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Abstract Background Appropriate language use is essential to ensure inclusion of diverse populations in research. We aimed to identify possible language-related barriers regarding the informed consent process and propose interventions to improve clarity and understanding of pregnant and breastfeeding women participating in research. Methods A cross-sectional qualitative study employing focus group discussions (FGD) was conducted in Uganda from August 2023 to September 2023, involving a diverse group of stakeholders from the community, including community members, research participants, and Community Advisory Board members. 19 FGD comprised adult participants representing at least six different mother tongues (Luganda, Acholi, Runyankole, Runyoro, Lugbara and English). An inductive thematic approach was utilized for data analysis using NVivo version 12 software to identify language factors that influence informed consent. A series of community validation workshops ensured concurrence. Results At the individual level, language barriers, and low levels of literacy contributed to poor comprehension, thus hindering ability to achieve genuine informed consent. At the health facility level, participants reported that there was use of inappropriate, unclear language including inaccurate translations, with poor and complicated grammar in some consent forms. Participants reported that complex medical terminologies are difficult to translate to local languages. Community members highlighted that social/cultural norms in language use affected cultural perceptions of informed consent. To enhance understanding for individuals without education in science, participants suggested simplification of terminologies and avoidance of complex medical jargon. Researchers should identify participants’ preferred languages and communicate in those languages whenever possible. If researchers are not fluent, trained interpreters should be identified. Informed consent documents must be translated into local languages to ensure participants comprehend the study’s purpose, procedures, risks, and benefits. Involving community members during development and translation of these documents can provide valuable insights into local dialects and culturally specific concepts, ensuring that study tools like surveys and consent forms are accurate and respectful. Conclusion Language barriers influence the informed consent process within communities in Uganda. These can potentially be resolved at individual, health system and community levels. Consideration of locally understandable terms in community-facing study documentation is likely to enhance understanding and could improve research participation, although further studies are needed to assess these. The use of appropriate language ensures that informed consent is genuine in keeping with principles of Good Clinical Practice, and developing a research communication strategy should be part of inclusive research design.

Abstract Pharmacokinetic studies are important for understanding drug disposition in the human body. However, pregnant and lactating women are often excluded from primary pharmacokinetic studies and as such there is often limited dosing information regarding drug use in pregnant and/or lactating women. The objectives of this interim analysis were to define the transfer of rifampicin to a breastfed infant and to determine the area under the concentration–time curve of rifampicin in maternal plasma, breastmilk and infant plasma. Performing this interim analysis enabled us to substantiate whether prior assumptions we made on several study design issues including patient sample size and pharmacokinetic sampling times held and whether we needed to amend our protocol or not. We enrolled lactating mothers on treatment for tuberculosis with their breastfeeding infants (below 12 months of age), performed intensive pharmacokinetic sampling (0–24 h post‐dose) on plasma samples from both the mother, infant(s) and breastmilk samples from the mother on two separate occasions (once during the initiation phase and another during the continuation phase of tuberculosis treatment). The initial study design, including sampling times, was informed by a stochastic simulation and estimation exercise, with very limited prior breastmilk data. An interim analysis after recruiting 6 mother–infant pairs ascertained that our initial assumptions were ideal for achieving our study objectives and no amendments to the sampling times were necessary. Initial data from 6 mother–infant pairs show that rifampicin penetrates breastmilk with an approximate milk‐to‐plasma ratio of 0.169 and 0.189 on two separate visits. However, it was undetectable in most infants.

Abstract Around 1.2 million women living with HIV give birth annually, majority of whom will breastfeed their infants while receiving antiretroviral therapy (ART). Lamivudine, a component of first‐line ART regimens crosses from maternal plasma to breast milk, with measurable concentrations in some breastfed infants. Wide variability in plasma‐to‐breast milk transfer has been reported within‐ or across studies, probably due to differences in sampling framework. This work sought to characterize the milk‐to‐plasma transfer of lamivudine, quantify inter‐patient variability and associated factors, and predict exposure of a breastfed infant. We explored data from an observational pharmacokinetic study that included 35 Ugandan mothers and their infants. Mothers received lamivudine doses of 150 mg twice daily or 300 mg once daily as part of their antiretroviral regimen. Pharmacokinetic sampling was undertaken across two visits approximately 8 weeks apart, providing 248 maternal plasma, 256 breast milk‐, and 151 infant blood concentrations, measured across a 24‐h sampling interval. A one‐compartmental model best described the plasma disposition of lamivudine, with first‐order absorption, interindividual variability on clearance and volume of distribution, and a proportional residual error model. A lag in time of plasma‐to‐breast milk drug accumulation was described using an effect compartment model with a milk‐to‐plasma ratio of 1.77. An estimated daily infant dose of 179.3 μg/kg (range: 125.8, 282.3) closely predicted the observed infant steady‐state concentrations and translated into 3.34% (2.13, 7.20) and 3.35% (1.10, 7.15) of the standard daily maternal dose in visits 1 and 2, respectively. The established modeling framework can be extended to other drugs.

