Pathologic vs. protective roles of hypoxia-inducible factor 1 in RPE and photoreceptors in wet vs. dry age-related macular degeneration.

It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced-while HIF-1 augmentation reduced-photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1α in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1α expression in photoreceptors contributes to the development of GA.

Impacts of intake of trichothecenes (Fusarium sporotrichioides) for dairy calves: Effects on animal growth, oxidative and inflammatory response.

The objective of the present study was to evaluate the impacts of trichothecenes (Fusarium sporotrichioides) for dairy calves on animal growth, oxidative and inflammatory responses in the presence or absence of essential oils. Twelve calves weaned at 70 days of age were divided into 2 groups: T-C (control) and T-EO (essential oils - oregano, thyme, basil and rosemary) in the period of 40 days consuming ration contaminated by trichothecenes (500 ppb). The animals in the T-EO group received a mixture of EOs via feed at a dosage of 0.75 mL per/kg of feed. Blood collections were performed on days 1, 20 and 40 for hematological and biochemical analyses; the fecal score was performed every 2 days on a scale of 1-5 and clinical examinations were performed 3 times during the experiment period. The animals were weighed at the beginning and at the end of the experiment; euthanasia of two calves per group for macroscopic and microscopic evaluation of several tissues (spleen, liver, duodenum, jejunum, ilium, cecum and colon) was performed at the end of the experiment. The calves in the T-EO group had a tendency (P = 0.07) of higher body weight when compared to the T-C. Treatment effect and treatment vs day interaction was detected for leukocytes and granulocytes variables, demonstrating a higher count of these cells in the T-EO group on both days (20 and 40), and the same behavior occurred for the distribution amplitude of erythrocytes (RDW). The enzymes alanine transferase (ALT), aspartate transferase (AST) and gamma glutamyl-transferase (GGT) showed higher serum activity in the T-C group (days 20 and 40). The levels of thiobarbituric acid reactive substances (TBARS) were lower in the serum of animals in the T-EO group. For calves in the T-EO group, glutathione S-transferase activity was higher in serum. Haptoglobulin and C-reactive protein levels were lower on days 20 and 40 in T-EO animals when compared to the T-C group. In the macroscopic and microscopic evaluations, which were collected at the end of the experiment after slaughtering the animals, liver and intestine did not show changes for the animals in the T-EO group, unlike the animals in the T-C group, which had moderately firm diffuse consistency of the liver and edema in the mesentery, as well as oxidative stress in tissues (liver, duodenum, jejunum, ileum, cecum and colon). The results concluded that the consumption of a mixture of EOs (essential oils - oregano, thyme, basil and rosemary) minimized the negative effects caused by trichothecenes in dairy calves, thus being an alternative to improving the immunological and antioxidant condition, as well as a possible adsorbent alternative.

Effect of calving to timed artificial insemination interval on fertility of beef cows.

The objectives of this study were to determine the effect of calving to timed artificial insemination (C-TAI) interval on fertility of Bos taurus and Bos indicus cows and to determine the best C-TAI interval to include postpartum cows in TAI programs in each genotype (B. taurus and B. indicus). In experiment 1, a retrospective study was performed, with data from 2,709 TAI in Bos taurus and Bos indicus cows with different C-TAI intervals. There was a positive linear effect of C-TAI interval on the pregnancy probability (p < .0001). However, there was no effect or interaction with the genotype. When C-TAI intervals were grouped in classes, pregnancy rate differed in groups (p < .05). Receiver operating characteristic (ROC) analysis was performed, and it was observed that 52 days would be the better C-TAI interval to maximize fertility in beef cows. According to the previous result, we further stratified into two C-TAI interval groups (≤ 52 days or > 52 days). Cows with C-TAI longer than 52 days (C-TAI > 52) had greater pregnancy rate (56%) than cows with short C-TAI (46%; p < .01). In experiment 2, 18 postpartum beef cows were subjected to TAI protocol at different C-TAI intervals (n = 6 cows per group): 40, 60 or 80 days postpartum. Cows with 60 days of C-TAI had a greater preovulatory follicle diameter than cows with 80 days postpartum (p < .05). The C-TAI interval did not affect (p > .05) the ovulation rate nor the proportion of endometrial polymorphonuclear leucocytes. We conclude that C-TAI interval affects pregnancy rate in both Bos taurus and Bos indicus. We recommend a C-TAI interval longer than 52 days to increase fertility of beef cows included in TAI programs.

