The impact of TRIPS Agreement on access to medicines in developing countries: Legal challenges faced by the pharmaceutical industry particularly in India

The impact of intellectual property rights in particular patent relating to public health has posed numerous challenges faced by developing countries who are members of World Trade Organisation (WTO).This paper examines the impact of TRIPS Agreement (Trade Related Intellectual Property Rights) in relation to developing countries in general with specifi cation made to India.Significant changes brought about by the TRIPS fl exibilities in particular usage of compulsory licensing and Bolar provision have to a certain extent benefited the developing countries in the field of public health during national emergency.The TRIPS flexibilities by way of amendment have helped countries that (do not possess manufacturing capacities) to import medicines. Some developing countries even utilised TRIPS fl exibilities in an aggressive manner to enforce their right to have access to medicines from other countries for the benefi t of their citizens.Further, TRIPs fl exibilities have helped developing countries to manufacture generic products to make it affordable to the people.This paper specifi cally examines the impact of the TRIPS Agreement on Indian generic pharmaceutical industry and the legal challenges faced by Indian pharmaceutical industry after the implementation of product patent regime effective from 1 January 2005.The Patent Amendment Act 2005(India) will be looked into especially on the controversy in respect of Section 3(d) of the Patent Amendment Act 2005(India) on the requirement of patentability.The new Section 92A of the Patent Amendment Act 2005(India) on the grounds to invoke compulsory licensing will be analysed to see whether Indian government has applied restrictive or broad approach, as compulsory licensing is certainly an important legal weapon for India to manufacture affordable generic medicines.The current challenges faced by India on data exclusivity provision often described as the TRIPS PLUS standard is impliedly stated in Article 39.3 of the TRIPS Agreement on undisclosed information.India needs to achieve legal certainty in complying with the TRIPS Agreement and also bearing in mind the TRIPS-PLUS standards before adopting those TRIPS provisions into its patent law legislation in order to promote innovation and to achieve public health as well as to serve the interest of the developing countrie

Diagnostic Accuracy of An Artificial Intelligence Based mHEALTH Intervention for Cataract Detection: A Multi-Center Prospective Study In Tamil Nadu, India

Background: E-Paarvai is an AI-based mHealth initiative piloted in Tamil Nadu, which enables frontline health workers to screen for cataract using a smartphone camera. The study aims to evaluate the diagnostic accuracy and reliability of e-Paarvai for cataract detection in primary care settings. Methodology: This prospective study was performed in 2022 in seven Upgraded Primary Health Centers across Tuticorin, India. Outpatients (age ≥ 50 years) without bilateral aphakia/pseudophakia, recruited by consecutive sampling, were each screened for cataract by e-Paarvai and an Ophthalmic assistant. Estimates of accuracy and reliability were reported along with their 95% confidence intervals (CI). Results: Among 337 participants (674 eyes) included in the analysis, 55 (16%) had unilateral and 168 (50%) participants had bilateral cataract on clinical eye examination. E-paarvai had a sensitivity and specificity of 83% and 53% at the subject level and 73% and 70.3% at the eye level respectively. Assuming 65% prevalence for cataract, PPV was 76% and 82%, while NPV was 62% and 58% in the per-subject and per-eye analysis respectively. The test-retest agreement was substantial with Kappa of 0.63. Conclusions: E-paarvai has an undeniable potential to improve detection and yield of cataract when implemented as a mass strategy in an eye care resource limited population

Molecular Cloning and Docking of speB Gene Encoding Cysteine Protease With Antibiotic Interaction in Streptococcus pyogenes NBMKU12 From the Clinical Isolates