Abstract Pregnant and breastfeeding women are often under-represented in clinical research, including pharmacokinetic studies, due to ethical and logistical challenges. This paper examines strategies to improve the recruitment and retention of this demographic in pharmacokinetic research, drawing on experiences from five studies conducted at the Infectious Diseases Institute, Makerere University, Uganda. Key strategies implemented include Community Advisory Board meetings, the involvement of Peer Mothers as Co-Investigators, established recruitment sites, the use of safety protocols, and the utilization of diverse communication platforms, including social media and stakeholder meetings. Despite these efforts, substantial barriers, such as scheduling conflicts and frequent staff turnover at recruitment sites, continue to threaten progress. The paper recommends flexible scheduling, strengthening public engagement, and transparent demonstration of adherence to ethical principles; justice, non-maleficence, respect, and beneficence to ensure the safety and inclusivity of pregnant and breastfeeding women. The inclusion of this population in pharmacokinetic studies is essential for providing evidence-based care that meets their unique health needs.

Aim – to identify a correlation between the somatotype of a patient with liver cirrhosis and changes in the composition of the intestinal microbiota. Material and methods. The study included 46 patients diagnosed with liver cirrhosis of various etiologies. The somatotype of the patients was determined using a bioimpedance analyzer of body composition (ABC-01 "Medass"). The intestinal microbiota was analyzed once by 16s rRNA sequencing. The processing of the received data was carried out using the program “Statistica". Results. Among 46 patients diagnosed with liver cirrhosis, the majority (26 patients) had a mesoendomorphic somatotype, 14 patients were representatives of endomesomorphs. The predominance of representatives of the genera Streptococcus (p-value = 0.02), Campylobacter (p-value = 0.049) and Holdemanella (p-value = 0.048) was statistically significant in the group of endomesomorphs, while bacteria from the genera Klebsiella (p-value = 0.01) and Gammaproteobacteria (p-value = 0.048) prevailed in the group of mesoendomorphs (p-value = 0.02). Taxa of the intestinal microbiota of Pyramidobacter were expressed in patients with the endomorphic somatotype (p-value = 0.016).

BackgroundThe language used in research and health programs is crucial in influencing participation and ensuring the acceptability of programs and the adoption of research outcomes. The use of alienating language may present a barrier for research participants hence the need to identify accurate, respectful, relevant, and acceptable terms for respective study populations. The study explored commonly used terminologies during research involving pregnant and lactating mothers using public engagement and participatory approaches in Uganda.MethodsA cross-sectional qualitative study was conducted in August 2023 among 5 ethnically diverse communities with different languages and from different regions across Uganda. Data were collected through 18 focus group discussions (FGDs) comprising community members and one comprising the community advisory board (CAB) using a participatory approach. An interview guide exploring perceptions and experiences on research, common and preferred terms for specific terminologies used among pregnant and lactating mothers as well as disliked words guided the discussion. Transcription was done verbatim in English. Nvivo version 14 software was used to organize and manage the data appropriately based on themes and subthemes.ResultsA consensus on the preferred terminologies to communicate about our research studies involving pregnant and lactating mothers was reached. The study revealed that words used in research that did not specify sex were described as disrespectful, inappropriate or confusing. Language defining a person on the basis of anatomical or physiological characteristics was considered ‘embarrassing’ and labelling individuals based on their conditions was construed as stigmatising. Participants recommended that researchers be mindful of any terms that could be perceived as embarrassing or inappropriate within the community, ensure clear communication of research terms to participants, and train healthcare workers on the use of appropriate health language. The importance of providing feedback regarding study findings was emphasised.ConclusionThe findings highlight the importance of using culturally sensitive language in health research to improve engagement and participation. By adopting community-preferred terms, researchers can avoid confusion and stigma fostering respectful health communication. The findings offer guidance for future research, advocating for community-driven inclusive language in research involving pregnant and breastfeeding women. For healthcare workers, training in empathetic communication and cultural competence is crucial to improve patient interactions and promote dignity in healthcare settings.

Two series of novel Cu (II) (4a–e) and Ni (II) (5a–e) complexes bearing 1-(N-phenylthiocarbamoyl)-pyrazoline ligands (3a–e) were synthesized and characterized. The structures of Ni (II) complexes 5a, c were confirmed by X-ray crystallography; both complexes have a distorted octahedral coordination environment of the Ni (II); metal atoms are coordinated by pyridyl and pyrazoline nitrogen atoms and thiocarbonyl sulfur of two ligand moiety, with two chloride anions in the outer sphere. The Cu (II) complex 4a derived from ligand 3a demonstrate a non-typical electrochemical behavior indicating Cu (I) complex formation which can be explained either by pyrazoline ligand ring opening in DMF solution or by a non-innocent nature of 3a. All of the synthesized complexes were cytotoxic against HCT116 and К562 cell lines; the most cytotoxic ligand was 3d, which is structurally related to combretastatin A4.

