Non-antibiotic antimicrobial agents for chronic rhinosinusitis: a narrative review.

OBJECTIVE: This narrative review explores alternative non-antibiotic antimicrobial agents for CRS management in adults. METHODS: Alternative antimicrobial agents using EPOS 2020 guidelines as reference were selected, and articles dated from 2003 to 2022 in English, Portuguese, or Spanish using PubMed and EMBASE databases. The parameters analyzed included study design, evidence level, population characteristics, CRS characteristics, interventions, outcomes, sample size, randomization, blinding, and side effects. Reviews, unrelated contexts,in vitro experiments, and duplicates were excluded. RESULTS: 148 articles were screened; 19 articles were selected for analysis. Randomized controlled trials and cohort studies assessing non-antibiotic antimicrobial treatments for CRS were included. Xylitol demonstrated effectiveness in reducing CRS symptoms, particularly SNOT-22 scores, surpassing saline irrigation benefits. Manuka honey showed potential microbiological benefits in recalcitrant CRS, but symptomatic and endoscopic improvements remained inconclusive. Baby shampoo irrigation improved nasal mucociliary clearance and postoperative outcomes. Colloidal silver nasal irrigation showed limited efficacy in reducing CRS symptoms or endoscopic scores. Povidone-Iodine (PI) nasal irrigation yielded mixed results, with varying effects on culture negativity and SNOT-20 scores. Bacteriophage treatment exhibited promise in decreasing specific bacterial strains and cytokine levels. CONCLUSION: Non-antibiotic antimicrobial therapies, including xylitol, manuka honey, baby shampoo, colloidal silver, PI, bacteriophages, lactoferrin, and carrageenan offer potential alternatives for CRS in adult patients. Xylitol, baby shampoo, and PI presented benefits in improving symptoms and nasal endoscopic scores, however, the number of studies is limited for conclusive recommendations and safety assessments. CRS management should adopt a comprehensive approach, particularly for non-infectious or immune-related cases, moving beyond antibiotics. Antibiotics should be reserved for confirmed bacterial infections. Overall, this review shows the importance of exploring non-antibiotic therapies to enhance the management of CRS.

Influence of malocclusion on sleep bruxism and orofacial pain: data from a study in school children.

OBJECTIVES: This cross-sectional school-based study explored the influence of malocclusion on temporomandibular disorders (TMD) pain complaints, and whether this association would be mediated by sleep bruxism in a representative sample of 7- to 8-year-old children. METHODS: Path analysis estimated direct, indirect, and total effects of occlusal features on sleep bruxism and TMD pain in 7- to 8-year-old children. Occlusal features were assessed with Dental Aesthetic Index (DAI), orofacial pain complaints using the TMD pain screener, possible sleep bruxism based on self-reports, and probable sleep bruxism based on self-reports combined with clinical findings. Structural equation modeling analyzed data with confounding factors. RESULTS: From 580 participants, possible sleep bruxism was observed in 136 children (31.5%), probable sleep bruxism in 30 children (6.7%), and TMD pain complaints in 78 children (13.8%). Malocclusion had no direct effect on either possible sleep bruxism [standardized coefficient (SC) 0.000; p = 0.992], or TMD pain complaints (SC - 0.01; p = 0.740). When probable sleep bruxism was set as the mediator of interest, malocclusion did not directly affect probable sleep bruxism (SC 0.01; p = 0.766), nor TMD pain complaints (SC - 0.02; p = 0.515). A direct effect of probable sleep bruxism on TMD pain complaints was observed with an SC of 0.60 (p < 0.001). However, in neither case, malocclusion indirectly affected TMD pain complaints via bruxism. CONCLUSION: Malocclusion in 7- to 8-year-old children did not directly influence possible or probable sleep bruxism or TMD pain complaints. Instead, probable sleep bruxism was strongly associated with TMD pain complaints. CLINICAL SIGNIFICANCE: The impact of occlusal features on TMD pain complaints and bruxism has been a long-standing controversy in dentistry. However, the scientific literature linking this association may be inconsistent, mainly due to biased sample selection methods with inadequate consideration of confounders. Further research should try to identify additional risk factors for TMD pain in addition to probable sleep bruxism in children.

Response of Mycobacterium smegmatis to the Cytochrome bcc Inhibitor Q203.

