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Abstract Objective Osteoarthritis (OA) causes significant musculoskeletal pain. This study assessed the efficacy and safety of fasinumab, an investigational nerve growth factor inhibitor, in patients with moderate-to-severe OA pain of the knee/hip. Methods In this Phase 3, randomized, double-blind, placebo- and non-steroidal anti-inflammatory drug (NSAID)-controlled study, patients with OA (Kellgren-Lawrence grade ≥ 2; Western Ontario and McMaster Universities Arthritis Index [WOMAC] pain score ≥ 4) received (2:1:1:1) fasinumab 1 mg every 4 weeks, diclofenac 75 mg twice daily, celecoxib 200 mg daily, or placebo for 24 weeks. Co‑primary endpoints were change in WOMAC pain and physical function scores to Week 24 versus placebo. For safety, joints were imaged in all patients at pre‑specified times, regardless of symptoms. Results Of 4531 patients screened, 1650 were randomized. At Week 24, greater improvements were observed for fasinumab versus placebo; least-squares mean difference: –0.63 (p = 0.0003) for WOMAC pain and –0.64 (p = 0.0003) for physical function. Improvements were numerically greater for fasinumab versus NSAIDs for physical function (–0.64 versus –0.31; nominal p

Background: Pain associated with osteoarthritis (OA) is frequently disabling; treatments are often ineffective or intolerable. Fasinumab selectively inhibits nerve-growth factor and has shown efficacy for the management of OA pain. Methods: In this randomized, double-blind, phase III safety study, patients with moderate-to-severe OA pain and history of inadequate pain relief received placebo or fasinumab (at 1, 3, 6, and 9 ​mg every 4 weeks [Q4W] and 1 and 6 ​mg every 8 weeks [Q8W] for 52 weeks). Primary safety endpoints included adverse events, adjudicated arthropathies (AAs), and joint replacements (JRs). Co-primary endpoints of an efficacy sub-study were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores. During the study, higher fasinumab doses were discontinued for safety; 1 ​mg doses continued. Results: Of 13,945 patients screened, 5331 were randomized; 1074 were included in the efficacy sub-study. AAs and JRs occurred in all groups. Increased severity of disease at baseline was associated with higher rates of AAs and JRs. A dose-dependent risk of AA or JR was observed for fasinumab; in the 1 ​mg groups, only a small percentage of patients with JR had prior AA. Fasinumab significantly improved WOMAC pain and physical function scores compared with placebo; least squares mean differences versus placebo were −1.22 and ​−1.20 for 1 ​mg Q4W and −0.73 and ​−0.74 for 1 ​mg Q8W, respectively (P

Abstract Background Carpal tunnel syndrome (CTS), an entrapment neuropathy caused by pressure of the median nerve, is a progressive condition that can lead to a decreased quality of life. Studies suggest an association between CTS and arthritis; however, previous studies examining osteoarthritis (OA) and CTS are limited in number, scope and study design. This study estimated the incidence and risk of CTS among patients with OA, both overall and by specific joints, in a large population-based cohort in the United States. Methods Patients from the Optum claims database aged ≥ 45 years and diagnosed with OA between January 1, 2018, and December 31, 2022, were eligible for the OA cohort. The non-OA cohort included those without a diagnosis of OA at the index date and no history of OA for 12 months pre-index. Baseline characteristics were balanced using propensity score matching. The risk of CTS in the OA and non-OA cohort were evaluated using incidence rates and adjusted hazard ratios that were estimated using Cox regression. Results After applying the inclusion/exclusion criteria, 3,610,240 of the 6,023,384 adults with a diagnosis of OA remained in the OA cohort. After propensity-score matching, each cohort included 1,033,439 individuals. The incidence rates for CTS per 1000 person-years were 7.35 (95% confidence interval [CI] 7.21–7.49) in the OA cohort and 1.44 (95% CI 1.38–1.50) in the non-OA cohort. The risk of developing CTS in patients with OA was ~ 4 times that of patients without (hazard ratio = 3.80; 95% CI 3.54–4.07). This increased risk was found across all OA joint types, with OA of the hand/wrist having the highest risk for CTS. Additionally, multiple OA joints presented a higher risk compared with a single affected joint. Conclusions OA increases the risk of CTS, but this is not limited to patients with hand/wrist OA, suggesting a systemic impact of OA on CTS. While the risk appears highest for patients with hand/wrist OA, patients with more distant affected joints like knee or hip also have an increased risk of CTS.

Clear and accessible lay summaries are essential for enhancing the public understanding of scientific knowledge. This study aimed to evaluate whether ChatGPT-4 can generate high-quality lay summaries that are both accurate and comprehensible for prostate cancer research in Current Oncology. To achieve this, it systematically assessed ChatGPT-4’s ability to summarize 80 prostate cancer articles published in the journal between July 2022 and June 2024 using two distinct prompt designs: a basic “simple” prompt and an enhanced “extended” prompt. Readability was assessed using established metrics, including the Flesch–Kincaid Reading Ease (FKRE), while content quality was evaluated with a 5-point Likert scale for alignment with source material. The extended prompt demonstrated significantly higher readability (median FKRE: 40.9 vs. 29.1, p < 0.001), better alignment with quality thresholds (86.2% vs. 47.5%, p < 0.001), and reduced the required reading level, making content more accessible. Both prompt designs produced content with high comprehensiveness (median Likert score: 5). This study highlights the critical role of tailored prompt engineering in optimizing large language models (LLMs) for medical communication. Limitations include the exclusive focus on prostate cancer, the use of predefined prompts without iterative refinement, and the absence of a direct comparison with human-crafted summaries. These findings underscore the transformative potential of LLMs like ChatGPT-4 to streamline the creation of lay summaries, reduce researchers’ workload, and enhance public engagement. Future research should explore prompt variability, incorporate patient feedback, and extend applications across broader medical domains.

