The role of gut microbiota in depression: an analysis of the gut-brain axis.

The gut-brain axis is a communication pathway that allows a two-way exchange of information between the microbiota of the gastrointestinal tract and the nervous system of humans. The vagus nerve, which is responsible for facilitating communication, provides support for this axis. The gut-brain axis is currently the subject of research, but studies into the diversity and stratification of the gut microbiota are just getting started. Researchers have discovered several positive trends by analyzing numerous studies examining the gut microbiota's impact on the effectiveness of SSRIs. It is common knowledge that a specific group of measurable, microbial markers has been recognized as being present in the feces of individuals suffering from depression. Specific bacterial species are a common denominator among therapeutic bacteria used to treat depression. It can also play a role in determining the severity of disease progression. Evidence that selective serotonin reuptake inhibitors (SSRIs) rely on the vagus nerve to exert their therapeutic effects has provided further support for the importance of the vagus nerve in the gut-brain axis, which is necessary for beneficial changes in the gut microbiota. This review will analyze the research linking gut microbiota to depression.

Analyzing risky behaviors among different minority and majority race in teenagers in the USA using latent classes.

Objective: This study is to ascertain any inconsistencies in the trend of co-occurrence by sex of teenage health risk behavior patterns such as smoking, behaviors contributing to deliberate and unintentional injuries, risky sexual behavior, and sedentary lifestyle. Methods: The study's purpose was accomplished using Youth Risk Behavior Surveillance System (YRBSS) 2013 data. A Latent Class Analysis (LCA) was conducted for the entire sample of teenagers as well as separately for each sex. Results: In this subset of youths, marijuana use was acknowledged by more than half of them, and smoking cigarettes was far more likely. More than half of the individuals in this subset engaged in risky sexual practices, like not using a condom during their most recent encounter. Males were split into three categories based on their involvement in risky behavior, while females were split into four subgroups. Conclusion: Regardless of gender, various risk behaviors among teenagers are connected. However, gender variations in the higher risk of particular trends, such as mood disorders and depression among females, underline the significance of creating treatments that take adolescent demographics into account.

Antibacterial potential and synergistic interaction between natural polyphenolic extracts and synthetic antibiotic on clinical isolates.

Emergence of antimicrobial resistance complicates treatment of infections by antibiotics. This has driven research on novel and combination antibacterial therapies. The present study evaluated synergistic antimicrobial activity of plant extracts and cefixime in resistant clinical isolates. Preliminary susceptibility profiling of antibiotics and antibacterial activity of extracts was done by disc diffusion and microbroth dilution assays. Checker-board, time-kill kinetics and protein content studies were performed to validate synergistic antibacterial activity. Results showed noteworthy quantities of gallic acid (0.24-19.7 µg/mg), quercetin (1.57-18.44 µg/mg) and cinnamic acid (0.02-5.93 µg/mg) in extracts of plants assessed by reverse-phase high performance liquid chromatography (RP-HPLC). Gram-positive (4/6) and Gram-negative (13/16) clinical isolates were intermediately susceptible or resistant to cefixime, which was used for synergistic studies. EA and M extracts of plants exhibited total synergy, partial synergy and indifferent characteristics whereas aqueous extracts did not show synergistic patterns. Time-kill kinetic studies showed that synergism was both time and concentration-dependent (2-8-fold decrease in concentration). Bacterial isolates treated with combinations at fractional inhibitory concentration index (FICI) showed significantly reduced bacterial growth, as well as protein content (5-62 %) as compared to extracts/cefixime alone treated isolates. This study acknowledges the selected crude extracts as adjuvants to antibiotics to treat resistant bacterial infections.

Mass Spectrometry-Based Proteomics of Minor Species in the Bulk: Questions to Raise with Respect to the Untargeted Analysis of Viral Proteins in Human Tissue.

(1) Background: Untargeted mass spectrometry (MS)-based proteomic analysis is highly amenable to automation. Software algorithms translate raw spectral data into protein information obtained by a comparison to sequence databases. However, the technology has limitations, especially for analytes measured at the limit of detection. In a protein expression study of human gastric biopsies, the question arose whether or not it is possible, as well as sensible, to search for viral proteins in addition to those from the human host. (2) Methods: Experimental data-independent MS data were analyzed using protein sequences for oncoviruses, and BLAST analyses were performed to elucidate the level of sequence homology to host proteins. (3) Results: About one hundred viral proteins were assigned, but there was also up to 43% sequence homology to human proteins. (4) Conclusions: There are at least two reasons why the matches to viral proteins should be used with care. First, it is not plausible that large amounts of viral proteins should be present in human gastric biopsies, so the spectral quality of the peptides derived from viral proteins is likely low. As a consequence, the number of false assignments is high. Second, homologous peptides found both in human and virus proteomes contribute to matching errors. Thus, though shotgun proteomics raw data can technically be analyzed using any database, meaningful results cannot be always expected and a sanity check must be performed. Both instrumentation and bioinformatic processing in MS-based proteomics are continuously improving at lowering the limit of detection even further. Nevertheless, data output should always be controlled in order to avoid the over-interpretation of results.

