Careful Evaluation Research Articles

How Pharmaceutical Residues Occur, Behave, and Affect the Soil Environment.

Many pharmaceuticals (PhMs), compounds for the treatment or prevention of diseases in humans and animals, have been identified as pollutants of emerging concern (PECs) due to their wide environmental distribution and potential adverse impact on nontarget organisms and populations. They are often found at significant levels in soils due to the continuous release of effluent and sludge from wastewater treatment plants (WWTPs), the release of which occurs much faster than the removal of PhMs. Although they are generally present at low environmental concentrations, conventional wastewater treatment cannot successfully remove PhMs from influent streams or biosolids. In addition, the soil application of animal manure can result in the pollution of soil, surface water, and groundwater with PhMs through surface runoff and leaching. In arid and semiarid regions, irrigation with reclaimed wastewater and the soil application of biosolids are usual agricultural practices, resulting in the distribution of a wide number of PhMs in agricultural soils. The ability to accurately study the fate of PhMs in soils is critical for careful risk evaluation associated with wastewater reuse or biosolid return to the environment. The behavior and fate of PhMs in soils are determined by a number of processes, including adsorption/desorption (accumulation) to soil colloids, biotic (biodegradation) and abiotic (chemical and photochemical degradation) degradation, and transfer (movement) through the soil profile. The sorption/desorption of PhMs in soils is the main determinant of the amount of organic chemicals taken up by plant roots. The magnitude of this process depends on several factors, such as crop type, the physicochemical properties of the compound, environmental properties, and soil-plant characteristics. PhMs are assumed to be readily bioavailable in soil solutions for uptake by plants, and such solutions act as carriers to transport PhMs into plants. Determining microbial responses under exposure conditions can assist in elucidating the impact of PhMs on soil microbial activity and community size. For all of the above reasons, soil remediation is critical when soil pollutants threaten the environment.

Opioids and Cannabinoids in Neurology Practice.

Opioid and cannabinoid therapies for chronic pain conditions including neuropathic pain are controversial. Understanding patient and prescribing factors contributing to risks and implementing risk mitigation strategies optimizes outcomes. The ongoing transformation from a biomedical model of pain care toward a biopsychosocial model has been accompanied by a shift away from opioid therapy for pain, in particular for chronic pain. Opioid overdose deaths and opioid use disorder have greatly increased in the last several decades, initially because of increases in opioid prescribing and more recently associated with illicit drug use, in particular fentanyl derivatives. Opioid risk mitigation strategies may reduce risks related to opioid prescribing and tapering or discontinuation. Opioid therapy guidelines from the Centers for Disease Control and Prevention have become the consensus best practice for opioid therapy. Regulatory agencies and licensing medical boards have implemented restrictions and other mandates regarding opioid therapy. Meanwhile, interest in and use of cannabinoids for chronic pain has grown in the United States. Opioid therapy is generally not recommended for the chronic treatment of neuropathic pain conditions. Opioids may be considered for temporary use in patients with severe pain related to selected neuropathic pain conditions (such as postherpetic neuralgia), and only as part of a multimodal treatment regimen. Opioid risk mitigation strategies include careful patient selection and evaluation, patient education and informed consent, querying the state prescription drug monitoring programs, urine drug testing, and issuance of naloxone as potential rescue medication. Close follow-up when initiating or adjusting opioid therapy and frequent reevaluation during long-term opioid therapy is required. There is evidence for the efficacy of cannabinoids for neuropathic pain, with meaningful response rates in select patient populations.

