Deciphering interactions between the marine dinoflagellate Prorocentrum lima and the fungus Aspergillus pseudoglaucus.

The comprehension of microbial interactions is one of the key challenges in marine microbial ecology. This study focused on exploring chemical interactions between the toxic dinoflagellate Prorocentrum lima and a filamentous fungal species, Aspergillus pseudoglaucus, which has been isolated from the microalgal culture. Such interspecies interactions are expected to occur even though they were rarely studied. Here, a co-culture system was designed in a dedicated microscale marine-like condition. This system allowed to explore microalgal-fungal physical and metabolic interactions in presence and absence of the bacterial consortium. Microscopic observation showed an unusual physical contact between the fungal mycelium and dinoflagellate cells. To delineate specialized metabolome alterations during microalgal-fungal co-culture metabolomes were monitored by high-performance liquid chromatography coupled to high-resolution mass spectrometry. In-depth multivariate statistical analysis using dedicated approaches highlighted (1) the metabolic alterations associated with microalgal-fungal co-culture, and (2) the impact of associated bacteria in microalgal metabolome response to fungal interaction. Unfortunately, only a very low number of highlighted features were fully characterized. However, an up-regulation of the dinoflagellate toxins okadaic acid and dinophysistoxin 1 was observed during co-culture in supernatants. Such results highlight the importance to consider microalgal-fungal interactions in the study of parameters regulating toxin production.

Quantification of Xylanolytic and Cellulolytic Activities of Fungal Strains Isolated from Palmaria palmata to Enhance R-Phycoerythrin Extraction of Palmaria palmata: From Seaweed to Seaweed.

R-phycoerythrin (R-PE) can be enzymatically extracted from red seaweeds such as Palmaria palmata. This pigment has numerous applications and is notably known as an antioxidant, antitumoral or anti-inflammatory agent. Enzymes secreted by P. palmata associated fungal strains were assumed to be efficient and adapted for R-PE extraction from this macroalga. The aim of the present study was to quantify both xylanolytic and cellulolytic activities of enzymatic extracts obtained from six Palmaria palmata derived fungal strains. Degradation of P. palmata biomass by fungal enzymatic extracts was also investigated, focused on soluble protein and R-PE extraction. Enzymatic extracts were obtained by solid state fermentation. Macroalgal degradation abilities were evaluated by measuring reducing sugar release using DNS assays. Soluble proteins and R-PE recovery yields were evaluated through bicinchoninic acid and spectrophotometric assays, respectively. Various enzymatic activities were obtained according to fungal isolates up to 978 U/mL for xylanase and 50 U/mL for cellulase. Enzymatic extract allowed high degrading abilities, with four of the six fungal strains assessed exhibiting at least equal results as the commercial enzymes for the reducing sugar release. Similarly, all six strains allowed the same soluble protein extraction yield and four of them led to an improvement of R-PE extraction. R-PE extraction from P. palamata using marine fungal enzymes appeared particularly promising. To the best of our knowledge, this study is the first on the use of enzymes of P. palmata associated fungi in the degradation of its own biomass for biomolecules recovery.

[Sexual and reproductive health needs of Venezuelan migrants in the municipality of Cali, ColombiaNecessidades de saúde sexual e reprodutiva de migrantes de origem venezuelana no município de Cali (Colômbia)]. / Necesidades en salud sexual y reproductiva en migrantes de origen venezolano en el municipio de Cali (Colombia).