Autoimmune blistering diseases (AIBDs) involve autoantibodies targeting proteins in the epidermal/epithelial desmosome (pemphigus) or basement membrane zone (pemphigoid). Despite widespread antigen distribution, lesions exhibit a scattered involvement pattern. This study maps the frequency/severity of AIBD lesions on various body parts and investigates whether differential antigen expression contributes to specific predilection sites. We analyzed affected sites presenting blisters/erosions, erythematous/urticarial lesions, and mucosal lesions in bullous pemphigoid (BP-cohort 1, n = 65; BP-cohort 2, n = 119), pemphigus vulgaris (PV, n = 67), and pemphigus foliaceus (PF, n = 20) patients. To assess antigen expression, we conducted indirect immunofluorescence (IF) staining of 11 AIBD antigens from 13 anatomical sites of 10 body donors without AIBD. In BP, blisters/erosions and erythematous/urticarial lesions predominantly affected arms and legs, while PV/PF patients exhibited frequent involvement of buccal mucosa and back, respectively. IF staining identified significant regional differences in BP180, BP230, and integrin β4 expression, although these variations did not correlate with a higher lesion frequency/severity. Other antigens showed consistent expression across all regions. Our findings suggest that predilection sites for BP and PV/PF are largely unaffected by regional variations in antigen expression but may be influenced by factors like microbiota, mechanical stress, sunlight exposure, local immunity, or genetics.

Physical activity guidelines are recognized as an important element of a national approach to promote physical activity. This publication summarizes the approach and process taken to update the Swiss Guidelines, presents a summary of the updated guidelines and discusses experiences and identifies challenges. The multistage project involved: 1) to summarize the scientific evidence underpinning the 2020-edition of the WHO guidelines; 2) to systematically analyze the existing Swiss guidelines for different target groups and to develop proposals for updates 3) a participatory process to gain consensus with the main interested groups 4) to finalize the guidelines. Updated guidelines were adopted for infants, pre-school children, children and young people, adults, older adults and pregnant and postpartum women, in most cases following the WHO guidelines. Children, young people and adults living with disability and adults and older adults with chronic conditions are specifically addressed in each of the general guidelines for healthy populations, rather than developing separate guidelines for each of these groups as done by the WHO. The systematic approach in identifying aspects to update, the participatory approach and a scientific consortium and project coordination group with different thematic backgrounds were key strengths in the process. Challenges included the large amount of feedback and finding scientifically sound compromises. The updated versions of the Swiss national guidelines provide an excellent basis to further promote physical activity in Switzerland. A remaining key task is to develop a range of communication tools and materials for different target groups beyond the circle of experts and interested groups, considering available evidence on optimal messaging and best outlet tools and channels. To track population prevalence, inform policy and evaluate physical activity promotion at national and sub-national level in a timely fashion, strengthening existing physical activity monitoring will be important.

Abstract Objective To estimate risks for all‐cause mortality and for severe COVID‐19 in multiple sclerosis patients and across relapsing–remitting multiple sclerosis patients exposed to disease‐modifying therapies. Methods We conducted a Swedish nationwide population‐based multi‐register linkage cohort study and followed all multiple sclerosis patients (n = 17,692 in March 2020), individually age‐, sex‐, and region‐matched to five population‐based controls (n = 86,176 in March 2020) during March 2020–June 2021. We compared annual all‐cause mortality within and across cohorts, and assessed incidence rates and relative risks for hospitalization, intensive care admission, and death due to COVID‐19 in relation to disease‐modifying therapy use, using Cox regression. Results Absolute all‐cause mortality among multiple sclerosis patients was higher from March to December 2020 than in previous years, but relative risks versus the population‐based controls were similar to preceding years. Incidence rates of hospitalization, intensive care admission, and death due to COVID‐19 remained in line with those for all‐cause hospitalization, intensive care admission, and mortality. Among relapsing–remitting patients on rituximab, trends for differences in risk of hospitalization due to COVID‐19 remained in the demographics‐, socioeconomic status‐, comorbidity‐, and multiple sclerosis severity‐adjusted model. Interpretation Risks of severe COVID‐19‐related outcomes were increased among multiple sclerosis patients as a whole compared to population controls, but risk increases were also seen for non‐COVID‐19 hospitalization, intensive care admission, and mortality, and did not significantly differ during the pandemic compared to pre‐pandemic years. The risk conveyed by disease‐modifying therapies was smaller than previously assumed, likely as a consequence of the possibility to better control for confounders.

T cells communicate with antigen-presenting cells (APC) via the signaling crosstalk at the immunological synapse (IS). Here the authors use bead-supported lipid bilayers as synthetic APCs to find that trans-synaptic vesicles produced by T cells in the IS carry specialized cargos distinct from constitutive extracellular vesicles to serve as intercellular messengers.

Hippocampal mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) mediate glucocorticoid hormone (GC) action in the hippocampus. These receptors bind to glucocorticoid responsive elements (GREs) within target genes, eliciting transcriptional effects in response to stress and circadian variation. Until recently, little was known about the genome-wide targets of hippocampal MRs and GRs under physiological conditions. Following on from our genome-wide MR and GR ChIP-seq and Ribo-Zero RNA-seq studies on rat hippocampus, we investigated the Krüppel-like factors (KLFs) as targets of MRs and GRs throughout the brain under circadian variation and after acute stress. In particular, Klf2, Klf9 and Klf15 are known to be stress and/or GC responsive and play a role in neurobiological processes including synaptic plasticity and neuronal differentiation. We found increased binding of MR and GR to GREs within Klf2, Klf9 and Klf15 in the hippocampus, amygdala, prefrontal cortex, and neocortex after acute stress and resulting from circadian variation, which was accompanied by upregulation of corresponding hnRNA and mRNA levels. Adrenalectomy abolished transcriptional upregulation of specific Klf genes. These results show that MRs and GRs regulate Klf gene expression throughout the brain following exposure to acute stress or in response to circadian variation, likely alongside other transcription factors.