Nano-Enabled Strategies for the Treatment of Lung Cancer: Potential Bottlenecks and Future Perspectives.

On a global scale, lung cancer is acknowledged to be the major driver of cancer death attributable to treatment challenges and poor prognosis. Classical cancer treatment regimens, such as chemotherapy or radiotherapy, can be used to treat lung cancer, but the appended adverse effects limit them. Because of the numerous side effects associated with these treatment modalities, it is crucial to strive to develop novel and better strategies for managing lung cancer. Attributes such as enhanced bioavailability, better in vivo stability, intestinal absorption pattern, solubility, prolonged and targeted distribution, and the superior therapeutic effectiveness of numerous anticancer drugs have all been boosted with the emergence of nano-based therapeutic systems. Lipid-based polymeric and inorganic nano-formulations are now being explored for the targeted delivery of chemotherapeutics for lung cancer treatment. Nano-based approaches are pioneering the route for primary and metastatic lung cancer diagnosis and treatment. The implementation and development of innovative nanocarriers for drug administration, particularly for developing cancer therapies, is an intriguing and challenging task in the scientific domain. The current article provides an overview of the delivery methods, such as passive and active targeting for chemotherapeutics to treat lung cancer. Combinatorial drug therapy and techniques to overcome drug resistance in lung cancer cells, as potential ways to increase treatment effectiveness, are also discussed. In addition, the clinical studies of the potential therapies at different stages and the associated challenges are also presented. A summary of patent literature has also been included to keep readers aware of the new and innovative nanotechnology-based ways to treat lung cancer.

Insertable cardiac monitoring devices versus external cardiac monitoring for detecting atrial fibrillation and preventing the recurrence of stroke: A systematic review and meta-analysis.

BACKGROUND: Atrial Fibrillation (AF) is a major risk factor for stroke, which is the second leading cause of death worldwide. It remains uncertain whether insertable cardiac monitors (ICMs) enhance the ability to recognize AF over external cardiac monitoring in patients who have experienced a stroke. AIM: We conducted a systematic review and meta-analysis to determine whether ICM devices are more effective than external cardiac monitoring for the detection of AF in stroke patients. METHODS: We included studies that reported an AF detection rate in stroke patients with a follow-up of at least 12 months. We analyzed the data of 1233 patients from 3 randomized control trials (RCTs). RESULTS: When compared to external cardiac monitoring, ICM devices (Medtronic Reveal LINQ and Reveal XT) showed a significantly higher detection rate of AF (RR = 5.04, 95% CI = 2.93-8.68; p < 0.05; ARR = 10.47%, NNT = 10). The ICM arm had significantly higher usage of oral anticoagulants (OAC) as compared to the control arm. (RR = 2.76, 95% CI = 1.89-4.02, p < 0.05). Additionally, ICM usage was associated with a higher incidence of mild to moderate adverse events (RR = 10.52, 95% CI =1.35-82.14; p = 0.02) and a higher number of severe adverse events as compared to the control arm (RR = 7.61, 95% CI = 1.36-42.51; p = 0.02). CONCLUSION: ICM devices are associated with better detection rates of AF and higher usage of OAC as compared to external cardiac monitoring in post-stroke patients. However, ICM insertion is associated with a higher incidence of mild/moderate and severe adverse effects.

Nitric Oxide and Salicylic Acid Regulate Glutathione and Ethylene Production to Enhance Heat Stress Acclimation in Wheat Involving Sulfur Assimilation.

