Rehabilitation strategies for low anterior resection syndrome. A systematic review

Objective. To summarize the evidence in the literature about rehabilitative treatments that reduce low anterior resection syndrome (LARS) symptoms in patients who underwent surgery for colorectal cancer.Methods. We have search in PubMed, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health and Scopus databases. Studies selected were limited to those including only patient undergone low rectal resection with sphincter preservation and with pre-post assessment with a LARS score. Five articles fit the criteria.Results. The percutaneous tibial nerve stimulation demonstrated moderate results and sacral nerve stimulation was found to be the best treatment with greater symptom improvement. Only one study considered sexual and urinary problems in the outcomes assessment.Conclusions. In clinical practice patients should evaluate with the LARS and other score for evaluation of urinary and sexual problems. Future research must be implemented with higher quality studies to identify the least invasive and most effective treatment/s.

Antitumor activity of the PI3K δ-sparing inhibitor MEN1611 in PIK3CA mutated, trastuzumab-resistant HER2 + breast cancer

PI3K inhibitor; PIK3CA mutations; Trastuzumab resistanceInhibidor de PI3K; Mutacions PIK3CA; Resistència al trastuzumabInhibidor de PI3K; Mutaciones PIK3CA; Resistencia a trastuzumabPurpose Dysregulation of the PI3K pathway is one of the most common events in breast cancer. Here we investigate the activity of the PI3K inhibitor MEN1611 at both molecular and phenotypic levels by dissecting and comparing its profile and efficacy in HER2 + breast cancer models with other PI3K inhibitors. Methods Models with different genetic backgrounds were used to investigate the pharmacological profile of MEN1611 against other PI3K inhibitors. In vitro studies evaluated cell viability, PI3K signaling, and cell death upon treatment with MEN1611. In vivo efficacy of the compound was investigated in cell line- and patient-derived xenografts models. Results Consistent with its biochemical selectivity, MEN1611 demonstrated lower cytotoxic activity in a p110δ-driven cellular model when compared to taselisib, and higher cytotoxic activity in the p110β-driven cellular model when compared to alpelisib. Moreover, MEN1611 selectively decreased the p110α protein levels in PIK3CA mutated breast cancer cells in a concentration- and proteasome-dependent manner. In vivo, MEN1611 monotherapy showed significant and durable antitumor activity in several trastuzumab-resistant PIK3CA-mutant HER2 + PDX models. The combination of trastuzumab and MEN1611 significantly improved the efficacy compared to single agent treatment. Conclusions The profile of MEN1611 and its antitumoral activity suggest an improved profile as compared to pan-inhibitors, which are limited by a less than ideal safety profile, and isoform selective molecules, which may potentially promote development of resistance mechanisms. The compelling antitumor activity in combination with trastuzumab in HER2 + trastuzumab-resistant, PIK3CA mutated breast cancer models is at the basis of the ongoing B-Precise clinical trial (NCT03767335).This work was supported by Regione Lazio, POR FESR 2014–2020 Bando “Life 2020_Progetti. integrati” for the project “PISTA (PI3K for Solid Tumor therApy)” (CUP F57H18000070007)

Effect of bovine lactoferrin on chlamydia trachomatis infection and inflammation.

Chlamydia trachomatis is an obligate, intracellular pathogen responsible for the most common sexually transmitted bacterial disease worldwide, causing acute and chronic infections. The acute infection is susceptible to antibiotics, whereas the chronic one needs prolonged therapies, thus increasing the risk of developing antibiotic resistance. Novel alternative therapies are needed. The intracellular development of C. trachomatis requires essential nutrients, including iron. Iron-chelating drugs inhibit C. trachomatis developmental cycle. Lactoferrin (Lf), a pleiotropic iron binding glycoprotein, could be a promising candidate against C. trachomatis infection. Similarly to the efficacy against other intracellular pathogens, bovine Lf (bLf) could both interfere with C. trachomatis entry into epithelial cells and exert an anti-inflammatory activity. In vitro and in vivo effects of bLf against C. trachomatis infectious and inflammatory process has been investigated. BLf inhibits C. trachomatis entry into host cells when incubated with cell monolayers before or at the moment of the infection and down-regulates IL-6/IL-8 synthesized by infected cells. Six out of 7 pregnant women asymptomatically infected by C. trachomatis, after 30 days of bLf intravaginal administration, were negative for C. trachomatis and showed a decrease of cervical IL-6 levels. This is the first time that the bLf protective effect against C. trachomatis infection has been demonstrated