Geochemical (δ13C, δ18O, 87Sr/86Sr, REEs) characterization of travertine in Tengchong, China: Insights into travertine origin and reservoir conditions

Geochemical characterization is extensively employed in travertine research, yet few studies have explored the potential of travertine geochemistry for elucidating the subterranean details of spring systems. In this study, we systematically characterized the geochemical signatures (δ13C, δ18O, 87Sr/86Sr, REEs, Zr, Th, Sr, Mn) of travertine from six spring systems in Tengchong (SW China) and compared them with those of potential reservoir rocks, aiming to understand travertine origin and assess reservoir conditions. Our results revealed substantial variations in the δ13C and δ18O of travertine among the examined systems, but the water temperature and parent CO2 assessments suggest a hot spring thermogene origin of the travertine. The 87Sr/86Sr of the studied travertine also varies significantly among the systems and overlaps with that of potential reservoir rocks. However, only the springs systems with reservoir temperatures exceeding 150 °C are likely to have precipitated travertine with 87Sr/86Sr resembling the whole-rock 87Sr/86Sr of the reservoir rocks. REE contamination by exogenous detritus and FeMn (oxyhydr)oxides was noted, emphasizing the need for careful REE contamination evaluation in travertine research. The REE comparison reveals that the studied travertine does not fully replicate the REE signature of its potential reservoir rocks, but the REE pattern, (Eu/Eu*)SN, and (Ce/Ce*)SN characteristics of the travertine reveal informative reservoir conditions. In summary, this study shows that the geochemistry of the travertine offers valuable insights into its origin and reservoir conditions. These findings could assist in the geochemical interpretation of travertine and the exaction of hypogean reservoir conditions from travertine.

Stool Xpert® MTB/RIF Ultra for TB diagnosis in children: experience from a national scale-up programme.

We describe the programmatic scale-up of stool testing using Xpert® MTB/RIF Ultra (Ultra), as recommended by the WHO to improve childhood pulmonary TB (PTB) diagnosis. USAID's Alliance for Combating TB in Bangladesh Activity, in collaboration with the National TB Control Programme, is implementing a stool-based diagnostic approach at 51 healthcare facilities in Bangladesh to improve PTB detection. Specimens from children (<15 years) with presumptive TB were tested using 'stool Ultra' with routine TB diagnostics. Physicians confirmed TB diagnosis and provided treatment as per national guidelines. Between March 2022 and December 2023, 16,429 specimens were tested, 871 (5.3%) were positive, and 642 (73.7%) showed 'trace detected' results. Positivity was significantly higher among females, and children presented with 'only cough ≥2 weeks', 'cough ≥2 weeks + weight loss', or 'fever ≥2 weeks, weight loss, fatigue + contact history'. Positivity was higher among '10-14 years old' children; however, 'trace detected' was highest among '5-9 years', followed by children aged '>2-<5 years' and '0-2 years'. Testing stools using Ultra provides a more effective way of diagnosing bacteriologically positive PTB in children. However, positivity varies with presenting symptoms/criteria, highlighting the need for careful diagnostic evaluation to ensure optimum use of limited diagnostic resources.

Investigation of malnutrition and sarcopenia in individuals staying in the elderly care center and evaluation of its effect on quality of life

Investigation of malnutrition and sarcopenia in individuals staying in the elderly care center and evaluation of its effect on quality of life

Vermian multinodular and vacuolating lesion of unknown significance discovered following syncope: a case report

Introduction and importance: Multinodular and Vacuolating Posterior Fossa Lesions of Unknown Significance (MV PLUS) are benign cystic lesions that, though typically asymptomatic, can present with neurological symptoms such as seizures, headaches, and syncope. These lesions are predominantly found in sub-tentorial brain structures but can also appear in supratentorial areas. MRI is crucial in detecting these lesions, characterized by small nodules with high intensity on T2-FLAIR sequences. Despite increasing awareness, the pathophysiology and classification of MV PLUS lesions remain unclear, necessitating further research and careful monitoring. Case presentation: A 52-year-old female presented with subjective dizziness and a recent syncope episode. Neurological examination showed ataxia and a positive Romberg sign. MRI revealed a multicystic and nodular lesion in the vermian and paravermian regions, with altered signal intensity on T1-weighted and FLAIR sequences. The lesion showed no pathological enhancement post-gadolinium administration, and spectroscopy revealed no significant metabolite peaks. Clinical improvement was observed following corticosteroid and antivertiginous therapy, and the patient was discharged with a recommendation for neuroradiological follow-up. Clinical discussion: MV PLUS lesions are a subset of multinodular and vacuolating lesions that present significant diagnostic challenges due to their complex radiological features. First described in 2013, these lesions have distinct MRI characteristics, including a nodular appearance with high T2-FLAIR intensity and occasional cystic components. Despite being benign and typically stable, the differential diagnosis includes various other intracranial lesions, requiring careful evaluation. The pathogenesis and optimal management strategies for MV PLUS lesions are still under investigation, emphasizing the need for continued research. Conclusion: MV PLUS lesions, although rare and benign, present unique diagnostic challenges due to their varied radiological features and potential neurological symptoms. Regular MRI monitoring is essential to track their stability, given the current lack of understanding regarding their pathophysiology and long-term implications. Further research is needed to elucidate the etiology, natural history, and optimal management of these intriguing lesions.

