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of cancer patients admitted to an exclusive palliative care unit at a reference institute in Rio de Janeiro. Method: An observational, descriptive, retrospective study with a quantitative approach was conducted. The population consisted of patients admitted and under pharmaceutical care monitoring from June 2022 to May 2023. Data were collected from physical medical records, institutional electronic systems, and specific spreadsheets. Sociodemographic, clinical, and pharmacotherapeutic variables were analyzed. Results: A total of 283 patients were evaluated, ranging in age from 21 to 85 years, with the majority being 60 years or older (n=153; 54.1%; mean age = 60.1; standard deviation = 8.2) and predominantly female (n=186; 65.7%). The most frequent primary tumor site was the digestive system (n=56; 19.8%) followed by breast and gynecological sites (n=55; 19.4%). Regarding comorbidities, most patients had at least one (n=166; 58.7%), with the circulatory system (n=121; 42.7%) being predominant. The percentage of patients with DRP was 50.9% (n=144). A total of 298 DRP were observed, among which the non-use of the necessary medication for the patient was highlighted (n=106; 35.6%). A total of 302 interventions were performed, mainly regarding the inclusion of a new medication (n=87; 28.8%). There was a 93% acceptance rate of the interventions performed. Conclusion: The clinical role of the pharmacist within a multidisciplinary team enables the identification of Drug-Related Problems (DRPs), thereby contributing to the rational and safe use of medications through the optimization of prescriptions and rationalization of pharmacotherapy.

Introdução: A revisão farmacoterapêutica consiste na análise dos fármacos utilizados por um paciente, objetivando a diminuição de problemas relacionados a medicamentos (PRM). O tratamento paliativo pode acarretar efeitos adversos e contribuir para a polifarmácia. Portanto, o farmacêutico é de grande valia para garantir a segurança e o uso racional associado ao tratamento farmacológico. Objetivo: Analisar a revisão da farmacoterapia realizada em pacientes oncológicos submetidos a cuidados paliativos exclusivos em um instituto de referência no Rio de Janeiro. Método: Estudo observacional, descritivo, retrospectivo, com abordagem quantitativa, envolvendo pacientes internados na unidade de cuidados paliativos exclusivos do Instituto Nacional de Câncer, que tiveram seu tratamento farmacológico revisado pelo farmacêutico, no período de 1 de junho de 2022 a 31 de maio 2023. Resultados: O tratamento farmacológico foi revisado em 171 pacientes, a maioria do sexo feminino (n=114; 66,7%) com idade igual ou maior do que 60 anos. Mais da metade dos pacientes apresentou pelo menos uma comorbidade (n=93; 54,4%), com predomínio daquelas relacionadas ao sistema circulatório (n=68; 43,9%). A porcentagem de PRM e de intervenções farmacêuticas forneceram resultados equivalentes (23,4%). O principal PRM foi a utilização de medicamento de que o paciente não necessitava (n=49; 53,3%) e a maioria das intervenções ocorreu para a exclusão de medicamentos (n=55; 56,7%). Houve 93,5% de aceitabilidade das intervenções. Conclusão: O estudo sinaliza a importância da revisão da farmacoterapia na otimização do tratamento medicamentoso em cuidados paliativos e reforça a necessidade de reduzir o número de medicamentos prescritos no final da vida.

This paper explores the mediating effect of entrepreneurial self-efficacy in the association between entrepreneurial knowledge, motivation, and intention in the Indian context. SEM is applied on a sample of 750 final year students from the undergraduate and post graduate management program of Rajasthan. The findings show significant and positive mediating effect of self-efficacy on the association among entrepreneurial knowledge and intentions. However, no such impact of entrepreneurial self-efficacy has been found in the linkage between entrepreneurial motivation and intentions. Thus, this study encourages universities to offer entrepreneurial training modules to boost their self-confidence and motivate them to have entrepreneurial intention.

The application of nano-fertilizers (NFs) is an emerging research field in agriculture. These are materials in the size range of 1–100 nm that support the nutrition of the plants. It is a novel way to optimize the nutrient supply, either alone or in combination. NFs are an economical alternative to ordinary chemical fertilizers that can increase global food production in a sustainable way. NFs are made up of nutrients and micronutrients and may act as carriers for nutrients. The nanocarriers deliver the nutrients to the right place, reducing the additional amount of active chemicals deposited in the plant, besides a slow release. Although nano-coated materials manage to penetrate through the stomata with a size exclusion limit greater than 10 nm, the nanoparticles appear to be able to make holes and enter the vascular system. This review addresses the potential benefits of NFs to agriculture, synthesis, mode of entry, mechanisms of action, and the fate of nanomaterials in soil. Finally, policy makers will have the bases to regulate the dose, frequency, and time period of NF applications for food production. We suggest formulating the integrated risk management frameworks for the possible applications of NFs in agriculture.

The objectives of this study is to examine the partnership agreement model between SMEs and Large Enterprises in creating shared prosperity and to examine the principles’ application of the agreement in partnership that can provide protection for SMEs in Indonesia. The research method used in this study is analytical descriptive which aims to obtain a comprehensive picture of the partnership agreement in Indonesia. Data about the business partnership agreement and its implementation are then analyzed to answer the research problem. Based on analysis, the results of this study showed that 1) the partnership agreement model between SMEs and Large Enterprises in creating shared prosperity must begin with efforts to apply the principles of the agreement and business ethics in the partnership agreement. 2) the application of the principles of agreement in partnership in practice has not yet run optimally, there are still many partnership agreements that have been deviated from the contents of the agreement. In this case the role of government is needed to provide protection to the SME group and also the Large Business group to realize social responsibility for the progress of the UKM business group.