For the design of next-generation tuberculosis chemotherapy, insight into bacterial defence against drugs is required. Currently, targeting respiration has attracted strong attention for combatting drug-resistant mycobacteria. Q203 (telacebec), an inhibitor of the cytochrome bcc complex in the mycobacterial respiratory chain, is currently evaluated in phase-2 clinical trials. Q203 has bacteriostatic activity against M. tuberculosis, which can be converted to bactericidal activity by concurrently inhibiting an alternative branch of the mycobacterial respiratory chain, cytochrome bd. In contrast, non-tuberculous mycobacteria, such as Mycobacterium smegmatis, show only very little sensitivity to Q203. In this report, we investigated factors that M. smegmatis employs to adapt to Q203 in the presence or absence of a functional cytochrome bd, especially regarding its terminal oxidases. In the presence of a functional cytochrome bd, M. smegmatis responds to Q203 by increasing the expression of cytochrome bcc as well as of cytochrome bd, whereas a M. smegmatisbd-KO strain adapted to Q203 by increasing the expression of cytochrome bcc. Interestingly, single-cell studies revealed cell-to-cell variability in drug adaptation. We also investigated the role of a putative second cytochrome bd isoform postulated for M. smegmatis. Although this putative isoform showed differential expression in response to Q203 in the M. smegmatisbd-KO strain, it did not display functional features similar to the characterised cytochrome bd variant.

[Consecutive Ankle Sprain Classification and Injury Systematization (CASCaIS), A New Lateral Ankle Sprain Classification Based on the Pivot Test: A Prospective Cohort Study]. / Consecutive Ankle Sprain Classification and Injury Systematization (CASCaIS), Uma Nova Classificação de Entorse Lateral do Tornozelo Baseada no Teste de Pivot: Estudo Prospetivo de Coorte.

INTRODUCTION: The biggest challenge in the treatment of acute ankle sprain is the uncertainty of the prognosis. The traditional classifications have several interpretations and little correlation with prognosis. In this study we propose a new classification for acute ankle sprain only based on clinical criteria. MATERIAL AND METHODS: We prospectively evaluated all patients with an ankle sprain, aged between 18 and 45 years, admitted to a hospital during a 24 month period. The minimum follow-up period was 12 months. The sprains were classified, in the first few days (CASCaIS-Initial), according to autonomous gait capacity, inspection and palpation. After a few weeks (CASCaIS-Deferred), it was complemented with the mechanical evaluation of ligaments through the ankle pivot test. RESULTS: Among the 49 patients who completed the follow-up, none of those who had a pivot-negative test progressed to chronic ankle instability (CAI). Nine of the 33 patients (27%) with a positive pivot progressed to CAI (p = 0.022). The evaluation of CASCaIS-Deferred demonstrated an association with CAI (p = 0.018). CONCLUSION: This classification proved to be a simple, inexpensive, and reliable tool that clinicians can use to determine the prognosis of the sprain.

Introdução: O maior desafio no tratamento da entorse aguda do tornozelo é a indefinição do prognóstico. As classificações clássicas têm várias interpretações e pouca correlação com o prognóstico. Com este trabalho propomos uma nova classificação baseada apenas em critérios clínicos.Material e Métodos: Foram prospectivamente avaliados doentes entre os 18 e os 45 anos com entorse aguda do tornozelo, admitidos numa instituição durante 24 meses. O seguimento mínimo teve uma duração de 12 meses. Estes doentes foram classificados nos primeiros dias após a entorse (CASCaIS-Inicial) com base na valorização da capacidade de marcha autónoma, inspeção do quadro inflamatório e palpação. Passadas algumas semanas (CASCaIS-Diferida) complementou-se com a avaliação ligamentar pelo teste de pivot do tornozelo.Resultados: Dos 49 doentes que completaram o seguimento, nenhum dos que tinha um teste pivot-negativo evoluiu para instabilidade crónica do tornozelo (ICT). Nove dos 33 doentes (27%) com um pivot-positivo evoluíram para ICT (p = 0,022). A avaliação da CASCaIS-Diferida demonstrou uma associação com a ICT (p = 0,018).Conclusão: Esta classificação demonstrou ser uma ferramenta simples, não dispendiosa e fiável que os clínicos poderão usar para determinar o prognóstico da entorse.

Progestin-Primed Ovarian Stimulation is a non-inferior alternative to the GnRH Antagonist Protocol in patients undergoing assisted reproductive techniques: a retrospective study.