Abstract Tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are prodrugs of the nucleotide analogue tenofovir, which acts intracellularly to inhibit HIV replication. Whereas TDF converts to tenofovir in plasma and may cause kidney and bone toxicity, TAF mostly converts to tenofovir intracellularly, so it can be administered at lower doses. TAF leads to lower tenofovir plasma concentrations and lower toxicity, but there are limited data on its use in Africa. We used data from 41 South African adults living with HIV from the ADVANCE trial and described, with a joint model, the population pharmacokinetics of tenofovir given as TAF or TDF. The TDF was modeled to appear in plasma as tenofovir with a simple first‐order process. Instead, two parallel pathways were used for a TAF dose: an estimated 32.4% quickly appeared as tenofovir into the systemic circulation with first‐order absorption, whereas the rest was sequestered intracellularly and released into the systemic circulation as tenofovir slowly. Once in plasma (from either TAF or TDF), tenofovir disposition followed two‐compartment kinetics and had a clearance of 44.7 L/h (40.2–49.5), for a typical 70‐kg individual. This semimechanistic model describes the population pharmacokinetics of tenofovir when dosed as either TDF or TAF in an African population living with HIV and can be used as a tool for exposure prediction in patients, and to simulate alternative regimes to inform further clinical trials.

Abstract Background In the United States, rare disease (RD) is defined as a condition that affects fewer than 200,000 individuals. Collectively, RD affects an estimated 30 million Americans. A significant portion of RD has an underlying genetic cause; however, this may go undiagnosed. To better serve these patients, the Mayo Clinic Program for Rare and Undiagnosed Diseases (PRaUD) was created under the auspices of the Center for Individualized Medicine (CIM) aiming to integrate genomics into subspecialty practice including targeted genetic testing, research, and education. Methods Patients were identified by subspecialty healthcare providers from 11 clinical divisions/departments. Targeted multi-gene panels or custom exome/genome-based panels were utilized. To support the goals of PRaUD, a new clinical service model, the Genetic Testing and Counseling (GTAC) unit, was established to improve access and increase efficiency for genetic test facilitation. The GTAC unit includes genetic counselors, genetic counseling assistants, genetic nurses, and a medical geneticist. Patients receive abbreviated point-of-care genetic counseling and testing through a partnership with subspecialty providers. Results Implementation of PRaUD began in 2018 and GTAC unit launched in 2020 to support program expansion. Currently, 29 RD clinical indications are included in 11 specialty divisions/departments with over 142 referring providers. To date, 1152 patients have been evaluated with an overall solved or likely solved rate of 17.5% and as high as 66.7% depending on the phenotype. Noteworthy, 42.7% of the solved or likely solved patients underwent changes in medical management and outcome based on genetic test results. Conclusion Implementation of PRaUD and GTAC have enabled subspecialty practices advance expertise in RD where genetic counselors have not historically been embedded in practice. Democratizing access to genetic testing and counseling can broaden the reach of patients with RD and increase the diagnostic yield of such indications leading to better medical management as well as expanding research opportunities.

The widespread use of the oral poliovaccine from Sabin strains (tOPV) radically reduced poliomyelitis incidence worldwide. However, OPV became a source of neurovirulent vaccine-derived polioviruses (VDPVs). Currently, circulating type 2 VDPVs (cVDPV2) are the leading cause of poliomyelitis. The novel OPV type 2 vaccine (nOPV2), based on genetically modified Sabin strain with increased genetic stability and reduced risk of cVDPV formation, has been used to combat cVDPV2 outbreaks, including one in Tajikistan in 2021. In order to identify the importation of cVDPV2 and nOPV2-derivates, stool samples from 12,127 healthy migrant children under 5 years of age arriving from Tajikistan were examined in Russia (March 2021–April 2022). Viruses were isolated in cell culture and identified via intratype differentiation RT-PCR, VP1 and whole-genome sequencing. cVDPV2 isolates closely related with the Tajikistan one were isolated from two children, and nOPV2-derived viruses were detected in specimens from 106 children from 37 regions of Russia. The duration of nOPV2 excretion ranged from 24 to 124 days post-vaccination. nOPV2 isolates contained 27 mutations per genome (0.36%) on average, with no critical genetic changes, which confirms the genetic stability of nOPV2 during field use. The possibility of epidemiologically significant poliovirus introduction into polio-free countries has been confirmed. The screening of special populations, including migrants, is required to maintain epidemiological well-being.

