Heterogeneous Group Research Articles

Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models

Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and improves cellular function in fibroblasts from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARγ) as a key nuclear receptor mediating CBD’s beneficial effects, while also providing proof of dysregulated PPARγ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.

Clinical outcome and prognostic factors for immunotherapy-based treatments in patients with platinum-refractory germ cell tumor

BackgroundGerm cell tumors (GCTs) are a heterogeneous group of cancers associated with a favorable prognosis when treated with platinum-based chemotherapy. However, patients with platinum-refractory GCTs face limited options and poorer outcomes, necessitating innovative treatment approaches. This study aims to evaluate the clinical outcomes and identify prognostic factors associated with immunotherapy-based treatments in this challenging patient population. MethodsThis retrospective analysis included individuals with platinum-refractory GCTs treated with immunotherapy between 2017 and 2023. Clinical outcomes, safety, and biomarkers were analyzed. ResultsThe study included 37 male patients with a median age of 26 years (range: 18–65). The overall response rate was 24.32 %, with a median progression-free survival (PFS) and overall survival (OS) of 4.67 months and 22.67 months, respectively. Patients with both serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) below 100 (AFP & hCG < 100) demonstrated significantly better PFS and OS. Multivariate analysis indicated that lower serum tumor marker levels (AFP & hCG < 100) and treatment initiation at earlier lines were significantly associated with improved PFS. Notably, genomic analysis revealed that one patient with an MDM4 mutation experienced hyperprogression after the initiation of immunotherapy. Immune-related adverse events occurred in two patients: one developed grade 1 hyperthyroidism, and the other experienced grade 2 immune-related pneumonitis. ConclusionsImmunotherapy offers a promising treatment option for selected patients with platinum-refractory GCTs, demonstrating moderate response rates and potential survival benefits in a real-world scenario. Identifying specific prognostic factors may help tailor treatment strategies and enhance outcomes in this challenging patient cohort.

Autoimmune Diseases Following Environmental Disasters: A Narrative Review of the Literature.

Environmental disasters are extreme environmental processes such as earthquakes, volcanic eruptions, landslides, tsunamis, floods, cyclones, storms, wildfires and droughts that are the consequences of the climate crisis due to human intervention in the environment. Their effects on human health have alarmed the global scientific community. Among them, autoimmune diseases, a heterogeneous group of disorders, have increased dramatically in many parts of the world, likely as a result of changes in our exposure to environmental factors. However, only a limited number of studies have attempted to discover and analyze the complex association between environmental disasters and autoimmune diseases. This narrative review has therefore tried to fill this gap. First of all, the activation pathways of autoimmunity after environmental disasters have been analyzed. It has also been shown that wildfires, earthquakes, desert dust storms and volcanic eruptions may damage human health and induce autoimmune responses to inhaled PM2.5, mainly through oxidative stress pathways, increased pro-inflammatory cytokines and epithelial barrier damage. In addition, it has been shown that heat stress, in addition to increasing pro-inflammatory cytokines, may also disrupt the intestinal barrier, thereby increasing its permeability to toxins and pathogens or inducing epigenetic changes. In addition, toxic volcanic elements may accelerate the progressive destruction of myelin, which may potentially trigger multiple sclerosis. The complex and diverse mechanisms by which vector-borne, water-, food-, and rodent-borne diseases that often follow environmental diseases may also trigger autoimmune responses have also been described. In addition, the association between post-disaster stress and the onset or worsening of autoimmune disease has been demonstrated. Given all of the above, the rapid restoration of post-disaster health services to mitigate the flare-up of autoimmune conditions is critical.

Building effective student project teams: what has problem-solving styles got to do with it?