Objective: This study seeks to understand the needs associated with the sexual and reproductive health of migrants of Venezuelan origin settled temporarily or permanently in Santiago de Cali, Colombia. Methods: A qualitative study was conducted with Venezuelan migrants between 15 and 60 years old. Participants were selected using the snowball technique. Information was initially gathered from people identified by migrant organizations, followed by information gathering in areas with high concentrations of migrants of Venezuelan origin. In-depth interviews were held, and thematic content was analyzed. Results: Of the 48 migrants who participated, 70.8% did not have legal migratory status and were living in conditions of socioeconomic vulnerability. The participants had scarce economic resources, a lack of job opportunities, precarious human capital, and varying levels of social capital, coupled with weak social integration that limited their awareness and appropriation of their rights. Immigration status constituted an access barrier to health services and other social services. There was a particular need for information on sexual and reproductive health rights, with increased risk among young people 15 to 29 years old and members of the LGBTIQ+ community, due to their greater vulnerability and exposure to unsafe spaces for self-care, personal hygiene, and privacy, in addition to their greater need for health care, treatment of sexually transmitted infections, psychosocial support for violence, substance abuse, family conflicts, and gender transition processes. Conclusions: The sexual and reproductive health needs of Venezuelan migrants are determined by their living conditions and migratory experiences.

Objetivo: Compreender as necessidades associadas à saúde sexual e reprodutiva (SSR) dos migrantes de origem venezuelana estabelecidos temporária ou permanentemente em Santiago de Cali, Colômbia. Método: Foi realizado um estudo qualitativo com migrantes de origem venezuelana entre 15 e 60 anos. Os participantes foram selecionados pela técnica de bola de neve. A coleta de informações começou com pessoas encaminhadas por organizações de migrantes e, posteriormente, percorrendo áreas com alta concentração de migrantes de origem venezuelana. Foram realizadas entrevistas em profundidade e análise de conteúdo temático. Resultados: Participaram 48 migrantes, dos quais 70,8% não tinham sua situação imigratória regularizada e se encontravam em situação de vulnerabilidade socioeconômica. Os participantes tinham poucos recursos econômicos, falta de oportunidades de trabalho, capital humano precário e níveis variáveis de capital social, somados a uma fraca integração social que limitava a efetivação dos direitos dos quais são titulares. O status migratório é uma barreira ao acesso aos serviços de saúde e outros serviços sociais. Destacam-se as necessidades de informação sobre direitos à saúde sexual e reprodutiva, maior risco entre jovens de 15 a 29 anos e na comunidade LGBTIQ+ ­ devido à maior vulnerabilidade e exposição a espaços inseguros para autocuidado, higiene pessoal e privacidade ­, necessidade de cuidados e tratamento de infecções sexualmente transmissíveis, apoio psicossocial em casos de violência, consumo de substâncias psicoativas, conflitos familiares e processos de transição de gênero. Conclusões: As necessidades em matéria de saúde sexual e reprodutiva dos migrantes de origem venezuelana são determinadas por suas condições de vida e trajetórias migratórias.

Pentadecaibins I-V: 15-Residue Peptaibols Produced by a Marine-Derived Trichoderma sp. of the Harzianum Clade.

In the course of investigations on peptaibol chemodiversity from marine-derived Trichoderma spp., five new 15-residue peptaibols named pentadecaibins I-V (1-5) were isolated from the solid culture of the strain Trichoderma sp. MMS1255 belonging to the T. harzianum species complex. Phylogenetic analyses allowed precise positioning of the strain close to T. lentiforme lineage inside the Harzianum clade. Peptaibol sequences were elucidated on the basis of their MS/MS fragmentation and extensive 2D NMR experiments. Amino acid configurations were determined by Marfey's analyses. The pentadecaibins are based on the sequences Ac-Aib1-Gly2-Ala3-Leu4-Aib/Iva5-Gln6-Aib/Iva7-Val/Leu8-Aib9-Ala10-Aib11-Aib12-Aib13-Gln14-Pheol15. Characteristic of the pentadecaibin sequences is the lack of the Aib-Pro motif commonly present in peptaibols produced by Trichoderma spp. Genome sequencing of Trichoderma sp. MMS1255 allowed the detection of a 15-module NRPS-encoding gene closely associated with pentadecaibin biosynthesis. Pentadecaibins were assessed for their potential antiproliferative and antimicrobial activities.

Steroids from Marine-Derived Fungi: Evaluation of Antiproliferative and Antimicrobial Activities of Eburicol.

