Evaluation of Matrix Metalloproteases by Artificial Intelligence Techniques in Negative Biopsies as New Diagnostic Strategy in Prostate Cancer.

Usually, after an abnormal level of serum prostate-specific antigen (PSA) or digital rectal exam, men undergo a prostate needle biopsy. However, the traditional sextant technique misses 15-46% of cancers. At present, there are problems regarding disease diagnosis/prognosis, especially in patients' classification, because the information to be handled is complex and challenging to process. Matrix metalloproteases (MMPs) have high expression by prostate cancer (PCa) compared with benign prostate tissues. To assess the possible contribution to the diagnosis of PCa, we evaluated the expression of several MMPs in prostate tissues before and after PCa diagnosis using machine learning, classifiers, and supervised algorithms. A retrospective study was conducted on 29 patients diagnosed with PCa with previous benign needle biopsies, 45 patients with benign prostatic hyperplasia (BHP), and 18 patients with high-grade prostatic intraepithelial neoplasia (HGPIN). An immunohistochemical study was performed on tissue samples from tumor and non-tumor areas using specific antibodies against MMP -2, 9, 11, and 13, and the tissue inhibitor of MMPs -3 (TIMP-3), and the protein expression by different cell types was analyzed to which several automatic learning techniques have been applied. Compared with BHP or HGPIN specimens, epithelial cells (ECs) and fibroblasts from benign prostate biopsies before the diagnosis of PCa showed a significantly higher expression of MMPs and TIMP-3. Machine learning techniques provide a differentiable classification between these patients, with greater than 95% accuracy, considering ECs, being slightly lower when considering fibroblasts. In addition, evolutionary changes were found in paired tissues from benign biopsy to prostatectomy specimens in the same patient. Thus, ECs from the tumor zone from prostatectomy showed higher expressions of MMPs and TIMP-3 compared to ECs of the corresponding zone from the benign biopsy. Similar differences were found for expressions of MMP-9 and TIMP-3, between fibroblasts from these zones. The classifiers have determined that patients with benign prostate biopsies before the diagnosis of PCa showed a high MMPs/TIMP-3 expression by ECs, so in the zone without future cancer development as in the zone with future tumor, compared with biopsy samples from patients with BPH or HGPIN. Expression of MMP -2, 9, 11, and 13, and TIMP-3 phenotypically define ECs associated with future tumor development. Also, the results suggest that MMPs/TIMPs expression in biopsy tissues may reflect evolutionary changes from prostate benign tissues to PCa. Thus, these findings in combination with other parameters might contribute to improving the suspicion of PCa diagnosis.

Outcomes after 20 years of experience in minimally invasive living-donor nephrectomy.

INTRODUCTION: The transperitoneal laparoscopic approach is considered the gold standard technique for living kidney donation. Other accepted laparoscopic techniques include the retroperitoneal approach, natural orifice transluminal endoscopic surgery (NOTES)-assisted, laparo-endoscopic single-site surgery (LESS), with excellent results in the donor and graft. Many studies have compared these techniques with open ones. Our objective is to describe our experience and results in minimally invasive living-donor nephrectomies (MILDN): laparoscopic, NOTES-assisted, and LESS since their introduction in March 2002. MATERIALS AND METHODS: We conducted a retrospective observational study of donors undergoing MILDN between March 2002 and March 2020. RESULTS: A total of 714 MILDNs were performed at our centre. All were completed, except for one, because of recipient death. The conventional laparoscopic approach was used in 541 cases (75.88%), NOTES in 116 (16.9%), LESS in 55 (7.7%), and one mini open (0.14%). Two-thirds of the donors were females (478 cases). The mean donor age was 52.87 years (SD 10.93). Six donors (0.8%) were diagnosed beforehand with a small renal mass, which was removed before transplantation in bench surgery. The right kidney was removed in 17.8% of cases. Warm ischaemia time was higher in the NOTES and LESS groups. We had eight conversions. The global intraoperative and postoperative complication rates were 6.8% and 4.9%, respectively. None of the donors developed renal disease during follow-up (mean 3.68 years). Five-year recipient and graft survival rates were 98.8% and 96.8%, respectively. CONCLUSIONS: MILDN techniques are safe for donors and grafts, with low complication.