This article describes the integration of lawsuits in breach of law or breach of contract which often found in court examination practice. First issue will analyze whether the integration of lawsuits can be conducted between breach of law and breach of contract claims pursuant to Indonesian Civil Procedures. The second issue will analyze the legal consideration of judges who reject the integration of lawsuits between breach of law and breach of contract claims pursuant to Indonesian Civil Procedures There are some of opinions of judges or expert against the integration of lawsuits between breach of law and breach of contract claims. A jurisprudence states that the integration of lawsuit between breach of law and breach of contract claim in lawsuit is violating the code of conduct since both shall be examined respectively. HIR, RBG and RV does not strictly stipulate and prohibit the integration of lawsuit, however, pursuant to Jurisprudence of The Supreme Court of the Republic of Indonesia No. 1875K/Pdt/1984 dated April 24, 1986, “the integration of lawsuits between the breach of law and breach of contract claims cannot be conducted since it is violating the civil procedures and accordingly it shall be examined respectively. In accordance with such jurisprudence, the Judex Jurist is authorized to declare that the integration of lawsuits between the breach of law and breach of contract claims is unacceptable lawsuit (NO/niet oontvankelijk verklaard).

Abstract The development of buying and selling both conventional and online transactions has an impact on the need for effective dispute resolution when there is a loss to consumers. Fast, simple, and low-cost consumer dispute resolution is needed to speed up the way the dispute is resolved. This article is part of the results of fundamental research conducted in a normative juridical method. The results showed that consumer dispute resolution in the court with a small claim value was not balanced with the mechanism of proceedings in the court, while the power of the decision through BPSK resolution was not final and binding. Small Claims Procedures are solutions that integrate informal and formal mechanisms as one of the concrete steps to achieve legal certainty in resolving consumer disputes in Indonesia. Abstrak Perkembangan jual beli baik transaksi secara konvensional maupun online berdampak pada kebutuhan penyelesaian sengketa yang efektif ketika terjadinya kerugian pada konsumen. Penyelesaian sengketa konsumen secara cepat, sederhana, dan berbiaya ringan diperlukan dengan mempercepat cara penyelesaian sengketa. Artikel ini merupakan bagian dari hasil penelitian fundamental yang dilakukan secara yuridis normatif. Hasil penelitian menunjukkan bahwa penyelesaian sengketa konsumen di pengadilan dengan nilai gugatan yang kecil tidak seimbang dengan mekanisme beracara di pengadilan, sementara itu penyelesaian melalui BPSK kekuatan putusannya tidak bersifat final and binding. Small Claims Procedures merupakan solusi yang memadukan mekanisme informal dan formal sebagai salah satu langkah konkret dalam rangka tercapainya kepastian hukum dalam penyelesaian sengketa konsumen di Indonesia.

We report the effect of various parameters, namely substrate concentration, time, pH and temperature, on the biosynthesis of silver nanoparticles (AgNPs) by using the extract of actinobacterial strains, which were isolated from the sediments of Lonar Crater Lake in India. It was found that the formation of AgNPs and its morphology depended on synthesis conditions. Visual observation of the reaction mixture, ultraviolet-vis spectroscopic analysis and mass of synthesized AgNPs indicated that 25°C, pH 7 and 3 days of incubation time were optimal for its efficient synthesis. The transmission electron microscopy (TEM) analysis revealed aggregation and irregular shape of AgNPs both at acidic pH and below 25°C. It was found that alkaline pH and temperature higher than optimal fostered the formation of nanoparticle aggregates. Based on the obtained results, it was concluded that the efficiency of biological synthesis by using actinobacteria as well as the size and shape of fabricated nanoparticles can be manipulated by controlled conditions of synthesis process. The use of desired nanoparticles increases its potential for medical applications.

Este artigo buscou levantar na literatura nacional os motivos pelos quais a relação entre as operadoras de planos de saúde e os cirurgiões-dentistas é conflituosa, traçando um histórico do mercado brasileiro na área, bem como o perfil do profissional deste segmento, destacando as implicações observadas quanto à autonomia profissional, remuneração e satisfação com o trabalho, a fim de fomentar uma reflexão crítica na categoria quanto às relações de trabalho no âmbito da assistência odontológica suplementar. A análise realizada evidenciou que o sistema de saúde suplementar se desenvolveu por mais de trinta anos sem interferência governamental, culminando em um crescimento alarmante, desordenado e desregulado, influenciado pelo excesso de oferta de dentistas e redução de pacientes que pagam por serviços privados. Dessa forma, grande parcela dos profissionais que têm se associado a planos de saúde na expectativa de expansão dos seus serviços são submetidos às demandas das operadoras que limitam seu trabalho àquele menos oneroso, interferem no plano de tratamento e utilizam tabelas de preços desatualizadas para o pagamento de procedimentos clínicos, levando a uma percepção negativa e descontentamento em relação ao desempenho das operadoras. Concluiu-se que de fato a relação é conflituosa, atingindo o profissional em diversas esferas, não apenas econômicas como pessoais, e está associada à expansão do sistema suplementar. Sendo assim, a prática odontológica é afetada na sua essência, sem que medidas de controle e supervisão, tão necessárias, sejam implementadas para corrigir assimetrias nas relações corporativas e evitar condições precárias da profissão.

Crop losses mainly occur due to biotic factors, which include soil-borne phytopathogens, insect pests, parasites, and predators. The major loss of food in the food industry is due to its spoilage by various microorganisms. With advancement in nanotechnology, the use of nanoparticles in food and agriculture crop yield can be improved. In this context, copper nanoparticles (CuNPs) have attracted a great deal of attention from all over the world due to their broad-spectrum antimicrobial activity. Copper is one of the key micronutrients, which plays an important role in growth and development of plants. CuNP-based fertilizer and herbicide can be used in agriculture. The small size of CuNPs facilitates their easy absorption by the plants. CuNPs can be promisingly used in the food packaging to avoid the growth of food spoilage microorganisms. The use of CuNP-based agar packaging materials has substantial potential to increase the shelf-life of food. The present review focuses on the application of Cu and CuNPs in food and agriculture. Moreover, antimicrobial and pesticidal properties of CuNPs are also discussed.

