Breaking Cycles: Saponification-Enhanced NMR Fingerprint Matching for the Identification and Stereochemical Evaluation of Cyclic Lipodepsipeptides from Natural Sources.

We previously described NMR based fingerprint matching with peptide backbone resonances as a fast and reliable structural dereplication approach for Pseudomonas cyclic lipodepsipeptides (CLiPs). In combination with total synthesis of a small library of configurational CLiP congeners this also allows unambiguous determination of stereochemistry, facilitating structure-activity relationship studies and enabling three-dimensional structure determination. However, the on-resin macrocycle formation in the synthetic workflow brings considerable burden and limits universal applicability. This drawback is here removed altogether by also transforming the native CLiP into a linearized analogue by controlled saponification of the ester bond. This eliminates the need for macrocycle formation, limiting the synthesis effort to linear peptide analogues. NMR fingerprints of such linear peptide analogues display a sufficiently distinctive chemical shift fingerprint to act as effective discriminators. The approach is developed using viscosin group CLiPs and subsequently demonstrated on putisolvin, leading to a structural revision, and tanniamide from Pseudomonas ekonensis COR58, a newly isolated lipododecapeptide that defines a new group characterized by a ten-residue large macrocycle, the largest to date in the Pseudomonas CLiP portfolio. These examples demonstrate the effectiveness of the saponification- enhanced approach that broadens applicability of NMR fingerprint matching for the determination of the stereochemistry of CLiPs.

IL-6-mediated endothelial injury impairs antiviral humoral immunity after bone marrow transplantation.

Endothelial function and integrity are compromised after allogeneic bone marrow transplantation (BMT), but how this affects immune responses broadly remains unknown. Using a preclinical model of CMV reactivation after BMT, we found compromised antiviral humoral responses induced by IL-6 signaling. IL-6 signaling in T cells maintained Th1 cells, resulting in sustained IFN-γ secretion, which promoted endothelial cell (EC) injury, loss of the neonatal Fc receptor (FcRn) responsible for IgG recycling, and rapid IgG loss. T cell-specific deletion of IL-6R led to persistence of recipient-derived, CMV-specific IgG and inhibited CMV reactivation. Deletion of IFN-γ in donor T cells also eliminated EC injury and FcRn loss. In a phase III clinical trial, blockade of IL-6R with tocilizumab promoted CMV-specific IgG persistence and significantly attenuated early HCMV reactivation. In sum, IL-6 invoked IFN-γ-dependent EC injury and consequent IgG loss, leading to CMV reactivation. Hence, cytokine inhibition represents a logical strategy to prevent endothelial injury, thereby preserving humoral immunity after immunotherapy.

Selenium reduction pathways in the colloidal synthesis of CdSe nanoplatelets.

Several established procedures are now available to prepare zinc blende CdSe nanoplatelets. While these protocols allow for detailed control over both thickness and lateral dimensions, the chemistry behind their formation is yet to be unraveled. In this work, we discuss the influence of the solvent on the synthesis of nanoplatelets. We confirmed that the presence of double bonds, as is the case for 1-octadecene, plays a key role in the evolution of nanoplatelets, through the isomerization of the alkene, as confirmed by nuclear magnetic resonance spectroscopy and mass spectrometry. Consequently, 1-octadecene can be replaced as a solvent (or solvent mixture), however, only by one that also contains α protons to CC double bonds. We confirm this via synthesis of nanoplatelets in hexadecane spiked with a small amount of 1-octadecene, and in the aromatic solvent 1,2,3,4-tetrahydronaphthalene (tetralin). At the same time, the chemical reaction leading to the formation of nanoplatelets occurs to some extent in saturated solvents. A closer examination revealed that an alternative formation pathway is possible, through interaction of carboxylic acids, such as octanoic acid, with selenium. Next to shedding more light on the synthesis of CdSe nanoplatelets, fundamental understanding of the precursor chemistry paves the way to use optimized solvent admixtures as an additional handle to control the nanoplatelet synthesis, as well as to reduce potential self-polymerization hurdles observed with 1-octadecene.