Mineralization of Phosphorylated Fish Skin Collagen/Mangosteen Scaffolds as Potential Materials for Bone Tissue Regeneration.

In this study, a potential hard tissue substitute was mimicked using collagen/mangosteen porous scaffolds. Collagen was extracted from Tilapia fish skin and mangosteen from the waste peel of the respective fruit. Sodium trimetaphosphate was used for the phosphorylation of these scaffolds to improve the nucleation sites for the mineralization process. Phosphate groups were incorporated in the collagen structure as confirmed by their attenuated total reflection Fourier transform infrared (ATR-FTIR) bands. The phosphorylation and mangosteen addition increased the thermal stability of the collagen triple helix structure, as demonstrated by differential scanning calorimetry (DSC) and thermogravimetry (TGA) characterizations. Mineralization was successfully achieved, and the presence of calcium phosphate was visualized by scanning electron microscopy (SEM). Nevertheless, the porous structure was maintained, which is an essential characteristic for the desired application. The deposited mineral was amorphous calcium phosphate, as confirmed by energy dispersive X-ray spectroscopy (EDX) results.

Bevacizumab versus triamcinolone for persistent diabetic macular edema: a randomized clinical trial.

PURPOSE: To evaluate 24-week visual acuity and anatomic outcomes of two "pro re nata" (prn) treatment strategies (intravitreal bevacizumab [IVB] prn versus intravitreal triamcinolone acetonide [IVT] prn) in patients with persistent diabetic macular edema (pDME) after 24 weeks of prn-IVB. METHODS: One hundred eyes with center-involving DME were enrolled and treated with prn-IVB for 24 weeks; at week 24, eyes with pDME (central subfield thickness [CST] on spectral domain optical coherence tomography > 300 µm) were randomized to IVB monthly prn (group I; prn-IVB) or IVT every 3 months prn (group II; prn-IVT) and eyes in which the CST was ≤ 300 µm were assigned to continue prn-IVB (group III). RESULTS: Seventy-four eyes completed a 48-week study period. At week 24, 65 (79.3%) eyes still had DME with CST > 300 µm and, therefore, were randomized to prn-IVB (group I, n = 33) or prn-IVT (group II, n = 32); the remaining 17 (20.7%) eyes had CST ≤ 300 µm and were assigned to continued treatment with prn-IVB (group III). At baseline, mean CST (µm) ± standard error of the mean (SEM) was 447.2 ± 24.4, 478.0 ± 19.7, and 386.0 ± 21.0 in groups I, II, and III, respectively (p > 0.05). At week 48, there was no significant difference in mean CST between groups I and II (369.9 ± 23.3 and 426.0 ± 26.1, respectively; p = 0.9995). A significant reduction in mean CST, compared with baseline, was noted at weeks 28 (p = 0.0002) and 44 (p = 0.0002) in group II. Group I did not show a significant reduction in mean CST compared with baseline at any study visit. There were no significant differences in mean CST between groups I and II at any study visit. At baseline, mean ± SEM best-corrected visual acuity (BCVA) (logMAR) was 0.50 ± 0.00, 0.60 ± 0.10, and 0.50 ± 0.10 in groups I, II, and III, respectively (p > 0.05). At week 48, there was no statistically significant difference in mean BCVA between groups I and II (0.50 ± 0.10 and 0.80 ± 0.10, respectively; p = 0.4473). There was no significant improvement in mean BCVA, as compared with baseline, at any study follow-up visit in any of the groups. Group II demonstrated significantly lower BCVA after 24 weeks of IVT (at week 48) compared with baseline (p = 0.0435). There was no significant difference in mean BCVA between groups I and II at any time-point. CONCLUSION: In eyes with pDME after 24 weeks of treatment with prn-IVB, there was no difference between continued treatment with prn-IVB versus a treatment switch to prn-IVT with respect to mean BCVA or mean CST at week 48. However, BCVA was stable in the prn-IVB group, while prn-IVT was associated with BCVA reduction from baseline and a higher risk of IOP elevation.