In bankruptcy law also known terms of peace, peace in bankruptcy law is one way to end an ongoing bankruptcy process. This article aims to know devoted to peace after the verdict of bankruptcy declaration, which will examine the implementation of peace in the Commercial Court of Jakarta and examine the factors that become obstacles for the parties to implement peace. This article is part of the research that has been done, with the normative juridical method that is not only limited to the research of the library but also require field research to obtain the primary data. Primary data were obtained from the Jakarta Commercial Court by interviewing commercial judges. Secondary data were obtained from library research by examining primary, secondary, and tertiary legal materials. Based on the results of field research, it is found that the mechanism of peace is rarely used by the parties, as long as the Commercial Court of Jakarta stands only 2 (two) signed peace treaties. The barriers that occur in practice so that peace can not be achieved by both parties in the Jakarta Commercial Court consists of several factors such as the absence of roles of judges and institutions, the absence of obligation to reconcile, the factors of the parties (HR) to reach an agreement, the existence procedures and mechanisms, the result of a peace agreement that gives less legal effect, thus providing a great opportunity for the debtor to violate a mutually agreed agreement is a constraint in practice so that peace will be difficult to achieve and utilized by the parties as a procedural procedure in solving the bankruptcy case.

RANKL, RANK e OPG têm sido apontados como reguladores da osteoclastogênese. O RANKL é produzido por células ósseas ou do ligamento periodontal em resposta a forças ortodônticas. Seu receptor de membrana RANK é encontrado em células precursoras de osteoclastos. Vários tipos de células produzem osteoprotegerina (OPG), uma citocina com afinidade ao RANKL e efeito inibitório sobre ele. O objetivo do presente trabalho foi buscar evidências científicas, por meio de pesquisa bibliográfica, do papel do sistema RANKL/RANK/OPG na remodelação óssea durante a movimentação dentária ortodôntica. Artigos foram recuperados nas bases de dados bibliográficos LILACS, MEDLINE, PubMed e SciELO, por meio dos termos de busca “rankl” e “orthodontic tooth movement”. Resultados de pesquisas sugerem que RANKL ativa a osteoclastogênese, com consequente aceleração do movimento do dente, enquanto a OPG o reduz, pela inibição da ligação RANKL/RANK. O controle de RANKL/RANK, em nível de receptores ou via de sinalização, pode ser uma ferramenta efetiva no tratamento de reabsorção óssea indesejada, abrindo campo promissor para novas abordagens farmacológicas no tratamento ortodôntico e remodelação óssea alveolar.

Objective: to analyze the impact of oral health on the quality of life of elderly diabetics attended in a family health unit. Material and Methods: this was a descriptive cross-sectional exploratory study with the application at home of the Oral Health Impact Profile questionnaire - OHIP-14 and a questionnaire on socioeconomic evaluation, reported oral morbidity, use of dental services, self-perception in oral health and adherence to healthy practices for the control of Diabetes Mellitus (DM). The data were submitted to bivariate analysis and non-parametric Mann-Whitney statistical tests for comparisons and Spearman’s for correlations, with a significance level of 5%, in order to determine the association between the OHIP-14 and the independent variables analyzed. Results: a total of 86 elderly diabetics, with a mean age of 70 years, mostly female, with per capita family of up to 1 minimum wage and literate. The total OHIP-14 average was 6.34. The domains that presented the most significant impact (p

The results of computer simulation of thermophysical phenomena in the contact zone during blade cutting of metals with multi-layer composite wear-resistant coatings that ensure the adaptability of the cutting wedge to friction conditions are presented. On-site experimental studies of the cutting temperature during turning with various coatings, structural-phase analysis of the surface layer of the cutting tool to explain the mechanism of formation of secondary structures with a shielding effect – the effect of selforganization.

Jasa keuangan merupakan salah satu sektor yang banyak berperan dalam pembangunan ekonomi suatu negara. Otoritas Jasa Keuangan Indonesia sebagai lembaga independen pengatur dan pengawas di sektor jasa keuangan memiliki salah satu tugas penting untuk memberikan perlindungan terhadap konsumen di sektor jasa keuangan, salah satunya dengan mengatur prosedur penanganan pengaduan serta penyelesaian sengketa konsumen secara sederhana, cepat, dan biaya terjangkau. Sebagai tindak lanjutnya, OJK menerbitkan POJK Nomor 1/POJK.07/2014 tentang Lembaga Alternatif Penyelesaian Sengketa di Sektor Jasa Keuangan. Artikel ini dimaksudkan untuk menggambarkan bagaimana konsep alternatif penyelesaian sengketa sebagaimana diatur di dalam POJK No. 1/2014 dikaitkan dengan sistem penyelesaian sengketa perdata yang ada. Lebih lanjut lagi, akan diuraikan pula Lembaga Alternatif Penyelesaian Sengketa yang telah ditetapkan OJK untuk melaksanakan tugas dan peranannya dalam penyelesaian sengketa dibidangnya masing-masing serta tantangan yang dihadapi dalam mewujudkan perlindungan terhadap konsumen sektor jasa keuangan. Abstract Financial service is one of the essential sectors in economic development of a country. Indonesian Financial Services Authority (OJK) is an independent institution which regulates and supervises the financial services sector and has its important role in providing consumer protection in financial services sector, i.e. by regulating the procedure of consumer complaint and dispute settlement in simple, prompt, and affordable manners. Following up such role, OJK issued Regulation 1/POJK.07/2014 regarding Alternative Dispute Resolution Institution in Financial Services Sector. This article is intended to describe the concept of alternative dispute resolution as stipulated in Regulation of OJK No. 1/2014 in connection with the existing private dispute settlement system. Furthermore, this article also describes the institutions of alternative dispute resolution assigned by OJK to conduct their duty and role in dispute settlement for each respective sectors and its challenge to provide consumer protection in financial services sector.

