Studying host genetic background effects on multimorbidity of intestinal cancer development,type 2 diabetes and obesity in response to oral bacterial infection and high‐fat diet using the collaborative cross (CC) lines

BackgroundMultimorbidity of intestinal cancer (IC), type 2 diabetes (T2D) and obesity is a complex set of diseases, affected by environmental and genetic risk factors. High‐fat diet (HFD) and oral bacterial infection play important roles in the etiology of these diseases through inflammation and various biological mechanisms.MethodsTo study the complexity of this multimorbidity, we used the collaborative cross (CC) mouse genetics reference population. We aimed to study the multimorbidity of IC, T2D, and obesity using CC lines, measuring their responses to HFD and oral bacterial infection. The study used 63 mice of both sexes generated from two CC lines (IL557 and IL711). For 12 weeks, experimental mice were maintained on specific dietary regimes combined with co‐infection with oral bacteria Porphyromonas gingivalis and Fusobacterium nucleatum, while control groups were not infected. Body weight (BW) and results of a intraperitoneal glucose tolerance test (IPGTT) were recorded at the end of 12 weeks, after which length and size of the intestines were assessed for polyp counts.ResultsPolyp counts ranged between 2 and 10 per CC line. The combination of HFD and infection significantly reduced (P < .01) the colon polyp size of IL557 females to 2.5 cm², compared to the other groups. Comparing BW gain, IL557 males on HFD gained 18 g, while the females gained 10 g under the same conditions and showed the highest area under curve (AUC) values of 40 000‐45 000 (min mg/dL) in the IPGTT.ConclusionThe results show that mice from different genetic backgrounds respond differently to a high fat diet and oral infection in terms of polyp development and glucose tolerance, and this effect is gender related.     

Novel KCNQ2 Mutation in a Large Emirati Family With Benign Familial Neonatal Seizures

Mutations in voltage-gated potassium channel Kv7.2 are responsible for benign familial neonatal seizures type 1, a rare monogenic autosomal dominant inherited epilepsy syndrome. We describe a novel mutation (c.1126_1127delA) in exon 9 of KCNQ2, the gene encoding for the Kv7.2 channel, in a large Emirati family with benign familial neonatal seizures type 1. The mutation leads to a frameshift at amino acid position 376, triggering loss of function and haploinsufficiency. Patients with this mutation manifest repeated clonic seizures with normal interictal electroencephalograms and favorable prognoses. Signs occur within the first days of age, lingering well into puberty. KCNQ2 mutation screening, alongside genetic counseling, should be included in diagnostic evaluations of neonatal epileptic patients, potentially sparing the need for unnecessary investigations and treatment. To our knowledge, this report is the first of a KCNQ2 mutation in an Emirati family with benign familial neonatal seizures type 1.     

Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer

Cancer Chemotherapy and Pharmacology - CC-486 is an oral formulation of azacitidine that allows for extended dosing schedules to prolong azacitidine exposure to malignant cells and maximize...     

¿Es más efectivo el tratamiento combinado de electroestimulación transcutánea del nervio tibial y electroestimulación vaginal que el tratamiento en monoterapia de electroestimulación del nervio tibial para la vejiga hiperactiva? Un ensayo controlado aleatorizado

Introduction and objectivesOveractive bladder (OAB) is a prevalent disorder that increases with age and impairs patients’ quality of life. Guidelines recommend behavior modifications as the first-line treatment; however, physiotherapy has also been used with success, safety, and low cost. Transcutaneous tibial nerve electrical stimulation (TTNS) and vaginal electrical stimulation (VS) are being used in clinical physiotherapy practice. This study aimed to verify whether the addition of VS to TTNS is more beneficial than TTNS alone for women with OAB.Patients and methodsIn all, 106 women aged >18 years diagnosed with OAB or mixed urinary incontinence with prevalent OAB symptoms were randomly divided into 2 groups: Group 1: TTNS (n = 52); Group 2: TTNS + VS (n = 54). The 3 day voiding diary, pelvic floor muscle strength (Ortiz Scale), King's Health Questionnaire, and Overactive Bladder Questionnaire were assessed before and after treatment. Urinary frequency was considered the primary outcome, and a reduction of ≥ 3 micturitions/day was considered clinically relevant. Mixed linear models were used to compare the 2 groups.ResultsInitially, the groups were similar in age, body mass index, number of pregnancies, time of OAB onset, and prevalence of OAB symptoms. After treatment, a reduction in urinary frequency of 1.5 micturitions was observed in Group 2, which was not clinically relevant despite being statistically significant.ConclusionsThe addition of VS to TTNS for the treatment of OAB was not more effective than TTNS as a single therapy.