Molecular and entomological surveillance of malaria vectors in urban and rural communities of Benguela Province, Angola.

BACKGROUND: Malaria is a major public health problem in Angola, with Anopheles gambiae sensu lato (s.l.) and An. funestus s.l. being the primary vectors. This study aimed to clarify the information gaps concerning local Anopheles mosquito populations. Our objectives were to assess their abundance, geographical dispersion, and blood-feeding patterns. We also investigated their insecticide resistance. Molecular methods were used to identify sibling species, determine the origin of blood meals, measure Plasmodium falciparum infection rates, and detect the presence of knockdown resistance (kdr) mutations. METHODS: Adult mosquitoes were collected indoors using CDC light traps from nine randomly selected households at two sentinel sites with distinct ecological characteristics. The samples were collected from 1 February to 30 June 2022. Anopheles mosquitoes were morphologically identified and subjected to molecular identification. Unfed Anopheles females were tested for the presence of P. falciparum DNA in head and thorax, and engorged females were screened for the source of the blood meals. Additionally, members of An. gambiae complex were genotyped for the presence of the L1014F and L1014S kdr mutations. RESULTS: In total, 2226 adult mosquitoes were collected, including 733 Anopheles females. Molecular identification revealed the presence of Anopheles coluzzii, An. gambiae senso stricto (s.s.), An. arabiensis, and An. funestus s.s. Notably, there was the first record of An. coluzzii/An. gambiae s.s. hybrid and An. vaneedeni in Benguela Province. Plasmodium falciparum infection rates for An. coluzzii at the urban sentinel site and An. funestus s.s. at the rural site were 23.1% and 5.7%, respectively. The L1014F kdr mutation was discovered in both resistant and susceptible An. coluzzii mosquitoes, while the L1014S mutation was detected in An. gambiae s.s. for the first time in Benguela Province. No kdr mutations were found in An. arabiensis. CONCLUSIONS: This study provides valuable insights into the molecular characteristics of malaria vectors from the province of Benguela, emphasising the need for continuous surveillance of local Anopheles populations regarding the establishment of both kdr mutations for tailoring vector control interventions.

Therapeutic response to four artemisinin-based combination therapies in Angola, 2021.

Monitoring antimalarial efficacy is important to detect the emergence of parasite drug resistance. Angola conducts in vivo therapeutic efficacy studies (TESs) every 2 years in its fixed sentinel sites in Benguela, Lunda Sul, and Zaire provinces. Children with uncomplicated Plasmodium falciparum malaria were treated with artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), dihydroartemisinin-piperaquine (DP), or artesunate-pyronaridine (ASPY) and followed for 28 (AL and ASAQ) or 42 days (DP and ASPY) to assess clinical and parasitological response to treatment. Two drugs were sequentially assessed in each site in February-July 2021. The primary indicator was the Kaplan-Meier estimate of the PCR-corrected efficacy at the end of the follow-up period. A total of 622 patients were enrolled in the study and 590 (95%) participants reached a study endpoint. By day 3, ≥98% of participants were slide-negative in all study sites and arms. After PCR correction, day 28 AL efficacy was 88.0% (95% CI: 82%-95%) in Zaire and 94.7% (95% CI: 90%-99%) in Lunda Sul. For ASAQ, day 28 efficacy was 92.0% (95% CI: 87%-98%) in Zaire and 100% in Lunda Sul. Corrected day 42 efficacy was 99.6% (95% CI: 99%-100%) for ASPY and 98.3% (95% CI: 96%-100%) for DP in Benguela. High day 3 clearance rates suggest no clinical evidence of artemisinin resistance. This was the fourth of five rounds of TES in Angola showing a corrected AL efficacy <90% in a site. For Zaire, AL has had an efficacy <90% in 2013, 2015, and 2021. ASAQ, DP, and ASPY are appropriate choices as artemisinin-based combination therapies in Angola.