The most common sterol in fungi is ergosterol, which has frequently been investigated in human pathogenic fungal strains. This sterol, and others isolated from fungal strains, has also demonstrated cytotoxicity against cancer cell lines and antimicrobial activities. Marine fungi can produce high amounts of bioactive compounds. So, a screening was performed to study sterol composition using GC/MS in 19 marine fungal strains and ergosterol was always the major one. One strain, Clonostachys rosea MMS1090, was selected due to its high amount of eburicol and a one strain many compounds approach was performed on seven culture media to optimize its production. After purification and structural identification by NMR, eburicol was assessed against four cancer cell lines, MCF-7, MDA-MB-231, NSCLC-N6-L16 and A549, and seven human pathogenic bacteria Staphylococcus aureus, Bacillus sp., Bacillus cereus, Listeria ivanovii, Escherichia coli, Citrobacter freundii and Salmonella spp. The most significant activity was cytotoxicity against MCF-7 cells (2 µM). This is the first report of such an accumulation of eburicol in the marine fungal strain C. rosea confirming its potential in the production of bioactive lipids.

How are 1,2,3-triazoles accommodated in helical secondary structures?

1,4-Disubstituted-1,2,3-triazole (Tz) is widely used in peptides as a trans-amide bond mimic, despite having hazardous effects on the native peptide activity. The impact of amide bond substitution by Tz on peptide secondary structures is scarcely documented. We performed a Tz scan, by systematically replacing peptide bonds following the Aib residues with Tz on two model peptaibols: alamethicin F50/5 and bergofungin D, which adopt stable α- and 310 helices, respectively. We observed that the Tz insertion, whatever its position in the peptide sequences, abolished their antimicrobial activity. The structural consequences of this insertion were further investigated using CD, NMR and X-ray diffraction. Importantly, five crystal structures that were incorporated with Tz were solved, showing various degrees of alteration of the helical structures, from minor structural perturbation of the helix to partial disorder. Together, these results showed that Tz insertions impair helical secondary structures.

Hyporientalin A, an anti-Candida peptaibol from a marine Trichoderma orientale.

A Trichoderma orientale strain LSBA1 was isolated from the Mediterranean marine sponge Cymbaxinella damicornis. The crude extract of T. orientale mycelium showed inhibitory activity against growth of Gram-positive and Gram-negative bacteria as well as clinical isolates of Candida albicans. Purification of the anti-Candida component was performed using a combination of open silica gel-60 column and reverse phase high performance liquid chromatography. The active compound called hyporientalin A has been identified as a peptaibol analogue of longibrachin-A-II using mass spectrometry. It exhibited fungicidal activity against clinical isolates of C. albicans with minimal inhibitory concentrations (MICs) ranging from 2.49 to 19.66 µM, comparable to that of the antifungal agent amphotericin B. Our data support the use of hyporientalin A as a promising new and efficient antifungal drug in the treatment of candidiasis while controlling toxicity.

Enhancing the Antimicrobial Activity of Alamethicin F50/5 by Incorporating N-terminal Hydrophobic Triazole Substituents.

A simple and efficient strategy is proposed to significantly improve the antibacterial activity of peptaibols and other antimicrobial peptides by N-terminal capping with 1,2,3-triazole bearing various hydrophobic substituents on C-4. Such N-terminal insertions on alamethicin F50/5 could enhance its antimicrobial activity on Gram-positive bacteria without modification of its overall three-dimensional structure. Although the native peptide and its analogues shared comparable helical contents, the crystal structure of one of the most active derivative showed a local slight distortion of the N-terminal extremity, which was also observed in solution using NMR spectroscopy. Importantly, fluorescence studies showed that the N-capped derivatives had increased affinity for liposomes, which may indicate they interacted more strongly with the bacterial membrane than alamethicin F50/5.

The Comparative Role of the Anterior Cruciate Ligament and Anterolateral Structures in Controlling Passive Internal Rotation of the Knee: A Biomechanical Study.