Phytohormones have a role in stress adaptation. The major mechanism underlying the role of exogenously-sourced nitric oxide (NO; as sodium nitroprusside, SNP: 50.0 µM) and salicylic acid (SA; 0.5 mM) in the presence of 2.0 mM SO4-2 was assessed in heat stress (HS; 40 °C for 6 h daily for 15 days) tolerance in wheat (Triticum aestivum L. cv. HD-3226). The cultivar HD-3226 possessed high photosynthetic sulfur use efficiency (p-SUE) among the six cultivars screened. Plants grown under HS exhibited an increased content of reactive oxygen species (ROS; including superoxide radical and hydrogen peroxide) and extent of lipid peroxidation with a consequent reduction in photosynthesis and growth. However, both NO and SA were found to be protective against HS via enhanced S assimilation. Their application reduced oxidative stress and increased the activity of antioxidant enzymes. NO or SA supplementation along with S under HS recovered the losses and improved photosynthesis and growth. The use of SA inhibitor (2-aminoindane-2-phosphonic acid; AIP) and NO scavenger (cPTIO) confirmed that the mitigating effects of SA and NO involved induction in S assimilation.

Chitosan Nanoparticles Loaded Poloxamer 407 Gel for Transungual Delivery of Terbinafine HCl.

The current study aimed to develop chitosan nanoparticles (CSNP) loaded poloxamer 407 (P407) gel formulation for transungual delivery of terbinafine HCl (TBN). TBN-CSNP were prepared by nanoprecipitation method and optimized by face-centered central composite design (FCCCD). Optimized TBN-CSNP formulation exhibited a spherical shape with hydrodynamic diameter; zeta potential and entrapment efficiency (EE) of 229 ± 5 nm; 37 ± 1.5 mV; and 75 ± 2% respectively. The solid state of TBN and its compatibility with formulation ingredients were confirmed through XRD and FTIR analysis respectively. TBN-CSNP loaded P407 gel exhibited pseudoplastic rheological behavior having a spreadability of 11 ± 2 g·cm/s. The washability study showed that 40 ± 2% of the gel was eroded after washing 12 times. Drug release from TBN-CSNP- and TBN-CSNP-loaded gel was 84 ± 5% and 57 ± 3%, respectively. The cumulative quantity of TBN permeated from TBN-CSNP-loaded P407 gel and TBN-loaded P407 gel was 25 ± 8 and 27 ± 4 µg/cm2, respectively. The nail uptake study showed that 3.6 ± 0.7 and 2.1 ± 0.3 µg of rhodamine was uptaken by the nail following 2 h topical application of TBN-CSNP loaded P407 gel and TBN loaded P407 gel, respectively. Hence, the developed CSNP-based P407 gel formulation can be a potential carrier for transungual delivery of TBN to topically treat onychomycosis.

Colibactin possessing E. coli isolates in association with colorectal cancer and their genetic diversity among Pakistani population.

Colorectal cancer (CRC) is the third most prevalent cause of tumorigenesis and several pathogenic bacteria have been correlated with aggressive cases of cancer i.e., genotoxin (colibactin) producing Escherichia coli (E. coli). This study was designed to investigate the genetic diversity of clb+clb+ E. coli strains and their association with CRC. Pathogenic E. coli isolates from colorectal biopsies were characterized based on phylotypes, antibiotic resistance pattern, and (Enterobacterial Repetitive Intergenic Consensus Sequence-based Polymerase Chain Reaction) ERIC-PCR. Furthermore, isolates were screened for the presence of the Pks (polyketide synthase) Island specifically targeting colibactin genes A and Q. The selective clb+clb+ isolates were subjected to cytotoxicity assay using Human embryonic kidney (HEK) cell lines. We revealed that 43.47% of the cancer-associated E. coli isolates were from phylogroup B2 comparatively more pathogenic than rest while in the case of healthy controls no isolate was found from B2. Moreover, 90% were found positive for colibactin and pks (polyketide synthase) island, while none of the healthy controls were found positive for colibactin genes. All healthy and cancer-associated isolates were tested against 15 antibiotic agents, we observed that cancer-associated isolates showed a wide range of resistance from 96% against Nalidixic acid to 48% against Doxycycline. Moreover, E. coli isolates were further genotyped using ERIC-PCR, and selected clb+clb+ E. coli isolates were subjected to cytotoxicity assay. We recorded the significant cytotoxic activity of clb+clb+ E. coli phylogroup B2 isolates that might have contributed towards the progression of CRC or dysbiosis of healthy gut microbiota protecting against CRC pathogenesis. Our results revealed a significant p<0.023 association of dietary habits and hygiene p<0.001with CRC. This is the first study to report the prevalence of E. coli phylogroups and the role of colibactin most virulent phylogroup B2 among Pakistani individuals from low socioeconomic setup.