Updates on conservative management of endometrial cancer in patients younger than 45 years.

Endometrial cancer is the most common gynecologic malignancy in developed country. Women under the age of 40 represent 5% of all endometrial cancer and the majority are nulliparous at the time of diagnosis. The aim of this review was to compare oncologic and fertility outcomes among different fertility-preserving therapies in patients under 45 years of age with grade 1 or 2 endometrial cancer. A systematic review was conducted, the MEDLINE, EMBASE, and CINAHL databases were searched for articles published during the period from January 2010 through January 2020 in accordance with PRISMA guidelines, using the terms endometrial cancer, fertility sparing treatment and conservative treatment. A total of 661 patients in 38 studies were included. The median age was 32.3 years (range 13--43). Regardless of the primary treatment, it is always accompanied by systemic or local hormonal treatment. The median follow-up time was 47.92 months (range 1-412), 54.9 months (range 3.4-412) for the progesterone group, 38.97 months (range 3-172) for the hysteroscopic resection group and 23.11 months (range 1-115.5) for the Levonorgestrel Intrauterine Device group. The overall complete response rate was 79.4%, [Hysteroscopic Resection: 90%, hormonal treatment: 77.7%, and Levonorgestrel Intrauterine Device: 71.3%] The p = 0.02 when the primary treatment is Hysteroscopic resection, always followed by hormonal therapy either oral progesterone or Levonorgestrel Intrauterine Device. Patients who had tumor resection had lower progression than those who received hormonal treatment or Levonorgestrel Intrauterine Device 3.5% vs. 12.1% vs. 19.5% respectively (p = 0.03). The complete response time was higher in the Hysteroscopic Resection group (p = 0.04) with fewer patients undergoing hysterectomy (p = 0.0001). Patients who underwent Hysteroscopic Resection had higher pregnancy rates compared to medical treatment or Levonorgestrel Intrauterine Device, 34.5%, 27.6% and 18.4%, respectively (p = 0.002). CONCLUSION: Patients who underwent Hysteroscopic Resection followed progestogens agent was associated to a better complete response, high pregnancy rates and minor numbers of hysterectomies.

Zinc deficiency associated with anaemia among young children in rural Guatemala.

One in four children younger than age five in Guatemala experiences anaemia (haemoglobin <11.0 g/dl). This study characterized the factors and micronutrient deficiencies associated with anaemia in a baseline cross-sectional sample of 182 Guatemalan infants/toddlers and 207 preschoolers, using generalized linear mixed models. Associations between anaemia and maternal, child and household variables, and biomarkers (soluble transferrin receptor, ferritin, zinc, folate, vitamin B12, C-reactive protein, and α1-acid glycoprotein) were explored. Rates of anaemia were 56% among infants/toddlers and 12.1% among preschoolers. In children with anaemia, rates of iron deficiency (low ferritin based on inflammation status, and/or high soluble transferrin receptor, ≥1.97 mg/L) and zinc deficiency (serum zinc <65 µg/dl) were 81.1% and 53.7%, respectively. Folate deficiency (either plasma folate <3 ng/ml or erythrocyte folate <100 ng/ml) was 3.3%. Vitamin B12 deficiency (plasma vitamin B12 <148 pmol/L) was 7.5%. For infants and toddlers (<24 months), the odds ratio of anaemia was lower when higher number of adults lived in the household (OR = 0.69; 95% CI [0.53, 0.90]), and higher when children were zinc deficient (OR = 3.40; 95% CI [1.54, 7.47]). For preschoolers (36-60 months), the odds ratio of anaemia was lower for every additional month of age (OR = 0.90; 95% CI [0.81, 1.00]). Findings suggest that micronutrient deficiencies coexist in Guatemalan rural children, and zinc deficiency is associated with anaemia in children <24 months, highlighting the need of continued multidisciplinary interventions with multiple micronutrients. Further research examining how household composition, feeding practices, and accessibility to micronutrient supplements and to animal source foods is needed to incorporate strategies to improve the nutritional status of Guatemalan children.

Experience of Perinatal Death From the Father's Perspective.