Clinical presentation of anterior pelvic tilt and trunk muscle endurance among patients with femoroacetabular impingement syndrome: a cross-sectional study.

Femoroacetabular impingement syndrome (FAIS) significantly affects the physical function and quality of life of the young and middle-aged population. Pelvic tilt and trunk muscle endurance are physical features poorly studied in FAIS. This study aimed to compare the anterior pelvic tilt and anterior, lateral, and posterior trunk muscles endurance between people with FAIS and healthy individuals, within FAIS sub types and between the symptomatic and asymptomatic hip in people with FAIS. Cross-sectional study. Participants were recruited and screened for potential eligibility at the Rehabilitation, Sports Medicine, and Physiotherapy Unit between April 2021 and February 2022. Sixty-nine patients with FAIS and 69 controls. A study adhering to STROBE guidelines recruited 138 participants (69 FAIS, 69 controls). The degree of pelvic tilt was measured by the palpation meter (PALM) tool. To assess trunk musculature endurance, isometric trunk tests described by McGill were performed (extension resistance test, flexion resistance test, and side plank test). Cases were classified based on FAIS subtypes. Differences between groups and subgroups were performed using t-tests and ANCOVA, respectively. Significant differences in anterior pelvic tilt were observed between the control and FAIS groups (P<0.001, d=0.72). Participants with FAIS exhibited greater pelvic tilt (MD=1.57, 95% CI=0.83 to 2.3). Trunk muscle endurance showed statistically significant differences (P<0.001, d=0.72) for posterior muscles. In comparisons between symptomatic and asymptomatic hips, significant differences were found in pelvic tilt (P<0.001, d=0.26) and lateral trunk muscle endurance (P<0.001, d=0.43). FAIS subtypes demonstrated significant differences in lateral trunk muscle endurance (P=0.002, η<inf>p</inf>2=0.209). This study found that patients with FAIS present large anterior pelvic tilt and lower posterior trunk muscle endurance. Although anterior pelvic tilt was comparable for all FAIS subtypes, Pincer-type with or without labral tear exhibited lower lateral trunk muscle endurance compared with Cam-type with or without labral tear. In addition, the symptomatic hip of FAIS patients showed lower lateral trunk muscle endurance compared to the asymptomatic hip. Incorporating rehabilitation strategies that address pelvic tilt and trunk muscle strengthening in individuals with FAIS might be considered as a potential means to improve these physical impairments, pending careful evaluation of their effectiveness.

Multidisciplinary Consideration for Managing Gingival Black Triangles in Aesthetic Dentistry: A Review

The importance of aesthetics in modern dentistry is paramount. Aesthetics has its different values and perceptions, which may be different from the eyes of the patient and those of the clinician [1]. It is dependent on the socio-economic status and the upbringing and mentality of each individual person. Open gingival embrasures or black triangle cause complex functional and aesthetic problems. Management of such problems requires careful evaluation of the underlying causes. In today’s aesthetic environment where both the dentist and the patient are aware of aesthetic value, the real challenge was to reconstruct this lost papilla and moreover to obtain stable and sustainable results. asure area, root angulations, interproximal contact position, triangular-shaped crowns and aging. Treatment of black triangles often requires an interdisciplinary approach, involving of periodontal; orthodontic and restorative treatment. In this review, the authors highlighted the important etiological factors that predispose to the occurrence of the black triangles. In addition to the common biological factors, dimensional changes of papilla during orthodontic alignment, the relevant consequences of periodontal disease treatment and iatrogenic treatment mishaps such as poor veneers and crowns are factors have also been discussed as factors that may lead to black triangles.