Purpose Accelometry is a very important tool to measure physical activity (PA) in preschoolers, as it can measure 24-hour PA and detect activity which cannot be captured by other methods. However, accelerometer validation for preschoolers is lacking (Altenburg et al. 2022). Specifically, for the ActiGraph wGT3X-BT and Move 4 (ActiGraph LLC; Move4 activity sensor, movisens GmbH) only a few, respectively no preschooler validation studies, were found. Thus, the purpose was to validate these two accelerometers in Swiss preschoolers with the System for Observing Children’s Activity and Relationships during Play (SOCARP; Ridgers et al., 2010). Methods and Design Preschoolers (2-5 years old) from two Swiss Sunday activity programs (MiniMove & Ä Halle wo’s fägt) were randomly selected as part of a larger program evaluation. PA was assessed SOCARP for a duration of 12 minutes per child. During the observation, the children wore both an ActiGraph and a Move4 device taped to their right hip to record steps. Step-counts from the ActiGraph and Move4 were correlated with each other and with moderate-to-vigorous (MV)PA from SOCARP (as SOCARP does not count steps). Results Valid PA data was available for 45/58 (77.6%) children (49% girls) for SOCARP and for 47/58 (81%) children (51% girls) for accelometry. Step count correlations between the accelerometers (Actigraph and Move4) and %MVPA (SOCARP) was medium and positive (r(43) = .34, p = .03 and r(43) = .37, p = .02; respectively). There was a strong step count correlation between the two devices (r(45) = .90, p < .001), although ActiGraph measured significantly more steps than Move4 (m = 557.74, SD = 255.77 versus m = 397.81, SD = 164.10); t(46)=8.47, p < .001). Discussion PA measurement in preschool children can be challenging. However, the correlation between step counts and observed %MVPA indicates criterion validity for both devices. The step-counts of Actigraph and Move4 validate each other, but there is a difference in the absolute number of measured steps. Due to different outcome parameters, calculation algorithms, and inaccessibility to raw acceleration the comparison of the two devices on movement intensity was not possible. Although promising preliminary indications of validity of device-based measurement of PA in Swiss preschool children, further investigations into the methodological approaches of comparing measurements of movement intensity are warranted. References Altenburg, T. M., de Vries, L., op den Buijsch, R., Eyre, E., Dobell, A., Duncan, M., & Chinapaw, M. J. M. (2022). Cross-validation of cut-points in preschool children using different accelerometer placements and data axes. Journal of Sports Sciences, 40(4), 379-385. https://doi.org/10.1080/02640414.2021.1994726 Ridgers, N. D., Stratton, G., & McKenzie, T. L. (2010). Reliability and validity of the system for observing children’s activity and relationships during play (SOCARP). Journal of Physical Activity and Health, 7(1), 17–25. https://doi.org/10.1123/jpah.7.1.17

Background Eighty-eight thousand fall accidents occur each year in Switzerland among people aged 65 and over, which cause a lot of personal suffering and economic costs Beratungsstelle für Unfallverhütung BFU, 2019). The exercise at home program “DomiGym - Bewegungsangebot zu Hause” (in short: DomiGym) of Pro Senectute Switzerland aims to maintain mobility, counteract the risk of falls and promote social contacts as well as social participation and psychosocial health. Vulnerable, elderly people enjoy with DomiGym an adapted, regular training program focused on strength and balance, in their own homes or in their neighborhoods. Methodology The implementation and effects of the DomiGym offers in the cantons of Zug and Zurich were evaluated using various methodological approaches: tests of strength (Chair-Stand-Test; Mehmet et al., 2019), of balance (Modified Romberg; Agrawa et al., 2011) and of functional mobility (Timed-Up-and-Go-Test; Marks, 2016) as well as written surveys of participants (based on standardized scales used in the Swiss Health Survey). Results On average participants reduced fall risk and improved functional mobility and leg strength (p < 0.05). In a subsample of the canton of Zug, the Timed-Up-and-Go-Test (functional mobility and fall risk) improved by an average of 2.3 seconds (p < 0.005) and the balance test (Romberg) improved by 1.8 seconds (p = 0.005). Over the course of a training series the reduction in fall risk proved clinically relevant in both cantons. Scores on the Timed-Up-and-Go-Test fell on average below the threshold of 13.5 seconds discriminating between fallers and non-fallers. Chair-stand test: Participants improved on average from an initial very high fall risk to an increased fall risk (below 15 seconds). In fact the subsample of canton Zug improved by an average of 3.96 seconds (clinically relevant with regard to the reduction of falls) and the subsample of canton Zurich improved by an average of 2.17 seconds (approximately clinically relevant; threshold value 2.3 seconds; Meretta et al., 2006). DomiGym improved the general health (67%) of most participants and either maintained the original walking level (80%) or even improved it (15%). The majority of DomiGym participants do gymnastic exercises at least weekly outside of DomiGym training. DomiGym participants positively change their movement behavior in everyday life. Conclusions Pro Senectute’s DomiGym reaches older people who cannot or do not want to attend out-of-home physical activity programs. The implementation of DomiGym improves the physical functions of leg strength, functional mobility, and balance, as well as the risk of falls in vulnerable elderly people. It can be assumed that DomiGym reduces the frequency of falls in the long term, contributes to the preservation of mobility and independence in everyday life, including a longer stay in their own homes. References Agrawa, Y., Carey, J. P., Hoffman, H. J., Sklare, D. A., & Schubert, M. C. (2011). The modified Romberg balance test: Normative data in US adults. Otology & Neurotology, 32(8), 1309-1311. https://doi.org/10.1097/MAO.0b013e31822e5bee Beratungsstelle für Unfallverhütung BFU. (2019). Status 2019: Statistik der Nichtberufsunfälle und des Sicherheitsniveaus in der Schweiz. Strassenverkehr, Sport, Haus und Freizeit [Status 2019: Statistics on non-occupational accidents and safety levels in Switzerland. Road traffic, sports, home and leisure]. BFU. https://doi.org/10.13100/bfu.2.360.01 Marks, D. (2016). Aufstehen – Gehen – Umdrehen – Gehen – Hinsetzen – Timed-up-and-go-Test [Stand up – walk – turn around – walk – sit down – timed-up-and-go test]. physiopraxis, 14(07/08), 56-57. https://doi.org/10.1055/s-0042-108951 Mehmet, H., Yang, A. W. H., & Robinson, S. R. (2019). What is the optimal chair stand test protocol for older adults? A systematic review. Disability and Rehabilitation, 42(20), 2828-2835. https://doi.org/10.1080/09638288.2019.1575922 Meretta, B. M., Whitney, S. L., Marchetti, G. F., Sparto, P. J., & Muirhead, R. J. (2006). The five times sit to stand test: Responsiveness to change and concurrent validity in adults undergoing vestibular rehabilitation. Journal of Vestibular Research, 16(4-5). 233-243. https://doi.org/10.3233/VES-2006-164-510

Glucocorticoid hormones (GCs) are of critical importance for maintaining brain health, but their involvement in mental disorders is poorly understood. Here the authors show how GCs act through hippocampal mineralocorticoid and glucocorticoid receptors to impact the gene regulatory programs underpinning neuronal plasticity, ciliogenesis and behavioral adaptation.