Effect of verbal cues on the coupling and stability of anti-phase bimanual coordination pattern in children with probable developmental coordination disorder.

The study of the emergence and stability of bimanual and interlimb coordination patterns in children with Developmental Coordination Disorder (DCD) has shown that they encounter greater difficulties in coupling their limbs compared to typically developing (TD) children. Verbal cues have been identified as strategies to direct children's attention to more relevant task information, thus potentially improving motor performance. Consequently, this study investigated the effect of providing verbal cues on the execution of bimanual tasks in children with and without probable DCD. Twenty-eight children aged 9-10, matched by age and gender, were divided into two groups: pDCD [n = 14] and TD. The children performed bilateral trajectory movements with both hands (horizontal back-and-forth), holding a pen on a tablet, in anti-phase (180°) coordination pattern, in two conditions: No cues and Verbal cues. In the last condition, children received verbal cues to maintain the anti-phase pattern even with an increase in hand oscillation frequency. Relative phase and variability of relative phase between the hands were calculated for analysis of pattern coupling and stability. Hand cycles, movement amplitude, and tablet pressure force were calculated to analyze pattern control parameters. All these variables were compared between groups and conditions. The results indicated that despite the pDCD group showing greater variability in the anti-phase coordination pattern compared to the TD group, both groups performed better in the Verbal cues than the No cues condition. Furthermore, the pDCD group exhibited more hand movement cycles and applied greater pressure force compared to the TD group, suggesting different motor control strategies during the bimanual task. It is suggested that the use of verbal cues during bimanual task execution improves children's performance, potentially by promoting interaction between attention, as a cognitive function, and intrinsic coordination dynamics, thereby reducing variability in the perceptual-motor system.

Microcystin influence on soil-plant microbiota: Unraveling microbiota modulations and assembly processes in the rhizosphere of Vicia faba.

Microcystins (MCs) are frequently detected in cyanobacterial bloom-impacted waterbodies and introduced into agroecosystems via irrigation water. They are widely known as phytotoxic cyanotoxins, which impair the growth and physiological functions of crop plants. However, their impact on the plant-associated microbiota is scarcely tackled and poorly understood. Therefore, we aimed to investigate the effect of MCs on microbiota-inhabiting bulk soil (BS), root adhering soil (RAS), and root tissue (RT) of Vicia faba when exposed to 100 µg L-1 MCs in a greenhouse pot experiment. Under MC exposure, the structure, co-occurrence network, and assembly processes of the bacterial microbiota were modulated with the greatest impact on RT-inhabiting bacteria, followed by BS and, to a lesser extent, RAS. The analyses revealed a significant decrease in the abundances of several Actinobacteriota-related taxa within the RT microbiota, including the most abundant and known genus of Streptomyces. Furthermore, MCs significantly increased the abundance of methylotrophic bacteria (Methylobacillus, Methylotenera) and other Proteobacteria-affiliated genera (e.g., Paucibacter), which are supposed to degrade MCs. The co-occurrence network of the bacterial community in the presence of MCs was less complex than the control network. In MC-exposed RT, the turnover in community composition was more strongly driven by deterministic processes, as proven by the beta-nearest taxon index. Whereas in MC-treated BS and RAS, both deterministic and stochastic processes can influence community assembly to some extent, with a relative dominance of deterministic processes. Altogether, these results suggest that MCs may reshape the structure of the microbiota in the soil-plant system by reducing bacterial taxa with potential phytobeneficial traits and increasing other taxa with the potential capacity to degrade MCs.

Subacute Neurotoxicity as an Adverse Reaction to Ceftazidime: A Case Report.