Objectives: The detection of a vaccine-derived poliovirus (VDPV) requires an epidemiological assessment and response. Using repeated stool sampling from a child who is immunocompetent and was vaccinated against poliomyelitis with acute flaccid paralysis, a case of an extremely rapid evolution of Sabin-like poliovirus (PV) type 3 was traced in the child's body. Methods: The case was independently identified in two countries—Tajikistan and Russia. Stool samples for the study were also independently collected in two countries on different days from the onset of paralysis. Virological, serological, and molecular methods; full genome Sanger; and high-throughput sequencing were performed to characterize isolates. Results: PV isolates from samples collected on days 2, 3, and 14 contained eight, seven, and seven mutations in the VP1-coding region, respectively, and were classified as Sabin-like PV type 3. The isolates from samples collected on days 15 and 18 had 11 mutations and were classified as vaccine-derived PVs, which required an epidemiological response in the two countries. Conclusion: The results indicate the need to continue acute flaccid paralysis surveillance, maintain high vaccination coverage, and develop and introduce new effective, genetically stable PV vaccines.

Abstract Background Current understanding about health care in the gender diverse population is limited by the lack of community-based, longitudinal data, especially in the USA. We sought to characterize a community-based cohort of transgender individuals including demographics, gender identities, social characteristics, psychiatric and medical conditions, and medical therapy for gender dysphoria/incongruence. Patients and methods We performed a retrospective chart review of gender diverse residents of Olmsted County, Minnesota, who sought gender-specific healthcare from January 1, 1974, through December 31, 2015, using an infrastructure that links medical records of Olmsted County residents from multiple institutions. Results The number of patients seeking gender-specific healthcare increased from 1 to 2 per 5-year interval during the 1970s–1990s to 41 from 2011 to 2015 (n = 82). Forty-nine (59.8%) were assigned male sex at birth (AMAB), 31 (37.8%) were assigned female (AFAB), and 2 (2.4%) were intersex. Gender identities evolved over time in 16.3% and 16.1% of patients AMAB and AFAB, respectively, and at most recent follow-up, 8.2% and 12.9% of patients AMAB and AFAB, respectively, were non-binary. Depression affected 78%, followed by anxiety (62.2%), personality disorder (22%), and post-traumatic stress disorder (14.6%). 58.5% experienced suicidal ideation, 22% attempted suicide, and 36.6% were victims of abuse. The most prevalent medical conditions and cardiovascular (CV) risk factors included obesity (42.7%), tobacco use (40.2%), fracture [34.1% (86.2% traumatic)], hypertension (25.6%), hyperlipidemia (25.6%), and hypertriglyceridemia (15.9%). 67.3% of patients AMAB used feminizing and 48.4% of patients AFAB used masculinizing hormone therapy. When compared to US CDC National Health Statistics, there was a significantly greater prevalence of depression and anxiety but no difference in the prevalence of obesity, hypertension, hypercholesterolemia, type 2 diabetes, or stroke. Conclusion Transgender and gender diverse individuals represent a population who express various gender identities and are seeking gender-specific healthcare at increasing rates. Psychiatric illness is highly prevalent compared to the US population but there is no difference in the prevalence of CV risk factors including obesity, type 2 diabetes, hypertension, and dyslipidemia.

Purpose: antigenic and genetic characterization of Streptococcus pneumoniae strains isolated from patients with invasive forms of pneumococcal infection using whole-genome sequencing.Materials and Methods. The study was performed on 46 S. pneumoniae strains isolated during the PEHASus multicenter studies in 2015-2018. Sequencing was performed using Illumina protocols and equipment. The SPAdes, SeroBA, PneumoCaT software were used for data processing, as well as BIGSdb software (PubMLST.org).Results and Discussion. Whole-genome sequences of strains were obtained; the information was entered into the PubMLST database (id: 51080-51125). Ten (21%) strains were found to have serotype 3. Five (11%) strains belonged to serotype 19F and five to serogroup 6; two of them belonged to serotype 6A; one strain had 6B and 1 had 6BE serotype; 1 strain showed discordant result (6A or 6BE). Serotype 15B was identified in 3 (6.5%) strains. Serotypes 7F, 8, 9V, 14, 22F, 23F and 28A were identified in two strains each; serotypes 1, 4, 9N, 10C, 12F, 18C, 35F, 37 and 38 were found once. The proportion of strains with serotypes included in PCV13 and PPV23 vaccines was 65% and 80%, respectively. 36 sequence types were found in strains; out of them, 6 sequence types were found for the first time. A dominant sequence type or clone complexes could not be identified using multilocus sequence typing except for serotype 3 strains. The inability to identify clonal complexes is in congruence with the previously obtained data on the absence of S. pneumoniae clones associated with pneumococcal meningitis in Russia.Conclusion. The information about serotypes of S. pneumoniae causing invasive infections together with epidemiologic data about strain sources and vaccination allows us to evaluate the effectiveness of pneumococcal vaccines and provide information for improving the PCR-based routine serotyping.