Ethylene Signaling under Stressful Environments: Analyzing Collaborative Knowledge.

Ethylene is a gaseous plant growth hormone that regulates various plant developmental processes, ranging from seed germination to senescence. The mechanisms underlying ethylene biosynthesis and signaling involve multistep mechanisms representing different control levels to regulate its production and response. Ethylene is an established phytohormone that displays various signaling processes under environmental stress in plants. Such environmental stresses trigger ethylene biosynthesis/action, which influences the growth and development of plants and opens new windows for future crop improvement. This review summarizes the current understanding of how environmental stress influences plants' ethylene biosynthesis, signaling, and response. The review focuses on (a) ethylene biosynthesis and signaling in plants, (b) the influence of environmental stress on ethylene biosynthesis, (c) regulation of ethylene signaling for stress acclimation, (d) potential mechanisms underlying the ethylene-mediated stress tolerance in plants, and (e) summarizing ethylene formation under stress and its mechanism of action.

Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer.

(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance.

Pharmacological Basis of Rumex hastatus D. Don in Gastrointestinal Diseases with Focusing Effects on H+/K+-ATPase, Calcium Channels Inhibition and PDE Mediated Signaling: Toxicological Evaluation on Vital Organs.

This present study aimed to delineate Rumex hastatus D. Don crude extract (Rh.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rh.n-Hex, Rh.ETAC, Rh.Aq) and rutin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti H. pylori, antiulcer effects, and toxicology. The preliminary phytochemical analysis of Rumex hastatus showed different phytoconstituents and shows different peaks in GC-MC chromatogram. Rumex hastatus crude extract (Rh.Cr), fractions, and rutin attributed dose-dependent (50-300 mg/kg) protection (0-100%) against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance traversed by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, Rh.Cr and Rh.ETAC caused a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contractions at a similar concentration range, whereas Rh.n-Hex, rutin, and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration-response curves (CRCs) to the right, Rh.Cr (0.3-1 mg/mL) and Rh.ETAC (0.1-0.3 mg/mL) shifted the isoprenaline-induced inhibitory CRCs to the left. Rh.n-Hex, Rh.ETAC and rutin showed anti-H. pylori effect, also shows an inhibitory effect against H+/K+-ATPase. Rumex hastatus showed gastroprotective and antioxidant effects. Histopathological evaluation showed improvement in cellular architecture and a decrease in the expression of inflammatory markers such as, cyclooxygenase (COX-2), tumor necrosis factor (TN,F-α) and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry and ELISA techniques. In RT-PCR it decreases H+/K+-ATPase mRNA levels. Rumex hastatus was found to be safe to consume up to a dose of 2000 mg/kg in a comprehensive toxicity profile. Docking studies revealed that rutin against H+/K+-ATPase pump and voltage-gated L-type calcium channel showed E-values of -8.7 and -9.4 Kcal/mol, respectively. MD simulations Molecular Mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area (MMPBSA/GBSA) findings are consistent with the in-vitro, in-vivo and docking results.

Gastric Cancer Pre-Stage Detection and Early Diagnosis of Gastritis Using Serum Protein Signatures.

BACKGROUND: A gastric cancer (GC) diagnosis relies on histopathology. Endoscopy rates are increasing. Helicobacter pylori infection is a major GC risk factor. In an effort to elucidate abundant blood biomarkers, and potentially reduce the number of diagnostic surgical interventions, we investigated sera and biopsies from a cohort of 219 H. pylori positive and negative patients diagnosed with GC, gastritis, and ulcers. This allowed the comparative investigation of the different gastroduodenal diseases, and the exclusion of protein changes resulting from bacterial infection or inflammation of the gastric mucosa when searching for GC-dependent proteins. METHODS: High-definition mass spectrometry-based expression analysis of tryptically digested proteins was performed, followed by multivariate statistical and network analyses for the different disease groups, with respect to H. pylori infection status. Significantly regulated proteins differing more than two-fold between groups were shortlisted, and their role in gastritis and GC discussed. RESULTS: We present data of comparative protein analyses of biopsies and sera from patients suffering from mild to advanced gastritis, ulcers, and early to advanced GC, in conjunction with a wealth of metadata, clinical information, histopathological evaluation, and H. pylori infection status. We used samples from pre-malignant stages to extract prospective serum markers for early-stage GC, and present a 29-protein marker panel containing, amongst others, integrin ß-6 and glutathione peroxidase. Furthermore, ten serum markers specific for advanced GC, independent of H. pylori infection, are provided. They include CRP, protein S100A9, and kallistatin. The majority of these proteins were previously discussed in the context of cancer or GC. In addition, we detected hypoalbuminemia and increased fibrinogen serum levels in gastritis. CONCLUSION: Two protein panels were suggested for the development of multiplex tests for GC serum diagnostics. For most of the elements contained in these panels, individual commercial tests are available. Thus, we envision the design of multi-protein assays, incorporating several to all of the panel members, in order to gain a level of specificity that cannot be achieved by testing a single protein alone. As their development and validation will take time, gastritis diagnosis based on the fibrinogen to albumin serum ratio may be a quick way forward. Its determination at the primary/secondary care level for early diagnosis could significantly reduce the number of referrals to endoscopy. Preventive measures are in high demand. The protein marker panels presented in this work will contribute to improved GC diagnostics, once they have been transferred from a research result to a practical tool.