PURPOSE: To determine the respective functions of the anterior cruciate ligament (ACL) and the anterolateral structures (ALSs) in controlling the tibia's passive internal rotation (IR) with respect to the femur, under uniaxial rotation. METHODS: To test the function of the ACL and the anterolateral ligament (ALL) in IR, we designed a sequential transection study of the ACL and the anterolateral structures (including the ALL) in 24 cadaveric knees divided in 2 groups. Two sequences were conducted successively: group 1 (12 knees) in which the ACL was sectioned first followed by the ALS, and group 2 (12 knees) with reversed transections. Each knee, in neutral rotation position and at flexion angle of 30°, was subjected to a 5 Nm torsion torque of IR. IR was measured using a rotatory laximeter, the Rotam with a gyroscope's measurement accuracy of 0.1°. Laxities were compared using paired t test within each group and using t test between groups. Fisher exact test was used to compare proportions. RESULTS: In group 1, IR increased from 22.1° ± 10.6° to 25.7° ± 10.9° after ACL transection then to 28.1° ± 10.5° after we sectioned the ALS. In group 2, IR increased from 22.5° ± 8.9° to 25.2° ± 8.4° after sectioning the ALS, then to 29.1° ± 8.8° after we sectioned the ACL. Total postsectioning increase in IR was 6.4° ± 2° in group 1, and 6.55° ± 0.9° in group 2. The IR increase after each stage of transection and final IR were statistically significant (P < .001). CONCLUSIONS: In a pure rotational cadaveric test model, the ACL and the ALS contribute to resistance to passive IR of the knee. CLINICAL RELEVANCE: In some specific clinical cases, peripheral lesions may be considered, and injuries to these structures may need to be addressed to improve results controlling postoperative IR.

Identification and Biological Activities of Long-Chain Peptaibols Produced by a Marine-Derived Strain of Trichoderma longibrachiatum.

Six long-chain peptaibols, 1 - 6, were identified from agar cultures of a marine-derived Trichoderma longibrachiatum Rifai strain (MMS151) isolated from blue mussels. The structure elucidation was carried out using electrospray ionization ion trap mass spectrometry (ESI-IT-MS) and GC/EI-MS. The long-chain peptaibols exhibited the general building scheme Ac-Aib-Ala-Aib-Ala-Aib-XXX-Gln-Aib-Vxx-Aib-Gly-XXX-Aib-Pro-Vxx-Aib-XXX-Gln-Gln-Pheol and were similar or identical to recurrent 20-residue peptaibols produced by Trichoderma spp. Three new sequences were identified and were called longibrachins A-0, A-II-a, and A-IV-b. The isolated peptaibols were assayed for cytotoxic, antibacterial, and antifungal activities, and acute toxicity on Dipteran larvae.

Do graft diameter or patient age influence the results of ACL reconstruction?

PURPOSE: Hamstring tendons are commonly used as a graft source for ACL reconstruction. This study seeks to determine whether either the diameter of the tendon graft or the age of the patient influences the outcome of the ACL reconstruction when measured using a standard, previously validated laxity measurement device. METHODS: This is a retrospective study of 88 patients who underwent ACL reconstruction with a short, quadrupled tendon technique, using the semitendinosus ± gracilis tendons. Patients included in this study were sequential, unilateral, complete ACL ruptures. The patients were followed for a minimum of 1 year postoperatively, with a mean follow-up of 26 months. Patients were divided into three groups according to the diameter (Ø) of the graft: group 1 (32 patients): 8 mm ≤ Ø ≤ 9 mm; group 2 (28 patients): 9 mm < Ø ≤ 10 mm; and group 3 (28 patients): Ø > 10 mm. Three groups with differential laxity at 134 N (Δ134 = healthy side vs. operated side) measured with the laximeter GNRB(®) were compared. The risk of residual laxity (OR) between the three groups taking age, gender, BMI and meniscus status into account was calculated. A side-to-side laxity >3 mm was considered as a residual laxity. RESULTS: The mean patient age at the time of reconstruction was 29.4 years. The three groups were comparable. Postoperative Δ134 was 1.50 ± 1.3, 1.59 ± 1.5 and 2 ± 1.7 mm for groups 1 through 3, respectively. Δ134 > 3 mm was observed in three patients in group 1, four patients in group 2 and nine patients in group 3. As compared to group 1, OR was 1.46 (95 % CI 0.35-6.05) and 3.31 (95 % CI 0.89-12.34) in groups 2 and 3, respectively. Adjustment for age, gender, BMI and meniscus did not change the estimates [OR 1.44 (95 % CI 0.34-6.16) and 3.92 (95 % CI 1-15.37)] in groups 2 and 3, respectively. Patients younger than 20 had a significantly higher average postoperative laximetry (2.4 ± 1.5 mm) compared to those aged 20 years and over (1.5 ± 1.5 mm) (p = 0.03), regardless of the diameter of the graft. CONCLUSION: The diameter of the graft between 8 and 10 mm does not affect the laximetric results of an ACL reconstruction. Therefore, there does not appear to be a benefit to harvesting and adding further tissue to increase the diameter of the graft above 10 mm. Patients younger than 20 represent a population at risk of graft elongation. In these patients at risk, postoperative management needs to be modified (delayed weight bearing, articulated splinting, slower rehabilitation) in the first months. LEVEL OF EVIDENCE: Retrospective case series, Level IV.