Neurotoxicity associated with cephalosporins is an increasingly recognized complication, although among cephalosporins, ceftazidime is rarely reported for such an adverse reaction. Moreover, subacute, rather than acute, presentation of neurotoxicity associated with cephalosporins is rare. A 77-year-old female patient with stage 4 chronic renal disease was admitted due to cellulitis in her right lower limb, multiorgan dysfunction complicated by oliguric acute kidney injury, and a need for hemodialysis via a central venous catheter. On the 13th day after admission, she became febrile, and bacteremia associated with a central venous catheter was identified, which prompted the initiation of empirical antibiotic therapy with vancomycin and ceftazidime. After 13 days of antibiotic therapy with vancomycin and ceftazidime, the patient became confused, with temporal-spatial disorientation and myoclonus, especially in the upper limbs, with worsening renal function. Ceftazidime was discontinued, and the patient's condition improved with complete remission of symptoms on the 8th day after symptom onset. Neurotoxicity associated with ceftazidime is a rare but probably underdiagnosed adverse reaction. It is more frequent in elderly patients with previous neurological dysfunction and end-stage kidney disease and/or acute kidney injury, and it usually manifests soon after starting treatment. Early identification and monitoring of risk factors and symptoms should lead the physician to a rapid withdrawal of the offending drug.

Outcomes of transcatheter pulmonary SAPIEN 3 valve implantation: an international registry.

BACKGROUND AND AIMS: Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI. METHODS: Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries. RESULTS: Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29 mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively. CONCLUSIONS: Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs.

The provision of malaria services in border districts of four countries in Southern Africa: results from a cross-sectional community assessment of malaria border health posts

Background The importation of parasites across borders remains a threat to malaria elimination. The Southern African Development Community Malaria Elimination Eight (E8) established 39 border health facilities on 5 key international borders between high and low-burden countries. These clinics aimed to improve access to prevention, diagnosis, and treatment of malaria for residents in border areas and for mobile and migrant populations who frequently cross borders. Studies were conducted in each of the four high-burden E8 countries (Angola, Mozambique, Zambia, and Zimbabwe) to evaluate malaria services in border areas. Methods Cross-sectional surveys were conducted within 30 km of recently established E8 Border Health Posts. Structured questionnaires were administered to randomly selected respondents to assess malaria-related knowledge and behavior, access to malaria prevention, diagnosis and treatment of malaria, and risk factors for malaria associated with local and cross-border travel. Results Results showed that most providers followed appropriate guidelines performing blood tests when individuals presented with fever, and that nearly all those who reported a positive blood test received medication. Lack of access to health care due to distance, cost or mistrust of the provider was rare. A minority of respondents reported not receiving timely diagnosis either because they did not seek help, or because they were not ofered a blood test when presenting with fever. There was a high level of correct knowledge of causes, symptoms, and prevention of malaria. A majority, of border residents had access to primary prevention against malaria through either long-lasting insecticidal nets (LLINs) or indoor residual spraying (IRS). Cross border travel was common with travellers reporting sleeping outside without protection against malaria. Conclusions The study demonstrated the importance of border health facilities in providing access to malaria services. Prevention needs to be improved for people who travel and sleep outdoors. Community health workers can play a key role in providing access to information, testing and treating malaria.

First Report of Kocuria kristinae in the Skin of a Cuban Boa (Epicrates angulifer).

During a routine clinical examination of a four-year-old female Cuban boa (Epicrates angulifer) belonging to a zoological park located in northern Portugal, a skin lesion was observed. A skin swab was taken. Bacteriological analysis conducted using the Vitek® 2 Compact system identified the presence of the bacteria species Kocuria kristinae, a new bacterial pathogen that may be a potential pathogen in wild animals. This K. kristinae strain was resistant to kanamycin, pradofloxacin, erythromycin, clindamycin, tetracycline, nitrofurantoin, and trimethoprim/sulphamethoxazole and was therefore classified as a multidrug-resistant bacterium. To the authors' knowledge, this is the first time that K. kristinae has been described in the skin of a Cuban boa. This report serves as a cautionary warning about the importance of recognising and investigating the potential pathogenicity of this agent, as well as contributing to the development of strategies to prevent the spread of antibiotic-resistant microorganisms.