Ganglion Cell Complex Thickness and Visual Function in Chronic Leber Hereditary Optic Neuropathy.

To evaluate the correlation between the macular ganglion cell complex (GCC) thickness measured with manually corrected segmentation and visual function in individuals with chronic Leber hereditary optic neuropathy (LHON). Twenty-six chronic LHON subjects (60% treated with idebenone or Q10) from the Swedish LHON registry were enrolled. Best-corrected visual acuity (BCVA), visual field tests, and optical coherence tomography (OCT) were performed. Visual field was evaluated with the Haag-Streit Octopus 900 with the Esterman test and a custom 30° test. Canon OCT-HS100 scans were exported to the Iowa Reference Algorithm. GCC thickness was obtained after the segmentation was corrected manually in nine macular sectors. The GCC thickness was overestimated by 16 to 30 µm in different macular sectors with the automated segmentation compared with the corrected (P < 0.001). GCC thickness in all sectors showed significant correlation with all functional parameters. The strongest correlation was seen for the external temporal sector (BCVA: r = 0.604, P < 0.001; mean defect: r = 0.457, P = 0.001; Esterman score: r = 0.421, P = 0.003). No differences were seen between treated and untreated subjects with regard to GCC and visual field scores (P > 0.05), but BCVA was better among treated subjects (P = 0.017). The corrected GCC thickness showed correlation with visual function in chronic LHON subjects. The frequently occurring segmentation errors in OCT measurements related to chronic LHON can potentially be misleading in monitoring of disease progression and in evaluating the treatment effects. Precise measurements of GCC could serve as a sensitive tool to monitor structural changes in LHON. We therefore emphasize the importance of careful evaluation of the accuracy of OCT segmentation.

Ticagrelor and Statins: Dangerous Liaisons?

Polypharmacy is often necessary in complex, chronic, comorbid and cardiovascular patients and is a known risk factor for potential drug-drug interaction (DDI) that can cause adverse reactions (toxicity or therapeutic failure). Anti-thrombotic drugs (largely low-dose aspirin and a platelet P2Y12 receptor inhibitor) and statins are among the most co-administered drugs in cardiovascular patients. Ticagrelor is a selective antagonist of the platelet P2Y12-receptor, highly effective in inhibiting platelet aggregation and bio-transformed by the CYP3A4 and substrate of transporters, such as the breast cancer resistance protein (BCRP). Statins have different pharmacokinetic profiles; some undergo CYP3A4-mediated metabolism; rosuvastatin is primarily metabolized by the CYP2C9; and they have different affinities for drug transporters. Rhabdomyolysis is a very rare but severe adverse event, which is specific for statins which can be triggered by DDIs that increase statin's concentrations through blockade of their biotransformation and/or elimination. Large pharmacovigilance and small observational studies reported increased rhabdomyolysis in patients treated with some statins and ticagrelor but not aspirin, clopidogrel or prasugrel. Recent studies in vitro, pharmacokinetic trials and in silico drug modelling identified and validated the BCRP inhibition by ticagrelor, as a mechanism contributing to the DDI with statins, as 'victim' drugs, leading to increased rhabdomyolysis. While the clinical impact of this DDI deserves further investigation, a careful evaluation should be advised when ticagrelor is co-prescribed with some statins.