Angiopoietin-like 4 is a potent angiogenic factor and a novel therapeutic target for patients with proliferative diabetic retinopathy.

Diabetic eye disease is the most common cause of severe vision loss in the working-age population in the developed world, and proliferative diabetic retinopathy (PDR) is its most vision-threatening sequela. In PDR, retinal ischemia leads to the up-regulation of angiogenic factors that promote neovascularization. Therapies targeting vascular endothelial growth factor (VEGF) delay the development of neovascularization in some, but not all, diabetic patients, implicating additional factor(s) in PDR pathogenesis. Here we demonstrate that the angiogenic potential of aqueous fluid from PDR patients is independent of VEGF concentration, providing an opportunity to evaluate the contribution of other angiogenic factor(s) to PDR development. We identify angiopoietin-like 4 (ANGPTL4) as a potent angiogenic factor whose expression is up-regulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. Expression of ANGPTL4 was increased in the aqueous and vitreous of PDR patients, independent of VEGF levels, correlated with the presence of diabetic eye disease, and localized to areas of retinal neovascularization. Inhibition of ANGPTL4 expression reduced the angiogenic potential of hypoxic Müller cells; this effect was additive with inhibition of VEGF expression. An ANGPTL4 neutralizing antibody inhibited the angiogenic effect of aqueous fluid from PDR patients, including samples from patients with low VEGF levels or receiving anti-VEGF therapy. Collectively, our results suggest that targeting both ANGPTL4 and VEGF may be necessary for effective treatment or prevention of PDR and provide the foundation for studies evaluating aqueous ANGPTL4 as a biomarker to help guide individualized therapy for diabetic eye disease.

Atypical retinal pigment epithelial defects with retained photoreceptor layers: a so far disregarded finding in age related macular degeneration.

BACKGROUND: To report patients with age-related macular degeneration and atypical central retinal pigment epithelium (RPE) defects not attributable to geographic atrophy (GA) or RPE-tears with overlying preserved photoreceptor layers. METHODS: Multimodal imaging case-series evaluating the course of atypical RPE- defects in patients with AMD using Color fundus images, Optical coherence tomography (OCT), OCT-Angiography, fundus autofluorescence (FAF) and fluorescein-angiography (FA). RESULTS: Ten patients were identified. Three patients had a prior RPE-rip and were excluded. Seven patients with a mean follow-up period of 47 ± 38 months after the occurrence of the RPE-defect were included (age range 71-87 years). Mean distance Best corrected visual acuity (BCVA) at initial presentation was 0.36 ± 0.29logMAR and at last follow-up visit 0.51 ± 0.43logMAR. Patients presented with clinically apparent GA on funduscopy and FAF, but preserved photoreceptor layers on optical coherence tomography (OCT). On FA there was early hyperfluorescence and late pooling visible. Over time, migration of RPE/drusenoid material right above the Bruch's membrane with concomitant decrease of hypoautofluorescence was detectable in 4 cases. An enlargement of the RPE-defect was apparent in the remaining 3 cases. The majority (n = 4) showed a drusenoid pigment epithelium detachment (PED) preceding the lesion. CONCLUSIONS: Beside GA and characteristic RPE-tears, another atypical form of RPE-defect with overlying preserved photoreceptor layers are found in AMD. This so far disregarded subgroup of patients present with reasonable visual function and long-term survival of photoreceptors layers. Repair mechanisms such as ingrowth of RPE/drusenoid material and persistent subretinal fluid (SRF), but also a RPE-independent visual cycle for cone photopigment within the neurosensory retina may contribute to their favorable course.