In spite of the limited sources of fossil fuels, energy demand has been considerably increased since the last century. The problems associated with global warming due to rising atmospheric greenhouse gas levels and scarcity of fossil fuels make it imperative to reduce our heavy dependency on fossil fuels. These reasons forced countries throughout the world to search for new fuel alternatives. Biofuel have gathered considerable attention due to their inherent benefits, like lower greenhouse gas emission, renewability, and sustainability. Commercially, biofuels are produced from vegetable oils, animal fats, and carbohydrates by using transesterification and fermentation. However, biofuel production suffers from high production costs and other technical barriers. Considering the environmental and economic issues, use of nanotechnology seems to be a viable solution. Nanoparticles have a number of interesting properties for the production of second-generation ethanol or transesterification of oils and fats to yield biodiesel. It is advantageous for recovery and reuse of catalysts. The present review discusses the role of nanotechnology in the production of bioethanol and biodiesel. Moreover, applications of nanoparticles for the production of biodiesel and second-generation ethanol with special reference to enzyme immobilization and chemical nano-catalysis have been described.

Komisi Pengawas Persaingan Usaha adalah suatu lembaga khusus yang dibentuk berdasarkan Undang-Undang Nomor 5 Tahun 1999 tentang Larangan Praktik Monopoli dan Persaingan Usaha Tidak Sehat untuk menegakkan hukum persaingan usaha. Tidak berkedudukan sebagai 'lembaga penegak hukum' yang sesungguhnya menyebabkan KPPU tidak memiliki daya paksa dalam hal pemanggilan para pihak maupun dalam pelaksanaan eksekusi. Selain itu, banyaknya putusan KPPU yang dibatalkan dalam proses upaya huku (yang disebut sebagai keberatan) yang diajukan pihak pelanggar pada akhirnya menyebabkan tidak terciptanya kepastian hukum bagi para pihak. Tulisan ini berupaya memperlihatkan gambaran pelaksanaan putusan persaingan usaha dalam praktik dalam tinjauan Undang-Undang Nomor 5 tahun 1999 tentang Larangan Praktik Monopoli dan Persaingan Usaha Tidak Sehat serta mengindentifikasi kendala-kendala dan upaya dalam penegakan hukum persaingan usaha di Indonesia agar tercipta kepastian hukum. Abtract The Commission for the Supervision of Business Competition (Komisi Persaingan Usaha) is a special institution established by Law Number 5 of 1999 concerning the Prohibition of Monopolistic Practices and Unfair Competition for enforcing competition law. Not functioning as a 'law enforcement agency' has led to KPPU to have no power to either forcibly summon the parties or execute its decisions. Moreover, a lot of KPPU's decisions are cancelled due to further legal action filed by the offender and thus undermining the legal centainty for the parties. The purpose of this article is to seek and analyze the enforcement of KPPU's decision in disputes regarding monopolistic practices and unfair competition as regulated in Law Number 5 of 1999. Furthermore, this article also aims to determine the obstacles in setting enforcement of competition law in order to not only establish legal certainty but also to achieve a healthy business climate in Indonesia.

Curcumin (diferuloylmethane) is one of the potent, nontoxic, and major bioactive components present in turmeric. The major drawbacks of curcumin are low absorption and poor bioavailability. The present review highlights on the methods for the fabrication of curcumin nanoparticles and their applications in treatment of cancer and wound infections. Curcumin nanoparticles possess remarkable antibacterial, antiviral, and antiprotozoan activity. Hence, curcumin nanoparticle-loaded nano-gel, microemulsion, and nano-cream can be used for drug delivery.

Buku ini membahas mengenai persoalan kredit macet dalam masalah dunia perbankan yang dihubungkan dengan pengaturan yang ada dalam Undang-Undang Nomor 40 Tahun 2007 tentang Perseroan Terbatas (UUPT). Buku ini terbagi dalam 6 bab, yang masing mempunyai pembahasan yang berbeda namun saling berkaitan. Bab 1 diberi judul Beberapa Hal dalam Hubungan dengan Kredit Macet, Bab 2 Menelaah Undang-Undang Perseroan, yang dalam hal ini adalah pembahasan dari UUPT, Bab 3 tentang Mengadili Keputusan Bisnis, Bab 4 adalah Pemeriksaan Pengadilan di Amerika dan Jepang, Bab 5 Keputusan Pemberian Kredit yang Memberikan Perlindungan Hukum dan Bab 6 yang merupakan bab terakhir berisi mengenai Intisari dan Saran dari penulis. Buku ini menarik untuk dijadikan bahan ulasan karena pembahasan mengenai dunia perbankan, khususnya masalah kredit macet serta tanggung jawab direksi, selaku organ perseroan yang menjalankan perusahaan, sangat menarik untuk diketahui karena masalah ini dialami oleh hampir setiap negara.

Research on the nanomaterials containing one or more transition metals is growing tremendously, thanks to the large number of preparation processes available and to the novel applications that can be envisaged in several fields. This review presents an overview of the selected studies in the field of antimicrobial textiles, employing bioactive nanophases of elements/compounds such as silver, copper, or zinc oxide. In addition, the history of use of these antimicrobials and their mechanism of action are shortly reported. Finally, a short description is provided of the deposition/preparation methods, which are being used in the authors’ labs for the development of the textiles modified by the novel nanoantimicrobials.