Sex is a biological variable in experimental models. In our previous diisopropylfluorophosphate (DFP) studies, female rats required a higher dose of DFP to achieve a somewhat similar severity of status epilepticus (SE) as males. In those studies, male and female rats were bought separately from the same vendor, housed in different rooms, and the DFP used was from different batches. We had also shown that surgery for epidural electrodes implantation reduces the threshold for SE. Our recent study in the soman (GD) model using a mixed-sex cohort of rats housed individually but in the same room showed that females achieved significantly higher SE severity than males for the same dose of GD. In this study, we demonstrate that housing the mixed-sex cohorts in the same room and treating them with DFP (4 mg/kg, s.c.) from the same pool, though from different batches, yielded reproducible SE severity in both sexes and both telemetry (surgery) and non-telemetry (non-surgery) groups. We conducted experiments in four mixed-sex cohorts of adult Sprague-Dawley rats. In females, the surgery for implanting the telemetry devices reduced the latency to convulsive seizure (CS) and increased SE severity compared to non-telemetry females. However, there were no sex differences in latency or SE severity within telemetry or non-telemetry groups. Once animals reached CS stage ≥3, they remained in CS stage in both sexes until midazolam was administered. Midazolam (3 mg/kg, i.m.) treatment 1-one-hour post-DFP significantly reduced epileptiform spikes in both sexes. The mortality was only 2% in 24 h. Irrespective of sex or stage of estrous cycle or surgery, the animals had continuous convulsive SE for ∼40 min. In telemetry rats, electrographic changes correlated with behavioral seizures. However, there was a significant difference in SE severity and the latency between directly-observed behavioral CS and EEG-based CS quantification in both sexes. Overall, these results suggest that housing both sexes in the same room and treating with DFP in a mixed-sex cohort from the same pool of reagents will minimize variability in SE severity. Such rigorous experiments will yield better outcomes while testing disease-modifying agents in epilepsy models.

BACKGROUND Type 1 diabetes (T1D) is a risk factor for dementia and structural brain changes. It remains to be determined whether transient insulin deprivation that frequently occurs in insulin-treated individuals with T1D alters brain function.METHODS We therefore performed functional and structural magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological testing at baseline and following 5.4 ± 0.6 hours of insulin deprivation in 14 individuals with T1D and compared results with those from 14 age-, sex-, and BMI-matched nondiabetic (ND) participants with no interventions.RESULTS Insulin deprivation in T1D increased blood glucose, and β-hydroxybutyrate, while reducing bicarbonate levels. Participants with T1D showed lower baseline brain N-acetyl aspartate and myo-inositol levels but higher cortical fractional anisotropy, suggesting unhealthy neurons and brain microstructure. Although cognitive functions did not differ between participants with T1D and ND participants at baseline, significant changes in fine motor speed as well as attention and short-term memory occurred following insulin deprivation in participants with T1D. Insulin deprivation also reduced brain adenosine triphosphate levels and altered the phosphocreatine/adenosine triphosphate ratio. Baseline differences in functional connectivity in brain regions between participants with T1D and ND participants were noted, and on insulin deprivation further alterations in functional connectivity between regions, especially cortical and hippocampus-caudate regions, were observed. These alterations in functional connectivity correlated to brain metabolites and to changes in cognition.CONCLUSION Transient insulin deprivation therefore caused alterations in executive aspects of cognitive function concurrent with functional connectivity between memory regions and the sensory cortex. These findings have important clinical implications, as many patients with T1D inadvertently have periods of transient insulin deprivation.TRIAL REGISTRATION ClinicalTrials.gov NCT03392441.FUNDING Clinical and Translational Science Award (UL1 TR002377) from the National Center for Advancing Translational Science; NIH grants (R21 AG60139 and R01 AG62859); the Mayo Foundation.

ABSTRACT: Objective: To describe a case of Graves disease (GD) and coexistent pancytopenia associated with autoimmune vitamin B12 deficiency. While thyrotoxicosis and antithyroid drugs can cause pancytopenia, other autoimmune conditions such as vitamin B12 deficiency can occur, leading to severe anemia and pancytopenia. Methods: A 19-year-old female with GD treated with methimazole presented with thyrotoxicosis and evidence of pancytopenia. Diagnostic studies included a complete blood cell count, peripheral blood smears, thyroid function tests, and a bone marrow biopsy. Results: White blood cells were 2.4 × 109 cells/L (reference range [RR] is 3.4 to 9.6 × 109 cells/L), hemoglobin was 7.9 g/dL (RR is 11.6 to 15.0 g/dL), neutrophil count was 1.2 × 109 cells/L, and platelets were 84 × 109 cells/L (RR is 157 to 371 × 109 cells/L). Thyroid-stimulating hormone was