PurposeThe purpose of this study was to examine if team composition based on adaption-innovation (A-I) problem-solving styles is related to the teamwork quality and team effectiveness (TE) of student project teams participating in a [state-gifted program (SGP)].Design/methodology/approachA correlational design was conducted with a sample of 72 (SGP) participants, consisting of 15 project teams (n = 15), which formed three groups: (1) the homogeneous adaptive group, which consists of five homogeneous adaptive teams (n = 5); (2) the homogeneous innovative group, which consists of five homogeneous innovative teams (n = 5), and (3) the heterogeneous group (i.e. a mix of innovative and adaptive individuals), which consists of five heterogeneous teams (n = 5).FindingsA one-way ANOVA and post-hoc test revealed that team composition based on problem-solving styles is related to teamwork quality and TE. Regarding TE, both homogeneous groups (i.e. all adaptive or all innovative individuals) were more effective than the heterogeneous group. However, regarding teamwork quality, only the adaptive group had significantly higher teamwork quality than the heterogeneous group.Practical implicationsWe recommend that leadership educators utilize Kirton’s adaption-innovation inventory (KAI) as a tool for building effective student project teams. KAI can be used by leadership educators in two major ways: to assign students to groups (as done in the current study) or for team building, where team members share their KAI scores to better understand their problem-solving preferences.Originality/valueThe findings add to the literature by specifying the type of homogeneous groups (i.e. homogeneous adaptive), which may offer an advantage over heterogeneous groups regarding teamwork quality.

Plasma N-terminal pro-brain natriuretic peptide concentrations may help to identify patients with very low-risk acute pulmonary embolism: A preliminary study.

Patients with an acute pulmonary embolism (APE) are a heterogeneous group, and some of them may benefit from early discharge and an ambulatory care referral. We aimed to evaluate the use of N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma level assessment in patients with low-risk APE based on clinical findings (0 points on the simplified Pulmonary Embolism Severity Index (sPESI)). Preliminary analysis of an ongoing prospective study including 1,151 normotensive patients with at least a segmental APE. In the final analysis, 348 patients with a 0-point sPESI were included. Blood samples were collected within the first 24 h of admission. The clinical endpoint (CE) included APE-related mortality and/or rescue thrombolysis in patients with clinical deterioration. Clinical endpoints occurred in 3 patients who had higher plasma NT-proBNP levels than study participants with a favorable clinical course (164 [64-650] pg/mL compared to 2,930 [2,285.5-13,965] pg/mL; p = 0.01). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) for NT-proBNP for the prediction of the CEs was 0.918 (95% confidence interval [95% CI]: 0.831-1.00; p = 0.013). We defined the cutoff value of NT-proBNP at ≥1,641 pg/mL. Among subjects with 0 points on the sPESI, those with concentrations of NT-proBNP exceeding 1,641 pg/mL might require closer attention; remaining patients could be considered candidates for outpatient treatment. However, these findings warrant further investigation in a large, prospective group of patients.

Attitudes Towards Dementia Among a Diverse Group of Refugees Resettled in the United States.

Forced migration results in exposure to trauma, interrupted access to healthcare, and loss of social support and may increase dementia risk. Literature on refugees' knowledge of dementia and its risk factors is scant. This study investigates refugee perspectives on dementia and their access to cognitive healthcare in the United States (US). We conducted 6 focus groups and 30 individual in-depth interviews (total of 69 participants) with Arab, African, and Afghan refugees resettled in San Diego, California. Data was coded using inductive thematic analysis. Organized by the socioecological model of health, the following themes emerged: (1) mental trauma due to migration was linked to dementia (individual); (2) fear of dementia and burdening caregivers due to limited support systems (interpersonal); (3) reliance on virtual communities for dementia information and the stress of local community loss increasing dementia risk (community); (4) healthcare providers, both in the US and in refugee camps, didn't address cognitive health concerns (institutions); and (5) discriminatory immigration and healthcare policies as barriers to healthy aging (policy). Despite being a heterogeneous group, refugees share specific experiences, knowledge gaps, and barriers to healthy aging. Tailored interventions and policies are needed to address this population's cognitive health needs. This includes addressing their mental health and social support concerns as well as training clinicians to screen for/discuss dementia with aging refugee patients.

Urban Flood Resilience Evaluation Based on Heterogeneous Data and Group Decision-Making.