The notion that tending ants provide protection to honeydew-producing hemipterans is widely accepted. Nevertheless, there have been debates about whether or not this protection can always disrupt the biological control of hemipterans. Although various hemipteran species interact with tending ants, most studies have focused on the mutualism between ants and aphids. Woolly whitefly Aleurothrixus floccosus (Maskell) is an important pest of citrus whose nymphs are frequently tended by ants such as Camponotus. However, it is unknown whether or not ants in this genus can disrupt biological control of woolly whitefly by protecting this pest’s nymphs from natural enemies. We investigated the impact of Camponotus ants on the biological control of woolly whitefly in the field by excluding or allowing the access of ants to whitefly nymph colonies in different tangerine trees. Furthermore, in a laboratory study we also assessed the behavior of Camponotus ants in response to woolly whitefly’s common predator cues (visual and scent). In summary, this field-laboratory study suggests that there is no mutualism between tending Camponotus ants and the whitefly A. floccosus; rather it indicates commensalism as an alternative interaction. Interactions as this may provide more benefits for the host plant, whereby Camponotus ants can reduce sooty mold by removing honeydew from the leaves and favor pest biological control by leaving the whiteflies unprotected.

Abstract Background IL8RA and IL8RB, encoded by CXCR1 and CXCR2, are receptors for interleukin (IL)-8 and other CXC chemokines involved in chemotaxis and activation of polymorphonuclear neutrophils (PMN). Variants at CXCR1 and CXCR2 have been associated with susceptibility to cutaneous and mucocutaneous leishmaniasis in Brazil. Here we investigate the role of CXCR1/CXCR2 in visceral leishmaniasis (VL) in India. Methods Three single nucleotide polymorphisms (SNPs) (rs4674259, rs2234671, rs3138060) that tag linkage disequilibrium blocks across CXCR1/CXCR2 were genotyped in primary family-based (313 cases; 176 nuclear families; 836 individuals) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between CXCR1/CXCR2 variants and VL. Quantitative RT/PCR was used to compare CXCR1/CXCR2 expression in mRNA from paired splenic aspirates taken before and after treatment from 19 VL patients. Results Family-based analysis using FBAT showed association between VL and SNPs CXCR1_rs2234671 (Z-score = 2.935, P = 0.003) and CXCR1_rs3138060 (Z-score = 2.22, P = 0.026), but not with CXCR2_rs4674259. Logistic regression analysis of the case-control data under an additive model of inheritance showed association between VL and SNPs CXCR2_rs4674259 (OR = 1.15, 95%CI = 1.01-1.31, P = 0.027) and CXCR1_rs3138060 (OR = 1.25, 95%CI = 1.02-1.53, P = 0.028), but not with CXCR1_rs2234671. The 3-locus haplotype T_G_C across these SNPs was shown to be the risk haplotype in both family- (TRANSMIT; P = 0.014) and population- (OR = 1.16, P = 0.028) samples (combined P = 0.002). CXCR2, but not CXCR1, expression was down regulated in pre-treatment compared to post-treatment splenic aspirates (P = 0.021). Conclusions This well-powered primary and replication genetic study, together with functional analysis of gene expression, implicate CXCR2 in determining outcome of VL in India.

Abstract Background SLC11A1 has pleiotropic effects on macrophage function and remains a strong candidate for infectious disease susceptibility. 5' and/or 3' polymorphisms have been associated with tuberculosis, leprosy, and visceral leishmaniasis (VL). Most studies undertaken to date were under-powered, and none has been replicated within a population. Association with tuberculosis has replicated variably across populations. Here we investigate SLC11A1 and VL in India. Methods Nine polymorphisms (rs34448891, rs7573065, rs2276631, rs3731865, rs17221959, rs2279015, rs17235409, rs17235416, rs17229009) that tag linkage disequilibrium blocks across SLC11A1 were genotyped in primary family-based (313 cases; 176 families) and replication (941 cases; 992 controls) samples. Family- and population-based analyses were performed to look for association between SLC11A1 variants and VL. Quantitative RT/PCR was used to compare SLC11A1 expression in mRNA from paired splenic aspirates taken before and after treatment from 24 VL patients carrying different genotypes at the functional promoter GTn polymorphism (rs34448891). Results No associations were observed between VL and polymorphisms at SLC11A1 that were either robust to correction for multiple testing or replicated across primary and replication samples. No differences in expression of SLC11A1 were observed when comparing pre- and post-treatment samples, or between individuals carrying different genotypes at the GTn repeat. Conclusions This is the first well-powered study of SLC11A1 as a candidate for VL, which we conclude does not have a major role in regulating VL susceptibility in India.

Abstract Background The rapidly growing availability of diverse full genome sequences from across the world is increasing the feasibility of studying the large-scale population processes that underly observable pattern of virus diversity. In particular, characterizing the genetic structure of virus populations could potentially reveal much about how factors such as geographical distributions, host ranges and gene flow between populations combine to produce the discontinuous patterns of genetic diversity that we perceive as distinct virus species. Among the richest and most diverse full genome datasets that are available is that for the dicotyledonous plant infecting genus, Begomovirus, in the Family Geminiviridae. The begomoviruses all share the same whitefly vector, are highly recombinogenic and are distributed throughout tropical and subtropical regions where they seriously threaten the food security of the world's poorest people. Results We focus here on using a model-based population genetic approach to identify the genetically distinct sub-populations within the global begomovirus meta-population. We demonstrate the existence of at least seven major sub-populations that can further be sub-divided into as many as thirty four significantly differentiated and genetically cohesive minor sub-populations. Using the population structure framework revealed in the present study, we further explored the extent of gene flow and recombination between genetic populations. Conclusions Although geographical barriers are apparently the most significant underlying cause of the seven major population sub-divisions, within the framework of these sub-divisions, we explore patterns of gene flow to reveal that both host range differences and genetic barriers to recombination have probably been major contributors to the minor population sub-divisions that we have identified. We believe that the global Begomovirus population structure revealed here could facilitate population genetics studies into how central parameters of population genetics namely selection, recombination, mutation, gene flow, and genetic drift shape the global begomovirus diversity.