Isolated dextrogastria with eventration of right hemidiaphragm and hiatal hernia in an adult male.

BACKGROUND: Type 2 isolated dextrogastria in conjunction with protrusion of the right hemidiaphragm and hiatal hernia is an uncommon anomaly among all transpositions of the viscera. Clear diagnosis is not straightforward in such cases both clinically and with various imaging techniques leaving often only laparotomy for diagnosis. CASE PRESENTATION: Here, we discuss the case of a so far asymptomatic 19-year-old male, who had a 3-month history of abdominal pain and 2 days of vomiting with absolute constipation, and reduced air entry in the base of the right lung. A large air fluid level was found in the right lower hemithorax, furthermore, a loss of the normal diaphragmatic outline, and paucity of the bowel gases in the rest of the abdomen. Computer tomography with contrast was suggestive of loss of right lung volume, with stomach and bowel loops herniating into the right hemithorax and compressive atelactatic changes in the adjacent lung alongside an enlarged liver. A barium test showed the stomach fundus and body posteriorly positioned, while both duodenal bulb loops and the duodeno-jejunal junction alongside the small and large bowels were detected in their normal positions. CONCLUSION: In case of visceral transpositions, routine diagnostic blood and radiological tests may lead the health care provider to misdiagnosis. It is necessary, in particular when surgery is required, to carefully elucidate the organ anomaly. The use of additional imaging and radiological methods may be called for; CT scan and a barium test were critical here. This is the first case of isolated dextrogastria with eventration of right hemidiaphragm and hiatal hernia reported from Pakistan providing insights for diagnostic procedures.

Preventive Measures and Active Response against COVID-19 Taken by All Four Provinces, Two Independent Territories, and the Federal State of Islamic Republic of Pakistan, Islamabad.

The novel coronavirus disease outbreak started in December, 2019 in Wuhan, China. On March 11, 2020, WHO declared COVID-19 outbreak as a pandemic due to uncontrolled situation. Pakistani government management against COVID-19 was excellent having 204.65 million population, all four provinces, two independent territories, and federal state took different initiative in pandamic situation c. that's why the situation was under control in Pakistan due to state respond urgently to halt the spread of disease. With rapid response and full support of the government of Pakistan, the situation was under control in all aspects of life, June 17, 2019, each district of Pakistan recorded at least one confirmed case of COVID-19 due to remarkable effort against pandemic. The state of Pakistan declare urgency and fastest action to control the situation, economic package, ventilator manufacturing, and diagnostic kits were manufactured locally. The DRAP Pakistan permitted to use different drugs against COVID-19 and purchased vaccines from China. Due to the planning and management of the Pakistani Government, the situation was under control as compared with neighborhood countries (China and India), in both countries COVID-19 waves was lethal.

Gastric metastasis before diagnosis of primary invasive lobular breast carcinoma: a rare case presentation from Pakistan.

Metastatic spread of invasive lobular breast carcinoma to stomach is rare especially before diagnosis of primary breast cancer. Incorrect diagnosis might result in delay of appropriate treatment for breast cancer. Recognition of this possibility enables better clinical management. A 62-year-old female presented with upper gastrointestinal symptoms and weight loss and was referred to a gastroenterologist for investigation. At the time of initial diagnosis of stomach cancer, patient was asymptomatic for breast cancer. Multiple gastric biopsies taken showed features suspicious of metastatic breast cancer. Consequently, the initial provisional diagnosis of stomach cancer changed into metastatic invasive lobular breast carcinoma. These findings were corroborated radiologically. The patient was treated with letrozole and zoledronic acid as first-line therapy for one year. Residual metastatic breast cancer was present in the gastric mucosa. The patient was treated with endocrine therapy containing ribociclib and treatment was ineffective confirmed by PET-CT scan. But her symptoms have resolved completely despite her presentation with stage IV. We present rare case of initial presentation of gastric metastasis before diagnosis of a primary invasive lobular breast carcinoma. Correct diagnosis and appropriate treatment were accomplished through initial clinical suspicion, accurate histological examination, and endoscopy together with analysis of disease-specific biomarkers.