In recent years, urban floods have occurred frequently in China. Therefore, there is an urgent need to strengthen urban flood resilience. This paper proposed a hybrid multi-criteria group decision-making method to assess urban flood resilience based on heterogeneous data, group decision-making methodologies, the pressure-state-response model, and social-economic-natural complex ecosystem theory (PSR-SENCE model). A qualitative and quantitative indicator system is formulated using the PSR-SENCE model. Additionally, a new weighting method for indicators, called the synthesis weighting-group analytic hierarchy process (SW-GAHP), is proposed by considering both intrapersonal consistency and interpersonal consistency of decision-makers. Furthermore, an extensional group decision-making technology (EGDMT) based on heterogeneous data is proposed to evaluate qualitative indicators. The flexible parameterized mapping function (FPMF) is introduced for the evaluation of quantitative indicators. The normal cloud model is employed to handle various uncertainties associated with heterogeneous data. The evaluations for Beijing from 2017 to 2021 reveal a consistent annual improvement in urban flood resilience, with a 14.1% increase. Subsequently, optimization recommendations are presented not only for favorable indicators such as regional economic status, drainability, and public transportation service capacity but also for unfavorable indicators like flood risk and population density. This provides a theoretical foundation and a guide for making decisions about the improvement of urban flood resilience. Finally, our proposed method shows superiority and robustness through comparative and sensitivity analyses.

A skeletal dysplasia leading to a perinatal death in 17th–19th century Lisbon, Portugal

AbstractCongenital skeletal disorders are a heterogeneous group of anomalies that become evident during gestation. They are expressed in the shape and growth of the bones during development because of a defective genetic background. With the follow‐up of pregnant women and the advances in prenatal ultrasonographic examination and molecular genetic tests, nowadays, congenital skeletal disorders are identified at an early gestational age. If they are considered lethal, the termination of pregnancy is advised. This work unveils an exceptional instance of a rare pathological condition identified in a perinate (birth ± 2 weeks) from the 17th to 19th centuries, recovered during an excavation at the cloister of the São Domingos Convent in Lisbon, Portugal. The skeleton presents with exuberant modifications that include, among others, severe shortening (micromelia) and bowing of the long bones of the upper and lower limbs. The main skeletal findings indicated a presumptive general diagnosis of skeletal dysplasia, while the differential diagnosis includes hypophosphatasia, campomelic dysplasia, achondrogenesis, thanatophoric dysplasia, and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) as the most plausible causes for the observed skeletal changes. Even though an exact diagnosis is unattainable based only on the macroscopic analysis of the bones, the phenotypic features observed in this perinate are more consistent with thanatophoric dysplasia type 1.

Clinical and Morphological Aspects of Aggressive Salivary Gland Mixed Tumors: A Narrative Review.

Salivary gland tumors are a rare and heterogeneous group of neoplasms of the head and neck region. The mixed category of these tumors include the following entities: pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CEPA), salivary carcinosarcoma (CS), and metastasizing PA (MPA). The most common benign tumor of the salivary glands is PA. Metastasis and malignant degeneration have been reported in cases of PA of a salivary gland origin. Judging by their behavior, MPA, CEPA, and CS can be considered aggressive tumors. Invasive CEPA has been identified in the parotid gland more frequently. MPA and CS cases reported in the current literature are rare. In this paper, we present, narratively, the clinico-morphological features of this group of mixed tumors.

Congenital Diarrhoeas and Enteropathies.

Congenital diarrhoeas and enteropathies (CODE) are a heterogeneous group of disorders. Many affected infants present with catastrophic dehydration in the first few days of life, although the clinical phenotype is variable. Advances in the understanding of underlying pathomechanisms and genetic testing, as well as improved management, in particular intravenous nutrition support, have allowed affected patients to survive well beyond childhood. Awareness and understanding of these rare diseases are hence needed, both amongst paediatricians and adult physicians. In this review, we discuss the different groups of disorders based on a review of the current literature and provide a diagnostic and therapeutic approach. Many of the subtypes of CODE result in the need for prolonged or indefinite parenteral nutrition. Further research is needed to identify new CODE to improve the recognition and management of these children, which can assist in developing new targeted therapies and potentially a long-term cure.

Immuno-related cardio-vascular adverse events associated with immuno-oncological treatments: an under-estimated threat for cancer patients.

Immunotherapy represents an emergent and heterogeneous group of anticancer treatments harnessing the human immune-surveillance system, including immune-checkpoint inhibitor monoclonal antibodies (mAbs), Chimeric Antigen Receptor T Cells (CAR-T) therapy, cancer vaccines and lymphocyte activation gene-3 (LAG-3) therapy. While remarkably effective against several malignancies, these therapies, often in combination with other cancer treatments, have showed unforeseen toxicity, including cardiovascular complications. The occurrence of immuno-mediated adverse (irAEs) events has been progressively reported in the last 10years. These irAEs present an extended range of severity, from self-limiting to life-threatening conditions. Although recent guidelines in CardioOncology have provided important evidence in managing cancer treatments, they often encompass general approaches. However, a specific focus is required due to the particular etiology, unique risk factors, and associated side effects of immunotherapy. This review aims to deepen the understanding of the prevalence and nature of cardiovascular issues in patients undergoing immunotherapy, offering insights into strategies for risk stratification and management.