Doctors for Brazil Program: first results. / Programa Médicos pelo Brasil: primeiros resultados.

Access to medical care is essential to achieve quality primary health care (PHC). In Brazil, access difficulties still persist. The Doctors for Brazil Program (PMpB in Portuguese) aims to expand the offer of medical services in places of difficult provision or high vulnerability. It innovates insofar as it prioritizes smaller and rather isolated cities, by selecting professionals through an isonomic process, offering them training in Family and Community Medicine and a chance to build their first federal medical career in PHC. The program offers competitive salaries, progression and financial incentives that value long-term commitment and performance. The PMpB is rolled out by the Agency for the Development of Primary Health Care (Adaps), which allows better management of public policies. The first nine months of the program showed promising results, as approximately 23,000 candidates seeking to join the program through its selection process, i.e., 97.1% vacancies were filled and retention rate after admittance was 95.4%. These results show to what extent PMpB has improved in quality compared to previous policies, as well as how essential it is to keep implementing the program so that it may reach its full PHC coverage potential within the Brazilian public health system.

O acesso ao cuidado médico é essencial para o alcance da atenção primária à saúde (APS) de qualidade. No Brasil, ainda persistem dificuldades de acesso. O Programa Médicos pelo Brasil (PMpB) pretende ampliar a oferta de serviços médicos em locais de difícil provimento ou alta vulnerabilidade. Traz como inovações a priorização das menores e mais isoladas cidades; a seleção de profissionais por processo isonômico; a formação em medicina de família e comunidade; e o fato de ser a primeira carreira médica federal na APS, com salários competitivos, progressão e incentivos financeiros que valorizam a longitudinalidade e o desempenho. O PMpB é executado pela Agência para o Desenvolvimento da Atenção Primária à Saúde (Adaps), o que permite mais eficiência na gestão da política pública. Os primeiros nove meses do programa mostram resultados promissores, com aproximadamente 23 mil médicos interessados em ingressar no programa por meio de seu processo seletivo, 97,1% de ocupação das vagas e 95,4% de permanência após o ingresso. Tais resultados sinalizam o avanço de qualidade do PMpB em relação às políticas anteriores, bem como a necessidade de continuar com sua implementação, a fim de que ela atinja todo o seu potencial de cobertura na APS do SUS.

Influence of Sex and a High-Fiber Diet on the Gut Microbiome of Alentejano Pigs Raised to Heavy Weights.

This study investigates the influence of sex and a dietary transition on the gut microbiota of a local Portuguese pig breed. Three groups of male Alentejano pigs (n = 10 each) were raised between ~40 and 160 kg LW. Group C included pigs that were surgically castrated, while the I group included intact ones; both were fed with commercial diets. The third group, IExp, included intact pigs that were fed commercial diets until ~130 kg, then replaced by an experimental diet based on legumes and agro-industrial by-products between ~130 and 160 kg. Fecal samples were collected two weeks before slaughter. The total DNA was extracted and used for 16S metabarcoding on a MiSeq® System. The dietary transition from a commercial diet to the experimental diet substantially increased and shifted the diversity observed. Complex carbohydrate fermenting bacteria, such as Ruminococcus spp. and Sphaerochaeta spp., were significantly more abundant in IExp (q < 0.05). On the other hand, castrated pigs presented a significantly lower abundance of the potential probiotic, Roseburia spp. and Lachnospiraceae NK4A136 group (q < 0.01), bacteria commonly associated with better gut health and lower body fat composition. Understanding the role of gut microbiota is paramount to ensure a low skatole deposition and consumers' acceptance of pork products from non-castrated male pigs.