Hypoxic retinal Muller cells promote vascular permeability by HIF-1-dependent up-regulation of angiopoietin-like 4.

Vision loss from ischemic retinopathies commonly results from the accumulation of fluid in the inner retina [macular edema (ME)]. Although the precise events that lead to the development of ME remain under debate, growing evidence supports a role for an ischemia-induced hyperpermeability state regulated, in part, by VEGF. Monthly treatment with anti-VEGF therapies is effective for the treatment of ME but results in a major improvement in vision in a minority of patients, underscoring the need to identify additional therapeutic targets. Using the oxygen-induced retinopathy mouse model for ischemic retinopathy, we provide evidence showing that hypoxic Müller cells promote vascular permeability by stabilizing hypoxia-inducible factor-1α (HIF-1α) and secreting angiogenic cytokines. Blocking HIF-1α translation with digoxin inhibits the promotion of endothelial cell permeability in vitro and retinal edema in vivo. Interestingly, Müller cells require HIF--but not VEGF--to promote vascular permeability, suggesting that other HIF-dependent factors may contribute to the development of ME. Using gene expression analysis, we identify angiopoietin-like 4 (ANGPTL4) as a cytokine up-regulated by HIF-1 in hypoxic Müller cells in vitro and the ischemic inner retina in vivo. ANGPTL4 is critical and sufficient to promote vessel permeability by hypoxic Müller cells. Immunohistochemical analysis of retinal tissue from patients with diabetic eye disease shows that HIF-1α and ANGPTL4 localize to ischemic Müller cells. Our results suggest that ANGPTL4 may play an important role in promoting vessel permeability in ischemic retinopathies and could be an important target for the treatment of ME.

Robotic-Assisted Resection of a Benign Schwannoma of the Obturator Nerve: A Rare Case.

BACKGROUND Neurilemmomas are rare tumors derived from the Schwann cells that comprise the peripheral nerve sheaths. They have a slow growth and rarely display malignancy. Early diagnosis is rare, and the treatment consists by surgical resection. Although robotic-assisted surgery is commonly used for treating retroperitoneal diseases, there are few reports of resection of retroperitoneal and pelvic schwannoma through robotic-assisted surgery. In the present study, we reported a case of complete excision of a benign retroperitoneal schwannoma of the obturator nerve by robotic-assisted surgery. CASE REPORT A 51-year-old woman was referred by her gynecologist for left pelvic discomfort of a 3-month duration. The physical examination was normal, but a computerized tomography scan of the abdomen and pelvis showed an expansive pelvic lesion in the topography of the left iliac vessels, a hypodense contrast enhancement measuring 4.6×3.4 cm. Magnetic resonance imaging showed an extraperitoneal lesion located medially and inferiorly to the left external iliac vessels, with a size of 4.9×3.7 cm, and of probable neural etiology. Surgical resection of the tumor was recommended because of the diagnostic hypothesis of obturator nerve schwannoma. CONCLUSIONS This case showed that retroperitoneal neurilemmomas are difficult to diagnose owing to a lack of specific symptoms, and the best treatment is complete tumor resection. The use of robotic techniques gives greater dexterity to the surgeon, since it provides high-definition 3-dimensional vision, which can make the removal of retroperitoneal tumors susceptible to minimally invasive resection in a safe and effective way.

Enemas with N-acetylcysteine can reduce the level of oxidative damage in cells of the colonic mucosa diverted from the faecal stream.