Abstract Background Tomato-infecting begomoviruses are widely distributed across the world and cause diseases of high economic impact on wide range of agriculturally important crops. Though recombination plays a pivotal role in diversification and evolution of these viruses, it is currently unknown whether there are differences in the number and quality of recombination events amongst different tomato-infecting begomovirus species. To examine this we sought to characterize the recombination events, estimate the frequency of recombination, and map recombination hotspots in tomato-infecting begomoviruses of South and Southeast Asia. Results Different methods used for recombination breakpoint analysis provided strong evidence for presence of recombination events in majority of the sequences analyzed. However, there was a clear evidence for absence or low Recombination events in viruses reported from North India. In addition, we provide evidence for non-random distribution of recombination events with the highest frequency of recombination being mapped in the portion of the N-terminal portion of Rep. Conclusion The variable recombination observed in these viruses signified that all begomoviruses are not equally prone to recombination. Distribution of recombination hotspots was found to be reliant on the relatedness of the genomic region involved in the exchange. Overall the frequency of phylogenetic violations and number of recombination events decreased with increasing parental sequence diversity. These findings provide valuable new information for understanding the diversity and evolution of tomato-infecting begomoviruses in Asia.

Background: A better understanding of the dynamics of human immunodeficiency virus (HIV) reservoirs in CD4+ T cells of people with HIV (PWH) receiving antiretroviral therapy (ART) is crucial for developing therapies to eradicate the virus., Methods: We conducted a study involving 28 aviremic PWH receiving ART with high and low levels of HIV DNA. We analyzed immunologic and virologic parameters and their association with the HIV reservoir size., Results: The frequency of CD4+ T cells carrying HIV DNA was associated with higher pre-ART plasma viremia, lower pre-ART CD4+ T-cell counts, and lower pre-ART CD4/CD8 ratios. During ART, the High group maintained elevated levels of intact HIV proviral DNA, cell-associated HIV RNA, and inducible virion-associated HIV RNA. HIV sequence analysis showed no evidence for preferential accumulation of defective proviruses nor higher frequencies of clonal expansion in the High versus Low group. Phenotypic and functional T-cell analyses did not show enhanced immune-mediated virologic control in the Low versus High group. Of considerable interest, pre-ART innate immunity was significantly higher in the Low versus High group., Conclusions: Our data suggest that innate immunity at the time of ART initiation may play an important role in modulating the dynamics and persistence of viral reservoirs in PWH., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Background: People living with HIV (PLWH) with multidrug-resistant (MDR) viruses have limited therapeutic options and present challenges regarding clinical management. Recent studies have shown that passive transfer of combination broadly neutralizing antibodies (bNAbs) against HIV and anti-domain 1 CD4 antibody UB-421 can sustain virologic suppression in PLWH in the absence of antiretroviral therapy (ART). Yet studies addressing the therapeutic potential of these antibodies and/or detailed characterization of immunologic and virologic parameters in PLWH with MDR HIV are lacking., Methods: We examined levels of immune activation and exhaustion markers on CD8 + T cells and the intact HIV proviral DNA burden in 11 PLWH with MDR viruses. For comparison purposes, we included a control group consisting of 27 ART-naïve viremic PLWH. In addition, we determined the sensitivity of infectious viral isolates obtained from the participants against eight bNAbs (3BNC117, 10-1074, VRC01, VRC07, N6, 10E8, PGDM1400, and PGT121) and two anti-CD4 antibodies (ibalizumab and UB-421) using a TZM-bl-based neutralization/suppression assay., Findings: The level of intact HIV proviral DNA was comparable between the two groups (P = 0.29). The levels of activation and exhaustion markers PD-1 (P = 0.0019), TIGIT (P = 0.0222), 2B4 (P = 0.0015), CD160 (P = 0.0015), and CD38 + /HLA-DR + (P = 0.0138) were significantly lower in the MDR group. The infectious viral isolates from each study participant with MDR HIV were resistant to at least 2 bNAbs; however, they were sensitive to at least one of the CD4-binding and non-CD4-binding site antibodies. The majority of participants had ibalizumab-sensitive viruses although the isolates from some participants showed reduced sensitivity to ibalizumab. Notably, none of the 93 viral isolates obtained from the participants were resistant to UB-421., Interpretation: Our data suggest that combination therapy with HIV-specific bNAbs and/or UB-421 in the presence of optimized background therapy could potentially provide sustained virologic suppression in PLWH with MDR HIV. However, this therapeutic strategy needs to be evaluated in human clinical trials., Funding: Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health., Competing Interests: Declaration of interests We declare no competing interests., (Published by Elsevier B.V.)