Facial palsy (FP) is a functional disorder of the facial nerve involving paralysis of the mimic muscles. According to the principle “time is muscle,” early surgical treatment is tremendously important for preserving the mimic musculature if there are no signs of nerve function recovery. In a 49-year-old female patient, even 19 months after onset of FP, successful neurotization was still possible by a V-to-VII nerve transfer and cross-face nerve grafting. Our patient suffered from complete FP after vestibular schwannoma surgery. With continuous application of electrostimulation (ES) therapy, the patient was able to bridge the period between the first onset of FP and neurotization surgery. The significance of ES for mimic musculature preservation in FP patients has not yet been fully clarified. More attention should be paid to this form of therapy in order to preserve the facial musculature, and its benefits should be evaluated in further prospective clinical studies.

We study the pedagogical potential and challenges posed in combining informal learning in a formal teaching programme of English for non-specialist university students by focusing on one of its optional elements: a hybrid exchange module (Kleban et al., 2021) which combines virtual exchange and physical mobility and engages learners in formal and informal educational activities. We use Activity Theory (Engeström, 2000 ; Mwanza & Engeström, 2003) and a diverse data set to analyse qualitatively the module’s design, the interactions and perceptions of participants, and the module’s integration into the teaching program. Third Generation Activity Theory (Engeström, 2009 ; Bradshaw et al., 2020) enables us to deconstruct the module’s hybrid design, to identify the means by which the teachers and students construct "Third Spaces'' (Gutiérrez et al., 1999) which enable the bridging and crossing of boundaries between complementary and at times contradictory formal and informal activity systems. Initial analysis of online interactions and student reported offline interactions reveals multiple examples of boundary crossing but also boundary setting by participants. While participant perceptions of competence development highlight this hybrid model’s pedagogical potential, there are also indications of its limitations. A comparison of the integration of the module in the program between 2018 and 2019 enables us to identify how contradictions in existing activity systems can lead to pedagogical transformation.

As the impacts of rising temperatures mount and the global transition to clean energy advances only gradually, scientists and policymakers are looking towards carbon dioxide removal (CDR) methods to prevent the worst impacts of climate change. Attention has increasingly focused on ocean CDR techniques, which enhance or restore marine systems to sequester carbon. Ocean CDR research presents the risk of uncertain impacts to human and environmental welfare, yet there are no domestic regulations aimed at ensuring the safety and efficacy of this research. A code of conduct that establishes principles of responsible research, fairness, and equity is needed in this field. This article presents fifteen key components of an ocean CDR research code of conduct.

The Swiss Entrepreneurs Foundation was established in late 2017, with Federal Councillor Guy Parmelin its current patron. The privately funded public-interest foundation has three primary objectives: 1) Helping bring the innovative technologies of the future to market; 2) Delivering improvements to the political environment for startups and innovative SMEs; 3) Channelling more Swiss growth capital to home-grown startups. It has implemented various initiatives to achieve these goals. It oversaw the creation of a fund to provide high-potential startups with financing, which had raised CHF 250 million by the end of 2019. The UpScaler programme can rapidly provide support to growing businesses looking to open up international markets while the recently established Swiss Entrepreneurs & Startup Association has pledged itself to creating even better political conditions. The Foundation can count on the support of a high-profile Advisory Board and has access to a pool of around 50 renowned entrepreneurs and specialists.

Background: A heightened stress reactivity to mental stress tasks has been shown in hypertensive patients and might contribute to a higher disease risk. We investigated this hyperreactivity with regard to an attachment related stressor that focuses on emotions instead of performance and we examined whether this effect can also be found in patients on antihypertensive drugs.Materials and Methods: Fifty patients with primary hypertension, treated with at least one antihypertensive drug, were compared with 25 healthy individuals. After 10 min of rest, they participated in an attachment-related interview (Adult Attachment Projective picture system, AAP) and were exposed to an attachment-related stressor (Separation Recall, SR), a short-time stressor which activates attachment-related emotions and thoughts by talking 5 min about a personal experience of loneliness. Blood samples to measure adrenocorticotrope hormone (ACTH), cortisol, norepinephrine, epinephrine, and dopamine were taken. Blood pressure, heart rate and arterial stiffness were measured at rest, after AAP, after SR and 10 min after recovery. Standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD) were calculated. Parameters were compared using Mann Whitney U-test and linear mixed-effects regression models controlling for age and body mass index (BMI) after logarithmic transformation if appropriate.Results: Healthy test persons were younger and had lower BMI than patients. Comparing the two groups there were no significant differences in blood pressure and heart rate at rest. Both stressors provoked a significant response in almost all parameters. Results of the post-estimation of contrasts from linear mixed-effects regression models showed a steeper rise in systolic BP and arterial stiffness as well as a more pronounced decline in SDNN in hypertensive patients than in healthy controls. Levels of cortisol rose earlier and higher in hypertensive patients than in healthy controls.Conclusion: Vascular, autonomic, and hypothalamic pituitary adrenal axis response is heightened in medicated subjects with hypertension in response to attachment-focused stressors compared to healthy subjects. We conclude that the remaining hyper-reactivity even with sufficient antihypertensive medication still poses a substantial risk for affected patients. New ways to diminish this risk should be developed.

Herein, we present the design, synthesis, and biological evaluation of novel integrin-targeting molecular hybrids combining RGD peptides and a potent cytotoxin presented on dextran polysaccharides. Based on an aglycosylated Fc as a centerpiece, endosomal-cleavable cytotoxic agent monomethyl auristatin E (MMAE) and dextran as multimerization site were covalently connected by two bioorthogonal enzyme-mediated reactions site-specifically. Decoration of dextran with cyclic RGD peptides, introduced by copper “click” reaction, resulted in the final constructs with the potential to kill integrin-overexpressing tumor cells. We found that these modifications had little impact on the stability of the Fc scaffold and the RGD-bearing construct showed good binding properties of αvβ3-expressing U87MG cells. Furthermore, the construct showed a remarkable antiproliferative activity. These results demonstrate the general capability of our design to provoke receptor-mediated endocytosis upon binding to the cellular surface, followed by endosomal cleavage of the linkage between Fc-dextran and MMAE and its subsequent release. Our approach opens new avenues to transcribe small molecule binders into tailor-made multimeric molecular hybrids with antitumor potential.