Charcot-Marie-Tooth type 2CC misdiagnosed as Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Charcot-Marie-Tooth (CMT) is a heterogeneous group of genetic neuropathies and is typically characterized by distal muscle weakness, sensory loss, pes cavus and areflexia. Herein we describe a case of CMT2CC presenting with proximal muscle weakness and equivocal electrophysiological features, that was misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). A 30-year-old woman complained of proximal muscle weakness with difficulty climbing stairs. Neurological examination showed weakness in lower limb (LL) muscles, that was marked proximally and mild distally, and absence of deep tendon reflexes in the ankles. Nerve conduction studies (NCS) showed sensory-motor neuropathy with non-uniform NC velocity and a partial conduction block (CBs) in peroneal nerve and tibial nerves. Thus, a diagnosis of CIDP was entertained and the patient underwent ineffective treatment with intravenous immunoglobulins. At electrophysiological revaluation CB in peroneal nerve was undetectable as also distal CMAP had decreased whereas the CBs persisted in tibial nerves. Hypothesizing a hereditary neuropathy, we examined the proband's son, who presented mild weakness of distal and proximal muscles at lower limbs. Neurophysiological investigation showed findings consistent with an intermediate-axonal electrophysiological pattern. A targeted-NGS including 136 CMT genes showed the heterozygous frameshift mutation (c.3057dupG; p.K1020fs*43) in the NEFH gene, coding for the neurofilament heavy chain and causing CMT2CC. Diagnosis of a genetic neuropathy may be challenging when clinical features are atypical and/or electrophysiological features are misleading. The most common misdiagnosis is CIDP. Our report suggests that also CMT2CC patients with proximal muscle weakness and equivocal electrophysiological features might be misdiagnosed as CIDP.

Use of Ketamine in Patients with Multifactorial Neuropathic Pain: A Systematic Review and Meta-Analysis.

Neuropathic pain (NP) is a heterogeneous group of conditions characterized by the experience of a number of sensory disturbances including pain, burning sensations, paroxysms of stabbing pain, dysesthesias, allodynia, and hyperalgesia. The above-mentioned sensations may occur in a specific dermatome area or other delimited region of the body. The objective of this review was to analyze the evidence for ketamine in multifactorial neuropathic pain. The research group systematically searched the databases MEDLINE (via PubMed), EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature (Cinahl), and the Web of Science. The findings of this review show that different forms of low doses of ketamine (LDK) do not present statistically significant changes for any of the scales included. In this study, the total symptom score [standardized mean difference (SMD) = -3.59, confidence interval (CI) = -4.16 to -3.02, and p < 0.00001], neuropathy impairment score (SMD = -1.42, CI = -3.68 to 0.84, and p = 0.22), and neuropathy symptom checklist (SMD = -0.09, CI = -0.15 to -0.02, and p = 0.01) were taken into account. For finality compared to the use of a placebo, the findings suggest that LDK does not exhibit significant differences in terms of pain reduction and functionality. Moreover, no specific dosages are identified to support the use of LDK in the reduction in NP.

"Misdiagnosis of diffuse large B-cell lymphoma in the maxillary sinus as a dental abscess"

Introduction: Diffuse large B-cell Lymphoma (DLBCL) is a heterogeneous group of malignant tumors with diverse prognoses, histological appearances, and clinical symptoms. While it commonly affects lymphoid tissues, its occurrence in the nasal cavity and paranasal sinuses is rare and poses significant diagnostic challenges. Case presentation: We present a case of a 53-year-old man with a history of testicular non-Hodgkin lymphoma treated five months prior. He presented with symptoms initially misdiagnosed as a dental abscess, which was later identified as DLBCL in the maxillary sinus. Discussion: The etiology of primary lymphoma in the oral region remains unclear. Due to its rarity, specific prognostic factors and optimal treatment strategies are not well-established. This case highlights the diagnostic challenges and underscores the importance of considering lymphoma in the differential diagnosis of non-responsive dental abscesses. Conclusion: This case underscores the importance of thorough investigation in patients with non-responsive dental abscesses. Early identification and appropriate management of DLBCL in uncommon sites require heightened clinical awareness and interdisciplinary collaboration. The optimal treatment approach remains debated and warrants further research.