Programa Médicos pelo Brasil: primeiros resultados / Doctors for Brazil Program: first results

Resumo O acesso ao cuidado médico é essencial para o alcance da atenção primária à saúde (APS) de qualidade. No Brasil, ainda persistem dificuldades de acesso. O Programa Médicos pelo Brasil (PMpB) pretende ampliar a oferta de serviços médicos em locais de difícil provimento ou alta vulnerabilidade. Traz como inovações a priorização das menores e mais isoladas cidades; a seleção de profissionais por processo isonômico; a formação em medicina de família e comunidade; e o fato de ser a primeira carreira médica federal na APS, com salários competitivos, progressão e incentivos financeiros que valorizam a longitudinalidade e o desempenho. O PMpB é executado pela Agência para o Desenvolvimento da Atenção Primária à Saúde (Adaps), o que permite mais eficiência na gestão da política pública. Os primeiros nove meses do programa mostram resultados promissores, com aproximadamente 23 mil médicos interessados em ingressar no programa por meio de seu processo seletivo, 97,1% de ocupação das vagas e 95,4% de permanência após o ingresso. Tais resultados sinalizam o avanço de qualidade do PMpB em relação às políticas anteriores, bem como a necessidade de continuar com sua implementação, a fim de que ela atinja todo o seu potencial de cobertura na APS do SUS.

Abstract Access to medical care is essential to achieve quality primary health care (PHC). In Brazil, access difficulties still persist. The Doctors for Brazil Program (PMpB in Portuguese) aims to expand the offer of medical services in places of difficult provision or high vulnerability. It innovates insofar as it prioritizes smaller and rather isolated cities, by selecting professionals through an isonomic process, offering them training in Family and Community Medicine and a chance to build their first federal medical career in PHC. The program offers competitive salaries, progression and financial incentives that value long-term commitment and performance. The PMpB is rolled out by the Agency for the Development of Primary Health Care (Adaps), which allows better management of public policies. The first nine months of the program showed promising results, as approximately 23,000 candidates seeking to join the program through its selection process, i.e., 97.1% vacancies were filled and retention rate after admittance was 95.4%. These results show to what extent PMpB has improved in quality compared to previous policies, as well as how essential it is to keep implementing the program so that it may reach its full PHC coverage potential within the Brazilian public health system.

Influence of Sex on Meat and Fat Quality from Heavy Alentejano Pigs Finished Outdoors on Commercial and High Fiber Diets.

This work aimed to examine the effects of sex on meat and fat quality traits from thirty Portuguese Alentejano (AL) pigs reared in outdoor conditions. These pigs were divided into three groups and fed ad libitum. From ~40 to 130 kg LW, castrated (C group) and intact animals (I and IExp) consumed commercial diets. Until slaughter (~160 kg), C and I pigs remained on commercial diets, and IExp changed to a more sustainable experimental diet with locally produced pulses and byproducts. Samples were collected from the Longissimus lumborum (LL), Psoas major (PM), and dorsal subcutaneous fat (DSF). At ~160 kg, the PM muscle of intact pigs presented lower intramuscular fat content than that of C pigs, while total collagen was higher. Additionally, PM myoglobin was lower and lightness (L*) was higher in intact pigs. Regarding DSF, moisture and total protein contents were higher and total lipids were lower in intact than in castrated pigs, while color parameters were not significantly different. Finally, antioxidant capacity measured in the LL muscle showed an overall lower value in intact pigs. However, lipid oxidation values were not significantly different between the experimental groups and only increased with storage time. Outdoor-reared intact AL pigs produced leaner and less saturated pork and fat compared to castrated ones. Despite the lower antioxidant activity observed in the LL muscles of intact pigs, the lipid oxidative stability of cooked meat was not different among the experimental groups.

Small Bowel Obstruction by a Phytobezoar in a Patient With Previous Antrectomy and Billroth II Reconstruction.