BACKGROUND: Although perinatal deaths are still a common pregnancy outcome in developing countries, little is known about the effect perinatal death has on fathers. OBJECTIVE: The aim of the study was to understand and describe the meaning of perinatal death in a sample of fathers from northeastern Colombia. METHODS: Using purposive and snowball sampling approaches, we identified 15 participants from northeastern Colombia who agreed to participate. We used a descriptive phenomenological design. Data were collected through in-depth, semistructured interviews. RESULTS: Men suffer in solitude and hide their emotions as they feel the need to be the main supporters of their partners. Three major themes emerged: experience of loss, coming to terms with an irreparable loss, and overcoming the loss. DISCUSSION: While women are receiving care, health staff may neglect or forget men. Men suffer alone while seeking ways of attunement with their partners' emotions to support them during the grieving process. Fathers can overcome and adjust to the loss when they transcend it and find new meaning. Men felt neglected and marginalized at hospitals while their partners were receiving treatment. Health professionals should recognize and acknowledge the pain of fathers who face perinatal death and include them as much as possible in the standard of care. The results identify opportunities for healthcare providers in clinical and outpatient settings to acknowledge the importance of men within the context of pregnancy and to learn about their pain and suffering when they face a perinatal death.

Septic Shock, Meningoencephalitis and Multiple Pulmonary Emboli: Case Report of an Uncommon Clinical Presentation of Ventricular Septal Defect Acute Infective Endocarditis.

The case is reported of a 55 year-old woman, with a previously known congenital septal defect, who was admitted to the emergency department with a diagnosis of meningoencephalitis, septic shock, and rapid clinical deterioration. Echocardiography revealed a vegetation occupying the right-side heart. Endocarditis affectation of the septal defect, aortic and tricuspid valves was noted and blood cultures were positive for Staphylococcus aureus. Urgent surgical treatment was performed whereby the ventricular septal defect was closed, a meticulous debridement of the affected area was conducted, and the aortic and tricuspid valves were replaced.

Asporin Is a Fibroblast-Derived TGF-ß1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer.

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-ß1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications. METHODS AND FINDINGS: Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1ß, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-ß1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher asporin expression (4-fold; p = 0.001). Assessment of asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort. CONCLUSIONS: Our data show that asporin is a stroma-derived inhibitor of TGF-ß1 and a tumor suppressor in breast cancer. High asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing asporin expression in TNBC as a promising strategy for targeted therapy.

Description of a new family with cryopyrin-associated periodic syndrome: risk of visual loss in patients bearing the R260W mutation.

OBJECTIVE: The aim of this study was to describe a family with cryopyrin-associated periodic syndrome (CAPS) in which the disease was unveiled after the ophthalmologic evaluation. METHODS: Family and personal histories from each of the patients were recorded. Each underwent a full ophthalmological examination along with the physical examination. The mutational analysis of the NLRP3 gene was performed by means of direct sequencing. RESULTS: The proband was admitted during an episode of unilateral anterior uveitis. She had a history of recurrent red eye and had been suffering episodes of skin rash and arthralgia induced by cold since childhood. At examination, she showed a reticulated corneal mid-stroma. Her mother and her younger sister also suffered from relapsing episodes of skin rash and fever triggered by cold as well as flares of red eye. They had developed premature hearing loss. In both cases, opacities in the corneal mid-stroma were evidenced with a slit lamp. The genetic analysis detected the heterozygous germline p.R260W mutation in the NLRP3 gene in the three women, confirming the diagnosis of CAPS. Treatment with anakinra resulted in complete remission of flares. CONCLUSION: In this family, a structural NLRP3 mutation was associated with classic MuckleWells features of different degrees of severity. Interstitial keratitis with corneal opacification, usually ascribed to neonatal-onset multisystem inflammatory disease, was found. We underscore that ocular involvement in MuckleWells syndrome should be carefully assessed, since it can lead to visual impairment.

Brief report novel mechanism for valproate-induced teratogenicity.

