impairments, are time and sex dependent. Moreover, these effects begin 2 hours after AHDECC and last for at least 24 hours, suggesting that treatments should target this time window in order to be effective.

Psychophysiological Impact of Touching Landscape Grass among Older Adults.

Few studies have investigated plants' healing effects, particularly through touch-based therapy, on older adults. As hypertension rates continue to climb worldwide, touch-based therapy for hypertension prevention has become a significant priority in public health initiatives. This study investigated the impact of tactile interaction with real grass (a landscape activity) versus artificial grass on older adults' physical and cognitive abilities. Employing a within-subject design, we assessed the physiological and emotional effects of touching real grass versus artificial glass for 10 min. Study participants included 50 Chinese individuals, with an average age of 85.64 ± 3.72 years. Measurements included blood pressure, electroencephalogram, State-Trait Anxiety Inventory, and standard deviation (SD). Analyzing the SD data revealed that participants experienced a heightened sense of relaxation and calmness after touching real grass, compared to artificial grass. Furthermore, the participants' brainwave patterns-measured in mean power units-exhibited an upward trend while interacting with real grass, whereas they exhibited a downward trend during the interaction with artificial grass. Moreover, the mean systolic blood pressure significantly decreased following interaction with real grass. These findings suggest that engaging with real grass through touch potentially alleviates mental stress, in contrast to the effects of artificial grass.

Evaluation of antifungal potentials of Albizia kalkora extract as a natural fungicide: In vitro and computational studies.

The antifungal bioactivity potential of the organic extract of silk tree (Albizia kalkora) was investigated in the current study. The crude extracts of A. kalkora and methanol, n-hexane, chloroform, and ethyl acetate fractions were prepared. The antifungal activity of obtained fractions of A. kalkora was studied at different concentrations ranging from 0.39-50 µg/mL. Dimethyl sulfoxide (DMSO) was taken as a toxicity control, whereas thiophanate methyl (TM) as a positive control. All the fractions significantly reduced the FOL growth (methanolic: 9.49-94.93 %, n-hexane: 11.12-100 %, chloroform: 20.96-91.41 %, and ethyl acetate: 18.75-96.70 %). The n-hexane fraction showed 6.25 µg/mL MIC as compared to TM with 64 µg/mL MIC. The non-polar (n-hexane) fraction showed maximum antifungal bioactivity against FOL in comparison with chloroform, methanol, and ethyl acetate fractions. GC/MS analysis exhibited that the n-hexane fraction contained hexadecanoic acid, 9,12,15-octadecatrienoic acid, 9,12-octadecadienoic acid, bis(2-ethylhexyl) phthalate, methyl stearate, and [1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylic acid. The results of in vitro antifungal inhibition were further reinforced by molecular docking analysis. Five virulence proteins of FOL i.e., pH-responsive PacC transcription factor (PACC), MeaB, TOR; target of rapamycin (FMK1), Signal transducing MAP kinase kinase (STE-STE7), and High Osmolarity Glycerol 1(HOG1) were docked with identified phytocompounds in the n-hexane fraction by GC/MS analysis. MEAB showed maximum binding affinities with zinnimide (-12.03 kcal/mol), HOG1 and FMK1with α-Tocospiro-B (-11.51 kcal/mol) and (-10.55 kcal/mol) respectively, STE-STE7 with docosanoic acid (-11.31 kcal/mol), and PACC with heptadecanoic acid (-9.88 kcal/mol) respectively with strong hydrophobic or hydrophilic interactions with active pocket residues. In conclusion, the n-hexane fraction of the A. kalkora can be used to manage FOL.

Radiolabeling and preclinical animal model evaluation of DTPA coupled 99mTc-labelled flutamide complex ([99mTc]DTPA-FLUT) as a potential radiotracer for cancer imaging.