BACKGROUND: Oxidative stress has been related to inflammation of the colonic mucosa in patients with diversion colitis (DC). AIM: The purpose of this study was to evaluate the antioxidants effects of n-acetylcysteine (NAC) in colon segments without faecal stream. METHODS: Thirty-six Wistar rats were subjected to diversion of the faecal stream by proximal colostomy and a distal mucosal colon fistula. They were distributed into three experimental groups of 12 animals each; the animals in each group underwent daily enemas containing saline solution (control group) or either a 25 or 100 mg/kg dose of NAC (treated groups). In each group, animals were sacrificed after 2 or 4 weeks. The degree of inflammation was determined by histopathological analysis and stratified by inflammatory grading scale. Oxidative DNA damage was measured by comet assay. The Mann-Whitney test and ANOVA were used for statistical analysis; p<0.05 was considered significant. RESULTS: The oxidative DNA damage in colon segments without faecal stream was significantly lower in animals treated with either concentration of NAC than in control group, regardless of the duration of intervention (p<0.01). CONCLUSIONS: Intrarectal application of NAC reduces the inflammation as well as DNA oxidative damage and could be beneficial as a complementary agent in the treatment of DC.

Seidel and India ink tests assessment of different clear cornea side-port incision configurations.

BACKGROUND: Post-cataract endophthalmitis has increased after introduction of clear cornea incisions (CCI). Laboratory models suggested that these incisions might not be competent at certain changes in intraocular pressure (IOP). Considering that side-port incisions (SPI) might behave similarly, the purpose of the present study was to determine the most stable side-port incision configuration. METHODS: Using four cadaveric human eyes, four different side-port incisions (SPI) were created in each cornea: 1.5 mm and 2.5 mm squared tunnel, 1.5 mm and 2.5 mm stab tunnel. Fluorescein was placed on the eye, and the IOP varied from 10 to 80 mmHg. IOP at which each SPI started leaking was recorded. In the second part of the study, India ink was applied to the corneal surface at normal IOP, and then rinsed with balanced salt solution (BSS). The ink influx was recorded by planimetry. IOP was elevated to 80 mmHg, ink was reapplied, and IOP was dropped to 0 mmHg. Ink influx was measured again. Histological examination was used to visualize ink inflow into each incision. RESULTS: There was no statistically significant difference in the IOP levels at which the different incisions leaked (p = 0.52). A significant increase in the length of India ink ingress in all incision types was measured after IOP variation (p < 0.05). The 2.5 mm squared incision showed the least increase in ink inflow in this test. CONCLUSION: All incision types of SPIs tested exhibited similar resistance to leakage after IOP variation. Good resistance to wound leakage may not predict adequate resistance to the inflow of bacterial-sized particles into the wound.

Combined intravitreal dexamethasone and bevacizumab injection for the treatment of persistent diabetic macular edema (DexaBe study): a phase I clinical study.

PURPOSE: The aim of this study is to investigate the safety of combined intravitreal injection of dexamethasone aqueous-solution (IVD) and bevacizumab (IVB) in patients with refractory diabetic macular edema (DME) and its effect on intraocular pressure (IOP), best-corrected visual acuity (BCVA) and central subfield thickness (CSFT). METHODS: This prospective study included 10 patients (10 eyes) with DME refractory to laser photocoagulation and/or anti-vascular endothelial growth factor (anti-VEGF) therapy. A complete ophthalmological examination was performed at baseline, during the first week of treatment, and monthly through week 24. Therapy consisted of monthly injections of combined IVD and IVB "pro re nata" (PRN) if CST > 300 µm. We investigated the impact of the injections on intraocular pressure (IOP), cataract development, Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA), and central sub-foveal thickness (CSFT) measured by spectral-domain optical coherence tomography (OCT). RESULTS: Eight patients (80%) completed 24 weeks of follow-up. Compared to baseline, mean IOP increased significantly (p < 0.05) and anti-glaucomatous eye drops were necessary for 50% of the patients, CSFT was significantly reduced at all follow-up visits (p < 0.05), although mean BCVA showed no significant improvement. One patient developed dense cataract progression and another showed vitreoretinal traction at week 24. No inflammation or endophthalmitis was observed. CONCLUSION: Treatment of DME refractory to laser and/or anti-VEGF therapy with combined PRN IV dexamethasone aqueous solution and bevacizumab was associated with adverse effects related to the use of corticosteroids. However, there was a significant improvement in CSFT meantime best-correct visual acuity remained stable or improved in 50% of patients.