The Marine-Derived Fungus Clonostachys rosea, Source of a Rare Conjugated 4-Me-6E,8E-hexadecadienoic Acid Reducing Viability of MCF-7 Breast Cancer Cells and Gene Expression of Lipogenic Enzymes.

A marine-derived strain of Clonostachys rosea isolated from sediments of the river Loire estuary (France) was investigated for its high lipid production. The fungal strain was grown on six different culture media to explore lipid production changes. An original branched conjugated fatty acid, mainly present in triglycerides and mostly produced when grown on DCA (23% of total fatty acid composition). It was identified as 4-Me-6E,8E-hexadecadienoic on the basis of spectroscopic analyses. This fatty acid reduced viability of MCF-7 breast cancer cells in a dose dependent manner (up to 63%) at physiological free fatty acid human plasma concentration (100 µM). Reduction of gene expression of two lipogenic enzymes, the acetyl CoA carboxylase (ACC) and the fatty acid synthase (FAS) was evaluated to explore the mechanisms of action of 4-Me-6E,8E-16:2 acid. At 50 µM, 50% and 35% of mRNA gene expression inhibition were observed for ACC and FAS, respectively.

Exploring the complementarity of fast multipulse and multidimensional NMR methods for metabolomics: a chemical ecology case study.

This study investigates the potential and complementarity of high-throughput multipulse and multidimensional NMR methods for metabolomics. Through a chemical ecology case study, three methods are investigated, offering a continuum of methods with complementary features in terms of resolution, sensitivity and experiment time. Ultrafast 2D COSY, adiabatic INEPT and SYMAPS HSQC are shown to provide a very good classification ability, comparable to the reference 1D 1H NMR method. Moreover, a detailed analysis of discriminant buckets upon supervised statistical analysis shows that all methods are highly complementary, since they are able to highlight discriminant signals that could not be detected by 1D 1H NMR. In particular, fast 2D methods appear very efficient to discriminate signals located in highly crowded regions of the 1H spectrum. Overall, the combination of these recent methods within a single NMR metabolomics workflow allows to maximize the accessible metabolic information, and also raises exciting challenges in terms of NMR data analysis for chemical ecology.

Indication, performance and outcomes of adrenal vein sampling in patients with primary hyperaldosteronism.

Primary hyperaldosteronism (PAH) is an important cause of secondary hypertension (HTN). The study of the same requires a high clinical suspicion in addition to a hormonal study that confirms hormonal hypersecretion. It is important to start the appropriate treatment once the diagnosis is confirmed, and for this is necessary to demonstrate whether the hormonal hypersecretion is unilateral (patients who could be candidates for surgical treatment) or bilateral (patients who are candidates for pharmacological treatment only). At the Hospital del Mar since 2016 there has been a multidisciplinary work team in which Nephrologists, Endocrinologists, Radiologists and Surgeons participate to evaluate cases with suspected hyperaldosteronism and agree on the best diagnostic-therapeutic approach for these patients, including the need for adrenal vein sampling, which is a technique that in recent years has become the gold standard for the study of PAH. In the present study we collect the experience of our centre in performing AVC and its usefulness for the management of these patients.