BACKGROUND: Valproic acid (VPA) is a commonly prescribed drug for those affected by epilepsy and bipolar disorders. VPA has a well known teratogenic potential, causing a variety of birth defects including neural tube defects (NTDs) and other congenital malformations, when women are treated with this medication during pregnancy. Unfortunately, the mechanism by which VPA is teratogenic remains unknown, although a range of potential mechanisms including histone deacetylase inhibition and folate antagonism have been proposed. The latter is of considerable importance, as clinicians need to know if additional folate supplements can prevent VPA-induced defects. METHODS: We herein approach this question experimentally, using enzyme-linked immunosorbent assay assays and cell culture modeling, to demonstrate that VPA serves as a noncompetitive inhibitor of the high affinity folate receptors. RESULTS: Binding affinities experimentally determined through enzyme-linked immunosorbent assay assays indicate that VPA serves as a noncompetitive substrate that can lessen the ability of the three primary folate forms to bind to the high affinity folate receptors. Tests in HEK293T cells indicate that the membrane-bound folate receptors of VPA treated cells bind significantly lower amounts of folic acid than do untreated cells. CONCLUSION: If these data translate to the overall transport and subsequent bioavailability of folates, noncompetitive inhibition of the folate receptors by VPA may serve to lower the bioavailable folates in VPA treated mothers. This represents a novel mechanism by which in utero VPA exposure could be disrupting developmental processes by noncompetitively binding to the folate receptors during embryogenesis, thus inducing the wide range of defects seen in babies born to VPA treated mothers.

A procedure for extending input selection algorithms to low quality data in modelling problems with application to the automatic grading of uploaded assignments.

When selecting relevant inputs in modeling problems with low quality data, the ranking of the most informative inputs is also uncertain. In this paper, this issue is addressed through a new procedure that allows the extending of different crisp feature selection algorithms to vague data. The partial knowledge about the ordinal of each feature is modelled by means of a possibility distribution, and a ranking is hereby applied to sort these distributions. It will be shown that this technique makes the most use of the available information in some vague datasets. The approach is demonstrated in a real-world application. In the context of massive online computer science courses, methods are sought for automatically providing the student with a qualification through code metrics. Feature selection methods are used to find the metrics involved in the most meaningful predictions. In this study, 800 source code files, collected and revised by the authors in classroom Computer Science lectures taught between 2013 and 2014, are analyzed with the proposed technique, and the most relevant metrics for the automatic grading task are discussed.

Capitalizing on Hope: Questionable Marketing Approval and Pricing of a New ALS Drug.

Regulatory agencies must balance patient demands to access new treatments for fatal diseases with limited treatment options while ensuring drug safety and efficacy. However, questionable U.S. regulatory actions resulted in the early approval of AMX0035 to treat amyotrophic lateral sclerosis (ALS) by reconvening advisory commissions to obtain positive decisions and designating the drug as a new molecular entity. Data from one randomized clinical trial suggests minimal delays in disease progression and longer survivability, but debate remains about the lack of confirmatory evidence of effectiveness owing to study limitations. A patient's decision-making process details the experience of using the drug, including perspectives on access, cost, effectiveness, and adverse effects. In line with the "nichebuster" business model, the drugmaker, Amylyx Pharmaceuticals, is charging US$158,000/year/patient and thus forecast to turn a profit on a drug with debatable clinical effectiveness prior to completing a Phase 3 trial. Early marketing approval, despite community demands, is unnecessary and may have reduced access because of the end of a compassionate use program, and the high price tag results in restricted coverage and high out-of-pocket costs. Also, the drug's key ingredients are available as a generic and a supplement.

Efficacy and Safety of the Extreme Lateral Interbody Fusion (XLIF) Technique in Spine Surgery: Meta-Analysis of 1409 Patients.