Dissecting the Gaia HR diagram II. The vertical structure of the star formation history across the Solar Cylinder

Starting from the Gaia DR3 HR diagram, we derive the star formation history (SFH) as a function of distance from the Galactic Plane within a cylinder centred on the Sun with a 200 pc radius and spanning 1.3 kpc above and below the Galaxy's midplane. We quantify both the concentration of the more recent star formation in the Galactic Plane, and the age-related increase in the scale height of the Galactic Disc stellar component, which is well-described by power-laws with indices ranging from 1/2 to 2/3. The vertically-integrated star formation rate falls from (1.147 ± 0.039) × 10-8 M⊙yr-1pc-2 at earlier times down to (6.2 ± 3.0) × 10-9 M⊙yr-1pc-2 at present times, but we find a significant peak of star formation in the 2 to 3 Gyr age bin. The total mass of stars formed per unit area over time is 118.7 ± 6.2 M⊙pc-2, which is nearly twice the present stellar mass derived from kinematics within 1 kpc from the Galactic Plane, implying a high degree of matter recycling in successive generations of stars. The method is then modified by adopting an age-dependent correlation between the SFH across the different slices, which results in less noisy and more symmetrical results without significantly changing the previously mentioned quantities. This appears to be a promising way to improve SFH recovery in external galaxies

Dissecting the Gaia HR diagram II. The vertical structure of the star formation history across the Solar Cylinder

Starting from the Gaia DR3 HR diagram, we derive the star formation history (SFH) as a function of distance from the Galactic Plane within a cylinder centred on the Sun with a 200~pc radius and spanning 1.3~kpc above and below the Galaxy's midplane. We quantify both the concentration of the more recent star formation in the Galactic Plane, and the age-related increase in the scale height of the Galactic Disc stellar component, which is well-described by power-laws with indices ranging from $1/2$ to $2/3$. The vertically-integrated star formation rate falls from $(1.147 \pm 0.039)\times10^{-8}\, \text{M}_{\odot} \text{yr}^{-1} \text{pc}^{-2}$ at earlier times down to $(6.2 \pm 3.0) \times10^{-9}\, \text{M}_{\odot} \text{yr}^{-1} \text{pc}^{-2}$ at present times, but we find a significant peak of star formation in the 2 to 3 Gyr age bin. The total mass of stars formed per unit area over time is $118.7 \pm 6.2\, \text{M}_{\odot} \text{pc}^{-2}$, which is nearly twice the present stellar mass derived from kinematics within 1~kpc from the Galactic Plane, implying a high degree of matter recycling in successive generations of stars. The method is then modified by adopting an age-dependent correlation between the SFH across the different slices, which results in less noisy and more symmetrical results without significantly changing the previously mentioned quantities. This appears to be a promising way to improve SFH recovery in external galaxies.Comment: Accepted for publication in MNRA

Efeitos do ACO isolado ou associado a antiandrogênios sobre a melhora do hirsutismo e perfil endócrino-metabólico em pacientes hirsutas

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Explorando os efeitos da sincronização do segundo estro e flushing alimentar sobre a incidência de cistos ovarianos em marrãs utilizando gonadotrofinas exógenas