A phytobezoar is a conglomerate of improperly digested fruit and vegetable debris, and its development is associated, amongst other factors, with previous gastric surgery. Most phytobezoars remain asymptomatic and are incidentally found during imaging or interventional procedures. However, in some patients, they can cause small bowel obstruction, which can subsequently lead to severe complications. Although the clinical findings are similar to other causes of intestinal obstruction, there are some particular diagnostic and treatment features more specific to phytobezoars. We present a case of an 85-year-old man with a history of previous antrectomy and Billroth II reconstruction who came to the emergency department with bilateral aspiration pneumonia and intestinal obstruction due to a bezoar. The CT scan showed bilateral inferior lobe pulmonary consolidation, as well as a marked dilation of the small bowel with gas-fluid levels and a transition to normal caliber in the terminal ileum, where an oval mottled-appearing mass suggesting a bezoar was present. An urgent laparotomy confirmed the diagnosis, and an enterotomy with removal of the bezoar was performed. Phytobezoars must be considered as a cause of intestinal obstruction, particularly when patients have a history of previous gastric surgery. Its radiological findings, particularly in CT scans, are specific and should be appreciated to establish the diagnosis promptly. The treatment of small bowel obstruction due to a phytobezoar requires surgery most of the time, and the surgeon must bear in mind the need to look for the existence of other bezoars in the gastrointestinal tract to prevent reoccurrence.

The provision of malaria services in border districts of four countries in Southern Africa: results from a cross-sectional community assessment of malaria border health posts.

BACKGROUND: The importation of parasites across borders remains a threat to malaria elimination. The Southern African Development Community Malaria Elimination Eight (E8) established 39 border health facilities on 5 key international borders between high and low-burden countries. These clinics aimed to improve access to prevention, diagnosis, and treatment of malaria for residents in border areas and for mobile and migrant populations who frequently cross borders. Studies were conducted in each of the four high-burden E8 countries (Angola, Mozambique, Zambia, and Zimbabwe) to evaluate malaria services in border areas. METHODS: Cross-sectional surveys were conducted within 30 km of recently established E8 Border Health Posts. Structured questionnaires were administered to randomly selected respondents to assess malaria-related knowledge and behavior, access to malaria prevention, diagnosis and treatment of malaria, and risk factors for malaria associated with local and cross-border travel. RESULTS: Results showed that most providers followed appropriate guidelines performing blood tests when individuals presented with fever, and that nearly all those who reported a positive blood test received medication. Lack of access to health care due to distance, cost or mistrust of the provider was rare. A minority of respondents reported not receiving timely diagnosis either because they did not seek help, or because they were not offered a blood test when presenting with fever. There was a high level of correct knowledge of causes, symptoms, and prevention of malaria. A majority, of border residents had access to primary prevention against malaria through either long-lasting insecticidal nets (LLINs) or indoor residual spraying (IRS). Cross border travel was common with travellers reporting sleeping outside without protection against malaria. CONCLUSIONS: The study demonstrated the importance of border health facilities in providing access to malaria services. Prevention needs to be improved for people who travel and sleep outdoors. Community health workers can play a key role in providing access to information, testing and treating malaria.

Stereomeric Lipopeptides from a Single Non-Ribosomal Peptide Synthetase as an Additional Source of Structural and Functional Diversification in Pseudomonas Lipopeptide Biosynthesis.