BACKGROUND: Advances in molecular imaging strategies have had an effect on precise diagnosis and treatment. Research has been intensified to develop more effective and versatile radiopharmaceuticals to uplift diagnostic efficiency and, consequently, the treatment. PURPOSE: To label the flutamide (FLUT) coupled with diethylenetriamine pentaacetate (DTPA) with technetium-99 m (99mTc) and to evaluate its binding efficiency with rhabdomyosarcoma (RMS) cancer cells. MATERIAL AND METHODS: Radiolabeling of FLUT with 185 MBq freshly eluted 99mTcO4-1 was carried out via DTPA bifunctional chelating agent using stannous chloride reducing agent at pH 5. The labeled compound was assessed for its purity using chromatography analysis, stability in saline and blood serum, AND charge using paper electrophoresis. Normal biodistribution was studied using a mouse model, while binding affinity with RMS cancer cells was studied using an internalization assay. The in vivo accumulation of RMS cancer cells in a rabbit model was monitored using a SPECT gamma camera. RESULTS: Radiolabeling reaction displayed a pharmaceutical yield of 97% and a stability assay showed >95% intact radiopharmaceutical up to 6 h in saline and blood serum. In vitro internalization studies showed the potential of [99mTc]DTPA-FLUT to enter into cancer cells. This biodistribution study showed rapid blood clearance and minimum uptake by body organs, and scintigraphy displayed the [99mTc]DTPA-FLUT uptake by lesion, induced by RMS cancer cell lines in rabbit. CONCLUSION: Stable, newly developed [99mTc]DTPA-FLUT seeks its way to internalize into RMS cancer cells, indicating it could be a potential candidate for the diagnosis of RMS cancer.

Calibration of Ring Oscillator-Based Integrated Temperature Sensors for Power Management Systems.

This paper details the development and validation of a temperature sensing methodology using an un-trimmed oscillator-based integrated sensor implemented in the 0.18-µm SOI XFAB process, with a focus on thermal monitoring in system-on-chip (SoC) based DC-DC converters. Our study identifies a quadratic relationship between the oscillator output frequency and temperature, which forms the basis of our proposed calibration mechanism. This mechanism aims at mitigating process variation effects, enabling accurate temperature-to-frequency mapping. Our research proposes and characterizes several trimming-free calibration techniques, covering a spectrum from zero to thirty-one frequency-temperature measurement points. Notably, the Corrected One-Point calibration method, requiring only a single ambient temperature measurement, emerges as a practical solution that removes the need for a temperature chamber. This method, after adjustment, successfully reduces the maximum error to within ±2.95 °C. Additionally, the Two-Point calibration method demonstrates improved precision with a maximum positive error of +1.56 °C at -15 °C and a maximum negative error of -3.13 °C at +10 °C (R2 value of 0.9958). The Three-Point calibration method performed similarly, yielding an R2 value of 0.9956. The findings of this study indicate that competitive results in temperature sensor calibration can be achieved without circuit trimming, offering a viable alternative or a complementary approach to traditional trimming techniques.

Supporting parenting among Syrian refugees in Lebanon: a randomized controlled trial of the caregiver support intervention.

BACKGROUND: Parenting interventions in humanitarian settings have prioritized the acquisition of parenting knowledge and skills, while overlooking the adverse effects of stress and distress on parenting-a key mediator of refugee children's mental health. We evaluated the effectiveness of the Caregiver Support Intervention (CSI), which emphasizes caregiver wellbeing together with training in positive parenting. METHODS: We conducted a two-arm randomized controlled trial of the CSI with Syrian refugees in Lebanon, with an intent-to-treat design, from September 2019-December 2020. A total of 480 caregivers from 240 families were randomized to the CSI or a waitlist control group (1:1). Retention from baseline to endline was 93%. Data on parenting and caregiver psychological wellbeing were collected at baseline, endline, and three-month follow-up. Prospective trial registration: ISRCTN22321773. RESULTS: We did not find a significant change on overall parenting skills at endline (primary outcome endpoint) (d = .11, p = .126) or at follow-up (Cohen's d = .15, p = .054). We did find a significant effect on overall parenting skills among participants receiving the full intervention-the sub-sample not interrupted by (COVID-19) (d = 0.25, p < .05). The CSI showed beneficial effects in the full sample at endline and follow-up on harsh parenting (d = -.17, p < .05; d = .19, p < .05), parenting knowledge (d = .63, p < .001; d = .50, p < .001), and caregiver distress (d = -.33, p < .001; d = .23, p < .01). We found no effects on parental warmth and responsiveness, psychosocial wellbeing, stress, or stress management. Changes in caregiver wellbeing partially mediated the impact of the CSI on harsh parenting, accounting for 37% of the reduction in harsh parenting. CONCLUSIONS: The CSI reduced harsh parenting and caregiver distress, and demonstrated the value of addressing caregiver wellbeing as a pathway to strengthening parenting in adversity. These effects were achieved despite a pandemic-related lockdown that impacted implementation, a severe economic crisis, and widespread social unrest. Replication under less extreme conditions may more accurately demonstrate the intervention's full potential.