Short-pulse laser plus subthreshold diffuse laser for serous retinal detachment in dome-shaped macula.

BACKGROUND: First described by Gaucher and associates in 2008, dome-shaped macula (DSM) is an anterior convex protrusion of the macula visible on OCT (optical coherence tomography). Visual impairment in DSM results mainly from sub-foveal serous retinal detachment (SRD). Herein, this original study from retrospective data analysis evaluate the anatomical and functional effects of Pascal® short-pulse (SP) laser plus endpoint management (EpM) subthreshold diffuse laser (SDL) in patients with SRD due to DSM. METHODS: This retrospective study included seven consecutive patients (eight eyes) with SRD secondary to dome-shaped macula who underwent a comprehensive ophthalmological evaluation including logMAR BCVA, slit-lamp biomicroscopy, indirect ophthalmoscopy, and spectral-domain optical coherence tomography (SD-OCT) (Spectralis; Heidelberg Engineering, Germany) before combined Pascal® SP laser plus EpM-SDL with 1 to 6 month intervals, postoperatively, with a mean ± standard error (SE) follow-up time of 12.92 ± 1.34 months. RESULTS: Eight eyes from seven patients were analyzed in this study. At baseline, mean BCVA (LogMAR) ± standard error (SE) and mean CST (central subfield thickness)(µm) ± SE were 0.6125 ± 0.14 and 412.50 ± 24.65, respectively. After a mean follow-up time of 12.92 ± 1.34 months, mean CST (µm) ± SE and BCVA (LogMAR) ± SE were 294.75 ± 19.68 (p = 0.0078) and 0.4537 ± 0.12 (p = 0.0313), respectively. A statistically significant reduction in mean CST and an improvement in mean BCVA were noted after SRD resolution with laser therapy application. The mean serous retinal detachment resolution time (months) ± SE was 3.75 ± 1.08. No adverse events were registered, including enlargement of atrophic alterations and choroidal neovascularization. CONCLUSIONS: The novel combined laser modality with Pascal® SP laser plus EpM-SDL treatment may induce subretinal fluid regression and BCVA improvement 1 year after treatment in DSM patients with SRD.

Internal post-bariatric hernia due to hepatic adhesion: a case report.

Roux-en-Y gastric bypass, a procedure proven effective for treating morbid obesity and metabolic disorders, carries the risk of complications such as the formation of internal hernias. These hernias are often difficult to diagnose and can be potentially fatal because they can cause structural obstruction. Most internal hernias occur in the jejunojejunostomy mesentery space, followed by Petersen's space hernias, although herniation at other locations can also occur. Our case report presents an example of a rare internal hernia after laparoscopic Roux-en-Y gastric bypass. A 36-year-old woman presented with an uncommon internal hernia located between the liver and alimentary loop, resulting in the formation of a new space and consequently incarcerating the entire biliopancreatic loop. This type of internal hernia is rare and has not been reported in the literature, indicating that this is the first report of such a case. In this case, we realized that the diagnosis was challenging and imaging examinations could not help determine the etiology of the pain and obstruction. Therefore, videolaparoscopy revealed an uncommon hernia formed by firm adhesion between the hepatic segment III and the alimentary loop mesentery. Our case is an example of an internal hernia that was not detected with a normal computed tomography scan of the abdomen and pelvis. Only diagnostic laparoscopy revealed herniation, effectively preventing further complications for the patient.