This article details a correction to the article: Chen, H., Shaw, T.A., Wang, J., Engelhart, S., Nikitina, D., Pilarczyk, J.E., Walker, J., García-Artola, A. and Horton, B.P., 2020. Salt-Marsh Foraminiferal Distributions from Mainland Northern Georgia, USA: An Assessment of Their Viability for Sea-Level Studies. 'Open Quaternary', 6(1), p. 6. DOI: http://doi.org/10.5334/oq.80

Abstract Antibody‐drug conjugates (ADCs) are multicomponent biomolecules that have emerged as a powerful tool for targeted tumor therapy. Combining specific binding of an immunoglobulin with toxic properties of a payload, they however often suffer from poor hydrophilicity when loaded with a high amount of toxins. To address these issues simultaneously, we developed dextramabs, a novel class of hybrid antibody‐drug conjugates. In these architectures, the therapeutic antibody trastuzumab is equipped with a multivalent dextran polysaccharide that enables efficient loading with a potent toxin in a controllable fashion. Our modular chemoenzymatic approach provides an access to synthetic dextramabs bearing monomethyl auristatin as releasable cytotoxic cargo. They possess high drug‐to‐antibody ratios, remarkable hydrophilicity, and high toxicity in vitro.

We investigated foraminiferal distributions from two salt-marsh sites at Thunderbolt and Georgetown, in mainland northern Georgia, U.S. Atlantic coast. We analyzed modern epifaunal foraminiferal assemblages across multiple transects consisting of 54 surface samples. Multivariate statistical analysis (Partitioning Around Medoids and Detrended Correspondence Analysis) revealed that dead foraminiferal assemblages are divided into three faunal zones, which are elevation-dependent and site-specific. At Thunderbolt, an intermediate salinity marsh (17‰), high marsh assemblages are dominated by 'Haplophragmoides' spp. with an elevational range of 1.19 to 1.68 m mean tide level (MTL) between Mean Higher High Water (MHHW) to Highest Astronomical Tide (HAT). Low marsh assemblages are dominated by 'Miliammina fusca' and 'Ammobaculites' spp. with an elevational range of – 0.05 to 1.14 m MTL (between MTL and MHHW). At Georgetown, a low salinity marsh (6‰), the assemblages are dominated by 'Ammoastuta inepta' with an elevational range of 0.43 to 1.16 m MTL (between MTL and MHHW). We also enumerated living infaunal foraminiferal populations from six 50-cm sediment cores from the two salt marshes to assess implications for interpretations of sea-level change. Peak concentrations of living foraminiferal populations occur in the upper 1-cm surface sediment in five of the six cores. An exception was observed in high marsh settings of Thunderbolt, where 'Haplophragmoides' spp. and 'Arenoparrella mexicana' were observed living down to 40 cm depth and both the live and dead abundance peaked (32 and 520 specimens per 10 cc respectively) between depths of 15–35 cm in the core. The dominant infaunal species were similar to those observed in modern surface samples, and the total number of infaunal foraminifera was typically less than 15% compared to the total number of dead specimens in the surface samples. Finally, we com­pared the down-core patterns of living and dead foraminiferal abundance that suggest that 90% of the tests were removed within the upper 10 cm of sediment in most cores. This may be due to taphonomic alteration from bioturbation and/or microbial processes. Selective preservation between resistant species such as 'A. mexicana' and fragile species like 'M. fusca' and 'Ammobaculites' spp. can change the subsurface foraminiferal assemblage. This has the potential to cause errors in sea-level reconstructions using foraminiferal assemblage from low marsh sediments. This study highlights the modern vertical distribution of salt-marsh foraminifera in mainland northern Georgia and their potential as modern analogues for fos­sil counterparts in reconstructing sea-level changes. Taphonomic processes may cause the absence of foraminiferal tests or differences between modern and fossil assemblages, which could be problematic when performing RSL reconstructions in low marsh environment.

This paper provides an overview of Human Machine Interface (HMI) design and command systems in commercial or experimental operation across transport modes. It presents and comments on different HMIs from the perspective of vehicle automation equipment and simulators of different application domains. Considering the fields of cognition and automation, this investigation highlights human factors and the experiences of different industries according to industrial and literature reviews. Moreover, to better focus the objectives and extend the investigated industrial panorama, the analysis covers the most effective simulators in operation across various transport modes for the training of operators as well as research in the fields of safety and ergonomics. Special focus is given to new technologies that are potentially applicable in future train cabins, e.g., visual displays and haptic-shared controls. Finally, a synthesis of human factors and their limits regarding support for monitoring or driving assistance is proposed.

This study uses mixed methodology adapted from Nexus Analysis (Scollon & Wong Scollon, 2004) to analyse the development of in-service and pre-service foreign language teacher identity and their perception of their roles with a potential normalisation of personal digital devices (Bax, 2003) and telecollaboration (O'Dowd, 2009) in the classroom. Diverse institutional, personal, professional and informal discourses were traced to determine a nexus of practice with its constitutive discourses in place, interaction orders and historical bodies. Transgressive, conservative or transformative uses of technology or practices were noted. In an attempt to challenge current visions of possible selves (Kubanyiova, 2009), the teachers were asked to imagine alternative scenarios of technology integration and telecollaboration. Findings suggest that teacher identity results from a complex interplay of institutional, professional, and informal discourses which may be both obstacles and bridges to pedagogical transformation. Confronted by a globally connected classroom, these teachers experience difficulties to redefine their roles and to envisage a foreign language curriculum which integrates new unfamiliar literacies and skills. Telecollaboration, we suggest, should be considered in the context of a digitally mediated networked cultural revolution and may be used as a means to leverage a profound transformation of education.

BACKGROUND AND OBJECTIVES:There is a lack of evidence concerning associations between novel parameters of arterial stiffness as cardiovascular risk markers and traditional structural and functional vascular biomarkers in a population-based Caucasian cohort. We examined these associations in the second follow-up of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA 3). METHODS:Arterial stiffness was measured oscillometrically by pulse wave analysis to derive the cardio-ankle vascular index (CAVI), brachial-ankle (baPWV) and aortic pulse wave velocity (aPWV), and amplitude of the forward and backward wave. Carotid ultrasonography was used to measure carotid intima-media thickness (cIMT) and carotid lumen diameter (LD), and to derive a distensibility coefficient (DC). We used multivariable linear regression models adjusted for several potential confounders for 2,733 people aged 50-81 years. RESULTS:CAVI, aPWV and the amplitude of the forward and backward wave were significant predictors of cIMT (p < 0.001). All parameters were significantly associated with LD (p < 0.001), with aPWV and the amplitude of the forward wave explaining the highest proportion of variance (2%). Only CAVI and baPWV were significant predictors of DC (p < 0.001), explaining more than 0.3% of the DC variance. CONCLUSION:We demonstrated that novel non-invasive oscillometric arterial stiffness parameters are differentially associated with specific established structural and functional local stiffness parameters. Longitudinal studies are needed to follow-up on these cross-sectional findings and to evaluate their relevance for clinical phenotypes.