Risk Factors for Post-ERCP Pancreatitis in Pediatric and Young Adult Patients.

OBJECTIVES: Post-ERCP pancreatitis (PEP) is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Limited existing data suggest that prophylactic pancreatic duct (PD) stenting in pediatric patients may increase the risk of PEP. The aim of this study is to identify factors associated with PEP in pediatric patients. METHODS: Patients at a single institution who underwent ERCP between 2012 and 2020 were retrospectively reviewed. Patient and procedure-related factors were collected. Data were analyzed using Chi-square or Fisher exact tests as appropriate and Mann-Whitney-Wilcoxon tests. RESULTS: Seven hundred thirty-six ERCPs were performed for 402 unique patients. Ninety-four cases were complicated by PEP (12.8%), of which 91 were mild and 3 were moderately severe. Pancreatic indication, native major papilla, PD cannulation and injection, and higher American Society for Gastrointestinal Endoscopy (ASGE) complexity were associated with PEP. A higher proportion of patients who received rectal indomethacin (65% vs 47%, P = 0.002), or who had placement of a prophylactic (31% vs 20%, P = 0.01) or therapeutic PD stent (37% vs 27%, P = 0.04) developed PEP; however, in a subgroup analysis of high-risk patients, this association was not persistent. A smaller proportion of PEP patients had PRSS1 mutation compared to non-PEP patients (22% vs 40%, P = 0.04). CONCLUSIONS: This study evaluates factors associated with developing PEP in a large pediatric cohort. A high rate of PEP was observed, likely secondary to higher rates of pancreatic indication and higher ASGE complexity scores compared to previously reported literature. Randomized prospective trials are needed to better define the utility of various interventions.

Subtrochanteric Shortening Osteotomy Provides Superior Function to Trochanter Slide Osteotomy in THA for Patients With Unilateral Crowe Type IV Dysplasia at a Minimum of 3 Years.

BACKGROUND: Performing THA in patients with high-riding developmental dysplasia of the hip (DDH) is associated with serious complications and technical challenges. Various methods of shortening osteotomy are available to facilitate femoral head reduction during THA in patients with high-riding hips; subtrochanteric shortening osteotomy and trochanteric slide osteotomy plus proximal shortening are the most common techniques. However, which approach is superior remains a topic of controversy. QUESTIONS/PURPOSES: (1) Is there any difference in clinical outcomes (defined as the Harris Hip Score [HHS] and residual limb length discrepancy) at a minimum of 3 years between subtrochanteric shortening osteotomy and trochanteric slide osteotomy in patients with Crowe Type IV DDH who underwent THA? (2) Is there any difference in the risk or type of complications between the two approaches? METHODS: We performed a retrospective, comparative study of two groups (subtrochanteric shortening osteotomy versus trochanteric slide osteotomy) matched for sex and preoperative HHS at a minimum of 3 years of follow-up. Between 2010 and 2018, we performed 67 THAs in patients with unilateral Crowe Type IV DDH. During that time, we generally used a trochanteric slide osteotomy for THA in all patients with Crowe Type IV hips and performed subtrochanteric shortening osteotomy when a conical stem was not available. A total of 42% (28) had THA with subtrochanteric shortening osteotomy, and 58% (39) had THA with trochanteric slide osteotomy. Of those, 89% (25) and 74% (29), respectively, were accounted for with complete datasets for possible matching at a minimum of 3 years of follow-up. Patients were matched for gender and preoperative HSS (within 10 points), leaving 22 patients in each group (79% of the subtrochanteric shortening osteotomy group and 56% of the trochanteric slide osteotomy group) for evaluation and analysis. Age (42 versus 46 years), gender (female: 73% versus 73%), preoperative HSS (40 versus 40), and preoperative leg length discrepancy (5.9 versus 5.3 cm) were comparable between the two groups (p > 0.05). The trochanteric slide osteotomy group exclusively received Cone Wagner (Zimmer) implants (100%), while Corail (DePuy Synthes) implants (77%) were the most commonly used in the subtrochanteric shortening osteotomy group. HHS at a minimum of 3 years as well as the presence or absence of a limp and Trendelenburg sign, functional leg length discrepancy, nonunion, nerve palsy, and other surgical complications were recorded and compared between the groups based on data drawn from a longitudinally maintained institutional database. RESULTS: At a mean follow-up of 73 months, improvement in HHS was greater in the subtrochanteric shortening osteotomy group than in the trochanteric slide osteotomy group (48 ± 4 points versus 36 ± 11 points, mean difference 12 points [95% CI 7 to 17 points]; p < 0.001). Although the preoperative leg length discrepancy was similar between the groups, there was a greater postoperative improvement in the subtrochanteric shortening osteotomy group (44 ± 8 mm and 38 ± 8 mm in the subtrochanteric shortening osteotomy and trochanteric slide osteotomy groups, respectively; p = 0.02). The risk of nonunion was higher with a trochanteric slide osteotomy than with a subtrochanteric shortening osteotomy (23% [5 of 22] versus 0% [0 of 22]; p = 0.048). Other complications, including intraoperative periprosthetic fractures, nerve palsy, heterotopic ossification, revision surgery, and dislocation, did not differ between the groups. CONCLUSION: In patients with Crowe Type IV hips undergoing THA, surgeons might consider subtrochanteric shortening osteotomy rather than trochanteric slide osteotomy to minimize the risk of nonunion and achieve superior hip function. Better correction of leg length discrepancy may also be possible with subtrochanteric shortening osteotomy. The long-term survivorship of hips after these two techniques, as well as the influence of the specific anatomy of the proximal femur on the choice of technique, remain to be explored in future studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Nanostructured material-based optical and electrochemical detection of amoxicillin antibiotic.

