Smooth muscle is a central structure involved in the regulation of airway tone. In addition, it plays an important role in the development of some pathologies generated by alterations in contraction, such as hypercontractility and the airway hyperresponsiveness observed in asthma. The molecular processes associated with smooth muscle contraction are centred around myosin light chain (MLC) phosphorylation, which is controlled by a balance in the activity of myosin light-chain kinase (MLCK) and myosin light-chain phosphatase (MLCP). MLCK activation depends on increasing concentrations of intracellular Ca2+, while MLCP activation is independent of Ca2+. MLCP contains a phosphatase subunit (PP1c) that is regulated through myosin phosphatase target subunit 1 (MYPT1) and other subunits, such as glycogen-associated regulatory subunit and myosin-binding subunit 85 kDa. Interestingly, MLCP inhibition may contribute to exacerbation of smooth muscle contraction by increasing MLC phosphorylation to induce hypercontractility. Many pathways inhibiting MLCP activity in airway smooth muscle have been proposed and are focused on inhibition of PP1c, inhibitory phosphorylation of MYPT1 and dissociation of the PP1c-MYPT1 complex.

Airway hyperresponsiveness is a key feature of asthma, but its mechanisms remain poorly understood. Leukotriene D₄(LTD₄) is one of the few molecules capable of producing airway hyperresponsiveness. In this study, LTD₄, but not leukotriene C₄(LTC₄), produced a leftward displacement of the concentration-response curve to histamine in bovine airway smooth muscle strips. Neither LTC₄nor LTD₄modified the concentration-response curve to carbachol. In simultaneous measurements of intracellular Ca²⁺([Ca²⁺]_i) and contraction, histamine or carbachol produced a transient Ca²⁺peak followed by a plateau, along with a contraction. LTD₄increased the histamine-induced transient Ca²⁺peak and contraction but did not modify responses to carbachol. Enhanced responses to histamine induced by LTD₄were not modified by staurosporine or chelerythrine but were abolished by genistein. Western blot showed that carbachol, but not histamine, caused intense phosphorylation of extracellular signal-regulated kinase 1/2 and that LTD₄significantly enhanced the phosphorylation induced by histamine, but not by carbachol. L-type Ca²⁺channel participation in the hyperresponsiveness to histamine was discarded because LTD₄did not modify the [Ca²⁺]_ichanges induced by KCl. In tracheal myocytes, LTD₄enhanced the transient Ca²⁺peak induced by histamine (but not by carbachol) and the sarcoplasmic reticulum (SR) Ca²⁺refilling. Genistein abolished this last LTD₄effect. Partial blockade of the SR-ATPase Ca²⁺pump with cyclopiazonic acid reduced the Ca²⁺transient peak induced by histamine but not by carbachol. These results suggested that LTD₄induces hyperresponsiveness to histamine through activation of the tyrosine kinase pathway and an increasing SR-ATPase Ca²⁺pump activity. L-type Ca²⁺channels seemed not to be involved in this phenomenon.

Nimotuzumab is a humanized IgG1 monoclonal antibody against the EGFR extracellular domain that has been evaluated in solid tumors as a single agent or in combination with chemotherapy and radiation. Cervical cancer patients who are refractory or progressive to first-line chemotherapy have a dismal prognosis, and no second- or third-line chemotherapy is considered standard. This pilot trial aimed to evaluate the efficacy and safety of nimotuzumab in 17 patients with pre-treated advanced refractory or progressive cervical cancer. Nimotuzumab was administered weekly at 200 mg/m² as single agent for 4 weeks (induction phase), then concurrent with 6 21-day cycles of gemcitabine (800 mg/m²) or cisplatin (50 mg/m²) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Nimotuzumab could be continued beyond disease progression. Seventeen patients were accrued and evaluated for safety and efficacy. The median number of nimotuzumab applications was 20 (5–96). The median number of chemotherapy cycles administered was 6 (1-6). No toxicity occurred during induction and maintenance phases (single agent nimotuzumab). In the concurrent phase, grade 3 toxicity events observed were leucopenia, anemia and diarrhea in 11.7%, 5.8% and 11.7% respectively. No complete or partial responses were observed. The stable disease (SD) rate was 35%. The median PFS and OS rates were163 days (95% CI, 104 to 222), and 299 days (95% IC, 177 to 421) respectively. Nimotuzumab is well tolerated and may have a role in the treatment of advanced cervical cancer.

The field of health sciences is constantly evolving, presenting significant challenges to student learning performance. Therefore, it is crucial to identify the factors influencing students' learning style preferences, as these relate to how they acquire, understand, interpret, organize, and process information from their courses. In this study, we evaluated whether there is a relationship between students' learning style preferences and their learning gains. A cross-sectional study was conducted between 2021 and 2022 using a convenience sampling approach with students of the School of Medicine and Health Sciences at the Mexico City Campus of Tecnológico de Monterrey. Students completed online questionnaires to assess normalized learning gains, as well as preference questionnaires from the VARK inventory (Visual, Auditory, Reading/Writing, and Kinesthetic types of learning preferences) and the Felder-Silverman learning style model, which is a framework that categorizes learners based on their preferences across several dimensions: active/reflective, sensing/intuitive, visual/verbal, and sequential/global. Descriptive statistics and Spearman’s correlation were used to analyze the data. In relation to the VARK inventory, students exhibited a tendency to prefer multimodal sensory learning, particularly favoring the kinesthetic style. The number of VARK styles and the preference for kinesthetic learning were significantly correlated with learning gains. The Felder-Silverman test indicated that students preferred sensing, visual, and sequential learning; however, the levels of preference for active, intuitive, and sequential learning were associated with higher learning gains. Reflective learning demonstrated an inverse correlation with learning gains. Our results indicate the importance of incorporating experience and practical skills in the classroom. Additionally, it is recommended that students work collaboratively, share and discuss learning materials, foster innovation and abstract learning, and follow logical and sequential approaches to optimize their educational achievements. It is fundamental to find learning models that improve the academic performance of students with a reflective learning preference.