We examined cross-sectional associations of self-reported PA intensities with arterial stiffness in elderly Caucasians of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). Mixed central and peripheral arterial stiffness was measured oscillometrically by the cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). The self-reported International Physical Activity Questionnaire (IPAQ) long version was administered to classify each subject’s PA level. We used univariable and multivariable mixed linear and logistic regression models for analyses in 1908 persons aged 50 years and older. After adjustment for several confounders moderate, vigorous and total PA were inversely associated with CAVI (p=0.02–0.03). BaPWV showed negative and marginally significant associations with vigorous and moderate PA (each p=0.06), but not with total PA (p=0.28). Increased arterial stiffness (CAVI≥9, upper tertile) was inversely and significantly associated with vigorous PA (Odds Ratio (OR)=0.65, 95% Confidence Interval (CI): 0.48–0.88), and marginally significantly with total PA (OR=0.76, 95% CI: 0.57–1.02) and moderate PA (OR=0.75, 95% CI: 0.56–1.01). The odds ratio for baPWV≥14.4 was 0.67 (95% CI: 0.48–0.93) across the vigorous PA levels, and was non-significant across the total (OR=0.91, 95% CI: 0.66–1.23) and moderate PA levels (OR=0.94, 95% CI: 0.69–1.28). In this general Caucasian population of older adults higher levels especially of vigorous PA were associated with lower arterial stiffness. These data support the importance of PA for improving cardiovascular health in elderly people.

We examined the effects of normal ageing on visual cognition in a sample of 112 healthy adults aged 60-75. A testbattery was designed to capture high-level measures of visual working memory and low-level measures of visuospatial attention and memory. To answer questions of how cognitive ageing affects specific aspects of visual processing capacity, we used confirmatory factor analyses in Structural Equation Modelling (SEM; Model 2), informed by functional structures that were modelled with path analyses in SEM (Model 1). The results show that ageing effects were selective to measures of visual processing speed compared to visual short-term memory (VSTM) capacity (Model 2). These results are consistent with some studies reporting selective ageing effects on processing speed, and inconsistent with other studies reporting ageing effects on both processing speed and VSTM capacity. In the discussion we argue that this discrepancy may be mediated by differences in age ranges, and variables of demography. The study demonstrates that SEM is a sensitive method to detect cognitive ageing effects even within a narrow age-range, and a useful approach to structure the relationships between measured variables, and the cognitive functional foundation they supposedly represent.

Regular physical activity has been shown to reduce cardiovascular disease risk in the general population. While smaller studies in specified groups (highly trained versus untrained individuals) indicate a certain dose-dependent effect of physical activity on the reduction of carotid stiffness (an indicator of subclinical vascular disease), it is unclear whether this association is present in a representative sample. Thus, we investigated this question cross-sectionally in participants from the population-based Swiss Cohort Study on Air Pollution And Lung and Heart Diseases In Adults (SAPALDIA).Self-reported total, moderate and vigorous physical activity and distensibility as a measure of local arterial stiffness among 1636 participants aged 50 to 81 years without clinically manifest diseases were evaluated. Mixed regression models were used to examine associations of physical activity intensity with distensibility.Vigorous physical activity, but not total nor moderate physical activity, was significantly associated with increased distensibility (= reduced carotid stiffness) in univariate analyses (percent change in the geometric mean and 95% confidence interval per 1 standard deviation increment in vigorous physical activity = 2.54 (0.69; 4.43), p < 0.01; in total physical activity = 1.62 (-0.22; 3.50), p = 0.08; in moderate physical activity = 0.70 (-1.12; 2.56), p = 0.45). These associations disappeared when we additionally adjusted for age.After adjustment for the most important confounders and risk factors, we found no evidence for an association of physical activity with carotid stiffness in the general middle aged to elderly population.

Visual perception serves as the basis for much of the higher level cognitive processing as well as human activity in general. Here we present normative estimates for the following components of visual perception: the visual perceptual threshold, the visual short-term memory capacity and the visual perceptual encoding/decoding speed (processing speed) of Visual Short-Term Memory (VSTM) based on an assessment of 91 healthy subjects aged 60-75. The estimates were modelled from input from a whole-report assessment based on A Theory of Visual Attention (TVA). In addition to the estimates themselves, we present correlational data, and multiple regression analyses between the estimates and self-reported demographic data and lifestyle variables. The regression statistics suggest that education level, video gaming activity and employment status may significantly impact the encoding/decoding speed of VTSM but not the capacity of VSTM nor the visual perceptual threshold. The estimates will be useful for future studies into the effects of various types of intervention and training on cognition in general and visual attention in particular.

We carried out a Capture-Mark-Recapture study on Martino's vole Dinaromys bogdanovi on Mt. Bjelašnica, central Bosnia. During two trapping sessions (June and September 2008) we recorded 21 individuals which were captured 33 times. Voles were trapped significantly more frequently during the night (85% of all captures). In June all the animals were adult females while three age classes (juvenile, subadult and adult) were distinguished in September. No reproductive activity was recorded in mid-June and not a single adult female was evidently pregnant in September. Also, subadults (N = 6) did not show reproductive activity. Martino’s voles proved sedentary and only two individuals moved between trap stations. Ten adults were captured in two sessions on an area of 5.67 ha, resulting in a population density of about 2.5 voles per hectare.

Michel Foucault's concept of bio-politics entails the management and regulation of life processes within the population as a whole. This administration of the biological was perhaps most manifest in the German state under National Socialism. Indeed, Foucault remarks that there was no other state of the period in which "the biological was so tightly, so insistently regulated." However while the Nazi regime evinced this bio-political concern with the management of life, it also released an unprecedented murderous potential. It is this paradox, that the care of life can become the administration of death, or what Foucault deemed the transition from bio-politics to thanato-politics, that I wish to investigate through an examination of the construction of the Jewish subject through Nazi medical discourse. This paper will examine how medico-political discourse facilitated the construction of medically authorized norms that constructed the Jew as both a biological and social threat to the body politic, and how this discursively produced "Other" informed the transition from bio-politics to thanato-politics within the confines of the German medical establishment.