The penicillin derivative amoxicillin (AMX) plays an important role in treating various types of infections caused by bacteria. However, excessive use of AMX may have negative health effects. Therefore, it is of utmost importance to detect and quantify the AMX in pharmaceutical drugs, biological fluids, and environmental samples with high sensitivity. Therefore, this review article provides valuable and up-to-date information on nanostructured material-based optical and electrochemical sensors to detect AMX in various biological and chemical samples. The role of using different nanostructured materials on the performance of important optical sensors such as colorimetric sensors, fluorescence sensors, surface-enhanced Raman scattering sensors, chemiluminescence/electroluminescence sensors, optical immunosensors, optical fibre-based sensors, and several important electrochemical sensors based on different electrode types have been discussed. Moreover, nanocomposites, polymer, and MXenes-based electrochemical sensors have also been discussed, in which such materials are being used to further enhance the sensitivity of these sensors. Furthermore, nanocomposite-based photo-electrochemical sensors and the market availability of biosensors including AMX have also been discussed briefly. Finally, the conclusion, challenges, and future perspectives of the above-mentioned sensing techniques for AMX detection are presented.

Gut Microbiota-Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice.

RATIONALE: The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown. OBJECTIVE: To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy. METHODS AND RESULTS: Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers (Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii, and Lactobacillus fermentum) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice. CONCLUSIONS: This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.

Towards Real-Time Monitoring of Thermal Peaks in Systems-on-Chip (SoC).

This paper presents a method to monitor the thermal peaks that are major concerns when designing Integrated Circuits (ICs) in various advanced technologies. The method aims at detecting the thermal peak in Systems on Chip (SoC) using arrays of oscillators distributed over the area of the chip. Measured frequencies are mapped to local temperatures that are used to produce a chip thermal mapping. Then, an indication of the local temperature of a single heat source is obtained in real-time using the Gradient Direction Sensor (GDS) technique. The proposed technique does not require external sensors, and it provides a real-time monitoring of thermal peaks. This work is performed with Field-Programmable Gate Array (FPGA), which acts as a System-on-Chip, and the detected heat source is validated with a thermal camera. A maximum error of 0.3 °C is reported between thermal camera and FPGA measurements.

Cooperative Power-Domain NOMA Systems: An Overview.