Robotic approach to remove four tailgut cyst cases in Brazil: a case series.

Tailgut cysts are rare congenital lesions that are remnants of the embryonic hindgut. This abnormality presents with non-specific symptoms or no symptoms; therefore, misdiagnosis is common. Here, we present four cases of tailgut cysts that were successfully removed using a robotic surgical approach. A 42-year-old woman with tenesmus, pain in the right gluteal region, and discomfort in the rectal region during evacuation was referred to our medical center. Another patient was a 28-year-old woman who presented with the same symptoms to our general practitioner. Both patients underwent upper abdominal and pelvic magnetic resonance imaging that revealed a tailgut cyst. Further, a 36-year-old woman was referred with coccyx and hypogastric pain. Magnetic resonance imaging revealed two pararectal cystic formations. She underwent robot-assisted surgery, and after analysis by a pathologist, the conclusion was that the tailgut cyst was associated with scarring fibrosis. A 55-year-old woman with posterior epigastric pelvic pain associated with heartburn underwent robot-assisted surgery to resect a retroperitoneal tumor. These cases highlighted the importance of tailgut cysts in the differential diagnosis of rectal lesions. Surgical treatment is preferred because malignant transformations can occur. The difference between laparoscopic and robotic approaches is the better visualization and stability of the latter, inducing less tissue damage. Robotic resection is a safe procedure, especially in patients with a narrow pelvis, because it reduces tissue damage.

Recent advances in the development of smart, active, and bioactive biodegradable biopolymer-based films containing betalains.

Betalains are natural nitrogenous water-soluble pigments found in species belonging to the Caryophyllales order and in mushrooms. Betalains can be considered multifunctional molecules due to their diverse bioactivities such as antioxidant, antimicrobial, anticancer, and anti-inflammatory. Furthermore, they can detect pH variations in foods and are considered promising colorimetric bioindicators. The bioactivities of betalains have improved their use as active and bioactive agents, and colorimetric indicators in the development of edible and biodegradable films for foods, which are trends in the food packaging market. Thus, this review presents the state-of-art information on the use of betalains as a multifunctional molecule in the development of smart, active, and bioactive edible and biodegradable packaging for foods. Studies have revealed that betalains can be successfully used to develop: smart films to indicate the freshness and spoilage of foods such as shrimp, fish, and chicken; active films with antimicrobial and antioxidant potentials to increase the shelf life of sausage and shrimp; and bioactive films with health benefits.

ANGPTL4 influences the therapeutic response of patients with neovascular age-related macular degeneration by promoting choroidal neovascularization.

Most patients with neovascular age-related macular degeneration (nvAMD), the leading cause of severe vision loss in elderly US citizens, respond inadequately to current therapies targeting a single angiogenic mediator, vascular endothelial growth factor (VEGF). Here, we report that aqueous fluid levels of a second vasoactive mediator, angiopoietin-like 4 (ANGPTL4), can help predict the response of patients with nvAMD to anti-VEGF therapies. ANGPTL4 expression was higher in patients who required monthly treatment with anti-VEGF therapies compared with patients who could be effectively treated with less-frequent injections. We further demonstrate that ANGPTL4 acts synergistically with VEGF to promote the growth and leakage of choroidal neovascular (CNV) lesions in mice. Targeting ANGPTL4 expression was as effective as targeting VEGF expression for treating CNV in mice, while simultaneously targeting both was more effective than targeting either factor alone. To help translate these findings to patients, we used a soluble receptor that binds to both VEGF and ANGPTL4 and effectively inhibited the development of CNV lesions in mice. Our findings provide an assay that can help predict the response of patients with nvAMD to anti-VEGF monotherapy and suggest that therapies targeting both ANGPTL4 and VEGF will be a more effective approach for the treatment of this blinding disease.