(1) Objectives: The objective of this study was to quantify the exact clinical-radiological efficacy and safety of the extreme lateral interbody fusion (XLIF) technique in spinal surgery; (2) Methods: A meta-analysis was performed using PubMed, Embase, Scopus, and Cochrane Collaboration Library. Studies focusing on patients surgically treated with XLIF were included. The outcomes were as follows: visual analog scale (VAS) and Oswestry disability index (ODI), radiological outcomes, and adverse events. Cohort studies and case series were also included. Clinical outcomes were assessed at 12 months of age. Data were combined using Review Manager 5.4 and WebPlotDigitizer 13.1.4; (3) Results: Nineteen studies with a pool of 1409 patients were included in this meta-analysis. Leg pain VAS and back pain VAS significantly improved at 12 months (SMD 2.75, 95% CI 0.59-4.90; SMD 4.54, 95% CI 1.39-7.69). ODI showed significant improvement (MD 32.51, 95% CI 24.01-41.00) at 12 months. Disc height increased significantly (SMD -2.73, 95% CI -3.58 to -1.88). Lumbar lordosis and segmental lordosis were significantly corrected postoperatively (MD -2.44, 95% CI -3.45 to -1.43; MD -2.55, 95% CI -3.61 to -1.48). The fusion rates at 12 months ranged from 85.0% to 93.3%. The most frequent complications were transient neurological conditions (2.2%), hardware failure (1.9%), and transient pain (1.8%). The most frequent serious complications were nerve root injury (1.0%), gastrointestinal impairment (0.7%), and vertebral fractures (0.6%); (4) Conclusions: This is the first meta-analysis of the specific use of XLIF in spinal surgery. This study demonstrates that the XLIF technique in spine surgery is associated with good clinical and radiological results and a low complication rate.

Prenatal sonographic findings of duodenal duplication: case report.

We report a rare case of duodenal duplication cyst that was suspected prenatally. Routine prenatal sonography (US) at 19 weeks' gestation showed an abdominal cystic mass on the left side of the abdomen. Follow-up US examinations showed a partial "double-wall" sign, highly suggestive of enteric duplication, and changes in cyst size and wall thickness. Postnatal US examination suggested enteric duplication cyst. A laparotomy revealed a duodenal cyst that was completely resected. The antenatal US findings associated with this condition, the accuracy of its antenatal diagnosis, and its differential diagnosis are discussed.

Characterization of folic acid, 5-methyltetrahydrofolate and synthetic folinic acid in the high-affinity folate transporters: impact on pregnancy and development.

Folates are B vitamins that are essential for several molecular, cellular, and biological processes, including nucleotide synthesis, methylation, and methionine cycling. The physiological impacts of these processes on health also extend to cell proliferation, folate deficiency anemia, and reduction of the risk of birth defects during pregnancy. The primary objective of this study was to characterize the binding affinities of different folate forms, folic acid (FA), 5-methyltetrahydrofolate (5MTHF), and folinic acid, to the folate receptors α and ß, and to the bovine milk folate binding protein. These three dietary forms of folate are found in enriched grains (FA), various fruits and leafy vegetables (folinic acid), and red blood cells (5MTHF). Methods: The half maximal inhibitory concentration values and binding curves of each of these folates for each receptor were determined. Results: Our results indicated that FA had the highest affinity for all folate receptors, followed by 5MTHF, and lastly, by folinic acid, examined by several orders of magnitudes. Conclusion: These data are expected to provide new insights into the therapeutic applications of the different forms of folate in a variety of diseases.

Parental Knowledge and Perceptions on Prevention of Sudden Unexpected Infant Death and Infant Care.

(1) Background: The study's purpose was to explore the knowledge, perceptions, and confidence of mothers about infant care to reduce the risk of sudden unexpected infant death. (2) Methods: A purposeful sampling method was used to recruit 15 first-time mothers from Georgia with infants under 1 year of age. The researchers utilized the Socio-ecological model to report the results. Participants also provided recommendations on how to improve infant care and reduce the risk of SUID. (3) Results: The confidence level of infant care among most participants was low but increased over time. Mothers' knowledge level about the prevention of SUID was high, but poor emotional health could hurt their parental abilities. Most participants recognized medical providers as the main source of reliable information. However, a lack of emotional and physical support was reported by mothers. (4) Conclusions: Results suggested that a more holistic approach to infant care is needed. The healthcare system and communities should provide more physical, social, and mental support to first-time mothers, a consolidated approach to care before and after birth, and easy access to services at all stages of the process to reduce the risk of SUID.

Clinical and Aberrometric Outcomes of a New Implantable Collamer Lens for Myopia and Presbyopia Correction in Phakic Patients.