Interference has been a key roadblock against the effectively deployment of applications for end-users in wireless networks including fifth-generation (5G) and beyond fifth-generation (B5G) networks. Protocols and standards for various communication types have been established and utilised by the community in the last few years. However, interference remains a key challenge, preventing end-users from receiving the quality of service (QoS) expected for many 5G applications. The increased need for better data rates and more exposure to multimedia information lead to a non-orthogonal multiple access (NOMA) scheme that aims to enhance spectral efficiency and link additional applications employing successive interference cancellation and superposition coding mechanisms. Recent work suggests that the NOMA scheme performs better when combined with suitable wireless technologies specifically by incorporating antenna diversity including massive multiple-input multiple-output architecture, data rate fairness, energy efficiency, cooperative relaying, beamforming and equalization, network coding, and space-time coding. In this paper, we discuss several cooperative NOMA systems operating under the decode-and-forward and amplify-and-forward protocols. The paper provides an overview of power-domain NOMA-based cooperative communication, and also provides an outlook of future research directions of this area.

Iron Oxide Nanoparticle-Based Ferro-Nanofluids for Advanced Technological Applications.

Iron oxide nanoparticle (ION)-based ferro-nanofluids (FNs) have been used for different technological applications owing to their excellent magneto-rheological properties. A comprehensive overview of the current advancement of FNs based on IONs for various engineering applications is unquestionably necessary. Hence, in this review article, various important advanced technological applications of ION-based FNs concerning different engineering fields are critically summarized. The chemical engineering applications are mainly focused on mass transfer processes. Similarly, the electrical and electronics engineering applications are mainly focused on magnetic field sensors, FN-based temperature sensors and tilt sensors, microelectromechanical systems (MEMS) and on-chip components, actuators, and cooling for electronic devices and photovoltaic thermal systems. On the other hand, environmental engineering applications encompass water and air purification. Moreover, mechanical engineering or magneto-rheological applications include dampers and sealings. This review article provides up-to-date information related to the technological advancements and emerging trends in ION-based FN research concerning various engineering fields, as well as discusses the challenges and future perspectives.

Elucidating the Role of Santalol as a Potent Inhibitor of Tyrosinase: In Vitro and In Silico Approaches.

This research work focuses on the potential application of an organic compound, santalol, obtained from santalum album, in the inhibition of the enzyme tyrosinase, which is actively involved in the biosynthesis of melanin pigment. Over-production of melanin causes undesirable pigmentation in humans as well as other organisms and significantly downgrades their aesthetic value. The study is designed to explain the purification of tyrosinase from the mushroom Agaricus bisporus, followed by activity assays and enzyme kinetics to give insight into the santalol-modulated tyrosinase inhibition in a dose-dependent manner. The multi-spectroscopic techniques such as UV-vis, fluorescence, and isothermal calorimetry are employed to deduce the efficiency of santalol as a potential candidate against tyrosinase enzyme activity. Experimental results are further verified by molecular docking. Santalol, derived from the essential oils of santalum album, has been widely used as a remedy for skin disorders and a potion for a fair complexion since ancient times. Based on enzyme kinetics and biophysical characterization, this is the first scientific evidence where santalol inhibits tyrosinase, and santalol may be employed in the agriculture, food, and cosmetic industries to prevent excess melanin formation or browning.

Not just an upset stomach: gastric perforation in a patient with anorexia nervosa.

Gastric perforation in patients with anorexia nervosa is a rare entity associated with high morbidity and mortality [Norris in Int J Eat Disord 49:216-237, 2016]. In cases reported in the literature, the perforation was often preceded by a binge episode, and the subsequent clinical presentation was rapid and acutely deteriorating with a fatality rate as high as 80% [Norris in Int J Eat Disord 49:216-237, 2016, Pitre in J Med Case Rep 15:61, 2021]. We present a case of gastric perforation in the context of restrictive anorexia nervosa unique both for the absence of a premorbid binge episode as well as delayed clinical manifestations of medical distress, leading to abdominal compartment syndrome.Level IV Evidence obtained from multiple time series analysis such as case studies.

An update on the novel and approved drugs for Alzheimer disease.