OBJECTIVE: To demonstrate the non-inferiority of Clinical Pregnancy Rates from Progestin-Primed Ovarian Stimulation compared to the GnRH Antagonist Protocol when the freeze-all and blastocyst transfer strategy is applied. METHODS: A retrospective study included all IVF cycles performed at Pró-Criar Reproductive Medicine Center, Belo Horizonte, Minas Gerais, Brazil, between May 2018 and May 2019 using a GnRH antagonist analogue or oral progestins to block the LH peak in IVF/intra-cytoplasmic sperm injection (ICSI) cycles for infertility treatment. RESULTS: The primary outcome of our study was Clinical Pregnancy Rate at the first ET (Blastocyst), which were 58.4% in the progestin group and 54.9% in the antagonist group (p=0.735), a finding consistent with most studies published to date using different progestins. The mean number of retrieved oocytes was 11 in the antagonist group and 9 oocytes in the progestin group (p=0.009). The fertilization rate was 80% for both groups (p=0.935). The rate of blastocyst formation per cycle was 50% in the antagonist group and 55.6% in the progestin group (p=0.106). The stimulation lasted a mean of 10 days in the two groups (p=0.403) and did not vary with patient age in either group. The gonadotropin dose used was higher in the antagonist group (2025 IU) than in the progestin group (1950 IU) (p=0.057). In addition, the blockade was effective: there was only one case of spontaneous ovulation, which corresponded to less than 1% of the cycles. CONCLUSIONS: Progestin-Primed Ovarian Stimulation is a non-inferior alternative to the GnRH Antagonist Protocol in patients undergoing assisted reproductive techniques. An incidence compatible with the 0.34 to 8% risk described in the literature for failure to control the premature LH surge in antagonist protocol cycles.

Neutron and Gamma-Ray Detection System Coupled to a Multirotor for Screening of Shipping Container Cargo.

In order to detect special nuclear materials and other radioactive materials in Security and Defense scenarios, normally, a combination of neutron and gamma-ray detection systems is used. In particular, to avoid illicit traffic of special nuclear materials and radioactive sources/materials, radiation portal monitors are placed at seaports to inspect shipping-container cargo. Despite their large volume (high efficiency), these detection systems are expensive, and therefore only a fraction of these containers are inspected. In this work, a novel mobile radiation detection system is presented, based on an EJ-200 plastic scintillator for the detection of gamma rays and beta particles, and a neutron detector EJ-426HD plastic scintillator (with 6Li) embedded in a compact and modular moderator. The use of silicon photomultipliers in both detectors presented advantages such as lightweight, compactness, and low power consumption. The developed detection system was integrated in a highly maneuverable multirotor. Monte Carlo simulations were validated by laboratory measurements and field tests were performed using real gamma-ray and neutron sources. The detection and localization within one meter was achieved using a maximum likelihood estimation algorithm for 137Cs sources (4 MBq), as well as the detection of 241Am-beryllium (1.45 GBq) source placed inside the shipping container.

Postpartum Ankle Pain: A Suspected Complex Regional Pain Syndrome or a Rare Cause of Septic Arthritis?

Ankle tuberculosis is a relatively rare condition and may develop after hematogenous dissemination from the pulmonary origin, particularly in cases of immunosuppression. Both pregnancy and delivery are relatively immunosuppressive states, and immune modulations during these periods can contribute to the pathogenesis of disseminated tuberculosis. A 26-year-old mother presented with severe, continuous, and debilitating pain in the left ankle, lasting for three months after delivery and associated with fever. Inspection demonstrated ankle swelling and redness, with a cold and cyanotic forefoot. Ankle radiograph and musculoskeletal ultrasound evaluation were obtained. Tibiotalar joint arthrocentesis revealed purulent liquid suggestive of septic arthritis and an emergent arthroscopic washout of the ankle was performed. The synovial mycobacterial culture was posteriorly positive and the diagnosis established was both pulmonary and osteoarticular tuberculosis. A comprehensive rehabilitation program was then implemented to achieve maximum functional gains. This report presents a rare case of ankle tuberculosis diagnosed in the postpartum period. Early evaluation, treatment, and adequate rehabilitation interventions can be crucial to promote functionality and enhance the quality of life.

Ankle and syndesmosis instability: consensus and controversies.