Unfavorable lipid levels during childhood are associated with subsequent development of atherosclerotic cardiovascular disease. The American Academy of Pediatrics and National Heart, Lung and Blood Institute in 2011 recommended universal lipid screening for children between ages 9–11years and between ages 17–21years. The objective of the study was to determine temporal trends in lipid testing among children and young adults in a mid-western population. The Rochester Epidemiology Project database was used to identify lipid testing in ages 2–21years (n=51,176) in the Olmsted County population from January 1, 2008 through December 31, 2014. Generalized estimating equations with Poisson distribution were used to test for temporal trends in lipid testing across the age groups. There was modest increase in lipid testing in children in the age groups, 9–11years and 17–21years (1.5% in 2008 to 2.2% in 2014, P

Background: The language used in research and health programs is crucial in influencing participation and ensuring the acceptability of programs and the adoption of research outcomes. The use of alienating language may present a barrier for research participants hence the need to identify accurate, respectful, relevant, and acceptable terms for respective study populations. The study explored commonly used terminologies during research involving pregnant and lactating mothers using public engagement and participatory approaches in Uganda. Methods: A cross-sectional qualitative study was conducted in August 2023 among 5 ethnically diverse communities with different languages and from different regions across Uganda. Data were collected through 18 focus group discussions (FGDs) comprising community members and one comprising the community advisory board (CAB) using a participatory approach. An interview guide exploring perceptions and experiences on research, common and preferred terms for specific terminologies used among pregnant and lactating mothers as well as disliked words guided the discussion. Transcription was done verbatim in English. Nvivo version 14 software was used to organize and manage the data appropriately based on themes and subthemes. Results: A consensus on the preferred terminologies to communicate about our research studies involving pregnant and lactating mothers was reached. The study revealed that words used in research that did not specify sex were described as disrespectful, inappropriate or confusing. Language defining a person on the basis of anatomical or physiological characteristics was considered 'embarrassing' and labelling individuals based on their conditions was construed as stigmatising. Participants recommended that researchers be mindful of any terms that could be perceived as embarrassing or inappropriate within the community, ensure clear communication of research terms to participants, and train healthcare workers on the use of appropriate health language. The importance of providing feedback regarding study findings was emphasised. Conclusion: The findings highlight the importance of using culturally sensitive language in health research to improve engagement and participation. By adopting community-preferred terms, researchers can avoid confusion and stigma fostering respectful health communication. The findings offer guidance for future research, advocating for community-driven inclusive language in research involving pregnant and breastfeeding women. For healthcare workers, training in empathetic communication and cultural competence is crucial to improve patient interactions and promote dignity in healthcare settings. [ABSTRACT FROM AUTHOR]

Everybody deserves access to evidence‐based information to make decisions about their health. However, in many situations, clinical trial eligibility criteria mean that specific data do not exist for certain groups of individuals. These include pregnant and breastfeeding women, children, older people, those with hepatic and renal dysfunction, those with acute severe illness, and those with multiple co‐morbidities and interacting medications. Resultantly, there may not be specific drug‐dosing information for many patients who are treated in a clinical setting. The ASCPT2024 Dolores Shockley Lecture focused on the equitable access to research with a specific focus on clinical pharmacology studies in pregnancy and breastfeeding. To ensure the safe, effective use of medication in pregnancy and breastfeeding, women should be included in clinical trials and pharmacokinetic studies when a medication is anticipated to be used in women of childbearing potential. Community groups should be involved at all stages of research to maintain transparency and trust. This ensures that local priorities are investigated, that communities understand the findings and are empowered to make evidence‐based decisions about their own medication use. Principles informing the design of such studies in pregnancy and lactation are in existence. Mathematical techniques such as physiologically‐based pharmacokinetic modeling and stochastic simulation and estimation can enhance study design, and population pharmacokinetic modeling be used to understand variability within and between individuals. Data should be made findable, accessible, interoperable, and reusable (FAIR). Information (and where necessary, training) regarding the use of these approaches should be provided to decision‐making stakeholders such as ethics committees and regulatory bodies. [ABSTRACT FROM AUTHOR]