PURPOSE: To assess the clinical and aberrometric outcomes of a new Implantable Collamer Lens (EVO Viva ICL; STAAR Surgical) to correct moderate to high myopia and presbyopia. METHODS: The study included 80 eyes of 40 patients who had bilateral EVO Viva ICL implantation. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, presbyopic add power, binocular through-focus visual acuity, total ocular spherical aberration (SA), coma aberration, and root mean square of ocular higher order aberrations (RMS HOAs) (i-Trace Aberrometer; Tracey Technologies) for a 4.5-mm pupil size were evaluated. RESULTS: The mean binocular postoperative UDVA and CDVA were 0.09 ± 0.19 and 0.02 ± 0.03 logMAR, respectively. The postoperative spherical equivalent was -0.61 ± 0.54 diopters (D). The presbyopic add power reduced from +1.31 ± 0.74 D preoperatively to +0.44 ± 0.58 D after surgery (P < .0001). The mean visual acuity was 0.1 logMAR or better (20/25 or better) across the vergence range from +0.50 to -1.50 D, better than 0.2 logMAR (20/32 or better) up to the vergence of -2.00 D, and remained better than 0.3 logMAR (20/40 or better) up to the vergence of -2.50 D. The total ocular aberrations induced by EVO Viva ICL were -0.34 ± 0.09 µm of SA, 0.24 ± 0.18 µm of coma, and 0.26 ± 0.12 µm of RMS HOAs. CONCLUSIONS: The outcomes support that the new ICL might be a good alternative for myopia and presbyopia correction in patients aged between 45 and 55 years. Further studies are needed to evaluate the threshold lens misalignment from which the patient´s visual quality would be affected. [J Refract Surg. 2023;39(9):589-596.].

Genetic variation in a tepary bean (Phaseolus acutifolius A. Gray) diversity panel reveals loci associated with biotic stress resistance.

Tepary bean (Phaseolus acutifolius A. Gray), indigenous to the arid climates of northern Mexico and the Southwest United States, diverged from common bean (Phaseolus vulgaris L.), approximately 2 million years ago and exhibits a wide range of resistance to biotic stressors. The tepary genome is highly syntenic to the common bean genome providing a foundation for discovery and breeding of agronomic traits between these two crop species. Although a limited number of adaptive traits from tepary bean have been introgressed into common bean, hybridization barriers between these two species required the development of bridging lines to alleviate this barrier. Thus, to fully utilize the extant tepary bean germplasm as both a crop and as a donor of adaptive traits, we developed a diversity panel of 422 cultivated, weedy, and wild tepary bean accessions which were then genotyped and phenotyped to enable population genetic analyses and genome-wide association studies for their response to a range of biotic stressors. Population structure analyses of the panel revealed eight subpopulations and the differentiation of botanical varieties within P. acutifolius. Genome-wide association studies revealed loci and candidate genes underlying biotic stress resistance including quantitative trait loci for resistance to weevils, common bacterial blight, Fusarium wilt, and bean common mosaic necrosis virus that can be harnessed not only for tepary bean but also common bean improvement.

Ten-Year Follow-up of Posterior Chamber Phakic Intraocular Lens with Central Port Design in patients with low- and normal-vault.

PURPOSE: To assess the clinical outcomes and postoperative complications of the Implantable Collamer Lens (ICL) with a central port throughout ten years of follow-up in patients with low- and normal-vault. SETTING: Fernández-Vega Ophthalmological Institute, Oviedo, Spain. DESIGN: Retrospective and comparative case series. METHODS: This study included eyes that underwent a V4c ICL implantation with ten years of follow-up. The eyes were divided into two groups according to the vault at one year postoperatively: Vault < 250 µm; and between 250 and 800 µm. Uncorrected (UDVA), corrected distance visual acuity (CDVA), intraocular pressure (IOP), endothelial cell density (ECD), vault, complications and secondary surgeries were analysed. RESULTS: 37 and 90 eyes were enrolled in the low- and normal-vault groups. No differences in UDVA, CDVA and refraction were found between groups at ten years of follow-up. No cases developed ICL-induced anterior subcapsular opacity over the follow-up. Two (5.4%) and eight eyes (8.9%) in the low- and normal-vault-groups required ICL exchange. One (2.8%) and two eyes (2.2%) in the low- and normal-low-vault groups required excimer laser to correct residual refractive error. The IOP remained stable throughout the 10-year follow-up. The loss in ECD from the preoperative at the 10-year postoperatively was 3.8% and 4.5% in the low- and normal-vault groups (P=0.4). No pigment dispersion glaucoma or other vision-threatening complications were reported. CONCLUSIONS: This study shows the good long-term outcomes of the V4c ICL, supporting that the central hole provides safety to the procedure and prevents the potential risk associated with the low vault.