Introduction: Given the severity of the condition and the increasing number of patients, developing effective therapies for Alzheimer's disease has become a significant necessity. Aggregation of Amyloid-Beta (Aß) plaques and Tau Protein Tangles in the brain's nerve tissue are two of the most histopathological/pathophysiological symptoms. Another important element involved in the etiology of Alzheimer's disease is the reduction in acetylcholine (ACh) levels in the brain. Currently available medications for Alzheimer's disease treatment, such as cholinesterase inhibitors and an antagonist of the N-methyl-d-aspartate receptor, can temporarily reduce dementia symptoms but not stop or reverse disease development. In addition, several medicinal plants have been shown to diminish the degenerative characteristics associated with Alzheimer's disease, either in its crude form or as isolated chemicals. Aim: This review summarises the results from previous studies that reflect an array of novel therapies underway in various phases of clinical trials. Many are discontinued due to non-adherence to the designed endpoints or the surfacing of unavoidable side effects. The present piece of article focuses on the approved drugs for the treatment of Alzheimer's disease and their related mode of action as well as the promising therapies for the treatment of the said disease. Special attention has been placed on the researched herbal drugs, with the pipeline of novel therapies underway in various phases of clinical trials. Result: The current article includes a list of approved pharmaceuticals for treating Alzheimer's disease, prospective therapies for the illness's treatment, and a pipeline of novel therapies in various stages of clinical trials. Conclusion: The results suggest that the drugs under clinical trials may open new pathways for the effective treatment of patients with Alzheimer's disease while improving their quality of life.

Design and evaluation of sustained release mucoadhesive film of sumatriptan succinate containing grafted co-polymer as the platform.

Purpose: The primary goal of this research is to improve the bioavailability and efficacy of Sumatriptan succinate by incorporating it in the mucoadhesive film for the treatment of migraine. Mucoadhesive film offers an excellent substitute to deliver the drug in the systemic circulation and eliminate the chance of first-pass metabolism. Method: Using central composite design (CCD), various formulations were created by incorporating polymer, plasticizer, and water, and an optimized preparation was created using statistical screening. The optimization has been performed by applying a 34 factorial method based on dependent variables such as Drug content (%), Swelling index (%), Folding endurance (Number of times), and Mucoadhesive strength (g). Results: The actual experimental values obtained were compared with those predicted by the mathematical models. Formulation S9 was selected as an optimized formulation because it showed the lowest standard deviation between predicted and actual values compared to other formulations. In the case of the S9 formulation, approximately 77.12% of the drug was released within 24 h, but initially, it showed burst release. In addition, the in-vitro release of pure drug suspension showed 99.32% drug release within 2 h. That signified that the developed formulation provides sustained release due to presence of grafted co-polymer. Conclusion: Formulation holding drug-loaded grafted film showed decent sustained and controlled drug release characteristics compared to a pure drug suspension. S9 formulation showed better results than other formulations in drug content, swelling index, folding endurance, and mucoadhesive strength, which is further used to treat migraine.

Effects of Host Species Identity and Diet on the Biodiversity of the Microbiota in Puerto Rican Bats.

Microbiota perform vital functions for their mammalian hosts, making them potential drivers of host evolution. Understanding effects of environmental factors and host characteristics on the composition and biodiversity of the microbiota may provide novel insights into the origin and maintenance of these symbiotic relationships. Our goals were to (1) characterize biodiversity of oral and rectal microbiota in bats from Puerto Rico; and (2) determine the effects of geographic location and host characteristics on that biodiversity. We collected bats and their microbiota from three sites, and used four metrics (species richness, Shannon diversity, Camargo evenness, Berger-Parker dominance) to characterize biodiversity. We quantified the relative importance of site, host sex, host species-identity, and host foraging-guild on biodiversity of the microbiota. Microbe biodiversity was highly variable among conspecifics. Geographical location exhibited consistent effects, whereas host sex did not. Within each host guild, host species exhibited consistent differences in biodiversity of oral microbiota and of rectal microbiota. Oral microbe biodiversity was indistinguishable between guilds, whereas rectal microbe biodiversity was significantly greater in carnivores than in herbivores. The high intraspecific and spatial variation in microbe biodiversity necessitate a relatively large number of samples to statistically isolate the effects of environmental or host characteristics on the microbiota. Species-specific biodiversity of oral microbiota suggests these communities are structured by direct interactions with the host immune system via epithelial receptors. In contrast, the number of microbial taxa that a host gut supports may be driven by host diet-diversity or composition.

Alternaria alternata causing Alternaria Leaf Spot of Cucumis melo (Muskmelon) in Pakistan.

