A tale of a threshing machine: Images of the Voigt-Leibniz mathematical-agricultural machine at the beginning of the 18th century.

This paper examines how a certain threshing machine was developed and improved by Jobst Heinrich Voigt and Gottfried Wilhelm Leibniz between 1699 and 1700. While this machine was based on various mechanical principles and instruments, including the pinned drum mechanism first noted by Georg Philipp Harsdörffer, it was later reconceptualized as a 'mathematical' machine. I claim that such a positioning was not unique to this machine, but part of a wider movement during the 18th century that considered various artisanal instruments as mathematical, as well as agricultural and artisanal knowledge as scientific. Examining the development and subsequent reception of this machine, I show that during the first decades of the 18th century these conceptions gave rise to a double image of this machine, and hence of agricultural knowledge in general: on the one hand, this machine was considered as more efficient and productive (while still in need of improvement); on the other hand, it was viewed, either implicitly or explicitly, as something that should be studied by mathematicians, thus reflecting a changing image of mathematics.

Association of Obesity With Psychological Distress in Young Adults: Patterns by Sex and Race or Ethnicity.

Background: Recent studies have emphasized the intricate relationship between obesity and psychological distress, unraveling the complex interplay of biological, psychological, and sociocultural factors. However, a conspicuous knowledge gap persists in understanding the association between obesity severity and psychological distress, particularly in young adults, marked by limited empirical data. Objectives: This study comprehensively investigates the link between obesity and psychological distress among young adults, emphasizing potential variations based on gender and race or ethnicity. Addressing this gap is crucial for informing targeted interventions and understanding the nuanced impact of obesity on mental health in this demographic. Methods: Utilizing data from the 2013 to 2018 National Health Interview Survey, individuals aged 18 to 26 years were analyzed. Body mass index served as the primary exposure variable, with the Kessler Psychological Distress Scale assessing the primary outcome. Fully-adjusted ordinal regression models were employed for analyses. Results: Among the 20,954 participants included in this study, representing 35,564,990 adults, 27% were overweight and 24% had obesity. In class III obesity, individuals experienced 1.4 times more psychological distress than those with normal weight (OR: 1.393; 95% CI: 1.181-1.644; P < 0.001). Subgroup analyses revealed consistent trends in non-Hispanic White (OR: 1.615; 95% CI: 1.283-2.032; P < 0.001) and female participants (OR: 1.408; 95% CI: 1.408-2.096; P < 0.001). Conclusions: This study underscores the association between obesity and psychological distress in young adults, notably impacting non-Hispanic White and female populations. The findings bear significant implications for shaping future health policies, addressing the mental health crisis, and mitigating the increasing prevalence of obesity among young U.S. adults.

Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression.

The tumor microenvironment (TME) profoundly influences tumorigenesis, with gene expression in the breast TME capable of predicting clinical outcomes. The TME is complex and includes distinct cancer-associated fibroblast (CAF) subtypes whose contribution to tumorigenesis remains unclear. Here, we identify a subset of myofibroblast CAFs (myCAF) that are senescent (senCAF) in mouse and human breast tumors. Utilizing the MMTV-PyMT;INK-ATTAC (INK) mouse model, we found that senCAF-secreted extracellular matrix specifically limits natural killer (NK) cell cytotoxicity to promote tumor growth. Genetic or pharmacologic senCAF elimination unleashes NK cell killing, restricting tumor growth. Finally, we show that senCAFs are present in HER2+, ER+, and triple-negative breast cancer and in ductal carcinoma in situ (DCIS) where they predict tumor recurrence. Together, these findings demonstrate that senCAFs are potently tumor promoting and raise the possibility that targeting them by senolytic therapy could restrain breast cancer development. Significance: senCAFs limit NK cell-mediated killing, thereby contributing to breast cancer progression. Thus, targeting senCAFs could be a clinically viable approach to limit tumor progression. See related article by Belle et al., p. 1324.

Storylines of family medicine III: core principles-primary care, systems and family.

Storylines of Family Medicine is a 12-part series of thematically linked mini-essays with accompanying illustrations that explore the many dimensions of family medicine, as interpreted by individual family physicians and medical educators in the USA and elsewhere around the world. In 'III: core principles-primary care, systems, and family', authors address the following themes: 'Continuity of care-building therapeutic relationships over time', 'Comprehensiveness-combining breadth and depth of scope', 'Coordination of care-managing multiple realities', 'Access to care-intersectional, systemic, and personal', 'Systems theory-a core value in patient-centered care', 'Family-oriented practice-supporting patients' health and well-being', 'Family physician as family member' and 'Family in the exam room'. May readers develop new understandings from these essays.

Sustained release varnish containing chlorhexidine for prevention of Streptococcus mutans biofilm formation on voice prosthesis surface: an in vitro study / Barniz de liberación sostenida que contiene clorhexidina para la prevención de la formación de biopelículas de Streptococcus mutans en la superficie de la prótesis de voz: un estudio in vitro

Objectives: In this study, we aimed to develop a novel, sustained release varnish (SRV) for voice prostheses (VP) releasing chlorhexidine (CHX), for the prevention of biofilm formation caused by the common oral bacteria Streptococcus mutans on VP surfaces. Methods: This study was performed in an in vitro model as a step towards future in vivo trials. VPs were coated with a SRV containing CHX (SRV-CHX) or SRV alone (placebo-SRV) that were daily exposed to S. mutans. The polymeric materials of SRV were composed of ethylcellulose and PEG-400. Biofilm formation was assessed by DNA quantification (qPCR), crystal violet staining, confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), and kinetics experiments. Results: The amount of DNA in the biofilms formed by S. mutans on VP surfaces coated once with SRV-CHX (1.024 ± 0.218 ng DNA/piece) was 58.5 ± 8.8% lower than that of placebo-SRV-coated VPs (2.465 ± 0.198 ng DNA/piece) after a 48-h exposure to S. mutans (p = 0.038). Reduced biofilm mass on SRV-CHX-coated VPs was visually confirmed by CLSM and SEM. CV staining of SRV-CHX single-coated VPs that have been exposed to S. mutans nine times showed a 98.1 ± 0.2% reduction in biofilm mass compared to placebo-SRV-coated VPs (p = 0.003). Kinetic experiments revealed that SRV-CHX triple-coated VPs could delay bacterial growth for 23 days. Conclusions: Coating VPs with SRV-CHX has an inhibitory effect on biofilm formation and prevents bacterial growth in their vicinities. This study is a proof-of-principle that paves the way for developing new clinical means for reducing both VPs’ bacterial biofilm formation and device failure.(AU)

Isolation perfusion for malignant melanoma of the extremity : a review

The role of perfusion, normothermic and hypothermic, in the curative treatment of melanoma remains controversial. Survival appears to be somewhat improved over that of surgery alone in all stages, especially with hyperthermic perfusion, but all comparisons have been retrospective and uncontrolled. In addition to the usual problems with historical controls, melanoma presents its own special problems because of its unpredictable natural history in any given individual and the multiplicity of factors known to affect prognosis. It is unfortunate that hundreds of patients have been treated in uncontrolled studies. Randomized trials continue to be necessary to define this role and even then careful attention will have to be paid to the distribution of known prognostic factors in each group to insure a comparable cohort of patients. The response of melanoma to perfusion is clearly significant, however, and the response rate seems to be improved with hyperthermic perfusion. Hyperthermic perfusion appears to be a useful palliative treatment for locally advanced melanoma of the extremity, especially for which the alternative surgical therapy would be amputation