Effectiveness of lactation cookies on human milk production rates: a randomized controlled trial.

BACKGROUND: Expensive lactation cookies (LCs) are marketed as milk boosters; however, their effectiveness remains unknown. OBJECTIVES: The objective of this study was to evaluate the effectiveness of the 1-mo daily intake of LCs on changes in objective and subjective milk production and breastfeeding self-efficacy. METHODS: This is a 1-mo, randomized controlled trial among 18-45-y-old exclusively lactating parents of healthy, term, 2-mo-old infants living in the United States from March to December 2021. Participants (n = 176) were randomly assigned to eat daily 56.5 g of either LCs with "galactagogues" (oatmeal, brewer's yeast, flax seeds, and fenugreek) or conventional cookies containing similar weight, calories, and presentation but lacking galactagogues. The primary outcome was baseline-to-1-mo changes in human milk production rate (HMPR), measured with a validated milk expression protocol. Secondary outcomes included changes in perceived insufficient milk (PIM) and lactation self-efficacy scores. RESULTS: Among 176 randomly assigned participants (age: 31.3 ± 5.8 y; 71.0% self-identified as White, 15.3% Hispanic/Latin, 6.3% Black, and 4.0% Asian), 90 participants (51.1%) completed endline HMPR measures and 129 (73.3%) completed secondary outcomes. Imputed models showed a mean increase in HMPR of 5.8 ± 15.7 mL/h in control participants and 5.5 ± 17.6 mL/h in the LC participants after 1 mo of daily intake of the cookie. No significant differences were observed with adjusted linear mixed models on the multiply imputed data comparing baseline-to-endline changes in HMPR, PIM, or breastfeeding self-efficacy: mean (SE) difference-in-differences for HMPR, -0.33 (4.97), P = 0.948; PIM scores (range: 5-50), -0.52 (1.83), P = 0.775; and self-efficacy scores (range: 14-70), 0.31 (2.23), P = 0.888, respectively. CONCLUSIONS: This study found no evidence for the effect of consuming LCs on HMPR, PIM, or breastfeeding self-efficacy in exclusively breastfeeding parents with an overall adequate perceived milk supply. Recommendations to consume LCs for increasing objective or subjective milk supply may deliver false hope and unnecessary financial costs at a vulnerable time. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT04805008.

The Effects of Multiple Micronutrient Fortified Beverage and Responsive Caregiving Interventions on Early Childhood Development, Hemoglobin, and Ferritin among Infants in Rural Guatemala.

Undernutrition and a lack of learning opportunities can jeopardize long-term growth and development among infants in low- and middle-income countries. We conducted a 6-month 2 × 2 cluster-randomized trial to assess the effects of multiple micronutrient-fortified beverages and responsive caregiving interventions among infants 6-18 months in 72 community sectors in southwest Guatemala. We administered baseline and endline assessments of childhood development (Bayley Scales of Infant and Toddler Development) and socioemotional development (Brief Infant Toddler Socio-Emotional Assessment) and measured ferritin and hemoglobin on a subsample. The trial was analyzed using linear mixed models. At the baseline, the mean age (SD) was 13.0 (4.6) months, including 49% males, 32% who were stunted, 55% who were anemic, and 58% who were iron deficient. At the endline (n = 328/386, 85% retention), there was no synergistic effect on the fortified beverage and responsive caregiving intervention. Compared to the non-fortified beverage group, socioemotional development improved in the fortified beverage group. There were no intervention effects on other measures of child development, hemoglobin, or ferritin. In a setting with high rates of anemia and iron deficiency, a multiple micronutrient-fortified beverage improved infants' socioemotional development.