Streptococcus pyogenes causes a variety of diseases ranging from mild diseases to severe invasive infections which result in significant morbidity and mortality. This study focuses on the antibiotic resistance of S. pyogenes and their interaction with cysteine protease. Around 36 beta-hemolytic isolates were collected from the clinical lab, of which seven isolates (19.4%) were identified as Streptococcus pyogenes. One of the seven isolates was collected from a urinary tract infection, which was identified by antibody agglutination and MALTI-TOF-MS, and it is designated as S. pyogenes NBMKU12. Around 8.3 to 66.6 % of the isolates were found to be resistant to one or more antimicrobial agents, especially, penicillin-G resistance was exhibited by 29.1% of the isolates. In the NBMKU12 isolate, the beta lactem (TEM) gene was detected among the 13 antibiotic genes for which it was tested. Furthermore, when analysis for presence of 13 virulence genes were carried out in NBMKU12 isolate, only speJ and speB were detected. The speB (streptococcal pyrogenic exotoxin B) encoding cysteine protease gene was cloned. This was followed by performing DNA sequencing to understand the putative cysteine protease interaction with antibiotics, inhibitors, and substrate. The speB gene consists of 1197 nucleotides and encodes a protein with multiple domains, including a signal peptide (aa 1–22), an inhibitor region (aa 27–156), and a catalytic cysteine domain (aa 160–367). The signal peptide cleavage site is predicted between Ala22 and Asn23. The putative 398 amino acid residues were found to have a theoretical pI of 8.76 and a molecular mass of 43,204.36 Da. The tested culture supernatants of NBMKU12 isolate exhibited the proteolytic activity against casein, papaya and pineapple used as substrates. The proteolytic activity suggests the expression of speB gene. Molecular docking analysis of cysteine protease showed that erythromycin (bond length 2.41 Å), followed by chloramphenicol (2.51 Å), exhibited a strong interaction; while penicillin-G (3.24 Å) exhibited a weak interaction, and this factor could be considered as a cause for penicillin-G resistance. The present study contributes to a better understanding of speB gene encoding cysteine protease, antibiotic resistance, and their interaction in the isolate, S. pyogenes NBMKU12. The antibiotics and cysteine protease interaction study confirms the resistance or sensitivity of S. pyogenes. Hence, it could be hypothesized that the isolate NBMKU12 is resistant to most of the tested antibiotics, and this resistance might be a cause for mutation

Prevalent Plant Growth Hormone Indole-3-acetic Acid Produced by Streptomyces sp. VSMKU1027 and its Potential Antifungal Activity against Phytofungal Pathogens

Microorganisms and plants can produce indole-3-acetic acid (IAA) by mechanisms that either involve tryptophan or do not involve tryptophan. The control of Zone of inhibition (ZOI) ranged from 1.2 cm to 1.0 cm. A promising antagonistic isolate, Streptomyces sp. VSMKU1027, exhibited robust antagonistic activity against two significant soil-borne phytopathogenic fungi, namely Rhizoctonia solani and Fusarium oxysporum, outperforming the control. The morphology of both R. solani and F. oxysporum, including their sclerotium and spores, became condensed and indistinct, and mycelial disintegration was observed due to the action of VSMKU1027, in contrast to the control. The isolate significantly produced antimicrobial traits and hydrolytic enzymes except hydrogen cyanide and cellulase. Furthermore, the promising isolate VSMKU1027 was identified as Streptomyces sp. based on its morphological, physiological, and biochemical characteristics. In comparison to the control, the isolate VSMKU1027 demonstrated increased synthesis of IAA and the hydrolytic enzyme protease with the corresponding substrates. The production of IAA was optimized on the sixth day, at 35°C and pH 6.5. The highest generation of IAA was recorded, with an ISP2 and 0.4% concentration of L-tryptophan

Screening the olive tree phyllosphere: Search and find potential antagonists against Pseudomonas savastanoi pv. savastanoi