Ankle sprains are mainly benign lesions, but if not well addressed can evolve into permanent disability. A non-treated lateral, syndesmotic or medial ankle instability can evolve into ankle osteoarthritis. For this reason, diagnosis and treatment of these entities is of extreme importance.In general, acute instabilities undergo conservative treatment, while chronic instabilities are better addressed with surgical treatment. It is important to identify which acute instabilities are better treated with early surgical treatment.Syndesmosis injuries are frequently overlooked and represent a cause for persistent pain in ankle sprains. Unstable syndesmotic lesions are always managed by surgery.Non-treated deltoid ligament ruptures can evolve into a progressive valgus deformity of the hindfoot, due to its links with the spring ligament complex. This concept would give new importance to the diagnosis and treatment of acute medial ligament lesions.Multi-ligament lesions are usually unstable and are better treated with early surgery. A high suspicion rate is required, especially for combined syndesmotic and medial lesions or lateral and medial lesions.Ankle arthroscopy is a powerful tool for both diagnostic and treatment purposes. It is becoming mandatory in the management of ankle instabilities and multiple arthroscopic lateral/syndesmotic/medial repair techniques are emerging. Cite this article: EFORT Open Rev 2021;6:420-431. DOI: 10.1302/2058-5241.6.210017.

Does ibuprofen, prednisolone, or amoxicillin reduce post-tonsillectomy pain in children? A prospective randomized controlled trial.

OBJECTIVE: To evaluate whether the use of anti-inflammatory or antibiotic in the postoperative period modifies pain in children undergoing tonsillectomy. METHODS: 225 children who underwent cold knife tonsillectomy ± adenoidectomy were randomized into five groups, receiving #1 metamizole/acetaminophen, #2 amoxicillin, #3 ibuprofen, #4 prednisolone, or #5 amoxicillin plus prednisolone. All groups received oral analgesics (metamizole/acetaminophen) to use as needed. Pain was monitored during the 7 days following surgery using the Parents' Postoperative Pain Measurement (PPPM) and the Faces Pain Scale - Revised (FPS-R). Pain was also indirectly evaluated by the dose of analgesics administered on each day and by the time needed to return to a solid diet. RESULTS: After losses (24%), 170 individuals were submitted for analysis. Multiple comparisons demonstrated that the evolution of pain between the different groups, as matched day-per-day, was not significantly different by either PPPM or FPS-R (p > 0.05). The instances of analgesic intake were also similar in all the groups (p > 0.05), as was the return to solid food ingestion (p = 0.41). All groups presented a similar standard of clinical improvement at intervals of 2 days (p < 0.01). Independent of postoperative pain management, patients developed significant pain up to the day 4 following surgery. CONCLUSION: The addition of amoxicillin, ibuprofen, prednisolone, or amoxicillin and prednisolone does not modify postoperative pain in children undergoing cold-knife tonsillectomy. Special pain control should be performed on the first 4 days following tonsillectomy in children.

Schwannoma of the First Webspace: A Case Report.

CASE: A 65-year-old man presented with plantar foot pain associated with a mass in the first webspace. A Morton neuroma was considered the probable diagnosis. Despite nonoperative treatment the pain continued. Surgical excision was performed, and histology was interpreted as a schwannoma. Symptoms resolved after surgery. CONCLUSION: Schwannoma of the foot is a rare condition, and to the best of our knowledge, this is the first case reported in the first webspace. Definitive treatment and diagnosis is surgical excision. Surgeons should consider schwannomas in the differential diagnosis of plantar foot pain because this can be misdiagnosed as a Morton neuroma.

Research priorities in infertility and assisted reproductive technology treatments - a James Lind Alliance priority setting partnership with brazilian patients.

OBJECTIVE: To identify the main research interests of Brazilian patients in the field of infertility and assisted reproductive technology (ART) treatments. METHODS: This prospective multicenter cross-sectional study was carried out in Brazil. Patients attending five fertility centers from the Huntington Group between October and December 2018 were invited to join the study, which consisted of answering an anonymous survey online. Two hundred and twenty-seven patients signed the informed consent form and were emailed the survey link. The survey was designed based on the James Lind Alliance Priority Setting Partnership protocol. In the area of infertility, patients were probed on issues such as somatic and psychological effects of treatment, prevention, assisted reproductive technology (medications and procedures), success rates, risks, and emotional aspects. RESULTS: The response rate (RR) was 47.58% (108 patients; 88 women - RR 51.46% and 20 men - RR 35.71%). Patient mean age was 36.5 years (SD 4.6). The top ten research priorities listed were 1) short- and long-term side effects of treatment; 2) how to cope with infertility; 3) risks associated with ART; 4) success rates in ART; 5) impact of diet on ART and fertility; 6) healthy habits; 7) alternative therapies; 8) impact of exercise on fertility and ART success; 9) oocyte quality and ovarian reserve; and 10) genetic or inherited causes of infertility. CONCLUSION: To better cater to the needs of patients and develop patient-centered care in the field of infertility and ART treatment, clinicians, healthcare providers, and the scientific community must identify patient concerns and priorities and make efforts to address them.