Recycling of membrane proteins enables the reuse of receptors, ion channels and transporters. A key component of the recycling machinery is the endosomal sorting complex for promoting exit 1 (ESCPE-1), which rescues transmembrane proteins from the endolysosomal pathway for transport to the trans-Golgi network and the plasma membrane. This rescue entails the formation of recycling tubules through ESCPE-1 recruitment, cargo capture, coat assembly and membrane sculpting by mechanisms that remain largely unknown. Herein, we show that ESCPE-1 has a single-layer coat organization and suggest how synergistic interactions between ESCPE-1 protomers, phosphoinositides and cargo molecules result in a global arrangement of amphipathic helices to drive tubule formation. Our results thus define a key process of tubule-based endosomal sorting., (© 2023. The Author(s).)

ATP-binding cassette (ABCG2) is an efflux transporter that extrudes xenotoxins from cells in liver, intestine, mammary gland, brain and other organs, affecting the pharmacokinetics, brain accumulation and secretion into milk of several compounds, including antitumoral, antimicrobial and anti-inflammatory drugs. The aim of this study was to investigate whether the widely used anti-inflammatory drug meloxicam is an Abcg2 sustrate, and how this transporter affects its systemic distribution. Using polarized ABCG2-transduced cell lines, we found that meloxicam is efficiently transported by murine Abcg2 and human ABCG2. After oral administration of meloxicam, the area under the plasma concentration-time curve in Abcg2 -/- mice was 2-fold higher than in wild type mice (146.06 ± 10.57 µg·h/ml versus 73.80 ± 10.00 µg·h/ml). Differences in meloxicam distribution were reported for several tissues after oral and intravenous administration, with a 20-fold higher concentration in the brain of Abcg2 -/- after oral administration. Meloxicam secretion into milk was also affected by the transporter, with a 2-fold higher milk-to-plasma ratio in wild-type compared with Abcg2 -/- lactating female mice after oral and intravenous administration. We conclude that Abcg2 is an important determinant of the plasma and brain distribution of meloxicam and is clearly involved in its secretion into milk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Impacted teeth predispose to periodontal disease and dental caries of adjacent teeth resulting in pain, discomfort and loss of function. This study analyzed the pattern of occurrence of impacted teeth, associated symptoms, treatment and complications of treatment in patients who presented at the Muhimbili National Hospital, Tanzania., Method: This was a crossectional descriptive study which utilized notes and x rays of patients who were treated for impacted teeth at the Oral and Maxillofacial firm in Muhimbili National Hospital over five years, from January 2005 to August 2010. These records were retrieved and examined for the major complaint of the patient at presentation to hospital, demography, impacted tooth, type of impaction (for third molars), treatment offered and complications after treatment. Similar information was collected from all patients with impacted teeth attended in the same centre from 1st September 2010 to 31st August 2011., Results: A total of 896 patients (496 males and 400 females) treated for complaints related to impacted teeth were recorded. The male to female ratio was 1.2:1, age range of 16 to 85 years and a mean age of 28.9 years (SD = 9.5). Slightly more than 84% of the patients presented with mandibular third molar impactions. Most (44.7%) of these patients had an impacted lower right third molar followed by those presenting with a lower left third molar impaction (39.7%). In 1.3% of the patients all the four third molars were impacted. Sixty nine (7.7%) patients had impacted upper 3rd molars while 2% had impacted upper canines. Of the mandibular 3rd molar impactions 738 (76%) were mesio-angular type, 87 (8.9%) horizontal type and 69 (7.1%) disto-angular. Patients presented with a variety of complaints. About 85% of the patients presented to hospital due to varying degrees of pain. In 4.9% the detection of the impacted tooth/teeth was coincidental after presenting to hospital for other reasons not related to the impaction. Majority of the patients with impacted mandibular third molars had carious lesions on the impacted teeth, neighbouring tooth or both. Four hundred and five (45.2%) patients had a carious lesion on one of the impacted teeth while 201(22.4%) patients had a carious lesion on the adjacent second molar. In 122 (13.6%) patients both the impacted third molar and the adjacent second molar were carious. In twelve patients who presented with a main complaint of fracture of the angle of the mandible there was an associated impacted 3rd molar. Eight hundred and fifteen (91%) patients with impacted teeth were treated by surgical removal. Among these only 15 (1.8%) had complications that ranged from excessive swellings, trismus and severe pain post operatively. One patient was reported to have fracture of the angle of the mandible sustained during surgical removal of an impacted 48., Conclusions: The majority of patients with impacted teeth were young with an almost equal sex distribution. The most commonly impacted teeth were mandibular third molars followed by the maxillary third molars. Patients with impacted teeth reported for health care predominantly because of pain due to dental caries or infection.

The results are reported of a clinical follow-up study on 32 selected but consecutive patients with mandibular ameloblastoma. They were all treated by a segmental resection and reconstructed, using two 2.3 mm reconstruction plates and an autogenous particulate bone graft, taken from the anterior iliac crest, and platelet rich plasma. Follow-up ranged from 12 to 39 months, with an average of 27.9 months. Undisturbed healing occurred in 29 patients, while three had postoperative infections, but in only one case did that result in failure of the graft. The patients' appreciation was measured using an adapted quality of life questionnaire. The results were compared with a similar group who did not undergo reconstruction. The eating of solid food, appearance and speech were considerably better in the reconstructed group. The conclusion is that this means of reconstruction is appropriate for patients with benign but aggressive odontogenic tumours of the mandible, particularly in developing countries, since the expenses seem to be affordable., (Copyright © 2012 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: To describe the presentation and management of maxillofacial trauma., Design: A retrospective study., Setting: Department of Oral and Maxillofacial Surgery, Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania., Subjects: Patients presenting with maxillofacial trauma at the oral and maxillofacial surgery department of the MNH over a six year period (2001-2007)., Method: Information was gathered including age, gender, length of interval between injury and presentation to the hospital, aetiology, pattern of soft tissue injury and fractures, therapy, co-morbidity, complications and number of hospitalisation days., Results: The 21-30-year old age group was most affected. The overall male to female ratio was 4.3:1. The major cause of maxillofacial trauma was road traffic accidents (42.3%), followed by assaults (39.1%). Over 90% of the patients sustained soft tissue injuries, with cut wounds seen most frequently (45.0%). Of the soft tissue injuries, 75% required surgical intervention. Most of the fractures were located in the mandible (52.8%). Accompanying injuries elsewhere in the body occurred in 51.5%. Complications occurred in 13.3% of the cases. The mean hospitalisation period was 4.3 days., Conclusion: Road traffic accidents and assaults were the most common causes of maxillofacial trauma. Males below forty years of age were the majority of the victims.