Comparison of the safety profile of tofacitinib and etanercept in rheumatoid arthritis patients aged 60 years and over: The real-life data from the HUR-BIO registry

Objective: To investigate the safety profile of tofacitinib in rheumatoid arthritis (RA) patients aged 60 and over and to compare these findings with etanercept. Materials and methods: HUR-BIO (Hacettepe University Rheumatology Biologic Registry) is a single-center registry for biological and targeted synthetic DMARDs since 2005. We included RA patients aged ≥ 60 years who were prescribed tofacitinib or etanercept as their first bDMARD or tsDMARD and had at least one control visit. MACE (major adverse cardiovascular event), VTE (venous thromboembolism), malignancy, herpes zoster, and infections requiring hospitalization were recorded for the safety profile. Incidence rate (IR) and incidence rate ratios (IRR) per 1000 patient years were calculated for all safety data. Results: This study consisted of 123 RA patients (tofacitinib n=70, etanercept n=53). In the overall population, the mean age was 67.9 ± 6.2 years and the median follow-up period was 2.1 years. Among the traditional cardiovascular risk factors, smoking history and hyperlipidemia were more common in the tofacitinib group. The IRR per 1000 patients years for MACE, herpes zoster, and infections requiring hospitalization was similar between the groups. All three patients who diagnosed with DVT or PE were in the tofacitinib group, and the significance level of the increase in IR was close to the statistical threshold (p=0.057). There was only one patient who developed non-melanoma skin cancer, and that patient was in the tofacitinib group. Conclusion: The incidence of MACE, herpes zoster, and infections requiring hospitalization was comparable between tofacitinib and etanercept. However, the occurrence of VTE exclusively in the tofacitinib group suggests that this issue needs careful evaluation for these patients.

Hospital Palliative Care Team Involvement in Inpatients with Hematologic Malignancies: A Retrospective Study.

Background: Data on the involvement of hospital palliative care teams (HPCT) in the management of patients with hematologic malignancies (HM) are limited. Objectives: To describe characteristics, symptom burden according to the German Hospice and Palliative Care Evaluation assessment tool, and course of inpatients with HM who were referred to a HPCT, and compare them with their counterparts with solid tumors (ST). Design: Retrospective analysis. Setting/Subjects: Inpatients with HM and ST who were referred to the HPCT of a comprehensive cancer center in Germany between January 1, 2015, and December 31, 2019. Results: The analysis included 2885 patients; 412 (14.3%) had HM and 2473 (85.7%) had ST. Patients with HM more often experienced depression (p = 0.003), tension (p < 0.001), and disorientation (p = 0.003); pain (p = 0.029), nausea (p = 0.003), weakness (p < 0.001), loss of appetite (p = 0.005), tiredness (p < 0.001), and need for assistance with activities of daily living (p < 0.001) were more common in patients with ST. Patients with HM were more often admitted to the intensive care unit (ICU) (p < 0.001), had longer ICU stays (p = 0.005), and had a higher death rate (p < 0.001) during their last stay in the hospital. The time between the first contact with the HPCT and death was shorter for patients with HM (p < 0.001). Patients with HM also had a shorter overall time of care by the HPCT (p < 0.001). Conclusions: As compared with their counterparts with ST, inpatients with HM were closer to death at referral to the HPCT, experienced a comparable overall symptom burden, and were admitted to the ICU more frequently after HPCT involvement.

Clinical approach to probable mixed vascular dementia and progressive supranuclear palsy

Probable mixed dementia, combining vascular dementia and progressive supranuclear palsy (PSP), presents diagnostic challenges due to overlapping clinical features and radiological findings. This case report highlights the complexities involved in diagnosing such cases, where clinical manifestations evolve, requiring careful evaluation and periodic reassessment. Imaging plays a crucial role, with characteristic features aiding in distinguishing between different etiologies. Management of mixed dementia poses therapeutic dilemmas, particularly given the lack of effective treatments for PSP. Nonetheless, a comprehensive approach involving education, vascular risk factor control, and family support is essential for optimizing long-term patient and caregiver outcomes. This case underscores the importance of a multidisciplinary clinical and radiological approach in navigating the complexities of mixed dementia cases.