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmicb.2020.02051/full#supplementary-materialOlive knot (OK) is a widespread bacterial disease, caused byPseudomonas savastanoipv.savastanoi(Pss), which currently has not effective control methods. The use of naturally occurring microbial antagonists, such as bacteria, as biocontrol agents could be a strategy to manage this disease. The objective of this work was to select bacteria from olive tree phyllosphere able to antagonizePssusingin vitroandin plantaexperiments. The elucidation of their modes of action and the potential relationship between antagonism and bacteria origin has been investigated, as well. To this end, 60 bacterial isolates obtained from the surface and inner tissues of different organs (leaves, twigs, and knots), from two olive cultivars of varying susceptibilities to OK, were screened for theirin vitroantagonistic effect againstPss. A total of 27 bacterial strains were able to significantly inhibitPssgrowth, being this effect linked to bacteria origin. Strains from OK-susceptible cultivar and colonizing the surface of plant tissues showed the strongest antagonistic potential. The antagonistic activity was potentially due to the production of volatile compounds, siderophores and lytic enzymes.Bacillus amyloliquefaciensP41 was the most effective antagonistic strain and their capacity to control OK disease was subsequently assayed usingin plantaexperiments. This strain significantly reduces OK disease severity (43.7%), knots weight (55.4%) and population size ofPss(26.8%), while increasing the shoot dry weight (55.0%) and root water content (39.6%) ofPss-infected olive plantlets. Bacterial isolates characterized in this study, in particularB. amyloliquefaciensP41, may be considered as promising biocontrol candidates for controlling OK disease.This work was funded by FEDER funds through COMPETE (Programa Operacional Factores de Competitividade), national funds through FCT (Fundacao para a Ciencia e a Tecnologia) and by Horizon 2020, the European Union's Framework Programme for Research and Innovation, within the project PRIMA/0002/2018 (INTOMED - Innovative tools to combat crop pests in the Mediterranean), and the Mountain Research Center - CIMO (UIDB/00690/2020 and UIDB/04046/2020)

Epidemiology of head injury in a tertiary care hospital in south India

Introduction:  The annual incidence of traumatic brain injury is around 28-70 million in the world which causes morbidity and mortality. In India, around 1 million suffer from severe head injury and the mortality rate is around 1 lakh per year. As time progresses there is an observable increase in rates of Head injuries. This study focuses on the epidemiology of traumatic head injury in a tertiary care centre (Madras Medical College, Chennai- India) Materials and methods: This study is a prospective study covering all head injury cases admitted from January 2022 – December 2022 in our tertiary care centre. These patients are treated according to the protocol of the Institute of Neurosurgery. This study covers the management, discharge and follow-up of these patients. Results: The total number of patients admitted with head injuries from January 2022 to December 2022 was 2061. Among them, RTA tops head injury mortality and morbidity. Among RTA, Two-wheeler-associated injuries were most common. Drunken driving, and not wearing helmets and protective gear played a vital role in head injuries. Conclusion: Primary prevention can be the key to reducing the national burden of head injuries

Prospective Randomized Study between Open Vs Closed Lateral Anal Internal Sphincterotomy in Patients with Chronic Fissure in Ano

Background: One of the the most common cause of pain during defecationin young patientsis chronic fissure in ano. Surgical treatment of choice for chronic fissure in ano is internal sphincterotomy. This procedure can be performed by open or closed method. The aim of the study was to compare the closed and open anal internal sphincterotomy in patients admitted in our hospital with chronic anal fissure. Subjects and Methods: 105 patients admitted in department of general surgery with chronic fissure in ano were divided into two groups. 50 patients (Group A) who were treated by closed method and 55 patients (Group B) who were managed by open lateralanal sphincterotomy method. A 3 months follow up done in both post-surgery to observe for pain, bleeding, infection, incontinence, and recurrence. Results: Significant difference was observed in postoperative acute complications between the two methods of internal anal sphincterotomy. Conclusion: Lateral anal sphincterotomy is the treatment of choice for chronic anal fissure, either open or closed method. However, the closed method was observed to have lesserpost operative complication compared to the open method.</jats:p