HLA-C*07 is associated with symptomatic HIV-1-associated neurocognitive disorders (HAND) and immune dysregulation.

BACKGROUND: HIV-1-associated neurocognitive disorders (HAND) in stable patients undergoing antiretroviral therapy (ART) may result from ongoing immune dysregulation and chronic inflammation. A contributing factor may result from the unstable HLA class I allele, HLA-C*07. OBJECTIVE: To assess the genetic profile of killer-cell immunoglobulin-like receptors (KIR), human leukocyte antigens (HLA), and immune activation or senescence markers and their association with HAND in stable HIV-1 patients receiving ART. METHODS: An observational cross-sectional study was carried out with 96 patients with asymptomatic or symptomatic HAND. HLA and KIR as well as immune activation/senescence biomarkers in peripheral blood cells were assessed by SSO-Luminex typing and flow cytometry, respectively. RESULTS: HLA-C*07 is associated with symptomatic HAND. The frequency of two copies of HLA-C*07 was higher in patients with symptomatic than with asymptomatic HAND (12.0 vs. 2.2%, ρ < 0.001). The percentage of senescent CD8+CD28- T-cells was higher in patients with two copies of HLA-C*07 (ρ < 0.05). In patients with symptomatic HAND, the percentages of non-senescent CD8+CD28+ T cells were inversely proportional to the number of copies of the HLA-C*07 (ρ < 0.05). CONCLUSION: Patients with symptomatic HAND showed a higher frequency of the homozygotic unstable HLA-C*07 allotype, which could be associated with neurocognitive complications. Two copies of HLA-C*07 were associated with immune senescent T lymphocyte profiles characterized by the loss of CD28 expression.

Antiprotozoal and antimycobacterial activities of Persea americana seeds.

BACKGROUND: Persea americana seeds are widely used in traditional Mexican medicine to treat rheumatism, asthma, infectious processes as well as diarrhea and dysentery caused by intestinal parasites. METHODS: The chloroformic and ethanolic extracts of P. americana seeds were prepared by maceration and their amoebicidal, giardicidal and trichomonicidal activity was evaluated. These extracts were also tested against Mycobacterium tuberculosis H37Rv, four mono-resistant and two multidrug resistant strains of M. tuberculosis as well as five non tuberculosis mycobacterium strains by MABA assay. RESULTS: The chloroformic and ethanolic extracts of P. americana seeds showed significant activity against E. histolytica, G. lamblia and T. vaginalis (IC50 <0.634 µg/ml). The chloroformic extract inhibited the growth of M. tuberculosis H37Rv, M. tuberculosis MDR SIN 4 isolate, three M. tuberculosis H37Rv mono-resistant reference strains and four non tuberculosis mycobacteria (M. fortuitum, M. avium, M. smegmatis and M. absessus) showing MIC values ≤50 µg/ml. Contrariwise, the ethanolic extract affected only the growth of two mono-resistant strains of M. tuberculosis H37Rv and M. smegmatis (MIC ≤50 µg/ml). CONCLUSIONS: The CHCl3 and EtOH seed extracts from P. americana showed amoebicidal and giardicidal activity. Importantly, the CHCl3 extract inhibited the growth of a MDR M. tuberculosis isolate and three out of four mono-resistant reference strains of M. tuberculosis H37Rv, showing a MIC = 50 µg/ml. This extract was also active against the NTM strains, M. fortuitum, M. avium, M. smegmatis and M. abscessus, with MIC values <50 µg/ml.

Unprecedented 17-residue peptaibiotics produced by marine-derived Trichoderma atroviride.