Idiopathic Inflammatory Myopathies-associated Interstitial Lung Disease in Adults.

Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases characterized by muscle involvement and various extramuscular manifestations. Interstitial lung disease (ILD) is one of the most common extramuscular manifestations of IIM and is associated with significant mortality and morbidity. The clinical phenotypes, treatment responses, and prognosis of IIM-ILD are significantly related to myositis-specific antibody (MSA) profiles, with some racial differences. The features associated with MSA in IIM-ILD could also be relevant to cases of ILD where MSA is present but does not meet the criteria for IIM. The anti-melanoma differentiation-associated gene 5 antibody is highly associated with rapidly progressive ILD (RP-ILD), especially in Asian populations, and with characteristic cutaneous manifestations, such as skin ulcers. Radiologically, ground-glass opacities, consolidations, and nonsegmental linear opacities were more predominant than reticular opacities and honeycombing. While the mortality rate is still around 30%, the prognosis can be improved with early intensive therapy with corticosteroids and multiple immunosuppressants. In contrast, anti-aminoacyl-tRNA synthetase (ARS) antibodies are associated with chronic ILD, although RP-ILD is also common. Patients with anti-ARS antibodies often show lung-predominant presentations, with subtle muscle and skin involvement. Radiologically, reticular opacities, with or without consolidation, are predominant and may progress to honeycombing over time. Combination therapy with corticosteroids and a single immunosuppressant is recommended to prevent relapses, which often lead to a decline in lung function and fatal long-term outcomes. Significant advances in immunology and genetics holds promise for fostering more personalized approaches to managing IIM-ILD.

The Complex and Changing Genus Bacillus: A Diverse Bacterial Powerhouse for Many Applications

For years, the Bacillus genus has encompassed a heterogeneous group of individuals whose main common trait was their ability to sporulate in the presence of oxygen. This criterion has been revised, resulting in the reclassification of several species into new genera and to a redefinition of the characteristics of the members of this taxon. Currently, the species of the genus are grouped into the Subtilis clade and the Cereus clade. The former, called Bacillus sensu stricto, initially composed of B. subtilis, B. licheniformis, B. pumilus, and B. amyloliquefaciens, has subsequently incorporated new species related to these. The Cereus clade, Bacillus cereus sensu lato, consists of pathogenic species (B. anthracis, B. cereus, and B. thuringiensis) as well as others of significance in agriculture and industry. Furthermore, identifying these individuals remains complex, requiring alternatives to 16S rRNA sequencing. The ability to form spores resistant to stressful conditions provides a significant advantage over other genera, with observable differences in sporulation rates and spore structure among different species. Additionally, Bacillus spp. are known for their capacity to produce antimicrobial substances, lytic enzymes, and volatile organic compounds, each with diverse applications. Some species are even used as probiotics. This review delves into aspects related to the taxonomy and identification of microorganisms belonging to the genus Bacillus, which often present challenges. The aim is to provide a comprehensive overview of the topic. In addition, it highlights the characteristics and applications of the genus, emphasizing its importance in biotechnology and microbiology.

Septal Perforation Quality of Life questionnaire (SEPEQOL): validation of a new instrument to assess patients undergoing endoscopic repair of a nasal septal perforation

PurposeNasoseptal perforations (NSP) are a clinically heterogeneous group of disorders with a wide range of available treatments. Patient-reported outcome measures (PROMs) can provide valuable insights for assessing clinical and surgical outcomes. This study aims to develop and validate a novel-specific questionnaire for patients with NSP.MethodsA multi-centre prospective observational study was conducted at two tertiary referral hospitals. “Septal Perforation Quality of Life” (SEPEQOL) was developed by a committee of experts. The psychometric properties, including reproducibility, reliability, validity, and responsiveness, were assessed.ResultsThe study included 96 symptomatic NSP patients and 30 healthy controls. SEPEQOL internal consistency was satisfactory [Cronbach´s α = 0.7843; 95% confidence interval (CI), 0.702–0.856]. Test-retest reliability was excellent, demonstrated by the absolute intraclass correlation (ICC = 0.974; 95% CI, 0.935–0.989, P-value < 0.001) and Bland-Altman plot (line bias = 1.6 ± 4.57; 95% CI -0.54–3.74, P-value < 0.001). The mean total SEPEQOL score was higher before surgery (25.16 ± 1.65) compared to 6-months after the procedure (13.72 ± 11.39), with a mean difference of 12.19 [standard deviation (SD) 10.76], P-value < 0.001.ConclusionsSEPEQOL is reliable, consistent, valid, and sensitive to change over time. SEPEQOL assesses the impact of health-related quality of life on NSP and its management in clinical practice. Moreover, it is easy to apply in clinical settings with minimal burden.