Background: Oropharyngeal candidiasis is the most common opportunistic infection affecting patients with human immunodeficiency virus (HIV) infection. Because of convenience, cost, and reluctance to complicate antiretroviral treatment regimens, single-dose fluconazole may be a favorable regimen for treatment of moderate to severe oropharyngeal candidiasis. We conducted a prospective, randomized, double-blind, placebo-controlled trial to compare the clinical and mycological responses, relapse rates, and safety of a single 750-mg dose and a 14-day course of treatment with fluconazole., Methods: A total of 220 HIV-infected patients with clinical and mycological evidence of oropharyngeal candidiasis were randomly assigned in a 1:1 ratio to receive either a 750-mg single dose of orally administered fluconazole (110 patients) or 150 mg of orally administered fluconazole once per day for 2 weeks (110 patients). The primary efficacy analysis was based on clinical and mycological responses at the end of treatment. Secondary parameters were safety and relapse rate., Results: Single-dose fluconazole was equivalent to a 14-day course of fluconazole in achieving clinical and mycological cure, with clinical cure rates of 94.5% and 95.5%, respectively (odds ratio, 0.825; 95% confidence interval, 0.244-2.789; P= .99), and mycological cure rates of 84.5% and 75.5%, respectively (odds ratio, 1.780; 95% confidence interval, 0.906-3.496; P= .129). Drug-related adverse events were uncommon and were not different between the treatment groups., Conclusion: A single dose of 750 mg of fluconazole was safe, well tolerated, and as effective as the standard 14-day fluconazole therapy in patients with HIV infection and acquired immunodeficiency syndrome who had oropharyngeal candidiasis coinfection.

Background: In Tanzania, little is known on the species distribution and antifungal susceptibility profiles of yeast isolates from HIV-infected patients with primary and recurrent oropharyngeal candidiasis., Methods: A total of 296 clinical oral yeasts were isolated from 292 HIV-infected patients with oropharyngeal candidiasis at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Identification of the yeasts was performed using standard phenotypic methods. Antifungal susceptibility to fluconazole, itraconazole, miconazole, clotrimazole, amphotericin B and nystatin was assessed using a broth microdilution format according to the guidelines of the Clinical and Laboratory Standard Institute (CLSI; M27-A2)., Results: Candida albicans was the most frequently isolated species from 250 (84.5%) patients followed by C. glabrata from 20 (6.8%) patients, and C. krusei from 10 (3.4%) patients. There was no observed significant difference in species distribution between patients with primary and recurrent oropharyngeal candidiasis, but isolates cultured from patients previously treated were significantly less susceptible to the azole compounds compared to those cultured from antifungal naïve patients., Conclusion: C. albicans was the most frequently isolated species from patients with oropharyngeal candidiasis. Oral yeast isolates from Tanzania had high level susceptibility to the antifungal agents tested. Recurrent oropharyngeal candidiasis and previous antifungal therapy significantly correlated with reduced susceptibility to azoles antifungal agents.

Background: Human bites in the maxillofacial region compromise function and aesthetics, resulting in social and psychological effects. There is paucity of information regarding human bite injuries in Tanzania. The aim of the study was to assess the occurrence, treatment modalities and prognosis of human bite injuries in the oro-facial region at the Muhimbili National Hospital Dar es Salaam, Tanzania., Methods: In a prospective study the details of patients with human bite injuries in the oro-facial region who attended at the Department of Oral and Maxillofacial Surgery of the Muhimbili National Hospital between January 2001 and December 2005 were recorded. Data included information on age, sex, site, duration of the injury at the time of reporting to hospital, reasons, details of treatment offered and outcome after treatment., Results: A total of 33 patients, 13 males and 20 females aged between 12 and 49 years with human bite injuries in the oro-facial region were treated. Thirty patients presented with clean uninfected wounds while 3 had infected wounds. The most (45.5%) frequently affected site was the lower lip. Treatment offered included thorough surgical cleansing with adequate surgical debridement and primary suturing. Tetanus prophylaxis and a course of broad-spectrum antibiotics were given to all the patients. In 90% of the 30 patients who were treated by suturing, the healing was uneventful with only 10% experiencing wound infection or necrosis. Three patients who presented with wounds that had signs of infection were treated by surgical cleansing with debridement, antibiotics and daily dressing followed by delayed primary suturing., Conclusion: Most of the human bite injuries in the oro-facial region were due to social conflicts. Although generally considered to be dirty or contaminated they could be successfully treated by surgical cleansing and primary suture with a favourable outcome. Management of such injuries often need multidisciplinary approach.

Background: There is hardly any information regarding oral health status of handicapped primary school pupils in Tanzania. Determination of their oral health status could help in planning sustainable intervention programmes for this disadvantaged group., Objectives: To determine caries and periodontal status and treatment needs of handicapped primary school pupils in Dar es Salaam, Tanzania., Design: A descriptive cross-sectional study., Setting: Uhuru Mchanganyiko and Buguruni special schools, Dar es Salaam., Results: The sample consisted of 179 (55.8%) males and 142 (44.2%) females aged between 7 and 22 years. Majority (71%) were deaf followed by blind (17.8%) and mentally retarded (8.7%). Six (1.9%) pupils were both deaf and blind, while one (0.3%) pupil was blind and mentally retarded. Forty one (12.8%) pupils had at least one decayed deciduous tooth, with the mean (dmfs) ranging from 0.25 to 3.24. The deaf had the highest mean decayed surfaces, followed by the mentally retarded and the blind. There was only one (0.3%) pupil who had a filled deciduous tooth. Thirty three (10.3%) pupils had decayed permanent teeth and 31 (9.7%) had missing permanent teeth. None of the decayed permanent teeth were restored. The blind had the lowest mean deciduous surfaces (DS) scores of between 0 and 1.0. In the mentally retarded group the mean DS ranged from 0.25 to 1.75. About 73.5% of the studied group had bleeding of the gums, with the blind having the highest mean bleeding index scores (p < 0.001) and about 82.8% of the pupils had calculus, with highest mean scores mainly among the blind (p = 0.008)., Conclusion: The caries prevalence among handicapped primary school pupils was quite low. However, there was relatively high level of gingival bleeding and calculus. Regarding treatment needs, 23% required dental fillings mainly of one and two surface restorations and 82% required scaling and polishing. Despite these treatment needs these pupils had not received any dental attention.