In Pseudomonas lipopeptides, the D-configuration of amino acids is generated by dedicated, dual-function epimerization/condensation (E/C) domains. The increasing attention to stereochemistry in lipopeptide structure elucidation efforts has revealed multiple examples where epimerization does not occur, even though an E/C-type domain is present. While the origin of the idle epimerization in those E/C-domains remains elusive, epimerization activity has so far shown a binary profile: it is either 'on' (active) or 'off' (inactive). Here, we report the unprecedented observation of an E/C-domain that acts 'on and off', giving rise to the production of two diastereoisomeric lipopeptides by a single non-ribosomal peptide synthetase system. Using dereplication based on solid-phase peptide synthesis and NMR fingerprinting, we first show that the two cyclic lipopeptides produced by Pseudomonas entomophila COR5 correspond to entolysin A and B originally described for P. entomophila L48. Next, we prove that both are diastereoisomeric homologues differing only in the configuration of a single amino acid. This configurational variability is maintained in multiple Pseudomonas strains and typically occurs in a 3:2 ratio. Bioinformatic analysis reveals a possible correlation with the composition of the flanking sequence of the N-terminal secondary histidine motif characteristic for dual-function E/C-type domains. In permeabilization assays, using propidium iodide entolysin B has a higher antifungal activity compared to entolysin A against Botrytis cinerea and Pyricularia oryzae spores. The fact that configurational homologues are produced by the same NRPS system in a Pseudomonas strain adds a new level of structural and functional diversification to those already known from substrate flexibility during the recruitment of the amino acids and fatty acids and underscores the importance of complete stereochemical elucidation of non-ribosomal lipopeptide structures.

Transcriptomic Profiling of Subcutaneous Backfat in Castrated and Intact Alentejano Pigs Finished Outdoors with Commercial and Fiber-Rich Diets.

In this work, we studied the backfat transcriptome of surgically castrated (C), intact (I) and intact fed an experimental diet (IE) outdoor-reared male Alentejano (AL) pigs. The experimental diet was a high-fiber diet with locally produced legumes and by-products associated with a boar taint reduction effect. At slaughter (~160 kg), backfat samples were collected for total RNA sequencing. Intact pigs presented leaner carcasses, more total collagen, and more unsaturated intramuscular fat content than C animals. A total of 2726 differentially expressed genes (DEGs, |log2 FC|> 0.58, q < 0.05) were identified between C and I with overexpressed genes related to muscular activity (MYH1, ACTA1) or collagen metabolism (COL1A1, COL1A2) in I pigs. Between C and IE, 1639 DEGs of genes involved in lipidic metabolism (LEP, ME1, FABP4, ELOVL6) were overexpressed in C. Finally, only 28 DEGs were determined between I and IE. Clustering results indicated a drastic influence of the testis in the transcriptome of subcutaneous fat of AL pigs, while the diet had a marginal effect. Diet can reduce stress by increasing satiety in animals, and could have induced an increase of skatole degradation due to the higher expression of the CYP2A19 gene in the IE group.

The influence of tonality, tempo, and musical sophistication on the listener's time-duration estimates.

Music listening affects time perception, with previous studies suggesting that a variety of factors may influence this: musical, individual, and environmental. Two experiments investigated the effect of musical factors (tonality and musical tempo) and individual factors (a listener's level of musical sophistication) on subjective estimates of duration. Participants estimated the duration of different versions of newly composed instrumental music stimuli under retrospective and prospective conditions. Stimuli varied in tempo (90-120 bpm) and tonality (tonal-atonal), in a 2 × 2 factorial design, while other musical parameters remained constant. Estimates were made using written estimates of minutes and seconds in Experiment 1, and the reproduction method in Experiment 2. Two-way analyses of variance (ANOVAs) showed no main effect of tonality on estimates and no significant interactions between tempo and tonality, under any condition. Musical tempo significantly affected estimates, with the faster tempo leading to longer estimates, but only in the prospective condition, and with the use of the reproduction method. Correlation matrices using the Pearson correlation coefficient found no correlation between musical sophistication scores (measured using the Goldsmiths Musical Sophistication Index [Gold-MSI]) and verbal or reproduction estimates. In conclusion, together with the existing literature, findings suggest that (1) changes in tonality, without further changes in rhythm, metre, or melodic contour, do not significantly affect estimates; (2) small changes in musical tempo influence only prospective reproduction estimates, with larger tempo differences or longer stimuli being needed to cause changes in retrospective estimates; (3) participants' level of musical sophistication does not impact estimates of musical duration; and (4) empirical research on music listening and subjective time must consider potential method-dependent results.