Around 1.2 million women living with HIV give birth annually, majority of whom will breastfeed their infants while receiving antiretroviral therapy (ART). Lamivudine, a component of first‐line ART regimens crosses from maternal plasma to breast milk, with measurable concentrations in some breastfed infants. Wide variability in plasma‐to‐breast milk transfer has been reported within‐ or across studies, probably due to differences in sampling framework. This work sought to characterize the milk‐to‐plasma transfer of lamivudine, quantify inter‐patient variability and associated factors, and predict exposure of a breastfed infant. We explored data from an observational pharmacokinetic study that included 35 Ugandan mothers and their infants. Mothers received lamivudine doses of 150 mg twice daily or 300 mg once daily as part of their antiretroviral regimen. Pharmacokinetic sampling was undertaken across two visits approximately 8 weeks apart, providing 248 maternal plasma, 256 breast milk‐, and 151 infant blood concentrations, measured across a 24‐h sampling interval. A one‐compartmental model best described the plasma disposition of lamivudine, with first‐order absorption, interindividual variability on clearance and volume of distribution, and a proportional residual error model. A lag in time of plasma‐to‐breast milk drug accumulation was described using an effect compartment model with a milk‐to‐plasma ratio of 1.77. An estimated daily infant dose of 179.3 μg/kg (range: 125.8, 282.3) closely predicted the observed infant steady‐state concentrations and translated into 3.34% (2.13, 7.20) and 3.35% (1.10, 7.15) of the standard daily maternal dose in visits 1 and 2, respectively. The established modeling framework can be extended to other drugs. [ABSTRACT FROM AUTHOR]

Pharmacokinetic studies are important for understanding drug disposition in the human body. However, pregnant and lactating women are often excluded from primary pharmacokinetic studies and as such there is often limited dosing information regarding drug use in pregnant and/or lactating women. The objectives of this interim analysis were to define the transfer of rifampicin to a breastfed infant and to determine the area under the concentration–time curve of rifampicin in maternal plasma, breastmilk and infant plasma. Performing this interim analysis enabled us to substantiate whether prior assumptions we made on several study design issues including patient sample size and pharmacokinetic sampling times held and whether we needed to amend our protocol or not. We enrolled lactating mothers on treatment for tuberculosis with their breastfeeding infants (below 12 months of age), performed intensive pharmacokinetic sampling (0–24 h post‐dose) on plasma samples from both the mother, infant(s) and breastmilk samples from the mother on two separate occasions (once during the initiation phase and another during the continuation phase of tuberculosis treatment). The initial study design, including sampling times, was informed by a stochastic simulation and estimation exercise, with very limited prior breastmilk data. An interim analysis after recruiting 6 mother–infant pairs ascertained that our initial assumptions were ideal for achieving our study objectives and no amendments to the sampling times were necessary. Initial data from 6 mother–infant pairs show that rifampicin penetrates breastmilk with an approximate milk‐to‐plasma ratio of 0.169 and 0.189 on two separate visits. However, it was undetectable in most infants. [ABSTRACT FROM AUTHOR]

Pregnant and breastfeeding women are often under-represented in clinical research, including pharmacokinetic studies, due to ethical and logistical challenges. This paper examines strategies to improve the recruitment and retention of this demographic in pharmacokinetic research, drawing on experiences from five studies conducted at the Infectious Diseases Institute, Makerere University, Uganda. Key strategies implemented include Community Advisory Board meetings, the involvement of Peer Mothers as Co-Investigators, established recruitment sites, the use of safety protocols, and the utilization of diverse communication platforms, including social media and stakeholder meetings. Despite these efforts, substantial barriers, such as scheduling conflicts and frequent staff turnover at recruitment sites, continue to threaten progress. The paper recommends flexible scheduling, strengthening public engagement, and transparent demonstration of adherence to ethical principles; justice, non-maleficence, respect, and beneficence to ensure the safety and inclusivity of pregnant and breastfeeding women. The inclusion of this population in pharmacokinetic studies is essential for providing evidence-based care that meets their unique health needs. [ABSTRACT FROM AUTHOR]

The widespread use of the oral poliovaccine from Sabin strains (tOPV) radically reduced poliomyelitis incidence worldwide. However, OPV became a source of neurovirulent vaccine-derived polioviruses (VDPVs). Currently, circulating type 2 VDPVs (cVDPV2) are the leading cause of poliomyelitis. The novel OPV type 2 vaccine (nOPV2), based on genetically modified Sabin strain with increased genetic stability and reduced risk of cVDPV formation, has been used to combat cVDPV2 outbreaks, including one in Tajikistan in 2021. In order to identify the importation of cVDPV2 and nOPV2-derivates, stool samples from 12,127 healthy migrant children under 5 years of age arriving from Tajikistan were examined in Russia (March 2021–April 2022). Viruses were isolated in cell culture and identified via intratype differentiation RT-PCR, VP1 and whole-genome sequencing. cVDPV2 isolates closely related with the Tajikistan one were isolated from two children, and nOPV2-derived viruses were detected in specimens from 106 children from 37 regions of Russia. The duration of nOPV2 excretion ranged from 24 to 124 days post-vaccination. nOPV2 isolates contained 27 mutations per genome (0.36%) on average, with no critical genetic changes, which confirms the genetic stability of nOPV2 during field use. The possibility of epidemiologically significant poliovirus introduction into polio-free countries has been confirmed. The screening of special populations, including migrants, is required to maintain epidemiological well-being. [ABSTRACT FROM AUTHOR]