We describe the immunologic and virologic impact of monkeypox (mpox) infection in a woman with human immunodeficiency virus (HIV) whose plasma HIV viremia was suppressed by clinically effective antiretroviral therapy. Extensive phenotypic analyses of B and T cells in peripheral blood and biomarkers in plasma showed significant immunologic perturbations despite the presence of mild mpox disease. Dramatic shifts were noted in the frequencies of total B cells, plasmablasts, and plasmablast immunoglobulin isotypes. Flow cytometric analyses showed a dramatic increase in the frequency of CD38+HLA-DR+ CD8+ T cells after mpox infection. Our data offer guidance for future studies involving mpox infection in affected populations., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Objective: HIV induces immunologic dysfunction in T cells of infected individuals. However, the impact of aging on T cell phenotypes in HIV-infected individuals receiving antiretroviral therapy (ART) has not been fully delineated. We evaluated the relationship between aging and the expression of immune activation and exhaustion markers on CD8 + T cells of age-matched HIV-infected and -uninfected male participants., Design: Levels of immune activation and exhaustion markers on peripheral blood CD8 + T cells of HIV-infected and -uninfected participants were examined., Methods: 110 HIV-infected aviremic male participants receiving ART and 146 HIV-uninfected male participants were studied. The levels of TIGIT, PD-1, CD38, and CD226 on CD8 + T cells of the study participants were determined by flow cytometry., Results: The level of TIGIT on CD8 + T cells was higher in aviremic HIV-infected compared to uninfected participants ( P  < 0.0001). In contrast, no significant differences were found in the levels of PD-1 and CD38 on CD8 + T cells between the two groups. Statistically significant correlations were observed between age and the levels of TIGIT + and CD38 + CD8 + T cells in both groups; however, no correlation was found between age and the level of PD-1 + CD8 + T cells in HIV-infected participants. Age-stratification of HIV-infected and -uninfected groups did not show any significant differences in the level of PD-1 expression on CD8 + T cells., Conclusions: The findings of our study highlight the role of aging in the expression of immune markers on CD8 + T cells and have important implications for therapies that target immune checkpoints in HIV-infected individuals., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

SARS-CoV-2 mRNA booster vaccines provide protection from severe disease, eliciting strong immunity that is further boosted by previous infection. However, it is unclear whether these immune responses are affected by the interval between infection and vaccination. Over a 2-month period, we evaluated antibody and B cell responses to a third-dose mRNA vaccine in 66 individuals with different infection histories. Uninfected and post-boost but not previously infected individuals mounted robust ancestral and variant spike-binding and neutralizing antibodies and memory B cells. Spike-specific B cell responses from recent infection (<180 days) were elevated at pre-boost but comparatively less so at 60 days post-boost compared with uninfected individuals, and these differences were linked to baseline frequencies of CD27 lo B cells. Day 60 to baseline ratio of BCR signaling measured by phosphorylation of Syk was inversely correlated to days between infection and vaccination. Thus, B cell responses to booster vaccines are impeded by recent infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

We investigated effects of the severe acute respiratory syndrome coronavirus 2 (SARV-CoV-2) booster vaccination on human immunodeficiency virus (HIV) reservoir size, immune markers, and host immune responses in people with HIV receiving antiretroviral therapy. Our data suggest that the SARS-CoV-2 booster vaccine is not likely to replenish the persistent HIV reservoir nor provide an immunologic environment to facilitate active HIV expression/replication., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022.)

Background: HIV associated neurocognitive disorders cause significant morbidity and mortality despite the advent of highly active antiretroviral therapy. A deeper understanding of fundamental mechanisms underlying HIV infection and pathogenesis in the central nervous system is warranted. Microglia are resident myeloid cells of the brain that are readily infected by HIV and may constitute a CNS reservoir. We evaluated two microglial model cell lines (C20, HMC3) and two sources of primary cell-derived microglia (monocyte-derived microglia [MMG] and induced pluripotent stem cell-derived microglia [iPSC-MG]) as potential model systems for studying HIV-microglia interactions., Results: All four microglial model cells expressed typical myeloid markers with the exception of low or absent CD45 and CD11b expression by C20 and HMC3, and all four expressed the microglia-specific markers P2RY12 and TMEM119. Marked differences were observed upon gene expression profiling, however, indicating that MMG and iPSC-MG cluster closely together with primary human microglial cells, while C20 and HMC3 were similar to each other but very different from primary microglia. Expression of HIV-relevant genes also revealed important differences, with iPSC-MG and MMG expressing relevant genes at levels more closely resembling primary microglia. iPSC-MG and MMG were readily infected with R5-tropic HIV, while C20 and HMC3 lack CD4 and require pseudotyping for infection. Despite many similarities, HIV replication dynamics and HIV-1 particle capture by Siglec-1 differed markedly between the MMG and iPSC-MG., Conclusions: MMG and iPSC-MG appear to be viable microglial models that are susceptible to HIV infection and bear more similarities to authentic microglia than two transformed microglia cell lines. The observed differences in HIV replication and particle capture between MMG and iPSC-MG warrant further study.

Introduction: There are 36.7 million people living with HIV with 20.9 million having access to antiretroviral therapy (ART). Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) remain the 'backbone' of ART. However, the currently available nine NRTIs and five non-nucleoside reverse transcriptase inhibitors (NNRTIs) have significant side effects and resistance profiles. Areas covered: We summarize the mechanisms of resistance and other limitations of the existing NRTIs/NNRTIs. GS-9131, MK-8591, Elsulfavirine and Doravirine are four new agents that are furthest along in development. Expert opinion: ART development has evolved with several new promising agents. Longer-acting agents, like MK-8591 are extremely attractive to enhance drug adherence and patient satisfaction. Doravirine offers an NNRTI effective against common mutations that has fewer side effects, limitations on dosing and drug interactions. GS-9131 is very potent and active against a variety of NRTI mutants but it is too early in its development to understand its full risks and benefits. Finally, Elsulfavirine has a long half-life and preliminary data suggests fewer side effects than the most commonly used NNRTI, efavirenz. Each of these new agents shows promise and potential to improve ART in the future. The newer generation of reverse transcriptase inhibitors have longer half-lives, more favorable adverse effect profiles, and fewer drug interactions.