A critical analysis of the impact of endocrine disruptors as a possible etiology of primary ovarian insufficiency.

Primary ovarian insufficiency is a cause of infertility that affects about 1% of women under 40 years old, and is considered as idiopathic in 75% of cases. This review aims to carry out a critical synthesis of the knowledge of the chemical agents likely to affect follicular stock in humans and / or animals, by direct toxicity to follicles, or by increasing their recruitments. For the majority of toxic agents, only experimental data are currently available. We propose a strategy to encourage progress in identifying occupational factors responsible for premature ovarian failure.

Identification of research priorities in infertility and assisted reproduction: an international, multicentre study.

RESEARCH QUESTION: What are the main research interests among patients of assisted reproductive technologies (ART)? DESIGN: Cross-sectional study consisting of an anonymous online survey sent to 2112 patients from eight centres in four countries in 2018. Patients were asked to identify research questions relevant to them in the field of infertility and ART. Answers were categorized into topics and ranked by frequency. A long list of the top 30 research topics was extracted from the aggregate results, from which a short list of the top 10 research topics was created. Ten research questions were finally formulated. RESULTS: A total of 945 responses were analysed. Main interests were side-effects, success rates, infertility prevention and emotional support. The 10 research questions were: 1. What are the side-effects of drugs used in ART treatments? (51.6%). 2. What are the most effective methods to cope with infertility from the psychological point of view? (35.7%). 3. What effects could diet have on fertility? (25.9%). 4. What are ART success rates per clinical profile? (24.8%). 5. Are there some habits and lifestyle factors that could prevent infertility? (20.0%). 6. What are the long-term risks associated with ART in mother and child? (18.5%). 7. Are alternative therapies such as acupuncture, yoga and meditation effective to treat/prevent infertility? (18.5%). 8. What is the impact of exercise on fertility? (15.4%). 9. How does oocyte quantity and quality affect fertility? (9.5%). 10. What are the genetic patterns or hereditary conditions causing/related to infertility? (9.5%). CONCLUSIONS: Researchers and clinicians should keep in mind that, in addition to success rates and safety, patients greatly value research into causes, prevention and emotional aspects of infertility.

Creating a Global Community of Practice for Oncofertility.

Fertility preservation in the cancer setting, known as oncofertility, is a field that requires cross-disciplinary interaction between physicians, basic scientists, clinical researchers, ethicists, lawyers, educators, and religious leaders. Funded by the National Institutes of Health, the Oncofertility Consortium (OC) was formed to be a scientifically grounded, transparent, and altruistic resource, both intellectual and monetary, for building this new field of practice capable of addressing the unique needs of young patients with cancer. The OC has expanded its attention to include other nonmalignant conditions that can threaten fertility, and the work of the OC now extends around the globe, involving partners who together have created a community of shared effort, resources, and practices. The OC creates materials that are translated, disseminated, and amended by all participants in the field, and local programs of excellence have developed worldwide to accelerate the pace and improve the quality of oncofertility research and practice. Here we review the global oncofertility programs and the capacity building activities that strengthen these research and clinical programs, ultimately improving patient care.

Cosmetic use of three topical moisturizers following glycolic acid facial peels.

BACKGROUND: Facial chemical exfoliation (peeling) involves using a chemical agent to insult the skin and damage the cutaneous barrier, to reduce the signs of aging. The use of a moisturizer is advised postprocedure to promote repair of the epidermis. Biomimic moisturizer formulations may be effective treatment options for repair following facial peeling. AIMS: The aim of this study was to assess the local tolerance and cosmetic efficacy of three topical moisturizers (Physiogel® moisturizing creams), used after a 70% glycolic acid facial peel. METHODS: Three randomized, evaluator-blind, parallel group studies were performed. Subjects were healthy females aged 30-60 years with moderate to advanced photoaged skin (Glogau photoaging type II-III). All included a screening visit, a 7-day washout period, a 70% glycolic acid facial peeling procedure, and randomization to a 14-day treatment period with one of the three test products vs control. RESULTS: The primary endpoint was reached in all three studies; all completed subjects in the test groups received a favorable dermatologist global assessment score for tolerance at Day 14 (postchemical peel). Secondary assessments of local tolerance based on dermatologist and subject self-assessment scores demonstrated improvements from baseline. No treatment-related adverse events were reported in any study. Benefits for the test products were also observed in secondary efficacy analyses of transepidermal water loss and moisturization. CONCLUSIONS: These studies have demonstrated the local tolerance and cosmetic efficacy of three moisturizing skin care products, when used for skin recovery after superficial chemical peeling on the face.