Chitosan/gelatin films with jatobá resin: Control of properties by vegetal resin inclusion and degree of acetylation modification.

Blending chitosan and gelatin, two biodegradable and non-toxic polymers, is a recurrent choice in food coating or biomaterials development. The incorporation of vegetal extracts into chitosan/gelatin films can improve or introduce some properties to these materials. Jatobá resin is a product of Hymenaea genus trees with antimicrobial and anti-inflammatory activities, interesting properties for films applied in several areas. The chitosan degree of acetylation (DA) influences the inter and intramolecular interactions of this polymer and, therefore, also implicates in changes of its properties. This research aims to study the influence of jatobá resin inclusion and chitosan DA modification on chitosan/gelatin films properties. Both jatobá resin and chitosan DA affected physicochemical, antimicrobial and barrier properties of the films, allowing the control of these properties by changes in these parameters. Jatobá resin incorporation and the decrease in chitosan DA significantly improved antimicrobial activity and water vapor permeability of films with the reduction of water solubility and swelling.

Modified impression technique for extreme mouth-opening limitation caused by systemic scleroderma.

Systemic scleroderma is a relatively rare, autoimmune, chronic, and debilitating disease, and its etiology is unknown. The disease is characterized by vasomotor disturbances causing skin and mucosa hardening, hand stiffness, excess production of collagen fibers, and impairment of the internal organs associated with the immune system. Extreme mouth-opening limitation is one of the symptoms in the oral cavity, and compromises dental intervention. One of the fundamental steps when performing a dental procedure is dental arch impression. In the presented clinical case, limited mouth opening hindered the impression accuracy. The objective was to present an alternative impression technique for a patient affected by scleroderma, with limited mouth opening and the need for oral rehabilitation with a removable partial prosthesis in the maxillary arch. An individualized tray was developed with design characteristics that allowed access to the oral cavity and removal, after which it was possible to perform the oral impression, reproducing the areas of interest without causing injury to the oral tissues. The orientation plan was elaborated after obtaining the cast. The teeth were assembled, tested in the mouth, and sent to the laboratory for acrylization. The prosthesis was placed once ready. The alternative impression technique enabled oral rehabilitation of the patient despite the mouth-opening limitation, and provided an accurate impression and a good prosthetic result.

Clinical manifestations and visual outcomes associated with ocular toxoplasmosis in a Brazilian population.

Ocular toxoplasmosis is the leading cause of posterior uveitis worldwide. We conducted an observational study of 262 consecutive individuals (n = 344 eyes) with ocular toxoplasmosis who were followed over a 34-month period. Most subjects were T. gondii IgG + /IgM- (n = 242; 92.4%; 317 eyes), and 140 eyes (40.7%) had active lesions. For eyes in which retinal lesions were active at recruitment and best-corrected visual acuity (BCVA) could be measured (n = 133), 21.0% (n = 28) remained blind (BCVA below 20/400) after inflammation resolved. In these eyes, atypical ocular toxoplasmosis (OR 4.99; 95% CI 1.14-22.85; p = 0.0330), macular lesion (OR 9.95; 95% CI 2.45-47.15; p = 0.0019) and any complication (OR 10.26; 95% CI 3.82-30.67; p < 0.0001) were associated with BCVA below 20/200. For eyes with only inactive lesions at recruitment and BCVA measured (n = 178), 28.1% (n = 50) were blind. In these eyes, having at least one lesion larger than one disc-diameter (OR 6.30; 95% CI 2.28-22.46; p = 0.0013) and macular lesion (OR 5.69; 95% CI 2.53-13.54; p < 0.0001) were associated with BCVA below 20/200. Older age (OR 1.02; 95% CI 1.00-1.05; p = 0.0493) and active disease at presentation (OR 4.74; 95% CI 1.95-12.91; p = 0.0011) were associated with recurrences. Additional clinical attention should be directed towards patients with risk factors for poor visual outcome.