The editorial discusses the role of pharmacokinetic modeling in optimizing treatment by integrating patient data, drug exposure, and clinical outcomes. It highlights the evolution of quantitative pharmacology and pharmacometrics, emphasizing their importance in drug development and clinical practice. Various case studies demonstrate the application of pharmacometrics in diverse scenarios, such as optimizing dosing for infants and pregnant women, and evaluating drug exposure in different populations. The field continues to expand, with a focus on individualized guidance for safe and effective medication use. [Extracted from the article]

Aims: Dolutegravir increases serum creatinine by inhibiting its renal tubular secretion and elimination. We investigated determinants of early changes in serum creatinine in a southern African cohort starting first‐line dolutegravir‐based antiretroviral therapy (ART). Methods: We conducted a secondary analysis of data from participants in a randomized controlled trial of dolutegravir, emtricitabine and tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide fumarate (TAF) (ADVANCE, NCT03122262). We assessed clinical, pharmacokinetic and genetic factors associated with change in serum creatinine from baseline to Week 4 using linear regression models adjusted for age, sex, baseline serum creatinine, HIV‐1 RNA concentration, CD4 T‐cell count, total body weight and co‐trimoxazole use. Results: We included 689 participants, of whom 470 had pharmacokinetic data and 315 had genetic data. Mean change in serum creatinine was 11.3 (SD 9.9) μmol.L−1. Factors that were positively associated with change in serum creatinine at Week 4 were increased log dolutegravir area under the 24‐h concentration–time curve (change in creatinine coefficient [β] = 2.78 μmol.L−1 [95% confidence interval (CI) 0.54, 5.01]), TDF use (β = 2.30 [0.53, 4.06]), male sex (β = 5.20 [2.92, 7.48]), baseline serum creatinine (β = −0.22 [−0.31, −0.12]) and UGT1A1 rs929596 A→G polymorphism with a dominant model (β = −2.33 [−4.49, −0.17]). The latter did not withstand correction for multiple testing. Conclusions: Multiple clinical and pharmacokinetic factors were associated with early change in serum creatinine in individuals initiating dolutegravir‐based ART. UGT1A1 polymorphisms may play a role, but further research on genetic determinants is needed. [ABSTRACT FROM AUTHOR]

This research aimed to synthesis of N-base compounds based on benzimidazole derivatives and their potential as antibacterials, antioxidants, and anticancer. The synthesis was conducted in two stages, namely the intermediate (benzimidazole derivatives) and the final product (N-mannich base), using five variations of organic acids and SiO2OAlCl2 as catalyst. The results showed that the catalyst was successfully synthesized and characterized by The Fourier transform infrared (FTIR), X-ray diffraction (XRD), and Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS). The purity of the synthesized compounds was monitored by Thin layer chromatography (TLC), melting point test, Ultraviolet-visible (UV–Vis), and Liquid chromatography-Mass spectrometry (LC-MS). The five intermediate compounds and five mannich base products yield 77 %-89 % and 65 %-85 %, respectively. The final products were applied through antibacterial testing against Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria) by disc diffusion. Mannich base compounds have potential antibacterial agents, but only 4A and 4E gave the best inhibition zone diameter. Meanwhile, the antioxidant testing result using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method showed the best activity in the mannich base compound 4E. The anticancer test result showed that the five mannich base compounds had potential as anticancer agents.

This study aims to analyze the influence of environmental awareness, information technology (IT) use, and access to credit as moderators on the sustainability of Indonesia’s micro, small, and medium enterprises (MSMEs). Data were obtained through a survey of 1,374 MSMEs. Sampling was carried out using purposive sampling techniques, targeting MSMEs that had been established for more than 3 years and had received loans from financial institutions. The analysis used the ordinary least square (OLS) regression method to evaluate the relationship between the independent variables and MSME sustainability. The results show that environmental awareness and IT use significantly positively affect MSME sustainability. Credit access was also found to have a significant and positive effect. However, the interaction between credit access, environmental awareness, and IT use resulted in a small but significantly negative effect. This suggests that an excessive increase in credit access might reduce the positive impact of environmental awareness and IT use on MSME sustainability. Overall, this study confirms the importance of environmental awareness and information technology in improving MSME sustainability and highlights the need for proper management of credit access. AcknowledgmentAppreciation is given to the Directorate General of Higher Education, Research and Technology, Ministry of Education, Culture, Research and Technology, which has provided a fundamental research grant with contract number 108/E5/PG.02.00.PL/2024. Acknowledgments are also expressed to higher education service institutions (LLDIKTI) Region 6 and the Institute of Research and Community Services (LPPM) Unisnu Jepara Indonesia, which has supported this research.