Estrus stimulation by exogenous gonadotropins (EG) in association with dietary flushing is an important tool for the improvement of gilt reproductive performance. However, there is evidence associating both flushing and EG with a disturbance in the endocrine balance that could lead to increased ovarian cysts. The aim of this study was to evaluate whether flushing or EG might affect the ovulation rate and the incidence of ovarian cysts. Seventy-one gilts were randomly distributed into 2x2 factorial design with four treatments: flushing and hormone (wFwH); no flushing and hormone (nFwH); flushing without hormone (wFnH); and neither flushing nor hormone (nFnH). Gilts were slaughtered for macroscopic and histopathological ovary examination approximately five days after AI. The characterization of these cysts was performed by optical microscopy in the following: follicular cysts (FC), luteinized cysts (LC) or cystic corpora lutea (CCL). The number of ovulations did not differ between treatments. There was no interaction between the factors in any analyzed variable. The frequency of gilts with CCL and LC was not affected by flushing and EG. No difference was found in the incidence of FC, with 12.5% and 5.88% in gilts from wFwH and nFwH treatments, respectively. There were no differences in the proportion of CCL between FC and LC (9.85 vs. 4.22 and 4.22%, respectively). In conclusion, the use of exogenous gonadotropins for second estrus synchronization in gilts, either alone or in association with dietary flushing, does not increase the incidence of ovarian cysts, nor does it decrease the ovulation rate.A estimulação do estro por gonadotrofinas exógenas (GE) associada ao flushing alimentar é uma ferramenta importante na melhoria do desempenho reprodutivo de marrãs. Contudo, há evidência da associação do flushing com GE levando ao desequilíbrio no sistema endócrino que poderia levar ao aumento de cistos ovarianos. O objetivo deste estudo foi avaliar se o flushing ou GE pode afetar a taxa de ovulação e a incidência de cistos ovarianos. Setenta e uma marrãs foram distribuídas aleatoriamente em arranjo fatorial 2x2 com quatro tratamentos: flushing e hormônio (cFcH); sem flushing e com hormônio (sFcH); com flushing e sem hormônio (cFsH) e sem flushing e hormônio (sFsH). Marrãs foram abatidas para exame macroscópico e histopatológico dos ovários, aproximadamente cinco dias após IA. A caracterização desses cistos foi realizada por microscopia óptica: cistos foliculares (CF), cistos luteinizados (CL) ou corpos lúteos císticos (CCL). O número de ovulações não diferiu entre os tratamentos. Não houve interação entre os fatores em qualquer variável analisada. A frequência de leitoas com CCL e CL não foi afetada pelo flushing e GE. Não houve diferença na incidência de CF, com 12,5% e 5,88 % em leitoas dos tratamentos cFcH e sFcH, respectivamente. Não foram obtidas diferenças na proporção de CCL entre CF e CL (9,85 vs. 4,22 e 4,22%, respectivamente). Em conclusão, a utilização de gonadotrofinas exógenas para sincronização do segundo estro de marrãs, isoladamente ou em associação com o flushing, não aumenta a incidência de cistos ovarianos e não diminui a taxa de ovulação

Constraining the thermally pulsing asymptotic giant branch phase with resolved stellar populations in the Large Magellanic Cloud

Reliable models of the thermally pulsing asymptotic giant branch (TP-AGB) phase are of critical importance across astrophysics, including our interpretation of the spectral energy distribution of galaxies, cosmic dust production, and enrichment of the interstellar medium. With the aim of improving sets of stellar isochrones that include a detailed description of the TP-AGB phase, we extend our recent calibration of the AGB population in the Small Magellanic Cloud (SMC) to the more metal-rich Large Magellanic Cloud (LMC). We model the LMC stellar populations with the trilegal code, using the spatially resolved star formation history derived from the VISTA survey. We characterize the efficiency of the third dredge-up by matching the star counts and the Ks-band luminosity functions of the AGB stars identified in the LMC. In line with previous findings, we confirm that, compared to the SMC, the third dredge-up in AGB stars of the LMC is somewhat less efficient, as a consequence of the higher metallicity. The predicted range of initial mass of C-rich stars is between Mi 48 1.7 and 3 M 99 at Zi = 0.008. We show how the inclusion of new opacity data in the carbon star spectra will improve the performance of our models. We discuss the predicted lifetimes, integrated luminosities, and mass-loss rate distributions of the calibrated models. The results of our calibration are included in updated stellar isochrones publicly available