Familial hypokalemic periodic paralysis: a case induced by concurrent hyperthyroidism

BackgroundFamilial hypokalemic periodic paralysis (HypoPP) is an uncommon genetic disorder characterized by recurrent episodes of muscle weakness and hypokalemia, typically starting in early adulthood. The existence of hyperthyroidism in the presence of HypoPP is more strongly associated with a diagnosis of thyrotoxic periodic paralysis (TPP), with most cases occurring in Asian males with pathogenic KCNJ2 or KCNJ18 variants and without a family history of the condition. This case is novel due to the combination of familial HypoPP and hyperthyroidism induced by Graves’ disease, a rare occurrence especially in non-Asian populations.Case presentationA 40-year-old African American man presented with profound muscle weakness after consuming a high-salt meal. He had a significant family history of hyperthyroidism and hypokalemia. On examination, he showed profound weakness in all extremities. Laboratory tests confirmed hypokalemia and hyperthyroidism, and genetic testing identified a pathogenic variant in the CACNA1S gene (c.1583 G > A, p. R528H), with normal SCN4A, KCNJ2 and KCNJ18 sequencing. He was diagnosed with familial HypoPP and hyperthyroidism due to Graves’ disease. He was started on PO methimazole 10 mg three times a day and PO acetazolamide 250 mg twice a day. He was advised to follow a low carbohydrate and low salt diet.ConclusionsThis case highlights the importance of considering a genetic basis for HypoPP in patients with a family history of the condition, even when hyperthyroidism is present. The combination of familial HypoPP and Graves’ disease is rare and emphasizes the need for careful genetic and clinical evaluation in similar cases. Management should focus on correcting hypokalemia, treating hyperthyroidism, and lifestyle modifications to prevent recurrence.

Missed Opportunities for use of Advanced Care Planning and Palliative Care in Open Aortic Surgery

Major vascular surgery, including open aortic procedures, is associated with having a 30-day mortality rate greater than 6% and a perioperative complication rate greater than 50%. Published literature suggests that patients undergoing high-risk procedures benefit from having a care plan in place to not only maximize quality of life but also to ensure medical interventions align with care goals. Currently, there is a paucity of published data on the prevalence of goals of care conversations, advance care planning documentation, and palliative care evaluations in patients undergoing high-risk vascular operations. A retrospective chart review of all patients who underwent open aortic surgery at a tertiary care academic medical center from July 2014 to March 2023 was performed. Patient demographics, comorbidities, type and timing of advanced care planning (ACP), palliative care evaluations, and clinical outcomes during the periprocedural period were recorded. For patients who died during the study period, the use of palliative care prior to death were noted. Patients who received ACP or palliative care were compared with those who did not. The cohort consisted of 192 patients who underwent major open aortic surgery. The mean age was 63 years (SD 12.3) and the majority of patients were male (73.4%) and white (64.1%). Thirty-nine (20.6%) operations were classified as emergent. At the time of their operation, 16.7% (n=32) of patients had an ACP document on file. Of the 38 documents on file, most were durable power of attorney (DPOA) (86.8%) documents while a smaller percentage were physician orders for life-sustaining treatment (POLST) (13.2%). There were no patients with Do Not Resuscitate and/or Intubate (DNR/DNI), living will, or organ/tissue donation orders noted in their chart prior to surgery. One percent (n=2) of patients had a palliative evaluation prior to their operation. During the perioperative period, an additional 2 (1%) of patients had advanced care planning documentation and 7 (3.7%) of patients underwent palliative care evaluation. Fifteen percent of patients (n=28) died during the perioperative period and an additional 21 patients died by the end of the study period for a total mortality of 25.2% in the study population. Among patients that died during the perioperative period, 28.6% (n=8 out of 28) received palliative care. Overall, 28.6% of all study patients that died (n=14 out of 49) received a palliative care evaluation prior to or during their terminal hospitalization. Patients who had ACP documents or who received palliative care consultations prior to surgery were older (p=0.01), more likely to be on Medicare or Medicaid (p=0.004), and more likely to have a history of solid organ malignancy (p=0.03). The median interval between surgery and receiving palliative care was 20 (IQR 3-71) days. The median interval between palliative care and death was 5 (IQR 2-13) days. Patients who utilized ACP or PC were more likely to die at home (p=0.05). Despite a high mortality and morbidity rate, ACP documentation is poor for patients undergoing major open aortic surgery. Palliative care interventions tend to be performed closer to the end of life, suggesting a missed opportunity to define goals of care.