Health of single mothers and fathers in Germany. Results of the GEDA studies 2019 - 2023.

The living situation of single parents is often characterised by sole responsibility for family and household, problems in reconciling work and family life, and a high risk of poverty. In a comparative perspective with parents in partner households, the health of single mothers and fathers was analysed, considering differences in their social status. The analyses are based on data from the GEDA studies 2019 - 2023 (7,999 women, 6,402 men). Prevalences for single mothers and fathers and mothers and fathers living in partner households were calculated for self-rated health, chronic diseases, depressive symptoms, smoking and utilisation of professional help for mental health problems. In multivariate models, adjustments were made for income, education, employment status and social support, and interactions with family type were included. Single mothers and fathers show higher prevalences for all health indicators in comparison to parents living in partner households. Also after adjustment, the differences between family types remain significant. The health of single mothers also varies partially with income, employment status and social support. Health promotion measures have to consider that single parents are a heterogeneous group. In addition to strengthening personal skills, policy and setting-based interventions aim to reduce health inequalities.

‘Lady Guardians’ of the Royal Society of Horticulture of Portugal, 1898–1906

In the second half of the nineteenth century gardening flourished in Portugal’s public sphere, having considerably expanded beyond the private realms of palaces and villas. Envisioned as a sophisticated branch of knowledge, horticulture became a hub for citizen science, commercial activities, public education, and civic events. This was a context that fostered and advanced women’s involvement and status as gardeners, horticulturists, and educators, a development influenced by popular Portuguese perceptions of women as protectors. The Royal Society of Horticulture of Portugal (founded in Lisbon as “National” in 1898, decreed “Royal” in 1900), instantiated this enmeshment of perception with status by designating women members as ‘Lady Guardians’ while promoting their participation, especially as competitors and jurists in the society’s flower exhibitions. The women of the society offer a window into the more general identities and professional statuses of women horticulturalists as ‘guardians’ in a generalized sense: they included landowners, writers, gardeners, and family business owners, with many assuming greater responsibility in widowhood. At a time when women’s participation in science was highly constricted, horticulture as a field, and the Royal Society of Horticulture as its premier institution, constituted a remarkable opportunity for women to be publicly engaged and recognized for their expertise as amateur botanists alongside their male counterparts. This article’s analysis demonstrates that women horticulturalists in Portugal were a quite heterogenous group, consisting of women from the highest ranks of the nobility, participating alongside women from further social ranks, inclusive of the aristocracy, bourgeoisie, and urban middle classes. Their participation in the society not only afforded them opportunities locally and civically, but also internationally, as will be illustrated by a few careers that reflect how education, travels, and professional engagement demonstrated the broad reach of Portuguese women’s horticultural activities.

Intravenous Lidocaine for Refractory Pain in Patients With Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Multicenter Prospective Nonrandomized Pilot Study.

Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively. Multicenter prospective nonrandomized pilot study included patients with moderate or severe pain (Numeric Rating Scale ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5 mg/kg was followed by continuous infusion at 1.5 mg/kg/hr. The dose was raised every 15 minutes until treatment response (up to a maximum 2 mg/kg/hr) and consecutively administered for 2 hours. Primary outcome was the mean difference in pain severity, preinfusion, and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥1.3 points was considered clinically relevant. Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day 1 was 1.1 (SD ± 1.3) points for patients with PDAC and 0.5 (SD ± 1.7) for patients with CP. A clinically relevant decrease in BPI on day 1 was reported in 9 of 29 patients (31%), and this response lasted up to 1 month. No serious complications were reported, and only 3 minor complications (vertigo, nausea, and tingling of mouth). Treatment with lidocaine did not impact quality of life. Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group.