We looked at our HIV + slow progressors cohort to determine if there were any human leukocyte antigen (HLA) correlates for protection. No statistically significant allelic differences were found between the HIV + and control cohorts using regression analysis, though trends were noted. Data for Elite Controllers showed an increased frequency of B*57. Likewise, no correlation was inferred with the clinical data of the HIV + cohort. We hypothesize that the protective effect of HLA alleles may have been lost over time.

Only few cases of ectopic third molar in relation to the roof of maxillary sinus and posteroinferior to the floor of the orbit have been reported in the literature. The diagnosis is usually done by plain-film radiography. "Caldwell-Luc" operation or endoscopic procedures have been used for the removal of such type of ectopic tooth. We report a case of 46-year-old female patient who presented with pain, swelling and watering of eye due to the ectopic tooth. The trans oral removal (via "Caldwell-Luc" operation) of the ectopic maxillary third molar situated superior to maxillary antrum and posteroinferior to the floor of orbit has been described in this case without any complication.

Three ellagitannins and one disulfated flavonol were isolated from the aerial parts of Reaumuria vermiculata L. Besides that, 16 known compounds were characterized as well. The structures of all compounds were elucidated on the basis of spectroscopic data including 1D and 2D NMR and ESI HR-FTMS. The in vivo antioxidant activity using the oxygen radical absorbance capacity (ORAC) method, of the extract, its column fractions and two of the isolated ellagitannins was accomplished. In addition, a possible cytotoxicity of the extract and two of the new ellagitannins on HaCaT human keratinocytes and the activity of both compounds against the prostate cancer cell line (PC-3) were also assessed, whereby a potent cytotoxicity with IC₅₀ less than 1 μg/ml was determined for both compounds. Besides, the extract exhibited a potential cytotoxic effect against four different solid tumor cell lines, namely liver (Huh-7), colorectal (HCT-116), breast (MCF-7) and prostate (PC-3). The IC₅₀s were found to be substantially low (ranged from 1.3±0.15 to 2.4±0.22 μg/ml) with relatively low resistance possibility reaching to 0% in the case of Huh-7 cell., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: We have previously reported a HIV-1 subtype A infection in a community of injection drug users (IDUs) in Karachi, Pakistan. We now show that this infection among the IDUs may have originated from a single source., Methods: Phylogenetic analysis was performed of partial gag sequences, generated using PCR, from 26 HIV-positive IDU samples., Results: Our results showed formation of a tight monophyletic group with an intra-sequence identity of < 98% indicating a "founder effect". Our data indicate that the HIV-1 epidemic in this community of IDUs may have been transmitted by an HIV positive overseas contract worker who admitted to having contact with commercial sex workers during stay abroad., Conclusion: Specific measures need to implemented to control transmission of HIV infection in Pakistan through infected migrant workers.

Increasing rates of HIV have been recorded amongst the Injection Drug User community from all parts of Pakistan. This has mobilized the health authorities into definitive action before there is a general spread of the epidemic into the Pakistani populace. Lacking any formal research as pertains to HIV policy development in Pakistan, international collaborating agencies, including the United Nations, are aiding in the formulation of a national policy to tackle HIV/AIDS. This article discusses the progress and importance of interventions being conducted amongst the Parliamentarians of Pakistan, relatively unchartered waters. The series of Seminars help to appraise the Parliamentarians of the ground situation as pertains to HIV in their constituencies, aiming to ultimately generate federal and provincial governmental policies, and a solid strategy to combat the spread of HIV/AIDS in Pakistan.

The Indian-subcontinent is becoming, what could be, the next big battle ground for the control of Extensively Drug Resistant Tuberculosis (XDR-TB). The region caters to not only an ever-increasing incidence of new TB cases, but also a huge burden of already existing TB cases, thereby facing a dual threat for spread of XDR-TB. Most of the health-care facilities are devoid of essential laboratory-based infra-structure which is essential for diagnosing XDR-TB. Coupled to this is the lack of knowledge regarding TB diagnosis and treatment amongst the General Practitioners of India and Pakistan, who still treat the bulk of the TB cases. The element of AIDS is also slowly creeping into the equation. Questions have already been raised about the effectiveness of the governmental responses to curb the TB threat. What is needed right away is an effective strategy, incorporating a broad-tiered approach between the government and social sector. This can facilitate greatly in preventing further spread of these resistant strains.

Background: On October 8, 2005, an earthquake of magnitude 7.6 hit the Northern parts of Pakistan. In the post-earthquake scenario, overcrowding, improper sewage disposal, contamination of food and drinking water, hasty surgical procedures, and unscreened blood transfusions to earthquake victims most likely promotes the spread of infections already prevalent in the area., Objective: The objective of the study reported here was to determine the prevalence of Human Immunodeficiency and Hepatitis C viruses (respectively, HIV and HCV) in the earthquake-affected communities of Pakistan. The samples were analyzed 2 months and then again 11 months after the earthquake to estimate the burden of HIV and HCV in these areas, and to determine any rise in the prevalence of these viral infections as a result of the earthquake., Methods: Blood samples were initially collected during December, 2005 to March 2006, from 245 inhabitants of the earthquake-affected areas. These samples were screened for HCV and HIV, using immunochromatography and Enzyme-Linked Immuno-Sorbent Assay (ELISA)., Results: Out of 245 samples tested, 8 (3.26%) were found positive for HCV, and 0 (0.0%) for HIV, indicating the existence of HCV infection in the earthquake-stricken areas. The same methods were used to analyze the samples collected in the second round of screening in the same area, in September, 2006 - 11 months after the earthquake. This time 290 blood samples were collected, out of which 16 (5.51%) samples were positive for HCV, and 0 for HIV., Conclusion: A slightly higher prevalence of HCV was recorded 11 months after the earthquake; this increase, however, was not statistically significant. None of the study participants was found HIV-infected.