A Randomized Controlled Tolerability Study to Evaluate Reformulated Benzoyl Peroxide Face Washes for Acne Vulgaris

Introduction: This randomized, evaluator-blind, single-center, parallel-group study sought to evaluate the tolerability of two reformulated face washes containing benzoyl peroxide (BPO) in adults with mild to moderate acne vulgaris. Methods: Healthy adults with mild to moderate acne vulgaris were randomly allocated (1:1:1) to one of two reformulated test products (containing BPO at a concentration of either 4% or 10%) or an older formulation containing 10% BPO (reference product), which they applied twice daily for 21±2 days. The primary tolerability assessment was clinical assessment of signs and symptoms of cutaneous irritation by a dermatologist. The primary outcome was the total dermatologist assessment score (maximum total assessment score=12, indicating the most severe skin irritation). Secondary assessments were ophthalmologist assessments, subject self-assessments, and adverse events. Results: 133 adults were randomized and treated. The total dermatologist score changed by a mean of -0.08 (95% confidence interval [CI] -0.192, 0.038) from baseline to day 21 in the 4% BPO cleanser group, by 0.05 (95% CI -0.021, 0.121) in the 10% BPO cleanser group, and by -0.02 (95% CI -0.105, 0.059) in the reference product group. There was no clinically significant difference between the reference product and the 4% BPO cleanser or 10% BPO cleanser in the mean change from baseline. Mean changes from baseline in ophthalmologist assessment scores and subject self-assessment scores for the 4% and 10% BPO test products were also comparable to those of the reference product. Dermal responses were consistent with the known effects of topical BPO application and no serious safety issues were reported. Discussion: There was no difference in the local tolerance profile of the reformulated BPO-containing face washes when compared with an older formulation. Study registration: www.gsk-clinicalstudyregister.com (study 206239). J Drugs Dermatol. 2019;18(4):350-356

Oocyte cryopreservation for future fertility: comparison of ovarian response between cancer and non-cancer patients.

OBJECTIVE: This study aimed to assess whether a diagnosis of cancer interferes with ovarian function prior to the treatment of the disease. METHODS: This observational retrospective study used data from medical records of ovarian stimulation cycles performed for purposes of oocyte cryopreservation. RESULTS: The included patients had a mean age of 35.13±3.72 years and 51.6% of them were aged between 36 and 40 years. More than half of the patients (57.6%) were single and 82.1% had a normal body mass index (BMI). Most women had not become pregnant (85.5%) or had babies (95.1%) or miscarriages (89.6%) prior to cryopreservation. The mean number of oocytes obtained from non-cancer patients was 11.4±8, while for cancer patients the number was 13.8±9. The mean number of frozen mature oocytes was 9.7±7 for the non-cancer group and 11.2±7.2 for the cancer group. The majority (63.1%) of the patients had up to 10 oocytes frozen per cycle. Breast cancer had the highest incidence among the included patients. There was no significant difference in ovarian response between patients with different types of cancer. CONCLUSION: The number of harvested and frozen oocytes from cancer and non-cancer patients indicated that in the two groups response to ovarian stimulation was similar.

Handling Handles: Nonplanar Integrability in N=4 Supersymmetric Yang-Mills Theory.

We propose an integrability setup for the computation of correlation functions of gauge-invariant operators in N=4 supersymmetric Yang-Mills theory at higher orders in the large N_{c} genus expansion and at any order in the 't Hooft coupling g_{YM}^{2}N_{c}. In this multistep proposal, one polygonizes the string world sheet in all possible ways, hexagonalizes all resulting polygons, and sprinkles mirror particles over all hexagon junctions to obtain the full correlator. We test our integrability-based conjecture against a nonplanar four-point correlator of large 1/2 Bogomol'nyi-Prasad-Sommerfield operators at one and two loops.