Imaging Insights Suggesting a Sinister Cause of a Breast Mass in Adolescents: A Case of Rhabdomyosarcoma in a Teenager.

Sarcomas of the breast are exceedingly rare, accounting for less than 1% of malignant breast tumors, with primary rhabdomyosarcomas being even rarer. Due to the scarcity of reported cases, the imaging characteristics of breast rhabdomyosarcoma are not well-defined, making diagnosis challenging, especially in adolescents. We present the case of a 17-year-old female diagnosed with embryonal rhabdomyosarcoma following a comprehensive workup for right breast masses. Initial imaging showed no distant metastasis, and the patient underwent a right mastectomy followed by adjuvant chemoradiotherapy. A few months post-treatment, she developed recurrent nodules in the chest wall. Further investigation confirmed the recurrence of embryonal rhabdomyosarcoma. This case underscores the importance of considering primary rhabdomyosarcoma as a differential diagnosis in adolescent breast lesions. Given its rare occurrence and potential imaging overlap with more common tumors like cystosarcoma phyllodes, awareness and careful evaluation are critical for accurate diagnosis and timely management. Critical imaging insights: The report provides valuable imaging characteristics that can help differentiate rhabdomyosarcoma from more common breast tumors like fibroadenoma and cystosarcoma phyllodes, resulting in more accurate and timely diagnosis.

Comparative assessment of genotyping-by-sequencing and whole-exome sequencing for estimating genetic diversity and geographic structure in small sample sizes: insights from wild jaguar populations.

Biologists currently have an assortment of high-throughput sequencing techniques allowing the study of population dynamics in increasing detail. The utility of genetic estimates depends on their ability to recover meaningful approximations while filtering out noise produced by artifacts. In this study, we empirically compared the congruence of two reduced representation approaches (genotyping-by-sequencing, GBS, and whole-exome sequencing, WES) in estimating genetic diversity and population structure using SNP markers typed in a small number of wild jaguar (Panthera onca) samples from South America. Due to its targeted nature, WES allowed for a more straightforward reconstruction of loci compared to GBS, facilitating the identification of true polymorphisms across individuals. We therefore used WES-derived metrics as a benchmark against which GBS-derived indicators were compared, adjusting parameters for locus assembly and SNP filtering in the latter. We observed significant variation in SNP call rates across samples in GBS datasets, leading to a recurrent miscalling of heterozygous sites. This issue was further amplified by small sample sizes, ultimately impacting the consistency of summary statistics between genotyping methods. Recognizing that the genetic markers obtained from GBS and WES are intrinsically different due to varying evolutionary pressures, particularly selection, we consider that our empirical comparison offers valuable insights and highlights critical considerations for estimating population genetic attributes using reduced representation datasets. Our results emphasize the critical need for careful evaluation of missing data and stringent filtering to achieve reliable estimates of genetic diversity and differentiation in elusive wildlife species.