In July 2019, leaf spot symptoms were observed on muskmelon (Cucumis melo L.) cv. Jackball-1 plants in an experimental field of 2.02 ha with a disease incidence of 30% (31°26'05.4"N 73°04'30.3"E) at the University of Agriculture, Faisalabad, Pakistan. Early symptoms consisted of small, circular, brown, necrotic spots 1 to 2 mm in size covering 10 to 30% of the leaf blade, which gradually enlarged and developed concentric rings. To identify the causal agent of the disease, a total of 20 symptomatic leaves were collected. Small pieces removed from the margin between healthy and diseased tissues were surface disinfected in 70% ethanol for 2 min, rinsed three times with sterile distilled water, plated on Potato dextrose agar and incubated at 25 ± 2°C with a 12-h photoperiod. Morphological observations were made on 7-day-old single-spore cultures. The colonies initially appeared white and then turned olive-green. All 20 fungal isolates were characterized by small, short-beaked, multicellular conidia. The conidia were ellipsoidal or ovoid and measured 11.5 to 30 µm × 7.5 to 15 µm (n = 50) with longitudinal and transverse septa. Conidia were produced on short conidiophores in chains. The beaks were short (often less than one-third the body length) and conical or cylindrical. These morphological features concur with the description of Alternaria alternata (Fr.) Keissler (Woudenberg et al. 2013). For molecular identification, genomic DNA of four representative isolates (HMSMZA 07, 08, 09, 10) were extracted and PCR amplification of the internal transcribed spacer (ITS)-rDNA, glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and translation elongation factor-1 alpha (TEF-1α) gene regions were performed (White et al. 1990, Berbee et al. 1999, Carbone & Kohn, 1999) respectively. The obtained sequences were deposited in GenBank with accession numbers MT253643.1-MT253646.1 (ITS-rDNA), MT318260.1-MT318263.1 (GAPDH), and MT318280.1-MT318283.1 (TEF-1α). BLASTn analysis of HMSMZA 07 sequences showed 100% identity with ITS rDNA (MN615420.1), GAPDH (MK637438.1) and TEF-1α (MN807795.1) sequences of A. alternata. To confirm pathogenicity, 5-6 weeks-old Muskmelon (Cucumis melo L.) cv. Jackball-1 plants (true leaf stage) were sprayed until runoff (1.5 to 2 ml per plant) with A. alternata conidial suspension (106 conidia/ml; obtained from 1 week-old cultures) amended with 0.1% (vol/vol) of Tween 20 using an atomizer in the green house. The experiment included four A. alternata isolates inoculated onto three muskmelon plants per each isolate, whereas control plants (n = 3) were sprayed with sterile distilled water amended with 0.1% Tween 20. The plants were incubated at 25 ± 2°C in a greenhouse and the experiment was conducted twice. After 5 to 7 days post inoculation, necrotic leaf spots were observed on the inoculated plants and A. alternata was reisolated and confirmed by morphological and molecular (ITS) features. No disease was observed on control plants. Previously, A. alternata on muskmelon has been reported in Pakistan (Ahmad et al. 1997), however this study provides a detailed description of disease symptoms, morphological and molecular identity of the causal agent including completion of Koch's postulates. The disease could represent a threat for muskmelon crop in Pakistan due to its increasing cultivation and therefore warrants the need to develop disease management strategies.

Beamforming Using Exact Evaluation of Leakage and Ergodic Capacity of MU-MIMO System.

Closed-form evaluation of key performance indicators (KPIs) of telecommunication networks help perform mathematical analysis under several network configurations. This paper deals with a recent mathematical approach of indefinite quadratic forms to propose simple albeit exact closed-form expressions of the expectation of two significant logarithmic functions. These functions formulate KPIs which include the ergodic capacity and leakage rate of multi-user multiple-input multiple-output (MU-MIMO) systems in Rayleigh fading channels. Our closed-form expressions are generic in nature and they characterize several network configurations under statistical channel state information availability. As a demonstrative example of the proposed characterization, the derived expressions are used in the statistical transmit beamformer design in a broadcast MU-MIMO system to portray promising diversity gains using standalone or joint maximization techniques of the ergodic capacity and leakage rate. The results presented are validated by Monte Carlo simulations.