Improving access to the treatment of hepatitis C in low- and middle-income countries: evaluation of a patient assistance programme.

Background Modern antiviral treatments have high cure rates against the hepatitis C virus however, the high cost associated with branded medicines and diagnostic tests, have resulted in poor access for many low-income patients residing in low-and-middle-income countries. Objective This study aimed to evaluate the role of a patient assistance programme and generic medicines in improving access to treatment of low-income hepatitis C patients in a low-and-middle-income country. Setting A major teaching public hospital in Islamabad, Pakistan. Methods Hepatitis C patients who presented and enrolled for the patient assistance programme during 12 months (1st July 2015 and 30th June 2016) were included. Demography, prescription characteristics, the total costs of Hepatitis C treatment, medicine cost supported by the programme, out-of-pocket cost borne by the patient and average cost effectiveness ratio per sustained virologic response were calculated and compared for different generic and branded regimens. Main outcome measure cost contribution of patient assistance programme. Results A total of 349 patients initiated the treatment through the programme and of those 334 (95.7%) completed the prescribed treatment. There were 294 (88.02%) patients who achieved sustained virologic response. Patient assistance programme contributed medicines cost averaging 60.28-86.26% of the total cost of treatment ($1634.6) per patient. The mean (SE) cost per patient for generic option (Sofosbuvir/Ribavirin) was the lowest [$658.36 (22.3) per patient, average cost effectiveness ratio = $720.1/SVR] than branded option (Sovaldi/Ribavirin) [$2218.66 (37.6) per patient, average cost effectiveness ratio = $2361.8/SVR] of the three available treatment regimens. From patients' perspectives, the mean (SE) out-of-pocket cost was $296.9 (6.7) which primarily included diagnostic cost (69.9%) of the total cost. Conclusions Patient assistance programme, combined with generic brands of newer hepatitis C treatment offered a significant reduction in cost and widens access to hepatitis C treatment in low-and middle-income countries. However, substantial out-of-pocket costs of the treatment presents an important barrier for service access. There is a scope to widen such financial assistance programme to offer other costs attributed to patients, specifically for diagnosis, to widen service use in low-and-middle-income countries.

A Case of Dengue Fever With Hemorrhagic Manifestations.

Dengue fever is an arboviral infection spread by the Aedes mosquito with a wide spectrum of presentations encompassing simple flu-like illness to hemorrhagic manifestations. Hemorrhagic complications range from simple petechiae and purpura to gastrointestinal bleeding, hematuria, and severe central nervous system (CNS) bleeds. Herein we present a case of a 38-year-old male with dengue fever along with its hemorrhagic manifestations. Additionally, we conducted an extensive review of the literature to elucidate pathophysiology, diagnosis, and management of hemorrhagic manifestations in dengue fever.

In vitro and in vivo anti-Helicobacter pylori activity of selected medicinal plants employed for the management of gastrointestinal disorders.

Five medicinal plants Mentha piperita L., Trachyspermum ammi L., Viola odorata Linn., Matricaria chamomilla L. and Foeniculum vulgare Mill. were selected for their in vitro and in vivo evaluation of anti-Helicobacter pylori activity. In vitro evaluation was performed by using disk diffusion method and minimum inhibitory concentrations were noted while rat models were selected for in vivo activity against four Helicobacter pylori strains isolated form gastric mucosa. Mentha piperita showed largest zone of inhibition with 9 mm diameter among all other extracts. All the plants showed promising anti-Helicobacter pylori activity against four isolates and a reference strain at concentrations of 125, 250, 500 and 1000 µg/ml in comparison with Amoxicillin 1 µg/ml but least MIC was exhibited by Mentha piperita followed by in vivo testing where it competed Amoxicillin at 1000 mg/kg by achieving 80% eradication of Helicobacter pylori in mucosa of infected rats justified by histological examination of stomach. It was concluded that medicinal plants possess strong anti-Helicobacter pylori activity and can be considered a potential source of safe and effective alternative regimens for the eradication of Helicobacter pylori.