Inbreeding and its effect on the gene fund in dog breeding

Aim. Identifying problems and approaches to dog breeding that emphasize the importance of the quality of parents and hereditary factors in determining the offspring's quality. Methods. Theoretical review of inbreeding and its impact on the gene pool in dog breeding, comparing it with outbreeding, and exploring natural selection mechanisms and their influence on animal reproduction. Results. The paper discusses the principles of selecting breeders in dog breeding and provides recommendations for avoiding mating dogs with deficiencies in a particular trait. It also highlights the study of genetic mechanisms and their impact on the inheritance of traits in dogs. Two main breeding methods are considered in animal husbandry – inbreeding and outbreeding. The study findings indicate types of inbreeding and their influence on the genetic homogeneity of the offspring. Conclusions. The breeder must clearly define the type of dog he wants to obtain, specifying desired characteristics such as appearance, health, and temperament. In the initial stages, the breeder must achieve stability in breeding offspring with desired characteristics, creating animals with a typical temperament. After achieving stability, one can begin fine-tuning specific traits by selecting for improvements in breed aspects. A dog should be viewed as a holistic system, striving for overall correctness and balance, paying attention to the interrelation between different aspects. The breeder must ensure the preservation of unique breed characteristics during selection. Effective selection involves careful planning, observation, evaluation, and collaboration with experienced veterinarians and breed specialists.

Evaluation of the efficacy of combined immune checkpoint inhibitors in advanced melanoma treatment - Long term outcomes and emerging therapeutic perspectives: a narrative review

Combination therapy with immune checkpoint inhibitors, specifically CTLA-4 and PD-1 blockade, has shown promise in treating advanced melanoma. However, this approach often results in increased toxicity, necessitating a careful evaluation of both efficacy and safety. This review explores clinical outcomes, survival rates, and adverse events associated with these therapies. A systematic review of PubMed, Scopus, and clinical trial databases was conducted for studies published from 2014 to 2024. Studies assessing the combined use of CTLA-4 and PD-1 inhibitors in melanoma patients were included, focusing on overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (AEs). The combination of CTLA-4 and PD-1 inhibitors significantly improved clinical outcomes in advanced melanoma. In trials like CheckMate 067, the five-year overall survival rate reached 52%, with a notable improvement in progression-free survival. However, these benefits came with substantial toxicity, as approximately 55% of patients experienced grade 3 or 4 treatment-related adverse events, including colitis, hepatitis, and pneumonitis. Despite these challenges, combination therapy led to durable responses in a subset of patients, underscoring its efficacy. The review emphasizes the need for balancing efficacy with toxicity management in clinical practice. While CTLA-4 and PD-1 inhibitor combinations improve survival in advanced melanoma, increased toxicity presents challenges. Further research is needed to optimize treatment strategies and enhance patient selection to balance efficacy and safety.

Perspectives on donor‐derived infections from Germany

AbstractAimOften, organ transplantation is the only option to improve the life expectancy and quality of life of patients with terminal organ failure. Despite improved donor and organ assessment, a residual risk remains for transmitting infection, tumor, or other disease from the donor to recipients. Analysis, reporting, and managing of donor‐derived diseases through a vigilance and surveillance system (V&amp;S) is mandatory in many countries. We report on suspected and proven/probable donor‐derived infections (DDI) in Germany over a period of 8 years (2016–2023).MethodsAll incoming serious‐adverse‐event and serious‐adverse‐reaction (SAE/SAR) reports from 01.01.2016 to 31.12.2023 were evaluated for suspected DDI. Analysis of imputability followed the definition of the US Disease Transmission Advisory Committee (DTAC). Only probable and proven cases according to DTAC classification were defined as DDI.ResultsDuring the study period, 9771 donors in Germany donated post‐mortem organs to 27 919 recipients. In that period 612 SAE/SAR cases were reported, 377 (62%) involved infections. 41 cases were proven/probable DDI affecting 58 recipients (seven recipients died, 12%). Suspected infections were bacterial (182/377, 48%), fungal (135/377, 36%), viral (55/377, 15%), and parasitic (5/377, 1%). In case of bacterial DDI, no recipient died, but organ loss occurred in six recipients. In case of fungal or viral DDI, 19% (3/16) and 21% (3/14) of the recipients died, respectively.ConclusionsDDI are rare in solid organ transplantation (58/27 919, 0.21%), but when they occur, they are associated with high morbidity and mortality in affected recipients. Careful and detailed donor evaluation and a reliable V&amp;S help improve recipient safety. image