In the course of investigations on marine-derived toxigenic fungi, five strains of Trichoderma atroviride were studied for their production of peptaibiotics. While these five strains were found to produce classical 19-residue peptaibols, three of them exhibited unusual peptidic sodium-adduct [M + 2 Na](2+) ion peaks at m/z between 824 and 854. The sequencing of these peptides led to two series of unprecedented 17-residue peptaibiotics based on the model Ac-XXX-Ala-Ala-XXX-XXX-Gln-Aib-Aib-Aib-Ala/Ser-Lxx-Aib-Pro-XXX-Aib-Lxx-[C(129) ]. The C-terminus of these new peptides was common to all of them, and its elemental formula C5 H9 N2 O2 was established by HR-MS. It could correspond to the cyclized form of N(δ) -hydroxyornithine which has already been observed at the C-terminus of various peptidic siderophores. The comparison of the sequences of 17- and 19-residue peptides showed similarities for positions 1-16. This observation seems to indicate a common biosynthesis pathway. Both new 17-residue peptaibiotics and 19-residue peptaibols exhibited weak in vitro cytotoxicities against KB cells.

Smart Polymer Surfaces with Complex Wrinkled Patterns: Reversible, Non-Planar, Gradient, and Hierarchical Structures.

This review summarizes the relevant developments in preparing wrinkled structures with variable characteristics. These include the formation of smart interfaces with reversible wrinkle formation, the construction of wrinkles in non-planar supports, or, more interestingly, the development of complex hierarchically structured wrinkled patterns. Smart wrinkled surfaces obtained using light-responsive, pH-responsive, temperature-responsive, and electromagnetic-responsive polymers are thoroughly described. These systems control the formation of wrinkles in particular surface positions and the reversible construction of planar-wrinkled surfaces. This know-how of non-planar substrates has been recently extended to other structures, thus forming wrinkled patterns on solid, hollow spheres, cylinders, and cylindrical tubes. Finally, this bibliographic analysis also presents some illustrative examples of the potential of wrinkle formation to create more complex patterns, including gradient structures and hierarchically multiscale-ordered wrinkles. The orientation and the wrinkle characteristics (amplitude and period) can also be modulated according to the requested application.

Effect of neoadjuvant chemotherapy on tumor immune infiltration in breast cancer patients: Systematic review and meta-analysis.

The tumor immune infiltrate has an impact on cancer control and progression, additionally a growing body of evidence has proposed the role of neoadjuvant chemotherapy in modulating the contexture of the tumor immune infiltrate. Here, we performed a systematic review to evaluate the effect of chemotherapy in the immune infiltration of breast cancer tumors. We systematically searched Pubmed/MEDLINE, EMBASE, CENTRAL, and BVS databases with a cutoff date of 11/06/2022. Studies in patients with pathological diagnosis of BC, whose first line of treatment was only NAC, were included. Only published experimental studies that measured tumor immune infiltrate before and after NAC by hematoxylin and eosin (H&E) staining, immunohistochemistry (IHQ), or transcriptome were included. Reviews, studies with animal models and in-vitro models were excluded. Studies in which BC was not the primary tumor or studies with patients who received other types of neoadjuvant therapy were also excluded. The NIH quality assessment tool for before and after studies without control was used. We included 32 articles that evaluated the proximal tumor microenvironment before and after neoadjuvant chemotherapy in 2072 patients who received NAC as first line of treatment and who were evaluated for immune infiltrate in the pre- and post-chemotherapy tumor sample. Results were divided into two major categories immune cells and in-situ expression of immune checkpoints and cytokines. Qualitative synthesis was performed with the 32 articles included, and in nine of them a quantitative analysis was achieved, resulting in six meta-analyses. Despite high heterogeneity among the articles regarding treatment received, type of tumor reported, and techniques used to evaluate immune infiltrate, we found a significant decrease of TILs and FoxP3 expression after neoadjuvant chemotherapy. The study protocol was registered in PROSPERO 2021 (Protocol ID: CRD42021243784) on 6/29/2021.